HUMAN ADULT CORTICAL REORGANIZATION AND

CONSEQUENT VISUAL DISTORTION

by

Daniel D. Dilks

A dissertation submitted to The Johns Hopkins University in conformity with the

requirements for the degree of Doctor of Philosophy

Baltimore, Maryland

September 2005

© Daniel D. Dilks

All rights reserved

Human Adult Cortical Reorganization and Consequent Visual Distortion

Daniel D. Dilks

Advisor: Dr. Michael McCloskey

ABSTRACT

The mature brain has remarkable capacity for change. In the visual system,

cortical reorganization has principally been demonstrated in studies of adult animals: If a

region of primary visual cortex (V1) loses its usual input (e.g., due to retinal damage),

neurons in that region begin responding to stimuli that normally activate adjacent V1

cortex. However, adult cortical reorganization has not been well documented in the

human visual system; nor have animal or human studies explored the consequences of

reorganization for visual perception. This dissertation asks whether cortical

reorganization occurs in the human adult visual system, and if so, what the perceptual

consequences might be. These questions are addressed by studying an adult stroke

patient, BL.

BL has damage to the right-hemisphere inferior optic radiations. This damage

caused a loss of sensory input to the V1 region representing the upper left visual field

(LVF), producing a left superior homonymous quadrantanopia (i.e., a scotoma or blind

area in the upper left quadrant). However, primary visual cortex itself is intact.

Interestingly, BL exhibits dramatic distortion of perceived shape for stimuli presented in

the lower LVF: The stimuli appear vertically elongated (toward and into the blind upper

quadrant). For example, when shown a circle, BL reports seeing a “cigar” extending

upward; when shown a square, he reports seeing a vertically-elongated “rectangle”; and

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when shown an upside down triangle, he reports seeing a “pencil” standing upright.

Psychophysical testing confirmed the perceptual distortion, and established that the

vertical but not the horizontal dimension was affected; that is, shapes presented below the

scotoma were perceived as vertically elongated, toward and into the scotoma. Given

these findings, I hypothesized that the perceptual distortion in the lower LVF was a

consequence of V1 reorganization. BL’s stroke did not damage V1 directly, but the V1

region representing most of the upper LVF was deprived of its usual input (due to optic

radiation damage). Neurons in the deafferented region may consequently have become

responsive to inputs from the lower LVF, such that stimuli presented in the lower LVF

activated not only the V1 region representing this area, but also the adjacent region that

previously received input from the upper LVF. If activation of this latter region were still

treated by BL’s visual system as representing upper LVF stimulation, stimuli in the lower

LVF might well appear vertically elongated. I will call this phenomenon phantom vision.

Additional psychophysical experiments confirmed several predictions following

from my hypothesis. Results revealed that the deficit is selective to vision (i.e., tactile

shape judgments are intact); that vertical distance as well as shape judgments are

affected; that the vertical distortion arises in a retinocentric frame of reference; that the

deficit affects not only vision-for-perception, but also vision-for-action (grip aperture);

and that the extent of vertical distortion monotonically decreases with distance from the

blind quadrant;. Additionally, I used functional magnetic resonance imaging (fMRI) to

seek evidence for cortical reorganization in BL (i.e., whether there are any changes in the

visual cortical topographical map). Results revealed that there is activation in the

deprived cortical area when a visual stimulus is presented below this area. Visual cortex

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deprived of input from the upper LVF has apparently become responsive to stimuli in the

lower LVF. Taken together, these studies show that BL’s perceptual distortion results

from V1 reorganization, providing the first clear demonstration of cortical reorganization

in the adult human visual system, and the first evidence that reorganization affects visual

perception.

CANDIDATE: Daniel D. Dilks READERS: Michael McCloskey (Advisor) Barbara Landau Steven Yantis Howard Egeth Stewart Hendry

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ACKNOWLEDGMENTS

This thesis would have never happened without the effort, mentoring, and support

of many special people to whom I will be forever grateful. My first and most heartfelt

thanks go to BL. Thank you for the countless hours you spent with me over a period of

four years. Your tireless effort is a true inspiration. I will miss the ‘testing’ time, the

‘after-testing’ conversations, and especially the jokes (which we will not talk about here).

BL – keep up the wonderful spirit.

Next, I would like to thank my advisors Michael McCloskey and Barbara Landau.

Thank you both for being the most extraordinary mentors one could ask for. Mike, thank

you for the guidance (some prefer to call it demanded attention, but not me) and

encouragement throughout this project. Perhaps most importantly, however, I want to

thank you for teaching me how to look deep into problems, pull out the fundamental

challenges and issues, and attack them firsthand. I hope to someday emulate your keen

insight and exceptional intelligence. Barbara, from the very beginning you have believed

in me, and I thank you deeply. I hope I have made you proud. Thank you also for the

constant support (although this was probably difficult considering an extremely jealous

graduate student who shall remain nameless – LL). And last, but certainly not least,

thank you for teaching me through example what it means to be a great thinker.

Of great support (both academically and SOCIALLY) to me during my time here

were my fellow graduate students and friends in Cognitive Science. To begin, I want to

thank the leaders of the ‘old’ crowd: Matt Goldrick and Lisa Davidson. Thanks for so

warmly welcoming me to the department, and for introducing me to Baltimore. Next, a

special thanks to the people who had to put up with me for my entire tenure (Note:

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names are in alphabetical order so as not to lose any of my dear friends): Adam

Buchwald (well, look who is first), Laura Lakusta (hmm, look who is second), Uyen Le,

Jared Medina, Tamara Nicol, Becky Piorkowski, and Oren Schwartz. Thank you for all

the wonderful times – I cannot imagine what it would have been like without you. I will

forever cherish your friendships. And finally, to my ‘newbie’ friends, Ari Goldberg and

Becca Morley, I pass the torch to you. Thank you also to my Psychology friends,

Christina Castelino and John Serences; my favorite postdoc, Kirsten O’Hearn-Donny;

and all my Landau lab mates. I am also extremely grateful for the endless support of my

undergraduate assistants. Thank you, thank you, thank you (for doing all my work).

Lastly, thanks to my dissertation committee, Mike McCloskey, Barbara Landau,

Steve Yantis, Howard Egeth, and Stewart Hendry. Thank you not only for taking the

time to read this thesis, but, more importantly, advising me along the way. I hope you

enjoyed this experience as much as I did.

This dissertation is dedicated to the two people that I owe everything – my

parents. Without your never-ending love, support, and confidence this would never have

happened. Mom and Dad, words cannot express how thankful I am to have you both.

This is for you!

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TABLE OF CONTENTS

Abstract ii

Acknowledgments v

Table of Contents vii

List of Tables ix

List of Figures x

I: Introduction 1

II: Cortical Reorganization 3

Somatosensory Cortex 3

Long-term effects of deafferentation in non-human animals 3

Short-term effects of deafferentation in non-human animals 6

Effects of deafferentation in humans 7

Visual Cortex 9

Long-term effects of deafferentation in non-human animals 9

Short-term effects of deafferentation in non-human animals 14

Effects of deafferentation in humans 16

III: Perceptual Consequences of Cortical Reorganization 19

Somatosensory Domain 19

Long-term reorganization 19

Short-term reorganization 23

Visual Domain 24

Long-term reorganization 24

Short-term reorganization 29

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IV: Case Description (BL) 33

V: Shape Perception 38

Visual Shape Perception 39

Vertical and Horizontal Judgment Experiments 39

Shape Judgment Experiment 45

Tactile Shape Perception 47

Vertical/Horizontal Judgment Experiments 49

VI: Hypothesis 49

VII: Locus of Deficit 53

Visual Distance Perception 53

Frame of Reference 56

Visually-guided Grasping 60

VIII. Extent of Distortion 64

IX: Overall Discussion of Behavioral Results 68

X: Retinotopic Mapping of V1 69

XI: General Discussion 77

References 85

Curriculum Vitae 98

viii

LIST OF TABLES

Table 1: Extent of stretching results for squares presented at various positions

in the LVF 65

ix

LIST OF FIGURES

Figure 1: Somatopic map (of the digits) of an Owl Monkey (A) before

and (B) after amputation of digit 3 5

Figure 2: Superior perspective of right arm amputee patient FA’s brain 8

Figure 3: Receptive field maps in a region of monkey cortex deafferented

by a retinal lesion, immediately before the lesion was made (left) and two

months following the lesion (right) 11

Figure 4: Depicts region on the left side of the face of patient VQ which

elicited localized referred sensations in the phantom digits 20

Figure 5: Penfield’s homonculus 22

Figure 6: Effect of looking to one side of a line 26

Figure 7: Effect of viewing annuli 27

Figure 8: Results from Kapadia et al. (1994) 30

Figure 9: Kapadia et al.’s explanation for perceptual mislocalization 31

Figure 10: MRI following BL’s stroke revealing right optic radiation damage 33

Figure 11: Kinetic bowl perimetry results 34

Figure 12: Results (percent that BL reported seeing anything) from

a visual field mapping procedure done with a 3.2º x 3.2º shape presented

at one of nine locations in each quadrant 36

Figure 13: BL’s drawings and descriptions 38

Figure 14: Sample displays for horizontal and vertical judgment experiments 39

Figure 15: Horizontal and vertical judgments 42

Figure 16: Vertical judgments for unfilled rectangles, black rectangles

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on a white background, rectangles whose primary axis of elongation

was horizontal, and parallelograms 44

Figure 17: Shape judgment by BL 46

Figure 18: Tactile horizontal and vertical judgments 48

Figure 19: Proposed hypothesis 50

Figure 20: Sample display for visual distance perception experiment 54

Figure 21: Visual distance perception 55

Figure 22: Retinotopic map 56

Figure 23: Drawing and verbal report by BL of perceived shape presented

in upper LVF when his head was tilted 90° 57

Figure 24: Sample display for frame of reference experiment 58

Figure 25: Frame of reference 59

Figure 26: Visually-guided grasping board 61

Figure 27: BL’s visually-guided grasping results collapsed over hand 62

Figure 28: Tested locations for the extent of stretching experiment 64

Figure 29: The effect of cortical magnification on extent of distortion 67

Figure 30: fMRI meridian mapping display and results 69

Figure 31: fMRI experimental display and results 73

Figure 32: fMRI results at various thresholds 74

Figure 33: fMRI results for wedge 5 only at various correlation

thresholds 75

Figure 34: Visual pathway representing possible connections involved

in cortical reorganization 79

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Figure 35: Example of the axon of a pyramidal cell in a primate visual

cortex forming long-range clustered horizontal connections 81

Figure 36: The horizontal connection account of cortical reorganization 83

Figure 37: The feedback connection account of cortical reorganization 84

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I: INTRODUCTION

Traditionally, primary sensory cortex (auditory, somatosensory, visual) was

considered largely immutable in the adult mammal, and was assumed to be fully-formed

after initial development. Over the past two decades, however, research has revealed that

primary sensory cortex exhibits a remarkable degree of plasticity that is not limited to the

first few months of life but extends throughout adulthood. For instance, numerous

studies on adult animals have shown that if a region of primary sensory cortex is deprived

of its normal input (e.g., by cochlear lesions, amputation of a digit, or retinal lesions),

neurons in the deprived region begin responding to stimuli that normally activate adjacent

cortex – a process referred to as cortical reorganization, remapping, or plasticity.1

Although some cortical reorganization has been reported in adult animals,

surprisingly little work has investigated cortical reorganization in the human adult.

Furthermore, even less work has explored the perceptual consequences of cortical

reorganization, and in fact, no work has directly addressed this issue in the visual domain.

This dissertation asks whether cortical reorganization occurs in the human adult visual

system, and if so, what the perceptual consequences might be.

This thesis begins with a review of the cortical reorganization literature focusing

on the somatosensory and visual cortices of both adult animals and humans. Some work

has been done on auditory cortical reorganization (e.g., Robertson & Irvine, 1989; Rajan,

Irvine, Wise, & Heil, 1993), but this will not be discussed. I then discuss the few studies

that have investigated the perceptual correlates of cortical reorganization (both in the

somatosensory and visual domains).

1 Recently, some controversy has arisen regarding cortical reorganization in both the adult animal and human visual systems. This issue will be discussed more thoroughly in the literature review section.

1

Next, I will describe a stroke patient, BL. BL’s stroke destroyed the optic radiation fibers

that normally provide input to the primary visual cortex (V1) region representing the

upper left visual field (LVF). As a consequence, BL is blind in his upper LVF. When

shapes are presented in the lower LVF (below the blind area), BL exhibits distorted

perception: Stimuli appear vertically elongated, toward and into the blind region. On the

basis of these findings, I offer the hypothesis that perceptual distortions result from

reorganization of V1 and present behavioral and functional magnetic resonance imaging

(fMRI) data supporting my hypothesis. These data provide a clear demonstration of

cortical reorganization in the adult human visual system, and the first evidence that

reorganization can affect visual perception.

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II: CORTICAL REORGANIZATION

Somatosensory Cortex

A wealth of evidence suggests that when a region of primary somatosensory

cortex (S1) is deprived of its normal input, the cortex reorganizes such that neurons in the

deprived area begin to respond to inputs from adjacent body surfaces. Past research on

adult animals has found cortical reorganization following long-term (weeks, months,

years) and short-term (hours, minutes) disruption of afferents.

Long-term effects of deafferentation in non-human animals

One of the first and most influential demonstrations of cortical reorganization

following long-term disruption of afferents was in adult monkey S1. Merzenich, Kaas,

Wall, Nelson, Sur, et al. (1983a, b) transected and ligated (tied off) the median nerve of

owl and squirrel monkeys, thus removing some of the normal input to somatosensory

cortical areas 3b and 1. These cortical areas normally respond to the ventral surface of

digits 1, 2, and 3 (i.e., thumb, index, and middle fingers). This manipulation did not

result in a permanent large area of unresponsive cortex; rather, it produced a dramatic

reorganization of the somatotopic map. Somatopic maps were derived by determining

the receptive fields (RFs) for multineuron activation in several hundred electrode

penetrations in and around areas 3b and 1. Over the course of 2-9 months after

denervation, mapping revealed that neurons in the deprived cortex became responsive to

inputs from bordering skin surfaces. Specifically, the deprived cortex (which originally

responded to the ventral surface of digits 1, 2, and 3) now responded to stimulation of the

dorsal surface of digits 1 and 2 and the ventral surface of palmar regions. Thus, it seems

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as if S1, as a result of being deprived of its normal input, has reorganized and neurons in

that region have begun to respond to inputs from adjacent body surfaces.

Similar results have been reported in the adult cat. Kalaska and Pomerantz (1979)

recorded from S1 neurons of eight operated and eight unoperated (control) cats. In the

operated cats, the front paw was partially denervated by transecting and ligating the

radial, median and ulnar nerves. Recordings were made 8-10 weeks following surgery.

While recording from cells in “paw cortex” (PC) – that normally respond to stimulation

only of the front paw (verified by the control cats) – the researchers found that PC cells

began responding to stimulation on the wrist and forearm (i.e., neighboring regions in

S1).

In a related experiment, Merzenich, Nelson, Stryker, Cynader, Schoppmann, et al.

(1984) demonstrated that removal of input by digit amputation also leads to similar

reorganization in adult owl monkeys. Using microelectrode mapping, Merzenich and

colleagues examined the cortical representations of the hand in cortical area 3b before

and after the amputation of either digit 3, or digits 2 and 3. Two to eight months after

amputation, most of the cortex that originally responded only to skin surfaces on the

amputated digit(s) now responded to inputs from immediately adjacent digits and or the

subjacent palm (Figure 1). There was not a significant increase of the representation of

more distant digits, for example, D5.

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Figure 1. Somatopic map (of the digits) of an Owl Monkey (A) before and (B) after amputation of digit 3 (Merzenich et al., 1984).

One of the most dramatic examples of the long-term effects of deafferentation

was reported by Pons, Garraghty, Ommaya, Kaas, Taub, et al. (1991). They mapped the

cortex of adult monkeys that had undergone limb deafferentation (C2-T4 rhizotomies)

twelve years before, thereby depriving the cortical area 3b of its normal input from the

arm and hand. Their maps revealed that all of the deprived area had developed novel

responses to neighboring skin areas, including the face and chin. Similar results were

found in the adult monkey two years after digit 2 amputation. Manger, Woods, and Jones

(1996) found that the cortex normally responsive to digit 2 became responsive to

stimulation from surrounding digits and palm.

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Short-term effects of deafferentation in non-human animals

The experiments described above demonstrated cortical changes occurring over

weeks, months, and years. Similar experiments also showed that extensive changes can

take place over much shorter periods of time, within minutes and perhaps seconds. In a

series of studies, Calford and Tweedale examined the short-term (i.e., as soon as stitching

after amputation was completed – which takes a few minutes) effects of thumb

amputation in the flying-fox. They found that neurons normally responsive to the thumb

were now responding to adjacent body areas (wrist, forearm, and prowing). Similar

initial effects were found when they used local anesthesia to provide a temporary

denervation. However, when responsiveness returned to the locally anesthesized area

(after 10-30 minutes), the deprived neurons (that had become responsive to adjacent body

areas) returned to their initial state and responded again to the thumb. In a similar study

by the same group, Calford and Tweedale (1991) investigated the short-term effects of

digit amputation and anaesthesia in area 3b of macaque monkeys. In two animals, as

quickly as 2 minutes after digit amputation, neurons that initially responded to the

amputated digit now responded to adjacent digits. In the three monkeys where local

anaethesia was used to provide temporary denervation, similar effects occurred between 7

and 10 minutes after anesthesia was administered. Again, however, soon after

responsiveness returned to the anesthesized area, the deprived neurons returned to their

initial state.

Similar results were found in numerous other species. Byrne and Calford (1991)

examined immediate cortical changes in the adult rat after hindpaw digit amputation.

They found that the deprived area of cortex (the area that normally responds to the

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hindpaw) now responded to stimulation of areas bordering the hindpaw region. In 22 of

the 29 rats studied this reorganization occurred within 5 minutes of the amputation.

Similarly, Wall and Cusick (1984) studied the effects of denervation of the hindpaw in

adult rats and compared the organization of S1 to that of normal rats. The study involved

transection of the sciatic nerve that, along with the saphenous nerve, innervates the

hindpaw of rats. Following this transection, mapping of cortex revealed that neurons

normally responsive to sciatic inputs began responding to inputs from the saphenous

nerve. These changes were observed within 1 day following the transection.

Short-term effects have also been examined in adult raccoons with amputated

digits (Kelahan & Doetsch, 1984). Neuronal recordings were done at various time periods

after amputation of digit 3 of adult raccoons. The findings were consistent with respect to

the rapid responsiveness of deprived cortex to inputs from neighboring skin areas. Within

one hour following amputation, cortex normally corresponding to digit 3 became

responsive to stimulation of digits 2 and 4. Additional changes were observed in this

responsiveness over the next few weeks. One to four weeks following amputation, this

area of cortex began to additionally respond to the “stump” of digit 3.

Effects of deafferentation in humans

While the majority of the work on somatosensory cortical reorganization has been

done in adult animals, several imaging studies in humans indicated that large-scale

reorganization can occur in human somatosensory cortical areas. Yang, Gallen,

Ramanchandran, Cobb, Schwartz, et al. (1994) investigated whether cortical

reorganization takes place in adult humans following upper extremity amputation. Using

magnetoencephalographic (MEG) recordings, Yang and colleagues mapped

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somatosensory cortex responses evoked by painless pneumatic stimuli applied to the face,

hand, and upper arm of four neurologically normal controls and two upper right arm

amputee patients. Somatotopy maps revealed that, unlike the control subjects (who

showed the expected bilateral symmetry with an inferior to superior homuncular

progression from face-to-hand-to arm regions), the amputees (in the affected

hemispheres) showed a pronounced intrusion of facial representations into the cortical

regions expected to be occupied by the hand and upper arm (Figure 2). The unaffected

hemispheres in both patients revealed the expected homuncular organization as seen in

normal controls.

Figure 2. Superior perspective of right arm amputee patient FA’s brain. The unaffected right hemisphere shows the expected homuncular organization - face region (squares), hand region (circles), and upper arm region (triangles). The affected left hemisphere shows the face (squares) and upper arm region (triangles) extending into the expected digits and hand territory (Yang et al., 1994).

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Additional MEG studies on limb amputees have provided further evidence that

extensive cortical reorganization persists in humans following limb amputation (Elbert,

Flor, Birbaumer, Knecht, et al., 1994; Flor, Elbert, Knecht, Wienbruch, et al., 1995).

These studies found that the equivalent-dipole source for stimulation of the face was

shifted into the cortical region that had previously responded to the hand and upper arm.

Visual Cortex

As is the case of S1, removal of the normal input to parts of V1 apparently results

in cortical reorganization. However, unlike research on S1, V1 research has generated

controversy regarding the occurrence of cortical reorganization in both the adult animal

and human visual systems.

Long-term effects of deafferentation in non-human animals

To examine the long-term effects of deafferentation on visual cortex, Kaas and

colleagues developed a paradigm in which V1 of adult cats was deprived of its normal

input by creating a retinal lesion in one eye and removing the other eye (enucleation).

Kaas, Krubitzer, Chino, Langston, Polley, et al. (1990) lesioned a 5-10° area of one retina

and enucleated the unlesioned eye. Two to six months after the lesion, recordings

revealed that the neurons in the deprived region of cortex acquired new receptive fields

corresponding to areas surrounding the retinal lesion. In a similar study, Chino, Kaas,

Smith, Langston, and Cheng (1992) mapped adult cat V1 two months after producing a

focal monocular lesion, creating a scotoma between 5-10°, in one retina and showed that

the topography was relatively unaltered. However, a few hours after enucleation of the

unlesioned eye, neurons initially responsive to the lesioned area developed responses to

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retinal locations surrounding the retinal lesion. These results suggest that total (i.e., input

from both eyes) deprivation is necessary for cortical reorganization to occur. Contrary to

this claim, other researchers have shown that cortical reorganization may occur following

circumscribed monocular lesions without the removal of the other eye (Chino et al.,

1992; Schmid, Rosa, Calford, & Ambler, 1996; Calford, Wang, Taglinetti, Waleszcyk, et

al., 2000; for a review see Dreher, Burke, & Calford, 2001).

Similar reorganization was shown with a paradigm involving matched binocular

lesions creating scotomas approximately 5° in diameter (Gilbert & Wiesel, 1992; Chino,

Smith, Kaas, Sasaki, et al., 1995). Two months after lesioning the retinas of both eyes,

recordings from adult cats and monkeys revealed that neurons in the deprived area of V1

acquired new receptive fields corresponding to areas surrounding the lesion (Figure 3).

In other words, the deprived neurons were now responsive to stimulation of retinal

regions adjacent to the lesion.

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Figure 3. Receptive field maps in a region of monkey cortex deafferented by a retinal lesion, immediately before the lesion was made (left) and two months following the lesion (right) (Gilbert & Wiesel, 1992). (Note: Dashed circles represent lesioned area)

Likewise, Heinen and Skavenski (1991) deactivated a large sector of V1 in adult

monkeys by producing bilateral foveal lesions creating scotomas approximately 3° in

diameter, and found that after 75 days of recovery, neurons in the deprived area of cortex

had much larger receptive fields (up to 5º in diameter) than the very small receptive fields

(about 1º in diameter) expected for foveal striate cortex neurons. In other words, the

deprived neurons became responsive to areas surrounding the retinal lesion. Similarly,

Darian-Smith and Gilbert (1995) created matched binocular lesions (creating scotomas

between 3.5-14° in diameter) in adult cats and monkeys. A cortical silent zone was found

immediately (between 5 and 60 minutes) following the retinal lesions; however, two to

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twelve months after lesioning, neurons inside the deprived region showed a substantial

increase in receptive field size (by as much as 10-fold), thus becoming responsive to

surrounding stimulation. Neurons located close to the deprived zone also showed an

increase in receptive field size.

One can also describe reorganization with respect to the size of the cortical

“scotoma” (the silenced cortical region) immediately following the lesion compared to

some months following. In the above studies, it was found that a cortical scotoma up to 6

to 7 mm in diameter can completely fill-in within 2-3 months. Larger scotomas are

generally left with a residual silent area in the center for periods up to 1 year. To get an

idea of the dimensions involved, in the primate, a lesion subtending 5° of visual field,

centered about 4° in the periphery, silences an area of cortex 10 mm in diameter (Gilbert

& Darian-Smith, 1995).

Standing in contrast to the above research, some studies have failed to find

evidence for long-term V1 reorganization in the adult macaque (Horton & Hocking,

1998; Smirnakis, Brewer, Schmid, Tolias, et al., 2005). For example, Horton and

Hocking found that after lesioning a 3-9° area in one retina in adult macaques,

cytochrome oxidase levels in the deafferented V1 region remain ‘severely depressed’ for

many months (up to 4.5 months), even after enucleation of the remaining eye. Horton

and Hocking contend that the delayed cortical recovery after retinal lesioning is related to

retinal healing (to be discussed in more detail shortly). In another study, Smirnakis and

colleagues applied functional magnetic imaging (fMRI) to detect changes in the cortical

topography of adult macaque V1 after lesioning a 4-8º area in the retinas of both eyes.

The deprived region was monitored every 2-8 weeks, starting 2-3 hours after lesioning

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and continuing for 18-30 weeks. They showed that, in contrast to previous studies, the

deprived V1 does not approach normal responsivity during 7.5 months of follow-up after

retinal lesions, and its topography does not change. Electrophysiological experiments

corroborated the fMRI results. Specifically, Smirnakis and colleagues found that neurons

located within the BOLD-defined deprived cortical area were unresponsive. These

results suggest that adult macaque V1 has limited potential for significant reorganization

in the months following retinal injury. Clearly then, these findings contrast with studies

indicating that long-term cortical reorganization occurs over 2-6 months. While the

reasons for this discrepancy are unclear, Smirnakis and colleagues offer several

suggestions. First, they argue that long-term reorganization might be restricted to a few

sparsely distributed single neurons, and that the BOLD response (reflecting the average

activation of ensembles of cells) might provide a more complete assessment of overall

neuronal recovery. Second, similar to the Horton and Hocking argument, Smirnakis et al.

assert that the so-called cortical reorganization (i.e., the shrinking of the cortical scotoma)

might occur because of retinal recovery from the swelling caused by retinal lesioning.

They state that most studies of long-term reorganization are suspectible to this effect

because they compare cortical activity immediately after retinal lesioning with activity

seen several months later. For example, a retinal lesion coupled with the accompanying

retinal swelling might initially deprive a region of cortex 10 mm in diameter. However,

after recovery from retinal swelling (some months later), the cortical scotoma is only 4

mm in diameter. It is this shrinking of the cortical scotoma (caused by the recovery) that

masquerades as long-term cortical reorganization. However, Smirnakis and colleagues

did not observe a significant shift of the cortical scotoma border from the day of the

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lesion onwards, so they concluded that it is unlikely that retinal swelling and subsequent

recovery played a major role. And third, Smirnakis et al. indicate that results of long-

term reorganization might be exaggerated by a systematic underestimation of rapid or

short-term reorganization (occurring within minutes to hours). Short-term reorganization

will be discussed next.

Short-term effects of deafferentation in non-human animals

As discussed above, there are some difficulties demonstrating rapid or short-term

reorganization in visual cortex induced by laser lesions. Specifically, with the laser-

lesion procedure, which is essentially a heating of the pigment epithelium, there is an

extensive secondary effect seen as a result of the biochemical activation of a number of

cell classes, including photoreceptors, Müller cells, and ganglion cells (Tassignon,

Stempels, Nguyen-Legros, Brihaye, et al., 1991; Yamamoto, Ogata, Yi, Takahashi, et al.,

1996; Humphrey, Chu, Mann & Rakoczy, 1997; Chu, Humphrey, Alder, & Constable,

1998). This biochemical activation appears to produce widespread temporary

deactivation, precluding the study of immediate effects. As a result, some researchers

have conducted experiments involving a less traumatic lesioning procedure, essentially

eliminating such widespread temporary deactivation (Schmid, Rosa, & Calford, 1995,

Schmid et al., 1996). In these studies, a lower power laser light was used to make a small

lesion in animals which had been preloaded with excess fluids, by intravenous infusion.

Hemodynamic forces induced a retinal detachment four to five times larger than the

initial lesion. With this procedure, Schmid and colleagues found that the responses of

cortical neurons within the deprived zone to stimulation in the unaffected part of the

retina were evident at 12 hours post-detachment. They found that the receptive field size

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of cells within the deprived zone were substantially (up to 10-fold) larger than their

normal counterparts in the unlesioned eye.

Others studying the short-term effects of visual cortex deafferentation have

developed a clever method of doing so using an ‘artificial scotoma’. In artificial scotoma

studies a region of retina is shielded from visual stimulation, while at the same time the

surrounding region is vigorously stimulated. Using this method, several researchers

independently showed that, after defining the classical receptive field area of a neuron, a

mask could be placed over the field area and the neuron would become responsive to

visual stimuli outside the deprived zone. For example, Pettet and Gilbert (1992) recorded

from single cells in V1 of the adult cat and stimulated the retina with a pattern of moving

lines, while masking out the region corresponding to the receptive field of the cell. After

a conditioning period of 10-15 minutes, this artificial scotoma resulted in an average 5-

fold expansion in receptive field size for neurons with receptive fields in the scotoma

region. Interestingly, stimulation of the classic receptive field caused a shrinkage of the

receptive field back to its original size. Further surround stimulation led to an additional

increase in area and the sequence of receptive field expansion and contraction could be

repeated. However, whether temporary reorganization resulting from brief exposure to

an artificial scotoma is similar to short-term reorganization after permanent

deafferentation remains an open question.

Similar results were obtained by Fiorani, Rosa, Gattass, and Rocha-Miranda

(1992) in adult monkeys. Recording from neurons in the parts of V1 corresponding to

the natural (optic disk) and artificially produced blind regions, they showed that neurons

within the cortical representation of these ‘blind’ areas were responsive to stimuli beyond

15

the boundaries of the ‘blind’ cortical area. Moreover, they found that masking the

receptive field increases it by up to 10 times. DeAngelis, Anzai, Ohzawa, and Freeman

(1995) also performed similar experiments, and found that cells in a masked region

responded to stimuli surrounding the artificial scotoma, but they interpreted their results

as indicating a change in response gain rather that a change in receptive field size.

DeAngelis and colleagues suggest that the major difference between their results and

those reported above involves the definition of receptive field size. If one measures size

using an absolute-response-level criterion, then changes in response amplitude or base

rate could be interpreted as changes in receptive field size. They contend, however, that

receptive field size should be defined independently of response amplitude. Regardless

of the interpretation, the above results clearly demonstrated the capacity for rapid

reorganization in primary visual cortex.

Effects of deafferentation in humans

Baseler, Brewer, Sharpe, Morland, Jagle et al. (2002) demonstrated compelling

abnormal cortical responsiveness in three rod monochromats (congenitally colorblind

individuals who lack cone photoreceptor function). Because rod monochromats lack

most or all input from cones, they provided the authors a unique opportunity to

investigate how the large area of primary visual cortex (representing foveal vision)

develops given the lack of cone input. Using fMRI responses to an expanding-ring

stimulus to determine the representation of visual field eccentricity, they found that

normal controls had a cortical region, spanning several cm2, that responded to stimuli

presented foveally under cone viewing conditions (photopic – bright light) but was

inactive to stimuli presented under rod viewing conditions (scotopic – dim light). By

16

contrast, in rod monochromats, this cortical region responded to stimuli presented under

rod viewing conditions; thus, the cortical zone normally driven by the central cone-rich

regions of the visual field had been recruited by rod-initiated inputs. Similarly, Morland,

Baseler, Hoffman, Sharpe, and Wandell (2001), using fMRI, demonstrated abnormal

retinotopic mapping in human visual cortex in a rod monochromat patient. They found

that V1 underwent a reorganization whereby regions that would normally represent

central field locations now mapped more peripheral positions in the visual field. Any of

the above results, however, could reflect early developmental plasticity (as opposed to

cortical plasticity occurring in adulthood).

To my knowledge, only two studies have examined reorganization following

cortical deprivation in human adults, and each one found different results (Sunness, Liu,

& Yantis, 2004; Baker, Peli, Knouf, & Kanwisher, 2005). Both studies investigated

patients with macular degeneration (MD). MD is a condition that damages the central

retina, and as a consequence, deprives of input the area of V1 that normally responds to

central stimuli. Using fMRI, the researchers asked whether the deafferented cortex

remains inactive in adult patients with MD, or whether it begins responding to stimuli

presented at retinal areas surrounding the damaged central retina. In one study (Sunness

et al., 2004), which explored a patient suffering from MD for about 3 years, found no

evidence for cortical reorganization: Cortex corresponding to the damaged retina was

unresponsive to stimulation of intact retina. In the second study (Baker et al., 2005), two

patients with MD dating back more than 20 years exhibited strong cortical responses

within the deafferented cortex to a stimulus presented in the periphery, suggesting

cortical reorganization. These differing results could be due in part to the amount of time

17

with MD (approximately 3 years in the first study, more than 20 years in the second).

Perhaps an extended period of deprivation is necessary for human cortical reorganization.

Another possible explanation might have to do with some sparing of the fovea (as in the

Sunness et al. study, but not in the Baker et al. study). For example, it has been

hypothesized that human cortical reorganization requires the active use and/or chronic

attention to a non-lesioned retinal location. Thus, when the fovea remains viable (as in

the Sunness et al. case), little to no active use of another retinal location is necessary, and

there may be little drive toward reorganization. Clearly, much more evidence is needed

about the extent of cortical reorganization in the adult human visual system, and the

conditions under which reorganization occurs. The data I report in this thesis, however,

will suggest that neither a prolonged period of deprivation (e.g., greater than 3 years as

suggested by the above studies) nor the active use to a non-lesioned retinal location are

necessary for cortical reorganization to occur.

18

III: PERCEPTUAL CONSEQUENCES OF CORTICAL REORGANIZATION

Given the ample evidence of cortical reorganization as a result of peripheral

deprivation, it is reasonable to suppose that such a change in sensory cortical

responsiveness might lead to perceptual changes. Surprisingly, little work has addressed

this issue. Nevertheless, a few important studies, mostly in the somatosensory domain,

have suggested that cortical reorganization may lead to perceptual changes. This section

will first review the literature in the somatosensory domain and then discuss the visual

domain.

Somatosensory Domain

Long-term reorganization

Perceptual effects have been shown in a few cases of reorganization of

somatosensory cortex caused by amputation. As discussed earlier, Pons et al. (1991)

found that after long-term (12 years) deafferentation of one limb in adult primates, the

region of cortex corresponding to the limb became responsive to stimuli applied to the

lower face region. Motivated partly by these results, the first study asked whether stimuli

applied to the face of amputees would be mislocalized to the arm (Ramachandran,

Stewart, & Rogers-Ramachandran, 1992; Ramachandran, Rogers-Ramachandran, &

Stewart, 1992). To explore this, Ramachandran et al. (1992) studied localization of touch

sensations in two human patients after amputation. The first patient, VQ, was a 17 year-

old whose left arm was amputated 6 centimeters above the elbow about 4 weeks prior to

testing. Ramachandran and colleagues studied localization of touch (and light pressure)

using a Q-tip that was brushed twice in rapid succession at various randomly selected

points on VQ’s skin surface. His eyes were shut during the entire procedure and he was

19

simply asked to describe any sensations that he felt and to report the perceived location of

these sensations. Ramachandran et al. found that even stimuli applied to points remote

from the amputation line were often systematically mislocalized to the phantom arm.

Furthermore, the distribution of these points was not random but appeared to be clustered

on the lower left side of the face (i.e., ipsilateral to amputation), with a systematic one-to-

one mapping between specific regions on the face and individual digits (e.g., from the

cheek to the thumb, from the philtrum (area below the nose to the upper lip) to the index

finger, and from the chin to digit 5 – the ‘pinky’) (Figure 4).

Figure 4. Depicts region on the left side of the face of patient VQ which elicited localized referred sensations in the phantom digits (Ramachandran, et al., 1992). (Note: T = thumb; P = pinky; I = index finger; B = ball of the thumb)

Typically, the patient reported that he simultaneously felt the Q-tip touching his

face and a tingling sensation in an individual digit. Stimuli applied to other parts of the

body such as the tongue, neck, shoulders, trunk, axilla and contralateral arm were never

20

mislocalized to the phantom hand and no referred sensations were ever felt in the other

(normal) hand. In addition, a second cluster of points was found about 7 centimeters

above the amputation line. Again there was a systematic one-to-one mapping with the

thumb being represented medially on the anterior surface of the arm and the ‘pinky’

laterally.

When a drop of warm water was placed on the patient’s face, he reported a

distinct feeling of warmth in his entire phantom hand. Finally, various points on the skin

surface were gently pricked with a pin. A pinprick delivered above the stump felt like a

pinprick on the phantom thumb, whereas when it was delivered more laterally it was felt

on the ‘pinky’.

In testing the second patient, WK (whose entire right arm was removed one year

before testing), Ramachandran and colleagues found a very similar pattern of results.

They had WK close his eyes and they rubbed the skin of his right lower jaw and cheek

with one of their fingers. A representation of the entire phantom arm was found on the

face with the hand being represented on the anterior lower jaw, the elbow on the angle of

the jaw, and the shoulder on the temporamandibular joint. Again, as in VQ, there

appeared to be a precise one-to-one correspondence between points on the lower jaw and

individual digits. In addition, movement of a Q-tip from one point to another on the face

evoked a referred sensation of movement down the phantom arm, beyond his elbow.

The researchers studying these two patients suggested that these patients

“referred” sensations (from the face and around the line of amputation) to the phantom

limb because of cortical reorganization. Their logic was as follows: The hand area in

21

Penfield’s homunculus is flanked on one side by the face and on the other side by the

upper arm and shoulders (Figure 5).

Figure 5. Penfield’s homunculus.

However, in these patients, as a result of amputation, the hand area is devoid of input.

Thus, the somatosensory map reorganizes such that the sensory input from the face and

upper arm regions “invades” the cortical hand area and provides a basis for referred

sensations.

Lastly, Ramachandran and colleagues studied a 45 year-old woman, DW, whose

middle finger (digit 3) had been amputated when she was 16 years old. Using a Q-tip,

they found that touching either digit 2 or 4 at various points on the side that was adjacent

22

to the amputated digit evoked referred sensations in roughly corresponding locations on

the phantom finger. Drops of warm or cold water at these sites evoked warm and cold

sensations on the phantom finger and when they tightly gripped and released her index

finger she felt her phantom finger being tightly gripped. These findings suggest a direct

perceptual correlate of the observations of Merzenich et al. (1984).

Additional studies on referred sensations following limb amputation in humans

have also been conducted. Using the procedure described above, Halligan, Marshall,

Wade, Davey, and Morrison (1993) studied an upper right arm amputee one year after

amputation, and found that stimuli applied to the right side of the face were

systematically mislocalized to parts of the phantom limb. Their results were consistent

with the Ramachandran et al. findings. Agliotti, Bonazzi, and Cortese (1994)

investigated whether skin areas eliciting phantom sensations can also be shown in lower

limb amputees, and whether they are distributed according to somatotopic representation.

Three lower limb amputees (tested anywhere between 5 months to 2 years after

amputation) were asked to report sensations evoked by touch delivered through finger

tips and pinpricks. Bodily areas including the upper limb, face, and back regions were

stimulated. In all patients, tactile stimuli delivered to particular points on the upper limb

were localized on the stimulated point and simultaneously mislocalized to a select point

of the phantom (with a very precise topographic mapping).

Short-term reorganization

While the above studies suggest perceptual effects of cortical reorganization over

weeks, months, and even years, Boorsook, Becerra, Fishman, Edwards, Jennings, et al.

(1998) studied a patient after amputation of an arm and found that in less than 24 hours

23

stimuli applied on the ipsilateral face were referred in a precise, topographically

organized manner to distinct points on the phantom hand. Functional magnetic resonance

imaging (fMRI) performed one month later showed that neural activity correlated with

perceptual changes in the phantom hand (i.e., areas typically responsive to stimuli applied

to the hand were activated by stimuli applied to the face). Similar rapid referred

sensations, albeit not from amputation, were reported by a patient studied by Clark,

Regli, Janzer, Assal, and de Tribolet (1996). This patient had parts of the right trigeminal

ganglion removed – leading to deafferentation of the right cheek. Seven and twelve days

after surgery, this patient reported a simultaneous sensation to the phantom cheek

following stimulation to the right hand and right forehead.

Visual Domain

Long-term reorganization

In the visual system, there have been almost no reports of perceptual effects of

cortical reorganization. Although macular disease is not uncommon in humans,

particularly in elderly people, surprisingly little work has been done looking at the

perceptual effects of these natural retinal lesions. One such study, however, was

conducted by Burke (1999) on himself. Six to nine months after suffering from a

macular hole in his right eye, Burke reported poor visual acuity in his right eye and a 1.5°

diameter central a scotoma. Thus, any visual stimulus placed within this region was

invisible. Interestingly, however, visual stimuli placed around (either surrounding,

above, or below) the scotoma were perceptually distorted. For example, if gaze was

directed just slightly above a line, the line was deflected upwards (toward the center of

24

the scotoma) and a small gap was perceived in the center of the line (Figure 6a). As the

gaze was moved upward, the deflection became greater and the gap disappeared (Figure

6b & c). The peak deflection occurred when the gaze was about 1º above the line (Figure

6c). Further upward movement of gaze resulted in a decrease in the reflection of the line

(Figure 6d). When the gaze is about 2.0° above the line, there was no deflection. If the

gaze was directed below the line, the deflection reversed with the line distorting

downward (again toward the scotoma) (Figure 6e).

25

Figure 6. Effect of looking to one side of a line (Burke, 1999). (Note: Figures on the left – labeled A – depict where the line was placed relative to the scotoma. Figures on the right – labeled B – denote the patient’s perception. Dashed circles represent size and position of scotoma)

26

Figure 7 illustrates other distortions reported by Burke. When an annulus was placed

around the scotoma, it appeared as a small circle with a hole in the center (inside the

scotoma). As the thickness of the annulus increased, it appeared as a solid circle inside

the scotoma.

Figure 7. Effect of viewing annuli (Burke, 1999). (Note: Dashed circles represent size and position of scotoma)

27

Burke interpreted these distortions as resulting from cortical reorganization: Deprived

neurons (as a result of the macular hole) have begun responding to stimuli presented in an

adjacent retinal location. In addition, neurons that typically respond to a stimulus in that

adjacent retinal location continue to do so. It is then the average of these multiple signals

that cause the perceived stimulus to be distorted toward the scotoma (see Kapadia et al.,

1994). This mechanism is discussed more fully below. While this seems like a plausible

explanation, there is a slight problem: With a macular hole the retina itself is distorted,

and thus the perceptual distortions could perhaps be explained at this level, rather than at

the level of V1.

In another case study, Craik (1966) observed perceptual distortions around a self-

induced foveal scotoma subtending about 1º (he looked directly at the sun with his right

eye for 2 minutes). After about a month, he noted that for objects presented just below

the scotoma, there was a “distortion of the image...identical in appearance with the barrel

distortion found in images cast by lenses showing spherical aberration.” Although Craik

did not offer an explanation as to why these distortions might occur, a plausible

interpretation is one of cortical reorganization. However, not enough information about

the scotoma or the reported distortion was given to draw any firm conclusion.

Disturbances of shape perception have also been observed in patients with

metamorphopsia (also known as dysmetropsia). In particular, metamorphopsia may be

very selective, so that only certain objects within the patient’s gaze may be distorted, or

the changes may appear only within a part of the visual field (Critchley, 1949).

Additionally, it may also affect the shape of an object in one dimension only; that is,

objects may seem squeezed or compressed downwards or sideways. For example,

28

Critchley (1951) described a patient who noticed that objects were apt to appear broader

than they actually were. When asked to guess at the length of a series of sticks, his

suggestions were accurate when the objects were held vertically, but when they were

placed horizontally, his answers were inaccurate and usually took the form of

overestimation. Additionally, a square sheet of paper would look to him rectangular,

with the longer edge lying transversely. Recently a number of studies have also shown

that the vertical and horizontal components of shape perception can be differentially

affected by cerebral damage (Pritchard, Dijkerman, McIntosh, & Milner, 2001; Frasinetti,

Nichelli, & Pellegrino, 1999; Irving-Bell, Small, & Cowey, 1999; Milner, Harvey, &

Pritchard, 1998). Although little is known about the anatomical correlates of

metamorphopsia, it has been associated with a variety of structural lesions from the retina

to the cerebral cortex (Young, Heros, Ehrenberg, & Hedges, 1989). Consequently, many

patients reporting metamorphopsia also have a variety of other visual disturbances

including visual field defects and prosopagnosia. However, in most of these studies,

visual field defects were noted but not taken into account. In my opinion, the association

of field defects and perceptual distortions deserves attention. It might be the case that

many of the reported perceptual distortions could be a result of cortical reorganization.

Unfortunately, not enough information about the visual field defects was given for any

firm conclusions to be drawn.

Short-term cortical reorganization

Perceptual distortion, albeit slightly different than those described above, has

been demonstrated by Kapadia, Gilbert, and Westheimer (1994). Kapadia and colleagues

investigated the perceptual consequences of artificially induced scotomas in human

29

adults, and found that the reported position of a short line segment presented near the

border of the artificial scotoma was slightly shifted (between 2.50 and 5.00 minutes of

arc) toward the interior of the scotoma (Figure 8) (see also Westheimer, 1996).

Amazingly, this shift occurred within 2 seconds of exposure to the artificial scotoma

display.

Figure 8. Results from Kapadia et al. (1994).

These researchers attributed the minute shift to (temporary) cortical reorganization, as

seen in the animal studies that found expansion of receptive fields in retinal areas

shielded from stimulation by an artificial scotoma (Pettet & Gilbert, 1992; Fiorani et al.,

1992; DeAngelis et al., 1995). Kapadia et al. were able to explain the shift by making

two assumptions. First, that the position of a target line, for example, is estimated by an

average, or vector sum, of all the discharges in the afferent sensory neurons stimulated by

30

the line (Figure 9A). Second, the receptive fields of the ‘silent’ neurons are enlarged as

in the Pettet and Gilbert (1992) experiment. Thus, when the target line is presented just

outside the scotoma region, additional neurons (those inside the scotoma) are also

excited, causing the estimation of the target line’s location to be biased towards the

scotoma (Figure 9B).

Figure 9. Kapadia et al.’s (1994) explanation for perceptual mislocalization. (Note: Circles represent the neuron’s receptive field size. Line denotes “target line”)

This interpretation may be plausible; however, Kapadia et al. do not provide

direct evidence of cortical reorganization in their participants. And, as previously stated,

whether temporary reorganization resulting from brief exposure to an artificial scotoma is

similar to long-term (or short-term) reorganization after permanent deafferentation

remains an open question. In a similar study, Tailby and Metha (2004) found that the

31

reported position of a Gabor patch presented near the border of the artificial scotoma was

shifted by a few minutes of arc toward the interior of the scotoma.

32

IV: CASE DESCRIPTION (BL)

BL is a 51-year-old right-handed man with a high school education. He worked

as a cabinet-maker before suffering a right posterior cerebral artery (PCA) stroke in

December, 2001. One and a half years prior to the stroke, BL experienced an episode of

complete vision loss while working. After approximately one minute, BL’s vision

returned but for about a week he felt as though he had to concentrate extremely hard even

when doing simple tasks like pouring a cup of coffee. BL did not seek medical attention

at the time of this episode.

Structural MRI after the stroke revealed damage to the right-hemisphere inferior

optic radiations – the fibers that carry upper LVF information from the lateral geniculate

nucleus (LGN) of the thalamus to V1 – but no involvement of optic nerve, optic tract,

lateral geniculate nucleus, or V1 (Figure 10). Other damage included the right fusiform

gyrus and right splenium (i.e., the posterior part of the corpus callosum).

Figure 10. MRI following BL’s stroke revealing right optic radiation damage.

33

Shortly after the stroke, kinetic bowl perimetry testing2, done by an

ophthalmologist, revealed a left superior homonymous3 quadrantanopia (an upper left

field cut or blind area) (Figure 11).

Figure 11. Kinetic bowl perimetry results. The ‘ ’ denotes the position at which BL first reported seeing with his right eye a spot of light coming in from the periphery. The ‘ ’ denotes the location at which BL first reported seeing with his left eye a spot of coming in from the periphery.

2 In kinetic bowl perimetry, the patient’s head is positioned inside a hemispheric bowl. The examiner projects a small spot of light on the bowl and moves it from a position outside the normal perimeter of the patient’s visual field to a point where the patient signals awareness of the target. This procedure is repeated over many positions throughout the visual field. 3 Homonymous meaning ‘the same’ in both eyes.

34

Visual acuity was normal (20/30 OD, 20/30 OS, 20/30 OU). Pupils reacted normally,

extraocular movements were full, and there was no nystagmus. Dilated fundus

examination revealed clear media with normal disks, maculae, and vessels.

Within the first few visits with BL, subsequent visual field mapping was

conducted in our laboratory using stimuli (i.e., shapes) similar to those that were used in

other experimental tests, and testing the central 46º x 36º region. This procedure

revealed a homonymous scotoma covering most of the upper LVF (except an

approximate 4º spared strip along the vertical meridian) and extending a few degrees into

the lower LVF, especially in the periphery (Figure 12). The scotoma remained stable

throughout testing.

35

Figure 12. Results (percent of trials in which BL reported seeing anything) from a visual field mapping procedure in which a 3.2º x 3.2º shape was presented repeatedly at each one of nine locations in each quadrant, in a random order. Percentages calculated from 18 observations per location.

BL’s main complaints following the stroke were: (1) inability to see in the upper

left visual field, (2) inability to see objects as clearly or vividly as he once had – “objects

sometimes look foggy or fuzzy, with the borders smearing out”, and (3) two occurrences

of palinopsia – “I was looking at a cup on the table. When I looked away, I still saw the

cup someplace else in the room.” After the two occurrences, BL reported never

experiencing palinopsia again.

36

BL appeared fully oriented in time and space and was very co-operative

throughout the testing period. His spontaneous speech was fluent and he showed no

problems in language comprehension. Verbal and visuo-spatial short-term memory were

investigated using the Digit-span subtest of the Differential Abilities Scale (DAS) (Elliot,

1990) and Corsi blocks task (Milner, 1971) and were found to be normal. Additionally,

BL scored within the normal range on the Warrington Recognition Memory Test for

words (he scored 47/50 – 70th percentile). BL accurately described the ‘Cookie Theft’

picture from the Boston Diagnostic Aphasia Exam (Goodglass & Kaplan, 1983),

suggesting that he was able to perceive simultaneously multiple objects in a scene. BL

also showed no signs of neglect as revealed by tests of line cancellation and direct

copying (a clock and a house scene).

By contrast, further testing revealed that BL was achromatopsic in portions of his

upper (i.e., along the spared vertical merdian) and lower left visual field. Additionally,

BL showed signs of prosopagnosia as revealed by the Warrington Recognition Memory

Test for faces (he scored 32/50 – 1st percentile). Although scoring at the lower end of

the normal range (i.e., 41/50, 16th percentile) on the Benton Facial Recognition Test, BL

reported that the test was very difficult and he was only able to do it by matching features

(e.g., “I was looking at the hair line, the tip of the nose, the ears, etc.”). BL’s

performance was consistent with the performance of other prosopagnosic patients on

such a test (Farah, 1995; Newcombe, 1979) and may be indicative of a feature-by-feature

strategy used by patients suffering from prosopagnosia to facilitate facial recognition.

Writing, although slow and deliberate, was not problematic while reading tended to be

difficult because BL reported “losing the left side of the word.”

37

V: SHAPE PERCEPTION

BL’s perceptual distortion first became apparent when he gave inaccurate

descriptions of shapes presented in the lower LVF (below the scotoma): Stimuli appear

vertically elongated, toward and into the blind region. For example, he described a circle

as a cigar shape extending toward the ceiling, a square as a tall rectangle, and a triangle

with the point facing down as a pencil standing upright (Figure 13). The following

experiments systematically investigated BL’s shape perception.

Stimulus:

“Cigar-like” “Rectangle” “Pencil-like”

Figure 13. BL’s drawings and descriptions.

38

Visual Shape Perception

Vertical and Horizontal Judgment Experiments

Behavioral testing confirmed BL’s initial reports of perceptual distortion, and

established that the vertical but not the horizontal dimension was affected. BL fixated a

central point on a computer monitor, and two white rectangles were presented

simultaneously on a black background for 150 ms, one in the lower LVF and one in the

(intact) lower RVF (Figure 14).

Figure 14. Sample displays for horizontal (left) and vertical (right) judgment experiments.

Rectangles were centered 14° horizontally from fixation, with the bases aligned

12.6° vertically from fixation. In each of four 25-trial blocks, all possible pairs of five

stimulus rectangles were presented in random order. In the vertical judgment task the

rectangles were 3.2º wide, but differed in height (3.2°, 4.8°, 6.4°, 8.0°, 9.6°); for the

horizontal judgment task the height and width dimensions were reversed. BL indicated

which rectangle was taller (vertical judgment task) or wider (horizontal judgment task) by

39

saying “left,” “right,” or “same.” Four adults with intact vision served as control

participants.

Responses were coded by assigning a -1 to each “left” response, a +1 to each

“right” response, and a 0 to each “same” response. A mean judgment score for each

stimulus size difference (in degrees of visual angle) was computed by averaging the

coded responses across trials. A negative mean judgment score indicates a predominance

of “left” responses, whereas a positive score indicates a predominance of “right”

responses. The mean judgment score was then plotted as a function of the size difference

between the left and right stimuli.

An additional analysis, using the method of probits, was conducted to identify the

point of subjective equality (PSE) (i.e., the 50% point on the psychometric function or, in

other words, the size difference of which BL perceived the two shapes as equal)4. A

positive PSE indicates an overestimation of the relative dimension (i.e., height or width)

of stimuli. For example, a PSE of 3° in a vertical judgment task would indicate that BL

perceived stimuli in the lower LVF as 3° taller than they actually were. By contrast, a

negative PSE indicates an underestimation of the relative dimension of stimuli.

Additionally, this analysis identified the 95% confidence interval around the PSE, and the

amount of elongation was considered significantly different from 0 if the confidence

interval did not include 0.

Results

Control participants were perfectly accurate in both the horizontal and vertical

judgment tasks. BL performed well in the horizontal judgment task, accurately judging

40

the width of the stimuli (Figure 15). The PSE was 0.34° which is not significantly

different from 0. By contrast, in the vertical judgment task BL systematically judged the

LVF rectangles to be taller than they actually were relative to the RVF rectangles (Figure

15). When the LVF and RVF stimuli were equal in height, BL virtually always judged

the left rectangle to be taller; the RVF rectangle had to be more than 3º (2 cm) taller than

the LVF rectangle for him to judge them equally tall. The PSE was 3.12°, which is

significantly different from 0.

4 Since the method of probits requires a dichotomous dependent variable (e.g., left or right response), the ‘same’ responses were equally divided between ‘left’ and ‘right’. This division was done to mimic a two-alternative forced choice procedure.

41

Horizontal judgment

Filled rectangles

-1

-0.5

0

0.5

1

-6.4 -4.8 -3.2 -1.6 0 1.6 3.2 4.8 6.4

Width difference between LVF and RVF stimuli (degrees)

Mea

n ju

dgm

ent

BL

ControlSubjects

Left larger Equal Right larger

Lef

t lar

ger

Eq

ual

R

ight

larg

er

Vertical judgmentFilled rectangles

-1

-0.5

0

0.5

1

-6.4 -4.8 -3.2 -1.6 0 1.6 3.2 4.8 6.4

Height difference between LVF and RVF stimuli (degrees)

Mea

n ju

dgm

ent

BL

Controlsubjects

Left larger Equal Right larger

Lef

t lar

ger

Eq

ual

R

ight

larg

er

Figure 15. Horizontal and vertical judgments. The dashed line depicts control participants’ performance, and the solid line shows BL’s performance. The rightward shift of the curve for BL (vertical judgment) indicates that he overestimated the height of rectangles presented in the lower LVF.

42

The same experiment (vertical judgment task) was also conducted with unfilled

rectangles (line-drawings), black rectangles on a white background, rectangles whose

primary axis of elongation was horizontal, and parallelograms. Results for these various

rectangle stimuli were nearly identical to the filled rectangle stimuli (Figure 16). The

PSEs for these experiments were 3.43°, 2.28°, 2.94°, and 3.71°, and all were found to be

significantly different than 0.

43

Vertical judgment

Primary Axis of Elongation - Horizontal 1

Figure 16. Vertical judgments for unfilled rectangles, black rectangles on a white background, rectangles whose primary axis of elongation was horizontal, and parallelograms. The dashed line depicts control participants’ performance, and the solid line shows BL’s performance. The rightward shift of the curves for BL indicate that he overestimated the height of the various types of rectangles presented in the lower LVF.

-1

-0.5

0.5

-6.4 -4.8 -3.2 -1.6 0 1.6 3.2 4.8 6.4

Height difference between LVF and RVF stimuli (degrees)

Mea

n ju

dgm

ent

0

BL

Controlsubjects

Left larger Equal Right larger

Lef

t lar

ger

Eq

ual

R

ight

larg

er

Vertical judgmentUnfilled rectangles

-1

-0.5

0

0.5

1

-6.4 -4.8 -3.2 -1.6 0 1.6 3.2 4.8 6.4

Height difference between LVF and RVF stimuli (degrees)

Mea

n ju

dgm

ent

BL

Controlsubjects

Left larger Equal Right larger

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t lar

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Vertical judgmentParallelograms

-1

-0.5

0

0.5

1

-6.4 -4.8 -3.2 -1.6 0 1.6 3.2 4.8 6.4

Height difference between LVF and RVF stimuli (degrees)

Mea

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Controlsubjects

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Vertical judgmentFilled rectangles (Black on a white background)

-1

-0.5

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-6.4 -4.8 -3.2 -1.6 0 1.6 3.2 4.8 6.4

Height difference between LVF and RVF stimuli (degrees)

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44

Shape Judgment Experiment

Vertical shape distortion was also observed in another task, in which BL judged

the shape of a single rectangle presented in the lower LVF or lower RVF. Rectangles

were centered 14° horizontally from fixation, with the bases aligned 12.6° vertically from

fixation. In each of three 25-trial blocks, each rectangle was presented five times in

random order. Five rectangles (3.2° wide, but differing in height – 1.2°, 2.2°, 3.2°, 4.2°,

5.2°) served as stimuli. On each trial BL judged whether the rectangle was “wider than a

square” (i.e, shorter than it is wide), “a square”, or “taller than a square” (i.e., taller than it

is short).

Responses were coded by assigning a -1 to each “taller than a square” response, a

+1 to each “wider than a square” response, and a 0 to each “square” response. A mean

judgment score for each stimulus size difference (in degrees of visual angle) was

computed by averaging the coded responses across trials. A negative mean judgment

score indicates a predominance of “taller than a square” responses, whereas a positive

score indicates a predominance of “wider than a square” responses. The PSE was also

computed.

Results

BL was accurate for shapes presented in the lower RVF, but systematically

overestimated the height of rectangles in the lower LVF (Figure 17). The PSE was 1.09°,

which is significantly different from 05.

5 The amount of overestimation appears somewhat smaller than in the vertical judgment experiment, perhaps due to a procedural difference between the vertical judgment and shape judgment tasks. Because the “wider than a square” shapes had to be shorter than a square in the vertical dimension, the top edge of the shapes in the shape judgment experiment were presented lower in the visual field than the top of most rectangles in the vertical judgment experiment. Given that shape distortion decreased with vertical distance from the blind upper visual field, the shape judgment distortions may have been smaller than the vertical

45

Shape judgment (BL)

-1

-0.5

0

0.5

1

-2.0 -1.0 0 1.0 2.0

Stimuli height/width difference from a square (degrees)

Mea

n ju

dgm

ent

LVF

RVF

Taller Equal Wider

Talle

r

Equ

al

Wid

er

Figure 17. Shape judgment by BL. The dashed line depicts BL’s performance for RVF stimuli, and the solid line shows BL’s performance for LVF stimuli. The rightward shift of the curve for BL (LVF stimuli) indicates that he overestimated the height of rectangles presented in the lower LVF.

judgment distortions because the shape judgment stimuli were farther from the blind area (to be discussed more thoroughly in the Extent of Distortion section).

46

Tactile Shape Perception

A third task investigating shape perception revealed that BL’s perceptual

distortion was selective to vision. Stimuli were pairs of wooden rectangles attached to a

vertical surface. In the vertical judgment task the rectangles were 2 cm wide, but differed

in height (2, 3, 4, 5, 6 cm); for the horizontal judgment task the rectangles were rotated

90° to vary in the horizontal dimension. BL was blindfolded and seated facing the center

of the vertical surface. Two wooden rectangles were presented simultaneously, one in

the lower LVF and one in the lower RVF. In each of two 25-trial blocks, all possible

pairs of the five rectangles were presented in random order. With his eyes closed, and

after simultaneously feeling the blocks (the left block with his left hand and the right

block with his right hand), BL judged which rectangle was taller (vertical judgment task)

or which was wider (horizontal judgment task) by saying “left”, “right”, or “same.”

Coding and analysis were the same as in the visual shape perception experiments.

Results

Both the horizontal and vertical tactile judgments were accurate (Figure 18). The

PSEs for these experiments were -0.36° and -0.52°, and both were found not to be

significantly different than 0. Additionally, note that the PSEs are negative, indicating an

underestimation of both the width and height of stimuli presented in the lower LVF. This

finding is in the opposite direction than for the visual vertical judgment task.

47

Tactile vertical judgment

-1

-0.5

0

0.5

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-6.4 -4.8 -3.2 -1.6 0 1.6 3.2 4.8 6.4

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Tactile horizontal judgment

-1

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Width difference between the LVF and RVF stimuli (degrees)

Mea

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BL

Controlsubjects

Left larger Equal Right larger

r L

eft l

arge

r

Equa

l

Rig

ht la

rge

Figure 18. Tactile horizontal and vertical judgments. The dashed line depicts control participants’ performance, and the solid line shows BL’s performance.

Discussion

Results from several experiments confirmed that BL’s distortion selectively

affects the vertical dimension of visually presented shapes, such that he perceived shapes

as extending toward the blind upper LVF. No such distortion was evident in the tactile

domain. Given these findings, the following hypothesis was developed.

48

VI: HYPOTHESIS

Given the above findings, I hypothesized that the perceptual distortion reported by

BL was a consequence of V1 reorganization. The logic is as follows. In the normal

visual system, V1 is retinotopically organized. For example, when a stimulus is

presented in the upper LVF (labeled ‘1’ in Figure 19A – Visual Field) neurons in the

corresponding region of cortex respond (labeled ‘1’ in Figure 19A – Primary Visual

Cortex). However, if this region of cortex is deprived of its normal input (e.g., as a result

of right hemisphere optic radiation damage), neurons in the deprived region of V1 no

longer respond to input from the upper LVF, and a scotoma ensues (Figure 19B – Visual

Field). In addition, consistent with the electrophysiological studies, these deprived

neurons take on new functional properties and become responsive to inputs from the

lower LVF (denoted by the crossed out 1 and re-labeled ‘4’ in Figure 19B – Primary

Visual Cortex). Thus, stimuli presented in the lower LVF activate not only the V1 region

representing this area, but also the adjacent region that previously received input from the

upper LVF (Figure 19C). If activation of this latter region were still experienced by BL

as representing stimulation of the upper LVF, stimuli in the lower LVF might well appear

vertically elongated (Figure 19D). I will call this phenomenon phantom vision.

49

Primary Visual Cortex (V1)

A. Visual

4

2

3

Optic Radiation

Optic Radiation

1

LH RH

2

4 3

1

Primary Visual

Cortex (V1)Visual

B.

4

2

3

X

Optic Radiation

Optic Radiation

1X4

LH RH

2

4 3

1

Figure 19. Proposed hypothesis. (Note: Hatched area indicates the scotoma).

50

C. Primary Visual Cortex

(V1) Visual Field

1

34

2 4

2

3

X

Optic Radiation

Optic Radiation

4

LH RH D. Primary Visual Cortex

(V1)Visual Field

1

34

2 4

2

3

X

Optic Radiation

Optic Radiation

4

LH RH Figure 19 (Continued). Proposed hypothesis. (Note: Hatched area indicates the scotoma).

51

As previously discussed, analogous hypotheses have been proposed in the

somatosensory domain (Aglioti, Bonazzi, & Cortese, 1994; Borsook et al., 1998,

Halligan, Wade, Davey, & Morrison, 1993; Ramachandran, Rogers-Ramachandran, &

Stewart, 1992). Next, I proceeded to test several predictions following from my

hypothesis, namely predictions about the locus of the deficit and the extent of distortion.

52

VII: LOCUS OF THE DEFICIT

The following experiments investigated the locus of the deficit – the hypothesis

predicts that the distortion arises at the level of V1.

Visual Distance Perception

First, a deficit at the level of V1 should affect perception not only for shape, but

also for other spatial properties such as distance. This prediction was tested by asking BL

to judge whether the vertical distance between two lines in the lower LVF was greater

than, the same as, or less than, the distance between two lines in the lower RVF.

Each stimulus consisted of two white horizontal lines, 3.2º in length, displayed

one above the other. Five stimuli were created by varying the vertical distance between

the lines (1.6°, 2.0°, 2.4°, 2.8°, 3.2°). In each of four 25-trial blocks, all possible pairs

of the five stimuli were presented in random order. Stimuli were centered 14°

horizontally from fixation, with the bottom line aligned 12.6° vertically from fixation.

On each trial two pairs of lines were presented, one in the lower LVF and one in the

lower RVF (Figure 20). BL judged whether the vertical distance between lines was

greater in the left stimulus, greater in the right stimulus, or the same in both. He was

instructed to base his judgment on the distance between the lower edge of the top

horizontal line and the upper edge of the bottom horizontal line, so that any perceived

vertical elongation (thickening) of the LVF lines would not lead to overestimation of the

distance between lines. (Perceived upward extension of the top line should have no

effect on the distance judgment, whereas upward extension of the bottom line should

53

work against finding vertical elongation of distance in the LVF.) Methods were

otherwise the same as in the visual shape perception experiments.

Figure 20. Sample display for visual distance perception experiment.

Results

BL systematically judged the left distance greater than the right (Figure 21). The

PSE was 1.07°, which is significantly different from 06.

6Again, the amount of overestimation appears somewhat smaller than in the vertical judgment experiment, perhaps due to a procedural difference between the vertical judgment and distance tasks. Because BL had difficulty seeing horizontal lines presented close to the scotoma, the top line of the distance stimuli was presented lower in the visual field than the top of most rectangles in the vertical judgment experiment. Given that shape distortion decreased with vertical distance from the blind upper visual field, the distance distortions may have been smaller than the shape distortions because the distance stimuli were farther from the blind area (to be discussed more thoroughly in the Extent of Distortion section). Note, however, that this amount of distortion in this task is nearly identical to that found in the shape judgment task. In both of these tasks, the stimuli were presented in the same location.

54

Visual distance perception

-1

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Figure 21. Visual distance perception. The dashed line depicts control participants’ performance, and the solid line shows BL’s performance. The rightward shift of the curve for BL indicates that he overestimated vertical distances in the lower LVF.

55

Frame of Reference

A second prediction concerned frames of reference: Because V1 is retinotopically

organized (i.e., each location in V1 corresponds to a particular location on the retina,

Figure 22), BL’s perceptual distortions should reflect a retinocentric reference frame. In

other words, the distortion should only occur when a stimulus is presented in a particular

retinal location (i.e., the lower LVF), as opposed to locations defined relative to BL’s

head (head-centered), the trunk of his body (body-centered), or some environmental

feature like the computer screen (environment-centered).

Figure 22. Retinotopic Map.

56

A preliminary investigation revealed that the distortion occurred within either a

retinocentric or head-centered frame of reference. We asked BL to view a computer

monitor with his body upright, but his head tilted 90º to the right, resting on a horizontal

pillow. When shapes were presented in the upper left quadrant of the monitor

(corresponding to BL’s lower LVF), he described them as elongated toward the right

edge of the monitor (toward and into the upper LVF). For example, a circle was

described as “a cigar facing the wall.” (Figure 23).

Stimulus:

“Cigar facing the wall”

Figure 23. Drawing and verbal report by BL of perceived shape presented in upper LVF when his head was tilted 90°.

Next, to tease apart whether the distortion reflected a retinocentric or body-

centered frame of reference, BL was tested with his head upright but turned to the left or

right, so that the entire monitor was on the right or left side of head-centered space,

respectively. In both conditions he kept his eyes fixed on a central point on the monitor,

57

and judged the relative height of rectangles in the lower LVF and RVF (vertical judgment

task) (Figure 24).

Figure 24. Sample display for frame of reference experiment.

Results

Regardless of head position, BL exhibited vertical distortion for lower-LVF

stimuli, demonstrating that the distortion arose in a retinocentric and not a head-centered

reference frame (Figure 25). The PSEs were 2.08° for the head left condition, and 2.73°

for the head right condition. Both PSEs are significantly different from 0.

58

Frame of reference

-1

-0.5

0

0.5

1

-6.4 -4.8 -3.2 -1.6 0 1.6 3.2 4.8 6.4

Height difference between LVF and RVF stimuli (degrees)

Mea

n ju

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BL - Head left; Eyes straight

BL - Head right; Eyes straight

Control subjects

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Figure 25. Frame of reference. The dashed line depicts control participants’ performance. The solid line with a square shows BL’s performance while his head was turned left and his eyes were fixated on a central point, and the solid line with a circle depicts BL’s performance while his head was turned right and his eyes were fixated on a central point. The rightward shift of both curves for BL indicates that he overestimated the height of rectangles presented in the lower LVF.

59

Visually-guided Grasping

A final prediction concerned visually-guided action. Milner and Goodale (1995)

proposed that subsequent to early cortical visual areas, the visual system bifurcates into

vision-for-perception and vision-for-action subsystems. If BL’s deficit is localized in V1,

prior to the bifurcation, vertical distortion should be evident not only in perceptual tasks,

but also in visually-guided action tasks, such as reaching for or grasping an object. While

reaching toward an object with the aim of grasping it, normal individuals scale their grip

aperture – the distance between thumb and index finger – to the size of the target object,

such that grip aperture increases with the target size. This scaling of grip aperture has

been viewed as a prototypical function of the vision-for-action subsystem (Goodale,

Jakobson, & Keillor, 1994; Jakobson & Goodale, 1991; Jeannerod, 1986). BL’s grip

apertures were recorded as he reached for a wooden rectangle in the lower LVF or lower

RVF. He was instructed to grasp the stimulus rectangle by the top and bottom, so that his

grip aperture would reflect the height (as opposed to the width) of the stimulus.

BL sat facing a black vertical surface. He fixated a central point on the surface,

and then closed his eyes while the experimenter mounted a white wooden rectangle in the

lower LVF or lower RVF (centered 14° horizontally, with the bottom of the rectangle

aligned 12.6° vertically from fixation). BL then opened his eyes and, while fixating the

central point, reached for the rectangle (Figure 26). Five rectangles differing in height

(3.2°, 4.8°, 6.4°, 8.0°, 9.6°) were tested; all were 3.2° wide. BL reached with his right

hand in one block of 50 trials, and with his left hand in a second block. In each block

each of the five rectangles was presented 5 times in the lower LVF, and 5 times in the

lower RVF, in random order.

60

Figure 26. Visually-guided grasping board.

Grip aperture (the distance between the thumb and index finger) was measured by

a Polhemus ISOTRAK II (Polhemus, Colchester, VT), which computed position and

orientation of sensors taped to BL’s thumb and index fingers as they moved through

space (using low-frequency magnetic transducing technology). The dependent measure

was grip aperture 2 cm prior to contact with the rectangle.

Results

Whether he was reaching with his left or right hand, BL’s grip apertures were

significantly larger for stimuli in the lower LVF than for stimuli in the lower RVF, t(99)

= 7.64, p < .001 (Figure 27). Although BL’s grip aperture for stimuli in the lower LVF

were larger than for stimuli in the lower RVF, like normal individuals, BL continued to

scale his grip aperture to the size of the target object, such that grip aperture increased

with rectangle height. These results imply that BL’s distortions in representing lower-

61

LVF stimuli arise at a level of the cortical visual system prior to the split into vision-for-

perception and vision-for-action subsystems.

Visually-guided grasping (BL)

0

2

4

6

8

10

2 cm 3 cm 4 cm 5 cm 6 cm

Block size

Grip

ape

rtur

e (c

m)

LVF RVF

Figure 27. BL’s visually-guided grasping results collapsed over hand.

Discussion

Taken together, the behavioral results indicate that BL’s perceptual distortions

arise early in the cortical visual system, consistent with the hypothesis that the distortions

are a consequence of V1 reorganization. The above studies, however, only tested one

location in the lower LVF, and according to the hypothesis the distortion should be most

pronounced for stimuli presented near the scotoma (i.e., stimuli that project to cortex

62

immediately adjacent to the deafferented cortex). The following experiment tested the

extent of distortion with respect to the scotoma.

63

VIII: EXTENT OF DISTORTION

The following procedure demonstrated that the extent of distortion is greatest for

stimuli placed just below the scotoma, and monotonically decreases with distance from

the blind region. A numerical scale ranging from 1-15 was displayed in the (intact) RVF

along the vertical meridian, with 1 and 15 positioned 11.2º below and above the

horizontal meridian, respectively, and 8 on the meridian. Scale numbers were 1.6º apart.

A square (3.2º x 3.2º) was presented in one of six positions in the lower LVF or lower

RVF (Figure 28). The top of the square was 0º, 4.8º, or 9.6º below the horizontal

meridian (positions High, Middle, or Low, respectively – what I will refer to as vertical

placement), and centered at 2.0º or 6.0º from the vertical meridian (positions Near or Far,

respectively – what I will call horizontal eccentricity). BL reported the number with

which the top of the square was aligned.

Middle

Low

High

NearFar

15 14 13 12 11 10 9 8 7 6 5 4 3 2 1

Figure 28. Tested locations for the extent of distortion experiment.

64

Results

BL was accurate for lower RVF stimuli, but systematically overestimated the

height of lower LVF stimuli (Table 1).

(3.5) 2.4º (2.3) 0.5º Low (correct = 2.0)

(7.6) 4.5º (5.5) 0.8º Middle (correct = 5.0)

(11.3) 5.3º (8.9) 1.4º High (correct = 8.0) FarNearPosition

Table 1. Extent of distortion results for squares presented at various positions in the lower LVF. Numbers in parentheses denote BL’s average responses, while numbers next to the parenthetical numbers indicate the amount of vertical elongation in degrees.

For example, when the square was presented at position High-Far in the LVF, the correct

response was 8, but BL’s mean response was 11.3, indicating that he perceived the square

as extending 5.3º vertically into the scotoma. Similarly, when the square was presented

at position Middle-Far in the LVF (i.e., the top edge aligned with the number 5), BL’s

mean response was 7.6, indicating that he perceived the square as extending 4.5º

vertically. And when the square was presented at position Low-Far in the LVF, the

correct answer was 2, but BL’s mean response was 3.5, indicating that he perceived the

square as extending about 2.4º vertically. A similar pattern is shown for positions High-

Near, Middle-Near, and Low-Near. Thus, the extent of vertical distortion decreased with

the distance of the stimulus from the blind area of BL’s visual field (i.e., with vertical

placement). In addition, the extent of vertical distortion increased as the stimulus was

presented more peripherally (i.e., with horizontal eccentricity). This finding is consistent

65

with cortical magnification in V1 (to be discussed below). A 2 (horizontal eccentricity)

X 3 (vertical placement) analysis of variance confirmed these impressions. There was a

significant main effect of horizontal eccentricity, F(1, 138) = 250.57, p < .001, with the

amount of elongation being significantly greater for stimuli presented in the Far versus

Near position. There was also a significant main effect of vertical placement, F(2, 138)

= 31.91, p < .001, and main effect contrasts revealed that the amount of elongation for

stimuli pr ented in position A was significantly greater than when the stimulus was

presented

significan

there was

contrasts r

Near posi

A

magnifica

to the repr

example,

depicted i

P1 and ext

stimulus w

only inclu

more cort

Figure 29

of newly r

esA

in position B, and the amount of elongation for stimuli in position B was

tly greater than when the stimulus was presented in position C. And finally,

a significant interaction, F(2, 138) = 9.75, p < .001, and simple main effect

evealed that elongation was significantly greater in the Far position than the

tion at all vertical placements (A, B, and C).

s previously stated, the horizontal eccentricity effect is consistent with cortical

tion in V1. In the normal visual system, substantially more cortex is devoted

esentation of the fovea and the region just around it than to the periphery. For

consider a stimulus presented in the foveal region (extending from F1 to F2 as

n Figure 29A) and the same size stimulus presented in the periphery (starting at

ending slightly beyond). In the cortex (as shown in Figure 29B), the foveal

ould encompass cortical areas F1 to F2 , while the peripheral stimulus would

de cortical area P1 and slightly beyond. Now consider the case of BL. Since

ex (i.e., the deprived cortex, say 2 mm more as depicted by dashed lines in

B) has become responsive to surrounding stimuli, and assuming that the amount

esponsive cortex is constant, then this cortical distance translates into more

66

elongation of stimuli presented in the periphery (extending from P1 to P2 as depicted by

the dashed line in Figure 29A) than stimuli presented in the fovea (starting at F1 and

extending slightly beyond F2 as depicted by the dashed line in Figure 29A).

Visual Field Cortex A. B.

P3

P3 F3P2 F3

2mm P2 F2F2 2mm

P1 F1 P1 F1

Figure 29. The effect of cortical magnification on extent of distortion.

67

IX: OVERALL DISCUSSION OF BEHAVIORAL RESULTS

Behavioral testing confirmed that BL’s distortion selectively affects the vertical

dimension (height) of visually presented shapes, such that he perceives shapes as

extending toward and into the blind quadrant. Additional behavioral testing established

that the distortion originates at the level of V1 – vertical distance as well as shape

judgments are affected; the vertical distortion arises in a retinocentric frame of reference;

and the deficit affects not only vision-for-perception, but also vision-for-action. A final

behavioral measure established that the extent of vertical distortion monotonically

decreases with distance from the scotoma. Taken together, these results are consistent

with the hypothesis that BL’s perceptual distortions are a consequence of V1

reorganization. Next, in collaboration with colleagues from the Department of

Psychological and Brain Sciences, I used fMRI to determine whether the deprived V1

cortex has reorganized.

68

X: RETINOTOPIC MAPPING OF V1

Functional magnetic resonance imaging was used to address the following

question: Did the region of V1 normally activated by stimuli in the upper LVF (the

region deprived of its usual input by BL’s stroke) become activated by stimuli in the

lower LVF? BL and a control participant (an adult with normal vision) were tested with

the same protocol. The ventral and dorsal boundaries of V1 were functionally defined

with a standard meridian mapping procedure (Figure 30). Defining the ventral boundary

for BL was possible because of some spared vision along the upper vertical meridian in

the LVF.

Figure 30. fMRI meridian mapping display and results. The leftmost panel shows an example of a black and white checkerboard stimulus along the vertical meridian. The next two panels depict inflated brain images of each participant’s right occipital cortex, labeled accordingly. Regions shown in red-yellow were more strongly activated when the bow-tie stimulus was presented along the vertical meridian compared to the horizontal meridian. The black lines denote the approximate center of the activations, corresponding to the upper and lower boundaries of V1. Both maps shown at a threshold of r = .15.

69

fMRI Method/Data Analysis

The ventral and dorsal boundaries of V1 were mapped using a counterphase

flickering (8 Hz) black and white checkerboard stimulus consisting of two 30º-wedges

arranged point-to-point (Figure 30). The wedges stimulated either the horizontal or the

vertical meridian in alternating 18s blocks.

Stimuli in the experimental task were solid white wedges, flickering at a rate of 8

Hz, presented in one of 12 locations for 5s on a black background (Figure 31a). Each

wedge extended from 5.6°-12.8° of visual angle from fixation, and subtended 30° of

polar angle. Each participant completed six experimental runs; each wedge was presented

5 times per run in a pseudo-random sequence with the constraint that two successive

wedges were separated by at least 60° of polar angle.

MRI scanning was carried out with a Philips Intera 3T scanner in the F.M. Kirby

Research Center for Functional Brain Imaging at the Kennedy Krieger Institute,

Baltimore. Anatomical images were acquired using an MP-RAGE T1-weighted sequence

that yielded images with a 1 mm isovoxel resolution (TR = 8.1 ms, TE = 3.7 ms, flip

angle = 8°, time between inversions = 3 s; inversion time = 748 ms). Whole brain

echoplanar functional images (EPI) were acquired with a SENSE (MRI Devices, Inc.,

Waukesha, Wisconsin) head coil in 35 transverse slices (TR = 2000 ms, run duration:

144 TRs for meridian mapping, 156 TRs for experimental task, TE = 30 ms, flip angle =

70°, matrix = 64 x 64, FOV = 192 mm, slice thickness = 3 mm, no gap, SENSE factor =

2).

Brain Voyager QX software (release 1.26, Brain Innovation, Maastricht, The

Netherlands) was used for the fMRI analyses. Each functional run was independently

70

coregistered to the anatomical volume to ensure accurate functional-anatomical

alignment and the in-plane data were resampled at 3mm3 during the conversion to 3-d

volume space. The data were then slice-time corrected and temporally filtered (high pass:

3 cycles/run, low pass Gaussian smoothing: 2.8 s). The cortical surface reconstructions in

Figures 30-33 were generated using Brain Voyager’s region growing and segmentation

tools; the accuracy of the segmented volume was checked slice by slice in the region of

V1 and hand corrected as necessary.

Six regression vectors were constructed by marking the temporal onset of each

wedge in the LVF with a boxcar model of each respective stimulation epoch convolved

with a gamma function (delta = 2.5 s, tau = 1.25 s) (Boynton, Engel, Glover, & Heeger,

1996). The six resultant regression vectors were independently cross-correlated with the

blood oxygenation level-dependent (BOLD) timeseries in each voxel within V1. The

regression vector producing the maximum correlation value determined the color

depicted in Figures 30-33.

Results

During the experimental task, BL (and the control participant) maintained central

fixation while passively viewing a flickering white wedge in one of twelve locations

(Figure 31a). Eye-tracking was performed during the scanning session; both participants

maintained accurate fixation. For the control participant, a wedge in location 1 (upper

LVF) activated the ventral boundary of V1, and a wedge in location 6 (lower LVF)

activated the dorsal V1 boundary (Figure 31b). Wedges in locations 2-5 activated

adjacent patches of cortex extending from the ventral to the dorsal aspects of V1,

respectively. This pattern of activation is consistent with the known topography of V1

71

(Engel, Rumelhart, Wandell, Lee, et al., 1994; Sereno, Dale, Reppas, Kwong, et al.,

1995).

BL’s results were different (Figure 31c). Little activation was observed in

response to wedges presented in the (largely-blind) upper LVF (locations 1-4); wedges

presented in location 1 – near the upper vertical meridian, where BL has some spared

vision – did activate a region corresponding to the lower boundary of V1 at very low

statistical thresholds, not shown in Fig. 31c. Wedges presented in location 6 activated the

dorsal boundary of V1, as in the control participant. However, wedges in location 5

(lower LVF) strongly activated a wide swath of V1. This swath extended to the ventral

V1 boundary, encompassing cortex that would normally receive input from the upper

LVF (locations 2 and 3). Thus, a large area of ventral V1 that would normally respond to

the upper LVF was not activated by upper-LVF stimuli but was activated by stimuli in

the lower LVF. This pattern of activation was consistent over various thresholds (Figure

32a), demonstrating cortical reorganization in BL’s deafferented V1 region.

72

Figure 31. fMRI experimental display and results. (a) An example of a wedge stimulus

and the tested locations during fMRI scanning; the numbers referring to each wedge

position were not present during scanning. (b & c) Inflated brain images of each

participant’s right occipital cortex, labeled accordingly. The upper and lower boundaries

of V1, as defined by the meridian mapping procedure, are marked by solid black lines.

The colors reflect the regions within V1 that were maximally correlated with each of the

six stimulated locations in the LVF (which activate the right cerebral hemisphere). All

maps shown at a threshold of r = .25.

Additional analyses provided converging evidence that BL’s ventral V1 area was

not activated by upper-LVF stimuli. Because V1 regions were delineated based on the

maximum correlation with a wedge presented in a specific spatial location, it was

possible that the area maximally stimulated by wedge 5 was also consistently activated –

to a somewhat lesser degree – by wedges presented in locations 2 and 3. However, no

activation was observed at thresholds .3, .25, and .2 (Figure 32b), confirming that stimuli

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presented in locations 2 and 3 (upper LVF) no longer activated the ventral region of V1

in a systematic pattern.

Figure 32. fMRI results at various thresholds. (a) Statistical maps for Patient BL showing maximum correlation in each voxel at different statistical thresholds, labeled accordingly. (b) Statistical maps for Patient BL in response to wedges 2 and 3 only, with the area found to be maximally correlated with a wedge in position 5 outlined in black. Various thresholds are labeled accordingly.

74

Further analyses examined activation to wedge 5 only, in BL and the control, at

several different correlation thresholds. It was possible that responses to wedge 5 extend

broadly in the control participant as well as in BL, but that this was masked by the

stronger response to wedge 4. As shown in Figures 33, the activation produced by wedge

5 alone in the control participant stays in the dorsal quadrant of V1, near the dorsal

boundary with V2d, whereas in BL, wedge 5 produces activation that reaches down to

almost touch the ventral boundary between V1 and V2v.

Figure 33. fMRI results for wedge 5 only at various correlation thresholds, labeled accordingly. (a) Statistical maps for the control participant. (b) Statistical maps for Patient BL.

75

After scanning, BL was asked to report what had seen, and these reports are

consistent with the fMRI results. BL reported never seeing stimuli in the region covered

by wedges 2-4, and correspondingly we measured little or no cortical activity in response

to these wedges. For the location of wedge 6, he reported seeing a wedge approximately

the same size as wedges presented in the RVF, and correspondingly we obtained only the

extent of activation normally expected for a wedge in this location (i.e., dorsal boundary

of V1). And for the location of wedge 5, BL reported seeing a shape extending vertically

into the upper LVF, consistent with our finding of a swath of V1 activation extending to

ventral V1. Furthermore, the fMRI results are consistent with the findings reported

earlier (visual shape perception) revealing little vertical distortion for shapes presented in

the general vicinity of wedge 6 (far away from the blind area), and much more distortion

for shapes presented in the neighborhood of wedge 5 (closer to the blind area).

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XI: GENERAL DISCUSSION

Over the past twenty years, opinions regarding adult cortical plasticity have

significantly changed. Numerous studies in different modalities (i.e., audition,

somatosensation, and vision) conducted in a variety of mammalian species, including

humans, have shown that the adult cortex reorganizes following peripheral loss of inputs

(e.g., cochlear lesions, digit amputation, retinal lesions). More recently, however, some

controversy has arisen regarding cortical reorganization in both the adult animal and

human visual systems. Furthermore, little work has explored the perceptual

consequences of cortical reorganization, and in fact, no work has directly investigated

this issue in the visual domain. This thesis addressed these issues, demonstrating that

cortical reorganization can occur in the human adult visual system following loss of

cortical input, and that the reorganization can cause systematic distortions in visual

perception. I presented evidence from a stroke patient, BL, with partially deafferented

V1. BL is blind in the upper LVF, and exhibits perceptual distortion in the lower LVF.

Behavioral testing confirmed that the distortion selectively affects the vertical dimension

(height) of shapes, such that BL perceives shapes as extending toward and into the blind

area. Additional behavioral testing established that the distortion originates early in the

visual system – vertical distance as well as shape judgments are affected; the vertical

distortion arises in a retinocentric frame of reference; and the deficit affects not only

vision-for-perception, but also vision-for-action. These findings are consistent with my

hypothesis that perceptual distortion is a consequence of V1 cortical reorganization. A

final behavioral measure established that the extent of vertical distortion is greatest for

stimuli presented near the scotoma, and monotonically decreases with distance from the

77

scotoma. This finding is consistent with the hypothesis since the deprived cortex receives

information from neighboring cortex, and not from distant cortex. While the behavioral

measurements are suggestive of V1 cortical reorganization, an fMRI study demonstrated

that reorganization has in fact occurred. Specifically, these results revealed that loss of

input to a large region of adult human V1 led to a dramatic reorganization: The

deafferented region now responds to stimuli that normally would activate only adjacent

cortical regions. The reorganization in turn alters perceptual experience: Because stimuli

in the lower LVF now activate both ventral and dorsal regions of right-hemisphere V1,

the stimuli are perceived as extending from the lower LVF into the upper LVF. Taken

together, the behavioral and fMRI findings provide the first clear demonstration of a

direct link between cortical reorganization in the adult human visual system and

subjective visual experience.

Although I have demonstrated that loss of normal sensory inputs in an adult

human induces cortical reorganization, the question still remains of how this change

arises. In the following discussion, I explore some of the proposed mechanisms of

cortical reorganization, and offer two conceptual models of the mechanisms that best

account for the data presented in this dissertation. As proposed by Gilbert (1992), there

are several potential sets of connections capable of sending visual input into the V1

cortical scotoma (Figure 34). For short-term reorganization, cortical reorganization

entails altering the effectiveness of preexisting connections, and for long-term

reorganization the sprouting of new axons may also come into play (Das & Gilbert, 1995;

Darian-Smith & Gilbert, 1994).

78

Figure 34. Visual pathway representing possible connections involved in cortical reorganization. The retinal lesion removes visual input from retinal ganglion cells (open triangles), which are left intact by the lesioning procedure. The ganglion cells project to the lateral geniculate nucleus (LGN), where horizontal connections by interneurons (A) allow a small amount of lateral spread of visual information. The principal cells of the LGN project to cortical layer IV; a subset of these have terminal fields spreading horizontally in the cortex for distances of roughly 2 mm (B). Horizontal connections of cortical pyramidal cells (C) extend up to 6-7 mm. There are also a number of feedback projections from higher cortical areas, such as area 18 (D). The area of the cortical scotoma in area 17 is represented by the bold outline, and the area of the residual deficit after recovery is represented by the shaded area. These data are from the adult cat (Gilbert, 1992).

79

First, V1 reorganization may be due to changes at earlier levels in the visual

pathway, such as the lateral geniculate nucleus (LGN) of the thalamus (denoted by an ‘A’

in Figure 34). However, researchers have shown that while lesions of the retina of the

adult cat produced atypical responses in deprived V1 areas, areas of the LGN

corresponding to the scotoma remained silent two months after lesioning (Darian-Smith,

Gilbert, & Weisel, 1992; Gilbert & Weisel, 1992). In other words, at the time when V1

had reorganized, the LGN still retained a large silent area, suggesting that the mechanism

of V1 reorganization resides at levels beyond the thalamus. Additionally, considering the

work in this thesis, the above proposed mechanism (i.e., changes in the LGN) does not

seem plausible given the deafferentation in BL was due to optic radiation damage (i.e.,

the fibers that send visual information from the LGN to V1). Thus, it seems clear that the

V1 reorganization is largely due to changes intrinsic to cortex.

Second, reorganization in the cortex could be mediated by geniculocortical

afferents with axons spreading horizontally in the cortex for distances of approximately 2

mm end to end (labeled ‘B’ in Figure 34). However, researchers have found that this

distance is too small to account for the cortical reorganization (Blasdel & Lund, 1983;

Ferster & LeVay, 1978; Gilbert & Weisel, 1979; Humphrey, Sur, Uhlrich, & Sherman,

1985). For example, visual input propagating from the edge of the scotoma toward its

center would be expected to travel half of the side-to-side spread of the axon mediating

this process, assuming that the axon collaterals are distributed symmetrically about the

main trunk. For geniculocortical afferents this would be a distance of 1 mm. The

reorganization seen after 2 months, however, is 3 to 3.5 mm from the edge of the

scotoma, allowing a complete filling-in of scotomas 6 to 7 mm in diameter, and

80

consequently too great a distance to be achieved by normal afferents. Similarly, given

the above findings coupled with the data in this thesis (i.e., the extent of vertical

elongation), the geniculocortical connection account seems unlikely. For example, to

explain the extensive vertical elongation experienced by BL, geniculocortical connections

would have to spread activation across several centimeters of cortex, farther than the

length of these connections in primate V1 (i.e., 2 mm).

A third possible source of cortical reorganization, and the one favored by many

researchers, involves the spread of corticocortical afferents, namely the long-range

horizontal connections formed by the axons of pyramidal cells in V1 (Darian-Smith &

Gilbert, 1994; Das & Gilbert, 1995) (Figure 35).

Figure 35. Example of the axon of a pyramidal cell in a primate visual cortex forming long-range clustered horizontal connections. The cell is located in layer 3 and its axon extends 6 mm parallel to the cortical surface. The shaded areas are cytochrome oxidase blobs (Gilbert, 1992). The idea that these horizontal connections might be responsible for the reorganization

seen in the adult cat and monkey is supported by the fact that the extent of reorganization,

roughly 6-7 mm in diameter, approximates the length of a pyramidal cell’s axon (denoted

81

by a ‘C’ in Figure 34). Furthermore, this idea was also supported by the finding that

post-reorganization, the orientation specificity of the deprived cells was similar to that

seen before the lesion was made, despite the fact that the receptive field of the cells had

changed (Das & Gilbert, 1995). Given that horizontal connections run primarily between

columns of similar orientation specificity (Ts’o, Gilbert, & Wiesel, 1986; Gilbert &

Wiesel, 1989), the involvement of a preexisting framework of horizontal connections

would cause the reorganized cortex to retain its original pattern of orientation specificity.

The corticocortical connection account, while attractive considering the above findings,

does not fully account for the data presented in this thesis. Again, in order to explain the

extent of vertical elongation reported by BL, horizontal connections would have to spread

activation farther than the length of typical horizontal connections in primate V1 (i.e., 6-7

mm). However, it is possible that a polysynaptic chain of horizontal connections might

be implicated.

And fourth, another potential source is the “feedback” input to V1 from higher

order visual areas, such as V2 and beyond (labeled ‘D’ in Figure 34). This mechanism

will be discussed in greater detail shortly. At this point, no experiments have been done

to tease apart the contribution of horizontal and feedback connections in the phenomenon

of cortical reorganization. Similarly, the findings in this thesis are not able to determine

which mechanism(s) play a role in V1 reorganization. However, to better conceptualize

how these two proposed mechanisms might account for the V1 reorganization

demonstrated in this thesis, I offer the following two models.

82

Stimulus (+)

(-)

(+)

(+)(+)

(-) xStimulus

V2/V3/V4 V1

V2/V3/V4 V1

Figure 36. The horizontal connection account of cortical reorganization. Levels of the visual system (V1, V2, V3, V4...) are labeled appropriately. Open circles (or nodes) denote an unactivated ensemble of neurons. Solid circles indicate an activated group of neurons. A ‘+’ indicates an excitatory connection, while a ‘–’ denotes an inhibitory connection. (A) The normal functioning visual system given a stimulus presented to a particular retinal location. Note that intrinsic to the system is an excitatory horizontal connection between the two groups of neurons in V1, and a local interneuron inhibitory connection. (B) The deafferented (denoted by the ‘ ’) and reorganized region of V1 as a result of disruption of some inhibition (indicated in gray) given a stimulus presented to a particular retinal location.

83

V1 V2/V3/V4

(+)Stimulus

(+)

(+)

(-)

(-)x (+)Stimulus

V2/V3/V4V1

(+)(+)

Figure 37. The feedback connection account of cortical reorganization. Levels of the visual system (V1, V2, V3, V4...) are labeled appropriately. Open circles (or nodes) denote an unactivated ensemble of neurons. Solid circles indicate an activated group of neurons. A ‘+’ indicates an excitatory connection, while a ‘–’ denotes an inhibitory connection. (A) The normal functioning visual system given a stimulus presented to a particular retinal location. Note that intrinsic to the system is an excitatory feedback connection from V2/V3/V4 to V1, and a local interneuron inhibitory connection. (B) The deafferented (denoted by the ‘ ’) and reorganized region of V1 as a result of disruption of some inhibition (indicated in gray) given a stimulus presented to a particular retinal location.

84

As depicted in Figure 36A (the normal functioning visual system), when a

stimulus is presented to a particular retinal location, the V1 neurons with receptive fields

corresponding to this location become active, and subsequently, send activation to

neurons in higher visual areas (i.e., V2 and beyond). Additionally, the activated V1

neurons also send information to adjacent V1 neurons via horizontal connections, but the

adjacent V1 neurons do not fire as a result of local interneuron inhibitory connections.

By contrast, as depicted in Figure 36B (the deafferented visual system), when a stimulus

is presented to a particular retinal location, the corresponding V1 neurons are activated,

and send activation to higher visual areas as well as adjacent V1 neurons. However, as a

result of deafferentation, some disruption of inhibition occurs thereby affecting the

balance of excitation and inhibition which normally shapes a cell’s response (Volchan &

Gilbert, 1995), and the previously inactive adjacent V1 neurons become active due to

lateral excitation. The precise synaptic mechanisms governing reorganization remain to

be worked out.

According to the feedback connection account, as shown in Figure 37A (the

normal functioning visual system), when a stimulus is presented to a particular retinal

location, the corresponding V1 neurons become active, and send activation to neurons in

higher visual areas (i.e., V2 and beyond). As a result, the activated V2 neurons, for

example, then send information back to the originally activated V1 neurons. In addition,

the activated V2 neurons send activation to other V1 neurons with receptive fields

encompassed by the V2 neurons’ receptive fields, but these additional V1 neurons do not

become active as a result of local interneuron inhibitory connections. As depicted in

Figure 37B (the deafferented visual system), however, all things remain the same as in

85

Figure 37A, except that the disruption of inhibition (as a result of deafferentation) allows

the feedback to activate the ‘other’ V1 neurons. Again, while the data in this thesis are

not able to tease apart these two mechanisms, the above models might prove beneficial

for future research trying to do so.

In summary, using behavioral and functional neuroimaging data, I have

demonstrated that cortical reorganization occurs in the human adult visual system

following loss of input. This finding corroborates the numerous animal studies

suggesting that V1 retains a remarkable degree of plasticity into adulthood, and

contradicts the recent claims questioning the existence of cortical reorganization in both

the adult animal and human visual systems. Furthermore, this thesis provided the first

evidence that cortical reorganization affects visual perception. Specifically, I have shown

that perceptual distortion – what I call phantom vision – results as consequence of

cortical reorganization. Future research will investigate whether cortical reorganization

leads to perceptual distortion in other subjects with similar visual deprivation (e.g.,

patients with MD), and explore the mechanisms underlying adult cortical reorganization.

86

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Daniel D. Dilks

Johns Hopkins University Department of Cognitive Science

Baltimore, MD 21218 (410) 516-7625

dilks@cogsci.jhu.edu

EDUCATION 2005-Present

Massachusetts Institute of Technology, Cambridge, MA. Postdoctoral Fellow, beginning September 2005. Advisor: Nancy Kanwisher

2001-2005 Johns Hopkins University, Baltimore, MD. Ph.D., Cognitive Science. Advisors: Michael McCloskey and Barbara Landau.

1997-1999 University of Pennsylvania, Philadelphia, PA. Post-Baccalaureate/Graduate Program, Cognitive Psychology.

1989-1991 Drexel University, Philadelphia, PA. M.B.A., Consumer Behavior.

1984-1988 Rutgers University, New Brunswick, NJ. B.S., Statistics/Marketing.

PUBLICATIONS & MANUSCRIPTS Landau, B., Hoffman, J.E., Reiss, J.E., Dilks, D.D., Lakusta, L., & Chunyo, G. (2004).

Specialization, Breakdown, and Sparing in Spatial Cognition: Lessons from Williams syndrome. In C. Morris, H. Lenhoff, & P. Wang (Eds.), Williams-Beuren Syndrome: Research and Clinical Perspectives. Baltimore: Johns Hopkins University Press.

Dilks, D.D. & McCloskey, M. (2004). [Review of the book Filling In: From Perceptual Completion to Cortical Reorganization]. Annals of Neurology, 56, 913.

Dilks, D.D., Landau, B. & Hoffman, J.E. (submitted). Vision for perception and vision for action: Normal and unusual development.

Dilks, D.D., Serences, J.T., Yantis, S., & McCloskey, M., (submitted). Human adult cortical reorganization and consequent visual distortion.

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Dilks, D.D., Reiss, J.E., Landau, B., & Hoffman, J.E. (in preparation). Representation of orientation in Williams syndrome.

Valtonen, J., McCloskey, M., & Dilks, D.D. (in preparation). Cognitive representation of line orientation: A case study.

ADDITIONAL PUBLICATIONS & MANUSCRIPTS

Dalton, P., Cowart, B., Dilks, D., Gould, M., Lees, P.S.J., Stefaniak, A., & Emmett, E. (2003). Olfactory function in workers exposed to styrene in the reinforced-plastic industry. American Journal of Industrial Medicine, 44, 1-11.

Dalton, P., Dilks D. and Banton, M. (2000). Evaluation of odor and sensory irritation thresholds for methyl iso-butyl ketone (MIBK) in humans. American Industrial Hygiene Association Journal, 61, 340-350.

PAPER & POSTER PRESENTATIONS Dilks, D.D., McCloskey, M., Serences, J., & Yantis, S. (2004). The “El Greco” effect:

Perceptual distortion from visual cortical reorganization. Paper presented at Psychonomics, Minneapolis, MN.

Dilks, D.D., Reiss, J.E., Landau, B., & Hoffman, J.E. (2004). Representation of orientation in Williams syndrome. Poster presented at Psychonomics, Minneapolis, MN.

Dilks, D.D., Landau, B., Hoffman, J.E., & Oberg, P. (2003). Vision for action vs. perception in Williams syndrome: Evidence for developmental delay in the dorsal stream. Poster presented at Cognitive Neuroscience, New York, NY.

McCloskey, M., Dilks, D.D., & Hillis, A. (2003). Visual size and distance representations: Evidence from a perceptual deficit. Poster presented at Cognitive Neuroscience, New York, NY.

Dilks, D., Landau, B., Hoffman, J. & Siegfried, J. (2001). Selective impairment of dorsal stream function in children with Williams Syndrome. Poster presented at Cognitive Neuroscience, New York, NY.

Whalen, J., Dilks, D. (2001). How do we solve multiplication problems? The veridicality of self-reports using ERP. Poster presented at Cognitive Neuroscience, New York, NY.

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HONORS & AWARDS 2001 – Present National Science Foundation Integrative Graduate Education &

Research Training (IGERT) Fellowship July 2001 Oxford University Summer School on Connectionist Modelling

Fellowship

RESEARCH EXPERIENCE Sept. 2005 – Present

POSTDOCTORAL FELLOW. Massachusetts Institute of Technology. Advisor: Nancy Kanwisher Investigating the perceptual consequences of cortical reorganization in the human adult visual system.

June 2001– Aug. 2005

IGERT GRADUATE RESEARCH FELLOW. Johns Hopkins University. Advisor: Michael McCloskey Investigated cortical reorganization in the human adult visual system, and its perceptual consequences. Advisor: Barbara Landau Investigated issues of spatial cognition and development by examining normally developing children and individuals with Williams syndrome.

Jan. 1997 – Aug. 1999

RESEARCH ASSISTANTSHIP. University of Pennsylvania. Advisor: Pamela Dalton Investigated human olfactory perception including the effects of short- and long-term exposures to odors, olfactory adaptation, chemesthesis and cognitive influences on chemosensory perception. Experimental approaches included psychophysical, electrophysiological and behavioral techniques. Responsibilities included idea generation, study design, data collection, analysis and report writing.

TEACHING EXPERIENCE 2002-2004

TEACHING ASSISTANT. Johns Hopkins University.

Cognitive Neuropsychology of Visual Perception (McCloskey) Introduction to Cognitive Neuropsychology (McCloskey) Advanced Topics in Neuropsychology (McCloskey)

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Sept. 1986 – Dec. 1991

STATISTICS TUTOR. Rutgers University. Assisted students in statistics, marketing research and various other related courses. Maintained and supervised department in absence of director.

EMPLOYMENT Nov. 1991 – Dec. 1996

STATISTICIAN. Consumer/Industrial Research Center, Chadds Ford, PA. Aided in the development of appropriate study design, sample size and questionnaire structure. Applied relevant statistical methodologies to detail analysis in consistent and valid forms. Communicated findings both written and verbally.

PROFESSIONAL AFFILIATIONS Cognitive Neuroscience Society Psychonomics Society Society for Neurosciences Vision Science Society

REFERENCES Michael McCloskey, Ph.D. Professor of Cognitive Science, Johns Hopkins University Department of Cognitive Science Baltimore, MD 21218 Phone: (410) 516-5325 Email: michael.mccloskey@jhu.edu Barbara Landau, Ph.D. Todd Professor of Cognitive Science, Johns Hopkins University Department of Cognitive Science Baltimore, MD 21218 Phone: (410) 516-5255 Email: landau@cogsci.jhu.edu Steven Yantis, Ph.D. Professor of Psychology, Johns Hopkins University Department of Psychological and Brain Sciences Baltimore, MD 21218 Phone: (410) 516-5328 Email: yantis@jhu.edu

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