Connection of Cerebellum

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Cerebellum: Connections and Functions

Mitchell Glickstein & Karl Doron

Published online: 11 November 2008# Springer Science + Business Media, LLC 2008

Abstract In addition to its role in motor control, reflex

adaptation, and motor learning, three sorts of evidence have been put forward to support the idea that the cerebellum

may also be involved in cognition. Patients with cerebellar

lesions are reported to have deficits in performing one or

another cognitive task. The cerebellum is often seen to be

activated when normal subjects perform such tasks. There

are connections to and from areas of the prefrontal cortex

that may be involved in cognition. In this paper, we review

the anatomical evidence to support the claim. We suggest

that there are only minor connections with cognitive areas

of the cerebral cortex and that some of the imaging

evidence may reflect the cerebellum’s role in the control

of eye movements rather than cognition.

Keywords Cerebellum . Eye movements . Pontine nuclei .

DTI . Cerebral peduncle

Introduction

From the earliest experimental studies in animals, it was

apparent that cerebellar lesions cause impairment in the

control of movement. Rolando [1] described the resultant

profound motor deficit that was caused by cerebellar

lesions. Fifteen years later, Flourens [2] argued that, after

such lesions animals can still move, but their coordinationis impaired. In the following 70 years, there were many

attempts to characterize more precisely the nature of the

deficit. In the most extensive of these studies, Luciani [3]

related the deficits to a fundamental impairment of muscle

control. According to Luciani’s careful observations and

conclusions, lesions of the cerebellum cause atonia or loss

of muscle tone, asthenia, or muscular weakness and astasia,

which, according to Luciani, manifests itself as tremor,

oscillation, and lack of coordination.

Although no one denied the obvious motor symptoms

that are caused by lesions of the cerebellum, there was an

occasional claim that they may also produce cognitive

deficits.

André-Thomas [4] dismissed such claims, basing his

conclusions on a systematic description of clinical symp-

toms and postmortem evidence. He wrote:

“While it is true that in a sufficiently large number of

observations the coincidence of intellectual disturbances

with cerebellar lesions has been noted, how many times

has a relation of cause and effect been established in a

rigorously scientific manner between the two? Those

who have thought that they have found this relation have

not taken into consideration the possibility of thecoexistence of cerebral lesions, or the insufficiency of

the examination of the cerebrum.”

For normal posture and movements, inputs from the

vestibular system as well as muscle, tendon, and joint

afferents are required. Sherrington [5] interpreted the

deficits that are caused by cerebellar lesions as being due

to loss of proprioceptive input to the motor system. The

cerebellum, he said, is the head ganglion of the proprio-

ceptive system.

Cerebellum (2008) 7:589 – 594

DOI 10.1007/s12311-008-0074-4

M. Glickstein (*)

Department of Cell and Developmental Biology,

University College London,

Gower Street,

London WC1E 6BT, UK

e-mail: [email protected]

K. Doron

Department of Psychology,

University of California at Santa Barbara,

Santa Barbara, CA 93106-9660, USA



At the time that these interpretations were put forward,

there were few anatomical techniques available for estab-

lishing fiber connections in the nervous system. Ramon y

Cajal [6] would sometimes attempt to follow the course and

termination of fiber tracts using the Golgi stain, but this

method is not really suitable for tracing long pathways.

Such connections were typically studied either by gross

dissection or by using the degeneration method of Marchi.But the Marchi technique stains degenerating myelin,

hence, it is strongly biased in favor of the largest diameter

axons.

Recent Suggestions of a Cognitive Function

for the Cerebellum

The idea that the cerebellum may be involved in cognition

has reappeared from time to time, and recently seems to

have become popular again [7]. Following the suggestions

in Leiner ’s paper, there are now hundreds of reports whichargue for a cognitive role for the cerebellum. The original

syllogism seems to be that the cerebellum, and particularly

the cerebellar hemispheres, is particularly large in humans,

monkeys, and apes; humans, apes, and monkeys are clever,

so the cerebellum is a likely brain structure for cleverness.

(An alternative syllogism might be that humans, apes, and

monkeys are most skillful in the use of their fingers…).

Three sorts of evidence have been put forward to support

the idea of a role for the cerebellum in cognitive functions;

neuropsychological deficits in patients with cerebellar

lesions, activation of the cerebellum in normal subjects as

they perform a cognitive task, and anatomical connections

showing links to and from the cerebellum of structures in

the cerebral cortex that are known or thought to be involved

in cognition. Some of this evidence is summarized in a

paper by Schmahmann [8].

In the past hundred years, there have been major advances

in the techniques available for studying connections within

the brain, and this evidence should help to clarify the

functions of the cerebellum. We can ask: what are the inputs

to the cerebellum and where does it project? In this paper, we

restrict ourselves largely to the anatomical evidence, al-

though we share with André-Thomas a skeptical view of the

alleged clinical evidence for a role for the cerebellum in

cognition and the associated claims based on imaging

techniques.

The cerebellum is concerned with the direct ongoing

regulation of movement, planning of movements, and motor

learning. Actual and planned movements may masquerade

as cognition. For example, much of what we do is preceded

by an eye movement [9], and the frontal cortex has several

regions that are involved in the control of eye movements

[10 – 12]. What we think we may do may be preceded by

activity in those same structures. Just as functional magnetic

resonance imaging (fMRI) activity may be associated with

planned as well as actual movement, so planned eye

movement may be associated with the activation of the

same brain structures that control eye movement. Some

of the inputs from the cerebral cortex to the cerebellum

that appear to be cognitive in function may be primarily

involved in eye movement control.

Gross Connections of the Cerebellum

The cerebellum is connected by three prominent paired

stalks, the cerebellar peduncles, which link it to the rest of

the brain. The inferior peduncle is largely afferent from

the inferior olivary nucleus as well as spinocerebellar and

vestibular systems. Few would argue that the inferior

peduncle is a link to cognitive structures. The alleged input

from cognitive areas of the cerebral cortex would reach the

cerebellum by way of a relay in the pontine nuclei. The axonsof pontine cells project to the cerebellar cortex by way of

the middle cerebellar peduncle, which is by far the largest

of the three peduncles in the human brain.

The output from the cerebellum is by way of the axons

of the cerebellar nuclei, most of which travel in the superior

cerebellar peduncle to the red nucleus and the thalamus.

The thalamus, in turn, relays that input to the cerebral

cortex. In this paper, we examine the nature of the input to

the pontine nuclei from the cerebral cortex and the output

targets of the cerebellar nuclei to the cerebral cortex.

Input to the Cerebellum

In humans and the higher primates, by far the largest source

of input to the pontine nuclei is from the cerebral cortex.

Two obvious questions can be asked about that input:

which cells in the cerebral cortex project to the pontine

nuclei and which areas of the cortex project there? The

second questions bears directly on the issue of a possible

role of the cerebellum in cognition. If an area of the

cerebral cortex that is known to function in cognitive tasks

projects to the pons or receives an input from the cerebellar

nuclei, that would be evidence for a role for the cerebellum

in such tasks. Both questions, which cells and how they are

distributed, can be addressed by filling the pontine nuclei

with a retrograde tracer and identifying the location and

distribution of retrogradely labeled cells in the cerebral

cortex. The answer to the first question is easy. All input

from the cerebral cortex to the pontine nuclei arises from

layer V pyramidal cells. Pontine-projecting cells often form

a continuous sublamina within layer V of the cerebral

cortex [13, 16] (Fig. 1).

590 Cerebellum (2008) 7:589 – 594



Corticopontine fibers enter the internal capsule and

proceed ventrally to join the cerebral peduncle at the base of

the midbrain. In rats, the projection from the cerebral cortex

through the cerebral peduncle is spatially ordered [14]. Fibers

arising from cells in the temporal and occipital cortex travel

in the dorsolateral region of the cerebral peduncle. Fibers

originating from the frontal cortex travel in the ventromedial

region of the peduncle. Parietal lobe-originating fibers are

between these two. In the rat barrel field, two sublaminae of

layer V can be distinguished. Cells in the superficial

sublamina Va project to the basal ganglia. Cells in the deeper

layer Vb project to the pontine nuclei [13]. The cells in layer

Vb appear darker in cytochrome oxidase preparations, and

unlike Va, Vb receives a direct projection from the thalamus.

Fig. 1. Distribution of labeled

cells in the cerebral cortex of a

monkey after an injection of a

retrograde tracer (W.G.A.H.R.P.)

into the pontine nuclei. a Plane

of sections illustrated in b. b

Extent of primary injection site

in pontine nuclei. c Location of

retrogradely labeled cells in the

cerebral cortex; each dot repre-sents 25 cells. d Representative

cross sections of cortex to show

location of labeled cells (from

Glickstein et al. [16])

Cerebellum (2008) 7:589 – 594 591591



Which Cortical Areas Project to the Pons in Monkeys?

Layer V cells provides the input to the pontine nuclei in

all mammals that have been studied, but there are major

species differences among mammals in the number of

cortical areas that give rise to corticopontine fibers. In rats,

all of the cerebral cortex projects to the pontine nuclei [15];

in monkey, only about half of the cerebral cortex projects tothe pontine nuclei [16].

The differential projection from cortical visual areas

provides a clue to the function of the corticopontocerebellar

system. In monkeys, there is a dense projection to the pons

from the dorsal visual stream of extrastriate visual areas, a

region in which most of the neurons are motion-sensitive.

There are few or no inputs from areas in the ventral stream

of cortical visual areas whose cells are involved in higher

visual processes, such as face recognition and form

discrimination. Lesions of the dorsal stream of visual areas

impair skilled visually guided use of the hand and fingers.

Control lesions of the ventral stream visual areas do not [17].

The kind of visual information that is sent to the

cerebellum in cats is similar to that which is sent in monkeys.

Corticopontine [18] and pontine visual cells of cats [19] are

sensitive to the direction and velocity of moving targets; they

are relatively uninfluenced by the precise shape or orienta-

tion of those targets.

Disconnection of Sensory Areas of the Cerebral Cortex

from the Cerebellum Impairs the Sensory Guidance

of Movement

A patient in Professor Hans Joachim Freund’s group [20]

suffered a stroke in the caudal limb of the internal capsule

without damage either to the cerebral cortex or to cortico-

cortical fiber systems. The lesion led to a profound deficit

in visuomotor control, most marked when the patient

attempted to use the hand opposite the side of the stroke.

Recently, we used diffusion tensor imaging (DTI) in a set

of 20 normal brains to confirm the origin and course of

the fibers in this region of the internal capsule. We

replicated the lesion site from the Classen et al. case in

stereotaxic space and demonstrated a subcortical circuit

whose interruptions at the site of the lesion blocked dorsal

stream visual input to the pontine nuclei and cerebellum.

Fibers in this region of the internal capsule receive their

input from the dorsal stream of visual areas. In the case of

this DTI study, we found that these fibers arise from the

superior parietal lobule. The fibers from this area trace

ventrally and caudally to the lateral edge of the cerebral

peduncle, which is consistent with monkey and human

neuropathology evidence.

In rats, all of the cerebral cortex projects to the pons. The

projection is orderly. It is as if there is a miniature

representation of the cerebral cortex in the cerebral peduncle

[14]. Because of that arrangement, it is possible to selectively

cut the fibers from different cortical areas. Rats were trained

to jump across a 16 cm gap between two platforms; a

distance that they could just manage to reach with their

whiskers [21]. If the second platform was 1 cm beyond thereach of the whiskers, the rat would refuse to jump. We cut

the fibers within the cerebral peduncle on one side,

disconnecting the barrel field connection to the pontine

nuclei, thus leaving the rat with only one set of whiskers

connected to the pons. When the whiskers connected to the

pons were cut, the rat refused to jump. In contrast, cutting the

whiskers that were disconnected from the pons had no effect

on jumping. When the whiskers connected to the pons were

allowed to regrow, the rat would jump again. In all cases,

jumping in the light was unimpaired. The sensory informa-

tion reaching the cerebellum from the rat barrel cortex plays

an important role for judging distance for jumping. It seemslikely that other cortical projections play a similar role in

motor control.

In addition to direct sensory control of movement, the

anatomical study of the corticopontine system suggest

another important role for this system. Ramon y Cajal and

later Ugolini and Kuypers [22] showed that pyramidal tract

fibers, as they descend through the pons, give off collaterals

that connect to cells in the pontine nuclei. These collaterals

are an obvious candidate to serve as an efference copy of a

given movement.

The densest area of cells projecting to the pontine nuclei

from the cerebral cortex is from the primary motor and

premotor cortex. There is also a strong projection from area

8, the frontal eye field. There is a much weaker projection

from more rostral prefrontal cortical areas [16]. Some of

these prefrontal regions are cognitive in function, but some

may be more closely related to the control of eye move-

ments [12].

Afferent Connections, Thalamic targets of the Cerebellar

Nuclei, on the Thalamic Input to Frontal Eye Fields

All links from the cerebellum to the cerebral cortex

originate from the cerebellar nuclei and relay to the cerebral

cortex by way of the thalamus. Middleton and Strick [23]

injected the prefrontal cortex of monkeys, areas 46 and 9,

with a virus-based label and showed that there were

retrograde transneuronal labeled cells in the ventral dentate

nucleus. Their data are unequivocal in demonstrating that

there is a link between the cerebellar hemispheres, which

project to the dentate nucleus and prefrontal cortex. We

suggest that this connection may be part of an eye

592 Cerebellum (2008) 7:589 – 594



movements’ circuit. May et al. [24] injected a retrograde

tracer into the superior colliculus and showed that this area

receives a direct projection from the cerebellar dentate

nucleus. See, for example, their Fig. 1 sections K and L and

Fig. 3 sections H, I, and J.

An alternative way to study the connections would be to

fill all of the cerebellar deep nuclei with an orthograde

tracer and map the distribution of the orthogradely labeledfibers in the thalamus. This evidence could then be

compared with the pattern of retrograde label in the

thalamus nuclei after an injection is made in the frontal

cortex. Sakai et al. [25] injected all three cerebellar nuclei

and traced the fibers to their termination in the thalamus.

Her interest was in comparing the distribution of cerebellar

input to the thalamus with that from the basal ganglia, but

her data serve to outline the thalamic targets of the cerebellar

nuclei. The great majority of the terminations that she saw

were in the ventral thalamus. There was a small extension

into the nucleus medialis dorsalis which was restricted to its

far lateral region, adjacent to the external medullary lamina.The cortical target of this thalamic area is the frontal eye

fields. She did not show a projection to the more central

parvocellular region of medialis dorsalis.

Middleton and Strick injected area 46 in some cases and

area 9 in others. Lynch [12] showed that area 46 in the

monkey and a corresponding cortical area in the human

brain is part of an eye movement controlling area.

If prefrontal cortical areas known to be involved in

cognitive functioning project to the pontine nuclei, then the

case might be made that the cerebellum is involved in

cognition. Ramnani and his colleagues [26] used DTI to

study efferent pathways from the cortex. They found that

nearly half of the cerebral peduncle contains efferent fibers

from the human prefrontal areas. But the areas that they

studied are known to be involved in eye movement control

as well as cognition. Their study of the efferent pathway

would not have distinguished between the two functions. In

an ongoing study, we divided the prefrontal cortical areas in

stereotaxic space into six regions. We then used DTI

tractography to confirm that, in humans, the origin of the

prefrontal projections to pons arise primarily from the

premotor regions and dorsal precentral sulcus. Our findings

to date suggest that the prefrontal areas that project to the

pons are similar to those that are seen in fMRI studies of

eye movements [11].

Conclusion

The cerebellum is involved in the regulation of movement

of the limbs, the eyes, and the fingers [27]. Anatomical

evidence at best reveals only a weak connection between the

cerebellum and cerebral cortical areas involved in cognition.

Many of the papers demonstrating cognitive deficits follow-

ing cerebellar damage may be due to concomitant damage to

other brain structures. Neural activity in the cerebellum

during cognitive tasks may be associated with actual or

planned eye movements.

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