IJ Hubbard 2012

Journal Club March 2012A Visual Presentation

Brain Reorganisation and Upper Limb Recovery

IJ Hubbard 2012

Objectives:

• Brain Reorganisation– What’s it all about?

• Neuroanatomy update– Brief review of brain topography

• Stroke: the disconnect– What’s happened and why?

• Upper limb (UL) recovery– Answering the all-important ‘so what’ question

Hmm…The elephant in the room, perhaps? Can we be certain that our stroke rehabilitation efforts are achieving better outcomes than if we did nothing at all (natural history)?

Hmm…The elephant in the room, perhaps? Can we be certain that our stroke rehabilitation efforts are achieving better outcomes than if we did nothing at all (natural history)?

This presentation is for your eyes only!

Work your way throughthe 22 slides, take thesuggested detours,

& then let’s chat!

Note from Isobel:

IJ Hubbard 2012

Presenter:

• Ms Isobel Hubbard– Occupational Therapist working as an Academic Researcher

• Lecturer at the University of Newcastle– Convenor of a stroke-specific Masters and Graduate Certificate– Coordinator of all stroke-specific postgraduate &

undergraduate courses

• PhD Student– Investigating early brain reorganisation & UL recovery post stroke– Track record in publications & presentations

Acknowledgingthe contribution of Drs

Parsons, Carey and Budd,the acute stroke team at John

Hunter hospital, NewcastleAustralia, the National Stroke Foundation and

the University of Newcastle’sPriority Research Centre for

Brain & Mental Health

IJ Hubbard 2012

Brain Reorganisation

Definition: Definition: Wiki plus IH: Neuroplasticity refers to the ability of the brain and nervous system.. to change structurally and functionally as a result of input from the environment. Plasticity occurs on a variety of levels, ranging from cellular changes involved in learning, to large-scale changes involved in cortical remapping in response to injury, eg stroke...During most of the 20th century, the general consensus.. was that the brain’s structure is relatively stable after a developmental period in early childhood. This belief has been challenged by new findings revealing that the brain is relatively plastic and

in turn, responsive to change, throughout an adult’s lifetime.

Definition: Definition: Wiki plus IH: Neuroplasticity refers to the ability of the brain and nervous system.. to change structurally and functionally as a result of input from the environment. Plasticity occurs on a variety of levels, ranging from cellular changes involved in learning, to large-scale changes involved in cortical remapping in response to injury, eg stroke...During most of the 20th century, the general consensus.. was that the brain’s structure is relatively stable after a developmental period in early childhood. This belief has been challenged by new findings revealing that the brain is relatively plastic and

in turn, responsive to change, throughout an adult’s lifetime.

Source: wikipedia.orgRef: T Elbert, C Pantev, C Wienbruch, B Rockstroh, E Taub. (1995) Increased cortical representation of the fingers of the left hand in string players. Science 270, 305-307.

We know from Elbert et al’s research (1995) that if you decided to learn to play the

violin, your brain would increase the cortical area

allocated to your non-dominant UL

IJ Hubbard 2012

Brain Reorganisation

To find out more: To find out more: Go to Rossini, Calautti, Pauri & Baron (2002) Post stroke plastic reorganisation in the adult brain.

Lancet Neurology, 2, 439-502Quote: “Our understanding of the mechanisms that promote or prevent recovery is fundamental to the design of

novel therapies…In this review we discuss brain imaging studies of reorganisation after stroke. Because motor function of the arms can be used to model the recovery of higher functions…we will focus on the recovery of the sensorimotor arm and hand function.

Carey & Seitz (2007) Functional neuroimaging in stroke recovery and neurorehabilitation: conceptual issues and perspectives. International Journal of Stroke, 2 (4), 245-264

Quote: “Our current mandate is to adopt a more active approach to rehabilitation by developing approaches that aim to restore underlying capacity and improve clinical outcome…Promising approaches

need to be systematically tested..”

To find out more: To find out more: Go to Rossini, Calautti, Pauri & Baron (2002) Post stroke plastic reorganisation in the adult brain.

Lancet Neurology, 2, 439-502Quote: “Our understanding of the mechanisms that promote or prevent recovery is fundamental to the design of

novel therapies…In this review we discuss brain imaging studies of reorganisation after stroke. Because motor function of the arms can be used to model the recovery of higher functions…we will focus on the recovery of the sensorimotor arm and hand function.

Carey & Seitz (2007) Functional neuroimaging in stroke recovery and neurorehabilitation: conceptual issues and perspectives. International Journal of Stroke, 2 (4), 245-264

Quote: “Our current mandate is to adopt a more active approach to rehabilitation by developing approaches that aim to restore underlying capacity and improve clinical outcome…Promising approaches

need to be systematically tested..”

Brain reorganisation: a neural mechanism that underpins stroke recovery because of its responsiveness to changes in behavioural demandsFunctional Magnetic Resonance Imaging (fMRI): a non-invasive neuroimaging technique that provides a “window” into brain reorganisation

IJ Hubbard 2012

Neuroanatomy 101

Inter-hemispheric fissure: hemispheres are similar but not exact opposites.

The surface of both hemispheres is made up of many gyri (ridges) & sulci (creases).

1. The Cortex: ≈ top 1cm of gyri and sulci2. The Subcortex: the supporting structure3. The Cerebellum, Brain Stem & Pons are

positioned to connect the brain & body.

The central sulci separates the:Pre-central and post-central gyri.

The human brain uses up 20% of

the body’s oxygen& nutrients

Before you go to the next slide, test your knowledge: Which regions of the brain are important to motor function and where are they? Where do you find the cingulate area and what is its primary function? What % of the corticospinal tracts arising from the right primary motor cortex (M1) go to the left UL?

Before you go to the next slide, test your knowledge: Which regions of the brain are important to motor function and where are they? Where do you find the cingulate area and what is its primary function? What % of the corticospinal tracts arising from the right primary motor cortex (M1) go to the left UL?

Cerebellum

IJ Hubbard 2012

Neuroanatomy 101

Left Hemisphere: Brodmanns Area (BA)

Frontal lobe

Temporal lobe

Source: wikipedia.org

Right hemisphere: similar but not exact mirror image

Pareital lobe

Central Sulci

Functional Regions of InterestFunctional Regions of InterestBA4: Primary motor cortex (M1)BA6: Premotor cortex (PMC) & Supplementary motor area (SMA) BA3,1,2: Primary somatosensory cortexBA5 & 7: Secondary somatosensory

Notes: The SMA, an area important to UL recovery post stroke, is positioned in the medial region of each hemispere (not shown). The two SMA “face-off” across the interhemispheric fissure. Do they communicate via the anterior commissure, a bundle of nerve fibres connecting the hemispheres?

To explore the imaged brain: To explore the imaged brain: Go to The Whole Brain Atlas atwww.med.harvard.edu/aanlib/home.html

Select: “NEW: normal anatomy in 3D..”. Use the arrows to navigate the imaged “slices” & try the ‘stroke’ links.

Functional Regions of InterestFunctional Regions of InterestBA4: Primary motor cortex (M1)BA6: Premotor cortex (PMC) & Supplementary motor area (SMA) BA3,1,2: Primary somatosensory cortexBA5 & 7: Secondary somatosensory

Notes: The SMA, an area important to UL recovery post stroke, is positioned in the medial region of each hemispere (not shown). The two SMA “face-off” across the interhemispheric fissure. Do they communicate via the anterior commissure, a bundle of nerve fibres connecting the hemispheres?

To explore the imaged brain: To explore the imaged brain: Go to The Whole Brain Atlas atwww.med.harvard.edu/aanlib/home.html

Select: “NEW: normal anatomy in 3D..”. Use the arrows to navigate the imaged “slices” & try the ‘stroke’ links.

IJ Hubbard 2012

Neuroanatomy 101

Neural System: a complex labyrinthNeural System: a complex labyrinth

Cortex: The end point or journey destinationSubcortex: The connection, journey or road map

Notes re: The brain’s neural system… Communicates inter- (between) & intra- (within)

hemispherically. Lots of connectivity! Is connected to the body via corticospinal tracts

≤90% contralateral (opposite side) ≥10% ispsilateral (same side)

Is dependent on the vascular system for a reliable supply of oxygen & nutrients

Neural System: a complex labyrinthNeural System: a complex labyrinth

Cortex: The end point or journey destinationSubcortex: The connection, journey or road map

Notes re: The brain’s neural system… Communicates inter- (between) & intra- (within)

hemispherically. Lots of connectivity! Is connected to the body via corticospinal tracts

≤90% contralateral (opposite side) ≥10% ispsilateral (same side)

Is dependent on the vascular system for a reliable supply of oxygen & nutrients

Source: wikipedia.org

The brain’s neural system is like a city’s road

network

IJ Hubbard 2012

Neuroanatomy 101

http://www.youtube.com/watch?v=hUZeuzXH-zA

To appreciate the complexity of the neural system go to this youtube link. You’re looking at tractography or connectivity mapping. The different colours represent different directions

of activity along the tracts.

http://en.wikipedia.org/wiki/Diffusion_MRI

Interhemispheric connectivity

The human brain makes up only 2% of body weight, yet it accounts for 20% of the body’s total O2 consumption & receives 11% of its cardiac output (Giedde, 2006)

Ref: Gjedde A. Brain energy metabolism and the physiological response, in Functional MRI: An introduction to methods, Jezzard, Mathews & Smith, Ed. 2006, Oxford University Press

IJ Hubbard 2012

Neuroanatomy 101

Vascular System: a supply lineVascular System: a supply line

Middle Cerebral artery (MCA): Supplies much of the brain’s motor-related neural regions

Circle of Willis: The largest of the brain’s unique contralateral/collateral supply lines

Notes: • This system is responsible for a reliable

supply of O2 & nutrients to the brain• A disruption to the blood supply impacts the

neural system: Time is brain!• Hyper-acute stroke management is

about restoring the integrity of the vascular system ASAP!! FAST!!

Vascular System: a supply lineVascular System: a supply line

Middle Cerebral artery (MCA): Supplies much of the brain’s motor-related neural regions

Circle of Willis: The largest of the brain’s unique contralateral/collateral supply lines

Notes: • This system is responsible for a reliable

supply of O2 & nutrients to the brain• A disruption to the blood supply impacts the

neural system: Time is brain!• Hyper-acute stroke management is

about restoring the integrity of the vascular system ASAP!! FAST!!Time is brain!

Each minute 1.9 millionneurons die without

O2 & nutrients

The brain’s vascular

system is like its trains &

underground

Saver, J.L. (2005) Time is brain – quantified. Stroke 2006 37: 10

IJ Hubbard 2012

Neuroanatomy 101

To find out more: To find out more: Go to The Internet Stroke Centre http://www.strokecenter.org/

and you’ll find this image and lots more

IJ Hubbard 2012

Stroke: the disconnect

Stroke is a disconnection phenomenaStroke is a disconnection phenomena

The integrity of the ‘up-stream’ neural regionsis immediately threatened after any disruptionto the vascular supply, such as strokestroke.

Ischemic Stroke: Blockage: 80-85% of all strokes• Results in permanent damage ‘up-stream’• Can present as a squid-like area of damage

that’s reached into closely located gyri

Hemorrhagic Stroke: Bleed:15-20% of all strokes• More easily identified via CT scan• Also results in up-stream damage• More life-threatening

Stroke is a disconnection phenomenaStroke is a disconnection phenomena

The integrity of the ‘up-stream’ neural regionsis immediately threatened after any disruptionto the vascular supply, such as strokestroke.

Ischemic Stroke: Blockage: 80-85% of all strokes• Results in permanent damage ‘up-stream’• Can present as a squid-like area of damage

that’s reached into closely located gyri

Hemorrhagic Stroke: Bleed:15-20% of all strokes• More easily identified via CT scan• Also results in up-stream damage• More life-threatening

Hmm…The day after a stroke am I right to

assume there’s nothing wrong with the

UL muscles?

If you’re unsure about recognising stroke and/or what to do, go to either of these links

http://www.youtube.com/watch?v=T_CXqfFGpvY&feature=relmfu

http://www.strokefoundation.com.au/

Time is Brain Act FAST: Face, Arm, Speech & Time

IJ Hubbard 2012

Predicting Recovery

Predicting Recovery: Acute therapists need to be able to quickly & accurately predict potential.

Notes: Strokes that affect the UL..1. Are usually an Anterior Circulation Infarct (ACI)2. Have usually impacted the pre- and/or post-central gyri

or sensorimotor ‘strip’. Ref: Oxfordshire Classification system:

http://www.strokecentre.org/trials/scales/oxford.html

Stroke topography: Imaging results assist in identifyingwhere a stroke is located. This is an important indicator ofrecovery potential:• Poorest potential: TACI (total)• Best potential: Lacuna infarct (LACI)

What about corticospinal tract integrity? Ref: Stinear et al (2007) Functional

potential in chronic stroke patients depends on corticospinal tract integrity. Brain, 130,

170-180

Predicting Recovery: Acute therapists need to be able to quickly & accurately predict potential.

Notes: Strokes that affect the UL..1. Are usually an Anterior Circulation Infarct (ACI)2. Have usually impacted the pre- and/or post-central gyri

or sensorimotor ‘strip’. Ref: Oxfordshire Classification system:

http://www.strokecentre.org/trials/scales/oxford.html

Stroke topography: Imaging results assist in identifyingwhere a stroke is located. This is an important indicator ofrecovery potential:• Poorest potential: TACI (total)• Best potential: Lacuna infarct (LACI)

What about corticospinal tract integrity? Ref: Stinear et al (2007) Functional

potential in chronic stroke patients depends on corticospinal tract integrity. Brain, 130,

170-180

Potential Poor Medium Good

Stroke type TACI PACI LACI or POCI

Supportive family

Incontinent

20/10 UL Club

Global aphasia

Stroke Unit

Care

Predicting good vs poor recovery potential

Those with ≥20°movement at the wrist & ≥10° in at least one finger

Another elephant…? Should therapists be spending their very

limited time on stroke patients who are unlikely to recover?

Another elephant…? Should therapists be spending their very

limited time on stroke patients who are unlikely to recover?

To find out more about the To find out more about the corticospinal tract: corticospinal tract: Go to

The Brain from Top to Bottom at http://thebrain.mcgill.ca/flash/i/i_06/i_06_cl/i

_06_cl_mou/i_06_cl_mou.html

IJ Hubbard 2012

Upper Limb Recovery

Before you move onto the next slide take some time-

out to consider & write down your 4 most importantmost important “best practice” principals for

post stroke upper limb rehabilitation.

IJ Hubbard 2012

Upper Limb Recovery

Four “Most Important” Principals (IH)Four “Most Important” Principals (IH)

As Early As Possible: As soon as the patient is medically stableAs Intense As Possible: As intense as the patient can reasonably tolerate, which can only be achieved if it’s mostly self-directedAs Client-centred As Possible: As meaningful as is environmentally possibleAs Task-specific As Possible: As close to real-life activities as is feasible and reasonably safe, which is only possible if we take some risks

Four “Most Important” Principals (IH)Four “Most Important” Principals (IH)

As Early As Possible: As soon as the patient is medically stableAs Intense As Possible: As intense as the patient can reasonably tolerate, which can only be achieved if it’s mostly self-directedAs Client-centred As Possible: As meaningful as is environmentally possibleAs Task-specific As Possible: As close to real-life activities as is feasible and reasonably safe, which is only possible if we take some risks

Hmm..a room of elephants..!!!Emerging evidence tells us that hospital

& rehabilitation wards are usually environmentally bereft and

occupationally de-challenging, perhaps making them the worst

spaces for people recovering from stroke!!

Ref: Hubbard.et al (2009) Task-specific training: Evidence for and translation to clinical practice. Occupational Therapy International, 16(3-4), 175-189

Time is function!In the first month after stroke

each day spent doing very littleis a lost opportunity for

better recovery

IJ Hubbard 2012

Upper Limb RecoveryUnderstanding the research

We asked this question & we’re finding differences in certain We asked this question & we’re finding differences in certain regions - we’re in the process of writing this up.regions - we’re in the process of writing this up.

Do you find it difficult to understand the reporting of research Investigating changes in brain activation? Terms often used: 1. Contralesional: the stroke-affected (lesioned) hemisphere2. Ipsilesional: the non-affected hemisphere

Researchers will use analysis methods such as “flipping” thehemispheres of one group of study participants, so that they can compare results between hemispheres – as we are doing.

3. Laterality Index (LI): Shifts in activation patterns between hemispheres over time – another way of reporting changes in activation

We asked this question & we’re finding differences in certain We asked this question & we’re finding differences in certain regions - we’re in the process of writing this up.regions - we’re in the process of writing this up.

Do you find it difficult to understand the reporting of research Investigating changes in brain activation? Terms often used: 1. Contralesional: the stroke-affected (lesioned) hemisphere2. Ipsilesional: the non-affected hemisphere

Researchers will use analysis methods such as “flipping” thehemispheres of one group of study participants, so that they can compare results between hemispheres – as we are doing.

3. Laterality Index (LI): Shifts in activation patterns between hemispheres over time – another way of reporting changes in activation

Typical research question: Do different intensities of UL intervention result in different

patterns of activation?

Glass MapsThe image above shows

the between-group differencesin activation over a nominatedp-value threshold. SPM is the

program used to do the analysis

IJ Hubbard 2012

Upper Limb RecoveryWhat’s the research telling us?

All systematic reviews found activation associated with the stroke-affected UL was in ipsilesional, motor-related areas eg, the M1 & SMA.

Systematic Review Review Aim Findings associated with recovery of the Stroke-affected UL

Buma et al (2010) Neurorehabilitation & Neural Repair, 24(7), 589-608

Studies ≤6mo post stroke

In the first weeks post stroke, profound overactivation, perilesional and contralesional activation in motor-related areas. Good recovery associated with return to more normal patterns. Poor recovery associated with persistent recruitment of contralesional activation in motor areas.

Hodics et al (2006) Arch of Phys Med & Rehab, 87(12), 36-42

Intervention-specific effects

Clinical improvement even late after stroke. Mostly motor-related studies. Constraint-based interventions resulted in ipsilesional M1, PMC & SMA. Bilateral UL training influences contralesional changes

Kokolito et al (2009) Journal of Neurologic Physical Therapy, 33(1), 45-55

Force production & modulation

Changes in activity in motor-related areas including M1, PMC & SMA associated with increasing severity of stroke. Reduced recruitment of motor areas increased over time. Rehabilitation can influence activity patterns. Early task-related activation observed in motor regions including SMA & CA

Richards et al (2008) Neuropshychologia, 46, 3-11

UL motor intervention & ipsilesional activity

Association between improved UL function following behavioural intervention & neural changes in ipsilesional S1M1 over time. Targeted UL intervention increases ipsilesional engagement of motor-related areas.

IJ Hubbard 2012

Upper Limb RecoveryGood versus Poor Recoverers

Dr Leeanne Carey et al (2006) Evolution of Brain Dr Leeanne Carey et al (2006) Evolution of Brain Activation with good and poor motor Activation with good and poor motor recovery after stroke.recovery after stroke.Neurorehab & Neural Repair, 20, 24-41.Neurorehab & Neural Repair, 20, 24-41.

Participants: n=9; baseline 2-7 wks post stroke; follow-up at 6 months

Method: Compared to healthy volunteer dataFindings: Good recoverersGood recoverers with moderate

impairment (n=5) had ipsilesional SM1 activation, bilateral SMA & contralesional PMC; the bilateral SMA activation reduced over time.

Poor recoverersPoor recoverers with severe impairment (n=4) had limited ipsilesional S1M1 and SMA activation & no significant change over time.

Conclusion: In the sub-acute phase, there is evidence of reversion to more normal patterns

in good recoverers over time. SMA is important to UL recovery SMA is important to UL recovery following stroke.following stroke.

Dr Leeanne Carey et al (2006) Evolution of Brain Dr Leeanne Carey et al (2006) Evolution of Brain Activation with good and poor motor Activation with good and poor motor recovery after stroke.recovery after stroke.Neurorehab & Neural Repair, 20, 24-41.Neurorehab & Neural Repair, 20, 24-41.

Participants: n=9; baseline 2-7 wks post stroke; follow-up at 6 months

Method: Compared to healthy volunteer dataFindings: Good recoverersGood recoverers with moderate

impairment (n=5) had ipsilesional SM1 activation, bilateral SMA & contralesional PMC; the bilateral SMA activation reduced over time.

Poor recoverersPoor recoverers with severe impairment (n=4) had limited ipsilesional S1M1 and SMA activation & no significant change over time.

Conclusion: In the sub-acute phase, there is evidence of reversion to more normal patterns

in good recoverers over time. SMA is important to UL recovery SMA is important to UL recovery following stroke.following stroke.

Important research question: Are there

differences in activation patterns between good and poor recoverers?

SMA

IJ Hubbard 2012

Upper Limb Recovery

Joining up the dots….. Knowing what activation

patterns are associated with good recovery means

researchers can investigate which UL interventions elicit

those patterns

IJ Hubbard 2012

Upper Limb RecoveryThe “hopping” problem

Post Stroke : Upper Limb vs Lower LimbPost Stroke : Upper Limb vs Lower Limb

Lower limb: Fortunately it’s more difficult to hop than walk, therefore learned non-use is not an issue.Upper Limb: Unfortunately it’s quite easy to learn to do things one-handed so learned non-use is a big problem that is best challenged ASAP!Constraint-based Intervention: Forces the person to stop UL “hopping”! It challenges learned non-use by forcing the engagement of the stroke-affected UL & demands involvement from both hemispheres. Not suitable for those with no observable movement.

Behavioural Demands: Brain reorganisation is a normal response to behavioural changes. Learn the violin and the brain reorganises! Have a stroke and the brain reorganises! Start to walk, speak and/or use the affected UL and the brain reorganises.

Post Stroke : Upper Limb vs Lower LimbPost Stroke : Upper Limb vs Lower Limb

Lower limb: Fortunately it’s more difficult to hop than walk, therefore learned non-use is not an issue.Upper Limb: Unfortunately it’s quite easy to learn to do things one-handed so learned non-use is a big problem that is best challenged ASAP!Constraint-based Intervention: Forces the person to stop UL “hopping”! It challenges learned non-use by forcing the engagement of the stroke-affected UL & demands involvement from both hemispheres. Not suitable for those with no observable movement.

Behavioural Demands: Brain reorganisation is a normal response to behavioural changes. Learn the violin and the brain reorganises! Have a stroke and the brain reorganises! Start to walk, speak and/or use the affected UL and the brain reorganises.

Time is function!Adequate dose should be a primary consideration

irrespective of time post stroke

IJ Hubbard 2012

In Conclusion

Evidence concerning post stroke brain activation patterns tells us that: • The brain can reorganise post stroke• Brain reorganisation underpins sub-acute recovery• Our selection of UL interventions should consider their impact on brain activation• Best practice for most stroke-affected upper limbs is early more intensive, task-specific intervention

In 2011 we built ourselves a new house with an upstairs and downstairs area. Q: Have we lost sight of the fact that stroke is an “upstairs” disconnection, because our UL assessments & interventions are often focussed on what’s happening “downstairs”. Journal Club Author: Isobel Hubbard

IJ Hubbard 2012

Thank you

Post your questions or comments in the March Journal Club discussion