Transcript Plasticity of the Immature Brain in Response to Sensory

Plasticity of the Immature Brain:
Sensory Deprivation,
Focal Lesions
Shani Hagler
Isabelle Rapin
Child Neurology:
September 25, 2013
No conflict of interest
Brain Plasticity
The structure of the brain is a function of
 the genetic programs that orchestrate its
development
and
 inputs from the environment
A. Sensory deprivation
Environmental effect on development of
cortical neurons in fish:
Brought up
alone
Brought up
with others
Cover of
Science !
Brain Plasticity
In humans and animals
damage or sensory deprivation
→
 structural alteration (limited) of
subcortical relays and sensory cortex
 potential for (partial) functional recovery /
substitution
Brain Plasticity
Lack of major sensory input
(deafness, blindness, limb amputation, etc.)
→
major reorganization of sensory cortex, with
spared modalities occupying (partially)
deafferented sensory areas
Variables that affect brain
reorganization
 Age at sensory deprivation
 Completeness of the sensory loss
 Interval since sensory loss
 Stimulation following the sensory loss
Unilaterally Deafened Animals:
Subcortical Plasticity
 More immature animals → greater effect
 Sound deprivation, cochlear destruction →
structural reorganization of brainstem
nuclei, competitive innervation
 Decreased number, smaller neurons
 Dendritic atrophy
e.g., Webster, Clopton, Parks, Rubel
Human: Subcortical Plasticity
 Down infant (middle ear effusion) →
♦ ventral cochlear nuclei smaller; fewer neurons
 Cockayne syndrome (cochlear degeneration) →
♦ ventral cochlear nucleus, medial olive, inferior
colliculus: neurons small
♦ medial geniculate, Heschl gyrus: neurons normal !
Gandolfi, 1981, 1993
Plasticity: Differences in Early
Sound Exposure in Animals →

Decrease affects sound localization and visual/auditory
maps in tectum

Patterned sound exposure affects sound selectivity of
collicular neurons in rats, mice

Selective cochlear lesions change tonotopic map in
auditory cortex in cats

Discrimination training changes tonotopic map in
auditory cortex in owls

Deafness increase visual responses in auditory cortex in
cats
Plasticity: Early Speech Sound
Exposure in Humans
 Neonate: makes many speech sound
discriminations
 1 year old: loss of irrelevant, honing of relevant
speech sound discriminations
 Toddler/preschooler: learn new language
accent-free
 Older child/adult: accented new language; do
not hear irrelevant contrasts (e.g. L/R)
Bilateral Congenital Vestibular
Dysfunction:
Effect on Sitting and Walking (N=22)
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No nystagmus or vertigo
May have delayed head control, hypotonia
( 6 – 24)
Age at sitting:
8 months
Age at walking:
16.5 months (10 – 48)
Danger: swimming under water
Rapin 1974
Brain differences in early
blindness
 Normally - 1/3 of cortex involved in visual processing
 Blinded animal studies: new projections from inferior colliculus
(auditory) to lateral geniculate nucleus (normally visual)
 Anatomy:
- Gray&white matter atrophy of visual networks
- Increase in cortical thickness in cuneus (decreased
pruning?)
 Metabolism:
- 15% ↑ glucose metabolism in striate and extrastriate cortex
Kupers et al, 2011
Brain imaging in congenital/early blindness
A. Gray matter - red, white matter - blue
B. Increased cortical thickness of cuneus
C. Increased glucose metabolism
Kupers et al. 2011
Cross-modal plasticity
 Occipital cortex (OC) - shift from processing visual  other sensory
modalities
 ? explains extraordinary auditory & tactile abilities in the blind
 TACTLE:
- ↑ tactile acuity
- Braille activates OC only in congenital/early onset blindness
- TMS disrupting occipital lobe  errors in Braille & paresthesias in fingers
- TDU (computer game) training for one week  blind activated visual
cortex
 AUDITORY:
- 1/2 EOB: ↑ localization mono-aural sound - activates specific OC areas
 SPACIAL PERCEPTION:
- CB unaffected by hand crossing in determining order of hand touched
Kupers et al 2011
Ptito et al 2008
Cohen et al 1999
Frasnelli et al 2011
Crossmodal plasticity in early
blind
 OLFACTION
- ↑ odor identification
- odor detection → ↑ blood oxygenation leveldependent (BOLD) responses in primary &
higher order olfactory & occipital cortices
 HIGHER CORTICAL FUNCTION
- repetition priming (-rTMS) over to visual
cortex → slows Braille reading
Kupers et al 2011
Brain consequence of sensory
deprivation
Cortical reorganization hypothesis
- cross-modal brain responses = formation of
new pathways in the sensory-deprived brain
vs.
Unmasking hypothesis
- loss of a sensory input → unmasking and
strengthening of preexisting neuronal
connections
Kupers et al 2011
Plasticity in focal early lesions in
visual pathway
 Less clearly correlated field cuts with early than late focal lesions
 Infant with perinatal stroke of L optic radiations 
- at 3 months: visual cortical activation only of unaffected side
- at 20 months: activation of visual cortex on affected side
 reorganization of thalamo-cortical pathway
 Early visual field defecit - less ↓ in environmental navigation
- in cats: entire visual cortex removed  visual orientation
unaffected due to reorganization of subcortical to extrastriatal
visual pathways
Seghier et al., 2004
Early lesions in central visual pathway in cat
Damage Lt
optic
radiation
Damage Rt
striate cortex:
-LEFT--potential by-pass of lesion  potential full recovery of conscious vision.
-RIGHT-- no full recovery of conscious vision. Expanded collicular -- extrastriate
cortex  ~ normal visual exploration & navigation
Cionni et al 2011
Hemiplegic CP
Corticospinal Tract Development
 Reaches cervical cord by 24 wks
Begins myelination by 40 weeks
 Newborn: both ipsi- and contralateral corticospinal
innervation of spinal motor neuron pools
 By 2yrs - Rapid differential development of the
ipsilateral and contralateral tracts. Dominance of the
contralateral (crossed) tract
 In hemiplegia: ipsilateral dominance progressively
detrimental  competes with residual contralateral
tract
JA Eyre et al., 2007
Sensorimotor Reorganization in CP*
 Motor: both ipsi- and contralesional cortical reorganization
 Somatosensory: predominantly ipsilesional reorganization
 motor + sensory lesion: interhemispheric dissociation of
motor/sensory functions
 Motor cortex lesion – total loss of crossed tract rare
- activity-dependent competition for ipsi- vs. contralesional access
to spinal motor neuron pool (TMS & EMG)
- role of somatosensory feedback from affected limb
*pattern depends on timing, size, & location of lesion.
Guzzella et al. 2007
Main types of sensorimotor reorganization in lateralized damage
Cionni et al. 2011
CP & Hand Function
 Finger dexterity: correlation atrophy of
thalamo-cortical > than cortico-spinal tract
 Contralateral slower than ipsilateral hand
 Bimanual: both slow
 “
: contralateral better than when
unimanual
Rose et al., 2011
Steenbergen et al., 2008
Hemiparetic CP in Perspective
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Dynamic motor deficit
 Immature cortico-spinal  hemi not present beforeof 6 mos
 Worsening hemi: competition of uncrossed and crossed
cortico-spinal tracts tract for spinal motor neurons
 Very early lesion: uncrossed tract may compensate
Importance of sensory deficit for prognosis
If sensory & motor reorginization in different hemispheres  severity
of deficits poorly coordinated
Neglect: Lt lesion  ± mild bilateral
Rt lesion  ± ↓ attention, ↓ spacial skills
Katz et al 1998
B. Focal lesions
Language areas in the left
hemisphere
Language in the brain:
distributed network
 Language processing is bi-hemispheric:
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♦ Lt >> Rt: phonology, syntax, semantics
♦ Rt >> Lt: prosody, pragmatics
♦ Both (L >> R): lexicon
Lt. superior temporal: phonologic decoding
Lt. inferior frontal: encoding phonology/syntax
Suprasylvian temporo-parietal: lexical processing
Cerebellum: encoding automaticity etc.
Etc.
Language in early lateralized brain
lesion
 Language will develop whether lesion in
the Rt or Lt hemisphere (plasticity)
 Location of lesion does not predict type of
language deficit !!
 Language is delayed, but catches up by
school age
 Price to pay for plasticity: visuo-spatial
deficits likely
E. Bates et al.
Early acquired aphasia vs.
developmental language disorder
Aphasia
Developmental
• Cause: early focal lesion
• Language delayed
• Lesion location:
• Cause: ~ genetic
• Language delayed
• Several subtypes:
• not predictive of type !
• articulation: OK
Prognosis:
• ~ good
• reading ± OK
• often ↓ visual/spatial skills
• CT/MRI: informative
• most receptive/expressive,
• others expressive, fluent
Prognosis:
• variable
• reading ~ impaired
• often: + other dev. disorder
• CT/MRI: ~ useless
Acquired aphasia in toddlers/
older children
 Parallel the aphasia syndromes of adults
 Recovery of language tends to be better than in
adults but is by no means necessarily complete
 Sequelae: depend on size/location of lesion
 Sequelae: almost invariably  reading/
academic problems ± cognitive deficits
Cortical Calculation Networks
Dehaene, 2001
Calculation: Relevant Cortical Circuitry
 Occipito-parietal (dorsal, “where”) visual
stream  intraparietal sulcus L > R
 Occipito-temporal (ventral, “what”) visual
stream  fusiform gyrus
 Lateral prefrontal cortex
♦ Working memory
♦ Attention
♦ Executive skills
Dyscalculia
 Difficulty acquiring basic arithmetic skills
 Detected later than dyslexia
 Requirements: adequate
♦ language skills
♦ visuo-spatial skills
♦ memory, working (& long-term)
♦ executive skills, including attention
Children with dyscalculia
Control children
Kucian et al. 2006
Gerstmann syndrome (1920s)
 In acquired Lt ~ angular gyrus lesion
♦ R-L confusion
♦ Finger agnosia
♦ Dyscalculia
♦ Dysgraphia
 Developmental Gerstmann syndrome
(Kinsbourne & Warrington 1963)
♦ All of the above
♦ Constructional dyspraxia
Roots of American lower SEM than Asians:
School hours/week on
language vs. math
Japan
Taiwan
U.S.
Stevenson et al.,
Science 1986
INTERVENTION
Effect of Practice on the Brain
 Violinists: ↑ cortical finger representation
 Musicians vs non-musicians: altered
hemispheric dominance for music
 Wine tasters: much enhanced smell
discrimintion
 Dancers, athletes: enhanced cerebellar
activation
Remediation
 Training / education is the most powerful
tool we have to alter / improve brain
structure and function
 But… brain plasticity is limited by
♦ severity of pathology
♦ location of pathology
♦ age at time of insult
♦ adequacy of the intervention!
Cochlear Implant
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Requirement: viable neurons in spiral ganglion
Early in prelingual deafness: activates the central
auditory pathway → quite effective
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Late in prelingual deafness: activates primary but
not secondary auditory cortex → more limited
effectiveness
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In previously hearing person → effective
In all cases: requires intensive and prolonged
training