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Brain 24/02/2007 17:45:00



Crandall et al 2007,x

Humans and songbirds learn vocalisation during a sensorimotor

sensitive period- “babbling phase”.

Prolonged bursting is key aspect of sensory critical period.

The „High Vocal Center‟ of songbirds is analogous to the cortex in

humans, and codes aspects of song structure including syllables, motifs

and higher-order patterns.

Zebra finches – rapid bursts of activity in premotor area HVC before

and after learned vocalisations. Show inverse correlation with song

maturation. Same neurons also respond to auditory stimuli. In other

words, prolonged motor discharge and sensory input coincide in these

neurons. This would provide the cellular basis for activity-dependent

mechanisms of sensorimotor shaping.





Wang 2004x

Cheng and Mersenich 2003

Continuous noise disrupted functional organisation of the rat auditory

cortex.

Normally the auditory cortex A1 is organised according to a

„tonographic map‟ of sound frequency, although in juveniles the neurons

tend to have a broader tuning frequency and the map is less organised.

Reorganisation has been shown to follow deafness or training, but is more

susceptible to effects of the inputs in infancy, leading to the postulate of a

„critical period‟.

Difficult to remove all input from auditory system, so used white

noise.

White noise led to „immature‟ cortex, pulses of one frequency led to

overreprentation of that in tonographic map.

Adult rats reared with white noise and then exposed to highly

structured noise showed changes like those in young rats.

Showed „critical period‟ not fixed as previously thought, but not

known if this is different. In normal development, critical period linked to

levels of NMDA receptors and BDNF – unknown whether early

disruptionaltered chemical signalling mechanisms or another mechanism

of cortical plasticity is responsible.

In humans- hearing begins at about 20 weeks gestation, so this

could have implications for pregnant mothers in noisy environments. Also

implications for deaf children given cochlear implants at later stage.

Berardi 2000x

Neurotrophins, NMDA receptors and GABAergic inhibition all play roles

in determining critical periods for experience-dependant plasticity.

Manipulation of levels of BDNF alters the timing of this critical period in

the mouse visual system, establishing a causal relation between

neurotrophins and the critical period.





Moore et al 1995x

Myelination of the human auditory pathway from the proximal end of the

cochlear nerve to the brainstem (inferior colliculus) occurs between the

26th and 29th week of gestation, but is not complete until the age of 1yr.

Coincides with acoustimotor reflexes and brainstem auditory evoked

responses, both of which require rapid, synchronised conduction of

impulses in the audit. Nerve and brainstem

Suports idea that 26-29 wks is a critical period.





Dmitrieva and Gottlieb 1994x

Ducklings- even a short period of auditory deprivation affected the

development of auditory sensitivity, as studied by brainstem auditory-

evoked potentials.

Thresholds and latencies of brainstem responses to auditory stimuli did

not show their normal decline in these ducks.

There was a species-specific critical period where this effect was most

pronounced.





Hung 1989x

Chinese children- recorded auditory brainstem evoked potentials.

Auditory clicks.

Peripheral transmission reached adult level at 3mths, brainstem

transmission matched adult at 1yr.

At 6mths waveforms matched adult.

Critical period for maturation of peripheral and central auditory

pathways?





Sadato et al 2004x

Middle superior temporal sulcus responds selectively to human voices.

Found that in deaf signers, makes shift from auditory to visual input in

age-dependant manner- less activation in late-deaf signers.





Chang et al 2005x





Investigated the role of inhibitory patterns in the development of

responses to auditory inputs differing in frequency and temporal

characteristics.

Initially both excitatory and inhibitory responses in A1 are tuned to a

broad frequency range. Temporal resolution is poor due to broad

inhibitory effects. With increasing age, the excitatory and inhibitory

effects become tuned to narrower frequencies. Tuning of inhibitory effects

lagged behind excitatory tuning, and corresponded with the critical

period.

Discrimination of rapid sounds is important to the processing of speech

sounds. Wide-ranging inhibitory effects prevent repeated firing in infant

rats.

The different effects of excitatory and inhibitory transmission were

investigated using a GABA antagonist and glutamate. Inhibitory receptive

fields were narrowed but not eliminated by the GABA antagonist, and this

effect was most pronounced in infant rats. Glutamate had no effect on the

excitatory receptive fields. Forward masking by asynchronous two-tonal

stimuli was not affected by GABA antagonist, and is thought to be

mediated by the thalmocortical synapse.

Rats reared with white noise failed to show this tuning of excitatory and

inhibitory responses. „Rescue‟ rats showed similar receptive fields to

normal adult rats after rearing in a normal environment, showing that the

sensitive period can be extended in these circumstances.

- local inhibitory circuits contribute to cortical spectral selectivity

- GABA makes intracortical contribution to simultaneous 2 tone inhibition.

-exposure to patterned sound input critical to A1 response maturation

- subcortical factors contribute to cortical response patterns- these

mature early

- anatomical and synaptic properties change over development, eg GABA

neurons in auditory cortex peak in late development, and large number of

projections throughout the auditory cortex from pyramidal neurons

probably contributes to the broad inhibitory effects.

These excitatory and inhibitory effects provide a mechanism for sorting

temporally synchronous inputs.

Lack of input keeps inhibitory network in prolonged state of immaturity,

and patterned stimuli + functional cortical inhibition contribute to normal

cortical development.





Nakahura et al 2004x

How are the cortical representations of dynamic sound shaped by the

spectro-temporal patterns of auditory input during development?

Two sequences of three tones (low/high)- region of poor response

separated them in A1. Third tone in sequence also showed decreased

reponse. Double peak of receptive fields also found- never seen in

controls.

Forward/reverse sequence- no response to second tone in reversed

condition shows temporal sequence important.

Effects endured into adulthood.

Relevant to phoneme-specific responses to native language?





Fishman et al 2001

Monkeys- auditory stream segregation.

At low presentation rates, both tones evoked responses resulting in a

corresponding pattern of activity.

At faster rates, response to the tone which was not the best frequency of

the neuronal field was suppressed, this effect increased with both speed

of presentation, and the difference in the sounds.

Suggests cortical origin of auditory stream segregation, including

masking effects which can be observed in humans.





Kohler et al 2002x

Monkey ventral premotor cortex- neurons which respond both when it

performs an action and when it hears the related sound.

Monkey homolog of Broca‟s Area: origins of language?

These neurons did not respond to non-action related sounds.

A large subset of these neurons responded to both sound and vision

alone as well as both. Neurons were found which were selective in their

responses eg to peanut being broken, paper ripping.

Multimodal mirror neurons had been described before, but this was the

first time they had been observed to code for actions when they could

only be heard, rather than for spatial stimuli.

They also fire whilst the monkey is performing the action: execution,

planning, goals?

Gestural communication?

Left-right asymmetry in ventral premotor cortex of great apes, together

with access to auditory input could mean this is where Broca‟s area

evolved from.





Raggio and Schreiner 1999x

Evaluated effects of auditory deprivation on spatial distribution of

response thresholds to electrical stimulation of the cochlea (cats).

Dorsal and ventral A1 are normally separated by a rostrocaudal band of

neurons with low thresholds and narrow frequency tuning. Electrical

cochlear stimulation reversed this threshold pattern.

Alternating patches of high and low threshold found along the

cochleotopic axis (dorsoventral) suggest functional modules in A1. This

was present even after many years of deafness, even when cochleotopic

mapping was absent. May provide framework for different auditory

processing streams. The spatial uniformity of these bands was however

compromised in long term deaf cats. Basic functional circuits may remain

operational? Implication for prognoses?

Loss of cochleotopic mapping may limit information flow to speech and

language cortex in humans, despite perfect channel separation

peripherally (cochlear implant).

Unexpected differences between acute and short term groups suggested

that adjustment of excitatory and inhibitory processes took place. In

particular, spatial extent of activation increased and suggested reduction

in inhibition.





Kral et al 2000x

Congenitally deaf cats: functional deficits of auditory cortex when

stimulated with cochlear implants.

Transient expression of acetylcholinesterase in auditory cortex during

critical time period : Ach is involved in learning effects in auditory cortex

and may play role in formation of thalmocortical projections.

Different layers of auditory cortex normally activated in well-defined

sequence. This was not found. Small currents in layer IV (input layer with

most thalmocortical synapses), but lacking fine structure, and in

infragranular layers, then in supragranular layers. The amplitude of

responses was also reduced. Activation of infragranular layers, caused by

supragranular activation, at longer latencies is substantially reduced. This

is the output layer of the cortex, projecting both to other cortical areas

and the thalamus. Thalamo-cortical loops are thus probably not

functional. Projections to the inferior colliculus are probably also affected.

In normal cats, all layers are activated in sequence, activation of layer IV

shows fine structure, and lastly the supragranular and infragranular layers

are activated in an alternating pattern. This may be crucial for complex

analysis in normals.

This shows substantial deficits in cortical function in response to

stimulation of the auditory nerve.

Cell morphology has also been shown to be different: synapses appear

immature, with reduction in branching of end bulbs and presynaptic

vesicles. There is reduction in dendrites of pyramidal cells.

Unknown whether caused by failure of maturation or degeneration of

cortico-cortico or cortico-thalamic connections.





Kitzes and Semple 1985x

Gerbil inferior colliculus: responses after ablation of contralateral cochlea

indicate that responses to ipsilateral ear result in part from interactions

with projections from contralateral ear.





Kilman et al 2002x

Neonatal rats: 2d of deprivation of activation of auditory cortex resulted

in reduction of staining for GABA receptors, and in number of synaptic

sites staining for GABA.

Showed that, like excitatory transmitters, inhibitory transmitter activity

can be scaled to match activity. Normal part of homeostatic mechanism

preventing either silence or epileptiform activity.





Kapfer et al 2002x

Medial superior olivary neurons encode microsecond differences in arrival

time of low-frequency sound at two ears.

Experience-dependant loss of synapses. This could minimise summation

of inputs, to refine temporal window. In the hippocampus, feed-forward

GABAergic inhibition has been shown to curtail this window, but the

timescale is much larger.

Propose that a mechanism may remove synapses activated too early or

too late.





Hirano et al 2000x

Auditory association area A2 in prelingually deaf.

Cochlear implants after age of 8.

Prelingually deaf showed high blood flow in A2 at rest (PET), indicating a

lack of synaptic revision (loss due to maturation). Suggests there was

little functional differentiation in processing for these subjects. There was

also no increase in blood flow when listening, unlike postlingually

deaf/hearing. Activation was observed during lipreading for prelingually

deaf lipreaders, and during listening for one who never learned to lipread

and had made progress with speech since the implant.

Suggests functional differentiation of A2 should differ according to what

modality used during critical periods of speech acquisition.





Francis and Manis 2000x

Cochlear ablation impairs afferent innervation of ventral cochlear

nucleus.

Electrical responses, cell and synaptic morphology of brainstem are

altered. Electrical properties of VCN neurons also altered.

Implications for cochlear implants?





Kotak et al 2005x

Hearing loss (gerbils) increades excitability in A1 and causes greater

thalmocortical excitation. This is as a result of attempt to maintain

optimum cortical excitability.

Includes increased susceptibility to NMDA receptor antagonist.





Semple and Scott 2003

Primate auditory cortex shows core (including A1) with sharp frequency

tuning and tonotopic organisation, surrounded by less tonotopic areas,

and then non-tonotopic areas.

Increased stimulus complexity (humans) associated with increased

activation throughout core and surrounding areas, but tonal stimuli just

activate the core (transverse temporal gyrus).

Core region shows intense staining in layer IV for parvalbumin (thalamic

projection neurons).

Thalmocortical auditory projections provide basis for hierarchical

transformation, as signal processed sequentially through core and

surrounding regions. Parallel processing in multiple core fields. Then

distributed to multimodal areas in temporal, parietal and frontal lobes.

2 major streams? What and where pathways.

Where- A1 to frontal eye field and parietal (spatial)

What- from anterior core and belt to temporal lobe.

But- localisation and pattern recognition are not necessarily independent.

Cross talk between streams.

GABAergic inhibitory circuits in top and deep layers of A1

Subcortical contribution to functional cortical maps- complex excitation

and inhibition from thalamus.

Temporal and spectral variation influence different areas of auditory

cortex- multiple time scales may encode single stimulus.

Hormones 24/02/2007 17:45:00



Beech and Beauvois 2006x

The possible influence of prenatal androgens on the temporal

processing of sounds in the left hemisphere.

Measured lengths of ring fingers on L/R hands, indicating exposure to

testosterone in utero.

Found that people exposed to more androgens were impaired on

phonology, and reading, and that auditory saltation (ability to

differentiate rapid sounds) was also impaired.





Campos-Barros et al 2000x

Thyroid hormone signalling is essential for cochlear development and

onset of hearing (mouse)

In humans, deafness associated with congenital hypothyroidism.

Tightly constrained to a critical period, after which addition of hormone

will not rescue cochlea formation.

Language 24/02/2007 17:45:00



Buchwald 1994x

Lack of exposure to specific types of sensory pattern during critical

periods can result in lack of responsiveness to those stimuli in adults.

Japanese adults show both behaviourally and electrophysiologically a

failure to discriminate English sounds /r/ and /l/.

Language structure produces measurable effect on aspects of brain

development and function.





Boothroyd 1993

Monaural hearing aid: 80 and 40 % phoneme rcognition

After several months of binaural hearing aid: 75% in previously unaided

ear

Critical Period 24/02/2007 17:45:00



Seebach et al 1994

Neural net model of early speech acquisition (consonants) did not require

innate knowledge of sppech or linguistic structure.





Kuhl 2000

Skinner- language learning as result of reinforcement.

Chomsky- innate language faculty puts constraints on language. Fodor-

language module.

New approach- infants map statistical properties of language they are

exposed to.

Partitioning at phonetic level not unique to humans. Although adults

show language-specific recognition of phonemes, infants and monkeys do

not have this bias. They are able to detect different speech sounds, and

prosodic cues. This implies speech has exploited auditory features.

Evidence that babies are exploiting statistical cues in speech, rather than

having modules for different phonemes or innate knowledge of language

structure.





Hurford 1991

Critical period for language acquisition ends at puberty.

Computer simulation of evolution of linguistic ability showed critical

periods ending at around puberty.





Gilbert 1994x

Neuronal plasticity in some form into adulthood.

Implicit sensory learning may take place in primary sensory cortex.

Properties of neurons and functional architecture of cortex may be

modified by experience.

Early sensory pathways implicated by specificity of learning effects.

„Critical period‟ thought to exist for sensory systems since Hubel and

Wiesel‟s kitten experiments (vision).

However eg size of cortical representation of trained frequency (audio)

and shift of best frequency of neurons toward trained frequency

demonstrates some plasticity remains.

Change in connection strengths, synaptic proliferation and collateral

sprouting.

All cortical areas are able to undergo dynamic changes in functional

architecture and specificity.

Feral children 24/02/2007 17:45:00



McCrone 2003 x

“Throughout history, feral children have seemed able to answer one of the biggest

questions about the human brain—what makes it different from that of an animal? Is

human consciousness innate, or is it the product of language and socialisation?”

“in the end, their fascinating tales lead nowhere in particular.”

-critical periods for language and other cognitive abilities

-3 way interaction of experience and synaptic pruning, genetic factors and cultural

factors

-no single experiment can unravel these

Bengal 1920s Rev. Joseph Singh described 2 girls raised by wolves aged 3 and 5.

Elder child survived but after extensive training never mastered more than about 40

words, but no sentences or conversation.

Showed that the human mind could not be innate- but also was not recovered

despite returning to human society.





Fujinaja et al 1990 x

extreme social isolation and to complex deprivation

we have found that their physical and motor development or recovery has

proceeded smoothly, whereas their linguistic and cognitive development has

continued to show such weaknesses as defective functioning of internal speech

(Vygotsky, 1962) and poor ability to deal with abstract, linguistic subjects



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