Atypical brain development
Goals
- To discuss typical development, sex differences, and aging on brain measures.
- To discuss neuronal correlates of intelligence.
- To discuss atypical brain development.
- To discuss sensory substitution.
- To demonstrate neural prosthetics in humans
Topic slide
Judith Rapoport (b. 1933) is a neuroscientist and psychiatrist who heads the Child Psychiatry Branch at the NIMH. Dr. Rapoport has conducted many investigations into brain differences associated with mental disorders and atypical development. You can read about her many contributions to the study of the developing brain here.
Helen Neville (1946-2018) was a psychologist at the University of Oregon and a member of the National Academy of Science. Dr. Neville conducted the first neuroimaging studies of plasticity in the congenitally deaf, and was a leader in the field of neurocognitive brain studies.
Reading
- Reading: PN6 Box 34C, pp. 780-781
Plasticity – ‘able to be molded’
Plasticity is a relatively new and fast-moving field. It is little covered in textbooks or secondary readings, and so I emphasized studies from the primary literature.
Brain development and plasticity research in humans has been revolutionized by non-invasive MRI methods that can be carried out in living humans, such as measures of brain volume, surface area of cortex, and regional cortical thickness.
Typical brain development
Development consists of both progressive (e.g., neurites [spines, dendrites, axons] growth) and regressive (e.g., axon pruning, programmed cell death, synapse elimination) processes.
- Most neurons are present at birth, but about 50% do not survive into adulthood. They die by programmed cell death.
- Birth of new neurons: neurogenesis in hippocampus and olfactory bulb.
Axon pruning and synapse elimination:
- We develop more synapses in the first two years of life than we keep.
- Some axonal connections are unusual – for example, visual system connections can go to motor targets in the brain stem.
- Over development, some synapses are eliminated and axons are pruned.
Quoting from Innocenti and Price (TICS, 2005):
The exuberant development of connections — that is, the overproduction of axons, axonal branches and synapses, followed by selection — is one of the algorithms that underlie the development of biological neural networks.
I showed slides illustrating the time course of synaptic density, gray matter density, glucose utilization, and myelination. The curves all peak in early childhood.
The myelination and cortical thickness curves indicate that prefrontal cortex develops later then other brain regions. It is interesting that many psychiatric disorders occur in the same broad time region as the development of prefrontal cortex.
Curves of cortical thickness were differentiated by brain region, with frontal regions peaking in cortical thickness much later than sensory and motor regions.
Parental Age
There is a curvilinear relationship between parental age and many measures of mental health. Could these effects be mediated by cortical thickness of offspring brains?
Advanced maternal age (>35 years) is associated with increased rates of mental retardation syndromes including Down’s syndrome. Advanced paternal age is associated with lower intelligence and elevated risk for neuropsychiatric disorders such as autism, Apert syndrome, hydrocephalus, and schizophrenia. There are risks associated with younger parental age (controlling for SSE), paternal age is associated with a child being less intelligent and having more behavior problems.
I discussed a study of 171 individuals (children and adolescents). Maternal and paternal age show similar effects on gray matter volume in offspring, with both age extremes being associated with lower volumes. There were no such effects on white matter volumes. The paternal age effect on cortical volumes appeared to be driven more by influencing surface area than cortical thickness; the reverse was true for maternal age.
Sex differences
Overall largest brain volume reached at 10.5 years in females and 14.5 years in males – but this includes subcortical volumes, white matter, etc.
Girls reach maximum cortical size 1-2 years before boys – may be related to puberty in girls.
Aging
The curves for aging are depressing, 'nuff said. Well, not quite enough. But cortical volume and cortical thickness decline linearly from about age 20 onwards. I showed graphs with regression lines.
Intelligence
What is intelligence?
Most investigators of intelligence distinguish between two aspects of intelligence:
- Fluid intelligence (Gf)
- Crystallized intelligence (Gc)
Here is a definition of these terms taken from the Wikipedia here.
Fluid intelligence or fluid reasoning is the capacity to reason and solve novel problems, independent of any knowledge from the past… It is the ability to analyze novel problems, identify patterns and relationships that underpin these problems and the extrapolation of these using logic. It is necessary for all logical problem solving. Fluid reasoning includes inductive reasoning and deductive reasoning.
Crystallized intelligence is the ability to use skills, knowledge, and experience. It does not equate to memory, but it does rely on accessing information from long-term memory. Crystallized intelligence is one's lifetime of intellectual achievement, as demonstrated largely through one's vocabulary and general knowledge. This improves somewhat with age, as experiences tend to expand one's knowledge. Crystallized intelligence is indicated by a person's depth and breadth of general knowledge, vocabulary, and the ability to reason using words and numbers. It is the product of educational and cultural experience in interaction with fluid intelligence.
General intelligence is predictive of mortality
General intelligence is strongly predictive of occupational attainment, social mobility and job performance. People with higher general intelligence in childhood or early adulthood have better health in middle and later life, and are less likely to die young. For example, among one million men followed for approximately 20 years after taking intelligence tests at about the age of 20, an advantage in general intelligence of one standard deviation was associated with a 32% reduction in mortality.
Intelligence is generally consistent across age.
A single 45-minute test of general intelligence had a correlation of 0.63 (0.73 when disattenuated for restriction of range) in people tested twice, at ages 11 and then 79 years.
Bigger brains are weakly correlated with higher intelligence and lower mortality.
Current data indicate that intelligence is correlated with head size (r ~0.20) and intracranial volume (r ~0.40). The clearest single body of evidence is that, in healthy people, total brain volume (measured using structural MRI) is moderately correlated with intelligence (r ~0.30–0.40).
People with higher general intelligence in childhood or early adulthood have better health in middle and later life, and are less likely to die young. For example, among one million men followed for approximately 20 years after taking intelligence tests at about the age of 20, an advantage in general intelligence of one standard deviation was associated with a 32% reduction in mortality.
This is reminiscent of the cognitive buffer hypothesis we discussed with respect to bird mortality in lecture 1.
There is high positive correlation across different domains of intelligence.
In typical test batteries consisting of 10–15 different cognitive tasks involving a wide range of materials and content, a 'g' (general) factor almost always accounts for 40% or more of the total variance.
Brain lesions and intelligence.
I discussed a study by Glascher and colleagues (2009) that showed regions changes in cortex where damage caused a change in one of four measures of intelligence: perceptual organization, verbal comprehension, working memory, and processing speed.
Parieto-frontal integration theory of intelligence.
Jung and Hairer proposed the parieto-frontal integration theory of intelligence on the basis of a meta-analysis of studies that examined structural and functional MRI correlates of (and white matter studies of intelligence). I presented a brain image in class that showed the brain areas most related to intelligence across studies in both the left and right hemisphere.
Cortical thickness, development, and intelligence
I described studies by Shaw and colleagues concerned with cortical thickness and intelligence over the course of development.
From their abstract:
“More intelligent children demonstrate a particularly plastic cortex, with an initial accelerated and prolonged phase of cortical increase, which yields to equally vigorous cortical thinning by early adolescence. This study indicates that the neuroanatomical expression of intelligence
in children is dynamic.”
Cortical thickness has a nuanced relationship with intelligence. In a study discussed in lecture, subjects who reached the highest level of performance on IQ tests had initially less cortical thickness in anterior brain regions than those who scored lower. However, the highest performing individuals than experienced a sustained increase in cortical thickness – primarily in prefrontal and parietal cortical regions. (it is interesting to note these are the same regions implicated in working memory performance – a key component of fluid intelligence).
I described a second cortical thickness cross-sectional study of intelligence over the lifespan. The conclusions were as follows:
- Cortex reaches its peak thickness later in children with a higher intellectual ability than in their peers.
- In (pre) adolescence, associations between cortical thinning and improved cognitive abilities have been found.
- In adulthood, higher intellectual ability is associated with more pronounced thickening and postponed thinning of specific areas of the cortex.
- These changes in cortical thickness and intelligence are heritable.
- Thus, individual differences in the developmental brain changes seem to play an important and specific role in human intelligence.
Cortical thickness, aging, and intelligence
I concluded the section on intelligence by describing the results of a 2018 study on cortical thickness, cortical volume, and intelligence (fluid and crystallized). In this same of older adults, crystallized intelligence remained stable over the adult years. However, fluid intelligence declined over the time span tested. Many brain regions showed a correlated decline in both cortical thickness and volume over the same frame.
For those interested in the general topic of the neuroscience of intelligence, I direct you to this 2010 review
Atypical brain development
Compared to typically developing healthy controls, having too much or too little brain volume can be problematic.
ADHD
ADHD is associated with lower brain volumes than controls. This is also true in a 33 year follow-up
Study of socially deprived orphans
Children raised institutionally have been extensively studied by Charles Nelson and his colleagues at Harvard. Children reared in institutions exhibited widespread reductions in cortical thickness across prefrontal, parietal, and temporal regions relative to community control subjects.Reduced thickness across numerous cortical areas was associated with higher levels of ADHD symptoms.
Severe early-life deprivation disrupts cortical development resulting in reduced thickness in regions with atypical function during attention tasks in children with ADHD, including the inferior parietal cortex, precuneus, and superior temporal cortex. These reductions in thickness are a neurodevelopmental mechanism explaining elevated ADHD symptoms in children exposed to institutional rearing.
Autism
Autism is associated with larger brain volumes than controls – perhaps a failure of axonal pruning.
Brain plasticity
I reminded the class of examples of plasticity discussed earlier in the semester:
- Sewing fingers together so they experience the same sensory events changes the somatotopic map for digits. Recall also changes associated with amputation of digits.
- Ocular dominance columns are present at birth, but are only maintained with appropriate sensory input. This example emphasizes the effects of an atypical development – i.e., eye deprivation – upon a neural structure.
In the following sections, we will discuss reorganization of sensory and motor cortices, a topic we have previously broached. In a 2018 TICS paper, Singh and colleagues asked the question why sensory cortex is reorganized. They proposed three possibilities for study:
- Reorganization is compensatory – leading to superior performance in one modality that compensates the individual for the loss of the affected modality.
- Reorganization is Inevitable – it unmasks latent connections that were always there. Thus it does not lead to superior performance.
- Reorganization Is Necessary to Avoid Maladaptive Consequences such as Paroxysmal Activity and Cortical Atrophy. Cortex without patterned input may be susceptible to abnormal electrical activity, potentially leading to seizures.
Brain plasticity in the congenitally deaf
In an fMRI study of the congenitally deaf – auditory cortex (A1 in Heschl’s gyrus) was activated by both visual and somatosensory (air puffs) stimuli.
In other fMRI studies – language areas in the left hemisphere, and homologous regions of the right hemisphere – were activated by American Sign Language in both deaf and hearing signers.
Brain plasticity in the blind
I described a series of studies in lecture that made the following points:
- Study showing increased cortical thickness of visual cortical regions in the early blind
- Blind subjects showed increased visual cortex activation when identifying auditory input and localizing sounds in space when compared to normally sighted controls. However, no difference in a very simple auditory detection task (is there a sound or not?)
- Reading Braille (with finger tips) activates primary visual cortex
- A bilateral visual cortical stroke in a Braille reading blind person caused difficulties in reading Braille, but no difficulties in other types of tactile discrimination.
- Transcranial Magnetic Stimulation (TMS) over both occipital and somatosensory cortex interrupts Braille reading in the blind.
- Primary visual (V1) activation correlates with verbal memory performance in the blind.
Sensory substitution
Tongue display unit
Using a Tongue Display Unit (TDU) developed by Paul Bach-y-Rita, both sighted and blind individuals were able to navigate a virtual route. In doing so, blind individuals activated some of the same visual regions that sighted individuals activated when navigating the virtual route using vision.
Echolocation
Some blind individuals can echolocate – that is, they can make clicking noises and use the resulting echoes to navigate. An fMRI experiment showed one such blind individual strongly activated visual cortex while echolocating. (may not be discussed in class if time is short)
Location cues in sound strongly activate area MT in blind individuals. MT is strongly activated by visual motion in sighted individuals. There is some evidence, however, that MT may be activated by sound cues for motion in sighted individuals – although this is not well established.
Soundscape
A sensory substitution study was described in which visual stimuli were encoded into auditory information using amplitude, time, and frequency. Behavioral evidence was shown indicating that individuals (sighted and blind) could discriminate different stimulus categories using this method of encoding visual objects into sounds. Of greatest interest was the demonstration that the so-called ‘visual’ word form area in ventral occipital-temporal cortex (which we had previously encountered earlier in the semester when discussing alexia without agraphia, or ‘pure alexia’) was activated when blind individuals used this sound substitution system to discriminate among letters.
Soundscape bodies and EBA
I described a study by Striet-Amin in blind individuals in which the extrastriate body area, or EBA, was activated in blind individuals when receiving an auditory soundscape representing body shapes compared to other object shapes.
Motor cortex plasticity
Earlier in the semester, we discussed the changes in sensory cortical maps associated with experimental amputation of digits in raccoons and the relevance of those studies to human studies of traumatic amputation. The experimental studies showed that the digits represented by nearby cortical regions 'invaded' or 'overtook' the now deafferented regions of cortex, thus expanding the cortical representation of those invading digits.
In a recent study, the motor cortices of individuals who were born with only one hand were studied using fMRI. These individuals performed routine tasks normally preformed by hand with their lips, arms or feet. It was interesting to note that the 'vacated' hand area was now representing foot, arm and lip movements. This suggested that cortical reorganization might depend upon task-based compensatory mechanisms.
General principle of sensory substitution
Cortices appear to maintain their computational algorithm, but apply it to different input modality. For example, MT does 'spatial localization' for visual stimuli in typically developing individuals, but MT is used for 'spatial localization' of auditory stimuli in blind individuals.
from Anurova et al. Cerebral Cortex, 2014
Thus, in very general terms, the original functions of nonprimary sensory areas seem to be preserved after sensory deprivation, although the modalities driving the neurons in the reorganized areas are altered..
From Striet-Amin, Current Biology, 2017
…these findings suggest that the organization of the brain is not limited by sensory modalities or sensory-motor experience. Instead they suggest that it is driven by an innate, evolutionarily developed template, based on the computations and outputs demanded from each region.
Neural prosthetics
Time permitting, I will show two short videos demonstrating retinal implants in blind humans and mind controlled robotic machines in paralyzed humans.
Video
Prerecorded lectures for 2020
The video embedded below was recorded in Fall, 2019.
