In earlier posts I wrote about Autism and Minicolumns and Autism and the Evolution of the Brain, based on research by Dr. Casanova et al. Minicolumns are the basic organizational unit of the cortex, and are vertical arrays of pyramidal cells (neurons). The underlying argument in these posts was that those with ASD have a higher number of minicolumns than average, but that those minicolumns are of a narrower than average width, with smaller neurons but the same average number of neurons per minicolumn. The net result is a brain structure that skews in favour of processing stimuli that require discrimination, potentially at the expense of generalizing the salience of a particular stimulus. Smaller and more densely packed minicolumns could also allow for more complex information processing.
These attributes come at a potential cost. The reduction in width is a result of a reduction in the minicolumn’s peripheral zone of inhibitory and disinhibitory activity. The inhibitory fibers act to keep stimuli within individual minicolumns, and the reduction in this space increases the chance of stimuli overflowing to adjacent minicolumns, providing an amplifier effect and potential hypersensitivity. Narrower minicolumns may also result in an increased number of minicolumns per macrocolumn, which can also result in an amplification of thalamic input, and as each minicolumn’s response to thalamic input is modulated by the activity of neighbouring columns, a reduction in GABAergic inhibitory activity could also result in a loss of inhibition and greater amplification. Stimuli ‘spill’ and greater amplification could result in the increased incidence of seizures in autistics.
An additional factor is the reduction in neuron size, which reduces the ability of neurons to sustain connections over distances. Smaller neurons result in a metabolic bias favouring shorter connections at the expense of both longer distance and inter-hemispheral connectivity. The result is that autistic brains have a bias towards local (intra-regional) over global (inter-regional) connectivity and processing. Short intra-regional processing functions include mathematical calculations and visual processing. Cognitive functions that require inter-regional processing would be less metabolically efficient, including language, face recognition, and joint attention (Casanova - Abnormalities Of Cortical Circuitry In The Brains Of Autistic Individuals). Given the high metabolic cost of the brain (2.5% of our body weight but 22% of our resting metabolism - Leonard and Robertson 1992, p 186), smaller neurons may be a response to resource constraints.
Of note, while reduced minicolumnar width appears to be a prerequisite for ASD, the reported minicolumn widths found within autistic brains are still within the normal distribution of minicolumnar width, albeit at the tail end (Casanova, 2006). In other words, people with narrow minicolumnar widths are not necessarily on the ASD spectrum.
Narrower Minicolumns Without ASD
Confirmation of this is suggested in "Comparison of the Minicolumnar Morphometry of Three Distinguished Neuroscientists and Controls", a new research paper by Dr. Casanova et al, currently in review. The research in question involved analyzing and comparing the minicolumns of three distinguished neuroscientists ("supernormals") and six normative controls. The ‘supernormals’ are described as:
"researchers of high distinction within the neurosciences. Although personal history and interviews with those who knew these neuroscientists emphasize their wide range of knowledge (polymaths) and divergent thinking no claim is made regarding their intelligence or creativity."
That being said, the descriptions of the three individuals in question clearly suggest that they were very intelligent, focused, productive, and intellectually self-assured.
The research found the following:
"Overall, there were significant differences (p < 0.001) between the comparison groups in both minicolumnar width (cw) and mean cell spacing (mcs). Although our supernormals did not exhibit deficits in communication or interpersonal skills the resultant minicolumnar phenotype bears similarity to that described for both autism and Asperger’s syndrome."
The findings in this paper are fascinating (at least to me) in that they clearly indicate both similarities and differences between the brains of autistics and those of the three neuroscientists, suggesting some answers and raising some interesting questions. The major reported similarity is the finding of narrow minicolumnar widths. As stated in the paper, "A minicolumnar phenotype that provides for discrimination and/or focused attention may help explain the savant abilities observed in the intellectually gifted." It is unknown at this point whether two other characteristics linked to narrower width minicolumns in autistics – i.e. smaller neurons and a higher number of minicolumns – also occurred in these neuroscientists’ brains, but it is a logical assumption that these characteristics were present too. Smaller neurons are hypothesized by Dr. Casanova to be a requirement for the existence of narrower width minicolumns, based on laws of conservation for brain grows and evolution (from personal correspondence, with permission).
There were also significant minicolumnar differences between the neuroscientist brains and ASD brains. First, the neuroscientists had a lower mean cell spacing (MCS) – i.e. a smaller average distance between neurons - than the controls. In other words, their neurons were closer together than in typical minicolumns with large mean cell spacing. Previously analyzed ASD brains had ‘normal’ or typical mean cell spacing. Unfortunately, no direct numerical comparisons of MCS between this research and previous analyses are possible due to the difference in age between the neuroscientists (58, 84, and 89) and the autistic patients (average age being 12 years).
Second, the neuroscientists differ from those with ASD in terms of the horizontal spacing between neurons (relative dispersion of cells). The neuroscientist minicolumns were similar to typical minicolumns in that they had a small relative dispersion, i.e. cells tended to be clustered closer to the axis of the column. Those with ASD have a large relative dispersion, with cells distributed more uniformly within the minicolumn core.
Figure 1 (below, based on Fig 2 from the research paper) is a hypothetical representation of both mean cell spacing and relative dispersion in minicolumns, (after disregarding both neuroscientist and ASD reduced minicolumnar width). The neuroscientist and typical minicolumns have a smaller relative dispersion than the ASD minicolumn (i.e. tighter clustering toward the column axis vs. more uniform distribution). The neuroscientist column also has a smaller mean cell spacing, with cells being closer to each other than in the other two minicolumnar types, regardless of their distribution around the minicolumn axis.
I would speculate that the differences between the neuroscientist and ASD minicolumns would have a significant - but incomplete - explanatory role in accounting for the differences between the two groups. In both groups, narrower width would increase the risk of ‘spill’ between minicolumns. But the reduced mean cell spacing in the neuroscientists would presumably result in greater integrity of processing within the column (as well as potentially an increase in speed), while the tighter grouping of neurons around the axis would increase the distance between the neurons and those in adjacent columns, maximizing the zone of interneuronal inhibitory activity between the adjacent vertical arrays of pyramidal cells. This is significant, in that this maximized inhibitory zone could at least partially compensate for any reductions due to the narrower column width.
In contrast, the higher ASD MCS could result in comparatively lower signal intensity and - along with a more uniform horizontal dispersion – result in a higher risk that neurons in adjacent columns might in fact be closer in distance than neurons within the same column, increasing the risk of ‘spill’. Plus, the more uniform horizontal dispersion would result in more neurons being found towards the outer periphery of the column, with an even smaller zone of inhibitory activity between these outer neurons and adjacent minicolumns.
This still leaves some significant questions for further research regarding differences between the neuroscientist and ASD minicolumns. For one, as the paper suggests:
"the widespread morphometric changes in our scientists suggest that any brain-related ability they may have possessed (e.g., cross-discipline learning, abstracting, dimensional thinking) involved multiple cortical regions. In developing these abilities the various association cortices acted as nodes or epicenters, binding multimodal information, within a neural network (Mesulam 1994; 1998). Contrary to earlier formulations, modern observations suggest that higher cognitive processes are encoded in flexible distributed networks rather than rigid convergent ones (Mesulam, 1994; 1998)."
As such, the neuroscientists had brains capable of exceptional thinking, combining deep focus and discrimination, but linked to distributed (global) processing. If the neuroscientist neurons were smaller, biasing against global connectivity, then was there a compensatory effect? Spindle neurons serve to connect more distant, non-neighbouring regions of the brain (Casanova - Big Brains Manuscript, in preparation for submission). From Wikipedia:
"Spindle cells appear to play a central role in the development of intelligent behavior and adaptive response to changing conditions and cognitive dissonance. They emerge postnatally [emphasis added] and eventually become widely connected with diverse parts of the brain, evidencing their essential contributions to the superior capacity of hominids to focus on difficult problems."
Spindle neurons are known to be found in reduced numbers in those with ASD. Perhaps they helped the neuroscientists compensate for – and even exploit the benefits of – the bias towards local processing inherent in reduced width minicolumns?
Another potential difference between the two groups might be found within their corpus callosi, the structure that connects the left and right cerebral hemispheres, which have consistently shown to be smaller in autistics. The research paper suggested that "the fact that the left hemisphere lags in development behind the right hemisphere may offer an alternate explanation to savant skills (Geschwind & Galaburda, 1986)." Examining the corpus callosi of the neuroscientists might also provide some insights regarding similarities and differences in connectivity between them and those with ASD.
Evolutionary Benefit and Risk
The neuroscientist finding also potentially answers some evolutionary questions. In my Autism, Genetics, and Evolution post, I suggested that the alleles that cause autism could have been with humanity for at least 40,000 years.
"Assuming 30 to 35 years per generation (which is conservative), there have been 1100 to 1300 generations since the two populations diverged. This presumably should have been enough time to eliminate the various alleles that cause autism from the gene pool, if they are in fact deleterious.
Obviously this has not occurred. This means that the individual alleles that in combination cause autism must individually or in lesser combinations have had a beneficial effect to compensate for the reduced reproductive rates of autistics."
As the neuroscientist paper indicates, the same narrower width minicolumnar structure found in ASD may be a competitive advantage in the case of the neuroscientists. If the same alleles that contribute to ASD can result in a competitive advantage in other circumstances through (intellectual) fitness, this would easily explain the continued existence of ASD over time. The research paper quotes T.G West from In the Mind’s Eye (1997):
"One of the most important lessons to be learned from the genetic study of many diseases in recent years has been that the paradoxically high frequency of certain conditions is explained by the fact that important advantages conferred on those who carry the predisposition to these conditions may outweigh the obvious dramatic disadvantages."
My Autism and Minicolumns post suggested that a) ASD has a minicolumnar underpinning, b) this underpinning is required (i.e. no narrow minicolumns means no ASD), c) it originates in the first 40 days of fetal development (i.e. it is not itself acquired post-natally), d) that this difference falls within the normal range (i.e. that having it does not ‘cause’ a diagnosis, although it may very well result in diversity of thought and cognition, i.e. neurodiversity), e) that something else is therefore required (with no significant speculation as to what that something else may be, other than to generically label it as a ‘second hit’), and f) that research needs to prove or exclude causality among the population of the vulnerable, i.e. proving that something does not cause ASD in those who are invulnerable does not prove that it does not cause ASD in those who are vulnerable.
I would suggest that the Neuroscientist research lends significant credence to the above, especially to point d, and suggests that the differences between the neuroscientists and those with ASD may point to the ‘something else required’ that follows.