A pedagogic aspect of a pathologist’s job is trying to explain symptoms based on autopsy findings.  This follows a long tradition in medicine where a professor does dissections while asking questions to participating students.  Occasionally, in order to elicit the opinion of other authorities, the more perplexing or challenging cases are presented to a larger group of faculty members in a more formal setting.  The latter effort is called a clinicopathological conference (CPC).

The same year in which I described a deficit in the organization of the cerebral cortex  of autistic individuals (i.e., abnormal minicolumns) (Casanova et al, 2002a) we published a follow-up article describing possible clinicopathological correlations.  Discoveries usually gain significance based on their explanatory powers.  In our case we wanted to explain not only how known symptoms of autism were generated, but also to predict important aspects of its pathophysiology.  In essence, by knowing the pathology (what is wrong in the brain) we could not only talk about the known symptoms but also try to predict aspects of the condition never previously addressed within the medical literature.

In this particular blog I will talk about how minicolumnar abnormalities can procreate symptoms related to cortical hyperexcitability.  I will leave for the future a discussion in which I draw an analogy between the abdominal symptoms of some autistic patients and a migraine equivalent. Besides cortical hyperexcitability,  the analogy to migraine based on similarities in their natural history, provoking agents, high levels of serotonin in the blood, biopsy results, and ability to treat both with certain diets.  This analogy has been published only as a hypothesis (Casanova, 2008). In addition, other blogs will describe how the same minicolumnar abnormalities may also provide for changes in both the brain’s blueprint of connectivity as well as its capacity to bind together different elements of cognition.  These are all ideas stemming from  studies in my laboratory and as such remain subject to further experimentation and verification.

As I have previously alluded in previous blogs, an abnormality in the peripheral surround of minicolumns (the so-called “shower curtain of inhibition”) allows for the leaking of signals, that is, information that was supposed to be processed by a single minicolumn now suffuses into adjacent minicolumns.   If unchecked, stimulating minicolumns lacking in surround inhibition will themselves recruit adjacent minicolumns and continue their spread in an avalanche of stimulation that in some cases will be manifested as a seizure. Approximately one third of autistic individuals have suffered at least 2 seizures by the time they get to puberty.  The percentage of autistic individuals with an abnormal EEG is considerably higher, about two thirds. In the end hyperexcitability disrupts the normal process of information processing within the cerebral cortex (see figure below).

Neurons react to stimuli (e.g., a square wave) by firing more often not by increasing the amplitude of their spike.  In the normal scenario the neuron is never silent, and even without apparent stimuli will fire occasionally thus  providing a background level of activity. In the hyperexcitable cortex neurons will fire more without appropriate stimulation.  In the pathological case (e.g., autism), the amount of firing is such that it makes it difficult to differentiate signal from noise.

The following are several paragraphs describing what happens when the nervous system is overstimulated and taxed in its abilities to cope with the environment. The paragraphs were taken from JJ Ratey Shadow Syndromes, 1997. The parallel to autism in Ratey’s description should be apparent.