Sub-Linear Response in the Autistic Brain to Paired Finger Stimulation

Background: The search for a neural phenotype for autism is ongoing. It is widely accepted that differences in the brains of persons with and without autism are expressed in neural circuitry and are pervasive through much of the brain. An attractive candidate proposed for a neural phenotype is reduced inhibition in the neural circuitry. To test this, an electrophysiological assay of synaptic inhibition is desirable. Objectives: Inhibition levels typically increase sharply with increase in stimulation level. The tactile stimulation of two neighboring parts of the body as compared to one will elicit a higher level of inhibition, and will reduce the evoked response. More specifically, the reduced inhibition hypothesis predicts that the response to the simultaneous stimulation of two fingers relative to the sum of responses to the stimulation of each finger individually will be larger in autistic than typically developing brains. We tested this prediction with magnetoencephalography (MEG). Methods: We recorded the neural response to passive tactile stimulation of the thumb (D1), index finger (D2), and both fingers combined (D1,D2) of the dominant (right) hand of young adult participants (13 high-functioning persons with autism spectrum disorder or ASDs and 17 typically developing persons or TDs, matched for gender and age) while they remained awake in an eyes-closed supine posture in a 248-sensor MEG scanner. For each participant, the sensor in the contralateral cortex that had the largest evoked response (0-300 ms from stimulus onset) to D1,D2 relative to baseline was automatically selected. We then computed the somatosensory evoked potentials (SEPs) in the chosen sensor to the stimulation of D1 alone, D2 alone, and D1,D2. For each of the two early SEP components, M50 (S1) and M100 (S2), group (ASD, TD) response to D1,D2 was linearly regressed to the sum of the responses to the stimulation of D1 and D2 each, and optimal least-squares slopes (D1,D2 vs. D1+D2) computed. In a complementary analysis, the three sensors that respectively recorded the largest evoked response to D1, D2 and D1,D2 were selected for otherwise identical calculations as before. Results: M50: In comparison to the sum of the responses to individual D1 and D2 stimulation (D1+D2), the response to D1,D2 was significantly sub-linear in ASDs but comparable in TDs; the difference in slopes of the two groups was significant. The complementary analysis also yielded identical results, which contradict the reduced inhibition hypothesis. M100: In ASDs, the response to D1,D2 was comparable to D1+D2; in TDs, the D1,D2 response was significantly sub-linear as compared to D1+D2; the difference in slopes between the two groups was significant. However, the complementary analysis found no such significant difference. Conclusions: The simultaneous stimulation of a pair of neighboring fingers elicited significant decline in the early response and increase in the mid-latency response in autism compared with control young adults. The findings fail to support the idea of reduced inhibition but suggest instead a more complex, evolving dynamical kind of inhibition in the circuits of autistic brains.