Translational Neuroscience in Autism: From Neuropathology to Transcranial Magnetic Stimulation Therapies

Abstract

The presence of heterotopias, increased regional density of neurons at the gray-white matter junction, and focal cortical dysplasias all suggest an abnormality of neuronal migration in autism spectrum disorder (ASD). The abnormality is borne from a dissonance in timing between radial and tangentially migrating neuroblasts to the developing cortical plate. The uncoupling of excitatory and inhibitory cortical cells disturbs the coordinated interactions of neurons within local networks, thus providing abnormal patterns of brainwave activity in the gamma bandwidth. In ASD, gamma oscillation abnormalities and autonomic markers offer measures of therapeutic progress and help in the identification of subgroups.

Keywords: Autism spectrum disorder; Executive function; Gamma oscillations; Minicolumns; Transcranial magnetic stimulation.

Conflict of interest statement

Disclosure This article is based on several studies partially supported by a grant from the National Institutes of Health (MH86784) awarded to M.F. Casanova.

Copyright © 2020 Elsevier Inc. All rights reserved.

Figures

Figure 1:

A figure of 8 electromagnetic coil is placed near the forehead of a child while she sits comfortably in a reclining chair. Repeatedly activating the electromagnet produces clicking sounds and a slight tapping on the forehead. Earplugs are provided for noise reduction.

Figure 2:

Induced gamma oscillations to target stimuli increased post-TMS as compared to baseline. From Sokhadze EM, Casanova MF, El-Baz AS, et al. TMS-based neuromodulation of evoked and induced gamma oscillations and event-related potentials in children with autism. NeuroRegulation 2016;3(3):115; with permission.

Figure 3:

Ritualistic/Sameness behavior (left) and Stereotype behavior (right) rating scores of RBS-R questionnaire at baseline, post waiting period, and post 12 and 18 sessions of rTMS. Most dramatic decrease of scores was observed in the 18 TSM group. Adapted from Sokhadze EM, Lamina EV, Casanova EL, et al. Exploratory study of rTMS neuromodulation effects on electrocortical functional measures of performance in an oddball test and behavioral symptoms in autism. Front Syst Neurosci 2018;12(20):10; with permission.

Figure 4:

At baseline P300 responses were similar to all 3 stimuli (target Kanizsa, nontarget Kanizsa, standard). Post-TMS responses to non-target stimuli decreased.

Figure 5:

Skin conductance level (SCL) showed statistically significant linear regression over 18 sessions of r The LF/HF ratio of HRV (cardiac autonomic balance index) showed a linear regression that was statistically significant (R=0.79, R2=0.62, adjusted R2=0.59, observed power=0.97, Fig.5.1).TMS (R=0.63, R2 = 0.40, adjusted R2=0.36, F=10.70, p=0.004, power=0.94, Fig.5.2). Adapted from Sokhadze GE, Casanova MF, Kelly DP, et al. Neuromodulation based on rTMS affects behavioral measures and autonomic nervous system activity in children with autism. NeuroRegulation 2017;4(2):65–78; with permission.