Maturation of interhemispheric signal propagation in autism spectrum disorder and typically developing controls: a TMS-EEG study

Abstract

Brain maturation from childhood to adulthood is associated with changes in structural and functional connectivity between remote brain regions. Altered connectivity plays an important role in the pathology of autism spectrum disorder (ASD), a severe neurodevelopmental disorder. ASD is associated with abnormal brain development and structurally altered interhemispheric connections. Cortico-cortical connectivity can be studied by a combination of transcranial magnetic stimulation (TMS) with concurrent EEG (TMS-EEG). TMS-evoked Interhemispheric Signal Propagation (ISP) is a correlate of interhemispheric connectivity related to the microstructure of the corpus callosum (CC). We used TMS-EEG to measure ISP in 22 ASD subjects (10-21 years) and 22 typically developing control subjects (9-19 years). We expected (1) maturational changes of ISP from childhood to young adulthood and also (2) reduced interhemispheric signal transfer in ASD. ISP was positively correlated with age in both ASD and typically developing control subjects. No difference in ISP between ASD and typically developing controls was found. Our findings demonstrate maturation of effective interhemispheric connectivity during adolescence. As ISP is related to the microstructure of the CC, the developmental change of ISP likely reflects maturation of the CC during the second life decade. The results support ISP as a valid parameter reflecting functional interhemispheric connectivity. Our results do not support a global deficit of interhemispheric connectivity in ASD.

Development of cortical motor circuits between childhood and adulthood: A navigated TMS‐HdEEG study

“…These time intervals were chosen because 150 ms represents the mean duration of the probable GABA B -receptormediated inhibitory neurotransmission [Fitzgerald et al, 2009] and the average interhemispheric transfer time of 10 ms was chosen to account for the time it takes for the signal to propagate from the site of stimulation to the opposite hemisphere in adults [Ferbert et al, 1992]. Interhemispheric signal propagation time of 10 ms has also been applied to pediatric populations [Jarczok et al, 2016]. Interhemispheric propagation between motor cortices was assessed by computing the ratio between M1 left and M1 right [(M1 right /M1 left ) * 100].…”

“…As activation of M1 in one hemisphere sends an excitatory signal transcallosally that excites inhibitory interneurons in the contralateral M1, reducing the net excitatory output [Daskalakis et al, 2002], spreading of the interhemispheric signal has been related to the microstructure of the corpus callosum [Voineskos et al, 2010], and the facilitation of interhemispheric transfer as a function of development was interpreted to reflect the maturation of the corpus callosum [Jarczok et al, 2016]. As activation of M1 in one hemisphere sends an excitatory signal transcallosally that excites inhibitory interneurons in the contralateral M1, reducing the net excitatory output [Daskalakis et al, 2002], spreading of the interhemispheric signal has been related to the microstructure of the corpus callosum [Voineskos et al, 2010], and the facilitation of interhemispheric transfer as a function of development was interpreted to reflect the maturation of the corpus callosum [Jarczok et al, 2016].…”

“…Jarczok et al [2016] addressed this question by comparing TMS-evoked interhemispheric transmission between different age groups, and found signal propagation to be higher in older subjects who can be assumed to have larger heads and therefore a longer distance between the two cortical areas (i.e., reduced effects of volume conduction). Jarczok et al [2016] addressed this question by comparing TMS-evoked interhemispheric transmission between different age groups, and found signal propagation to be higher in older subjects who can be assumed to have larger heads and therefore a longer distance between the two cortical areas (i.e., reduced effects of volume conduction).…”

“…Later studies have demonstrated that N100 modulation in the Go/NoGo task can differentiate between neurotypical children and children with attention deficit hyperactivity disorder [D'Agati et al, 2014] further supporting the role of N100 as a marker of inhibition. Moreover, according to a recent TMS-EEG study, interhemispheric signal propagation increases as a function of age in healthy subjects and patients with autism spectrum disorder [Jarczok et al, 2016].…”

The Current and Future Potential of Transcranial Magnetic Stimulation With Electroencephalography in Psychiatry

“…It should be noted that although the scope of this review was focused on TMS‐EEG biomarkers for MDD, BPD, and SCZ, there are a number of promising studies that have brought insights into the clinical neurophysiology of other psychiatric disorders, including attention‐deficit hyperactive disorder and autism . Very recently, TMS‐EEG has also been used to investigate the neural and network changes underlying substance‐use disorders .…”