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Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case – Control Pilot Study

View Article: PubMed Central - PubMed

ABSTRACT

Objective:: This case–control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long-term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD.

Methods:: We studied youth with ASD aged 11–18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor-evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS.

Results:: Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons.

Conclusion:: In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of ASD based on behavioral and cognitive testing.

No MeSH data available.


Related in: MedlinePlus

Linear mixed model estimates of post-iTBS motor-evoked potential amplitude over baseline for each timepoint (minutes) by group. Post-hoc comparison indicated a significant difference at 20 minutes, with ASD demonstrating significantly less facilitation than TDC (Control). ASD, autism spectrum disorder group; Control, typically developing children; iTBS, intermittent theta burst stimulation.
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f1: Linear mixed model estimates of post-iTBS motor-evoked potential amplitude over baseline for each timepoint (minutes) by group. Post-hoc comparison indicated a significant difference at 20 minutes, with ASD demonstrating significantly less facilitation than TDC (Control). ASD, autism spectrum disorder group; Control, typically developing children; iTBS, intermittent theta burst stimulation.

Mentions: The majority of TDC (6/9) and ASD (6/9) subjects demonstrated a positive AUC estimate following iTBS over 30 minutes (see AUC, Table 2). A robust interpretation of an AUC is limited, as it does not account for time course, that is, facilitation early in the time course can be offset by later suppression. As expected, there was no significant group difference between baseline raw MEP amplitudes, RMT, or iTBS stimulus intensity (Table 3). At baseline, the LMM analysis identified a significant intersubject differences in raw MEP amplitudes (F1,15 = 0.44; p = 0.52). Therefore, this was included as a covariate in the model. A significant Time × Group interaction was identified (F9,144 = 2.05; p = 0.038), while neither Group (F1,15 = 0.44; p = 0.52) nor TIME (F9,144 = 0.75; p = 0.67) alone were statistically significant. Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons (Tukey–Kramer; t = −2.37; p = 0.02). Full results of the LMM findings, including post-hoc comparisons, are listed in Table 3. Adding age as a covariate did not have a significant effect in either analysis (data not shown). The mean modeled MEP amplitude estimates for each time point by group are illustrated in Figure 1. No significant difference of mean AUC between the groups was identified (t = 0.13; p = 0.89). No significant relationship was found between IQ and AUC (r = 0.46, p = 0.21), ADOS social affect total (r = 0.38, p = 0.31), ADOS restrictive and repetitive behavior total (r = −0.46, p = 0.22), and ADOS total score (r = 0.02, p = 0.95).


Abnormal Cortical Plasticity in Youth with Autism Spectrum Disorder: A Transcranial Magnetic Stimulation Case – Control Pilot Study
Linear mixed model estimates of post-iTBS motor-evoked potential amplitude over baseline for each timepoint (minutes) by group. Post-hoc comparison indicated a significant difference at 20 minutes, with ASD demonstrating significantly less facilitation than TDC (Control). ASD, autism spectrum disorder group; Control, typically developing children; iTBS, intermittent theta burst stimulation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5035833&req=5

f1: Linear mixed model estimates of post-iTBS motor-evoked potential amplitude over baseline for each timepoint (minutes) by group. Post-hoc comparison indicated a significant difference at 20 minutes, with ASD demonstrating significantly less facilitation than TDC (Control). ASD, autism spectrum disorder group; Control, typically developing children; iTBS, intermittent theta burst stimulation.
Mentions: The majority of TDC (6/9) and ASD (6/9) subjects demonstrated a positive AUC estimate following iTBS over 30 minutes (see AUC, Table 2). A robust interpretation of an AUC is limited, as it does not account for time course, that is, facilitation early in the time course can be offset by later suppression. As expected, there was no significant group difference between baseline raw MEP amplitudes, RMT, or iTBS stimulus intensity (Table 3). At baseline, the LMM analysis identified a significant intersubject differences in raw MEP amplitudes (F1,15 = 0.44; p = 0.52). Therefore, this was included as a covariate in the model. A significant Time × Group interaction was identified (F9,144 = 2.05; p = 0.038), while neither Group (F1,15 = 0.44; p = 0.52) nor TIME (F9,144 = 0.75; p = 0.67) alone were statistically significant. Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons (Tukey–Kramer; t = −2.37; p = 0.02). Full results of the LMM findings, including post-hoc comparisons, are listed in Table 3. Adding age as a covariate did not have a significant effect in either analysis (data not shown). The mean modeled MEP amplitude estimates for each time point by group are illustrated in Figure 1. No significant difference of mean AUC between the groups was identified (t = 0.13; p = 0.89). No significant relationship was found between IQ and AUC (r = 0.46, p = 0.21), ADOS social affect total (r = 0.38, p = 0.31), ADOS restrictive and repetitive behavior total (r = −0.46, p = 0.22), and ADOS total score (r = 0.02, p = 0.95).

View Article: PubMed Central - PubMed

ABSTRACT

Objective:: This case–control study investigated the use of a low-intensity repetitive transcranial magnetic stimulation (rTMS) protocol to measure motor cortex (M1) plasticity in youth with autism spectrum disorder (ASD) compared with typically developing children (TDC). We hypothesized that impairments in long-term potentiation-like properties represent a neurophysiological biomarker of abnormal cortical function in ASD.

Methods:: We studied youth with ASD aged 11–18 years and matched controls (TDC). Intermittent theta burst stimulation (iTBS) was delivered to the dominant M1 at an intensity of 70% of resting motor threshold. Suprathreshold single-pulse TMS was performed to compare amplitudes of motor-evoked potentials (MEP) measured from surface electromyography electrodes on a target muscle before (20 pulses) and after (10 pulses/time point) iTBS at predefined timepoints (up to 30 minutes) to measure any potentiation effects. A linear mixed model was used to examine group differences in MEP amplitudes over time following iTBS.

Results:: Nine youth with ASD (mean age 15.6; 7 males; 6 right-hand dominant) and 9 TDC (mean age 14.5; 5 males; 9 right-hand dominant) participated. All subjects tolerated the procedure well. Both groups had a mean increase in excitability after iTBS for 30 minutes; however, the time course of excitability changes differed (F9,144 = 2.05; p = 0.038). Post-hoc testing identified a significant decrease in amplitude of the ASD group at 20 minutes following iTBS compared with the TDC after correcting for multiple comparisons.

Conclusion:: In this study, we demonstrate early evidence for a potential physiological biomarker of cortical plasticity in youth with ASD using a rapid low-intensity rTMS protocol with a discriminate measure at 20 minutes following stimulation. The procedure was well tolerated by all 18 participants. Future work will include modification of the protocol to improve the ability to distinguish subtypes of ASD based on behavioral and cognitive testing.

No MeSH data available.


Related in: MedlinePlus