scholarly journals Modulation of motor cortical excitability by continuous theta-burst stimulation in adults with autism spectrum disorder: The roles of BDNF and APOE polymorphisms

2020 ◽  
Author(s):  
Ali Jannati ◽  
Mary A Ryan ◽  
Gabrielle Block ◽  
Fae B. Kayarian ◽  
Lindsay M. Oberman ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Cortical Excitability ◽  
Motor Evoked Potentials ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Adults With Autism ◽  
Theta Burst ◽  
Continuous Theta Burst Stimulation

Objective. To assess the utility of the modulation of motor cortex (M1) excitability by continuous theta-burst stimulation (cTBS) as a physiologic biomarker for adults with autism spectrum disorder (ASD), and to evaluate the influences of brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) polymorphisms on cTBS aftereffects. Methods. 44 neurotypical individuals (NT; age 21-65, 34 males) and 19 age-matched adults with high-functioning ASD (age 21-58, 17 males) underwent M1 cTBS. Cortico-motor reactivity was assessed before cTBS and thereafter every 5-10 minutes for 60 minutes (T5-T60). Results. Logistic regressions found cTBS-induced change in amplitude of motor evoked potentials (ΔMEP) at T15 was a significant predictor of ASD diagnosis (p=0.04). ΔMEP at T15 remained a significant predictor of diagnosis among BDNF Met+ subjects and APOEε4- subjects (p-values < 0.05) but not BDNF Met- subjects. ΔMEP at T30 was the best predictor of diagnosis among APOEε4+ subjects (p = 0.08). Conclusions. We confirm previous findings on the utility of cTBS measures of plasticity for adults with ASD, and we find the diagnostic utility of cTBS is modulated by BDNF and APOE SNPs. Significance. It is important to control for BDNF and APOE polymorphisms when comparing TBS aftereffects in ASD and NT individuals.

scholarly journals Variability in cTBS Aftereffects Attributed to the Interaction of Stimulus Intensity With BDNF Val66Met Polymorphism

2021 ◽  
Vol 15 ◽  
Author(s):  
Denise Y. Harvey ◽  
Laura DeLoretta ◽  
Priyanka P. Shah-Basak ◽  
Rachel Wurzman ◽  
Daniela Sacchetti ◽  
...  
Keyword(s):  
Primary Motor Cortex ◽  
Cortical Excitability ◽  
Motor Evoked Potentials ◽  
Individual Variability ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Bdnf Val66met Polymorphism ◽  
Theta Burst ◽  
Continuous Theta Burst Stimulation ◽  
Insight Into

Objective: To evaluate whether a common polymorphism (Val66Met) in the gene for brain-derived neurotrophic factor (BDNF)—a gene thought to influence plasticity—contributes to inter-individual variability in responses to continuous theta-burst stimulation (cTBS), and explore whether variability in stimulation-induced plasticity among Val66Met carriers relates to differences in stimulation intensity (SI) used to probe plasticity.Methods: Motor evoked potentials (MEPs) were collected from 33 healthy individuals (11 Val66Met) prior to cTBS (baseline) and in 10 min intervals immediately following cTBS for a total of 30 min post-cTBS (0 min post-cTBS, 10 min post-cTBS, 20 min post cTBS, and 30 min post-cTBS) of the left primary motor cortex. Analyses assessed changes in cortical excitability as a function of BDNF (Val66Val vs. Val66Met) and SI.Results: For both BDNF groups, MEP-suppression from baseline to post-cTBS time points decreased as a function of increasing SI. However, the effect of SI on MEPs was more pronounced for Val66Met vs. Val66Val carriers, whereby individuals probed with higher vs. lower SIs resulted in paradoxical cTBS aftereffects (MEP-facilitation), which persisted at least 30 min post-cTBS administration.Conclusions: cTBS aftereffects among BDNF Met allele carriers are more variable depending on the SI used to probe cortical excitability when compared to homozygous Val allele carriers, which could, to some extent, account for the inconsistency of previously reported cTBS effects.Significance: These data provide insight into the sources of cTBS response variability, which can inform how best to stratify and optimize its use in investigational and clinical contexts.

Intermittent theta burst stimulation over the posterior superior temporal sulcus for children with autism spectrum disorder: A 4-week randomized blinded controlled trial followed by another 4-week open-label intervention

Autism ◽  
2021 ◽  
pp. 136236132199053
Author(s):  
Hsing-Chang Ni ◽  
Yi-Lung Chen ◽  
Yi-Ping Chao ◽  
Chen-Te Wu ◽  
Yu-Yu Wu ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Cognitive ◽  
Children With Autism ◽  
Superior Temporal Sulcus ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Theta Burst ◽  
Posterior Superior Temporal Sulcus

The posterior superior temporal sulcus is a potential therapeutic target of brain stimulation for autism spectrum disorder. We conducted a 4-week randomized, single-blind parallel sham-controlled trial, followed by additional 4-week open-label intervention to evaluate the feasibility and efficacy regarding intermittent theta burst stimulation over the bilateral posterior superior temporal sulcus in autism spectrum disorder. In total, 78 intellectually able children and adolescents were randomized to the active ( n = 40) and sham groups ( n = 38). During the first 4 weeks, the active group received two-session/week intermittent theta burst stimulation, whereas the sham group received the same number of sham stimulation. After unblinding, both groups received eight-session real stimulation over the additional 4 weeks. In total, 91% participants completed the protocol with mild and transitory side-effects. There was no significant group-by-time interaction for active versus sham group on clinical symptoms and social cognitive performances in the first 4 weeks. The within-group analysis revealed 8 weeks (including a 4-week blind trial and a 4-week open-label intervention) of intermittent theta burst stimulation achieved greater efficacy than 4-week interventions. Participants with higher intelligence, better social cognitive performances, alongside less attention-deficit hyperactivity disorder severity at baseline, were more likely to be responders. Our study demonstrated the feasibility of long-term intermittent theta burst stimulation over the posterior superior temporal sulcus in children and adolescents with autism spectrum disorder. However, the findings from the first 4-week blind trial do not support the therapeutic efficacy of intermittent theta burst stimulation over the posterior superior temporal sulcus on the clinical symptoms and cognitive performance of social impairment, given the current stimulation protocol. The exploratory analyses suggest that the therapeutic efficacy might be moderated by several individual characteristics and more intermittent theta burst stimulation sessions. Lay abstract Intermittent theta burst stimulation is a varied form of repetitive transcranial magnetic non-invasive brain stimulation technique used to treat several neurological and psychiatric disorders. Its feasibility and therapeutic effects on the bilateral posterior superior temporal sulcus in children with autism are unknown. We conducted a single-blind, sham-controlled parallel randomized clinical trial in a hitherto largest sample of intellectually able children with autism ( N = 78). Participants randomized to the active group received two-session/week intermittent theta burst stimulation for continuous 8 weeks. Those in the sham group received two-session/week sham stimulations in the first 4 weeks and then active intervention for the following 4 weeks after unblinding. First, we found that continuous 8-week intermittent theta burst stimulation on the bilateral posterior superior temporal sulcus in children with autism is safe and tolerable. Second, we found that 8-week intermittent theta burst stimulation produced greater therapeutic efficacy, although we did not find any significant effects of 4-week intermittent theta burst stimulation on core symptoms and social cognitive performances in autism. Further analysis revealed that participants with higher intelligence and better social cognitive performance, alongside less attention-deficit hyperactivity disorder severity at baseline, were more likely to be responders. This study identified that the factors contribute to responders and the results suggest that longer courses of non-invasive brain stimulation may be needed to produce therapeutic benefits in autism, with consideration of heterogeneous responses.

scholarly journals Determining the optimal pulse number for theta burst induced change in cortical excitability

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel M. McCalley ◽  
Daniel H. Lench ◽  
Jade D. Doolittle ◽  
Julia P. Imperatore ◽  
Michaela Hoffman ◽  
...  
Keyword(s):  
Cortical Excitability ◽  
Motor Evoked Potentials ◽  
Pulse Number ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Non Invasive ◽  
Subject Variability ◽  
Secondary Analyses ◽  
Effective Doses ◽  
Theta Burst

AbstractTheta-burst stimulation (TBS) is a form of non-invasive neuromodulation which is delivered in an intermittent (iTBS) or continuous (cTBS) manner. Although 600 pulses is the most common dose, the goal of these experiments was to evaluate the effect of higher per-dose pulse numbers on cortical excitability. Sixty individuals were recruited for 2 experiments. In Experiment 1, participants received 600, 1200, 1800, or sham (600) iTBS (4 visits, counterbalanced, left motor cortex, 80% active threshold). In Experiment 2, participants received 600, 1200, 1800, 3600, or sham (600) cTBS (5 visits, counterbalanced). Motor evoked potentials (MEP) were measured in 10-min increments for 60 min. For iTBS, there was a significant interaction between dose and time (F = 3.8296, p = 0.01), driven by iTBS (1200) which decreased excitability for up to 50 min (t = 3.1267, p = 0.001). For cTBS, there was no overall interaction between dose and time (F = 1.1513, p = 0.33). Relative to sham, cTBS (3600) increased excitability for up to 60 min (t = 2.0880, p = 0.04). There were no other significant effects of dose relative to sham in either experiment. Secondary analyses revealed high within and between subject variability. These results suggest that iTBS (1200) and cTBS (3600) are, respectively, the most effective doses for decreasing and increasing cortical excitability.

scholarly journals Plasticity Induced by Intermittent Theta Burst Stimulation in Bilateral Motor Cortices Is Not Altered in Older Adults

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Daina S. E. Dickins ◽  
Martin V. Sale ◽  
Marc R. Kamke
Keyword(s):  
Older Adults ◽  
Cortical Excitability ◽  
Motor Evoked Potentials ◽  
Single Pulse ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Motor Tasks ◽  
Age Related ◽  
Before And After ◽  
Theta Burst

Numerous studies have reported that plasticity induced in the motor cortex by transcranial magnetic stimulation (TMS) is attenuated in older adults. Those investigations, however, have focused solely on the stimulated hemisphere. Compared to young adults, older adults exhibit more widespread activity across bilateral motor cortices during the performance of unilateral motor tasks, suggesting that the manifestation of plasticity might also be altered. To address this question, twenty young (<35 years old) and older adults (>65 years) underwent intermittent theta burst stimulation (iTBS) whilst attending to the hand targeted by the plasticity-inducing procedure. The amplitude of motor evoked potentials (MEPs) elicited by single pulse TMS was used to quantify cortical excitability before and after iTBS. Individual responses to iTBS were highly variable, with half the participants showing an unexpected decrease in cortical excitability. Contrary to predictions, however, there were no age-related differences in the magnitude or manifestation of plasticity across bilateral motor cortices. The findings suggest that advancing age does not influence the capacity for, or manifestation of, plasticity induced by iTBS.

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