scholarly journals Genetic and neurophysiological biomarkers of neuroplasticity inform post-stroke language recovery

2021 ◽  
Author(s):  
Haley C Dresang ◽  
Denise Y Harvey ◽  
Priyanka P Shah-Basak ◽  
Laura DeLoretta ◽  
Rachel Wurzman ◽  
...  
Keyword(s):  
Primary Motor Cortex ◽  
Cortical Excitability ◽  
Motor Evoked Potentials ◽  
Stroke Recovery ◽  
Lesion Volume ◽  
Theta Burst Stimulation ◽  
Genetic Biomarkers ◽  
Language Recovery ◽  
Theta Burst ◽  
Continuous Theta Burst Stimulation

Background: There is high variability in poststroke aphasia severity, and predicting language recovery remains imprecise. Standard prognostic measures do not include neurophysiological indicators or genetic biomarkers of neuroplasticity, which may be critical sources of variability. Objective: To evaluate whether a common polymorphism (Val66Met) in the gene for brain derived neurotrophic factor (BDNF; a gene related to neuroplasticity) contributes to variability in poststroke language recovery, and to assess whether BDNF polymorphism interacts with neurophysiological indicators of neuroplasticity (cortical excitability and stimulation induced plasticity in response to continuous theta burst stimulation [cTBS]) to improve estimates of aphasia severity. Methods: Saliva samples and motor evoked potentials (MEPs) were collected from participants with chronic aphasia subsequent to a left hemisphere ischemic stroke. MEPs were collected prior to cTBS (index for cortical excitability) and 10 minutes following cTBS (index for stimulation induced neuroplasticity) to the left primary motor cortex. Analyses assessed the extent to which BDNF polymorphism interacted with cortical excitability and stimulation induced neuroplasticity to predict aphasia severity beyond established predictors. Results: Val66Val carriers showed less aphasia severity than Met allele carriers, after controlling for lesion volume and time poststroke. Furthermore, Val66Val carriers showed expected responses of strong effects of age on aphasia severity, and positive associations between both cortical excitability and stimulation induced neuroplasticity and severity. In contrast, Met allele carriers showed weaker effects of age and unexpected negative associations between cortical excitability, stimulation induced neuroplasticity and aphasia severity. Conclusions: Neurophysiological indicators and genetic biomarkers of neuroplasticity improved ability to predict poststroke aphasia severity. Furthermore, BDNF polymorphism interacted with cortical excitability and stimulation-induced neuroplasticity to predict aphasia recovery. These findings provide novel insights into mechanisms of variability in stroke recovery and may improve aphasia prognostics.

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.

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 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.

Speed of processing in the primary motor cortex: A continuous theta burst stimulation study

2014 ◽  
Vol 261 ◽  
pp. 177-184 ◽  
Author(s):  
Bimal Lakhani ◽  
David A.E. Bolton ◽  
Veronica Miyasike-daSilva ◽  
Albert H. Vette ◽  
William E. McIlroy
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Speed Of Processing ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Theta Burst ◽  
Continuous Theta Burst Stimulation

The effect of continuous theta burst stimulation over premotor cortex on circuits in primary motor cortex and spinal cord

2009 ◽  
Vol 120 (4) ◽  
pp. 796-801 ◽  
Author(s):  
Ying-Zu Huang ◽  
John C. Rothwell ◽  
Chin-Song Lu ◽  
JiunJie Wang ◽  
Yi-Hsin Weng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Premotor Cortex ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Theta Burst ◽  
Continuous Theta Burst Stimulation

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.

scholarly journals M1 disruption delays motor processes but not deliberation about action choices

2018 ◽  
Author(s):  
Gerard Derosiere ◽  
David Thura ◽  
Paul Cisek ◽  
Julie Duque
Keyword(s):  
Motor Cortex ◽  
Decision Process ◽  
Primary Motor Cortex ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Sham Stimulation ◽  
Motor Processes ◽  
The Impact ◽  
Theta Burst ◽  
Continuous Theta Burst Stimulation

AbstractDecisions about actions typically involve a period of deliberation that ends with the commitment to a choice and the motor processes overtly expressing that choice. Previous studies have shown that neural activity in sensorimotor areas, including the primary motor cortex (M1), correlates with deliberation features during action selection. Yet, the causal contribution of these areas to the decision process remains unclear. Here, we investigated whether M1 determines choice commitment, or whether it simply reflects decision signals coming from upstream structures and instead mainly contributes to the motor processes that follow commitment. To do so, we tested the impact of a disruption of M1 activity, induced by continuous theta burst stimulation (cTBS), on the behavior of human subjects in (1) a simple reaction time (SRT) task allowing us to estimate the duration of the motor processes and (2) a modified version of the tokens task (Cisek et al., 2009), which allowed us to estimate subjects’ time of commitment as well as accuracy criterion. The efficiency of cTBS was attested by a reduction in motor evoked potential amplitudes following M1 disruption, as compared to those following a sham stimulation. Furthermore, M1 cTBS lengthened SRTs, indicating that motor processes were perturbed by the intervention. Importantly, all of the behavioral results in the tokens task were similar following M1 disruption and sham stimulation, suggesting that the contribution of M1 to the deliberation process is potentially negligible. Taken together, these findings favor the view that M1 contribution is downstream of the decision process.New and noteworthyDecisions between actions are ubiquitous in the animal realm. Deliberation during action choices entails changes in the activity of the sensorimotor areas controlling those actions, but the causal role of these areas is still often debated. Using continuous theta burst stimulation, we show that disrupting the primary motor cortex (M1) delays the motor processes that follow instructed commitment but does not alter volitional deliberation, suggesting that M1 contribution may be downstream of the decision process.

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