Corticomotor excitability during precision motor tasks

The aim of this preliminary study was to investigate motor cortex (cortical) excitability between a similar fine visuomotor task of varying difficulty. Ten healthy adults (three female, seven male; 20—45 years of age) participated in the study. Participants were instructed to perform a fine visuomotor task by statically abducting their first index finger against a force transducer which displayed the level of force (represented as a marker) on a computer monitor. This marker was to be maintained between two stationary bars, also displayed on the computer monitor. The level of difficulty was increased by amplifying the position of the marker, making the task more difficult to control. Cortical measures of motor evoked potential (MEP) and silent period (SP) duration in first dorsal interosseous (FDI) muscle were obtained using transcranial magnetic stimulation (TMS) while the participant maintained the ‘‘easy’’ or ‘‘difficult’’ static task. An 11.8% increase in MEP amplitude was observed when subjects undertook the ‘‘difficult’’ task, but no differences in MEP latency or SP duration. The results from this preliminary study suggest that cortical excitability increases reflect the demand required to perform tasks requiring greater precision with suggestions for further research discussed

Measurement of mental attention: Assessing a cognitive component underlying performance on standardized intelligence tests

Despite the widespread use of standardized IQ tests to measure human intelligence, problems with such measures have led some to suggest that better indices may derive from measurement of cognitive processes underlying performance on IQ tests (e.g., working memory capacity). However, measures from both approaches may exhibit performance biases in favour of majority groups, due to the influence of prior learning and experience. Mental attentional (M-) capacity is proposed to be a causal factor underlying developmental growth in working memory. Measures of M-capacity index important cognitive variance underlying performance on standardized intelligence tests. These measures appear to be reasonably culture-fair and invariant across content domains. The current study tested theoretical predictions regarding the content-invariance of M-measures and the development of M-capacity for groups of children differing in performance on standardized IQ tests. 91 participants differentiated on the basis of academic stream (intellectually gifted vs. mainstream) and age (grade 4 vs. grade 8) received measures of M-capacity in the verbal and visuo-spatial domains. Children identified as gifted scored about one stage higher on both measures. Results suggest that measures of M-capacity may be useful adjuncts to standardized intelligence measures

Review: Non‐invasive brain stimulation in behavioral addictions: insights from direct comparisons with substance use disorders

Background and Objectives Treatment models developed for substance use disorders (SUDs) are often applied to behavioral addictions (BAs), even though the correspondence between these forms of addiction is unclear. This is also the case for noninvasive brain stimulation (NIBS) techniques being investigated as potential treatment interventions for SUDs and BAs. Objectives: to contribute to the development of more effective NIBS protocols for BAs. Methods Two literature searches using PubMed and Google Scholar were conducted identifying a total of 35 studies. The first search identified 25 studies examining the cognitive and neurophysiological overlap between BAs and SUDs. The second search yielded 10 studies examining the effects of NIBS in BAs. Results Impulsivity and cravings show behavioral and neurophysiologic overlaps between BAs and SUDs, however, other outcomes like working‐memory abilities or striatal connectivity, differ between BAs and SUDs. The most‐employed NIBS target in BAs was dorsolateral prefrontal cortex (DLPFC), which was associated with a decrease in cravings, and less frequently with a reduction of addiction severity. Conclusions and Scientific Significance Direct comparisons between BAs and SUDs revealed discrepancies between behavioral and neurophysiological outcomes, but overall, common and distinctive characteristics underlying each disorder. The lack of complete overlap between BAs and SUDs suggests that investigating the cognitive and neurophysiological features of BAs to create individual NIBS protocols that target risk‐factors associated specifically with BAs, might be more effective than transferring protocols from SUDs to BAs. Individualizing NIBS protocols to target specific risk‐factors associated with each BA might help to improve treatment interventions for BAs. (Am J Addict 2019;00:1–23

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases

In Older Adults the Antidepressant Effect of Repetitive Transcranial Magnetic Stimulation Is Similar but Occurs Later Than in Younger Adults

Funding Information: AJO-M was the national coordinator for Portugal of a non-interventional study (EDMS-ERI-143085581, 4.0) to characterize a Treatment-Resistant Depression Cohort in Europe, sponsored by Janssen-Cilag, Ltd (2019–2020), is the recipient of a grant from Schuhfried GmBH for norming and validation of cognitive tests, and is the national coordinator for Portugal of trials of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd (EudraCT number 2017-003288-36), and of esketamine for treatment-resistant depression, sponsored by the Janssen-Cilag, Ltd (EudraCT NUMBER: 2019-002992-33). AP-L is a co-founder of Linus Health and TI Solutions AG; serves on the scientific advisory boards for Starlab Neuroscience, Magstim Inc., Radiant Hearts, and MedRhythms; and is listed as an inventor on several issued and pending patents on the real-time integration of non-invasive brain stimulation with electroencephalography and magnetic resonance imaging. None of the aforementioned agencies or companies had a role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, in the preparation, review, or approval of the manuscript, nor in the decision to submit the manuscript for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding Information: GC was funded by the Fundação para a Ciência e Tecnologia (FCT; Portugal) through a PhD Scholarship (SFRH/BD/130210/2017). AB was supported by the NIH (NS114405-02, MH120441-01). AJO-M was funded by the FCT (Portugal) through a Junior Research and Career Development Award from the Harvard Medical School—Portugal Program (HMSP-ICJ/0020/2011). GC and AJO-M were supported by grant PTDC/MED-NEU/31331/2017, and AJO-M by grant PTDC/MED-NEU/30302/2017, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020—Programa Operacional Regional de Lisboa. AJO-M was also funded by a Starting Grant from the European Research Council under the European Union's Horizon 2020 research and innovation program (Grant Agreement No. 950357). Publisher Copyright: Copyright © 2022 Cotovio, Boes, Press, Oliveira-Maia and Pascual-Leone.Background: Treatment resistant depression is common in older adults and treatment is often complicated by medical comorbidities and polypharmacy. Repetitive transcranial magnetic stimulation (rTMS) is a treatment option for this group due to its favorable profile. However, early influential studies suggested that rTMS is less effective in older adults. This evidence remains controversial. Methods: Here, we evaluated the rTMS treatment outcomes in a large international multicenter naturalistic cohort of >500 patients comparing older vs. younger adults. Results: We show that older adults, while having similar antidepressant response to younger adults, respond more slowly, which may help to explain differences from earlier studies when the duration of a treatment course was shorter. Conclusions: Such evidence helps to resolve a long-standing controversy in treating older depressed patients with rTMS. Moreover, these findings provide an important data point in the call to revise policy decisions from major insurance providers that have unfairly excluded older adults.publishersversionpublishe

The effects of waveform and current direction on the efficacy and test–retest reliability of transcranial magnetic stimulation

[Abstract] The pulse waveform and current direction of transcranial magnetic stimulation (TMS) influence its interactions with the neural substrate; however, their role in the efficacy and reliability of single- and paired-pulse TMS measures is not fully understood. We investigated how pulse waveform and current direction affect the efficacy and test–retest reliability of navigated, single- and paired-pulse TMS measures. 23 healthy adults (aged 18–35 years) completed two identical TMS sessions, assessing resting motor threshold (RMT), motor-evoked potentials (MEPs), cortical silent period (cSP), short- and long-interval intra-cortical inhibition (SICI and LICI), and intracortical facilitation (ICF) using either monophasic posterior–anterior (monoPA; n = 9), monophasic anterior–posterior (monoAP; n = 7), or biphasic (biAP-PA; n = 7) pulses. Averages of each TMS measure were compared across the three groups and intraclass correlation coefficients were calculated to assess test–retest reliability. RMT was the lowest and cSP was the longest with biAP-PA pulses, whereas MEP latency was the shortest with monoPA pulses. SICI and LICI had the largest effect with monoPA pulses, whereas only monoAP and biAP-PA pulses resulted in significant ICF. MEP amplitude was more reliable with either monoPA or monoAP than with biAP-PA pulses. LICI was the most reliable with monoAP pulses, whereas ICF was the most reliable with biAP-PA pulses. Waveform/current direction influenced RMT, MEP latency, cSP, SICI, LICI, and ICF, as well as the reliability of MEP amplitude, LICI, and ICF. These results show the importance of considering TMS pulse parameters for optimizing the efficacy and reliability of TMS neurophysiologic measures

Test–Retest Reliability of the Effects of Continuous Theta-Burst Stimulation

ObjectivesThe utility of continuous theta-burst stimulation (cTBS) as index of cortical plasticity is limited by inadequate characterization of its test–retest reliability. We thus evaluated the reliability of cTBS aftereffects, and explored the roles of age and common single-nucleotide polymorphisms in the brain-derived neurotrophic factor (BDNF) and apolipoprotein E (APOE) genes.MethodsTwenty-eight healthy adults (age range 21–65) underwent two identical cTBS sessions (median interval = 9.5 days) targeting the motor cortex. Intraclass correlation coefficients (ICCs) of the log-transformed, baseline-corrected amplitude of motor evoked potentials (ΔMEP) at 5–60 min post-cTBS (T5–T60) were calculated. Adjusted effect sizes for cTBS aftereffects were then calculated by taking into account the reliability of each cTBS measure.ResultsΔMEP at T50 was the most-reliable cTBS measure in the whole sample (ICC = 0.53). Area under-the-curve (AUC) of ΔMEPs was most reliable when calculated over the full 60 min post-cTBS (ICC = 0.40). cTBS measures were substantially more reliable in younger participants (< 35 years) and in those with BDNF Val66Val and APOE ε4– genotypes.ConclusioncTBS aftereffects are most reliable when assessed 50 min post-cTBS, or when cumulative ΔMEP measures are calculated over 30–60 min post-cTBS. Reliability of cTBS aftereffects is influenced by age, and BDNF and APOE polymorphisms. Reliability coefficients are used to adjust effect-size calculations for interpretation and planning of cTBS studies

Modulation of Motor Cortex Excitability Predicts Antidepressant Response to Prefrontal Cortex Repetitive Transcranial Magnetic Stimulation

Background: Repetitive transcranial magnetic stimulation (RTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is a treatment option for patients with medication-resistant major depressive disorder (MDD). However, antidepressant response is variable and there are currently no response predictors with sufficient accuracy for clinical use. Objective: We report on results of an observational open-label study to determine whether the modulatory effect of 10 Hz motor cortex (MC) rTMS is predictive of the antidepressant effect of 10 Hz DLPFC rTMS. Methods: Fifty-one medication-resistant MDD patients were enrolled for a 10-day treatment course of DLPFC rTMS and antidepressant response was assessed according to post-treatment reduction of the 17-item Hamilton Rating Scale for Depression score. Prior to treatment, we assessed the modulation of motor evoked potential (MEP) amplitude by MC rTMS. MEP's were induced with single TMS pulses and measured using surface electromyography. MEP modulation was calculated as the change of mean MEP amplitude after MC rTMS. Results: MEP modulation proved to be a robust predictor of reduction of clinician-rated depression severity following the course of DLPFC rTMS: larger MC rTMS-induced increase of corticospinal excitability anticipated a better antidepressant response. This was found both in univariate analyses (Spearman regression: rho=0.43, p<0.005) and a multivariable linear regression model (β=0.25, p<0.0001) controlling for baseline depression severity, age and resting motor threshold. Conclusions: These findings suggest that MC rTMS-induced modulation of corticospinal excitability warrants further evaluation as a potential predictive biomarker of antidepressant response to left DLPFC 10 Hz rTMS