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A Framework for Combining rTMS with Behavioral Therapy.

ABSTRACT: Upon its inception, repetitive transcranial magnetic stimulation (rTMS) was delivered at rest, without regard to the potential impact of activity occurring during or around the time of stimulation. rTMS was considered an experimental intervention imposed on the brain; therefore, the myriad features that might suppress or enhance its desired effects had not yet been explored. The field of rTMS has since grown substantially and therapeutic benefits have been reported, albeit with modest and inconsistent improvements. Work in this field accelerated following approval of a psychiatric application (depression), and it is now expanding to other applications and disciplines. In the last decade, experimental enquiry has sought new ways to improve the therapeutic benefits of rTMS, intended to enhance underlying brain reorganization and functional recovery by combining it with behavioral therapy. This concept is appealing, but poorly defined and requires clarity. We provide an overview of how combined rTMS and behavioral therapy has been delineated in the literature, highlighting the diversity of approaches. We outline a framework for study design and reporting such that the effects of this emerging method can be better understood.

SUBMITTER: Tsagaris KZ

PROVIDER: S-EPMC5108775 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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A Framework for Combining rTMS with Behavioral Therapy.

Tsagaris K Zoe KZ Labar Douglas R DR Edwards Dylan J DJ

Frontiers in systems neuroscience 20161115

Upon its inception, repetitive transcranial magnetic stimulation (rTMS) was delivered at rest, without regard to the potential impact of activity occurring during or around the time of stimulation. rTMS was considered an experimental intervention imposed on the brain; therefore, the myriad features that might suppress or enhance its desired effects had not yet been explored. The field of rTMS has since grown substantially and therapeutic benefits have been reported, albeit with modest and incons ...[more]

PMID: 27895557

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Project description:Neuromodulation technologies, such as transcranial magnetic stimulation (TMS), are promising tools for neurorehabilitation, aphasia therapy included, but not yet in common clinical use. Combined with behavioral techniques, in particular treatment-efficient Intensive Language-Action Therapy (ILAT, previously CIAT or CILT), TMS could substantially amplify the beneficial effect of such behavioral therapy alone (Thiel et al., 2013; Martin et al., 2014; Mendoza et al., 2016; Kapoor, 2017). In this randomized study of 17 subjects with post-stroke aphasia in the chronic stage, we studied the combined effect of ILAT and 1-Hz placebo-controlled navigated repetitive TMS (rTMS) to the right-hemispheric inferior frontal cortex-that is, to the anterior part of the non-dominant hemisphere's homolog Broca's area (pars triangularis). Patients were randomized to groups A and B. Patients in group A received a 2-week period of rTMS during naming training where they named pictures displayed on the screen once every 10 s, followed by 2 weeks of rTMS and naming combined with ILAT. Patients in group B received the same behavioral therapy but TMS was replaced by sham stimulation. The primary outcome measures for changes in language performance were the Western Aphasia Battery's aphasia quotient AQ; the secondary outcome measures were the Boston naming test (BNT) and the Action naming test (Action BNT, ANT). All subjects completed the study. At baseline, no statistically significant group differences were discovered for age, post-stroke time or diagnosis. ILAT was associated with significant improvement across groups, as documented by both primary and secondary outcome measures. No significant effect of rTMS could be documented. Our results agree with previous results proving ILAT's ability to improve language in patients with chronic aphasia. In contrast with earlier claims, however, a beneficial effect of rTMS in chronic post-stroke aphasia rehabilitation was not detected in this study. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03629665.

Project description:Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation tool potentially modulating pathological brain activity. Its clinical effectiveness is hampered by varying results and characterized by inter-individual variability in treatment responses. RTMS individualization might constitute a useful strategy to overcome this variability. A precondition for this approach would be that repeatedly applied protocols result in reliable effects. The condition tinnitus provides the advantage of immediate behavioral consequences (tinnitus loudness changes) after interventions and thus offers an excellent model to exemplify TMS personalization. The aim was to investigate the test-retest reliability of short rTMS stimulations in modifying tinnitus loudness and oscillatory brain activity as well as to examine the feasibility of rTMS individualization in tinnitus. Three short verum (1, 10, 20 Hz; 200 pulses) and one sham (0.1 Hz; 20 pulses) rTMS protocol were administered on two different days in 22 tinnitus patients. Before and after each protocol, oscillatory brain activity was recorded with electroencephalography (EEG), together with behavioral tinnitus loudness ratings. RTMS individualization was executed on the basis of behavioral and electrophysiological responses. Stimulation responders were identified via consistent sham-superior increases in tinnitus loudness (behavioral responders) and alpha power increases or gamma power decreases (alpha responders/gamma responders) in accordance with the prevalent neurophysiological models for tinnitus. It was feasible to identify individualized rTMS protocols featuring reliable tinnitus loudness changes (55% behavioral responder), alpha increases (91% alpha responder) and gamma decreases (100% gamma responder), respectively. Alpha responses primary occurred over parieto-occipital areas, whereas gamma responses mainly appeared over frontal regions. On the contrary, test-retest correlation analyses per protocol at a group level were not significant neither for behavioral nor for electrophysiological effects. No associations between behavioral and EEG responses were found. RTMS individualization via behavioral and electrophysiological data in tinnitus can be considered as a feasible approach to overcome low reliability at the group level. The present results open the discussion favoring personalization utilizing neurophysiological markers rather than behavioral responses. These insights are not only useful for the rTMS treatment of tinnitus but also for neuromodulation interventions in other pathologies, as our results suggest that the individualization of stimulation protocols is feasible despite absent group-level reliability.

Project description:Tobacco-related deaths exceed those resulting from homicides, suicides, motor vehicle accidence, alcohol consumption, illicit substance use, and acquired immunodeficiency syndrome (AIDS), combined. Amongst U.S. veterans, this trend is particularly concerning given that those suffering from posttraumatic stress disorder (PTSD)-about 11% of those receiving care from the Department of Veterans Affairs (VA)-have triple the risk of developing tobacco use disorder (TUD). The most efficacious strategies being used at the VA for smoking cessation only result in a 23% abstinence rate, and veterans with PTSD only achieve a 4.5% abstinence rate. Therefore, there is a critical need to develop more effective treatments for smoking cessation. Recent studies have revealed the insula as integrally involved in the neurocircuitry of TUD, specifically showing that individuals with brain lesions involving this region had drastically improved quit rates. Some of these studies show a probability of quitting up to 5 times greater compared to non-insula lesioned regions). Altered activity of the insula may be involved in the disruption of the salience network's (SN) connectivity to the executive control network (ECN), which compromises that patient's ability to switch between interoceptive states focused on cravings to executive and cognitive control. Thus, we propose a feasibility phase II randomized controlled trial (RCT) to study a patterned form of repetitive transcranial magnetic stimulation (rTMS), intermittent theta burst stimulation (iTBS), at 90% of the subject's resting motor threshold (rMT) applied over a region in the right post-central gyrus most functionally connected to the right posterior insula. We hypothesize that by increasing functional connectivity between the SN with the ECN to enhance executive control and by decreasing connectivity with the default mode network (DMN) to reduce interoceptive focus on withdrawal symptoms, we will improve smoking cessation outcomes. Fifty eligible veterans with comorbid TUD and PTSD will be randomly assigned to two conditions: active-iTBS + cognitive behavioral therapy (CBT) + nicotine replacement therapy (NRT) (n=25) or sham-iTBS + CBT + NRT (n=25). The primary outcome, feasibility, will be determined by achieving a recruitment of 50 participants and retention rate of 80%. The success of iTBS will be evaluated through self-reported nicotine use, cravings, withdrawal symptoms, and abstinence following quit date (confirmed by bioverification) along with evaluation for target engagement through neuroimaging changes, specifically connectivity differences between the insula and other regions of interest.

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A Framework for Combining rTMS with Behavioral Therapy.

Publications

A Framework for Combining rTMS with Behavioral Therapy.

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