TMS Impact on Cognitive Sequencing
Recruiting in Palo Alto (17 mi)
Overseen byJohn E Desmond, Ph.D.
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Johns Hopkins University
Must not be taking: Anxiolytics, Antidepressants, Neuroleptics, Sedatives
Disqualifiers: Neurological disorder, Stroke, Epilepsy, others
No Placebo Group
Trial Summary
What is the purpose of this trial?Although there is increasing recognition that the cerebellum is involved in cognition as well as motor function, the manner in which the cerebellum contributes to cognition is uncertain. One theory that might account for both motor and cognitive contributions of the cerebellum is that the cerebellum is involved in sequencing of relevant events or stimuli. Previous experiments have suggested that disruption of the cerebellum impairs the prediction of the next event in a sequence. The present experiment will examine the impact of cerebellar stimulation on brain activation during the performance of both sequence-demanding and non-sequence-demanding tasks.
Will I have to stop taking my current medications?
Yes, you will need to stop taking anxiolytic, antidepressant, neuroleptic, or sedative medications to participate in this trial.
What data supports the effectiveness of the treatment TMS Impact on Cognitive Sequencing?
Research shows that repetitive transcranial magnetic stimulation (rTMS) can influence cognitive tasks, such as improving working memory and modulating sequence learning, by targeting specific brain areas like the dorsolateral prefrontal cortex. This suggests that rTMS might be effective in enhancing cognitive sequencing by altering brain activity in targeted regions.
12345Is transcranial magnetic stimulation (TMS) generally safe for humans?
Transcranial magnetic stimulation (TMS) is generally considered safe, but it can cause seizures in rare cases and may have temporary effects on brain function. Most studies suggest that serious problems are unlikely, but further research is needed to fully understand all potential side effects.
678910How does the TMS treatment for cognitive sequencing differ from other treatments?
This TMS treatment is unique because it uses non-invasive brain stimulation to specifically target cognitive sequencing tasks, allowing researchers to explore causal brain-behavior relationships and the timing of neural processes, unlike traditional treatments that may not provide such precise control over brain activity.
13111213Eligibility Criteria
This trial is for individuals aged 18-50 who can consent, have at least an 8-year education, speak English fluently, and are right-handed. It's not for those with recent drug use, cognitive impairments due to neurological disorders, psychiatric disorders including substance abuse, stroke history, MRI contraindications or visual deficits.Inclusion Criteria
I am between 18 and 50 years old.
I understand the study and can agree to participate.
You have completed at least 8 years of formal education.
+2 more
Exclusion Criteria
Uncorrected visual deficits by self-report
Illicit drug use within 30 days of MRI scanning
Contraindications for MRI scanning
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants undergo TMS stimulation during sequence-demanding and non-sequence-demanding tasks, with brain activation measured via fMRI
1 hour per session
Multiple sessions (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study tests the effect of cerebellar stimulation on brain activity during tasks that require sequencing and those that don't. Participants will undergo Transcranial Magnetic Stimulation (TMS) while performing these tasks to see how it affects their brain function.
2Treatment groups
Experimental Treatment
Active Control
Group I: Cerebellar StimulationExperimental Treatment4 Interventions
TMS will be administered to the cerebellum on half the trials of a sequence-demanding task, and on half the trials of a non-sequence-demanding task. Task order will be counterbalanced.
Group II: Occipital StimulationActive Control4 Interventions
TMS will be administered to an occipital control region on half the trials of a sequence-demanding task, and on half the trials of a non-sequence-demanding task. Task order will be counterbalanced.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns Hopkins University School of MedicineBaltimore, MD
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Who Is Running the Clinical Trial?
Johns Hopkins UniversityLead Sponsor
National Institute of Mental Health (NIMH)Collaborator
References
Modulating Visuomotor Sequence Learning by Repetitive Transcranial Magnetic Stimulation: What Do We Know So Far? [2023]Predictive processes and numerous cognitive, motor, and social skills depend heavily on sequence learning. The visuomotor Serial Reaction Time Task (SRTT) can measure this fundamental cognitive process. To comprehend the neural underpinnings of the SRTT, non-invasive brain stimulation stands out as one of the most effective methodologies. Nevertheless, a systematic list of considerations for the design of such interventional studies is currently lacking. To address this gap, this review aimed to investigate whether repetitive transcranial magnetic stimulation (rTMS) is a viable method of modulating visuomotor sequence learning and to identify the factors that mediate its efficacy. We systematically analyzed the eligible records (n = 17) that attempted to modulate the performance of the SRTT with rTMS. The purpose of the analysis was to determine how the following factors affected SRTT performance: (1) stimulated brain regions, (2) rTMS protocols, (3) stimulated hemisphere, (4) timing of the stimulation, (5) SRTT sequence properties, and (6) other methodological features. The primary motor cortex (M1) and the dorsolateral prefrontal cortex (DLPFC) were found to be the most promising stimulation targets. Low-frequency protocols over M1 usually weaken performance, but the results are less consistent for the DLPFC. This review provides a comprehensive discussion about the behavioral effects of six factors that are crucial in designing future studies to modulate sequence learning with rTMS. Future studies may preferentially and synergistically combine functional neuroimaging with rTMS to adequately link the rTMS-induced network effects with behavioral findings, which are crucial to develop a unified cognitive model of visuomotor sequence learning.
Facilitation of performance in a working memory task with rTMS stimulation of the precuneus: frequency- and time-dependent effects. [2019]Although improvements in performance due to TMS have been demonstrated with some cognitive tasks, performance improvement has not previously been demonstrated with working memory tasks. In the present study, a delayed match-to-sample task was used in which repetitive TMS (rTMS) at 1, 5, or 20 Hz was applied to either left dorsolateral prefrontal or midline parietal cortex during the retention (delay) phase of the task. Only 5 Hz stimulation to the parietal site resulted in a significant decrease in reaction time (RT) without a corresponding decrease in accuracy. This finding was replicated in a second experiment, in which 5 Hz rTMS at the parietal site was applied during the retention phase or during presentation of the recognition probe. Significant speeding of RT occurred in the retention phase but not the probe phase. This finding suggests that TMS may improve working memory performance, in a manner that is specific to the timing of stimulation relative to performance of the task, and to stimulation frequency.
Neural effects of TMS trains on the human prefrontal cortex. [2023]How does a train of TMS pulses modify neural activity in humans? Despite adoption of repetitive TMS (rTMS) for the treatment of neuropsychiatric disorders, we still do not understand how rTMS changes the human brain. This limited understanding stems in part from a lack of methods for noninvasively measuring the neural effects of a single TMS train - a fundamental building block of treatment - as well as the cumulative effects of consecutive TMS trains. Gaining this understanding would provide foundational knowledge to guide the next generation of treatments. Here, to overcome this limitation, we developed methods to noninvasively measure causal and acute changes in cortical excitability and evaluated this neural response to single and sequential TMS trains. In 16 healthy adults, standard 10 Hz trains were applied to the dorsolateral prefrontal cortex (dlPFC) in a randomized, sham-controlled, event-related design and changes were assessed based on the TMS-evoked potential (TEP), a measure of cortical excitability. We hypothesized that single TMS trains would induce changes in the local TEP amplitude and that those changes would accumulate across sequential trains, but primary analyses did not indicate evidence in support of either of these hypotheses. Exploratory analyses demonstrated non-local neural changes in sensor and source space and local neural changes in phase and source space. Together these results suggest that single and sequential TMS trains may not be sufficient to modulate local cortical excitability indexed by typical TEP amplitude metrics but may cause neural changes that can be detected outside the stimulation area or using phase or source space metrics. This work should be contextualized as methods development for the monitoring of transient noninvasive neural changes during rTMS and contributes to a growing understanding of the neural effects of rTMS.
Suppressing versus releasing a habit: frequency-dependent effects of prefrontal transcranial magnetic stimulation. [2006]When subjects are required to generate a random sequence of numbers they typically produce too many forward and backward 'counts' (e.g. 5-6, 4-3). This counting bias is interpreted as the consequence of an interference by overlearned tendencies to arrange numbers according to their natural order. Inhibition of such well-learned routines is known to rely on frontal lobe functioning. We examined differential effects of slow (1 Hz) and fast (10 Hz) repetitive transcranial magnetic stimulation (rTMS) over the left or right dorsolateral prefrontal cortex (DLPFC) on random number generation (RNG) performance. Eighteen healthy men performed an RNG task. Those subjects stimulated over the left DLPFC showed a frequency-dependent rTMS effect: counting bias was significantly reduced after the 1 Hz stimulation compared with baseline, but significantly exaggerated after the 10 Hz stimulation compared with 1 Hz stimulation. In contrast, the sequences of the subjects stimulated over the right DLPFC showed the well-known excess of counting in all conditions (i.e. baseline, 1 Hz and 10 Hz). These findings confirm the functional importance of specifically the left DLPFC in sequential response production and show, for the first time, that rTMS affects cognitive processing in a frequency-dependent manner.
Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation. [2020]Understanding interactions between brain areas is important for the study of goal-directed behavior. Functional neuroimaging of brain connectivity has provided important insights into fundamental processes of the brain like cognition, learning, and motor control. However, this approach cannot provide causal evidence for the involvement of brain areas of interest. Transcranial magnetic stimulation (TMS) is a powerful, noninvasive tool for studying the human brain that can overcome this limitation by transiently modifying brain activity. Here, we highlight recent advances using a paired-pulse, dual-site TMS method with two coils that causally probes cortico-cortical interactions in the human motor system during different task contexts. Additionally, we describe a dual-site TMS protocol based on cortical paired associative stimulation (cPAS) that transiently enhances synaptic efficiency in two interconnected brain areas by applying repeated pairs of cortical stimuli with two coils. These methods can provide a better understanding of the mechanisms underlying cognitive-motor function as well as a new perspective on manipulating specific neural pathways in a targeted fashion to modulate brain circuits and improve behavior. This approach may prove to be an effective tool to develop more sophisticated models of brain-behavior relations and improve diagnosis and treatment of many neurological and psychiatric disorders.
Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. [2022]The methodology used for the application of repetitive transcranial magnetic stimulation (TMS) is such that it may induce a placebo effect. Respectively, adverse events (AEs) can occur when using a placebo, a phenomenon called nocebo. The primary aim of our meta-analysis is to establish the nocebo phenomena during TMS. Safety and tolerability of TMS were also studied.
Side effects of repetitive transcranial magnetic stimulation. [2005]The side effects of repetitive transcranial magnetic stimulation are largely unexplored and the limits of safe exposure have not been determined except as regards the acute production of seizures. Although tissue damage is unlikely, however, cognitive and other adverse effects have been observed and the possibility of unintended long-term changes in brain function are theoretically possible.
Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. [2022]Single-pulse transcranial magnetic stimulation (TMS) is a safe and useful tool for investigating various aspects of human neurophysiology, particularly corticospinal function, in health and disease. Repetitive TMS (rTMS), however, is a more powerful and potentially dangerous modality, capable of regionally blocking or facilitating cortical processes. Although there is evidence that rTMS is useful for treating clinical depression, and possibly other brain disorders, it had caused 7 known seizures by 1996 and could have other undesirable effects. In June 1996 a workshop was organized to review the available data on the safety of rTMS and to develop guidelines for its safe use. This article summarizes the workshop's deliberations. In addition to issues of risk and safety, it also addresses the principles and applications of rTMS, nomenclature, and potential therapeutic effects of rTMS. The guidelines for the use of rTMS, which are summarized in an appendix, cover the ethical issues, recommended limits on stimulation parameters, monitoring of subjects (both physiologically and neuropsychologically), expertise and function of the rTMS team, medical and psychosocial management of induced seizures, and contra-indications to rTMS.
Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. [2021]Transcranial magnetic stimulation (TMS) can cause seizures in healthy individuals and patients. However, the rate at which this occurs is unknown. We estimated the risk of seizure and other adverse events with TMS.
The safety of transcranial magnetic stimulation reconsidered: evidence regarding cognitive and other cerebral effects. [2007]The potential of transcranial magnetic stimulation (TMS) to cause undesired or unexpected effects on cognition and other cerebral functions has received only limited study, although extensive clinical use has suggested that obvious problems are unlikely. Evidence so far accumulated suggests that exposure to TMS in the expected clinical situations will have no persistent effects on the electroencephalogram (EEG) or on cognitive function, although transient effects may occur. The absence of increases in either prolactin or adrenocorticotropic hormone (ACTH) in subjects undergoing TMS indicates that seizure-like events do not routinely occur, although recent evidence suggests that TMS may cause seizures or enhance the occurrence of epileptiform abnormalities in circumstances of heightened susceptibility. Despite these observations, treated seizure patients are unlikely to experience seizures with TMS. The technique is generally safe, but not entirely free from unwanted effects, and further study to define those effects is warranted.
Transcranial magnetic stimulation for investigating causal brain-behavioral relationships and their time course. [2022]Transcranial magnetic stimulation (TMS) is a safe, non-invasive brain stimulation technique that uses a strong electromagnet in order to temporarily disrupt information processing in a brain region, generating a short-lived "virtual lesion." Stimulation that interferes with task performance indicates that the affected brain region is necessary to perform the task normally. In other words, unlike neuroimaging methods such as functional magnetic resonance imaging (fMRI) that indicate correlations between brain and behavior, TMS can be used to demonstrate causal brain-behavior relations. Furthermore, by varying the duration and onset of the virtual lesion, TMS can also reveal the time course of normal processing. As a result, TMS has become an important tool in cognitive neuroscience. Advantages of the technique over lesion-deficit studies include better spatial-temporal precision of the disruption effect, the ability to use participants as their own control subjects, and the accessibility of participants. Limitations include concurrent auditory and somatosensory stimulation that may influence task performance, limited access to structures more than a few centimeters from the surface of the scalp, and the relatively large space of free parameters that need to be optimized in order for the experiment to work. Experimental designs that give careful consideration to appropriate control conditions help to address these concerns. This article illustrates these issues with TMS results that investigate the spatial and temporal contributions of the left supramarginal gyrus (SMG) to reading.
Combining transcranial magnetic stimulation and functional imaging in cognitive brain research: possibilities and limitations. [2019]Transcranial magnetic stimulation (TMS) is a widely used tool for the non-invasive study of basic neurophysiological processes and the relationship between brain and behavior. We review the physical and physiological background of TMS and discuss the large body of perceptual and cognitive studies, mainly in the visual domain, that have been performed with TMS in the past 15 years. We compare TMS with other neurophysiological and neuropsychological research tools and propose that TMS, compared with the classical neuropsychological lesion studies, can make its own unique contribution. As the main focus of this review, we describe the different approaches of combining TMS with functional neuroimaging techniques. We also discuss important shortcomings of TMS, especially the limited knowledge concerning its physiological effects, which often make the interpretation of TMS results ambiguous. We conclude with a critical analysis of the resulting conceptual and methodological limitations that the investigation of functional brain-behavior relationships still has to face. We argue that while some of the methodological limitations of TMS applied alone can be overcome by combination with functional neuroimaging, others will persist until its physical and physiological effects can be controlled.
Pre-stimulus sham TMS facilitates target detection. [2022]Transcranial magnetic stimulation (TMS) allows non-invasive manipulation of brain activity during active task performance. Because every TMS pulse is accompanied by non-neural effects such as a clicking sound and somato-sensation on the head, control conditions are required to ensure that changes in task behavior are indeed due to the induced neural effects. However, the non-neural effects of TMS in the context of a given task performance are largely unknown and, consequently, it is unclear what constitutes a valid control condition. We explored the non-neural effects of TMS on visual target detection. Participants received single pulse sham TMS to each hemisphere at different time points prior to target appearance during a visual target detection task. It was hypothesized that the clicking sound of a sham TMS pulse differentially affects performance depending on the location of the coil and the timing of the pulse.Our results show that, first, sham TMS caused a facilitation of reaction times when preceding the target stimulus by 150, 200, and 250 ms, whereas earlier and later time windows were not effective. Second, positioning the TMS coil ipsilateral instead of contralateral relative to the target stimulus improved reaction times. Third, infrequent noTMS trials that were interleaved with sham TMS trials had oddball-like properties resulting in increased reaction times during noTMS. The clicking sound produced by sham TMS influences task performance in multiple ways. These non-neural effects of TMS need to be controlled for in TMS research and the present findings provide an empirical basis for deciding what constitutes a valid control condition.