- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03114488
Modulating Human Cortical Plasticity With Transcranial Electrical Stimulation
Study Overview
Detailed Description
Experience dependent plasticity is a fundamental property of the brain. It allows neural systems to adapt in response to environmental input and subserves the vital functions of learning and memory. Deficits in plasticity are thought play a causal role in the pathophysiology of several psychiatric disorders, including schizophrenia (SZ). Treatments that can probe or even enhance plasticity have potential to be of great clinical value. Non-invasive neuromodulation via transcranial direct current stimulation (tDCS) is a promising method for modulating neural plasticity. tDCS delivers low-intensity direct current to cortical areas, thereby facilitating or inhibiting neural activity in a polarity specific manner. Its positive effects in a wide range of neurological conditions, as well as its tolerability and low cost, have catalyzed the use of tDCS as a clinical tool. However, issues regarding efficacy and variability of outcomes continue to limit the clinical potential of this promising intervention. Investigation of the physiological mechanisms that subserve tDCS effects in humans is needed to inform treatment protocols and enhance efficacy.
Studies in tissue models have revealed that direct current application alters membrane polarization and modulates long-term potentiation and depression (LTP/D), key mechanisms of synaptic plasticity. In Vivo application of tDCS has been shown to modulate LTP and learning in the rat hippocampus and motor cortex. This modulation was shown to be, persistent, input-specific, and N-methyl-D-aspartate receptor (NMDAR) dependent. These works demonstrate the utility of tDCS in modifying plasticity and learning. Given the limitations placed on invasive procedures, investigating the effects of tDCS on plasticity in the human brain has proved to be much more challenging, limiting the translation and thus the practical utility of the basic research. Utilizing modern, non-invasive methods to probe plasticity in humans has the potential to bridge this translational gap.
Recently developed techniques utilizing electroencephalography (EEG) now enable the non-invasive interrogation of plasticity in the human cortex. Clapp et al., (2005) demonstrated the feasibility of inducing LTP in the cortex by rapid presentation of visual or auditory stimuli, observable as changes in sensory evoked potentials recorded from the scalp. This paradigm, termed stimulus specific plasticity (SSP), is a direct parallel to the high frequency electrical stimulation protocols used to elicit LTP in tissue preparations and satisfies the cardinal features of Hebbian plasticity. Thus sensory-induced plasticity is a useful measure of cortical plasticity that is readily translatable from animals to humans. Further, several studies have used SSP to reveal plasticity deficits in SZ and bipolar disorder, demonstrating the clinical relevance of this assay. In addition, because SSP is a functionally relevant manifestation of LTP, it enables assessment of the efficacy of interventions that target plasticity mechanisms, making it the perfect tool to use for evaluating tDCS effects.
The premise of this proposal is based on prior findings demonstrating the modulatory effect of tDCS on synaptic plasticity in animal and tissue models. Due to methodological limitations, very little work has been done to translate these findings to humans. Because the direct effects of tDCS on plasticity in the humans remains uninvestigated, the overarching goal of this proposal is to assess the in vivo efficacy of tDCS in modulating synaptic plasticity in the auditory cortex of the human brain. To this end, the researchers will conduct a study featuring simultaneous tDCS and EEG recording in a both healthy participants and SZ patients. The two separate cohorts will be randomized into either three or two treatment arms (cathodal, anodal, sham - healthy participants / Anodal and Sham - SZ patients). All subjects will undergo EEG recording during presentation of auditory tones to establish baseline auditory evoked potentials (AEP). LTP will be induced by a high frequency presentation (sensory tetanus) of that same tone for 5 min. Stimulation will begin 10 min prior to the LTP induction and will stop at the end the 5 min period. Post-tetanus EEG recordings of AEP's will be compared to baseline AEP's to analyze the impact of tDCS on neural plasticity.
Specific Aim 1: Evaluate the effects of Anodal tDCS vs. Cathodal tDCS vs. Sham on induction of LTP in a healthy population: Significant findings demonstrate that anodal tDCS impacts neuronal function by enhancing LTP induction. Based on these findings in animal and tissue models, it is expected that anodal tDCS will lead to a greater facilitation of LTP than cathodal or sham stimulation Specific Aim 2: Evaluate the efficacy of Anodal tDCS in enhancing induction of LTP in a population of SZ Patients: SZ patients show deficient capacity to support LTP in the auditory cortex. Effect of tDCS are putatively emergent from modulation of NMDAR dependent plasticity mechanisms. Using the SSP paradigm the study will evaluate the efficacy of tDCS in modulating LTP measures. Based on mechanistic work in animals demonstrating the NMDAR dependent action of tDCS, it is expected that anodal tDCS will enhance the induction of LTP compared to sham.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Minnesota
-
Minneapolis, Minnesota, United States, 55414
- Kelvin O. Lim
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 18-50
- No psychiatric medication prescription
- No clinically significant head injury or neurological disease
- No dependence in the past 6 month or no substance abuse in the past month
- Sufficient spoken english to understand testing procedures
- Ability to give informed consent
Exclusion Criteria:
- History of transcranial electrical stimulation (tES) or other cortical energy exposure in the past 12 months; including
- participation in any neuromodulation studies
- History of seizures or epilepsy
- History of metallic cranial plates, screws, or implanted device
- History of craniotomy
- History of eczema on the scalp
- History of traumatic brain injury
- History of mental illness (Healthy group)
- Diagnosis of bipolar disorder
- Diagnosis of major depression
- Unable to give informed consent
- Hairstyle that is braided in cornrows or in dreadlocks
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Sham Comparator: Sham Stimulation
|
Transcranial electrical stimulator
|
Experimental: Anodal Stimulation
|
Transcranial electrical stimulator
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Amplitude of N100 Component of the Auditory Evoked Potential
Time Frame: approximately 1 hour
|
The amplitude of the N100 component will be averaged across individuals in each group.
Grand averages from the two groups will be compared.
Outcome is reported as the change from baseline to post-treatment (approximately 1 hour).
|
approximately 1 hour
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1703M09401
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Healthy
-
Prevent Age Resort "Pervaya Liniya"RecruitingHealthy Aging | Healthy Diet | Healthy LifestyleRussian Federation
-
Maastricht University Medical CenterCompletedHealthy Volunteers | Healthy Subjects | Healthy AdultsNetherlands
-
Yale UniversityNot yet recruitingHealth-related Benefits of Introducing Table Olives Into the Diet of Young Adults: Olives For HealthHealthy Diet | Healthy Lifestyle | Healthy Nutrition | CholesterolUnited States
-
University of PennsylvaniaActive, not recruitingHealthy | Healthy AgingUnited States
-
Chalmers University of TechnologyGöteborg UniversityCompletedHealthy | Nutrition, HealthySweden
-
Hasselt UniversityRecruitingHealthy | Healthy AgingBelgium
-
Galera Therapeutics, Inc.Syneos HealthCompleted
-
Galera Therapeutics, Inc.Syneos HealthCompletedHealthy | Healthy VolunteersAustralia
-
University of ManitobaNot yet recruitingHealthy | Healthy Diet
-
King's College LondonUniversity of ReadingCompletedHealthy | Healthy AgingUnited Kingdom
Clinical Trials on tDCS
-
Hôpital le VinatierCompletedSchizophrenia | Auditory HallucinationsFrance, Tunisia
-
Universidad de AlmeriaSecretaría General de Universidades, Investigación y Tecnología, Junta de...Enrolling by invitationSubstance-Related DisordersSpain
-
Northeastern UniversityMassachusetts General Hospital; National Institute on Aging (NIA)Unknown
-
Nachum Soroker, MDUnknown
-
Bambino Gesù Hospital and Research InstituteCompleted
-
University of North Carolina, Chapel HillNational Institute of Mental Health (NIMH)CompletedMotor Activity | Motor NeuroplasticityUnited States
-
Charite University, Berlin, GermanyCompletedMigraine With Aura | CADASIL | Cerebral Microangiopathy | ICA StenosisGermany
-
Universidade Federal de PernambucoCompleted
-
Thorsten RudroffTerminatedMultiple Sclerosis | Neuropathic PainUnited States
-
University of California, Los AngelesNational Institute of Mental Health (NIMH)Completed