Modulating Human Cortical Plasticity With Transcranial Electrical Stimulation

January 28, 2020 updated by: University of Minnesota
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 also thought play a causal role in the pathophysiology of several psychiatric disorders, specifically schizophrenia (SZ). Treatments that can probe or even enhance plasticity have potential to be of great clinical and research 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. Due to its low cost and safety, tDCS has been employed in a wide variety of studies, but much remains unknown regarding its mechanism of action in humans. Experiments carried out in animal and tissue models indicate that tDCS modulates synaptic plasticity mechanisms of long term potentiation and depression (LTP/D), however, these findings have never been translated to human subjects, limiting the practical utility of the research. Recently developed electroencephalographic (EEG) based measures now allow the interrogation of synaptic plasticity non-invasively in humans, making it possible to explore the effects of tDCS on human brain plasticity.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

41

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Minneapolis, Minnesota, United States, 55414
        • Kelvin O. Lim

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2017

Primary Completion (Actual)

October 5, 2018

Study Completion (Actual)

October 5, 2018

Study Registration Dates

First Submitted

March 22, 2017

First Submitted That Met QC Criteria

April 10, 2017

First Posted (Actual)

April 14, 2017

Study Record Updates

Last Update Posted (Actual)

February 10, 2020

Last Update Submitted That Met QC Criteria

January 28, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Other Study ID Numbers

  • 1703M09401

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

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.

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