TMS as a Biological Marker of Neuroplasticity

Completed

• Conditions: Aphasia; Stroke
• Interventions: Device: Transcranial Magnetic Stimulation

• Registration Number: NCT02867670
• Lead Sponsor: University of Pennsylvania

Brief Summary

TMS is a non-invasive brain stimulation technique, which can be used to change the activity of a person's brain cells without needles or surgery. In this study, the invesigators are interested in the brain's ability to adapt (also called "neuroplasticity") and regain language functioning after a stroke-specifically, they want to determine whether how a person's brain responds to TMS in the short term can be used to predict how well they will recover language abilities in the long term.

Detailed Description

Aphasia is an impairment of language that may occur after a stroke (or other brain injuries). A person with aphasia may experience difficulties speaking, understanding speech, reading, writing, or any combination of these symptoms. Despite advances in understanding of language systems and functional neuroplasticity after brain injury, accurate predictors of aphasia recovery after stroke remain elusive. In order to better understand, predict, and enhance language improvement after stroke, there is a critical need to develop tools that can assess the influence of neuroplasticity on recovery.

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation tool that has been used to predict the brain's neuroplastic capacity by assessing physiological responses observed immediately following administration of TMS. Additionally, difference in the physiological response to TMS have been shown to be affected by polymorphism in the gene coding for brain derived neurotrophic factor (BDNF). The current project explores the idea that because neural mechanisms of plasticity are essential determinants of both recovery after brain injury and physiologic response to TMS, magnetic brain stimulation could be employed as an indicator of the capacity for clinically relevant neuroplasticity, and potentially as a predictor of recovery from post-stroke deficits such as aphasia

The goals of this protocol are to 1) explore the utility of theta burst stimulation (TBS), a type of transcranial magnetic stimulation (TMS), as a tool for assessing neuroplasticity in the language system in patients with aphasia due to stroke, 2) and to assess the utility of TBS as a biomarker and predictor of functional recovery in patients with aphasia.

This protocol will encompass two separate but related experiments. In the first experiment, the investigators will apply TBS to brain regions that control language functions in aphasic patients in order to determine whether we can induce a transient improvement in naming ability. They will use a statistical model they have developed to categorize patients as either having High Plasticity or Low Plasticity. The investigators will determine whether this distinction predicts which patients are likely to have greater TBS-induced changes in language performance. In the second experiment, in the same patients, the investigators will apply TBS to the motor cortex to elicit changes in motor evoked potentials (MEPs). Using the same model to form matched groups, we predict that MEPs will be more attenuated in High Plasticity groups compared to the Low Plasticity group.

Study Timeline

• Study Start: 2013-07
• Study First Submitted: 2016-06-03
• Study First Submitted QC: 2016-08-11
• Study First Posted: 2016-08-16
• Primary Completion: 2019-06
• Study Completion: 2020-06
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-07
• Last Update Posted: 2020-07-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

• Must have Aphasia due to stroke
• Stroke must have occurred at least 6 months ago
• Native English speaker
• Willing & able to have a MRI

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Exclusion Criteria

• Disorders of the brain other than stroke (i.e. tumor, Parkinsons, cancer... etc.)
• History of seizures/ or epilepsy
• Pacemaker or other implanted electronic devices
• Consumption of medications that lower seizure threshold
• History of psychiatric disorders
• History of tinnitus
• Current abuse of drugs or alcohol
• Pregnant or plan to get pregnant

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Transcranial Magnetic Stimulation of Motor Cortex	Transcranial Magnetic Stimulation	All study participants will receive real TMS stimulation over the primary motor cortex in order to collect physiological measures which will later be correlated with measures of neuroplasticity. There is NO placebo stimulation.
Transcranial Magnetic Stimulation of Language Cortex	Transcranial Magnetic Stimulation	All study participants will receive real TMS stimulation over the language cortex and a control site (i.e. vertex). Transient changes in speech production will be recorded and compared to measures of neuroplasticity. There is NO placebo stimulation.

Primary Outcome Measures

Name	Time	Method
Transient TBS-induced changes in language performance	Up to 4 weeks	Participants will be asked to perform a 40-item picture naming task pre/post TBS stimulation. Stimulation will occur at language cortex and vertex (order will be counterbalanced). Transient changes in naming abilities will be measured directly by assessing naming performance.
Transient TBS-induced changes in motor evoked potentials (MEPs)	Up to 2 week	Single-Pulse TMS will be used to measure MEPs prior to and after stimulation. When measuring MEPs, single pulses of TMS will be administered at approximately 120% of motor threshold, and with a minimum interstimulus interval of 5 seconds. Mean MEP amplitudes will be calculated by averaging the MEP amplitudes generated by 20 pulses. MEP measures will be obtained three times in order to establish a stable baseline. This procedure will be followed by TBS delivered to the optimal site in the motor cortex. TBS will be applied to the region of the primary motor cortex (M1) representing the hand. After TBS, MEPs will be acquired, at 0-, 10-, 20-, 30-, 40-, and 60-min post-stimulation.

Secondary Outcome Measures

Name	Time	Method
Safety and Tolerability of TBS in patient with aphasia	Through study completion	We will collect the number of patients with TMS-related adverse events.

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States