Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation

Summary

This article describes new approaches to measure and strengthen functionally specific neural pathways with transcranial magnetic stimulation. These advanced noninvasive brain stimulation methodologies can provide new opportunities for the understanding of brain-behavior relations and development of new therapies to treat brain disorders.

Abstract

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.

Introduction

Noninvasive brain stimulation is a promising assessment tool and treatment for many neurological disorders, such as Parkinson's disease, Alzheimer's disease, and stroke^1,2,3,4. There is accumulating evidence establishing the relationship between the behavioral manifestations of neurological diseases and abnormalities of cortical excitability, neuroplasticity, cortico-cortical and cortico-subcortical connectivity^5,6. Therefore, basic knowledge about brain network dynamics and ....

Protocol

The following three TMS methods are described below. First, two methods are described to measure cortico-cortical connectivity using dual-site transcranial magnetic stimulation (dsTMS) while participants are either 1) at rest (resting state) or 2) performing an object-directed reach-to-grasp movement (task-dependent). Second, a cortical paired associative stimulation (cPAS) method is described to modulate the interplay between two brain areas in a controlled manner by pairing cortical stimuli (e.g., posterior parietal and primary motor cortices) to strengthen functional specific neural pathways with TMS and induce changes in cortical excitability. A representative dat....

Results

Figure 5 shows the size of an exemplar MEP response elicited in the FDI muscle by TMS for an unconditioned test stimuli (TS alone to M1, blue trace) or conditioned stimuli from PPC (CS-TS, red trace) while the participant was at rest (top panel) or planning a goal-directed grasping action to an object (bottom panel). At rest, the PPC exerts an inhibitory influence on ipsilateral M1, as shown by the decrease in MEP amplitudes potentiated by a subthreshold CS delivered over PPC 5 ms before a s.......

Discussion

The dual-site TMS method described here can be employed to investigate functional interactions between different cortical areas interconnected with the primary motor cortex while a participant is at rest or planning a goal-directed action. While brain imaging is correlative, basic knowledge from dual-site TMS methods can reveal causal brain-behavior relations associated with changes in cortico-cortical circuits. In addition, cortical paired associative stimulation with two TMS coils applied in areas interconnected with M.......

Materials

Name	Company	Catalog Number	Comments
Alpha B.I. D50 coil (coated)	Magstim		50mm coil
BrainSight 2.0 Software	Rogue Research		Neuronavigation software
BrainSight frameless Stereotactic System	Rogue Research		Neuronavigation equiptment
D702 Coil	Magstim		70mm coil
Discovery MR750	General Electric		3.0T MRI machine
Disposable Earplugs	3M		Foam earplugs
ECG Electrodes 30mm x 24mm	Coviden-Kendall	H124SG	Disposable electrodes
Four Channel Isolated Amplifier	Intronix Technologies Corporation	2024F	EMG amplifier
gGAMMAcap	g.tec Medical Engineering		EEG head cap
Micro1401-3	Cambridge Electronic Design		Scientific data recorder and processing machine
Nuprep Skin Prep Gel	Weaver and Company		Skin prep abrasive gel
Signal v.7	Cambridge Electronic Design		Data acquisition and analysis software
The Magstim BiStim2	Magstim		Transcranial magnetic stimulator (two 2002 units)