A Review of Transcranial Magnetic Stimulation and Multimodal Neuroimaging to Characterize Post-Stroke Neuroplasticity

Abstract

Following stroke, the brain undergoes various stages of recovery where the central nervous system can reorganize neural circuitry (neuroplasticity) both spontaneously and with the aid of behavioral rehabilitation and non-invasive brain stimulation. Multiple neuroimaging techniques can characterize common structural and functional stroke-related deficits, and importantly, help predict recovery of function. Diffusion tensor imaging (DTI) typically reveals increased overall diffusivity throughout the brain following stroke, and is capable of indexing the extent of white matter damage. Magnetic resonance spectroscopy (MRS) provides an index of metabolic changes in surviving neural tissue after stroke, serving as a marker of brain function. The neural correlates of altered brain activity after stroke have been demonstrated by abnormal activation of sensorimotor cortices during task performance, and at rest, using functional magnetic resonance imaging (fMRI). Electroencephalography (EEG) has been used to characterize motor dysfunction in terms of increased cortical amplitude in the sensorimotor regions when performing upper limb movement, indicating abnormally increased cognitive effort and planning in individuals with stroke. Transcranial magnetic stimulation (TMS) work reveals changes in ipsilesional and contralesional cortical excitability in the sensorimotor cortices. The severity of motor deficits indexed using TMS has been linked to the magnitude of activity imbalance between the sensorimotor cortices. In this paper, we will provide a narrative review of data from studies utilizing DTI, MRS, fMRI, EEG, and brain stimulation techniques focusing on TMS and its combination with uni- and multimodal neuroimaging methods to assess recovery after stroke. Approaches that delineate the best measures with which to predict or positively alter outcomes will be highlighted.

Keywords: diffusion tensor imaging; electroencephalography; functional MRI; magnetic resonance spectroscopy; multimodal neuroimaging; sensorimotor recovery; stroke; transcranial magnetic stimulation.

Figure 1

A summary of our current understanding of factors that contribute to post-stroke impairment (I) and the assessment tools available for quantifying these changes (II). Loss of white matter projections is illustrated as a decreased number of CST projections (IA). Diaschisis, a remote functional depression, can impact intra- and interhemispheric areas (IB). A focal lesion can disrupt the mutual balanced inhibition between hemispheres. Damage from stroke disrupts the balance by decreasing the inhibition of the contralesional hemisphere, which results in increased inhibition of the injured hemisphere (IC). FreeSurfer-based volumetric analysis, using structural T1s, can be manually modified to correct for errors in the automated segmentation of injured brains (IIA). Identification of CST and CC in an individual with chronic stroke utilizing tractography of diffusion-weighted images (IIB). The axial brain image identifies the voxel placement in the hand knob of an individual with chronic stroke, the resulting spectra quantifies multiple neurotransmitters (IIC). BOLD signal during movements of the unaffected and affected hand in individuals with left-sided subcortical stroke; modified, with permission, from Grefkes et al. (16) (IID). EEG trace from an electrode located at Cz (over primary motor cortex) in an individual with chronic stroke and a healthy control as they take a step (time 0) (IIE). Transcallosal inhibition evoked from stimulation over ipsilesional and contralesional primary motor cortex (IIF). Ipsilesional stimulation failed to produce an observable iSP in the ipsilateral (to the TMS pulse) limb, whereas contralesional stimulation evoked a quantifiable iSP in the ipsilateral (to the TMS pulse) limb. iSP occurs in the time between the green (onset) and red (offset) lines. CST, cortical spinal tract; CC, corpus callosum; fMRI, functional MRI; BOLD, blood oxygen level dependent; iSP, ipsilateral silent period; TMS, transcranial magnetic stimulation.

Figure 2

A schematic of TMS-evoked measures of single and paired-pulse corticospinal excitability. Examples of TMS-evoked measures of corticospinal excitability recorded by surface electrodes over the extensor carpi radialis (ECR) muscle. Displayed are examples of motor-evoked potential (MEP), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), transcallosal inhibition (TCI), and cortical silent period (CSP). TMS, transcranial magnetic stimulation; EMG, electromyography.

Figure 3

A schematic of the theoretical effects of excitatory rTMS over the ipsilesional cortex. Decreased ipsilesional cortical excitability may contribute to decreased corticospinal transmission resulting in diminished motor function of the paretic upper limb. Ipsilesional excitatory rTMS may increase the excitability of the damaged cortex, thereby contributing to enhanced corticospinal transmission potentially leading to better motor function of the paretic upper limb. rTMS, repetitive transcranial magnetic stimulation.

Figure 4

A schematic of the theoretical effects of inhibitory rTMS over the contralesional cortex. Increased interhemispheric inhibition (IHI) from the contralesional to ipsilesional cortex via the corpus callosum may contribute to decreased ipsilesional corticospinal excitability and diminished motor function of the paretic upper limb. Contralesional inhibitory rTMS may suppress contralesional to ipsilesional IHI and assist in improving ipsilesional corticospinal transmission, potentially leading to better motor function of the paretic upper limb. rTMS, repetitive transcranial magnetic stimulation.