Evaluating the Abnormality of Bilateral Motor Cortex Activity in Subacute Stroke Patients Executing a Unimanual Motor Task With Increasing Demand on Precision

Abstract

Abnormal contralesional M1 activity is consistently reported in patients with compromised upper limb and hand function after stroke. The underlying mechanisms and functional implications of this activity are not clear, which hampers the development of treatment strategies targeting this brain area. The goal of the present study was to determine the extent to which contralesional M1 activity can be explained by the demand of a motor task, given recent evidence for increasing ipsilateral M1 activity with increasing demand in healthy age-matched controls. We hypothesized that higher activity in contralesional M1 is related to greater demand on precision in a hand motor task. fMRI data were collected from 19 patients with ischemic stroke affecting hand function in the subacute recovery phase and 31 healthy, right-handed, age-matched controls. The hand motor task was designed to parametrically modulate the demand on movement precision. Electromyography data confirmed strictly unilateral task performance by all participants. Patients showed significant impairment relative to controls in their ability to perform the task in the fMRI scanner. However, patients and controls responded similarly to an increase in demand for precision, with better performance for larger targets and poorer performance for smaller targets. Patients did not show evidence of elevated ipsilesional or contralesional M1 blood oxygenation level-dependent (BOLD) activation relative to healthy controls and mean BOLD activation levels were not elevated for patients with poorer performance relative to patients with better task performance. While both patients and healthy controls showed demand-dependent increases in BOLD activation in both ipsilesional/contralateral and contralesional/ipsilateral hemispheres, patients with stroke were less likely to show evidence of a linear relationship between the demand on precision and BOLD activation in contralesional M1 than healthy controls. Taken together, the findings suggest that task demand affects the BOLD response in contralesional M1 in patients with stroke, though perhaps less strongly than in healthy controls. This has implications for the interpretation of reported abnormal bilateral M1 activation in patients with stroke because in addition to contralesional M1 reorganization processes it could be partially related to a response to the relatively higher demand of a motor task when completed by patients rather than by healthy controls.

Hemodynamic activity is not parsimoniously tuned to index-of-difficulty in movement with dual requirements on speed-accuracy

“…For instance, a reach from the far left to the far right may entail an elbow movement from flexion to extension in our study, whereas movements with short distance may involve only elbow extension. Additionally, our reaching paradigm involves large-extent whole-arm movements, which is different from the pointing movements used in many studies (Winstein et al, 1997 ; Seidler et al, 2004 ; Buetefisch et al, 2014 ; Barany et al, 2020 ; Revill et al, 2022 ) and this would potentially explain the differences in cortical activation. Therefore, when reasoning about the motor-related cortical activation, it is insufficient to focus only on ID since it ignores the subtlety with muscle activation and movement paradigm.…”

“…Inconsistent findings were also reported regarding whether cortical activation was mainly explained by index-of-difficulty. In reaching movements with high ID, both healthy individuals and stroke patients demonstrated intensified activation in Brodmann Areas 4 (mainly the primary motor cortex) (Barany et al, 2020 ; Revill et al, 2022 ). Additionally, healthy individuals exhibited increased activation in BA6 (mainly the supplementary motor cortex and premotor cortex) (Winstein et al, 1997 ; Seidler et al, 2004 ) detected using fMRI; on the contrary, other studies using the same movement paradigm did not elicit notable differences in BA4 (Buetefisch et al, 2014 ) or BA6 (Haar et al, 2017 ).…”

Stroke Lesion Volume and Injury to Motor Cortex Output Determines Extent of Contralesional Motor Cortex Reorganization

“…However, emerging evidence, suggests a potentially supportive role of M1 CL because abnormally increased excitatory neural activity and activation in M1 CL was also seen in patients with good hand function. 9,[17][18][19][20][21][22][23] Decreasing M1 CL excitability in these patients may result in deterioration of dexterity of hand performance. 22 Furthermore, in non-human primates and rats the extent of M1 injury is related to motor area reorganization in the contralesional hemisphere, which includes longterm changes in neurotransmitter systems, dendritic growth, and synapse formation (for review see Ref.…”