Early parietofrontal network upregulation relates to future persistent deficits after severe stroke-a prospective cohort study

Abstract

Recent brain imaging has evidenced that parietofrontal networks show alterations after stroke which also relate to motor recovery processes. There is converging evidence for an upregulation of parietofrontal coupling between parietal brain regions and frontal motor cortices. The majority of studies though have included only moderately to mildly affected patients, particularly in the subacute or chronic stage. Whether these network alterations will also be present in severely affected patients and early after stroke and whether such information can improve correlative models to infer motor recovery remains unclear. In this prospective cohort study, 19 severely affected first-ever stroke patients (mean age 74 years, 12 females) were analysed which underwent resting-state functional MRI and clinical testing during the initial week after the event. Clinical evaluation of neurological and motor impairment as well as global disability was repeated after three and six months. Nineteen healthy participants of similar age and gender were also recruited. MRI data were used to calculate functional connectivity values between the ipsilesional primary motor cortex, the ventral premotor cortex, the supplementary motor area and the anterior and caudal intraparietal sulcus of the ipsilesional hemisphere. Linear regression models were estimated to compare parietofrontal functional connectivity between stroke patients and healthy controls and to relate them to motor recovery. The main finding was a significant increase in ipsilesional parietofrontal coupling between anterior intraparietal sulcus and the primary motor cortex in severely affected stroke patients (P <0.003). This upregulation significantly contributed to correlative models explaining variability in subsequent neurological and global disability as quantified by National Institute of Health Stroke Scale and modified Rankin Scale, respectively. Patients with increased parietofrontal coupling in the acute stage showed higher levels of persistent deficits in the late subacute stage of recovery (P <0.05). This study provides novel insights that parietofrontal networks of the ipsilesional hemisphere undergo neuroplastic alteration already very early after severe motor stroke. The association between early parietofrontal upregulation and future levels of persistent functional deficits and dependence from help in daily living might be useful in models to enhance clinical neurorehabilitative decision making.

Keywords: coupling; fMRI; functional connectivity; intraparietal sulcus; resting-state.

© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.

Figures

Graphical Abstract

Figure 1

Stroke lesions and motor network ROIs. All masks of stroke lesions are displayed on the left hemisphere, overlaying a T1-weighted template in MNI space (z-coordinates below each slice). The colour intensity indicates the number of subjects of whom lesion voxels lay within the coloured region. Motor ROIs (M1, PMV, SMA, AIPS and CIPS) are displayed respective to the stroke lesions.

Figure 2

Functional connectivity of the ipsilesional hemisphere. Coloured lines indicate significant coupling estimates for each group (left; P < 0.05, FDR-corrected for 20 tests over both groups) or significant absolute group difference for AIPS-M1 (right; P < 0.05, FDR corrected for 10 tests).

Figure 3

Influence of ipsilesional AIPS-M1 functional connectivity on future persistent deficits after stroke. Effect plots are shown for AIPS-M1 functional connectivity (FC) of the ipsilesional hemisphere contributing to the explanation of variability in follow-up NIHSS, UEFM, MRS and BI in severe stroke patients. P-value of FC AIPS-M1 as the predictor of interest (within-model) is given (uncorrected). There were significant associations between AIPS-M1 FC at T1 and MRS and NIHSS at T2/3 with higher FC values early after stroke found in patients which are likely to show more severe persistent deficits in follow-up, independent from the initial impairment level. A similar correlation was not detected for UEFM or BI.