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, nineteen 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.

Brain network topology early after stroke relates to recovery

“…The same holds true for the combined time point of the outcome measure at T 2 , either after 3 or 6 months. 30 The additional consideration of this factor in the models did not alter the findings. Second, group allocation was conducted based on a clustering analysis based on NIHSS and UEFM scores.…”

“…This work has been designed as an exploratory re-analysis of two independent cohorts of stroke patients which have been already published. 29 , 30 Hence, caution is advised when interpreting the present findings, prospective studies are needed to obtain further insights.…”

“…In fact, imaging studies have repeatedly shown that, at least in part, results might be specific to certain outcome measures and not easily generalized across others. 17 , 30 , 48 As an alternative explanation, a strong relationship between UEFM at T 1 and T 2 might explain why GE was not capable to explain additional variances. Taking NIHSS at T 1 into account for the initial deficit, GE would show a significant association with UEFM at T 2 across the complete cohort ( Supplementary Table 2 ).…”

“…Detailed inclusion and exclusion criteria are given in our recent report on parietofrontal functional connectivity. 30 In brief, inclusion criteria for both studies were: first-ever unilateral ischaemic stroke, upper extremity motor deficit involving hand function, no history of previous neurological or psychiatric illness, age ≥18 years. In both cohorts, acute stroke patients underwent T 1 -, T 2 - and diffusion-weighted MRI in the first days after the event as time point T 1 (C 1 : Days 3–5, C 2 : Days 3–14).…”

“…The follow-up time point T 2 was defined in the late subacute stage of recovery 31 after 3 months, or, as in seven cases of cohort C 2 in which clinical data for this time point was not available, after 6 months. 30 Across both cohorts, clinical assessments included scores of neurological symptom burden (NIHSS, range 0–42), global disability (modified Rankin Scale, mRS, range 0–6), activity-related disability [Barthel Index (BI), range 0–100] and motor functions (Upper-Extremity Score of the Fugl-Meyer Assessment, UEFM, range 0–66). Data of healthy participants, similar in age and gender, were also re-analysed from both cohorts.…”