Mechanisms Of Congnitive Impairment In Post-stroke Patients: A Study Using Resting-state FMRI Technique

Part 1: A correlation between the aberrant spontaneous neuronal activity of the posterior cingulate cortex (PCC) and the cognitive level in subcortical stroke patientsObjective: This study utilized three different evaluation indexes (ALFF, ReHo and FC) of resting-state fMRI to demonstrate that the posterior cingulate cortex (PCC) plays a pivotal role in the default mode network (DMN) in post subcortical stroke patients and there is a correlation between the aberrant spontaneous neuronal activity of PCC and the cognitive level.Materials and Methods: Subcortical stroke patients (n=27) and age-, sex-, and education-matched healthy controls subjects (n=30) underwent resting state-fMRI scanning and a battery of cognitive function tests. Regional homogeneity (ReHo) and amplitude of low frequency fluctuation (ALFF)were calculated within the DMN between the two groups to obtain the brain area with significant difference. The group comparison analyses of functional connectivity (FC) were also performed by choosing the significant difference brain area above-mentioned as the seed spot. The potential relationships between ALFF, ReHo and FC values and cognitive performance were evaluated via partial correlation analysis.RESULTS: The patients exhibited significant deficiencies in some cognitive domains (all P < 0.05).ALFF and ReHo values both significantly decreased in the PCC in post-stroke patients compared with healthy controls. We observed significantly decreased FC values between the PCC and some regions, including the right medial frontal gyrus, bilateral thalamus (medial dorsal nucleus) and right cerebellar subregion (crus Ⅱ) in stroke patients. Moreover, a significant positive correlation was found between the PCC-right cerebellar subregion (crus Ⅱ) connectivity and MOCA (r = 0.397;P = 0.040), Symbol Digit Modalities Test scores (r = 0.484; P = 0.011) in stroke patients. A significant negative correlation was found between the PCC-right cerebellar subregion (crus Ⅱ)connectivity and Trail Making Test B scores (r = -0.544; P = 0.003) in the subcortical stroke patients.CONCLUSION: Compared with healthy controls, post-stroke patients develop aberrant ALFF,ReHo and FC of the PCC respectively. Resting-state connectivity disturbance of PCC-cerebellar subregion (crus Ⅱ) may be a central role for evaluating the cognitive dysfunction in stroke patients.Part 2: Regional coherence alterations revealed by resting-state fMRI in post-stroke patients with cognitive dysfunctionObjectives: Post-stroke cognitive dysfunction greatly influences patients’ quality of life after stroke.However, its neurophysiological basis remains unknown. This study utilized resting-state functional magnetic resonance imaging (fMRI) to investigate the alterations in regional coherence in patients after subcortical stroke.Methods: Resting-state fMRI measurements were acquired from 16 post-stroke patients with cognitive impairment (CI), 16 post-stroke patients with normal cognitive function (CN) and 30 well-matched healthy controls (HC). Regional homogeneity (ReHo) was used to detect alterations in regional coherence. Abnormalities in regional coherence correlated with scores on neuropsychological scales.Results: Compared to the HC and the CN, the CI showed remarkably decreased ReHo in the bilateral anterior cingulate cortex(ACC) and the left PCC/precuneus. ReHo in the bilateral ACC positively correlated with the scores on the Symbol Digit Modalities Test (r = 0.399, P = 0.036) and the Complex Figure Test-delayed recall subtest (r = 0.397, P = 0.036) in all post-stroke patients.Moreover, ReHo in the left PCC/precuneus positively correlated with the scores on the Forward Digit Span Test (r = 0.485, P = 0.009) in all post-stroke patients.Conclusions: Aberrant regional coherence was observed in the anterior and posterior cingulate cortices in post-stroke patients with cognitive dysfunction. ReHo could represent a promising indicator of neurobiological deficiencies in post-stroke patients.Part 3: Disrupted functional connectivity within the default-mode network in brainstem ischemic stroke patients with cognitive impairmentObjectives: Ischemic stroke patients suffer different levels of cognitive impairment. Patients with impaired cognition often show default-mode network (DMN) disruption. We aimed to investigate the integrity of DMN in brainstem ischemic stroke patients by using independent component analysis (ICA) , and to explore the relationship between the disrupted intrinsic connectivity within DMN, neurocognitive performance and the serum total homocysteine (tHcy) levels.Materials and Methods: Thirty-two brainstem ischemic stroke patients and 34 well-matched healthy controls were included and underwent resting-state functional MRI. ICA was adopted to extract the DMN, including its anterior and posterior components. Z-maps of both sub-networks were compared between the two groups and correlated with each clinical variable.RESULTS: Post-stroke patients showed decreased connectivity around the middle frontal cortex in the anterior sub-network and the posterior cingulate cortex in the posterior sub-network of DMN.The decreased connectivity in the posterior DMN was significantly correlated with the scores on Auditory Verbal Learning Test -delay recall test (r = 0.532, P = 0.006), the Complex Figure Test-delay recall test (r = 0.494, P = 0.012), and the tHcy level (r = -0.555, P = 0.007).CONCLUSION: Decreased connectivity within the DMN was found in brainstem ischemic stroke patients, which might provide powerful new insights into the neural mechanisms that underlie the post- stroke cognitive decline.