Prominent Changes in Cerebro-Cerebellar Functional Connectivity During Continuous Cognitive Processing

While task-dependent responses of specific brain areas during cognitive tasks are well established, much less is known about the changes occurring in resting state networks (RSNs) in relation to continuous cognitive processing. In particular, the functional involvement of cerebro-cerebellar loops connecting the posterior cerebellum to associative cortices, remains unclear. In this study, 22 healthy volunteers underwent a multi-session functional magnetic resonance imaging (fMRI) protocol composed of four consecutive 8-min resting state fMRI (rs-fMRI) scans. After a first control scan, participants listened to a narrated story for the entire duration of the second rs-fMRI scan; two further rs-fMRI scans followed the end of story listening. The story plot was purposely designed to stimulate specific cognitive processes that are known to involve the cerebro-cerebellar loops. Almost all of the identified 15 RSNs showed changes in functional connectivity (FC) during and for several minutes after the story. The FC changes mainly occurred in the frontal and prefrontal cortices and in the posterior cerebellum, especially in Crus I-II and lobule VI. The FC changes occurred in cerebellar clusters belonging to different RSNs, including the cerebellar network (CBLN), sensory networks (lateral visual network, LVN; medial visual network, MVN) and cognitive networks (default mode network, DMN; executive control network, ECN; right and left ventral attention networks, RVAN and LVAN; salience network, SN; language network, LN; and working memory network, WMN). Interestingly, a k-means analysis of FC changes revealed clustering of FCN, ECN, and WMN, which are all involved in working memory functions, CBLN, DMN, and SN, which play a key-role in attention switching, and RSNs involved in visual imagery. These results show that the cerebellum is deeply entrained in well-structured network clusters, which reflect multiple aspects of cognitive processing, during and beyond the conclusion of auditory stimulation

Quantifying neurodegeneration of the cervical cord and brain in degenerative cervical myelopathy : A multicentre study using quantitative magnetic resonance imaging

BACKGROUND AND PURPOSE Simultaneous assessment of neurodegeneration in both the cervical cord and brain across multiple centres can enhance the effectiveness of clinical trials. Thus, this study aims to simultaneously assess microstructural changes in the cervical cord and brain above the stenosis in degenerative cervical myelopathy (DCM) using quantitative magnetic resonance imaging (MRI) in a multicentre study. METHODS We applied voxelwise analysis with a probabilistic brain/spinal cord template embedded in statistical parametric mappin (SPM-BSC) to process multi parametric mapping (MPM) including effective transverse relaxation rate (R2*), longitudinal relaxation rate (R1), and magnetization transfer (MT), which are indirectly sensitive to iron and myelin content. Regression analysis was conducted to establish associations between neurodegeneration and clinical impairment. Thirty-eight DCM patients (mean age ± SD = 58.45 ± 11.47 years) and 38 healthy controls (mean age ± SD = 41.18 ± 12.75 years) were recruited at University Hospital Balgrist, Switzerland and Toronto Western Hospital, Canada. RESULTS Remote atrophy was observed in the cervical cord (p = 0.002) and in the left thalamus (0.026) of the DCM group. R1 was decreased in the periaqueductal grey matter (p = 0.014), thalamus (p = 0.001), corpus callosum (p = 0.0001), and cranial corticospinal tract (p = 0.03). R2* was increased in the primary somatosensory cortices (p = 0.008). Sensory impairments were associated with increased iron-sensitive R2* in the thalamus and periaqueductal grey matter in DCM. CONCLUSIONS Simultaneous assessment of the spinal cord and brain revealed DCM-induced demyelination, iron deposition, and atrophy. The extent of remote neurodegeneration was associated with sensory impairment, highlighting the intricate and expansive nature of microstructural neurodegeneration in DCM, reaching beyond the stenosis level

Exploring patterns of alteration in Alzheimer’s disease brain networks: a combined structural and functional connectomics analysis

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the disconnection syndrome hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC). In the default mode network (DMN), that was the most affected, axonal loss and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN), disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN), neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI) but also with subcortical alterations (revealed by diffusion MRI) that extend beyond the areas primarily damaged by neurodegeneration, towards the support of an emerging concept of AD as a disconnection syndrome. Since only AD but not MCI patients were characterized by a significant decrease in structural connectivity, integrated structural/functional connectomics could provide a useful tool for assessing disease progression from MCI to AD