Loss of brain inter-frequency hubs in Alzheimer's disease

Alzheimer's disease (AD) causes alterations of brain network structure and function. The latter consists of connectivity changes between oscillatory processes at different frequency channels. We proposed a multi-layer network approach to analyze multiple-frequency brain networks inferred from magnetoencephalographic recordings during resting-states in AD subjects and age-matched controls. Main results showed that brain networks tend to facilitate information propagation across different frequencies, as measured by the multi-participation coefficient (MPC). However, regional connectivity in AD subjects was abnormally distributed across frequency bands as compared to controls, causing significant decreases of MPC. This effect was mainly localized in association areas and in the cingulate cortex, which acted, in the healthy group, as a true inter-frequency hub. MPC values significantly correlated with memory impairment of AD subjects, as measured by the total recall score. Most predictive regions belonged to components of the default-mode network that are typically affected by atrophy, metabolism disruption and amyloid-beta deposition. We evaluated the diagnostic power of the MPC and we showed that it led to increased classification accuracy (78.39%) and sensitivity (91.11%). These findings shed new light on the brain functional alterations underlying AD and provide analytical tools for identifying multi-frequency neural mechanisms of brain diseases.Comment: 27 pages, 6 figures, 3 tables, 3 supplementary figure

The gray matter structural connectome and its relationship to alcohol relapse: Reconnecting for recovery.

Gray matter (GM) atrophy associated with alcohol use disorders (AUD) affects predominantly the frontal lobes. Less is known how frontal lobe GM loss affects GM loss in other regions and how it influences drinking behavior or relapse after treatment. The profile similarity index (PSI) combined with graph analysis allows to assess how GM loss in one region affects GM loss in regions connected to it, ie, GM connectivity. The PSI was used to describe the pattern of GM connectivity in 21 light drinkers (LDs) and in 54 individuals with AUD (ALC) early in abstinence. Effects of abstinence and relapse were determined in a subgroup of 36 participants after 3 months. Compared with LD, GM losses within the extended brain reward system (eBRS) at 1-month abstinence were similar between abstainers (ABST) and relapsers (REL), but REL had also GM losses outside the eBRS. Lower GM connectivities in ventro-striatal/hypothalamic and dorsolateral prefrontal regions and thalami were present in both ABST and REL. Between-networks connectivity loss of the eBRS in ABST was confined to prefrontal regions. About 3 months later, the GM volume and connectivity losses had resolved in ABST, and insula connectivity was increased compared with LD. GM losses and GM connectivity losses in REL were unchanged. Overall, prolonged abstinence was associated with a normalization of within-eBRS connectivity and a reconnection of eBRS structures with other networks. The re-formation of structural connectivities within and across networks appears critical for cognitive-behavioral functioning related to the capacity to maintain abstinence after outpatient treatment

Altered functional and structural brain network organization in autism.

Structural and functional underconnectivity have been reported for multiple brain regions, functional systems, and white matter tracts in individuals with autism spectrum disorders (ASD). Although recent developments in complex network analysis have established that the brain is a modular network exhibiting small-world properties, network level organization has not been carefully examined in ASD. Here we used resting-state functional MRI (n = 42 ASD, n = 37 typically developing; TD) to show that children and adolescents with ASD display reduced short and long-range connectivity within functional systems (i.e., reduced functional integration) and stronger connectivity between functional systems (i.e., reduced functional segregation), particularly in default and higher-order visual regions. Using graph theoretical methods, we show that pairwise group differences in functional connectivity are reflected in network level reductions in modularity and clustering (local efficiency), but shorter characteristic path lengths (higher global efficiency). Structural networks, generated from diffusion tensor MRI derived fiber tracts (n = 51 ASD, n = 43 TD), displayed lower levels of white matter integrity yet higher numbers of fibers. TD and ASD individuals exhibited similar levels of correlation between raw measures of structural and functional connectivity (n = 35 ASD, n = 35 TD). However, a principal component analysis combining structural and functional network properties revealed that the balance of local and global efficiency between structural and functional networks was reduced in ASD, positively correlated with age, and inversely correlated with ASD symptom severity. Overall, our findings suggest that modeling the brain as a complex network will be highly informative in unraveling the biological basis of ASD and other neuropsychiatric disorders

Cerebellar atrophy in Parkinson's disease and its implication for network connectivity.

Pathophysiological and atrophic changes in the cerebellum are documented in Parkinson's disease. Without compensatory activity, such abnormalities could potentially have more widespread effects on both motor and non-motor symptoms. We examined how atrophic change in the cerebellum impacts functional connectivity patterns within the cerebellum and between cerebellar-cortical networks in 42 patients with Parkinson's disease and 29 control subjects. Voxel-based morphometry confirmed grey matter loss across the motor and cognitive cerebellar territories in the patient cohort. The extent of cerebellar atrophy correlated with decreased resting-state connectivity between the cerebellum and large-scale cortical networks, including the sensorimotor, dorsal attention and default networks, but with increased connectivity between the cerebellum and frontoparietal networks. The severity of patients' motor impairment was predicted by a combination of cerebellar atrophy and decreased cerebellar-sensorimotor connectivity. These findings demonstrate that cerebellar atrophy is related to both increases and decreases in cerebellar-cortical connectivity in Parkinson's disease, identifying potential cerebellar driven functional changes associated with sensorimotor deficits. A post hoc analysis exploring the effect of atrophy in the subthalamic nucleus, a cerebellar input source, confirmed that a significant negative relationship between grey matter volume and intrinsic cerebellar connectivity seen in controls was absent in the patients. This suggests that the modulatory relationship of the subthalamic nucleus on intracerebellar connectivity is lost in Parkinson's disease, which may contribute to pathological activation within the cerebellum. The results confirm significant changes in cerebellar network activity in Parkinson's disease and reveal that such changes occur in association with atrophy of the cerebellum