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Highlights • Sub-optimal brain-wide organization and integration is present in patients with GAD. • Network abnormalities in GAD are not restricted to the amygdala-PFC circuit. • Whole-brain connectivity mirrors anxiety symptoms at two time points in GAD. Abstract Generalized anxiety disorder (GAD) has excessive anxiety and uncontrollable worry as core symptoms. Abnormal cerebral functioning underpins the expression and perhaps pathogenesis of GAD:. Studies implicate impaired communication between the amygdala and the pre-frontal cortex (PFC). Our aim was to longitudinally investigate whether such network abnormalities are spatially restricted to this circuit or if the integrity of functional brain networks is globally disrupted in GAD. We acquired resting-state functional magnetic resonance imaging data from 16 GAD patients and 16 matched controls at baseline and after 1 year. Using network modeling and graph-theory, whole-brain connectivity was characterized from local and global perspectives. Overall lower global efficiency , indicating sub-optimal brain-wide organization and integration, was present in patients with GAD compared to controls. The amygdala and midline cortices showed higher betweenness centrality, reflecting functional dominance of these brain structures. Third, lower betweenness centrality and lower degree emerged for PFC, suggesting weakened inhibitory control. Overall, network organization showed impairments consistent with neurobiological models of GAD (involving amygdala, PFC, and cingulate cortex) and further pointed to an involvement of temporal regions. Such impairments tended to progress over time and predict anxiety symptoms. A graph-analytic approach represents a powerful approach to deepen our understanding of GAD. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) is a neuromodulation technique that can alter cortical excitability and modulate behaviour in a polarity-dependent way. Despite the widespread use of this method in the neuroscience field, its effects on ongoing local or global (network level) neuronal activity are still not foreseeable. A way to shed light on the neuronal mechanisms underlying the cortical connectivity changes induced by tDCS is provided by the combination of tDCS with electroencephalography (EEG). In this study, twelve healthy subjects underwent online tDCS-EEG recording (i.e., simultaneous), during resting-state, using 19 EEG channels. The protocol involved anodal, cathodal and sham stimulation conditions, with the active and the reference electrodes in the left frontocentral area (FC3) and on the forehead over the right eyebrow, respectively. The data were processed using a network model, based on graph theory and the synchronization likelihood. The resulting graphs were analysed for four frequency bands (theta, alpha, beta and gamma) to evaluate the presence of tDCS-induced differences in synchronization patterns and graph theory measures. The resting state network connectivity resulted altered during tDCS, in a polarity-specific manner for theta and alpha bands. Anodal tDCS weakened synchronization with respect to the baseline over the fronto-central areas in the left hemisphere, for theta band (p < 0.05). In contrast, during cathodal tDCS a significant increase in inter-hemispheric synchronization connectivity was observed over the centro-parietal, centro-occipital and parieto-occipital areas for the alpha band (p < 0.05). Local graph measures showed a tDCS-induced polarity-specific differences that regarded modifications of network activities rather than specific region properties. Our results show that applying tDCS during the resting state modulates local synchronization as well as network properties in slow frequency bands, in a polarity-specific manner. [ABSTRACT FROM AUTHOR]

• Monoamines contribute to the pathogenesis of MS and explain some clinical features. • We used RS-fMRI to study monoaminergic functional connectivity within the brain. • Monoaminergic nuclei are functionally connected with central brain networks in HC. • These connections are dysfunctional in MS patients. : brainstem monoaminergic (dopaminergic, noradrenergic, and serotoninergic) nuclei (BrMn) contain a variety of ascending neurons that diffusely project to the whole brain, crucially regulating normal brain function. BrMn are directly affected in multiple sclerosis (MS) by inflammation and neurodegeneration. Moreover, inflammation reduces the synthesis of monoamines. Aberrant monoaminergic neurotransmission contributes to the pathogenesis of MS and explains some clinical features of MS. We used resting-state functional MRI (RS-fMRI) to characterize abnormal patterns of BrMn functional connectivity (FC) in MS. : BrMn FC was studied with multi-echo RS-fMRI in n = 68 relapsing-remitting MS patients and n = 39 healthy controls (HC), by performing a seed-based analysis, after producing standard space seed masks of the BrMn. FC was assessed between ventral tegmental area (VTA), locus coeruleus (LC), median raphe (MR), dorsal raphe (DR), and the rest of the brain and compared between MS patients and HC. Between-group comparisons were carried out only within the main effect observed in HC, setting p <0.05 family-wise-error corrected (FWE). : in HC, VTA displayed FC with the core regions of the default-mode network. As compared to HC, MS patients showed altered FC between VTA and posterior cingulate cortex (p <0.05 FWE). LC displayed FC with core regions of the executive-control network with a reduced functional connection between LC and right prefrontal cortex in MS patients (p <0.05 FWE). Raphe nuclei was functionally connected with cerebellar cortex, with a significantly lower FC between these nuclei and cerebellum in MS patients, as compared to HC (p <0.05 FWE). : our study demonstrated in MS patients a functional disconnection between BrMn and cortical/subcortical efferent targets of central brain networks, possibly due to a loss or a dysregulation of BrMn neurons. This adds new information about how monoaminergic systems contribute to MS pathogenesis and suggests new potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Behavioral and psychological symptoms of dementia (BPSD) are commonly observed since the early stage of Alzheimer's disease (AD) associated with structural brain changes. It is conceivable that they may also relate to functional brain changes. This resting-state functional MRI (RS-fMRI) study investigated the alterations within functional brain networks of a cohort of AD patients at different clinical stages who presented with BPSD. One hundred one AD patients and 56 patients with amnestic mild cognitive impairment underwent a neuropsychological evaluation including the Neuropsychiatry Inventory-12 (NPI-12). All patients and 35 healthy controls (HS) underwent 3T-MRI. Factor analysis was used to extract the principal factors from NPI-12, while RS-fMRI data were processed using graph theory to investigate functional connectivity. Five factors were extracted from NPI-12. Sixty-two percent of patients showed BPSD and functional brain connectivity changes in various networks compared to those without BPSD and HS. These changes contributed to account for patients' BPSD. This work opens new perspectives in terms of nonpharmacological interventions that might be designed to modulate brain connectivity and improve patients' BPSD. • Behavioral and psychological symptoms of dementia (BPSD) are observed since early stage of Alzheimer's disease. • BPSD are grouped in main factors. • Patients with BPSD show changes in brain functional connectivity. • Different factors associate with reduced brain functional connectivity in different networks. • This has potential implications for nonpharmacological interventions. [ABSTRACT FROM AUTHOR]