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Background: Clustering analysis is employed in brain dynamic functional connectivity (dFC) to cluster the data into a set of dynamic states. These states correspond to different patterns of functional connectivity that iterate through time. Although several cluster validity index (CVI) methods to determine the best clustering partition exists, the appropriateness of methods to apply in the case of dynamic connectivity analysis has not been determined., New Method: Currently employed indexes do not provide a crisp answer on what is the best number of clusters. In addition, there is a lack of CVI testing in the context of dFC data. This work tests a comprehensive set of twenty four cluster validity indexes applied to addiction data and suggest the best ones for clustering dynamic functional connectivity., Results: Out of the twenty four considered CVIs, Davies-Bouldin and Ray-Turi were the most suitable methods to find the number of clusters in both simulation and real data. The solution for these two CVIs is to find a local minimum critical point, which can be automated using computational algorithms., Comparison With Existing Methods: Elbow-Criterion, Silhouette and GAP-Statistic methods have been widely used in dFC studies. These methods are included among the tested CVIs where the performances of all twenty four CVIs are compared., Conclusions: Davies-Bouldin and Ray-Turi CVIs showed better performance among a group of twenty four CVIs in determining the number of clusters to use in dFC analysis., Competing Interests: Declaration of Competing Interest No competing financial interests exist., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Clustering analysis is employed in brain dynamic functional connectivity to cluster the data into a set of dynamic states. These states correspond to different patterns of functional connectivity that iterate through time. Although several methods to determine the best clustering partition exists, the appropriateness of methods to apply in the case of dynamic connectivity analysis has not been determined. In this work we examine the use of the Davies-Bouldin clustering validity index via simulation and real data analysis. Currently employed indexes, such as the Silhouette index, do not provide an effective estimation requiring the use of an elbow criterion. All elbow criteria rely on users experience and introduce uncertainty into the estimation. We demonstrate the feasibility of using the Davies-Bouldin index as a method delivering a unique discrete response to provide automated selection of the number of clusters.

Dynamic functional network connectivity (dFNC) is an expansion of traditional, static FNC that measures connectivity variation among brain networks throughout scan duration. We used a large resting-state fMRI (rs-fMRI) sample from the PREDICT-HD study (N = 183 Huntington disease gene mutation carriers [HDgmc] and N = 78 healthy control [HC] participants) to examine whole-brain dFNC and its associations with CAG repeat length as well as the product of scaled CAG length and age, a variable representing disease burden. We also tested for relationships between functional connectivity and motor and cognitive measurements. Group independent component analysis was applied to rs-fMRI data to obtain whole-brain resting state networks. FNC was defined as the correlation between RSN time-courses. Dynamic FNC behavior was captured using a sliding time window approach, and FNC results from each window were assigned to four clusters representing FNC states, using a k-means clustering algorithm. HDgmc individuals spent significantly more time in State-1 (the state with the weakest FNC pattern) compared to HC. However, overall HC individuals showed more FNC dynamism than HDgmc. Significant associations between FNC states and genetic and clinical variables were also identified. In FNC State-4 (the one that most resembled static FNC), HDgmc exhibited significantly decreased connectivity between the putamen and medial prefrontal cortex compared to HC, and this was significantly associated with cognitive performance. In FNC State-1, disease burden in HDgmc participants was significantly associated with connectivity between the postcentral gyrus and posterior cingulate cortex, as well as between the inferior occipital gyrus and posterior parietal cortex., (© 2019 Wiley Periodicals, Inc.)

Background: Gray matter (GM) atrophy in the striatum and across the brain is a consistently reported feature of the Huntington Disease (HD) prodrome. More recently, widespread prodromal white matter (WM) degradation has also been detected. However, longitudinal WM studies are limited and conflicting, and most analyses comparing WM and clinical functioning have also been cross-sectional., Objective: We simultaneously assessed changes in WM and cognitive and motor functioning at various prodromal HD stages., Methods: Data from 1,336 (1,047 prodromal, 289 control) PREDICT-HD participants were analyzed (3,700 sessions). MRI images were used to create GM, WM, and cerebrospinal fluid probability maps. Using source-based morphometry, independent component analysis was applied to WM probability maps to extract covarying spatial patterns and their subject profiles. WM profiles were analyzed in two sets of linear mixed model (LMM) analyses: one to compare WM profiles across groups cross-sectionally and longitudinally, and one to concurrently compare WM profiles and clinical variables cross-sectionally and longitudinally within each group., Results: Findings illustrate widespread prodromal changes in GM-adjacent-WM, with premotor, supplementary motor, middle frontal and striatal changes early in the prodrome that subsequently extend sub-gyrally with progression. Motor functioning agreed most with WM until the near-onset prodromal stage, when Stroop interference was the best WM indicator. Across groups, Trail-Making Test part A outperformed other cognitive variables in its similarity to WM, particularly cross-sectionally., Conclusions: Results suggest that distinct regions coincide with cognitive compared to motor functioning. Furthermore, at different prodromal stages, distinct regions appear to align best with clinical functioning. Thus, the informativeness of clinical measures may vary according to the type of data available (cross-sectional or longitudinal) as well as age and CAG-number.

Studies have used resting-state functional magnetic resonance imaging (rs-fMRI) to examine associations between psychopathy and brain connectivity in selected regions of interest as well as networks covering the whole-brain. One of the limitations of these approaches is that brain connectivity is modeled as a constant state through the scan duration. To address this limitation, we apply group independent component analysis (GICA) and dynamic functional network connectivity (dFNC) analysis to uncover whole-brain, time-varying functional network connectivity (FNC) states in a large forensic sample. We then examined relationships between psychopathic traits (PCL-R total scores, Factor 1 and Factor 2 scores) and FNC states obtained from dFNC analysis. FNC over the scan duration was better represented by five states rather than one state previously shown in static FNC analysis. Consistent with prior findings, psychopathy was associated with networks from paralimbic regions (amygdala and insula). In addition, whole-brain FNC identified 15 networks from nine functional domains (subcortical, auditory, sensorimotor, cerebellar, visual, salience, default mode network, executive control and attentional) related to psychopathy traits (Factor 1 and PCL-R scores). Results also showed that individuals with higher Factor 1 scores (affective and interpersonal traits) spend more time in a state with weaker connectivity overall, and changed states less frequently compared to those with lower Factor 1 scores. On the other hand, individuals with higher Factor 2 scores (impulsive and antisocial behaviors) showed more dynamism (changes to and from different states) than those with lower scores., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Psychopathy is a personality disorder characterized by antisocial behavior, lack of remorse and empathy, and impaired decision making. The disproportionate amount of crime committed by psychopaths has severe emotional and economic impacts on society. Here we examine the neural correlates associated with psychopathy to improve early assessment and perhaps inform treatments for this condition. Previous resting-state functional magnetic resonance imaging (fMRI) studies in psychopathy have primarily focused on regions of interest. This study examines whole-brain functional connectivity and its association to psychopathic traits. Psychopathy was hypothesized to be characterized by aberrant functional network connectivity (FNC) in several limbic/paralimbic networks. Group-independent component and regression analyses were applied to a data set of resting-state fMRI from 985 incarcerated adult males. We identified resting-state networks (RSNs), estimated FNC between RSNs, and tested their association to psychopathy factors and total summary scores (Factor 1, interpersonal/affective; Factor 2, lifestyle/antisocial). Factor 1 scores showed both increased and reduced functional connectivity between RSNs from seven brain domains (sensorimotor, cerebellar, visual, salience, default mode, executive control, and attentional). Consistent with hypotheses, RSNs from the paralimbic system-insula, anterior and posterior cingulate cortex, amygdala, orbital frontal cortex, and superior temporal gyrus-were related to Factor 1 scores. No significant FNC associations were found with Factor 2 and total PCL-R scores. In summary, results suggest that the affective and interpersonal symptoms of psychopathy (Factor 1) are associated with aberrant connectivity in multiple brain networks, including paralimbic regions., (© 2018 Wiley Periodicals, Inc.)

Huntington's disease (HD) is an inherited brain disorder characterized by progressive motor, cognitive, and behavioral dysfunctions. It is caused by abnormally large trinucleotide cytosine-adenine-guanine (CAG) repeat expansions on exon 1 of the Huntingtin gene. CAG repeat length (CAG-RL) inversely correlates with an earlier age of onset. Region-based studies have shown that HD gene mutation carrier (HDgmc) individuals (CAG-RL ≥36) present functional connectivity alterations in subcortical (SC) and default mode networks. In this analysis, we expand on previous HD studies by investigating associations between CAG-RL and connectivity in the whole brain, as well as between CAG-dependent connectivity and motor and cognitive performances. We used group-independent component analysis on resting-state functional magnetic resonance imaging scans of 261 individuals (183 HDgmc and 78 healthy controls) from the PREDICT-HD study, to obtain whole-brain resting state networks (RSNs). Regression analysis was applied within and between RSNs connectivity (functional network connectivity [FNC]) to identify CAG-RL associations. Connectivity within the putamen RSN is negatively correlated with CAG-RL. The FNC between putamen and insula decreases with increasing CAG-RL, and also shows significant associations with motor and cognitive measures. The FNC between calcarine and middle frontal gyri increased with CAG-RL. In contrast, FNC in other visual (VIS) networks declined with increasing CAG-RL. In addition to observed effects in SC areas known to be related to HD, our study identifies a strong presence of alterations in VIS regions less commonly observed in previous reports and provides a step forward in understanding FNC dysfunction in HDgmc.