L-Dopa modulates functional connectivity in striatal cognitive and motor networks: A double-blind placebo-controlled study

Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect of L-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults. We examined the FC of 6 striatal regions of interest (ROIs) previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen (Di Martino et al., 2008). In addition to replicating the previously demonstrated patterns of striatal FC, we observed robust effects of L-dopa. Specifically, L-dopa increased FC in motor pathways connecting the putamen ROIs with the cerebellum and brainstem. Although L-dopa also increased FC between the inferior ventral striatum and ventrolateral prefrontal cortex, it disrupted ventral striatal and dorsal caudate FC with the default mode network. These alterations in FC are consistent with studies that have demonstrated dopaminergic modulation of cognitive and motor striatal networks in healthy participants. Recent studies have demonstrated altered resting state FC in several conditions believed to be characterized by abnormal dopaminergic neurotransmission. Our findings suggest that the application of similar experimental pharmacological manipulations in such populations may further our understanding of the role of dopaminergic neurotransmission in those conditions

Enhancing studies of the connectome in autism using the autism brain imaging data exchange II

The second iteration of the Autism Brain Imaging Data Exchange (ABIDE II) aims to enhance the scope of brain connectomics research in Autism Spectrum Disorder (ASD). Consistent with the initial ABIDE effort (ABIDE I), that released 1112 datasets in 2012, this new multisite open-data resource is an aggregate of resting state functional magnetic resonance imaging (MRI) and corresponding structural MRI and phenotypic datasets. ABIDE II includes datasets from an additional 487 individuals with ASD and 557 controls previously collected across 16 international institutions. The combination of ABIDE I and ABIDE II provides investigators with 2156 unique cross-sectional datasets allowing selection of samples for discovery and/or replication. This sample size can also facilitate the identification of neurobiological subgroups, as well as preliminary examinations of sex differences in ASD. Additionally, ABIDE II includes a range of psychiatric variables to inform our understanding of the neural correlates of co-occurring psychopathology; 284 diffusion imaging datasets are also included. It is anticipated that these enhancements will contribute to unraveling key sources of ASD heterogeneity

Ventral striatal hyporesponsiveness during reward anticipation in attention-deficit/hyperactivity disorder

Item does not contain fulltextBackground: Although abnormalities in reward processing have been proposed to underlie attention-deficit/hyperactivity disorder (ADHD), this link has not been tested explicitly with neural probes. Methods: This hypothesis was tested by using fMRI to compare neural activity within the striatum in individuals with ADHD and healthy controls during a reward-anticipation task that has been shown previously to produce reliable increases in ventral striatum activity in healthy adults and healthy adolescents. Eleven adolescents with ADHD (5 off medication and 6 medication-naive) and 11 healthy controls (ages 12-17 y) were included. Groups were matched for age, gender, and intelligence quotient. Results: We found reduced ventral striatal activation in adolescents with ADHD during reward anticipation, relative to healthy controls. Moreover, ventral striatal activation was negatively correlated with parent-rated hyperactive/impulsive symptoms across the entire sample. Conclusions: These findings provide neural evidence that symptoms of ADHD, and impulsivity or hyperactivity in particular, may involve diminished reward anticipation, in addition to commonly observed executive dysfunction

Network centrality in the human functional connectome

Item does not contain fulltextThe network architecture of functional connectivity within the human brain connectome is poorly understood at the voxel level. Here, using resting state functional magnetic resonance imaging data from 1003 healthy adults, we investigate a broad array of network centrality measures to provide novel insights into connectivity within the whole-brain functional network (i.e., the functional connectome). We first assemble and visualize the voxel-wise (4 mm) functional connectome as a functional network. We then demonstrate that each centrality measure captures different aspects of connectivity, highlighting the importance of considering both global and local connectivity properties of the functional connectome. Beyond "detecting functional hubs," we treat centrality as measures of functional connectivity within the brain connectome and demonstrate their reliability and phenotypic correlates (i.e., age and sex). Specifically, our analyses reveal age-related decreases in degree centrality, but not eigenvector centrality, within precuneus and posterior cingulate regions. This implies that while local or (direct) connectivity decreases with age, connections with hub-like regions within the brain remain stable with age at a global level. In sum, these findings demonstrate the nonredundancy of various centrality measures and raise questions regarding their underlying physiological mechanisms that may be relevant to the study of neurodegenerative and psychiatric disorders

Toward next-generation primate neuroscience: a collaboration-based strategic plan for integrative neuroimaging

Open science initiatives are creating opportunities to increase research coordination and impact in nonhuman primate (NHP) imaging. The PRIMatE Data and Resource Exchange community recently developed a collaboration-based strategic plan to advance NHP imaging as an integrative approach for multiscale neuroscience

Functional Connectivity of Human Striatum: A Resting State fMRI Study

Item does not contain fulltextClassically regarded as motor structures, the basal ganglia subserve a wide range of functions, including motor, cognitive, motivational, and emotional processes. Consistent with this broad-reaching involvement in brain function, basal ganglia dysfunction has been implicated in numerous neurological and psychiatric disorders. Despite recent advances in human neuroimaging, models of basal ganglia circuitry continue to rely primarily upon inference from animal studies. Here, we provide a comprehensive functional connectivity analysis of basal ganglia circuitry in humans through a functional magnetic resonance imaging examination during rest. Voxelwise regression analyses substantiated the hypothesized motor, cognitive, and affective divisions among striatal subregions, and provided in vivo evidence of a functional organization consistent with parallel and integrative loop models described in animals. Our findings also revealed subtler distinctions within striatal subregions not previously appreciated by task-based imaging approaches. For instance, the inferior ventral striatum is functionally connected with medial portions of orbitofrontal cortex, whereas a more superior ventral striatal seed is associated with medial and lateral portions. The ability to map multiple distinct striatal circuits in a single study in humans, as opposed to relying on meta-analyses of multiple studies, is a principal strength of resting state functional magnetic resonance imaging. This approach holds promise for studying basal ganglia dysfunction in clinical disorders

Residual functional connectivity in the split-brain revealed with resting-state functional MRI

Item does not contain fulltextSplit-brain patients present a unique opportunity to address controversies regarding subcortical contributions to interhemispheric coordination. We characterized residual functional connectivity in a complete commissurotomy patient by examining patterns of low-frequency BOLD functional MRI signal. Using independent components analysis and region-of-interest-based functional connectivity analyses, we demonstrate bilateral resting state networks in a patient lacking all major cerebral commissures. Compared with a control group, the patient's interhemispheric correlation scores fell within the normal range for two out of three regions examined. Thus, we provide evidence for bilateral resting state networks in a patient with complete commissurotomy. Such continued interhemispheric interaction suggests that, at least in part, cortical networks in the brain can be coordinated by subcortical mechanisms

Towards robust and replicable sex differences in the intrinsic brain function of autism

Contains fulltext : 231788.pdf (publisher's version ) (Open Access)BACKGROUND: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data. METHODS: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z > 3.1, cluster-level P < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research. RESULTS: Discovery analyses in ABIDE revealed significant main effects of diagnosis and sex across the intrinsic functional connectivity of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples-EU-AIMS LEAP. LIMITATIONS: Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability. CONCLUSIONS: Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies