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Non-invasive neuroimaging has revealed specific network-based resting-state dynamics in the human brain, yet the underlying neurophysiological mechanism remains unclear. We employed intracranial electroencephalography to characterize local field potentials within the default mode network (DMN), frontoparietal network (FPN), and salience network (SN) in 42 participants. We identified stronger within-network phase coherence at low frequencies (θ and α band) within the DMN, and at high frequencies (γ band) within the FPN. Hidden Markov modeling indicated that the DMN exhibited preferential low frequency phase coupling. Phase-amplitude coupling (PAC) analysis revealed that the low-frequency phase in the DMN modulated the high-frequency amplitude envelopes of the FPN, suggesting frequency-dependent characterizations of intrinsic brain networks at rest. These findings provide intracranial electrophysiological evidence in support of the network model for intrinsic organization of human brain and shed light on the way brain networks communicate at rest.

Post-traumatic stress disorder (PTSD) is a highly prevalent psychological disorder characterized by intense feelings of fear or helplessness after experiencing a traumatic event. PTSD is highly comorbid with mood disorders and patients are at increased risk for suicide. The present study aimed to identify neural connectivity alterations associated with suicidal ideation (SI) in PTSD patients by using resting-state functional magnetic resonance imaging. Voxel-to-voxel intrinsic connectivity was compared between PTSD patients with no (N-SI; N = 26) and high (H-SI; N = 7) SI. Region-to-voxel functional connectivity analysis was performed to identify the regions that contributed to intrinsic connectivity changes. H-SI patients had increased connectivity to various brain regions representing the central executive network, salience network, and default mode network in the frontal, temporal, and occipital lobes as well as subcortical structures involved in executive and limbic functioning, and motor systems. These results suggest SI is associated with large network-level alterations in PTSD patients and is not the result of neuronal abnormalities in any one specific area.

Post‐traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) often co‐occur in the context of threat to one's life. These conditions also have an overlapping symptomatology and include symptoms of anxiety, poor concentration and memory problems. A major challenge has been articulating the underlying neurobiology of these overlapping conditions. The primary aim of this study was to compare intrinsic functional connectivity between mTBI (without PTSD) and PTSD (without mTBI). The study included functional MRI data from 176 participants: 42 participants with mTBI, 67 with PTSD and a comparison group of 66 age and sex‐matched healthy controls. We used network‐based statistical analyses for connectome‐wide comparisons of intrinsic functional connectivity between mTBI relative to PTSD and controls. Our results showed no connectivity differences between mTBI and PTSD groups. However, we did find that mTBI had significantly reduced connectivity relative to healthy controls within an extensive network of regions including default mode, executive control, visual and auditory networks. The mTBI group also displayed hyperconnectivity between dorsal and ventral attention networks and perceptual regions. The PTSD group also demonstrated abnormal connectivity within these networks relative to controls. Connectivity alterations were not associated with severity of PTSD or post‐concussive symptoms in either clinical group. Taken together, the similar profiles of intrinsic connectivity alterations in these two conditions provide neural evidence that can explain, in part, the overlapping symptomatology between mTBI and PTSD. [ABSTRACT FROM AUTHOR]

• Our findings provide novel intracranial electrophysiological evidence supporting the network model of intrinsic brain architecture. • Our phase-amplitude coupling analysis revealed that the low-frequency phase in the DMN modulates the high-frequency amplitude envelopes within the FPN. • Our work sheds light on the frequency-dependent oscillatory communications of intrinsic brain networks. Non-invasive neuroimaging has revealed specific network-based resting-state dynamics in the human brain, yet the underlying neurophysiological mechanism remains unclear. We employed intracranial electroencephalography to characterize local field potentials within the default mode network (DMN), frontoparietal network (FPN), and salience network (SN) in 42 participants. We identified stronger within-network phase coherence at low frequencies (θ and α band) within the DMN, and at high frequencies (γ band) within the FPN. Hidden Markov modeling indicated that the DMN exhibited preferential low frequency phase coupling. Phase-amplitude coupling (PAC) analysis revealed that the low-frequency phase in the DMN modulated the high-frequency amplitude envelopes of the FPN, suggesting frequency-dependent characterizations of intrinsic brain networks at rest. These findings provide intracranial electrophysiological evidence in support of the network model for intrinsic organization of human brain and shed light on the way brain networks communicate at rest. [ABSTRACT FROM AUTHOR]

Decomposition of whole-brain functional connectivity patterns reveals a principal gradient that captures the separation of sensorimotor cortex from heteromodal regions in the default mode network (DMN). Functional homotopy is strongest in sensorimotor areas, and weakest in heteromodal cortices, suggesting there may be differences between the left and right hemispheres (LH/RH) in the principal gradient, especially towards its apex. This study characterised hemispheric differences in the position of large-scale cortical networks along the principal gradient, and their functional significance. We collected resting-state fMRI and semantic, working memory and non-verbal reasoning performance in 175 + healthy volunteers. We then extracted the principal gradient of connectivity for each participant, tested which networks showed significant hemispheric differences on the gradient, and regressed participants' behavioural efficiency in tasks outside the scanner against interhemispheric gradient differences for each network. LH showed a higher overall principal gradient value, consistent with its role in heteromodal semantic cognition. One frontotemporal control subnetwork was linked to individual differences in semantic cognition: when it was nearer heteromodal DMN on the principal gradient in LH, participants showed more efficient semantic retrieval—and this network also showed a strong hemispheric difference in response to semantic demands but not working memory load in a separate study. In contrast, when a dorsal attention subnetwork was closer to the heteromodal end of the principal gradient in RH, participants showed better visual reasoning. Lateralization of function may reflect differences in connectivity between control and heteromodal regions in LH, and attention and visual regions in RH. [ABSTRACT FROM AUTHOR]

Control processes allow us to constrain the retrieval of semantic information from long-term memory so that it is appropriate for the task or context. Control demands are influenced by the strength of the target information itself and by the circumstances in which it is retrieved, with more control needed when relatively weak aspects of knowledge are required and after the sustained retrieval of related concepts. To investigate the neurocognitive basis of individual differences in these aspects of semantic control, we used resting-state fMRI to characterise the intrinsic connectivity of left ventrolateral prefrontal cortex (VLPFC), implicated in controlled retrieval, and examined associations on a paced serial semantic task, in which participants were asked to detect category members amongst distractors. This task manipulated both the strength of target associations and the requirement to sustain retrieval within a narrow semantic category over time. We found that individuals with stronger connectivity between VLPFC and medial prefrontal cortex within the default mode network (DMN) showed better retrieval of strong associations (which are thought to be recalled more automatically). Stronger connectivity between the same VLPFC seed and another DMN region in medial parietal cortex was associated with larger declines in retrieval over the course of the category. In contrast, participants with stronger connectivity between VLPFC and cognitive control regions within the ventral attention network (VAN) had better controlled retrieval of weak associations and were better able to sustain their comprehension throughout the category. These effects overlapped in left insular cortex within the VAN, indicating that a common pattern of connectivity is associated with different aspects of controlled semantic retrieval induced by both the structure of long-term knowledge and the sustained retrieval of related information.

Dynamic causal modeling (DCM) is a method for analyzing functional magnetic resonance imaging (fMRI) and other functional neuroimaging data that provides information about directionality of connectivity between brain regions. A review of the neuropsychiatric fMRI DCM literature suggests that there may be a historical trend to under-report self-connectivity (within brain regions) compared to between brain region connectivity findings. These findings are an integral part of the neurologic model represented by DCM and serve an important neurobiological function in regulating excitatory and inhibitory activity between regions. We reviewed the literature on the topic as well as the past 13 years of available neuropsychiatric DCM literature to find an increasing (but still, perhaps, and inadequate) trend in reporting these results. The focus of this review is fMRI as the majority of published DCM studies utilized fMRI and the interpretation of the self-connectivity findings may vary across imaging methodologies. About 25% of articles published between 2007 and 2019 made any mention of self-connectivity findings. We recommend increased attention toward the inclusion and interpretation of self-connectivity findings in DCM analyses in the neuropsychiatric literature, particularly in forthcoming effective connectivity studies of substance use disorders. [ABSTRACT FROM AUTHOR]

The common and specific involvement of brain networks in clinical variants of Alzheimer's disease (AD) is not well understood. We performed task-free ("resting-state") functional imaging in 60 nonfamilial AD patients, including 20 early-onset AD (age at onset

Dynamic causal modeling (DCM) is a method for analyzing functional magnetic resonance imaging (fMRI) and other functional neuroimaging data that provides information about directionality of connectivity between brain regions. A review of the neuropsychiatric fMRI DCM literature suggests that there may be a historical trend to under-report self-connectivity (within brain regions) compared to between brain region connectivity findings. These findings are an integral part of the neurologic model represented by DCM and serve an important neurobiological function in regulating excitatory and inhibitory activity between regions. We reviewed the literature on the topic as well as the past 13 years of available neuropsychiatric DCM literature to find an increasing (but still, perhaps, and inadequate) trend in reporting these results. The focus of this review is fMRI as the majority of published DCM studies utilized fMRI and the interpretation of the self-connectivity findings may vary across imaging methodologies. About 25% of articles published between 2007 and 2019 made any mention of self-connectivity findings. We recommend increased attention toward the inclusion and interpretation of self-connectivity findings in DCM analyses in the neuropsychiatric literature, particularly in forthcoming effective connectivity studies of substance use disorders.

Animal imaging studies have the potential to further establish resting‐state fMRI (rs‐fMRI) and enable its validation for clinical use. The rabbit subjects used in this work are an ideal model system for studying learning and behavior and are also an excellent established test subject for awake scanning given their natural tolerance for restraint. We found that analysis of rs‐fMRI conducted on a cohort of rabbits undergoing eyeblink conditioning can reveal functional brain connectivity changes associated with learning, and that rs‐fMRI can be used to capture differences between subjects with different levels of cognitive performance. rs‐fMRI sessions were conducted on a cohort of rabbits before and after trace eyeblink conditioning. MRI results were analyzed using independent component analysis (ICA) and network analysis. Behavioral data were collected with standard methods using an infrared reflective sensor aimed at the cornea to detect blinks. Behavioral results were analyzed, and a median split was used to create two groups of rabbits based on their performance. The cohort of rabbits undergoing eyeblink conditioning exhibited increased functional connectivity in the cingulate cortex, retrosplenial cortex, and thalamus consistent with brain reorganization associated with increased learning. Differences in the striatum and right cerebellum were also identified between rabbits in the top or bottom halves of the group as measured by the behavioral assay. Thus, rs‐fMRI can provide not only a tool to detect and monitor functional brain changes associated with learning, but also to discriminate between different levels of cognitive performance. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a highly prevalent psychological disorder characterized by intense feelings of fear or helplessness after experiencing a traumatic event. PTSD is highly comorbid with mood disorders and patients are at increased risk for suicide. The present study aimed to identify neural connectivity alterations associated with suicidal ideation (SI) in PTSD patients by using resting-state functional magnetic resonance imaging. Voxel-to-voxel intrinsic connectivity was compared between PTSD patients with no (N-SI; N = 26) and high (H-SI; N = 7) SI. Region-to-voxel functional connectivity analysis was performed to identify the regions that contributed to intrinsic connectivity changes. H-SI patients had increased connectivity to various brain regions representing the central executive network, salience network, and default mode network in the frontal, temporal, and occipital lobes as well as subcortical structures involved in executive and limbic functioning, and motor systems. These results suggest SI is associated with large network-level alterations in PTSD patients and is not the result of neuronal abnormalities in any one specific area. • Shows PTSD-specific connectivity changes associated with suicidal ideation. • Uses an exploratory intrinsic connectivity analysis to guide seed selection. • Implicates sensory system abnormality in suicidal ideation in PTSD patients. [ABSTRACT FROM AUTHOR]

There is striking overlap between the spatial distribution of amyloid-β pathology in patients with Alzheimer's disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-β and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-β plaque accumulation on intrinsic connectivity in areas of high connectivity in heteromodal hubs, and particularly in the default mode network. However, the observed spatial extent of amyloid-β exceeds these tightly circumscribed areas, suggesting that previous studies may have underestimated the negative impact of amyloid-β on intrinsic connectivity. We hypothesized that the known positive baseline correlation between patterns of amyloid-β and intrinsic connectivity may mask the larger extent of the negative effects of amyloid-β on connectivity. Crucially, a test of this hypothesis requires the within-patient comparison of intrinsic connectivity and amyloid-β distributions. Here we compared spatial patterns of amyloid-β-plaques (measured by Pittsburgh compound B positron emission tomography) and intrinsic functional connectivity (measured by resting-state functional magnetic resonance imaging) in patients with prodromal Alzheimer's disease via spatial correlations in intrinsic networks covering fronto-parietal heteromodal cortices. At the global network level, we found that amyloid-β and intrinsic connectivity patterns were positively correlated in the default mode and several fronto-parietal attention networks, confirming that amyloid-β aggregates in areas of high intrinsic connectivity on a within-network basis. Further, we saw an internetwork gradient of the magnitude of correlation that depended on network plaque-load. After accounting for this globally positive correlation, local amyloid-β-plaque concentration in regions of high connectivity co-varied negatively with intrinsic connectivity, indicating that amyloid-β pathology adversely reduces connectivity anywhere in an affected network as a function of local amyloid-β-plaque concentration. The local negative association between amyloid-β and intrinsic connectivity was much more pronounced than conventional group comparisons of intrinsic connectivity would suggest. Our findings indicate that the negative impact of amyloid-β on intrinsic connectivity in heteromodal networks is underestimated by conventional analyses. Moreover, our results provide first within-patient evidence for correspondent patterns of amyloid-β and intrinsic connectivity, with the distribution of amyloid-β pathology following functional connectivity gradients within and across intrinsic networks.

Our recent work suggests that non-lesional epileptic brain tissue is capable of generating normal neurophysiological responses during cognitive tasks, which are then seized by ongoing pathologic epileptic activity. Here, we aim to extend the scope of our work to epileptic periventricular heterotopias (PVH) and examine whether the PVH tissue also exhibits normal neurophysiological responses and network-level integration with other non-lesional cortical regions. As part of routine clinical assessment, three adult patients with PVH underwent implantation of intracranial electrodes and participated in experimental cognitive tasks. We obtained simultaneous recordings from PVH and remote cortical sites during rest as well as controlled experimental conditions. In all three subjects (two females), cognitive experimental conditions evoked significant electrophysiological responses in discrete locations within the PVH tissue that were correlated with responses seen in non-epileptic cortical sites. Moreover, the responsive PVH sites exhibited correlated electrophysiological activity with responsive, non-lesional cortical sites during rest conditions. Taken together, our work clearly demonstrates that the PVH tissue may be functionally organized and it may be functionally integrated within cognitively engaged cortical networks despite its anatomic displacement during neurodevelopment. [ABSTRACT FROM AUTHOR]

Based on the joint investigation in 287 healthy volunteers (150 left-Handers (LH)) of language task-induced asymmetries and intrinsic connectivity strength of the sentence-processing supramodal network, we show that individuals with atypical rightward language lateralization (N = 30, 25 LH) do not rely on an organization that simply mirrors that of typical leftward lateralized individuals. Actually, the resting-state organization in the atypicals showed that their sentence processing was underpinned by left and right networks both wired for language processing and highly interacting by strong interhemispheric intrinsic connectivity and larger corpus callosum volume. Such a loose hemispheric specialization for language permits the hosting of language in either the left and/or right hemisphere as assessed by a very high incidence of dissociations across various language task-induced asymmetries in this group.

In mammals, the hippocampus, entorhinal, perirhinal, and parahippocampal cortices (i.e., core regions of the human medial temporal lobes, MTL) are locally interlaced with the adjacent amygdala nuclei at the structural and functional levels. At the global brain level, the human MTL has been described as part of the default mode network and amygdala nuclei as parts of the salience network, with both networks collectively forming a large-scale brain system supporting allostatic-interoceptive functions. We hypothesized (i) that intrinsic functional connectivity of slow activity fluctuations would reveal human MTL subsystems locally extending to the amygdala; and (ii) that these extended local subsystems would be globally embedded in large-scale brain systems supporting allostatic-interoceptive functions. Capitalizing on resting-state fMRI data of three independent samples of cognitively healthy adults (one main and two replication samples: N ​= ​101, 60, and 29, respectively), we analyzed the functional connectivity of fluctuating ongoing BOLD-activity within and outside the amygdala-MTL in a data-driven way using masked independent component and dual-regression analyses. We found that at the local level, MTL subsystems extend to the amygdala and are functionally organized along the longitudinal amygdala-MTL axis. These subsystems are characterized by consistent involvement of amygdala, hippocampus, and entorhinal cortex, but variable participation of perirhinal and parahippocampal regions. At the global level, amygdala-MTL subsystems selectively connect to salience, thalamic-brainstem, and default mode networks – the major cortical and subcortical components of the allostatic-interoceptive system. These findings provide evidence for integrated amygdala-MTL subsystems in humans, which are embedded within a larger allostatic-interoceptive system.

Objective: This study evaluated the hypothesis that methylphenidate immediate release (MPH-IR) treatment would improve Default Mode Network (DMN) within-connectivity. Method: Resting-state functional connectivity of the main nodes of DMN was evaluated in a highly homogeneous sample of 18 drug-naive male adult participants with ADHD. Results: Comparing resting-state functional connectivity functional magnetic resonance imaging (R-fMRI) scans before and after MPH treatment focusing exclusively on within-DMN connectivity, we evidenced the strengthening of functional connectivity between two nodes of the DMN: posterior cingulate cortex (PCC) and left lateral parietal cortex (LLP). Conclusion: Our results contribute to the further understanding on how MPH affects functional connectivity within DMN of male adults with ADHD and corroborate the hypothesis of ADHD being a delayed neurodevelopmental disorder. [ABSTRACT FROM AUTHOR]

Extending beyond the motor domain, the cerebellum is involved in various aspects of cognition and affect. Multidisciplinary evidence has demonstrated topographic organization of higher-order cognitive functions within the cerebellum. We here review recent neuroimaging research that indicates cerebellar contributions to major depressive disorder (MDD). At the structural level, increased volume of lobule IX has been demonstrated in MDD patients, independent of acute or remitted disease state. Successful treatment with electroconvulsive therapy has been associated with increased lobule VIIA volume in depressed patients. At the functional level, connectivity analyses have shown reduced cerebro-cerebellar coupling of lobules VI and VIIA/B with prefrontal, posterior parietal, and limbic regions in patients with MDD. As a limitation, most of this evidence is based on smaller patient samples with incomplete phenotypic and neuropsychological characterization and with heterogenous medication. Some studies did not apply cerebellum-optimized data analysis protocols. Taken together, MDD pathophysiology affects distinct subregions of the cerebellum that communicate with cortical networks subserving cognitive and self-referential processing. This mini-review synthesizes research evidence from cerebellar structural and functional neuroimaging in depression, and provides future perspectives for neuroimaging of cerebellar contributions to MDD.

Background and purpose: Significant clinical recovery has commonly been observed in ischaemic stroke patients with irreversible brain structural damage. However, brain mechanisms that help to maintain clinical function remain unclear. Methods: Sixty‐two patients with acute ischaemic stroke underwent longitudinal clinical assessments and magnetic resonance scanning. The clinical recovery trajectory was evaluated using a hierarchical linear model and intrinsic connectivity was analysed with a seed‐based approach to examine its changing pattern based on the regional volume changes calculated using voxel‐wise analysis. Results: It was observed that clinical outcome measures improved mainly in the short‐term period (baseline versus 3 weeks) and then remained stable. Grey matter volume was reduced significantly in the bilateral caudate over the entire 3‐year long‐term period. Significant intrinsic connectivity increases were observed in the caudate–middle cingulum over the short‐term period and in the caudate–precuneus and caudate–calcarine over the long‐term period. Finally, it was found that increased caudate–calcarine connectivity was associated with reduced right caudate volume, and a positive correlation was found between increased caudate–middle cingulum connectivity and the amount of modified Rankin score changes. Conclusions: The increased intrinsic connectivity found in this study tends to be a compensatory mechanism for post‐stroke structural damage, associated with clinical recovery. The study helps in understanding the significance of enhanced intrinsic connectivity in post‐stroke long‐term assessment and rehabilitation. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) has been assumed to be associated with aberrant brain connectivity. However, research suggests that brain connectivity abnormalities should not be restricted to extrinsic white matter connectivity, but may also impact on intrinsic gray matter connectivity. Therefore, our study aimed to investigate the intrinsic gray-matter connectivity in MDD.Methods: The participants were 16 first-episode, drug-naïve patients with MDD and 16 healthy controls matched on age and gender. All participants were scanned by 3.0T structural magnetic resonance imaging. Global and local intrinsic gray-matter connectivity were measured based on surface-based geodesic distances, including mean coritical separation distances (MSDs), perimeter function, and radius function.Results: MDD patients had significantly lower MSDs in the left postcentral gyrus and higher MSDs in the left superior parietal cortex. Marginally significant correlation was observed between MSDs in the left postcentral gyrus and symptoms of depression. Compared with healthy controls, depressed subjects had abnormal local intrinsic gray-matter connectivity in the left postcentral gyrus, the left transverse temporal gyrus, the right lingual gyrus, the right lateral occipital cortex, and the right superior frontal gyrus. Furthermore, local intrinsic gray matter connections of these brain areas were associated with some symptoms of depression.Limitations: The small sample size limited the interpretability of our potential conclusions.Conclusion: Aberrant intrinsic gray-matter connectivity was observed in depressed subjects, indicating abnormal intrinsic wiring cost of brain architecture. This might help explain the aberrant topological properties of brain functional connectivity and provide insights into the vulnerability of MDD. [ABSTRACT FROM AUTHOR]

We herein propose an atlas of 32 sentence-related areas based on a 3-step method combining the analysis of activation and asymmetry during multiple language tasks with hierarchical clustering of resting-state connectivity and graph analyses. 144 healthy right-handers performed fMRI runs based on language production, reading and listening, both with sentences and lists of over-learned words. Sentence minus word-list BOLD contrast and left-minus-right BOLD asymmetry for each task were computed in pairs of homotopic regions of interest (hROIs) from the AICHA atlas. Thirty-two hROIs were identified that were conjointly activated and leftward asymmetrical in each of the three language contrasts. Analysis of resting-state temporal correlations of BOLD variations between these 32 hROIs allowed the segregation of a core network, SENT_CORE including 18 hROIs. Resting-state graph analysis applied to SENT_CORE hROIs revealed that the pars triangularis of the inferior frontal gyrus and the superior temporal sulcus were hubs based on their degree centrality (DC), betweenness, and participation values corresponding to epicentres of sentence processing. Positive correlations between DC and BOLD activation values for SENT_CORE hROIs were observed across individuals and across regions regardless of the task: the more a SENT_CORE area is connected at rest the stronger it is activated during sentence processing. DC measurements in SENT_CORE may thus be a valuable index for the evaluation of inter-individual variations in language areas functional activity in relation to anatomical or clinical patterns in large populations. SENSAAS (SENtence Supramodal Areas AtlaS), comprising the 32 supramodal sentence areas, including SENT_CORE network, can be downloaded at http://www.gin.cnrs.fr/en/tools/. [ABSTRACT FROM AUTHOR]

Extending beyond the motor domain, the cerebellum is involved in various aspects of cognition and affect. Multidisciplinary evidence has demonstrated topographic organization of higher-order cognitive functions within the cerebellum. We here review recent neuroimaging research that indicates cerebellar contributions to major depressive disorder (MDD). At the structural level, increased volume of lobule IX has been demonstrated in MDD patients, independent of acute or remitted disease state. Successful treatment with electroconvulsive therapy has been associated with increased lobule VIIA volume in depressed patients. At the functional level, connectivity analyses have shown reduced cerebro-cerebellar coupling of lobules VI and VIIA/B with prefrontal, posterior parietal, and limbic regions in patients with MDD. As a limitation, most of this evidence is based on smaller patient samples with incomplete phenotypic and neuropsychological characterization and with heterogenous medication. Some studies did not apply cerebellum-optimized data analysis protocols. Taken together, MDD pathophysiology affects distinct subregions of the cerebellum that communicate with cortical networks subserving cognitive and self-referential processing. This mini-review synthesizes research evidence from cerebellar structural and functional neuroimaging in depression, and provides future perspectives for neuroimaging of cerebellar contributions to MDD. [ABSTRACT FROM AUTHOR]

Abstract We frequently guide our decisions about when and how to act based on the meanings of perceptual inputs: we might avoid treading on a flower, but not on a leaf. However, most research on response inhibition has used simple perceptual stimuli devoid of meaning. In two Go/No-Go experiments, we examined whether the neural mechanisms supporting response inhibition are influenced by the relevance of meaning to the decision, and by presentation modality (whether concepts were presented as words or images). In an on-line fMRI experiment, we found common regions for response inhibition across perceptual and conceptual decisions. These included the bilateral intraparietal sulcus and the right inferior frontal sulcus, whose neural responses have been linked to diverse cognitive demands in previous studies. In addition, we identified a cluster in ventral lateral occipital cortex that was sensitive to the modality of input, with a stronger response to No-Go than Go trials for meaningful images, compared to words with the same semantic content. In a second experiment, using resting-state fMRI, we explored how individual variation in the intrinsic connectivity of these activated regions related to variation in behavioural performance. Participants who showed stronger connectivity between common inhibition regions and limbic areas in medial temporal and subgenual anterior cingulate cortex were better at inhibition when this was driven by the meaning of the items. In addition, regions with a specific role in picture inhibition were more connected to a cluster in the thalamus/caudate for participants who were better at performing the picture task outside of the scanner. Together these studies indicate that the capacity to appropriately withhold action depends on interactions between common control regions, which are important across multiple types of input and decision, and other brain regions linked to specific inputs (i.e., visual features) or representations (e.g., memory). [ABSTRACT FROM AUTHOR]

Abstract The transition from childhood to adolescence is marked by distinct changes in behavior, including how one values waiting for a large reward compared to receiving an immediate, yet smaller, reward. While previous research has emphasized the relationship between this preference and age, it is also proposed that this behavior is related to circuitry between valuation and cognitive control systems. In this study, we examined how age and intrinsic functional connectivity strength within and between these neural systems relate to changes in discounting behavior across the transition into adolescence. We used mixed-effects modeling and linear regression to assess the contributions of age and connectivity strength in predicting discounting behavior. First, we identified relevant connections in a longitudinal sample of 64 individuals who completed MRI scans and behavioral assessments 2–3 times across ages 7–15 years (137 scans). We then repeated the analysis in a separate, cross-sectional, sample of 84 individuals (7–13 years). Both samples showed an age-related increase in preference for waiting for larger rewards. Connectivity strength within and between valuation and cognitive control systems accounted for further variance not explained by age. These results suggest that individual differences in functionalbrain organization can account for behavioral changes typically associated with age. [ABSTRACT FROM AUTHOR]

According to the triple network hypothesis the brain is equipped with three core neurocognitive networks: the default mode (DMN), the salience (SN), and the central executive (CEN) network. Moreover, the so called dorsal nexus, has met growing interest as it is a hub region connecting these three networks. Assessment of resting-state functional connectivity (rsFC) of these networks enables the elucidation of drug-induced brain alterations. Gamma-hydroxybutyrate (GHB) is a GHB/GABA-B receptor agonist that induces a paradoxical state of mixed stimulation and sedation at moderate doses, which makes it a valuable tool to investigate neural signatures of subjective drug effects. Employing a placebo-controlled, double-blind, randomized, cross-over design, we assessed the effects of GHB (35 mg/kg p. o.) in 19 healthy male subjects on DMN-, SN-, CEN-, and dorsal nexus-rsFC measured by functional magnet resonance imaging and applying independent component as well as seed-based analyses, while subjective drug effects were investigated using visual analog scales (VAS). Subjectively, GHB increased VAS ratings of a general drug effect, stimulation, and sedation. Intrinsic DMN-, and CEN-rsFC remained largely unchanged under GHB, but the drug increased SN-DMN-rsFC and SN-dorsal nexus-rsFC, while dorsal nexus-rsFC was reciprocally increased to both the SN (right anterior insula) and to the CEN (right middle frontal gyrus). Increased sedation significantly predicted the observed SN-dorsal nexus-rsFC. In conclusion, GHB generates a unique stimulant/sedative subjective state that is paralleled by a complex pattern of increased functional connectivity encompassing all three core neurocognitive networks of the brain, while increased SN-dorsal nexus-rsFC was demonstrated to be a potential signature of the sedative component of the drug effect. [ABSTRACT FROM AUTHOR]

Background Interventions that promote mindfulness consistently show salutary effects on cognition and emotional wellbeing in adults, and more recently, in children and adolescents. However, we lack understanding of the neurobiological mechanisms underlying mindfulness in youth that should allow for more judicious application of these interventions in clinical and educational settings. Methods Using multi-echo multi-band fMRI, we examined dynamic (i.e., time-varying) and conventional static resting-state connectivity between core neurocognitive networks (i.e., salience/emotion, default mode, central executive) in 42 children and adolescents (ages 6–17). Results We found that trait mindfulness in youth relates to dynamic but not static resting-state connectivity. Specifically, more mindful youth transitioned more between brain states over the course of the scan, spent overall less time in a certain connectivity state, and showed a state-specific reduction in connectivity between salience/emotion and central executive networks. The number of state transitions mediated the link between higher mindfulness and lower anxiety, providing new insights into potential neural mechanisms underlying benefits of mindfulness on psychological health in youth. Conclusions Our results provide new evidence that mindfulness in youth relates to functional neural dynamics and interactions between neurocognitive networks, over time. [ABSTRACT FROM AUTHOR]

The ability to quantify synaptic function at the level of cortical microcircuits from non-invasive data would be enormously useful in the study of neuronal processing in humans and the pathophysiology that attends many neuropsychiatric disorders. Here, we provide proof of principle that one can estimate inter-and intra-laminar interactions among specific neuronal populations using induced gamma responses in the visual cortex of human subjects – using dynamic causal modelling based upon the canonical microcircuit (CMC; a simplistic model of a cortical column). Using variability in induced (spectral) responses over a large cohort of normal subjects, we find that the predominant determinants of gamma responses rest on recurrent and intrinsic connections between superficial pyramidal cells and inhibitory interneurons. Furthermore, variations in beta responses were mediated by inter-subject differences in the intrinsic connections between deep pyramidal cells and inhibitory interneurons. Interestingly, we also show that increasing the self-inhibition of superficial pyramidal cells suppresses the amplitude of gamma activity, while increasing its peak frequency. This systematic and nonlinear relationship was only disclosed by modelling the causes of induced responses. Crucially, we were able to validate this form of neurophysiological phenotyping by showing a selective effect of the GABA re-uptake inhibitor tiagabine on the rate constants of inhibitory interneurons. Remarkably, we were able to recover the pharmacodynamics of this effect over the course of several hours on a per subject basis. These findings speak to the possibility of measuring population specific synaptic function – and its response to pharmacological intervention – to provide subject-specific biomarkers of mesoscopic neuronal processes using non-invasive data. Finally, our results demonstrate that, using the CMC as a proxy, the synaptic mechanisms that underlie the gain control of neuronal message passing within and between different levels of cortical hierarchies may now be amenable to quantitative study using non-invasive (MEG) procedures. [ABSTRACT FROM AUTHOR]

The voluntary allocation of visuospatial attention depends upon top-down influences from the frontal eye field (FEF) and intraparietal sulcus (IPS)-the core regions of the dorsal attention network (DAN)-to visual occipital cortex (VOC), and has been further associated with within-DAN influences, particularly from the FEF to IPS. However, the degree to which these influences manifest at rest and are then modulated during anticipatory visuospatial attention tasks remains poorly understood. Here, we measured both undirected and directed functional connectivity (UFC, DFC) between the FEF, IPS, and VOC at rest and during an anticipatory visuospatial attention task, using a slow event-related design. Whereas the comparison between rest and task indicated FC modulations that persisted throughout the task duration, the large number of task trials we collected further enabled us to measure shorter timescale modulations of FC across the trial. Relative to rest, task engagement induced enhancement of both top-down influences from the DAN to VOC, as well as bidirectional influences between the FEF and IPS. These results suggest that task performance induces enhanced interaction within the DAN and a greater top-down influence on VOC. While resting FC generally showed right hemisphere dominance, task-related enhancement favored the left hemisphere, effectively balancing a resting hemispheric asymmetry, particularly within the DAN. On a shorter (within-trial) timescale, VOC-to-DAN and bidirectional FEF-IPS influences were transiently elevated during the anticipatory period of the trial, evincing phasic modulations related to changing attentional demands. In contrast to these task-specific effects, resting and task-related influence patterns were highly correlated, suggesting a predisposing role for resting organization, which requires minimal tonic and phasic modulations for control of visuospatial attention. [ABSTRACT FROM AUTHOR]

Background Functional dyspepsia ( FD) is a common functional gastrointestinal disorder. Accumulating evidence suggests the crucial role of central nervous system in the development and maintenance of FD. In particular, periaqueductal gray ( PAG) has demonstrated an important role in modulation of pain and emotion, which may be related to FD. However, the study of the PAG in FD is still limited. This study aimed to assess intrinsic connectivity of the PAG in FD patients. Methods Resting-state functional magnetic imaging ( fMRI) data were collected from 66 FD patients and 42 healthy controls ( HCs). Functional connectivity analysis was performed to investigate the PAG connectivity pattern differences between the patients and HCs. We then examined the relationships between functional connectivity within the PAG networks and FD symptoms. Key Results Compared to HCs, patients had increased PAG connectivity with the insula, and decreased PAG connectivity with the orbitofrontal cortex ( OFC), dorsolateral prefrontal cortex (dl PFC) and hippocampus/parahippocampus ( HIPP/para HIPP). There were positive correlations between disease duration and PAG connectivity with the putamen and supplementary motor area ( SMA), and positive correlations between symptom severity and PAG connectivity with the insula. FD patients with high level of anxiety and depression had altered PAG connectivity with the anterior cingulate cortex ( ACC), precuneus, dl PFC and caudate, compared to other patients. Conclusions & Inferences These findings indicate that abnormal intrinsic network of the PAG might be associated with abnormality of pain processing and disruption of emotion processing in FD patients. Our study further complements neuroimaging findings about FD. [ABSTRACT FROM AUTHOR]

The 'dysconnection hypothesis' of psychosis suggests that a disruption of functional integration underlies cognitive deficits and clinical symptoms. Impairments in the P300 potential are well documented in psychosis. Intrinsic (self-)connectivity in a frontoparietal cortical hierarchy during a P300 experiment was investigated. Dynamic Causal Modeling was used to estimate how evoked activity results from the dynamics of coupled neural populations and how neural coupling changes with the experimental factors. Twenty-four patients with psychotic disorder, twenty-four unaffected relatives, and twenty-five controls underwent EEG recordings during an auditory oddball paradigm. Sixteen frontoparietal network models (including primary auditory, superior parietal, and superior frontal sources) were analyzed and an optimal model of neural coupling, explaining diagnosis and genetic risk effects, as well as their interactions with task condition were identified. The winning model included changes in connectivity at all three hierarchical levels. Patients showed decreased self-inhibition-that is, increased cortical excitability-in left superior frontal gyrus across task conditions, compared with unaffected participants. Relatives had similar increases in excitability in left superior frontal and right superior parietal sources, and a reversal of the normal synaptic gain changes in response to targets relative to standard tones. It was confirmed that both subjects with psychotic disorder and their relatives show a context-independent loss of synaptic gain control at the highest hierarchy levels. The relatives also showed abnormal gain modulation responses to task-relevant stimuli. These may be caused by NMDA-receptor and/or GABAergic pathologies that change the excitability of superficial pyramidal cells and may be a potential biological marker for psychosis. Hum Brain Mapp 38:3262-3276, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The neurological disturbances of migraine aura are caused by transient cortical dysfunction due to waves of spreading depolarization that disrupt neuronal signaling. The effects of these cortical events on intrinsic brain connectivity during attacks of migraine aura have not previously been investigated. Studies of spontaneous migraine attacks are notoriously challenging due to their unpredictable nature and patient discomfort. We investigated 16 migraine patients with visual aura during attacks and in the attack-free state using resting state fMRI. We applied a hypothesis-driven seed-based approach focusing on cortical visual areas and areas involved in migraine pain, and a data-driven independent component analysis approach to detect changes in intrinsic brain signaling during attacks. In addition, we performed the analyses after mirroring the MRI data according to the side of perceived aura symptoms. We found a marked increase in connectivity during attacks between the left pons and the left primary somatosensory cortex including the head and face somatotopic areas (peak voxel: P = 0.0096, ( x, y, z) = (−54, −32, 32), corresponding well with the majority of patients reporting right-sided pain. For aura-side normalized data, we found increased connectivity during attacks between visual area V5 and the lower middle frontal gyrus in the symptomatic hemisphere (peak voxel: P = 0.0194, ( x, y, z) = (40, 40, 12). The present study provides evidence of altered intrinsic brain connectivity during attacks of migraine with aura, which may reflect consequences of cortical spreading depression, suggesting a link between aura and headache mechanisms. Hum Brain Mapp 38:2635-2642, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Much of the literature exploring differences between intrinsic and task-evoked brain architectures has examined changes in functional connectivity patterns between specific brain regions. While informative, this approach overlooks important overall functional changes in hub organization and network topology that may provide insights about differences in integration between intrinsic and task-evoked states. Examination of changes in overall network organization, such as a change in the concentration of hub nodes or a quantitative change in network organization, is important for understanding the underlying processes that differ between intrinsic and task-evoked brain architectures. The present study used graph-theoretical techniques applied to publicly available neuroimaging data collected from a large sample of individuals ( N = 202), and a within-subject design where resting-state and several task scans were collected from each participant as part of the Human Connectome Project. We demonstrate that differences between intrinsic and task-evoked brain networks are characterized by a task-general shift in high-connectivity hubs from primarily sensorimotor/auditory processing areas during the intrinsic state to executive control/salience network areas during task performance. In addition, we demonstrate that differences between intrinsic and task-evoked architectures are associated with changes in overall network organization, such as increases in network clustering, global efficiency and integration between modules. These findings offer a new perspective on the principles guiding functional brain organization by identifying unique and divergent properties of overall network organization between the resting-state and task performance. Hum Brain Mapp 38:1992-2007, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The human brain is highly dynamic, supporting a remarkable range of cognitive abilities that emerge over the course of development. While flexible and dynamic coordination between neural systems is firmly established for children, our understanding of brain functional organization in early life has been built largely on the implicit assumption that functional connectivity (FC) is static. Understanding the nature of dynamic neural interactions during development is a critical issue for cognitive neuroscience, with implications for neurodevelopmental pathologies that involve anomalies in brain connectivity. In this work, FC dynamics of neurocognitive networks in a sample of 146 youth from varied sociodemographic backgrounds were delineated. Independent component analysis, sliding time window correlation, and k-means clustering were applied to resting-state fMRI data. Results revealed six dynamic FC states that re-occur over time and that complement, but significantly extend, measures of static FC. Moreover, the occurrence and amount of time spent in specific FC states are related to the content of self-generated thought during the scan. Additionally, some connections are more variable over time than are others, including those between inferior parietal lobe and precuneus. These regions contribute to multiple networks and likely play a role in adaptive processes in childhood. Age-related increases in temporal variability of FC among neurocognitive networks were also found. Taken together, these findings lay the groundwork for understanding how variation in the developing chronnectome is related to risk for neurodevelopmental disorders. Understanding how brain systems reconfigure with development should provide insight into the ontogeny of complex, flexible cognitive processes. Hum Brain Mapp 38:97-108, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Asymmetry in intra-hemispheric intrinsic connectivity, and its association with handedness and hemispheric dominance for language, were investigated in a sample of 290 healthy volunteers enriched in left-handers (52.7%). From the resting-state FMRI data of each participant, we derived an intra-hemispheric intrinsic connectivity asymmetry (HICA) matrix as the difference between the left and right intra-hemispheric matrices of intrinsic correlation computed for each pair of the AICHA atlas ROIs. We defined a similarity measure between the HICA matrices of two individuals as the correlation coefficient of their corresponding elements, and computed for each individual an index of intra-hemispheric intrinsic connectivity asymmetry as the average similarity measure of his HICA matrix to those of the other subjects of the sample (HICAs). Gaussian-mixture modeling of the age-corrected HICAs sample distribution revealed that two types of HICA patterns were present, one (Typical_HICA) including 92.4% of the participants while the other (Atypical_HICA) included only 7.6% of them, mostly left-handers. In addition, we investigated the relationship between asymmetry in intra-hemispheric intrinsic connectivity and language hemispheric dominance, including a potential effect of handedness on this relationship, thanks to an FMRI acquisition during language production from which an hemispheric functional lateralization index for language (HFLI) and a type of hemispheric dominance for language, namely leftward, ambilateral, or rightward, were derived for each individual. There was a significant association between the types of language hemispheric dominance and of intra-hemispheric intrinsic connectivity asymmetry, occurrence of Atypical_HICAs individuals being very high in the group of individuals rightward-lateralized for language (80%), reduced in the ambilateral group (19%) and rare in individuals leftward-lateralized for language (less than 3%). Quantitatively, we found a significant positive linear relationship between the HICAs and HFLI indices, with an effect of handedness on the intercept but not on the slope of this relationship. These findings demonstrate that handedness and hemispheric dominance for language are significantly but independently associated with the asymmetry of intra-hemispheric intrinsic connectivity. These findings suggest that asymmetry in intra-hemispheric connectivity is a variable phenotype shaped in part by hemispheric lateralization for language, but possibly also depending on other lateralized functions. [ABSTRACT FROM AUTHOR]

The identification and characterization of organization principals is essential for the understanding of neural function of brain areas. The inferior colliculus (IC) represents a midbrain nexus involved in numerous aspects of auditory processing. Likewise, neurons throughout the IC are tuned to a diverse range of specific stimulus features. Yet beyond a topographic arrangement of the cochlea-inherited frequency tuning, the functional organization of the IC is not well understood. Particularly, a common principle that links the diverse tuning characteristics is unknown. Here we used in vitro patch clamp recordings combined with laser-uncaging, and in vivo single cell recordings to study the spatial and functional organization principles of the central IC. We identified a topographic bias of ascending synaptic input timing that is balanced between inhibition and excitation and co-varies with in vivo first–spike latency. This bias was paralleled post-synaptically by differences in biophysical membrane properties and firing patterns, with integrating neurons predominantly found in the dorso-medial part, and coincidence-detector neurons biased to the ventro-lateral IC. Importantly, these cellular and network features translated into distinct temporal processing capabilities irrespectively of the neurons' characteristic frequency. Our data therefore imply that heterogeneity of synaptic inputs, intrinsic properties and temporal processing are functional principles that underlie the spatial organization of the central IC. [ABSTRACT FROM AUTHOR]

Multiple functional MRI (fMRI)-based functional connectivity networks were obtained by Yeo et al. (2011), and the visualization of these complex networks is a difficult task. Also, the combination of functional connectivity networks determined by fMRI with electroencephalography (EEG) data could be a very useful tool. Mobile devices are becoming increasingly common among users, and for this reason, we describe here two applications for Android and iOS mobile devices: one that shows in an interactive way the seven Yeo functional connectivity networks, and another application that shows the relative position of 10-20 EEG electrodes with Yeo's seven functional connectivity networks. [ABSTRACT FROM AUTHOR]

Task-based fMRI has been used to study the effects of experimental inflammation on the human brain, but it remains unknown whether intrinsic connectivity in the brain at rest changes during a sickness response. Here, we investigated the effect of experimental inflammation on connectivity between areas relevant for monitoring of bodily states, motivation, and subjective symptoms of sickness. In a double-blind randomized controlled experiment, 52 healthy volunteers were injected with 0.6 ng/kg LPS (lipopolysaccharide) or placebo, and participated in a resting state fMRI experiment after approximately 2 h 45 min. Resting state fMRI data were available from 48 participants, of which 28 received LPS and 20 received placebo. Bilateral anterior and bilateral posterior insula sections were used as seed regions and connectivity with bilateral orbitofrontal and cingulate (anterior and middle) cortices was investigated. Back pain, headache and global sickness increased significantly after as compared to before LPS, while a non-significant trend was shown for increased nausea. Compared to placebo, LPS was followed by increased connectivity between left anterior insula and left midcingulate cortex. This connectivity was significantly correlated to increase in back pain after LPS and tended to be related to increased global sickness, but was not related to increased headache or nausea. LPS did not affect the connectivity from other insular seeds. In conclusion, the finding of increased functional connectivity between left anterior insula and middle cingulate cortex suggests a potential neurophysiological mechanism that can be further tested to understand the subjective feeling of malaise and discomfort during a sickness response. [ABSTRACT FROM AUTHOR]

SEE SCHMAHMANN DOI101093/BRAIN/AWW064 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Neurodegenerative diseases are associated with distinct and distributed patterns of atrophy in the cerebral cortex. Emerging evidence suggests that these atrophy patterns resemble intrinsic connectivity networks in the healthy brain, supporting the network-based degeneration framework where neuropathology spreads across connectivity networks. An intriguing yet untested possibility is that the cerebellar circuits, which share extensive connections with the cerebral cortex, could be selectively targeted by major neurodegenerative diseases. Here we examined the structural atrophy in the cerebellum across common types of neurodegenerative diseases, and characterized the functional connectivity patterns of these cerebellar atrophy regions. Our results showed that Alzheimer's disease and frontotemporal dementia are associated with distinct and circumscribed atrophy in the cerebellum. These cerebellar atrophied regions share robust and selective intrinsic connectivity with the atrophied regions in the cerebral cortex. These findings for the first time demonstrated the selective vulnerability of the cerebellum to common neurodegenerative disease, extending the network-based degeneration framework to the cerebellum. Our work also has direct implications on the cerebellar contribution to the cognitive and affective processes that are compromised in neurodegeneration as well as the practice of using the cerebellum as reference region for ligand neuroimaging studies. [ABSTRACT FROM AUTHOR]

Resting-state functional magnetic resonance imaging is a powerful technique to study the whole-brain neural connectivity that underlies cognitive systems. The present study aimed to define the changes in neural connectivity in their relation to language development. Longitudinal resting-state functional data were acquired from a cohort of preschool children at age 5 and one year later, and changes in functional connectivity were correlated with language performance in sentence comprehension. For this, degree centrality, a voxel-based network measure, was used to assess age-related differences in connectivity at the whole-brain level. Increases in connectivity with age were found selectively in a cluster within the left posterior superior temporal gyrus and sulcus (STG/STS). In order to further specify the connection changes, a secondary seed-based functional connectivity analysis on this very cluster was performed. The correlations between resting-state functional connectivity (RSFC) and language performance revealed developmental effects with age and, importantly, also dependent on the advancement in sentence comprehension ability over time. In children with greater advancement in language abilities, the behavioral improvement was positively correlated with RSFC increase between left posterior STG/STS and other regions of the language network, i.e., left and right inferior frontal cortex. The age-related changes observed in this study provide evidence for alterations in the language network as language develops and demonstrates the viability of this approach for the investigation of normal and aberrant language development. [ABSTRACT FROM AUTHOR]

Interactions between the cerebellum and primary motor cortex are crucial for the acquisition of new motor skills. Recent neuroimaging studies indicate that learning motor skills is associated with subsequent modulation of resting-state functional connectivity in the cerebellar and cerebral cortices. The neuronal processes underlying the motor-learning-induced plasticity are not well understood. Here, we investigate changes in functional connectivity in source-reconstructed electroencephalography (EEG) following the performance of a single session of a dynamic force task in twenty young adults. Source activity was reconstructed in 112 regions of interest (ROIs) and the functional connectivity between all ROIs was estimated using the imaginary part of coherence. Significant changes in resting-state connectivity were assessed using partial least squares (PLS). We found that subjects adapted their motor performance during the training session and showed improved accuracy but with slower movement times. A number of connections were significantly upregulated after motor training, principally involving connections within the cerebellum and between the cerebellum and motor cortex. Increased connectivity was confined to specific frequency ranges in the mu- and beta-bands. Post hoc analysis of the phase spectra of these cerebellar and cortico-cerebellar connections revealed an increased phase lag between motor cortical and cerebellar activity following motor practice. These findings show a reorganization of intrinsic cortico-cerebellar connectivity related to motor adaptation and demonstrate the potential of EEG connectivity analysis in source space to reveal the neuronal processes that underpin neural plasticity. [ABSTRACT FROM AUTHOR]

The hippocampus (HPC) is functionally heterogeneous along the longitudinal anterior-posterior axis. In rodent models, gene expression maps define at least three discrete longitudinal subregions, which also differ in function, and in anatomical connectivity with the rest of the brain. In humans, equivalent HPC subregions are less well defined, resulting in a lack of consensus in neuroimaging approaches that limits translational study. This study determined whether a data-driven analysis, namely independent component analysis (ICA), could reproducibly define human HPC subregions, and map their respective intrinsic functional connectivity (iFC) with the rest of the brain. Specifically, we performed ICA of resting-state fMRI activity spatially restricted within the HPC, to determine the configuration and reproducibility of functional HPC components. Using dual regression, we then performed multivariate analysis of iFC between resulting HPC components and the whole brain, including detailed connectivity with the hypothalamus, a functionally important connection not yet characterized in human. We found hippocampal ICA resulted in highly reproducible longitudinally discrete components, with greater functional heterogeneity in the anterior HPC, consistent with animal models. Anterior hippocampal components shared iFC with the amygdala, nucleus accumbens, medial prefrontal cortex, posterior cingulate cortex, midline thalamus, and periventricular hypothalamus, whereas posterior hippocampal components shared iFC with the anterior cingulate cortex, retrosplenial cortex, and mammillary bodies. We show that spatially masked hippocampal ICA with dual regression reproducibly identifies functional subregions in the human HPC, and maps their respective brain intrinsic connectivity. Hum Brain Mapp 37:462-476, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Atlases of brain anatomical ROIs are widely used for functional MRI data analysis. Recently, it was proposed that an atlas of ROIs derived from a functional brain parcellation could be advantageous, in particular for understanding how different regions share information. However, functional atlases so far proposed do not account for a crucial aspect of cerebral organization, namely homotopy, i.e. that each region in one hemisphere has a homologue in the other hemisphere. New method We present AICHA (for Atlas of Intrinsic Connectivity of Homotopic Areas), a functional brain ROIs atlas based on resting-state fMRI data acquired in 281 individuals. AICHA ROIs cover the whole cerebrum, each having 1—homogeneity of its constituting voxels intrinsic activity, and 2—a unique homotopic contralateral counterpart with which it has maximal intrinsic connectivity. AICHA was built in 4 steps: (1) estimation of resting-state networks (RSNs) using individual resting-state fMRI independent components, (2) k -means clustering of voxel-wise group level profiles of connectivity, (3) homotopic regional grouping based on maximal inter-hemispheric functional correlation, and (4) ROI labeling. Results AICHA includes 192 homotopic region pairs (122 gyral, 50 sulcal, and 20 gray nuclei). As an application, we report inter-hemispheric (homotopic and heterotopic) and intra-hemispheric connectivity patterns at different sparsities. Comparison with existing method ROI functional homogeneity was higher for AICHA than for anatomical ROI atlases, but slightly lower than for another functional ROI atlas not accounting for homotopy. Conclusion AICHA is ideally suited for intrinsic/effective connectivity analyses, as well as for investigating brain hemispheric specialization. [ABSTRACT FROM AUTHOR]

We previously reported that effective treatment of chronic low back pain (CLBP) reversed abnormal brain structure and functional MRI (fMRI) activity during cognitive task performance, particularly in the left dorsolateral prefrontal cortex (DLPFC). Here, we used resting-state fMRI to examine how chronic pain affects connectivity of brain networks supporting cognitive functioning and the effect of treatment in 14 CLBP patients and 16 healthy, pain-free controls (scans were acquired at baseline for all subjects and at 6-months post-treatment for patients and a matched time-point for 10 controls). The main networks activated during cognitive task performance, task-positive network (TPN) and task-negative network (TNN) (aka default mode) network, were identified in subjects' task fMRI data and used to define matching networks in resting-state data. The connectivity of these cognitive restingstate networks was compared between groups, and before and after treatment. Our findings converged on the bilateral insula (INS) as the region of aberrant cognitive resting-state connectivity in patients pretreatment versus controls. These findings were complemented by an independent, data-driven approach showing altered global connectivity of the INS. Detailed investigation of the INS confirmed reduced connectivity to widespread TPN and TNN areas, which was partially restored post-treatment. Furthermore, analysis of diffusion-tensor imaging (DTI) data revealed structural changes in white matter supporting these findings. The left DLPFC also showed aberrant connectivity that was restored post-treatment. Altogether, our findings implicate the bilateral INS and left DLPFC as key nodes of disrupted cognition-related intrinsic connectivity in CLBP, and the resulting imbalance between TPN and TNN function is partially restored with treatment. [ABSTRACT FROM AUTHOR]

Background and purpose Functional neuroimaging studies have shown hyperresponsiveness of cortical areas to visual stimuli in migraine patients with aura outside of attacks. This may be a key feature in the initiation of aura episodes and possibly also migraine headache attacks. It is unknown if cortical dysfunction is present at rest, i.e. in the absence of any external stimuli. Functional magnetic resonance imaging is a powerful technique for evaluating resting state functional connectivity, i.e. coherence of brain activity across cerebral areas. The objective of this study was to investigate resting-state functional brain connectivity in migraineurs with aura outside of attacks using functional magnetic resonance imaging. Methods Forty patients suffering from migraine with visual aura and 40 individually age and gender matched healthy controls with no history or family history of migraine were investigated. Following advanced denoising, the data were analyzed both in a hypothesis-driven fashion, testing for abnormalities involving 27 different brain areas of potential relevance to migraine with aura including the cortical visual areas, the amygdala and peri-aqueductal grey matter, and in a data-driven exploratory fashion (dual regression) in order to reveal any possible between-group differences of resting state networks. Age, gender, attack frequency and disease duration were included as nuisance variables. Results No differences of functional connectivity were found between patients and controls. Conclusions The previously reported increased cortical hyperresponsivity in the interictal phase of migraine with aura is unlikely to be caused by abnormalities of intrinsic brain connectivity. The interictal migraine aura brain may be abnormally functioning only during exposure to external stimuli. [ABSTRACT FROM AUTHOR]