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Schizophrenia is a devastating brain disorder that disturbs sensory perception, motor action, and abstract thought. Its clinical phenotype implies dysfunction of various mental domains, which has motivated a series of theories regarding the underlying pathophysiology. Aiming at a predictive benchmark of a catalog of cognitive functions, we developed a data‐driven machine‐learning strategy and provide a proof of principle in a multisite clinical dataset (n = 324). Existing neuroscientific knowledge on diverse cognitive domains was first condensed into neurotopographical maps. We then examined how the ensuing meta‐analytic cognitive priors can distinguish patients and controls using brain morphology and intrinsic functional connectivity. Some affected cognitive domains supported well‐studied directions of research on auditory evaluation and social cognition. However, rarely suspected cognitive domains also emerged as disease relevant, including self‐oriented processing of bodily sensations in gustation and pain. Such algorithmic charting of the cognitive landscape can be used to make targeted recommendations for future mental health research. [ABSTRACT FROM AUTHOR]

Abstract: It is argued that the mesolimbic system has a more general function in processing all salient events, including and extending beyond rewards. Saliency was defined as an event that is unexpected due to its frequency of occurrence and elicits an attentional‐behavioral switch. Using functional magnetic resonance imaging (fMRI), signals were measured in response to the modulation of salience of rewarding and nonrewarding events during a reward‐based decision making task, the so called desire‐reason dilemma paradigm (DRD). Replicating previous findings, both frequent and infrequent, and therefore salient, reward stimuli elicited reliable activation of the ventral tegmental area (VTA) and ventral striatum (vStr). When immediate reward desiring contradicted the superordinate task‐goal, we found an increased activation of the VTA and vStr when the salient reward stimuli were presented compared to the nonsalient reward stimuli, indicating a boosting of activation in these brain regions. Furthermore, we found a significantly increased functional connectivity between the VTA and vStr, confirming the boosting of vStr activation via VTA input. Moreover, saliency per se without a reward association led to an increased activation of brain regions in the mesolimbic reward system as well as the orbitofrontal cortex (OFC), inferior frontal gyrus (IFG), and anterior cingulate cortex (ACC). Finally, findings uncovered multiple increased functional interactions between cortical saliency‐processing brain areas and the VTA and vStr underlying detection and processing of salient events and adaptive decision making. [ABSTRACT FROM AUTHOR]

Abstract: Schizophrenia is a devastating mental disease with an apparent disruption in the highly associative default mode network (DMN). Interplay between this canonical network and others probably contributes to goal‐directed behavior so its disturbance is a candidate neural fingerprint underlying schizophrenia psychopathology. Previous research has reported both hyperconnectivity and hypoconnectivity within the DMN, and both increased and decreased DMN coupling with the multimodal saliency network (SN) and dorsal attention network (DAN). This study systematically revisited network disruption in patients with schizophrenia using data‐derived network atlases and multivariate pattern‐learning algorithms in a multisite dataset (n = 325). Resting‐state fluctuations in unconstrained brain states were used to estimate functional connectivity, and local volume differences between individuals were used to estimate structural co‐occurrence within and between the DMN, SN, and DAN. In brain structure and function, sparse inverse covariance estimates of network coupling were used to characterize healthy participants and patients with schizophrenia, and to identify statistically significant group differences. Evidence did not confirm that the backbone of the DMN was the primary driver of brain dysfunction in schizophrenia. Instead, functional and structural aberrations were frequently located outside of the DMN core, such as in the anterior temporoparietal junction and precuneus. Additionally, functional covariation analyses highlighted dysfunctional DMN‐DAN coupling, while structural covariation results highlighted aberrant DMN‐SN coupling. Our findings reframe the role of the DMN core and its relation to canonical networks in schizophrenia. We thus underline the importance of large‐scale neural interactions as effective biomarkers and indicators of how to tailor psychiatric care to single patients. [ABSTRACT FROM AUTHOR]

Previous whole-brain functional connectivity studies achieved successful classifications of patients and healthy controls but only offered limited specificity as to affected brain systems. Here, we examined whether the connectivity patterns of functional systems affected in schizophrenia (SCZ), Parkinson's disease (PD), or normal aging equally translate into high classification accuracies for these conditions. We compared classification performance between pre-defined networks for each group and, for any given network, between groups. Separate support vector machine classifications of 86 SCZ patients, 80 PD patients, and 95 older adults relative to their matched healthy/young controls, respectively, were performed on functional connectivity in 12 task-based, meta-analytically defined networks using 25 replications of a nested 10-fold cross-validation scheme. Classification performance of the various networks clearly differed between conditions, as those networks that best classified one disease were usually non-informative for the other. For SCZ, but not PD, emotion-processing, empathy, and cognitive action control networks distinguished patients most accurately from controls. For PD, but not SCZ, networks subserving autobiographical or semantic memory, motor execution, and theory-of-mind cognition yielded the best classifications. In contrast, young-old classification was excellent based on all networks and outperformed both clinical classifications. Our pattern-classification approach captured associations between clinical and developmental conditions and functional network integrity with a higher level of specificity than did previous whole-brain analyses. Taken together, our results support resting-state connectivity as a marker of functional dysregulation in specific networks known to be affected by SCZ and PD, while suggesting that aging affects network integrity in a more global way. Hum Brain Mapp 38:5845-5858, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Based on higher prevalence rates of several mental disorders for city dwellers, psychosocial stress effects of urban living have been proposed as an environmental risk factor contributing to the development of mental disorders. Recently, it was shown that amygdala activation differs between city dwellers and rural residents in response to a cognitive-social stressor. Besides its influence on the amygdala, chronic stress also affects mesocorticolimbic brain regions involved in reward processing and stress-related dysregulation of the mesocorticolimbic dopamine system is thought to contribute to onset and manifestation of psychiatric disorders. Here, we investigated differences in reward systems functioning in 147 healthy subjects living either in cities or in less urban areas by means of functional magnetic resonance imaging during performance of the desire-reason-dilemma paradigm, which permits a targeted investigation of bottom-up activation and top-down regulation of the reward circuit. Compared with subjects from less urban areas, city dwellers showed an altered activation and modulation capability of the midbrain (VTA) dopamine system. City dwellers also revealed increased responses in other brain regions involved in reward processing and in the regulation of stress and emotions, such as amygdala, orbitofrontal and pregenual anterior cingulate cortex. These results provide further evidence for effects of an urban environment on the mesolimbic dopamine system and the limbic system which may increase the risk to develop mental disorders. [ABSTRACT FROM AUTHOR]

Advances in functional brain imaging have improved the search for potential endophenotypic markers in schizophrenia. Here, we employed independent component analysis (ICA) and dynamic causal modeling (DCM) in resting state fMRI on a sample of 35 schizophrenia patients, 20 first-degree relatives and 35 control subjects. Analysis on ICA-derived networks revealed increased functional connectivity between the left frontoparietal network (FPN) and left temporal and parietal regions in schizophrenia patients ( P < 0.001). First-degree relatives shared this hyperconnectivity, in particular in the supramarginal gyrus (SMG; P = 0.008). DCM analysis was employed to further explore underlying effective connectivity. Results showed increased inhibitory connections to the left angular gyrus (AG) in schizophrenia patients from all other nodes of the left FPN ( P < 0.001), and in particular from the left SMG ( P = 0.001). Relatives also showed a pattern of increased inhibitory connections to the left AG ( P = 0.008). Furthermore, the patient group showed increased excitatory connectivity between the left fusiform gyrus and the left SMG ( P = 0.002). This connection was negatively correlated to inhibitory afferents to the left AG ( P = 0.005) and to the negative symptom score on the PANSS scale ( P = 0.001, r = −0.51). Left frontoparietotemporal dysfunction in schizophrenia has been previously associated with a range of abnormalities, including formal thought disorder, working memory dysfunction and sensory hallucinations. Our analysis uncovered new potential endophenotypic markers of schizophrenia and shed light on the organization of the left FPN in patients and their first-degree relatives. Hum Brain Mapp 38:1741-1750, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) involves impairment in cognitive and interpersonal functioning. The right temporoparietal junction (RTPJ) is a key brain region subserving cognitive-attentional and social processes. Yet, findings on the involvement of the RTPJ in the pathophysiology of MDD have so far been controversial. Recent connectivity-based parcellation data revealed a topofunctional dualism within the RTPJ, linking its anterior and posterior part (aRTPJ/pRTPJ) to antagonistic brain networks for attentional and social processing, respectively. Comparing functional resting-state connectivity of the aRTPJ and pRTPJ in 72 MDD patients and 76 well-matched healthy controls, we found a seed (aRTPJ/pRTPJ) × diagnosis (MDD/controls) interaction in functional connectivity for eight regions. Employing meta-data from a large-scale neuroimaging database, functional characterization of these regions exhibiting differentially altered connectivity with the aRTPJ/pRTPJ revealed associations with cognitive (dorsolateral prefrontal cortex, parahippocampus) and behavioral (posterior medial frontal cortex) control, visuospatial processing (dorsal visual cortex), reward (subgenual anterior cingulate cortex, medial orbitofrontal cortex, posterior cingulate cortex), as well as memory retrieval and social cognition (precuneus). These findings suggest that an imbalance in connectivity of subregions, rather than disturbed connectivity of the RTPJ as a whole, characterizes the connectional disruption of the RTPJ in MDD. This imbalance may account for key symptoms of MDD in cognitive, emotional, and social domains. Hum Brain Mapp 37:2931-2942, 2016. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Misdiagnosing bipolar depression can lead to very deleterious consequences of mistreatment. Although depressive symptoms may be similarly expressed in unipolar and bipolar disorder, changes in specific brain networks could be very distinct, being therefore informative markers for the differential diagnosis. We aimed to characterize specific alterations in candidate large-scale networks (frontoparietal, cingulo-opercular, and default mode) in symptomatic unipolar and bipolar patients using resting state fMRI, a cognitively low demanding paradigm ideal to investigate patients. Methods Networks were selected after independent component analysis, compared across 40 patients acutely depressed (20 unipolar, 20 bipolar), and 20 controls well-matched for age, gender, and education levels, and alterations were correlated to clinical parameters. Results Despite comparable symptoms, patient groups were robustly differentiated by large-scale network alterations. Differences were driven in bipolar patients by increased functional connectivity in the frontoparietal network, a central executive and externally-oriented network. Conversely, unipolar patients presented increased functional connectivity in the default mode network, an introspective and self-referential network, as much as reduced connectivity of the cingulo-opercular network to default mode regions, a network involved in detecting the need to switch between internally and externally oriented demands. These findings were mostly unaffected by current medication, comorbidity, and structural changes. Moreover, network alterations in unipolar patients were significantly correlated to the number of depressive episodes. Conclusion: Unipolar and bipolar groups displaying similar symptomatology could be clearly distinguished by characteristic changes in large-scale networks, encouraging further investigation of network fingerprints for clinical use. Hum Brain Mapp 37:808-818, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The ability to resist immediate rewards is crucial for lifetime success and individual well-being. Using functional magnetic resonance imaging, we assessed the association between trait impulsivity and the neural underpinnings of the ability to control immediate reward desiring. Low and high extreme impulsivity groups were compared with regard to their behavioral performance and brain activation in situations, in which they had to forego immediate rewards with varying value to achieve a superordinate long-term goal. We found that highly impulsive (HI) individuals, who successfully compensated for their lack in behavioral self-control, engaged two complementary brain mechanisms when choosing actions in favor of a long-term goal, but at the expense of an immediate reward. First, self-controlled decisions led to a general attenuation of reward-related activation in the nucleus accumbens, which was accompanied by an increased inverse connectivity with the anteroventral prefrontal cortex. Second, HI subjects controlled their desire for increasingly valuable, but suboptimal rewards through a linear reduction of activation in the ventromedial prefrontal cortex (VMPFC). This was achieved by an increased inverse coupling between the VMPFC and the ventral striatum. Importantly, the neural mechanisms observed in the HI group differed from those in extremely controlled individuals, despite similar behavioral performance. Collectively, these results suggest trait-specific neural mechanisms that allow HI individuals to control their desire for immediate reward. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Selvaraj S, Arnone D, Job D, Stanfield A, Farrow TFD, Nugent AC, Scherk H, Gruber O, Chen X, Sachdev PS, Dickstein DP, Malhi GS, Ha TH, Ha K, Phillips ML, McIntosh AM. Grey matter differences in bipolar disorder: a meta-analysis of voxel-based morphometry studies. Bipolar Disord 2012: 14: 135-145. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Several neuroimaging studies have reported structural brain differences in bipolar disorder using automated methods. While these studies have several advantages over those using region of interest techniques, no study has yet estimated a summary effect size or tested for between-study heterogeneity. We sought to address this issue using meta-analytic techniques applied for the first time in bipolar disorder at the level of the individual voxel. Methods: A systematic review identified 16 voxel-based morphometry (VBM) studies comparing individuals with bipolar disorder with unaffected controls, of which eight were included in the meta-analysis. In order to take account of heterogeneity, summary effect sizes were computed using a random-effects model with appropriate correction for multiple testing. Results: Compared with controls, subjects with bipolar disorder had reduced grey matter in a single cluster encompassing the right ventral prefrontal cortex, insula, temporal cortex, and claustrum. Study heterogeneity was widespread throughout the brain; though the significant cluster of grey matter reduction remained once these extraneous voxels had been removed. We found no evidence of publication bias (Eggers p = 0.63). Conclusions: Bipolar disorder is consistently associated with reductions in right prefrontal and temporal lobe grey matter. Reductions elsewhere may be obscured by clinical and methodological heterogeneity. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that deficits of working memory may be a promising neurocognitive endophenotype of bipolar affective disorder. However, little is known about the neurobiological correlates of these deficits. The aim of this study was to determine possible pathophysiological trait markers of bipolar disorder in neural circuits involved in working memory. Functional magnetic resonance imaging was performed in 18 euthymic bipolar patients and 18 matched healthy volunteers using two circuit-specific experimental tasks established by prior systematic neuroimaging studies of working memory. Both euthymic bipolar patients and healthy controls showed working memory-related brain activations that were highly consistent with findings from previous comparable neuroimaging studies in healthy subjects. While these patterns of brain activation were completely preserved in the bipolar patients, only the patients exhibited activation of the right amygdala during the articulatory rehearsal task. In the same task, functional activation in right frontal and intraparietal cortex and in the right cerebellum was significantly enhanced in the patients. These findings indicate that the right amygdala is pathologically activated in euthymic bipolar patients during performance of a circuit-specific working memory task (articulatory rehearsal). This pathophysiological abnormality appears to be a trait marker in bipolar disorders that can be observed even in the euthymic state and that seems to be largely independent of task performance and medication. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Previous studies using advanced imaging techniques have suggested subtle structural and functional changes in patients with juvenile myoclonic epilepsy (JME), mainly associated with the frontal lobes. In addition, it has been reported that these patients show neuropsychological deficits, often summarized as frontal lobe dysfunction. The aim of this study was a comprehensive analysis of neuropsychological parameters, and functional and structural magnetic resonance imaging (MRI) in an independent cohort of patients with JME. We studied 19 JME patients and 20 age-, sex-, and education-matched controls using a battery of standardized neuropsychological tests, optimized voxel-based morphometry (VBM), and two domain-specific working-memory paradigms combined with functional MRI (fMRI). Our investigations did not reveal statistically significant differences between the groups of JME patients and normal controls in either the VBM or the fMRI study of working memory. The neuropsychological examination showed a slightly worse performance for the JME patients across most tests used, reaching statistical significance for semantic and verbal fluency. In our cohort of JME patients, we could not reproduce the findings of frontal gray matter changes from previous studies, and we could not detect an fMRI correlate of previously reported differences in working memory in JME. The neuropsychological deficits may be attributed partially to antiepileptic medication. We conclude that structural and functional frontal lobe deficits in JME patients have to be interpreted with care. One reason for a variation between different cohorts may be the genetic heterogeneity of the disease. [ABSTRACT FROM AUTHOR]

This study investigates the functional architecture of working memory (WM) for verbal and tonal information during rehearsal and articulatory suppression. Participants were presented with strings of four sung syllables with the task to remember either the pitches (tonal information) or the syllables (verbal information). Rehearsal of verbal, as well as of tonal information activated a network comprising ventrolateral premotor cortex (encroaching Broca's area), dorsal premotor cortex, the planum temporale, inferior parietal lobe, the anterior insula, subcortical structures (basal ganglia and thalamus), as well as the cerebellum. The topography of activations was virtually identical for the rehearsal of syllables and pitches, showing a remarkable overlap of the WM components for the rehearsal of verbal and tonal information. When the WM task was performed under articulatory suppression, activations in those areas decreased, while additional activations arose in anterior prefrontal areas. These prefrontal areas might contain additional storage components of verbal and tonal WM that are activated when auditory information cannot be rehearsed. As in the rehearsal conditions, the topography of activations under articulatory suppression was nearly identical for the verbal as compared to the tonal task. Results indicate that both the rehearsal of verbal and tonal information, as well as storage of verbal and tonal information relies on strongly overlapping neuronal networks. These networks appear to partly consist of sensorimotor-related circuits which provide resources for the representation and maintenance of information, and which are remarkably similar for the production of speech and song. Hum Brain Mapp, 2009. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

High-resolution magnetic resonance images obtained in a patient several months after carbon monoxide (CO) intoxication revealed nearly symmetric regional atrophy of both lateral temporal lobes. This pattern of cortical lesions after CO exposure has not been reported before. The patient suffered from severe cognitive deficits including a transient Klüver-Bucy-like behavior. This report underlines the value of high-resolution magnetic resonance imaging in chronic stages of CO intoxication in the attempt to understand the neuroanatomical bases of the observed behavior. [ABSTRACT FROM AUTHOR]

The ability to quickly decide on the nature of unexpected environmental changes is vital for adaptive behavior. Converging evidence suggests that the orbitofrontal cortex plays an important role in the rapid assignment of motivational significance and goal relevance to environmental stimuli. However, its putative role as a central part of a network involved in the prioritization of attentional selection, particulary when significant environmental changes occur unexpectedly or outside of attentional focus, remains to be established. Therefore, we used functional magnetic resonance imaging with a subsequent psychophysiological interaction analysis to reveal the functional connectivity of the right posterior orbitofrontal cortex (pOFC) in a context, in which subjects had to adjust goal-directed behavior to behaviorally relevant events presented outside of the current attentional focus. As expected, an increased functional interaction between pOFC and regions involved in the modulation of selective attention (pulvinar nucleus and inferior parietal lobule) and processing of 'bottom-up' salience (substantia nigra) could be observed when unattended, but significant changes were relevant for behavior. Moreover, a positive correlation between level of accuracy and an increased functional connectivity between pOFC and extrastriate cortex suggested that a motivationally-triggered signal from pOFC may have increased visual processing of the relevant but currently unattended stimulus attribute. These data provide evidence that the interplay between the pOFC and these regions underlies a mechanism by which organisms rapidly achieve voluntary control of attentional resources to deal with behaviorally significant changes that occur outside of current attentional focus. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]