Schizophrenia is thought as a self-disorder with dysfunctional brain connectivity. This self-disorder is often attributed to high-order cognitive impairment. Yet due to the frequent report of sensorial and perceptual deficits, it has been hypothesized that self-disorder in schizophrenia is dysfunctional communication between sensory and cognitive processes. To further verify this assumption, the present study comprehensively examined dynamic reconfigurations of resting-state functional connectivity (rsFC) in schizophrenia at voxel level, region level, and network levels (102 patients vs. 124 controls). We found patients who show consistently increased rsFC variability in sensory and perceptual system, including visual network, sensorimotor network, attention network, and thalamus at all the three levels. However, decreased variability in high-order networks, such as default mode network and frontal–parietal network were only consistently observed at region and network levels. Taken together, these findings highlighted the rudimentary role of elevated instability of information communication in sensory and perceptual system and attenuated whole-brain integration of high-order network in schizophrenia, which provided novel neural evidence to support the hypothesis of disrupted perceptual and cognitive function in schizophrenia. The foci of effects also highlighted that targeting perceptual deficits can be regarded as the key to enhance our understanding of pathophysiology in schizophrenia and promote new treatment intervention.

An extensive body of literature has indicated that there is increased activity in the frontoparietal control network (FPC) and decreased activity in the default mode network (DMN) during working memory (WM) tasks. The FPC and DMN operate in a competitive relationship during tasks requiring externally directed attention. However, the association between this FPC-DMN competition and performance in social WM tasks has rarely been reported in previous studies. To investigate this question, we measured FPC-DMN connectivity during resting state and two emotional face recognition WM tasks using the 2-back paradigm. Thirty-four individuals were instructed to perform the tasks based on either the expression [emotion (EMO)] or the identity (ID) of the same set of face stimuli. Consistent with previous studies, an increased anti-correlation between the FPC and DMN was observed during both tasks relative to the resting state. Specifically, this anti-correlation during the EMO task was stronger than during the ID task, as the former has a higher social load. Intriguingly, individual differences in self-reported empathy were significantly correlated with the FPC-DMN anti-correlation in the EMO task. These results indicate that the top-down signals from the FPC suppress the DMN to support social WM and empathy.

Background Animal models of addiction suggest that the transition from incentive-driven to habitual and ultimately compulsive drug use is mediated by a shift from ventral to dorsal striatal cue-control over drug seeking. Previous studies in human cannabis users reported elevated trait impulsivity and cue-reactivity in striatal circuits, however, these studies were not able to separate addiction-related from exposure-related adaptations.Methods To differentiate the adaptive changes, the present functional magnetic resonance imaging study examined behavioral and neural cue-reactivity in dependent (n = 18) and nondependent (n = 20) heavy cannabis users and a non-using reference group (n = 44). ResultsIrrespective of dependence status, cannabis users demonstrated elevated trait impulsivity as well as increased ventral striatal reactivity and striato-frontal coupling in response to drug cues. Dependent users selectively exhibited dorsal-striatal reactivity and decreased striato-limbic coupling during cue-exposure. An exploratory analysis revealed that higher ventral caudate cue-reactivity was associated with stronger cue-induced arousal and craving in dependent users, whereas this pattern was reversed in non-dependent users.Conclusions Together the present findings suggest that an incentive sensitization of the ventral striatal reward system may promote excessive drug use in humans, whereas adaptations in dorsal striatal systems engaged in habit formation may promote the transition to addictive use.

Extinction is considered a core mechanism underlying exposure-based therapy in anxiety-related disorders. However, marked impairments in threat extinction learning coupled with impaired neuroplasticity in patients strongly impede the efficacy of exposure-based interventions. Recent translational research suggests a role of the renin-angiotensin (RA) system in both these processes. However, the efficacy of pharmacological modulation of the RA system to enhance threat extinction in humans and the underlying neural mechanisms remain unclear. The present pre-registered, randomized placebo-controlled pharmacological neuroimaging trial demonstrates that pre-extinction administration of the angiotensin II type 1 receptor antagonist losartan accelerated attenuation of the psychophysiological threat response during extinction.On the neural level the acceleration of extinction was accompanied by threat-signal specific enhanced ventromedial prefrontal cortex (vmPFC) activation and its coupling with the basolateral amygdala. Multivoxel pattern analysis and voxel-wise mediation analysis further revealed that that losartan reduced the neural threat expression, particularly in the vmPFC, and confirmed that acceleration of extinction critically involved treatment-induced modulation of vmPFC activation. Overall the results provide the first evidence for a pivotal role of the RA system in extinction learning in humans and suggest that adjunct losartan administration can be leveraged to facilitate the efficacy of extinction-based therapies..

The transition from voluntary to addictive behavior is characterized by a loss of regulatory control in favor of reward driven behavior. Animal models indicate that this process is neurally underpinned by a shift in ventral–dorsal striatal control of behavior; however, this shift has not been directly examined in humans. The present resting state functional magnetic resonance imaging (fMRI) study employed a two‐step approach to: (a) precisely map striatal alterations using a novel, data‐driven network classification strategy combining intrinsic connectivity contrast with multivoxel pattern analysis and, (b) to determine whether a ventral to dorsal striatal shift in connectivity with reward and regulatory control regions can be observed in abstinent (28 days) male cannabis‐dependent individuals (n = 24) relative to matched controls (n = 28). Network classification revealed that the groups can be reliably discriminated by global connectivity profiles of two striatal regions that mapped onto the ventral (nucleus accumbens) and dorsal striatum (caudate). Subsequent functional connectivity analysis demonstrated a relative shift between ventral and dorsal striatal communication with fronto‐limbic regions that have been consistently involved in reward processing (rostral anterior cingulate cortex [ACC]) and executive/regulatory functions (dorsomedial prefrontal cortex [PFC]). Specifically, in the cannabis‐dependent subjects, connectivity between the ventral striatum with the rostral ACC increased, whereas both striatal regions were uncoupled from the regulatory dorsomedial PFC. Together, these findings suggest a shift in the balance between dorsal and ventral striatal control in cannabis dependence. Similar changes have been observed in animal models and may promote the loss of control central to addictive behavior.

Background Schizophrenia has been primarily conceptualized as a disorder of high-order cognitive functions with deficits in executive brain regions. Yet due to the increasing reports of early sensory processing deficit, recent models focus more on the developmental effects of impaired sensory process on high-order functions. The present study examined whether this pathological interaction relates to an overarching system-level imbalance, specifically a disruption in macroscale hierarchy affecting integration and segregation of unimodal and transmodal networks. Methods We applied a novel combination of connectome gradient and stepwise connectivity analysis to resting-state fMRI to characterize the sensorimotor-to-transmodal cortical hierarchy organization (96 patients v. 122 controls). Results We demonstrated compression of the cortical hierarchy organization in schizophrenia, with a prominent compression from the sensorimotor region and a less prominent compression from the frontal−parietal region, resulting in a diminished separation between sensory and fronto-parietal cognitive systems. Further analyses suggested reduced differentiation related to atypical functional connectome transition from unimodal to transmodal brain areas. Specifically, we found hypo-connectivity within unimodal regions and hyper-connectivity between unimodal regions and fronto-parietal and ventral attention regions along the classical sensation-to-cognition continuum (voxel-level corrected, p < 0.05). Conclusions The compression of cortical hierarchy organization represents a novel and integrative system-level substrate underlying the pathological interaction of early sensory and cognitive function in schizophrenia. This abnormal cortical hierarchy organization suggests cascading impairments from the disruption of the somatosensory−motor system and inefficient integration of bottom-up sensory information with attentional demands and executive control processes partially account for high-level cognitive deficits characteristic of schizophrenia.

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