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Background: Working-memory deficit is associated with aberrant degree distribution of the brain connectome in schizophrenia. However, the brain neural mechanism underlying the degree redistribution pattern in schizophrenia is still uncertain. Methods: We examined the functional degree distribution of the connectome in 81 patients with schizophrenia and 77 healthy controls across different working-memory loads during an n-back task. We tested the associations between altered degree distribution and clinical symptoms, and we conducted functional connectivity analyses to investigate the neural mechanism underlying altered degree distribution. We repeated these analyses in a second independent data set of 96 participants. In the second data set, we employed machine-learning analysis to study whether the degree distribution pattern of one data set could be used to discriminate between patients with schizophrenia and controls in the other data set. Results: Patients with schizophrenia showed decreased centrality in the dorsal posterior cingulate cortex (dPCC) for the '2-back versus 0-back' contrast compared to healthy controls. The dPCC centrality pattern across all working-memory loads was an inverted U shape, with a left shift of this pattern in patients with schizophrenia. This reduced centrality was correlated with the severity of delusions and related to reduced functional connectivity between the dPCC and the dorsal precuneus. We replicated these results with the second data set, and the machine-learning analyses achieved an accuracy level of 71%. Limitations: We used a limited n-back paradigm that precluded the examination of higher working-memory loads. Conclusion: Schizophrenia is characterized by a load-dependent reduction of centrality in the dPCC, related to the severity of delusions. We suggest that restoring dPCC centrality in the presence of cognitive demands might have a therapeutic effect on persistent delusions in people with schizophrenia., Introduction Working-memory deficit--the failure to represent, maintain and update information in a short period of time--is a key feature of neurocognitive deficit in schizophrenia. (1) It emerges in the prodromal [...]

Background: We have previously reported activation in reward, salience and executive control regions during functional MRI (fMRI) using an approach-avoidance conflict (AAC) decision-making task with healthy adults. Further investigations into how anxiety and depressive disorders relate to differences in neural responses during AAC can inform their understanding and treatment. We tested the hypothesis that people with anxiety or depression have altered neural activation during AAC. Methods: We compared 118 treatment-seeking adults with anxiety or depression and 58 healthy adults using linear mixed-effects models to examine group-level differences in neural activation (fMRI) during AAC decision-making. Correlational analyses examined relationships between behavioural and neural measures. Results: Adults with anxiety or depression had greater striatal engagement when reacting to affective stimuli (p = 0.008, d = 0.31) regardless of valence, and weaker striatal engagement during reward feedback (p = 0.046, d = -0.27) regardless of the presence of monetary reward. They also had blunted amygdala activity during decision-making (p = 0.023, d = -0.32) regardless of the presence of conflict. Across groups, approach behaviour during conflict decision-making was inversely correlated with striatal activation during affective stimuli (p < 0.001, r = -0.28) and positively related to striatal activation during reward feedback (p < 0.001, r = 0.27). Limitations: Our transdiagnostic approach did not allow for comparisons between specific anxiety disorders, and our cross-sectional approach did not allow for causal inference. Conclusion: Anxiety and depression were associated with altered neural responses to AAC. Findings were consistent with the role of the striatum in action selection and reward responsivity, and they point toward striatal reactivity as a future treatment target. Blunting of amygdala activity in anxiety or depression may indicate a compensatory response to inhibit affective salience and maintain approach., Introduction Approach-avoidance conflict (AAC) occurs when a person makes a behavioural choice that might have rewarding or threatening outcomes. (1-3) Neural and behavioural mechanisms during AAC decision-making are relevant across [...]

The ability to suppress actions that lead to a negative outcome and explore alternative actions is necessary for optimal decision making. Although the basal ganglia have been implicated in these processes.sup.1-5, the circuit mechanisms underlying action selection and exploration remain unclear. Here, using a simple lateralized licking task, we show that indirect striatal projection neurons (iSPN) in the basal ganglia contribute to these processes through modulation of the superior colliculus (SC). Optogenetic activation of iSPNs suppresses contraversive licking and promotes ipsiversive licking. Activity in lateral superior colliculus (lSC), a region downstream of the basal ganglia, is necessary for task performance and predicts lick direction. Furthermore, iSPN activation suppresses ipsilateral lSC, but surprisingly excites contralateral lSC, explaining the emergence of ipsiversive licking. Optogenetic inactivation reveals inter-collicular competition whereby each hemisphere of the superior colliculus inhibits the other, thus allowing the indirect pathway to disinhibit the contralateral lSC and trigger licking. Finally, inactivating iSPNs impairs suppression of devalued but previously rewarded licking and reduces exploratory licking. Our results reveal that iSPNs engage the competitive interaction between lSC hemispheres to trigger a motor action and suggest a general circuit mechanism for exploration during action selection. Indirect striatal projection neurons in the basal ganglia modulate activity in the superior colliculus, thereby controlling selection and exploration of actions in response to a reward omission., Author(s): Jaeeon Lee [sup.1] , Bernardo L. Sabatini [sup.1] Author Affiliations: (1) Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, USA Main Activities of direct- and indirect-pathway [...]

Accurate navigation to a desired goal requires consecutive estimates of spatial relationships between the current position and future destination throughout the journey. Although neurons in the hippocampal formation can represent the position of an animal as well as its nearby trajectories.sup.1-7, their role in determining the destination of the animal has been questioned.sup.8,9. It is, thus, unclear whether the brain can possess a precise estimate of target location during active environmental exploration. Here we describe neurons in the rat orbitofrontal cortex (OFC) that form spatial representations persistently pointing to the subsequent goal destination of an animal throughout navigation. This destination coding emerges before the onset of navigation, without direct sensory access to a distal goal, and even predicts the incorrect destination of an animal at the beginning of an error trial. Goal representations in the OFC are maintained by destination-specific neural ensemble dynamics, and their brief perturbation at the onset of a journey led to a navigational error. These findings suggest that the OFC is part of the internal goal map of the brain, enabling animals to navigate precisely to a chosen destination that is beyond the range of sensory perception. Dedicated cells in the hippocampus and entorhinal cortex map an animal s instantaneous position in space; by contrast, its future goal location is represented in the orbitofrontal cortex, a structure within the broader circuit., Author(s): Raunak Basu [sup.1] , Robert Gebauer [sup.1] , Tim Herfurth [sup.1] , Simon Kolb [sup.1] , Zahra Golipour [sup.1] , Tatjana Tchumatchenko [sup.1] [sup.2] , Hiroshi T. Ito [sup.1] [...]

Purpose: Stuttering is characterized by intermittent speech disfluencies, which are dramatically reduced when speakers synchronize their speech with a steady beat. The goal of this study was to characterize the neural underpinnings of this phenomenon using functional magnetic resonance imaging. Method: Data were collected from 16 adults who stutter and 17 adults who do not stutter while they read sentences aloud either in a normal, self-paced fashion or paced by the beat of a series of isochronous tones ('rhythmic'). Task activation and task-based functional connectivity analyses were carried out to compare neural responses between speaking conditions and groups after controlling for speaking rate. Results: Adults who stutter produced fewer disfluent trials in the rhythmic condition than in the normal condition. Adults who stutter did not have any significant changes in activation between the rhythmic condition and the normal condition, but when groups were collapsed, participants had greater activation in the rhythmic condition in regions associated with speech sequencing, sensory feedback control, and timing perception. Adults who stutter also demonstrated increased functional connectivity among cerebellar regions during rhythmic speech as compared to normal speech and decreased connectivity between the left inferior cerebellum and the left prefrontal cortex. Conclusions: Modulation of connectivity in the cerebellum and prefrontal cortex during rhythmic speech suggests that this fluency-inducing technique activates a compensatory timing system in the cerebellum and potentially modulates top-down motor control and attentional systems. These findings corroborate previous work associating the cerebellum with fluency in adults who stutter and indicate that the cerebellum may be targeted to enhance future therapeutic interventions. Supplemental Material: https://doi.org/10.23641/asha. 14417681, Stuttering is a speech disorder that impacts the production of smooth and timely articulations of planned utterances. Stuttering typically emerges early in childhood and persists over the life span for [...]