Background Deficits in social cognition, including impairments in self-awareness, contribute to the overall functional disability associated with schizophrenia. Studies in healthy subjects have shown that social cognitive functions, including self-reflection, rely on the medial prefrontal cortex (mPFC) and posterior cingulate gyrus, and these regions exhibit highly correlated activity during “resting” states. In this study, we tested the hypothesis that patients with schizophrenia show dysfunction of this network during self-reflection and that this abnormal activity is associated with changes in the strength of resting-state correlations between these regions. Methods Activation during self-reflection and control tasks was measured with functional magnetic resonance imaging in 19 patients with schizophrenia and 20 demographically matched control subjects. In addition, the resting-state functional connectivity of midline cortical areas showing abnormal self-reflection-related activation in schizophrenia was measured. Results Compared with control subjects, the schizophrenia patients demonstrated lower activation of the right ventral mPFC and greater activation of the mid/posterior cingulate gyri bilaterally during self-reflection, relative to a control task. A similar pattern was seen during overall social reflection. In addition, functional connectivity between the portion of the left mid/posterior cingulate gyrus showing abnormally elevated activity during self-reflection in schizophrenia, and the dorsal anterior cingulate gyrus was lower in the schizophrenia patients compared with control subjects. Conclusions Schizophrenia is associated with an anterior-to-posterior shift in introspection-related activation, as well as changes in functional connectivity, of the midline cortex. These findings provide support for the hypothesis that aberrant midline cortical function contributes to social cognitive impairment in schizophrenia.

A parietal-frontal network in primates is thought to support many behaviors occurring in the space around the body, including interpersonal interactions and maintenance of a particular "comfort zone" or distance from other people ("personal space"). To better understand this network in humans, we used functional MRI to measure the responses to moving objects (faces, cars, simple spheres) and the functional connectivity of two regions in this network, the dorsal intraparietal sulcus (DIPS) and the ventral premotor cortex (PMv). We found that both areas responded more strongly to faces that were moving toward (vs away from) subjects, but did not show this bias in response to comparable motion in control stimuli (cars or spheres). Moreover, these two regions were functionally interconnected. Tests of activity-behavior associations revealed that the strength of DIPS-PMv connectivity was correlated with the preferred distance that subjects chose to stand from an unfamiliar person (personal space size). In addition, the magnitude of DIPS and PMv responses was correlated with the preferred level of social activity. Together, these findings suggest that this parietal-frontal network plays a role in everyday interactions with others.

Context Abnormalities in associative memory processes, such as Pavlovian fear conditioning and extinction, have been observed in schizophrenia. The retrieval of fear extinction memories (‘safety signals’) may be particularly affected; although schizophrenia patients can extinguish conditioned fear, they show a deficit in retrieving fear extinction memories after a delay. The neurobiological basis of this abnormality is unknown, but clues have emerged from studies in rodents and humans demonstrating that the ventromedial prefrontal cortex (vmPFC) is a key mediator of extinction memory retrieval. Objective To measure autonomic and neural responses during the acquisition and extinction of conditioned fear and the delayed recall of fear and extinction memories in patients with schizophrenia and healthy controls. Design Cross-sectional case-control, functional magnetic resonance imaging study. Setting Academic medical center. Participants Twenty patients with schizophrenia and 17 healthy control participants, demographically-matched to the patient group. Main Outcome Measures Skin conductance and blood oxygen level dependent (BOLD) responses. Results During fear conditioning, patients with schizophrenia showed blunted autonomic responses and abnormal BOLD responses, relative to controls, within the posterior cingulate gyrus, hippocampus and other regions. Several of these abnormalities were linked to negative symptoms. During extinction learning, patients with schizophrenia and controls showed comparable autonomic and neural responses. Twenty-four hours after the learning phases, the control subjects exhibited decreased fear and increased vmPFC responses in the extinction (safe) context as expected, indicating successful retention of the extinction memory. In contrast, the schizophrenia patients showed inappropriately elevated fear and poor vmPFC responses in the safe context. Conclusion Failure of extinction memory retrieval in schizophrenia is associated with vmPFC dysfunction. In future studies, abnormalities in fear learning and extinction recall may serve as quantitative phenotypes that can be linked to genetic, symptom or outcome profiles in schizophrenia and those at risk for the disorder.

The application of digital technology to psychiatry research is rapidly leading to new discoveries and capabilities in the field of mobile health. However, the increase in opportunities to passively collect vast amounts of detailed information on study participants coupled with advances in statistical techniques that enable machine learning models to process such information has raised novel ethical dilemmas regarding researchers' duties to: (i) monitor adverse events and intervene accordingly; (ii) obtain fully informed, voluntary consent; (iii) protect the privacy of participants; and (iv) increase the transparency of powerful, machine learning models to ensure they can be applied ethically and fairly in psychiatric care. This review highlights emerging ethical challenges and unresolved ethical questions in mobile health research and provides recommendations on how mobile health researchers can address these issues in practice. Ultimately, the hope is that this review will facilitate continued discussion on how to achieve best practice in mobile health research within psychiatry.

Seventy-seven undergraduates, primed for autonomous or controlled motivation, were videotaped and physiologically monitored during a stressful interview and subsequent speech. Interview videotapes were coded for behavioral measures of threat response; speech videotapes were coded for performance. It was hypothesized that relative to controlled motivation, autonomous motivation would decrease interview threat response and enhance speech performance, and that threat response would mediate the effect of motivation on performance. Results support the prediction across measures of verbal, paralinguistic, smiling, vocal fundamental frequency, and cardiovascular response. Autonomously primed participants continued to show less cardiovascular threat throughout the later speech and gave better speeches. Finally, speech performance was mediated by interview threat response. Results demonstrate that relative to controlled motivation, autonomous motivation lowers threat response, which enhances performance.

Schizophrenia is associated with subtle abnormalities in day-to-day social behaviors, including a tendency in some patients to “keep their distance” from others in physical space. The neural basis of this abnormality, and related changes in social functioning, is unknown. Here we examined, in schizophrenic patients and healthy control subjects, the functioning of a parietal–frontal network involved in monitoring the space immediately surrounding the body (“personal space”). Using fMRI, we found that one region of this network, the dorsal intraparietal sulcus (DIPS), was hyper-responsive in schizophrenic patients to face stimuli appearing to move towards the subjects, intruding into personal space. This hyper-responsivity was predicted both by the size of personal space (which was abnormally elevated in the schizophrenia group) and the severity of negative symptoms. In contrast, in a second study, the activity of two lower-level visual areas that send information to DIPS (the fusiform face area and middle temporal area) was normal in schizophrenia. Together, these findings suggest that changes in parietal–frontal networks that support the sensory-guided initiation of behavior, including actions occurring in the space surrounding the body, contribute to social dysfunction and negative symptoms in schizophrenia.

Patients with schizophrenia may have altered pain perception, as suggested by clinical reports of pain insensitivity, and recent neuroimaging findings. Here, we examined neural responses to an aversive electrical stimulus and the immediate anticipation of such a stimulus using fMRI and a classical conditioning paradigm, which involved pairing an electrical shock with a neutral photograph. Fifteen men with schizophrenia and 13 healthy men, matched for demographic characteristics, electrical stimulation level and scan movement, were studied. The shock induced robust responses in midbrain, thalamus, cingulate gyrus, insula and somatosensory cortex in both groups. However, compared to controls, the schizophrenic patients displayed significantly lower activation of the middle insula (pFWE = 0.002, T=5.72, cluster size =24 voxels). Moreover, the lack of insula reactivity in the schizophrenia group was predicted by the magnitude of positive symptoms (r = −0.46, p=0.04). In contrast, there were no significant differences between the two groups in the magnitude of neural responses during anticipation of the shock. These findings provide support for the existence of a basic deficit in interoceptive perception in schizophrenia, which could play a role in the generation and/or maintenance of psychotic states.

BackgroundPrevious studies have shown that the activity of the amygdala is elevated in people experiencing clinical and subclinical levels of anxiety and depression (negative affect). It has been proposed that a reduction in inhibitory input to the amygdala from the prefrontal cortex and resultant over-activity of the amygdala underlies this association. Prior studies have found relationships between negative affect and 1) amygdala over-activity and 2) reduced amygdala-prefrontal connectivity. However, it is not known whether elevated amygdala activity is associated with decreased amygdala-prefrontal connectivity during negative affect states.MethodsHere we used resting-state arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in combination to test this model, measuring the activity (regional cerebral blood flow, rCBF) and functional connectivity (correlated fluctuations in the BOLD signal) of one subregion of the amygdala with strong connections with the prefrontal cortex, the basolateral nucleus (BLA), and subsyndromal anxiety levels in 38 healthy subjects.ResultsBLA rCBF was strongly correlated with anxiety levels. Moreover, both BLA rCBF and anxiety were inversely correlated with the strength of the functional coupling of the BLA with the caudal ventromedial prefrontal cortex. Lastly, BLA perfusion was found to be a mediator of the relationship between BLA-prefrontal connectivity and anxiety.ConclusionsThese results show that both perfusion of the BLA and a measure of its functional coupling with the prefrontal cortex directly index anxiety levels in healthy subjects, and that low BLA-prefrontal connectivity may lead to increased BLA activity and resulting anxiety. Thus, these data provide key evidence for an often-cited circuitry model of negative affect, using a novel, multi-modal imaging approach.