1. Emotional Disturbances in Schizophrenia

My earlier work examined frequency of negative emotional experience among individuals with schizophrenia and how it is related to their community functioning. It is well-documented in the literature that deficits in “cold” cognition (such as memory and executive functions) and social cognition (such as ability to recognize facial emotions, infer others’ mental state) are associated with poorer community functioning in schizophrenia. We added to the literature that increased negative emotional experience makes unique contributions to poor functional outcomes (Tso et al., 2010). Our 1-year follow-up data further showed that patients’ subjective psychological distress is able to predict their long-term social functioning better than symptom ratings done by clinicians (Tso et al., 2012). We extended this work and used functional neuroimaging (fMRI), to show that emotion processing in schizophrenia is associated with altered brain activity in distributed brain regions, including the medial prefrontal cortex, amgydala, interior insula, and visual cortex (Taylor et al., 2012). We recently combined fMRI and pharmacological challenge techniques to show that altered GABAergic functions in the visual cortex, in addition to the medial prefrontal cortex, are related to excessive negative affect in schizophrenia (Taylor et al., 2014; Tso et al., 2015). This work underscores the role of impaired visual processing, in addition to higher-level cognitive deficits, in socio-emotional disturbances in schizophrenia.

2. Eye Gaze Perception in Psychiatric Disorders

Eye gaze is a ubiquitous social cue that conveys one’s attention and mental state. The ability to accurately and efficiently discriminate others’ eye gaze direction (in particular, when it is self-directed) is a critical to understanding others and navigating the social environment competently. Therefore, understanding whether and how this basic social cognitive process is disrupted in psychiatric disorders accompanied with significant social difficulties would advance our understanding of the disorder and help us devise better treatments to improve patients’ social functioning and quality of life. We use multiple methods in this line of investigation.

Psychophysics. Psychophysics is an experimental method that examines the properties of human perception through systemic manipulation of the intensity of sensory stimulus. We have applied psychophysics method to study how patients’ eye-contact perception changes as the gaze direction of the viewed face changes. This method allows us to deconstruct eye gaze perception into two constituent cognitive components and demonstrate that schizophrenia patients are less precise in processing visual information and are more biased to perceive ambiguous gaze direction as self-directed compared with healthy comparisons (Tso et al., 2012). We also showed that compromised gaze perception accounts for impairment in socio-emotional functioning in schizophrenia (Tso et al., 2012). Further, we showed that deficits in basic visual perception may have a cascade effect on gaze perception (Tso et al., 2014), consistent with our finding of the role of visual cortex dysfunction in socio-emotional disturbances in psychosis as mentioned above. We have also collected data in bipolar disorder for these experiments and show that gaze perception deficits are also present in bipolar disorder (Yao et al., 2018). We recently showed that these gaze perception measures are stable over time and predict higher-level social cognition (Lasagna et al., 2020). We are currently extending this investigation to other psychiatric disorders displaying significant social dysfunction, such as autism-spectrum disorders and social anxiety.

Electrophysiology. By examining electrical brain activity recorded from the scalp (electroencephalography, EEG), we can gain understanding of the neurophysiology contributing to abnormal eye gaze perception in schizophrenia. One of the analytic techniques that utilizes EEG is called event-related potentials (ERP), which time-locks electrical brain activity to events of interest and then averages such activity across many trials to obtain a stable signal. Using ERP, we showed that abnormal gaze perception in schizophrenia is characterized by reduced visual integration of facial features as well as heightened threat detection (Tso et al., 2015). In another study, we showed that ERP patterns of patients with bipolar disorder were different from those of schizophrenia patients, even though their behavioral responses in a gaze perception task were similar (Tso et al., 2018). We are currently examining the neuronal rhythms of different brain regions (through analyses of neural oscillations and synchrony) in schizophrenia and bipolar patients during a gaze perception task (Grove et al., 2020). This will give us insight into the communicative patterns of the brain that contribute to abnormal gaze perception, offering clues on ways to modulate brain activity to improve patients’ social cognition.

Functional magnetic resonance imaging (fMRI). fMRI is a safe, non-radioactive neuroimaging technique that allows researchers to take pictures of the brain while the participant is performing a cognitive task, so that we can “see the brain at work.” We are currently studying gaze perception in schizophrenia and bipolar disorder using fMRI. We expect to gain knowledge of the neural mechanisms responsible for the observed changes in gaze perception in patients, which would help us design more targeted interventions.

Transcranial magnetic stimulation (TMS). TMS is a brain stimulation tool that uses magnetic energy to activate or suppress parts of the brain temporarily. TMS can provide evidence that a given brain region is necessary for certain processes that happen in a brain. We are currently applying TMS to understand the causal contribution of specific brain regions to eye gaze perception. This study is currently recruiting healthy individuals to participate (link).

3. Schizophrenia-Bipolar Psychosis Spectrum

While we have found in a large, integrated analysis that negative affect (including depression, anxiety, and distress) predicts social functioning across schizophrenia, schizoaffective disorder, and bipolar disorder (Grove et al., 2016), our other studies show that some behavioral, affective, and neural characteristics may be effective endophenotypes distinguishing affective disorders from psychotic disorders. Specifically, we have shown that self-report reward-related drive and affective forecast (Tso, Grove, & Taylor, 2014), the P300 brain wave of response inhibition (Chun et al., 2013), and the N170 wave of face encoding during gaze discrimination (Tso et al., 2018) can distinguish bipolar disorder from schizophrenia and schizoaffective disorder. We showed in a large cross-sectional sample that psychosis is highly prevalent in bipolar disorder but does not necessarily represent a more severe case of illness in terms of neurocognitive and functional outcomes (Burton et al., 2018). This challenges the conventional view of psychosis as a unified process across the schizophrenia-bipolar spectrum. However, some basic cognitive functions, such as visual integration, appear to be related to psychosis, regardless of primary diagnosis (i.e., bipolar disorder or schizoaffective disorder or schizophrenia) (Grove et al., 2018). These findings call for further research on the disease mechanisms of affective disorders and psychotic disorders.

4. Psychosis-Risk Syndromes: Symptoms and Prediction

In collaboration with the Early Detection and Intervention for the Prevention of Psychosis Program (EDIPPP), a multisite study funded by the Robert Wood Johnson Foundation (Principle Investigator: William McFarlane), we examined the symptom structure of psychosis risk syndromes and its predictive value of long-term functioning in a large cohort of help-seeking youth at clinical high risk for psychosis. We found that while the symptom structure shows similarities to schizophrenia, there are notable differences in the manifestation of core positive symptoms and the relative prominence of distress (Tso et al., 2017). We also found that the negative symptom and thought deterioration dimensions significantly predict worse functioning over time, and positive symptoms moderate the effect of negative symptoms (Burton et al., 2019). Using the EDIPPP data, we were able to perform an independent validation of the NAPLS 2 psychosis risk calculator, the first and only one available in psychiatry, further informing early identification and intervention strategies (Carrión et al., 2016).

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