Dodell-Feder, D., Tully, L. M., & Hooker, C. I. (2015). Social impairment in schizophrenia: New approaches to treating a persistent problem. Current Opinion in Psychiatry , 28 (00), 1-7.Abstract

Purpose of review: Deficits in social cognition are an important determinant of social functioning in schizophrenia, a core feature of the illness that persists despite treatment. Recent research in neuroplasticity-based therapeutics shows that neural systems supporting core cognitive skills improve after targeted cognitive training, suggesting that social cognition, and concomitant social functioning, may be improved by targeting the neural systems supporting social cognition. However, the success of this approach depends on the extent to which the social brain is malleable. We review the neural effects of training programs focused on improving social cognition in healthy, schizophrenia, and other clinical samples.
Recent findings: The current literature suggests that the neural mechanisms underlying social cognition show neuroplastic changes after behavioral training and these neural changes confer concomitant benefits to social cognition and social behavior. Most research in schizophrenia has focused on emotion recognition, and although emotion recognition training has behavioral and neural benefits for schizophrenia, more advanced social cognitive processes need to be examined.
Summary: The data suggest that targeting neural systems underlying social cognition through socially focused behavioral interventions may improve social functioning impairments in schizophrenia. Questions remain regarding how to optimize training, which should be addressed in future work.

Tully, L. M., Lincoln, S. H., & Hooker, C. I. (2014). Attentional control mediates the relationship between social anhedonia and social impairment. Frontiers in Psychopathology , 5.Abstract

Social anhedonia, a traitlike disinterest in social contact and diminished capacity to experience pleasure from social interactions, is consistently associated with social impairments in both healthy and clinical populations. However, the mechanisms underlying the relationship between social anhedonia and social impairment are poorly understood. Attentional control, selecting and focusing on relevant information and inhibiting irrelevant, may be one such mechanism. We examined individual differences in social anhedonia, attentional control, and social impairment in 108 healthy adults. High social anhedonia related to low attentional control and high social impairment. Moreover, attentional control mediated the relationship between social anhedonia and social impairment, establishing attentional control as one mechanism underlying aberrations in the fundamental human need for social contact. Although both attentional deficits and social impairment have been separately noted in social anhedonia, the relationship between social anhedonia, attentional control and social impairment in this nonclinical sample reflects a novel contribution.

Lincoln, S. H., & Hooker, C. I. (2014). Neural structure and social dysfunction in individuals at clinical high risk for psychosis. Psychiatry Research: Neuroimaging , 224, 152-8.Abstract

Individuals at a clinical high risk (CHR) for psychosis have gray matter volume (GMV) abnormalities that are similar to, though less severe than, those in individuals with schizophrenia. Less GMV in schizophrenia is related to worse social cognition and social functioning, but the relationship between GMV and social functioning in CHR individuals has yet to be investigated. The aim of this study was to (1) investigate differences in GMV between healthy controls (HC) and CHR individuals, and (2) evaluate the relationship between GMV and social functioning in these two groups. Participants comprised 22 CHR and 21 HC individuals who completed a structural magnetic resonance imaging (MRI) scan as well as self-reported and interviewer-rated measures of social functioning. Processing and analysis of structural images were completed using voxel based morphometry (VBM). Results showed that the CHR group had less GMV in the left postcentral gyrus, bilateral parahippocampual gyri, and left anterior cingulate cortex. Reduced GMV in the postcentral gyrus and the anterior cingulate was related to self- reported social impairment across the whole group. This study has implications for the neurobiological basis of social dysfunction present before the onset of psychosis. 

Nahum, M., Fisher, M., Loewy, R., Poelke, G., Ventura, J., Neuchterlein, K., Hooker, C. I., et al. (2014). A novel, online social cognitive training program for young adults with schizophrenia: A pilot study. Schizophrenia Research: Cognition , 1 (1), e11-e19.Abstract

Background: Pervasive social cognition deficits are evident early in the course of schizophrenia and are directly linked to functional outcome, making them an important target for intervention. Here, we tested the fea- sibility of use, and initiated the evaluation of efficacy, of a novel, neuroplasticity-based online training program (SocialVille) in young adults with schizophrenia. Methods: Schizophrenia patients (n = 17) completed 24 hours of online SocialVille game play either from home or at a clinic, over a 6–10 week period. We examined training feasibility, gains on the SocialVille exercises relative to matched healthy controls (n = 17), and changes on measures of social cognition, social functioning, global functioning and motivation. Results: Subjects adhered to training requirements, and rated SocialVille in the medium to high range in satisfaction, enjoyment, and ease of use. Subjects demonstrated significant, large improvements on the speeded SocialVille tasks, and small to moderate improvements on the working memory tasks. Post-training performance on the SocialVille tasks were similar to initial performance of the healthy controls. Subjects also showed improvements on standard measures of social cognition, social functioning, and motivation. No im- provements were recorded for emotion recognition indices of the MSCEIT, or on quality of life scales. Conclusion: This study provides an initial proof of concept for online social cognition training in schizophrenia. This form of training demonstrated feasibility and resulted in within-subject gains in social functioning and motivation. This pilot study represents a first step towards validating this training approach; randomized controlled trials, now underway, are designed to confirm and extend these findings.

Goerlich-Dobre, K. S., Bruce, L., Martens, S., Aleman, A., & Hooker, C. I. (2014). Distinct associations of insula and cingulate volume with the cognitive and affective dimensions of alexithymia. Neuropsychologia , 53, 284-92.Abstract

Alexithymia ("no words for feelings") is a major risk factor for psychosomatic and psychiatric conditions characterized by affect dysregulation. The alexithymia personality construct comprises an affective dimension, the level of subjective emotional experience (emotionalizing and fantasizing), and a cognitive dimension, referring to the cognitive control of emotions (identifying, analyzing, and verbalizing feelings). These two dimensions may differentially put individuals at risk for psychopathology, but their specific neural bases have rarely been investigated. Therefore, the aim of the present study was to find out whether the two alexithymia dimensions are associated with discriminable neural correlates. By means of voxel-based morphometry (VBM), differences in gray matter volumes were compared between 20 (10 male) high-scorers and 20 (9 male) low-scorers on the Toronto Alexithymia Scale (TAS-20), reflecting the cognitive alexithymia dimension. In a subset of 32 subjects, the impact of the affective alexithymia dimension was tested in addition, as assessed with the affective subscale of the Bermond-Vorst Alexithymia Questionnaire (BVAQ). Analysis 1 (cognitive alexithymia dimension) revealed significantly larger gray matter volumes in the right posterior insula in high-scorers compared to low-scorers on the TAS-20. Analysis 2 (affective alexithymia dimension) revealed that the affective alexithymia dimension, specifically the emotionalizing factor indicative of low emotional reactivity, was associated with larger gray matter volumes of the right cingulate cortex. These results suggest that the two alexithymia dimensions are associated with distinct structural correlates.

Tully, L. M., Lincoln, S. H., & Hooker, C. I. (2014). Lateral prefrontal cortex activity during cognitive control of emotion predicts response to social stress in schizophrenia. NeuroImage: Clinical , 6 43-53.Abstract

LPFC dysfunction is a well-established neural impairment in schizophrenia and is associated with worse symptoms. However, how LPFC activation influences symptoms is unclear. Previous findings in healthy individuals demonstrate that lateral prefrontal cortex (LPFC) activation during cognitive control of emotional information predicts mood and behavior in response to interpersonal conflict, thus impairments in these processes may contribute to symptom exacerbation in schizophrenia. We investigated whether schizophrenia participants show LPFC deficits during cognitive control of emotional information, and whether these LPFC deficits prospectively predict changes in mood and symptoms following real-world interpersonal conflict. During fMRI, 23 individuals with schizophrenia or schizoaffective disorder and 24 healthy controls completed the Multi-Source Interference Task superimposed on neutral and negative pictures. Afterwards, schizophrenia participants completed a 21-day online daily-diary in which they rated the extent to which they experienced mood and schizophrenia-spectrum symptoms, as well as the occurrence and response to interpersonal conflict. Schizophrenia participants had lower dorsal LPFC activity (BA9) during cognitive control of task-irrelevant negative emotional information. Within schizophrenia participants, DLPFC activity during cognitive control of emotional information predicted changes in positive and negative mood on days following highly distressing interpersonal conflicts. Results have implications for understanding the specific role of LPFC in response to social stress in schizophrenia, and suggest that treatments targeting LPFC-mediated cognitive control of emotion could promote adaptive response to social stress in schizophrenia.

Hooker, C. I., Carol, E. E., Eisenstein, T. J., Yin, H., Lincoln, S. H., Tully, L. M., Dodell-Feder, D., et al. (2014). A pilot study of cognitive training in clinical high risk for psychosis: Initial evidence of cognitive benefit. Schizophrenia Research , 157, 314-6. [pdf]
Krabbendam, L., Hooker, C. I., & Aleman, A. (2014). Neural effects of the social environment. Schizophr Bull , 40 (2), 248-51.Abstract

Epidemiological studies have suggested that the association between city upbringing and minority status with risk for schizophrenia can be explained by social mechanisms. Neuroimaging approaches hold promise for investigating this claim. Recent studies have shown that in healthy individuals, city upbringing and minority status are associated with increased activity in brain circuits involved in emotion regulation during social evaluative processing. These findings support the hypothesis that changes in the ability to regulate social stress contribute to the mechanism of risk. This is in accordance with a body of evidence demonstrating the sensitivity of the human brain to social stress, based on observational studies investigating the neurological sequelae of interpersonal trauma and experimental studies manipulating exposure to interpersonal distress. In this report, we summarize these initial findings, discuss methodological and conceptual challenges of pursuing this line of inquiry in schizophrenia, and suggest an outline for future research.

Hooker, C. I., Benson, T. L., Gyurak, A., Yin, H., Tully, L. M., & Lincoln, S. H. (2014). Neural activity to positive expressions predicts daily experience of schizophrenia-spectrum symptoms in adults with high social anhedonia. J Abnorm Psychol , 123 (1), 190-204.Abstract

Social anhedonia (SA), the diminished pleasure from social relationships, is a prominent characteristic of the vulnerability and manifestation of schizophrenia disorder. However, SA can develop for multiple reasons and little is known about its neural basis; these 2 issues hinder the utility and sensitivity of SA as a marker of schizophrenia pathology. This study investigated whether lateral prefrontal cortex (LPFC) deficits in social reward processing are associated with both SA and other schizophrenia-spectrum symptoms. During functional MRI (fMRI), a community sample of healthy adults (N = 30) with high and low SA viewed positive, negative, and neutral facial expressions. Afterward, participants completed an online daily diary in which they rated schizophrenia-spectrum symptoms and occurrence of interpersonal conflict each day for 21 days. Compared with low SA, high SA participants had less ventral (V)LPFC activity to positive versus neutral expressions. In addition, participants with a combination of high SA and low VLPFC activity to positive versus neutral expressions had worse daily diary ratings of schizophrenia-spectrum symptoms, including worse cognition, paranoia, motivation/productivity, and vigor/positive affect (i.e., psychomotor activation). Finally, among high SA participants, VLPFC activity predicted the daily relationship between distress from interpersonal conflict and symptom-severity; specifically, high SA participants with low VLPFC activity had worse paranoia on days of high conflict distress. These findings indicate that VLPFC deficits in positive emotion are associated with both SA and other schizophrenia-spectrum symptoms and that understanding the interaction of SA, VLPFC function, and social stress could facilitate the use of SA in the prevention and treatment of schizophrenia.

Dodell-Feder, D., Delisi, L. E., & Hooker, C. I. (2014). The relationship between default mode network connectivity and social functioning in individuals at familial high-risk for schizophrenia. Schizophr Res , 156 (1), 87-95.Abstract

Unaffected first-degree relatives of individuals with schizophrenia (i.e., those at familial high-risk [FHR]), demonstrate social dysfunction qualitatively similar though less severe than that of their affected relatives. These social difficulties may be the consequence of genetically conferred disruption to aspects of the default mode network (DMN), such as the dMPFC subsystem, which overlaps with the network of brain regions recruited during social cognitive processes. In the present study, we investigate this possibility, testing DMN connectivity and its relationship to social functioning in FHR using resting-state fMRI. Twenty FHR individuals and 17 controls underwent fMRI during a resting-state scan. Hypothesis-driven functional connectivity analyses examined ROI-to-ROI correlations between the DMN's hubs, and regions of the dMPFC subsystem and MTL subsystem. Connectivity values were examined in relationship to a measure of social functioning and empathy/perspective-taking. Results demonstrate that FHR exhibit reduced connectivity specifically within the dMPFC subsystem of the DMN. Certain ROI-to-ROI correlations predicted aspects of social functioning and empathy/perspective-taking across all participants. Together, the data indicate that disruption to the dMPFC subsystem of the DMN may be associated with familial risk for schizophrenia, and that these intrinsic connections may carry measurable consequences for social functioning.

Dodell-Feder, D., Delisi, L. E., & Hooker, C. I. (2014). Neural disruption to theory of mind predicts daily social functioning in individuals at familial high-risk for schizophrenia. Social Cognitive and Affective Neuroscience , nst186.Abstract

Theory-of-mind (ToM) ability is foundational for successful social relationships, and dependent on a neurocognitive system, which includes temporo-parietal junction and medial prefrontal cortex. Schizophrenia is associated with ToM impairments, and initial studies demonstrate similar, though more subtle deficits, in unaffected first-degree relatives, indicating that ToM deficits are a potential biomarker for the disorder. Importantly, the social consequences of ToM deficits could create an additional vulnerability factor for individuals at familial high-risk (FHR). However, behavioral studies of ToM are inconsistent and virtually nothing is known about the neural basis of ToM in FHR or the relationship between ToM and social functioning. Here, FHR and nonFHR control participants underwent fMRI scanning while reasoning about a story character's thoughts, emotions, or physical appearance. Afterwards, participants completed a 28-day online 'daily-diary' questionnaire in which they reported daily social interactions and degree of ToM reasoning. FHR participants demonstrated less neural activity in bilateral temporo-parietal junction when reasoning about thoughts and emotions. Moreover, across all participants, the degree of neural activity during ToM reasoning predicted several aspects of daily social behavior. Results suggest that vulnerability for schizophrenia is associated with neurocognitive deficits in ToM and the degree of deficit is related to day-to-day social functioning.

Tully, L. M., Lincoln, S. H., Liyanage-Don, N., & Hooker, C. I. (2014). Impaired cognitive control mediates the relationship between cortical thickness of the superior frontal gyrus and role functioning in schizophrenia. Schizophrenia Research , 152 (2), 358-64.Abstract

Structural abnormalities in the lateral prefrontal cortex (LPFC) are well-documented in schizophrenia and recent evidence suggests that these abnormalities relate to functional outcome. Cognitive control mechanisms, reliant on the LPFC, are impaired in schizophrenia and predict functional outcome, thus impaired cognitive control could mediate the relationship between neuroanatomical abnormalities in the LPFC and functional outcome. We used surface-based morphometry to investigate relationships between cortical surface characteristics, cognitive control, and measures of social and role functioning in 26 individuals with schizophrenia and 29 healthy controls. Results demonstrate that schizophrenia participants had thinner cortex in a region of the superior frontal gyrus (BA10). Across all participants, decreased cortical thickness in this region related to decreased cognitive control and decreased role functioning. Moreover, cognitive control fully mediated the relationship between cortical thickness in the superior frontal gyrus and role functioning, indicating that neuroanatomical abnormalities in the LPFC adversely impact role functioning via impaired cognitive control processes.

Dodell-Feder, D., Tully, L. M., Lincoln, S. H., & Hooker, C. I. (2014). The neural basis of theory of mind and its relationship to social functioning and social anhedonia in individuals with schizophrenia. NeuroImage: Clinical , 4 154-163.Abstract
Theory of mind (ToM), the ability to attribute and reason about the mental states of others, is a strong determinant of social functioning among individuals with schizophrenia. Identifying the neural bases of ToM and their relationship to social functioning may elucidate functionally relevant neurobiological targets for intervention. ToM ability may additionally account for other social phenomena that affect social functioning, such as social anhedonia (SocAnh). Given recent research in schizophrenia demonstrating improved neural functioning in response to increased use of cognitive skills, it is possible that SocAnh, which decreases one's opportunity to engage in ToM, could compromise social functioning through its deleterious effect on ToM-related neural circuitry. Here, twenty individuals with schizophrenia and 18 healthy controls underwent fMRI while performing the False-Belief Task. Aspects of social functioning were assessed using multiple methods including self-report (Interpersonal Reactivity Index, Social Adjustment Scale), clinician-ratings (Global Functioning Social Scale), and performance-based tasks (MSCEIT—Managing Emotions). SocAnh was measured with the Revised Social Anhedonia Scale. Region-of-interest and whole-brain analyses revealed reduced recruitment of medial prefrontal cortex (MPFC) for ToM in individuals with schizophrenia. Across all participants, activity in this region correlated with most social variables. Mediation analysis revealed that neural activity for ToM in MPFC accounted for the relationship between SocAnh and social functioning. These findings demonstrate that reduced recruitment of MPFC for ToM is an important neurobiological determinant of social functioning. Furthermore, SocAhn may affect social functioning through its impact on ToM-related neural circuitry. Together, these findings suggest ToM ability as an important locus for intervention.
Padmanabhan, J., Hooker, C. I., & Keshavan, M. S. (2013). Brain structural abnormalities, social function, and psychopathology in schizophrenia. In Brain Evolution, Language, and Psychopathology in Schizophrenia (pp. 135-150).
Hooker, C. I., Bruce, L., Fisher, M., Verosky, S. C., Miyakawa, A., D'Esposito, M., & Vinogradov, S. (2013). The influence of combined cognitive plus social-cognitive training on amygdala response during face emotion recognition in schizophrenia. Psychiatry Research: Neuroimaging , 213 (2), 99-107.Abstract

Both cognitive and social-cognitive deficits impact functional outcome in schizophrenia. Cognitive remediation studies indicate that targeted cognitive and/or social-cognitive training improves behavioral performance on trained skills. However, the neural effects of training in schizophrenia and their relation to behavioral gains are largely unknown. This study tested whether a 50-h intervention which included both cognitive and social-cognitive training would influence neural mechanisms that support social ccognition. Schizophrenia participants completed a computer-based intervention of either auditory-based cognitive training (AT) plus social-cognition training (SCT) (N=11) or non-specific computer games (CG) (N=11). Assessments included a functional magnetic resonance imaging (fMRI) task of facial emotion recognition, and behavioral measures of cognition, social cognition, and functional outcome. The fMRI results showed the predicted group-by-time interaction. Results were strongest for emotion recognition of happy, surprise and fear: relative to CG participants, AT+SCT participants showed a neural activity increase in bilateral amygdala, right putamen and right medial prefrontal cortex. Across all participants, pre-to-post intervention neural activity increase in these regions predicted behavioral improvement on an independent emotion perception measure (MSCEIT: Perceiving Emotions). Among AT+SCT participants alone, neural activity increase in right amygdala predicted behavioral improvement in emotion perception. The findings indicate that combined cognition and social-cognition training improves neural systems that support social-cognition skills.

Dodell-Feder, D., Lincoln, S. H., Coulson, J. P., & Hooker, C. I. (2013). Using fiction to assess mental state understanding: a new task for assessing theory of mind in adults. PLoS One , 8 (11), e81279. Publisher's VersionAbstract

Social functioning depends on the ability to attribute and reason about the mental states of others - an ability known as theory of mind (ToM). Research in this field is limited by the use of tasks in which ceiling effects are ubiquitous, rendering them insensitive to individual differences in ToM ability and instances of subtle ToM impairment. Here, we present data from a new ToM task - the Short Story Task (SST) - intended to improve upon many aspects of existing ToM measures. More specifically, the SST was designed to: (a) assess the full range of individual differences in ToM ability without suffering from ceiling effects; (b) incorporate a range of mental states of differing complexity, including epistemic states, affective states, and intentions to be inferred from a first- and second-order level; (c) use ToM stimuli representative of real-world social interactions; (d) require participants to utilize social context when making mental state inferences; (e) exhibit adequate psychometric properties; and (f) be quick and easy to administer and score. In the task, participants read a short story and were asked questions that assessed explicit mental state reasoning, spontaneous mental state inference, and comprehension of the non-mental aspects of the story. Responses were scored according to a rubric that assigned greater points for accurate mental state attributions that included multiple characters' mental states. Results demonstrate that the SST is sensitive to variation in ToM ability, can be accurately scored by multiple raters, and exhibits concurrent validity with other social cognitive tasks. The results support the effectiveness of this new measure of ToM in the study of social cognition. The findings are also consistent with studies demonstrating significant relationships among narrative transportation, ToM, and the reading of fiction. Together, the data indicate that reading fiction may be an avenue for improving ToM ability.  See here for Fiction Passage and Questions and Scoring Guide.

[pdf] [Questions and Scoring Guide] [Fiction Passage]
Sacks, S., Fisher, M., Garrett, C., Alexander, P., Holland, C., Rose, D., Hooker, C., et al. (2013). Combining Computerized Social Cognitive Training with Neuroplasticity-Based Auditory Training in Schizophrenia. Clin Schizophr Relat Psychoses , 7 (2), 78-86A.Abstract

Objective: Social cognitive deficits are an important treatment target in schizophrenia, but it is unclear to what degree they require specialized interventions and which specific components of behavioral interventions are effective. In this pilot study, we explored the effects of a novel computerized neuroplasticity-based auditory training delivered in conjunction with computerized social cognition training (SCT) in patients with schizophrenia.Methods: Nineteen clinically stable schizophrenia subjects performed 50 hours of computerized exercises that place implicit, increasing demands on auditory perception, plus 12 hours of computerized training in emotion identification, social perception, and theory of mind tasks. All subjects were assessed with MATRICS-recommended measures of neurocognition and social cognition, plus a measure of self-referential source memory before and after the computerized training.Results: Subjects showed significant improvements on multiple measures of neurocognition. Additionally, subjects showed significant gains on measures of social cognition, including the MSCEIT Perceiving Emotions, MSCEIT Managing Emotions, and self-referential source memory, plus a significant decrease in positive symptoms.Conclusions: Computerized training of auditory processing/verbal learning in schizophrenia results in significant basic neurocognitive gains. Further, addition of computerized social cognition training results in significant gains in several social cognitive outcome measures. Computerized cognitive training that directly targets social cognitive processes can drive improvements in these crucial functions.

Germine, L., Benson, T. L., Cohen, F., & Hooker, C. I. (2013). Psychosis-proneness and the rubber hand illusion of body ownership. Psychiatry Res , 207, 45-52.Abstract

Psychosis and psychosis-proneness are associated with abnormalities in subjective experience of the self, including distortions in bodily experience that are difficult to study experimentally due to lack of structured methods. In 55 healthy adults, we assessed the relationship between self-reported psychosis-like characteristics and susceptibility to the rubber hand illusion of body ownership. In this illusion, a participant sees a rubber hand being stroked by a brush at the same time that they feel a brush stroking their own hand. In some individuals, this creates the bodily sense that the rubber hand is their own hand. Individual differences in positive (but not negative) psychosis-like characteristics predicted differences in susceptibility to experiencing the rubber hand illusion. This relationship was specific to the subjective experience of rubber hand ownership, and not other unusual experiences or sensations, and absent when a small delay was introduced between seeing and feeling the brush stroke. This indicates that individual differences in susceptibility are related to visual-tactile integration and cannot be explained by differences in the tendency to endorse unusual experiences. Our findings suggest that susceptibility to body representation distortion by sensory information may be related or contribute to the development of psychosis and positive psychosis-like characteristics.

Tully, L. M., Lincoln, S. H., & Hooker, C. I. (2012). Impaired executive control of emotional information in social anhedonia. Psychiatry Res , 197 (1-2), 29-35.Abstract
We examined the executive control of emotional information and its relationship to social functioning in individuals at risk for schizophrenia, defined by high social anhedonia (SA). Using the same structure as the Attentional Network Test (ANT), we developed a measure of executive control of emotional information (ANT-Emotion) in which subjects identify the direction of an arrow flanked by irrelevant angry or neutral faces. Subjects completed the ANT, ANT-Emotion, and the Social Adjustment Scale, Self-Report (SAS-SR), a measure of social functioning. While there were no group differences in the alerting, orienting, and executive control networks assessed by the ANT, high SA individuals exhibited a specific impairment in the executive control of emotional information. High SA individuals also reported poorer social functioning. However, executive control of emotional information did not mediate the relationship between SA and social functioning. These findings indicate that, in high-risk populations, the impaired ability to inhibit emotional information allows negative affective stimuli to exert inappropriate influence on cognitive processes. These results are consistent with studies indicating similar findings in schizophrenia patients, suggesting that impaired inhibition of negative emotion may be part of the liability for the disorder.