Dysconnectivity between the anterior insula and the dorsal anterior cingulate cortex during an emotion go/nogo paradigm is associated with aggressive behaviors in male schizophrenia patients.

This study aimed to investigate the association between past-reported violent/aggressive behaviors and brain functional connectivity in male patients suffering from schizophrenia using a task modeling the interaction between negative emotion processing and response inhibition. Forty-four male patients with schizophrenia and twenty-two healthy male controls performed an emotional go/no-go task using angry and neutral faces during a functional magnetic resonance imaging session. Generalized psycho-physiological interaction was conducted to explore task-based functional connectivity and a negative binomial regression was used to evaluate the relationship between neural alterations and violent/aggressive behaviors. Regions involved in response inhibition and emotion regulation, such as the anterior insula, dorsal anterior cingulate cortex (dACC) and dorsolateral prefrontal cortex (DLPFC), were used as seed regions. During emotion-related response inhibition, patients with schizophrenia displayed altered connectivity between the anterior insula and amygdala, the DLPFC and lateral orbitofrontal cortex (OFC), as well as the anterior insula and the dACC when compared to healthy individuals. The latter was negatively associated with aggressive behaviors in participants with schizophrenia (Wald χ2 = 9.51; p < 0.05, p-FDR corrected). Our results highlight alterations in functional connectivity in brain regions involved in cognitive control and emotion processing which are associated with aggressive behaviors in schizophrenia.

Increased cingulo-orbital connectivity is associated with violent behaviours in schizophrenia.

OBJECTIVE: Although schizophrenia patients are at a heightened risk of exhibiting violent behaviours compared to the general population, few functional neuroimaging studies have explored the aberrant neurocircuitry underpinning such behaviours. This study aimed to identify disrupted resting-state activity and functional connectivity in schizophrenia patients with a history of violence. METHODS: Resting state functional magnetic resonance imaging data was collected from 62 schizophrenia patients and 25 healthy controls. Voxel-wise analyses of fractional amplitude of low frequency fluctuations (fALFF) were implemented to investigate disrupted regional patterns of spontaneous brain activity. Brain regions which yielded significant differences between groups were subsequently used as data-driven seeds for functional connectivity analyses. Finally, significant alterations (activity and connectivity) were correlated with lifetime violent behaviours. RESULTS: When compared to healthy controls, schizophrenia patients exhibited reduced fALFF in multiple brain regions including the (subgenual) anterior cingulate cortex (ACC), posterior cingulate cortex, precuneus cortex and left lateral orbitofrontal cortex (OFC). Seed-to-voxel analyses yielded significantly enhanced connectivity between the ACC and left OFC. The heightened functional connectivity between the latter two regions predicted the number of violent behaviours reported by schizophrenia patients. CONCLUSION: The current study demonstrated that the functional connectivity of brain regions associated with emotion regulation is impaired in schizophrenia and associated with violent antecedents among patients. This result is consistent with predominant theoretical models proposing that the OFC plays a critical role in the neurobiology of violence.

Functional connectivity abnormalities of the long-axis hippocampal subregions in schizophrenia during episodic memory.

Past evidence suggests that hippocampal subregions, namely the anterior and posterior parts, may be engaged in distinct networks underlying the memory functions which may be altered in patients with schizophrenia. However, of the very few studies that have investigated the hippocampal longitudinal axis subdivisions functional connectivity in patients with schizophrenia, the majority was based on resting-state data, and yet, none aimed to examine these during an episodic memory task. A total of 41 patients with schizophrenia and 45 healthy controls were recruited for a magnetic resonance imaging protocol in which they performed an explicit memory task. Seed-based functional connectivity analysis was employed to assess connectivity abnormalities between hippocampal subregions and voxel-wise connectivity targets in patients with schizophrenia. We observed a significantly reduced connectivity between the posterior hippocampus and regions from the default mode network, but increased connectivity with the primary visual cortex, in patients with schizophrenia compared to healthy subjects. Increased connectivity between the anterior hippocampus and anterior temporal regions also characterized patients with schizophrenia. In the current study, we provided evidence and support for studying hippocampal subdivisions along the longitudinal axis in schizophrenia. Our results suggest that the abnormalities in hippocampal subregions functional connectivity reflect deficits in episodic memory that may be implicated in the pathophysiology of schizophrenia.

Violent Behavior Is Associated With Emotion Salience Network Dysconnectivity in Schizophrenia.

Background: Despite individuals with schizophrenia being at an elevated risk of violence compared to the general population, limited efforts have been invested in investigating the neurobiological etiology explaining the increase. Among the few studies examining functional disruptions pertaining to violent schizophrenia patients using fMRI, only one study has considered functional connectivity. The current state of knowledge does not allow to infer deficits in functional connectivity specific to distinct cognitive/emotional states that have been associated with the emergence of violence in schizophrenia, such as negative emotion processing. This study sought to identify disrupted connectivity among men with schizophrenia and a history of violence (SCZ+V), compared to men with schizophrenia without a history of violence (SCZ-V) and healthy controls, during negative emotion processing using fMRI. Methods: Twenty SCZ+V, 19 SCZ-V, and 21 healthy men were scanned while viewing negative images. Results: Negative images elicited an increased connectivity between the dorsal anterior cingulate cortex (dACC) and the bilateral rostral prefrontal cortex (rPFC), as well as a decreased functional connectivity between the frontal regions (bilateral rPFC and dACC) and the putamen and hippocampus in SCZ+V men as compared to SCZ-V men and healthy controls. Concurrently, the centrality of the dACC within the network was reduced in SCV+V subjects. Conclusions: These results suggest an inefficient integration of the information by the dACC between frontal and limbic regions in SCZ+V men during negative emotion processing and highlight the importance of the ACC in the neurobiological bases of violent behavior in schizophrenia.

Reward-related decision-making in schizophrenia: A multimodal neuroimaging study.

Schizophrenia is a severe psychiatric disorder characterized by important cognitive deficits, which ultimately compromise the patients' ability to make optimal decisions. Unfortunately, the neurobiological bases of impaired reward-related decision-making in schizophrenia have rarely been studied. The objective of this study is to examine the neural mechanisms involved in reward-related decision-making in schizophrenia, using functional magnetic resonance imaging (fMRI). Forty-seven schizophrenia patients (DSM-IV criteria) and 23 healthy subjects with no psychiatric disorders were scanned using fMRI while performing the Balloon Analogue Risk Task (BART). A rapid event-related fMRI paradigm was used, separating decision and outcome events. Between-group differences in grey matter volumes were assessed with voxel-based morphometry. During the reward outcomes, increased activations were observed in schizophrenia in the left anterior insula, the putamen, and frontal sub-regions. Reduced grey matter volumes were observed in the left anterior insula in schizophrenia which spatially overlapped with functional alterations. Finally, schizophrenia patients made fewer gains on the BART. The fact that schizophrenia patients had increased activations in sub-cortical regions such as the striatum and insula in response to reward events suggests that the impaired decision-making abilities of these patients are mostly driven by an overvaluation of outcome stimuli.

History of Suicide Attempt Is Associated with Reduced Medial Prefrontal Cortex Activity during Emotional Decision-Making among Men with Schizophrenia: An Exploratory fMRI Study.

Despite the high prevalence of suicidal ideas/attempts in schizophrenia, only a handful of neuroimaging studies have examined the neurobiological differences associated with suicide risk in this population. The main objective of the current exploratory study is to examine the neurofunctional correlates associated with a history of suicide attempt in schizophrenia, using a risky decision-making task, in order to show alterations in brain reward regions in this population. Thirty-two male outpatients with schizophrenia were recruited: 13 patients with (SCZ + S) and 19 without a history of suicidal attempt (SCZ - S). Twenty-one healthy men with no history of mental disorders or suicidal attempt/idea were also recruited. Participants were scanned using fMRI while performing the Balloon Analogue Risk Task. A rapid event-related fMRI paradigm was used, separating decision and outcome events, and the explosion probabilities were included as parametric modulators. The most important finding of this study is that SCZ + S patients had reduced activations of the medial prefrontal cortex during the success outcome event (with parametric modulation), relative to both SCZ - S patients and controls, as illustrated by a spatial conjunction analysis. These exploratory results suggest that a history of suicidal attempt in schizophrenia is associated with blunted brain reward activity during emotional decision-making.

Reduced dorsolateral prefrontal cortex activation during affective Go/NoGo in violent schizophrenia patients: An fMRI study.

We investigated the influence of anger processing on cognitive control in male schizophrenia patients presenting violent behaviors. We recruited 23 patients without and 24 patients with (SCZ+V) a history of violent behaviors, as well as 22 healthy non-violent men. Participants were administered an affective (angry-neutral faces) Go/NoGo task while undergoing functional magnetic resonance imaging. We found a reduced activation in the dorsolateral prefrontal cortex in SCZ+V patients specifically when inhibiting a response while viewing angry faces. These results show an inability of SCZ+V to recruit a core region of the (inhibitory) cognitive control network in the context of anger.

Impaired Coupling between the Dorsomedial Prefrontal Cortex and the Amygdala in Schizophrenia Smokers Viewing Anti-smoking Images.

BACKGROUND: Cigarette smoking is highly prevalent in schizophrenia and is one of the main factors contributing to the significantly decreased life expectancy in this population. Schizophrenia smokers, compared to their counterparts with no comorbid psychiatric disorder, are largely unaware and indifferent to the long-term negative consequences of cigarette smoking. The objective of this study was to determine, for the first time, if these meta-cognitive deficits are associated with neuro-functional alterations in schizophrenia smokers. METHODS: Twenty-four smokers with no psychiatric disorder and 21 smokers with schizophrenia (DSM-IV criteria) were scanned using functional magnetic resonance imaging and exposed to anti-smoking images. Granger causality analyses were used to examine the effective connectivity between brain regions found to be significantly activated. RESULTS: Across groups, potent activations were observed in the left ventro-lateral prefrontal cortex, the left amygdala (AMG), and the dorsomedial prefrontal cortex (dmPFC). Using the dmPFC as a seed region, we found an abnormal negative connectivity from the dmPFC to the AMG in schizophrenia smokers during the viewing of anti-smoking stimuli. This abnormal connectivity was not present during the viewing of aversive stimuli unrelated to tobacco. DISCUSSION: Given the well-established roles of the dmPFC in social cognition and of the AMG in emotional processing, our results suggest that the relative indifference of schizophrenia smokers regarding the negative consequences of tobacco smoking could be explained by a cognitive-affective dissonance.

Abnormal effective fronto-limbic connectivity during emotion processing in schizophrenia.

BACKGROUND: Schizophrenia is associated with core emotional dysfunctions. At the neural level, functional neuro-imaging studies have highlighted fronto-limbic alterations during emotion processing in schizophrenia, as well as impaired connectivity between the amygdala and the prefrontal cortex. However, the direction of the impaired fronto-limbic connections remains largely unknown. To clarify this issue, we performed an effective connectivity study on emotion processing in schizophrenia. METHODS: Forty-one healthy individuals and 39 schizophrenia patients (DSM-IV criteria) viewed negative, positive and neutral images during an fMRI session. Effective connectivity between significantly activated regions was examined using Granger causality and psychophysical interaction analyses. RESULTS: Subjective ratings of emotionally neutral images were higher in schizophrenia patients than in controls. Across groups, significant activations were observed in the dorso-medial prefrontal cortex (dmPFC) and the bilateral amygdala. The Granger connectivity from the right amygdala to the dmPFC was significantly reduced in schizophrenia patients, relative to controls, during the negative and neutral conditions. The Granger connectivity from the left amygdala to the dmPFC was significantly reduced in schizophrenia patients, relative to controls, during the positive condition. DISCUSSION: The finding of a reduced lagged connectivity from the bilateral amygdala to the dmPFC in schizophrenia suggests that the bottom-up mechanisms involved in the processing of highly arousing emotional stimuli are impaired in this disorder. The finding of an impaired lagged connectivity from the right amygdala to the dmPFC during the processing of emotionally neutral stimuli in schizophrenia is novel and may explain why these patients tend to confer emotional significance to irrelevant stimuli.

Increased spinal pain sensitization in major depressive disorder: A pilot study.

Although patients suffering from major depressive disorder (MDD) often complain from painful symptoms, the relationship between experimental pain processes and depression has yet to be clearly characterized. Only recently have studies employing temporal summation (TS) paradigms offered preliminary insight into the co-occurrence of pain and depression. This study sets out to evaluate the contribution of spinal and supraspinal processes in pain sensitization in MDD using a TS paradigm. Thirteen volunteers with no psychiatric disorders (controls) and fourteen MDD subjects were included in the analysis. Low-(0.14Hz) and high-(1Hz) frequency intermittent stimulations of the sural nerve were used to induce TS. Spinal pain sensitization was quantified by measuring the change in the amplitude of the nociceptive-specific flexion reflex (NFR) response, and supraspinal pain sensitization was obtained by measuring change in subjective pain rating, from the low- to high-frequency stimulation condition. We found an increased sensitization in the NFR response (p<0.05) in MDD subjects in the high-frequency condition, which did not translate into an increase of their subjective responses. However, we found a positive association between spinal sensitization and painful somatic symptoms in MDD subjects. Together, these results suggest increased spinal pain sensitization in MDD, which might explain the high prevalence of painful somatic symptoms in these patients.

Anterior cingulate hyperactivations during negative emotion processing among men with schizophrenia and a history of violent behavior.

BACKGROUND: Evidence suggests a 2.1-4.6 times increase in the risk of violent behavior in schizophrenia compared to the general population. Current theories propose that the processing of negative emotions is defective in violent individuals and that dysfunctions within the neural circuits involved in emotion processing are implicated in violence. Although schizophrenia patients show enhanced sensitivity to negative stimuli, there are only few functional neuroimaging studies that have examined emotion processing among men with schizophrenia and a history of violence. OBJECTIVE: The present study aimed to identify the brain regions with greater neurofunctional alterations, as detected by functional magnetic resonance imaging during an emotion processing task, of men with schizophrenia who had engaged in violent behavior compared with those who had not. METHODS: Sixty men were studied; 20 with schizophrenia and a history of violence, 19 with schizophrenia and no violence, and 21 healthy men were scanned while viewing positive, negative, and neutral images. RESULTS: Negative images elicited hyperactivations in the anterior cingulate cortex (ACC), left and right lingual gyrus, and the left precentral gyrus in violent men with schizophrenia, compared to nonviolent men with schizophrenia and healthy men. Neutral images elicited hyperactivations in the right and left middle occipital gyrus, left lingual gyrus, and the left fusiform gyrus in violent men with schizophrenia, compared to the other two groups. DISCUSSION: Violent men with schizophrenia displayed specific increases in ACC in response to negative images. Given the role of the ACC in information integration, these results indicate a specific dysfunction in the processing of negative emotions that may trigger violent behavior in men with schizophrenia.

Emotionally Neutral Stimuli Are Not Neutral in Schizophrenia: A Mini Review of Functional Neuroimaging Studies.

Reliable evidence shows that schizophrenia patients tend to experience negative emotions when presented with emotionally neutral stimuli. Similarly, several functional neuroimaging studies show that schizophrenia patients have increased activations in response to neutral material. However, results are heterogeneous. Here, we review the functional neuroimaging studies that have addressed this research question. Based on the 36 functional neuroimaging studies that we retrieved, it seems that the increased brain reactivity to neutral stimuli is fairly common in schizophrenia, but that the regions involved vary considerably, apart from the amygdala. Prefrontal and cingulate sub-regions and the hippocampus may also be involved. By contrasts, results in individuals at risk for psychosis are less consistent. In schizophrenia patients, results are less consistent in the case of studies using non-facial stimuli, explicit processing paradigms, and/or event-related designs. This means that human faces may convey subtle information (e.g., trustworthiness) other than basic emotional expressions. It also means that the aberrant brain reactivity to neutral stimuli is less likely to occur when experimental paradigms are too cognitively demanding as well as in studies lacking statistical power. The main hypothesis proposed to account for this increased brain reactivity to neutral stimuli is the aberrant salience hypothesis of psychosis. Other investigators propose that the aberrant brain reactivity to neutral stimuli in schizophrenia results from abnormal associative learning, untrustworthiness judgments, priming effects, and/or reduced habituation to neutral stimuli. In the future, the effects of antipsychotics on this aberrant brain reactivity will need to be determined, as well as the potential implication of sex/gender.

Cigarette Cravings, Impulsivity, and the Brain.

Craving is a core feature of tobacco use disorder as well as a significant predictor of smoking relapse. Studies have shown that appetitive smoking-related stimuli (e.g., someone smoking) trigger significant cravings in smokers impede their self-control capacities and promote drug seeking behavior. In this review, we begin by an overview of functional magnetic resonance imaging (fMRI) studies investigating the neural correlates of smokers to appetitive smoking cues. The literature reveals a complex and vastly distributed neuronal network underlying smokers' craving response that recruits regions involved in self-referential processing, planning/regulatory processes, emotional responding, attentional biases, and automatic conducts. We then selectively review important factors contributing to the heterogeneity of results that significantly limit the implications of these findings, namely between- (abstinence, smoking expectancies, and self-regulation) and within-studies factors (severity of smoking dependence, sex-differences, motivation to quit, and genetic factors). Remarkably, we found that little to no attention has been devoted to examine the influence of personality traits on the neural correlates of cigarette cravings in fMRI studies. Impulsivity has been linked with craving and relapse in substance and tobacco use, which prompted our research team to examine the influence of impulsivity on cigarette cravings in an fMRI study. We found that the influence of impulsivity on cigarette cravings was mediated by fronto-cingulate mechanisms. Given the high prevalence of cigarette smoking in several psychiatric disorders that are characterized by significant levels of impulsivity, we conclude by identifying psychiatric patients as a target population whose tobacco-smoking habits deserve further behavioral and neuro-imaging investigation.

Psychopathology in Substance Use Disorder Patients with and without Substance-Induced Psychosis.

Background. Substance-induced psychotic disorder (SIPD) is a diagnosis constructed to distinguish substance-induced psychotic states from primary psychotic disorders. A number of studies have compared SIPD persons with primary psychotic patients, but there is little data on what differentiates substance use disorder (SUD) individuals with and without SIPD. Here, we compared psychopathology, sociodemographic variables, and substance use characteristics between SUD patients with and without SIPD. Methods. A retrospective chart review was conducted on newly admitted patients at a rehabilitation centre between 2007 and 2012. Results. Of the 379 patients included in the study, 5% were diagnosed with SIPD (n = 19) and 95% were diagnosed with SUDs without SIPD (n = 360). More SIPD patients reported using cannabis and psychostimulants, and fewer SIPD patients reported using alcohol than SUDs patients without SIPD. SIPD patients scored higher on the "schizophrenia nuclear symptoms" dimension of the SCL-90R psychoticism scale and exhibited more ClusterB personality traits than SUD patients without SIPD. Discussion. These data are consistent with previous studies suggesting that psychopathology, substance type, and sociodemographic variables play important role in the development of SIPD. More importantly, the results highlight the need for paying greater attention to the types of self-reported psychotic symptoms during the assessment of psychotomimetic effects associated with psychoactive substances.

Emotion processing in treatment-resistant schizophrenia patients treated with clozapine: An fMRI study.

OBJECTIVES: To examine the neural correlates of emotion processing in treatment-resistant patients with schizophrenia (SCZ-TR). METHODS: Twenty-two SCZ-TR patients on clozapine, 24 schizophrenia patients on antipsychotics other than clozapine, and 39 healthy controls were scanned using functional neuroimaging while viewing positive, negative and neutral images. RESULTS: Emotionally-laden images (positive and negative) elicited hyper-activations in the dorso-medial prefrontal cortex and left cerebellum in SCZ-TR patients, compared to the two other groups. Similarly, neutral images prompted hyper-activations in the cingulate gyrus in SCZ-TR patients, relative to the two other groups. CONCLUSIONS: Treatment resistance is associated with neuro-functional hyper-activations in schizophrenia patients during emotion processing.

Sex differences in effective fronto-limbic connectivity during negative emotion processing.

BACKGROUND: In view of the greater prevalence of depression and anxiety disorders in women than in men, functional magnetic resonance imaging (fMRI) studies have examined sex-differences in brain activations during emotion processing. Comparatively, sex-differences in brain connectivity received little attention, despite evidence for important fronto-limbic connections during emotion processing across sexes. Here, we investigated sex-differences in fronto-limbic connectivity during negative emotion processing. METHODS: Forty-six healthy individuals (25 women, 21 men) viewed negative, positive and neutral images during an fMRI session. Effective connectivity between significantly activated regions was examined using Granger causality and psychophysical interaction analyses. Sex steroid hormones and feminine-masculine traits were also measured. RESULTS: Subjective ratings of negative emotional images were higher in women than in men. Across sexes, significant activations were observed in the dorso-medial prefrontal cortex (dmPFC) and the right amygdala. Granger connectivity from right amygdala was significantly greater than that from dmPFC during the 'high negative' condition, an effect driven by men. Magnitude of this effect correlated negatively with highly negative image ratings and feminine traits and positively with testosterone levels. DISCUSSION: These results highlight critical sex differences in brain connectivity during negative emotion processing and point to the fact that both biological (sex steroid hormones) and psychosocial (gender role and identity) variables contribute to them. As the dmPFC is involved in social cognition and action planning, and the amygdala-in threat detection, the connectivity results suggest that compared to women, men have a more evaluative, rather than purely affective, brain response during negative emotion processing.