Josiane Bourque

Progesterone and Cerebral Function during Emotion Processing in Men and Women with Schizophrenia

Schizophrenia has been associated with disturbed levels of sex-steroid hormones, including estrogen and testosterone. In the present study we have examined the implication of a less studied hormone progesterone. Forty-three patients with schizophrenia (21 women) and 43 control participants (21 women) underwent functional MRI while viewing emotionally positive, negative, and neutral images. Blood samples were taken prior to the scanning session to evaluate progesterone levels. Simple regression analyses between levels of progesterone and brain activations associated with emotion processing were performed using SPM5. A positive correlation was found between progesterone levels and brain activations during processing of emotionally charged images in both healthy and schizophrenia men, but no significant relationship was revealed in women. These preliminary results indicate that progesterone is significantly associated with brain activations during processing of positive and negative affect in healthy and schizophrenia men, but not in women. Further investigation is warranted.

Neural Circuitry of Impulsivity in a Cigarette Craving Paradigm

Impulsivity has been shown to play a pivotal role in the onset, pattern of consumption, relapse and, most notably, craving of illicit and licit drugs such as cigarette smoking. The goal of this study was to examine the neurobiological influence of trait impulsivity during cue-induced cigarette craving. Thirty-one chronic smokers passively viewed appetitive smoking-related and neutral images while being scanned and reported their feelings of craving. They completed the Barratt Impulsiveness Scale, a measure of trait impulsivity. We conducted functional connectivity analyses using the psycho-physiological interaction method. During the processing of smoking stimuli, participants presented increased activations in the cingulate and prefrontal cortices. We observed a significant positive relationship between impulsivity scores and reported craving. A negative correlation was observed between the impulsivity score and activity in the posterior cingulate cortex (PCC). The insula, dorsal anterior cingulate cortex (dACC) as well as the dorsolateral prefrontal cortex (DLPFC) presented a negative connectivity with the PCC. Consistent with the view that the PCC is related to the ability to resist cigarette craving, our results suggest that high impulsive smokers have greater difficulty in controlling their cravings, and that this weakness may be mediated by lower PCC activity. Moreover, we argue that the less PCC activity, the greater the probability of a stronger emotional, physiological, and biased attentional response to smoking cues mediated by insula, dACC, and DLPFC activity. This is the first study on this topic, and so, results will need to be replicated in both licit and illicit drug abusers. Our findings also highlight a need for more emphasis on the PCC in drug addiction research, as it is one of the most consistently activated regions in functional magnetic resonance imaging studies examining the neural correlates of cue-induced alcohol, drug, and tobacco cravings.

Cannabis abuse is associated with better emotional memory in schizophrenia: A functional magnetic resonance imaging study

In schizophrenia cannabis abuse/dependence is associated with poor compliance and psychotic relapse. Despite this, the reasons for cannabis abuse remain elusive, but emotions may play a critical role in this comorbidity. Accordingly, we performed a functional magnetic resonance imaging study of emotional memory in schizophrenia patients with cannabis abuse (dual-diagnosis, DD). Participants comprised 14 DD patients, 14 non-abusing schizophrenia patients (SCZ), and 21 healthy controls (HC) who had to recognize positive and negative pictures while being scanned. Recognition of positive and negative emotions was prominently impaired in SCZ patients, relative to HC, while differences between DD and HC were smaller. For positive and negative stimuli, we observed significant activations in frontal, limbic, temporal and occipital regions in HC; in frontal, limbic and temporal regions in DD; and in temporal, parietal, limbic and occipital regions in the SCZ group. Our results suggest that emotional memory and prefrontal lobe functioning are preserved in DD relative to SCZ patients. These results are consistent with previous findings showing that cannabis abuse is associated with fewer negative symptoms and better cognitive functioning in schizophrenia. Longitudinal studies will need to determine whether the relative preservation of emotional memory is primary or secondary to cannabis abuse in schizophrenia.

Sex Differences and Menstrual Cycle Phase-Dependent Modulation of Craving for Cigarette: An fMRI Pilot Study

While overall more men than women smoke cigarettes, women and girls take less time to become dependent after initial use and have more difficulties quitting the habit. One of the factors contributing to these differences may be that women crave cigarettes more than men and that their desire to smoke is influenced by hormonal fluctuations across the menstrual cycle. Therefore, the purpose of the present study was twofold: (a) to examine potential sex/gender differences in functional neuroanatomy of craving and to (b) delineate neural correlates of cigarette cravings in women across their menstrual cycle. Fifteen tobacco-smoking men and 19 women underwent a functional MRI during presentation of neutral and smoking-related images, known to elicit craving. Women were tested twice: once during early follicular phase and once during midluteal phase of their menstrual cycle. The analysis did not reveal any significant sex differences in the cerebral activations associated with craving. Nevertheless, the pattern of activations in women varied across their menstrual cycle with significant activations in parts of the frontal, temporal, and parietal lobe, during follicular phase, and only limited activations in the right hippocampus during the luteal phase.

Where there's smoke, there's fire: the brain reactivity of chronic smokers when exposed to the negative value of smoking.

RATIONAL The addictive nature of smoking is characterized by responses to cigarette stimuli that significantly impede smoking cessation efforts. Studies have shown that smokers are roused by appetitive smoking-related stimuli, and their consumption tends to be unaffected by the negative value of smoking. PURPOSE Using functional magnetic resonance imaging, the goal of this study was two-fold: to examine the brain reactivity of chronic smokers when processing the negative value of smoking using aversive smoking-related cues; to further characterize this response by comparing the latter to the processing of aversive nonsmoking-related and appetitive smoking-related cues. METHOD Thirty chronic smokers passively viewed aversive smoking-related, aversive nonsmoking-related, appetitive smoking-related and neutral images presented in a block design while being scanned. RESULTS Aversive smoking-related stimuli elicited significantly greater activation in the medial prefrontal cortex, amygdala, inferior frontal gyrus and lateral orbitofrontal cortex than neutral stimuli. Aversive smoking-related stimuli elicited lower activation in the parahippocampal gyrus, insula and inferior frontal gyrus compared to the aversive nonsmoking-related condition, as well as lower activation in the posterior cingulate, precuneus and medial prefrontal cortices compared to appetitive smoking-related cues. CONCLUSION The brain activation pattern observed suggests that chronic smokers experience an aversive response when processing aversive smoking-related stimuli, however we argue that the latter triggers a weaker negative emotional and driving response than the aversive non-smoking-related and appetitive smoking-related cues respectively. These fMRI results highlight potentially important processes underlying the insensitivity to the negative value of smoking, an important characteristic of addiction.

Clozapine and visuospatial processing in treatment-resistant schizophrenia

Introduction. Clozapine, the most widely used option in treatment-resistant schizophrenia, has been shown to be superior to other antipsychotic medications in improving cognitive function in patients. However, the results have not been consistent and the mechanisms underlying this effect have not been elucidated. Thus, the purpose of the present study was to evaluate verbal and nonverbal cognition (using visuospatial processing tests) in patients treated with clozapine (initially treatment resistant) and those treated with other second-generation antipsychotics, relative healthy control subjects. Furthermore, we examined neural correlates of visuospatial processing in the three groups. Methods. Twenty schizophrenia patients treated with clozapine (TR-C group), 23 patients stabilised with atypical antipsychotics other than clozapine (NTR group), and 21 healthy control participants completed a battery of verbal and visuospatial cognitive tests. In addition, participants underwent functional magnetic resonance imaging (fMRI) while performing one of the visuospatial tests (the mental rotation task). The fMRI data were analysed separately in each group using Statistical Parametric Mapping software (SPM5). Results. Overall, schizophrenia patients exhibited deficit on verbal and nonverbal processing relative to the healthy controls, but we observed some interesting differences between the two groups of patients. Specifically, the NTR group performed better than the TR-C group on the Block Design and the Ravens Progressive Matrices. With respect to brain function during mental rotation, the NTR group showed significant activations in regions of the temporal and occipital cortex, whereas the TR-C patients did not. The relative deactivations associated with the task were also more robust in NTR compared to the other group of patients, despite a similar performance. Conclusion. Present results suggest better visuospatial processing in the NTR relative to the TR-C group. This difference could be attributed to the treatment resistance itself or a lack of beneficial effect of clozapine relative to other atypical antipsychotics in ameliorating nonverbal abilities. Future studies of the relationship between clozapine and cognition, as well as between treatment resistance and cognition, are warranted.

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.

Emotion processing in women with schizophrenia is menstrual cycle phase and affective valence dependent: an FMRI study.

Despite a large number of functional neuroimaging investigations of emotion processing in schizophrenia, very few have included women. In the present study 21 schizophrenia and 23 healthy women underwent functional MRI (3T) on two occasions (during the follicular and luteal phase of their menstrual cycle) while viewing blocks of emotionally negative, positive and neutral images. During exposure to negatively charged images patients showed relatively less activations than controls during the luteal phase, but no between-group differences were observed during the follicular phase. In contrast, the exposure to positively valenced material produced no significant interaction, but the main effect of group; schizophrenia patients exhibited less activation than healthy controls during both phases of the menstrual cycle. This is the first study demonstrating that atypical neural activations associated with emotion processing in women diagnosed with schizophrenia depend on the menstrual cycle phase and on the affective valence of presented stimuli.

The Neural Correlates of Mental Rotation Abilities in Cannabis-Abusing Patients with Schizophrenia: An fMRI Study

Growing evidence suggests that cannabis abuse/dependence is paradoxically associated with better cognition in schizophrenia. Accordingly, we performed a functional magnetic resonance imaging (fMRI) study of visuospatial abilities in 14 schizophrenia patients with cannabis abuse (DD), 14 nonabusing schizophrenia patients (SCZ), and 21 healthy controls (HCs). Participants performed a mental rotation task while being scanned. There were no significant differences in the number of mistakes between schizophrenia groups, and both made more mistakes on the mental rotation task than HC. Relative to HC, SCZ had increased activations in the left thalamus, while DD patients had increased activations in the right supramarginal gyrus. In both cases, hyper-activations are likely to reflect compensatory efforts. In addition, SCZ patients had decreased activations in the left superior parietal gyrus compared to both HC and DD patients. This latter result tentatively suggests that the neurophysiologic processes underlying visuospatial abilities are partially preserved in DD, relative to SCZ patients, consistently with the findings showing that cannabis abuse in schizophrenia is associated with better cognitive functioning. Further fMRI studies are required to examine the neural correlates of other cognitive dysfunctions in schizophrenia patients with and without comorbid cannabis use disorder.

Functional Neuroimaging Predictors of Self-Reported Psychotic Symptoms in Adolescents

OBJECTIVE This study investigated the neural correlates of psychotic-like experiences in youths during tasks involving inhibitory control, reward anticipation, and emotion processing. A secondary aim was to test whether these neurofunctional correlates of risk were predictive of psychotic symptoms 2 years later. METHOD Functional imaging responses to three paradigms-the stop-signal, monetary incentive delay, and faces tasks-were collected in youths at age 14, as part of the IMAGEN study. At baseline, youths from London and Dublin sites were assessed on psychotic-like experiences, and those reporting significant experiences were compared with matched control subjects. Significant brain activity differences between the groups were used to predict, with cross-validation, the presence of psychotic symptoms in the context of mood fluctuation at age 16, assessed in the full sample. These prediction analyses were conducted with the London-Dublin subsample (N=246) and the full sample (N=1,196). RESULTS Relative to control subjects, youths reporting psychotic-like experiences showed increased hippocampus/amygdala activity during processing of neutral faces and reduced dorsolateral prefrontal activity during failed inhibition. The most prominent regional difference for classifying 16-year-olds with mood fluctuation and psychotic symptoms relative to the control groups (those with mood fluctuations but no psychotic symptoms and those with no mood symptoms) was hyperactivation of the hippocampus/amygdala, when controlling for baseline psychotic-like experiences and cannabis use. CONCLUSIONS The results stress the importance of the limbic networks increased response to neutral facial stimuli as a marker of the extended psychosis phenotype. These findings might help to guide early intervention strategies for at-risk youths.