Irina Falkenberg

Cannabinoid Modulation of Functional Connectivity within Regions Processing Attentional Salience

There is now considerable evidence to support the hypothesis that psychotic symptoms are the result of abnormal salience attribution, and that the attribution of salience is largely mediated through the prefrontal cortex, the striatum, and the hippocampus. Although these areas show differential activation under the influence of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), the two major derivatives of cannabis sativa, little is known about the effects of these cannabinoids on the functional connectivity between these regions. We investigated this in healthy occasional cannabis users by employing event-related functional magnetic resonance imaging (fMRI) following oral administration of delta-9-THC, CBD, or a placebo capsule. Employing a seed cluster-based functional connectivity analysis that involved using the average time series from each seed cluster for a whole-brain correlational analysis, we investigated the effect of drug condition on functional connectivity between the seed clusters and the rest of the brain during an oddball salience processing task. Relative to the placebo condition, delta-9-THC and CBD had opposite effects on the functional connectivity between the dorsal striatum, the prefrontal cortex, and the hippocampus. Delta-9-THC reduced fronto-striatal connectivity, which was related to its effect on task performance, whereas this connection was enhanced by CBD. Conversely, mediotemporal-prefrontal connectivity was enhanced by delta-9-THC and reduced by CBD. Our results suggest that the functional integration of brain regions involved in salience processing is differentially modulated by single doses of delta-9-THC and CBD and that this relates to the processing of salient stimuli.

Keep smiling! Facial reactions to emotional stimuli and their relationship to emotional contagion in patients with schizophrenia.

IntroductionEmotional contagion is a common phenomenon in verbal and nonverbal communication between individuals. Perception and mimicry of facial movements play an important role in this process. Several studies have demonstrated impaired facial expression recognition in patients with schizophrenia and differences in their facial behavior compared to healthy subjects, but so far, the relationship between facial mimicry and emotional contagion has not been studied in this group.MethodsSeventeen schizophrenic patients and an equal number of matched healthy controls were presented with digital versions of happy, sad and neutral faces from the “Pictures of facial affect” (Ekman and Friesen, Consulting Psychologists Press, Palo Alto, 1976) and were asked to pull their lip corners up or down (like in smiling or showing a sad face) according to the direction of two arrows that were presented simultaneously. In healthy subjects, congruous movements (i.e. pulling the lip corners up when seeing a happy face or pulling them down when seeing a sad face) are facilitated and dissonant movements are inhibited; these tendencies were considered as indicators of emotional contagion.ResultsIn schizophrenic patients, these tendencies were significantly diminished. The patients were more apt to display a smile as a reaction to a sad face. We found a positive correlation between these effects and the PANSS—Scores for General Psychopathology.DiscussionPatients’ tendencies towards positive reactions even when a negative stimulus was presented could function as a protective mechanism against overwhelming emotional experiences.

Early detection and intervention in bipolar affective disorder: targeting the development of the disorder.

The diagnosis of bipolar affective disorder (BD) is often delayed, and preceded by incorrect diagnoses and potentially harmful treatment, while the development of the disorder is associated with suicidal behavior and help seeking. Several clinical features have been linked to an increased risk of going on to develop BD, in particular attenuated symptoms of BD, personality traits such as cyclothymia, and general psychopathologic symptoms. Several of these show high specificity, indicating that it may be possible to target detection and intervention in individuals at high risk of BD and perhaps moderate the course of the illness and improve treatment outcome. This article summarizes recent evidence on the characteristics of the prodrome to BD and discusses the potential value and challenges of early detection and intervention in BD.

Neural correlates of aberrant emotional salience predict psychotic symptoms and global functioning in high-risk and first-episode psychosis

Neurobiological and behavioral findings suggest that psychosis is associated with corticolimbic hyperactivity during the processing of emotional salience. This has not been widely studied in the early stages of psychosis, and the impact of these abnormalities on psychotic symptoms and global functioning is unknown. We sought to address this issue in 18 patients with first-episode psychosis (FEP), 18 individuals at ultra high risk of psychosis (UHR) and 22 healthy controls (HCs). Corticolimbic response and subjective ratings to emotional and neutral scenes were measured using functional magnetic resonance imaging. The clinical and functional impact of corticolimbic abnormalities was assessed with regression analyses. The FEP and UHR groups reported increased subjective emotional arousal to neutral scenes compared with HCs. Across groups, emotional vs neutral scenes elicited activation in the dorsomedial prefrontal cortex, inferior frontal gyrus/anterior insula and amygdala. Although FEP and UHR participants showed reduced activation in these regions when viewing emotional scenes compared with controls, this was driven by increased activation to neutral scenes. Corticolimbic hyperactivity to neutral scenes predicted higher levels of positive symptoms and poorer levels of functioning. These results indicate that disruption of emotional brain systems may represent an important biological substrate for the pathophysiology of early psychosis and UHR states.

Clinical utility of magnetic resonance imaging in first-episode psychosis

BackgroundThere is no consensus as to whether magnetic resonance imaging (MRI) should be used as part of the initial clinical evaluation of patients with first-episode psychosis (FEP).Aims(a) To assess the logistical feasibility of routine MRI; (b) to define the clinical significance of radiological abnormalities in patients with FEP.MethodRadiological reports from MRI scans of two FEP samples were reviewed; one comprised 108 patients and 98 healthy controls recruited to a research study and the other comprised 241 patients scanned at initial clinical presentation plus 66 healthy controls.ResultsIn the great majority of patients, MRI was logistically feasible. Radiological abnormalities were reported in 6% of the research sample and in 15% of the clinical sample (odds ratio (OR)=3.1, 95% CI 1.26-7.57, χ2(1) = 6.63, P = 0.01). None of the findings necessitated a change in clinical management.ConclusionsRates of neuroradiological abnormalities in FEP are likely to be underestimated in research samples that often exclude patients with organic abnormalities. However, the majority of findings do not require intervention.

The role of the right temporo-parietal junction in social decision-making

Identifying someone elses noncooperative intentions can prevent exploitation in social interactions. Hence, the inference of another persons mental state might be most pronounced in order to improve social decision‐making. Here, we tested the hypothesis that brain regions associated with Theory of Mind (ToM), particularly the right temporo–parietal junction (rTPJ), show higher neural responses when interacting with a selfish person and that the rTPJ‐activity as well as cooperative tendencies will change over time. We used functional magnetic resonance imaging (fMRI) and a modified prisoners dilemma game in which 20 participants interacted with three fictive playing partners who behaved according to stable strategies either competitively, cooperatively or randomly during seven interaction blocks. The rTPJ and the posterior–medial prefrontal cortex showed higher activity during the interaction with a competitive compared with a cooperative playing partner. Only the rTPJ showed a high response during an early interaction phase, which preceded participants increase in defective decisions. Enhanced functional connectivity between the rTPJ and the left hippocampus suggests that social cognition and learning processes co‐occur when behavioral adaptation seems beneficial.

Personality modulates amygdala and insula connectivity during humor appreciation: An event-related fMRI study

ABSTRACT Previous research and theory implicate that personality traits, such as extraversion and neuroticism, influence the processing of humor, as indicated by alterations in the activation of fronto-temporal and mesocorticolimbic brain regions during humor processing. In the current study, we sought to complement these findings by testing whether inter-individual differences in functional connectivity of humor-related brain regions are modulated by stable personality characteristics during humor processing. Using fMRI techniques, we studied 19 healthy subjects during the processing of standardized humorous and neutral cartoons. In order to isolate the specific effects of humor appreciation, subjective funniness ratings, collected during the scanning procedure, were implemented in the analysis as parametric modulation. Two distinct clusters in the right amygdala and the left insula were identified. Seed-to-voxel connectivity analysis investigating the effects of personality on inter-individual differences in functional connectivity revealed that amygdala and insula connectivity with brain areas previously related to humor comprehension (e.g. middle temporal gyrus) and appreciation (e.g. caudate nucleus) were significantly modulated by personality dimensions. These results underscore the sensitivity of humor processing to moderating influences, such as personality, and call attention to the importance of brain connectivity measures for the investigation of inter-individual differences in the processing of humor.

Corticolimbic dysfunction during facial and prosodic emotional recognition in first-episode psychosis patients and individuals at ultra-high risk

Emotional processing dysfunction is widely reported in patients with chronic schizophrenia and first-episode psychosis (FEP), and has been linked to functional abnormalities of corticolimbic regions. However, corticolimbic dysfunction is less studied in people at ultra-high risk for psychosis (UHR), particularly during processing prosodic voices. We examined corticolimbic response during an emotion recognition task in 18 UHR participants and compared them with 18 FEP patients and 21 healthy controls (HC). Emotional recognition accuracy and corticolimbic response were measured during functional magnetic resonance imaging (fMRI) using emotional dynamic facial and prosodic voice stimuli. Relative to HC, both UHR and FEP groups showed impaired overall emotion recognition accuracy. Whilst during face trials, both UHR and FEP groups did not show significant differences in brain activation relative to HC, during voice trials, FEP patients showed reduced activation across corticolimbic networks including the amygdala. UHR participants showed a trend for increased response in the caudate nucleus during the processing of emotionally valenced prosodic voices relative to HC. The results indicate that corticolimbic dysfunction seen in FEP patients is also present, albeit to a lesser extent, in an UHR cohort, and may represent a neural substrate for emotional processing difficulties prior to the onset of florid psychosis.

Frontal hypoactivation and alterations in the reward-system during humor processing in patients with schizophrenia spectrum disorders

Humor is a ubiquitous human ability with important implications for both social and emotional functioning. Patients with neuropsychiatric disorders, such as schizophrenia, experience difficulties in the comprehension and appreciation of humor. However, the specific neural mechanisms underlying these deficits are unknown. In the current study, we sought to elucidate the neural correlates of humor processing in patients with schizophrenia spectrum disorders (SSD). Functional Magnetic Resonance Imaging (fMRI) was used in thirty-one patients with SSD and a control group, performing a humor processing paradigm. Both regional brain activation and parametric modulation of brain responses via subjective funniness ratings were collected during the scanning procedure. On a neural level, large overlaps in fronto-temporal brain activation was found in both groups. However, patients compared to healthy control subjects showed attenuated responses in frontal brain regions, including the anterior cingulate cortex, medial prefrontal cortex (mPFC), superior frontal gyrus and middle frontal gyrus, as well as in the striatum (i.e. caudate nucleus, putamen). Furthermore, parametric modulation of subjective funniness ratings resulted in attenuated responses in the mPFC, bilateral insula, and left hippocampus. Analysis of functional connectivity revealed alterations in mPFC-caudate nucleus coupling in patients with SSD, which might reflect impairments in reward-related processing. Notably, alterations in mPFC-caudate nucleus coupling in patients were significantly associated to subjective funniness ratings. Our results extend previous findings demonstrating the relevance of frontal hypoactivation for humor processing impairments in patients with SSD and first point towards alterations in humor appreciation processes.

T202. HUMOR-SKILLS TRAINING IN PATIENTS WITH SCHIZOPHRENIA: EFFECTS ON SYMPTOMS AND SOCIAL FUNCTIONING

Abstract Background Humor can provide a method of coping with a variety of stressful situations. Training of humor-related skills has proven effective in clinical samples, although humor training in patients with schizophrenia is relatively rare. Methods In the present study, patients with schizophrenia have been randomly assigned to either a training of humor abilities or a training of social skills. Training effects on measures of psychopathology, psychosocial functioning and stress were compared between groups. Results Preliminary analyses revealed that level of negative symptoms, stress and psychosocial dysfunction were significantly reduced in the humor group over the course of the training. Discussion These results suggest that humor training may improve important clinical and functional outcomes in patients with schizophrenia.