Recognition and perception of emotions in juvenile myoclonic epilepsy.

OBJECTIVE: Perception and recognition of emotions are fundamental prerequisites of human life. Patients with juvenile myoclonic epilepsy (JME) may have emotional and behavioral impairments that might influence socially desirable interactions. We aimed to investigate perception and recognition of emotions in patients with JME by means of neuropsychological tests and functional magnetic resonance imaging (fMRI). METHODS: Sixty-five patients with JME (median age = 27 years, interquartile range [IQR] = 23-34) were prospectively recruited at the Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria. Patients were compared to 68 healthy controls (median age = 24 years, IQR = 21-31), matched for sex, age, and education. All study participants underwent the Networks of Emotion Processing test battery (NEmo), an fMRI paradigm of "dynamic fearful faces," a structured interview for psychiatric and personality disorders, and comprehensive neuropsychological testing. RESULTS: JME patients versus healthy controls demonstrated significant deficits in emotion recognition in facial and verbal tasks of all emotions, especially fear. fMRI revealed decreased amygdala activation in JME patients as compared to healthy controls. Patients were at a higher risk of experiencing psychiatric disorders as compared to healthy controls. Cognitive evaluation revealed impaired attentional and executive functioning, namely psychomotor speed, tonic alertness, divided attention, mental flexibility, and inhibition of automated reactions. Duration of epilepsy correlated negatively with parallel prosodic and facial emotion recognition in NEmo. Deficits in emotion recognition were not associated with psychiatric comorbidities, impaired attention and executive functions, types of seizures, and treatment. SIGNIFICANCE: This prospective study demonstrated that as compared to healthy subjects, patients with JME had significant deficits in recognition and perception of emotions as shown by neuropsychological tests and fMRI. The results of this study may have importance for psychological/psychotherapeutic interventions in the management of patients with JME.

Intrinsic neural timescales in autism spectrum disorder and schizophrenia. A replication and direct comparison study.

Intrinsic neural timescales (INT) reflect the duration for which brain areas store information. A posterior-anterior hierarchy of increasingly longer INT has been revealed in both typically developed individuals (TD), as well as persons diagnosed with autism spectrum disorder (ASD) and schizophrenia (SZ), though INT are, overall, shorter in both patient groups. In the present study, we aimed to replicate previously reported group differences by comparing INT of TD to ASD and SZ. We partially replicated the previously reported result, showing reduced INT in the left lateral occipital gyrus and the right post-central gyrus in SZ compared to TD. We also directly compared the INT of the two patient groups and found that these same two areas show significantly reduced INT in SZ compared to ASD. Previously reported correlations between INT and symptom severity were not replicated in the current project. Our findings serve to circumscribe the brain areas that can potentially play a determinant role in observed sensory peculiarities in ASD and SZ.

Emotional Word Processing in Patients With Juvenile Myoclonic Epilepsy.

Objective: According to Panksepp's hierarchical emotion model, emotion processing relies on three functionally and neuroanatomically distinct levels. These levels comprise subcortical networks (primary level), the limbic system (secondary level), and the neocortex (tertiary level) and are suggested to serve differential emotional processing. We aimed to validate and extend previous evidence of discrete and dimensional emotion processing in patient with juvenile myoclonic epilepsy (JME). Methods: We recorded brain activity of patients with JME and healthy controls in response to lexical decisions to words reflecting the discrete emotion fear and the affective dimension negativity previously suggested to rely on different brain regions and to reflect different levels of processing. In all study participants, we tested verbal cognitive functions, as well as the relationship of psychiatric conditions, seizure types and duration of epilepsy and emotional word processing. Results: In support of the hierarchical emotion model, we found an interaction of discrete emotion and affective dimensional processing in the right amygdala likely to reflect secondary level processing. Brain activity related to affective dimensional processing was found in the right inferior frontal gyrus and is suggested to reflect tertiary level processing. Psychiatric conditions, type of seizure nor mono- vs. polytherapy and duration of epilepsy within patients did not have any effect on the processing of emotional words. In addition, no differences in brain activity or response times between patients and controls were observed, despite neuropsychological testing revealed slightly decreased verbal intelligence, verbal fluency and reading speed in patients with JME. Significance: These results were interpreted to be in line with the hierarchical emotion model and to highlight the amygdala's role in processing biologically relevant stimuli, as well as to suggest a semantic foundation of affective dimensional processing in prefrontal cortex. A lack of differences in brain activity of patients with JME and healthy controls in response to the emotional content of words could point to unaffected implicit emotion processing in patients with JME.

Reduced intrinsic neural timescales in schizophrenia along posterior parietal and occipital areas.

We computed intrinsic neural timescales (INT) based on resting-state functional magnetic resonance imaging (rsfMRI) data of healthy controls (HC) and patients with schizophrenia spectrum disorder (SZ) from three independently collected samples. Five clusters showed decreased INT in SZ compared to HC in all three samples: right occipital fusiform gyrus (rOFG), left superior occipital gyrus (lSOG), right superior occipital gyrus (rSOG), left lateral occipital cortex (lLOC) and right postcentral gyrus (rPG). In other words, it appears that sensory information in visual and posterior parietal areas is stored for reduced lengths of time in SZ compared to HC. Finally, we found that symptom severity appears to modulate INT of these areas in SZ.

Pathologically reduced neural flexibility recovers during psychotherapy of OCD patients.

Flexibility is a key feature of psychological health, allowing the individual to dynamically adapt to changing environmental demands, which is impaired in many psychiatric disorders like obsessive-compulsive disorder (OCD). Adequately responding to varying demands requires the brain to switch between different patterns of neural activity, which are represented by different brain network configurations (functional connectivity patterns). Here, we operationalize neural flexibility as the dissimilarity between consecutive connectivity matrices of brain regions (jump length). In total, 132 fMRI scans were obtained from 17 patients that were scanned four to five times during inpatient psychotherapy, and from 17 controls that were scanned at comparable time intervals. Significant negative correlations were found between the jump lengths and the symptom severity scores of OCD, depression, anxiety, and stress, suggesting that high symptom severity corresponds to inflexible brain functioning. Further analyses revealed that impaired reconfiguration (pattern stability) of the brain seems to be more related to general psychiatric impairment rather than to specific symptoms, e.g., of OCD or depression. Importantly, the group × time interaction of a repeated measures ANOVA was significant, as well as the post-hoc paired t-tests of the patients (first vs. last scan). The results suggest that psychotherapy is able to significantly increase the neural flexibility of patients. We conclude that psychiatric symptoms like anxiety, stress, depression, and OCD are associated with an impaired adaptivity of the brain. In general, our results add to the growing evidence that dynamic functional connectivity captures meaningful properties of brain functioning.

Effective Connectivity of the Hippocampus Can Differentiate Patients with Schizophrenia from Healthy Controls: A Spectral DCM Approach.

We applied spectral dynamic causal modelling (Friston et al. in Neuroimage 94:396-407. https://doi.org/10.1016/j.neuroimage.2013.12.009 , 2014) to analyze the effective connectivity differences between the nodes of three resting state networks (i.e. default mode network, salience network and dorsal attention network) in a dataset of 31 male healthy controls (HC) and 25 male patients with a diagnosis of schizophrenia (SZ). Patients showed increased directed connectivity from the left hippocampus (LHC) to the: dorsal anterior cingulate cortex (DACC), right anterior insula (RAI), left frontal eye fields and the bilateral inferior parietal sulcus (LIPS & RIPS), as well as increased connectivity from the right hippocampus (RHC) to the: bilateral anterior insula (LAI & RAI), right frontal eye fields and RIPS. In SZ, negative symptoms predicted the connectivity strengths from the LHC to: the DACC, the left inferior parietal sulcus (LIPAR) and the RHC, while positive symptoms predicted the connectivity strengths from the LHC to the LIPAR and from the RHC to the LHC. These results reinforce the crucial role of hippocampus dysconnectivity in SZ pathology and its potential as a biomarker of disease severity.

Preserved intention understanding during moral judgments in schizophrenia.

INTRODUCTION: Although there is convincing evidence for socio-cognitive impairments in schizophrenia spectrum disorder (SSD), little evidence is found for deficient moral cognition. We investigated whether patients with SSD showed altered moral judgments in a story task where the protagonist either had a neutral or malicious intention towards another person. This paradigm examined whether SSD relates to altered moral cognition in general or specifically to impaired integration of prior information (such as beliefs) in moral judgments. METHODS: 23 patients and 32 healthy controls read vignettes created in a 2 x 2 design. The protagonist in each story either had a neutral or negative intention towards another person which, as a result, either died (negative outcome) or did not die (neutral outcome). Participants rated the moral permissibility of the protagonist's action. Standard null hypothesis significance testing and equivalent Bayes analyses are reported. RESULTS: Schizophrenia patients did not differ significantly in permissibility ratings from healthy controls. This finding was supported by the Bayes analyses which favoured the null hypothesis. Task performance was not related to symptom severity or medication. CONCLUSIONS: The current findings do not support the notion that moral judgments are deficient in schizophrenia. Furthermore, the current study shows that patients do not have observable difficulties in integrating the protagonist's belief in the rating of the moral permissibility of the action-outcome.

Cortical Morphometry and Its Relationship with Cognitive Functions in Children after non-CNS Cancer.

Background: Childhood cancer survivors (Ccs) are at risk for cognitive late-effects, which might result from cortical alterations, even if cancer does not affect the brain. The study aimed to examine gray and white matter volume and its relationship to cognition. Methods: Forty-three Ccs of non-central nervous system cancers and 43 healthy controls, aged 7-16 years, were examined. Cognitive functions and fine motor coordination were assessed and T1-weighted images were collected for voxel-based morphometry. Results: Executive functions (p = .024, d = .31) were poorer in Ccs than controls, however still within the normal range. The volume of the amygdala (p = .011, ŋ2 = .117) and the striatum (p = .03, ŋ2 = .102) was reduced in Ccs. No significant structure-function correlations were found, neither in patients nor controls. Conclusion: Non-CNS childhood cancer and its treatment impacts on brain structures relevant to emotion processing.

Impact of non-CNS childhood cancer on resting-state connectivity and its association with cognition.

INTRODUCTION: Non-central nervous system cancer in childhood (non-CNS CC) and its treatments pose a major threat to brain development, with implications for functional networks. Structural and functional alterations might underlie the cognitive late-effects identified in survivors of non-CNS CC. The present study evaluated resting-state functional networks and their associations with cognition in a mixed sample of non-CNS CC survivors (i.e., leukemia, lymphoma, and other non-CNS solid tumors). METHODS: Forty-three patients (off-therapy for at least 1 year and aged 7-16 years) were compared with 43 healthy controls matched for age and sex. High-resolution T1-weighted structural magnetic resonance and resting-state functional magnetic resonance imaging were acquired. Executive functions, attention, processing speed, and memory were assessed outside the scanner. RESULTS: Cognitive performance was within the normal range for both groups; however, patients after CNS-directed therapy showed lower executive functions than controls. Seed-based connectivity analyses revealed that patients exhibited stronger functional connectivity between fronto- and temporo-parietal pathways and weaker connectivity between parietal-cerebellar and temporal-occipital pathways in the right hemisphere than controls. Functional hyperconnectivity was related to weaker memory performance in the patients' group. CONCLUSION: These data suggest that even in the absence of brain tumors, non-CNS CC and its treatment can lead to persistent cerebral alterations in resting-state network connectivity.

Multi-level assessment of obsessive-compulsive disorder (OCD) reveals relations between neural and neurochemical levels.

BACKGROUND: While considerable progress has been made in exploring the psychological, the neural, and the neurochemical dimensions of OCD separately, their interplay is still an open question, especially their changes during psychotherapy. METHODS: Seventeen patients were assessed at these three levels by psychological questionnaires, fMRI, and venipuncture before and after inpatient psychotherapy. Seventeen controls were scanned at comparable time intervals. First, pre/post treatment changes were investigated for all three levels separately: symptom severity, whole-brain and regional activity, and the concentrations of cortisol, serotonin, dopamine, brain-derived neurotrophic factor (BDNF), and immunological parameters (IL-6, IL-10, TNFα). Second, stepwise linear modeling was used to find relations between the variables of the levels. RESULTS: The obsessive-compulsive, depressive, and overall symptom severity was significantly reduced after psychotherapy. At the neural level, the activity in the anterior cingulate cortex (ACC), in frontal regions, in the precuneus, and in the putamen had significantly decreased. No significant changes were found on the neurochemical level. When connecting the levels, a highly significant model was found that explains the decrease in neural activity of the putamen by increases of the concentrations of cortisol, IL-6, and dopamine. CONCLUSION: Multivariate approaches offer insight on the influences that the different levels of the psychiatric disorder OCD have on each other. More research and adapted models are needed.

Reduced spontaneous perspective taking in schizophrenia.

Judgments about another person's visual perspective are impaired when the self-perspective is inconsistent with the other-perspective. This is a robust finding in healthy samples as well as in schizophrenia (SZ). Studies show evidence for the existence of a reverse effect, where an inconsistent other-perspective impairs the self-perspective. Such spontaneous perspective taking processes are not yet explored in SZ. In the current fMRI experiment, 24 healthy and 24 schizophrenic participants performed a visual perspective taking task in the scanner. Either a social or a non-social stimulus was presented and their visual perspectives were consistent or inconsistent with the self-perspective of the participant. We replicated previous findings showing that healthy participants show increased reaction times when the human avatar's perspective is inconsistent to the self-perspective. Patients with SZ, however, did not show this effect, neither in the social nor in the non-social condition. BOLD responses revealed similar patterns in occipital areas and group differences were identified in the middle occipital gyrus. These findings suggest that patients with SZ are less likely to spontaneously compute the visual perspectives of others.

Erroneously Disgusted: fMRI Study Supports Disgust-Related Neural Reuse in Obsessive-Compulsive Disorder (OCD).

Objective: fMRI scans of patients with obsessive-compulsive disorder (OCD) consistently show a hyperactivity of the insular cortex, a region responsible for disgust-processing, when confronted with symptom-triggering stimuli. This asks for an investigation of the role of disgust and the insula in OCD patients. Methods: Seventeen inpatients with OCD and 17 healthy controls (HC) underwent fMRI scanning. Whole-brain contrasts were calculated for "Disgust vs. Neutral" for both groups, plus an analysis of variance (ANOVA) to assess the interaction between group and condition. Additionally, the emotional dimensions of valence and arousal, along with the ability to cope, were assessed by picture ratings. Results: The picture ratings confirmed the patients' heightened sensitivity to disgust with higher values for arousal and inability to cope, but not for valence. fMRI scans revealed no hyperactivity of the insula in patients compared to controls for the condition "Disgust vs. Neutral," indicating no basic hypersensitivity to disgusting stimuli. Increased activity in the precuneus in controls for this condition might correspond to the downregulation of arousal. Conclusions: The absent differences in neural activity of the insula in patients compared to controls for the disgust-condition, but heightened activity for symptom-provoking conditions, suggests that the illness is due to an erroneous recruitment of the insula cortex for OCD-stimuli. The finding is interpreted within the framework of the neural reuse hypothesis.

Individual OCD-provoking stimuli activate disorder-related and self-related neuronal networks in fMRI.

For patients with Obsessive-Compulsive Disorder (OCD), whose triggers are highly idiosyncratic, individual stimulus material has been used in several fMRI studies. This study aims at comparing individual to standardized picture sets and at investigating a possible overlap of the former with the self-referential neuronal network. During fMRI-scanning, 17 inpatients with OCD and 17 healthy controls were exposed to pictures of their personal triggers, photographed in their domestic environments, to standardized pictures designed to provoke OCD symptoms, and to neutral pictures. Whole-brain analyses were calculated and the pictures were rated by both patients and controls with respect to valence, arousal, and coping. Patients rated the individualized stimuli lower in valence and coping and higher in arousal compared to controls, and also compared to standardized OCD- and neutral stimuli. The individual stimuli elicited neuronal activity in the cingulate cortex, hippocampus, insula, middle frontal/precentral gyrus, superior/inferior parietal lobe, and precuneus, while no group difference was detected by the standardized OCD-stimuli. In conclusion, individual picture sets facilitate the detection of neuronal activity, but the results might be confounded due to the overlap with the network of self-referential processing and memory retrieval. The use of individual symptom-provoking and individual neutral stimuli would therefore be optimal.

Perceptual Expectations of Object Stimuli Modulate Repetition Suppression in a Delayed Repetition Design.

Several fMRI and EEG/MEG studies show that repetition suppression (RS) effects are stronger when a stimulus repetition is expected compared to when a stimulus repetition is less expected. To date, the prevalent way to assess the influence of expectations on RS is via immediate stimulus repetition designs, that is, no intervening stimuli appear between the initial and repeated presentation of a stimulus. Since there is evidence that repetition lag may alter RS effects in a qualitative manner, the current study investigated how perceptual expectations modify RS effects on object stimuli when repetition lag is relatively long. Region of interest analyses in the left occipital cortex revealed a similar activation pattern as identified in previous studies on immediate lag: RS effects were strongest when repetitions were expected compared to decreased RS effects when repetitions were less expected. Therefore, the current study expands previous research in two ways: First, we replicate prior studies showing that perceptual expectation effects can be observed in object-sensitive occipital areas. Second, the finding that expectation effects can be found even for several-minute lags proposes that Bayesian inference processes are a relatively robust component in visual stimulus processing.

Schizophrenia and Category-Selectivity in the Brain: Normal for Faces but Abnormal for Houses.

Face processing is regularly found to be impaired in schizophrenia (SZ), thus suggesting that social malfunctioning might be caused by dysfunctional face processing. Most studies focused on emotional face processes, whereas non-emotional face processing received less attention. While current reports on abnormal face processing in SZ are mixed, examinations of non-emotional face processing compared to adequate control stimuli may clarify whether SZ is characterized by a face-processing deficit. Patients with SZ (n = 28) and healthy controls (n = 30) engaged in an fMRI scan where images of non-emotional faces and houses were presented. A simple inverted-picture detection task warranted the participants' attention. Region of interest (ROI) analyses were conducted on face-sensitive regions including the fusiform face area, the occipital face area, and the superior temporal sulcus. Scene-sensitivity was assessed in the parahippocampal place area (PPA) and served as control condition. Patients did not show aberrant face-related neural processes in face-sensitive regions. This finding was also evident when analyses were done on individually defined ROIs or on in-house-localizer ROIs. Patients revealed a decreased specificity toward house stimuli as reflected in decreased neural response toward houses in the PPA. Again, this result was supported by supplementary analyses. Neural activation toward neutral faces was not found to be impaired in SZ, therefore speaking against an overall face-processing deficit. Aberrant activation in scene-sensitive PPA is also found in assessments of memory processes in SZ. It is up to future studies to show how impairments in PPA relate to functional outcome in SZ.

The Importance of the Left Occipitotemporal Cortex in Developmental Dyslexia.

PURPOSE OF REVIEW: Developmental dyslexia is characterized by an impaired acquisition of fluent and skilled reading ability. Numerous studies have explored the neural correlates of this neurodevelopmental disorder, with most classic accounts strongly focussing on left temporoparietal regions. We will review recent findings from structural and functional MRI studies that suggest a more important role of occipitotemporal cortex abnormalities in dyslexia. RECENT FINDINGS: Recent findings highlight the role of the occipitotemporal cortex which exhibits functional as well as structural abnormalities in dyslexic readers and in children at risk for dyslexia and suggest a more central role for the occipitotemporal cortex in the pathophysiology of dyslexia. SUMMARY: We demonstrate the importance of the occipitotemporal cortex in for understanding impaired reading acquisition and point out how future research might enhance our understanding of functional and structural impairments in the reading network via large-scale data analysis approaches.

Abnormal Brain Activation During Theory of Mind Tasks in Schizophrenia: A Meta-Analysis.

Social cognition abilities are severely impaired in schizophrenia (SZ). The current meta-analysis used foci of 21 individual studies on functional abnormalities in the schizophrenic brain in order to identify regions that reveal convergent under- or over-activation during theory of mind (TOM) tasks. Studies were included in the analyses when contrasting tasks that require the processing of mental states with tasks which did not. Only studies that investigated patients with an ICD or DSM diagnosis were included. Quantitative voxel-based meta-analyses were done using Seed-based d Mapping software. Common TOM regions like medial-prefrontal cortex and temporo-parietal junction revealed abnormal activation in schizophrenic patients: Under-activation was identified in the medial prefrontal cortex, left orbito-frontal cortex, and in a small section of the left posterior temporo-parietal junction. Remarkably, robust over-activation was identified in a more dorsal, bilateral section of the temporo-parietal junction. Further abnormal activation was identified in medial occipito-parietal cortex, right premotor areas, left cingulate gyrus, and lingual gyrus. The findings of this study suggest that SZ patients simultaneously show over- and under-activation in TOM-related regions. Especially interesting, temporo-parietal junction reveals diverging activation patterns with an under-activating left posterior and an over-activating bilateral dorsal section. In conclusion, SZ patients show less specialized brain activation in regions linked to TOM and increased activation in attention-related networks suggesting compensatory effects.