Christian H. Röder

Abnormalities in emotion processing within cortical and subcortical regions in criminal psychopaths: evidence from a functional magnetic resonance imaging study using pictures with emotional content

BACKGROUND Neurobiology of psychopathy is important for our understanding of current neuropsychiatric questions. Despite a growing interest in biological research in psychopathy, its neural underpinning remains obscure. METHODS We used functional magnetic resonance imaging to study the influence of affective contents on brain activation in psychopaths. Series containing positive and negative pictures from the International Affective Picture System were shown to six male psychopaths and six male control subjects while 100 whole-brain echo-planar-imaging measurements were acquired. Differences in brain activation were evaluated using BrainVoyager software 4.6. RESULTS In psychopaths, increased activation through negative contents was found right-sided in prefrontal regions and amygdala. Activation was reduced right-sided in the subgenual cingulate and the temporal gyrus, and left-sided in the dorsal cingulate and the parahippocampal gyrus. Increased activation through positive contents was found left-sided in the orbitofrontal regions. Activation was reduced in right medial frontal and medial temporal regions. CONCLUSIONS These findings underline the hypotheses that psychopathy is neurobiologically reflected by dysregulation and disturbed functional connectivity of emotion-related brain regions. These findings may be interpreted within a framework including prefrontal regions that provide top-down control to and regulate bottom-up signals from limbic areas. Because of the small sample size, the results of this study have to be regarded as preliminary.

The spatiotemporal pattern of auditory cortical responses during verbal hallucinations.

Functional magnetic resonance imaging (fMRI) studies can provide insight into the neural correlates of hallucinations. Commonly, such studies require self-reports about the timing of the hallucination events. While many studies have found activity in higher-order sensory cortical areas, only a few have demonstrated activity of the primary auditory cortex during auditory verbal hallucinations. In this case, using self-reports as a model of brain activity may not be sensitive enough to capture all neurophysiological signals related to hallucinations. We used spatial independent component analysis (sICA) to extract the activity patterns associated with auditory verbal hallucinations in six schizophrenia patients. SICA decomposes the functional data set into a set of spatial maps without the use of any input function. The resulting activity patterns from auditory and sensorimotor components were further analyzed in a single-subject fashion using a visualization tool that allows for easy inspection of the variability of regional brain responses. We found bilateral auditory cortex activity, including Heschls gyrus, during hallucinations of one patient, and unilateral auditory cortex activity in two more patients. The associated time courses showed a large variability in the shape, amplitude, and time of onset relative to the self-reports. However, the average of the time courses during hallucinations showed a clear association with this clinical phenomenon. We suggest that detection of this activity may be facilitated by examining hallucination epochs of sufficient length, in combination with a data-driven approach.

Executive functions and cognitive subprocesses in patients with obstructive sleep apnoea.

In recent years, special interest has been focused on impairments of executive functions in patients with obstructive sleep apnoea syndrome (OSAS). However, the majority of studies have not clearly separated deficits in executive functions from impairments in other cognitive processes involved in task solving. In the present study, working memory (WM) functions of 20 patients with OSAS were compared with those of 10 age‐, sex‐ and education‐matched healthy subjects. Cognitive functions were measured four times a day; each of these measurements was accompanied by an assessment of subjective and objective daytime sleepiness. To separate dysfunctions of WM from those of additionally involved processes, n‐back tasks were applied embedded in a reaction‐time‐decomposition approach. Deficits in n‐back tasks could be observed in OSAS patients in accuracy and reaction times. However, the slowing could already be observed in simple reaction time tasks. The drop in 1‐back accuracy in the morning was related to daytime sleepiness. During the afternoon, accuracy of OSAS patients dropped in 2‐back tasks, an effect which correlated neither with sleepiness nor with the extent of sleep apnoea or oxygen desaturation. In conclusion, our data reflect a complex perspective upon cognitive deficits in OSAS. Cross‐group differences in processing time on the higher level WM task appeared to be attributable to slowing at a more elementary cognitive processing level. In contrast, reduced accuracy during the WM task in the OSAS group could not be explained by deficits in more elementary cognitive processes.

Pain response in depersonalization: A functional imaging study using hypnosis in healthy subjects

Background: Depersonalization (DP) is characterized by persistent or recurrent episodes of detachment from one’s self with reduced pain perception being a common feature. Alterations in the body schema similar to the cortico-limbic disconnection syndrome of pain asymbolia are suggested to be responsible for DP. In this study we used hypnosis to induce DP in healthy subjects and to examine neural patterns of pain perception in the state of DP by means of functional magnetic resonance imaging (fMRI). Methods: Pain perception was investigated in 7 healthy subjects with high susceptibility to hypnosis in three different mental states: waking state (N-W), hypnotic relaxation (H-R) and hypnotic DP (H-DP). Pain was induced with electrical stimulation to the median nerve at the right wrist. fMRI measurements were performed during all states. Results: Nociceptive stimuli led to an activation of the well described pain network including somatosensory and insular regions and the cerebellum. Activation was markedly reduced in the contralateral somatosensory cortex, parietal cortex (Brodmann area 40, BA40), prefrontal cortex (BA9), putamen and the ipsilateral amygdala during H-DP. Subjects also reported a significant decrease in pain intensity from N-W to H-DP. Conclusion: Pain response during H-DP was reduced in sensory and affective pain-related areas, reflecting the diminished intensity of the perceived pain. Moreover, a network of cortical and subcortical areas that have been implicated in the perception of the own body was less responsive during DP, which might point to a specific neural mechanism underlying the ‘out-of-body’ experience. Although the small number of subjects does not allow a generalization of our findings, H-DP seems to be a promising tool for the investigation of psychological and biological mechanisms of self-inflicted injuries as well as the mind-body interplay within the realm of psychosomatic disorders.

Motor-induced brain activation in cortical, subcortical and cerebellar regions in schizophrenic inpatients. A whole brain fMRI fingertapping study

Motor symptoms including neurological soft signs have been found to be more prevalent in schizophrenic patients. In addition, catatonic symptoms and neuroleptic treatment as well may influence cortical and subcortical motor organization in schizophrenia. The results of previous neuroimaging studies exploring motor function in patients with schizophrenia are inhomogenous reporting on a decreased activity in cortical motor regions in some studies and normal activity in others. Using fMRI, we studied 40 subjects performing a unilateral self-paced fingertapping task. Analyzing a general linear model of four groups, we compared patients with schizophrenia according to DSM-IV treated with olanzapine (OL; 10) or haloperidol (HA; 10) to healthy controls (HC; 10) and untreated patients (UN; 10). Brainvoyager software was used for data analyzing. In all groups, the contralateral motor cortex was significantly activated. Significant activation of the ipsilateral cerebellum was found in the UN group, the control group and the OL group. The contralateral basal ganglia were activated in UN and in controls. Motor-induced cortical and subcortical brain activation in HC was significantly higher than in patients with schizophrenia. UN with schizophrenia showed a significant overactivation than the other groups. In conclusion, we revealed a diminished activation in the patient group treated with neuroleptic drugs. This study outlines the importance of further fMRI studies to investigate interindividual activation differences under different conditions especially focusing on basal ganglia.

Body image distortions in bulimia nervosa: investigating body size overestimation and body size satisfaction by fMRI

BACKGROUND Body image distortion is a key symptom of eating disorders. In behavioral research two components of body image have been defined: attitudes towards the body and body size estimation. Only few fMRI-studies investigated the neural correlates of body image in bulimia; those are constrained by the lack of a direct distinction between these different body image components. METHODS The present study investigates the neural correlates of two aspects of the body image using fMRI: satisfaction rating and size estimation of distorted own body photographs in bulimia nervosa patients (15) and controls (16). RESULTS Patients were less satisfied with their current body shape than controls and preferred to be thinner. The amount of insula activity reflects the pattern of the satisfaction rating for patients and controls. Patients also overestimated their own body size. For control subjects, an activated cluster in lateral occipital cortex was sensitive for body size distortions, whereas bulimic patients did not demonstrate such a modulation. Furthermore, bulimic subjects did not recruit the middle frontal gyrus (MFG) in contrast to controls during the body size estimation task, maybe indicating a reduced spatial manipulation capacity. Therefore, this activation pattern of lateral occipital cortex and MFG might be responsible for body size overestimation in bulimia. CONCLUSIONS The present results show that bulimic patients exhibit two distinct deficits in body image representations similar to anorectic patients and that specifically associated neuronal correlates can be identified. Concludingly, our study support psychotherapeutic strategies specifically targeting these two aspects of body image distortions.

Subcortical overactivation in untreated schizophrenic patients: A functional magnetic resonance image finger‐tapping study

Abstract Functional magnetic resonance imaging (fMRI) is a well established, non‐invasive technique for mapping the working brain. Yet imaging of subcortical regions has proven to be difficult. We studied 40 subjects performing an unilateral self‐paced finger‐tapping task. Patients with schizophrenia according to DSM‐IV treated with olanzapine (n = 10) or haloperidol (n = 10) were compared to healthy controls (n = 10) and untreated patients (n = 10). Brainvoyager software was used for data‐analyzing. All subjects showed highly significant activation in the contralateral sensorimotor area, the supplementary motor area and the ipsilateral cerebellum. In every investigated subject contralateral subcortical regions were also significantly activated (P < 0.001). Activation in ipsilateral pallidum was significantly higher in untreated patients compared with the other groups indicating an increase in subcortical coactivation. In addition, significant correlations were revealed within groups. This study emphasizes the possibility of investigating subcortical brain activation in patients with schizophrenia. The results of the present study outline the importance of further fMRI studies to investigate interindividual activation differences under different conditions especially focusing on basal ganglia.

Diurnal cortisol patterns of young male patients with schizophrenia

Aims:  It has been suggested that schizophrenic patients are more vulnerable to stress than healthy persons, and that stressors can trigger a psychotic episode or worsen symptoms. The biological system often studied in relation to stress is the hypothalamic–pituitary–adrenal (HPA) axis, which controls the release of cortisol. We investigated whether the diurnal basal activity of the HPA axis differed between young male patients with schizophrenia and healthy controls.

Marked reduction of AKT1 expression and deregulation of AKT1-associated pathways in peripheral blood mononuclear cells of schizophrenia patients

Background Recent studies have suggested that deregulated AKT1 signaling is associated with schizophrenia. We hypothesized that if this is indeed the case, we should observe both decreased AKT1 expression as well as deregulation of AKT1 regulated pathways in Peripheral Blood Mononuclear Cells (PBMCs) of schizophrenia patients. Objectives To examine PBMC expression levels of AKT1 in schizophrenia patients versus controls, and to examine whether functional biological processes in which AKT1 plays an important role are deregulated in schizophrenia patients. Methods/Results A case-control study, investigating whole-genome PBMC gene expression in male, recent onset (<5 years) schizophrenia patients (N = 41) as compared to controls (N = 29). Genes, differentially expressed between patients and controls were identified using ANOVA with Benjamini-Hochberg correction (false discovery rate (FDR) = 0.05). Functional aspects of the deregulated set of genes were investigated with the Ingenuity Pathway Analysis (IPA) Software Tool. We found significantly decreased PBMC expression of AKT1 (p<0.001, t = −4.25) in the patients. AKT1 expression was decreased in antipsychotic-free or -naive patients (N = 11), in florid psychotic (N = 20) and in remitted (N = 21) patients. A total of 1224 genes were differentially expressed between patients and controls (FDR = 0.05). Functional analysis of the entire deregulated gene set indicated deregulated canonical pathways involved in a large number of cellular processes: immune system, cell adhesion and neuronal guidance, neurotrophins and (neural) growth factors, oxidative stress and glucose metabolism, and apoptosis and cell-cycle regulation. Many of these processes are associated with AKT1. Conclusions We show significantly decreased PBMC gene expression of AKT1 in male, recent-onset schizophrenia patients. Our observations suggest that decreased PBMC AKT1 expression is a stable trait in recent onset, male schizophrenia patients. We identified several AKT related cellular processes which are potentially affected in these patients, a majority of which play a prominent role in current schizophrenia hypotheses.

Cardiovascular variability during treatment with haloperidol, olanzapine or risperidone in recent-onset schizophrenia

Abstract This study aimed to investigate the effects of treatment with haloperidol, olanzapine and risperidone on cardiovascular variability in patients with recent-onset schizophrenia by means of spectral analysis. Unmedicated patients (n = 18) had a higher mean heart rate and a tendency for a lower high-frequency power of heart rate variability than healthy control subjects (n = 57), indicating a decreased cardiac vagal control in unmedicated patients with schizophrenia. Patients treated with haloperidol (n = 10) showed significantly lower low-frequency power of heart rate and systolic blood pressure variability compared with olanzapine-treated patients, suggesting that haloperidol attenuated sympathetic functioning. On the contrary, olanzapine-treated patients (n = 10) showed the highest power in the low-frequency range of heart rate and systolic blood pressure variability, suggesting an increased sympathetic cardiac functioning. No significant effects of risperidone (n = 13) were found. None of the antipsychotic agents differed in their parasympathetic cardiovascular effects. We conclude that young, unmedicated patients with schizophrenia differed from controls in their parasympathetic functioning, but the antipsychotic agents haloperidol, risperidone and olanzapine induced only minor cardiovascular side effects.