Correlation of passivity symptoms and dysfunctional visuomotor action monitoring in psychosis

Passivity experiences are hallmark symptoms of schizophrenia that can be characterized by the belief that one's thoughts or actions are controlled by an external agent. It has recently been suggested that these psychotic experiences result from defective monitoring of one's own actions, i.e. disturbed comparison of actions and perceived outcomes. In this study, we examined the function of the previously characterized action monitoring network of the inferior parietal lobule (IPL), medial (mPFC) and lateral prefrontal cortices in patients with different levels of passivity symptoms with an fMRI task. The visuomotor fMRI task demanded control of visually perceived object movements by alternating button presses with the left and the right index finger. In the monitoring condition of this task subjects stopped their actions whenever they detected visuomotor incongruence. fMRI and behavioural data from 15 patients were tested for correlation with passivity symptoms using standardized Scale for Assessment of Positive Symptoms (SAPS)- and AMDP- passivity symptom ratings. Both types of data were tested for differences between the patients group and 15 healthy controls. In the patient group we found the expected correlation of passivity symptoms and visuomotor monitoring performance. There was a significant positive correlation of passivity symptoms with increased latency of incongruence detection and a negative correlation of SAPS-passivity with the number of detected events. fMRI data revealed correlations of passivity symptoms with activation in bilateral IPL, primary motor and sensory cortices in the action monitoring condition. A correlation of passivity symptoms with the main experimental effect (actions with - actions without monitoring) was found in the posterior cingulate cortex (PCC) and in the left IPL. No group differences or group by task interactions were found within the visuomotor-action-monitoring network. Our results demonstrate the association between passivity symptoms and the dysfunction of visuomotor action monitoring and support the idea that psychotic passivity experiences result from dysfunctions of central action monitoring mechanisms: According to pre-existing concepts of parietal cortex function, IPL-hyperactivation may represent an increase in false detections of visuomotor incongruence while the correlation between passivity and the differential effect of monitoring on PCC-activation assumedly represents greater self-monitoring effort in passivity experience

TRIMAGE: A dedicated trimodality (PET/MR/EEG) imaging tool for schizophrenia

Simultaneous PET/MR/EEG (Positron Emission Tomography - Magnetic Resonance - Electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here within the framework of the European Union Project TRIMAGE. The trimodal, cost-effective PET/MR/EEG imaging tool makes use of cutting edge technology both in PET and in MR fields. A novel type of magnet (1.5T, non-cryogenic) has been built together with a PET scanner that makes use of the most advanced photodetectors (i.e., SiPM matrices), scintillators matrices (LYSO) and digital electronics. The combined PET/MR/EEG system is dedicated to brain imaging and has an inner diameter of 260 mm and an axial Field-of-View of 160 mm. It enables the acquisition and assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. The dopaminergic system and the glutamatergic system in schizophrenic patients are investigated via PET, the same physiological/pathophysiological conditions with regard to functional connectivity, via fMRI, and its electrophysiological signature via EEG. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases. The preliminary performances of two components of the imaging tool (PET and MR) are discussed. Initial results of the search of possible candidates for suitable schizophrenia biomarkers are also presented as obtained with PET/MR systems available to the collaboration

Correlation of passivity symptoms and dysfunctional visuomotor action monitoring in psychosis

Passivity experiences are hallmark symptoms of schizophrenia that can be characterized by the belief that one's thoughts or actions are controlled by an external agent. It has recently been suggested that these psychotic experiences result from defective monitoring of one's own actions, i.e. disturbed comparison of actions and perceived outcomes. In this study, we examined the function of the previously characterized action monitoring network of the inferior parietal lobule (IPL), medial (mPFC) and lateral prefrontal cortices in patients with different levels of passivity symptoms with an fMRI task. The visuomotor fMRI task demanded control of visually perceived object movements by alternating button presses with the left and the right index finger. In the monitoring condition of this task subjects stopped their actions whenever they detected visuomotor incongruence. fMRI and behavioural data from 15 patients were tested for correlation with passivity symptoms using standardized Scale for Assessment of Positive Symptoms (SAPS)- and AMDP- passivity symptom ratings. Both types of data were tested for differences between the patients group and 15 healthy controls. In the patient group we found the expected correlation of passivity symptoms and visuomotor monitoring performance. There was a significant positive correlation of passivity symptoms with increased latency of incongruence detection and a negative correlation of SAPS-passivity with the number of detected events. fMRI data revealed correlations of passivity symptoms with activation in bilateral IPL, primary motor and sensory cortices in the action monitoring condition. A correlation of passivity symptoms with the main experimental effect (actions with – actions without monitoring) was found in the posterior cingulate cortex (PCC) and in the left IPL. No group differences or group by task interactions were found within the visuomotor-action-monitoring network. Our results demonstrate the association between passivity symptoms and the dysfunction of visuomotor action monitoring and support the idea that psychotic passivity experiences result from dysfunctions of central action monitoring mechanisms: According to pre-existing concepts of parietal cortex function, IPL-hyperactivation may represent an increase in false detections of visuomotor incongruence while the correlation between passivity and the differential effect of monitoring on PCC-activation assumedly represents greater self-monitoring effort in passivity experiences

Psychiatric Acute Day Hospital as an Alternative to Inpatient Treatment

For the first time in the Swiss health care system, this evaluation study examined whether patients with acute psychiatric illness who were admitted for inpatient treatment could be treated in an acute day hospital instead. The acute day hospital is characterized by the possibility of direct admission of patients without preliminary consultation or waiting time and is open every day of the week. In addition, it was examined whether and to what extent there are cost advantages for day hospital treatment. Patients who were admitted to the hospital with a referral to an inpatient admission were treated randomly either fully inpatient or in the acute day hospital. As a pilot study, 44 patients were admitted to the study. Evidence of efficacy could be provided for both treatment settings based on significant reduction in psychopathological symptoms and improvement in functional level in the course of treatment. There were no significant differences between the two settings in terms of external assessment of symptoms, subjective symptom burden, functional level, quality of life, treatment satisfaction, and number of treatment days. Treatment in the day hospital was about 45% cheaper compared to inpatient treatment. The results show that acutely ill psychiatric patients of different symptom severity can be treated just as well in an acute day hospital instead of being admitted to the hospital. In addition, when direct treatment costs are considered, there are clear cost advantages for day hospital treatment

Mismatch negativity generation in subjects at risk for psychosis: source analysis is more sensitive than surface electrodes in risk prediction

Background: Deficits of mismatch negativity (MMN) in patients with schizophrenia have been demonstrated many times and there is growing evidence that alterations of MMN already exist in individuals at risk for psychosis. The present study examines differences in MMN between subjects fulfilling ultra-high risk (UHR) or only basic symptoms criteria and it addresses the question, if MMN source analysis can improve prediction of transition to psychosis. Methods: The MMN to duration, frequency, and intensity deviants was recorded in 50 healthy controls and 161 individuals at risk for psychosis classified into three subgroups: only basic symptoms (n = 74), only ultra-high risk (n = 13) and persons who fulfill both risk criteria (n = 74). Based on a three-source model of MMN generation, we conducted an MMN source analysis and compared the amplitudes of surface electrodes and sources among the three groups. Results: Significant differences in MMN generation among the four groups were revealed at surface electrodes Cz and C4 (p < 0.05) and at the frontal source (p < 0.001) for duration deviant stimuli. The 15 subjects from the risk groups who subsequently developed a manifest psychosis had a significantly lower MMN amplitude at frontal source (p = 0.019) without showing significant differences at surface electrodes. Low activity at frontal MMN source increased the risk of transition to manifest disease by the factor 3.12 in UHR subjects. Conclusion: MMN activity differed significantly between subjects presenting only basic symptoms and subjects which additionally meet UHR criteria. The largest differences between groups as well as between individuals with and without transition were observed at the frontal source. The present results suggest that source analysis is more sensitive than surface electrodes in psychosis risk prediction by MMN

Early Somatosensory Processing Over Time in Individuals at Risk to Develop Psychosis

Objective: Somatosensory evoked potentials (SEPs) enable the investigation of thalamocortical and early cortical processing. Previous studies reported alterations of SEPs in patients with schizophrenia as well as in individuals in the prodromal stage. Moreover, cannabis use as an environmental risk factor for the development of schizophrenia has been demonstrated to influence SEP parameters in individuals at risk to develop psychosis. The aim of this study was to explore the course of SEP changes and the impact of concomitant cannabis use in individuals at risk to develop psychosis who sought medical help.Methods: Median nerve SEPs including high-frequency oscillations (HFOs) superimposed on the primary cortical response (N20) were investigated using multichannel EEG in individuals (n = 54 at baseline) remaining at risk to develop psychosis at follow-up after 1 year (high-risk: n = 19; ultra-high-risk: n = 27) vs. subjects with conversion to psychosis (n = 8) and a healthy control group (n = 35). Longitudinal and cross-sectional analyses of SEP components as estimated by dipole source analysis were performed.Results: The longitudinal development of the N20 strength depended on cannabis use. In cannabis non-users, a greater decrease of N20 strengths over time was associated with more negative symptoms at baseline. At baseline, converters did not differ from subjects remaining at risk. At follow-up, converters showed increased low- and high-frequency activity than at-risk subjects and did not differ from controls.Conclusion: The results of this study lead to the suggestion that the deficits in early somatosensory processing in individuals at risk to develop psychosis may not represent a marker for a genetic risk for psychosis but rather reflect state-dependent factors such as negative symptoms. On the other hand, the transition to psychosis seems to represent an interstage between reduced sensory registration from the at-risk state and gating deficits in the chronic state

mGluR5 receptor availability is associated with lower levels of negative symptoms and better cognition in male patients with chronic schizophrenia

Consistent findings postulate disturbed glutamatergic function (more specifically a hypofunction of the ionotropic NMDA receptors) as an important pathophysiologic mechanism in schizophrenia. However, the role of the metabotropic glutamatergic receptors type 5 (mGluR5) in this disease remains unclear. In this study, we investigated their significance (using [11 C]ABP688) for psychopathology and cognition in male patients with chronic schizophrenia and healthy controls. In the patient group, lower mGluR5 binding potential (BPND ) values in the left temporal cortex and caudate were associated with higher general symptom levels (negative and depressive symptoms), lower levels of global functioning and worse cognitive performance. At the same time, in both groups, mGluR5 BPND were significantly lower in smokers (F[27,1] = 15.500; p = .001), but without significant differences between the groups. Our findings provide support for the concept that the impaired function of mGluR5 underlies the symptoms of schizophrenia. They further supply a new perspective on the complex relationship between tobacco addiction and schizophrenia by identifying glutamatergic neurotransmission-in particularly mGluR5-as a possible connection to a shared vulnerability. Keywords: chronic schizophrenia; cognition; mGluR5 receptor; negative symptoms; positron emission tomography