From brain to body: exploring the connection between altered reward processing and physical fitness in schizophrenia.

Understanding the underlying mechanisms that link psychopathology and physical comorbidities in schizophrenia is crucial since decreased physical fitness and overweight pose major risk factors for cardio-vascular diseases and decrease the patients' life expectancies. We hypothesize that altered reward anticipation plays an important role in this. We implemented the Monetary Incentive Delay task in a MR scanner and a fitness test battery to compare schizophrenia patients (SZ, n = 43) with sex- and age-matched healthy controls (HC, n = 36) as to reward processing and their physical fitness. We found differences in reward anticipation between SZs and HCs, whereby increased activity in HCs positively correlated with overall physical condition and negatively correlated with psychopathology. On the other handy, SZs revealed stronger activity in the posterior cingulate cortex and in cerebellar regions during reward anticipation, which could be linked to decreased overall physical fitness. These findings demonstrate that a dysregulated reward system is not only responsible for the symptomatology of schizophrenia, but might also be involved in physical comorbidities which could pave the way for future lifestyle therapy interventions.

Exploring the link between functional connectivity of ventral tegmental area and physical fitness in schizophrenia and healthy controls.

Decreased physical fitness and being overweight are highly prevalent in schizophrenia, represent a major risk factor for comorbid cardio-vascular diseases and decrease the life expectancy of the patients. Thus, it is important to understand the underlying mechanisms that link psychopathology and weight gain. We hypothesize that the dopaminergic reward system plays an important role in this. We analyzed the seed-based functional connectivity (FC) of the ventral tegmental area (VTA) in a group of schizophrenic patients (n=32) and age-, as well as gender-, matched healthy controls (n=27). We then correlated the resting-state results with physical fitness parameters, obtained in a fitness test, and psychopathology. The FC analysis revealed decreased functional connections between the VTA and the anterior cingulate cortex (ACC), as well as the dorsolateral prefrontal cortex, which negatively correlated with psychopathology, and increased FC between the VTA and the middle temporal gyrus in patients compared to healthy controls, which positively correlated with psychopathology. The decreased FC between the VTA and the ACC of the patient group further positively correlated with total body fat (p = .018, FDR-corr.) and negatively correlated with the overall physical fitness (p = .022). This study indicates a link between decreased physical fitness and higher body fat with functional dysconnectivity between the VTA and the ACC. These findings demonstrate that a dysregulated reward system might also be involved in comorbidities and could pave the way for future lifestyle therapy interventions.

Brain states govern the spatio-temporal dynamics of resting-state functional connectivity.

Previously, using simultaneous resting-state functional magnetic resonance imaging (fMRI) and photometry-based neuronal calcium recordings in the anesthetized rat, we identified blood oxygenation level-dependent (BOLD) responses directly related to slow calcium waves, revealing a cortex-wide and spatially organized correlate of locally recorded neuronal activity (Schwalm et al., 2017). Here, using the same techniques, we investigate two distinct cortical activity states: persistent activity, in which compartmentalized network dynamics were observed; and slow wave activity, dominated by a cortex-wide BOLD component, suggesting a strong functional coupling of inter-cortical activity. During slow wave activity, we find a correlation between the occurring slow wave events and the strength of functional connectivity between different cortical areas. These findings suggest that down-up transitions of neuronal excitability can drive cortex-wide functional connectivity. This study provides further evidence that changes in functional connectivity are dependent on the brain's current state, directly linked to the generation of slow waves.