Association between aerobic fitness and the functional connectome in patients with schizophrenia

Abstract

Background Schizophrenia is accompanied by widespread alterations in static functional connectivity associated with symptom severity and cognitive deficits. Improvements in aerobic fitness have been demonstrated to ameliorate symptomatology and cognition in people with schizophrenia, but the intermediary role of macroscale connectivity patterns remains unknown. Objective Therefore, we aim to explore the relation between aerobic fitness and the functional connectome in individuals with schizophrenia. Further, we investigate clinical and cognitive relevance of the identified fitness-connectivity links. Methods Patients diagnosed with schizophrenia were included in this cross-sectional resting-state fMRI analysis. Multilevel Bayesian partial correlations between aerobic fitness and functional connections across the whole brain as well as between static functional connectivity patterns and clinical and cognitive outcome were performed. Preliminary causal inferences were enabled based on mediation analyses. Results Static functional connectivity between the subcortical nuclei and the cerebellum as well as between temporal seeds mediated the attenuating relation between aerobic fitness and total symptom severity. Functional connections between cerebellar seeds affected the positive link between aerobic fitness and global cognition, while the functional interplay between central and limbic seeds drove the beneficial association between aerobic fitness and emotion recognition. Conclusion The current study provides first insights into the interactions between aerobic fitness, the functional connectome and clinical and cognitive outcome in people with schizophrenia, but causal interpretations are preliminary. Further interventional aerobic exercise studies are needed to replicate the current findings and to enable conclusive causal inferences. Trial registration The study which the manuscript is based on is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Effects of Exercise on Structural and Functional Brain Patterns in Schizophrenia—Data From a Multicenter Randomized-Controlled Study

“…Apart from the effects of aerobic exercise on the default-mode network and the cortico-striatopallido-thalamo-cortical circuit, we observe that aerobic exercise reduces FC between the thalamus and the cerebellum in our sample of people with schizophrenia. This is in line with our previous analysis, demonstrating that patients with higher aerobic fitness levels have lower FC between the thalamus and the cerebellum 65 . As described by the cognitive dysmetria hypothesis, schizophrenia is characterized by deteriorations in the cerebello-thalamo-cortical circuit, leading to an impaired ability to coordinate mental processes and thus accounting for a broad range of clinical symptoms 86 .…”

“…Additionally, our findings suggest that aerobic exercise enhances FC within the default-mode network. These results are in line with previous evidence in people with schizophrenia, indicating that aerobic exercise interventions, enhanced aerobic fitness levels or higher amounts of physical activity in general are associated with increases in cortical thickness in middle frontal areas and with increased FC within the default-mode network 61,[63][64][65] . Importantly, volume reductions, cortical thinning, increased gyrification and reduced FC within the default-mode network have been widely reported in people with schizophrenia and other psychiatric conditions [27][28][29][30][33][34][35][36] .…”

“…Likewise, cross-sectional studies indicate that patients with higher levels of physical activity have larger grey matter volumes and cortical thickness in the prefrontal cortex 64 . On the functional level, higher aerobic fitness levels in people with schizophrenia have been linked to an attenuation of cerebello-thalamic hyperconnectivity and to a strengthening of FC within the cerebellum and the default-mode network 65 . Importantly, findings regarding the clinical implications of these structural and functional adaptations linked to aerobic exercise and fitness remain scarce and heterogeneous 59-62, 64, 65 .…”

Sporttherapie bei schizophrenen Psychosen: Von der Idee bis zur Leitlinie

“…For example, there was an increase in the thickness of the cortex in the anterior cingulate 65 , an increase in the volume of the left hemisphere 66 , and an improvement in the integrity of the white matter 67 . In our own large multicenter study, we demonstrated a positive effect on cortex thickness, gyrification as a measure of atrophy, and centrally important functional networks 68 69 . In summary, aerobic exercise has an effect on brain structure and function, and according to our closer findings, a subgroup of 40% of patients in particular are able to benefit and thus also show a proplastic effect 70 , which explains the heterogeneity in the literature.…”

“…So fand sich eine Zunahme der Dicke des Cortex im vorderen Cingulum [65], eine Volumenzunahme der linken Hemisphäre [66] und eine Verbesserung der Integrität der weißen Substanz [67]. In einer eigenen großen multizentrischen Studie konnten wir einen positiven Effekt auf die Kortexdicke, die Gyrifizierung als Maß für die Atrophie und zentral wichtige funktionale Netzwerke nachweisen [68,69]. Zusammenfassend hat aerobes Training einen Effekt auf Gehirnstruktur und -funktion, wobei nach unseren näheren Erkenntnissen insbesondere eine Subgruppe von 40 % der PatientInnen zu profitieren vermögen und somit auch einen proplastischen Effekt zeigen [70], was die Heterogenität in der Literatur erklärt.…”