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Background: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. Methods: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6–65) was divided into six successive 6–10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. Results: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6–13 and adults aged 50–65 with OCD taking SRIs (Cohen's d = −0.24 to −0.74). Volumes of putamen, pallidum (d = 0.18–0.40), and ventricles (d = 0.31–0.66) were greater in patients aged 20–29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = −0.27 to −1.31). Conclusions: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20–29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1,024 OCD patients and 1,028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen’s d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen’s d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC=0.702) than unmedicated (AUC=0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Motor conflicts arise when we need to quickly overwrite prepotent behavior. It has been proposed that affective stimuli modulate the neural processing of motor conflicts. However, previous studies have come to inconsistent conclusions regarding the neural impact of affective information on conflict processing. We employed functional magnetic resonance imaging during a Go/Change-Go task, where motor conflicts were either evoked by neutral or emotionally negative stimuli. Dynamic causal modeling was used to investigate how motor conflicts modulate the intercommunication between the anterior cingulate cortex (ACC) and the anterior insula (AI) as 2 central regions for cognitive control. Conflicts compared to standard actions were associated with increased BOLD activation in several brain areas, including the dorsal ACC and anterior insula. There were no differences in neural activity between emotional and non-emotional conflict stimuli. Conflicts compared to standard actions lowered neural self-inhibition of the ACC and AI and led to increased effective connectivity from the ACC to AI contralateral to the acting hand. Thus, our study indicates that neural conflict processing is primarily driven by the functional relevance of action-related stimuli, not their inherent affective meaning. Furthermore, it sheds light on the role of interconnectivity between ACC and AI for the implementation of flexible behavioral change.

Alzheimer&rsquo, s disease (AD) is characterized by neuronal loss and impaired synaptic transmission, ultimately leading to cognitive deficits. Early in the disease, the olfactory track seems most sensitive to tauopathy, while most plasticity studies focused on the hippocampal circuits. Functional network connectivity (FC) and long-term potentiation (LTP), considered as the plasticity substrate of learning and memory, were longitudinally assessed in mice of the P301S model of tauopathy following the course (time and location) of progressively neurodegenerative pathology (i.e., at 3, 6, and 9 months of age) and in their wild type (WT) littermates. Using in vivo local field potential (LFP) recordings, early (at three months) dampening in the gamma oscillatory activity and impairments in the phase-amplitude theta-gamma coupling (PAC) were found in the olfactory bulb (OB) circuit of P301S mice, which were maintained through the whole course of pathology development. In contrast, LFP oscillatory activity and PAC indices were normal in the entorhinal cortex, hippocampal CA1 and CA3 nuclei. Field excitatory postsynaptic potential (fEPSP) recordings from the Shaffer collateral (SC)-CA1 hippocampal stratum pyramidal revealed a significant altered synaptic LTP response to high-frequency stimulation (HFS): at three months of age, no significant difference between genotypes was found in basal synaptic activity, while signs of a deficit in short term plasticity were revealed by alterations in the fEPSPs. At six months of age, a slight deviance was found in basal synaptic activity and significant differences were observed in the LTP response. The alterations in network oscillations at the OB level and impairments in the functioning of the SC-CA1 pyramidal synapses strongly suggest that the progression of tau pathology elicited a brain area, activity-dependent disturbance in functional synaptic transmission. These findings point to early major alterations of neuronal activity in the OB circuit prior to the disturbance of hippocampal synaptic plasticity, possibly involving tauopathy in the anomalous FC. Further research should determine whether those early deficits in the OB network oscillations and FC are possible mechanisms that potentially promote the emergence of hippocampal synaptic impairments during the progression of tauopathy.

Highlights • First study investigating ICA-based structural covariance in patient with OCD. • Results show significantly altered structural covariance patterns in patients with OCD. • Common characteristics associated with the disorder may lead to a disorder-specific grey matter pattern organization., Background Changes in grey matter volume have frequently been reported in patients with obsessive-compulsive disorder (OCD). Most studies performed whole brain or region-of-interest based analyses whereas grey matter volume based on structural covariance networks has barely been investigated up to now. Therefore, the present study investigated grey matter volume within structural covariance networks in a sample of 228 participants (n = 117 OCD patients, n = 111 healthy controls). Methods First, an independent component analysis (ICA) was performed on all subjects’ preprocessed T1 images to derive covariance-dependent morphometric networks. Then, grey matter volume from each of the ICA-derived morphometric networks was extracted and compared between the groups. In addition, we performed logistic regressions and receiver operating characteristic (ROC) analyses to investigate whether network-related grey matter volume could serve as a characteristic that allows to differentiate patients from healthy volunteers. Moreover, we assessed grey matter pattern organization by correlating grey matter volume in all networks across all participants. Finally, we explored a potential association between grey matter volume or whole-brain grey matter pattern organization and clinical characteristics in terms of symptom severity and duration of illness. Results There were only subtle group differences in network-related grey matter volume. Network-related grey matter volume had moreover a very poor discrimination performance. We found, however, significant group differences with regard to grey matter pattern organization. When correlating grey matter volume in all networks across all participants, patients showed a significantly higher homogeneity across all networks and a significantly lower heterogeneity, as assessed by the coefficient of variation across all networks as well as in several single networks. There was no association with clinical characteristics. Conclusion The findings of the present study suggest that the pathological mechanisms of OCD reduce interindividual grey matter variability. We assume that common characteristics associated with the disorder may lead to a more uniform, disorder-specific morphometry.