Mechanisms of imbalanced frontostriatal functional connectivity in obsessive-compulsive disorder.

The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is lacking, and the mechanistic understanding of these effects is incomplete. To confirm and advance knowledge on changes in frontostriatal functional connectivity in OCD, participants with OCD and matched healthy controls underwent resting-state functional, structural and diffusion neuroimaging. Functional connectivity changes in frontostriatal systems were here replicated in individuals with OCD (n = 52) compared with controls (n = 45). OCD participants showed greater functional connectivity (t = 4.3, PFWE = 0.01) between the nucleus accumbens (NAcc) and the orbitofrontal cortex (OFC) but lower functional connectivity between the dorsal putamen and lateral prefrontal cortex (t = 3.8, PFWE = 0.04) relative to controls. Computational modelling suggests that NAcc-OFC connectivity changes reflect an increased influence of NAcc over OFC activity and reduced OFC influence over NAcc activity (posterior probability, Pp > 0.66). Conversely, dorsal putamen showed reduced modulation over lateral prefrontal cortex activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalizing frontostriatal dynamics in OCD.

Revisiting deficits in threat and safety appraisal in obsessive-compulsive disorder.

Current behavioural treatment of obsessive-compulsive disorder (OCD) is informed by fear conditioning and involves iteratively re-evaluating previously threatening stimuli as safe. However, there is limited research investigating the neurobiological response to conditioning and reversal of threatening stimuli in individuals with OCD. A clinical sample of individuals with OCD (N = 45) and matched healthy controls (N = 45) underwent functional magnetic resonance imaging. While in the scanner, participants completed a well-validated fear reversal task and a resting-state scan. We found no evidence for group differences in task-evoked brain activation or functional connectivity in OCD. Multivariate analyses encompassing all participants in the clinical and control groups suggested that subjective appraisal of threatening and safe stimuli were associated with a larger difference in brain activity than the contribution of OCD symptoms. In particular, we observed a brain-behaviour continuum whereby heightened affective appraisal was related to increased bilateral insula activation during the task (r = 0.39, pFWE = .001). These findings suggest that changes in conditioned threat-related processes may not be a core neurobiological feature of OCD and encourage further research on the role of subjective experience in fear conditioning.

Stimulating task unrelated thoughts: tDCS of prefrontal and parietal cortices leads to polarity specific increases in mind wandering.

Mind wandering has been associated with both adaptive outcomes and performance impairment, depending on the context. Recently, non-invasive brain stimulation has been applied in several studies with the aim to investigate the neural region(s) casually involved in mind wandering. However, to date there has been little definitive work assessing whether or not the stimulation of different brain regions leads to distinct mind wandering outcomes. The present preregistered study considered the role of the prefrontal cortex and inferior parietal lobule in mind wandering using two stimulation intensities (1mA and 2mA) and two stimulation polarity montages. One-hundred and fifty subjects were randomly allocated to one of the four active stimulation groups or a sham group. Participants' mind wandering propensity was measured via a task unrelated thought probe dispersed throughout an attention-based task completed directly after stimulation. Anodal stimulation to the prefrontal cortex, and cathodal stimulation to the inferior parietal lobule, increased mind wandering propensity and this effect was relatively unaffected by stimulation dosage. These findings support a causal role for these two regions in mind wandering, one that is polarity specific.

Expression analysis of melatonin receptor subtypes in the ovary of domestic chicken.

Melatonin (N-acetyl-5-methoxytryptamine), an indole hormone, regulates various biological functions through three different receptor subtypes (Mel-1a, Mel-1b, and Mel-1c). However, the distribution of different melatonin receptor subtypes in chicken reproductive tissues was not known. In the present investigation, the partial sequences of ovarian melatonin receptor subtypes (Mel-1a, Mel-1b, and Mel-1c) were characterized. Further, the expression profile of melatonin receptor subtypes in the granulosa and theca layers of different preovulatory and postovulatory follicles (POF) were studied by semi-quantitative RT-PCR. The expression of all three subtypes of melatonin receptors were observed in the ovary of domestic chicken. Analysis of partial sequences of ovarian melatonin receptors revealed that the melatonin subtypes were identical to the brain receptors. In small white ovary follicles, we observed only the expression of mel-1b receptors, but not mel-1a or mel-1c receptors. In yellow follicles, all the three subtypes of receptors expression were noticed. Interestingly, we observed the expression of mel-1a receptor only in thecal layer, but not in granulosa layer. In contrast, mel-1b and -1c receptors were expressed in both granulosa and thecal layer. During the regression of POF, we observed significant upregulation of melatonin receptors (mel-1a and 1c) expression, that downregulated in the later stages of regression. We assume that the expression of melatonin receptors might have been influenced by the atresia or apoptosis of different follicular layers in POF. Our findings suggest that the differential distribution of melatonin receptor subtypes might have distinct downstream cellular functions in the ovarian tissues.

Caspase-mediated apoptosis in chicken postovulatory follicle regression.

Chicken postovulatory follicle (POF) regression occurs via the process of apoptosis. However, the signals and initiator pathways responsible for regression of the POF are unknown. In the current study, we examined gene expression patterns of various caspases (caspase-1, -2 and -3) involved in apoptosis by semi-quantitative RT-PCR. The percentage of apoptotic cells during POF regression was also quantified by flow cytometry. Expression of caspase-3 mRNA was noted in the largest preovulatory follicle (F1). However, the initiator caspases (caspase-1 and -2) were not expressed in F1. During the regression of the POF, caspase-3 was activated during initial stages, whereas the initiator caspases were upregulated at the later stages (POF4 and POF5). The percentage of apoptotic cells was significantly higher during the regression of the POF. It might be possible that levels of caspase-3 mRNA do not necessarily reflect the cell's potential for facilitating apoptosis, as activation of the caspase-3 by initiator caspases is required for its function. We presume that both caspase-1 and caspase-2 were key initiators in the regression of chicken POF and that the apoptosis-mediated regression of POFs might be similar to mammalian corpus luteum involution.

Hybridizing semiconductor nanocrystals with metal-organic frameworks for visible and near-infrared photon upconversion.

Hybrid materials consisting of semiconductor nanocrystals and metal-organic frameworks (MOFs) were prepared for the first time to achieve photon upconversion based on triplet-triplet annihilation (TTA-UC) in the solid-state, which allowed TTA-UC with large anti-Stokes shifts in the visible and near-infrared regions.