Clinical and electrophysiological correlates of hopelessness in the context of suicide risk✰.

Hopelessness is a key risk factor for suicide. This analysis explored whether hopelessness indicates a recent suicide crisis state and is linked with magnetoencephalography (MEG) oscillatory power and effective connectivity differences. Change in hopelessness ratings and effective connectivity post-ketamine were also evaluated in a subsample of high-risk individuals to evaluate correlates of dynamic changes over time. Participants (66F;44 M;1 transgender) included individuals with suicide crisis in the last two weeks (High Risk (HR), n = 14), those with past suicide attempt but no recent suicide ideation (SI) (Low Risk (LR), n = 37), clinical controls (CC, n = 33), and healthy volunteers at minimal risk (MinR, n = 27). MEG oscillatory power and clinical hopelessness ratings (via the Beck Hopelessness Scale (BHS)) were evaluated across groups. Dynamic casual modeling (DCM) evaluated connectivity within and between the anterior insula (AI) and anterior cingulate cortex (ACC). A subsample of HR individuals who received ketamine (n = 10) were evaluated at Day 1 post-infusion. The HR group reported the highest levels of hopelessness, even when adjusting for SI. MEG results linked hopelessness with reduced activity across frequency bands in salience network regions, with no group or group-by-interaction effects. Using DCM, the HR group had reduced intrinsic drive from granular Layer IV stellate cells to superficial pyramidal cells in the ACC and AI. In the pilot HR study, reduced hopelessness was linked with increased drive for this same connection post-ketamine. Hopelessness is a possible proxy for suicide risk. Electrophysiological targets for hopelessness include widespread reductions in salience network activity, particularly in the ACC and AI.

Errors elicit frontoparietal theta-gamma coupling that is modulated by endogenous estradiol levels.

Cognitive control-related error monitoring is intimately involved in behavioral adaptation, learning, and individual differences in a variety of psychological traits and disorders. Accumulating evidence suggests that a focus on women's health and ovarian hormones is critical to the study of such cognitive brain functions. Here we sought to identify a novel index of error monitoring using a time-frequency based phase amplitude coupling (t-f PAC) measure and examine its modulation by endogenous levels of estradiol in females. Forty-three healthy, naturally cycling young adult females completed a flanker task while continuous electroencephalogram was recorded on four occasions across the menstrual cycle. Results revealed significant error-related t-f PAC between theta phase generated in fronto-central areas and gamma amplitude generated in parietal-occipital areas. Moreover, this error-related theta-gamma coupling was enhanced by endogenous levels of estradiol both within females across the cycle as well as between females with higher levels of average circulating estradiol. While the role of frontal midline theta in error processing is well documented, this paper extends the extant literature by illustrating that error monitoring involves the coordination between multiple distributed systems with the slow midline theta activity modulating the power of gamma-band oscillatory activity in parietal regions. They further show enhancement of inter-regional coupling by endogenous estradiol levels, consistent with research indicating modulation of cognitive control neural functions by the endocrine system in females. Together, this work identifies a novel neurophysiological marker of cognitive control-related error monitoring in females that has implications for neuroscience and women's health.

Stimulation of nucleus accumbens 5-HT6 receptors increases both appetitive and consummatory motivation in an effort-based choice task.

Activity of the serotonin 6(5-HT6) receptor impacts food intake and body weight in animal models and has also shown potential as a target for treatment of anhedonia, a symptom of major depressive disorder. The nucleus accumbens (NAc) is a key region involved in motivational processes and has been implicated in the neural mechanisms underlying anhedonia. Here, we assessed the potential role that 5-HT6 receptors in the NAc play in regulating motivation towards food. Rats received surgical implantation of guide cannulas above the NAc shell. On testing days, they were injected with either the selective 5-HT6 agonist EMD 386088 (at 0.0, 1.0, and 4.0 mg/0.5 mL/side) or the 5-HT6 antagonist SB 252585 (at 0, 1.0, and 4.0 µg/0.5 µL/side) prior to completing a 1-h long effort-based choice task. The task simultaneously examined the impact of NAc 5-HT6 receptor manipulation on appetitive motivation, measured as the breakpoint for earning a preferred sugar pellet in a progressive ratio task, and consummatory motivation, quantified as the grams of freely-available rat chow consumed during the session. Stimulation of NAc 5-HT receptors significantly increased both appetitive and consummatory motivation as assessed in this effort-based choice task. In contrast, 5-HT6 antagonism did not affect break point nor the consumption of the freely-available chow. These data suggest that 5-HT6 receptors are functional within the NAc, that their stimulation increases motivated behavior, and that they may therefore be a viable target for the treatment of anhedonia and disorders that inhibit motivational processes.

The mental health impact of contact with COVID-19 patients on healthcare workers in the United States.

This study assessed the relationship between contact with COVID-19 patients and the mental health of healthcare workers (HCWs) in the United States (US). In a convenience sample of 957 HCWs who completed an anonymous online survey between April-May 2020, HCWs who provided direct care to confirmed or suspected COVID-19 patients reported increased depressive and posttraumatic symptoms compared to HCWs with no COVID-19 patient contact. Additionally, more frequent contact was associated with higher distress. More data drawn from diverse samples that better represent US HCWs are needed to fully assess the scope of this association.