Tuned to Tremor: Increased Sensitivity of Cortico-Basal Ganglia Neurons to Tremor Frequency in the MPTP Nonhuman Primate Model of Parkinson's Disease.

Rest tremor is one of the most prominent clinical features of Parkinson's disease (PD). Here, we hypothesized that cortico-basal ganglia neurons tend to fire in a pattern that matches PD tremor frequency, suggesting a resonance phenomenon. We recorded spiking activity in the primary motor cortex (M1) and globus pallidus external segment of 2 female nonhuman primates, before and after parkinsonian state induction with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The arm of nonhuman primates was passively rotated at seven different frequencies surrounding and overlapping PD tremor frequency. We found entrainment of the spiking activity to arm rotation and a significant sharpening of the tuning curves in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine state, with a peak response at frequencies that matched the frequency of PD tremor. These results reveal increased sensitivity of the cortico-basal ganglia network to tremor frequency and could indicate that this network acts not only as a tremor switch but is involved in setting its frequency.SIGNIFICANCE STATEMENT Tremor is a prominent clinical feature of Parkinson's disease; however, its underlying pathophysiology is still poorly understood. Using electrophysiological recordings of single cortico-basal ganglia neurons before and after the induction of a parkinsonian state, and in response to passive arm rotation, this study reports increased sensitivity to tremor frequency in Parkinson's disease. We found sharpening of the population tuning to the midrange of the tested frequencies (1-13.3 Hz) in the healthy state that further increased in the parkinsonian state. These results hint at the increased frequency-tuned sensitivity of cortico-basal ganglia neurons and suggest that they tend to resonate with the tremor.

A Following Wave Pattern of Suicide-Related Pediatric Emergency Room Admissions during the COVID-19 Pandemic.

The COVID-19 pandemic and response, which included physical distancing and stay-at-home orders, disrupted the daily lives of children and adolescents, isolating them from their peers, school, and other meaningful contacts. The present study aims to add to the accumulating evidence on the pandemic's impact on child and adolescent suicidal behavior. Data were extracted from Schneider Children's Medical Center of Israel's pediatric emergency room (ER) admissions for psychiatric consultation for suicidal-risk assessment between 1 January 2020, and 16 April 2022. We applied time-lagged cross-correlation analysis and a Granger causality test to assess the temporal relationships between COVID-19 infection waves and patterns of suicide-related ER admissions. The results revealed a significant lagged correlation between national COVID-19 infection rates and ER admission rates. The highest correlation was above 0.4 and was found with a lag of 80 to 100 days from infection rate to ER admission rate. The findings show that the effects of public crises change over time and may be lagged. This may have important implications for mental health services' readiness to serve growing numbers of children and adolescents at risk for suicide.

Comparative Epidemiology of Attempted and Fatal Suicide in a Defined Catchment Area in Israel.

BACKGROUND: Both attempted and fatal suicides are important public health issues and the relationship between these behaviors has great relevance to clinical practice. AIMS: To determine how the epidemiology of attempted and fatal suicide relate to each other over time. METHOD: In an 18-year period consecutive admissions for suicide attempts (n = 4,645) to the emergency room of the central hospital of a well-defined catchment area were assessed using a structured interview. Data were compared with records of 425 fatal suicides from the same catchment area. RESULTS: The relative rates of attempted and fatal suicide changed over time independent of both age and gender up to age 64. Rates of suicide and attempted suicide did not correlate over time in this age group. This was not true for the over 65 age group where attempted suicide and fatal suicide were significantly correlated over time in both men and women. CONCLUSIONS: In subjects over 65 attempted suicide is highly associated with eventual suicide. This relationship is much less clear in younger age groups. Thus age of attempt is of great importance when considering the prognostic import of a suicide attempt.

The relationship between the plasma proinflammatory cytokine levels of depressed/anxious children and their parents.

Recent studies suggest immune function dysregulation in depression and anxiety disorders. Elevated pro-inflammatory cytokines may be a marker for immune system dysregulation. No study assessed the correlation between the levels of cytokines in children and adolescents with depression/anxiety disorders and their parents. In this study, 92 children and adolescents (mean age 13.90 ± 2.41 years) with depression and/or anxiety disorders were treated with fluoxetine. Blood samples were collected before initiation of treatment. One hundred and sixty-four of their parents (mean age 50.6 ± 6.2 years) and 25 parents of healthy children (mean age 38.5 ± 6.2 years) also gave blood samples. Plasma levels of three pro-inflammatory cytokine (TNF-α, IL-6, IL-1ß) were measured by enzyme linked immunosorbent assays (ELISA) and compared between depressed/anxious children and their parents. We also compared cytokine levels between parents of children with depression/anxiety and control parents. Mothers of depressed children had higher TNF-α levels than mothers of controls. No significant difference was detected in the fathers. A positive correlation was found between the IL-1ß levels of the depressed/anxious boys and their mothers. No such correlation was observed in the fathers. Our conclusions are that higher levels of proinflammatory cytokines may indicate immune system activation in mothers in response to the distress associated with having depressed/anxious offspring. The correlation between IL-1ß levels in the mothers and their depressed/anxious children may indicate familial vulnerability to depression and anxiety. Our observation highlights the need for a better understanding of sexual dimorphism in inflammatory responses to stress.

Keep Calm and Stay Safe: The Relationship between Anxiety and Other Psychological Factors, Media Exposure and Compliance with COVID-19 Regulations.

The COVID-19 pandemic has led many countries to employ public health regulations to achieve behavioral change and stop the transmission of the virus. The factors influencing compliance with these regulations may differ from "classic" predictors for medical compliance. This study attempted to assess the effect of social communication and psychological factors on intention to comply. A cross-sectional online survey was conducted on healthy adults living in Israel (n = 697). The survey assessed the intention to comply with the state COVID-19 regulations and explored possible correlations with demographic and psychosocial factors. Data were collected during May 2020 using a Qualtrics online survey. Data were analyzed to find correlations between anxiety, uncertainty, media exposure and other variables and the level of intention to comply as self-reported. Moderation and mediation effects were studied by an integrative model of influencing factors. We found that media exposure change, trust in responsible agencies and anxiety were positively correlated with compliance, while uncertainty was correlated with noncompliance. The effect of media exposure on compliance had two components. First, media exposure was positively correlated with compliance. On the other hand, media exposure was positively correlated with uncertainty, and uncertainty was negatively correlated with compliance. Interestingly, anxiety, which was positively correlated with media exposure, also moderated the negative correlation between uncertainty and compliance. Our results highlight the important role of uncertainty and anxiety as moderators between media exposure and compliance. To increase public compliance with COVID-19 regulations, efforts should be directed at decreasing uncertainty and anxiety.

[EXCORIATION (SKIN-PICKING) DISORDER].

INTRODUCTION: Excoriation (Skin-Picking) disorder is a clinically recognized condition which was recently included in the Diagnostic and Statistical manual of the American Psychiatric Association (DSM) - fifth edition, as OCD (obsessive compulsive disorder) related disorder. The disorder's official status has been achieved due to its high frequency and unique clinical picture involving both mental and physical impairment. In this article, we would like to present a concise review of the literature together with an illustrative case. Epidemiological surveys show a prevalence of 3% to 5% for the general population, with heterogeneous gender and age distribution. In recent years the disorder has been categorized under the family of BFRB's (Body Focused Repetitive Behaviours). However, there are some elements associated with movement suppression and tic disorders, as well as disorders belonging to obsessive-compulsive spectrum. The treatment of this disorder may be pharmacological and/or psychological. There is some evidence for the benefit of some SSRI (Selective Serotonin Reuptake Inhibitors) agents as well as for N-Acetyl-Cysteine. Various psychological treatments have been investigated and some of them have proven to be effective. These include cognitive behavioural protocols, some of which have been developed specifically for this disorder.

Subthalamic theta activity: a novel human subcortical biomarker for obsessive compulsive disorder.

Obsessive-compulsive disorder (OCD) is a common and serious psychiatric disorder. Although subthalamic nucleus deep brain stimulation (DBS) has been studied as a treatment for OCD patients the underlying mechanism of this treatment and the optimal method of stimulation are unknown. To study the neural basis of subthalamic nucleus DBS in OCD patients we used a novel, implantable DBS system with long-term local field potential sensing capability. We focus our analysis on two patients with OCD who experienced severe treatment-resistant symptoms and were implanted with subthalamic nucleus DBS systems. We studied them for a year at rest and during provocation of OCD symptoms (46 recording sessions) and compared them to four Parkinson's disease (PD) patients implanted with subthalamic nucleus DBS systems (69 recording sessions). We show that the dorsal (motor) area of the subthalamic nucleus in OCD patients displays a beta (25-35 Hz) oscillatory activity similar to PD patients whereas the ventral (limbic-cognitive) area of the subthalamic nucleus displays distinct theta (6.5-8 Hz) oscillatory activity only in OCD patients. The subthalamic nucleus theta oscillatory activity decreases with provocation of OCD symptoms and is inversely correlated with symptoms severity over time. We conclude that beta oscillations at the dorsal subthalamic nucleus in OCD patients challenge their pathophysiologic association with movement disorders. Furthermore, theta oscillations at the ventral subthalamic nucleus in OCD patients suggest a new physiological target for OCD therapy as well as a promising input signal for future emotional-cognitive closed-loop DBS.