Long-term trajectories of depressive symptoms in deployed military personnel: A 10-year prospective study.

BACKGROUND: Military missions, especially those involving combat exposure, are associated with an increased risk of depression. Understanding the long-term course of depressive symptoms post-deployment is important to improve decision-making regarding deployment and mental health policies in the military. This study investigates trajectories of depressive symptoms in the Dutch army, exploring the influence of factors such as demographics, early-life trauma, posttraumatic stress disorder (PTSD) symptoms, and deployment stressors. METHODS: A cohort of 1032 military men and women deployed to Afghanistan (2005-2008) was studied from pre- to 10 years post-deployment. Depressive and PTSD symptoms were assessed using the Symptom CheckList-90 and the Self-Rating Inventory for PTSD. Demographics, early trauma, and deployment experiences were collected at baseline and after deployment, respectively. Latent Class Growth Analysis was used to explore heterogeneity in trajectories of depressive symptoms over time. RESULTS: Four trajectories were found: resilient (65%), intermediate-stable (20%), symptomatic-chronic (9%), and late-onset-increasing (6%). The resilient group experienced fewer deployment stressors, while the symptomatic-chronic group reported more early life traumas. Trajectories with elevated depressive symptoms consistently demonstrated higher PTSD symptoms. LIMITATIONS: Potential nonresponse bias and missing information due to the longitudinal design and extensive follow-up times. CONCLUSIONS: This study identified multiple trajectories of depressive symptoms in military personnel up to 10 years post-deployment, associated with early trauma, deployment stressors, adverse life events and PTSD symptoms. The prevalence of the resilient trajectory suggests a substantial level of resilience among deployed military personnel. These findings provide valuable insights and a foundation for further research.

The Prevalence of mRNA Related Discussions During the Post-COVID-19 Era.

Vaccinations are one of the most significant interventions to public health, but vaccine hesitancy and skepticism are raising serious concerns for a portion of the population in many countries, including Sweden. In this study, we use Swedish social media data and structural topic modeling to automatically identify mRNA-vaccine related discussion themes and gain deeper insights into how people's refusal or acceptance of the mRNA technology affects vaccine uptake. Our point of departure is a scientific study published in February 2022, which seems to once again sparked further suspicion and concern and highlight the necessity to focus on issues about the nature and trustworthiness in vaccine safety. Structural topic modelling is a statistical method that facilitates the study of topic prevalence, temporal topic evolution, and topic correlation automatically. Using such a method, our research goal is to identify the current understanding of the mechanisms on how the public perceives the mRNA vaccine in the light of new experimental findings.

Prefrontal Cortical to Mediodorsal Thalamus Projection Neurons Regulate Posterror Adaptive Control of Behavior.

Adaptive control is the online adjustment of behavior to guide and optimize responses after errors or conflict. The neural circuits involved in monitoring and adapting behavioral performance following error are poorly understood. The prefrontal cortex (PFC) plays a critical role in this form of control. However, these brain areas are densely connected with many other regions, and it is unknown which projections are critical for adaptive behavior. Here, we tested the involvement of four distinct dorsal and ventral prefrontal cortical projections to striatal and thalamic target areas in adaptive control. We re-analyzed data from published experiments, using trial-by-trial analyses of behavior in an operant task for attention and impulsivity. We find that male rats slow their responses and perform worse following errors. Moreover, by combining retrograde labeling and chemogenetic silencing, we find that dorsomedial prefrontal pyramidal neurons that project to the lateral nucleus of the mediodorsal thalamus (MDL) are involved in posterror performance and timing of responses, specifically with unpredictable delays until stimulus presentation. Together, these data show that dorsal medial PFC (mPFC) projection neurons targeting the lateral MDT regulate adaptive control to flexibly optimize behavioral responses in goal-directed behavior.

Bi-directional regulation of cognitive control by distinct prefrontal cortical output neurons to thalamus and striatum.

The medial prefrontal cortex (mPFC) steers goal-directed actions and withholds inappropriate behavior. Dorsal and ventral mPFC (dmPFC/vmPFC) circuits have distinct roles in cognitive control, but underlying mechanisms are poorly understood. Here we use neuroanatomical tracing techniques, in vitro electrophysiology, chemogenetics and fiber photometry in rats engaged in a 5-choice serial reaction time task to characterize dmPFC and vmPFC outputs to distinct thalamic and striatal subdomains. We identify four spatially segregated projection neuron populations in the mPFC. Using fiber photometry we show that these projections distinctly encode behavior. Postsynaptic striatal and thalamic neurons differentially process synaptic inputs from dmPFC and vmPFC, highlighting mechanisms that potentially amplify distinct pathways underlying cognitive control of behavior. Chemogenetic silencing of dmPFC and vmPFC projections to lateral and medial mediodorsal thalamus subregions oppositely regulate cognitive control. In addition, dmPFC neurons projecting to striatum and thalamus divergently regulate cognitive control. Collectively, we show that mPFC output pathways targeting anatomically and functionally distinct striatal and thalamic subregions encode bi-directional command of cognitive control.

Prefrontal Cortical Projection Neurons Targeting Dorsomedial Striatum Control Behavioral Inhibition.

A neural pathway from prefrontal cortex (PFC) to dorsal striatum (DS) has been suggested to mediate cognitive control of behavior, including proactive inhibitory control and attention. However, a direct causal demonstration thereof is lacking. Here, we show that selective chemogenetic silencing of corticostriatal PFC neurons in rats increases premature responses. Wireless single-unit electrophysiological recordings of optogenetically identified corticostriatal PFC neurons revealed that the majority of these neurons encode behavioral trial outcome with persistent changes in firing rate. Attentional parameters were not affected by silencing corticostriatal PFC neurons, suggesting that these projection neurons encode a specific subset of cognitive behaviors. Compared to the general non-identified neuronal population in the PFC, frontostriatal neurons showed selective engagement during periods of inhibitory control. Our results demonstrate a role for corticostriatal neurons in inhibitory control and possibly suggest that distinct domains of cognitive control over behavior are encoded by specific projection neuron populations.

Author Correction: Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention.

Neocortical choline acetyltransferase (ChAT)-expressing interneurons are a subclass of vasoactive intestinal peptide (ChAT-VIP) neurons of which circuit and behavioural function are unknown. Here, we show that ChAT-VIP neurons directly excite neighbouring neurons in several layers through fast synaptic transmission of acetylcholine (ACh) in rodent medial prefrontal cortex (mPFC). Both interneurons in layers (L)1-3 as well as pyramidal neurons in L2/3 and L6 receive direct inputs from ChAT-VIP neurons mediated by fast cholinergic transmission. A fraction (10-20%) of postsynaptic neurons that received cholinergic input from ChAT-VIP interneurons also received GABAergic input from these neurons. In contrast to regular VIP interneurons, ChAT-VIP neurons did not disinhibit pyramidal neurons. Finally, we show that activity of these neurons is relevant for behaviour and they control attention behaviour distinctly from basal forebrain ACh inputs. Thus, ChAT-VIP neurons are a local source of cortical ACh that directly excite neurons throughout cortical layers and contribute to attention.

The Sleeping Cerebellum.

We sleep almost one-third of our lives and sleep plays an important role in critical brain functions like memory formation and consolidation. The role of sleep in cerebellar processing, however, constitutes an enigma in the field of neuroscience; we know little about cerebellar sleep-physiology, cerebro-cerebellar interactions during sleep, or the contributions of sleep to cerebellum-dependent memory consolidation. Likewise, we do not understand why cerebellar malfunction can lead to changes in the sleep-wake cycle and sleep disorders. In this review, we evaluate how sleep and cerebellar processing may influence one another and highlight which scientific routes and technical approaches could be taken to uncover the mechanisms underlying these interactions.

Deep Brain Stimulation of the Nucleus Accumbens Core Affects Trait Impulsivity in a Baseline-Dependent Manner.

Deep brain stimulation (DBS) of the nucleus accumbens (NA) is explored as a treatment for refractory psychiatric disorders, such as obsessive-compulsive disorder (OCD), depressive disorder (MDD), and substance use disorder (SUD). A common feature of some of these disorders is pathological impulsivity. Here, the effects of NAcore DBS on impulsive choice and impulsive action, two distinct forms of impulsive behavior, were investigated in translational animal tasks, the delayed reward task (DRT) and five-choice serial reaction time task (5-CSRTT), respectively. In both tasks, the effects of NAcore DBS were negatively correlated with baseline impulsive behavior, with more pronounced effects in the 5-CSRTT. To further examine the effects of DBS on trait impulsive action, rats were screened for high (HI) and low (LI) impulsive responding in the 5-CSRTT. NAcore DBS decreased impulsive, premature responding in HI rats under conventional conditions. However, upon challenged conditions to increase impulsive responding, NAcore DBS did not alter impulsivity. These results strongly suggest a baseline-dependent effect of DBS on impulsivity, which is in line with clinical observations.

Sustained Attentional States Require Distinct Temporal Involvement of the Dorsal and Ventral Medial Prefrontal Cortex.

Attending the sensory environment for cue detection is a cognitive operation that occurs on a time scale of seconds. The dorsal and ventral medial prefrontal cortex (mPFC) contribute to separate aspects of attentional processing. Pyramidal neurons in different parts of the mPFC are active during cognitive behavior, yet whether this activity is causally underlying attentional processing is not known. We aimed to determine the precise temporal requirements for activation of the mPFC subregions during the seconds prior to cue detection. To test this, we used optogenetic silencing of dorsal or ventral mPFC pyramidal neurons at defined time windows during a sustained attentional state. We find that the requirement of ventral mPFC pyramidal neuron activity is strictly time-locked to stimulus detection. Inhibiting the ventral mPFC 2 s before or during cue presentation reduces response accuracy and hampers behavioral inhibition. The requirement for dorsal mPFC activity on the other hand is temporally more loosely related to a preparatory attentional state, and short lapses in pyramidal neuron activity in dorsal mPFC do not affect performance. This only occurs when the dorsal mPFC is inhibited during the entire preparatory period. Together, our results reveal that a dissociable temporal recruitment of ventral and dorsal mPFC is required during attentional processing.