Control of working memory by phase-amplitude coupling of human hippocampal neurons.

Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference1,2. However, how cognitive control regulates working memory storage is unclear. Here we show that interactions of frontal control and hippocampal persistent activity are coordinated by theta-gamma phase-amplitude coupling (TG-PAC). We recorded single neurons in the human medial temporal and frontal lobe while patients maintained multiple items in their working memory. In the hippocampus, TG-PAC was indicative of working memory load and quality. We identified cells that selectively spiked during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons was coordinated with frontal theta activity when cognitive control demand was high. By introducing noise correlations with persistently active neurons in the hippocampus, PAC neurons shaped the geometry of the population code. This led to higher-fidelity representations of working memory content that were associated with improved behaviour. Our results support a multicomponent architecture of working memory1,2, with frontal control managing maintenance of working memory content in storage-related areas3-5. Within this framework, hippocampal TG-PAC integrates cognitive control and working memory storage across brain areas, thereby suggesting a potential mechanism for top-down control over sensory-driven processes.

Social buffering diminishes fear response but does not equal improved fear extinction.

Social support during exposure-based psychotherapy is believed to diminish fear and improve therapy outcomes. However, some clinical trials challenge that notion. Underlying mechanisms remain unknown, hindering the understanding of benefits and pitfalls of such approach. To study social buffering during fear extinction, we developed a behavioral model in which partner's presence decreases response to fear-associated stimuli. To identify the neuronal background of this phenomenon, we combined behavioral testing with c-Fos mapping, optogenetics, and chemogenetics. We found that the presence of a partner during fear extinction training causes robust inhibition of freezing; the effect, however, disappears in subjects tested individually on the following day. It is accompanied by lowered activation of the prelimbic (PL) and anterior cingulate (ACC) but not infralimbic (IL) cortex. Accordingly, blocking of IL activity left social buffering intact. Similarly, inhibition of the ventral hippocampus-PL pathway, suppressing fear response after prolonged extinction training, did not diminish the effect. In contrast, inhibition of the ACC-central amygdala pathway, modulating social behavior, blocked social buffering. By reporting that social modulation of fear inhibition is transient and insensitive to manipulation of the fear extinction-related circuits, we show that the mechanisms underlying social buffering during extinction are different from those of individual extinction.

Changes in Metabolism and Content of Chlorophyll in Common Duckweed (Lemna minor L.) Caused by Environmental Contamination with Fluorides.

The impact of fluorine on plants remains poorly understood. We examined duckweed growth in extracts of soil contaminated with fluorine leached from chicken manure. Additionally, fluorine levels were analyzed in fresh manure, outdoor-stored manure, and soil samples at varying distances from the manure pile. Fresh manure contained 37-48 mg F- × kg-1, while soil extracts contained 2.1 to 4.9 mg F- × kg-1. We evaluated the physiological effects of fluorine on duckweed cultured on soil extracts or in 50% Murashige-Skoog (MS) medium supplemented with fluorine concentrations matching those in soil samples (2.1 to 4.9 mg F- × L-1), as well as at 0, 4, and 210 mg × L-1. Duckweed exposed to fluorine displayed similar toxicity symptoms whether in soil extracts or supplemented medium. Fluoride at concentrations of 2.1 to 4.9 mg F- × L-1 reduced the intact chlorophyll content, binding the porphyrin ring at position 32 without affecting Mg2+. This reaction resulted in chlorophyll a absorption peak shifted towards shorter wavelengths and formation of a new band of the F--chlorophyll a complex at λ = 421 nm. Moreover, plants exposed to low concentrations of fluorine exhibited increased activities of aminolevulinic acid dehydratase and chlorophyllase, whereas the activities of both enzymes sharply declined when the fluoride concentration exceeded 4.9 mg × L-1. Consequently, fluorine damages chlorophyll a, disrupts the activity of chlorophyll-metabolizing enzymes, and diminishes the plant growth rate, even when the effects of these disruptions are too subtle to be discerned by the naked human eye.

[Sports psychiatry and psychotherapy]. / Sportpsychiatrie und -psychotherapie.

Sports psychiatry and psychotherapy is a relatively young field and is comprised of two key segments: the special features of the diagnostics and therapy of mental disorders in elite athletes and the use of exercise and sports in the development and treatment of mental disorders. Although all mental disorders can in principle also occur in (elite) athletes, there are additionally sport-specific mental disorders, such as anorexia athletica and other eating disorders, chronic traumatic encephalopathy, misuse of and dependency on performance-enhancing substances (doping) and muscle dysmorphia. Many high-quality clinical trials over the past two decades have been able to demonstrate a therapeutic efficacy of physical activity and sport in the treatment of various mental disorders. All clinicians active in psychiatry and psychotherapy should possess a basic knowledge of sports psychiatry.

Working Memory Load-related Theta Power Decreases in Dorsolateral Prefrontal Cortex Predict Individual Differences in Performance.

Holding information in working memory (WM) is an active and effortful process that is accompanied by sustained load-dependent changes in oscillatory brain activity. These proportional power increases are often reported in EEG studies recording theta over frontal midline sites. Intracranial recordings, however, yield mixed results, depending on the brain area being recorded from. We recorded intracranial EEG with depth electrodes in 13 patients with epilepsy who were performing a Sternberg WM task. Here, we investigated patterns of theta power changes as a function of memory load during maintenance in three areas critical for WM: dorsolateral prefrontal cortex (DLPFC), dorsal ACC (dACC), and hippocampus. Theta frequency power in both hippocampus and dACC increased during maintenance. In contrast, theta frequency power in the DLPFC decreased during maintenance, and this decrease was proportional to memory load. Only the power decreases in DLPFC, but not the power increases in hippocampus and dACC, were predictive of behavior in a given trial. The extent of the load-related theta power decreases in the DLPFC in a given participant predicted a participant's RTs, revealing that DLPFC theta explains individual differences in WM ability between participants. Together, these data reveal a pattern of theta power decreases in the DLPFC that is predictive of behavior and that is opposite of that in other brain areas. This result suggests that theta band power changes serve different cognitive functions in different brain areas and specifically that theta power decreases in DLPFC have an important role in maintenance of information.

Frontal EEG alpha band asymmetry as a predictor of reasoning deficiency in depressed people.

Cognitive deficits in depression are mostly apparent in executive functions, especially when integration of information and reasoning is required. In parallel, there are also numerous studies pointing to the frontal alpha band asymmetry as a psychophysiological marker of depression. In this study, we explored the role of frontal alpha asymmetry as a potential factor explaining the cognitive problems accompanying depression. Twenty-six depressed and 26 control participants completed a reasoning task and underwent 5 minutes of electroencephalography recording. In line with the previous studies, depressed people showed difficulties with reasoning but we did not observe the relationship between frontal asymmetry in the alpha band and depression. However, we found that in the depressed group the frontal alpha asymmetry index was characterised by larger variance than in the control group, and it was also a strong predictor of cognitive functioning exclusively in the depressed group. Our results point to the disruption of a psychophysiological balance, reflected in changed frontal alpha asymmetry (into more left-sided frontal asymmetry in the alpha band, reflecting more right-sided cortical activity) as a possible brain correlate of cognitive disturbances present in depressive disorders.

Alertness opens the effective flow of sensory information through rat thalamic posterior nucleus.

Behavioural reactions to sensory stimuli vary with the level of arousal, but little is known about the underlying reorganization of neuronal networks. In this study, we use chronic recordings from the somatosensory regions of the thalamus and cortex of behaving rats together with a novel analysis of functional connectivity to show that during low arousal tactile signals are transmitted via the ventral posteromedial thalamic nucleus (VPM), a first-order thalamic relay, to the primary somatosensory (barrel) cortex and then from the cortex to the posterior medial thalamic nucleus (PoM), which plays a role of a higher-order thalamic relay. By contrast, during high arousal this network scheme is modified and both VPM and PoM transmit peripheral input to the barrel cortex acting as first-order relays. We also show that in urethane anaesthesia PoM is largely excluded from the thalamo-cortical loop. We thus demonstrate a way in which the thalamo-cortical system, despite its fixed anatomy, is capable of dynamically reconfiguring the transmission route of a sensory signal in concert with the behavioural state of an animal.

The impact of degree of hearing loss on auditory brainstem response predictions of behavioral thresholds.

OBJECTIVES: Diagnosis of hearing loss and prescription of amplification for infants and young children require accurate estimates of ear- and frequency-specific behavioral thresholds based on auditory brainstem response (ABR) measurements. Although the overall relationship between ABR and behavioral thresholds has been demonstrated, the agreement is imperfect, and the accuracy of predictions of behavioral threshold based on ABR may depend on degree of hearing loss. Behavioral thresholds are lower than ABR thresholds, at least in part due to differences in calibration interacting with the effects of temporal integration, which are manifest in behavioral measurements but not ABR measurements and depend on behavioral threshold. Listeners with sensory hearing loss exhibit reduced or absent temporal integration, which could impact the relationship between ABR and behavioral thresholds as degree of hearing loss increases. The present study evaluated the relationship between ABR and behavioral thresholds in infants and children over a range of hearing thresholds, and tested an approach for adjusting the correction factor based on degree of hearing loss as estimated by ABR measurements. DESIGN: A retrospective review of clinical records was completed for 309 ears of 177 children with hearing thresholds ranging from normal to profound hearing loss and for whom both ABR and behavioral thresholds were available. Children were required to have the same middle ear status at both evaluations. The relationship between ABR and behavioral thresholds was examined. Factors that potentially could affect the relationship between ABR and behavioral thresholds were analyzed, including degree of hearing loss observed on the ABR, behavioral test method (visual reinforcement, conditioned play, or conventional audiometry), the length of time between ABR and behavioral assessments, and clinician-reported reliability of the behavioral assessment. Predictive accuracy of a correction factor based on the difference between ABR and behavioral thresholds as a function of ABR threshold was compared to the predictive accuracy achieved by two other correction approaches in current clinical use. RESULTS: As expected, ABR threshold was a significant predictor of behavioral threshold. The agreement between ABR and behavioral thresholds varied as a function of degree of hearing loss. The test method, length of time between assessments, and reported reliability of the behavioral test results were not related to the differences between ABR and behavioral thresholds. A correction factor based on the linear relationship between the differences in ABR and behavioral thresholds as a function of ABR threshold resulted in more accurately predicted behavioral thresholds than other correction factors in clinical use. CONCLUSIONS: ABR is a valid predictor of behavioral threshold in infants and children. A correction factor that accounts for the effect of degree of hearing loss on the differences between ABR and behavioral thresholds resulted in more accurate predictions of behavioral thresholds than methods that used a constant correction factor regardless of degree of hearing loss. These results are consistent with predictions based on previous research on temporal integration for listeners with hearing loss.

Exercise as Treatment for "Stress-Related" Mental Disorders.

The beneficial impact of physical activity on preventing and treating mental disorders has captured growing (research) interest. This article aims to provide a concise overview of essential evidence regarding the effectiveness and underlying mechanisms of physical activity for individuals with mental disorders clustered as "stress-related" conditions. Empirical findings (e.g., longitudinalprospective studies, interventional randomized-controlled-trials, reviews, meta-analyses) regarding the effects of physical activity in the prevention and treatment of stress-related mental disorders are summarized. Furthermore, potential mechanisms underlying these effects are discussed, and recommendations regarding the use of physical activity are outlined. The majority of studies indicate good efficacy of physical activity in prospectively lowering the risk for the incidence of subsequent stress-related mental disorders as well as in the treatment of manifest disorders. Most evidence targets unipolar depressive disorder and, secondly, anxiety disorders. Research regarding posttraumatic stress disorder, obsessive-compulsive disorders, and somatoform disorders is promising but scarce. Physical activity seems to be useful as a stand-alone-treatment as well as in combination with other psychotherapeutic or pharmacological treatments. Multiple intertwined physiological, psychological, and social mechanisms are assumed to mediate the beneficial effects. Recommendations regarding physical activity can orientate on official guidelines but should consider the individual needs and circumstances of each subject. In summary, physical activity seems to be effective in the prevention and treatment of stressrelated mental disorders and, therefore, should be fostered in healthcare-settings. Future studies are needed to clarify partly inconsistent patterns of results and to close research gaps, e.g., concerning somatoform disorders.

Dataset of human-single neuron activity during a Sternberg working memory task.

We present a dataset of 1809 single neurons recorded from the human medial temporal lobe (amygdala and hippocampus) and medial frontal lobe (anterior cingulate cortex, pre-supplementary motor area, ventral medial prefrontal cortex) across 41 sessions from 21 patients that underwent seizure monitoring with depth electrodes. Subjects performed a screening task (907 neurons) to identify images for which highly selective cells were present. Subjects then performed a working memory task (902 neurons), in which they were sequentially presented with 1-3 images for which highly selective cells were present and, following a maintenance period, were asked if the probe was identical to one of the maintained images. This Neurodata Without Borders formatted dataset includes spike times, extracellular spike waveforms, stimuli presented, behavior, electrode locations, and subject demographics. As validation, we replicate previous findings on the selectivity of concept cells and their persistent activity during working memory maintenance. This large dataset of rare human single-neuron recordings and behavior enables the investigation of the neural mechanisms of working memory in humans.

Spinal inhibitory neurons degenerate before motor neurons and excitatory neurons in a mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of somatic motor neurons. A major focus has been directed to motor neuron intrinsic properties as a cause for degeneration, while less attention has been given to the contribution of spinal interneurons. In the present work, we applied multiplexing detection of transcripts and machine learning-based image analysis to investigate the fate of multiple spinal interneuron populations during ALS progression in the SOD1G93A mouse model. The analysis showed that spinal inhibitory interneurons are affected early in the disease, before motor neuron death, and are characterized by a slow progressive degeneration, while excitatory interneurons are affected later with a steep progression. Moreover, we report differential vulnerability within inhibitory and excitatory subpopulations. Our study reveals a strong interneuron involvement in ALS development with interneuron specific degeneration. These observations point to differential involvement of diverse spinal neuronal circuits that eventually may be determining motor neuron degeneration.

Local resource depletion hypothesis as a mechanism for action selection in the brain.

As a comment on Kurzban et al.'s opportunity cost model, we propose an alternative view of mental effort and the action selection mechanism in the brain. Our hypothesis utilizes local resource depletion within neuronal networks, which justifies from a neurophysiological perspective why mental fatigue diminishes after switching to a novel task and explains action selection by means of neural competition theory.

Resistance Training in Depression.

BACKGROUND: More than 320 million people around the world suffer from depression. Physical activity and sports are effective treatment strategies. Endurance training has already been intensively studied, but any potential antidepressant effect of resistance training is unknown at present, nor is it clear whether this could yield any relevant benefit in clinical use. METHODS: The PubMed database was selectively searched for recent studies and review articles concerning the use, efficacy, and safety of resistance training in persons with depressive symptoms and diagnosed depression. RESULTS: Two meta-analyses revealed that resistance training alleviated depressive symptoms with a low to moderate effect size (0.39-0.66). Resistance training in patients with diagnosed depression was studied in seven randomized controlled trials, in which the duration of the intervention ranged from eight weeks to eight months. In six of these trials, the depressive symptoms were reduced. In one trial, a persistent benefit was seen in the resistance-training group at 26 months of follow-up (adherence, 33%). Moreover, resistance training improved strength, quality of life, and quality of sleep. No serious adverse events occurred; this indicates that resistance training in depression is safe. CONCLUSION: Resistance training seems to have an antidepressant effect. Open questions remain concerning its effects in different age groups, as well as the optimal training parameters. Further high-quality trials will be needed to document the effect of resistance training more conclusively and to enable the formulation of treatment recommendations.

Pylabianca: comprehensive and user­friendly Python package for single­neuron data analysis.

In the area of electrophysiology, the availability of comprehensive and user­friendly tools for single-neuron data processing, statistical analysis, and fast, intuitive data visualization is limited. To address this gap, we introduce pylabianca, a Python library tailored for robust single and multi­unit data processing. Pylabianca leverages the power of standard Python packages and adopts the application programming interface of MNE­Python, one of the most widely used electrophysiology packages. One of pylabianca's primary objectives is to provide a low entry threshold for scientists, requiring only basic Python programming skills. Pylabianca was designed to streamline most common analyses of single neuron data, and provide convenient data structures to serve as a foundation for building custom analysis pipelines. We believe that pylabianca will contribute to enhancing researchers' capabilities and efficiency in the field of single-neuron electrophysiology.

Predicting Behavioral Threshold at 6 and 8 kHz for Children and Adults Based on the Auditory Brainstem Response.

PURPOSE: Common clinical application of auditory brainstem response (ABR) testing is limited to 0.25-4 kHz. Prior research has demonstrated associations between ABR and behavioral thresholds for tone burst stimuli > 4 kHz in adults, but there are no comparable data for children. The ability to predict behavioral thresholds > 4 kHz clinically based on the ABR would provide valuable audiologic information for individuals who are unable to provide behavioral thresholds. This study included children with hearing loss and children with normal hearing to determine the association between ABR and behavioral thresholds at 6 and 8 kHz. METHOD: ABR and behavioral thresholds were obtained for children ages 4.7-16.7 years (M = 10.5, SD = 3.4) with sensorineural hearing loss (n = 24) or normal hearing sensitivity (n = 16) and for adults ages 18.4-54.4 years (M = 32.7, SD = 10.4) with sensorineural hearing loss (n = 13) or normal hearing sensitivity (n = 11). Thresholds obtained for 6 and 8 kHz using ABR and conventional audiometry were compared. RESULTS: Differences between ABR and behavioral thresholds averaged 5-6 dB for both children and adults for both test frequencies, with differences of ≤ 20 dB in all instances. Linear mixed modeling for data from participants with hearing loss suggested that ABR threshold is a good predictor of behavioral threshold at 6 and 8 kHz for both children and adults. Test specificity was 100%; no participants with behavioral thresholds ≤ 20 dB HL had ABR thresholds > 25 dB nHL. CONCLUSIONS: Initial evidence suggests that ABR testing at 6 and 8 kHz is reliable for estimating behavioral threshold in listeners with hearing loss and accurately identifies normal hearing sensitivity. The results of this study contribute to efforts to improve outcomes for vulnerable populations by reducing barriers to clinical implementation of ABR testing at > 4 kHz.