Biology subjects

Bergman, H.

Publications and source records attributed to Bergman, H..

15 recordsLinked to original sources

bioRxiv2026

REM Sleep Disengagement of β Oscillations Permits Rapid Dream Movements in Parkinsonism

REM sleep behavior disorder is a hallmark of prodromal -synucleinopathies, yet why patients with Parkinsons disease can generate rapid, coordinated movements during REM sleep despite daytime bradykinesia remains unknown. Here we combined recordings of eye movements, cortical electroencephalography, and basal ganglia-thalamic neuronal activity across vigilance states in non-human primates before and after MPTP-induced parkinsonism. Parkinsonism enhanced {beta} oscillations and impaired movement-related neural dynamics during wakefulness and NREM sleep, whereas both pathological {beta} activity and motor impairments were attenuated during REM sleep. {beta} suppression preceded the onset of REM sleep, indicating that network reconfiguration begins before REM becomes behaviorally apparent. These findings demonstrate that Parkinsonian network dysfunction is dynamically gated by brain state rather than continuously imposed by dopamine depletion. REM sleep is a natural physiological condition in which {beta} oscillations are disengaged, uncovering a latent capacity, normally masked by REM atonia, for rapid movement even in the dopamine-depleted motor network.

neuroscience↗

bioRxiv2025

Basal ganglia-independent thalamic bursts do not wake cortex during sleep

The thalamus is a key forebrain structure that gates peripheral, subcortical, and cortico-cortical communication1,2. Awake thalamic bursts provide the cortex with a "wake-up" signal2-4. Paradoxically, thalamic neurons discharge tonically during cellular depolarization and activated brain states (wakefulness, REM sleep) but burst during hyperpolarization and NREM sleep5-9. It has been proposed that NREM thalamic bursts do not awaken the cortex because of their periodic and synchronized nature2-4; however, this has never been tested in vivo during natural sleep. We simultaneously recorded polysomnographic signals, local field potentials, and spiking activity from multiple thalamic neurons in the ventral anterior and centromedian nuclei of two female non-human primates during naturally occurring vigilance states. These nuclei receive GABAergic output from the basal ganglia10,11, with discharge rate and GABA outflow decreasing during NREM sleep12. We found that despite the expected thalamic depolarization, bursting increased significantly. NREM bursts were neither periodic nor highly synchronized. However, EEG activity time-locked to burst onset during NREM sleep differed markedly from that observed during wakefulness and REM sleep. These results support a modulatory, rather than a driving, relationship between the basal ganglia and thalamus. NREM thalamic bursts do not awaken the cortex, probably due to unique state-dependent thalamocortical dynamics.

neuroscience↗

bioRxiv2024

Behavioural Investigations of Psilocybin in Animals 1962-2021: A Scoping Review

Background and AimsPsilocybin is a psychedelic drug that may hold promise for a wide range of human health conditions, yet the identification of therapeutic processes and mechanisms of action remains exploratory. We conducted a scoping review on pre-clinical behavioural investigations of psilocybin in non-human animals to help determine the behavioural effects of psilocybin in non-human animals, to identify studies completed, behavioural tests employed, and what dosing modalities had been studied. MethodsA librarian-conducted literature search was performed using predefined key terms and search criteria and additional searching was conducted by reviewers, using electronic databases, grey literature sources, and reference lists of relevant articles or reviews. The final search updated occurred in October, 2021. Studies were reviewed, screened and selected against an a priori protocol using Covidence software by multiple reviewers with results plotted across the Research Domains Criteria construct. ResultsFrom 4124 records identified by database searching, 260 publications were subjected to full-text review with 77 studies included in this scoping review, published between 1962-2021. The preponderance of studies (n=64) investigated behavioural outcomes in rodents. Only 43 studies (55.8%) reported on housing conditions, and seventeen studies (22.1%) failed to report sample size. All studies reported behavioural outcomes following drug administration, with fifty-one studies (66.2%) using psilocybin, thirty studies (42.9%) psilocin, four studies (5.2%) administering whole mushroom extracts (WME), and a further eight studies investigating both psilocybin and psilocin and one study reporting the effects of both psilocin and WME. One hundred and thirty distinct behavioural investigations using fifty different behavioral paradigms were identified. Few adverse events were reported, and even exceedingly high doses were apparently well tolerated. ConclusionWith seventy-seven publications spanning close to sixty years, there is huge variation in study design and quality. Overall psilocybin presents a unique and strong safety profile with no evidence of biological toxicity, is characterized by unique time and dose-dependent effects, and its pattern of drug action is significantly context and training-sensitive. Data suggest putative effects of psilocybin include acute arousal, dose-dependent sedation, reductions in fear conditioning at low doses, reduced aggression, improved valence, acute disruption of working memory, the rescuing of deficits from chronic stress, and improved learning when combined with repeated environmental exposure after resolution of drug effect.

animal behavior and cognition↗

bioRxiv2023

Non-linear input-output relationships in the subthalamic nucleus of Parkinson's patients

Both local field potentials (LFP) and spiking (SPK) activity in the subthalamic nucleus (STN) are related to Parkinsons disease (PD) symptoms; however, their relationship is poorly understood. We explore it by separating STN signals of 146 PD patients (308 trajectories, >25,000 recording sites) into aperiodic and periodic components and whitening these signals using their corresponding aperiodic parameters. The LFP aperiodic exponents resemble Brown noise ( = 2.20 {+/-} 0.40) and are significantly higher than SPK aperiodic exponents ( = 0.11 {+/-} 0.22, White noise). The periodic oscillations of LFP are overwhelmingly distributed in the high beta frequency domain while those of SPK are in both low and high beta domains. Beta oscillation center frequencies were downshifted in SPK relative to simultaneously recorded LFP. This demonstrates that the STN synaptic input (LFP) undergoes significant modifications when transformed into STN output (SPK) of PD patients, and may explain the critical role of STN in PD physiology and STN-Deep-Brain-Stimulation therapeutic efficacy.

neuroscience↗

bioRxiv2023

Basal Ganglia Stimulation Ameliorates Schizophrenia Exploration Anomalies

Any learning agent must balance between exploiting its knowledge and exploring new alternatives. Schizophrenia patients are known to have maladaptive exploration-exploitation (E-E) balance1,2 and are impaired at reversal learning tasks as early as their first psychotic episode. The cortico-basal ganglia (BG)-dorsolateral prefrontal cortex (DLPFC) network plays a significant role in learning processes3,4. However, how this network maintains the E-E balance and what alters the balance in schizophrenia remains elusive. Using a combination of extracellular recordings, pharmacological manipulations, macro-stimulation techniques, and an adaptive reinforcement learning model, we show that in the non-human primate (NHP), the external segment of the globus pallidus (GPe, the central nucleus of the BG network) maintain this balance. Furthermore, whereas the chronic, low-dose administration of N-methyl-D-aspartate (NMDA) receptor (NMDA-R) antagonist, phencyclidine (PCP) leads to E-E imbalance, low-frequency GPe macro-stimulation restores it. E-E balance provides a holistic framework to resolve some of the apparent paradoxes that have emerged within schizophrenia research2. Our findings suggest that Schizophrenia symptoms may reflect abnormal DLPFC-BG E-E balance, and GPe stimulation may be advantageous for these patients.

neuroscience↗

bioRxiv2022

Entrainment to sleep spindles reflects dissociable patterns of connectivity between cortex and basal ganglia

Communication between the basal ganglia (BG) and cortex is crucial for behavior as it allows learning through external reinforcement. Non-REM sleep benefits learning in the corticostriatal system through the sleep spindle-associated reactivation of previously active neuronal ensembles and the subsequent modification of synaptic weights. However, how sleep spindles coordinate cross-region spiking, and whether spindle-driven reactivation occurs in other BG structures, remains unknown. We recorded field potentials (FP) and spiking activity in cortex and BG during sleep in two non-human primates immediately following a task that involved the learning of new cue-reward contingencies. FP sleep spindles were widespread in the BG, and they were similar to cortical spindles in morphology, spectral content and response to learning prior to sleep. Further, BG FP spindles were concordant with EEG spindles and associated with increased cortico-BG correlation. However, spindles across the BG differed markedly in their entrainment of local spiking. The spiking activity of striatal projection neurons exhibited consistent phase locking to striatal FP spindles and EEG spindles, producing phase windows of peaked cross-region spindling. In contrast, in the subthalamic nucleus (STN), which like the striatum receives substantial thalamocortical input, and in BG nuclei downstream to the striatum and STN, neuronal firing was not entrained to either local or EEG sleep spindles. These results dissociate striatal projection neurons from the rest of the BG, and suggest corticostriatal synapses as the main hub for offline communication between cortex and BG.

neuroscience↗

bioRxiv2021

Dichotomous Activity and Function of Neurons with Low- and High-Frequency Discharge in the External Globus Pallidus of Non-Human Primates

To date, there is a consensus that there are at least two neuronal populations in the non-human primate (NHP) external globus pallidus (GPe): the low- and high-frequency discharge (LFD and HFD) neurons. Nevertheless, almost all NHP physiological studies have neglected the functional importance of LFD neurons. This study examined the discharge features of these two GPe neuronal subpopulations recorded in four NHPs engaged in a classical conditioning task with cues predicting reward, neutral and aversive outcomes. The results show that LFD neurons tended to burst, encoded the salience of behavioral cues, and exhibited correlated spiking activity. By contrast, the HFD neurons tended to pause, encoded cue valence, and exhibited uncorrelated spiking activity. Overall, these findings point to the dichotomic organization of the NHP GPe which is likely to be critical to the implementation of normal basal ganglia functions and computations.

neuroscience↗

bioRxiv2021

Non-uniform distribution of dendritic nonlinearities differentially engages thalamostriatal and corticostriatal inputs onto cholinergic interneurons

The tonic activity of striatal cholinergic interneurons (CINs) is modified differentially by their afferent inputs. Although their unitary synaptic currents are identical, in most CINs cortical inputs onto distal dendrites only weakly entrain them, whereas proximal thalamic inputs trigger abrupt pauses in discharge in response to salient external stimuli. To test whether the dendritic expression of the active conductances that drive autonomous discharge contribute to the CINs capacity to dissociate cortical from thalamic inputs, we used an optogenetics-based method to quantify dendritic excitability. We found that the persistent sodium (NaP) current gave rise to dendritic boosting, and that the hyperpolarization-activated cyclic nucleotide-gated (HCN) current gave rise to a subhertz membrane resonance. This resonance may underlie our novel finding of an association between CIN pauses and internally-generated slow wave events in sleeping non-human primates. Moreover, our method indicated that dendritic NaP and HCN currents were preferentially expressed in proximal dendrites. We validated the non-uniform distribution of NaP currents pharmacologically; with two-photon imaging of dendritic back-propagating action potentials; and by demonstrating boosting of thalamic, but not cortical, inputs by NaP currents. Thus, the localization of active dendritic conductances in CIN dendrites mirrors the spatial distribution of afferent terminals and may promote their differential responses to thalamic vs. cortical inputs.

neuroscience↗

bioRxiv2021

Spontaneous pauses in firing of external pallidum neurons are associated with exploratory behavior

Spontaneous pauses in firing are the hallmark of external pallidum (GPe) neurons. However, their role in the basal ganglia (BG) network remains unknown. Pupil size and saccades have been linked to attention and exploration. Here, we show that pauses are associated with dilated pupils and increased saccade rate. Our results suggest that pauses are a powerful mechanism by which the GPe may influence BG downstream structures and affect behavioral output.

neuroscience↗

bioRxiv2020

Toward asleep DBS: Cortico basal-ganglia neural activity during interleaved propofol/ketamine sedation mimics NREM/REM sleep activity

Deep brain stimulation (DBS) is currently a standard long-term treatment for advanced motor symptoms in Parkinsons disease (PD). In an effort to enable DBS under sedation, asleep DBS, we characterized the cortico-basal ganglia neuronal network of two non-human primates under propofol, ketamine and interleaved propofol-ketamine (IPK) sedation. Further, we compared these sedation states in the healthy and Parkinsonian condition to those of healthy sleep. Ketamine increases high frequency power and synchronization while propofol increases low frequency power and synchronization in polysomnography and neuronal activity recordings. Thus, ketamine does not mask the low frequency oscillations used for physiological navigation toward basal ganglia DBS targets. The brain state under ketamine and propofol mimicked rapid eye movement (REM) and Non-REM (NREM) sleep activity, respectively, and the IPK protocol imitates the NREM-REM sleep cycle. These promising results are the first step towards asleep DBS with non-distorted physiological navigation.

neuroscience↗

bioRxiv2020

Frequency matters: Up- and Down-Regulation of Dopamine Tone Induces Similar Frequency Shifts in Cortico-Basal Ganglia Beta Oscillations

Beta oscillatory activity (13-30Hz) is pervasive within the cortico-basal ganglia (CBG) network. Studies in Parkinsons disease (PD) patients and animal models suggested that beta-power increases with dopamine depletion. However, the exact relationship between oscillatory power, frequency and dopamine-tone remains unclear. We recorded neural activity in the CBG network of non-human-primates (NHP) while acutely up- and down-modulating dopamine levels. Further, we assessed changes in beta oscillations of PD patients following acute and chronic changes in dopamine-tone. Beta oscillation frequency was strongly coupled with dopamine-tone in both NHPs and human patients. In contrast, power, coherence between single-units and LFP, and spike-LFP phase-locking were not systematically regulated by dopamine levels. These results demonstrate via causal manipulations that frequency, rather than other properties, is the key property of pathological oscillations in the CBG networks. These insights can lead to improvements in understanding of CBG physiology, PD progression tracking and patient care.

neuroscience↗

bioRxiv2019

Phase-specific microstimulation in brain-machine interface setting differentially modulates beta oscillations and affects behavior

It is widely accepted that beta-band oscillations play a role in sensorimotor behavior. To further explore this role, we developed a novel hybrid platform to combine operant conditioning and phase-specific intracortical microstimulation (ICMS). We trained monkeys, implanted with 96 electrodes arrays in motor cortex, to volitionally enhance local field potential (LFP) beta-band (20-30Hz) activity at selected sites using a brain-machine interface (BMI). We demonstrate that beta oscillations of LFP and single-unit spiking activity increased dramatically with BMI training, and that pre-movement Beta-power was anti-correlated with task performance. We also show that phase-specific ICMS modulated the power and phase of oscillations, shifting local networks between oscillatory and non-oscillatory states. Furthermore, ICMS induced phase-dependent effects in animal reaction times and success rates. These findings contribute to unraveling of the functional role of cortical oscillations, and to future development of clinical tools for ameliorating abnormal neuronal activities in brain diseases.

neuroscience↗

bioRxiv2019

Neuronal activity and learning in local cortical networks are modulated by the action-perception state

During sensorimotor learning, neuronal networks change to optimize the associations between action and perception. In this study, we examine how the brain harnesses neuronal patterns that correspond to the current action-perception state during learning. To this end, we recorded activity from motor cortex while monkeys either performed a familiar motor task (movement-state) or learned to control the firing rate of a target neuron using a brain-machine interface (BMI-state). Before learning, monkeys were placed in an observation-state, where no action was required. We found that neuronal patterns during the BMI-state were markedly different from the movement-state patterns. BMI-state patterns were initially similar to those in the observation-state and evolved to produce an increase in the firing rate of the target neuron. The overall activity of the non-target neurons remained similar after learning, suggesting that excitatory-inhibitory balance was maintained. Indeed, a novel neural-level reinforcement-learning network model operating in a chaotic regime of balanced excitation and inhibition predicts our results in detail. We conclude that during BMI learning, the brain can adapt patterns corresponding to the current action-perception state to gain rewards. Moreover, our results show that we can predict activity changes that occur during learning based on the pre-learning activity. This new finding may serve as a key step toward clinical brain-machine interface applications to modify impaired brain activity.

neuroscience↗

bioRxiv2018

Urinary biomarkers and cardiovascular outcomes in the UK Biobank: observational and Mendelian randomization analyses

BackgroundUrinary biomarkers are associated with hypertension and cardiovascular disease (CVD), but the nature of these associations is incompletely understood.\n\nMethodsWe performed multivariable-adjusted regression models to assess associations of urinary sodium-potassium ratio (UNa/UK), and urinary albumin adjusted for creatinine (UAlb/UCr) with cardiovascular risk factors, CVD and type 2 diabetes (T2D) in 478,311 participants of the UK Biobank. Further, we studied above associations separately in men and women, and assessed the causal relationships of these kidney biomarkers with cardiovascular outcomes using the two-sample Mendelian randomization (MR) approach.\n\nResultsIn observational analyses, UNa/UK showed significant inverse associations with atrial fibrillation (AF), coronary artery disease (CAD), ischemic stroke, lipid-lowering medication and T2D. In contrast, UAlb/UCr showed significant positive associations with AF, CAD, heart failure, hemorrhagic stroke, lipid-lowering medication and T2D. We found a positive association between UNa/UK and albumin with blood pressure (BP), as well as with adiposity-related measures. Generally, we detected consistent directionality in sex-stratified analyses, with some evidence for sex differences in the associations of urinary biomarkers with T2D and obesity. After correcting for potential horizontal pleiotropy, we found evidence of causal associations of UNa/UK and albumin with systolic BP (betaSBP[≥]2.63; betaDBP[≥]0.85 SD increase in systolic BP per SD change UNa/UK and UAlb/UCr; P[≤]0.038), and of albumin with T2D (odds ratio=1.33 per SD change in albumin, P=0.023).\n\nConclusionOur Mendelian randomization analyses mirror and extend findings from randomized interventional trials which have established sodium intake as a risk factor for hypertension. In addition, we detect a feed-back causal loop between albumin and hypertension, and our finding of a bidirectional causal association between albumin and T2D reflects the well-known nephropathy in T2D.

epidemiology↗

bioRxiv2018

Human Subthalamic Nucleus Selectively Decreases its Response to the Go-Signal in a Motor Inhibition Context

To better understand the mechanism of movement facilitation and inhibition in the subthalamic nucleus (STN), we recorded subthalamic multiunit activity intra-operatively while parkinsonian patients (n=43 patients, 173 sites) performed increasingly complex oddball paradigms: auditory ( None-Go, n=7, 28), simple movement ( All-Go, n=7, 26) and movement inhibition ( Go-NoGo, n=29, 119) tasks. To enable physiological sampling of the different subthalamic nucleus domains in both hemispheres, each patient performed one of the oddball paradigms several times.\n\nThe human STN responded mainly to movement-involving tasks: movement execution at the motor STN and movement planning at the limbic-associative STN. In the limbic-associative STN, responses to the inhibitory cue (deviant tone) in the movement inhibition task were not significantly different from the simple movement task. However, responses to the go cue (frequent tone) were significantly reduced. The reduction was mainly in the negative component of the evoked response amplitude. Successful movement inhibition was correlated with higher baseline activity before the inhibitory cue.\n\nWe suggest that the STN adapts to movement inhibition context by selectively decreasing the amplitude of neuronal activity. Thus, the STN enables movement inhibition not by increasing responses to the inhibitory cue but by reducing responses to the release cue. The negative component of the evoked response probably facilitates movement and a higher baseline activity enables successful inhibition of movement. These discharge modulations were found in the ventromedial, non-motor domain of the STN and therefore suggest a significant role of the associative-limbic domains in movement planning and in global movement regulation.

neuroscience↗