Pathological slow-wave activity and impaired working memory binding in post-traumatic amnesia

The mechanism by which information is bound together in working memory is a central question for cognitive neuroscience. This binding is transiently disrupted during periods of post-traumatic amnesia following significant head injuries. The reason for this impairment is unclear but may be due to electrophysiological changes produced by head impacts. These are common and include pathological low frequency activity, which is associated with poorer neurological outcomes and may disrupt cortical communication. Here, we investigate associative memory binding during post-traumatic amnesia and test the hypothesis that misbinding is caused by a disruption in cortical communication produced by the pathological slowing of brain activity. Thirty acute moderate-severe traumatic brain injury patients (mean time since injury = 10 days) and 26 healthy controls were tested with a precision working memory paradigm that required the association of object and location information. A novel entropy ratio measure was calculated from behavioural performance. This provided a continuous measure of the degree of misbinding and the influence of distracting information. Resting state EEG was used to assess the electrophysiological effects of traumatic brain injury. Patients in post-traumatic amnesia showed abnormalities in working memory function and made significantly more misbinding errors than patients who were not in post-traumatic amnesia and controls. Patients showed a higher entropy ratio in the distribution of spatial responses, indicating that working memory recall was abnormally biased by the locations of non-target items suggesting a specific impairment of object and location binding. Slow wave activity was increased following traumatic brain injury. Increases in the delta-alpha ratio indicative of an increase in low frequency power specifically correlated with binding impairment in working memory. In contrast, although connectivity was increased in the theta band and decreased in the alpha band after traumatic brain injury, this did not correlate with working memory impairment. Working memory and electrophysiological abnormalities both normalised at six-month follow-up, in keeping with a transient increase in slow-wave activity causing post-traumatic amnesia that impaired working memory function. These results show that patients in post-traumatic amnesia show high rates of working memory misbinding that are associated with a pathological shift towards lower frequency oscillations.

The neural architecture of sleep regulation – insights from Drosophila

The neural mechanisms that balance waking and sleep to ensure adequate sleep quality in mammals are highly complex, often eluding functional insight. In the last two decades, researchers made impressive progress in studying the less complex brain of the invertebrate model organism Drosophila melanogaster, which has led to a deeper understanding of the neural principles of sleep regulation. Here, we will review these findings to illustrate that neural networks require sleep to undergo synaptic reorganization that allows for the incorporation of experiences made during the waking hours. Sleep need, therefore, can arise as a consequence of sensory processing, often signalized by neural networks as they synchronize their electrical patterns to generate slow-wave activity. The slow-wave activity provides the neurophysiological basis to establish a sensory gate that suppresses sensory processing to provide a resting phase which promotes synaptic rescaling and clearance of metabolites from the brain. Moreover, we demonstrate how neural networks for homeostatic and circadian sleep regulation interact to consolidate sleep into a specific daily period. We particularly highlight that the basic functions and physiological principles of sleep are highly conserved throughout the phylogenetic spectrum, allowing us to identify the functional components and neural interactions that construct the neural architecture of sleep regulation.

Input zone-selective dysrhythmia in motor thalamus after dopamine depletion

The cerebral cortex, basal ganglia and motor thalamus form circuits important for purposeful movement. In Parkinsonism, basal ganglia neurons often exhibit dysrhythmic activity during, and with respect to, the slow (∼1 Hz) and beta-band (15–30 Hz) oscillations that emerge in cortex in a brain state-dependent manner. There remains, however, a pressing need to elucidate the extent to which motor thalamus activity becomes similarly dysrhythmic after dopamine depletion relevant to Parkinsonism. To address this, we recorded single-neuron and ensemble outputs in the ‘basal ganglia-recipient zone’ (BZ) and ‘cerebellar-recipient zone’ (CZ) of motor thalamus in anesthetized male dopamine-intact rats and 6-OHDA-lesioned rats during two brain states, respectively defined by cortical slow-wave activity and activation. Two forms of thalamic input zone-selective dysrhythmia manifested after dopamine depletion: First, BZ neurons, but not CZ neurons, exhibited abnormal phase-shifted firing with respect to cortical slow oscillations prevalent during slow-wave activity; secondly, BZ neurons, but not CZ neurons, inappropriately synchronized their firing and engaged with the exaggerated cortical beta oscillations arising in activated states. These dysrhythmias were not accompanied by the thalamic hypoactivity predicted by canonical firing rate-based models of circuit organization in Parkinsonism. Complementary recordings of neurons in substantia nigra pars reticulata suggested their altered activity dynamics could underpin the BZ dysrhythmias. Finally, pharmacological perturbations demonstrated that ongoing activity in the motor thalamus bolsters exaggerated beta oscillations in motor cortex. We conclude that BZ neurons are selectively primed to mediate the detrimental influences of abnormal slow and beta-band rhythms on circuit information processing in Parkinsonism.

A-79 Case Series Evaluating Quantitative Electroencephalograph and Neuropsychological Function in Neurological Lyme Disease

Objectives The purpose of this study was to investigate the characteristics of physician diagnosed Neurological Lyme disease (NLD) using Quantitative EEG and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We hypothesize that findings would include more slow wave (Delta/Theta) activity that is consistent with the severity reported dysfunction. Methods Subjects consisted of four adult females with a physician provided diagnosis of NLD. EEG was recorded from 21 sites during an eyes open and eyes-closed resting conditions. Raw EEG data was made quantifiable (qEEG) through Fourier transformation to determine z-score derived cortical and subcortical slow wave activity. The RBANS was used to assess each subject’s functioning. Results (See Imaging). Subject 1. Theta: 3.7. Alpha: 2.3. Theta: 3.2. Alpha: 2.5. RBANS - 96. Subject 2. Theta: 1.9. Alpha: 3.1. Theta: 2.3. Alpha: 4.4. RBANS - 76. Subject 3. Theta: 3.4. Alpha: 2.8. Theta: 3.5. Alpha: 2.1. RBANS - 110. Subject 4. Theta: 3.6. Alpha: 3.0. Theta: 3.3. Alpha: 2.8. RBANS - 100. Conclusions NLD subjects within this study all demonstrated elevated subcortical frontal and frontotemporal theta and alpha. Elevation in cortical slow wave activity was found for subjects with greater reported symptomatology and may suggest either less severe course of disease or serve as a recovery marker. RBANS assessment variables were not completely sensitive in detection of subject reported challenges. Implications for conceptualization, treatment, and disease monitoring are highlighted. Directions for future research will also be discussed.

Cortical Thinning and Sleep Slow Wave Activity Reductions Mediate Age-Related Improvements in Cognition During Mid-Late Adolescence

Study Objectives Gains in cognitive test performance that occur during adolescence are associated with brain maturation. Cortical thinning and reduced sleep slow wave activity (SWA) are markers of such developmental changes. Here we investigate whether they mediate age-related improvements in cognition. Methods 109 adolescents aged 15-19y (49 males) underwent magnetic resonance imaging, polysomnography (PSG) and a battery of cognitive tasks within a 2-month time window. Cognitive tasks assessed non-verbal intelligence, sustained attention, speed of processing and working memory and executive function. To minimize the effect of sleep history on SWA and cognitive performance, PSG and test batteries were administered only after at least 8 nights of 9-h time-in-bed (TIB) sleep opportunity. Results Age-related improvements in speed of processing (r = 0.33, p = 0.001) and non-verbal intelligence (r = 0.24, p = 0.01) domains were observed. These cognitive changes were associated with reduced cortical thickness, particularly in bilateral temporoparietal regions (rs = -0.21 to -0.45, ps < 0.05), as well as SWA (r = -0.35, p < 0.001). Serial mediation models found that ROIs in the middle/superior temporal cortices, together with SWA mediated the age-related improvement observed on cognition. Conclusions During adolescence, age-related improvements in cognition are mediated by reductions in cortical thickness and sleep slow wave activity.

EEG findings in patients with angelman syndrome. Notched slow waves and age-specific characteristics of the main EEG patterns

Angelman syndrome (AS) is a genetic disorder caused by a mutation in the maternal copy of the UBE3A gene and characterized by typical clinical manifestations (such as mental retardation, difficulty walking, and laughter) and specific changes on the electroencephalogram (EEG).The aim of this study was to analyze age-specific characteristics of the main EEG patterns, including high-amplitude frontal delta activity with spikes, slow-wave delta-theta activity with spikes in the posterior regions, and diffuse continuous rhythmic theta activity. In addition to that, we assessed the frequency of a rare and highly specific for AS EEG pattern: notched slow waves.We have identified and described additional criteria for EEG during sleep: high index of pathological slow-wave activity and the ratio of pathological slow-wave activity index to epileptiform activity index during sleep. We also analyzed all EEG patterns at the age most significant for the detection of this syndrome (up to 3 years) and their age-specific dynamics.We covered the frequency and characteristics of EEG patterns rare in AS patients, such as three-phase bifrontal delta waves, reactive pathological activity in the posterior areas, EEG patterns of focal seizures originating from the posterior areas, benign epileptiform discharges of childhood, and migrating continuous slow-wave activity.We analyzed the differences between main EEG patterns in AS and frontal and occipital intermittent rhythmic delta activity (fIRDA and OIRDA patterns).

Zebrafish as a tool in the study of sleep and memory-related disorders

: Sleep is an evolutionarily conserved phenomenon, being an essential biological necessity for the learning process and memory consolidation. The brain displays two types of electrical activity during sleep: slow-wave activity or non-rapid eye movement (NREM) sleep and desynchronized brain wave activity or rapid eye movement (REM) sleep. There are many theories about “Why we need to sleep?” among them the synaptic homeostasis. This theory proposes that the role of sleep is the restoration of synaptic homeostasis, which is destabilized by synaptic strengthening triggered by learning during waking and by synaptogenesis during development. Sleep diminishes the plasticity load on neurons and other cells to normalize synaptic strength. In contrast, it re-establishes neuronal selectivity and the ability to learn, leading to the consolidation and integration of memories. The use of zebrafish as a tool to assess sleep and its disorders is growing, although sleep in this animal is not yet divided, for example, into REM and NREM states. However, zebrafish are known to have a regulated daytime circadian rhythm. Their sleep state is characterized by periods of inactivity accompanied by an increase in arousal threshold, preference for resting place, and the “rebound sleep effect” phenomenon, which causes an increased slow-wave activity after a forced waking period. In addition, drugs known to modulate sleep, such as melatonin, nootropics, and nicotine, have been tested in zebrafish. In this review, we discuss the use of zebrafish as a model to investigate sleep mechanisms and their regulation, demonstrating this species as a promising model for sleep research.