87 research outputs found

    Water and Brain Function: Effects of Hydration Status on Neurostimulation and Neurorecording

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    Introduction: TMS and EEG are used to study normal neurophysiology, diagnose, and treat clinical neuropsychiatric conditions, but can produce variable results or fail. Both techniques depend on electrical volume conduction, and thus brain volumes. Hydration status can affect brain volumes and functions (including cognition), but effects on these techniques are unknown. We aimed to characterize the effects of hydration on TMS, EEG, and cognitive tasks. Methods: EEG and EMG were recorded during single-pulse TMS, paired-pulse TMS, and cognitive tasks from 32 human participants on dehydrated (12-hour fast/thirst) and rehydrated (1 Liter oral water ingestion in 1 hour) testing days. Hydration status was confirmed with urinalysis. MEP, ERP, and network analyses were performed to examine responses at the muscle, brain, and higher-order functioning. Results: Rehydration decreased motor threshold (increased excitability) and shifted the motor hotspot. Significant effects on TMS measures occurred despite being re-localized and re-dosed to these new parameters. Rehydration increased SICF of the MEP, magnitudes of specific TEP peaks in inhibitory protocols, specific ERP peak magnitudes and reaction time during the cognitive task. Rehydration amplified nodal inhibition around the stimulation site in inhibitory paired-pulse networks and strengthened nodes outside the stimulation site in excitatory and CSP networks. Cognitive performance was not improved by rehydration, although similar performance was achieved with generally weaker network activity. Discussion: Results highlight differences between mild dehydration and rehydration. The rehydrated brain was easier to stimulate with TMS and produced larger responses to external and internal stimuli. This is explainable by the known physiology of body water dynamics, which encompass macroscopic and microscopic volume changes. Rehydration can shift 3D cortical positioning, decrease scalp cortex distance (bringing cortex closer to stimulator/recording electrodes), and cause astrocyte swelling-induced glutamate release. Conclusions: Previously unaccounted variables like osmolarity, astrocyte and brain volumes likely affect neurostimulation/neurorecording. Controlling for and carefully manipulating hydration may reduce variability and improve therapeutic outcomes of neurostimulation. Dehydration is common and produces less excitable circuits. Rehydration should offer a mechanism to macroscopically bring target cortical areas closer to an externally applied neurostimulation device to recruit greater volumes of tissue and microscopically favor excitability in the stimulated circuits

    Abnormal reactivity of resting-state EEG alpha rhythms during eyes open in patients with Alzheimer's and Lewy body diseases

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    Previous studies suggest that resting-state electroencephalographic (rsEEG) rhythms recorded in old patients with dementia due to different neurodegenerative diseases have a significant heuristic and clinical potential in identifying peculiar abnormalities of the ascending activating systems and reciprocal thalamocortical circuits in which oscillatory (de)synchronizing signals dynamically underpin cortical arousal in the regulation of quiet vigilance. In the present PhD program, a new methodological approach based on rsEEG cortical source estimation and individually-based frequency bands was used to test the hypothesis of significant abnormalities in the neurophysiological oscillatory mechanisms underlying the regulation of the quiet vigilance during the transition from an eyes-closed to an eyes-open condition in patients with the most prevalent neurodegenerative dementing disorders such as Alzheimer’s disease and Lewy Body and Parkinson’s diseases and initial abnormalities in the prodromal stage of ADD, characterized by mild cognitive impairment. Three rsEEG studies were performed for that purpose. In the first study, we tested if the reactivity of posterior rsEEG alpha rhythms from the eye- closed to the eyes-open condition may differ in patients with dementia due to Lewy Bodies (DLB) and Alzheimer’s disease (ADD) as a functional probe of the dominant neural synchronization mechanisms regulating the vigilance in posterior visual systems. We used clinical, demographical, and rsEEG datasets in 28 healthy elderly (Healthy) seniors, 42 DLB, and 48 ADD participants. The eLORETA freeware estimated rsEEG cortical sources at individual delta, theta, and alpha frequencies. Results showed a substantial (> -10%) reduction in the posterior alpha activities during the eyes-open condition in 24 Healthy, 26 ADD, and 22 DLB subjects. There were lower reductions in the posterior alpha activities in the ADD and DLB groups than in the Healthy group. The reduction in the occipital region was lower in the DLB than in the ADD group. These results suggest that DLB patients may suffer a greater alteration in the neural synchronization mechanisms regulating vigilance in occipital cortical systems compared to ADD patients. In the second study, we hypothesized that the vigilance dysregulation seen in PDD patients might be reflected by altered reactivity of posterior rsEEG alpha rhythms during the vigilance transition from an eyes-closed to an eyes-open condition. We used clinical, demographical, and rsEEG datasets in 28 healthy elderly (Healthy), 73 PDD, and 35 ADD participants. We have applied the same methodology used for the first study. Results showed substantial (> -10%) reduction (reactivity) in the posterior alpha source activities from the eyes-closed to the eyes-open condition in 88% of the Healthy seniors, 57% of the ADD patients, and only 35% of the PDD patients. In these alpha-reactive participants, there was lower reactivity in the parietal alpha source activities in the PDD group than in the Healthy and the ADD groups. These results suggest that PDD is characterized by poor reactivity of mechanisms desynchronizing posterior rsEEG alpha rhythms in response to visual inputs. This finding could be an interesting biomarker of impaired vigilance regulation in quiet wakefulness in PDD patients. Indeed, such biomarkers may provide endpoints for pharmacological intervention and brain electromagnetic stimulations to improve the PDD patients’ general ability to regulate vigilance and primary visual consciousness in the activities of daily living. In the third study, we tested the exploratory hypothesis that rsEEG alpha rhythms may predict and be sensitive to mild cognitive impairment due to AD (ADMCI) progression at a 6-month follow- up (a relevant feature for intervention clinical trials). Clinical, neuroimaging, and rsEEG datasets in 52 ADMCI and 60 Healthy seniors were used. We applied the same methodology used for the first and the second studies. Results showed a substantial (> -10%) reduction in the posterior alpha source activities during the eyes-open condition in about 90% and 70% of the Healthy and ADMCI participants, respectively. In the younger ADMCI patients (mean age of 64.3±1.1) with “reactive” rsEEG alpha source activities, posterior alpha source activities during the eyes closed condition predicted the global cognitive status at the 6-month follow-up. In all ADMCI participants with “reactive” rsEEG alpha source activities, posterior alpha source activities during the eyes-closed condition reduced in magnitude at that follow-up. These effects could not be explained by neuroimaging and neuropsychological biomarkers of AD. These results suggest that in ADMCI patients, the true (“reactive”) posterior rsEEG alpha rhythms, when present, predict (in relation to younger age) and are quite sensitive to the effects of the disease progression on neurophysiological mechanisms underpinning vigilance regulation. The results of the three studies unveiled the significant extent to which the well-known impairments in the cholinergic and dopaminergic neuromodulatory ascending systems could affect the brain neurophysiological oscillatory mechanisms underpinning the reactivity of rsEEG alpha rhythms during eyes open and, then, the regulation of quiet vigilance in ADD, PDD, and DLB patients, thus enriching the neurophysiological model underlying their known difficulties to remain awake in quiet environmental conditions during daytime

    Respiratory influences on pupil size dynamics and visual recognition memory

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    Breathing, a fundamental rhythm of life, has traditionally been associated with the exchange of oxygen and carbon dioxide. However, recent research in both animal models and humans has unveiled additional roles of respiration in modulating cortical neuronal activity, influencing sensory, motor, emotional, and cognitive processes. This dissertation aims to explore the impact of respiration on pupil size dynamics and visual recognition memory in humans. In Study I, we synthesized the research conducted on respiratory influences on pupil size dynamics in humans by conducting a systematic literature review. We discovered that the evidence for respiratory influences on pupil size dynamics in humans is less solid and extensive than previously believed. After more than 50 years of research, only 12 studies have directly investigated this topic. Not only was the underlying evidence for an effect of breathing phase, depth, and rate on pupil size dynamics weak, but the influence of breathing route (oral or nasal breathing) had not been investigated at all. In Study II, we conducted an experimental study to answer the outstanding questions identified in Study I. We collected pupil size data from participants during periods of rest while they breathed through their nose and mouth, on separate occasions. We demonstrated small but significant effects of breathing phase on pupil size and a spurious correlation and phase synchronization between the breathing and the pupil signal that is largely driven by breathing rate. After accounting for this spurious correlation and phase synchronization, we show that a small but significant interaction between the breathing and the pupil signal remains. Importantly, we show that, contrary to common belief, pupil size does not increase during inhalation, but rather during exhalation. Furthermore, we did not find any changes in pupil size in the time around inhalation and exhalation, and our results were not affected by the breathing route. In conclusion, we confirmed the influence of breathing on pupil size dynamics, while uncovering a more complex and intricate relationship than previously conceived. In Study III, we investigated the influence of breathing phase and breathing route on performance in a visual recognition memory task with a within-subject design and with stimuli presentation phase-locked to the inhalation or exhalation onset. We show that neither breathing phase nor breathing route affect memory performance. However, we did find an effect of breathing phase on response bias, with participants using a more conservative response bias during exhalation. Furthermore, we found that breathing route and breathing phase shape the Late Parietal Effect (LPE), but not the Frontal Negative Component (FN400), amplitude during encoding. Additionally, during recognition, both the LPE and FN400 component amplitudes were not, or only to a small extent, affected by breathing route and phase. While we demonstrated that breathing does not shape visual recognition memory performance, we also showed that breathing influences brain activity related to memory functions. Therefore, we highlight the importance of further research to elucidate the extent of respiratory influence on perception, cognition, and behavior. In Study IV, we further investigated the impact of breathing on visual memory performance by investigating the effects of nasal breathing phase on memory of repeated images presented in a rapid serial visual presentation (RSVP) task. In two separate, high-powered experiments, we did not find an effect of breathing phase on task performance. An exploratory analysis in the first experiment discovered a potential performance increase for stimuli presented approximately one second after inhalation. However, this was not replicated in the second, larger, and pre-registered study. Thus, we find no effect of breathing phase on performance in this RSVP task and urge for caution regarding the notion that visual memory is broadly affected by the breathing phase. Finally, in Study V, we investigated whether oral hormonal contraceptives (OC) affect chemosensory sensitivity and perception. Whereas previous research focused nearly exclusively on olfaction, we expanded this to also study the taste and trigeminal sense. Making use of Bayesian statistics, we evaluated the performance differences between a group of women taking OC, and a control group of normal cycling women. Our results indicated that the use of OC does not affect odor, trigeminal, or taste detection thresholds. Furthermore, neither odor nor taste perception were affected, with Bayes factors weighing the evidence in favor of the null hypothesis. We therefore conclude it to be unlikely that OC affect chemosensory perception to a degree that is of behavioral relevance. Collectively, this doctoral thesis challenges prevailing myths while paving the way for a more intricate understanding of the relationship between respiration and pupil size, and perceptual and cognitive processes. Importantly, it underscores the importance of implementing rigorous methodological paradigms in future research

    Identification of the brain areas that mediate insulin action

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    It is becoming increasingly apparent that insulin signaling regulates neural circuits in the brain, playing roles in the control of appetite, cognition and memory. Interestingly, in humans, intranasal delivery of insulin to specifically target the brain, has an effect on feeding behaviour, glucose regulation and cognition. However, the action of intranasally administered insulin in the brain has not yet been fully explained, especially in respect to food intake. Here, to determine the effect of intranasal insulin in vivo, the mice were placed in metabolic cages after intranasal injection of standard human insulin, the results show that intranasal insulin remarkably reduced food consumption within 2-5 hours after treatment. Then intranasal fluorescence insulin was delivered to track the distribution of insulin receptors in mouse brain to highlight the areas of the brain that intranasal insulin can reach. Results suggest that insulin receptors are located in many areas of the murine brain, including olfactory bulb, hippocampus, brainstem and a novel area nucleus of the horizontal limb of the diagonal band (HDB). Furthermore, knockdown of the insulin receptor in the HDB leads to a significant increase in food intake in male rats but not female rats. Besides, impaired insulin signaling in the HDB also results in hyperactive in female rats but not male rats. Retrograde tracing data show that the HDB receives afferents from the ventral tegmental area (VTA) and mitral cell layer of olfactory bulb, which might be involved in regulating in metabolism. Overall, our data indicates that intranasal delivery of insulin is a good way to target areas of the brain important for controlling energy balance. Due to the metabolic effect that intranasal insulin has both in rodents and humans, further studies are warranted in order to understand which insulin sensitive brain regions and neurons are involved in this process

    25th Annual Computational Neuroscience Meeting: CNS-2016

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    Abstracts of the 25th Annual Computational Neuroscience Meeting: CNS-2016 Seogwipo City, Jeju-do, South Korea. 2–7 July 201

    Enhancing memory-related sleep spindles through learning and electrical brain stimulation

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    Sleep has been strongly implicated in mediating memory consolidation through hippocampal-neocortical communication. Evidence suggests offline processing of encoded information in the brain during slow wave sleep (SWS), specifically during slow oscillations and spindles. In this work, we used active exploration and learning tasks to study post-experience sleep spindle density changes in rats. Experiences lead to subsequent changes in sleep spindles, but the strength and timing of the effect was task-dependent. Brain stimulation in humans and rats have been shown to enhance memory consolidation. However, the exact stimulation parameters which lead to the strongest memory enhancement have not been fully explored. We tested the efficacy of both cortical sinusoidal direct current stimulation and intracortical pulse stimulation to enhance slow oscillations and spindle density. Pulse stimulation reliably evoked state-dependent slow oscillations and spindles during SWS with increased hippocampal ripple-spindle coupling, demonstrating potential in memory enhancement
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