QEEG characteristics and spectrum weighted frequency for children diagnosed as autistic spectrum disorder.

PubMed

Pop-Jordanova, Nada; Zorcec, Tatjana; Demerdzieva, Aneta; Gucev, Zoran

2010-09-30

Autistic spectrum disorders are a group of neurological and developmental disorders associated with social, communication, sensory, behavioral and cognitive impairments, as well as restricted, repetitive patterns of behavior, activities, or interests.The aim of this study was a) to analyze QEEG findings of autistic patients and to compare the results with data base; and b) to introduce the calculation of spectrum weighted frequency (brain rate) as an indicator of general mental arousal in these patients. Results for Q-EEG shows generally increased delta-theta activity in frontal region of the brain. Changes in QEEG pattern appeared to be in a non-linear correlation with maturational processes.Brain rate measured in CZ shows slow brain activity (5. 86) which is significantly lower than normal and corresponds to low general mental arousal.Recent research has shown that autistic disorders have as their basis disturbances of neural connectivity. Neurofeedback seems capable of remediating such disturbances when these data are considered as part of treatment planning. Prognosis of this pervasive disorder depends on the intellectual abilities: the better intellectual functioning, the possibilities for life adaptation are higherQEEG shows generally increased delta-theta activity in frontal region of the brain which is related to poor cognitive abilities.Brain rate measured in CZ shows slow brain activity related to under arousal.Pharmacotherapy combined with behavior therapy, social support and especially neurofeedback technique promise slight improvements.

Evaluating the features of the brain waves to quantify ADHD improvement by neurofeedback.

PubMed

Dehghanpour, Peyman; Einalou, Zahra

2017-10-23

Attention-deficit/hyperactivity disorder (ADHD), as one of the most common neurological disorders in children and adolescents, is characterized by decentralization, slow learning, distraction and hyperactivity. Studies have shown that in addition to medication, neurofeedback training can also be used to partially control the brain activity of these patients. In this study, using the brain signals processing before and after the treatment in 10 children treated by neurofeedback, the changes were evaluated by non-parametric statistical analysis and impact of neurofeedback on brain frequency bands was investigated. Finally, the results were compared with the protocols introduced in this paper and before researches. The results of Kruskal-Wallis test showed an approximately significant increase in the relative power of gamma and an approximately significant reduction in the ratio of relative power of alpha/beta. It represents the emotional response, elicited by the successful learning and diminished ratio of slow learning to active learning respectively.

Dynamic Interaction of Spindles and Gamma Activity during Cortical Slow Oscillations and Its Modulation by Subcortical Afferents

PubMed Central

Valencia, Miguel; Artieda, Julio; Bolam, J. Paul; Mena-Segovia, Juan

2013-01-01

Slow oscillations are a hallmark of slow wave sleep. They provide a temporal framework for a variety of phasic events to occur and interact during sleep, including the expression of high-frequency oscillations and the discharge of neurons across the entire brain. Evidence shows that the emergence of distinct high-frequency oscillations during slow oscillations facilitates the communication among brain regions whose activity was correlated during the preceding waking period. While the frequencies of oscillations involved in such interactions have been identified, their dynamics and the correlations between them require further investigation. Here we analyzed the structure and dynamics of these signals in anesthetized rats. We show that spindles and gamma oscillations coexist but have distinct temporal dynamics across the slow oscillation cycle. Furthermore, we observed that spindles and gamma are functionally coupled to the slow oscillations and between each other. Following the activation of ascending pathways from the brainstem by means of a carbachol injection in the pedunculopontine nucleus, we were able to modify the gain in the gamma oscillations that are independent of the spindles while the spindle amplitude was reduced. Furthermore, carbachol produced a decoupling of the gamma oscillations that are dependent on the spindles but with no effect on their amplitude. None of the changes in the high-frequency oscillations affected the onset or shape of the slow oscillations, suggesting that slow oscillations occur independently of the phasic events that coexist with them. Our results provide novel insights into the regulation, dynamics and homeostasis of cortical slow oscillations. PMID:23844020

CONTROL OF SLEEP AND WAKEFULNESS

PubMed Central

Brown, Ritchie E.; Basheer, Radhika; McKenna, James T.; Strecker, Robert E.; McCarley, Robert W.

2013-01-01

This review summarizes the brain mechanisms controlling sleep and wakefulness. Wakefulness promoting systems cause low-voltage, fast activity in the electroencephalogram (EEG). Multiple interacting neurotransmitter systems in the brain stem, hypothalamus, and basal forebrain converge onto common effector systems in the thalamus and cortex. Sleep results from the inhibition of wake-promoting systems by homeostatic sleep factors such as adenosine and nitric oxide and GABAergic neurons in the preoptic area of the hypothalamus, resulting in large-amplitude, slow EEG oscillations. Local, activity-dependent factors modulate the amplitude and frequency of cortical slow oscillations. Non-rapid-eye-movement (NREM) sleep results in conservation of brain energy and facilitates memory consolidation through the modulation of synaptic weights. Rapid-eye-movement (REM) sleep results from the interaction of brain stem cholinergic, aminergic, and GABAergic neurons which control the activity of glutamatergic reticular formation neurons leading to REM sleep phenomena such as muscle atonia, REMs, dreaming, and cortical activation. Strong activation of limbic regions during REM sleep suggests a role in regulation of emotion. Genetic studies suggest that brain mechanisms controlling waking and NREM sleep are strongly conserved throughout evolution, underscoring their enormous importance for brain function. Sleep disruption interferes with the normal restorative functions of NREM and REM sleep, resulting in disruptions of breathing and cardiovascular function, changes in emotional reactivity, and cognitive impairments in attention, memory, and decision making. PMID:22811426

Interacting Turing-Hopf Instabilities Drive Symmetry-Breaking Transitions in a Mean-Field Model of the Cortex: A Mechanism for the Slow Oscillation

NASA Astrophysics Data System (ADS)

Steyn-Ross, Moira L.; Steyn-Ross, D. A.; Sleigh, J. W.

2013-04-01

Electrical recordings of brain activity during the transition from wake to anesthetic coma show temporal and spectral alterations that are correlated with gross changes in the underlying brain state. Entry into anesthetic unconsciousness is signposted by the emergence of large, slow oscillations of electrical activity (≲1Hz) similar to the slow waves observed in natural sleep. Here we present a two-dimensional mean-field model of the cortex in which slow spatiotemporal oscillations arise spontaneously through a Turing (spatial) symmetry-breaking bifurcation that is modulated by a Hopf (temporal) instability. In our model, populations of neurons are densely interlinked by chemical synapses, and by interneuronal gap junctions represented as an inhibitory diffusive coupling. To demonstrate cortical behavior over a wide range of distinct brain states, we explore model dynamics in the vicinity of a general-anesthetic-induced transition from “wake” to “coma.” In this region, the system is poised at a codimension-2 point where competing Turing and Hopf instabilities coexist. We model anesthesia as a moderate reduction in inhibitory diffusion, paired with an increase in inhibitory postsynaptic response, producing a coma state that is characterized by emergent low-frequency oscillations whose dynamics is chaotic in time and space. The effect of long-range axonal white-matter connectivity is probed with the inclusion of a single idealized point-to-point connection. We find that the additional excitation from the long-range connection can provoke seizurelike bursts of cortical activity when inhibitory diffusion is weak, but has little impact on an active cortex. Our proposed dynamic mechanism for the origin of anesthetic slow waves complements—and contrasts with—conventional explanations that require cyclic modulation of ion-channel conductances. We postulate that a similar bifurcation mechanism might underpin the slow waves of natural sleep and comment on the possible consequences of chaotic dynamics for memory processing and learning.

QEEG characteristics and spectrum weighted frequency for children diagnosed as autistic spectrum disorder

PubMed Central

2010-01-01

Background Autistic spectrum disorders are a group of neurological and developmental disorders associated with social, communication, sensory, behavioral and cognitive impairments, as well as restricted, repetitive patterns of behavior, activities, or interests. The aim of this study was a) to analyze QEEG findings of autistic patients and to compare the results with data base; and b) to introduce the calculation of spectrum weighted frequency (brain rate) as an indicator of general mental arousal in these patients. Results Results for Q-EEG shows generally increased delta-theta activity in frontal region of the brain. Changes in QEEG pattern appeared to be in a non-linear correlation with maturational processes. Brain rate measured in CZ shows slow brain activity (5. 86) which is significantly lower than normal and corresponds to low general mental arousal. Recent research has shown that autistic disorders have as their basis disturbances of neural connectivity. Neurofeedback seems capable of remediating such disturbances when these data are considered as part of treatment planning. Conclusions Prognosis of this pervasive disorder depends on the intellectual abilities: the better intellectual functioning, the possibilities for life adaptation are higher QEEG shows generally increased delta-theta activity in frontal region of the brain which is related to poor cognitive abilities. Brain rate measured in CZ shows slow brain activity related to under arousal. Pharmacotherapy combined with behavior therapy, social support and especially neurofeedback technique promise slight improvements PMID:20920283

Transcranial Electrical Currents to Probe EEG Brain Rhythms and Memory Consolidation during Sleep in Humans

PubMed Central

Marshall, Lisa; Kirov, Roumen; Brade, Julian; Mölle, Matthias; Born, Jan

2011-01-01

Previously the application of a weak electric anodal current oscillating with a frequency of the sleep slow oscillation (∼0.75 Hz) during non-rapid eye movement sleep (NonREM) sleep boosted endogenous slow oscillation activity and enhanced sleep-associated memory consolidation. The slow oscillations occurring during NonREM sleep and theta oscillations present during REM sleep have been considered of critical relevance for memory formation. Here transcranial direct current stimulation (tDCS) oscillating at 5 Hz, i.e., within the theta frequency range (theta-tDCS) is applied during NonREM and REM sleep. Theta-tDCS during NonREM sleep produced a global decrease in slow oscillatory activity conjoint with a local reduction of frontal slow EEG spindle power (8–12 Hz) and a decrement in consolidation of declarative memory, underlining the relevance of these cortical oscillations for sleep-dependent memory consolidation. In contrast, during REM sleep theta-tDCS appears to increase global gamma (25–45 Hz) activity, indicating a clear brain state-dependency of theta-tDCS. More generally, results demonstrate the suitability of oscillating-tDCS as a tool to analyze functions of endogenous EEG rhythms and underlying endogenous electric fields as well as the interactions between EEG rhythms of different frequencies. PMID:21340034

Fast and slow brain rhythms in rule/expectation violation tasks: focusing on evaluation processes by excluding motor action.

PubMed

Tzur, Gabriel; Berger, Andrea

2009-03-17

Theta rhythm has been connected to ERP components such as the error-related negativity (ERN) and the feedback-related negativity (FRN). The nature of this theta activity is still unclear, that is, whether it is related to error detection, conflict between responses or reinforcement learning processes. We examined slow (e.g., theta) and fast (e.g., gamma) brain rhythms related to rule violation. A time-frequency decomposition analysis on a wide range of frequencies band (0-95 Hz) indicated that the theta activity relates to evaluation processes, regardless of motor/action processes. Similarities between the theta activities found in rule-violation tasks and in tasks eliciting ERN/FRN suggest that this theta activity reflects the operation of general evaluation mechanisms. Moreover, significant effects were found also in fast brain rhythms. These effects might be related to the synchronization between different types of cognitive processes involving the fulfillment of a task (e.g., working memory, visual perception, mathematical calculation, etc.).

Synchronization Properties of Slow Cortical Oscillations

NASA Astrophysics Data System (ADS)

Takekawa, T.; Aoyagi, T.; Fukai, T.

During slow-wave sleep, the brain shows slow oscillatory activity with remarkable long-range synchrony. Intracellular recordings show that the slow oscillation consists of two phases: an textit{up} state and a textit{down} state. Deriving the phase-response function of simplified neuronal systems, we examine the synchronization properties on slow oscillations between the textit{up} state and the textit{down} state. As a result, the strange interaction functions are found in some parameter ranges. These functions indicate that the states with the smaller phase lag than a critical value are all stable.

Electroencephalography as a Tool for Assessment of Brain Ischemic Alterations after Open Heart Operations

PubMed Central

Golukhova, Elena Z.; Polunina, Anna G.; Lefterova, Natalia P.; Begachev, Alexey V.

2011-01-01

Cardiac surgery is commonly associated with brain ischemia. Few studies addressed brain electric activity changes after on-pump operations. Eyes closed EEG was performed in 22 patients (mean age: 45.2 ± 11.2) before and two weeks after valve replacement. Spouses of patients were invited to participate as controls. Generalized increase of beta power most prominent in beta-1 band was an unambiguous pathological sign of postoperative cortex dysfunction, probably, manifesting due to gamma-activity slowing (“beta buzz” symptom). Generalized postoperative increase of delta-1 mean frequency along with increase of slow-wave activity in right posterior region may be hypothesized to be a consequence of intraoperative ischemia as well. At the same time, significant changes of alpha activity were observed in both patient and control groups, and, therefore, may be considered as physiological. Unexpectedly, controls showed prominent increase of electric activity in left temporal region whereas patients were deficient in left hemisphere activity in comparison with controls at postoperative followup. Further research is needed in order to determine the true neurological meaning of the EEG findings after on-pump operations. PMID:21776370

Long-range correlation of the membrane potential in neocortical neurons during slow oscillation

PubMed Central

Volgushev, Maxim; Chauvette, Sylvain; Timofeev, Igor

2012-01-01

Large amplitude slow waves are characteristic for the summary brain activity, recorded as electroencephalogram (EEG) or local field potentials (LFP), during deep stages of sleep and some types of anesthesia. Slow rhythm of the synchronized EEG reflects an alternation of active (depolarized, UP) and silent (hyperpolarized, DOWN) states of neocortical neurons. In neurons, involvement in the generalized slow oscillation results in a long-range synchronization of changes of their membrane potential as well as their firing. Here, we aimed at intracellular analysis of details of this synchronization. We asked which components of neuronal activity exhibit long-range correlations during the synchronized EEG? To answer this question, we made simultaneous intracellular recordings from two to four neocortical neurons in cat neocortex. We studied how correlated is the occurrence of active and silent states, and how correlated are fluctuations of the membrane potential in pairs of neurons located close one to the other or separated by up to 13 mm. We show that strong long-range correlation of the membrane potential was observed only (i) during the slow oscillation but not during periods without the oscillation, (ii) during periods which included transitions between the states but not during within-the-state periods, and (iii) for the low-frequency (<5 Hz) components of membrane potential fluctuations but not for the higher-frequency components (>10 Hz). In contrast to the neurons located several millimeters one from the other, membrane potential fluctuations in neighboring neurons remain strongly correlated during periods without slow oscillation. We conclude that membrane potential correlation in distant neurons is brought about by synchronous transitions between the states, while activity within the states is largely uncorrelated. The lack of the generalized fine-scale synchronization of membrane potential changes in neurons during the active states of slow oscillation may allow individual neurons to selectively engage in short living episodes of correlated activity—a process that may be similar to dynamical formation of neuronal ensembles during activated brain states. PMID:21854963

Role of biological membranes in slow-wave sleep.

PubMed

Karnovsky, M L

1991-02-01

Two involvements of cellular membranes in slow-wave sleep (SWS) are discussed. In the first the endoplasmic reticulum (ER) is focussed upon, and in the second, the plasmalemma, where specific binding sites (receptors?) for promoters of slow-wave sleep are believed to be located. The study concerning the ER focuses on an enzyme in the brain, glucose-6-phosphatase, which, although present at low levels, manifests greatly increased activity during SWS compared to the waking state. The work on the plasmalemma has to do with the specific binding of muramyl peptides, inducers of slow-wave sleep, to various cells, and membrane preparations of various sorts, including those from brain tissue. Such cells as macrophages from mice, B-lymphocytes from human blood, and cells from a cell line (C-6 glioma) have been examined in this context.

Prediction of general mental ability based on neural oscillation measures of sleep.

PubMed

Bódizs, Róbert; Kis, Tamás; Lázár, Alpár Sándor; Havrán, Linda; Rigó, Péter; Clemens, Zsófia; Halász, Péter

2005-09-01

The usual assessment of general mental ability (or intelligence) is based on performance attained in reasoning and problem-solving tasks. Differences in general mental ability have been associated with event-related neural activity patterns of the wakeful working brain or physical, chemical and electrical brain features measured during wakeful resting conditions. Recent evidences suggest that specific sleep electroencephalogram oscillations are related to wakeful cognitive performances. Our aim is to reveal the relationship between non-rapid eye movement sleep-specific oscillations (the slow oscillation, delta activity, slow and fast sleep spindle density, the grouping of slow and fast sleep spindles) and general mental ability assessed by the Raven Progressive Matrices Test (RPMT). The grouping of fast sleep spindles by the cortical slow oscillation in the left frontopolar derivation (Fp1) as well as the density of fast sleep spindles over the right frontal area (Fp2, F4), correlated positively with general mental ability. Data from those selected electrodes that showed the high correlations with general mental ability explained almost 70% of interindividual variance in RPMT scores. Results suggest that individual differences in general mental ability are reflected in fast sleep spindle-related oscillatory activity measured over the frontal cortex.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields.

PubMed

Garcia-Cossio, Eliana; Witkowski, Matthias; Robinson, Stephen E; Cohen, Leonardo G; Birbaumer, Niels; Soekadar, Surjo R

2016-10-15

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0-4Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields

PubMed Central

Garcia-Cossio, Eliana; Witkowski, Matthias; Robinson, Stephen E.; Cohen, Leonardo G.; Birbaumer, Niels; Soekadar, Surjo R.

2016-01-01

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0–4 Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. PMID:26455796

The Fate of Incoming Stimuli during NREM Sleep is Determined by Spindles and the Phase of the Slow Oscillation.

PubMed

Schabus, Manuel; Dang-Vu, Thien Thanh; Heib, Dominik Philip Johannes; Boly, Mélanie; Desseilles, Martin; Vandewalle, Gilles; Schmidt, Christina; Albouy, Geneviève; Darsaud, Annabelle; Gais, Steffen; Degueldre, Christian; Balteau, Evelyne; Phillips, Christophe; Luxen, André; Maquet, Pierre

2012-01-01

The present study aimed at identifying the neurophysiological responses associated with auditory stimulation during non-rapid eye movement (NREM) sleep using simultaneous electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) recordings. It was reported earlier that auditory stimuli produce bilateral activation in auditory cortex, thalamus, and caudate during both wakefulness and NREM sleep. However, due to the spontaneous membrane potential fluctuations cortical responses may be highly variable during NREM. Here we now examine the modulation of cerebral responses to tones depending on the presence or absence of sleep spindles and the phase of the slow oscillation. Thirteen healthy young subjects were scanned successfully during stage 2-4 NREM sleep in the first half of the night in a 3 T scanner. Subjects were not sleep-deprived and sounds were post hoc classified according to (i) the presence of sleep spindles or (ii) the phase of the slow oscillation during (±300 ms) tone delivery. These detected sounds were then entered as regressors of interest in fMRI analyses. Interestingly wake-like responses - although somewhat altered in size and location - persisted during NREM sleep, except during present spindles (as previously published in Dang-Vu et al., 2011) and the negative going phase of the slow oscillation during which responses became less consistent or even absent. While the phase of the slow oscillation did not alter brain responses in primary sensory cortex, it did modulate responses at higher cortical levels. In addition EEG analyses show a distinct N550 response to tones during the presence of light sleep spindles and suggest that in deep NREM sleep the brain is more responsive during the positive going slope of the slow oscillation. The presence of short temporal windows during which the brain is open to external stimuli is consistent with the fact that even during deep sleep meaningful events can be detected. Altogether, our results emphasize the notion that spontaneous fluctuations of brain activity profoundly modify brain responses to external information across all behavioral states, including deep NREM sleep.

Sleep characteristics in the quail Coturnix coturnix.

PubMed

Mexicano, Graciela; Montoya-Loaiza, Bibiana; Ayala-Guerrero, Fructuoso

2014-04-22

As mammals, birds exhibit two sleep phases, slow wave sleep (SWS) and REM (Rapid Eye Movement) sleep characterized by presenting different electrophysiological patterns of brain activity. During SWS a high amplitude slow wave pattern in brain activity is observed. This activity is substituted by a low amplitude fast frequency pattern during REM sleep. Common quail (Coturnix coturnix) is an animal model that has provided information related to different physiological mechanisms present in man. There are reports related to its electrophysiological brain activity, however the sleep characteristics that have been described are not. The objectives of this study is describing the sleep characteristics throughout the nychthemeral cycle of the common quail and consider this bird species as an avian model to analyze the regulatory mechanisms of sleep. Experiments were carried out in implanted exemplars of C. coturnix. Under general anesthesia induced by ether inhalation, stainless steel electrodes were placed to register brain activity from the anterior and posterior areas during 24 continuous hours throughout the sleep-wake cycle. Ocular and motor activities were visually monitored. Quail showed four electrophysiologically and behaviorally different states of vigilance: wakefulness (53.28%), drowsiness (14.27%), slow wave sleep (30.47%) and REM sleep (1.98%). The animals presented 202 REM sleep episodes throughout the nychthemeral cycle. Sleep distribution was polyphasic; however sleep amount was significantly greater during the period corresponding to the night. The number of nocturnal REM sleep episodes was significantly greater than that of diurnal one. The quail C. coturnix shows a polyphasic distribution of sleep; however the amount of this state of vigilance is significantly greater during the nocturnal period. Copyright © 2014 Elsevier Inc. All rights reserved.

Auditory closed-loop stimulation of the sleep slow oscillation enhances memory.

PubMed

Ngo, Hong-Viet V; Martinetz, Thomas; Born, Jan; Mölle, Matthias

2013-05-08

Brain rhythms regulate information processing in different states to enable learning and memory formation. The <1 Hz sleep slow oscillation hallmarks slow-wave sleep and is critical to memory consolidation. Here we show in sleeping humans that auditory stimulation in phase with the ongoing rhythmic occurrence of slow oscillation up states profoundly enhances the slow oscillation rhythm, phase-coupled spindle activity, and, consequently, the consolidation of declarative memory. Stimulation out of phase with the ongoing slow oscillation rhythm remained ineffective. Closed-loop in-phase stimulation provides a straight-forward tool to enhance sleep rhythms and their functional efficacy. Copyright © 2013 Elsevier Inc. All rights reserved.

Age-Dependency of Location of Epileptic Foci in "Continuous Spike-and-Waves during Sleep": A Parallel to the Posterior-Anterior Trajectory of Slow Wave Activity.

PubMed

Bölsterli Heinzle, Bigna Katrin; Bast, Thomas; Critelli, Hanne; Huber, Reto; Schmitt, Bernhard

2017-02-01

Epileptic encephalopathy with continuous spike-and-waves during sleep (CSWS) occurs during childhood and is characterized by an activation of spike wave complexes during slow wave sleep. The location of epileptic foci is variable, as is etiology. A relationship between the epileptic focus and age has been shown in various focal epilepsies following a posterior-anterior trajectory, and a link to brain maturation has been proposed. We hypothesize that in CSWS, maximal spike wave activity, corresponding to the epileptic focus, is related to age and shows a posterior-anterior evolution. In a retrospective cross-sectional study on CSWS (22 EEGs of 22 patients aged 3.1–13.5 years), the location of the epileptic focus is related to age and follows a posterior-anterior course. Younger patients are more likely to have posterior foci than older ones. We propose that the posterior-anterior trajectory of maximal spike waves in CSWS might reflect maturational changes of maximal expression of sleep slow waves, which follow a comparable course. Epileptic spike waves, that is, “hyper-synchronized slow waves” may occur at the place where the highest and therefore most synchronized slow waves meet brain tissue with an increased susceptibility to synchronization. Georg Thieme Verlag KG Stuttgart · New York.

The Effects of Caffeine on Sleep and Maturational Markers in the Rat

PubMed Central

Olini, Nadja; Kurth, Salomé; Huber, Reto

2013-01-01

Adolescence is a critical period for brain maturation during which a massive reorganization of cortical connectivity takes place. In humans, slow wave activity (<4.5 Hz) during NREM sleep was proposed to reflect cortical maturation which relies on use-dependent processes. A stimulant like caffeine, whose consumption has recently increased especially in adolescents, is known to affect sleep wake regulation. The goal of this study was to establish a rat model allowing to assess the relationship between cortical maturation and sleep and to further investigate how these parameters are affected by caffeine consumption. To do so, we assessed sleep and markers of maturation by electrophysiological recordings, behavioral and structural readouts in the juvenile rat. Our results show that sleep slow wave activity follows a similar inverted U-shape trajectory as already known in humans. Caffeine treatment exerted short-term stimulating effects and altered the trajectory of slow wave activity. Moreover, caffeine affected behavioral and structural markers of maturation. Thus, caffeine consumption during a critical developmental period shows long lasting effects on sleep and brain maturation. PMID:24023748

Unexpected Events Induce Motor Slowing via a Brain Mechanism for Action-Stopping with Global Suppressive Effects

PubMed Central

Aron, Adam R.

2013-01-01

When an unexpected event occurs in everyday life (e.g., a car honking), one experiences a slowing down of ongoing action (e.g., of walking into the street). Motor slowing following unexpected events is a ubiquitous phenomenon, both in laboratory experiments as well as such everyday situations, yet the underlying mechanism is unknown. We hypothesized that unexpected events recruit the same inhibition network in the brain as does complete cancellation of an action (i.e., action-stopping). Using electroencephalography and independent component analysis in humans, we show that a brain signature of successful outright action-stopping also exhibits activity following unexpected events, and more so in blocks with greater motor slowing. Further, using transcranial magnetic stimulation to measure corticospinal excitability, we show that an unexpected event has a global motor suppressive effect, just like outright action-stopping. Thus, unexpected events recruit a common mechanism with outright action-stopping, moreover with global suppressive effects. These findings imply that we can now leverage the considerable extant knowledge of the neural architecture and functional properties of the stopping system to better understand the processing of unexpected events, including perhaps how they induce distraction via global suppression. PMID:24259571

Network-dependent modulation of brain activity during sleep.

PubMed

Watanabe, Takamitsu; Kan, Shigeyuki; Koike, Takahiko; Misaki, Masaya; Konishi, Seiki; Miyauchi, Satoru; Miyahsita, Yasushi; Masuda, Naoki

2014-09-01

Brain activity dynamically changes even during sleep. A line of neuroimaging studies has reported changes in functional connectivity and regional activity across different sleep stages such as slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. However, it remains unclear whether and how the large-scale network activity of human brains changes within a given sleep stage. Here, we investigated modulation of network activity within sleep stages by applying the pairwise maximum entropy model to brain activity obtained by functional magnetic resonance imaging from sleeping healthy subjects. We found that the brain activity of individual brain regions and functional interactions between pairs of regions significantly increased in the default-mode network during SWS and decreased during REM sleep. In contrast, the network activity of the fronto-parietal and sensory-motor networks showed the opposite pattern. Furthermore, in the three networks, the amount of the activity changes throughout REM sleep was negatively correlated with that throughout SWS. The present findings suggest that the brain activity is dynamically modulated even in a sleep stage and that the pattern of modulation depends on the type of the large-scale brain networks. Copyright © 2014 Elsevier Inc. All rights reserved.

A transition in brain state during propofol-induced unconsciousness.

PubMed

Mukamel, Eran A; Pirondini, Elvira; Babadi, Behtash; Wong, Kin Foon Kevin; Pierce, Eric T; Harrell, P Grace; Walsh, John L; Salazar-Gomez, Andres F; Cash, Sydney S; Eskandar, Emad N; Weiner, Veronica S; Brown, Emery N; Purdon, Patrick L

2014-01-15

Rhythmic oscillations shape cortical dynamics during active behavior, sleep, and general anesthesia. Cross-frequency phase-amplitude coupling is a prominent feature of cortical oscillations, but its role in organizing conscious and unconscious brain states is poorly understood. Using high-density EEG and intracranial electrocorticography during gradual induction of propofol general anesthesia in humans, we discovered a rapid drug-induced transition between distinct states with opposite phase-amplitude coupling and different cortical source distributions. One state occurs during unconsciousness and may be similar to sleep slow oscillations. A second state occurs at the loss or recovery of consciousness and resembles an enhanced slow cortical potential. These results provide objective electrophysiological landmarks of distinct unconscious brain states, and could be used to help improve EEG-based monitoring for general anesthesia.

Resting-state slow wave power, healthy aging and cognitive performance.

PubMed

Vlahou, Eleni L; Thurm, Franka; Kolassa, Iris-Tatjana; Schlee, Winfried

2014-05-29

Cognitive functions and spontaneous neural activity show significant changes over the life-span, but the interrelations between age, cognition and resting-state brain oscillations are not well understood. Here, we assessed performance on the Trail Making Test and resting-state magnetoencephalographic (MEG) recordings from 53 healthy adults (18-89 years old) to investigate associations between age-dependent changes in spontaneous oscillatory activity and cognitive performance. Results show that healthy aging is accompanied by a marked and linear decrease of resting-state activity in the slow frequency range (0.5-6.5 Hz). The effects of slow wave power on cognitive performance were expressed as interactions with age: For older (>54 years), but not younger participants, enhanced delta and theta power in temporal and central regions was positively associated with perceptual speed and executive functioning. Consistent with previous work, these findings substantiate further the important role of slow wave oscillations in neurocognitive function during healthy aging.

Once upon a (slow) time in the land of recurrent neuronal networks….

PubMed

Huang, Chengcheng; Doiron, Brent

2017-10-01

The brain must both react quickly to new inputs as well as store a memory of past activity. This requires biology that operates over a vast range of time scales. Fast time scales are determined by the kinetics of synaptic conductances and ionic channels; however, the mechanics of slow time scales are more complicated. In this opinion article we review two distinct network-based mechanisms that impart slow time scales in recurrently coupled neuronal networks. The first is in strongly coupled networks where the time scale of the internally generated fluctuations diverges at the transition between stable and chaotic firing rate activity. The second is in networks with finitely many members where noise-induced transitions between metastable states appear as a slow time scale in the ongoing network firing activity. We discuss these mechanisms with an emphasis on their similarities and differences. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuronal oscillations on an ultra-slow timescale: daily rhythms in electrical activity and gene expression in the mammalian master circadian clockwork.

PubMed

Belle, Mino D C; Diekman, Casey O

2018-02-03

Neuronal oscillations of the brain, such as those observed in the cortices and hippocampi of behaving animals and humans, span across wide frequency bands, from slow delta waves (0.1 Hz) to ultra-fast ripples (600 Hz). Here, we focus on ultra-slow neuronal oscillators in the hypothalamic suprachiasmatic nuclei (SCN), the master daily clock that operates on interlocking transcription-translation feedback loops to produce circadian rhythms in clock gene expression with a period of near 24 h (< 0.001 Hz). This intracellular molecular clock interacts with the cell's membrane through poorly understood mechanisms to drive the daily pattern in the electrical excitability of SCN neurons, exhibiting an up-state during the day and a down-state at night. In turn, the membrane activity feeds back to regulate the oscillatory activity of clock gene programs. In this review, we emphasise the circadian processes that drive daily electrical oscillations in SCN neurons, and highlight how mathematical modelling contributes to our increasing understanding of circadian rhythm generation, synchronisation and communication within this hypothalamic region and across other brain circuits. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Slow oscillating transcranial direct current stimulation during sleep has a sleep-stabilizing effect in chronic insomnia: a pilot study.

PubMed

Saebipour, Mohammad R; Joghataei, Mohammad T; Yoonessi, Ali; Sadeghniiat-Haghighi, Khosro; Khalighinejad, Nima; Khademi, Soroush

2015-10-01

Recent evidence suggests that lack of slow-wave activity may play a fundamental role in the pathogenesis of insomnia. Pharmacological approaches and brain stimulation techniques have recently offered solutions for increasing slow-wave activity during sleep. We used slow (0.75 Hz) oscillatory transcranial direct current stimulation during stage 2 of non-rapid eye movement sleeping insomnia patients for resonating their brain waves to the frequency of sleep slow-wave. Six patients diagnosed with either sleep maintenance or non-restorative sleep insomnia entered the study. After 1 night of adaptation and 1 night of baseline polysomnography, patients randomly received sham or real stimulation on the third and fourth night of the experiment. Our preliminary results show that after termination of stimulations (sham or real), slow oscillatory transcranial direct current stimulation increased the duration of stage 3 of non-rapid eye movement sleep by 33 ± 26 min (P = 0.026), and decreased stage 1 of non-rapid eye movement sleep duration by 22 ± 17.7 min (P = 0.028), compared with sham. Slow oscillatory transcranial direct current stimulation decreased stage 1 of non-rapid eye movement sleep and wake time after sleep-onset durations, together, by 55.4 ± 51 min (P = 0.045). Slow oscillatory transcranial direct current stimulation also increased sleep efficiency by 9 ± 7% (P = 0.026), and probability of transition from stage 2 to stage 3 of non-rapid eye movement sleep by 20 ± 17.8% (P = 0.04). Meanwhile, slow oscillatory transcranial direct current stimulation decreased transitions from stage 2 of non-rapid eye movement sleep to wake by 12 ± 6.7% (P = 0.007). Our preliminary results suggest a sleep-stabilizing role for the intervention, which may mimic the effect of sleep slow-wave-enhancing drugs. © 2015 European Sleep Research Society.

Initiation of sleep-dependent cortical-hippocampal correlations at wakefulness-sleep transition.

PubMed

Haggerty, Daniel C; Ji, Daoyun

2014-10-01

Sleep is involved in memory consolidation. Current theories propose that sleep-dependent memory consolidation requires active communication between the hippocampus and neocortex. Indeed, it is known that neuronal activities in the hippocampus and various neocortical areas are correlated during slow-wave sleep. However, transitioning from wakefulness to slow-wave sleep is a gradual process. How the hippocampal-cortical correlation is established during the wakefulness-sleep transition is unknown. By examining local field potentials and multiunit activities in the rat hippocampus and visual cortex, we show that the wakefulness-sleep transition is characterized by sharp-wave ripple events in the hippocampus and high-voltage spike-wave events in the cortex, both of which are accompanied by highly synchronized multiunit activities in the corresponding area. Hippocampal ripple events occur earlier than the cortical high-voltage spike-wave events, and hippocampal ripple incidence is attenuated by the onset of cortical high-voltage spike waves. This attenuation leads to a temporary weak correlation in the hippocampal-cortical multiunit activities, which eventually evolves to a strong correlation as the brain enters slow-wave sleep. The results suggest that the hippocampal-cortical correlation is established through a concerted, two-step state change that first synchronizes the neuronal firing within each brain area and then couples the synchronized activities between the two regions. Copyright © 2014 the American Physiological Society.

Brain penetration of telmisartan, a unique centrally acting angiotensin II type 1 receptor blocker, studied by PET in conscious rhesus macaques.

PubMed

Noda, Akihiro; Fushiki, Hiroshi; Murakami, Yoshihiro; Sasaki, Hiroshi; Miyoshi, Sosuke; Kakuta, Hirotoshi; Nishimura, Shintaro

2012-11-01

Telmisartan is a widely used, long-acting antihypertensive agent. Known to be a selective angiotensin II type 1 (AT(1)) receptor (AT(1)R) blocker (ARB), telmisartan acts as a partial agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and inhibits centrally mediated effects of angiotensin II in rats following peripheral administration, although the brain penetration of telmisartan remains unclear. We investigated the brain concentration and localization of telmisartan using (11)C-labeled telmisartan and positron emission tomography (PET) in conscious rhesus macaques. Three male rhesus macaques were bolus intravenously administered [(11)C]telmisartan either alone or as a mixture with unlabeled telmisartan (1mg/kg). Dynamic PET images were acquired for 95min following administration. Blood samples were collected for the analysis of plasma concentration and metabolites, and brain and plasma concentrations were calculated from detected radioactivity using the specific activity of the administered drug preparation, in which whole blood radioactivity was used for the correction of intravascular blood radioactivity in brain. Telmisartan penetrated into the brain little but enough to block AT(1)R and showed a consistently increasing brain/plasma ratio within the PET scanning period, suggesting slow clearance of the compound from the brain compared to the plasma clearance. Brain/plasma ratios at 30, 60, and 90min were 0.06, 0.13, and 0.18, respectively. No marked localization according to the AT(1)R distribution was noted over the entire brain, even on tracer alone dosing. Telmisartan penetrated into the brain enough to block AT(1)R and showed a slow clearance from the brain in conscious rhesus macaques, supporting the long-acting and central responses of telmisartan as a unique property among ARBs. Copyright © 2012 Elsevier Inc. All rights reserved.

Role of local network oscillations in resting-state functional connectivity.

PubMed

Cabral, Joana; Hugues, Etienne; Sporns, Olaf; Deco, Gustavo

2011-07-01

Spatio-temporally organized low-frequency fluctuations (<0.1 Hz), observed in BOLD fMRI signal during rest, suggest the existence of underlying network dynamics that emerge spontaneously from intrinsic brain processes. Furthermore, significant correlations between distinct anatomical regions-or functional connectivity (FC)-have led to the identification of several widely distributed resting-state networks (RSNs). This slow dynamics seems to be highly structured by anatomical connectivity but the mechanism behind it and its relationship with neural activity, particularly in the gamma frequency range, remains largely unknown. Indeed, direct measurements of neuronal activity have revealed similar large-scale correlations, particularly in slow power fluctuations of local field potential gamma frequency range oscillations. To address these questions, we investigated neural dynamics in a large-scale model of the human brain's neural activity. A key ingredient of the model was a structural brain network defined by empirically derived long-range brain connectivity together with the corresponding conduction delays. A neural population, assumed to spontaneously oscillate in the gamma frequency range, was placed at each network node. When these oscillatory units are integrated in the network, they behave as weakly coupled oscillators. The time-delayed interaction between nodes is described by the Kuramoto model of phase oscillators, a biologically-based model of coupled oscillatory systems. For a realistic setting of axonal conduction speed, we show that time-delayed network interaction leads to the emergence of slow neural activity fluctuations, whose patterns correlate significantly with the empirically measured FC. The best agreement of the simulated FC with the empirically measured FC is found for a set of parameters where subsets of nodes tend to synchronize although the network is not globally synchronized. Inside such clusters, the simulated BOLD signal between nodes is found to be correlated, instantiating the empirically observed RSNs. Between clusters, patterns of positive and negative correlations are observed, as described in experimental studies. These results are found to be robust with respect to a biologically plausible range of model parameters. In conclusion, our model suggests how resting-state neural activity can originate from the interplay between the local neural dynamics and the large-scale structure of the brain. Copyright © 2011 Elsevier Inc. All rights reserved.

[Are subcortical signs in the EEG a reliable indication of brain stem displacement and impaction processes by intracranial space-occupying processes? A comparative computer tomography-electroencephalography study].

PubMed

Zettler, H; Järisch, M; Leonhard, T

1985-01-01

Within the scope of an elektroencephalographic-computertomographic comperative study carried out in 430 patients, the concurrence of secondary brain stem damage due to mass displacement and herniation processes and parroxysmal generalised slow activity in the EEG ("intermittant frontal delta rhythms", "projected discharges", "subcortical signs") in intracranial space-occupying processes were studied among others. The occurrence of the EEG pattern was independent of the presence of brain stem displacements in about 20 and 25 per cent, respectively, of the 152 patients with supratentorial space occupations. The absence of the characteristics on 80 per cent of the patients with clear CT criteria for a secondary brain stem impairment shows that it is not suitable as a warning sign of an imminent intracranial decompensation and that in particular from the non-occurrence in the EEG no contribution to the operative risk and to the choice of the time of the operation can be derived. A relation between the occurrence of paroxysmal slow activity and the acuity of the course of the disease or the degree of malignity of cerebral tumours could not be verified. Possible causes of the inconstant occurrence of this EEG pattern in brain stem alterations are discussed.

Spatiotemporal Dissociation of Brain Activity Underlying Subjective Awareness, Objective Performance and Confidence

PubMed Central

Li, Qi; Hill, Zachary

2014-01-01

Despite intense recent research, the neural correlates of conscious visual perception remain elusive. The most established paradigm for studying brain mechanisms underlying conscious perception is to keep the physical sensory inputs constant and identify brain activities that correlate with the changing content of conscious awareness. However, such a contrast based on conscious content alone would not only reveal brain activities directly contributing to conscious perception, but also include brain activities that precede or follow it. To address this issue, we devised a paradigm whereby we collected, trial-by-trial, measures of objective performance, subjective awareness, and the confidence level of subjective awareness. Using magnetoencephalography recordings in healthy human volunteers, we dissociated brain activities underlying these different cognitive phenomena. Our results provide strong evidence that widely distributed slow cortical potentials (SCPs) correlate with subjective awareness, even after the effects of objective performance and confidence were both removed. The SCP correlate of conscious perception manifests strongly in its waveform, phase, and power. In contrast, objective performance and confidence were both contributed by relatively transient brain activity. These results shed new light on the brain mechanisms of conscious, unconscious, and metacognitive processing. PMID:24647958

Urodynamic function during sleep-like brain states in urethane anesthetized rats.

PubMed

Crook, J; Lovick, T

2016-01-28

The aim was to investigate urodynamic parameters and functional excitability of the periaqueductal gray matter (PAG) during changes in sleep-like brain states in urethane anesthetized rats. Simultaneous recordings of detrusor pressure, external urethral sphincter (EUS) electromyogram (EMG), cortical electroencephalogram (EEG), and single-unit activity in the PAG were made during repeated voiding induced by continuous infusion of saline into the bladder. The EEG cycled between synchronized, high-amplitude slow wave activity (SWA) and desynchronized low-amplitude fast activity similar to slow wave and 'activated' sleep-like brain states. During (SWA, 0.5-1.5 Hz synchronized oscillation of the EEG waveform) voiding became more irregular than in the 'activated' brain state (2-5 Hz low-amplitude desynchronized EEG waveform) and detrusor void pressure threshold, void volume threshold and the duration of bursting activity in the external urethral sphincter EMG were raised. The spontaneous firing rate of 23/52 neurons recorded within the caudal PAG and adjacent tegmentum was linked to the EEG state, with the majority of responsive cells (92%) firing more slowly during SWA. Almost a quarter of the cells recorded (12/52) showed phasic changes in firing rate that were linked to the occurrence of voids. Inhibition (n=6), excitation (n=4) or excitation/inhibition (n=2) was seen. The spontaneous firing rate of 83% of the micturition-responsive cells was sensitive to changes in EEG state. In nine of the 12 responsive cells (75%) the responses were reduced during SWA. We propose that during different sleep-like brain states changes in urodynamic properties occur which may be linked to changing excitability of the micturition circuitry in the periaqueductal gray. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Task-dependent activation of distinct fast and slow(er) motor pathways during motor imagery.

PubMed

Keller, Martin; Taube, Wolfgang; Lauber, Benedikt

2018-02-22

Motor imagery and actual movements share overlapping activation of brain areas but little is known about task-specific activation of distinct motor pathways during mental simulation of movements. For real contractions, it was demonstrated that the slow(er) motor pathways are activated differently in ballistic compared to tonic contractions but it is unknown if this also holds true for imagined contractions. The aim of the present study was to assess the activity of fast and slow(er) motor pathways during mentally simulated movements of ballistic and tonic contractions. H-reflexes were conditioned with transcranial magnetic stimulation at different interstimulus intervals to assess the excitability of fast and slow(er) motor pathways during a) the execution of tonic and ballistic contractions, b) motor imagery of these contraction types, and c) at rest. In contrast to the fast motor pathways, the slow(er) pathways displayed a task-specific activation: for imagined ballistic as well as real ballistic contractions, the activation was reduced compared to rest whereas enhanced activation was found for imagined tonic and real tonic contractions. This study provides evidence that the excitability of fast and slow(er) motor pathways during motor imagery resembles the activation pattern observed during real contractions. The findings indicate that motor imagery results in task- and pathway-specific subliminal activation of distinct subsets of neurons in the primary motor cortex. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

A Comprehensive Analysis of the Correlations between Resting-State Oscillations in Multiple-Frequency Bands and Big Five Traits

PubMed Central

Ikeda, Shigeyuki; Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Yokoyama, Ryoichi; Kotozaki, Yuka; Nakagawa, Seishu; Sekiguchi, Atsushi; Iizuka, Kunio; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Miyauchi, Carlos Makoto; Sakaki, Kohei; Nozawa, Takayuki; Yokota, Susumu; Magistro, Daniele; Kawashima, Ryuta

2017-01-01

Recently, the association between human personality traits and resting-state brain activity has gained interest in neuroimaging studies. However, it remains unclear if Big Five personality traits are represented in frequency bands (~0.25 Hz) of resting-state functional magnetic resonance imaging (fMRI) activity. Based on earlier neurophysiological studies, we investigated the correlation between the five personality traits assessed by the NEO Five-Factor Inventory (NEO-FFI), and the fractional amplitude of low-frequency fluctuation (fALFF) at four distinct frequency bands (slow-5 (0.01–0.027 Hz), slow-4 (0.027–0.073 Hz), slow-3 (0.073–0.198 Hz) and slow-2 (0.198–0.25 Hz)). We enrolled 835 young subjects and calculated the correlations of resting-state fMRI signals using a multiple regression analysis. We found a significant and consistent correlation between fALFF and the personality trait of extraversion at all frequency bands. Furthermore, significant correlations were detected in distinct brain regions for each frequency band. This finding supports the frequency-specific spatial representations of personality traits as previously suggested. In conclusion, our data highlight an association between human personality traits and fALFF at four distinct frequency bands. PMID:28680397

A Comprehensive Analysis of the Correlations between Resting-State Oscillations in Multiple-Frequency Bands and Big Five Traits.

PubMed

Ikeda, Shigeyuki; Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Yokoyama, Ryoichi; Kotozaki, Yuka; Nakagawa, Seishu; Sekiguchi, Atsushi; Iizuka, Kunio; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Miyauchi, Carlos Makoto; Sakaki, Kohei; Nozawa, Takayuki; Yokota, Susumu; Magistro, Daniele; Kawashima, Ryuta

2017-01-01

Recently, the association between human personality traits and resting-state brain activity has gained interest in neuroimaging studies. However, it remains unclear if Big Five personality traits are represented in frequency bands (~0.25 Hz) of resting-state functional magnetic resonance imaging (fMRI) activity. Based on earlier neurophysiological studies, we investigated the correlation between the five personality traits assessed by the NEO Five-Factor Inventory (NEO-FFI), and the fractional amplitude of low-frequency fluctuation (fALFF) at four distinct frequency bands (slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), slow-3 (0.073-0.198 Hz) and slow-2 (0.198-0.25 Hz)). We enrolled 835 young subjects and calculated the correlations of resting-state fMRI signals using a multiple regression analysis. We found a significant and consistent correlation between fALFF and the personality trait of extraversion at all frequency bands. Furthermore, significant correlations were detected in distinct brain regions for each frequency band. This finding supports the frequency-specific spatial representations of personality traits as previously suggested. In conclusion, our data highlight an association between human personality traits and fALFF at four distinct frequency bands.

Slow Spatial Recruitment of Neocortex during Secondarily Generalized Seizures and Its Relation to Surgical Outcome

PubMed Central

Martinet, Louis-Emmanuel; Ahmed, Omar J.; Lepage, Kyle Q.; Cash, Sydney S.

2015-01-01

Understanding the spatiotemporal dynamics of brain activity is crucial for inferring the underlying synaptic and nonsynaptic mechanisms of brain dysfunction. Focal seizures with secondary generalization are traditionally considered to begin in a limited spatial region and spread to connected areas, which can include both pathological and normal brain tissue. The mechanisms underlying this spread are important to our understanding of seizures and to improve therapies for surgical intervention. Here we study the properties of seizure recruitment—how electrical brain activity transitions to large voltage fluctuations characteristic of spike-and-wave seizures. We do so using invasive subdural electrode arrays from a population of 16 patients with pharmacoresistant epilepsy. We find an average delay of ∼30 s for a broad area of cortex (8 × 8 cm) to be recruited into the seizure, at an estimated speed of ∼4 mm/s. The spatiotemporal characteristics of recruitment reveal two categories of patients: one in which seizure recruitment of neighboring cortical regions follows a spatially organized pattern consistent from seizure to seizure, and a second group without consistent spatial organization of activity during recruitment. The consistent, organized recruitment correlates with a more regular, compared with small-world, connectivity pattern in simulation and successful surgical treatment of epilepsy. We propose that an improved understanding of how the seizure recruits brain regions into large amplitude voltage fluctuations provides novel information to improve surgical treatment of epilepsy and highlights the slow spread of massive local activity across a vast extent of cortex during seizure. PMID:26109670

Changes of brain response induced by simulated weightlessness

NASA Astrophysics Data System (ADS)

Wei, Jinhe; Yan, Gongdong; Guan, Zhiqiang

The characteristics change of brain response was studied during 15° head-down tilt (HDT) comparing with 45° head-up tilt (HUT). The brain responses evaluated included the EEG power spectra change at rest and during mental arithmetic, and the event-related potentials (ERPs) of somatosensory, selective attention and mental arithmetic activities. The prominent feature of brain response change during HDT revealed that the brain function was inhibited to some extent. Such inhibition included that the significant increment of "40Hz" activity during HUT arithmetic almost disappeared during HDT arithmetic, and that the positive-potential effect induced by HDT presented in all kinds of ERPs measured, but the slow negative wave reflecting mental arithmetic and memory process was elongated. These data suggest that the brain function be affected profoundly by the simulated weightlessness, therefore, the brain function change during space flight should be studied systematically.

Residual number processing in dyscalculia☆

PubMed Central

Cappelletti, Marinella; Price, Cathy J.

2013-01-01

Developmental dyscalculia – a congenital learning disability in understanding numerical concepts – is typically associated with parietal lobe abnormality. However, people with dyscalculia often retain some residual numerical abilities, reported in studies that otherwise focused on abnormalities in the dyscalculic brain. Here we took a different perspective by focusing on brain regions that support residual number processing in dyscalculia. All participants accurately performed semantic and categorical colour-decision tasks with numerical and non-numerical stimuli, with adults with dyscalculia performing slower than controls in the number semantic tasks only. Structural imaging showed less grey-matter volume in the right parietal cortex in people with dyscalculia relative to controls. Functional MRI showed that accurate number semantic judgements were maintained by parietal and inferior frontal activations that were common to adults with dyscalculia and controls, with higher activation for participants with dyscalculia than controls in the right superior frontal cortex and the left inferior frontal sulcus. Enhanced activation in these frontal areas was driven by people with dyscalculia who made faster rather than slower numerical decisions; however, activation could not be accounted for by response times per se, because it was greater for fast relative to slow dyscalculics but not greater for fast controls relative to slow dyscalculics. In conclusion, our results reveal two frontal brain regions that support efficient number processing in dyscalculia. PMID:24266008

Residual number processing in dyscalculia.

PubMed

Cappelletti, Marinella; Price, Cathy J

2014-01-01

Developmental dyscalculia - a congenital learning disability in understanding numerical concepts - is typically associated with parietal lobe abnormality. However, people with dyscalculia often retain some residual numerical abilities, reported in studies that otherwise focused on abnormalities in the dyscalculic brain. Here we took a different perspective by focusing on brain regions that support residual number processing in dyscalculia. All participants accurately performed semantic and categorical colour-decision tasks with numerical and non-numerical stimuli, with adults with dyscalculia performing slower than controls in the number semantic tasks only. Structural imaging showed less grey-matter volume in the right parietal cortex in people with dyscalculia relative to controls. Functional MRI showed that accurate number semantic judgements were maintained by parietal and inferior frontal activations that were common to adults with dyscalculia and controls, with higher activation for participants with dyscalculia than controls in the right superior frontal cortex and the left inferior frontal sulcus. Enhanced activation in these frontal areas was driven by people with dyscalculia who made faster rather than slower numerical decisions; however, activation could not be accounted for by response times per se, because it was greater for fast relative to slow dyscalculics but not greater for fast controls relative to slow dyscalculics. In conclusion, our results reveal two frontal brain regions that support efficient number processing in dyscalculia.

AMPK modulates tissue and organismal aging in a cell-non-autonomous manner

PubMed Central

Ulgherait, Matthew; Rana, Anil; Rera, Michael; Graniel, Jacqueline; Walker, David W.

2014-01-01

AMPK exerts pro-longevity effects in diverse species; however, the tissue-specific mechanisms involved are poorly understood. Here, we show that up-regulation of AMPK in the adult Drosophila nervous system induces autophagy both in the brain and also in the intestinal epithelium. Induction of autophagy is linked to improved intestinal homeostasis during aging and extended lifespan. Neuronal up-regulation of the autophagy-specific protein kinase Atg1 is both necessary and sufficient to induce these inter-tissue effects during aging and to prolong lifespan. Furthermore, up-regulation of AMPK in the adult intestine induces autophagy both cell autonomously and non-autonomously in the brain, slows systemic aging and prolongs lifespan. We show that the organism-wide response to tissue-specific AMPK/Atg1 activation is linked to reduced insulin-like peptide levels in the brain and a systemic increase in 4E-BP expression. Together, these results reveal that localized activation of AMPK and/or Atg1 in key tissues can slow aging in a cell-non-autonomous manner. PMID:25199830

Flurazepam

MedlinePlus

... by slowing activity in the brain to allow sleep. ... nights after you stop taking the medication.Your sleep problems should improve within 7 to 10 days ... start taking flurazepam. Call your doctor if your sleep problems do not improve during this time, if ...

Estazolam

MedlinePlus

... by slowing activity in the brain to allow sleep. ... full night after you take the medication.Your sleep problems should improve within 7 to 10 days ... start taking estazolam. Call your doctor if your sleep problems do not improve during this time, if ...

Prefrontal atrophy, disrupted NREM slow waves, and impaired hippocampal-dependent memory in aging

PubMed Central

Mander, Bryce A.; Rao, Vikram; Lu, Brandon; Saletin, Jared M.; Lindquist, John R.; Ancoli-Israel, Sonia; Jagust, William; Walker, Matthew P.

2014-01-01

Aging has independently been associated with regional brain atrophy, reduced non-rapid eye movement (NREM) slow-wave activity (SWA), and impaired long-term retention of episodic memories. However, that the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. Here, we show that age-related medial prefrontal cortex (mPFC) grey-matter atrophy is associated with reduced NREM SWA activity in older adults, the extent to which statistically mediates the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represent a novel contributing factor to age-related cognitive decline in later life. PMID:23354332

Slow waves, sharp waves, ripples, and REM in sleeping dragons.

PubMed

Shein-Idelson, Mark; Ondracek, Janie M; Liaw, Hua-Peng; Reiter, Sam; Laurent, Gilles

2016-04-29

Sleep has been described in animals ranging from worms to humans. Yet the electrophysiological characteristics of brain sleep, such as slow-wave (SW) and rapid eye movement (REM) activities, are thought to be restricted to mammals and birds. Recording from the brain of a lizard, the Australian dragon Pogona vitticeps, we identified SW and REM sleep patterns, thus pushing back the probable evolution of these dynamics at least to the emergence of amniotes. The SW and REM sleep patterns that we observed in lizards oscillated continuously for 6 to 10 hours with a period of ~80 seconds. The networks controlling SW-REM antagonism in amniotes may thus originate from a common, ancient oscillator circuit. Lizard SW dynamics closely resemble those observed in rodent hippocampal CA1, yet they originate from a brain area, the dorsal ventricular ridge, that has no obvious hodological similarity with the mammalian hippocampus. Copyright © 2016, American Association for the Advancement of Science.

Brain state-dependent recruitment of high-frequency oscillations in the human hippocampus.

PubMed

Billeke, Pablo; Ossandon, Tomas; Stockle, Marcelo; Perrone-Bertolotti, Marcela; Kahane, Philippe; Lachaux, Jean-Philippe; Fuentealba, Pablo

2017-09-01

Ripples are high-frequency bouts of coordinated hippocampal activity believed to be crucial for information transfer and memory formation. We used intracortical macroelectrodes to record neural activity in the human hippocampus of awake subjects undergoing surgical treatment for refractory epilepsy and distinguished two populations of ripple episodes based on their frequency spectrum. The phase-coupling of one population, slow ripples (90-110 Hz), to cortical delta oscillations was differentially modulated by cognitive task; whereas the second population, fast ripples (130-170 Hz), was not seemingly correlated to local neural activity. Furthermore, as cognitive tasks changed, the ongoing coordination of neural activity associated to slow ripples progressively augmented along the parahippocampal axis. Thus, during resting states, slow ripples were coordinated in restricted hippocampal territories; whereas during active states, such as attentionally-demanding tasks, high frequency activity emerged across the hippocampus and parahippocampal cortex, that was synchronized with slow ripples, consistent with ripples supporting information transfer and coupling anatomically distant regions. Hence, our results provide further evidence of neural diversity in hippocampal high-frequency oscillations and their association to cognitive processing in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

Slow Breathing and Hypoxic Challenge: Cardiorespiratory Consequences and Their Central Neural Substrates

PubMed Central

Critchley, Hugo D.; Nicotra, Alessia; Chiesa, Patrizia A.; Nagai, Yoko; Gray, Marcus A.; Minati, Ludovico; Bernardi, Luciano

2015-01-01

Controlled slow breathing (at 6/min, a rate frequently adopted during yoga practice) can benefit cardiovascular function, including responses to hypoxia. We tested the neural substrates of cardiorespiratory control in humans during volitional controlled breathing and hypoxic challenge using functional magnetic resonance imaging (fMRI). Twenty healthy volunteers were scanned during paced (slow and normal rate) breathing and during spontaneous breathing of normoxic and hypoxic (13% inspired O2) air. Cardiovascular and respiratory measures were acquired concurrently, including beat-to-beat blood pressure from a subset of participants (N = 7). Slow breathing was associated with increased tidal ventilatory volume. Induced hypoxia raised heart rate and suppressed heart rate variability. Within the brain, slow breathing activated dorsal pons, periaqueductal grey matter, cerebellum, hypothalamus, thalamus and lateral and anterior insular cortices. Blocks of hypoxia activated mid pons, bilateral amygdalae, anterior insular and occipitotemporal cortices. Interaction between slow breathing and hypoxia was expressed in ventral striatal and frontal polar activity. Across conditions, within brainstem, dorsal medullary and pontine activity correlated with tidal volume and inversely with heart rate. Activity in rostroventral medulla correlated with beat-to-beat blood pressure and heart rate variability. Widespread insula and striatal activity tracked decreases in heart rate, while subregions of insular cortex correlated with momentary increases in tidal volume. Our findings define slow breathing effects on central and cardiovascular responses to hypoxic challenge. They highlight the recruitment of discrete brainstem nuclei to cardiorespiratory control, and the engagement of corticostriatal circuitry in support of physiological responses that accompany breathing regulation during hypoxic challenge. PMID:25973923

Higher-Order Activity beyond the Word Level: Cortical Dynamics of Simple Transitive Sentence Comprehension

ERIC Educational Resources Information Center

Martin-Loeches, M.; Casado, P.; Hinojosa, J.A.; Carretie, L.; Munoz, F.; Pozo, M.A.

2005-01-01

Slow electrophysiological effects, which fluctuate throughout the course of a sentence, independent of transient responses to individual words, have been reported. However, this type of activity has scarcely been studied, and with only limited use of electrophysiological information, so that the brain areas in which these variations originate have…

Spontaneous activity of single neurones in the hypothalamus of rabbits during sleep and waking

PubMed Central

Findlay, Alan L. R.; Hayward, James N.

1969-01-01

1. A method is described for recording from single cells in the hypothalamus of unanaesthetized freely moving rabbits. Behaviour, bodily movement, skin and brain temperatures and e.e.g. were monitored. 2. Patterns of unit firing during slow sleep, paradoxical sleep and waking were studied in several regions of the hypothalamus, thalamus and in the septum. 3. Of the 144 cells analysed from waking to slow sleep, fifty-six (39%) decreased mean firing rates, thirty (21%) increased spike discharges and fifty-eight (40%) showed no marked change. Dorsal hypothalamic and massa intermedia thalamic cells fired in brief high frequency clusters during slow sleep with a characteristic `bimodal' interspike interval histogram. Waking and paradoxical sleep abolished these cluster discharges with a concomitant change to an `asymmetric' histogram. 4. Of the thirty-two cells observed during the three states of waking, slow sleep and paradoxical sleep, a majority (twenty-five or 78%) showed their highest rates of spontaneous discharge during paradoxical sleep. Discharge rates of cells sometimes changed in the course of paradoxical sleep according to the presence or absence of phasic events such as myoclonic motor activity. Two hypothalmic cells were almost totally arrested during paradoxical sleep. 5. Analysis of unit firing rates during spontaneous rises in brain temperature during waking and paradoxical sleep revealed that a majority of the neurones (22/24) changed their discharge rates in relation to behaviour rather than to brain temperature. Two cells did appear to respond specifically to the central thermal stimulus. 6. Hypothalamic cells do not behave as a homogeneous population in relation to changes in the state of arousal of the rabbit. Spontaneous changes in cell discharge related to sleep-waking behaviour must be considered in any interpretation of hypothalamic unit activity as related to neuroendocrine or autonomic mechanisms. PMID:4304342

Monoamines and glycogen levels in cerebral cortices of fast and slow methionine sulfoximine-inbred mice.

PubMed

Boissonnet, Arnaud; Hévor, Tobias; Landemarre, Ludovic; Cloix, Jean-François

2013-05-01

The experimental model of seizures which depends upon methionine sulfoximine (MSO) simulates the most striking form of human epilepsy. MSO generates epileptiform seizures in a large variety of animals, increases brain glycogen content and induces brain monoamines modifications. We selected two inbred lines of mice based upon their latency toward MSO-dependent seizures, named as MSO-Fast (sensitive), having short latency toward MSO, and MSO-Slow (resistant) with a long latency. We determined 13 monoamines and glycogen contents in brain cortices of the MSO-Fast and slow lines in order to determine the relationships with MSO-dependent seizures. The present data show that using these MSO-Fast and MSO-Slow inbred lines it could be demonstrated that: (1) in basal conditions the neurotransmitter 5-HT is significantly higher in MSO-Fast mice than in MSO-Slow ones; (2) MSO in both lines induced a significant increase in brain content of DOPAC (3,4-dihydroxyphenylacetic acid), HVA (homovanillic acid), MHPG (3-methoxy-4-hydroxyphenylglycol), and 5-HT (serotonin); a significant decrease in MSO-Slow mice in brain content of NME (normetepinephrine), and 5-HIAA (5-hydroxyindoleacetic acid) and the variation of other monoamines were not significant; (3) the brain glycogen content is significantly higher in MSO-Fast mice than in MSO-Slow ones, both in basal conditions and after MSO administration. From our data, we propose that brain glycogen content may constitute a defense against epileptic attack, as glycogen may be degraded down to glucose-6-phosphate that can be used to either postpone the epileptic attack or to provide neurons with energy when they needed it. Brain glycogen might therefore be considered as a molecule that can contribute to struggle seizures, at least in MSO-dependent seizure. The 5-HT content may constitute a defense against MSO-dependent epilepsy. Copyright © 2013 Elsevier B.V. All rights reserved.

Induction of slow oscillations by rhythmic acoustic stimulation.

PubMed

Ngo, Hong-Viet V; Claussen, Jens C; Born, Jan; Mölle, Matthias

2013-02-01

Slow oscillations are electrical potential oscillations with a spectral peak frequency of ∼0.8 Hz, and hallmark the electroencephalogram during slow-wave sleep. Recent studies have indicated a causal contribution of slow oscillations to the consolidation of memories during slow-wave sleep, raising the question to what extent such oscillations can be induced by external stimulation. Here, we examined whether slow oscillations can be effectively induced by rhythmic acoustic stimulation. Human subjects were examined in three conditions: (i) with tones presented at a rate of 0.8 Hz ('0.8-Hz stimulation'); (ii) with tones presented at a random sequence ('random stimulation'); and (iii) with no tones presented in a control condition ('sham'). Stimulation started during wakefulness before sleep and continued for the first ∼90 min of sleep. Compared with the other two conditions, 0.8-Hz stimulation significantly delayed sleep onset. However, once sleep was established, 0.8-Hz stimulation significantly increased and entrained endogenous slow oscillation activity. Sleep after the 90-min period of stimulation did not differ between the conditions. Our data show that rhythmic acoustic stimulation can be used to effectively enhance slow oscillation activity. However, the effect depends on the brain state, requiring the presence of stable non-rapid eye movement sleep. © 2012 European Sleep Research Society.

Effects of oral temazepam on slow waves during non-rapid eye movement sleep in healthy young adults: A high-density EEG investigation.

PubMed

Plante, D T; Goldstein, M R; Cook, J D; Smith, R; Riedner, B A; Rumble, M E; Jelenchick, L; Roth, A; Tononi, G; Benca, R M; Peterson, M J

2016-03-01

Slow waves are characteristic waveforms that occur during non-rapid eye movement (NREM) sleep that play an integral role in sleep quality and brain plasticity. Benzodiazepines are commonly used medications that alter slow waves, however, their effects may depend on the time of night and measure used to characterize slow waves. Prior investigations have utilized minimal scalp derivations to evaluate the effects of benzodiazepines on slow waves, and thus the topography of changes to slow waves induced by benzodiazepines has yet to be fully elucidated. This study used high-density electroencephalography (hdEEG) to evaluate the effects of oral temazepam on slow wave activity, incidence, and morphology during NREM sleep in 18 healthy adults relative to placebo. Temazepam was associated with significant decreases in slow wave activity and incidence, which were most prominent in the latter portions of the sleep period. However, temazepam was also associated with a decrease in the magnitude of high-amplitude slow waves and their slopes in the first NREM sleep episode, which was most prominent in frontal derivations. These findings suggest that benzodiazepines produce changes in slow waves throughout the night that vary depending on cortical topography and measures used to characterize slow waves. Further research that explores the relationships between benzodiazepine-induced changes to slow waves and the functional effects of these waveforms is indicated. Copyright © 2016 Elsevier B.V. All rights reserved.

Resting State EEG in Children With Learning Disabilities: An Independent Component Analysis Approach.

PubMed

Jäncke, Lutz; Alahmadi, Nsreen

2016-01-01

In this study, the neurophysiological underpinnings of learning disabilities (LD) in children are examined using resting state EEG. We were particularly interested in the neurophysiological differences between children with learning disabilities not otherwise specified (LD-NOS), learning disabilities with verbal disabilities (LD-Verbal), and healthy control (HC) children. We applied 2 different approaches to examine the differences between the different groups. First, we calculated theta/beta and theta/alpha ratios in order to quantify the relationship between slow and fast EEG oscillations. Second, we used a recently developed method for analyzing spectral EEG, namely the group independent component analysis (gICA) model. Using these measures, we identified substantial differences between LD and HC children and between LD-NOS and LD-Verbal children in terms of their spectral EEG profiles. We obtained the following findings: (a) theta/beta and theta/alpha ratios were substantially larger in LD than in HC children, with no difference between LD-NOS and LD-Verbal children; (b) there was substantial slowing of EEG oscillations, especially for gICs located in frontal scalp positions, with LD-NOS children demonstrating the strongest slowing; (c) the estimated intracortical sources of these gICs were mostly located in brain areas involved in the control of executive functions, attention, planning, and language; and (d) the LD-Verbal children demonstrated substantial differences in EEG oscillations compared with LD-NOS children, and these differences were localized in language-related brain areas. The general pattern of atypical neurophysiological activation found in LD children suggests that they suffer from neurophysiological dysfunction in brain areas involved with the control of attention, executive functions, planning, and language functions. LD-Verbal children also demonstrate atypical activation, especially in language-related brain areas. These atypical neurophysiological activation patterns might provide a helpful guide for rehabilitation strategies to treat the deficiencies in these children with LD. © EEG and Clinical Neuroscience Society (ECNS) 2015.

Dwelling quietly in the rich club: brain network determinants of slow cortical fluctuations

PubMed Central

Gollo, Leonardo L.; Zalesky, Andrew; Hutchison, R. Matthew; van den Heuvel, Martijn; Breakspear, Michael

2015-01-01

For more than a century, cerebral cartography has been driven by investigations of structural and morphological properties of the brain across spatial scales and the temporal/functional phenomena that emerge from these underlying features. The next era of brain mapping will be driven by studies that consider both of these components of brain organization simultaneously—elucidating their interactions and dependencies. Using this guiding principle, we explored the origin of slowly fluctuating patterns of synchronization within the topological core of brain regions known as the rich club, implicated in the regulation of mood and introspection. We find that a constellation of densely interconnected regions that constitute the rich club (including the anterior insula, amygdala and precuneus) play a central role in promoting a stable, dynamical core of spontaneous activity in the primate cortex. The slow timescales are well matched to the regulation of internal visceral states, corresponding to the somatic correlates of mood and anxiety. In contrast, the topology of the surrounding ‘feeder’ cortical regions shows unstable, rapidly fluctuating dynamics likely to be crucial for fast perceptual processes. We discuss these findings in relation to psychiatric disorders and the future of connectomics. PMID:25823864

Problem-Based Learning Revisited, Introduction of Active and Self-Directed Learning to Reduce Fatigue among Students

ERIC Educational Resources Information Center

Czabanowska, Katarzyna; Moust, Jos H. C.; Meijer, Andre W. M.; Schroder-Back, Peter; Roebertsen, Herma

2012-01-01

Despite several years of successfully applying problem-based learning at Maastricht University, the Faculty of Medicine observed a slow erosion of problem-based practices and "PBL fatigue" among themselves and students. In response to this fatigue and new research into the development of the young adult brain, Active Self-Directed…

Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial

PubMed Central

Smith, Stephen M.; de Jager, Celeste A.; Whitbread, Philippa; Johnston, Carole; Agacinski, Grzegorz; Oulhaj, Abderrahim; Bradley, Kevin M.; Jacoby, Robin

2010-01-01

Background An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. Objective To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159). Methods and Findings Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans. Results A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94–1.22] in the placebo group (P = 0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine >13 µmol/L was 53% lower in the active treatment group (P = 0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category. Conclusions and Significance The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer's disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer's disease, trials are needed to see if the same treatment will delay the development of Alzheimer's disease. Trial Registration Controlled-Trials.com ISRCTN94410159 PMID:20838622

Impact of playing American professional football on long-term brain function.

PubMed

Amen, Daniel G; Newberg, Andrew; Thatcher, Robert; Jin, Yi; Wu, Joseph; Keator, David; Willeumier, Kristen

2011-01-01

The authors recruited 100 active and former National Football League players, representing 27 teams and all positions. Players underwent a clinical history, brain SPECT imaging, qEEG, and multiple neuropsychological measures, including MicroCog. Relative to a healthy-comparison group, players showed global decreased perfusion, especially in the prefrontal, temporal, parietal, and occipital lobes, and cerebellar regions. Quantitative EEG findings were consistent, showing elevated slow waves in the frontal and temporal regions. Significant decreases from normal values were found in most neuropsychological tests. This is the first large-scale brain-imaging study to demonstrate significant differences consistent with a chronic brain trauma pattern in professional football players.

Multiscale energy reallocation during low-frequency steady-state brain response.

PubMed

Wang, Yifeng; Chen, Wang; Ye, Liangkai; Biswal, Bharat B; Yang, Xuezhi; Zou, Qijun; Yang, Pu; Yang, Qi; Wang, Xinqi; Cui, Qian; Duan, Xujun; Liao, Wei; Chen, Huafu

2018-05-01

Traditional task-evoked brain activations are based on detection and estimation of signal change from the mean signal. By contrast, the low-frequency steady-state brain response (lfSSBR) reflects frequency-tagging activity at the fundamental frequency of the task presentation and its harmonics. Compared to the activity at these resonant frequencies, brain responses at nonresonant frequencies are largely unknown. Additionally, because the lfSSBR is defined by power change, we hypothesize using Parseval's theorem that the power change reflects brain signal variability rather than the change of mean signal. Using a face recognition task, we observed power increase at the fundamental frequency (0.05 Hz) and two harmonics (0.1 and 0.15 Hz) and power decrease within the infra-slow frequency band (<0.1 Hz), suggesting a multifrequency energy reallocation. The consistency of power and variability was demonstrated by the high correlation (r > .955) of their spatial distribution and brain-behavior relationship at all frequency bands. Additionally, the reallocation of finite energy was observed across various brain regions and frequency bands, forming a particular spatiotemporal pattern. Overall, results from this study strongly suggest that frequency-specific power and variability may measure the same underlying brain activity and that these results may shed light on different mechanisms between lfSSBR and brain activation, and spatiotemporal characteristics of energy reallocation induced by cognitive tasks. © 2018 Wiley Periodicals, Inc.

Blood-Brain Barrier Breakdown Following Traumatic Brain Injury: A Possible Role in Posttraumatic Epilepsy

PubMed Central

Tomkins, Oren; Feintuch, Akiva; Benifla, Moni; Cohen, Avi; Friedman, Alon; Shelef, Ilan

2011-01-01

Recent animal experiments indicate a critical role for opening of the blood-brain barrier (BBB) in the pathogenesis of post-traumatic epilepsy (PTE). This study aimed to investigate the frequency, extent, and functional correlates of BBB disruption in epileptic patients following mild traumatic brain injury (TBI). Thirty-seven TBI patients were included in this study, 19 of whom suffered from PTE. All underwent electroencephalographic (EEG) recordings and brain magnetic resonance imaging (bMRI). bMRIs were evaluated for BBB disruption using novel quantitative techniques. Cortical dysfunction was localized using standardized low-resolution brain electromagnetic tomography (sLORETA). TBI patients displayed significant EEG slowing compared to controls with no significant differences between PTE and nonepileptic patients. BBB disruption was found in 82.4% of PTE compared to 25% of non-epileptic patients (P = .001) and could be observed even years following the trauma. The volume of cerebral cortex with BBB disruption was significantly larger in PTE patients (P = .001). Slow wave EEG activity was localized to the same region of BBB disruption in 70% of patients and correlated to the volume of BBB disrupted cortex. We finally present a patient suffering from early cortical dysfunction and BBB breakdown with a gradual and parallel resolution of both pathologies. Our findings demonstrate that BBB pathology is frequently found following mild TBI. Lasting BBB breakdown is found with increased frequency and extent in PTE patients. Based on recent animal studies and the colocalization found between the region of disrupted BBB and abnormal EEG activity, we suggest a role for a vascular lesion in the pathogenesis of PTE. PMID:21436875

Actions of circulating angiotensin II and aldosterone in the brain contributing to hypertension.

PubMed

Leenen, Frans H H

2014-08-01

In the past 1-2 decades, it has become apparent that the brain renin-angiotensin-aldosterone system (RAAS) plays a crucial role in the regulation of blood pressure (BP) by the circulating RAAS. In the brain, angiotensinergic sympatho-excitatory pathways do not contribute to acute, second-to-second regulation but play a major role in the more chronic regulation of the setpoint for sympathetic tone and BP. Increases in plasma angiotensin II (Ang II) or aldosterone and in cerebrospinal fluid [Na(+)] can directly activate these pathways and chronically further activate/maintain enhanced activity by a slow neuromodulatory pathway involving local aldosterone, mineralocorticoid receptors (MRs), epithelial sodium channels, and endogenous ouabain. Blockade of any step in this slow pathway prevents Ang II-, aldosterone-, or salt and renal injury-induced forms of hypertension. It appears that the renal and arterial actions of circulating aldosterone and Ang II act as amplifiers but are not sufficient to cause chronic hypertension if their central actions are prevented, except perhaps at high concentrations. From a clinical perspective, oral treatment with an angiotensin type 1 (AT1)-receptor blocker at high doses can cause central AT1-receptor blockade and, in humans, lower sympathetic nerve activity. Low doses of the MR blocker spironolactone appear sufficient to cause central MR blockade and a decrease in sympathetic nerve activity. Integrating the brain actions of the circulating RAAS with its direct renal and arterial actions provides a better framework to understand the role of the circulating RAAS in the pathophysiology of hypertension and heart failure and to direct therapeutic strategies. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparison of simultaneously recorded [H2(15)O]-PET and LORETA during cognitive and pharmacological activation.

PubMed

Gamma, Alex; Lehmann, Dietrich; Frei, Edi; Iwata, Kazuki; Pascual-Marqui, Roberto D; Vollenweider, Franz X

2004-06-01

The complementary strengths and weaknesses of established functional brain imaging methods (high spatial, low temporal resolution) and EEG-based techniques (low spatial, high temporal resolution) make their combined use a promising avenue for studying brain processes at a more fine-grained level. However, this strategy requires a better understanding of the relationship between hemodynamic/metabolic and neuroelectric measures of brain activity. We investigated possible correspondences between cerebral blood flow (CBF) as measured by [H2O]-PET and intracerebral electric activity computed by Low Resolution Brain Electromagnetic Tomography (LORETA) from scalp-recorded multichannel EEG in healthy human subjects during cognitive and pharmacological stimulation. The two imaging modalities were compared by descriptive, correlational, and variance analyses, the latter carried out using statistical parametric mapping (SPM99). Descriptive visual comparison showed a partial overlap between the sets of active brain regions detected by the two modalities. A number of exclusively positive correlations of neuroelectric activity with regional CBF were found across the whole EEG frequency range, including slow wave activity, the latter finding being in contrast to most previous studies conducted in patients. Analysis of variance revealed an extensive lack of statistically significant correspondences between brain activity changes as measured by PET vs. EEG-LORETA. In general, correspondences, to the extent they were found, were dependent on experimental condition, brain region, and EEG frequency. Copyright 2004 Wiley-Liss, Inc.

Endogenous Delta/Theta Sound-Brain Phase Entrainment Accelerates the Buildup of Auditory Streaming.

PubMed

Riecke, Lars; Sack, Alexander T; Schroeder, Charles E

2015-12-21

In many natural listening situations, meaningful sounds (e.g., speech) fluctuate in slow rhythms among other sounds. When a slow rhythmic auditory stream is selectively attended, endogenous delta (1‒4 Hz) oscillations in auditory cortex may shift their timing so that higher-excitability neuronal phases become aligned with salient events in that stream [1, 2]. As a consequence of this stream-brain phase entrainment [3], these events are processed and perceived more readily than temporally non-overlapping events [4-11], essentially enhancing the neural segregation between the attended stream and temporally noncoherent streams [12]. Stream-brain phase entrainment is robust to acoustic interference [13-20] provided that target stream-evoked rhythmic activity can be segregated from noncoherent activity evoked by other sounds [21], a process that usually builds up over time [22-27]. However, it has remained unclear whether stream-brain phase entrainment functionally contributes to this buildup of rhythmic streams or whether it is merely an epiphenomenon of it. Here, we addressed this issue directly by experimentally manipulating endogenous stream-brain phase entrainment in human auditory cortex with non-invasive transcranial alternating current stimulation (TACS) [28-30]. We assessed the consequences of these manipulations on the perceptual buildup of the target stream (the time required to recognize its presence in a noisy background), using behavioral measures in 20 healthy listeners performing a naturalistic listening task. Experimentally induced cyclic 4-Hz variations in stream-brain phase entrainment reliably caused a cyclic 4-Hz pattern in perceptual buildup time. Our findings demonstrate that strong endogenous delta/theta stream-brain phase entrainment accelerates the perceptual emergence of task-relevant rhythmic streams in noisy environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Ketogenic Diet Does Not Affect Growth of Hedgehog Pathway Medulloblastoma in Mice

PubMed Central

Dang, Mai T.; Wehrli, Suzanne; Dang, Chi V.; Curran, Tom

2015-01-01

The altered metabolism of cancer cells has long been viewed as a potential target for therapeutic intervention. In particular, brain tumors often display heightened glycolysis, even in the presence of oxygen. A subset of medulloblastoma, the most prevalent malignant brain tumor in children, arises as a consequence of activating mutations in the Hedgehog (HH) pathway, which has been shown to promote aerobic glycolysis. Therefore, we hypothesized that a low carbohydrate, high fat ketogenic diet would suppress tumor growth in a genetically engineered mouse model of medulloblastoma. However, we found that the ketogenic diet did not slow the growth of spontaneous tumors or allograft flank tumors, and it did not exhibit synergy with a small molecule inhibitor of Smoothened. Serum insulin was significantly reduced in mice fed the ketogenic diet, but no alteration in PI3 kinase activity was observed. These findings indicate that while the ketogenic diet may be effective in inhibiting growth of other tumor types, it does not slow the growth of HH-medulloblastoma in mice. PMID:26192445

Seizures and electroencephalography findings in 61 patients with fetal alcohol spectrum disorders.

PubMed

Boronat, S; Vicente, M; Lainez, E; Sánchez-Montañez, A; Vázquez, E; Mangado, L; Martínez-Ribot, L; Del Campo, M

2017-01-01

Fetal alcohol spectrum disorders (FASD) cause neurodevelopmental abnormalities. However, publications about epilepsy and electroencephalographic features are scarce. In this study, we prospectively performed electroencephalography (EEG) and brain magnetic resonance (MR) imaging in 61 patients with diagnosis of FASD. One patient had multiple febrile seizures with normal EEGs. Fourteen children showed EEG anomalies, including slow background activity and interictal epileptiform discharges, focal and/or generalized, and 3 of them had epilepsy. In one patient, seizures were first detected during the EEG recording and one case had an encephalopathy with electrical status epilepticus during slow sleep (ESES). Focal interictal discharges in our patients did not imply the presence of underlying visible focal brain lesions in the neuroimaging studies, such as cortical dysplasia or polymicrogyria. However, they had nonspecific brain MR abnormalities, including corpus callosum hypoplasia, vermis hypoplasia or cavum septum pellucidum. The latter was significantly more frequent in the group with EEG abnormal findings (p < 0.01). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Ongoing compound field potentials from octopus brain are labile and vertebrate-like.

PubMed

Bullock, T H

1984-05-01

Ongoing electrical activity was recorded from the brain of the virtually intact, semirestrained, unanesthetized octopus by semimicroelectrodes thrust through the cartilage into the optic, vertical or basal lobe. With flexible lead-in wires such electrodes were carried by and moved with the head without causing movement artifacts. Controls suggest that the activity reported comes from the brain; it is reversibly flattened by doses of urethane that do not embarrass respiration. Muscle potentials are only troublesome on occasion. Seen through a wideband filter, neuronal spikes are usually small or below noise level under these conditions; slow waves (1-70 Hz) dominate, with a maximum less than 25 Hz, usually less than 10 Hz and no consistent sharp peaks. The fall in power above ca. 25 Hz is usually slower than in the typical vertebrate EEG but the average power spectrum is much more like those of vertebrate brains than of cerebral ganglia of other invertebrates (insect, crustacean, gastropod). Variance among sample epochs is large, e.g. short spells may have relatively much more low frequency (less than 25 Hz) or more 'hashy' high frequency (greater than 50 Hz) energy; there may be runs of spikes. Fluctuation in the composition of ongoing activity is graphically shown by writing out in parallel the outputs of several narrow band (one octave) filters; this shows irregular low frequency waxing and waning of the amplitude in each band. The envelopes were computed and their peak power is around 1 Hz or lower; the waxing and waning in the several bands is sometimes strongly correlated, especially when the envelope amplitude is large and slow. Optic lobe activity tends usually to be faster, with more small spikey hash than in the vertical lobe. The described electrical activity of the brain is strikingly episodic; it is recorded during seconds or minutes separated by long intervals of nearly electrical silence (10-40 dB lower power; the difference larger at frequencies greater than 20 Hz). Active and quiet periods are usually not correlated with differences in visible behavior. Under my conditions the animal is usually not moving except for quiet ventilation and occasional local writhing of an arm. Potentials evoked by single flashes of light (0.2-1/sec) are conspicuous in the optic but not in the vertical lobe. They form a sequence of large, slow waves; the first peak may be at about 40 msec, others up to at least 400 msec.(ABSTRACT TRUNCATED AT 400 WORDS)

Is There a Relation between EEG-Slow Waves and Memory Dysfunction in Epilepsy? A Critical Appraisal

PubMed Central

Höller, Yvonne; Trinka, Eugen

2015-01-01

Is there a relationship between peri-ictal slow waves, loss of consciousness, memory, and slow-wave sleep, in patients with different forms of epilepsy? We hypothesize that mechanisms, which result in peri-ictal slow-wave activity as detected by the electroencephalogram, could negatively affect memory processes. Slow waves (≤4 Hz) can be found in seizures with impairment of consciousness and also occur in focal seizures without impairment of consciousness but with inhibited access to memory functions. Peri-ictal slow waves are regarded as dysfunctional and are probably caused by mechanisms, which are essential to disturb the consolidation of memory entries in these patients. This is in strong contrast to physiological slow-wave activity during deep sleep, which is thought to group memory-consolidating fast oscillatory activity. In patients with epilepsy, slow waves may not only correlate with the peri-ictal clouding of consciousness, but could be the epiphenomenon of mechanisms, which interfere with normal brain function in a wider range. These mechanisms may have transient impacts on memory, such as temporary inhibition of memory systems, altered patterns of hippocampal–neocortical interactions during slow-wave sleep, or disturbed cross-frequency coupling of slow and fast oscillations. In addition, repeated tonic–clonic seizures over the years in uncontrolled chronic epilepsy may cause a progressive cognitive decline. This hypothesis can only be assessed in long-term prospective studies. These studies could disentangle the reversible short-term impacts of seizures, and the impacts of chronic uncontrolled seizures. Chronic uncontrolled seizures lead to irreversible memory impairment. By contrast, short-term impacts do not necessarily lead to a progressive cognitive decline but result in significantly impaired peri-ictal memory performance. PMID:26124717

The effects of Thalamic Deep Brain Stimulation on speech dynamics in patients with Essential Tremor: An articulographic study.

PubMed

Mücke, Doris; Hermes, Anne; Roettger, Timo B; Becker, Johannes; Niemann, Henrik; Dembek, Till A; Timmermann, Lars; Visser-Vandewalle, Veerle; Fink, Gereon R; Grice, Martine; Barbe, Michael T

2018-01-01

Acoustic studies have revealed that patients with Essential Tremor treated with thalamic Deep Brain Stimulation (DBS) may suffer from speech deterioration in terms of imprecise oral articulation and reduced voicing control. Based on the acoustic signal one cannot infer, however, whether this deterioration is due to a general slowing down of the speech motor system (e.g., a target undershoot of a desired articulatory goal resulting from being too slow) or disturbed coordination (e.g., a target undershoot caused by problems with the relative phasing of articulatory movements). To elucidate this issue further, we here investigated both acoustics and articulatory patterns of the labial and lingual system using Electromagnetic Articulography (EMA) in twelve Essential Tremor patients treated with thalamic DBS and twelve age- and sex-matched controls. By comparing patients with activated (DBS-ON) and inactivated stimulation (DBS-OFF) with control speakers, we show that critical changes in speech dynamics occur on two levels: With inactivated stimulation (DBS-OFF), patients showed coordination problems of the labial and lingual system in terms of articulatory imprecision and slowness. These effects of articulatory discoordination worsened under activated stimulation, accompanied by an additional overall slowing down of the speech motor system. This leads to a poor performance of syllables on the acoustic surface, reflecting an aggravation either of pre-existing cerebellar deficits and/or the affection of the upper motor fibers of the internal capsule.

Modulation of electroencephalograph activity by manual acupuncture stimulation in healthy subjects: An autoregressive spectral analysis

NASA Astrophysics Data System (ADS)

Yi, Guo-Sheng; Wang, Jiang; Deng, Bin; Wei, Xi-Le; Han, Chun-Xiao

2013-02-01

To investigate whether and how manual acupuncture (MA) modulates brain activities, we design an experiment where acupuncture at acupoint ST36 of the right leg is used to obtain electroencephalograph (EEG) signals in healthy subjects. We adopt the autoregressive (AR) Burg method to estimate the power spectrum of EEG signals and analyze the relative powers in delta (0 Hz-4 Hz), theta (4 Hz-8 Hz), alpha (8 Hz-13 Hz), and beta (13 Hz-30 Hz) bands. Our results show that MA at ST36 can significantly increase the EEG slow wave relative power (delta band) and reduce the fast wave relative powers (alpha and beta bands), while there are no statistical differences in theta band relative power between different acupuncture states. In order to quantify the ratio of slow to fast wave EEG activity, we compute the power ratio index. It is found that the MA can significantly increase the power ratio index, especially in frontal and central lobes. All the results highlight the modulation of brain activities with MA and may provide potential help for the clinical use of acupuncture. The proposed quantitative method of acupuncture signals may be further used to make MA more standardized.

Mapping brain activity with flexible graphene micro-transistors

NASA Astrophysics Data System (ADS)

Blaschke, Benno M.; Tort-Colet, Núria; Guimerà-Brunet, Anton; Weinert, Julia; Rousseau, Lionel; Heimann, Axel; Drieschner, Simon; Kempski, Oliver; Villa, Rosa; Sanchez-Vives, Maria V.; Garrido, Jose A.

2017-06-01

Establishing a reliable communication interface between the brain and electronic devices is of paramount importance for exploiting the full potential of neural prostheses. Current microelectrode technologies for recording electrical activity, however, evidence important shortcomings, e.g. challenging high density integration. Solution-gated field-effect transistors (SGFETs), on the other hand, could overcome these shortcomings if a suitable transistor material were available. Graphene is particularly attractive due to its biocompatibility, chemical stability, flexibility, low intrinsic electronic noise and high charge carrier mobilities. Here, we report on the use of an array of flexible graphene SGFETs for recording spontaneous slow waves, as well as visually evoked and also pre-epileptic activity in vivo in rats. The flexible array of graphene SGFETs allows mapping brain electrical activity with excellent signal-to-noise ratio (SNR), suggesting that this technology could lay the foundation for a future generation of in vivo recording implants.

Effects of load and maintenance duration on the time course of information encoding and retrieval in working memory: from perceptual analysis to post-categorization processes.

PubMed

Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

2014-01-01

information encoding, maintenance, and retrieval; these are supported by brain activity in a network of frontal, parietal and temporal regions. Manipulation of WM load and duration of the maintenance period can modulate this activity. Although such modulations have been widely studied using the event-related potentials (ERP) technique, a precise description of the time course of brain activity during encoding and retrieval is still required. Here, we used this technique and principal component analysis to assess the time course of brain activity during encoding and retrieval in a delayed match to sample task. We also investigated the effects of memory load and duration of the maintenance period on ERP activity. Brain activity was similar during information encoding and retrieval and comprised six temporal factors, which closely matched the latency and scalp distribution of some ERP components: P1, N1, P2, N2, P300, and a slow wave. Changes in memory load modulated task performance and yielded variations in frontal lobe activation. Moreover, the P300 amplitude was smaller in the high than in the low load condition during encoding and retrieval. Conversely, the slow wave amplitude was higher in the high than in the low load condition during encoding, and the same was true for the N2 amplitude during retrieval. Thus, during encoding, memory load appears to modulate the processing resources for context updating and post-categorization processes, and during retrieval it modulates resources for stimulus classification and context updating. Besides, despite the lack of differences in task performance related to duration of the maintenance period, larger N2 amplitude and stronger activation of the left temporal lobe after long than after short maintenance periods were found during information retrieval. Thus, results regarding the duration of maintenance period were complex, and future work is required to test the time-based decay theory predictions.

N-isopropyl-(/sup 123/I)p-iodoamphetamine: single-pass brain uptake and washout; binding to brain synaptosomes; and localization in dog and monkey brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Winchell, H.S.; Horst, W.D.; Braun, L.

1980-10-01

The kinetics of N-isopropyl-p-(/sup 123/I)iodoamphetamine in rat brains were determined by serial measurements of brain uptake index (BUI) after intracarotid injection; also studied were its effects on amine uptake and release in rat's brain cortical synaptosomes; and its in vivo distribution in the dog and monkey. No specific localization in brain nuclei of the dog was seen, but there was progressive accumulation in the eyes. Rapid initial brain uptake in the ketamine-sedated monkey was noted, and further slow brain uptake occurred during the next 20 min but without retinal localization. High levels of brain activity were maintained for several hours.more » The quantitative initial single-pass clearance of the agent in the brain suggests its use in evaluation of regional brain perfusion. Its interaction with brain amine-binding sites suggests its possible application in studies of cerebral amine metabolism.« less

Emergence of Slow Collective Oscillations in Neural Networks with Spike-Timing Dependent Plasticity

NASA Astrophysics Data System (ADS)

Mikkelsen, Kaare; Imparato, Alberto; Torcini, Alessandro

2013-05-01

The collective dynamics of excitatory pulse coupled neurons with spike-timing dependent plasticity is studied. The introduction of spike-timing dependent plasticity induces persistent irregular oscillations between strongly and weakly synchronized states, reminiscent of brain activity during slow-wave sleep. We explain the oscillations by a mechanism, the Sisyphus Effect, caused by a continuous feedback between the synaptic adjustments and the coherence in the neural firing. Due to this effect, the synaptic weights have oscillating equilibrium values, and this prevents the system from relaxing into a stationary macroscopic state.

A pilot study on the optimal speeds for passive wrist movements by a rehabilitation robot of stroke patients: A functional NIRS study.

PubMed

Bae, Sung Jin; Jang, Sung Ho; Seo, Jeong Pyo; Chang, Pyung Hun

2017-07-01

The optimal conditions inducing proper brain activation during performance of rehabilitation robots should be examined to enhance the efficiency of robot rehabilitation based on the concept of brain plasticity. In this study, we attempted to investigate differences in cortical activation according to the speeds of passive wrist movements performed by a rehabilitation robot for stroke patients. 9 stroke patients with right hemiparesis participated in this study. Passive movements of the affected wrist were performed by the rehabilitation robot at three different speeds: 0.25 Hz; slow, 0.5Hz; moderate and 0.75 Hz; fast. We used functional near-infrared spectroscopy to measure the brain activity during the passive movements performed by a robot. Group-average activation map and the relative changes in oxy-hemoglobin (ΔOxyHb) in two regions of interest: the primary sensory-motor cortex (SM1); premotor area (PMA) and region of all channels were measured. In the result of group-averaged activation map, the contralateral SM1, PMA and somatosensory association cortex (SAC) showed the greatest significant activation according to the movements at 0.75 Hz, while there is no significantly activated area at 0.5 Hz. Regarding ΔOxyHb, no significant diiference was observed among three speeds regardless of region. In conclusion, the contralateral SM1, PMA and SAC showed the greatest activation by a fast speed (0.75 Hz) rather than slow (0.25 Hz) and moderate (0. 5 Hz) speed. Our results suggest an optimal speed for execution of the wrist rehabilitation robot. Therefore, we believe that our findings might point to several promising applications for future research regarding useful and empirically-based robot rehabilitation therapy.

Single-subject-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mild traumatic brain injury

PubMed Central

Huang, Ming-Xiong; Nichols, Sharon; Baker, Dewleen G.; Robb, Ashley; Angeles, Annemarie; Yurgil, Kate A.; Drake, Angela; Levy, Michael; Song, Tao; McLay, Robert; Theilmann, Rebecca J.; Diwakar, Mithun; Risbrough, Victoria B.; Ji, Zhengwei; Huang, Charles W.; Chang, Douglas G.; Harrington, Deborah L.; Muzzatti, Laura; Canive, Jose M.; Christopher Edgar, J.; Chen, Yu-Han; Lee, Roland R.

2014-01-01

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI) can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1–4 Hz) that can be measured and localized by resting-state magnetoencephalography (MEG). In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1–4 Hz) from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes), our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes), blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI. PMID:25009772

Dwelling quietly in the rich club: brain network determinants of slow cortical fluctuations.

PubMed

Gollo, Leonardo L; Zalesky, Andrew; Hutchison, R Matthew; van den Heuvel, Martijn; Breakspear, Michael

2015-05-19

For more than a century, cerebral cartography has been driven by investigations of structural and morphological properties of the brain across spatial scales and the temporal/functional phenomena that emerge from these underlying features. The next era of brain mapping will be driven by studies that consider both of these components of brain organization simultaneously--elucidating their interactions and dependencies. Using this guiding principle, we explored the origin of slowly fluctuating patterns of synchronization within the topological core of brain regions known as the rich club, implicated in the regulation of mood and introspection. We find that a constellation of densely interconnected regions that constitute the rich club (including the anterior insula, amygdala and precuneus) play a central role in promoting a stable, dynamical core of spontaneous activity in the primate cortex. The slow timescales are well matched to the regulation of internal visceral states, corresponding to the somatic correlates of mood and anxiety. In contrast, the topology of the surrounding 'feeder' cortical regions shows unstable, rapidly fluctuating dynamics likely to be crucial for fast perceptual processes. We discuss these findings in relation to psychiatric disorders and the future of connectomics. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Motoric Aids to Perceptual Training. The Slow Learner Series.

ERIC Educational Resources Information Center

Chaney, Clara M.; Kephart, Newell C.

Written from a developmental viewpoint, this book for parents and teachers presents both a theoretical orientation and perceptual motor activities for training children with learning disabilities, both the brain injured and the retarded. The theoretical basis for training generalized motor responses is considered in terms of motor perceptual…

Slow sleep spindle and procedural memory consolidation in patients with major depressive disorder.

PubMed

Nishida, Masaki; Nakashima, Yusaku; Nishikawa, Toru

2016-01-01

Evidence has accumulated, which indicates that, in healthy individuals, sleep enhances procedural memory consolidation, and that sleep spindle activity modulates this process. However, whether sleep-dependent procedural memory consolidation occurs in patients medicated for major depressive disorder remains unclear, as are the pharmacological and physiological mechanisms that underlie this process. Healthy control participants (n=17) and patients medicated for major depressive disorder (n=11) were recruited and subjected to a finger-tapping motor sequence test (MST; nondominant hand) paradigm to compare the averaged scores of different learning phases (presleep, postsleep, and overnight improvement). Participants' brain activity was recorded during sleep with 16 electroencephalography channels (between MSTs). Sleep scoring and frequency analyses were performed on the electroencephalography data. Additionally, we evaluated sleep spindle activity, which divided the spindles into fast-frequency spindle activity (12.5-16 Hz) and slow-frequency spindle activity (10.5-12.5 Hz). Sleep-dependent motor memory consolidation in patients with depression was impaired in comparison with that in control participants. In patients with depression, age correlated negatively with overnight improvement. The duration of slow-wave sleep correlated with the magnitude of motor memory consolidation in patients with depression, but not in healthy controls. Slow-frequency spindle activity was associated with reduction in the magnitude of motor memory consolidation in both groups. Because the changes in slow-frequency spindle activity affected the thalamocortical network dysfunction in patients medicated for depression, dysregulated spindle generation may impair sleep-dependent memory consolidation. Our findings may help to elucidate the cognitive deficits that occur in patients with major depression both in the waking state and during sleep.

Serotonergic raphe magnus cell discharge reflects ongoing autonomic and respiratory activities.

PubMed

Mason, Peggy; Gao, Keming; Genzen, Jonathan R

2007-10-01

Serotonergic cells are located in a restricted number of brain stem nuclei, send projections to virtually all parts of the CNS, and are critical to normal brain function. They discharge tonically at a rate modulated by the sleep-wake cycle and, in the case of medullary serotonergic cells in raphe magnus and the adjacent reticular formation (RM), are excited by cold challenge. Yet, beyond behavioral state and cold, endogenous factors that influence serotonergic cell discharge remain largely mysterious. The present study in the anesthetized rat investigated predictors of serotonergic RM cell discharge by testing whether cell discharge correlated to three rhythms observed in blood pressure recordings that averaged >30 min in length. A very slow frequency rhythm with a period of minutes, a respiratory rhythm, and a cardiac rhythm were derived from the blood pressure recording. Cross-correlations between each of the derived rhythms and cell activity revealed that the discharge of 38 of the 40 serotonergic cells studied was significantly correlated to the very slow and/or respiratory rhythms. Very few serotonergic cells discharged in relation to the cardiac cycle and those that did, did so weakly. The correlations between serotonergic cell discharge and the slow and respiratory rhythms cannot arise from baroreceptive input. Instead we hypothesize that they are by-products of ongoing adjustments to homeostatic functions that happen to alter blood pressure. Thus serotonergic RM cells integrate information about multiple homeostatic activities and challenges and can consequently modulate spinal processes according to the most pressing need of the organism.

An Event Related Potentials Study of the Effects of Age, Load and Maintenance Duration on Working Memory Recognition.

PubMed

Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

2015-01-01

Age-related decline in cognitive capacities has been attributed to a generalized slowing of processing speed and a reduction in working memory (WM) capacity. Nevertheless, it is unclear how age affects visuospatial WM recognition and its underlying brain electrical activity. Whether age modulates the effects of memory load or information maintenance duration, which determine the limits of WM, remains also elusive. In this exploratory study, performance in a delayed match to sample task declined with age, particularly in conditions with high memory load. Event related potentials analysis revealed longer N2 and P300 latencies in old than in young adults during WM recognition, which may reflect slowing of stimulus evaluation and classification processes, respectively. Although there were no differences between groups in N2 or P300 amplitudes, the latter was more homogeneously distributed in old than in young adults, which may indicate an age-related increased reliance in frontal vs parietal resources during WM recognition. This was further supported by an age-related reduced posterior cingulate activation and increased superior frontal gyrus activation revealed through standardized low resolution electromagnetic tomography. Memory load and maintenance duration effects on brain activity were similar in both age groups. These behavioral and electrophysiological results add evidence in support of age-related decline in WM recognition theories, with a slowing of processing speed that may be limited to stimulus evaluation and categorization processes--with no effects on perceptual processes--and a posterior to anterior shift in the recruitment of neural resources.

[Microinjections of heat shock protein 70 kDa into the nucleus reticularis pontis oralis induce inhibition of rapid eye movement sleep in pigeons].

PubMed

Gusel'nikova, E A; Pastukhov, Iu F

2008-03-01

Recently it was indicated that microinjections of heat shock proteins 70 kDa (Hsp70) into the third ventricle of brain in pigeons results in an increase in the duration of slow wave sleep and a decrease in somato-visceral indices. It is suggested that Hsp70 effect may be related to GABA(A) receptors activation in the preoptic area of the hypothalamus. However, what transmitter mechanisms of activation are related to the removal effect (in 2-3 hrs) of rapid eye movement sleep inhibition still remains poorly understood. To solve this problem in the present study, microinjections of Hsp70 into the Nucleus reticularis pontis oralis (NRPO) were done. It is well known that cholinergic neurons of the NRPO are crucial for rapid eye movement sleep generation. The data show that Hsp70 produces more early (for first two hrs) a decrease in number of episodes and total time of rapid eye movement sleep, a diminution of electroencephalogram (EEG) power spectra in the 9-14 Hz band, a decrease in contractile muscle activity and brain temperature. It is suggested that Hsp70 effects are realized due to activation of GABA(A) receptors in the NRPO and induced inhibition of cholinergic mechanisms of rapid eye movement sleep triggering. The microinjections of Hsp70 into the NRPO increase the slow wave sleep total time with long latency (for 8-12 hrs). This effect may be related to influence of Hsp70 on neurons population, which are responsible for slow wave sleep maintenance outside the NRPO.

An Event Related Potentials Study of the Effects of Age, Load and Maintenance Duration on Working Memory Recognition

PubMed Central

Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

2015-01-01

Age-related decline in cognitive capacities has been attributed to a generalized slowing of processing speed and a reduction in working memory (WM) capacity. Nevertheless, it is unclear how age affects visuospatial WM recognition and its underlying brain electrical activity. Whether age modulates the effects of memory load or information maintenance duration, which determine the limits of WM, remains also elusive. In this exploratory study, performance in a delayed match to sample task declined with age, particularly in conditions with high memory load. Event related potentials analysis revealed longer N2 and P300 latencies in old than in young adults during WM recognition, which may reflect slowing of stimulus evaluation and classification processes, respectively. Although there were no differences between groups in N2 or P300 amplitudes, the latter was more homogeneously distributed in old than in young adults, which may indicate an age-related increased reliance in frontal vs parietal resources during WM recognition. This was further supported by an age-related reduced posterior cingulate activation and increased superior frontal gyrus activation revealed through standardized low resolution electromagnetic tomography. Memory load and maintenance duration effects on brain activity were similar in both age groups. These behavioral and electrophysiological results add evidence in support of age-related decline in WM recognition theories, with a slowing of processing speed that may be limited to stimulus evaluation and categorization processes -with no effects on perceptual processes- and a posterior to anterior shift in the recruitment of neural resources. PMID:26569113

Integrating EEG and fMRI in epilepsy.

PubMed

Formaggio, Emanuela; Storti, Silvia Francesca; Bertoldo, Alessandra; Manganotti, Paolo; Fiaschi, Antonio; Toffolo, Gianna Maria

2011-02-14

Integrating electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) studies enables to non-invasively investigate human brain function and to find the direct correlation of these two important measures of brain activity. Presurgical evaluation of patients with epilepsy is one of the areas where EEG and fMRI integration has considerable clinical relevance for localizing the brain regions generating interictal epileptiform activity. The conventional analysis of EEG-fMRI data is based on the visual identification of the interictal epileptiform discharges (IEDs) on scalp EEG. The convolution of these EEG events, represented as stick functions, with a model of the fMRI response, i.e. the hemodynamic response function, provides the regressor for general linear model (GLM) analysis of fMRI data. However, the conventional analysis is not automatic and suffers of some subjectivity in IEDs classification. Here, we present an easy-to-use and automatic approach for combined EEG-fMRI analysis able to improve IEDs identification based on Independent Component Analysis and wavelet analysis. EEG signal due to IED is reconstructed and its wavelet power is used as a regressor in GLM. The method was validated on simulated data and then applied on real data set consisting of 2 normal subjects and 5 patients with partial epilepsy. In all continuous EEG-fMRI recording sessions a good quality EEG was obtained allowing the detection of spontaneous IEDs and the analysis of the related BOLD activation. The main clinical finding in EEG-fMRI studies of patients with partial epilepsy is that focal interictal slow-wave activity was invariably associated with increased focal BOLD responses in a spatially related brain area. Our study extends current knowledge on epileptic foci localization and confirms previous reports suggesting that BOLD activation associated with slow activity might have a role in localizing the epileptogenic region even in the absence of clear interictal spikes. Copyright © 2010 Elsevier Inc. All rights reserved.

How heart rate variability affects emotion regulation brain networks.

PubMed

Mather, Mara; Thayer, Julian

2018-02-01

Individuals with high heart rate variability tend to have better emotional well-being than those with low heart rate variability, but the mechanisms of this association are not yet clear. In this paper, we propose the novel hypothesis that by inducing oscillatory activity in the brain, high amplitude oscillations in heart rate enhance functional connectivity in brain networks associated with emotion regulation. Recent studies using daily biofeedback sessions to increase the amplitude of heart rate oscillations suggest that high amplitude physiological oscillations have a causal impact on emotional well-being. Because blood flow timing helps determine brain network structure and function, slow oscillations in heart rate have the potential to strengthen brain network dynamics, especially in medial prefrontal regulatory regions that are particularly sensitive to physiological oscillations.

Histamine Induces Alzheimer's Disease-Like Blood Brain Barrier Breach and Local Cellular Responses in Mouse Brain Organotypic Cultures

PubMed Central

Sedeyn, Jonathan C.; Wu, Hao; Hobbs, Reilly D.; Levin, Eli C.; Nagele, Robert G.; Venkataraman, Venkat

2015-01-01

Among the top ten causes of death in the United States, Alzheimer's disease (AD) is the only one that cannot be cured, prevented, or even slowed down at present. Significant efforts have been exerted in generating model systems to delineate the mechanism as well as establishing platforms for drug screening. In this study, a promising candidate model utilizing primary mouse brain organotypic (MBO) cultures is reported. For the first time, we have demonstrated that the MBO cultures exhibit increased blood brain barrier (BBB) permeability as shown by IgG leakage into the brain parenchyma, astrocyte activation as evidenced by increased expression of glial fibrillary acidic protein (GFAP), and neuronal damage-response as suggested by increased vimentin-positive neurons occur upon histamine treatment. Identical responses—a breakdown of the BBB, astrocyte activation, and neuronal expression of vimentin—were then demonstrated in brains from AD patients compared to age-matched controls, consistent with other reports. Thus, the histamine-treated MBO culture system may provide a valuable tool in combating AD. PMID:26697497

Lag threads organize the brain’s intrinsic activity

PubMed Central

Mitra, Anish; Snyder, Abraham Z.; Blazey, Tyler; Raichle, Marcus E.

2015-01-01

It has been widely reported that intrinsic brain activity, in a variety of animals including humans, is spatiotemporally structured. Specifically, propagated slow activity has been repeatedly demonstrated in animals. In human resting-state fMRI, spontaneous activity has been understood predominantly in terms of zero-lag temporal synchrony within widely distributed functional systems (resting-state networks). Here, we use resting-state fMRI from 1,376 normal, young adults to demonstrate that multiple, highly reproducible, temporal sequences of propagated activity, which we term “lag threads,” are present in the brain. Moreover, this propagated activity is largely unidirectional within conventionally understood resting-state networks. Modeling experiments show that resting-state networks naturally emerge as a consequence of shared patterns of propagation. An implication of these results is that common physiologic mechanisms may underlie spontaneous activity as imaged with fMRI in humans and slowly propagated activity as studied in animals. PMID:25825720

Slow sleep spindle and procedural memory consolidation in patients with major depressive disorder

PubMed Central

Nishida, Masaki; Nakashima, Yusaku; Nishikawa, Toru

2016-01-01

Introduction Evidence has accumulated, which indicates that, in healthy individuals, sleep enhances procedural memory consolidation, and that sleep spindle activity modulates this process. However, whether sleep-dependent procedural memory consolidation occurs in patients medicated for major depressive disorder remains unclear, as are the pharmacological and physiological mechanisms that underlie this process. Methods Healthy control participants (n=17) and patients medicated for major depressive disorder (n=11) were recruited and subjected to a finger-tapping motor sequence test (MST; nondominant hand) paradigm to compare the averaged scores of different learning phases (presleep, postsleep, and overnight improvement). Participants’ brain activity was recorded during sleep with 16 electroencephalography channels (between MSTs). Sleep scoring and frequency analyses were performed on the electroencephalography data. Additionally, we evaluated sleep spindle activity, which divided the spindles into fast-frequency spindle activity (12.5–16 Hz) and slow-frequency spindle activity (10.5–12.5 Hz). Result Sleep-dependent motor memory consolidation in patients with depression was impaired in comparison with that in control participants. In patients with depression, age correlated negatively with overnight improvement. The duration of slow-wave sleep correlated with the magnitude of motor memory consolidation in patients with depression, but not in healthy controls. Slow-frequency spindle activity was associated with reduction in the magnitude of motor memory consolidation in both groups. Conclusion Because the changes in slow-frequency spindle activity affected the thalamocortical network dysfunction in patients medicated for depression, dysregulated spindle generation may impair sleep-dependent memory consolidation. Our findings may help to elucidate the cognitive deficits that occur in patients with major depression both in the waking state and during sleep. PMID:26869818

Excessive sleep need following traumatic brain injury: a case-control study of 36 patients.

PubMed

Sommerauer, Michael; Valko, Philipp O; Werth, Esther; Baumann, Christian R

2013-12-01

Increased sleep need following traumatic brain injury, referred to in this study as post-traumatic pleiosomnia, is common, but so far its clinical impact and therapeutic implications have not been characterized. We present a case-control study of 36 patients with post-traumatic pleiosomnia, defined by an increased sleep need of at least 2 h per 24 h after traumatic brain injury, compared to 36 controls. We assessed detailed history, sleep-activity patterns with sleep logs and actigraphy, nocturnal sleep with polysomnography and daytime sleep propensity with multiple sleep latency tests. Actigraphy recordings revealed that traumatic brain injury (TBI) patients had longer estimated sleep durations than controls (10.8 h per 24 h, compared to 7.3 h). When using sleep logs, TBI patients underestimated their sleep need. During nocturnal sleep, patients had higher amounts of slow-wave sleep than controls (20 versus 13.8%). Multiple sleep latency tests revealed excessive daytime sleepiness in 15 patients (42%), and 10 of them had signs of chronic sleep deprivation. We conclude that post-traumatic pleiosomnia may be even more frequent than reported previously, because affected patients often underestimate their actual sleep need. Furthermore, these patients exhibit an increase in slow-wave sleep which may reflect recovery mechanisms, intrinsic consequences of diffuse brain damage or relative sleep deprivation. © 2013 European Sleep Research Society.

Modeling resting-state functional networks when the cortex falls asleep: local and global changes.

PubMed

Deco, Gustavo; Hagmann, Patric; Hudetz, Anthony G; Tononi, Giulio

2014-12-01

The transition from wakefulness to sleep represents the most conspicuous change in behavior and the level of consciousness occurring in the healthy brain. It is accompanied by similarly conspicuous changes in neural dynamics, traditionally exemplified by the change from "desynchronized" electroencephalogram activity in wake to globally synchronized slow wave activity of early sleep. However, unit and local field recordings indicate that the transition is more gradual than it might appear: On one hand, local slow waves already appear during wake; on the other hand, slow sleep waves are only rarely global. Studies with functional magnetic resonance imaging also reveal changes in resting-state functional connectivity (FC) between wake and slow wave sleep. However, it remains unclear how resting-state networks may change during this transition period. Here, we employ large-scale modeling of the human cortico-cortical anatomical connectivity to evaluate changes in resting-state FC when the model "falls asleep" due to the progressive decrease in arousal-promoting neuromodulation. When cholinergic neuromodulation is parametrically decreased, local slow waves appear, while the overall organization of resting-state networks does not change. Furthermore, we show that these local slow waves are structured macroscopically in networks that resemble the resting-state networks. In contrast, when the neuromodulator decrease further to very low levels, slow waves become global and resting-state networks merge into a single undifferentiated, broadly synchronized network. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Interhemispheric correlations of slow spontaneous neuronal fluctuations revealed in human sensory cortex

PubMed Central

Nir, Yuval; Mukamel, Roy; Dinstein, Ilan; Privman, Eran; Harel, Michal; Fisch, Lior; Gelbard-Sagiv, Hagar; Kipervasser, Svetlana; Andelman, Fani; Neufeld, Miri Y; Kramer, Uri; Arieli, Amos; Fried, Itzhak; Malach, Rafael

2009-01-01

Animal studies have shown robust electrophysiological activity in the sensory cortex in the absence of stimuli or tasks. Similarly, recent human functional magnetic resonance imaging (fMRI) revealed widespread, spontaneously emerging cortical fluctuations. However, it is unknown what neuronal dynamics underlie this spontaneous activity in the human brain. Here we studied this issue by combining bilateral single-unit, local field potentials (LFPs) and intracranial electrocorticography (ECoG) recordings in individuals undergoing clinical monitoring. We found slow (<0.1 Hz, following 1/f-like profiles) spontaneous fluctuations of neuronal activity with significant interhemispheric correlations. These fluctuations were evident mainly in neuronal firing rates and in gamma (40–100 Hz) LFP power modulations. Notably, the interhemispheric correlations were enhanced during rapid eye movement and stage 2 sleep. Multiple intracranial ECoG recordings revealed clear selectivity for functional networks in the spontaneous gamma LFP power modulations. Our results point to slow spontaneous modulations in firing rate and gamma LFP as the likely correlates of spontaneous fMRI fluctuations in the human sensory cortex. PMID:19160509

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate

PubMed Central

Falcone, Mary; Cao, Wen; Bernardo, Leah; Tyndale, Rachel F; Loughead, James; Lerman, Caryn

2017-01-01

Background Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (NMR, 3′-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance, and a well validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers. Methods Sixty-nine treatment-seeking smokers (30 slow, 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once following 24 hours of smoking abstinence. Results In whole brain analysis, normal (compared to slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were even more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke. Conclusion Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy. PMID:26805583

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate.

PubMed

Falcone, Mary; Cao, Wen; Bernardo, Leah; Tyndale, Rachel F; Loughead, James; Lerman, Caryn

2016-08-01

Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (3'-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance and a well-validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers. Treatment-seeking smokers (N = 69; 30 slow metabolizers and 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once after 24 hours of smoking abstinence. In whole-brain analysis, normal (compared with slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke. Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Different event-related patterns of gamma-band power in brain waves of fast- and slow-reacting subjects.

PubMed Central

Jokeit, H; Makeig, S

1994-01-01

Fast- and slow-reacting subjects exhibit different patterns of gamma-band electroencephalogram (EEG) activity when responding as quickly as possible to auditory stimuli. This result appears to confirm long-standing speculations of Wundt that fast- and slow-reacting subjects produce speeded reactions in different ways and demonstrates that analysis of event-related changes in the amplitude of EEG activity recorded from the human scalp can reveal information about event-related brain processes unavailable using event-related potential measures. Time-varying spectral power in a selected (35- to 43-Hz) gamma frequency band was averaged across trials in two experimental conditions: passive listening and speeded reacting to binaural clicks, forming 40-Hz event-related spectral responses. Factor analysis of between-subject event-related spectral response differences split subjects into two near-equal groups composed of faster- and slower-reacting subjects. In faster-reacting subjects, 40-Hz power peaked near 200 ms and 400 ms poststimulus in the react condition, whereas in slower-reacting subjects, 40-Hz power just before stimulus delivery was larger in the react condition. These group differences were preserved in separate averages of relatively long and short reaction-time epochs for each group. gamma-band (20-60 Hz)-filtered event-related potential response averages did not differ between the two groups or conditions. Because of this and because gamma-band power in the auditory event-related potential is small compared with the EEG, the observed event-related spectral response features must represent gamma-band EEG activity reliably induced by, but not phase-locked to, experimental stimuli or events. PMID:8022783

Characterization of EEG patterns in brain-injured subjects and controls after a Snoezelen(®) intervention.

PubMed

Gómez, Carlos; Poza, Jesús; Gutiérrez, María T; Prada, Esther; Mendoza, Nuria; Hornero, Roberto

2016-11-01

The aim of this study was to assess the changes induced in electroencephalographic (EEG) activity by a Snoezelen(®) intervention on individuals with brain-injury and control subjects. EEG activity was recorded preceding and following a Snoezelen(®) session in 18 people with cerebral palsy (CP), 18 subjects who have sustained traumatic brain-injury (TBI) and 18 controls. EEG data were analyzed by means of spectral and nonlinear measures: median frequency (MF), individual alpha frequency (IAF), sample entropy (SampEn) and Lempel-Ziv complexity (LZC). Our results showed decreased values for MF, IAF, SampEn and LZC as a consequence of the therapy. The main changes between pre-stimulation and post-stimulation conditions were found in occipital and parietal brain areas. Additionally, these changes are more widespread in controls than in brain-injured subjects, which can be due to cognitive deficits in TBI and CP groups. Our findings support the notion that Snoezelen(®) therapy affects central nervous system, inducing a slowing of oscillatory activity, as well as a decrease of EEG complexity and irregularity. These alterations seem to be related with higher levels of relaxation of the participants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Neural Correlates of Encoding Predict Infants' Memory in the Paired-Comparison Procedure

ERIC Educational Resources Information Center

Snyder, Kelly A.

2010-01-01

The present study used event-related potentials (ERPs) to monitor infant brain activity during the initial encoding of a previously novel visual stimulus, and examined whether ERP measures of encoding predicted infants' subsequent performance on a visual memory task (i.e., the paired-comparison task). A late slow wave component of the ERP measured…

Effects of Cognitive-Communication Stimulation for Alzheimer's Disease Patients Treated with Donepezil.

ERIC Educational Resources Information Center

Chapman, Sandra Bond; Weiner, Myron F.; Rackley, Audette; Hynan, Linda S.; Zientz, Jennifer

2004-01-01

ds to growing evidence that active cognitive stimulation may slow the rate of verbal and functional decline and decrease negative emotional symptoms in AD when combined with acetylcholinesterase inhibitors, indicating a need to advance research in the area of cognitive treatments. The fact that AD is a progressive brain disease should not preclude…

Effect of acute hypoxic shock on the rat brain morphology and tripeptidyl peptidase I activity.

PubMed

Petrova, Emilia B; Dimitrova, Mashenka B; Ivanov, Ivaylo P; Pavlova, Velichka G; Dimitrova, Stella G; Kadiysky, Dimitar S

2016-06-01

Hypoxic events are known to cause substantial damage to the hippocampus, cerebellum and striatum. The impact of hypoxic shock on other brain parts is not sufficiently studied. Recent studies show that tripeptidyl peptidase I (TPPI) activity in fish is altered after a hypoxic stress pointing out at a possible enzyme involvement in response to hypoxia. Similar studies are not performed in mammals. In this work, the effect of sodium nitrite-induced acute hypoxic shock on the rat brain was studied at different post-treatment periods. Morphological changes in cerebral cortex, cerebellum, medulla oblongata, thalamus, mesencephalon and pons were assessed using silver-copper impregnation for neurodegeneration. TPPI activity was biochemically assayed and localized by enzyme histochemistry. Although less vulnerable to oxidative stress, the studied brain areas showed different histopathological changes, such as neuronal loss and tissue vacuolization, dilatation of the smallest capillaries and impairment of neuronal processes. TPPI activity was strictly regulated following the hypoxic stress. It was found to increase 12-24h post-treatment, then decreased followed by a slow process of recovery. The enzyme histochemistry revealed a temporary enzyme deficiency in all types of neurons. These findings indicate a possible involvement of the enzyme in rat brain response to hypoxic stress. Copyright © 2016 Elsevier GmbH. All rights reserved.

Hippocampal memory consolidation during sleep: a comparison of mammals and birds

PubMed Central

Rattenborg, Niels C.; Martinez-Gonzalez, Dolores; Roth, Timothy C.; Pravosudov, Vladimir V.

2010-01-01

The transition from wakefulness to sleep is marked by pronounced changes in brain activity. The brain rhythms that characterize the two main types of mammalian sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to be involved in the functions of sleep. In particular, recent theories suggest that the synchronous slow-oscillation of neocortical neuronal membrane potentials, the defining feature of SWS, is involved in processing information acquired during wakefulness. According to the Standard Model of memory consolidation, during wakefulness the hippocampus receives input from neocortical regions involved in the initial encoding of an experience and binds this information into a coherent memory trace that is then transferred to the neocortex during SWS where it is stored and integrated within preexisting memory traces. Evidence suggests that this process selectively involves direct connections from the hippocampus to the prefrontal cortex (PFC), a multimodal, high-order association region implicated in coordinating the storage and recall of remote memories in the neocortex. The slow-oscillation is thought to orchestrate the transfer of information from the hippocampus by temporally coupling hippocampal sharp-wave/ripples (SWRs) and thalamocortical spindles. SWRs are synchronous bursts of hippocampal activity, during which waking neuronal firing patterns are reactivated in the hippocampus and neocortex in a coordinated manner. Thalamocortical spindles are brief 7–14 Hz oscillations that may facilitate the encoding of information reactivated during SWRs. By temporally coupling the readout of information from the hippocampus with conditions conducive to encoding in the neocortex, the slow-oscillation is thought to mediate the transfer of information from the hippocampus to the neocortex. Although several lines of evidence are consistent with this function for mammalian SWS, it is unclear whether SWS serves a similar function in birds, the only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on our review of research on avian sleep, neuroanatomy, and memory, although involved in some forms of memory consolidation, avian sleep does not appear to be involved in transferring hippocampal memories to other brain regions. Despite exhibiting the slow-oscillation, SWRs and spindles have not been found in birds. Moreover, although birds independently evolved a brain region – the caudolateral nidopallium (NCL) – involved in performing high-order cognitive functions similar to those performed by the PFC, direct connections between the NCL and hippocampus have not been found in birds, and evidence for the transfer of information from the hippocampus to the NCL or other extra-hippocampal regions is lacking. Although based on the absence of evidence for various traits, collectively, these findings suggest that unlike mammalian SWS, avian SWS may not be involved in transferring memories from the hippocampus. Furthermore, it suggests that the slow-oscillation, the defining feature of mammalian and avian SWS, may serve a more general function independent of that related to coordinating the transfer of information from the hippocampus to the PFC in mammals. Given that SWS is homeostatically regulated (a process intimately related to the slow-oscillation) in mammals and birds, functional hypotheses linked to this process may apply to both taxonomic groups. PMID:21070585

Hippocampal memory consolidation during sleep: a comparison of mammals and birds.

PubMed

Rattenborg, Niels C; Martinez-Gonzalez, Dolores; Roth, Timothy C; Pravosudov, Vladimir V

2011-08-01

The transition from wakefulness to sleep is marked by pronounced changes in brain activity. The brain rhythms that characterize the two main types of mammalian sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to be involved in the functions of sleep. In particular, recent theories suggest that the synchronous slow-oscillation of neocortical neuronal membrane potentials, the defining feature of SWS, is involved in processing information acquired during wakefulness. According to the Standard Model of memory consolidation, during wakefulness the hippocampus receives input from neocortical regions involved in the initial encoding of an experience and binds this information into a coherent memory trace that is then transferred to the neocortex during SWS where it is stored and integrated within preexisting memory traces. Evidence suggests that this process selectively involves direct connections from the hippocampus to the prefrontal cortex (PFC), a multimodal, high-order association region implicated in coordinating the storage and recall of remote memories in the neocortex. The slow-oscillation is thought to orchestrate the transfer of information from the hippocampus by temporally coupling hippocampal sharp-wave/ripples (SWRs) and thalamocortical spindles. SWRs are synchronous bursts of hippocampal activity, during which waking neuronal firing patterns are reactivated in the hippocampus and neocortex in a coordinated manner. Thalamocortical spindles are brief 7-14 Hz oscillations that may facilitate the encoding of information reactivated during SWRs. By temporally coupling the readout of information from the hippocampus with conditions conducive to encoding in the neocortex, the slow-oscillation is thought to mediate the transfer of information from the hippocampus to the neocortex. Although several lines of evidence are consistent with this function for mammalian SWS, it is unclear whether SWS serves a similar function in birds, the only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on our review of research on avian sleep, neuroanatomy, and memory, although involved in some forms of memory consolidation, avian sleep does not appear to be involved in transferring hippocampal memories to other brain regions. Despite exhibiting the slow-oscillation, SWRs and spindles have not been found in birds. Moreover, although birds independently evolved a brain region--the caudolateral nidopallium (NCL)--involved in performing high-order cognitive functions similar to those performed by the PFC, direct connections between the NCL and hippocampus have not been found in birds, and evidence for the transfer of information from the hippocampus to the NCL or other extra-hippocampal regions is lacking. Although based on the absence of evidence for various traits, collectively, these findings suggest that unlike mammalian SWS, avian SWS may not be involved in transferring memories from the hippocampus. Furthermore, it suggests that the slow-oscillation, the defining feature of mammalian and avian SWS, may serve a more general function independent of that related to coordinating the transfer of information from the hippocampus to the PFC in mammals. Given that SWS is homeostatically regulated (a process intimately related to the slow-oscillation) in mammals and birds, functional hypotheses linked to this process may apply to both taxonomic groups. © 2010 The Authors. Biological Reviews © 2010 Cambridge Philosophical Society.

Resting-State Functional Connectivity Emerges from Structurally and Dynamically Shaped Slow Linear Fluctuations

PubMed Central

Deco, Gustavo; Mantini, Dante; Romani, Gian Luca; Hagmann, Patric; Corbetta, Maurizio

2013-01-01

Brain fluctuations at rest are not random but are structured in spatial patterns of correlated activity across different brain areas. The question of how resting-state functional connectivity (FC) emerges from the brain's anatomical connections has motivated several experimental and computational studies to understand structure–function relationships. However, the mechanistic origin of resting state is obscured by large-scale models' complexity, and a close structure–function relation is still an open problem. Thus, a realistic but simple enough description of relevant brain dynamics is needed. Here, we derived a dynamic mean field model that consistently summarizes the realistic dynamics of a detailed spiking and conductance-based synaptic large-scale network, in which connectivity is constrained by diffusion imaging data from human subjects. The dynamic mean field approximates the ensemble dynamics, whose temporal evolution is dominated by the longest time scale of the system. With this reduction, we demonstrated that FC emerges as structured linear fluctuations around a stable low firing activity state close to destabilization. Moreover, the model can be further and crucially simplified into a set of motion equations for statistical moments, providing a direct analytical link between anatomical structure, neural network dynamics, and FC. Our study suggests that FC arises from noise propagation and dynamical slowing down of fluctuations in an anatomically constrained dynamical system. Altogether, the reduction from spiking models to statistical moments presented here provides a new framework to explicitly understand the building up of FC through neuronal dynamics underpinned by anatomical connections and to drive hypotheses in task-evoked studies and for clinical applications. PMID:23825427

Resting-state functional connectivity emerges from structurally and dynamically shaped slow linear fluctuations.

PubMed

Deco, Gustavo; Ponce-Alvarez, Adrián; Mantini, Dante; Romani, Gian Luca; Hagmann, Patric; Corbetta, Maurizio

2013-07-03

Brain fluctuations at rest are not random but are structured in spatial patterns of correlated activity across different brain areas. The question of how resting-state functional connectivity (FC) emerges from the brain's anatomical connections has motivated several experimental and computational studies to understand structure-function relationships. However, the mechanistic origin of resting state is obscured by large-scale models' complexity, and a close structure-function relation is still an open problem. Thus, a realistic but simple enough description of relevant brain dynamics is needed. Here, we derived a dynamic mean field model that consistently summarizes the realistic dynamics of a detailed spiking and conductance-based synaptic large-scale network, in which connectivity is constrained by diffusion imaging data from human subjects. The dynamic mean field approximates the ensemble dynamics, whose temporal evolution is dominated by the longest time scale of the system. With this reduction, we demonstrated that FC emerges as structured linear fluctuations around a stable low firing activity state close to destabilization. Moreover, the model can be further and crucially simplified into a set of motion equations for statistical moments, providing a direct analytical link between anatomical structure, neural network dynamics, and FC. Our study suggests that FC arises from noise propagation and dynamical slowing down of fluctuations in an anatomically constrained dynamical system. Altogether, the reduction from spiking models to statistical moments presented here provides a new framework to explicitly understand the building up of FC through neuronal dynamics underpinned by anatomical connections and to drive hypotheses in task-evoked studies and for clinical applications.

Dynamic functional connectivity shapes individual differences in associative learning.

PubMed

Fatima, Zainab; Kovacevic, Natasha; Misic, Bratislav; McIntosh, Anthony Randal

2016-11-01

Current neuroscientific research has shown that the brain reconfigures its functional interactions at multiple timescales. Here, we sought to link transient changes in functional brain networks to individual differences in behavioral and cognitive performance by using an active learning paradigm. Participants learned associations between pairs of unrelated visual stimuli by using feedback. Interindividual behavioral variability was quantified with a learning rate measure. By using a multivariate statistical framework (partial least squares), we identified patterns of network organization across multiple temporal scales (within a trial, millisecond; across a learning session, minute) and linked these to the rate of change in behavioral performance (fast and slow). Results indicated that posterior network connectivity was present early in the trial for fast, and later in the trial for slow performers. In contrast, connectivity in an associative memory network (frontal, striatal, and medial temporal regions) occurred later in the trial for fast, and earlier for slow performers. Time-dependent changes in the posterior network were correlated with visual/spatial scores obtained from independent neuropsychological assessments, with fast learners performing better on visual/spatial subtests. No relationship was found between functional connectivity dynamics in the memory network and visual/spatial test scores indicative of cognitive skill. By using a comprehensive set of measures (behavioral, cognitive, and neurophysiological), we report that individual variations in learning-related performance change are supported by differences in cognitive ability and time-sensitive connectivity in functional neural networks. Hum Brain Mapp 37:3911-3928, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Does the cycad genotoxin MAM implicated in Guam ALS-PDC induce disease-relevant changes in mouse brain that includes olfaction?

PubMed

Kisby, Glen; Palmer, Valerie; Lasarev, Mike; Fry, Rebecca; Iordanov, Mihail; Magun, Eli; Samson, Leona; Spencer, Peter

2011-11-01

Western Pacific amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia complex (PDC), a prototypical neurodegenerative disease (tauopathy) affecting distinct genetic groups with common exposure to neurotoxic chemicals in cycad seed, has many features of Parkinson's and Alzheimer's diseases (AD), including early olfactory dysfunction. Guam ALS-PDC incidence correlates with cycad flour content of cycasin and its aglycone methylazoxymethanol (MAM), which produces persistent DNA damage (O(6)-methylguanine) in the brains of mice lacking O(6)-methylguanine methyltransferase (Mgmt(-/-)). We described in Mgmt(-/-)mice up to 7 days post-MAM treatment that brain DNA damage was linked to brain gene expression changes found in human neurological disease, cancer, and skin and hair development. This addendum reports 6 months post-MAM treatment- related brain transcriptional changes as well as elevated mitogen activated protein kinases and increased caspase-3 activity, both of which are involved in tau aggregation and neurofibrillary tangle formation typical of ALS-PDC and AD, plus transcriptional changes in olfactory receptors. Does cycasin act as a "slow (geno)toxin" in ALS-PDC?

β oscillation during slow wave sleep and rapid eye movement sleep in the electroencephalogram of a transgenic mouse model of Huntington's disease.

PubMed

Jeantet, Yannick; Cayzac, Sebastien; Cho, Yoon H

2013-01-01

To search for early abnormalities in electroencephalogram (EEG) during sleep which may precede motor symptoms in a transgenic mouse model of hereditary neurodegenerative Huntington's disease (HD). In the R6/1 transgenic mouse model of HD, rhythmic brain activity in EEG recordings was monitored longitudinally and across vigilance states through the onset and progression of disease. Mice with chronic electrode implants were recorded monthly over wake-sleep cycles (4 hours), beginning at 9-11 weeks (presymptomatic period) through 6-7 months (symptomatic period). Recording data revealed a unique β rhythm (20-35 Hz), present only in R6/1 transgenic mice, which evolves in close parallel with the disease. In addition, there was an unusual relationship between this β oscillation and vigilance states: while nearly absent during the active waking state, the β oscillation appeared with drowsiness and during slow wave sleep (SWS) and, interestingly, strengthened rather than dissipating when the brain returned to an activated state during rapid eye movement (REM) sleep. In addition to providing a new in vivo biomarker and insight into Huntington's disease pathophysiology, this serendipitous observation opens a window onto the rarely explored neurophysiology of the cortico-basal ganglia circuit during SWS and REM sleep.

Older age, traumatic brain injury, and cognitive slowing: some convergent and divergent findings.

PubMed

Bashore, Theodore R; Ridderinkhof, K Richard

2002-01-01

Reaction time (RT) meta-analyses of cognitive slowing indicate that all stages of processing slow equivalently and task independently among both older adults (J. Cerella & S. Hale, 1994) and adults who have suffered a traumatic brain injury (TBI; F. R. Ferraro, 1996). However, meta-analyses using both RT and P300 latency have revealed stage-specific and task-dependent changes among older individuals (T. R. Bashore, K. R. Ridderinkhof, & M. W. van der Molen, 1998). Presented in this article are a meta-analysis of the effect of TBI on processing speed, assessed using P300 latency and RT, and a qualitative review of the literature. They suggest that TBI induces differential slowing. Similarities in the effects of older age and TBI on processing speed are discussed and suggestions for future research on TBI-induced cognitive slowing are offered.

Old Brains Come Uncoupled in Sleep: Slow Wave-Spindle Synchrony, Brain Atrophy, and Forgetting.

PubMed

Helfrich, Randolph F; Mander, Bryce A; Jagust, William J; Knight, Robert T; Walker, Matthew P

2018-01-03

The coupled interaction between slow-wave oscillations and sleep spindles during non-rapid-eye-movement (NREM) sleep has been proposed to support memory consolidation. However, little evidence in humans supports this theory. Moreover, whether such dynamic coupling is impaired as a consequence of brain aging in later life, contributing to cognitive and memory decline, is unknown. Combining electroencephalography (EEG), structural MRI, and sleep-dependent memory assessment, we addressed these questions in cognitively normal young and older adults. Directional cross-frequency coupling analyses demonstrated that the slow wave governs a precise temporal coordination of sleep spindles, the quality of which predicts overnight memory retention. Moreover, selective atrophy within the medial frontal cortex in older adults predicted a temporal dispersion of this slow wave-spindle coupling, impairing overnight memory consolidation and leading to forgetting. Prefrontal-dependent deficits in the spatiotemporal coordination of NREM sleep oscillations therefore represent one pathway explaining age-related memory decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Background norepinephrine primes astrocytic calcium responses to subsequent norepinephrine stimuli in the cerebral cortex.

PubMed

Nuriya, Mutsuo; Takeuchi, Miyabi; Yasui, Masato

2017-01-29

Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This priming effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

[The pharmacology of memory (results and prospects)].

PubMed

Borodkin, Iu S; Zaĭtsev, Iu V

1984-07-01

Principal possibilities and limits of using the pharmacological approach for control of memory in studies of neurophysiological and neurochemical mechanisms of learning and memory in humans and animals are reviewed as well as its place in experimental and clinical therapy of memory disorders. Using an unspecific connector aethimizol as a pharmacological probe aided to assess changes accompanying the formation and consolidation of memory traces. The significance of fast and slow bioelectrical brain activity in the memory processing, the role of enzymes involved in transcription and template chromatine activity of the neurons under the effect of drugs on memory and learning, the correlation between time-depending learning and the pattern of RNA synthesis in brain cells, as well as possibilities and pathways of utilization of drugs in the correction of the long-term memory matrix formed by a stable pathological state of the brain, are discussed.

Spatiotemporal dynamics of the brain at rest--exploring EEG microstates as electrophysiological signatures of BOLD resting state networks.

PubMed

Yuan, Han; Zotev, Vadim; Phillips, Raquel; Drevets, Wayne C; Bodurka, Jerzy

2012-05-01

Neuroimaging research suggests that the resting cerebral physiology is characterized by complex patterns of neuronal activity in widely distributed functional networks. As studied using functional magnetic resonance imaging (fMRI) of the blood-oxygenation-level dependent (BOLD) signal, the resting brain activity is associated with slowly fluctuating hemodynamic signals (~10s). More recently, multimodal functional imaging studies involving simultaneous acquisition of BOLD-fMRI and electroencephalography (EEG) data have suggested that the relatively slow hemodynamic fluctuations of some resting state networks (RSNs) evinced in the BOLD data are related to much faster (~100 ms) transient brain states reflected in EEG signals, that are referred to as "microstates". To further elucidate the relationship between microstates and RSNs, we developed a fully data-driven approach that combines information from simultaneously recorded, high-density EEG and BOLD-fMRI data. Using independent component analysis (ICA) of the combined EEG and fMRI data, we identified thirteen microstates and ten RSNs that are organized independently in their temporal and spatial characteristics, respectively. We hypothesized that the intrinsic brain networks that are active at rest would be reflected in both the EEG data and the fMRI data. To test this hypothesis, the rapid fluctuations associated with each microstate were correlated with the BOLD-fMRI signal associated with each RSN. We found that each RSN was characterized further by a specific electrophysiological signature involving from one to a combination of several microstates. Moreover, by comparing the time course of EEG microstates to that of the whole-brain BOLD signal, on a multi-subject group level, we unraveled for the first time a set of microstate-associated networks that correspond to a range of previously described RSNs, including visual, sensorimotor, auditory, attention, frontal, visceromotor and default mode networks. These results extend our understanding of the electrophysiological signature of BOLD RSNs and demonstrate the intrinsic connection between the fast neuronal activity and slow hemodynamic fluctuations. Copyright © 2012 Elsevier Inc. All rights reserved.

Brain self-regulation in criminal psychopaths.

PubMed

Konicar, Lilian; Veit, Ralf; Eisenbarth, Hedwig; Barth, Beatrix; Tonin, Paolo; Strehl, Ute; Birbaumer, Niels

2015-03-24

Psychopathic individuals are characterized by impaired affective processing, impulsivity, sensation-seeking, poor planning skills and heightened aggressiveness with poor self-regulation. Based on brain self-regulation studies using neurofeedback of Slow Cortical Potentials (SCPs) in disorders associated with a dysregulation of cortical activity thresholds and evidence of deficient cortical functioning in psychopathy, a neurobiological approach seems to be promising in the treatment of psychopathy. The results of our intensive brain regulation intervention demonstrate, that psychopathic offenders are able to gain control of their brain excitability over fronto-central brain areas. After SCP self-regulation training, we observed reduced aggression, impulsivity and behavioral approach tendencies, as well as improvements in behavioral-inhibition and increased cortical sensitivity for error-processing. This study demonstrates improvements on the neurophysiological, behavioral and subjective level in severe psychopathic offenders after SCP-neurofeedback training and could constitute a novel neurobiologically-based treatment for a seemingly change-resistant group of criminal psychopaths.

Primate energy expenditure and life history

PubMed Central

Pontzer, Herman; Raichlen, David A.; Gordon, Adam D.; Schroepfer-Walker, Kara K.; Hare, Brian; O’Neill, Matthew C.; Muldoon, Kathleen M.; Dunsworth, Holly M.; Wood, Brian M.; Isler, Karin; Burkart, Judith; Irwin, Mitchell; Shumaker, Robert W.; Lonsdorf, Elizabeth V.; Ross, Stephen R.

2014-01-01

Humans and other primates are distinct among placental mammals in having exceptionally slow rates of growth, reproduction, and aging. Primates’ slow life history schedules are generally thought to reflect an evolved strategy of allocating energy away from growth and reproduction and toward somatic investment, particularly to the development and maintenance of large brains. Here we examine an alternative explanation: that primates’ slow life histories reflect low total energy expenditure (TEE) (kilocalories per day) relative to other placental mammals. We compared doubly labeled water measurements of TEE among 17 primate species with similar measures for other placental mammals. We found that primates use remarkably little energy each day, expending on average only 50% of the energy expected for a placental mammal of similar mass. Such large differences in TEE are not easily explained by differences in physical activity, and instead appear to reflect systemic metabolic adaptation for low energy expenditures in primates. Indeed, comparisons of wild and captive primate populations indicate similar levels of energy expenditure. Broad interspecific comparisons of growth, reproduction, and maximum life span indicate that primates’ slow metabolic rates contribute to their characteristically slow life histories. PMID:24474770

Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms

PubMed Central

Petzold, Anne; Valencia, Miguel; Pál, Balázs; Mena-Segovia, Juan

2015-01-01

Cholinergic neurons of the pedunculopontine nucleus (PPN) are most active during the waking state. Their activation is deemed to cause a switch in the global brain activity from sleep to wakefulness, while their sustained discharge may contribute to upholding the waking state and enhancing arousal. Similarly, non-cholinergic PPN neurons are responsive to brain state transitions and their activation may influence some of the same targets of cholinergic neurons, suggesting that they operate in coordination. Yet, it is not clear how the discharge of distinct classes of PPN neurons organize during brain states. Here, we monitored the in vivo network activity of PPN neurons in the anesthetized rat across two distinct levels of cortical dynamics and their transitions. We identified a highly structured configuration in PPN network activity during slow-wave activity that was replaced by decorrelated activity during the activated state (AS). During the transition, neurons were predominantly excited (phasically or tonically), but some were inhibited. Identified cholinergic neurons displayed phasic and short latency responses to sensory stimulation, whereas the majority of non-cholinergic showed tonic responses and remained at high discharge rates beyond the state transition. In vitro recordings demonstrate that cholinergic neurons exhibit fast adaptation that prevents them from discharging at high rates over prolonged time periods. Our data shows that PPN neurons have distinct but complementary roles during brain state transitions, where cholinergic neurons provide a fast and transient response to sensory events that drive state transitions, whereas non-cholinergic neurons maintain an elevated firing rate during global activation. PMID:26582977

Familial History of Reading Difficulty Is Associated with Diffused Bilateral Brain Activation during Reading and Greater Association with Visual Attention Abilities

ERIC Educational Resources Information Center

Horowitz-Kraus, Tzipi

2017-01-01

Reading difficulty (RD; or dyslexia) is a heritable condition characterized by slow, inaccurate reading accompanied by executive dysfunction, specifically with respect to visual attention. The current study was designed to examine the effect of familial history of RD on the relationship between reading and visual attention abilities in children…

[EFFECTS OF ELECTRICAL STIMULATION OF NUCLEUS RETICULARIS PONTIS ORALIS ON THE SLEEP-WAKING STATES IN KRUSHINSKII-MOLODKINA STRAIN RATS].

PubMed

Vataev, S I; Malgina, N A; Oganesyan, G A

2015-07-01

The effects of electrical stimulation of nucleus reticularis pontis oralis on the behavior and brain electrical activity during all phases of the sleep-waking cycle was studied in Krushinskii-Molodkina strain rats, which have an inherited predisposition to audiogenic seizures. Electrical stimulation with 7 Hz frequency in the deep stage of slow-wave sleep cause appearance the fast-wave sleep. Similar stimulation during fast-wave sleep periods did not effects on the electrographic patterns and EEG spectral characteristics of hippocampus, visual, auditory and somatocnen nrnrenc nf the cnrtey ThPe sfimul1stinns did nnt break a fast-wave sleenhut increased almost twice due the duration of these sleep episodes. After electrical stimulation by same frequency during the wakeftlness and superficial slow-wave sleep states, the patterns and spectral characteristics of brain electrical activity in rats showed no significant changes as compared with controls. The results of this study indicate that the state of the animals sleep-waking cycle at the time of stimulation is a critical variable that influences the responses which are induced by electrical stimulation of the nucleus reticularis pontis oralis.

Sound Asleep: Processing and Retention of Slow Oscillation Phase-Targeted Stimuli

PubMed Central

Cox, Roy; Korjoukov, Ilia; de Boer, Marieke; Talamini, Lucia M.

2014-01-01

The sleeping brain retains some residual information processing capacity. Although direct evidence is scarce, a substantial literature suggests the phase of slow oscillations during deep sleep to be an important determinant for stimulus processing. Here, we introduce an algorithm for predicting slow oscillations in real-time. Using this approach to present stimuli directed at both oscillatory up and down states, we show neural stimulus processing depends importantly on the slow oscillation phase. During ensuing wakefulness, however, we did not observe differential brain or behavioral responses to these stimulus categories, suggesting no enduring memories were formed. We speculate that while simpler forms of learning may occur during sleep, neocortically based memories are not readily established during deep sleep. PMID:24999803

Sound asleep: processing and retention of slow oscillation phase-targeted stimuli.

PubMed

Cox, Roy; Korjoukov, Ilia; de Boer, Marieke; Talamini, Lucia M

2014-01-01

The sleeping brain retains some residual information processing capacity. Although direct evidence is scarce, a substantial literature suggests the phase of slow oscillations during deep sleep to be an important determinant for stimulus processing. Here, we introduce an algorithm for predicting slow oscillations in real-time. Using this approach to present stimuli directed at both oscillatory up and down states, we show neural stimulus processing depends importantly on the slow oscillation phase. During ensuing wakefulness, however, we did not observe differential brain or behavioral responses to these stimulus categories, suggesting no enduring memories were formed. We speculate that while simpler forms of learning may occur during sleep, neocortically based memories are not readily established during deep sleep.

Functional neuroimaging insights into the physiology of human sleep.

PubMed

Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Sterpenich, Virginie; Bonjean, Maxime; Maquet, Pierre

2010-12-01

Functional brain imaging has been used in humans to noninvasively investigate the neural mechanisms underlying the generation of sleep stages. On the one hand, REM sleep has been associated with the activation of the pons, thalamus, limbic areas, and temporo-occipital cortices, and the deactivation of prefrontal areas, in line with theories of REM sleep generation and dreaming properties. On the other hand, during non-REM (NREM) sleep, decreases in brain activity have been consistently found in the brainstem, thalamus, and in several cortical areas including the medial prefrontal cortex (MPFC), in agreement with a homeostatic need for brain energy recovery. Benefiting from a better temporal resolution, more recent studies have characterized the brain activations related to phasic events within specific sleep stages. In particular, they have demonstrated that NREM sleep oscillations (spindles and slow waves) are indeed associated with increases in brain activity in specific subcortical and cortical areas involved in the generation or modulation of these waves. These data highlight that, even during NREM sleep, brain activity is increased, yet regionally specific and transient. Besides refining the understanding of sleep mechanisms, functional brain imaging has also advanced the description of the functional properties of sleep. For instance, it has been shown that the sleeping brain is still able to process external information and even detect the pertinence of its content. The relationship between sleep and memory has also been refined using neuroimaging, demonstrating post-learning reactivation during sleep, as well as the reorganization of memory representation on the systems level, sometimes with long-lasting effects on subsequent memory performance. Further imaging studies should focus on clarifying the role of specific sleep patterns for the processing of external stimuli, as well as the consolidation of freshly encoded information during sleep.

Comparative study on the inhibitory effect of caffeic and chlorogenic acids on key enzymes linked to Alzheimer's disease and some pro-oxidant induced oxidative stress in rats' brain-in vitro.

PubMed

Oboh, Ganiyu; Agunloye, Odunayo M; Akinyemi, Ayodele J; Ademiluyi, Adedayo O; Adefegha, Stephen A

2013-02-01

This study sought to investigate and compare the interaction of caffeic acid and chlorogenic acid on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and some pro-oxidants (FeSO(4), sodium nitroprusside and quinolinic acid) induced oxidative stress in rat brain in vitro. The result revealed that caffeic acid and chlorogenic acid inhibited AChE and BChE activities in dose-dependent manner; however, caffeic acid had a higher inhibitory effect on AChE and BChE activities than chlorogenic acid. Combination of the phenolic acids inhibited AChE and BChE activities antagonistically. Furthermore, pro-oxidants such as, FeSO(4), sodium nitroprusside and quinolinic acid caused increase in the malondialdehyde (MDA) contents of the brain which was significantly decreased dose-dependently by the phenolic acids. Inhibition of AChE and BChE activities slows down acetylcholine and butyrylcholine breakdown in the brain. Therefore, one possible mechanism through which the phenolic acids exert their neuroprotective properties is by inhibiting AChE and BChE activities as well as preventing oxidative stress-induced neurodegeneration. However, esterification of caffeic acid with quinic acid producing chlorogenic acid affects these neuroprotective properties.

Evaluation of [11C]TAZA for amyloid β plaque imaging in postmortem human Alzheimer's disease brain region and whole body distribution in rodent PET/CT.

PubMed

Pan, Min-Liang; Mukherjee, Meenakshi T; Patel, Himika H; Patel, Bhavin; Constantinescu, Cristian C; Mirbolooki, M Reza; Liang, Christopher; Mukherjee, Jogeshwar

2016-04-01

Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aβ plaques in the brain. The aim of this study was to evaluate the effectiveness of a novel radiotracer, 4-[(11) C]methylamino-4'-N,N-dimethylaminoazobenzene ([(11)C]TAZA), for binding to Aβ plaques in postmortem human brain (AD and normal control (NC)). Radiosyntheses of [(11)C]TAZA, related [(11)C]Dalene ((11)C-methylamino-4'-dimethylaminostyrylbenzene), and reference [(11)C]PIB were carried out using [(11)C]methyltriflate prepared from [(11) C]CO(2) and purified using HPLC. In vitro binding affinities were carried out in human AD brain homogenate with Aβ plaques labeled with [(3) H]PIB. In vitro autoradiography studies with the three radiotracers were performed on hippocampus of AD and NC brains. PET/CT studies were carried out in normal rats to study brain and whole body distribution. The three radiotracers were produced in high radiochemical yields (>40%) and had specific activities >37 GBq/μmol. TAZA had an affinity, K(i) = 0.84 nM and was five times more potent than PIB. [(11)C]TAZA bound specifically to Aβ plaques present in AD brains with gray matter to white matter ratios >20. [(11)C]TAZA was displaced by PIB (>90%), suggesting similar binding site for [(11)C]TAZA and [(11)C]PIB. [(11)C]TAZA exhibited slow kinetics of uptake in the rat brain and whole body images showed uptake in interscapular brown adipose tissue (IBAT). Binding in brain and IBAT were affected by preinjection of atomoxetine, a norepinephrine transporter blocker. [(11)C]TAZA exhibited high binding to Aβ plaques in human AD hippocampus. Rat brain kinetics was slow and peripheral binding to IBAT needs to be further evaluated. © 2016 Wiley Periodicals, Inc.

Beneficial effects of anti-inflammatory therapy in a mouse model of Niemann-Pick disease type C1.

PubMed

Smith, David; Wallom, Kerri-Lee; Williams, Ian M; Jeyakumar, Mylvaganam; Platt, Frances M

2009-11-01

Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal disorder characterized by sphingolipid and cholesterol storage in the late endocytic system. In common with other neurodegenerative diseases, activation of the innate immune system occurs in the brain resulting in neuro-inflammation. Targeting inflammation in the brain therefore represents a potential clinical intervention strategy that aims to slow the rate of disease progression and improve quality of life. We evaluated non-steroidal anti-inflammatory drugs (NSAIDs) and an anti-oxidant to determine whether these agents are disease modifying in an acute mouse model of NPC1. NSAIDs significantly prolonged the lifespan of NPC1 mice and slowed the onset of clinical signs. However, anti-oxidant therapy was of no significant benefit. Combining NSAID therapy with substrate reduction therapy (SRT) resulted in additive benefit. These data suggest that anti-inflammatory therapy may be a useful adjunctive treatment in the clinical management of NPC1, alone or combined with SRT.

Correlations between the Signal Complexity of Cerebral and Cardiac Electrical Activity: A Multiscale Entropy Analysis

PubMed Central

Lin, Pei-Feng; Lo, Men-Tzung; Tsao, Jenho; Chang, Yi-Chung; Lin, Chen; Ho, Yi-Lwun

2014-01-01

The heart begins to beat before the brain is formed. Whether conventional hierarchical central commands sent by the brain to the heart alone explain all the interplay between these two organs should be reconsidered. Here, we demonstrate correlations between the signal complexity of brain and cardiac activity. Eighty-seven geriatric outpatients with healthy hearts and varied cognitive abilities each provided a 24-hour electrocardiography (ECG) and a 19-channel eye-closed routine electroencephalography (EEG). Multiscale entropy (MSE) analysis was applied to three epochs (resting-awake state, photic stimulation of fast frequencies (fast-PS), and photic stimulation of slow frequencies (slow-PS)) of EEG in the 1–58 Hz frequency range, and three RR interval (RRI) time series (awake-state, sleep and that concomitant with the EEG) for each subject. The low-to-high frequency power (LF/HF) ratio of RRI was calculated to represent sympatho-vagal balance. With statistics after Bonferroni corrections, we found that: (a) the summed MSE value on coarse scales of the awake RRI (scales 11–20, RRI-MSE-coarse) were inversely correlated with the summed MSE value on coarse scales of the resting-awake EEG (scales 6–20, EEG-MSE-coarse) at Fp2, C4, T6 and T4; (b) the awake RRI-MSE-coarse was inversely correlated with the fast-PS EEG-MSE-coarse at O1, O2 and C4; (c) the sleep RRI-MSE-coarse was inversely correlated with the slow-PS EEG-MSE-coarse at Fp2; (d) the RRI-MSE-coarse and LF/HF ratio of the awake RRI were correlated positively to each other; (e) the EEG-MSE-coarse at F8 was proportional to the cognitive test score; (f) the results conform to the cholinergic hypothesis which states that cognitive impairment causes reduction in vagal cardiac modulation; (g) fast-PS significantly lowered the EEG-MSE-coarse globally. Whether these heart-brain correlations could be fully explained by the central autonomic network is unknown and needs further exploration. PMID:24498375

Cerebral correlates of delta waves during non-REM sleep revisited.

PubMed

Dang-Vu, Thien Thanh; Desseilles, Martin; Laureys, Steven; Degueldre, Christian; Perrin, Fabien; Phillips, Christophe; Maquet, Pierre; Peigneux, Philippe

2005-10-15

We aimed at characterizing the neural correlates of delta activity during Non Rapid Eye Movement (NREM) sleep in non-sleep-deprived normal young adults, based on the statistical analysis of a positron emission tomography (PET) sleep data set. One hundred fifteen PET scans were obtained using H(2)(15)O under continuous polygraphic monitoring during stages 2-4 of NREM sleep. Correlations between regional cerebral blood flow (rCBF) and delta power (1.5-4 Hz) spectral density were analyzed using statistical parametric mapping (SPM2). Delta power values obtained at central scalp locations negatively correlated during NREM sleep with rCBF in the ventromedial prefrontal cortex, the basal forebrain, the striatum, the anterior insula, and the precuneus. These regions embrace the set of brain areas in which rCBF decreases during slow wave sleep (SWS) as compared to Rapid Eye Movement (REM) sleep and wakefulness (Maquet, P., Degueldre, C., Delfiore, G., Aerts, J., Peters, J.M., Luxen, A., Franck, G., 1997. Functional neuroanatomy of human slow wave sleep. J. Neurosci. 17, 2807-S2812), supporting the notion that delta activity is a valuable prominent feature of NREM sleep. A strong association was observed between rCBF in the ventromedial prefrontal regions and delta power, in agreement with electrophysiological studies. In contrast to the results of a previous PET study investigating the brain correlates of delta activity (Hofle, N., Paus, T., Reutens, D., Fiset, P., Gotman, J., Evans, A.C., Jones, B.E., 1997. Regional cerebral blood flow changes as a function of delta and spindle activity during slow wave sleep in humans. J. Neurosci. 17, 4800-4808), in which waking scans were mixed with NREM sleep scans, no correlation was found with thalamus activity. This latter result stresses the importance of an extra-thalamic delta rhythm among the synchronous NREM sleep oscillations. Consequently, this rCBF distribution might preferentially reflect a particular modulation of the cellular processes involved in the generation of cortical delta waves during NREM sleep.

The significance of selegiline/(-)-deprenyl after 50 years in research and therapy (1965-2015).

PubMed

Miklya, I

2016-11-01

Deprenyl/Selegiline (DEP), created by Joseph Knoll in the 1960s, registered in more than 60 countries to treat Parkinson's disease, Alzheimer's disease, major depressive disorder; and used as an anti-aging drug, achieved its place in research and therapy as the first selective inhibitor of B-type monoamine oxidase (MAO-B). The demonstration that the DEP analog (-)-1-phenyl-2-propylaminopentane devoid of MAO inhibitory property, enhanced like DEP the activity of the catecholaminergic brain engine revealed that this effect is unrelated to the selective inhibition of MAO-B. β-Phenylethylamine (PEA), the important trace-amine in the mammalian brain, is known to be a releaser of catecholamines. Amphetamine and methamphetamine, the best known synthetic PEA derivatives are also releasers of catecholamines like their parent compound. DEP is a unique synthetic PEA derivative devoid of the catecholamine releasing property. As the releasing effect conceals the catecholaminergic activity enhancer (CAE) effect, it remained undiscovered until DEP uncovered that PEA is a natural CAE substance; and only releases catecholamines in high concentration. Discovering that tryptamine is a natural enhancer of catecholaminergic and serotonergic neurons catalyzed the development of R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane (BPAP); the most potent and selective enhancer substance, and it exerts its enhancer effect in 0.0001 mg kg -1 . DEP and BPAP initiated an analysis of the enhancer regulation in the mammalian brain. Studies regarding the nature of the enhancer regulation revealed that this regulation is enhanced after weaning and sex hormones return it to the pre-weaning level. Thus, sex hormones elicit the transition of the developmental phase of life into the post-developmental, downhill (aging) period. The aging-related, slow decline in the enhancer regulation of the catecholaminergic brain engine, the main activator of the cortex, is the prime factor of brain aging. The enhancer regulation's decay in the most rapidly aging dopaminergic system is, for example, mainly responsible for the decline in learning ability and sexual activity over time. According to the Knoll concept, based on two longevity studies performed on male rats, to keep the catecholaminergic brain engine, from the beginning of the downhill period of life, via the administration of a small daily dose of a CAE substance (presently DEP is the only available drug) on a higher activity level, thus to fight against the physiological aging-related slow decay of the catecholaminergic system, is a suitable anti-aging therapy. As our present knowledge regarding the enhancer regulation in the mammalian brain is like seeing a peak of an iceberg, the future of this new line of brain research looks promising from both theoretical and practical aspects.

The human brain pacemaker: Synchronized infra-slow neurovascular coupling in patients undergoing non-pulsatile cardiopulmonary bypass.

PubMed

Zanatta, Paolo; Toffolo, Gianna Maria; Sartori, Elisa; Bet, Anna; Baldanzi, Fabrizio; Agarwal, Nivedita; Golanov, Eugene

2013-05-15

In non-pulsatile cardiopulmonary bypass surgery, middle cerebral artery blood flow velocity (BFV) is characterized by infra-slow oscillations of approximately 0.06Hz, which are paralleled by changes in total EEG power variability (EEG-PV), measured in 2s intervals. Since the origin of these BFV oscillations is not known, we explored their possible causative relationships with oscillations in EEG-PV at around 0.06Hz. We monitored 28 patients undergoing non-pulsatile cardiopulmonary bypass using transcranial Doppler sonography and scalp electroencephalography at two levels of anesthesia, deep (prevalence of burst suppression rhythm) and moderate (prevalence of theta rhythm). Under deep anesthesia, the EEG bursts suppression pattern was highly correlative with BFV oscillations. Hence, a detailed quantitative picture of the coupling between electrical brain activity and BFV was derived, both in deep and moderate anesthesia, via linear and non linear processing of EEG-PV and BFV signals, resorting to widely used measures of signal coupling such as frequency of oscillations, coherence, Granger causality and cross-approximate entropy. Results strongly suggest the existence of coupling between EEG-PV and BFV. In moderate anesthesia EEG-PV mean dominant frequency is similar to frequency of BFV oscillations (0.065±0.010Hz vs 0.045±0.019Hz); coherence between the two signals was significant in about 55% of subjects, and the Granger causality suggested an EEG-PV→BFV causal effect direction. The strength of the coupling increased with deepening anesthesia, as EEG-PV oscillations mean dominant frequency virtually coincided with the BFV peak frequency (0.062±0.017Hz vs 0.060±0.024Hz), and coherence became significant in a larger number (65%) of subjects. Cross-approximate entropy decreased significantly from moderate to deep anesthesia, indicating a higher level of synchrony between the two signals. Presence of a subcortical brain pacemaker that drives vascular infra-slow oscillations in the brain is proposed. These findings allow to suggest an original hypothesis explaining the mechanism underlying infra-slow neurovascular coupling. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of motion speed in action representations

PubMed Central

van Dam, Wessel O.; Speed, Laura J.; Lai, Vicky T.; Vigliocco, Gabriella; Desai, Rutvik H.

2017-01-01

Grounded cognition accounts of semantic representation posit that brain regions traditionally linked to perception and action play a role in grounding the semantic content of words and sentences. Sensory-motor systems are thought to support partially abstract simulations through which conceptual content is grounded. However, which details of sensory-motor experience are included in, or excluded from these simulations, is not well understood. We investigated whether sensory-motor brain regions are differentially involved depending on the speed of actions described in a sentence. We addressed this issue by examining the neural signature of relatively fast (The old lady scurried across the road) and slow (The old lady strolled across the road) action sentences. The results showed that sentences that implied fast motion modulated activity within the right posterior superior temporal sulcus and the angular and middle occipital gyri, areas associated with biological motion and action perception. Sentences that implied slow motion resulted in greater signal within the right primary motor cortex and anterior inferior parietal lobule, areas associated with action execution and planning. These results suggest that the speed of described motion influences representational content and modulates the nature of conceptual grounding. Fast motion events are represented more visually whereas motor regions play a greater role in representing conceptual content associated with slow motion. PMID:28160739

Inward rectifier potassium current IKir promotes intrinsic pacemaker activity of thalamocortical neurons.

PubMed

Amarillo, Yimy; Tissone, Angela I; Mato, Germán; Nadal, Marcela S

2018-06-01

Slow repetitive burst firing by hyperpolarized thalamocortical (TC) neurons correlates with global slow rhythms (<4 Hz), which are the physiological oscillations during non-rapid eye movement sleep or pathological oscillations during idiopathic epilepsy. The pacemaker activity of TC neurons depends on the expression of several subthreshold conductances, which are modulated in a behaviorally dependent manner. Here we show that upregulation of the small and neglected inward rectifier potassium current I Kir induces repetitive burst firing at slow and delta frequency bands. We demonstrate this in mouse TC neurons in brain slices by manipulating the Kir maximum conductance with dynamic clamp. We also performed a thorough theoretical analysis that explains how the unique properties of I Kir enable this current to induce slow periodic bursting in TC neurons. We describe a new ionic mechanism based on the voltage- and time-dependent interaction of I Kir and hyperpolarization-activated cationic current I h that endows TC neurons with the ability to oscillate spontaneously at very low frequencies, even below 0.5 Hz. Bifurcation analysis of conductance-based models of increasing complexity demonstrates that I Kir induces bistability of the membrane potential at the same time that it induces sustained oscillations in combination with I h and increases the robustness of low threshold-activated calcium current I T -mediated oscillations. NEW & NOTEWORTHY The strong inwardly rectifying potassium current I Kir of thalamocortical neurons displays a region of negative slope conductance in the current-voltage relationship that generates potassium currents activated by hyperpolarization. Bifurcation analysis shows that I Kir induces bistability of the membrane potential; generates sustained subthreshold oscillations by interacting with the hyperpolarization-activated cationic current I h ; and increases the robustness of oscillations mediated by the low threshold-activated calcium current I T . Upregulation of I Kir in thalamocortical neurons induces repetitive burst firing at slow and delta frequency bands (<4 Hz).

Slow-Theta-to-Gamma Phase–Amplitude Coupling in Human Hippocampus Supports the Formation of New Episodic Memories

PubMed Central

Lega, Bradley; Burke, John; Jacobs, Joshua; Kahana, Michael J.

2016-01-01

Phase–amplitude coupling (PAC) has been proposed as a neural mechanism for coordinating information processing across brain regions. Here we sought to characterize PAC in the human hippocampus, and in temporal and frontal cortices, during the formation of new episodic memories. Intracranial recordings taken as 56 neurosurgical patients studied and recalled lists of words revealed significant hippocampal PAC, with slow-theta activity (2.5–5 Hz) modulating gamma band activity (34–130 Hz). Furthermore, a significant number of hippocampal electrodes exhibited greater PAC during successful than unsuccessful encoding, with the gamma activity at these sites coupled to the trough of the slow-theta oscillation. These same conditions facilitate LTP in animal models, providing a possible mechanism of action for this effect in human memory. Uniquely in the hippocampus, phase preference during item encoding exhibited a biphasic pattern. Overall, our findings help translate between the patterns identified during basic memory tasks in animals and those present during complex human memory encoding. We discuss the unique properties of human hippocampal PAC and how our findings relate to influential theories of information processing based on theta–gamma interactions. PMID:25316340

Altered fast- and slow-twitch muscle fibre characteristics in female mice with a (S248F) knock-in mutation of the brain neuronal nicotinic acetylcholine receptor.

PubMed

Cannata, David J; Finkelstein, David I; Gantois, Ilse; Teper, Yaroslav; Drago, John; West, Jan M

2009-01-01

We generated a mouse line with a missense mutation (S248F) in the gene (CHRNA4) encoding the alpha4 subunit of neuronal nicotinic acetylcholine receptor (nAChR). Mutant mice demonstrate brief nicotine induced dystonia that resembles the clinical events seen in patients with the same mutation. Drug-induced dystonia is more pronounced in female mice, thus our aim was to determine if the S248F mutation changed the properties of fast- and slow-twitch muscle fibres from female mutant mice. Reverse transcriptase-PCR confirmed CHRNA4 gene expression in the brain but not skeletal muscles in normal and mutant mice. Ca(2+) and Sr(2+) force activation curves were obtained using skinned muscle fibres prepared from slow-twitch (soleus) and fast-twitch (EDL) muscles. Two significant results were found: (1) the (pCa(50) - pSr(50)) value from EDL fibres was smaller in mutant mice than in wild type (1.01 vs. 1.30), (2) the percentage force produced at pSr 5.5 was larger in mutants than in wild type (5.76 vs. 0.24%). Both results indicate a shift to slow-twitch characteristics in the mutant. This conclusion is supported by the identification of the myosin heavy chain (MHC) isoforms. Mutant EDL fibres expressed MHC I (usually only found in slow-twitch fibres) as well as MHC IIa. Despite the lack of spontaneous dystonic events, our findings suggest that mutant mice may be having subclinical events or the mutation results in a chronic alteration to muscle neural input.

Implication of the Slow-5 Oscillations in the Disruption of the Default-Mode Network in Healthy Aging and Stroke

PubMed Central

Nair, Veena A.; Mossahebi, Pouria; Young, Brittany M.; Chacon, Marcus; Jensen, Matthew; Birn, Rasmus M.; Meyerand, Mary E.; Prabhakaran, Vivek

2016-01-01

Abstract The processes of normal aging and aging-related pathologies subject the brain to an active re-organization of its brain networks. Among these, the default-mode network (DMN) is consistently implicated with a demonstrated reduction in functional connectivity within the network. However, no clear stipulation on the underlying mechanisms of the de-synchronization has yet been provided. In this study, we examined the spectral distribution of the intrinsic low-frequency oscillations (LFOs) of the DMN sub-networks in populations of young normals, older subjects, and acute and subacute ischemic stroke patients. The DMN sub-networks were derived using a mid-order group independent component analysis with 117 eyes-closed resting-state functional magnetic resonance imaging (rs-fMRI) sessions from volunteers in those population groups, isolating three robust components of the DMN among other resting-state networks. The posterior component of the DMN presented noticeable differences. Measures of amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) of the network component demonstrated a decrease in resting-state cortical oscillation power in the elderly (normal and patient), specifically in the slow-5 (0.01–0.027 Hz) range of oscillations. Furthermore, the contribution of the slow-5 oscillations during the resting state was diminished for a greater influence of the slow-4 (0.027–0.073 Hz) oscillations in the subacute stroke group, not only suggesting a vulnerability of the slow-5 oscillations to disruption but also indicating a change in the distribution of the oscillations within the resting-state frequencies. The reduction of network slow-5 fALFF in the posterior DMN component was found to present a potential association with behavioral measures, suggesting a brain–behavior relationship to those oscillations, with this change in behavior potentially resulting from an altered network integrity induced by a weakening of the slow-5 oscillations during the resting state. The repeated identification of those frequencies in the disruption of DMN stresses a critical role of the slow-5 oscillations in network disruption, and it accentuates the importance of managing those oscillations in the health of the DMN. PMID:27130180

The time-course of cortico-limbic neural responses to air hunger.

PubMed

Binks, Andrew P; Evans, Karleyton C; Reed, Jeffrey D; Moosavi, Shakeeb H; Banzett, Robert B

2014-12-01

Several studies have mapped brain regions associated with acute dyspnea perception. However, the time-course of brain activity during sustained dyspnea is unknown. Our objective was to determine the time-course of neural activity when dyspnea is sustained. Eight healthy subjects underwent brain blood oxygen level dependent functional magnetic imaging (BOLD-fMRI) during mechanical ventilation with constant mild hypercapnia (∼ 45 mm Hg). Subjects rated dyspnea (air hunger) via visual analog scale (VAS). Tidal volume (V(T)) was alternated every 90 s between high VT (0.96 ± 0.23 L) that provided respiratory comfort (12 ± 6% full scale) and low V(T) (0.48 ± 0.08 L) which evoked air hunger (56 ± 11% full scale). BOLD signal was extracted from a priori brain regions and combined with VAS data to determine air hunger related neural time-course. Air hunger onset was associated with BOLD signal increases that followed two distinct temporal profiles within sub-regions of the anterior insula, anterior cingulate and prefrontal cortices (cortico-limbic circuitry): (1) fast, BOLD signal peak <30s and (2) slow, BOLD signal peak >40s. BOLD signal during air hunger offset followed fast and slow temporal profiles symmetrical, but inverse (signal decreases) to the time-courses of air hunger onset. We conclude that differential cortico-limbic circuit elements have unique contributions to dyspnea sensation over time. We suggest that previously unidentified sub-regions are responsible for either the acute awareness or maintenance of dyspnea. These data enhance interpretation of previous studies and inform hypotheses for future dyspnea research. Copyright © 2014 Elsevier B.V. All rights reserved.

Fingolimod's Impact on MRI Brain Volume Measures in Multiple Sclerosis: Results from MS-MRIUS.

PubMed

Zivadinov, Robert; Medin, Jennie; Khan, Nasreen; Korn, Jonathan R; Bergsland, Niels; Dwyer, Michael G; Chitnis, Tanuja; Naismith, Robert T; Alvarez, Enrique; Kinkel, Peter; Cohan, Stanley; Hunter, Samuel F; Silva, Diego; Weinstock-Guttman, Bianca

2018-05-11

Evidence is needed to understand the effect of fingolimod on slowing down brain atrophy progression in multiple sclerosis (MS) patients in clinical practice. We investigated the effect of fingolimod on brain atrophy in MS patients with active disease (clinically and/or magnetic resonance imaging [MRI]) versus no evidence of active disease (NEAD). MS and clinical outcome and MRI in the United States (MS-MRIUS) is a multicenter, retrospective study that included 590 relapsing-remitting MS patients, who initiated fingolimod, and were followed for a median of 16 months. Patients with active disease at baseline (245, 41.5%) were defined as those who had one or more relapses in the year previous starting fingolimod, and/or displayed gadolinium enhancing lesions(s) at baseline MRI scan, whereas patients with NEAD at baseline (345, 58.5%) did not fulfill these criteria. Annualized percentage brain volume change (PBVC) and percentage lateral ventricle volume change (PLVVC) over the follow-up were analyzed in both groups. Over the follow-up, the rate of PBVC was -.38% in active disease and -.25% in NEAD patients (P = .076), whereas PLLVC was 1.76% in active disease and .28% in NEAD patients (P = .046). No changes in timed 25-foot walk (P = .619) and Expanded Disability Status Scale (P = .275) scores or MRI lesion accumulation (P > 0.08) were detected, although the active disease group had a higher proportion of relapses during the follow-up period (P = .02). The study provides real-world evidence that rate of brain atrophy in MS patients with underlying active disease and NEAD in fingolimod treated patients is below the established pathological cutoff for loss of whole brain volume (>-.4%) or expansion of lateral ventricles (> 3.5%). Copyright © 2018 by the American Society of Neuroimaging.

Brain potentials during mental arithmetic: effects of extensive practice and problem difficulty.

PubMed

Pauli, P; Lutzenberger, W; Rau, H; Birbaumer, N; Rickard, T C; Yaroush, R A; Bourne, L E

1994-07-01

Recent behavioral investigations indicate that the processes underlying mental arithmetic change systematically with practice from deliberate, conscious calculation to automatic, direct retrieval of answers from memory [Bourne, L.E.Jr. and Rickard, T.C., Mental calculation: The development of a cognitive skill, Paper presented at the Interamerican Congress of Psychology, San Jose, Costa Rica, 1991: Psychol. Rev., 95 (1988) 492-527]. Results reviewed by Moscovitch and Winocur [In: The handbook of aging and cognition, Erlbaum, Hillsdale, NJ, 1992, pp. 315-372] suggest that consciously controlled processes are more dependent on frontal lobe function than are automatic processes. It is appropriate, therefore to determine whether transitions in the locus of primary brain activity occur with practice on mental calculation. In this experiment, we examine the relationship between characteristics of event-related brain potentials (ERPs) and mental arithmetic. Single-digit mental multiplication problems varying in difficulty (problem size) were used, and subjects were trained on these problems for four sessions. Problem-size and practice effects were reliably found in behavioral measures (RT). The ERP was characterized by a pronounced late positivity after task presentation followed by a slow wave, and a negativity during response indication. These components responded differentially to the practice and problem-size manipulations. Practice mainly affected topography of the amplitude of positivity and offset latency of slow wave, and problem-size mainly offset latency of slow wave and pre-response negativity. Fronto-central positivity diminished from session to session, and the focus of positivity centered finally at centro-parietal regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential Activation of Medullary Vagal Nuclei Caused by Stimulation of Different Esophageal Mechanoreceptors

PubMed Central

Lang, Ivan M.; Medda, Bidyut K.; Shaker, Reza

2010-01-01

Esophageal mechanorecptors, i.e. muscular slowly adapting tension receptors and mucosal rapidly adapting touch receptors, mediate different sets of reflexes. The aim of this study was to determine the medullary vagal nuclei involved in the reflex responses to activation of these receptors. Thirty-three cats were anesthetized with alpha-chloralose and the esophagus was stimulated by slow balloon or rapid air distension. The physiological effects of the stimuli (N=4) were identified by recording responses from the pharyngeal, laryngeal, and hyoid muscles, esophagus, and the lower esophageal sphincter (LES). The effects on the medullary vagal nuclei of the stimuli: slow distension (N=10), rapid distension (N=9), and in control animals (N=10) were identified using the immunohistochemical analysis of c-fos. The experimental groups were stimulated 3 times per minute for 3 hours. After the experiment, the brains were removed and processed for c-fos immunoreactivity or thioinin. We found that slow balloon distension activated the esophago-UES contractile reflex and esophago LES relaxation response, and rapid air injection activated the belch and its component reflexes. Slow balloon distension activated the NTSce, NTSdl, NTSvl, DMNc, DMNr and NAr; and rapid air injection primarily activated AP, NTScd, NTSim, NTSis, NTSdm, NTSvl, NAc and NAr. We concluded that different sets of medullary vagal nuclei mediate different reflexes of the esophagus activated from different sets of mechanoreceptors. The NTScd is the primary NTS subnucleus mediating reflexes from the mucosal rapidly adapting touch receptors, and the NTSce is the primary NTS subnucleus mediating reflexes from the muscular slowly adapting tension receptors. The AP may be involved in mediation of belching. PMID:20971087

Rhythm generation, coordination, and initiation in the vocal pathways of male African clawed frogs

PubMed Central

Cavin Barnes, Jessica; Appleby, Todd

2016-01-01

Central pattern generators (CPGs) in the brain stem are considered to underlie vocalizations in many vertebrate species, but the detailed mechanisms underlying how motor rhythms are generated, coordinated, and initiated remain unclear. We addressed these issues using isolated brain preparations of Xenopus laevis from which fictive vocalizations can be elicited. Advertisement calls of male X. laevis that consist of fast and slow trills are generated by vocal CPGs contained in the brain stem. Brain stem central vocal pathways consist of a premotor nucleus [dorsal tegmental area of medulla (DTAM)] and a laryngeal motor nucleus [a homologue of nucleus ambiguus (n.IX-X)] with extensive reciprocal connections between the nuclei. In addition, DTAM receives descending inputs from the extended amygdala. We found that unilateral transection of the projections between DTAM and n.IX-X eliminated premotor fictive fast trill patterns but did not affect fictive slow trills, suggesting that the fast and slow trill CPGs are distinct; the slow trill CPG is contained in n.IX-X, and the fast trill CPG spans DTAM and n.IX-X. Midline transections that eliminated the anterior, posterior, or both commissures caused no change in the temporal structure of fictive calls, but bilateral synchrony was lost, indicating that the vocal CPGs are contained in the lateral halves of the brain stem and that the commissures synchronize the two oscillators. Furthermore, the elimination of the inputs from extended amygdala to DTAM, in addition to the anterior commissure, resulted in autonomous initiation of fictive fast but not slow trills by each hemibrain stem, indicating that the extended amygdala provides a bilateral signal to initiate fast trills. NEW & NOTEWORTHY Central pattern generators (CPGs) are considered to underlie vocalizations in many vertebrate species, but the detailed mechanisms underlying their functions remain unclear. We addressed this question using an isolated brain preparation of African clawed frogs. We discovered that two vocal phases are mediated by anatomically distinct CPGs, that there are a pair of CPGs contained in the left and right half of the brain stem, and that mechanisms underlying initiation of the two vocal phases are distinct. PMID:27760822

Common oscillatory mechanisms across multiple memory systems

NASA Astrophysics Data System (ADS)

Headley, Drew B.; Paré, Denis

2017-01-01

The cortex, hippocampus, and striatum support dissociable forms of memory. While each of these regions contains specialized circuitry supporting their respective functions, all structure their activities across time with delta, theta, and gamma rhythms. We review how these oscillations are generated and how they coordinate distinct memory systems during encoding, consolidation, and retrieval. First, gamma oscillations occur in all regions and coordinate local spiking, compressing it into short population bursts. Second, gamma oscillations are modulated by delta and theta oscillations. Third, oscillatory dynamics in these memory systems can operate in either a "slow" or "fast" mode. The slow mode happens during slow-wave sleep and is characterized by large irregular activity in the hippocampus and delta oscillations in cortical and striatal circuits. The fast mode occurs during active waking and rapid eye movement (REM) sleep and is characterized by theta oscillations in the hippocampus and its targets, along with gamma oscillations in the rest of cortex. In waking, the fast mode is associated with the efficacious encoding and retrieval of declarative and procedural memories. Theta and gamma oscillations have similar relationships with encoding and retrieval across multiple forms of memory and brain regions, despite regional differences in microcircuitry and information content. Differences in the oscillatory coordination of memory systems during sleep might explain why the consolidation of some forms of memory is sensitive to slow-wave sleep, while others depend on REM. In particular, theta oscillations appear to support the consolidation of certain types of procedural memories during REM, while delta oscillations during slow-wave sleep seem to promote declarative and procedural memories.

Determination of Vascular Dementia Brain in Distinct Frequency Bands with Whole Brain Functional Connectivity Patterns

PubMed Central

Zhang, Delong; Liu, Bo; Chen, Jun; Peng, Xiaoling; Liu, Xian; Fan, Yuanyuan; Liu, Ming; Huang, Ruiwang

2013-01-01

Recent studies have shown that multivariate pattern analysis (MVPA) can be useful for distinguishing brain disorders into categories. Such analyses can substantially enrich and facilitate clinical diagnoses. Using MPVA methods, whole brain functional networks, especially those derived using different frequency windows, can be applied to detect brain states. We constructed whole brain functional networks for groups of vascular dementia (VaD) patients and controls using resting state BOLD-fMRI (rsfMRI) data from three frequency bands - slow-5 (0.01∼0.027 Hz), slow-4 (0.027∼0.073 Hz), and whole-band (0.01∼0.073 Hz). Then we used the support vector machine (SVM), a type of MVPA classifier, to determine the patterns of functional connectivity. Our results showed that the brain functional networks derived from rsfMRI data (19 VaD patients and 20 controls) in these three frequency bands appear to reflect neurobiological changes in VaD patients. Such differences could be used to differentiate the brain states of VaD patients from those of healthy individuals. We also found that the functional connectivity patterns of the human brain in the three frequency bands differed, as did their ability to differentiate brain states. Specifically, the ability of the functional connectivity pattern to differentiate VaD brains from healthy ones was more efficient in the slow-5 (0.01∼0.027 Hz) band than in the other two frequency bands. Our findings suggest that the MVPA approach could be used to detect abnormalities in the functional connectivity of VaD patients in distinct frequency bands. Identifying such abnormalities may contribute to our understanding of the pathogenesis of VaD. PMID:23359801

Prolonged dry apnoea: effects on brain activity and physiological functions in breath-hold divers and non-divers.

PubMed

Ratmanova, Patricia; Semenyuk, Roxana; Popov, Daniil; Kuznetsov, Sergey; Zelenkova, Irina; Napalkov, Dmitry; Vinogradova, Olga

2016-07-01

The aim of the study was to investigate the effects of voluntary breath-holding on brain activity and physiological functions. We hypothesised that prolonged apnoea would trigger cerebral hypoxia, resulting in a decrease of brain performance; and the apnoea's effects would be more pronounced in breath-hold divers. Trained breath-hold divers and non-divers performed maximal dry breath-holdings. Lung volume, alveolar partial pressures of O2 and CO2, attention and anxiety levels were estimated. Heart rate, blood pressure, arterial blood oxygenation, brain tissue oxygenation, EEG, and DC potential were monitored continuously during breath-holding. There were a few significant changes in electrical brain activity caused by prolonged apnoea. Brain tissue oxygenation index and DC potential were relatively stable up to the end of the apnoea in breath-hold divers and non-divers. We also did not observe any decrease of attention level or speed of processing immediately after breath-holding. Interestingly, trained breath-hold divers had some peculiarities in EEG activity at resting state (before any breath-holding): non-spindled, sharpened alpha rhythm; slowed-down alpha with the frequency nearer to the theta band; and untypical spatial pattern of alpha activity. Our findings contradicted the primary hypothesis. Apnoea up to 5 min does not lead to notable cerebral hypoxia or a decrease of brain performance in either breath-hold divers or non-divers. It seems to be the result of the compensatory mechanisms similar to the diving response aimed at centralising blood circulation and reducing peripheral O2 uptake. Adaptive changes during apnoea are much more prominent in trained breath-hold divers.

How do children fall asleep? A high-density EEG study of slow waves in the transition from wake to sleep.

PubMed

Spiess, Mathilde; Bernardi, Giulio; Kurth, Salome; Ringli, Maya; Wehrle, Flavia M; Jenni, Oskar G; Huber, Reto; Siclari, Francesca

2018-05-17

Slow waves, the hallmarks of non-rapid eye-movement (NREM) sleep, are thought to reflect maturational changes that occur in the cerebral cortex throughout childhood and adolescence. Recent work in adults has revealed evidence for two distinct synchronization processes involved in the generation of slow waves, which sequentially come into play in the transition to sleep. In order to understand how these two processes are affected by developmental changes, we compared slow waves between children and young adults in the falling asleep period. The sleep onset period (starting 30s before end of alpha activity and ending at the first slow wave sequence) was extracted from 72 sleep onset high-density EEG recordings (128 electrodes) of 49 healthy subjects (age 8-25). Using an automatic slow wave detection algorithm, the number, amplitude and slope of slow waves were analyzed and compared between children (age 8-11) and young adults (age 20-25). Slow wave number and amplitude increased linearly in the falling asleep period in children, while in young adults, isolated high-amplitude slow waves (type I) dominated initially and numerous smaller slow waves (type II) with progressively increasing amplitude occurred later. Compared to young adults, children displayed faster increases in slow wave amplitude and number across the falling asleep period in central and posterior brain regions, respectively, and also showed larger slow waves during wakefulness immediately prior to sleep. Children do not display the two temporally dissociated slow wave synchronization processes in the falling asleep period observed in adults, suggesting that maturational factors underlie the temporal segregation of these two processes. Our findings provide novel perspectives for studying how sleep-related behaviors and dreaming differ between children and adults. Copyright © 2018 Elsevier Inc. All rights reserved.

Dynamics of brain activity in motor and frontal cortical areas during music listening: a magnetoencephalographic study.

PubMed

Popescu, Mihai; Otsuka, Asuka; Ioannides, Andreas A

2004-04-01

There are formidable problems in studying how 'real' music engages the brain over wide ranges of temporal scales extending from milliseconds to a lifetime. In this work, we recorded the magnetoencephalographic signal while subjects listened to music as it unfolded over long periods of time (seconds), and we developed and applied methods to correlate the time course of the regional brain activations with the dynamic aspects of the musical sound. We showed that frontal areas generally respond with slow time constants to the music, reflecting their more integrative mode; motor-related areas showed transient-mode responses to fine temporal scale structures of the sound. The study combined novel analysis techniques designed to capture and quantify fine temporal sequencing from the authentic musical piece (characterized by a clearly defined rhythm and melodic structure) with the extraction of relevant features from the dynamics of the regional brain activations. The results demonstrated that activity in motor-related structures, specifically in lateral premotor areas, supplementary motor areas, and somatomotor areas, correlated with measures of rhythmicity derived from the music. These correlations showed distinct laterality depending on how the musical performance deviated from the strict tempo of the music score, that is, depending on the musical expression.

Aberrant temporal and spatial brain activity during rest in patients with chronic pain

PubMed Central

Malinen, Sanna; Vartiainen, Nuutti; Hlushchuk, Yevhen; Koskinen, Miika; Ramkumar, Pavan; Forss, Nina; Kalso, Eija; Hari, Riitta

2010-01-01

In the absence of external stimuli, human hemodynamic brain activity displays slow intrinsic variations. To find out whether such fluctuations would be altered by persistent pain, we asked 10 patients with unrelenting chronic pain of different etiologies and 10 sex- and age-matched control subjects to rest with eyes open during 3-T functional MRI. Independent component analysis was used to identify functionally coupled brain networks. Time courses of an independent component comprising the insular cortices of both hemispheres showed stronger spectral power at 0.12 to 0.25 Hz in patients than in control subjects, with the largest difference at 0.16 Hz. A similar but weaker effect was seen in the anterior cingulate cortex, whereas activity of the precuneus and early visual cortex, used as a control site, did not differ between the groups. In the patient group, seed point-based correlation analysis revealed altered spatial connectivity between insulae and anterior cingulate cortex. The results imply both temporally and spatially aberrant activity of the affective pain-processing areas in patients suffering from chronic pain. The accentuated 0.12- to 0.25-Hz fluctuations in the patient group might be related to altered activity of the autonomic nervous system. PMID:20308545

Sleep spindles in humans: insights from intracranial EEG and unit recordings

PubMed Central

Andrillon, Thomas; Nir, Yuval; Staba, Richard J.; Ferrarelli, Fabio; Cirelli, Chiara; Tononi, Giulio; Fried, Itzhak

2012-01-01

Sleep spindles are an electroencephalographic (EEG) hallmark of non-rapid eye movement (NREM) sleep and are believed to mediate many sleep-related functions, from memory consolidation to cortical development. Spindles differ in location, frequency, and association with slow waves, but whether this heterogeneity may reflect different physiological processes and potentially serve different functional roles remains unclear. Here we utilized a unique opportunity to record intracranial depth EEG and single-unit activity in multiple brain regions of neurosurgical patients to better characterize spindle activity in human sleep. We find that spindles occur across multiple neocortical regions, and less frequently also in the parahippocampal gyrus and hippocampus. Most spindles are spatially restricted to specific brain regions. In addition, spindle frequency is topographically organized with a sharp transition around the supplementary motor area between fast (13-15Hz) centroparietal spindles often occurring with slow wave up-states, and slow (9-12Hz) frontal spindles occurring 200ms later on average. Spindle variability across regions may reflect the underlying thalamocortical projections. We also find that during individual spindles, frequency decreases within and between regions. In addition, deeper sleep is associated with a reduction in spindle occurrence and spindle frequency. Frequency changes between regions, during individual spindles, and across sleep may reflect the same phenomenon, the underlying level of thalamocortical hyperpolarization. Finally, during spindles neuronal firing rates are not consistently modulated, although some neurons exhibit phase-locked discharges. Overall, anatomical considerations can account well for regional spindle characteristics, while variable hyperpolarization levels can explain differences in spindle frequency. PMID:22159098

EEG in Sarcoidosis Patients Without Neurological Findings.

PubMed

Bilgin Topçuoğlu, Özgür; Kavas, Murat; Öztaş, Selahattin; Arınç, Sibel; Afşar, Gülgün; Saraç, Sema; Midi, İpek

2017-01-01

Sarcoidosis is a multisystem granulomatous disease affecting nervous system in 5% to 10% of patients. Magnetic resonance imaging (MRI) is accepted as the most sensitive method for detecting neurosarcoidosis. However, the most common findings in MRI are the nonspecific white matter lesions, which may be unrelated to sarcoidosis and can occur because of hypertension, diabetes mellitus, smoking, and other inflammatory or infectious disorders, as well. Autopsy studies report more frequent neurological involvement than the ante mortem studies. The aim of this study is to assess electroencephalography (EEG) in sarcoidosis patients without neurological findings in order to display asymptomatic neurological dysfunction. We performed EEG on 30 sarcoidosis patients without diagnosis of neurosarcoidosis or prior neurological comorbidities. Fourteen patients (46.7%) showed intermittant focal and/or generalized slowings while awake and not mentally activated. Seven (50%) of these 14 patients with EEG slowings had nonspecific white matter changes while the other half showed EEG slowings in the absence of MRI changes. We conclude that EEG slowings, when normal variants (psychomotor variant, temporal theta of elderly, frontal theta waves) are eliminated, may be an indicator of dysfunction in brain activity even in the absence of MRI findings. Hence, EEG may contribute toward detecting asymptomatic neurological dysfunction or probable future neurological involvement in sarcoidosis patients. © EEG and Clinical Neuroscience Society (ECNS) 2016.

β Oscillation during Slow Wave Sleep and Rapid Eye Movement Sleep in the Electroencephalogram of a Transgenic Mouse Model of Huntington’s Disease

PubMed Central

Jeantet, Yannick; Cayzac, Sebastien; Cho, Yoon H.

2013-01-01

Study objectives To search for early abnormalities in electroencephalogram (EEG) during sleep which may precede motor symptoms in a transgenic mouse model of hereditary neurodegenerative Huntington’s disease (HD). Design In the R6/1 transgenic mouse model of HD, rhythmic brain activity in EEG recordings was monitored longitudinally and across vigilance states through the onset and progression of disease. Measurements and results Mice with chronic electrode implants were recorded monthly over wake-sleep cycles (4 hours), beginning at 9–11 weeks (presymptomatic period) through 6–7 months (symptomatic period). Recording data revealed a unique β rhythm (20–35 Hz), present only in R6/1 transgenic mice, which evolves in close parallel with the disease. In addition, there was an unusual relationship between this β oscillation and vigilance states: while nearly absent during the active waking state, the β oscillation appeared with drowsiness and during slow wave sleep (SWS) and, interestingly, strengthened rather than dissipating when the brain returned to an activated state during rapid eye movement (REM) sleep. Conclusions In addition to providing a new in vivo biomarker and insight into Huntington's disease pathophysiology, this serendipitous observation opens a window onto the rarely explored neurophysiology of the cortico-basal ganglia circuit during SWS and REM sleep. PMID:24244517

Sleep and wakefulness in somnambulism: a spectral analysis study.

PubMed

Guilleminault, C; Poyares, D; Aftab, F A; Palombini, L; Abat, F

2001-08-01

The sleep structure and the dynamics of EEG slow-wave activity (SWA) were investigated in 12 young adults and age- and gender-matched controls. Polysomnography was performed in subjects with well-documented chronic sleepwalking and in matched controls. Blinded visual scoring was performed using the international criteria from the Rechtschaffen and Kales atlas [A manual of standardized technology, techniques and scoring systems for sleep stages of human subjects. Los Angeles: UCLA Brain Information Service, Brain Research Institute, 1968.] and by determining the presence of microarousals as defined in the American Sleep Disorders Association (ASDA) atlas [Sleep 15 (1992) 173.]. An evaluation of SWA overnight was performed on total nocturnal sleep to determine if a difference existed between groups of subjects, since sleepwalking usually originates with slow-wave sleep. Investigation of the delta power in successive nonoverlapping 4-second windows in the 32 seconds just prior to EMG activity associated with a confusional arousal was also conducted. One central EEG lead was used for all analyses. Somnambulistic individuals experienced more disturbed sleep than controls during the first NREM-REM sleep cycle. They had a higher number of ASDA arousals and presented lower peak of SWA during the first cycle that led to a lower SWA decline overnight. When the investigation focused on the short segment immediately preceding a confusional arousal, they presented an important increase in the relative power of low delta (0.75-2 Hz) just prior to the confusional arousal. Sleepwalkers undergo disturbed nocturnal sleep at the beginning of the night. The increased power of low delta just prior to the confusional arousal experienced may not be related to Stages 3-4 NREM sleep. We hypothesize that it may be translated as a cortical reaction to brain activation.

Neuropeptide transmission in brain circuits

PubMed Central

van den Pol, Anthony N.

2014-01-01

Neuropeptides are found in many mammalian CNS neurons where they play key roles in modulating neuronal activity. In contrast to amino acid transmitter release at the synapse, neuropeptide release is not restricted to the synaptic specialization, and after release, a neuropeptide may diffuse some distance to exert its action through a G-protein coupled receptor. Some neuropeptides such as hypocretin/orexin are synthesized only in single regions of the brain, and the neurons releasing these peptides probably have similar functional roles. Other peptides such as neuropeptide Y (NPY) are synthesized throughout the brain, and neurons that synthesize the peptide in one region have no anatomical or functional connection with NPY neurons in other brain regions. Here, I review converging data revealing a complex interaction between slow-acting neuromodulator peptides and fast-acting amino acid transmitters in the control of energy homeostasis, drug addiction, mood and motivation, sleep-wake states, and neuroendocrine regulation. PMID:23040809

Exercise benefits for the aging brain depend on the accompanying cognitive load: insights from sleep electroencephalogram.

PubMed

Horne, Jim

2013-11-01

Although exercise clearly offsets aging effects on the body, its benefits for the aging brain are likely to depend on the extent that physical activity (especially locomotion) facilitates multisensory encounters, curiosity, and interactions with novel environments; this is especially true for exploratory activity, which occupies much of wakefulness for most mammals in the wild. Cognition is inseparable from physical activity, with both interlinked to promote neuroplasticity and more successful brain aging. In these respects and for humans, exercising in a static, featureless, artificially lit indoor setting contrasts with exploratory outdoor walking within a novel environment during daylight. However, little is known about the comparative benefits for the aging brain of longer-term daily regimens of this latter nature including the role of sleep, to the extent that sleep enhances neuroplasticity as shown in short-term laboratory studies. More discerning analyses of sleep electroencephalogram (EEG) slow-wave activity especially 0.5-2-Hz activity would provide greater insights into use-dependent recovery processes during longer-term tracking of these regimens and complement slower changing waking neuropsychologic and resting functional magnetic resonance imaging (fMRI) measures, including those of the brain's default mode network. Although the limited research only points to ephemeral small sleep EEG effects of pure exercise, more enduring effects seem apparent when physical activity incorporates cognitive challenges. In terms of "use it or lose it," curiosity-driven "getting out and about," encountering, interacting with, and enjoying novel situations may well provide the brain with its real exercise, further reflected in changes to the dynamics of sleep. Copyright © 2013 Elsevier B.V. All rights reserved.

Intravenous Heroin Induces Rapid Brain Hypoxia and Hyperglycemia that Precede Brain Metabolic Response.

PubMed

Solis, Ernesto; Cameron-Burr, Keaton T; Shaham, Yavin; Kiyatkin, Eugene A

2017-01-01

Heroin use and overdose have increased in recent years as people transition from abusing prescription opiates to using the cheaper street drug. Despite a long history of research, many physiological effects of heroin and their underlying mechanisms remain unknown. Here, we used high-speed amperometry to examine the effects of intravenous heroin on oxygen and glucose levels in the nucleus accumbens (NAc) in freely-moving rats. Heroin within the dose range of human drug use and rat self-administration (100-200 μg/kg) induced a rapid, strong, but transient drop in NAc oxygen that was followed by a slower and more prolonged rise in glucose. Using oxygen recordings in the subcutaneous space, a densely-vascularized site with no metabolic activity, we confirmed that heroin-induced brain hypoxia results from decreased blood oxygen, presumably due to drug-induced respiratory depression. Respiratory depression and the associated rise in CO 2 levels appear to drive tonic increases in NAc glucose via local vasodilation. Heroin-induced changes in oxygen and glucose were rapid and preceded the slow and prolonged increase in brain temperature and were independent of enhanced intra-brain heat production, an index of metabolic activation. A very high heroin dose (3.2 mg/kg), corresponding to doses used by experienced drug users in overdose conditions, caused strong and prolonged brain hypoxia and hyperglycemia coupled with robust initial hypothermia that preceded an extended hyperthermic response. Our data suggest heroin-induced respiratory depression as a trigger for brain hypoxia, which leads to hyperglycemia, both of which appear independent of subsequent changes in brain temperature and metabolic neural activity.

Rapid changes in brain aromatase activity in the female quail brain following expression of sexual behaviour.

PubMed

de Bournonville, C; Ball, G F; Balthazart, J; Cornil, C A

2017-11-01

In male quail, oestrogens produced in the brain (neuro-oestrogens) exert a dual action on male sexual behaviour: they increase sexual motivation within minutes via mechanisms activated at the membrane but facilitate sexual performance by slower, presumably nuclear-initiated, mechanisms. Recent work indicates that neuro-oestrogens are also implicated in the control of female sexual motivation despite the presence of high circulating concentrations of oestrogens of ovarian origin. Interestingly, aromatase activity (AA) in the male brain is regulated in time domains corresponding to the slow "genomic" and faster "nongenomic" modes of action of oestrogens. Furthermore, rapid changes in brain AA are observed in males after sexual interactions with a female. In the present study, we investigated whether similar rapid changes in brain AA are observed in females allowed to interact sexually with males. A significant decrease in AA was observed in the medial preoptic nucleus after interactions that lasted 2, 5 or 10 minutes, although this decrease was no longer significant after 15 minutes of interaction. In the bed nucleus of the stria terminalis, a progressive decline of average AA was observed between 2 and 15 minutes, although it never reached statistical significance. AA in this nucleus was, however, negatively correlated with the sexual receptivity of the female. These data indicate that sexual interactions affect brain AA in females as in males in an anatomically specific manner and suggest that rapid changes in brain oestrogens production could also modulate female sexual behaviour. © 2017 British Society for Neuroendocrinology.

Attention and driving in traumatic brain injury: a question of coping with time-pressure.

PubMed

Brouwer, Wiebo H; Withaar, Frederiec K; Tant, Mark L M; van Zomeren, Adriaan H

2002-02-01

Diffuse and focal traumatic brain injury (TBI) can result in perceptual, cognitive, and motor dysfunction possibly leading to activity limitations in driving. Characteristic dysfunctions for severe diffuse TBI are confronted with function requirements derived from the hierarchical task analysis of driving skill. Specifically, we focus on slow information processing, divided attention, and the development of procedural knowledge. Also the effects of a combination of diffuse and focal dysfunctions, specifically homonymous hemianopia and the dysexecutive syndrome, are discussed. Finally, we turn to problems and challenges with regard to assessment and rehabilitation methods in the areas of driving and fitness to drive.

What does brain response to neutral faces tell us about major depression? evidence from machine learning and fMRI.

PubMed

Oliveira, Leticia; Ladouceur, Cecile D; Phillips, Mary L; Brammer, Michael; Mourao-Miranda, Janaina

2013-01-01

A considerable number of previous studies have shown abnormalities in the processing of emotional faces in major depression. Fewer studies, however, have focused specifically on abnormal processing of neutral faces despite evidence that depressed patients are slow and less accurate at recognizing neutral expressions in comparison with healthy controls. The current study aimed to investigate whether this misclassification described behaviourally for neutral faces also occurred when classifying patterns of brain activation to neutral faces for these patients. TWO INDEPENDENT DEPRESSED SAMPLES: (1) Nineteen medication-free patients with depression and 19 healthy volunteers and (2) Eighteen depressed individuals and 18 age and gender-ratio-matched healthy volunteers viewed emotional faces (sad/neutral; happy/neutral) during an fMRI experiment. We used a new pattern recognition framework: first, we trained the classifier to discriminate between two brain states (e.g. viewing happy faces vs. viewing neutral faces) using data only from healthy controls (HC). Second, we tested the classifier using patterns of brain activation of a patient and a healthy control for the same stimuli. Finally, we tested if the classifier's predictions (predictive probabilities) for emotional and neutral face classification were different for healthy controls and depressed patients. Predictive probabilities to patterns of brain activation to neutral faces in both groups of patients were significantly lower in comparison to the healthy controls. This difference was specific to neutral faces. There were no significant differences in predictive probabilities to patterns of brain activation to sad faces (sample 1) and happy faces (samples 2) between depressed patients and healthy controls. Our results suggest that the pattern of brain activation to neutral faces in depressed patients is not consistent with the pattern observed in healthy controls subject to the same stimuli. This difference in brain activation might underlie the behavioural misinterpretation of the neutral faces content by the depressed patients.

Nonimpact brain injury: neuropsychological and behavioral correlates with consideration of physiological findings.

PubMed

Henry, G K; Gross, H S; Herndon, C A; Furst, C J

2000-01-01

This retrospective clinical study investigated the neuropsychological, physiological, and behavioral functioning of 32 adult outpatients up to 65 months following nonimpact brain injury (i.e., whiplash). All participants were administered a flexible battery of cognitive tests, and some underwent neurodiagnostic procedures and sleep studies. Compared with published norms, neuropsychological data revealed significant and persistent age-adjusted cognitive deficits, primarily in the area of executive functioning. Participants frequently complained of problems with behavioral control, sleep, and sexuality. Although structural neuroimaging was not sensitive in detecting brain pathology, quantitative electroencephalography was abnormal in all the participants evaluated, showing frontocentral slowing and increased spike wave activity. We propose that whiplash injury can produce wide-ranging circuitry dysfunction and that test selection is critical in identifying cognitive deficits.

The temporal structure of behaviour and sleep homeostasis.

PubMed

Vyazovskiy, Vladyslav V; Tobler, Irene

2012-01-01

The amount and architecture of vigilance states are governed by two distinct processes, which occur at different time scales. The first, a slow one, is related to a wake/sleep dependent homeostatic Process S, which occurs on a time scale of hours, and is reflected in the dynamics of NREM sleep EEG slow-wave activity. The second, a fast one, is manifested in a regular alternation of two sleep states--NREM and REM sleep, which occur, in rodents, on a time scale of ~5-10 minutes. Neither the mechanisms underlying the time constants of these two processes--the slow one and the fast one, nor their functional significance are understood. Notably, both processes are primarily apparent during sleep, while their potential manifestation during wakefulness is obscured by ongoing behaviour. Here, we find, in mice provided with running wheels, that the two sleep processes become clearly apparent also during waking at the level of behavior and brain activity. Specifically, the slow process was manifested in the total duration of waking periods starting from dark onset, while the fast process was apparent in a regular occurrence of running bouts during the waking periods. The dynamics of both processes were stable within individual animals, but showed large interindividual variability. Importantly, the two processes were not independent: the periodic structure of waking behaviour (fast process) appeared to be a strong predictor of the capacity to sustain continuous wakefulness (slow process). The data indicate that the temporal organization of vigilance states on both the fast and the slow time scales may arise from a common neurophysiologic mechanism.

Slow pupillary light responses in infants at high risk of cerebral palsy were associated with periventricular leukomalacia and neurological outcome.

PubMed

Hamer, Elisa G; Vermeulen, R Jeroen; Dijkstra, Linze J; Hielkema, Tjitske; Kos, Claire; Bos, Arend F; Hadders-Algra, Mijna

2016-12-01

Having observed slow pupillary light responses (PLRs) in infants at high risk of cerebral palsy, we retrospectively evaluated whether these were associated with specific brain lesions or unfavourable outcomes. We carried out neurological examinations on 30 infants at very high risk of cerebral palsy five times until the corrected age of 21 months, classifying each PLR assessment as normal or slow. The predominant reaction during development was determined for each infant. Neonatal brain scans were classified based on the type of brain lesion. Developmental outcome was evaluated at 21 months of corrected age with a neurological examination, the Bayley Scales of Infant Development Second Edition and the Infant Motor Profile. Of the 30 infants, 16 developed cerebral palsy. Predominantly slow PLRs were observed in eight infants and were associated with periventricular leukomalacia (p = 0.007), cerebral palsy (p = 0.039), bilateral cerebral palsy (p = 0.001), poorer quality of motor behaviour (p < 0.0005) and poorer cognitive outcome (p = 0.045). This explorative study suggested that predominantly slow PLR in infants at high risk of cerebral palsy were associated with periventricular leukomalacia and poorer developmental outcome. Slow PLR might be an expression of white matter damage, resulting in dysfunction of the complex cortico-subcortical circuitries. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Brain processing of meter and rhythm in music. Electrophysiological evidence of a common network.

PubMed

Kuck, Heleln; Grossbach, Michael; Bangert, Marc; Altenmüller, Eckart

2003-11-01

To determine cortical structures involved in "global" meter and "local" rhythm processing, slow brain potentials (DC potentials) were recorded from the scalp of 18 musically trained subjects while listening to pairs of monophonic sequences with both metric structure and rhythmic variations. The second sequence could be either identical to or different from the first one. Differences were either of a metric or a rhythmic nature. The subjects' task was to judge whether the sequences were identical or not. During processing of the auditory tasks, brain activation patterns along with the subjects' performance were assessed using 32-channel DC electroencephalography. Data were statistically analyzed using MANOVA. Processing of both meter and rhythm produced sustained cortical activation over bilateral frontal and temporal brain regions. A shift towards right hemispheric activation was pronounced during presentation of the second stimulus. Processing of rhythmic differences yielded a more centroparietal activation compared to metric processing. These results do not support Lerdhal and Jackendoff's two-component model, predicting a dissociation of left hemispheric rhythm and right hemispheric meter processing. We suggest that the uniform right temporofrontal predominance reflects auditory working memory and a pattern recognition module, which participates in both rhythm and meter processing. More pronounced parietal activation during rhythm processing may be related to switching of task-solving strategies towards mental imagination of the score.

Resting-state activity in development and maintenance of normal brain function.

PubMed

Pizoli, Carolyn E; Shah, Manish N; Snyder, Abraham Z; Shimony, Joshua S; Limbrick, David D; Raichle, Marcus E; Schlaggar, Bradley L; Smyth, Matthew D

2011-07-12

One of the most intriguing recent discoveries concerning brain function is that intrinsic neuronal activity manifests as spontaneous fluctuations of the blood oxygen level-dependent (BOLD) functional MRI signal. These BOLD fluctuations exhibit temporal synchrony within widely distributed brain regions known as resting-state networks. Resting-state networks are present in the waking state, during sleep, and under general anesthesia, suggesting that spontaneous neuronal activity plays a fundamental role in brain function. Despite its ubiquitous presence, the physiological role of correlated, spontaneous neuronal activity remains poorly understood. One hypothesis is that this activity is critical for the development of synaptic connections and maintenance of synaptic homeostasis. We had a unique opportunity to test this hypothesis in a 5-y-old boy with severe epileptic encephalopathy. The child developed marked neurologic dysfunction in association with a seizure disorder, resulting in a 1-y period of behavioral regression and progressive loss of developmental milestones. His EEG showed a markedly abnormal pattern of high-amplitude, disorganized slow activity with frequent generalized and multifocal epileptiform discharges. Resting-state functional connectivity MRI showed reduced BOLD fluctuations and a pervasive lack of normal connectivity. The child underwent successful corpus callosotomy surgery for treatment of drop seizures. Postoperatively, the patient's behavior returned to baseline, and he resumed development of new skills. The waking EEG revealed a normal background, and functional connectivity MRI demonstrated restoration of functional connectivity architecture. These results provide evidence that intrinsic, coherent neuronal signaling may be essential to the development and maintenance of the brain's functional organization.

BCIs in the Laboratory and at Home: The Wadsworth Research Program

NASA Astrophysics Data System (ADS)

Sellers, Eric W.; McFarland, Dennis J.; Vaughan, Theresa M.; Wolpaw, Jonathan R.

Many people with severe motor disabilities lack the muscle control that would allow them to rely on conventional methods of augmentative communication and control. Numerous studies over the past two decades have indicated that scalp-recorded electroencephalographic (EEG) activity can be the basis for non-muscular communication and control systems, commonly called brain-computer interfaces (BCIs) [55]. EEG-based BCI systems measure specific features of EEG activity and translate these features into device commands. The most commonly used features are rhythms produced by the sensorimotor cortex [38, 55, 56, 59], slow cortical potentials [4, 5, 23], and the P300 event-related potential [12, 17, 46]. Systems based on sensorimotor rhythms or slow cortical potentials use oscillations or transient signals that are spontaneous in the sense that they are not dependent on specific sensory events. Systems based on the P300 response use transient signals in the EEG that are elicited by specific stimuli.

Cycle-Triggered Cortical Stimulation during Slow Wave Sleep Facilitates Learning a BMI Task: A Case Report in a Non-Human Primate

PubMed Central

Rembado, Irene; Zanos, Stavros; Fetz, Eberhard E.

2017-01-01

Slow wave sleep (SWS) has been identified as the sleep stage involved in consolidating newly acquired information. A growing body of evidence has shown that delta (1–4 Hz) oscillatory activity, the characteristic electroencephalographic signature of SWS, is involved in coordinating interaction between the hippocampus and the neocortex and is thought to take a role in stabilizing memory traces related to a novel task. This case report describes a new protocol that uses neuroprosthetics training of a non-human primate to evaluate the effects of surface cortical electrical stimulation triggered from SWS cycles. The results suggest that stimulation phase-locked to SWS oscillatory activity promoted learning of the neuroprosthetic task. This protocol could be used to elucidate mechanisms of synaptic plasticity underlying off-line learning during sleep and offers new insights into the role of brain oscillations in information processing and memory consolidation. PMID:28450831

Evidence accumulation detected in BOLD signal using slow perceptual decision making.

PubMed

Krueger, Paul M; van Vugt, Marieke K; Simen, Patrick; Nystrom, Leigh; Holmes, Philip; Cohen, Jonathan D

2017-04-01

We assessed whether evidence accumulation could be observed in the BOLD signal during perceptual decision making. This presents a challenge since the hemodynamic response is slow, while perceptual decisions are typically fast. Guided by theoretical predictions of the drift diffusion model, we slowed down decisions by penalizing participants for incorrect responses. Second, we distinguished BOLD activity related to stimulus detection (modeled using a boxcar) from activity related to integration (modeled using a ramp) by minimizing the collinearity of GLM regressors. This was achieved by dissecting a boxcar into its two most orthogonal components: an "up-ramp" and a "down-ramp." Third, we used a control condition in which stimuli and responses were similar to the experimental condition, but that did not engage evidence accumulation of the stimuli. The results revealed an absence of areas in parietal cortex that have been proposed to drive perceptual decision making but have recently come into question; and newly identified regions that are candidates for involvement in evidence accumulation. Previous fMRI studies have either used fast perceptual decision making, which precludes the measurement of evidence accumulation, or slowed down responses by gradually revealing stimuli. The latter approach confounds perceptual detection with evidence accumulation because accumulation is constrained by perceptual input. We slowed down the decision making process itself while leaving perceptual information intact. This provided a more sensitive and selective observation of brain regions associated with the evidence accumulation processes underlying perceptual decision making than previous methods. Copyright © 2017 Elsevier B.V. All rights reserved.

Contributions of glycogen to astrocytic energetics during brain activation.

PubMed

Dienel, Gerald A; Cruz, Nancy F

2015-02-01

Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 μmol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K(+) level, oxidative stress management, and memory consolidation; it is a multi-functional compound.

Contributions of Glycogen to Astrocytic Energetics during Brain Activation

PubMed Central

Dienel, Gerald A.; Cruz, Nancy F.

2014-01-01

Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 mol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K+ level, oxidative stress management, and memory consolidation; it is a multi-functional compound. PMID:24515302

Ketamine, sleep, and depression: current status and new questions.

PubMed

Duncan, Wallace C; Zarate, Carlos A

2013-09-01

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has well-described rapid antidepressant effects in clinical studies of individuals with treatment-resistant major depressive disorder (MDD). Preclinical studies investigating the effects of ketamine on brain-derived neurotrophic factor (BDNF) and on sleep slow wave activity (SWA) support its use as a prototype for investigating the neuroplastic mechanisms presumably involved in the mechanism of rapidly acting antidepressants. This review discusses human EEG slow wave sleep parameters and plasma BDNF as central and peripheral surrogate markers of plasticity, and their use in assessing ketamine's effects. Acutely, ketamine elevates BDNF levels, as well as early night SWA and high-amplitude slow waves; each of these measures correlates with change in mood in depressed patients who respond to ketamine. The slow wave effects are limited to the first night post-infusion, suggesting that their increase is part of an early cascade of events triggering improved mood. Increased total sleep and decreased waking occur during the first and second night post infusion, suggesting that these measures are associated with the enduring treatment response observed with ketamine.

Background norepinephrine primes astrocytic calcium responses to subsequent norepinephrine stimuli in the cerebral cortex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nuriya, Mutsuo; Keio Advanced Research Center for Water Biology and Medicine, Keio University, Shinjuku, Tokyo, 160-8582; Graduate School of Environment and Information Sciences, Yokohama National University, Yokohama, Kanagawa, 240-8501

Norepinephrine (NE) levels in the cerebral cortex are regulated in two modes; the brain state is correlated with slow changes in background NE concentration, while salient stimuli induce transient NE spikes. Previous studies have revealed their diverse neuromodulatory actions; however, the modulatory role of NE on astrocytic activity has been poorly characterized thus far. In this study, we evaluated the modulatory action of background NE on astrocytic responses to subsequent stimuli, using two-photon calcium imaging of acute murine cortical brain slices. We find that subthreshold background NE significantly augments calcium responses to subsequent pulsed NE stimulation in astrocytes. This primingmore » effect is independent of neuronal activity and is mediated by the activation of β-adrenoceptors and the downstream cAMP pathway. These results indicate that background NE primes astrocytes for subsequent calcium responses to NE stimulation and suggest a novel gliomodulatory role for brain state-dependent background NE in the cerebral cortex. - Highlights: • Background NE augments the responsiveness of astrocytes to subsequent NE stimulation. • The priming effect is independent of neuronal activity and mediated by βadrenoceptor. • Background subthreshold NE may play gliomodulatory roles in the cerebral cortex.« less

Low-resolution electromagnetic brain tomography (LORETA) of monozygotic twins discordant for chronic fatigue syndrome.

PubMed

Sherlin, Leslie; Budzynski, Thomas; Kogan Budzynski, Helen; Congedo, Marco; Fischer, Mary E; Buchwald, Dedra

2007-02-15

Previous work using quantified EEG has suggested that brain activity in individuals with chronic fatigue syndrome (CFS) and normal persons differs. Our objective was to investigate if specific frequency band-pass regions and spatial locations are associated with CFS using low-resolution electromagnetic brain tomography (LORETA). We conducted a co-twin control study of 17 pairs of monozygotic twins where 1 twin met criteria for CFS and the co-twin was healthy. Twins underwent an extensive battery of tests including a structured psychiatric interview and a quantified EEG. Eyes closed EEG frequency-domain analysis was computed and the entire brain volume was compared of the CFS and healthy twins using a multiple comparison procedure. Compared with their healthy co-twins, twins with CFS differed in current source density. The CFS twins had higher delta in the left uncus and parahippocampal gyrus and higher theta in the cingulate gyrus and right superior frontal gyrus. These findings suggest that neurophysiological activity in specific areas of the brain may differentiate individuals with CFS from those in good health. The study corroborates that slowing of the deeper structures of the limbic system is associated with affect. It also supports the neurobiological model that the right forebrain is associated with sympathetic activity and the left forebrain with the effective management of energy. These preliminary findings await replication.

Dynamic change of ERPs related to selective attention to signals from left and right visual field during head-down tilt

NASA Astrophysics Data System (ADS)

Wei, Jinhe; Zhao, Lun; Van, Gongdong; Chen, Wenjuan; Ren, Wei; Duan, Ran

To study further the effect of head-down tilt(HDT) on slow positive potential in the event-related potentials(ERPs), the temporal and spatial features of visual ERPs changes during 2 hour HDT(-10 °) were compared with that during HUT(+20°) in 15 normal subjects. The stimuli were consisted of two color LED flashes appeared randomly in left or right visual field(LVF or RVF) with same probability. The subjects were asked to make switch response to target signals(T) differentially: switching to left for T in LVF and to right for T in RVF, ignoring non-target signals(N). Five sets of tests were made during HUT and HDT. ERPs were obtained from 9 locations on scalp. The mean value of the ERPs in the period from 0.32-0.55 s was taken as the amplitude of slow positive potential(P400). The main results were as follows. 1)The mean amplitude of P400 decreased during HDT which was more significant at the 2nd, 3rd and 5th set of tests; 2)spatially, the reduction of mean P400 amplitude during HDT was more significant for signals from RVF and was more significant at posterior and central brain regions than that on frontal locations. As that the positive potential probably reflects the active inhibition activity in the brain during attention process, these data provide further evidence showing that the higher brain function was affected by the simulated weightlessness and that this effect was not only transient but also with interesting spatial characteristics.

Functional Neuroimaging Insights into the Physiology of Human Sleep

PubMed Central

Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Sterpenich, Virginie; Bonjean, Maxime; Maquet, Pierre

2010-01-01

Functional brain imaging has been used in humans to noninvasively investigate the neural mechanisms underlying the generation of sleep stages. On the one hand, REM sleep has been associated with the activation of the pons, thalamus, limbic areas, and temporo-occipital cortices, and the deactivation of prefrontal areas, in line with theories of REM sleep generation and dreaming properties. On the other hand, during non-REM (NREM) sleep, decreases in brain activity have been consistently found in the brainstem, thalamus, and in several cortical areas including the medial prefrontal cortex (MPFC), in agreement with a homeostatic need for brain energy recovery. Benefiting from a better temporal resolution, more recent studies have characterized the brain activations related to phasic events within specific sleep stages. In particular, they have demonstrated that NREM sleep oscillations (spindles and slow waves) are indeed associated with increases in brain activity in specific subcortical and cortical areas involved in the generation or modulation of these waves. These data highlight that, even during NREM sleep, brain activity is increased, yet regionally specific and transient. Besides refining the understanding of sleep mechanisms, functional brain imaging has also advanced the description of the functional properties of sleep. For instance, it has been shown that the sleeping brain is still able to process external information and even detect the pertinence of its content. The relationship between sleep and memory has also been refined using neuroimaging, demonstrating post-learning reactivation during sleep, as well as the reorganization of memory representation on the systems level, sometimes with long-lasting effects on subsequent memory performance. Further imaging studies should focus on clarifying the role of specific sleep patterns for the processing of external stimuli, as well as the consolidation of freshly encoded information during sleep. Citation: Dang-Vu TT; Schabus M; Desseilles M; Sterpenich V; Bonjean M; Maquet P. Functional neuroimaging insights into the physiology of human sleep. SLEEP 2010;33(12):1589-1603. PMID:21120121

Rivastigmine

MedlinePlus

... in people with Parkinson's disease (a brain and nervous system disease with symptoms of slowing of movement, muscle ... develops abnormal protein structures, and the brain and nervous system are destroyed over time). Talk to your doctor ...

ACE inhibition with captopril retards the development of signs of neurodegeneration in an animal model of Alzheimer's disease.

PubMed

AbdAlla, Said; Langer, Andreas; Fu, Xuebin; Quitterer, Ursula

2013-08-16

Increased generation of reactive oxygen species (ROS) is a significant pathological feature in the brains of patients with Alzheimer's disease (AD). Experimental evidence indicates that inhibition of brain ROS could be beneficial in slowing the neurodegenerative process triggered by amyloid-beta (Abeta) aggregates. The angiotensin II AT1 receptor is a significant source of brain ROS, and AD patients have an increased brain angiotensin-converting enzyme (ACE) level, which could account for an excessive angiotensin-dependent AT1-induced ROS generation. Therefore, we analyzed the impact of ACE inhibition on signs of neurodegeneration of aged Tg2576 mice as a transgenic animal model of AD. Whole genome microarray gene expression profiling and biochemical analyses demonstrated that the centrally active ACE inhibitor captopril normalized the excessive hippocampal ACE activity of AD mice. Concomitantly, the development of signs of neurodegeneration was retarded by six months of captopril treatment. The neuroprotective profile triggered by captopril was accompanied by reduced amyloidogenic processing of the amyloid precursor protein (APP), and decreased hippocampal ROS, which is known to enhance Abeta generation by increased activation of beta- and gamma-secretases. Taken together, our data present strong evidence that ACE inhibition with a widely used cardiovascular drug could interfere with Abeta-dependent neurodegeneration.

ACE Inhibition with Captopril Retards the Development of Signs of Neurodegeneration in an Animal Model of Alzheimer’s Disease

PubMed Central

AbdAlla, Said; Langer, Andreas; Fu, Xuebin; Quitterer, Ursula

2013-01-01

Increased generation of reactive oxygen species (ROS) is a significant pathological feature in the brains of patients with Alzheimer’s disease (AD). Experimental evidence indicates that inhibition of brain ROS could be beneficial in slowing the neurodegenerative process triggered by amyloid-beta (Abeta) aggregates. The angiotensin II AT1 receptor is a significant source of brain ROS, and AD patients have an increased brain angiotensin-converting enzyme (ACE) level, which could account for an excessive angiotensin-dependent AT1-induced ROS generation. Therefore, we analyzed the impact of ACE inhibition on signs of neurodegeneration of aged Tg2576 mice as a transgenic animal model of AD. Whole genome microarray gene expression profiling and biochemical analyses demonstrated that the centrally active ACE inhibitor captopril normalized the excessive hippocampal ACE activity of AD mice. Concomitantly, the development of signs of neurodegeneration was retarded by six months of captopril treatment. The neuroprotective profile triggered by captopril was accompanied by reduced amyloidogenic processing of the amyloid precursor protein (APP), and decreased hippocampal ROS, which is known to enhance Abeta generation by increased activation of beta- and gamma-secretases. Taken together, our data present strong evidence that ACE inhibition with a widely used cardiovascular drug could interfere with Abeta-dependent neurodegeneration. PMID:23959119

Strategies for preservation of memory function in patients with brain metastases.

PubMed

Dye, Nicholas B; Gondi, Vinai; Mehta, Minesh P

2015-06-01

Cognitive decline, particularly in memory, is a side effect seen in patients with brain metastases and when severe, can have a significant impact on their quality of life. It is most often the result of multiple intersecting etiologic factors, including the use of whole brain radiation therapy, effects of which, in part, are mediated by damage within the hippocampus. A variety of clinical factors and comorbidities may impact the likelihood and severity of this cognitive decline, and affected patients should be considered for evaluation in a comprehensive neuro-rehabilitation or "brain fitness" program. Avoiding WBRT is warranted for some patients with brain metastases; particularly those <50 years old. However, when WBRT is clinically indicated, hippocampal avoidance WBRT (HA-WBRT) has been shown to significantly reduce memory decline compared to historical controls without compromising treatment efficacy. Additionally, the NMDA receptor antagonist memantine and renin-angiotensin-aldosterone system (RAAS) blockers have shown promise as neuroprotective agents that could be used prophylactically with radiation. After the onset of neurocognitive decline the treatment is largely symptom-driven, however simply screening for and treating depression, fatigue, anxiety, cognitive slowing, and other processes may alleviate some impairment. Stimulants such as methylphenidate may be useful in treating symptoms of fatigue and cognitive slowing. Other treatments including donepezil and cognitive rehabilitation have been extensively tested in the population at risk for dementia, although they have not been adequately studied in patients following cranial radiotherapy. An innovative hypothetical approach is the use of intranasal metabolic stimulants such as low dose insulin, which could be valuable in improving cognition and memory, by reversing impaired brain metabolic activity. Prevention of neurocognitive decline in patients with brain metastases requires a multimodal approach tailored to each patient's need, avoiding WBRT in some, altering the WBRT plan in others, and/or using neuroprotective prophylaxis in those in whom avoidance cannot be utilized. Likewise treatment will require a personalized combination of strategies optimized to address the patient's symptoms.

Intravenous Heroin Induces Rapid Brain Hypoxia and Hyperglycemia that Precede Brain Metabolic Response

PubMed Central

Cameron-Burr, Keaton T.; Shaham, Yavin

2017-01-01

Heroin use and overdose have increased in recent years as people transition from abusing prescription opiates to using the cheaper street drug. Despite a long history of research, many physiological effects of heroin and their underlying mechanisms remain unknown. Here, we used high-speed amperometry to examine the effects of intravenous heroin on oxygen and glucose levels in the nucleus accumbens (NAc) in freely-moving rats. Heroin within the dose range of human drug use and rat self-administration (100–200 μg/kg) induced a rapid, strong, but transient drop in NAc oxygen that was followed by a slower and more prolonged rise in glucose. Using oxygen recordings in the subcutaneous space, a densely-vascularized site with no metabolic activity, we confirmed that heroin-induced brain hypoxia results from decreased blood oxygen, presumably due to drug-induced respiratory depression. Respiratory depression and the associated rise in CO2 levels appear to drive tonic increases in NAc glucose via local vasodilation. Heroin-induced changes in oxygen and glucose were rapid and preceded the slow and prolonged increase in brain temperature and were independent of enhanced intra-brain heat production, an index of metabolic activation. A very high heroin dose (3.2 mg/kg), corresponding to doses used by experienced drug users in overdose conditions, caused strong and prolonged brain hypoxia and hyperglycemia coupled with robust initial hypothermia that preceded an extended hyperthermic response. Our data suggest heroin-induced respiratory depression as a trigger for brain hypoxia, which leads to hyperglycemia, both of which appear independent of subsequent changes in brain temperature and metabolic neural activity. PMID:28593192

Scanning fast and slow: current limitations of 3 Tesla functional MRI and future potential

NASA Astrophysics Data System (ADS)

Boubela, Roland N.; Kalcher, Klaudius; Nasel, Christian; Moser, Ewald

2014-02-01

Functional MRI at 3T has become a workhorse for the neurosciences, e.g., neurology, psychology, and psychiatry, enabling non-invasive investigation of brain function and connectivity. However, BOLD-based fMRI is a rather indirect measure of brain function, confounded by fluctuation related signals, e.g. head or brain motion, brain pulsation, blood flow, intermixed with susceptibility differences close or distant to the region of neuronal activity. Even though a plethora of preprocessing strategies have been published to address these confounds, their efficiency is still under discussion. In particular, physiological signal fluctuations closely related to brain supply may mask BOLD signal changes related to "true" neuronal activation. Here we explore recent technical and methodological advancements aimed at disentangling the various components, employing fast multiband vs. standard EPI, in combination with fast temporal ICA.Our preliminary results indicate that fast (TR< 0.5s) scanning may help to identify and eliminate physiologic components, increasing tSNR and functional contrast. In addition, biological variability can be studied and task performance better correlated to other measures. This should increase specificity and reliability in fMRI studies. Furthermore, physiological signal changes during scanning may then be recognized as a source of information rather than a nuisance. As we are currently still undersampling the complexity of the brain, even at a rather coarse macroscopic level, we should be very cautious in the interpretation of neuroscientific findings, in particular when comparing different groups (e.g., age, sex, medication, pathology, etc.). From a technical point of view our goal should be to sample brain activity at layer specific resolution with low TR, covering as much of the brain as possible without violating SAR limits. We hope to stimulate discussion towards a better understanding and a more quantitative use of fMRI.

Ultra-slow mechanical stimulation of olfactory epithelium modulates consciousness by slowing cerebral rhythms in humans.

PubMed

Piarulli, A; Zaccaro, A; Laurino, M; Menicucci, D; De Vito, A; Bruschini, L; Berrettini, S; Bergamasco, M; Laureys, S; Gemignani, A

2018-04-26

The coupling between respiration and neural activity within olfactory areas and hippocampus has recently been unambiguously demonstrated, its neurophysiological basis sustained by the well-assessed mechanical sensitivity of the olfactory epithelium. We herein hypothesize that this coupling reverberates to the whole brain, possibly modulating the subject's behavior and state of consciousness. The olfactory epithelium of 12 healthy subjects was stimulated with periodical odorless air-delivery (frequency 0.05 Hz, 8 s on, 12 off). Cortical electrical activity (High Density-EEG) and perceived state of consciousness have been studied. The stimulation induced i) an enhancement of delta-theta EEG activity over the whole cortex mainly involving the Limbic System and Default Mode Network structures, ii) a reversal of the overall information flow directionality from wake-like postero-anterior to NREM sleep-like antero-posterior, iii) the perception of having experienced an Altered State of Consciousness. These findings could shed further light via a neurophenomenological approach on the links between respiration, cerebral activity and subjective experience, suggesting a plausible neurophysiological basis for interpreting altered states of consciousness induced by respiration-based meditative practices.

Promoting Sleep Oscillations and Their Functional Coupling by Transcranial Stimulation Enhances Memory Consolidation in Mild Cognitive Impairment.

PubMed

Ladenbauer, Julia; Ladenbauer, Josef; Külzow, Nadine; de Boor, Rebecca; Avramova, Elena; Grittner, Ulrike; Flöel, Agnes

2017-07-26

Alzheimer's disease (AD) not only involves loss of memory functions, but also prominent deterioration of sleep physiology, which is already evident at the stage of mild cognitive impairment (MCI). Cortical slow oscillations (SO; 0.5-1 Hz) and thalamocortical spindle activity (12-15 Hz) during sleep, and their temporal coordination, are considered critical for memory formation. We investigated the potential of slow oscillatory transcranial direct current stimulation (so-tDCS), applied during a daytime nap in a sleep-state-dependent manner, to modulate these activity patterns and sleep-related memory consolidation in nine male and seven female human patients with MCI. Stimulation significantly increased overall SO and spindle power, amplified spindle power during SO up-phases, and led to stronger synchronization between SO and spindle power fluctuations in EEG recordings. Moreover, visual declarative memory was improved by so-tDCS compared with sham stimulation and was associated with stronger synchronization. These findings indicate a well-tolerated therapeutic approach for disordered sleep physiology and memory deficits in MCI patients and advance our understanding of offline memory consolidation. SIGNIFICANCE STATEMENT In the light of increasing evidence that sleep disruption is crucially involved in the progression of Alzheimer's disease (AD), sleep appears as a promising treatment target in this pathology, particularly to counteract memory decline. This study demonstrates the potential of a noninvasive brain stimulation method during sleep in patients with mild cognitive impairment (MCI), a precursor of AD, and advances our understanding of its mechanism. We provide first time evidence that slow oscillatory transcranial stimulation amplifies the functional cross-frequency coupling between memory-relevant brain oscillations and improves visual memory consolidation in patients with MCI. Copyright © 2017 the authors 0270-6474/17/377111-14$15.00/0.

Sleep and Plasticity in Schizophrenia

PubMed Central

Sprecher, Kate E.; Ferrarelli, Fabio

2016-01-01

Schizophrenia is a devastating mental illness with a worldwide prevalence of approximately 1 %. Although the clinical features of the disorder were described over one hundred years ago, its neurobiology is still largely elusive despite several decades of research. Schizophrenia is associated with marked sleep disturbances and memory impairment. Above and beyond altered sleep architecture, sleep rhythms including slow waves and spindles are disrupted in schizophrenia. In the healthy brain, these rhythms reflect and participate in plastic processes during sleep. This chapter discusses evidence that schizophrenia patients exhibit dysfunction of sleep-mediated plasticity on a behavioral, cellular, and molecular level and offers suggestions on how the study of sleeping brain activity can shed light on the pathophysiological mechanisms of the disorder. PMID:25608723

Fingolimod inhibits brain atrophy and promotes brain-derived neurotrophic factor in an animal model of multiple sclerosis.

PubMed

Smith, Paul A; Schmid, Cindy; Zurbruegg, Stefan; Jivkov, Magali; Doelemeyer, Arno; Theil, Diethilde; Dubost, Valérie; Beckmann, Nicolau

2018-05-15

Longitudinal brain atrophy quantification is a critical efficacy measurement in multiple sclerosis (MS) clinical trials and the determination of No Evidence of Disease Activity (NEDA). Utilising fingolimod as a clinically validated therapy we evaluated the use of repeated brain tissue volume measures during chronic experimental autoimmune encephalomyelitis (EAE) as a new preclinical efficacy measure. Brain volume changes were quantified using magnetic resonance imaging (MRI) at 7 Tesla and correlated to treatment-induced brain derived neurotrophic factor (BDNF) measured in blood, cerebrospinal fluid, spinal cord and brain. Serial brain MRI measurements revealed slow progressive brain volume loss in vehicle treated EAE mice despite a stable clinical score. Fingolimod (1 mg/kg) significantly ameliorated brain tissue atrophy in the cerebellum and striatum when administered from established EAE disease onwards. Fingolimod-dependent tissue preservation was associated with induction of BDNF specifically within the brain and co-localized with neuronal soma. In contrast, therapeutic teriflunomide (3 mg/kg) treatment failed to inhibit CNS autoimmune mediated brain degeneration. Finally, weekly anti-IL-17A antibody (15 mg/kg) treatment was highly efficacious and preserved whole brain, cerebellum and striatum volume. Fingolimod-mediated BDNF increases within the CNS may contribute to limiting progressive tissue loss during chronic neuroinflammation. Copyright © 2018 Elsevier B.V. All rights reserved.

Fast associative memory + slow neural circuitry = the computational model of the brain.

NASA Astrophysics Data System (ADS)

Berkovich, Simon; Berkovich, Efraim; Lapir, Gennady

1997-08-01

We propose a computational model of the brain based on a fast associative memory and relatively slow neural processors. In this model, processing time is expensive but memory access is not, and therefore most algorithmic tasks would be accomplished by using large look-up tables as opposed to calculating. The essential feature of an associative memory in this context (characteristic for a holographic type memory) is that it works without an explicit mechanism for resolution of multiple responses. As a result, the slow neuronal processing elements, overwhelmed by the flow of information, operate as a set of templates for ranking of the retrieved information. This structure addresses the primary controversy in the brain architecture: distributed organization of memory vs. localization of processing centers. This computational model offers an intriguing explanation of many of the paradoxical features in the brain architecture, such as integration of sensors (through DMA mechanism), subliminal perception, universality of software, interrupts, fault-tolerance, certain bizarre possibilities for rapid arithmetics etc. In conventional computer science the presented type of a computational model did not attract attention as it goes against the technological grain by using a working memory faster than processing elements.

Metabolic acceleration and the evolution of human brain size and life history.

PubMed

Pontzer, Herman; Brown, Mary H; Raichlen, David A; Dunsworth, Holly; Hare, Brian; Walker, Kara; Luke, Amy; Dugas, Lara R; Durazo-Arvizu, Ramon; Schoeller, Dale; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Thompson, Melissa Emery; Shumaker, Robert W; Ross, Stephen R

2016-05-19

Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history.

Continuous High Frequency Activity: A peculiar SEEG pattern related to specific brain regions

PubMed Central

Melani, Federico; Zelmann, Rina; Mari, Francesco; Gotman, Jean

2015-01-01

Objective While visually marking the high frequency oscillations in the stereo-EEG of epileptic patients, we observed a continuous/semicontinuous activity in the ripple band (80–250 Hz), which we defined continuous High Frequency Activity (HFA). We aim to analyze in all brain regions the occurrence and significance of this particular pattern. Methods Twenty patients implanted in mesial temporal and neocortical areas were studied. One minute of slow-wave sleep was reviewed. The background was classified as continuous/semicontinuous, irregular, or sporadic based on the duration of the fast oscillations. Each channel was classified as inside/outside the seizure onset zone (SOZ) or a lesion. Results The continuous/semicontinuous HFA occurred in 54 of the 790 channels analyzed, with a clearly higher prevalence in hippocampus and occipital lobe. No correlation was found with the SOZ or lesions. In the occipital lobe the continuous/semicontinuous HFA was present independently of whether eyes were open or closed. Conclusions We describe what appears to be a new physiological High Frequency Activity, independent of epileptogenicity, present almost exclusively in the hippocampus and occipital cortex but independent of the alpha rhythm. Significance The continuous HFA may be an intrinsic characteristic of specific brain regions, reflecting a particular type of physiological neuronal activity. PMID:23768436

Left Posterior Orbitofrontal Cortex Is Associated With Odor-Induced Autobiographical Memory: An fMRI Study.

PubMed

Watanabe, Keiko; Masaoka, Yuri; Kawamura, Mitsuru; Yoshida, Masaki; Koiwa, Nobuyoshi; Yoshikawa, Akira; Kubota, Satomi; Ida, Masahiro; Ono, Kenjiro; Izumizaki, Masahiko

2018-01-01

Autobiographical odor memory (AM-odor) accompanied by a sense of realism of a specific memory elicits strong emotions. AM-odor differs from memory triggered by other sensory modalities, possibly because olfaction involves a unique sensory process. Here, we examined the orbitofrontal cortex (OFC), using functional magnetic resonance imaging (fMRI) to determine which OFC subregions are related to AM-odor. Both AM-odor and a control odor successively increased subjective ratings of comfortableness and pleasantness. Importantly, AM-odor also increased arousal levels and the vividness of memories, and was associated with a deep and slow breathing pattern. fMRI analysis indicated robust activation in the left posterior OFC (L-POFC). Connectivity between the POFC and whole brain regions was estimated using psychophysiological interaction analysis (PPI). We detected several trends in connectivity between L-POFC and bilateral precuneus, bilateral rostral dorsal anterior cingulate cortex (rdACC), and left parahippocampus, which will be useful for targeting our hypotheses for future investigations. The slow breathing observed in AM-odor was correlated with rdACC activation. Odor associated with emotionally significant autobiographical memories was accompanied by slow and deep breathing, possibly involving rdACC processing.

Increased Sleep Depth in Developing Neural Networks: New Insights from Sleep Restriction in Children

PubMed Central

Kurth, Salome; Dean, Douglas C.; Achermann, Peter; O’Muircheartaigh, Jonathan; Huber, Reto; Deoni, Sean C. L.; LeBourgeois, Monique K.

2016-01-01

Brain networks respond to sleep deprivation or restriction with increased sleep depth, which is quantified as slow-wave activity (SWA) in the sleep electroencephalogram (EEG). When adults are sleep deprived, this homeostatic response is most pronounced over prefrontal brain regions. However, it is unknown how children’s developing brain networks respond to acute sleep restriction, and whether this response is linked to myelination, an ongoing process in childhood that is critical for brain development and cortical integration. We implemented a bedtime delay protocol in 5- to 12-year-old children to obtain partial sleep restriction (1-night; 50% of their habitual sleep). High-density sleep EEG was assessed during habitual and restricted sleep and brain myelin content was obtained using mcDESPOT magnetic resonance imaging. The effect of sleep restriction was analyzed using statistical non-parametric mapping with supra-threshold cluster analysis. We observed a localized homeostatic SWA response following sleep restriction in a specific parieto-occipital region. The restricted/habitual SWA ratio was negatively associated with myelin water fraction in the optic radiation, a developing fiber bundle. This relationship occurred bilaterally over parieto-temporal areas and was adjacent to, but did not overlap with the parieto-occipital region showing the most pronounced homeostatic SWA response. These results provide evidence for increased sleep need in posterior neural networks in children. Sleep need in parieto-temporal areas is related to myelin content, yet it remains speculative whether age-related myelin growth drives the fading of the posterior homeostatic SWA response during the transition to adulthood. Whether chronic insufficient sleep in the sensitive period of early life alters the anatomical generators of deep sleep slow-waves is an important unanswered question. PMID:27708567

Relationships among neuroscore, magnetic resonance imaging features, and intracranial pressure in sheep affected by slow-growing brain lesions.

PubMed

Evangelisti, Maria A; Deiana, Roberta; Melosu, Valentino; Burrai, Giovanni P; Ballocco, Isabella; Varcasia, Antonio; Scala, Antonio; Manunta, Maria L

2018-05-01

Diagnosing high intracranial pressure by clinical and diagnostic imaging is particularly challenging for chronic or slow-growing lesions. The aim of this prospective case-control study is to determine whether the neuroscore and brain magnetic resonance imaging (MRI) are related to the direct measurement of intracranial pressure in sheep affected by intracranial slow-growing lesions due to chronic cerebral coenurosis (Coenurus cerebralis). Seventeen affected and 10 control sheep were included. All animals underwent a neurological examination, MRI of the brain, and direct measurement of intracranial pressure. The severity of clinical signs and MRI findings were scored. Data were statistically analyzed. The invasive intracranial pressure value was higher in affected animals. A severely altered neuroscore is related to an increased intracranial pressure beyond the normal threshold (P < 0.05). The volume of the calvarium was larger in affected animals than in control animals (P = 0.0001) and was positively influenced by the presence and volume of the parasitic cyst (r = 0.7881, P < 0.01). Several degrees of deviation and deformation of both the ventricular system and brain parenchyma were detected by MRI. Subjective MRI findings were not associated with intracranial hypertension. In conclusion, this study shows that in sheep affected by slow-growing lesions, severe alterations in the neuroscore and the results of objective MRI are related to an increased intracranial pressure beyond the normal threshold. © 2017 American College of Veterinary Radiology.

Rapid transport of CCL11 across the blood-brain barrier: regional variation and importance of blood cells.

PubMed

Erickson, Michelle A; Morofuji, Yoichi; Owen, Joshua B; Banks, William A

2014-06-01

Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine.

Rapid Transport of CCL11 across the Blood-Brain Barrier: Regional Variation and Importance of Blood Cells

PubMed Central

Erickson, Michelle A.; Morofuji, Yoichi; Owen, Joshua B.

2014-01-01

Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine. PMID:24706984

Why does brain metabolism not favor burning of fatty acids to provide energy? - Reflections on disadvantages of the use of free fatty acids as fuel for brain

PubMed Central

Schönfeld, Peter; Reiser, Georg

2013-01-01

It is puzzling that hydrogen-rich fatty acids are used only poorly as fuel in the brain. The long-standing belief that a slow passage of fatty acids across the blood–brain barrier might be the reason. However, this has been corrected by experimental results. Otherwise, accumulated nonesterified fatty acids or their activated derivatives could exert detrimental activities on mitochondria, which might trigger the mitochondrial route of apoptosis. Here, we draw attention to three particular problems: (1) ATP generation linked to β-oxidation of fatty acids demands more oxygen than glucose, thereby enhancing the risk for neurons to become hypoxic; (2) β-oxidation of fatty acids generates superoxide, which, taken together with the poor anti-oxidative defense in neurons, causes severe oxidative stress; (3) the rate of ATP generation based on adipose tissue-derived fatty acids is slower than that using blood glucose as fuel. Thus, in periods of extended continuous and rapid neuronal firing, fatty acid oxidation cannot guarantee rapid ATP generation in neurons. We conjecture that the disadvantages connected with using fatty acids as fuel have created evolutionary pressure on lowering the expression of the β-oxidation enzyme equipment in brain mitochondria to avoid extensive fatty acid oxidation and to favor glucose oxidation in brain. PMID:23921897

Brain-machine interfaces in neurorehabilitation of stroke.

PubMed

Soekadar, Surjo R; Birbaumer, Niels; Slutzky, Marc W; Cohen, Leonardo G

2015-11-01

Stroke is among the leading causes of long-term disabilities leaving an increasing number of people with cognitive, affective and motor impairments depending on assistance in their daily life. While function after stroke can significantly improve in the first weeks and months, further recovery is often slow or non-existent in the more severe cases encompassing 30-50% of all stroke victims. The neurobiological mechanisms underlying recovery in those patients are incompletely understood. However, recent studies demonstrated the brain's remarkable capacity for functional and structural plasticity and recovery even in severe chronic stroke. As all established rehabilitation strategies require some remaining motor function, there is currently no standardized and accepted treatment for patients with complete chronic muscle paralysis. The development of brain-machine interfaces (BMIs) that translate brain activity into control signals of computers or external devices provides two new strategies to overcome stroke-related motor paralysis. First, BMIs can establish continuous high-dimensional brain-control of robotic devices or functional electric stimulation (FES) to assist in daily life activities (assistive BMI). Second, BMIs could facilitate neuroplasticity, thus enhancing motor learning and motor recovery (rehabilitative BMI). Advances in sensor technology, development of non-invasive and implantable wireless BMI-systems and their combination with brain stimulation, along with evidence for BMI systems' clinical efficacy suggest that BMI-related strategies will play an increasing role in neurorehabilitation of stroke. Copyright © 2014. Published by Elsevier Inc.

Why does brain metabolism not favor burning of fatty acids to provide energy? Reflections on disadvantages of the use of free fatty acids as fuel for brain.

PubMed

Schönfeld, Peter; Reiser, Georg

2013-10-01

It is puzzling that hydrogen-rich fatty acids are used only poorly as fuel in the brain. The long-standing belief that a slow passage of fatty acids across the blood-brain barrier might be the reason. However, this has been corrected by experimental results. Otherwise, accumulated nonesterified fatty acids or their activated derivatives could exert detrimental activities on mitochondria, which might trigger the mitochondrial route of apoptosis. Here, we draw attention to three particular problems: (1) ATP generation linked to β-oxidation of fatty acids demands more oxygen than glucose, thereby enhancing the risk for neurons to become hypoxic; (2) β-oxidation of fatty acids generates superoxide, which, taken together with the poor anti-oxidative defense in neurons, causes severe oxidative stress; (3) the rate of ATP generation based on adipose tissue-derived fatty acids is slower than that using blood glucose as fuel. Thus, in periods of extended continuous and rapid neuronal firing, fatty acid oxidation cannot guarantee rapid ATP generation in neurons. We conjecture that the disadvantages connected with using fatty acids as fuel have created evolutionary pressure on lowering the expression of the β-oxidation enzyme equipment in brain mitochondria to avoid extensive fatty acid oxidation and to favor glucose oxidation in brain.

Multimodal imaging of temporal processing in typical and atypical language development.

PubMed

Kovelman, Ioulia; Wagley, Neelima; Hay, Jessica S F; Ugolini, Margaret; Bowyer, Susan M; Lajiness-O'Neill, Renee; Brennan, Jonathan

2015-03-01

New approaches to understanding language and reading acquisition propose that the human brain's ability to synchronize its neural firing rate to syllable-length linguistic units may be important to children's ability to acquire human language. Yet, little evidence from brain imaging studies has been available to support this proposal. Here, we summarize three recent brain imaging (functional near-infrared spectroscopy (fNIRS), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG)) studies from our laboratories with young English-speaking children (aged 6-12 years). In the first study (fNIRS), we used an auditory beat perception task to show that, in children, the left superior temporal gyrus (STG) responds preferentially to rhythmic beats at 1.5 Hz. In the second study (fMRI), we found correlations between children's amplitude rise-time sensitivity, phonological awareness, and brain activation in the left STG. In the third study (MEG), typically developing children outperformed children with autism spectrum disorder in extracting words from rhythmically rich foreign speech and displayed different brain activation during the learning phase. The overall findings suggest that the efficiency with which left temporal regions process slow temporal (rhythmic) information may be important for gains in language and reading proficiency. These findings carry implications for better understanding of the brain's mechanisms that support language and reading acquisition during both typical and atypical development. © 2014 New York Academy of Sciences.

Vagus-brain communication in atherosclerosis-related inflammation: a neuroimmunomodulation perspective of CAD.

PubMed

Gidron, Yori; Kupper, Nina; Kwaijtaal, Martijn; Winter, Jobst; Denollet, Johan

2007-12-01

The current understanding of the pathophysiology of atherosclerosis leading to coronary artery disease (CAD) emphasizes the role of inflammatory mediators. Given the bidirectional communication between the immune and central nervous systems, an important question is whether the brain can be "informed" about and modulate CAD-related inflammation. A candidate communicator and modulator is the vagus nerve. Until now, the vagus nerve has received attention in cardiology mainly due to its role in the parasympathetic cardiovascular response. However, the vagus nerve can also "inform" the brain about peripheral inflammation since its paraganglia have receptors for interleukin-1. Furthermore, its efferent branch has a local anti-inflammatory effect. These effects have not been considered in research on the vagus nerve in CAD or in vagus nerve stimulation trials in CAD. In addition, various behavioural interventions, including relaxation, may influence CAD prognosis by affecting vagal activity. Based on this converging evidence, we propose a neuroimmunomodulation approach to atherogenesis. In this model, the vagus nerve "informs" the brain about CAD-related cytokines; in turn, activation of the vagus (via vagus nerve stimulation, vagomimetic drugs or relaxation) induces an anti-inflammatory response that can slow down the chronic process of atherogenesis.

Motor cortical representation of the pelvic floor muscles.

PubMed

Schrum, A; Wolff, S; van der Horst, C; Kuhtz-Buschbeck, J P

2011-07-01

Pelvic floor muscle training involves rhythmical voluntary contractions of the external urethral sphincter and ancillary pelvic floor muscles. The representation of these muscles in the motor cortex has not been located precisely and unambiguously. We used functional magnetic resonance imaging to determine brain activity during slow and fast pelvic floor contractions. Cerebral responses were recorded in 17 healthy male volunteers, 21 to 47 years old, with normal bladder control. Functional magnetic resonance imaging was performed during metronome paced slow (0.25 Hertz) and fast (0.7 Hertz) contractions of the pelvic floor that mimicked the interruption of voiding. To study the somatotopy of the cortical representations, flexion-extension movements of the right toes were performed as a control task. Functional magnetic resonance imaging during pelvic floor contractions detected activity of the supplementary motor area in the medial wall and of the midcingulate cortex, insula, posterior parietal cortex, putamen, thalamus, cerebellar vermis and upper ventral pons. There were no significant differences in activation between slow and fast contractions. Toe movements involved significantly stronger activity of the paracentral lobule (ie the medial primary motor cortex) than did the pelvic floor contractions. Otherwise the areas active during pelvic floor and leg muscle contractions overlapped considerably. The motor cortical representation of pelvic floor muscles is located mostly in the supplementary motor area. It extends further ventrally and anteriorly than the representation of distal leg muscles. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

EEG frequency tagging using ultra-slow periodic heat stimulation of the skin reveals cortical activity specifically related to C fiber thermonociceptors

PubMed Central

Colon, Elisabeth; Liberati, Giulia; Mouraux, André

2017-01-01

The recording of event-related brain potentials triggered by a transient heat stimulus is used extensively to study nociception and diagnose lesions or dysfunctions of the nociceptive system in humans. However, these responses are related exclusively to the activation of a specific subclass of nociceptive afferents: quickly-adapting thermonociceptors. In fact, except if the activation of Aδ fibers is avoided or if A fibers are blocked, these responses specifically reflect activity triggered by the activation of Type 2 quickly-adapting A fiber mechano-heat nociceptors (AMH-2). Here, we propose a novel method to isolate, in the human electroencephalogram (EEG), cortical activity related to the sustained periodic activation of heat-sensitive thermonociceptors, using very slow (0.2 Hz) and long-lasting (75 s) sinusoidal heat stimulation of the skin between baseline and 50°C. In a first experiment, we show that when such long-lasting thermal stimuli are applied to the hand dorsum of healthy volunteers, the slow rises and decreases of skin temperature elicit a consistent periodic EEG response at 0.2 Hz and its harmonics, as well as a periodic modulation of the magnitude of theta, alpha and beta band EEG oscillations. In a second experiment, we demonstrate using an A fiber block that these EEG responses are predominantly conveyed by unmyelinated C fiber nociceptors. The proposed approach constitutes a novel mean to study C fiber function in humans, and to explore the cortical processing of tonic heat pain in physiological and pathological conditions. PMID:27871921

Inhibitory motor control based on complex stopping goals relies on the same brain network as simple stopping

PubMed Central

Wessel, Jan R.; Aron, Adam R.

2014-01-01

Much research has modeled action-stopping using the stop-signal task (SST), in which an impending response has to be stopped when an explicit stop-signal occurs. A limitation of the SST is that real-world action-stopping rarely involves explicit stop-signals. Instead, the stopping-system engages when environmental features match more complex stopping goals. For example, when stepping into the street, one monitors path, velocity, size, and types of objects; and only stops if there is a vehicle approaching. Here, we developed a task in which participants compared the visual features of a multidimensional go-stimulus to a complex stopping-template, and stopped their go-response if all features matched the template. We used independent component analysis of EEG data to show that the same motor inhibition brain network that explains action-stopping in the SST also implements motor inhibition in the complex-stopping task. Furthermore, we found that partial feature overlap between go-stimulus and stopping-template lead to motor slowing, which also corresponded with greater stopping-network activity. This shows that the same brain system for action-stopping to explicit stop-signals is recruited to slow or stop behavior when stimuli match a complex stopping goal. The results imply a generalizability of the brain’s network for simple action-stopping to more ecologically valid scenarios. PMID:25270603

Dosha brain-types: A neural model of individual differences.

PubMed

Travis, Frederick T; Wallace, Robert Keith

2015-01-01

This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain-type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations.

Frequency dependent hub role of the dorsal and ventral right anterior insula.

PubMed

Wang, Yifeng; Zhu, Lixia; Zou, Qijun; Cui, Qian; Liao, Wei; Duan, Xujun; Biswal, Bharat; Chen, Huafu

2018-01-15

The right anterior insula (rAI) plays a crucial role in generating adaptive behavior by orchestrating multiple brain networks. Based on functional separation findings of the insula and spectral fingerprints theory of cognitive functions, we hypothesize that the hub role of the rAI is region and frequency dependent. Using the Human Connectome Project dataset and backtracking approach, we segregate the rAI into dorsal and ventral parts at frequency bands from slow 6 to slow 3, indicating the frequency dependent functional separation of the rAI. Functional connectivity analysis shows that, within lower than 0.198 Hz frequency range, the dorsal and ventral parts of rAI form a complementary system to synchronize with externally and internally-oriented networks. Moreover, the relationship between the dorsal and ventral rAIs predicts the relationship between anti-correlated networks associated with the dorsal rAI at slow 6 and slow 5, suggesting a frequency dependent regulation of the rAI to brain networks. These findings could improve our understanding of the rAI by supporting the region and frequency dependent function of rAI and its essential role in coordinating brain systems relevant to internal and external environments. Copyright © 2017 Elsevier Inc. All rights reserved.

Dynamic correlations between heart and brain rhythm during Autogenic meditation

PubMed Central

Kim, Dae-Keun; Lee, Kyung-Mi; Kim, Jongwha; Whang, Min-Cheol; Kang, Seung Wan

2013-01-01

This study is aimed to determine significant physiological parameters of brain and heart under meditative state, both in each activities and their dynamic correlations. Electrophysiological changes in response to meditation were explored in 12 healthy volunteers who completed 8 weeks of a basic training course in autogenic meditation. Heart coherence, representing the degree of ordering in oscillation of heart rhythm intervals, increased significantly during meditation. Relative EEG alpha power and alpha lagged coherence also increased. A significant slowing of parietal peak alpha frequency was observed. Parietal peak alpha power increased with increasing heart coherence during meditation, but no such relationship was observed during baseline. Average alpha lagged coherence also increased with increasing heart coherence during meditation, but weak opposite relationship was observed at baseline. Relative alpha power increased with increasing heart coherence during both meditation and baseline periods. Heart coherence can be a cardiac marker for the meditative state and also may be a general marker for the meditative state since heart coherence is strongly correlated with EEG alpha activities. It is expected that increasing heart coherence and the accompanying EEG alpha activations, heart brain synchronicity, would help recover physiological synchrony following a period of homeostatic depletion. PMID:23914165

Dynamic correlations between heart and brain rhythm during Autogenic meditation.

PubMed

Kim, Dae-Keun; Lee, Kyung-Mi; Kim, Jongwha; Whang, Min-Cheol; Kang, Seung Wan

2013-01-01

This study is aimed to determine significant physiological parameters of brain and heart under meditative state, both in each activities and their dynamic correlations. Electrophysiological changes in response to meditation were explored in 12 healthy volunteers who completed 8 weeks of a basic training course in autogenic meditation. Heart coherence, representing the degree of ordering in oscillation of heart rhythm intervals, increased significantly during meditation. Relative EEG alpha power and alpha lagged coherence also increased. A significant slowing of parietal peak alpha frequency was observed. Parietal peak alpha power increased with increasing heart coherence during meditation, but no such relationship was observed during baseline. Average alpha lagged coherence also increased with increasing heart coherence during meditation, but weak opposite relationship was observed at baseline. Relative alpha power increased with increasing heart coherence during both meditation and baseline periods. Heart coherence can be a cardiac marker for the meditative state and also may be a general marker for the meditative state since heart coherence is strongly correlated with EEG alpha activities. It is expected that increasing heart coherence and the accompanying EEG alpha activations, heart brain synchronicity, would help recover physiological synchrony following a period of homeostatic depletion.

A comprehensive picture of 4-year outcome of severe brain injuries. Results from the PariS-TBI study.

PubMed

Jourdan, C; Bayen, E; Pradat-Diehl, P; Ghout, I; Darnoux, E; Azerad, S; Vallat-Azouvi, C; Charanton, J; Aegerter, P; Ruet, A; Azouvi, P

2016-04-01

Survivors of severe traumatic brain injury have a great variety of impairments and participation restrictions. Detailed descriptions of their long-term outcome are critical. We aimed to assess brain injury outcome for subjects with traumatic brain injury in terms of the International classification of functioning, disability and health. Four-year follow-up of an inception cohort of adults with severe traumatic brain injury by using face-to-face interviews with patients and proxies. Among 245 survivors at 4 years, 147 were evaluated (80% male, mean age: 32.5±14.2 years at injury); 46 (32%) presented severe disability, 58 (40%) moderate disability, and 40 (28%) good recovery. Most frequent somatic problems were fatigue, headaches, other pain, and balance. One quarter of subjects had motor impairments. Rates of cognitive complaints ranged from 25 to 68%, the most frequent being memory, irritability, slowness and concentration. With the Hospital Anxiety and Depression Scale, 43% had anxiety and 25% depression. Overall, 79% were independent in daily living activities and 40 to 50% needed help for outdoor or organizational activities on the BICRO-39. Most had regular contacts with relatives or close friends but few contacts with colleagues or new acquaintances. Subjects spent little time in productive activities such as working, studying, looking after children or voluntary work. Quality of life on the QOLIBRI scale was associated with disability level (P<0.0001). Management of late brain injury needs to focus on cognitive difficulties, particularly social skills, to enhance patient participation in life. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Electroencephalograph (EEG) study on self-contemplating image formation

NASA Astrophysics Data System (ADS)

Meng, Qinglei; Hong, Elliot; Choa, Fow-Sen

2016-05-01

Electroencephalography (EEG) is one of the most widely used electrophysiological monitoring methods and plays a significant role in studies of human brain electrical activities. Default mode network (DMN), is a functional connection of brain regions that are activated while subjects are not in task positive state or not focused on the outside world. In this study, EEG was used for human brain signals recording while all subjects were asked to sit down quietly on a chair with eyes closed and thinking about some parts of their own body, such as left and right hands, left and right ears, lips, nose, and the images of faces that they were familiar with as well as doing some simple mathematical calculation. The time is marker when the image is formed in the subject's mind. By analyzing brain activity maps 300ms right before the time marked instant for each of the 4 wave bands, Delta, Theta, Alpha and Beta waves. We found that for most EEG datasets during this 300ms, Delta wave activity would mostly locate at the frontal lobe or the visual cortex, and the change and movement of activities are slow. Theta wave activity tended to rotate along the edge of cortex either clockwise or counterclockwise. Beta wave behaved like inquiry types of oscillations between any two regions spread over the cortex. Alpha wave activity looks like a mix of the Theta and Beta activities but more close to Theta activity. From the observation we feel that Beta and high Alpha are playing utility role for information inquiry. Theta and low Alpha are likely playing the role of binding and imagination formation in DMN operations.

Probing Intrinsic Resting-State Networks in the Infant Rat Brain

PubMed Central

Bajic, Dusica; Craig, Michael M.; Borsook, David; Becerra, Lino

2016-01-01

Resting-state functional magnetic resonance imaging (rs-fMRI) measures spontaneous fluctuations in blood oxygenation level-dependent (BOLD) signal in the absence of external stimuli. It has become a powerful tool for mapping large-scale brain networks in humans and animal models. Several rs-fMRI studies have been conducted in anesthetized and awake adult rats, reporting consistent patterns of brain activity at the systems level. However, the evolution to adult patterns of resting-state activity has not yet been evaluated and quantified in the developing rat brain. In this study, we hypothesized that large-scale intrinsic networks would be easily detectable but not fully established as specific patterns of activity in lightly anesthetized 2-week-old rats (N = 11). Independent component analysis (ICA) identified 8 networks in 2-week-old-rats. These included Default mode, Sensory (Exteroceptive), Salience (Interoceptive), Basal Ganglia-Thalamic-Hippocampal, Basal Ganglia, Autonomic, Cerebellar, as well as Thalamic-Brainstem networks. Many of these networks consisted of more than one component, possibly indicative of immature, underdeveloped networks at this early time point. Except for the Autonomic network, infant rat networks showed reduced connectivity with subcortical structures in comparison to previously published adult networks. Reported slow fluctuations in the BOLD signal that correspond to functionally relevant resting-state networks in 2-week-old rats can serve as an important tool for future studies of brain development in the settings of different pharmacological applications or disease. PMID:27803653

Contrasting Acute and Slow-Growing Lesions: A New Door to Brain Plasticity

ERIC Educational Resources Information Center

Desmurget, Michel; Bonnetblanc, FranCois; Duffau, Hugues

2007-01-01

The concept of plasticity describes the mechanisms that rearrange cerebral organization following a brain injury. During the last century, plasticity has been mainly investigated in humans with acute strokes. It was then shown: (i) that the brain is organized into highly specialized functional areas, often designated "eloquent" areas and (ii) that…

Effects of neurofeedback therapy in healthy young subjects.

PubMed

Altan, Sümeyra; Berberoglu, Bercim; Canan, Sinan; Dane, Şenol

2016-12-01

Neurofeedback refers to a form of operant conditioning of electrical brain activity, in which desirable brain activity is rewarded and undesirable brain activity is inhibited. The research team aimed to examine the efficacy of neurofeedback therapy on electroencephalogram (EEG) for heart rate, electrocardiogram (ECG) and galvanic skin resistance (GSR) parameters in a healthy young male population. Forty healthy young male subjects aged between 18 to 30 years participated in this study. Neurofeedback application of one session was made with bipolar electrodes placed on T3 and T4 (temporal 3 and 4) regions and with reference electrode placed on PF1 (prefrontal 1). Electroencephalogram (EEG), electrocardiogram (ECG) and galvanic skin resistance (GSR) were assessed during Othmer neurofeedback application of one session to regulate slow wave activity for forty minutes thorough the session. Data assessed before neurofeedback application for 5 minutes and during neurofeedback application of 30 minutes and after neurofeedback application for 5 minutes throughout the session of 40 minutes. Means for each 5 minutes, that is to say, a total 8 data points for each subjects over 40 minutes, were assessed. Galvanic skin resistance increased and heart rate decreased after neurofeedback therapy. Beta activity in EEG increased and alfa activity decreased after neurofeedback therapy. These results suggest that neurofeedback can be used to restore sympathovagal imbalances. Also, it may be accepted as a preventive therapy for psychological and neurological problems.

Protecting against vascular disease in brain

PubMed Central

2011-01-01

Endothelial cells exert an enormous influence on blood vessels throughout the circulation, but their impact is particularly pronounced in the brain. New concepts have emerged recently regarding the role of this cell type and mechanisms that contribute to endothelial dysfunction and vascular disease. Activation of the renin-angiotensin system plays a prominent role in producing these abnormalities. Both oxidative stress and local inflammation are key mechanisms that underlie vascular disease of diverse etiology. Endogenous mechanisms of vascular protection are also present, including antioxidants, anti-inflammatory molecules, and peroxisome proliferator-activated receptor-γ. Despite their clear importance, studies of mechanisms that underlie cerebrovascular disease continue to lag behind studies of vascular biology in general. Identification of endogenous molecules and pathways that protect the vasculature may result in targeted approaches to prevent or slow the progression of vascular disease that causes stroke and contributes to the vascular component of dementia and Alzheimer's disease. PMID:21335467

Transparent, Flexible, Low Noise Graphene Electrodes for Simultaneous Electrophysiology and Neuroimaging

PubMed Central

Kuzum, Duygu; Takano, Hajime; Shim, Euijae; Reed, Jason C; Juul, Halvor; Richardson, Andrew G.; de Vries, Julius; Bink, Hank; Dichter, Marc A.; Lucas, Timothy H.; Coulter, Douglas A.; Cubukcu, Ertugrul; Litt, Brian

2014-01-01

Calcium imaging is a versatile experimental approach capable of resolving single neurons with single-cell spatial resolution in the brain. Electrophysiological recordings provide high temporal, but limited spatial resolution, due to the geometrical inaccessibility of the brain. An approach that integrates the advantages of both techniques could provide new insights into functions of neural circuits. Here, we report a transparent, flexible neural electrode technology based on graphene, which enables simultaneous optical imaging and electrophysiological recording. We demonstrate that hippocampal slices can be imaged through transparent graphene electrodes by both confocal and two-photon microscopy without causing any light-induced artifacts in the electrical recordings. Graphene electrodes record high frequency bursting activity and slow synaptic potentials that are hard to resolve by multi-cellular calcium imaging. This transparent electrode technology may pave the way for high spatio-temporal resolution electrooptic mapping of the dynamic neuronal activity. PMID:25327632

Conflict processing in the anterior cingulate cortex constrains response priming.

PubMed

Pastötter, Bernhard; Hanslmayr, Simon; Bäuml, Karl-Heinz T

2010-05-01

A prominent function of the anterior cingulate cortex (ACC) is to process conflict between competing response options. In this study, we investigated the role of conflict processing in a response-priming task in which manual responses were either validly or invalidly cued. Examining electrophysiological measurements of oscillatory brain activity on the source level, we found response priming to be related to a beta power decrease in the premotor cortex and conflict processing to be linked to a theta power increase in the ACC. In particular, correlation of oscillatory brain activities in the ACC and the premotor cortex showed that conflict processing reduces response priming by slowing response time in valid trials and lowering response errors in invalid trials. This relationship emerged on a between subjects level as well as within subjects, on a single trial level. These findings suggest that conflict processing in the ACC constrains the automatic priming process. 2010 Elsevier Inc. All rights reserved.

High-density EEG characterization of brain responses to auditory rhythmic stimuli during wakefulness and NREM sleep.

PubMed

Lustenberger, Caroline; Patel, Yogi A; Alagapan, Sankaraleengam; Page, Jessica M; Price, Betsy; Boyle, Michael R; Fröhlich, Flavio

2018-04-01

Auditory rhythmic sensory stimulation modulates brain oscillations by increasing phase-locking to the temporal structure of the stimuli and by increasing the power of specific frequency bands, resulting in Auditory Steady State Responses (ASSR). The ASSR is altered in different diseases of the central nervous system such as schizophrenia. However, in order to use the ASSR as biological markers for disease states, it needs to be understood how different vigilance states and underlying brain activity affect the ASSR. Here, we compared the effects of auditory rhythmic stimuli on EEG brain activity during wake and NREM sleep, investigated the influence of the presence of dominant sleep rhythms on the ASSR, and delineated the topographical distribution of these modulations. Participants (14 healthy males, 20-33 years) completed on the same day a 60 min nap session and two 30 min wakefulness sessions (before and after the nap). During these sessions, amplitude modulated (AM) white noise auditory stimuli at different frequencies were applied. High-density EEG was continuously recorded and time-frequency analyses were performed to assess ASSR during wakefulness and NREM periods. Our analysis revealed that depending on the electrode location, stimulation frequency applied and window/frequencies analysed the ASSR was significantly modulated by sleep pressure (before and after sleep), vigilance state (wake vs. NREM sleep), and the presence of slow wave activity and sleep spindles. Furthermore, AM stimuli increased spindle activity during NREM sleep but not during wakefulness. Thus, (1) electrode location, sleep history, vigilance state and ongoing brain activity needs to be carefully considered when investigating ASSR and (2) auditory rhythmic stimuli during sleep might represent a powerful tool to boost sleep spindles. Copyright © 2017 Elsevier Inc. All rights reserved.

Neurotrophin regulation of sodium and calcium channels in human neuroblastoma cells.

PubMed

Urbano, F J; Buño, W

2000-01-01

Neurotrophins, acting through tyrosine kinase family genes, are essential for neuronal differentiation. The expression of tyrosine kinase family genes is prognostic in neuroblastoma, and neurotrophins reduce proliferation and induce differentiation, indicating that neuroblastomas are regulated by neurotrophins. We tested the effects of nerve growth factor and brain-derived neurotrophic factor on Na(+) and Ca(2+) currents, using the whole-cell patch-clamp technique, in human neuroblastoma NB69 cells. Control cells exhibited a slow tetrodotoxin-resistant (IC(50)=98 nM) Na(+) current and a high-voltage-activated Ca(2+) current. Exposure to nerve growth factor (50 ng/ml) and/or brain-derived neurotrophic factor (5 ng/ml) produced the expression of a fast tetrodotoxin-sensitive (IC(50)=10 nM) Na(+) current after day 3, and suppressed the slow tetrodotoxin-resistant variety. The same type of high-voltage-activated Ca(2+) current was expressed in control and treated cells. The treatment increased the surface density of both Na(+) and Ca(2+) currents with time after plating, from 17 pA/pF at days 3-5 and 1-5 to 34 and 30 pA/pF after days 6-10, respectively. Therefore, both nerve growth factor and brain-derived neurotrophic factor, acting through different receptors of the tyrosine kinase family and also possibly the tumor necrosis factor receptor-II, were able to regulate differentiation and the expression of Na(+) and Ca(2+) channels, partially reproducing the modifications induced by diffusible astroglial factors. We show that neurotrophins induced differentiation to a neuronal phenotype and modified the expression of Na(+) and Ca(2+) currents, partially reproducing the effects of diffusible astroglial factors.

Cerebral blood flow and metabolism during exercise: implications for fatigue.

PubMed

Secher, Neils H; Seifert, Thomas; Van Lieshout, Johannes J

2008-01-01

During exercise: the Kety-Schmidt-determined cerebral blood flow (CBF) does not change because the jugular vein is collapsed in the upright position. In contrast, when CBF is evaluated by (133)Xe clearance, by flow in the internal carotid artery, or by flow velocity in basal cerebral arteries, a approximately 25% increase is detected with a parallel increase in metabolism. During activation, an increase in cerebral O(2) supply is required because there is no capillary recruitment within the brain and increased metabolism becomes dependent on an enhanced gradient for oxygen diffusion. During maximal whole body exercise, however, cerebral oxygenation decreases because of eventual arterial desaturation and marked hyperventilation-related hypocapnia of consequence for CBF. Reduced cerebral oxygenation affects recruitment of motor units, and supplemental O(2) enhances cerebral oxygenation and work capacity without effects on muscle oxygenation. Also, the work of breathing and the increasing temperature of the brain during exercise are of importance for the development of so-called central fatigue. During prolonged exercise, the perceived exertion is related to accumulation of ammonia in the brain, and data support the theory that glycogen depletion in astrocytes limits the ability of the brain to accelerate its metabolism during activation. The release of interleukin-6 from the brain when exercise is prolonged may represent a signaling pathway in matching the metabolic response of the brain. Preliminary data suggest a coupling between the circulatory and metabolic perturbations in the brain during strenuous exercise and the ability of the brain to access slow-twitch muscle fiber populations.

Criticality in the brain

NASA Astrophysics Data System (ADS)

de Arcangelis, L.; Lombardi, F.; Herrmann, H. J.

2014-03-01

Spontaneous brain activity has been recently characterized by avalanche dynamics with critical features for systems in vitro and in vivo. In this contribution we present a review of experimental results on neuronal avalanches in cortex slices, together with numerical results from a neuronal model implementing several physiological properties of living neurons. Numerical data reproduce experimental results for avalanche statistics. The temporal organization of avalanches can be characterized by the distribution of waiting times between successive avalanches. Experimental measurements exhibit a non-monotonic behaviour, not usually found in other natural processes. Numerical simulations provide evidence that this behaviour is a consequence of the alternation between states of high and low activity, leading to a balance between excitation and inhibition controlled by a single parameter. During these periods both the single neuron state and the network excitability level, keeping memory of past activity, are tuned by homoeostatic mechanisms. Interestingly, the same homoeostatic balance is detected for neuronal activity at the scale of the whole brain. We finally review the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules and the learning dynamics exhibits universal features as a function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

A Multimodal, SU-8 - Platinum - Polyimide Microelectrode Array for Chronic In Vivo Neurophysiology

PubMed Central

Márton, Gergely; Orbán, Gábor; Kiss, Marcell; Fiáth, Richárd; Pongrácz, Anita; Ulbert, István

2015-01-01

Utilization of polymers as insulator and bulk materials of microelectrode arrays (MEAs) makes the realization of flexible, biocompatible sensors possible, which are suitable for various neurophysiological experiments such as in vivo detection of local field potential changes on the surface of the neocortex or unit activities within the brain tissue. In this paper the microfabrication of a novel, all-flexible, polymer-based MEA is presented. The device consists of a three dimensional sensor configuration with an implantable depth electrode array and brain surface electrodes, allowing the recording of electrocorticographic (ECoG) signals with laminar ones, simultaneously. In vivo recordings were performed in anesthetized rat brain to test the functionality of the device under both acute and chronic conditions. The ECoG electrodes recorded slow-wave thalamocortical oscillations, while the implanted component provided high quality depth recordings. The implants remained viable for detecting action potentials of individual neurons for at least 15 weeks. PMID:26683306

A Multimodal, SU-8 - Platinum - Polyimide Microelectrode Array for Chronic In Vivo Neurophysiology.

PubMed

Márton, Gergely; Orbán, Gábor; Kiss, Marcell; Fiáth, Richárd; Pongrácz, Anita; Ulbert, István

2015-01-01

Utilization of polymers as insulator and bulk materials of microelectrode arrays (MEAs) makes the realization of flexible, biocompatible sensors possible, which are suitable for various neurophysiological experiments such as in vivo detection of local field potential changes on the surface of the neocortex or unit activities within the brain tissue. In this paper the microfabrication of a novel, all-flexible, polymer-based MEA is presented. The device consists of a three dimensional sensor configuration with an implantable depth electrode array and brain surface electrodes, allowing the recording of electrocorticographic (ECoG) signals with laminar ones, simultaneously. In vivo recordings were performed in anesthetized rat brain to test the functionality of the device under both acute and chronic conditions. The ECoG electrodes recorded slow-wave thalamocortical oscillations, while the implanted component provided high quality depth recordings. The implants remained viable for detecting action potentials of individual neurons for at least 15 weeks.

Cognitive reserve in ageing and Alzheimer's disease

PubMed Central

Stern, Yaakov

2012-01-01

The concept of reserve accounts for individual differences in susceptibility to age-related brain changes or Alzheimer's disease-related pathology. There is evidence that some people can tolerate more of these changes than others and still maintain function. Epidemiologic studies suggest that lifetime exposures including educational and occupational attainment, and leisure activities in late life, can increase this reserve. For example, there is a reduced risk of developing Alzheimer's disease in individuals with higher educational or occupational attainment. It is convenient to think of two types of reserve: brain reserve, which refers to actual differences in the brain itself that may increase tolerance of pathology, and cognitive reserve. Cognitive reserve refers to individual differences in how tasks are performed that may allow some people to be more resilient than others. The concept of cognitive reserve holds out the promise of interventions that could slow cognitive aging or reduce the risk of dementia. PMID:23079557

Long-acting κ opioid antagonists nor-BNI, GNTI and JDTic: pharmacokinetics in mice and lipophilicity.

PubMed

Munro, Thomas A; Berry, Loren M; Van't Veer, Ashlee; Béguin, Cécile; Carroll, F Ivy; Zhao, Zhiyang; Carlezon, William A; Cohen, Bruce M

2012-05-29

Nor-BNI, GNTI and JDTic induce κ opioid antagonism that is delayed by hours and can persist for months. Other effects are transient. It has been proposed that these drugs may be slowly absorbed or distributed, and may dissolve in cell membranes, thus slowing elimination and prolonging their effects. Recent evidence suggests, instead, that they induce prolonged desensitization of the κ opioid receptor. To evaluate these hypotheses, we measured relevant physicochemical properties of nor-BNI, GNTI and JDTic, and the timecourse of brain and plasma concentrations in mice after intraperitoneal administration (using LC-MS-MS). In each case, plasma levels were maximal within 30 min and declined by >80% within four hours, correlating well with previously reported transient effects. A strong negative correlation was observed between plasma levels and the delayed, prolonged timecourse of κ antagonism. Brain levels of nor-BNI and JDTic peaked within 30 min, but while nor-BNI was largely eliminated within hours, JDTic declined gradually over a week. Brain uptake of GNTI was too low to measure accurately, and higher doses proved lethal. None of the drugs were highly lipophilic, showing high water solubility (> 45 mM) and low distribution into octanol (log D7.4 < 2). Brain homogenate binding was within the range of many shorter-acting drugs (>7% unbound). JDTic showed P-gp-mediated efflux; nor- BNI and GNTI did not, but their low unbound brain uptake suggests efflux by another mechanism. The negative plasma concentration-effect relationship we observed is difficult to reconcile with simple competitive antagonism, but is consistent with desensitization. The very slow elimination of JDTic from brain is surprising given that it undergoes active efflux, has modest affinity for homogenate, and has a shorter duration of action than nor-BNI under these conditions. We propose that this persistence may result from entrapment in cellular compartments such as lysosomes.

Do false belief and verb non-factivity share similar neural circuits?

PubMed

Chen, Lan; Cheung, Him; Szeto, Ching-Yee; Zhu, Zude; Wang, Suiping

2012-02-21

The present study investigates whether the complement falsity elicited by strong non-factive verbs and the false belief activated by a standard nonverbal false belief task produce similar electrophysiological activities in the brain. The hypothesis is based on the notion that both complement falsity and false belief involve decoupling a false mental representation from reality. Some previous studies have reported a behavioral correlation between children's false belief reasoning and interpretation of strong non-factive verbs together with their false complements, but a neural basis for this correlation has not been found. Our event-related potential (ERP) results with normal adults showed that both nonverbal false belief and strong non-factive verb comprehension elicited a negative late slow waveform divergence compared to their respective baselines. Although these slow waves due to the two types of stimuli had slightly different scalp distributions, both were regarded as reflecting primarily frontal activation. Such ERP similarity provides evidence for a common neural basis shared by nonverbal false belief reasoning and comprehension of strong non-factive verbs. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Postictal psychosis and its electrophysiological correlates in invasive EEG: a case report study and literature review.

PubMed

Kuba, Robert; Brázdil, Milan; Rektor, Ivan

2012-04-01

We identified two patients with medically refractory temporal lobe epilepsy, from whom intracranial EEG recordings were obtained at the time of postictal psychosis. Both patients had mesial temporal epilepsy associated with hippocampal sclerosis. In both patients, the postictal psychosis was associated with a continual "epileptiform" EEG pattern that differed from their interictal and ictal EEG findings (rhythmical slow wave and "abortive" spike-slow wave complex activity in the right hippocampus and lateral temporal cortex in case 1 and a periodic pattern of triphasic waves in the contacts recording activity from the left anterior cingulate gyrus). Some cases of postictal psychosis might be caused by the transient impairment of several limbic system structures due to the "continual epileptiform discharge" in some brain regions. Case 2 is the first report of a patient with TLE in whom psychotic symptoms were associated with the epileptiform impairment of the anterior cingulate gyrus. Copyright © 2012 Elsevier Inc. All rights reserved.

Flexible traffic control of the synfire-mode transmission by inhibitory modulation: Nonlinear noise reduction

NASA Astrophysics Data System (ADS)

Shinozaki, Takashi; Okada, Masato; Reyes, Alex D.; Câteau, Hideyuki

2010-01-01

Intermingled neural connections apparent in the brain make us wonder what controls the traffic of propagating activity in the brain to secure signal transmission without harmful crosstalk. Here, we reveal that inhibitory input but not excitatory input works as a particularly useful traffic controller because it controls the degree of synchrony of population firing of neurons as well as controlling the size of the population firing bidirectionally. Our dynamical system analysis reveals that the synchrony enhancement depends crucially on the nonlinear membrane potential dynamics and a hidden slow dynamical variable. Our electrophysiological study with rodent slice preparations show that the phenomenon happens in real neurons. Furthermore, our analysis with the Fokker-Planck equations demonstrates the phenomenon in a semianalytical manner.

Brain potentials in affective picture processing: covariation with autonomic arousal and affective report.

PubMed

Cuthbert, B N; Schupp, H T; Bradley, M M; Birbaumer, N; Lang, P J

2000-03-01

Emotionally arousing picture stimuli evoked scalp-recorded event-related potentials. A late, slow positive voltage change was observed, which was significantly larger for affective than neutral stimuli. This positive shift began 200-300 ms after picture onset, reached its maximum amplitude approximately 1 s after picture onset, and was sustained for most of a 6-s picture presentation period. The positive increase was not related to local probability of content type, but was accentuated for pictures that prompted increased autonomic responses and reports of greater affective arousal (e.g. erotic or violent content). These results suggest that the late positive wave indicates a selective processing of emotional stimuli, reflecting the activation of motivational systems in the brain.

Acetylcholine Mediates a Slow Synaptic Potential in Hippocampal Pyramidal Cells

NASA Astrophysics Data System (ADS)

Cole, A. E.; Nicoll, R. A.

1983-09-01

The hippocampal slice preparation was used to study the role of acetylcholine as a synaptic transmitter. Bath-applied acetylcholine had three actions on pyramidal cells: (i) depolarization associated with increased input resistance, (ii) blockade of calcium-activated potassium responses, and (iii) blockade of accommodation of cell discharge. All these actions were reversed by the muscarinic antagonist atropine. Stimulation of sites in the slice known to contain cholinergic fibers mimicked all the actions. Furthermore, these evoked synaptic responses were enhanced by the cholinesterase inhibitor eserine and were blocked by atropine. These findings provide electrophysiological support for the role of acetylcholine as a synaptic transmitter in the brain and demonstrate that nonclassical synaptic responses involving the blockade of membrane conductances exist in the brain.

[Neuropsychopharmacology of delta-9-tetrahydrocannabinol].

PubMed

Costentin, J

2008-08-01

Today, the main route of introduction of tetrahydrocannabinol (THC), the main active substance of cannabis, into the human body is via the lungs, from smokes produced by combustion of a haschich-tobacco mixture. The use of a water pipe (nargileh-like) intensifies its fast supply to the body. THC reaches the brain easily where it stimulates CB1 receptors; their ubiquity underlies a wide variety of effects. THC disappears from extracellular spaces by dissolving in lipid rich membranes, and not by excretion from the body. This is followed by a slow release, leading to long lasting effects originating from brain areas containing a large proportion of spare receptors ("reserve receptors"). Far from mimicking the effects of endocannabinoids, THC caricatures and disturbs them. It induces both psychical and physical dependencies, but the perception of withdrawal is weak on account of its very slow elimination. THC disturbs cognition. Acutely, it develops anxiolytic- and antidepressant-like effects, which causes a lot of users to abuse THC, thus leading to a tolerance (desensitization of CB1 receptors) making anxiety and depression to reappear more intensely than originally. THC has close relationships with schizophrenia. It incites to tobacco, alcohol and heroine abuses.

Linking state regulation, brain laterality, and self-reported attention-deficit/hyperactivity disorder (ADHD) symptoms in adults.

PubMed

Mohamed, Saleh M H; Börger, Norbert A; Geuze, Reint H; van der Meere, Jaap J

2016-10-01

Many clinical studies have shown that performance of subjects with attention-deficit/hyperactivity disorder (ADHD) is impaired when stimuli are presented at a slow rate compared to a medium or fast rate. According to the cognitive-energetic model, this finding may reflect difficulty in allocating sufficient effort to regulate the motor activation state. Other studies have shown that the left hemisphere is relatively responsible for keeping humans motivated, allocating sufficient effort to complete their tasks. This leads to a prediction that poor effort allocation might be associated with an affected left-hemisphere functioning in ADHD. So far, this prediction has not been directly tested, which is the aim of the present study. Seventy-seven adults with various scores on the Conners' Adult ADHD Rating Scale performed a lateralized lexical decision task in three conditions with stimuli presented in a fast, a medium, and a slow rate. The left-hemisphere functioning was measured in terms of visual field advantage (better performance for the right than for the left visual field). All subjects showed an increased right visual field advantage for word processing in the slow presentation rate of stimuli compared to the fast and the medium rate. Higher ADHD scores were related to a reduced right visual field advantage in the slow rate only. The present findings suggest that ADHD symptomatology is associated with less involvement of the left hemisphere when extra effort allocation is needed to optimize the low motor activation state.

Time-frequency dynamics during sleep spindles on the EEG in rodents with a genetic predisposition to absence epilepsy (WAG/Rij rats)

NASA Astrophysics Data System (ADS)

Hramov, Alexander E.; Sitnikova, Evgenija Y.; Pavlov, Alexey N.; Grubov, Vadim V.; Koronovskii, Alexey A.; Khramova, Marina V.

2015-03-01

Sleep spindles are known to appear spontaneously in the thalamocortical neuronal network of the brain during slow-wave sleep; pathological processes in the thalamocortical network may be the reason of the absence epilepsy. The aim of the present work is to study developed changes in the time-frequency structure of sleep spindles during the progressive development of the absence epilepsy in WAG/Rij rats. EEG recordings were made at age 7 and 9 months. Automatic recognition and subsequent analysis of sleep spindles on the EEG were performed using the continuous wavelet transform. The duration of epileptic discharges and the total duration of epileptic activity were found to increase with age, while the duration of sleep spindles, conversely, decreased. In terms of the mean frequency, sleep spindles could be divided into three classes: `slow' (mean frequency 9.3Hz), `medium' (11.4Hz), and `fast' (13.5Hz). Slow and medium (transitional) spindles in five-month-old animals showed increased frequency from the beginning to the end of the spindle. The more intense the epilepsy is, the shorter are the durations of spindles of all types. The mean frequencies of `medium' and `fast' spindles were higher in rats with more intense signs of epilepsy. Overall, high epileptic activity in WAG/Rij rats was linked with significant changes in spindles of the transitional type, with less marked changes in the two traditionally identified types of spindle, slow and fast.

Analysis of Zolpidem in Postmortem Fluids and Tissues Using Ultra-Performance Liquid Chromatography-Mass Spectrometry

DTIC Science & Technology

2014-02-01

16. Abstract Zolpidem is a nonbenzodiazepine sedative hypnotic drug used for the short-term treatment of insomnia. Its use is common and wide-spread...Classif. (of this page) 21. No. of Pages 22. Price Unclassified Unclassified 15 Form DOT F 1700.7 (8-72) Reproduction of completed page authorized iii...INTRODUCTION Zolpidem is a nonbenzodiazepine sedative hypnotic drug used to treat insomnia by slowing the activity in the brain. It is prescribed as a short

[Electrophysiological correlates of efficacy of nootropic drugs in the treatment of consequences of traumatic brain injury in adolescents].

PubMed

Iznak, E V; Iznak, A F; Pankratova, E A; Zavadenko, N N; Guzilova, L S; Guzilova, Iu I

2010-01-01

To assess objectively a dynamics of brain functional state, EEG spectral power and peak latency of the P300 component of cognitive auditory evoked potentials have been analyzed in adolescents during the course of nootropic therapy of residual asthenic consequences of traumatic brain injury (ICD-10 F07.2). The study included 76 adolescents, aged 12-18 years, who have undergone severe closed head trauma with brain commotion 1/2--5 years ago. Patients have been divided into 3 groups treated during one month with cerebrolysin, piracetam or magne-B6, respectively. After the end of the nootropic therapy, 77% of patients treated with cerebrolysin as well as 50% of patients treated with piracetam and magne-B6 have demonstrated the positive dynamics of their brain functional state that manifested itself in the appearance of occipital EEG alpha rhythm or in the increase of its spectral power; in the normalization of alpha rhythm frequency; in the decrease in the spectral power of slow wave (theta and delta) EEG activity, in the amount (up to the disappearance) of paroxysmal EEG activity, in the EEG response to hyperventilation and in the shortening of the P300 peak latency. Such positive changes of neurophysiological parameters have been associated with the improvement of clinical conditions of patients and correlated significantly with the dynamics of psychometric scores of attention and memory.

Electrophysiological CNS-processes related to associative learning in humans.

PubMed

Christoffersen, Gert R J; Schachtman, Todd R

2016-01-01

The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS-process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.

Individual differences in brain activity during visuo-spatial processing assessed by slow cortical potentials and LORETA.

PubMed

Lamm, Claus; Fischmeister, Florian Ph S; Bauer, Herbert

2005-12-01

Using slow-cortical potentials (SCPs), Vitouch et al. demonstrated that subjects with low ability to solve a complex visuo-spatial imagery task show higher activity in occipital, parietal and frontal cortex during task processing than subjects with high ability. This finding has been interpreted in the sense of the so-called "neural efficiency" hypothesis, which assumes that the central nervous system of individuals with higher intellectual abilities is functioning in a more efficient way than the one of individuals with lower abilities. Using a higher spatial resolution of SCP recordings, and by employing the source localization method of LORETA (low-resolution electromagnetic tomography), we investigated this hypothesis by performing an extended replication of Vitouch et al.'s study. SCPs during processing of a visuo-spatial imagery task were recorded in pre-selected subjects with either high or low abilities in solving the imagery task. Topographic and LORETA analyses of SCPs revealed that a distributed network of extrastriate occipital, superior parietal, temporal, medial frontal and prefrontal areas was active during task solving. This network is well in line with former studies of the functional neuroanatomy of visuo-spatial imagery. Contrary to our expectations, however, the results of Vitouch et al. as well as of other studies supporting the neural efficiency hypothesis could not be confirmed since no difference in brain activity between groups was observed. This inconsistency between studies might be due to differing task processing strategies. While subjects with high abilities in the Vitouch et al. study seemed to use a visuo-perceptual task solving approach, all other subjects relied upon a visuo-motor task processing strategy.

Effect of PMA-induced protein kinase C activation on development and apoptosis in early zebrafish embryos.

PubMed

Hrubik, Jelena; Glisic, Branka; Samardzija, Dragana; Stanic, Bojana; Pogrmic-Majkic, Kristina; Fa, Svetlana; Andric, Nebojsa

2016-12-01

Protein kinase C (PKC) isoforms have been implicated in several key steps during early development, but the consequences of xenobiotic-induced PKC activation during early embryogenesis are still unknown. In this study, zebrafish embryos were exposed to a range of phorbol 12-myristate 13-acetate (PMA) concentrations (0-200μg/L) at different time points after fertilization. Results showed that 200μgPMA/L caused development of yolk bags, cardiac edema, slow blood flow, pulsating blood flow, slow pulse, elongated heart, lack of tail fins, curved tail, and coagulation. PMA exposure decreased survival rate of the embryos starting within the first 24h and becoming more pronounced after prolonged exposure (96h). PMA increased the number of apoptotic cells in the brain region as demonstrated by acridine orange staining and caused up-regulation of caspase 9 (casp9) and p53 up-regulated modulator of apoptosis (puma) mRNA in whole embryos. PMA caused oxidative stress in the embryos as demonstrated by decreased mRNA expression of catalase and superoxide dismutase 2. Inhibition of Pkc with GF109203X improved overall survival rate, reduced apoptosis in the brain and decreased expression of casp9 and puma in the PMA-exposed embryos. However, Pkc inhibition neither prevented development of deformities nor reversed oxidative stress in the PMA-exposed embryos. These data suggest that direct over-activation of Pkc during early embryogenesis of zebrafish is associated with apoptosis and decreased survival rate of the embryos. Copyright © 2016 Elsevier Inc. All rights reserved.

Intuition and deliberation: two systems for strategizing in the brain.

PubMed

Kuo, Wen-Jui; Sjöström, Tomas; Chen, Yu-Ping; Wang, Yen-Hsiang; Huang, Chen-Ying

2009-04-24

Dual-process theories distinguish between intuition (fast and emotional) and reasoning (slow and controlled) as a basis for human decision-making. We contrast dominance-solvable games, which can be solved by step-by-step deliberative reasoning, with pure coordination games, which must be solved intuitively. Using functional magnetic resonance imaging, we found that the middle frontal gyrus, the inferior parietal lobule, and the precuneus were more active in dominance-solvable games than in coordination games. The insula and anterior cingulate cortex showed the opposite pattern. Moreover, precuneus activity correlates positively with how "effortful" a dominance-solvable game is, whereas insula activity correlates positively with how "effortless" a coordination game is.

Resting state low-frequency fluctuations in prefrontal cortex reflect degrees of harm avoidance and novelty seeking: an exploratory NIRS study

PubMed Central

Nakao, Takashi; Matsumoto, Tomoya; Shimizu, Daisuke; Morita, Machiko; Yoshimura, Shinpei; Northoff, Georg; Morinobu, Shigeru; Okamoto, Yasumasa; Yamawaki, Shigeto

2013-01-01

Harm avoidance (HA) and novelty seeking (NS) are temperament dimensions defined by Temperament and Character Inventory (TCI), respectively, reflecting a heritable bias for intense response to aversive stimuli or for excitement in response to novel stimuli. High HA is regarded as a risk factor for major depressive disorder and anxiety disorder. In contrast, higher NS is linked to increased risk for substance abuse and pathological gambling disorder. A growing body of evidence suggests that patients with these disorders show abnormality in the power of slow oscillations of resting-state brain activity. It is particularly interesting that previous studies have demonstrated that resting state activities in medial prefrontal cortex (MPFC) are associated with HA or NS scores, although the relation between the power of resting state slow oscillations and these temperament dimensions remains poorly elucidated. This preliminary study investigated the biological bases of these temperament traits by particularly addressing the resting state low-frequency fluctuations in MPFC. Regional hemodynamic changes in channels covering MPFC during 5-min resting states were measured from 22 healthy participants using near-infrared spectroscopy (NIRS). These data were used for correlation analyses. Results show that the power of slow oscillations during resting state around the dorsal part of MPFC is negatively correlated with the HA score. In contrast, NS was positively correlated with the power of resting state slow oscillations around the ventral part of MPFC. These results suggest that the powers of slow oscillation at rest in dorsal or ventral MPFC, respectively, reflect the degrees of HA and NS. This exploratory study therefore uncovers novel neural bases of HA and NS. We discuss a neural mechanism underlying aversion-related and reward-related processing based on results obtained from this study. PMID:24381545

Identification of potential novel interaction partners of the sodium-activated potassium channels Slick and Slack in mouse brain.

PubMed

Rizzi, Sandra; Schwarzer, Christoph; Kremser, Leopold; Lindner, Herbert H; Knaus, Hans-Günther

2015-12-01

The sodium-activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are paralogous channels of the Slo family of high-conductance potassium channels. Slick and Slack channels are widely distributed in the mammalian CNS and they play a role in slow afterhyperpolarization, generation of depolarizing afterpotentials and in setting and stabilizing the resting potential. In the present study we used a combined approach of (co)-immunoprecipitation studies, Western blot analysis, double immunofluorescence and mass spectrometric sequencing in order to investigate protein-protein interactions of the Slick and Slack channels. The data strongly suggest that Slick and Slack channels co-assemble into identical cellular complexes. Double immunofluorescence experiments revealed that Slick and Slack channels co-localize in distinct mouse brain regions. Moreover, we identified the small cytoplasmic protein beta-synuclein and the transmembrane protein 263 (TMEM 263) as novel interaction partners of both, native Slick and Slack channels. In addition, the inactive dipeptidyl-peptidase (DPP 10) and the synapse associated protein 102 (SAP 102) were identified as constituents of the native Slick and Slack channel complexes in the mouse brain. This study presents new insights into protein-protein interactions of native Slick and Slack channels in the mouse brain.

The neurological basis of occupation.

PubMed

Gutman, Sharon A; Schindler, Victoria P

2007-01-01

The purpose of the present paper was to survey the literature about the neurological basis of human activity and its relationship to occupation and health. Activities related to neurological function were organized into three categories: those that activate the brain's reward system; those that promote the relaxation response; and those that preserve cognitive function into old age. The results from the literature review correlating neurological evidence and activities showed that purposeful and meaningful activities could counter the effects of stress-related diseases and reduce the risk for dementia. Specifically, it was found that music, drawing, meditation, reading, arts and crafts, and home repairs, for example, can stimulate the neurogical system and enhance health and well-being, Prospective research studies are needed to examine the effects of purposeful activities on reducing stress and slowing the rate of cognitive decline.

Preterm EEG: a multimodal neurophysiological protocol.

PubMed

Stjerna, Susanna; Voipio, Juha; Metsäranta, Marjo; Kaila, Kai; Vanhatalo, Sampsa

2012-02-18

Since its introduction in early 1950s, electroencephalography (EEG) has been widely used in the neonatal intensive care units (NICU) for assessment and monitoring of brain function in preterm and term babies. Most common indications are the diagnosis of epileptic seizures, assessment of brain maturity, and recovery from hypoxic-ischemic events. EEG recording techniques and the understanding of neonatal EEG signals have dramatically improved, but these advances have been slow to penetrate through the clinical traditions. The aim of this presentation is to bring theory and practice of advanced EEG recording available for neonatal units. In the theoretical part, we will present animations to illustrate how a preterm brain gives rise to spontaneous and evoked EEG activities, both of which are unique to this developmental phase, as well as crucial for a proper brain maturation. Recent animal work has shown that the structural brain development is clearly reflected in early EEG activity. Most important structures in this regard are the growing long range connections and the transient cortical structure, subplate. Sensory stimuli in a preterm baby will generate responses that are seen at a single trial level, and they have underpinnings in the subplate-cortex interaction. This brings neonatal EEG readily into a multimodal study, where EEG is not only recording cortical function, but it also tests subplate function via different sensory modalities. Finally, introduction of clinically suitable dense array EEG caps, as well as amplifiers capable of recording low frequencies, have disclosed multitude of brain activities that have as yet been overlooked. In the practical part of this video, we show how a multimodal, dense array EEG study is performed in neonatal intensive care unit from a preterm baby in the incubator. The video demonstrates preparation of the baby and incubator, application of the EEG cap, and performance of the sensory stimulations.

Fisetin Acts on Multiple Pathways to Reduce the Impact of Age and Disease on CNS Function

PubMed Central

Maher, Pamela

2017-01-01

It is becoming increasingly clear that neurological diseases are multi-factorial involving disruptions in multiple cellular systems. Thus, while each disease has its own initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological diseases described to date. Thus, it is unlikely that modulating only a single factor will be effective at either preventing disease development or slowing disease progression. A better approach is to identify small (< 900 daltons) molecules that have multiple biological activities relevant to the maintenance of brain function. Over the last few years, we have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also activate key neurotrophic factor signaling pathways. In addition, it has anti-inflammatory activity against microglial cells and inhibits the activity of lipoxygenases, thereby reducing the production of pro-inflammatory eicosanoids and their by-products. This wide range of actions suggests that fisetin has the ability to reduce the impact of age-related neurological diseases on brain function. PMID:25961687

The Brain Tourniquet: Physiological Isolation of Brain Regions Damaged by Traumatic Head Injury

DTIC Science & Technology

2008-06-19

brain slices were treated after injury with either a nootropic agent ( aniracetam , cyclothiazide, IDRA 21, or 1-BCP) or the antiepileptic drug...tourniquet approach. Four well-known nootropic agents were evaluated: aniracetam , a pyrrolidione analog that slows non-NMDA (AMPA/kainate) receptor...to improve cognition in rats [Stdubli et al., 1994], and has more potent effects than aniracetam in rat brain slices [Arai et al., 1994]. In

Metabolic costs and evolutionary implications of human brain development.

PubMed

Kuzawa, Christopher W; Chugani, Harry T; Grossman, Lawrence I; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R; Wildman, Derek E; Sherwood, Chet C; Leonard, William R; Lange, Nicholas

2014-09-09

The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain's glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain-body metabolic trade-offs using the ratios of brain glucose uptake to the body's resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate.

Disulfiram-induced acute organic brain syndrome.

PubMed

Kump, J G; Flaten, P A; Greenlaw, C W

1979-08-01

Reversible acute organic brain syndrome is described in a patient receiving disulfiram, 250 mg daily. Slowing of the electroencephalogram (3 to 4 cycles per second) in the occipital region resolved ten days after discontinuation of disulfiram. Acute organic brain syndrome induced by disulfiram is not rare but is often not correlated, and it should always be considered a possibility in patients receiving disulfiram therapy.

Scanning fast and slow: current limitations of 3 Tesla functional MRI and future potential

PubMed Central

Boubela, Roland N.; Kalcher, Klaudius; Nasel, Christian; Moser, Ewald

2017-01-01

Functional MRI at 3T has become a workhorse for the neurosciences, e.g., neurology, psychology, and psychiatry, enabling non-invasive investigation of brain function and connectivity. However, BOLD-based fMRI is a rather indirect measure of brain function, confounded by physiology related signals, e.g., head or brain motion, brain pulsation, blood flow, intermixed with susceptibility differences close or distant to the region of neuronal activity. Even though a plethora of preprocessing strategies have been published to address these confounds, their efficiency is still under discussion. In particular, physiological signal fluctuations closely related to brain supply may mask BOLD signal changes related to “true” neuronal activation. Here we explore recent technical and methodological advancements aimed at disentangling the various components, employing fast multiband vs. standard EPI, in combination with fast temporal ICA. Our preliminary results indicate that fast (TR <0.5 s) scanning may help to identify and eliminate physiologic components, increasing tSNR and functional contrast. In addition, biological variability can be studied and task performance better correlated to other measures. This should increase specificity and reliability in fMRI studies. Furthermore, physiological signal changes during scanning may then be recognized as a source of information rather than a nuisance. As we are currently still undersampling the complexity of the brain, even at a rather coarse macroscopic level, we should be very cautious in the interpretation of neuroscientific findings, in particular when comparing different groups (e.g., age, sex, medication, pathology, etc.). From a technical point of view our goal should be to sample brain activity at layer specific resolution with low TR, covering as much of the brain as possible without violating SAR limits. We hope to stimulate discussion toward a better understanding and a more quantitative use of fMRI. PMID:28164083

Adolescent Changes in Homeostatic Regulation of EEG Activity in the Delta and Theta Frequency Bands during NREM Sleep

PubMed Central

Campbell, Ian G.; Darchia, Nato; Higgins, Lisa M.; Dykan, Igor V.; Davis, Nicole M.; de Bie, Evan; Feinberg, Irwin

2011-01-01

Study Objectives: Slow wave EEG activity in NREM sleep decreases by more than 60% between ages 10 and 20 years. Slow wave EEG activity also declines across NREM periods (NREMPs) within a night, and this decline is thought to represent the dynamics of sleep homeostasis. We used longitudinal data to determine whether these homeostatic dynamics change across adolescence. Design: All-night sleep EEG was recorded semiannually for 6 years. Setting: EEG was recorded with ambulatory recorders in the subjects' homes. Participants: Sixty-seven subjects in 2 cohorts, one starting at age 9 and one starting at age 12 years. Measurements and Results: For NREM delta (1-4 Hz) and theta (4-8 Hz) EEG, we tested whether the proportion of spectral energy contained in the first NREMP changes with age. We also tested for age changes in the parameters of the process S exponential decline. For both delta and theta, the proportion of energy in the first NREMP declined significantly across ages 9 to 18 years. Process S parameters SWA0 and TWA0, respectively, represent slow wave (delta) activity and theta wave activity at the beginning of the night. SWA0 and TWA0 declined significantly (P < 0.0001) across ages 9 to 18. Conclusions: These declines indicate that the intensity of the homeostatic or restorative processes at the beginning of sleep diminished across adolescence. We propose that this change in sleep regulation is caused by the synaptic pruning that occurs during adolescent brain maturation. Citation: Campbell IG; Darchia N; Higgins LM; Dykan IV; Davis NM; de Bie E; Feinberg I. Adolescent changes in homeostatic regulation of EEG activity in the delta and theta frequency bands during NREM sleep. SLEEP 2011;34(1):83-91. PMID:21203377

Permutation auto-mutual information of electroencephalogram in anesthesia

NASA Astrophysics Data System (ADS)

Liang, Zhenhu; Wang, Yinghua; Ouyang, Gaoxiang; Voss, Logan J.; Sleigh, Jamie W.; Li, Xiaoli

2013-04-01

Objective. The dynamic change of brain activity in anesthesia is an interesting topic for clinical doctors and drug designers. To explore the dynamical features of brain activity in anesthesia, a permutation auto-mutual information (PAMI) method is proposed to measure the information coupling of electroencephalogram (EEG) time series obtained in anesthesia. Approach. The PAMI is developed and applied on EEG data collected from 19 patients under sevoflurane anesthesia. The results are compared with the traditional auto-mutual information (AMI), SynchFastSlow (SFS, derived from the BIS index), permutation entropy (PE), composite PE (CPE), response entropy (RE) and state entropy (SE). Performance of all indices is assessed by pharmacokinetic/pharmacodynamic (PK/PD) modeling and prediction probability. Main results. The PK/PD modeling and prediction probability analysis show that the PAMI index correlates closely with the anesthetic effect. The coefficient of determination R2 between PAMI values and the sevoflurane effect site concentrations, and the prediction probability Pk are higher in comparison with other indices. The information coupling in EEG series can be applied to indicate the effect of the anesthetic drug sevoflurane on the brain activity as well as other indices. The PAMI of the EEG signals is suggested as a new index to track drug concentration change. Significance. The PAMI is a useful index for analyzing the EEG dynamics during general anesthesia.

Sleep and rhythm changes at the time of Trypanosoma brucei invasion of the brain parenchyma in the rat.

PubMed

Seke Etet, Paul F; Palomba, Maria; Colavito, Valeria; Grassi-Zucconi, Gigliola; Bentivoglio, Marina; Bertini, Giuseppe

2012-05-01

Human African trypanosomiasis (HAT), or sleeping sickness, is a severe disease caused by Trypanosoma brucei (T.b.). The disease hallmark is sleep alterations. Brain involvement in HAT is a crucial pathogenetic step for disease diagnosis and therapy. In this study, a rat model of African trypanosomiasis was used to assess changes of sleep-wake, rest-activity, and body temperature rhythms in the time window previously shown as crucial for brain parenchyma invasion by T.b. to determine potential biomarkers of this event. Chronic radiotelemetric monitoring in Sprague-Dawley rats was used to continuously record electroencephalogram, electromyogram, rest-activity, and body temperature in the same animals before (baseline recording) and after infection. Rats were infected with T.b. brucei. Data were acquired from 1 to 20 d after infection (parasite neuroinvasion initiates at 11-13 d post-infection in this model), and were compared to baseline values. Sleep parameters were manually scored from electroencephalographic-electromyographic tracings. Circadian rhythms of sleep time, slow-wave activity, rest-activity, and body temperature were studied using cosinor rhythmometry. Results revealed alterations of most of the analyzed parameters. In particular, sleep pattern and sleep-wake organization plus rest-activity and body temperature rhythms exhibited early quantitative and qualitative alterations, which became marked around the time interval crucial for parasite neuroinvasion or shortly after. Data derived from actigrams showed close correspondence with those from hypnograms, suggesting that rest-activity could be useful to monitor sleep-wake alterations in African trypanosomiasis.

Electroencephalographic profiles for differentiation of disorders of consciousness

PubMed Central

2013-01-01

Background Electroencephalography (EEG) is best suited for long-term monitoring of brain functions in patients with disorders of consciousness (DOC). Mathematical tools are needed to facilitate efficient interpretation of long-duration sleep-wake EEG recordings. Methods Starting with matching pursuit (MP) decomposition, we automatically detect and parametrize sleep spindles, slow wave activity, K-complexes and alpha, beta and theta waves present in EEG recordings, and automatically construct profiles of their time evolution, relevant to the assessment of residual brain function in patients with DOC. Results Above proposed EEG profiles were computed for 32 patients diagnosed as minimally conscious state (MCS, 20 patients), vegetative state/unresponsive wakefulness syndrome (VS/UWS, 11 patients) and Locked-in Syndrome (LiS, 1 patient). Their interpretation revealed significant correlations between patients’ behavioral diagnosis and: (a) occurrence of sleep EEG patterns including sleep spindles, slow wave activity and light/deep sleep cycles, (b) appearance and variability across time of alpha, beta, and theta rhythms. Discrimination between MCS and VS/UWS based upon prominent features of these profiles classified correctly 87% of cases. Conclusions Proposed EEG profiles offer user-independent, repeatable, comprehensive and continuous representation of relevant EEG characteristics, intended as an aid in differentiation between VS/UWS and MCS states and diagnostic prognosis. To enable further development of this methodology into clinically usable tests, we share user-friendly software for MP decomposition of EEG (http://braintech.pl/svarog) and scripts used for creation of the presented profiles (attached to this article). PMID:24143892

Spirocyclic β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors: from hit to lowering of cerebrospinal fluid (CSF) amyloid β in a higher species.

PubMed

Hunt, Kevin W; Cook, Adam W; Watts, Ryan J; Clark, Christopher T; Vigers, Guy; Smith, Darin; Metcalf, Andrew T; Gunawardana, Indrani W; Burkard, Michael; Cox, April A; Geck Do, Mary K; Dutcher, Darrin; Thomas, Allen A; Rana, Sumeet; Kallan, Nicholas C; DeLisle, Robert K; Rizzi, James P; Regal, Kelly; Sammond, Douglas; Groneberg, Robert; Siu, Michael; Purkey, Hans; Lyssikatos, Joseph P; Marlow, Allison; Liu, Xingrong; Tang, Tony P

2013-04-25

A hallmark of Alzheimer's disease is the brain deposition of amyloid beta (Aβ), a peptide of 36-43 amino acids that is likely a primary driver of neurodegeneration. Aβ is produced by the sequential cleavage of APP by BACE1 and γ-secretase; therefore, inhibition of BACE1 represents an attractive therapeutic target to slow or prevent Alzheimer's disease. Herein we describe BACE1 inhibitors with limited molecular flexibility and molecular weight that decrease CSF Aβ in vivo, despite efflux. Starting with spirocycle 1a, we explore structure-activity relationships of core changes, P3 moieties, and Asp binding functional groups in order to optimize BACE1 affinity, cathepsin D selectivity, and blood-brain barrier (BBB) penetration. Using wild type guinea pig and rat, we demonstrate a PK/PD relationship between free drug concentrations in the brain and CSF Aβ lowering. Optimization of brain exposure led to the discovery of (R)-50 which reduced CSF Aβ in rodents and in monkey.

Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based chemotherapy.

PubMed

Moruno-Manchon, Jose F; Uzor, Ndidi-Ese; Kesler, Shelli R; Wefel, Jeffrey S; Townley, Debra M; Nagaraja, Archana Sidalaghatta; Pradeep, Sunila; Mangala, Lingegowda S; Sood, Anil K; Tsvetkov, Andrey S

2018-01-01

Doxorubicin, a commonly used anti-neoplastic agent, causes severe neurotoxicity. Doxorubicin promotes thinning of the brain cortex and accelerates brain aging, leading to cognitive impairment. Oxidative stress induced by doxorubicin contributes to cellular damage. In addition to mitochondria, peroxisomes also generate reactive oxygen species (ROS) and promote cell senescence. Here, we investigated if doxorubicin affects peroxisomal homeostasis in neurons. We demonstrate that the number of peroxisomes is increased in doxorubicin-treated neurons and in the brains of mice which underwent doxorubicin-based chemotherapy. Pexophagy, the specific autophagy of peroxisomes, is downregulated in neurons, and peroxisomes produce more ROS. 2-hydroxypropyl-β-cyclodextrin (HPβCD), an activator of the transcription factor TFEB, which regulates expression of genes involved in autophagy and lysosome function, mitigates damage of pexophagy and decreases ROS production induced by doxorubicin. We conclude that peroxisome-associated oxidative stress induced by doxorubicin may contribute to neurotoxicity, cognitive dysfunction, and accelerated brain aging in cancer patients and survivors. Peroxisomes might be a valuable new target for mitigating neuronal damage caused by chemotherapy drugs and for slowing down brain aging in general. Copyright © 2017 Elsevier Inc. All rights reserved.

Memory traces of long-range coordinated oscillations in the sleeping human brain.

PubMed

Piantoni, Giovanni; Van Der Werf, Ysbrand D; Jensen, Ole; Van Someren, Eus J W

2015-01-01

Cognition involves coordinated activity across distributed neuronal networks. Neuronal activity during learning triggers cortical plasticity that allows for reorganization of the neuronal network and integration of new information. Animal studies have shown post-learning reactivation of learning-elicited neuronal network activity during subsequent sleep, supporting consolidation of the reorganization. However, no previous studies, to our knowledge, have demonstrated reactivation of specific learning-elicited long-range functional connectivity during sleep in humans. We here show reactivation of learning-induced long-range synchronization of magnetoencephalography power fluctuations in human sleep. Visuomotor learning elicited a specific profile of long-range cortico-cortical synchronization of slow (0.1 Hz) fluctuations in beta band (12-30 Hz) power. The parieto-occipital part of this synchronization profile reappeared in delta band (1-3.5 Hz) power fluctuations during subsequent sleep, but not during the intervening wakefulness period. Individual differences in the reactivated synchronization predicted postsleep performance improvement. The presleep resting-state synchronization profile was not reactivated during sleep. The findings demonstrate reactivation of long-range coordination of neuronal activity in humans, more specifically of reactivation of coupling of infra-slow fluctuations in oscillatory power. The spatiotemporal profile of delta power fluctuations during sleep may subserve memory consolidation by echoing coordinated activation elicited by prior learning. © 2014 Wiley Periodicals, Inc.

Anti-Ma2-associated encephalitis with normal FDG-PET: a case of pseudo-Whipple's disease.

PubMed

Castle, James; Sakonju, Ai; Dalmau, Josep; Newman-Toker, David E

2006-10-01

A 39-year-old man presented with a history of several months of progressive personality changes, social withdrawal, bradykinesia, mutism, dysphagia, worsening gait, and difficulty with daily living activities. Examination revealed an atypical parkinsonian appearance with incomplete supranuclear ophthalmoplegia and an unusual oculomotor disorder characterized by both low-amplitude, intermittent opsoclonus, and slow, nystagmoid intrusions. Routine laboratory testing, autoimmune and infectious serologies, brain MRI, lumbar puncture, electroencephalogram, whole-body CT scan, paraneoplastic serologies, small bowel biopsy, 18F-fluorodeoxyglucose positron emission tomography CT scan, brain biopsy, and testicular ultrasound. Anti-Ma2 paraneoplastic encephalitis in association with metastatic testicular cancer; initially misdiagnosed as CNS Whipple's disease. Corticosteroids, intravenous immunoglobulins, orchiectomy, muscle relaxants, mycophenolate mofetil, plasmapheresis, and bleomycin, etoposide and platinum chemotherapy.

USE OF NEUROFEEDBACK AND MINDFULNESS TO ENHANCE RESPONSE TO HYPNOSIS TREATMENT IN INDIVIDUALS WITH MULTIPLE SCLEROSIS: Results From a Pilot Randomized Clinical Trial.

PubMed

Jensen, Mark P; Battalio, Samuel L; Chan, Joy F; Edwards, Karlyn A; Day, Melissa A; Sherlin, Leslie H; Ehde, Dawn M

2018-01-01

This pilot study evaluated the possibility that 2 interventions hypothesized to increase slower brain oscillations (e.g., theta) may enhance the efficacy of hypnosis treatment, given evidence that hypnotic responding is associated with slower brain oscillations. Thirty-two individuals with multiple sclerosis and chronic pain, fatigue, or both, were randomly assigned to 1 of 2 interventions thought to increase slow wave activity (mindfulness meditation or neurofeedback training) or no enhancing intervention, and then given 5 sessions of self-hypnosis training targeting their presenting symptoms. The findings supported the potential for both neurofeedback and mindfulness to enhance response to hypnosis treatment. Research using larger sample sizes to determine the generalizability of these findings is warranted.

Anti-Aβ single-chain variable fragment antibodies exert synergistic neuroprotective activities in Drosophila models of Alzheimer's disease

PubMed Central

Fernandez-Funez, Pedro; Zhang, Yan; Sanchez-Garcia, Jonatan; de Mena, Lorena; Khare, Swati; Golde, Todd E.; Levites, Yona; Rincon-Limas, Diego E.

2015-01-01

Both active and passive immunotherapy protocols decrease insoluble amyloid-ß42 (Aß42) peptide in animal models, suggesting potential therapeutic applications against the main pathological trigger in Alzheimer's disease (AD). However, recent clinical trials have reported no significant benefits from humanized anti-Aß42 antibodies. Engineered single-chain variable fragment antibodies (scFv) are much smaller and can easily penetrate the brain, but identifying the most effective scFvs in murine AD models is slow and costly. We show here that scFvs against the N- and C-terminus of Aß42 (scFv9 and scFV42.2, respectively) that decrease insoluble Aß42 in CRND mice are neuroprotective in Drosophila models of Aß42 and amyloid precursor protein neurotoxicity. Both scFv9 and scFv42.2 suppress eye toxicity, reduce cell death in brain neurons, protect the structural integrity of dendritic terminals in brain neurons and delay locomotor dysfunction. Additionally, we show for the first time that co-expression of both anti-Aß scFvs display synergistic neuroprotective activities, suggesting that combined therapies targeting distinct Aß42 epitopes can be more effective than targeting a single epitope. Overall, we demonstrate the feasibility of using Drosophila as a first step for characterizing neuroprotective anti-Aß scFvs in vivo and identifying scFv combinations with synergistic neuroprotective activities. PMID:26253732

Neural Signatures of Stimulus Features in Visual Working Memory—A Spatiotemporal Approach

PubMed Central

Jackson, Margaret C.; Klein, Christoph; Mohr, Harald; Shapiro, Kimron L.; Linden, David E. J.

2010-01-01

We examined the neural signatures of stimulus features in visual working memory (WM) by integrating functional magnetic resonance imaging (fMRI) and event-related potential data recorded during mental manipulation of colors, rotation angles, and color–angle conjunctions. The N200, negative slow wave, and P3b were modulated by the information content of WM, and an fMRI-constrained source model revealed a progression in neural activity from posterior visual areas to higher order areas in the ventral and dorsal processing streams. Color processing was associated with activity in inferior frontal gyrus during encoding and retrieval, whereas angle processing involved right parietal regions during the delay interval. WM for color–angle conjunctions did not involve any additional neural processes. The finding that different patterns of brain activity underlie WM for color and spatial information is consistent with ideas that the ventral/dorsal “what/where” segregation of perceptual processing influences WM organization. The absence of characteristic signatures of conjunction-related brain activity, which was generally intermediate between the 2 single conditions, suggests that conjunction judgments are based on the coordinated activity of these 2 streams. PMID:19429863

Non-fluent aphasia and neural reorganization after speech therapy: insights from human sleep electrophysiology and functional magnetic resonance imaging.

PubMed

Sarasso, S; Santhanam, P; Määtta, S; Poryazova, R; Ferrarelli, F; Tononi, G; Small, S L

2010-09-01

Stroke is associated with long-term functional deficits. Behavioral interventions are often effective in promoting functional recovery and plastic changes. Recent studies in normal subjects have shown that sleep, and particularly slow wave activity (SWA), is tied to local brain plasticity and may be used as a sensitive marker of local cortical reorganization after stroke. In a pilot study, we assessed the local changes induced by a single exposure to a therapeutic session of IMITATE (Intensive Mouth Imitation and Talking for Aphasia Therapeutic Effects), a behavioral therapy used for recovery in patients with post-stroke aphasia. In addition, we measured brain activity changes with functional magnetic resonance imaging (fMRI) in a language observation task before, during and after the full IMITATE rehabilitative program. Speech production improved both after a single exposure and the full therapy program as measured by the Western Aphasia Battery (WAB) Repetition subscale. We found that IMITATE induced reorganization in functionally-connected, speech-relevant areas in the left hemisphere. These preliminary results suggest that sleep hd-EEGs, and the topographical analysis of SWA parameters, are well suited to investigate brain plastic changes underpinning functional recovery in neurological disorders.

Dynamics of large-scale brain activity in normal arousal states and epileptic seizures

NASA Astrophysics Data System (ADS)

Robinson, P. A.; Rennie, C. J.; Rowe, D. L.

2002-04-01

Links between electroencephalograms (EEGs) and underlying aspects of neurophysiology and anatomy are poorly understood. Here a nonlinear continuum model of large-scale brain electrical activity is used to analyze arousal states and their stability and nonlinear dynamics for physiologically realistic parameters. A simple ordered arousal sequence in a reduced parameter space is inferred and found to be consistent with experimentally determined parameters of waking states. Instabilities arise at spectral peaks of the major clinically observed EEG rhythms-mainly slow wave, delta, theta, alpha, and sleep spindle-with each instability zone lying near its most common experimental precursor arousal states in the reduced space. Theta, alpha, and spindle instabilities evolve toward low-dimensional nonlinear limit cycles that correspond closely to EEGs of petit mal seizures for theta instability, and grand mal seizures for the other types. Nonlinear stimulus-induced entrainment and seizures are also seen, EEG spectra and potentials evoked by stimuli are reproduced, and numerous other points of experimental agreement are found. Inverse modeling enables physiological parameters underlying observed EEGs to be determined by a new, noninvasive route. This model thus provides a single, powerful framework for quantitative understanding of a wide variety of brain phenomena.

Directional analysis of coherent oscillatory field potentials in the cerebral cortex and basal ganglia of the rat

PubMed Central

Sharott, Andrew; Magill, Peter J; Bolam, J Paul; Brown, Peter

2005-01-01

Population activity in cortico-basal ganglia circuits is synchronized at different frequencies according to brain state. However, the structures that are likely to drive the synchronization of activity in these circuits remain unclear. Furthermore, it is not known whether the direction of transmission of activity is fixed or dependent on brain state. We have used the directed transfer function (DTF) to investigate the direction in which coherent activity is effectively driven in cortico-basal ganglia circuits. Local field potentials (LFPs) were simultaneously recorded in the subthalamic nucleus (STN), globus pallidus (GP) and substantia nigra pars reticulata (SNr), together with the ipsilateral frontal electrocorticogram (ECoG) of anaesthetized rats. Directional analysis was performed on recordings made during robust cortical slow-wave activity (SWA) and ‘global activation’. During SWA, there was coherence at ∼1 Hz between ECoG and basal ganglia LFPs, with much of the coherent activity directed from cortex to basal ganglia. There were similar coherent activities at ∼1 Hz within the basal ganglia, with more activity directed from SNr to GP and STN, and from STN to GP rather than vice versa. During global activation, peaks in coherent activity were seen at higher frequencies (15–60 Hz), with most coherence also directed from cortex to basal ganglia. Within the basal ganglia, however, coherence was predominantly directed from GP to STN and SNr. Together, these results highlight a lead role for the cortex in activity relationships with the basal ganglia, and further suggest that the effective direction of coupling between basal ganglia nuclei is dynamically organized according to brain state, with activity relationships involving the GP displaying the greatest capacity to change. PMID:15550466

Hypothalamic Tuberomammillary Nucleus Neurons: Electrophysiological Diversity and Essential Role in Arousal Stability.

PubMed

Fujita, Akie; Bonnavion, Patricia; Wilson, Miryam H; Mickelsen, Laura E; Bloit, Julien; de Lecea, Luis; Jackson, Alexander C

2017-09-27

Histaminergic (HA) neurons, found in the posterior hypothalamic tuberomammillary nucleus (TMN), extend fibers throughout the brain and exert modulatory influence over numerous physiological systems. Multiple lines of evidence suggest that the activity of HA neurons is important in the regulation of vigilance despite the lack of direct, causal evidence demonstrating its requirement for the maintenance of arousal during wakefulness. Given the strong correlation between HA neuron excitability and behavioral arousal, we investigated both the electrophysiological diversity of HA neurons in brain slices and the effect of their acute silencing in vivo in male mice. For this purpose, we first validated a transgenic mouse line expressing cre recombinase in histidine decarboxylase-expressing neurons ( Hdc -Cre) followed by a systematic census of the membrane properties of both HA and non-HA neurons in the ventral TMN (TMNv) region. Through unsupervised hierarchical cluster analysis, we found electrophysiological diversity both between TMNv HA and non-HA neurons, and among HA neurons. To directly determine the impact of acute cessation of HA neuron activity on sleep-wake states in awake and behaving mice, we examined the effects of optogenetic silencing of TMNv HA neurons in vivo We found that acute silencing of HA neurons during wakefulness promotes slow-wave sleep, but not rapid eye movement sleep, during a period of low sleep pressure. Together, these data suggest that the tonic firing of HA neurons is necessary for the maintenance of wakefulness, and their silencing not only impairs arousal but is sufficient to rapidly and selectively induce slow-wave sleep. SIGNIFICANCE STATEMENT The function of monoaminergic systems and circuits that regulate sleep and wakefulness is often disrupted as part of the pathophysiology of many neuropsychiatric disorders. One such circuit is the posterior hypothalamic histamine (HA) system, implicated in supporting wakefulness and higher brain function, but has been difficult to selectively manipulate owing to cellular heterogeneity in this region. Here we use a transgenic mouse to interrogate both the characteristic firing properties of HA neurons and their specific role in maintaining wakefulness. Our results demonstrate that the acute, cell type-specific silencing of HA neurons during wakefulness is sufficient to not only impair arousal but to rapidly and selectively induce slow-wave sleep. This work furthers our understanding of HA-mediated mechanisms that regulate behavioral arousal. Copyright © 2017 the authors 0270-6474/17/379575-19$15.00/0.

Hypothalamic Tuberomammillary Nucleus Neurons: Electrophysiological Diversity and Essential Role in Arousal Stability

PubMed Central

Fujita, Akie; Mickelsen, Laura E.; Bloit, Julien

2017-01-01

Histaminergic (HA) neurons, found in the posterior hypothalamic tuberomammillary nucleus (TMN), extend fibers throughout the brain and exert modulatory influence over numerous physiological systems. Multiple lines of evidence suggest that the activity of HA neurons is important in the regulation of vigilance despite the lack of direct, causal evidence demonstrating its requirement for the maintenance of arousal during wakefulness. Given the strong correlation between HA neuron excitability and behavioral arousal, we investigated both the electrophysiological diversity of HA neurons in brain slices and the effect of their acute silencing in vivo in male mice. For this purpose, we first validated a transgenic mouse line expressing cre recombinase in histidine decarboxylase-expressing neurons (Hdc-Cre) followed by a systematic census of the membrane properties of both HA and non-HA neurons in the ventral TMN (TMNv) region. Through unsupervised hierarchical cluster analysis, we found electrophysiological diversity both between TMNv HA and non-HA neurons, and among HA neurons. To directly determine the impact of acute cessation of HA neuron activity on sleep–wake states in awake and behaving mice, we examined the effects of optogenetic silencing of TMNv HA neurons in vivo. We found that acute silencing of HA neurons during wakefulness promotes slow-wave sleep, but not rapid eye movement sleep, during a period of low sleep pressure. Together, these data suggest that the tonic firing of HA neurons is necessary for the maintenance of wakefulness, and their silencing not only impairs arousal but is sufficient to rapidly and selectively induce slow-wave sleep. SIGNIFICANCE STATEMENT The function of monoaminergic systems and circuits that regulate sleep and wakefulness is often disrupted as part of the pathophysiology of many neuropsychiatric disorders. One such circuit is the posterior hypothalamic histamine (HA) system, implicated in supporting wakefulness and higher brain function, but has been difficult to selectively manipulate owing to cellular heterogeneity in this region. Here we use a transgenic mouse to interrogate both the characteristic firing properties of HA neurons and their specific role in maintaining wakefulness. Our results demonstrate that the acute, cell type-specific silencing of HA neurons during wakefulness is sufficient to not only impair arousal but to rapidly and selectively induce slow-wave sleep. This work furthers our understanding of HA-mediated mechanisms that regulate behavioral arousal. PMID:28874450

Metabolic costs and evolutionary implications of human brain development

PubMed Central

Kuzawa, Christopher W.; Chugani, Harry T.; Grossman, Lawrence I.; Lipovich, Leonard; Muzik, Otto; Hof, Patrick R.; Wildman, Derek E.; Sherwood, Chet C.; Leonard, William R.; Lange, Nicholas

2014-01-01

The high energetic costs of human brain development have been hypothesized to explain distinctive human traits, including exceptionally slow and protracted preadult growth. Although widely assumed to constrain life-history evolution, the metabolic requirements of the growing human brain are unknown. We combined previously collected PET and MRI data to calculate the human brain’s glucose use from birth to adulthood, which we compare with body growth rate. We evaluate the strength of brain–body metabolic trade-offs using the ratios of brain glucose uptake to the body’s resting metabolic rate (RMR) and daily energy requirements (DER) expressed in glucose-gram equivalents (glucosermr% and glucoseder%). We find that glucosermr% and glucoseder% do not peak at birth (52.5% and 59.8% of RMR, or 35.4% and 38.7% of DER, for males and females, respectively), when relative brain size is largest, but rather in childhood (66.3% and 65.0% of RMR and 43.3% and 43.8% of DER). Body-weight growth (dw/dt) and both glucosermr% and glucoseder% are strongly, inversely related: soon after birth, increases in brain glucose demand are accompanied by proportionate decreases in dw/dt. Ages of peak brain glucose demand and lowest dw/dt co-occur and subsequent developmental declines in brain metabolism are matched by proportionate increases in dw/dt until puberty. The finding that human brain glucose demands peak during childhood, and evidence that brain metabolism and body growth rate covary inversely across development, support the hypothesis that the high costs of human brain development require compensatory slowing of body growth rate. PMID:25157149

The effects of aerobic exercise on the structure and function of DMN-related brain regions: a systematic review.

PubMed

Li, Mo-Yi; Huang, Mao-Mao; Li, Shu-Zhen; Tao, Jing; Zheng, Guo-Hua; Chen, Li-Dian

2017-07-01

Physical activity may play a role in both the prevention and slowing of brain volume loss and may be beneficial in terms of improving the functional connectivity of brain regions. But much less is known about the potential benefit of aerobic exercise for the structure and function of the default mode network (DMN) brain regions. This systematic review examines the effects of aerobic exercise on the structure and function of DMN brain regions in human adulthood. Seven electronic databases were searched for prospective controlled studies published up to April 2015. The quality of the selected studies was evaluated with the Cochrane Collaboration's tool for assessing the risk of bias. RevMan 5.3 software was applied for data analysis. Finally, 14 studies with 631 participants were identified. Meta-analysis revealed that aerobic exercise could significantly increase right hippocampal volume (SMD = 0.26, 95% CI 0.01-0.51, p = 0.04, I 2 = 7%, 4 studies), and trends of similar effects were observed in the total (SMD = 0.12, 95% CI -0.17 to 0.41, p = 0.43, I 2 = 0%, 5 studies), left (SMD = 0.12, 95% CI -0.13 to 0.37, p = 0.33, I 2 = 14%, 4 studies), left anterior (SMD = 0.12, 95% CI -0.16 to 0.40, p = 0.41, I 2 = 74%, 2 studies) and right anterior (SMD = 0.10, 95% CI -0.17 to 0.38, p = 0.46, I 2 = 76%, 4 studies) hippocampal volumes compared to the no-exercise interventions. A few studies reported that relative to no-exercise interventions, aerobic exercise could significantly decrease the atrophy of the medial temporal lobe, slow the anterior cingulate cortex (ACC) volume loss, increase functional connectivity within the hippocampus and improve signal activation in the cingulate gyrus and ACC. The current review suggests that aerobic exercise may have positive effects on the right hippocampus and potentially beneficial effects on the overall and other parts of the hippocampus, the cingulate cortex and the medial temporal areas of the DMN. Moreover, aerobic exercise may increase functional connectivity or activation in the hippocampus, cingulate cortex and parahippocampal gyrus regions of the DMN. However, considering the quantity and limitations of the included studies, the conclusion could not be drawn so far. Additional randomized controlled trials (RCTs) with rigorous designs and longer intervention periods are needed in the future.

Temporal Coupling with Cortex Distinguishes Spontaneous Neuronal Activities in Identified Basal Ganglia-Recipient and Cerebellar-Recipient Zones of the Motor Thalamus

PubMed Central

Nakamura, Kouichi C.; Sharott, Andrew; Magill, Peter J.

2014-01-01

Neurons of the motor thalamus mediate basal ganglia and cerebellar influences on cortical activity. To elucidate the net result of γ-aminobutyric acid-releasing or glutamatergic bombardment of the motor thalamus by basal ganglia or cerebellar afferents, respectively, we recorded the spontaneous activities of thalamocortical neurons in distinct identified “input zones” in anesthetized rats during defined cortical activity states. Unexpectedly, the mean rates and brain state dependencies of the firing of neurons in basal ganglia-recipient zone (BZ) and cerebellar-recipient zone (CZ) were matched during slow-wave activity (SWA) and cortical activation. However, neurons were distinguished during SWA by their firing regularities, low-threshold spike bursts and, more strikingly, by the temporal coupling of their activities to ongoing cortical oscillations. The firing of neurons across the BZ was stronger and more precisely phase-locked to cortical slow (∼1 Hz) oscillations, although both neuron groups preferentially fired at the same phase. In contrast, neurons in BZ and CZ fired at different phases of cortical spindles (7–12 Hz), but with similar strengths of coupled firing. Thus, firing rates do not reflect the predicted inhibitory–excitatory imbalance across the motor thalamus, and input zone-specific temporal coding through oscillatory synchronization with the cortex could partly mediate the different roles of basal ganglia and cerebellum in behavior. PMID:23042738

Optogenetic stimulation of cholinergic projection neurons as an alternative for deep brain stimulation for Alzheimer's treatment

NASA Astrophysics Data System (ADS)

Mancuso, James; Chen, Yuanxin; Zhao, Zhen; Li, Xuping; Xue, Zhong; Wong, Stephen T. C.

2013-03-01

Deep brain stimulation (DBS) of the cholinergic nuclei has emerged as a powerful potential treatment for neurodegenerative disease and is currently in a clinical trial for Alzheimer's therapy. While effective in treatment for a number of conditions from depression to epilepsy, DBS remains somewhat unpredictable due to the heterogeneity of the projection neurons that are activated, including glutamatergic, GABAergic, and cholinergic neurons, leading to unacceptable side effects ranging from apathy to depression or even suicidal behavior. It would be highly advantageous to confine stimulation to specific populations of neurons, particularly in brain diseases involving complex network interactions such as Alzheimer's. Optogenetics, now firmly established as an effective approach to render genetically-defined populations of cells sensitive to light activation including mice expressing Channelrhodopsin-2 specifically in cholinergic neurons, provides just this opportunity. Here we characterize the light activation properties and cell density of cholinergic neurons in healthy mice and mouse models of Alzheimer's disease in order to evaluate the feasibility of using optogenetic modulation of cholinergic synaptic activity to slow or reverse neurodegeneration. This paper is one of the very first reports to suggest that, despite the anatomical depth of their cell bodies, cholinergic projection neurons provide a better target for systems level optogenetic modulation than cholinergic interneurons found in various brain regions including striatum and the cerebral cortex. Additionally, basal forebrain channelrhodopsin-expressing cholinergic neurons are shown to exhibit normal distribution at 60 days and normal light activation at 40 days, the latest timepoints observed. The data collected form the basis of ongoing computational modeling of light stimulation of entire populations of cholinergic neurons.

A different pattern of lateralised brain activity during processing of loved faces in men and women: a MEG study.

PubMed

Tiedt, Hannes O; Beier, Klaus M; Lueschow, Andreas; Pauls, Alfred; Weber, Joachim E

2014-12-01

Viewing personally familiar and loved faces evokes a distinct pattern of brain activity as demonstrated by research employing imaging and electrophysiological methods. The aim of the current investigation was to study the perception of loved faces combined with recalling past emotional experiences using whole-head magnetoencephalograpy (MEG). Twenty-eight participants (fourteen female) viewed photographs of their romantic partner as well as of two long-term friends while imagining a positive emotional encounter with the respective person. Face-stimuli evoked a slow and sustained shift of magnetic activity from 300ms post-stimulus onwards which differentiated loved from friends' faces in female participants and left-sided sensors only. This late-latency evoked magnetic field resembled (as its magnetic counterpart) ERP-modulations by affective content and memory, most notably the late positive potential (LPP). We discuss our findings in the light of studies suggesting greater responsiveness to affective cues in women as well as sex differences in autobiographical and emotional memory. Copyright © 2014 Elsevier B.V. All rights reserved.

Differential distribution of the sodium‐activated potassium channels slick and slack in mouse brain

PubMed Central

Knaus, Hans‐Günther; Schwarzer, Christoph

2015-01-01

ABSTRACT The sodium‐activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are high‐conductance potassium channels of the Slo family. In neurons, Slick and Slack channels are involved in the generation of slow afterhyperpolarization, in the regulation of firing patterns, and in setting and stabilizing the resting membrane potential. The distribution and subcellular localization of Slick and Slack channels in the mouse brain have not yet been established in detail. The present study addresses this issue through in situ hybridization and immunohistochemistry. Both channels were widely distributed and exhibited distinct distribution patterns. However, in some brain regions, their expression overlapped. Intense Slick channel immunoreactivity was observed in processes, varicosities, and neuronal cell bodies of the olfactory bulb, granular zones of cortical regions, hippocampus, amygdala, lateral septal nuclei, certain hypothalamic and midbrain nuclei, and several regions of the brainstem. The Slack channel showed primarily a diffuse immunostaining pattern, and labeling of cell somata and processes was observed only occasionally. The highest Slack channel expression was detected in the olfactory bulb, lateral septal nuclei, basal ganglia, and distinct areas of the midbrain, brainstem, and cerebellar cortex. In addition, comparing our data obtained from mouse brain with a previously published study on rat brain revealed some differences in the expression and distribution of Slick and Slack channels in these species. J. Comp. Neurol. 524:2093–2116, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:26587966

Stomach-brain synchrony reveals a novel, delayed-connectivity resting-state network in humans

PubMed Central

Devauchelle, Anne-Dominique; Béranger, Benoît; Tallon-Baudry, Catherine

2018-01-01

Resting-state networks offer a unique window into the brain’s functional architecture, but their characterization remains limited to instantaneous connectivity thus far. Here, we describe a novel resting-state network based on the delayed connectivity between the brain and the slow electrical rhythm (0.05 Hz) generated in the stomach. The gastric network cuts across classical resting-state networks with partial overlap with autonomic regulation areas. This network is composed of regions with convergent functional properties involved in mapping bodily space through touch, action or vision, as well as mapping external space in bodily coordinates. The network is characterized by a precise temporal sequence of activations within a gastric cycle, beginning with somato-motor cortices and ending with the extrastriate body area and dorsal precuneus. Our results demonstrate that canonical resting-state networks based on instantaneous connectivity represent only one of the possible partitions of the brain into coherent networks based on temporal dynamics. PMID:29561263

On Teaching Brains To Think: A Conversation with Robert Sylwester.

ERIC Educational Resources Information Center

Brandt, Ron

2000-01-01

Sylwester says education must begin relying more on biology than social and behavioral science. All brain systems move from a slow, awkward functional level to a fast, efficient level. Contributions of metacognition, self-regulation, emotions, reflective and reflexive responses, comparison, and classification to cognitive development are…

Reactivation of emergent task-related ensembles during slow-wave sleep after neuroprosthetic learning

PubMed Central

Gulati, Tanuj; Ramanathan, Dhakshin; Wong, Chelsea; Ganguly, Karunesh

2017-01-01

Brain-Machine Interfaces can allow neural control over assistive devices. They also provide an important platform to study neural plasticity. Recent studies indicate that optimal engagement of learning is essential for robust neuroprosthetic control. However, little is known about the neural processes that may consolidate a neuroprosthetic skill. Based on the growing body of evidence linking slow-wave activity (SWA) during sleep to consolidation, we examined if there is ‘offline’ processing after neuroprosthetic learning. Using a rodent model, here we show that after successful learning, task-related units specifically experienced increased locking and coherency to SWA during sleep. Moreover, spike-spike coherence among these units was significantly enhanced. These changes were not present with poor skill acquisition or after control awake periods, demonstrating specificity of our observations to learning. Interestingly, time spent in SWA predicted performance gains. Thus, SWA appears to play a role in offline processing after neuroprosthetic learning. PMID:24997761

Enhancing Performance and Bit Rates in a Brain-Computer Interface System With Phase-to-Amplitude Cross-Frequency Coupling: Evidences From Traditional c-VEP, Fast c-VEP, and SSVEP Designs.

PubMed

Dimitriadis, Stavros I; Marimpis, Avraam D

2018-01-01

A brain-computer interface (BCI) is a channel of communication that transforms brain activity into specific commands for manipulating a personal computer or other home or electrical devices. In other words, a BCI is an alternative way of interacting with the environment by using brain activity instead of muscles and nerves. For that reason, BCI systems are of high clinical value for targeted populations suffering from neurological disorders. In this paper, we present a new processing approach in three publicly available BCI data sets: (a) a well-known multi-class ( N = 6) coded-modulated Visual Evoked potential (c-VEP)-based BCI system for able-bodied and disabled subjects; (b) a multi-class ( N = 32) c-VEP with slow and fast stimulus representation; and (c) a steady-state Visual Evoked potential (SSVEP) multi-class ( N = 5) flickering BCI system. Estimating cross-frequency coupling (CFC) and namely δ-θ [δ: (0.5-4 Hz), θ: (4-8 Hz)] phase-to-amplitude coupling (PAC) within sensor and across experimental time, we succeeded in achieving high classification accuracy and Information Transfer Rates (ITR) in the three data sets. Our approach outperformed the originally presented ITR on the three data sets. The bit rates obtained for both the disabled and able-bodied subjects reached the fastest reported level of 324 bits/min with the PAC estimator. Additionally, our approach outperformed alternative signal features such as the relative power (29.73 bits/min) and raw time series analysis (24.93 bits/min) and also the original reported bit rates of 10-25 bits/min . In the second data set, we succeeded in achieving an average ITR of 124.40 ± 11.68 for the slow 60 Hz and an average ITR of 233.99 ± 15.75 for the fast 120 Hz. In the third data set, we succeeded in achieving an average ITR of 106.44 ± 8.94. Current methodology outperforms any previous methodologies applied to each of the three free available BCI datasets.

Distribution of lacosamide in the rat brain assessed by in vitro slice technique.

PubMed

Gáll, Zsolt; Vancea, Szende

2018-01-01

Lacosamide is a newer anticonvulsant and is the only one that enhances the slow inactivation of voltage gated sodium channels. It is also claimed to have disease-modifying potential, but its pharmacokinetic properties have been much less discussed in the literature. In rats, lacosamide shows restricted distribution to tissues, and the brain-to-plasma partition coefficient (K p ) is only 0.553. In this study, the brain disposition of lacosamide was evaluated in rat brains, and its neuropharmacokinetic parameters (i.e., protein binding and intracellular accumulation) were assessed using in vitro methods. Brain slice experiments and brain homogenate binding studies were performed for several drugs acting on the central nervous system, and drugs were assayed by using a liquid chromatography-mass spectrometry system. By applying a combined approach, it was found that (1) the unbound volume of distribution in the brain for lacosamide (V u,brain  = 1.37) was lower than that of other classical anticonvulsants; (2) the unbound fraction of lacosamide in the brain (0.899) was slightly lower than its unbound fraction in plasma (0.96); (3) the unbound intracellular-to-extracellular concentration ratio of lacosamide was 1.233, meaning that lacosamide was accumulated in the intracellular space because of its physicochemical properties and zwitterionic structure; and (4) the unbound brain-to-plasma concentration ratio of lacosamide was lower than the total brain-to-plasma concentration ratio (K p,uu,brain  = 0.42 vs. K p  = 0.553). In conclusion, the limited brain distribution of lacosamide is not related to its nonspecific protein-binding capacity; rather, an active transport mechanism across the blood-brain barrier may be involved, which reduces the anticonvulsant and/or antiepileptogenic actions of this drug.

Slow spontaneous hemodynamic oscillations during sleep measured with near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Virtanen, Jaakko; Näsi, Tiina; Noponen, Tommi; Toppila, Jussi; Salmi, Tapani; Ilmoniemi, Risto J.

2011-07-01

Spontaneous cerebral hemodynamic oscillations below 100 mHz reflect the level of cerebral activity, modulate hemodynamic responses to tasks and stimuli, and may aid in detecting various pathologies of the brain. Near-infrared spectroscopy (NIRS) is ideally suited for both measuring spontaneous hemodynamic oscillations and monitoring sleep, but little research has been performed to combine these two applications. We analyzed 30 all-night NIRS-electroencephalography (EEG) sleep recordings to investigate spontaneous hemodynamic activity relative to sleep stages determined by polysomnography. Signal power of hemodynamic oscillations in the low-frequency (LF, 40-150 mHz) and very-low-frequency (VLF, 3-40 mHz) bands decreased in slow-wave sleep (SWS) compared to light sleep (LS) and rapid-eye-movement (REM) sleep. No statistically significant (p < 0.05) differences in oscillation power between LS and REM were observed. However, the period of VLF oscillations around 8 mHz increased in REM sleep in line with earlier studies with other modalities. These results increase our knowledge of the physiology of sleep, complement EEG data, and demonstrate the applicability of NIRS to studying spontaneous hemodynamic fluctuations during sleep.

Brain extracellular glucose assessed by voltammetry throughout the rat sleep-wake cycle.

PubMed

Netchiporouk, L; Shram, N; Salvert, D; Cespuglio, R

2001-04-01

In the present study, cortical extracellular levels of glucose were monitored for the first time throughout the sleep-wake states of the freely moving rat. For this purpose, polygraphic recordings (electroencephalogram of the fronto-occipital cortices and electromyogram of the neck muscles) were achieved in combination with differential normal pulse voltammetry (DNPV) using a specific glucose sensor. Data obtained reveal that the basal extracellular glucose concentration in the conscious rat is 0.59 +/- 0.3 m M while under chloral hydrate anaesthesia (0.4 g/kg, i.p.) it increases up to 180% of its basal concentration. Regarding the sleep-wake cycle, the existence of spontaneous significant variations in the mean glucose level during slow-wave sleep (SWS = +13%) and paradoxical sleep (PS = -11%) compared with the waking state (100%) is also reported. It is to be noticed that during long periods of active waking, glucose level tends towards a decrease that becomes significant after 15 min (active waking = -32%). On the contrary, during long episodes of slow-wave sleep, it tends towards an increase which becomes significant after 12 min (SWS = +28%). It is suggested that voltammetric techniques using enzymatic biosensors are useful tools allowing direct glucose measurements in the freely moving animal. On the whole, paradoxical sleep is pointed out as a state highly dependent on the availability of energy and slow-wave sleep as a period of energy saving.

Effect of the 5-HT(1A) partial agonist buspirone on regional brain electrical activity in man: a functional neuroimaging study using low-resolution electromagnetic tomography (LORETA).

PubMed

Anderer, P; Saletu, B; Pascual-Marqui, R D

2000-12-04

In a double-blind, placebo-controlled study, the effects of 20 mg buspirone - a 5-HT(1A) partial agonist - on regional electrical generators within the human brain were investigated utilizing three-dimensional EEG tomography. Nineteen-channel vigilance-controlled EEG recordings were carried out in 20 healthy subjects before and 1, 2, 4, 6 and 8 h after drug intake. Low-resolution electromagnetic tomography (LORETA; Key Institute for Brain-Mind Research, software: http://www.keyinst.unizh.ch) was computed from spectrally analyzed EEG data, and differences between drug- and placebo-induced changes were displayed as statistical parametric maps. Data were registered to the Talairach-Tournoux human brain atlas available as a digitized MRI (McConnell Brain Imaging Centre: http://www.bic.mni.mcgill.ca). At the pharmacodynamic peak (1st hour), buspirone increased theta and decreased fast alpha and beta sources. Areas of theta increase were mainly the left temporo-occipito-parietal and left prefrontal cortices, which is consistent with PET studies on buspirone-induced decreases in regional cerebral blood flow and fenfluramine-induced serotonin activation demonstrated by changes in regional cerebral glucose metabolism. In later hours (8th hour) with lower buspirone plasma levels, delta, theta, slow alpha and fast beta decreased, predominantly in the prefrontal and anterior limbic lobe. Whereas the results of the 1st hour speak for a slight CNS sedation (more in the sense of relaxation), those obtained in the 8th hour indicate activation. Thus, LORETA may provide useful and direct information on drug-induced changes in central nervous system function in man.

Optogenetics through windows on the brain in the nonhuman primate

PubMed Central

Ruiz, Octavio; Lustig, Brian R.; Nassi, Jonathan J.; Cetin, Ali; Reynolds, John H.; Albright, Thomas D.; Callaway, Edward M.; Stoner, Gene R.

2013-01-01

Optogenetics combines optics and genetics to control neuronal activity with cell-type specificity and millisecond temporal precision. Its use in model organisms such as rodents, Drosophila, and Caenorhabditis elegans is now well-established. However, application of this technology in nonhuman primates (NHPs) has been slow to develop. One key challenge has been the delivery of viruses and light to the brain through the thick dura mater of NHPs, which can only be penetrated with large-diameter devices that damage the brain. The opacity of the NHP dura prevents visualization of the underlying cortex, limiting the spatial precision of virus injections, electrophysiological recordings, and photostimulation. Here, we describe a new optogenetics approach in which the native dura is replaced with an optically transparent artificial dura. This artificial dura can be penetrated with fine glass micropipettes, enabling precisely targeted injections of virus into brain tissue with minimal damage to cortex. The expression of optogenetic agents can be monitored visually over time. Most critically, this optical window permits targeted, noninvasive photostimulation and concomitant measurements of neuronal activity via intrinsic signal imaging and electrophysiological recordings. We present results from both anesthetized-paralyzed (optical imaging) and awake-behaving NHPs (electrophysiology). The improvements over current methods made possible by the artificial dura should enable the widespread use of optogenetic tools in NHP research, a key step toward the development of therapies for neuropsychiatric and neurological diseases in humans. PMID:23761700

A pilot treatment study for mild traumatic brain injury: Neuroimaging changes detected by MEG after low-intensity pulse-based transcranial electrical stimulation.

PubMed

Huang, Ming-Xiong; Swan, Ashley Robb; Quinto, Annemarie Angeles; Matthews, Scott; Harrington, Deborah L; Nichols, Sharon; Bruder, Barry J; Snook, Corey C; Huang, Charles W; Baker, Dewleen G; Lee, Roland R

2017-01-01

Mild traumatic brain injury (mTBI) is a leading cause of sustained impairments in military service members, Veterans, and civilians. However, few treatments are available for mTBI, partially because the mechanism of persistent mTBI deficits is not fully understood. We used magnetoencephalography (MEG) to investigate neuronal changes in individuals with mTBI following a passive neurofeedback-based treatment programme called IASIS. This programme involved applying low-intensity pulses using transcranial electrical stimulation (LIP-tES) with electroencephalography monitoring. Study participants included six individuals with mTBI and persistent post-concussive symptoms (PCS). MEG exams were performed at baseline and follow-up to evaluate the effect of IASIS on brain functioning. At the baseline MEG exam, all participants had abnormal slow-waves. In the follow-up MEG exam, the participants showed significantly reduced abnormal slow-waves with an average reduction of 53.6 ± 24.6% in slow-wave total score. The participants also showed significant reduction of PCS scores after IASIS treatment, with an average reduction of 52.76 ± 26.4% in PCS total score. The present study demonstrates, for the first time, the neuroimaging-based documentation of the effect of LIP-tES treatment on brain functioning in mTBI. The mechanisms of LIP-tES treatment are discussed, with an emphasis on LIP-tES's potentiation of the mTBI healing process.

Glucose and lactate as metabolic constraints on presynaptic transmission at an excitatory synapse.

PubMed

Lucas, Sarah J; Michel, Christophe B; Marra, Vincenzo; Smalley, Joshua L; Hennig, Matthias H; Graham, Bruce P; Forsythe, Ian D

2018-05-01

Synapses have high energy demands which increase during intense activity. We show that presynaptic terminals can utilise extracellular glucose or lactate to generate energy to maintain synaptic transmission. Reducing energy substrates induces a metabolic stress: presynaptic ATP depletion impaired synaptic transmission through a reduction in the number of functional synaptic vesicle release sites and a slowing of vesicle pool replenishment, without a consistent change in release probability. Metabolic function is compromised in many pathological conditions (e.g. stroke, traumatic brain injury and neurodegeneration). Knowledge of how synaptic transmission is constrained by metabolic stress, especially during intense brain activity, will provide insights to improve cognition following pathological insults. The synapse has high energy demands, which increase during intense activity. Presynaptic ATP production depends on substrate availability and usage will increase during activity, which in turn could influence transmitter release and information transmission. We investigated transmitter release at the mouse calyx of Held synapse using glucose or lactate (10, 1 or 0 mm) as the extracellular substrates while inducing metabolic stress. High-frequency stimulation (HFS) and recovery paradigms evoked trains of EPSCs monitored under voltage-clamp. Whilst postsynaptic intracellular ATP was stabilised by diffusion from the patch pipette, depletion of glucose increased EPSC depression during HFS and impaired subsequent recovery. Computational modelling of these data demonstrated a reduction in the number of functional release sites and slowed vesicle pool replenishment during metabolic stress, with little change in release probability. Directly depleting presynaptic terminal ATP impaired transmitter release in an analogous manner to glucose depletion. In the absence of glucose, presynaptic terminal metabolism could utilise lactate from the aCSF and this was blocked by inhibition of monocarboxylate transporters (MCTs). MCT inhibitors significantly suppressed transmission in low glucose, implying that lactate is a presynaptic substrate. Additionally, block of glycogenolysis accelerated synaptic transmission failure in the absence of extracellular glucose, consistent with supplemental supply of lactate by local astrocytes. We conclude that both glucose and lactate support presynaptic metabolism and that limited availability, exacerbated by high-intensity firing, constrains presynaptic ATP, impeding transmission through a reduction in functional presynaptic release sites as vesicle recycling slows when ATP levels are low. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist

PubMed Central

Mifflin, Steve W.

2017-01-01

μ-Opioid receptors are distributed widely in the brain stem respiratory network, and opioids with selectivity for μ-type receptors slow in vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and interspike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brain stem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid-mediated disinhibition and postsynaptic enhancement of N-methyl-d- aspartate receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO2/pH chemosensitivity. PMID:28202437

Oscillation patterns are enhanced and firing threshold is lowered in medullary respiratory neuron discharges by threshold doses of a μ-opioid receptor agonist.

PubMed

Lalley, Peter M; Mifflin, Steve W

2017-05-01

μ-Opioid receptors are distributed widely in the brain stem respiratory network, and opioids with selectivity for μ-type receptors slow in vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed. Doses of fentanyl that were just sufficient for prolongation of discharges and slowing of the three-phase respiratory rhythm also produced pronounced enhancement of spike train properties. Oscillation and burst patterns detected by autocorrelation measurements were greatly enhanced, and interspike intervals were prolonged. Spike train properties under control conditions and after fentanyl were uniform within each experiment, but varied considerably between experiments, which might be related to variability in acid-base balance in the brain stem extracellular fluid. Discharge threshold was shifted to more negative levels of membrane potential. The effects on threshold are postulated to result from opioid-mediated disinhibition and postsynaptic enhancement of N -methyl-d- aspartate receptor current. Lowering of firing threshold, enhancement of spike train oscillations and bursts and prolongation of discharges by lowest effective doses of fentanyl could represent compensatory adjustments in the brain stem respiratory network to override opioid blunting of CO 2 /pH chemosensitivity. Copyright © 2017 the American Physiological Society.

Distinguishing rhythmic from non-rhythmic brain activity during rest in healthy neurocognitive aging.

PubMed

Caplan, Jeremy B; Bottomley, Monica; Kang, Pardeep; Dixon, Roger A

2015-05-15

Rhythmic brain activity at low frequencies (<12Hz) during rest are thought to increase in neurodegenerative disease, but findings in healthy neurocognitive aging are mixed. Here we address two reasons conventional spectral analyses may have led to inconsistent results. First, spectral-power measures are compared to a baseline condition; when resting activity is the signal of interest, it is unclear what the baseline should be. Second, conventional methods do not clearly differentiate power due to rhythmic versus non-rhythmic activity. The Better OSCillation detection method (BOSC; Caplan et al., 2001; Whitten et al., 2011) avoids these problems by using the signal's own spectral characteristics as a reference to detect elevations in power lasting a few cycles. We recorded electroencephalographic (EEG) signal during rest, alternating eyes open and closed, in healthy younger (18-25 years) and older (60-74 years) participants. Topographic plots suggested the conventional and BOSC analyses measured different sources of activity, particularly at frequencies, like delta (1-4Hz), at which rhythms are sporadic; topographies were more similar in the 8-12Hz alpha band. There was little theta-band activity meeting the BOSC method's criteria, suggesting prior findings of theta power in healthy aging may reflect non-rhythmic signal. In contrast, delta oscillations were present at higher levels than theta in both age groups. In summary, applying strict and standardized criteria for rhythmicity, slow rhythms appear present in the resting brain at delta and alpha, but not theta frequencies, and appear unchanged in healthy aging. Copyright © 2015 Elsevier Inc. All rights reserved.

Distinguishing rhythmic from non-rhythmic brain activity during rest in healthy neurocognitive aging

PubMed Central

Caplan, Jeremy B.; Bottomley, Monica; Kang, Pardeep; Dixon, Roger A.

2015-01-01

Rhythmic brain activity at low frequencies (<12 Hz) during rest are thought to increase in neurodegenerative disease, but findings in healthy neurocognitive aging are mixed. Here we address two reasons conventional spectral analyses may have led to inconsistent results. First, spectral-power measures are compared to a baseline condition; when resting activity is the signal of interest, it is unclear what the baseline should be. Second, conventional methods do not clearly differentiate power due to rhythmic versus non-rhythmic activity. The Better OSCillation detection method (BOSC; [10], [65]) avoids these problems by using the signal’s own spectral characteristics as a reference to detect elevations in power lasting a few cycles. We recorded electroencephalographic (EEG) signal during rest, alternating eyes open and closed, in healthy younger (18–25 years) and older (60–74 years) participants. Topographic plots suggested the conventional and BOSC analyses measured different sources of activity, particularly at frequencies, like delta (1–4 Hz), at which rhythms are sporadic (but topographies were more similar in the 8–12 Hz alpha band). There was little theta-band activity meeting the BOSC method’s criteria, suggesting prior findings of theta power in healthy aging may reflect non-rhythmic signal. In contrast, delta oscillations were present at higher levels than theta in both age groups. In sum, applying strict and standardized criteria for rhythmicity, slow rhythms appear present in the resting brain at delta and alpha, but not theta frequencies, and appear unchanged in healthy aging. PMID:25769279

Long-term history and immediate preceding state affect EEG slow wave characteristics at NREM sleep onset in C57BL/6 mice.

PubMed

Cui, N; Mckillop, L E; Fisher, S P; Oliver, P L; Vyazovskiy, V V

2014-01-01

The dynamics of cortical activity across the 24-h day and at vigilance state transitions is regulated by an interaction between global subcortical neuromodulatory influences and local shifts in network synchrony and excitability. To address the role of long-term and immediate preceding history in local and global cortical dynamics, we investigated cortical EEG recorded from both frontal and occipital regions during an undisturbed 24-h recording in mice. As expected, at the beginning of the light period, under physiologically increased sleep pressure, EEG slow waves were more frequent and had higher amplitude and slopes, compared to the rest of the light period. Within discrete NREM sleep episodes, the incidence, amplitude and slopes of individual slow waves increased progressively after episode onset in both derivations by approximately 10-30%. Interestingly, at the beginning of NREM sleep episodes slow waves in the frontal and occipital derivations frequently occurred in isolation, as quantified by longer latencies between consecutive slow waves in the two regions. Notably, slow waves during the initial period of NREM sleep following REM sleep episodes were significantly less frequent, lower in amplitude and exhibited shallower slopes, compared to those that occurred in NREM episodes after prolonged waking. Moreover, the latencies between consecutive frontal and occipital NREM slow waves were substantially longer when they occurred directly after REM sleep compared to following consolidated wakefulness. Overall these data reveal a complex picture, where both time of day and preceding state contribute to the characteristics and dynamics of slow waves within NREM sleep. These findings suggest that NREM sleep initiates in a more "local" fashion when it occurs following REM sleep episodes as opposed to sustained waking bouts. While the mechanisms and functional significance of such a re-setting of brain state after individual REM sleep episodes remains to be investigated, we suggest that it may be an essential feature of physiological sleep regulation.

Slow cortical potentials and "inner time consciousness" - A neuro-phenomenal hypothesis about the "width of present".

PubMed

Northoff, Georg

2016-05-01

William James postulated a "stream of consciousness" that presupposes temporal continuity. The neuronal mechanisms underlying the construction of such temporal continuity remain unclear, however, in my contribution, I propose a neuro-phenomenal hypothesis that is based on slow cortical potentials and their extension of the present moment as described in the phenomenal term of "width of present". More specifically, I focus on the way the brain's neural activity needs to be encoded in order to make possible the "stream of consciousness." This leads us again to the low-frequency fluctuations of the brain's neural activity and more specifically to slow cortical potentials (SCPs). Due to their long phase duration as low-frequency fluctuations, SCPs can integrate different stimuli and their associated neural activity from different regions in one converging region. Such integration may be central for consciousness to occur, as it was recently postulated by He and Raichle. They leave open, however, the question of the exact neuronal mechanisms, like the encoding strategy, that make possible the association of the otherwise purely neuronal SCP with consciousness and its phenomenal features. I hypothesize that SCPs allow for linking and connecting different discrete points in physical time by encoding their statistically based temporal differences rather than the single discrete time points by themselves. This presupposes difference-based coding rather than stimulus-based coding. The encoding of such statistically based temporal differences makes it possible to "go beyond" the merely physical features of the stimuli; that is, their single discrete time points and their conduction delays (as related to their neural processing in the brain). This, in turn, makes possible the constitution of "local temporal continuity" of neural activity in one particular region. The concept of "local temporal continuity" signifies the linkage and integration of different discrete time points into one neural activity in a particular region. How does such local temporal continuity predispose the experience of time in consciousness? For that, I turn to phenomenological philosopher Edmund Husserl and his description of what he calls "inner time consciousness" (Husserl and Brough, 1990). One hallmark of humans' "inner time consciousness" is that we experience events and objects in succession and duration in our consciousness; according to Husserl, this amounts to what he calls the "width of [the] present." The concept of the width of present describes the extension of the present beyond the single discrete time point, such as, for instance, when we perceive different tones as a melody. I now hypothesize the degree of the width of present to be directly dependent upon and thus predisposed by the degree of the temporal differences between two (or more) discrete time points as they are encoded into neural activity. I therefore conclude that the SCPs and their encoding of neural activity in terms of temporal differences must be regarded a neural predisposition of consciousness (NPC) as distinguished from a neural correlate of consciousness (NCC). Copyright © 2015 Elsevier B.V. All rights reserved.

Going local: insights from EEG and stereo-EEG studies of the human sleep-wake cycle.

PubMed

Ferrara, Michele; De Gennaro, Luigi

2011-01-01

In the present paper, we reviewed a large body of evidence, mainly from quantitative EEG studies of our laboratory, supporting the notion that sleep is a local and use-dependent process. Quantitative analyses of sleep EEG recorded from multiple cortical derivations clearly indicate that every sleep phenomenon, from sleep onset to the awakening, is strictly local in nature. Sleep onset first occurs in frontal areas, and a frontal predominance of low-frequency power persists in the first part of the night, when the homeostatic processes mainly occur, and then it vanishes. Upon awakening, we showed an asynchronous EEG activation of different cortical areas, the more anterior ones being the first to wake up. During extended periods of wakefulness, the increase of sleepiness-related low-EEG frequencies is again evident over the frontal derivations. Similarly, experimental manipulations of sleep length by total sleep deprivation, partial sleep curtailment or even selective slow-wave sleep deprivation lead to a slow-wave activity rebound localized especially on the anterior derivations. Thus, frontal areas are crucially involved in sleep homeostasis. According to the local use-dependent theory, this would derive from a higher sleep need of the frontal cortex, which in turn is due to its higher levels of activity during wakefulness. The fact that different brain regions can simultaneously exhibit different sleep intensities indicates that sleep is not a spatially global and uniform state, as hypothesized in the theory. We have also reviewed recent evidence of localized effects of learning and plasticity on EEG sleep measures. These studies provide crucial support to a key concept in the theory, the one claiming that local sleep characteristics should be use-dependent. Finally, we have reported data corroborating the notion that sleep is not necessarily present simultaneously in the entire brain. Our stereo-EEG recordings clearly indicate that sleep and wakefulness can co-exist in different areas, suggesting that vigilance states are not necessarily temporally discrete states. We conclude that understanding local variations in sleep propensity and depth, especially as a result of brain plasticity, may provide in the near future insightful hints into the fundamental functions of sleep.

Investigation of Slow-wave Activity Saturation during Surgical Anesthesia Reveals a Signature of Neural Inertia in Humans.

PubMed

Warnaby, Catherine E; Sleigh, Jamie W; Hight, Darren; Jbabdi, Saad; Tracey, Irene

2017-10-01

Previously, we showed experimentally that saturation of slow-wave activity provides a potentially individualized neurophysiologic endpoint for perception loss during anesthesia. Furthermore, it is clear that induction and emergence from anesthesia are not symmetrically reversible processes. The observed hysteresis is potentially underpinned by a neural inertia mechanism as proposed in animal studies. In an advanced secondary analysis of 393 individual electroencephalographic data sets, we used slow-wave activity dose-response relationships to parameterize slow-wave activity saturation during induction and emergence from surgical anesthesia. We determined whether neural inertia exists in humans by comparing slow-wave activity dose responses on induction and emergence. Slow-wave activity saturation occurs for different anesthetics and when opioids and muscle relaxants are used during surgery. There was wide interpatient variability in the hypnotic concentrations required to achieve slow-wave activity saturation. Age negatively correlated with power at slow-wave activity saturation. On emergence, we observed abrupt decreases in slow-wave activity dose responses coincident with recovery of behavioral responsiveness in ~33% individuals. These patients are more likely to have lower power at slow-wave activity saturation, be older, and suffer from short-term confusion on emergence. Slow-wave activity saturation during surgical anesthesia implies that large variability in dosing is required to achieve a targeted potential loss of perception in individual patients. A signature for neural inertia in humans is the maintenance of slow-wave activity even in the presence of very-low hypnotic concentrations during emergence from anesthesia.

Therapeutic effects of antimotion sickness medications on the secondary symptoms of motion sickness

NASA Technical Reports Server (NTRS)

Wood, C. D.; Stewart, J. J.; Wood, M. J.; Manno, J. E.; Manno, B. R.

1990-01-01

In addition to nausea and vomiting, motion sickness involves slowing of brain waves, loss of performance, inhibition of gastric motility and the Sopite Syndrome. The therapeutic effects of antimotion sickness drugs on these reactions were evaluated. The subjects were rotated to the M-III end-point of motion sickness. Intramuscular (IM) medications were then administered. Side effects before and after rotation were reported on the Cornell Medical Index. Brain waves were recorded on a Grass Model 6 Electroencephalograph (EEG), and gastric emptying was studied after an oral dose of 1 mCi Technetium 99m DTPA in 10 oz. isotonic saline. An increase in dizziness and drowsiness was reported with placebo after rotation. This was not prevented by IM scopolamine 0.1 mg or ephedrine 25 mg. EEG recordings indicated a slowing of alpha waves with some thea and delta waves from the frontal areas after rotation. IM ephedine and dimenhydrinate counteracted the slowing while 0.3 mg scopolamine had an additive effect. Alterations of performance on the pursuit meter correlated with the brain wave changes. Gastric emptying was restored by IM metoclopramide. Ephedrine IM but not scopolamine is effective for some of the secondary effects of motion sickness after it is established.

A Computational Model of Major Depression: the Role of Glutamate Dysfunction on Cingulo-Frontal Network Dynamics

PubMed Central

Ramirez-Mahaluf, Juan P.; Roxin, Alexander; Mayberg, Helen S.; Compte, Albert

2017-01-01

Abstract Major depression disease (MDD) is associated with the dysfunction of multinode brain networks. However, converging evidence implicates the reciprocal interaction between midline limbic regions (typified by the ventral anterior cingulate cortex, vACC) and the dorso-lateral prefrontal cortex (dlPFC), reflecting interactions between emotions and cognition. Furthermore, growing evidence suggests a role for abnormal glutamate metabolism in the vACC, while serotonergic treatments (selective serotonin reuptake inhibitor, SSRI) effective for many patients implicate the serotonin system. Currently, no mechanistic framework describes how network dynamics, glutamate, and serotonin interact to explain MDD symptoms and treatments. Here, we built a biophysical computational model of 2 areas (vACC and dlPFC) that can switch between emotional and cognitive processing. MDD networks were simulated by slowing glutamate decay in vACC and demonstrated sustained vACC activation. This hyperactivity was not suppressed by concurrent dlPFC activation and interfered with expected dlPFC responses to cognitive signals, mimicking cognitive dysfunction seen in MDD. Simulation of clinical treatments (SSRI or deep brain stimulation) counteracted this aberrant vACC activity. Theta and beta/gamma oscillations correlated with network function, representing markers of switch-like operation in the network. The model shows how glutamate dysregulation can cause aberrant brain dynamics, respond to treatments, and be reflected in EEG rhythms as biomarkers of MDD. PMID:26514163

Hippocampal-prefrontal theta-gamma coupling during performance of a spatial working memory task.

PubMed

Tamura, Makoto; Spellman, Timothy J; Rosen, Andrew M; Gogos, Joseph A; Gordon, Joshua A

2017-12-19

Cross-frequency coupling supports the organization of brain rhythms and is present during a range of cognitive functions. However, little is known about whether and how long-range cross-frequency coupling across distant brain regions subserves working memory. Here we report that theta-slow gamma coupling between the hippocampus and medial prefrontal cortex (mPFC) is augmented in a genetic mouse model of cognitive dysfunction. This increased cross-frequency coupling is observed specifically when the mice successfully perform a spatial working memory task. In wild-type mice, increasing task difficulty by introducing a long delay or by optogenetically interfering with encoding, also increases theta-gamma coupling during correct trials. Finally, epochs of high hippocampal theta-prefrontal slow gamma coupling are associated with increased synchronization of neurons within the mPFC. These findings suggest that enhancement of theta-slow gamma coupling reflects a compensatory mechanism to maintain spatial working memory performance in the setting of increased difficulty.

Real-time monitoring of human blood-brain barrier disruption

PubMed Central

Kiviniemi, Vesa; Korhonen, Vesa; Kortelainen, Jukka; Rytky, Seppo; Keinänen, Tuija; Tuovinen, Timo; Isokangas, Matti; Sonkajärvi, Eila; Siniluoto, Topi; Nikkinen, Juha; Alahuhta, Seppo; Tervonen, Osmo; Turpeenniemi-Hujanen, Taina; Myllylä, Teemu; Kuittinen, Outi; Voipio, Juha

2017-01-01

Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery. PMID:28319185

User Experience May be Producing Greater Heart Rate Variability than Motor Imagery Related Control Tasks during the User-System Adaptation in Brain-Computer Interfaces

PubMed Central

Alonso-Valerdi, Luz M.; Gutiérrez-Begovich, David A.; Argüello-García, Janet; Sepulveda, Francisco; Ramírez-Mendoza, Ricardo A.

2016-01-01

Brain-computer interface (BCI) is technology that is developing fast, but it remains inaccurate, unreliable and slow due to the difficulty to obtain precise information from the brain. Consequently, the involvement of other biosignals to decode the user control tasks has risen in importance. A traditional way to operate a BCI system is via motor imagery (MI) tasks. As imaginary movements activate similar cortical structures and vegetative mechanisms as a voluntary movement does, heart rate variability (HRV) has been proposed as a parameter to improve the detection of MI related control tasks. However, HR is very susceptible to body needs and environmental demands, and as BCI systems require high levels of attention, perceptual processing and mental workload, it is important to assess the practical effectiveness of HRV. The present study aimed to determine if brain and heart electrical signals (HRV) are modulated by MI activity used to control a BCI system, or if HRV is modulated by the user perceptions and responses that result from the operation of a BCI system (i.e., user experience). For this purpose, a database of 11 participants who were exposed to eight different situations was used. The sensory-cognitive load (intake and rejection tasks) was controlled in those situations. Two electrophysiological signals were utilized: electroencephalography and electrocardiography. From those biosignals, event-related (de-)synchronization maps and event-related HR changes were respectively estimated. The maps and the HR changes were cross-correlated in order to verify if both biosignals were modulated due to MI activity. The results suggest that HR varies according to the experience undergone by the user in a BCI working environment, and not because of the MI activity used to operate the system. PMID:27458384

Antiemesis effect and brain fMRI response of gastric electrical stimulation with different parameters in dogs.

PubMed

Yu, X; Tu, L; Lei, P; Song, J; Xu, H; Hou, X

2014-07-01

The aims of this study were to investigate the effect of gastric electrical stimulation (GES) with different parameters on emesis induced by apomorphine, and possible center mechanisms by brain functional magnetic resonance imaging (fMRI). Six dogs implanted with electrodes on gastric serosa were used in this study. Part 1: Apomorphine was injected in the control session and GES sessions. GESs with different parameters were applied in GES session. Gastric slow waves and emesis and behaviors suggestive of nausea were recorded in each session. Part 2: Each dog was anesthetized and given GESs with different parameters or sham stimulation for 15 min after baseline (5 min), respectively. The location of cerebral activation induced by GES was investigated by fMRI. Apomorphine induced emesis and behaviors suggestive of nausea, and gastric dysrhythmia. The emesis frequency in control session was 5.5 ± 0.99, and symptoms score was 22.17 ± 1.01. GES with short pulse and long pulse could not improve emesis and symptoms induced by apomorphine. The emesis frequency (4.5 ± 0.76 in short pulse and 6.33 ± 1.05 in long pulse) and symptoms scores had no significant difference compared to control session (each p > 0.05). GES with trains of short pulse reduced emesis time frequency (3.83 ± 0.7, p = 0.042 vs control) and symptoms score (p = 0.037 vs control) obviously. Brain fMRI showed that GES with short pulse and long pulse activated brain stem region, and trains of short pulse made amygdala and occipital lobe activation. Apomorphine induced emesis and gastric dysrhythmia. GES with trains of short pulses relieves emetic responses through activation of amygdala region. © 2014 John Wiley & Sons Ltd.

Self-organized dynamical complexity in human wakefulness and sleep: different critical brain-activity feedback for conscious and unconscious states.

PubMed

Allegrini, Paolo; Paradisi, Paolo; Menicucci, Danilo; Laurino, Marco; Piarulli, Andrea; Gemignani, Angelo

2015-09-01

Criticality reportedly describes brain dynamics. The main critical feature is the presence of scale-free neural avalanches, whose auto-organization is determined by a critical branching ratio of neural-excitation spreading. Other features, directly associated to second-order phase transitions, are: (i) scale-free-network topology of functional connectivity, stemming from suprathreshold pairwise correlations, superimposable, in waking brain activity, with that of ferromagnets at Curie temperature; (ii) temporal long-range memory associated to renewal intermittency driven by abrupt fluctuations in the order parameters, detectable in human brain via spatially distributed phase or amplitude changes in EEG activity. Herein we study intermittent events, extracted from 29 night EEG recordings, including presleep wakefulness and all phases of sleep, where different levels of mentation and consciousness are present. We show that while critical avalanching is unchanged, at least qualitatively, intermittency and functional connectivity, present during conscious phases (wakefulness and REM sleep), break down during both shallow and deep non-REM sleep. We provide a theory for fragmentation-induced intermittency breakdown and suggest that the main difference between conscious and unconscious states resides in the backwards causation, namely on the constraints that the emerging properties at large scale induce to the lower scales. In particular, while in conscious states this backwards causation induces a critical slowing down, preserving spatiotemporal correlations, in dreamless sleep we see a self-organized maintenance of moduli working in parallel. Critical avalanches are still present, and establish transient auto-organization, whose enhanced fluctuations are able to trigger sleep-protecting mechanisms that reinstate parallel activity. The plausible role of critical avalanches in dreamless sleep is to provide a rapid recovery of consciousness, if stimuli are highly arousing.

Self-organized dynamical complexity in human wakefulness and sleep: Different critical brain-activity feedback for conscious and unconscious states

NASA Astrophysics Data System (ADS)

Allegrini, Paolo; Paradisi, Paolo; Menicucci, Danilo; Laurino, Marco; Piarulli, Andrea; Gemignani, Angelo

2015-09-01

Criticality reportedly describes brain dynamics. The main critical feature is the presence of scale-free neural avalanches, whose auto-organization is determined by a critical branching ratio of neural-excitation spreading. Other features, directly associated to second-order phase transitions, are: (i) scale-free-network topology of functional connectivity, stemming from suprathreshold pairwise correlations, superimposable, in waking brain activity, with that of ferromagnets at Curie temperature; (ii) temporal long-range memory associated to renewal intermittency driven by abrupt fluctuations in the order parameters, detectable in human brain via spatially distributed phase or amplitude changes in EEG activity. Herein we study intermittent events, extracted from 29 night EEG recordings, including presleep wakefulness and all phases of sleep, where different levels of mentation and consciousness are present. We show that while critical avalanching is unchanged, at least qualitatively, intermittency and functional connectivity, present during conscious phases (wakefulness and REM sleep), break down during both shallow and deep non-REM sleep. We provide a theory for fragmentation-induced intermittency breakdown and suggest that the main difference between conscious and unconscious states resides in the backwards causation, namely on the constraints that the emerging properties at large scale induce to the lower scales. In particular, while in conscious states this backwards causation induces a critical slowing down, preserving spatiotemporal correlations, in dreamless sleep we see a self-organized maintenance of moduli working in parallel. Critical avalanches are still present, and establish transient auto-organization, whose enhanced fluctuations are able to trigger sleep-protecting mechanisms that reinstate parallel activity. The plausible role of critical avalanches in dreamless sleep is to provide a rapid recovery of consciousness, if stimuli are highly arousing.

High Resolution Topography of Age-Related Changes in Non-Rapid Eye Movement Sleep Electroencephalography

PubMed Central

Sprecher, Kate E.; Riedner, Brady A.; Smith, Richard F.; Tononi, Giulio; Davidson, Richard J.; Benca, Ruth M.

2016-01-01

Sleeping brain activity reflects brain anatomy and physiology. The aim of this study was to use high density (256 channel) electroencephalography (EEG) during sleep to characterize topographic changes in sleep EEG power across normal aging, with high spatial resolution. Sleep was evaluated in 92 healthy adults aged 18–65 years old using full polysomnography and high density EEG. After artifact removal, spectral power density was calculated for standard frequency bands for all channels, averaged across the NREM periods of the first 3 sleep cycles. To quantify topographic changes with age, maps were generated of the Pearson’s coefficient of the correlation between power and age at each electrode. Significant correlations were determined by statistical non-parametric mapping. Absolute slow wave power declined significantly with increasing age across the entire scalp, whereas declines in theta and sigma power were significant only in frontal regions. Power in fast spindle frequencies declined significantly with increasing age frontally, whereas absolute power of slow spindle frequencies showed no significant change with age. When EEG power was normalized across the scalp, a left centro-parietal region showed significantly less age-related decline in power than the rest of the scalp. This partial preservation was particularly significant in the slow wave and sigma bands. The effect of age on sleep EEG varies substantially by region and frequency band. This non-uniformity should inform the design of future investigations of aging and sleep. This study provides normative data on the effect of age on sleep EEG topography, and provides a basis from which to explore the mechanisms of normal aging as well as neurodegenerative disorders for which age is a risk factor. PMID:26901503

ERP Subsequent Memory Effects Differ between Inter-Item and Unitization Encoding Tasks

PubMed Central

Kamp, Siri-Maria; Bader, Regine; Mecklinger, Axel

2017-01-01

The “subsequent memory paradigm” is an analysis tool to identify brain activity elicited during episodic encoding that is associated with successful subsequent retrieval. Two commonly observed event-related potential “subsequent memory effects” (SMEs) are the parietal SME in the P300 time window and the frontal slow wave SME, but to date a clear characterization of the circumstances under which each SME is observed is missing. To test the hypothesis that the parietal SME occurs when aspects of an experience are unitized into a single item representation, while inter-item associative encoding is reflected in the frontal slow wave effect, participants were assigned to one of two conditions that emphasized one of the encoding types under otherwise matched study phases of a recognition memory experiment. Word pairs were presented either in the context of a definition that allowed to combine the word pairs into a new concept (unitization or item encoding) or together with a sentence frame (inter-item encoding). Performance on the recognition test did not differ between the groups. The parietal SME was only found in the definition group, supporting the idea that this SME occurs when the components of an association are integrated in a unitized item representation. An early prefrontal negativity also exhibited an SME only in this group, suggesting that the formation of novel units occurs through interactions of multiple brain areas. The frontal slow wave SME was pronounced in both groups and may thus reflect processes generally involved in encoding of associations. Our results provide evidence for a partial dissociation of the eliciting conditions of the two types of SMEs and therefore provide a tool for future studies to characterize the different types of episodic encoding. PMID:28194105

ERP Subsequent Memory Effects Differ between Inter-Item and Unitization Encoding Tasks.

PubMed

Kamp, Siri-Maria; Bader, Regine; Mecklinger, Axel

2017-01-01

The "subsequent memory paradigm" is an analysis tool to identify brain activity elicited during episodic encoding that is associated with successful subsequent retrieval. Two commonly observed event-related potential "subsequent memory effects" (SMEs) are the parietal SME in the P300 time window and the frontal slow wave SME, but to date a clear characterization of the circumstances under which each SME is observed is missing. To test the hypothesis that the parietal SME occurs when aspects of an experience are unitized into a single item representation, while inter-item associative encoding is reflected in the frontal slow wave effect, participants were assigned to one of two conditions that emphasized one of the encoding types under otherwise matched study phases of a recognition memory experiment. Word pairs were presented either in the context of a definition that allowed to combine the word pairs into a new concept (unitization or item encoding) or together with a sentence frame (inter-item encoding). Performance on the recognition test did not differ between the groups. The parietal SME was only found in the definition group, supporting the idea that this SME occurs when the components of an association are integrated in a unitized item representation. An early prefrontal negativity also exhibited an SME only in this group, suggesting that the formation of novel units occurs through interactions of multiple brain areas. The frontal slow wave SME was pronounced in both groups and may thus reflect processes generally involved in encoding of associations. Our results provide evidence for a partial dissociation of the eliciting conditions of the two types of SMEs and therefore provide a tool for future studies to characterize the different types of episodic encoding.

Conflict Resolution as Near-Threshold Decision-Making: A Spiking Neural Circuit Model with Two-Stage Competition for Antisaccadic Task

PubMed Central

Wang, Xiao-Jing

2016-01-01

Automatic responses enable us to react quickly and effortlessly, but they often need to be inhibited so that an alternative, voluntary action can take place. To investigate the brain mechanism of controlled behavior, we investigated a biologically-based network model of spiking neurons for inhibitory control. In contrast to a simple race between pro- versus anti-response, our model incorporates a sensorimotor remapping module, and an action-selection module endowed with a “Stop” process through tonic inhibition. Both are under the modulation of rule-dependent control. We tested the model by applying it to the well known antisaccade task in which one must suppress the urge to look toward a visual target that suddenly appears, and shift the gaze diametrically away from the target instead. We found that the two-stage competition is crucial for reproducing the complex behavior and neuronal activity observed in the antisaccade task across multiple brain regions. Notably, our model demonstrates two types of errors: fast and slow. Fast errors result from failing to inhibit the quick automatic responses and therefore exhibit very short response times. Slow errors, in contrast, are due to incorrect decisions in the remapping process and exhibit long response times comparable to those of correct antisaccade responses. The model thus reveals a circuit mechanism for the empirically observed slow errors and broad distributions of erroneous response times in antisaccade. Our work suggests that selecting between competing automatic and voluntary actions in behavioral control can be understood in terms of near-threshold decision-making, sharing a common recurrent (attractor) neural circuit mechanism with discrimination in perception. PMID:27551824

Conflict Resolution as Near-Threshold Decision-Making: A Spiking Neural Circuit Model with Two-Stage Competition for Antisaccadic Task.

PubMed

Lo, Chung-Chuan; Wang, Xiao-Jing

2016-08-01

Automatic responses enable us to react quickly and effortlessly, but they often need to be inhibited so that an alternative, voluntary action can take place. To investigate the brain mechanism of controlled behavior, we investigated a biologically-based network model of spiking neurons for inhibitory control. In contrast to a simple race between pro- versus anti-response, our model incorporates a sensorimotor remapping module, and an action-selection module endowed with a "Stop" process through tonic inhibition. Both are under the modulation of rule-dependent control. We tested the model by applying it to the well known antisaccade task in which one must suppress the urge to look toward a visual target that suddenly appears, and shift the gaze diametrically away from the target instead. We found that the two-stage competition is crucial for reproducing the complex behavior and neuronal activity observed in the antisaccade task across multiple brain regions. Notably, our model demonstrates two types of errors: fast and slow. Fast errors result from failing to inhibit the quick automatic responses and therefore exhibit very short response times. Slow errors, in contrast, are due to incorrect decisions in the remapping process and exhibit long response times comparable to those of correct antisaccade responses. The model thus reveals a circuit mechanism for the empirically observed slow errors and broad distributions of erroneous response times in antisaccade. Our work suggests that selecting between competing automatic and voluntary actions in behavioral control can be understood in terms of near-threshold decision-making, sharing a common recurrent (attractor) neural circuit mechanism with discrimination in perception.

Understanding Epileptiform After-Discharges as Rhythmic Oscillatory Transients.

PubMed

Baier, Gerold; Taylor, Peter N; Wang, Yujiang

2017-01-01

Electro-cortical activity in patients with epilepsy may show abnormal rhythmic transients in response to stimulation. Even when using the same stimulation parameters in the same patient, wide variability in the duration of transient response has been reported. These transients have long been considered important for the mapping of the excitability levels in the epileptic brain but their dynamic mechanism is still not well understood. To investigate the occurrence of abnormal transients dynamically, we use a thalamo-cortical neural population model of epileptic spike-wave activity and study the interaction between slow and fast subsystems. In a reduced version of the thalamo-cortical model, slow wave oscillations arise from a fold of cycles (FoC) bifurcation. This marks the onset of a region of bistability between a high amplitude oscillatory rhythm and the background state. In vicinity of the bistability in parameter space, the model has excitable dynamics, showing prolonged rhythmic transients in response to suprathreshold pulse stimulation. We analyse the state space geometry of the bistable and excitable states, and find that the rhythmic transient arises when the impending FoC bifurcation deforms the state space and creates an area of locally reduced attraction to the fixed point. This area essentially allows trajectories to dwell there before escaping to the stable steady state, thus creating rhythmic transients. In the full thalamo-cortical model, we find a similar FoC bifurcation structure. Based on the analysis, we propose an explanation of why stimulation induced epileptiform activity may vary between trials, and predict how the variability could be related to ongoing oscillatory background activity. We compare our dynamic mechanism with other mechanisms (such as a slow parameter change) to generate excitable transients, and we discuss the proposed excitability mechanism in the context of stimulation responses in the epileptic cortex.

Differential Go/NoGo Activity in Both Contingent Negative Variation and Spectral Power

PubMed Central

Funderud, Ingrid; Lindgren, Magnus; Løvstad, Marianne; Endestad, Tor; Voytek, Bradley; Knight, Robert T.; Solbakk, Anne-Kristin

2012-01-01

We investigated whether both the contingent negative variation (CNV), an event-related potential index of preparatory brain activity, and event-related oscillatory EEG activity differentiated Go and NoGo trials in a delayed response task. CNV and spectral power (4–100 Hz) were calculated from EEG activity in the preparatory interval in 16 healthy adult participants. As previously reported, CNV amplitudes were higher in Go compared to NoGo trials. In addition, event-related spectral power of the Go condition was reduced in the theta to low gamma range compared to the NoGo condition, confirming that preparing to respond is associated with modulation of event-related spectral activity as well as the CNV. Altogether, the impact of the experimental manipulation on both slow event-related potentials and oscillatory EEG activity may reflect coordinated dynamic changes in the excitability of distributed neural networks involved in preparation. PMID:23119040

Phosphatidylserine and the human brain.

PubMed

Glade, Michael J; Smith, Kyl

2015-06-01

The aim of this study was to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry, physiology, and function. A scientific literature search was conducted on MEDLINE for relevant articles regarding PS and the human brain published before June 2014. Additional publications were identified from references provided in original papers; 127 articles were selected for inclusion in this review. A large body of scientific evidence describes the interactions among PS, cognitive activity, cognitive aging, and retention of cognitive functioning ability. Phosphatidylserine is required for healthy nerve cell membranes and myelin. Aging of the human brain is associated with biochemical alterations and structural deterioration that impair neurotransmission. Exogenous PS (300-800 mg/d) is absorbed efficiently in humans, crosses the blood-brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells. It supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and the ability to communicate. It also supports locomotor functions, especially rapid reactions and reflexes. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain structure and function correlates of cognitive subtypes in schizophrenia.

PubMed

Geisler, Daniel; Walton, Esther; Naylor, Melissa; Roessner, Veit; Lim, Kelvin O; Charles Schulz, S; Gollub, Randy L; Calhoun, Vince D; Sponheim, Scott R; Ehrlich, Stefan

2015-10-30

Stable neuropsychological deficits may provide a reliable basis for identifying etiological subtypes of schizophrenia. The aim of this study was to identify clusters of individuals with schizophrenia based on dimensions of neuropsychological performance, and to characterize their neural correlates. We acquired neuropsychological data as well as structural and functional magnetic resonance imaging from 129 patients with schizophrenia and 165 healthy controls. We derived eight cognitive dimensions and subsequently applied a cluster analysis to identify possible schizophrenia subtypes. Analyses suggested the following four cognitive clusters of schizophrenia: (1) Diminished Verbal Fluency, (2) Diminished Verbal Memory and Poor Motor Control, (3) Diminished Face Memory and Slowed Processing, and (4) Diminished Intellectual Function. The clusters were characterized by a specific pattern of structural brain changes in areas such as Wernicke's area, lingual gyrus and occipital face area, and hippocampus as well as differences in working memory-elicited neural activity in several fronto-parietal brain regions. Separable measures of cognitive function appear to provide a method for deriving cognitive subtypes meaningfully related to brain structure and function. Because the present study identified brain-based neural correlates of the cognitive clusters, the proposed groups of individuals with schizophrenia have some external validity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Subthalamic nucleus stimulation impairs emotional conflict adaptation in Parkinson's disease.

PubMed

Irmen, Friederike; Huebl, Julius; Schroll, Henning; Brücke, Christof; Schneider, Gerd-Helge; Hamker, Fred H; Kühn, Andrea A

2017-10-01

The subthalamic nucleus (STN) occupies a strategic position in the motor network, slowing down responses in situations with conflicting perceptual input. Recent evidence suggests a role of the STN in emotion processing through strong connections with emotion recognition structures. As deep brain stimulation (DBS) of the STN in patients with Parkinson's disease (PD) inhibits monitoring of perceptual and value-based conflict, STN DBS may also interfere with emotional conflict processing. To assess a possible interference of STN DBS with emotional conflict processing, we used an emotional Stroop paradigm. Subjects categorized face stimuli according to their emotional expression while ignoring emotionally congruent or incongruent superimposed word labels. Eleven PD patients ON and OFF STN DBS and eleven age-matched healthy subjects conducted the task. We found conflict-induced response slowing in healthy controls and PD patients OFF DBS, but not ON DBS, suggesting STN DBS to decrease adaptation to within-trial conflict. OFF DBS, patients showed more conflict-induced slowing for negative conflict stimuli, which was diminished by STN DBS. Computational modelling of STN influence on conflict adaptation disclosed DBS to interfere via increased baseline activity. © The Author (2017). Published by Oxford University Press.

Pharmacological benefits of selective modulation of cannabinoid receptor type 2 (CB2) in experimental Alzheimer's disease.

PubMed

Jayant, Shalini; Sharma, Brij Mohan; Bansal, Rani; Sharma, Bhupesh

2016-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that pervasively affects the population across the world. Currently, there is no effective treatment available for this and existing drugs merely slow the progression of cognitive function decline. Thus, massive effort is required to find an intended therapeutic target to overcome this condition. The present study has been framed to investigate the ameliorative role of selective modulator of cannabinoid receptor type 2 (CB2), 1-phenylisatin in experimental AD condition. We have induced experimental AD in mice by using two induction models viz., intracerebroventricular (i.c.v.) administration of streptozotocin (STZ) and aluminum trichloride (AlCl3)+d-galactose. Morris water maze (MWM) and attentional set shifting test (ASST) were used to assess learning and memory. Hematoxylin-eosin and Congo red staining were used to examine the structural variation in brain. Brain oxidative stress (thiobarbituric acid reactive substance and glutathione), nitric oxide levels (nitrites/nitrates), acetyl cholinesterase activity, myeloperoxidase and calcium levels were also estimated. i.c.v. STZ as well as AlCl3+d-galactose have impaired spatial and reversal learning with executive functioning, increased brain oxidative and nitrosative stress, cholinergic activity, inflammation and calcium levels. Furthermore, these agents have also enhanced the burden of Aβ plaque in the brain. Treatment with 1-phenylisatin and donepezil attenuated i.c.v. STZ as well as AlCl3+d-galactose induced impairment of learning-memory, brain biochemistry and brain damage. Hence, this study concludes that CB2 receptor modulation can be a potential therapeutic target for the management of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Psychophysiological correlates of aggression and violence: an integrative review.

PubMed

Patrick, Christopher J

2008-08-12

This paper reviews existing psychophysiological studies of aggression and violent behaviour including research employing autonomic, electrocortical and neuroimaging measures. Robust physiological correlates of persistent aggressive behaviour evident in this literature include low baseline heart rate, enhanced autonomic reactivity to stressful or aversive stimuli, enhanced EEG slow wave activity, reduced P300 brain potential response and indications from structural and functional neuroimaging studies of dysfunction in frontocortical and limbic brain regions that mediate emotional processing and regulation. The findings are interpreted within a conceptual framework that draws on two integrative models in the literature. The first is a recently developed hierarchical model of impulse control (externalizing) problems, in which various disinhibitory syndromes including aggressive and addictive behaviours of different kinds are seen as arising from common as well as distinctive aetiologic factors. This model represents an approach to organizing these various interrelated phenotypes and investigating their common and distinctive aetiologic substrates. The other is a neurobiological model that posits impairments in affective regulatory circuits in the brain as a key mechanism for impulsive aggressive behaviour. This model provides a perspective for integrating findings from studies employing different measures that have implicated varying brain structures and physiological systems in violent and aggressive behaviour.

Sensorimotor Slowing with Ageing is Mediated by a Functional Dysregulation of Motor-Generation Processes: Evidence from High-Resolution Event-Related Potentials

ERIC Educational Resources Information Center

Yordanova, Juliana; Kolev, Vasil; Hohnsbein, Joachim; Falkenstein, Michael

2004-01-01

The objective of the present study was to identify the origin(s) of aging-related behavioral slowing in sensorimotor tasks. For this aim, event-related potentials (ERPs) were analyzed at 64 electrodes to evaluate the strength and timing of different stages of information processing in the brain. Electrophysiological induces of stimulus processing,…

[Nootropics and antioxidants in the complex therapy of symptomatic posttraumatic epilepsy].

PubMed

Savenkov, A A; Badalian, O L; Avakian, G N

2013-01-01

To study the possibility of application of nootropics and antioxidants in the complex antiepileptic therapy, we examined 75 patients with symptomatic focal posttraumatic epilepsy. A statistically significant reduction in the number of epileptic seizures, improvement of cognitive function and quality of life of the patients as well as a decrease in the severity of depression and epileptic changes in the EEG were identified. The potentiation of antiepileptic activity of basic drugs, normalization of brain's electrical activity and reduction in EEG epileptiform activity, in particular coherent indicators of slow-wave activity, were noted after treatment with the antioxidant mexidol. A trend towards the improvement of neuropsychological performance and quality of life was observed. There was a lack of seizure aggravation typical of many nootropic drugs. Thus, phenotropil and mexidol can be recommended for complex treatment of symptomatic posttraumatic epilepsy.

Glucose Induces Slow-Wave Sleep by Exciting the Sleep-Promoting Neurons in the Ventrolateral Preoptic Nucleus: A New Link between Sleep and Metabolism.

PubMed

Varin, Christophe; Rancillac, Armelle; Geoffroy, Hélène; Arthaud, Sébastien; Fort, Patrice; Gallopin, Thierry

2015-07-08

Sleep-active neurons located in the ventrolateral preoptic nucleus (VLPO) play a crucial role in the induction and maintenance of slow-wave sleep (SWS). However, the cellular and molecular mechanisms responsible for their activation at sleep onset remain poorly understood. Here, we test the hypothesis that a rise in extracellular glucose concentration in the VLPO can promote sleep by increasing the activity of sleep-promoting VLPO neurons. We find that infusion of a glucose concentration into the VLPO of mice promotes SWS and increases the density of c-Fos-labeled neurons selectively in the VLPO. Moreover, we show in patch-clamp recordings from brain slices that VLPO neurons exhibiting properties of sleep-promoting neurons are selectively excited by glucose within physiological range. This glucose-induced excitation implies the catabolism of glucose, leading to a closure of ATP-sensitive potassium (KATP) channels. The extracellular glucose concentration monitors the gating of KATP channels of sleep-promoting neurons, highlighting that these neurons can adapt their excitability according to the extracellular energy status. Together, these results provide evidence that glucose may participate in the mechanisms of SWS promotion and/or consolidation. Although the brain circuitry underlying vigilance states is well described, the molecular mechanisms responsible for sleep onset remain largely unknown. Combining in vitro and in vivo experiments, we demonstrate that glucose likely contributes to sleep onset facilitation by increasing the excitability of sleep-promoting neurons in the ventrolateral preoptic nucleus (VLPO). We find here that these neurons integrate energetic signals such as ambient glucose directly to regulate vigilance states accordingly. Glucose-induced excitation of sleep-promoting VLPO neurons should therefore be involved in the drowsiness that one feels after a high-sugar meal. This novel mechanism regulating the activity of VLPO neurons reinforces the fundamental and intimate link between sleep and metabolism. Copyright © 2015 the authors 0270-6474/15/359900-12$15.00/0.

Differential distribution of the sodium-activated potassium channels slick and slack in mouse brain.

PubMed

Rizzi, Sandra; Knaus, Hans-Günther; Schwarzer, Christoph

2016-07-01

The sodium-activated potassium channels Slick (Slo2.1, KCNT2) and Slack (Slo2.2, KCNT1) are high-conductance potassium channels of the Slo family. In neurons, Slick and Slack channels are involved in the generation of slow afterhyperpolarization, in the regulation of firing patterns, and in setting and stabilizing the resting membrane potential. The distribution and subcellular localization of Slick and Slack channels in the mouse brain have not yet been established in detail. The present study addresses this issue through in situ hybridization and immunohistochemistry. Both channels were widely distributed and exhibited distinct distribution patterns. However, in some brain regions, their expression overlapped. Intense Slick channel immunoreactivity was observed in processes, varicosities, and neuronal cell bodies of the olfactory bulb, granular zones of cortical regions, hippocampus, amygdala, lateral septal nuclei, certain hypothalamic and midbrain nuclei, and several regions of the brainstem. The Slack channel showed primarily a diffuse immunostaining pattern, and labeling of cell somata and processes was observed only occasionally. The highest Slack channel expression was detected in the olfactory bulb, lateral septal nuclei, basal ganglia, and distinct areas of the midbrain, brainstem, and cerebellar cortex. In addition, comparing our data obtained from mouse brain with a previously published study on rat brain revealed some differences in the expression and distribution of Slick and Slack channels in these species. J. Comp. Neurol. 524:2093-2116, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Short-term memory and critical clusterization in brain neurons spike series

NASA Astrophysics Data System (ADS)

Bershadskii, A.; Dremencov, E.; Yadid, G.

2003-06-01

A new phenomenon: critical clusterization, is observed in the neuron firing of a genetically defined rat model of depression. The critical clusterization is studied using a multiscaling analysis of the data obtained from the neurons belonging to the Red Nucleus area of the depressive brains. It is suggested that this critical phenomenon can be partially responsible for the observed ill behavior of the depressive brains: loss of short-term motor memory and slow motor reaction.

LOCAL CORTICAL ACTIVITY OF DISTANT BRAIN AREAS CAN PHASE-LOCK TO THE OLFACTORY BULB'S RESPIRATORY RHYTHM IN THE FREELY BEHAVING RAT.

PubMed

Rojas-Líbano, Daniel; Wimmer Del Solar, Jonathan; Aguilar-Rivera, Marcelo; Montefusco-Siegmund, Rodrigo; Maldonado, Pedro Esteban

2018-05-16

An important unresolved question about neural processing is the mechanism by which distant brain areas coordinate their activities and relate their local processing to global neural events. A potential candidate for the local-global integration are slow rhythms such as respiration. In this article, we asked if there are modulations of local cortical processing which are phase-locked to (peripheral) sensory-motor exploratory rhythms. We studied rats on an elevated platform where they would spontaneously display exploratory and rest behaviors. Concurrent with behavior, we monitored whisking through EMG and the respiratory rhythm from the olfactory bulb (OB) local field potential (LFP). We also recorded LFPs from dorsal hippocampus, primary motor cortex, primary somatosensory cortex and primary visual cortex. We defined exploration as simultaneous whisking and sniffing above 5 Hz and found that this activity peaked at about 8 Hz. We considered rest as the absence of whisking and sniffing, and in this case, respiration occurred at about 3 Hz. We found a consistent shift across all areas toward these rhythm peaks accompanying behavioral changes. We also found, across areas, that LFP gamma (70-100 Hz) amplitude could phase-lock to the animal's OB respiratory rhythm, a finding indicative of respiration-locked changes in local processing. In a subset of animals, we also recorded the hippocampal theta activity and found that occurred at frequencies overlapped with respiration but was not spectrally coherent with it, suggesting a different oscillator. Our results are consistent with the notion of respiration as a binder or integrator of activity between brain regions.

The prestimulus default mode network state predicts cognitive task performance levels on a mental rotation task.

PubMed

Kamp, Tabea; Sorger, Bettina; Benjamins, Caroline; Hausfeld, Lars; Goebel, Rainer

2018-06-22

Linking individual task performance to preceding, regional brain activation is an ongoing goal of neuroscientific research. Recently, it could be shown that the activation and connectivity within large-scale brain networks prior to task onset influence performance levels. More specifically, prestimulus default mode network (DMN) effects have been linked to performance levels in sensory near-threshold tasks, as well as cognitive tasks. However, it still remains uncertain how the DMN state preceding cognitive tasks affects performance levels when the period between task trials is long and flexible, allowing participants to engage in different cognitive states. We here investigated whether the prestimulus activation and within-network connectivity of the DMN are predictive of the correctness and speed of task performance levels on a cognitive (match-to-sample) mental rotation task, employing a sparse event-related functional magnetic resonance imaging (fMRI) design. We found that prestimulus activation in the DMN predicted the speed of correct trials, with a higher amplitude preceding correct fast response trials compared to correct slow response trials. Moreover, we found higher connectivity within the DMN before incorrect trials compared to correct trials. These results indicate that pre-existing activation and connectivity states within the DMN influence task performance on cognitive tasks, both effecting the correctness and speed of task execution. The findings support existing theories and empirical work on relating mind-wandering and cognitive task performance to the DMN and expand these by establishing a relationship between the prestimulus DMN state and the speed of cognitive task performance. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Hospital-School Collaboration to Serve the Needs of Children with Traumatic Brain Injury

ERIC Educational Resources Information Center

Chesire, David J.; Canto, Angela I.; Buckley, Valerie A.

2011-01-01

Traumatic brain injuries are the leading cause of death and disability for children and adolescents each year in the United States. Children who survive these injuries often suffer from a range of impairments including intellectual, academic, behavioral, affective, and social problems, but they often become mired in a slow-moving process while…

Attention reorganizes connectivity across networks in a frequency specific manner.

PubMed

Kwon, Soyoung; Watanabe, Masataka; Fischer, Elvira; Bartels, Andreas

2017-01-01

Attention allows our brain to focus its limited resources on a given task. It does so by selective modulation of neural activity and of functional connectivity (FC) across brain-wide networks. While there is extensive literature on activity changes, surprisingly few studies examined brain-wide FC modulations that can be cleanly attributed to attention compared to matched visual processing. In contrast to prior approaches, we used an ultra-long trial design that avoided transients from trial onsets, included slow fluctuations (<0.1Hz) that carry important information on FC, and allowed for frequency-segregated analyses. We found that FC derived from long blocks had a nearly two-fold higher gain compared to FC derived from traditional (short) block designs. Second, attention enhanced intrinsic (negative or positive) correlations across networks, such as between the default-mode network (DMN), the dorsal attention network (DAN), and the visual system (VIS). In contrast attention de-correlated the intrinsically correlated visual regions. Third, the de-correlation within VIS was driven primarily by high frequencies, whereas the increase in DAN-VIS predominantly by low frequencies. These results pinpoint two fundamentally distinct effects of attention on connectivity. Information flow increases between distinct large-scale networks, and de-correlation within sensory cortex indicates decreased redundancy. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of copper from water and food: changes of serum nonceruloplasmin copper and brain's amyloid-beta in mice.

PubMed

Wu, Min; Han, Feifei; Gong, Weisha; Feng, Lifang; Han, Jianzhong

2016-09-14

Copper is an essential element and also produces adverse health consequences when overloaded. Food and water are the main sources of copper intake, however few studies have been conducted to investigate the difference between the ways of its intake in water and food in animals. In this study, copper was fed to mice with food as well as water (two groups: water and diet) for three months at concentrations of 6, 15 and 30 ppm. The copper concentration in water was adjusted for keeping the same amount during its intake in food. The experimental studies show a slow growth rate, lower hepatic reduced glutathione (GSH)/superoxide dismutase (SOD) activity and higher serum 'free' copper in the water group. The brain's soluble amyloid-beta 1-42 (Aβ42) of the water group was significantly higher than that of the diet group at the levels of 6 and 15 ppm. In conclusion, copper in the water group significantly increased the soluble Aβ42 in the brain and the 'free' copper in the serum, decreased the growth rate and hepatic GSH/SOD activity. The research studies carried out suggest that the copper in water is more 'toxic' than copper in diet and may increase the risk of Alzheimer's disease (AD).

[EFFECT OF SYNTHETIC PEPTIDES ON AGING OF PATIENTS WITH CHRONIC POLYMORBIDITY AND ORGANIC BRAIN SYNDROME OF THE CENTRAL NERVOUS SYSTEM IN REMISSION].

PubMed

Meshchaninov, V N; Tkachenko, E L; Zharkov, S V; Gavrilov, I V; Katyreva, Iu E

2015-01-01

We've estimated the cellular and metabolic part of geroprophylactic effects of short synthetic tripeptides vesugen and pinealon for correction of the biological age. 32 people (18 men, 12 women) aged 41-83 years with polymorbidity and the organic brain syndrome in remission participated in the study. The preparations of "Pinealon" and "Vesugen" have had the significant anabolic effect. They have improved the activity of the Central nervous system and other vital organs, which slows the rate of aging by biological age indicators. Vesugen has demonstrated more visible geroprophylactic effect than Pinealon. At the same time we've found the prooxidant activity through chemiluminescence. Decrease of markers CD34+ positive hematopoietic polypotent cells in blood has shown significant inhibition of hemopoiesis. Apparently, the cells have not been involved in the adaptive reactions. Pinealon and Vesugen haven't affected the degree of chromatin condensation, so they are safe on nuclear genetic level. This property should be studied in future. In geriatric practice, we recommend to apply the peptides Pinealon and Vesugen as geroprotectors anabolic neuroprotective and no antioxidant type for reducing the rate of aging in patients with the organic brain syndrome vascular and/or traumatic genesis.

Source localization of intermittent rhythmic delta activity in a patient with acute confusional migraine: cross-spectral analysis using standardized low-resolution brain electromagnetic tomography (sLORETA).

PubMed

Kim, Dae-Eun; Shin, Jung-Hyun; Kim, Young-Hoon; Eom, Tae-Hoon; Kim, Sung-Hun; Kim, Jung-Min

2016-01-01

Acute confusional migraine (ACM) shows typical electroencephalography (EEG) patterns of diffuse delta slowing and frontal intermittent rhythmic delta activity (FIRDA). The pathophysiology of ACM is still unclear but these patterns suggest neuronal dysfunction in specific brain areas. We performed source localization analysis of IRDA (in the frequency band of 1-3.5 Hz) to better understand the ACM mechanism. Typical IRDA EEG patterns were recorded in a patient with ACM during the acute stage. A second EEG was obtained after recovery from ACM. To identify source localization of IRDA, statistical non-parametric mapping using standardized low-resolution brain electromagnetic tomography was performed for the delta frequency band comparisons between ACM attack and non-attack periods. A difference in the current density maximum was found in the dorsal anterior cingulated cortex (ACC). The significant differences were widely distributed over the frontal, parietal, temporal and limbic lobe, paracentral lobule and insula and were predominant in the left hemisphere. Dorsal ACC dysfunction was demonstrated for the first time in a patient with ACM in this source localization analysis of IRDA. The ACC plays an important role in the frontal attentional control system and acute confusion. This dysfunction of the dorsal ACC might represent an important ACM pathophysiology.

Individual variation in the neural processes of motor decisions in the stop signal task: the influence of novelty seeking and harm avoidance personality traits.

PubMed

Hu, Jianping; Lee, Dianne; Hu, Sien; Zhang, Sheng; Chao, Herta; Li, Chiang-Shan R

2016-06-01

Personality traits contribute to variation in human behavior, including the propensity to take risk. Extant work targeted risk-taking processes with an explicit manipulation of reward, but it remains unclear whether personality traits influence simple decisions such as speeded versus delayed responses during cognitive control. We explored this issue in an fMRI study of the stop signal task, in which participants varied in response time trial by trial, speeding up and risking a stop error or slowing down to avoid errors. Regional brain activations to speeded versus delayed motor responses (risk-taking) were correlated to novelty seeking (NS), harm avoidance (HA) and reward dependence (RD), with age and gender as covariates, in a whole brain regression. At a corrected threshold, the results showed a positive correlation between NS and risk-taking responses in the dorsomedial prefrontal, bilateral orbitofrontal, and frontopolar cortex, and between HA and risk-taking responses in the parahippocampal gyrus and putamen. No regional activations varied with RD. These findings demonstrate that personality traits influence the neural processes of executive control beyond behavioral tasks that involve explicit monetary reward. The results also speak broadly to the importance of characterizing inter-subject variation in studies of cognition and brain functions.

Laquinimod dampens hyperactive cytokine production in Huntington's disease patient myeloid cells.

PubMed

Dobson, Lucianne; Träger, Ulrike; Farmer, Ruth; Hayardeny, Liat; Loupe, Pippa; Hayden, Michael R; Tabrizi, Sarah J

2016-06-01

Huntington's disease (HD) is a neurodegenerative condition characterized by pathology in the brain and peripheral tissues. Hyperactivity of the innate immune system, due in part to NFκB pathway dysregulation, is an early and active component of HD. Evidence suggests targeting immune disruption may slow disease progression. Laquinimod is an orally active immunomodulator that down-regulates proinflammatory cytokine production in peripheral blood mononuclear cells, and in the brain down-regulates astrocytic and microglial activation by modulating NFκB signalling. Laquinimod had beneficial effects on inflammation, brain atrophy and disease progression in multiple sclerosis (MS) in two phase III clinical trials. This study investigated the effects of laquinimod on hyperactive proinflammatory cytokine release and NFκB signalling in HD patient myeloid cell cultures. Monocytes from manifest (manHD) and pre-manifest (preHD) HD gene carriers and healthy volunteers (HV) were treated with laquinimod and stimulated with lipopolysaccharide. After 24 h pre-treatment with 5 μM laquinimod, manHD monocytes released lower levels of IL-1β, IL-5, IL-8, IL-10, IL-13 and TNFα in response to stimulation. PreHD monocytes released lower levels of IL-8, IL-10 and IL-13, with no reduction observed in HV monocytes. The effects of laquinimod on dysfunctional NFκB signalling in HD was assessed by inhibitor of kappa B (IκB) degradation kinetics, nuclear translocation of NFκB and interactions between IκB kinase (IKK) and HTT, in HD myeloid cells. No differences were observed between laquinimod-treated and untreated conditions. These results provide evidence that laquinimod dampens hyper-reactive cytokine release from manHD and preHD monocytes, with a much reduced effect on HV monocytes. Evidence suggests targeting CNS and peripheral immune disruption may slow Huntington's disease (HD) neurodegenerative processes. The effects of laquinimod, an orally active immunomodulator, on hyperactive cytokine release and dysfunctional NFκB signalling in stimulated myeloid cell cultures from pre-manifest and manifest HD gene carriers and healthy volunteers were investigated. Laquinimod dampened cytokine release but did not impact NFκB signalling. Read the Editorial Highlight for this article on page 670. © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

Scale-Free Music of the Brain

PubMed Central

Wu, Dan; Li, Chao-Yi; Yao, De-Zhong

2009-01-01

Background There is growing interest in the relation between the brain and music. The appealing similarity between brainwaves and the rhythms of music has motivated many scientists to seek a connection between them. A variety of transferring rules has been utilized to convert the brainwaves into music; and most of them are mainly based on spectra feature of EEG. Methodology/Principal Findings In this study, audibly recognizable scale-free music was deduced from individual Electroencephalogram (EEG) waveforms. The translation rules include the direct mapping from the period of an EEG waveform to the duration of a note, the logarithmic mapping of the change of average power of EEG to music intensity according to the Fechner's law, and a scale-free based mapping from the amplitude of EEG to music pitch according to the power law. To show the actual effect, we applied the deduced sonification rules to EEG segments recorded during rapid-eye movement sleep (REM) and slow-wave sleep (SWS). The resulting music is vivid and different between the two mental states; the melody during REM sleep sounds fast and lively, whereas that in SWS sleep is slow and tranquil. 60 volunteers evaluated 25 music pieces, 10 from REM, 10 from SWS and 5 from white noise (WN), 74.3% experienced a happy emotion from REM and felt boring and drowsy when listening to SWS, and the average accuracy for all the music pieces identification is 86.8%(κ = 0.800, P<0.001). We also applied the method to the EEG data from eyes closed, eyes open and epileptic EEG, and the results showed these mental states can be identified by listeners. Conclusions/Significance The sonification rules may identify the mental states of the brain, which provide a real-time strategy for monitoring brain activities and are potentially useful to neurofeedback therapy. PMID:19526057

Intensive language training enhances brain plasticity in chronic aphasia

PubMed Central

Meinzer, Marcus; Elbert, Thomas; Wienbruch, Christian; Djundja, Daniela; Barthel, Gabriela; Rockstroh, Brigitte

2004-01-01

Background Focal clusters of slow wave activity in the delta frequency range (1–4 Hz), as measured by magnetencephalography (MEG), are usually located in the vicinity of structural damage in the brain. Such oscillations are usually considered pathological and indicative of areas incapable of normal functioning owing to deafferentation from relevant input sources. In the present study we investigated the change in Delta Dipole Density in 28 patients with chronic aphasia (>12 months post onset) following cerebrovascular stroke of the left hemisphere before and after intensive speech and language therapy (3 hours/day over 2 weeks). Results Neuropsychologically assessed language functions improved significantly after training. Perilesional delta activity decreased after therapy in 16 of the 28 patients, while an increase was evident in 12 patients. The magnitude of change of delta activity in these areas correlated with the amount of change in language functions as measured by standardized language tests. Conclusions These results emphasize the significance of perilesional areas in the rehabilitation of aphasia even years after the stroke, and might reflect reorganisation of the language network that provides the basis for improved language functions after intensive training. PMID:15331014

Shared Genetic Control of Brain Activity During Sleep and Insulin Secretion: A Laboratory-Based Family Study.

PubMed

Morselli, Lisa L; Gamazon, Eric R; Tasali, Esra; Cox, Nancy J; Van Cauter, Eve; Davis, Lea K

2018-01-01

Over the past 20 years, a large body of experimental and epidemiologic evidence has linked sleep duration and quality to glucose homeostasis, although the mechanistic pathways remain unclear. The aim of the current study was to determine whether genetic variation influencing both sleep and glucose regulation could underlie their functional relationship. We hypothesized that the genetic regulation of electroencephalographic (EEG) activity during non-rapid eye movement sleep, a highly heritable trait with fingerprint reproducibility, is correlated with the genetic control of metabolic traits including insulin sensitivity and β-cell function. We tested our hypotheses through univariate and bivariate heritability analyses in a three-generation pedigree with in-depth phenotyping of both sleep EEG and metabolic traits in 48 family members. Our analyses accounted for age, sex, adiposity, and the use of psychoactive medications. In univariate analyses, we found significant heritability for measures of fasting insulin sensitivity and β-cell function, for time spent in slow-wave sleep, and for EEG spectral power in the delta, theta, and sigma ranges. Bivariate heritability analyses provided the first evidence for a shared genetic control of brain activity during deep sleep and fasting insulin secretion rate. © 2017 by the American Diabetes Association.

Voluntary running enhances glymphatic influx in awake behaving, young mice.

PubMed

von Holstein-Rathlou, Stephanie; Petersen, Nicolas Caesar; Nedergaard, Maiken

2018-01-01

Vascular pathology and protein accumulation contribute to cognitive decline, whereas exercise can slow vascular degeneration and improve cognitive function. Recent investigations suggest that glymphatic clearance measured in aged mice while anesthetized is enhanced following exercise. We predicted that exercise would also stimulate glymphatic activity in awake, young mice with higher baseline glymphatic function. Therefore, we assessed glymphatic function in young female C57BL/6J mice following five weeks voluntary wheel running and in sedentary mice. The active mice ran a mean distance of 6km daily. We injected fluorescent tracers in cisterna magna of awake behaving mice and in ketamine/xylazine anesthetized mice, and later assessed tracer distribution in coronal brain sections. Voluntary exercise consistently increased CSF influx during wakefulness, primarily in the hypothalamus and ventral parts of the cortex, but also in the middle cerebral artery territory. While glymphatic activity was higher under ketamine/xylazine anesthesia, we saw a decrease in glymphatic function during running in awake mice after five weeks of wheel running. In summary, daily running increases CSF flux in widespread areas of the mouse brain, which may contribute to the pro-cognitive effects of exercise. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetically targeted magnetic control of the nervous system

PubMed Central

Wheeler, Michael A.; Smith, Cody J.; Ottolini, Matteo; Barker, Bryan S.; Purohit, Aarti M.; Grippo, Ryan M.; Gaykema, Ronald P.; Spano, Anthony J.; Beenhakker, Mark P.; Kucenas, Sarah; Patel, Manoj K.; Deppmann, Christopher D.; Güler, Ali D.

2016-01-01

Optogenetic and chemogenetic actuators are critical for deconstructing the neural correlates of behavior. However, these tools have several limitations, including invasive modes of stimulation or slow on/off kinetics. We have overcome these disadvantages by synthesizing a single component, magnetically sensitive actuator, “Magneto,” comprised of the cation channel, TRPV4, fused to the paramagnetic protein, ferritin. We validate non-invasive magnetic control over neuronal activity by demonstrating remote stimulation of cells using in vitro calcium imaging assays, electrophysiological recordings in brain slices, in vivo electrophysiological recordings in the brains of freely moving mice, and behavioral outputs in zebrafish and mice. As proof of concept, we used Magneto to delineate a causal role of striatal dopamine receptor 1 neurons in mediating reward behavior in mice. Together, our results present Magneto as a novel actuator capable of remotely controlling circuits associated with complex animal behaviors. PMID:26950006

A PRESTO-SENSE sequence with alternating partial-Fourier encoding for rapid susceptibility-weighted 3D MRI time series.

PubMed

Klarhöfer, Markus; Dilharreguy, Bixente; van Gelderen, Peter; Moonen, Chrit T W

2003-10-01

A 3D sequence for dynamic susceptibility imaging is proposed which combines echo-shifting principles (such as PRESTO), sensitivity encoding (SENSE), and partial-Fourier acquisition. The method uses a moderate SENSE factor of 2 and takes advantage of an alternating partial k-space acquisition in the "slow" phase encode direction allowing an iterative reconstruction using high-resolution phase estimates. Offering an isotropic spatial resolution of 4 x 4 x 4 mm(3), the novel sequence covers the whole brain including parts of the cerebellum in 0.5 sec. Its temporal signal stability is comparable to that of a full-Fourier, full-FOV EPI sequence having the same dynamic scan time but much less brain coverage. Initial functional MRI experiments showed consistent activation in the motor cortex with an average signal change slightly less than that of EPI. Copyright 2003 Wiley-Liss, Inc.

Brain Activity Elicited by Positive and Negative Feedback in Preschool-Aged Children

PubMed Central

Mai, Xiaoqin; Tardif, Twila; Doan, Stacey N.; Liu, Chao; Gehring, William J.; Luo, Yue-Jia

2011-01-01

To investigate the processing of positive vs. negative feedback in children aged 4–5 years, we devised a prize-guessing game that is analogous to gambling tasks used to measure feedback-related brain responses in adult studies. Unlike adult studies, the feedback-related negativity (FRN) elicited by positive feedback was as large as that elicited by negative feedback, suggesting that the neural system underlying the FRN may not process feedback valence in early childhood. In addition, positive feedback, compared with negative feedback, evoked a larger P1 over the occipital scalp area and a larger positive slow wave (PSW) over the right central-parietal scalp area. We believe that the PSW is related to emotional arousal and the intensive focus on positive feedback that is present in the preschool and early school years has adaptive significance for both cognitive and emotional development during this period. PMID:21526189

Magnetization transfer studies of the fast and slow tissue water diffusion components in the human brain.

PubMed

Mulkern, Robert V; Vajapeyam, Sridhar; Haker, Steven J; Maier, Stephan E

2005-05-01

Magnetization transfer (MT) properties of the fast and slow diffusion components recently observed in the human brain were assessed experimentally. One set of experiments, performed at 1.5 T in healthy volunteers, was designed to determine whether the amplitudes of fast and slow diffusion components, differentiated on the basis of biexponential fits to signal decays over a wide range of b-factors, demonstrated a different or similar magnetization transfer ratio (MTR). Another set of experiments, performed at 3 T in healthy volunteers, was designed to determine whether MTRs differed when measured from high signal-to-noise images acquired with b-factor weightings of 350 vs 3500 s/mm2. The 3 T studies included measurements of MTR as a function of off-resonance frequency for the MT pulse at both low and high b-factors. The primary conclusion drawn from all the studies is that there appears to be no significant difference between the magnetization transfer properties of the fast and slow tissue water diffusion components. The conclusions do not lend support to a direct interpretation of the 'components' of the biexponential diffusion decay in terms of the 'compartments' associated with intra- and extracellular water. Copyright 2004 John Wiley & Sons, Ltd.

CAP, epilepsy and motor events during sleep: the unifying role of arousal.

PubMed

Parrino, Liborio; Halasz, Peter; Tassinari, Carlo Alberto; Terzano, Mario Giovanni

2006-08-01

Arousal systems play a topical neurophysiologic role in protecting and tailoring sleep duration and depth. When they appear in NREM sleep, arousal responses are not limited to a single EEG pattern but are part of a continuous spectrum of EEG modifications ranging from high-voltage slow rhythms to low amplitude fast activities. The hierarchic features of arousal responses are reflected in the phase A subtypes of CAP (cyclic alternating pattern) including both slow arousals (dominated by the <1Hz oscillation) and fast arousals (ASDA arousals). CAP is an infraslow oscillation with a periodicity of 20-40s that participates in the dynamic organization of sleep and in the activation of motor events. Physiologic, paraphysiologic and pathologic motor activities during NREM sleep are always associated with a stereotyped arousal pattern characterized by an initial increase in EEG delta power and heart rate, followed by a progressive activation of faster EEG frequencies. These findings suggest that motor patterns are already written in the brain codes (central pattern generators) embraced with an automatic sequence of EEG-vegetative events, but require a certain degree of activation (arousal) to become visibly apparent. Arousal can appear either spontaneously or be elicited by internal (epileptic burst) or external (noise, respiratory disturbance) stimuli. Whether the outcome is a physiologic movement, a muscle jerk or a major epileptic attack will depend on a number of ongoing factors (sleep stage, delta power, neuro-motor network) but all events share the common trait of arousal-activated phenomena.

A challenge to chaotic itinerancy from brain dynamics

NASA Astrophysics Data System (ADS)

Kay, Leslie M.

2003-09-01

Brain hermeneutics and chaotic itinerancy proposed by Tsuda are attractive characterizations of perceptual dynamics in the mammalian olfactory system. This theory proposes that perception occurs at the interface between itinerant neural representation and interaction with the environment. Quantifiable application of these dynamics has been hampered by the lack of definable history and action processes which characterize the changes induced by behavioral state, attention, and learning. Local field potentials measured from several brain areas were used to characterize dynamic activity patterns for their use as representations of history and action processes. The signals were recorded from olfactory areas (olfactory bulb, OB, and pyriform cortex) and hippocampal areas (entorhinal cortex and dentate gyrus, DG) in the brains of rats. During odor-guided behavior the system shows dynamics at three temporal scales. Short time-scale changes are system-wide and can occur in the space of a single sniff. They are predictable, associated with learned shifts in behavioral state and occur periodically on the scale of the intertrial interval. These changes occupy the theta (2-12 Hz), beta (15-30 Hz), and gamma (40-100 Hz) frequency bands within and between all areas. Medium time-scale changes occur relatively unpredictably, manifesting in these data as alterations in connection strength between the OB and DG. These changes are strongly correlated with performance in associated trial blocks (5-10 min) and may be due to fluctuations in attention, mood, or amount of reward received. Long time-scale changes are likely related to learning or decline due to aging or disease. These may be modeled as slow monotonic processes that occur within or across days or even weeks or years. The folding of different time scales is proposed as a mechanism for chaotic itinerancy, represented by dynamic processes instead of static connection strengths. Thus, the individual maintains continuity of experience within the stability of fast periodic and slow monotonic processes, while medium scale events alter experience and performance dramatically but temporarily. These processes together with as yet to be determined action effects from motor system feedback are proposed as an instantiation of brain hermeneutics and chaotic itinerancy.

A Stimulus-Locked Vector Autoregressive Model for Slow Event-Related fMRI Designs

PubMed Central

Siegle, Greg

2009-01-01

Summary Neuroscientists have become increasingly interested in exploring dynamic relationships among brain regions. Such a relationship, when directed from one region toward another, is denoted by “effective connectivity.” An fMRI experimental paradigm which is well-suited for examination of effective connectivity is the slow event-related design. This design presents stimuli at sufficient temporal spacing for determining within-trial trajectories of BOLD activation, allowing for the analysis of stimulus-locked temporal covariation of brain responses in multiple regions. This may be especially important for emotional stimuli processing, which can evolve over the course of several seconds, if not longer. However, while several methods have been devised for determining fMRI effective connectivity, few are adapted to event-related designs, which include non-stationary BOLD responses and multiple levels of nesting. We propose a model tailored for exploring effective connectivity of multiple brain regions in event-related fMRI designs - a semi-parametric adaptation of vector autoregressive (VAR) models, termed “stimulus-locked VAR” (SloVAR). Connectivity coefficients vary as a function of time relative to stimulus onset, are regularized via basis expansions, and vary randomly across subjects. SloVAR obtains flexible, data-driven estimates of effective connectivity and hence is useful for building connectivity models when prior information on dynamic regional relationships is sparse. Indices derived from the coefficient estimates can also be used to relate effective connectivity estimates to behavioral or clinical measures. We demonstrate the SloVAR model on a sample of clinically depressed and normal controls, showing that early but not late cortico-amygdala connectivity appears crucial to emotional control and early but not late cortico-cortico connectivity predicts depression severity in the depressed group, relationships that would have been missed in a more traditional VAR analysis. PMID:19236927

Thalamic Atrophy Contributes to Low Slow Wave Sleep in Neuromyelitis Optica Spectrum Disorder.

PubMed

Su, Lei; Han, Yujuan; Xue, Rong; Wood, Kristofer; Shi, Fu-Dong; Liu, Yaou; Fu, Ying

2016-12-01

Slow wave sleep abnormality has been reported in neuromyelitis optica spectrum disorder (NMOSD), but mechanism for such abnormality is unknown. To determine the structural defects in the brain that account for the decrease of slow wave sleep in NMOSD patients. Thirty-three NMOSD patients and 18 matched healthy controls (HC) were enrolled. Polysomnography was used to monitor slow wave sleep and three-dimensional T1-weighted MRIs were obtained to assess the alterations of grey matter volume. The percentage of deep slow wave sleep decreased in 93% NMOSD patients. Compared to HC, a reduction of grey matter volume was found in the bilateral thalamus of patients with a lower percentage of slow wave sleep (FWE corrected at cluster-level, p < 0.05, cluster size > 400 voxels). Furthermore, the right thalamic fraction was positively correlated with the decrease in the percentage of slow wave sleep in NMOSD patients (p < 0.05, FDR corrected, cluster size > 200 voxels). Our study identified that thalamic atrophy is associated with the decrease of slow wave sleep in NMOSD patients. Further studies should evaluate whether neurotransmitters or hormones which stem from thalamus are involved in the decrease of slow wave sleep.

Alzheimer’s disease: biological aspects, therapeutic perspectives and diagnostic tools

NASA Astrophysics Data System (ADS)

Di Carlo, M.; Giacomazza, D.; San Biagio, P. L.

2012-06-01

Alzheimer’s disease (AD) is the most common form of dementia among older people. Dementia is an irreversible brain disorder that seriously affects a person’s ability to carry out daily activities. It is characterized by loss of cognitive functioning and behavioral abilities, to such an extent that it interferes with the daily life and activities of the affected patients. Although it is still unknown how the disease process begins, it seems that brain damage starts a decade or more before problems become evident. Scientific data seem to indicate that changes in the generation or the degradation of the amyloid-b peptide (Aβ) lead to the formation of aggregated structures that are the triggering molecular events in the pathogenic cascade of AD. This review summarizes some characteristic features of Aβ misfolding and aggregation and how cell damage and death mechanisms are induced by these supramolecular and toxic structures. Further, some interventions for the early diagnosis of AD are described and in the last part the potential therapeutic strategies adoptable to slow down, or better block, the progression of the pathology are reported.

Preparing hearts and minds: cardiac slowing and a cortical inhibitory network.

PubMed

Jennings, J R; van der Molen, M W; Tanase, C

2009-11-01

Preparing for a cued, speeded response induces a set of physiological changes. A review of the psychophysiology of preparation suggested that inhibition of action was an important process among the constellation of changes constituting attentive preparation. The current experiment combined event-related functional magnetic resonance imaging and cardiac inter-beat interval measures in an experiment that compared preparing for a response, watching stimuli without responding, and responding in the absence of preparation. Ten college-aged participants were tested in an initial psychophysiological experiment followed by two scanning sessions during which reverse spiral imaging was performed concurrent with inter-beat interval measurement. Two analytic approaches were used to confirm blood oxygenation level dependent responses during preparation, and these converged to show inferior prefrontal and related subthalamic nuclei activity in the context of other known changes related to brain attentional networks. Subthalamic nuclei changes were related to the depth of preparatory cardiac deceleration. This pattern of findings suggests that preparation involves the activation of a complex inhibitory neural network implicating brain and autonomic nervous systems.

Hsp90 activator Aha1 drives production of pathological tau aggregates

PubMed Central

Shelton, Lindsey B.; Baker, Jeremy D.; Zheng, Dali; Sullivan, Leia E.; Solanki, Parth K.; Webster, Jack M.; Sun, Zheying; Sabbagh, Jonathan J.; Nordhues, Bryce A.; Koren, John; Ghosh, Suman; Blagg, Brian S. J.; Dickey, Chad A.

2017-01-01

The microtubule-associated protein tau (MAPT, tau) forms neurotoxic aggregates that promote cognitive deficits in tauopathies, the most common of which is Alzheimer’s disease (AD). The 90-kDa heat shock protein (Hsp90) chaperone system affects the accumulation of these toxic tau species, which can be modulated with Hsp90 inhibitors. However, many Hsp90 inhibitors are not blood–brain barrier-permeable, and several present associated toxicities. Here, we find that the cochaperone, activator of Hsp90 ATPase homolog 1 (Aha1), dramatically increased the production of aggregated tau. Treatment with an Aha1 inhibitor, KU-177, dramatically reduced the accumulation of insoluble tau. Aha1 colocalized with tau pathology in human brain tissue, and this association positively correlated with AD progression. Aha1 overexpression in the rTg4510 tau transgenic mouse model promoted insoluble and oligomeric tau accumulation leading to a physiological deficit in cognitive function. Overall, these data demonstrate that Aha1 contributes to tau fibril formation and neurotoxicity through Hsp90. This suggests that therapeutics targeting Aha1 may reduce toxic tau oligomers and slow or prevent neurodegenerative disease progression. PMID:28827321

Modulation of thalamocortical oscillations by TRIP8b, an auxiliary subunit for HCN channels.

PubMed

Zobeiri, Mehrnoush; Chaudhary, Rahul; Datunashvili, Maia; Heuermann, Robert J; Lüttjohann, Annika; Narayanan, Venu; Balfanz, Sabine; Meuth, Patrick; Chetkovich, Dane M; Pape, Hans-Christian; Baumann, Arnd; van Luijtelaar, Gilles; Budde, Thomas

2018-04-01

Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels have important functions in controlling neuronal excitability and generating rhythmic oscillatory activity. The role of tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) in regulation of hyperpolarization-activated inward current, I h , in the thalamocortical system and its functional relevance for the physiological thalamocortical oscillations were investigated. A significant decrease in I h current density, in both thalamocortical relay (TC) and cortical pyramidal neurons was found in TRIP8b-deficient mice (TRIP8b -/- ). In addition basal cAMP levels in the brain were found to be decreased while the availability of the fast transient A-type K + current, I A , in TC neurons was increased. These changes were associated with alterations in intrinsic properties and firing patterns of TC neurons, as well as intrathalamic and thalamocortical network oscillations, revealing a significant increase in slow oscillations in the delta frequency range (0.5-4 Hz) during episodes of active-wakefulness. In addition, absence of TRIP8b suppresses the normal desynchronization response of the EEG during the switch from slow-wave sleep to wakefulness. It is concluded that TRIP8b is necessary for the modulation of physiological thalamocortical oscillations due to its direct effect on HCN channel expression in thalamus and cortex and that mechanisms related to reduced cAMP signaling may contribute to the present findings.

Distribution of the messenger RNA for the small conductance calcium-activated potassium channel SK3 in the adult rat brain and correlation with immunoreactivity.

PubMed

Tacconi, S; Carletti, R; Bunnemann, B; Plumpton, C; Merlo Pich, E; Terstappen, G C

2001-01-01

Small conductance calcium-activated potassium channels are voltage independent potassium channels which modulate the firing patterns of neurons by activating the slow component of the afterhyperpolarization. The genes encoding a family of small conductance calcium-activated potassium channels have been cloned and up to now three known members have been described and named small conductance calcium-activated potassium channel type 1, small conductance calcium-activated potassium channel type 2 and small conductance calcium-activated potassium channel type 3; the distribution of their messenger RNA in the rat CNS has already been performed but only in a limited detail. The present study represents the first detailed analysis of small conductance calcium-activated potassium channel type 3 mRNA distribution in the adult rat brain and resulted in a strong to moderate expression of signal in medial habenular nucleus, substantia nigra compact part, suprachiasmatic nucleus, ventral tegmental area, lateral septum, dorsal raphe and locus coeruleus. Immunohistological experiments were also performed and confirmed the presence of small conductance calcium-activated potassium channel type 3 protein in medial habenular nucleus, locus coeruleus and dorsal raphe. Given the importance of dorsal raphe, locus coeruleus and substantia nigra/ventral tegmental area for serotonergic, noradrenergic and dopaminergic transmission respectively, our results pose the morphological basis for further studies on the action of small conductance calcium-activated potassium channel type 3 in serotonergic, noradrenergic and dopaminergic transmission.

Insulin-like Growth Factor 1 (IGF-1) as a marker of cognitive decline in normal ageing: A review.

PubMed

Frater, Julanne; Lie, David; Bartlett, Perry; McGrath, John J

2018-03-01

Insulin-like Growth Factor 1 (IGF-1) and its signaling pathway play a primary role in normal growth and ageing, however serum IGF-1 is known to reduce with advancing age. Recent findings suggest IGF-1 is essential for neurogenesis in the adult brain, and this reduction of IGF-1 with ageing may contribute to age-related cognitive decline. Experimental studies have shown manipulation of the GH/GF-1 axis can slow rates of cognitive decline in animals, making IGF-1 a potential biomarker of cognition, and/or its signaling pathway a possible therapeutic target to prevent or slow age-related cognitive decline. A systematic literature review and qualitative narrative summary of current evidence for IGF-1 as a biomarker of cognitive decline in the ageing brain was undertaken. Results indicate IGF-1 concentrations do not confer additional diagnostic information for those with cognitive decline, and routine clinical measurement of IGF-1 is not currently justified. In cases of established cognitive impairment, it remains unclear whether increasing circulating or brain IGF-1 may reverse or slow down the rate of further decline. Advances in neuroimaging, genetics, neuroscience and the availability of large well characterized biobanks will facilitate research exploring the role of IGF-1 in both normal ageing and age-related cognitive decline. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic evidence for role of integration of fast and slow neurotransmission in schizophrenia.

PubMed

Devor, A; Andreassen, O A; Wang, Y; Mäki-Marttunen, T; Smeland, O B; Fan, C-C; Schork, A J; Holland, D; Thompson, W K; Witoelar, A; Chen, C-H; Desikan, R S; McEvoy, L K; Djurovic, S; Greengard, P; Svenningsson, P; Einevoll, G T; Dale, A M

2017-06-01

The most recent genome-wide association studies (GWAS) of schizophrenia (SCZ) identified hundreds of risk variants potentially implicated in the disease. Further, novel statistical methodology designed for polygenic architecture revealed more potential risk variants. This can provide a link between individual genetic factors and the mechanistic underpinnings of SCZ. Intriguingly, a large number of genes coding for ionotropic and metabotropic receptors for various neurotransmitters-glutamate, γ-aminobutyric acid (GABA), dopamine, serotonin, acetylcholine and opioids-and numerous ion channels were associated with SCZ. Here, we review these findings from the standpoint of classical neurobiological knowledge of neuronal synaptic transmission and regulation of electrical excitability. We show that a substantial proportion of the identified genes are involved in intracellular cascades known to integrate 'slow' (G-protein-coupled receptors) and 'fast' (ionotropic receptors) neurotransmission converging on the protein DARPP-32. Inspection of the Human Brain Transcriptome Project database confirms that that these genes are indeed expressed in the brain, with the expression profile following specific developmental trajectories, underscoring their relevance to brain organization and function. These findings extend the existing pathophysiology hypothesis by suggesting a unifying role of dysregulation in neuronal excitability and synaptic integration in SCZ. This emergent model supports the concept of SCZ as an 'associative' disorder-a breakdown in the communication across different slow and fast neurotransmitter systems through intracellular signaling pathways-and may unify a number of currently competing hypotheses of SCZ pathophysiology.

Parkinson's disease and exposure to infectious agents and pesticides and the occurrence of brain injuries: role of neuroinflammation.

PubMed Central

Liu, Bin; Gao, Hui-Ming; Hong, Jau-Shyong

2003-01-01

Idiopathic Parkinson's disease (PD) is a devastating movement disorder characterized by selective degeneration of the nigrostriatal dopaminergic pathway. Neurodegeneration usually starts in the fifth decade of life and progresses over 5-10 years before reaching the fully symptomatic disease state. Despite decades of intense research, the etiology of sporadic PD and the mechanism underlying the selective neuronal loss remain unknown. However, the late onset and slow-progressing nature of the disease has prompted the consideration of environmental exposure to agrochemicals, including pesticides, as a risk factor. Moreover, increasing evidence suggests that early-life occurrence of inflammation in the brain, as a consequence of either brain injury or exposure to infectious agents, may play a role in the pathogenesis of PD. Most important, there may be a self-propelling cycle of inflammatory process involving brain immune cells (microglia and astrocytes) that drives the slow yet progressive neurodegenerative process. Deciphering the molecular and cellular mechanisms governing those intricate interactions would significantly advance our understanding of the etiology and pathogenesis of PD and aid the development of therapeutic strategies for the treatment of the disease. PMID:12826478

Developmental trajectories of EEG sleep slow wave activity as a marker for motor skill development during adolescence: a pilot study.

PubMed

Lustenberger, Caroline; Mouthon, Anne-Laure; Tesler, Noemi; Kurth, Salome; Ringli, Maya; Buchmann, Andreas; Jenni, Oskar G; Huber, Reto

2017-01-01

Reliable markers for brain maturation are important to identify neural deviations that eventually predict the development of mental illnesses. Recent studies have proposed topographical EEG-derived slow wave activity (SWA) during NREM sleep as a mirror of cortical development. However, studies about the longitudinal stability as well as the relationship with behavioral skills are needed before SWA topography may be considered such a reliable marker. We examined six subjects longitudinally (over 5.1 years) using high-density EEG and a visuomotor learning task. All subjects showed a steady increase of SWA at a frontal electrode and a decrease in central electrodes. Despite these large changes in EEG power, SWA topography was relatively stable within each subject during development indicating individual trait-like characteristics. Moreover, the SWA changes in the central cluster were related to the development of specific visuomotor skills. Taken together with the previous work in this domain, our results suggest that EEG sleep SWA represents a marker for motor skill development and further supports the idea that SWA mirrors cortical development during childhood and adolescence. © 2016 Wiley Periodicals, Inc.

Neurotrophins, their receptors and KI-67 in human GH-secreting pituitary adenomas: an immunohistochemical analysis.

PubMed

Artico, M; Bianchi, E; Magliulo, G; De Vincentiis, M; De Santis, E; Orlandi, A; Santoro, A; Pastore, F S; Giangaspero, F; Caruso, R; Re, M; Fumagalli, L

2012-01-01

Pituitary adenomas are a diverse group of tumors arising from the pituitary gland. Typically, they are small, slow-growing, hormonally inactive lesions that come to light as incidental findings on radiologic or postmortem examinations, although some small, slow-growing lesions with excessive hormonal activity may manifest with a clinical syndrome. The family of neurotrophins plays a key role in the development and maintenance of the pituitary endocrine cell function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. The objective of our experimental study is to investigate the localization of the neurotrophins, their relative receptors and to detect the expression level of Ki-67 to determine whether all these factors participate in the transformation and development of human pituitary adenomas. A very strong expression of Neurotrophin-3 (NT-3) and its receptor TrKC was observed in the extracellular matrix (ECM) and vessel endothelium, together with a clear/marked presence of Brain-derived neurotrophic factor (BDNF), and its receptor TrKB, thus confirming their direct involvement in the progression of pituitary adenomas. On the contrary, NGF (Nerve growth factor) and its receptor TrKA and p75NTR were weakly expressed in the epithelial gland cells and the ECM.

β-Secretase BACE1 regulates hippocampal and reconstituted M-currents in a β-subunit-like fashion.

PubMed

Hessler, Sabine; Zheng, Fang; Hartmann, Stephanie; Rittger, Andrea; Lehnert, Sandra; Völkel, Meike; Nissen, Matthias; Edelmann, Elke; Saftig, Paul; Schwake, Michael; Huth, Tobias; Alzheimer, Christian

2015-02-25

The β-secretase BACE1 is widely known for its pivotal role in the amyloidogenic pathway leading to Alzheimer's disease, but how its action on transmembrane proteins other than the amyloid precursor protein affects the nervous system is only beginning to be understood. We report here that BACE1 regulates neuronal excitability through an unorthodox, nonenzymatic interaction with members of the KCNQ (Kv7) family that give rise to the M-current, a noninactivating potassium current with slow kinetics. In hippocampal neurons from BACE1(-/-) mice, loss of M-current enhanced neuronal excitability. We relate the diminished M-current to the previously reported epileptic phenotype of BACE1-deficient mice. In HEK293T cells, BACE1 amplified reconstituted M-currents, altered their voltage dependence, accelerated activation, and slowed deactivation. Biochemical evidence strongly suggested that BACE1 physically associates with channel proteins in a β-subunit-like fashion. Our results establish BACE1 as a physiologically essential constituent of regular M-current function and elucidate a striking new feature of how BACE1 impacts on neuronal activity in the intact and diseased brain. Copyright © 2015 the authors 0270-6474/15/353298-14$15.00/0.

Kin Rejection: Social Signals, Neural Response and Perceived Distress During Social Exclusion

PubMed Central

Sreekrishnan, Anirudh; Herrera, Tania A.; Wu, Jia; Borelli, Jessica L.; White, Lars O.; Rutherford, Helena J. V.; Mayes, Linda C.; Crowley, Michael J.

2014-01-01

Across species, kin bond together to promote survival. We sought to understand the dyadic effect of exclusion by kin (as opposed to non-kin strangers) on brain activity of the mother and her child and their subjective distress. To this end, we probed mother-child relationships with a computerized ball-toss game Cyberball. When excluded by one another, rather than by a stranger, both mothers and children exhibited a significantly pronounced frontal P2. Moreover, upon kin-rejection versus stranger-rejection, both mothers and children showed incremented left frontal positive slow waves for rejection events. Children reported more distress upon exclusion than their own mothers. Similar to past work, relatively augmented negative frontal slow wave activity predicted greater self-reported ostracism distress. This effect, generalized to the P2, was limited to mother or child- rejection by kin, with comparable magnitude of effect across kin identity (mothers vs. children). For both mothers and children, the frontal P2 peak was significantly pronounced for kin-rejection versus stranger rejection. Taken together, our results document the rapid categorization of social signals as kin-relevant and the specificity of early and late neural markers for predicting felt ostracism. PMID:24909389

Concurrent tACS-fMRI Reveals Causal Influence of Power Synchronized Neural Activity on Resting State fMRI Connectivity.

PubMed

Bächinger, Marc; Zerbi, Valerio; Moisa, Marius; Polania, Rafael; Liu, Quanying; Mantini, Dante; Ruff, Christian; Wenderoth, Nicole

2017-05-03

Resting state fMRI (rs-fMRI) is commonly used to study the brain's intrinsic neural coupling, which reveals specific spatiotemporal patterns in the form of resting state networks (RSNs). It has been hypothesized that slow rs-fMRI oscillations (<0.1 Hz) are driven by underlying electrophysiological rhythms that typically occur at much faster timescales (>5 Hz); however, causal evidence for this relationship is currently lacking. Here we measured rs-fMRI in humans while applying transcranial alternating current stimulation (tACS) to entrain brain rhythms in left and right sensorimotor cortices. The two driving tACS signals were tailored to the individual's α rhythm (8-12 Hz) and fluctuated in amplitude according to a 1 Hz power envelope. We entrained the left versus right hemisphere in accordance to two different coupling modes where either α oscillations were synchronized between hemispheres (phase-synchronized tACS) or the slower oscillating power envelopes (power-synchronized tACS). Power-synchronized tACS significantly increased rs-fMRI connectivity within the stimulated RSN compared with phase-synchronized or no tACS. This effect outlasted the stimulation period and tended to be more effective in individuals who exhibited a naturally weak interhemispheric coupling. Using this novel approach, our data provide causal evidence that synchronized power fluctuations contribute to the formation of fMRI-based RSNs. Moreover, our findings demonstrate that the brain's intrinsic coupling at rest can be selectively modulated by choosing appropriate tACS signals, which could lead to new interventions for patients with altered rs-fMRI connectivity. SIGNIFICANCE STATEMENT Resting state fMRI (rs-fMRI) has become an important tool to estimate brain connectivity. However, relatively little is known about how slow hemodynamic oscillations measured with fMRI relate to electrophysiological processes. It was suggested that slowly fluctuating power envelopes of electrophysiological signals synchronize across brain areas and that the topography of this activity is spatially correlated to resting state networks derived from rs-fMRI. Here we take a novel approach to address this problem and establish a causal link between the power fluctuations of electrophysiological signals and rs-fMRI via a new neuromodulation paradigm, which exploits these power synchronization mechanisms. These novel mechanistic insights bridge different scientific domains and are of broad interest to researchers in the fields of Medical Imaging, Neuroscience, Physiology, and Psychology. Copyright © 2017 the authors 0270-6474/17/374766-12$15.00/0.

Supersensitive Ras activation in dendrites and spines revealed by two-photon fluorescence lifetime imaging.

PubMed

Yasuda, Ryohei; Harvey, Christopher D; Zhong, Haining; Sobczyk, Aleksander; van Aelst, Linda; Svoboda, Karel

2006-02-01

To understand the biochemical signals regulated by neural activity, it is necessary to measure protein-protein interactions and enzymatic activity in neuronal microcompartments such as axons, dendrites and their spines. We combined two-photon excitation laser scanning with fluorescence lifetime imaging to measure fluorescence resonance energy transfer at high resolutions in brain slices. We also developed sensitive fluorescent protein-based sensors for the activation of the small GTPase protein Ras with slow (FRas) and fast (FRas-F) kinetics. Using FRas-F, we found in CA1 hippocampal neurons that trains of back-propagating action potentials rapidly and reversibly activated Ras in dendrites and spines. The relationship between firing rate and Ras activation was highly nonlinear (Hill coefficient approximately 5). This steep dependence was caused by a highly cooperative interaction between calcium ions (Ca(2+)) and Ras activators. The Ras pathway therefore functions as a supersensitive threshold detector for neural activity and Ca(2+) concentration.

A Biphasic Change of Regional Blood Volume in the Frontal Cortex during Non-Rapid Eye Movement Sleep: A Near-Infrared Spectroscopy Study.

PubMed

Zhang, Zhongxing; Khatami, Ramin

2015-08-01

Current knowledge on hemodynamics in sleep is limited because available techniques do not allow continuous recordings and mainly focus on cerebral blood flow while neglecting other important parameters, such as blood volume (BV) and vasomotor activity. Observational study. Continuous measures of hemodynamics over the left forehead and biceps were performed using near-infrared spectroscopy (NIRS) during nocturnal polysomnography in 16 healthy participants in sleep laboratory. Temporal dynamics and mean values of cerebral and muscular oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HHb), and BV during different sleep stages were compared. A biphasic change of cerebral BV was observed which contrasted a monotonic increase of muscular BV during non-rapid eye movement sleep. A significant decrement in cerebral HbO2 and BV accompanied by an increase of HHb was recorded at sleep onset (Phase I). Prior to slow wave sleep (SWS) HbO2 and BV turned to increase whereas HHb began to decrease in subsequent Phase II suggested increased brain perfusion during SWS. The cerebral HbO2 slope correlated to BV slope in Phase I and II, but it only correlated to HHb slope in Phase II. The occurrence time of inflection points correlated to SWS latencies. Initial decrease of brain perfusion with decreased blood volume (BV) and oxygenated hemoglobin (HbO2) together with increasing muscular BV fit thermoregulation process at sleep onset. The uncorrelated and correlated slopes of HbO2 and deoxygenated hemoglobin indicate different mechanisms underlying the biphasic hemodynamic process in light sleep and slow wave sleep (SWS). In SWS, changes in vasomotor activity (i.e., increased vasodilatation) may mediate increasing cerebral and muscular BV. © 2015 Associated Professional Sleep Societies, LLC.

Large-scale recording of thalamocortical circuits: in vivo electrophysiology with the two-dimensional electronic depth control silicon probe

PubMed Central

Fiáth, Richárd; Beregszászi, Patrícia; Horváth, Domonkos; Wittner, Lucia; Aarts, Arno A. A.; Ruther, Patrick; Neves, Hercules P.; Bokor, Hajnalka; Acsády, László

2016-01-01

Recording simultaneous activity of a large number of neurons in distributed neuronal networks is crucial to understand higher order brain functions. We demonstrate the in vivo performance of a recently developed electrophysiological recording system comprising a two-dimensional, multi-shank, high-density silicon probe with integrated complementary metal-oxide semiconductor electronics. The system implements the concept of electronic depth control (EDC), which enables the electronic selection of a limited number of recording sites on each of the probe shafts. This innovative feature of the system permits simultaneous recording of local field potentials (LFP) and single- and multiple-unit activity (SUA and MUA, respectively) from multiple brain sites with high quality and without the actual physical movement of the probe. To evaluate the in vivo recording capabilities of the EDC probe, we recorded LFP, MUA, and SUA in acute experiments from cortical and thalamic brain areas of anesthetized rats and mice. The advantages of large-scale recording with the EDC probe are illustrated by investigating the spatiotemporal dynamics of pharmacologically induced thalamocortical slow-wave activity in rats and by the two-dimensional tonotopic mapping of the auditory thalamus. In mice, spatial distribution of thalamic responses to optogenetic stimulation of the neocortex was examined. Utilizing the benefits of the EDC system may result in a higher yield of useful data from a single experiment compared with traditional passive multielectrode arrays, and thus in the reduction of animals needed for a research study. PMID:27535370

Ketamine: differential neurophysiological dynamics in functional networks in the rat brain

PubMed Central

Ahnaou, A; Huysmans, H; Biermans, R; Manyakov, N V; Drinkenburg, W H I M

2017-01-01

Recently, the N-methyl-d-aspartate-receptor (NMDAR) antagonist ketamine has emerged as a fast-onset mechanism to achieve antidepressant activity, whereas its psychomimetic, dissociative and amnestic effects have been well documented to pharmacologically model schizophrenia features in rodents. Sleep–wake architecture, neuronal oscillations and network connectivity are key mechanisms supporting brain plasticity and cognition, which are disrupted in mood disorders such as depression and schizophrenia. In rats, we investigated the dynamic effects of acute and chronic subcutaneous administration of ketamine (2.5, 5 and 10 mg kg−1) on sleep–wake cycle, multichannels network interactions assessed by coherence and phase–amplitude cross-frequency coupling, locomotor activity (LMA), cognitive information processing as reflected by the mismatch negativity-like (MMN) component of event-related brain potentials (ERPs). Acute ketamine elicited a short, lasting inhibition of rapid eye movement (REM) sleep, increased coherence in higher gamma frequency oscillations independent of LMA, altered theta-gamma phase–amplitude coupling, increased MMN peak-amplitude response and evoked higher gamma oscillations. In contrast, chronic ketamine reduced large-scale communication among cortical regions by decreasing oscillations and coherent activity in the gamma frequency range, shifted networks activity towards slow alpha rhythm, decreased MMN peak response and enhanced aberrant higher gamma neuronal network oscillations. Altogether, our data show that acute and chronic ketamine elicited differential changes in network connectivity, ERPs and event-related oscillations (EROs), supporting possible underlying alterations in NMDAR–GABAergic signaling. The findings underscore the relevance of intermittent dosing of ketamine to accurately maintain the functional integrity of neuronal networks for long-term plastic changes and therapeutic effect. PMID:28926001

Resting State Brain Entropy Alterations in Relapsing Remitting Multiple Sclerosis.

PubMed

Zhou, Fuqing; Zhuang, Ying; Gong, Honghan; Zhan, Jie; Grossman, Murray; Wang, Ze

2016-01-01

Brain entropy (BEN) mapping provides a novel approach to characterize brain temporal dynamics, a key feature of human brain. Using resting state functional magnetic resonance imaging (rsfMRI), reliable and spatially distributed BEN patterns have been identified in normal brain, suggesting a potential use in clinical populations since temporal brain dynamics and entropy may be altered in disease conditions. The purpose of this study was to characterize BEN in multiple sclerosis (MS), a neurodegenerative disease that affects millions of people. Since currently there is no cure for MS, developing treatment or medication that can slow down its progression represents a high research priority, for which validating a brain marker sensitive to disease and the related functional impairments is essential. Because MS can start long time before any measurable symptoms and structural deficits, assessing the dynamic brain activity and correspondingly BEN may provide a critical way to study MS and its progression. Because BEN is new to MS, we aimed to assess BEN alterations in the relapsing-remitting MS (RRMS) patients using a patient versus control design, to examine the correlation of BEN to clinical measurements, and to check the correlation of BEN to structural brain measures which have been more often used in MS studies. As compared to controls, RRMS patients showed increased BEN in motor areas, executive control area, spatial coordinating area, and memory system. Increased BEN was related to greater disease severity as measured by the expanded disability status scale (EDSS) and greater tissue damage as indicated by the mean diffusivity. Patients also showed decreased BEN in other places, which was associated with less disability or fatigue, indicating a disease-related BEN re-distribution. Our results suggest BEN as a novel and useful tool for characterizing RRMS.

A Biologically Constrained, Mathematical Model of Cortical Wave Propagation Preceding Seizure Termination

PubMed Central

González-Ramírez, Laura R.; Ahmed, Omar J.; Cash, Sydney S.; Wayne, C. Eugene; Kramer, Mark A.

2015-01-01

Epilepsy—the condition of recurrent, unprovoked seizures—manifests in brain voltage activity with characteristic spatiotemporal patterns. These patterns include stereotyped semi-rhythmic activity produced by aggregate neuronal populations, and organized spatiotemporal phenomena, including waves. To assess these spatiotemporal patterns, we develop a mathematical model consistent with the observed neuronal population activity and determine analytically the parameter configurations that support traveling wave solutions. We then utilize high-density local field potential data recorded in vivo from human cortex preceding seizure termination from three patients to constrain the model parameters, and propose basic mechanisms that contribute to the observed traveling waves. We conclude that a relatively simple and abstract mathematical model consisting of localized interactions between excitatory cells with slow adaptation captures the quantitative features of wave propagation observed in the human local field potential preceding seizure termination. PMID:25689136

Fast Uptake and Long-Lasting Binding of Methamphetamine in the Human Brain

PubMed Central

Fowler, Joanna S.; Volkow, Nora D.; Logan, Jean; Alexoff, David; Telang, Frank; Wang, Gene-Jack; Wong, Christopher; Ma, Yeming; Kriplani, Aarti; Pradhan, Kith; Schlyer, David; Jayne, Millard; Hubbard, Barbara; Carter, Pauline; Warner, Donald; King, Payton; Shea, Colleen; Xu, Youwen; Muench, Lisa; Apelskog, Karen

2008-01-01

Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U.S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokinetics in brain between Caucasians and African Americans along with the measurement of dopamine transporter availability in striatum. Methamphetamine’s uptake in brain was fast (peak uptake at 9 minutes) with accumulation in cortical and subcortical brain regions and in white matter. Its clearance from brain was slow (except for white matter which did not clear over the 90 minutes) and there was no difference in pharmacokinetics between Caucasians and African Americans. In contrast cocaine’s brain uptake and clearance were both fast, distribution was predominantly in striatum and uptake was higher in African Americans. Among individuals, those with the highest striatal (but not cerebellar) methamphetamine accumulation also had the highest dopamine transporter availability suggesting a relationship between METH exposure and DAT availability. Methamphetamine’s fast brain uptake is consistent with its highly reinforcing effects, its slow clearance with its long lasting behavioral effects and its widespread distribution with its neurotoxic effects that affect not only striatal but also cortical and white matter regions. The absence of significant differences between Caucasians and African Americans suggests that variables other than methamphetamine pharmacokinetics and bioavailability account for the lower abuse prevalence in African Americans. PMID:18708148

Fast uptake and long-lasting binding of methamphetamine in the human brain: comparison with cocaine.

PubMed

Fowler, Joanna S; Volkow, Nora D; Logan, Jean; Alexoff, David; Telang, Frank; Wang, Gene-Jack; Wong, Christopher; Ma, Yeming; Kriplani, Aarti; Pradhan, Kith; Schlyer, David; Jayne, Millard; Hubbard, Barbara; Carter, Pauline; Warner, Donald; King, Payton; Shea, Colleen; Xu, Youwen; Muench, Lisa; Apelskog, Karen

2008-12-01

Methamphetamine is one of the most addictive and neurotoxic drugs of abuse. It produces large elevations in extracellular dopamine in the striatum through vesicular release and inhibition of the dopamine transporter. In the U.S. abuse prevalence varies by ethnicity with very low abuse among African Americans relative to Caucasians, differentiating it from cocaine where abuse rates are similar for the two groups. Here we report the first comparison of methamphetamine and cocaine pharmacokinetics in brain between Caucasians and African Americans along with the measurement of dopamine transporter availability in striatum. Methamphetamine's uptake in brain was fast (peak uptake at 9 min) with accumulation in cortical and subcortical brain regions and in white matter. Its clearance from brain was slow (except for white matter which did not clear over the 90 min) and there was no difference in pharmacokinetics between Caucasians and African Americans. In contrast cocaine's brain uptake and clearance were both fast, distribution was predominantly in striatum and uptake was higher in African Americans. Among individuals, those with the highest striatal (but not cerebellar) methamphetamine accumulation also had the highest dopamine transporter availability suggesting a relationship between METH exposure and DAT availability. Methamphetamine's fast brain uptake is consistent with its highly reinforcing effects, its slow clearance with its long-lasting behavioral effects and its widespread distribution with its neurotoxic effects that affect not only striatal but also cortical and white matter regions. The absence of significant differences between Caucasians and African Americans suggests that variables other than methamphetamine pharmacokinetics and bioavailability account for the lower abuse prevalence in African Americans.

Semantic and Phonological Encoding Times in Adults Who Stutter: Brain Electrophysiological Evidence.

PubMed

Maxfield, Nathan D

2017-10-17

Some psycholinguistic theories of stuttering propose that language production operates along a different time course in adults who stutter (AWS) versus typically fluent adults (TFA). However, behavioral evidence for such a difference has been mixed. Here, the time course of semantic and phonological encoding in picture naming was compared in AWS (n = 16) versus TFA (n = 16) by measuring 2 event-related potential (ERP) components: NoGo N200, an ERP index of response inhibition, and lateralized readiness potential, an ERP index of response preparation. Each trial required a semantic judgment about a picture in addition to a phonemic judgment about the target label of the picture. Judgments were mapped onto a dual-choice (Go-NoGo/left-right) push-button response paradigm. On each trial, ERP activity time-locked to picture onset was recorded at 32 scalp electrodes. NoGo N200 was detected earlier to semantic NoGo trials than to phonemic NoGo trials in both groups, replicating previous evidence that semantic encoding generally precedes phonological encoding in language production. Moreover, N200 onset was earlier to semantic NoGo trials in TFA than in AWS, indicating that semantic information triggering response inhibition became available earlier in TFA versus AWS. In contrast, the time course of N200 activity to phonemic NoGo trials did not differ between groups. Lateralized readiness potential activity was influenced by strategic response preparation and, thus, could not be used to index real-time semantic and phonological encoding. NoGo N200 results point to slowed semantic encoding in AWS versus TFA. Discussion considers possible factors in slowed semantic encoding in AWS and how fluency might be impacted by slowed semantic encoding.

Semantic and Phonological Encoding Times in Adults Who Stutter: Brain Electrophysiological Evidence

PubMed Central

2017-01-01

Purpose Some psycholinguistic theories of stuttering propose that language production operates along a different time course in adults who stutter (AWS) versus typically fluent adults (TFA). However, behavioral evidence for such a difference has been mixed. Here, the time course of semantic and phonological encoding in picture naming was compared in AWS (n = 16) versus TFA (n = 16) by measuring 2 event-related potential (ERP) components: NoGo N200, an ERP index of response inhibition, and lateralized readiness potential, an ERP index of response preparation. Method Each trial required a semantic judgment about a picture in addition to a phonemic judgment about the target label of the picture. Judgments were mapped onto a dual-choice (Go–NoGo/left–right) push-button response paradigm. On each trial, ERP activity time-locked to picture onset was recorded at 32 scalp electrodes. Results NoGo N200 was detected earlier to semantic NoGo trials than to phonemic NoGo trials in both groups, replicating previous evidence that semantic encoding generally precedes phonological encoding in language production. Moreover, N200 onset was earlier to semantic NoGo trials in TFA than in AWS, indicating that semantic information triggering response inhibition became available earlier in TFA versus AWS. In contrast, the time course of N200 activity to phonemic NoGo trials did not differ between groups. Lateralized readiness potential activity was influenced by strategic response preparation and, thus, could not be used to index real-time semantic and phonological encoding. Conclusion NoGo N200 results point to slowed semantic encoding in AWS versus TFA. Discussion considers possible factors in slowed semantic encoding in AWS and how fluency might be impacted by slowed semantic encoding. PMID:28973156

Relationship between cortical state and spiking activity in the lateral geniculate nucleus of marmosets

PubMed Central

Pietersen, Alexander N.J.; Cheong, Soon Keen; Munn, Brandon; Gong, Pulin; Solomon, Samuel G.

2017-01-01

Key points How parallel are the primate visual pathways? In the present study, we demonstrate that parallel visual pathways in the dorsal lateral geniculate nucleus (LGN) show distinct patterns of interaction with rhythmic activity in the primary visual cortex (V1).In the V1 of anaesthetized marmosets, the EEG frequency spectrum undergoes transient changes that are characterized by fluctuations in delta‐band EEG power.We show that, on multisecond timescales, spiking activity in an evolutionary primitive (koniocellular) LGN pathway is specifically linked to these slow EEG spectrum changes. By contrast, on subsecond (delta frequency) timescales, cortical oscillations can entrain spiking activity throughout the entire LGN.Our results are consistent with the hypothesis that, in waking animals, the koniocellular pathway selectively participates in brain circuits controlling vigilance and attention. Abstract The major afferent cortical pathway in the visual system passes through the dorsal lateral geniculate nucleus (LGN), where nerve signals originating in the eye can first interact with brain circuits regulating visual processing, vigilance and attention. In the present study, we investigated how ongoing and visually driven activity in magnocellular (M), parvocellular (P) and koniocellular (K) layers of the LGN are related to cortical state. We recorded extracellular spiking activity in the LGN simultaneously with local field potentials (LFP) in primary visual cortex, in sufentanil‐anaesthetized marmoset monkeys. We found that asynchronous cortical states (marked by low power in delta‐band LFPs) are linked to high spike rates in K cells (but not P cells or M cells), on multisecond timescales. Cortical asynchrony precedes the increases in K cell spike rates by 1–3 s, implying causality. At subsecond timescales, the spiking activity in many cells of all (M, P and K) classes is phase‐locked to delta waves in the cortical LFP, and more cells are phase‐locked during synchronous cortical states than during asynchronous cortical states. The switch from low‐to‐high spike rates in K cells does not degrade their visual signalling capacity. By contrast, during asynchronous cortical states, the fidelity of visual signals transmitted by K cells is improved, probably because K cell responses become less rectified. Overall, the data show that slow fluctuations in cortical state are selectively linked to K pathway spiking activity, whereas delta‐frequency cortical oscillations entrain spiking activity throughout the entire LGN, in anaesthetized marmosets. PMID:28116750

Dendritic Learning as a Paradigm Shift in Brain Learning.

PubMed

Sardi, Shira; Vardi, Roni; Goldental, Amir; Tugendhaft, Yael; Uzan, Herut; Kanter, Ido

2018-06-20

Experimental and theoretical results reveal a new underlying mechanism for fast brain learning process, dendritic learning, as opposed to the misdirected research in neuroscience over decades, which is based solely on slow synaptic plasticity. The presented paradigm indicates that learning occurs in closer proximity to the neuron, the computational unit, dendritic strengths are self-oscillating, and weak synapses, which comprise the majority of our brain and previously were assumed to be insignificant, play a key role in plasticity. The new learning sites of the brain call for a reevaluation of current treatments for disordered brain functionality and for a better understanding of proper chemical drugs and biological mechanisms to maintain, control and enhance learning.

Penetration of blood-brain barrier and antitumor activity and nerve repair in glioma by doxorubicin-loaded monosialoganglioside micelles system.

PubMed

Zou, Dan; Wang, Wei; Lei, Daoxi; Yin, Ying; Ren, Peng; Chen, Jinju; Yin, Tieying; Wang, Bochu; Wang, Guixue; Wang, Yazhou

2017-01-01

For the treatment of glioma and other central nervous system diseases, one of the biggest challenges is that most therapeutic drugs cannot be delivered to the brain tumor tissue due to the blood-brain barrier (BBB). The goal of this study was to construct a nanodelivery vehicle system with capabilities to overcome the BBB for central nervous system administration. Doxorubicin as a model drug encapsulated in ganglioside GM1 micelles was able to achieve up to 9.33% loading efficiency and 97.05% encapsulation efficiency by orthogonal experimental design. The in vitro study demonstrated a slow and sustainable drug release in physiological conditions. In the cellular uptake studies, mixed micelles could effectively transport into both human umbilical vein endothelial cells and C6 cells. Furthermore, biodistribution imaging of mice showed that the DiR/GM1 mixed micelles were accumulated sustainably and distributed centrally in the brain. Experiments on zebrafish confirmed that drug-loaded GM1 micelles can overcome the BBB and enter the brain. Among all the treatment groups, the median survival time of C6-bearing rats after administering DOX/GM1 micelles was significantly prolonged. In conclusion, the ganglioside nanomicelles developed in this work can not only penetrate BBB effectively but also repair nerves and kill tumor cells at the same time.

Exploring resting-state EEG brain oscillatory activity in relation to cognitive functioning in multiple sclerosis.

PubMed

Keune, Philipp M; Hansen, Sascha; Weber, Emily; Zapf, Franziska; Habich, Juliane; Muenssinger, Jana; Wolf, Sebastian; Schönenberg, Michael; Oschmann, Patrick

2017-09-01

Neurophysiologic monitoring parameters related to cognition in Multiple Sclerosis (MS) are sparse. Previous work reported an association between magnetoencephalographic (MEG) alpha-1 activity and information processing speed. While this remains to be replicated by more available electroencephalographic (EEG) methods, also other established EEG markers, e.g. the slow-wave/fast-wave ratio (theta/beta ratio), remain to be explored in this context. Performance on standard tests addressing information processing speed and attention (Symbol-Digit Modalities Test, SDMT; Test of Attention Performance, TAP) was examined in relation to resting-state EEG alpha-1 and alpha-2 activity and the theta/beta ratio in 25MS patients. Increased global alpha-1 and alpha-2 activity and an increased frontal theta/beta ratio (pronounced slow-wave relative to fast-wave activity) were associated with lower SDMT processing speed. In an exploratory analysis, clinically impaired attention was associated with a significantly increased frontal theta/beta ratio whereas alpha power did not show sensitivity to clinical impairment. EEG global alpha power and the frontal theta/beta ratio were both associated with attention. The theta/beta ratio involved potential clinical sensitivity. Resting-state EEG recordings can be obtained during the routine clinical process. The examined resting-state measures may represent feasible monitoring parameters in MS. This notion should be explored in future intervention studies. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Selective Coupling between Theta Phase and Neocortical Fast Gamma Oscillations during REM-Sleep in Mice

PubMed Central

Scheffzük, Claudia; Kukushka, Valeriy I.; Vyssotski, Alexei L.; Draguhn, Andreas

2011-01-01

Background The mammalian brain expresses a wide range of state-dependent network oscillations which vary in frequency and spatial extension. Such rhythms can entrain multiple neurons into coherent patterns of activity, consistent with a role in behaviour, cognition and memory formation. Recent evidence suggests that locally generated fast network oscillations can be systematically aligned to long-range slow oscillations. It is likely that such cross-frequency coupling supports specific tasks including behavioural choice and working memory. Principal Findings We analyzed temporal coupling between high-frequency oscillations and EEG theta activity (4–12 Hz) in recordings from mouse parietal neocortex. Theta was exclusively present during active wakefulness and REM-sleep. Fast oscillations occurred in two separate frequency bands: gamma (40–100 Hz) and fast gamma (120–160 Hz). Theta, gamma and fast gamma were more prominent during active wakefulness as compared to REM-sleep. Coupling between theta and the two types of fast oscillations, however, was more pronounced during REM-sleep. This state-dependent cross-frequency coupling was particularly strong for theta-fast gamma interaction which increased 9-fold during REM as compared to active wakefulness. Theta-gamma coupling increased only by 1.5-fold. Significance State-dependent cross-frequency-coupling provides a new functional characteristic of REM-sleep and establishes a unique property of neocortical fast gamma oscillations. Interactions between defined patterns of slow and fast network oscillations may serve selective functions in sleep-dependent information processing. PMID:22163023

Functional Anatomy of Non-REM Sleep

PubMed Central

de Andrés, Isabel; Garzón, Miguel; Reinoso-Suárez, Fernando

2011-01-01

The state of non-REM sleep (NREM), or slow wave sleep, is associated with a synchronized EEG pattern in which sleep spindles and/or K complexes and high-voltage slow wave activity (SWA) can be recorded over the entire cortical surface. In humans, NREM is subdivided into stages 2 and 3–4 (presently named N3) depending on the proportions of each of these polygraphic events. NREM is necessary for normal physical and intellectual performance and behavior. An overview of the brain structures involved in NREM generation shows that the thalamus and the cerebral cortex are absolutely necessary for the most significant bioelectric and behavioral events of NREM to be expressed; other structures like the basal forebrain, anterior hypothalamus, cerebellum, caudal brain stem, spinal cord and peripheral nerves contribute to NREM regulation and modulation. In NREM stage 2, sustained hyperpolarized membrane potential levels resulting from interaction between thalamic reticular and projection neurons gives rise to spindle oscillations in the membrane potential; the initiation and termination of individual spindle sequences depends on corticothalamic activities. Cortical and thalamic mechanisms are also involved in the generation of EEG delta SWA that appears in deep stage 3–4 (N3) NREM; the cortex has classically been considered to be the structure that generates this activity, but delta oscillations can also be generated in thalamocortical neurons. NREM is probably necessary to normalize synapses to a sustainable basal condition that can ensure cellular homeostasis. Sleep homeostasis depends not only on the duration of prior wakefulness but also on its intensity, and sleep need increases when wakefulness is associated with learning. NREM seems to ensure cell homeostasis by reducing the number of synaptic connections to a basic level; based on simple energy demands, cerebral energy economizing during NREM sleep is one of the prevalent hypotheses to explain NREM homeostasis. PMID:22110467

Odors enhance slow-wave activity in non-rapid eye movement sleep

PubMed Central

Perl, Ofer; Arzi, Anat; Sela, Lee; Secundo, Lavi; Holtzman, Yael; Samnon, Perry; Oksenberg, Arie; Sobel, Noam

2016-01-01

Most forms of suprathreshold sensory stimulation perturb sleep. In contrast, presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. In fact, some odors promote objective and subjective measures of sleep quality in humans and rodents. The brain mechanisms underlying these sleep-protective properties of olfaction remain unclear. Slow oscillations in the electroencephalogram (EEG) are a marker of deep sleep, and K complexes (KCs) are an EEG marker of cortical response to sensory interference. We therefore hypothesized that odorants presented during sleep will increase power in slow EEG oscillations. Moreover, given that odorants do not drive sleep interruption, we hypothesized that unlike other sensory stimuli odorants would not drive KCs. To test these hypotheses we used polysomnography to measure sleep in 34 healthy subjects (19 women, 15 men; mean age 26.5 ± 2.5 yr) who were repeatedly presented with odor stimuli via a computer-controlled air-dilution olfactometer over the course of a single night. Each participant was exposed to one of four odorants, lavender oil (n = 13), vetiver oil (n = 5), vanillin (n = 12), or ammonium sulfide (n = 4), for durations of 5, 10, and 20 s every 9–15 min. Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5–4 Hz) and slow spindle (9–12 Hz) frequencies during non-rapid eye movement sleep. The increase was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow-frequency oscillations. PMID:26888107

Odors enhance slow-wave activity in non-rapid eye movement sleep.

PubMed

Perl, Ofer; Arzi, Anat; Sela, Lee; Secundo, Lavi; Holtzman, Yael; Samnon, Perry; Oksenberg, Arie; Sobel, Noam; Hairston, Ilana S

2016-05-01

Most forms of suprathreshold sensory stimulation perturb sleep. In contrast, presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. In fact, some odors promote objective and subjective measures of sleep quality in humans and rodents. The brain mechanisms underlying these sleep-protective properties of olfaction remain unclear. Slow oscillations in the electroencephalogram (EEG) are a marker of deep sleep, and K complexes (KCs) are an EEG marker of cortical response to sensory interference. We therefore hypothesized that odorants presented during sleep will increase power in slow EEG oscillations. Moreover, given that odorants do not drive sleep interruption, we hypothesized that unlike other sensory stimuli odorants would not drive KCs. To test these hypotheses we used polysomnography to measure sleep in 34 healthy subjects (19 women, 15 men; mean age 26.5 ± 2.5 yr) who were repeatedly presented with odor stimuli via a computer-controlled air-dilution olfactometer over the course of a single night. Each participant was exposed to one of four odorants, lavender oil (n = 13), vetiver oil (n = 5), vanillin (n = 12), or ammonium sulfide (n = 4), for durations of 5, 10, and 20 s every 9-15 min. Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5-4 Hz) and slow spindle (9-12 Hz) frequencies during non-rapid eye movement sleep. The increase was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow-frequency oscillations. Copyright © 2016 the American Physiological Society.

In Silico Docking and Electrophysiological Characterization of Lacosamide Binding Sites on Collapsin Response Mediator Protein-2 Identifies a Pocket Important in Modulating Sodium Channel Slow Inactivation*

PubMed Central

Wang, Yuying; Brittain, Joel M.; Jarecki, Brian W.; Park, Ki Duk; Wilson, Sarah M.; Wang, Bo; Hale, Rachel; Meroueh, Samy O.; Cummins, Theodore R.; Khanna, Rajesh

2010-01-01

The anti-epileptic drug (R)-lacosamide ((2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide (LCM)) modulates voltage-gated sodium channels (VGSCs) by preferentially interacting with slow inactivated sodium channels, but the observation that LCM binds to collapsin response mediator protein 2 (CRMP-2) suggests additional mechanisms of action for LCM. We postulated that CRMP-2 levels affects the actions of LCM on VGSCs. CRMP-2 labeling by LCM analogs was competitively displaced by excess LCM in rat brain lysates. Manipulation of CRMP-2 levels in the neuronal model system CAD cells affected slow inactivation of VGSCs without any effects on other voltage-dependent properties. In silico docking was performed to identify putative binding sites in CRMP-2 that may modulate the effects of LCM on VGSCs. These studies identified five cavities in CRMP-2 that can accommodate LCM. CRMP-2 alanine mutants of key residues within these cavities were functionally similar to wild-type CRMP-2 as assessed by similar levels of enhancement in dendritic complexity of cortical neurons. Next, we examined the effects of expression of wild-type and mutant CRMP-2 constructs on voltage-sensitive properties of VGSCs in CAD cells: 1) steady-state voltage-dependent activation and fast-inactivation properties were not affected by LCM, 2) CRMP-2 single alanine mutants reduced the LCM-mediated effects on the ability of endogenous Na+ channels to transition to a slow inactivated state, and 3) a quintuplicate CRMP-2 alanine mutant further decreased this slow inactivated fraction. Collectively, these results identify key CRMP-2 residues that can coordinate LCM binding thus making it more effective on its primary clinical target. PMID:20538611

Control channels in the brain and their influence on brain executive functions

NASA Astrophysics Data System (ADS)

Meng, Qinglei; Choa, Fow-Sen; Hong, Elliot; Wang, Zhiguang; Islam, Mohammad

2014-05-01

In a computer network there are distinct data channels and control channels where massive amount of visual information are transported through data channels but the information streams are routed and controlled by intelligent algorithm through "control channels". Recent studies on cognition and consciousness have shown that the brain control channels are closely related to the brainwave beta (14-40 Hz) and alpha (7-13 Hz) oscillations. The high-beta wave is used by brain to synchronize local neural activities and the alpha oscillation is for desynchronization. When two sensory inputs are simultaneously presented to a person, the high-beta is used to select one of the inputs and the alpha is used to deselect the other so that only one input will get the attention. In this work we demonstrated that we can scan a person's brain using binaural beats technique and identify the individual's preferred control channels. The identified control channels can then be used to influence the subject's brain executive functions. In the experiment, an EEG measurement system was used to record and identify a subject's control channels. After these channels were identified, the subject was asked to do Stroop tests. Binaural beats was again used to produce these control-channel frequencies on the subject's brain when we recorded the completion time of each test. We found that the high-beta signal indeed speeded up the subject's executive function performance and reduced the time to complete incongruent tests, while the alpha signal didn't seem to be able to slow down the executive function performance.

Brain and muscle oxygenation monitoring using near-infrared spectroscopy (NIRS) during all-night sleep

NASA Astrophysics Data System (ADS)

Zhang, Zhongxing; Khatami, Ramin

2013-03-01

The hemodynamic changes during natural human sleep are still not well understood. NIRS is ideally suited for monitoring the hemodynamic changes during sleep due to the properties of local measurement, totally safe application and good tolerance to motion. Several studies have been conducted using NIRS in both normal subjects and patients with various sleep disorders during sleep to characterize the hemodynamic changing patterns during different sleep stages and during different symptoms such as obstructive apneas. Here we assessed brain and muscle oxygenation changes in 7 healthy adults during all-night sleep with combined polysomnography measurement to test the notion if hemodynamic changes in sleep are indeed brain specific. We found that muscle and brain showed similar hemodynamic changes during sleep initiation. A decrease in HbO2 and tissue oxygenation index (TOI) while an increase in HHb was observed immediately after sleep onset, and an opposite trend was found after transition with progression to deeper slow-wave sleep (SWS) stage. Spontaneous low frequency oscillations (LFO) and very low frequency oscillations (VLFO) were smaller (Levene's test, p<0.05) during SWS compared to light sleep (LS) and rapid-eye-movement (REM) sleep in both brain and muscle. Spectral analysis of the NIRS signals measured from brain and muscle also showed reductions in VLFO and LFO powers during SWS with respect to LS and REM sleep. These results indicate a systemic attenuation rather than local cerebral reduction of spontaneous hemodynamic activity in SWS. A systemic physiological mechanism may exist to regulate the hemodynamic changes in brain and muscle during sleep.

Metabotropic glutamate receptors in auditory processing

PubMed Central

Lu, Yong

2014-01-01

As the major excitatory neurotransmitter used in the vertebrate brain, glutamate activates ionotropic and metabotropic glutamate receptors (mGluRs), which mediate fast and slow neuronal actions, respectively. Important modulatory roles of mGluRs have been shown in many brain areas, and drugs targeting mGluRs have been developed for treatment of brain disorders. Here, I review the studies on mGluRs in the auditory system. Anatomical expression of mGluRs in the cochlear nucleus has been well characterized, while data for other auditory nuclei await more systematic investigations at both the light and electron microscopy levels. The physiology of mGluRs has been extensively studied using in vitro brain slice preparations, with a focus on the lower auditory brainstem in both mammals and birds. These in vitro physiological studies have revealed that mGluRs participate in neurotransmission, regulate ionic homeostasis, induce synaptic plasticity, and maintain the balance between excitation and inhibition in a variety of auditory structures. However, very few in vivo physiological studies on mGluRs in auditory processing have been undertaken at the systems level. Many questions regarding the essential roles of mGluRs in auditory processing still remain unanswered and more rigorous basic research is warranted. PMID:24909898

Electroencephalographic Variation during End Maintenance and Emergence from Surgical Anesthesia

PubMed Central

MacColl, Jono N.; Illing, Sam; Sleigh, Jamie W.

2014-01-01

The re-establishment of conscious awareness after discontinuing general anesthesia has often been assumed to be the inverse of loss of consciousness. This is despite the obvious asymmetry in the initiation and termination of natural sleep. In order to characterize the restoration of consciousness after surgery, we recorded frontal electroencephalograph (EEG) from 100 patients in the operating room during maintenance and emergence from general anesthesia. We have defined, for the first time, 4 steady-state patterns of anesthetic maintenance based on the relative EEG power in the slow-wave (<14 Hz) frequency bands that dominate sleep and anesthesia. Unlike single-drug experiments performed in healthy volunteers, we found that surgical patients exhibited greater electroencephalographic heterogeneity while re-establishing conscious awareness after drug discontinuation. Moreover, these emergence patterns could be broadly grouped according to the duration and rapidity of transitions amongst these slow-wave dominated brain states that precede awakening. Most patients progressed gradually from a pattern characterized by strong peaks of delta (0.5–4 Hz) and alpha/spindle (8–14 Hz) power (‘Slow-Wave Anesthesia’) to a state marked by low delta-spindle power (‘Non Slow-Wave Anesthesia’) before awakening. However, 31% of patients transitioned abruptly from Slow-Wave Anesthesia to waking; they were also more likely to express pain in the post-operative period. Our results, based on sleep-staging classification, provide the first systematized nomenclature for tracking brain states under general anesthesia from maintenance to emergence, and suggest that these transitions may correlate with post-operative outcomes such as pain. PMID:25264892

Effects of different correlation metrics and preprocessing factors on small-world brain functional networks: a resting-state functional MRI study.

PubMed

Liang, Xia; Wang, Jinhui; Yan, Chaogan; Shu, Ni; Xu, Ke; Gong, Gaolang; He, Yong

2012-01-01

Graph theoretical analysis of brain networks based on resting-state functional MRI (R-fMRI) has attracted a great deal of attention in recent years. These analyses often involve the selection of correlation metrics and specific preprocessing steps. However, the influence of these factors on the topological properties of functional brain networks has not been systematically examined. Here, we investigated the influences of correlation metric choice (Pearson's correlation versus partial correlation), global signal presence (regressed or not) and frequency band selection [slow-5 (0.01-0.027 Hz) versus slow-4 (0.027-0.073 Hz)] on the topological properties of both binary and weighted brain networks derived from them, and we employed test-retest (TRT) analyses for further guidance on how to choose the "best" network modeling strategy from the reliability perspective. Our results show significant differences in global network metrics associated with both correlation metrics and global signals. Analysis of nodal degree revealed differing hub distributions for brain networks derived from Pearson's correlation versus partial correlation. TRT analysis revealed that the reliability of both global and local topological properties are modulated by correlation metrics and the global signal, with the highest reliability observed for Pearson's-correlation-based brain networks without global signal removal (WOGR-PEAR). The nodal reliability exhibited a spatially heterogeneous distribution wherein regions in association and limbic/paralimbic cortices showed moderate TRT reliability in Pearson's-correlation-based brain networks. Moreover, we found that there were significant frequency-related differences in topological properties of WOGR-PEAR networks, and brain networks derived in the 0.027-0.073 Hz band exhibited greater reliability than those in the 0.01-0.027 Hz band. Taken together, our results provide direct evidence regarding the influences of correlation metrics and specific preprocessing choices on both the global and nodal topological properties of functional brain networks. This study also has important implications for how to choose reliable analytical schemes in brain network studies.

Rivastigmine Transdermal Patch

MedlinePlus

... also used to treat dementia in people with Parkinson's disease (a brain system disease with symptoms of slowing ... cure Alzheimer's disease or dementia in people with Parkinson's disease. Continue to use transdermal rivastigmine even if you ...

Striatonigral Degeneration

MedlinePlus

... NINDS Focus on Disorders Alzheimer's & Related Dementias Epilepsy Parkinson's Disease Spinal Cord Injury Traumatic Brain Injury Focus On ... the disorder resemble some of those seen in Parkinson's disease, including rigidity, instability, impaired speech, and slow movements. × ...

[The complex approach to the rehabilitation of post-stroke patients with movement disorders in the early rehabilitation period].

PubMed

Khabirov, F A; Khaĭbullin, T I; Grigor'eva, O V

2011-01-01

We studied 110 patients, aged 34-71 years, in the early rehabilitation period after stroke who were admitted to a rehabilitation neurologic department of Kazan. The rehabilitation approach was based on the combination of several methods: kinesitherapy, transcranial magnetic stimulation and cerebrolysin treatment. This complex reanimation allowed to achieve the marked functional restoration of movement abilities in many cases that was correlated with the normalization of brain bioelectric activity (the increase of alpha-rhythm spectral power, the decrease of slow-wave EEG components). The combined use of these three methods was more effective than a combination of any two of them.

Possible mechanisms for sensitivity to organophosphorus and carbamate insecticides in eastern screech-owls and American kestrels.

PubMed

Vyas, N B; Thiele, L A; Garland, S C

1998-07-01

Effects of a single dietary exposure to fenthion and carbofuran on the survival, feeding behavior and brain ChE activity of eastern screech-owls, Otus asio and American kestrels, Falco sparverius, were evaluated. Birds were exposed to fenthion (23.6-189.0 ppm) or carbofuran (31.7-253.6 ppm) via meatballs. Carbofuran-exposed owls ate either < or = 10% or > or = 80% of the meatball whereas all kestrels ate < or = 10% of the meatball before exhibiting acute signs of toxicity. Fenthion-exposed owls and kestrels displayed a wide spectrum of meatball consumption (< 10-100%). Significant brain ChE inhibition was observed in dead and surviving kestrels exposed to fenthion and carbofuran and dead owls exposed to fenthion (P < 0.0001). Brain ChE activity of owls exposed to carbofuran that survived was not different from that of controls (P = 0.25). Data suggest: (1) slow feeding on a carbamate-contaminated item may provide limited protection from the toxicity of the chemical at certain rates of exposure; (2) the degree of ChE inhibition at neuromuscular junctions may be critical in determining the sensitivity of a species to a carbamate insecticide; (3) sensitivity may be a function of the ChE affinity for the carbamate inhibitor; and (4) the importance of neuromuscular junction ChE depression in determining the sensitivity of an animal may be species-specific.

Possible mechanisms for sensitivity to organophosphorus and carbamate insecticides in eastern screech-owls and American kestrels

USGS Publications Warehouse

Vyas, N.B.; Thiele, L.A.; Garland, S.C.

1998-01-01

Effects of a single dietary exposure to fenthion and carbofuran on the survival, feeding behavior and brain ChE activity of eastern screech-owls, Otus asio and American kestrels, Falco sparverius, were evaluated. Birds were exposed to fenthion (23.6–189.0 ppm) or carbofuran (31.7–253.6 ppm) via meatballs. Carbofuran-exposed owls ate either ≤10% or ≥80% of the meatball whereas all kestrels ate ≤10% of the meatball before exhibiting acute signs of toxicity. Fenthion-exposed owls and kestrels displayed a wide spectrum of meatball consumption (<10–100%). Significant brain ChE inhibition was observed in dead and surviving kestrels exposed to fenthion and carbofuran and dead owls exposed to fenthion (P<0.0001). Brain ChE activity of owls exposed to carbofuran that survived was not different from that of controls (P=0.25). Data suggest: (1) slow feeding on a carbamate-contaminated item may provide limited protection from the toxicity of the chemical at certain rates of exposure; (2) the degree of ChE inhibition at neuromuscular junctions may be critical in determining the sensitivity of a species to a carbamate insecticide; (3) sensitivity may be a function of the ChE affinity for the carbamate inhibitor; and (4) the importance of neuromuscular junction ChE depression in determining the sensitivity of an animal may be species-specific.

CT Evolution of Hematoma and Surrounding Hypodensity in a Cadaveric Model of Intracerebral Hemorrhage.

PubMed

Majidi, Shahram; Rahim, Basit; Gilani, Sarwat I; Gilani, Waqas I; Adil, Malik M; Qureshi, Adnan I

2016-05-01

The evolution of intracerebral hematoma and perihematoma edema in the ultra-early period on computed tomographic (CT) scans in patients with intracerebral hemorrhage (ICH) is not well understood. We aimed to investigate hematoma and perihematoma changes in "neutral brain" models of ICH. One human and five goat cadaveric heads were used as "neutral brains" to provide physical properties of brain without any biological activity or new bleeding. ICH was induced by slow injection of 4 ml of fresh human blood into the right basal ganglia of the goat brains. Similarly, 20 ml of fresh blood was injected deep into the white matter of the human cadaver head in each hemisphere. Serial CT scans of the heads were obtained immediately after hematoma induction and then 1, 3, and 5 hours afterward. Analyze software (AnalyzeDirect, Overland Park, KS, USA) was used to measure hematoma and perihematoma hypodensity volumes in the baseline and follow-up CT scans. The initial hematoma volumes of 11.6 ml and 10.5 ml in the right and left hemispheres of the cadaver brains gradually decreased to 6.6 ml and 5.4 ml at 5 hours, showing 43% and 48% retraction of hematoma, respectively. The volume of the perihematoma hypodensity in the right and left hemisphere increased from 2.6 ml and 2.2 ml in the 1-hour follow-up CT scans to 4.9 ml and 4.4 ml in the 5-hour CT scan, respectively. Hematoma retraction was also observed in all five goat brains ICH models with the mean ICH volume decreasing from 1.49 ml at baseline scan to 1.01 ml at the 5-hour follow-up CT scan (29.6% hematoma retraction). Perihematoma hypodensity was visualized in 70% of ICH in goat brains, with an increasing mean hypodensity volume of 0.4 ml in the baseline CT scan to 0.8 ml in the 5-hour follow-up CT scan. Our study demonstrated that substantial hematoma retraction and perihematoma hypodensity occurs in ICH in the absence of any new bleeding or biological activity of surrounding brain. Such observations suggest that active bleeding is underestimated in patients with no or small hematoma expansion and our understanding of perihematoma hypodensity needs to be reconsidered. Copyright © 2015 by the American Society of Neuroimaging.

A cerebellar thalamic cortical circuit for error-related cognitive control.

PubMed

Ide, Jaime S; Li, Chiang-shan R

2011-01-01

Error detection and behavioral adjustment are core components of cognitive control. Numerous studies have focused on the anterior cingulate cortex (ACC) as a critical locus of this executive function. Our previous work showed greater activation in the dorsal ACC and subcortical structures during error detection, and activation in the ventrolateral prefrontal cortex (VLPFC) during post-error slowing (PES) in a stop signal task (SST). However, the extent of error-related cortical or subcortical activation across subjects was not correlated with VLPFC activity during PES. So then, what causes VLPFC activation during PES? To address this question, we employed Granger causality mapping (GCM) and identified regions that Granger caused VLPFC activation in 54 adults performing the SST during fMRI. These brain regions, including the supplementary motor area (SMA), cerebellum, a pontine region, and medial thalamus, represent potential targets responding to errors in a way that could influence VLPFC activation. In confirmation of this hypothesis, the error-related activity of these regions correlated with VLPFC activation during PES, with the cerebellum showing the strongest association. The finding that cerebellar activation Granger causes prefrontal activity during behavioral adjustment supports a cerebellar function in cognitive control. Furthermore, multivariate GCA described the "flow of information" across these brain regions. Through connectivity with the thalamus and SMA, the cerebellum mediates error and post-error processing in accord with known anatomical projections. Taken together, these new findings highlight the role of the cerebello-thalamo-cortical pathway in an executive function that has heretofore largely been ascribed to the anterior cingulate-prefrontal cortical circuit. Copyright © 2010 Elsevier Inc. All rights reserved.

Lateralized hyperkinetic motor behavior.

PubMed

Krishnaiah, Balaji; Acharya, Jayant; Ahmed, Aiesha

2018-01-01

Seizures are followed by a post-ictal period, which is characterized by usual slowing of brain activity. This case report describes a 68-year old woman who presented with right-sided rhythmic, non-voluntary, semi-purposeful motor behavior that started 2 days after an episode of generalized seizure. Her initial electroencephalogram (EEG) showed beta activity with no evidence of epileptiform discharges. Computed tomography scan showed hypodensity in the left parieto-occipital region. Magnetic resonance imaging (MRI) showed restricted diffusion/fluid-attenuated inversion recovery hyperintensities in the left precentral and post-central gyrus. Unilateral compulsive motor behavior during the post-ictal state should be considered, and not confused with partial status epilepticus to avoid unnecessary treatment. Abnormal magnetic resonance imaging (MRI) findings, which are reversible, can help with the diagnostic and therapeutic approach.

Temporal Dynamics of Parvalbumin-Expressing Axo-axonic and Basket Cells in the Rat Medial Prefrontal Cortex In Vivo

PubMed Central

Hartwich, Katja; Borhegyi, Zsolt; Somogyi, Peter; Klausberger, Thomas

2015-01-01

Axo-axonic interneurons, innervating exclusively axon initial segments, and parvalbumin-expressing basket interneurons, targeting somata, dendrites, and spines of pyramidal cells, have been proposed to control neuronal activity in prefrontal circuits. We recorded the spike-timing of identified neurons in the prelimbic cortex of anesthetized rats, and show that axo-axonic cells increase their firing during tail pinch-induced brain state-activation. In addition, axo-axonic cells differ from other GABAergic parvalbumin-expressing cells in their spike timing during DOWN- to UP-state transitions of slow oscillations and in their coupling to gamma and spindle oscillations. The distinct firing dynamics and synaptic targets of axo-axonic and other parvalbumin-expressing cells provide differential contributions to the temporal organization of prefrontal networks. PMID:23152631

Glioblastoma—Unraveling the Threads to Make Progress

Cancer.gov

Progress against the brain cancer glioblastoma has been slow. In this Cancer Currents post, Drs. Mark Gilbert and Terri Armstrong of NCI’s Neuro-Oncology Branch discuss what’s being done to change that.

Early and Later Life Stress Alter Brain Activity and Sleep in Rats

PubMed Central

Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

2013-01-01

Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2–14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way. PMID:23922857

The Nucleus Reuniens Controls Long-Range Hippocampo-Prefrontal Gamma Synchronization during Slow Oscillations.

PubMed

Ferraris, Maëva; Ghestem, Antoine; Vicente, Ana F; Nallet-Khosrofian, Lauriane; Bernard, Christophe; Quilichini, Pascale P

2018-03-21

Gamma oscillations are involved in long-range coupling of distant regions that support various cognitive operations. Here we show in adult male rats that synchronized bursts of gamma oscillations bind the hippocampus (HPC) and prefrontal cortex (mPFC) during slow oscillations and slow-wave sleep, a brain state that is central for consolidation of memory traces. These gamma bursts entrained the firing of the local HPC and mPFC neuronal populations. Neurons of the nucleus reuniens (NR), which is a structural and functional hub between HPC and mPFC, demonstrated a specific increase in their firing before gamma burst onset, suggesting their involvement in HPC-mPFC binding. Chemical inactivation of NR disrupted the temporal pattern of gamma bursts and their synchronization, as well as mPFC neuronal firing. We propose that the NR drives long-range hippocampo-prefrontal coupling via gamma bursts providing temporal windows for information exchange between the HPC and mPFC during slow-wave sleep. SIGNIFICANCE STATEMENT Long-range coupling between hippocampus (HPC) and prefrontal cortex (mPFC) is believed to support numerous cognitive functions, including memory consolidation occurring during sleep. Gamma-band synchronization is a fundamental process in many neuronal operations and is instrumental in long-range coupling. Recent evidence highlights the role of nucleus reuniens (NR) in consolidation; however, how it influences hippocampo-prefrontal coupling is unknown. In this study, we show that HPC and mPFC are synchronized by gamma bursts during slow oscillations in anesthesia and natural sleep. By manipulating and recording the NR-HPC-mPFC network, we provide evidence that the NR actively promotes this long-range gamma coupling. This coupling provides the hippocampo-prefrontal circuit with a novel mechanism to exchange information during slow-wave sleep. Copyright © 2018 the authors 0270-6474/18/383026-13$15.00/0.

No effect of odor-induced memory reactivation during REM sleep on declarative memory stability

PubMed Central

Cordi, Maren J.; Diekelmann, Susanne; Born, Jan; Rasch, Björn

2014-01-01

Memory reactivations in hippocampal brain areas are critically involved in memory consolidation processes during sleep. In particular, specific firing patterns of hippocampal place cells observed during learning are replayed during subsequent sleep and rest in rodents. In humans, experimentally inducing hippocampal memory reactivations during slow-wave sleep (but not during wakefulness) benefits consolidation and immediately stabilizes declarative memories against future interference. Importantly, spontaneous hippocampal replay activity can also be observed during rapid eye movement (REM) sleep and some authors have suggested that replay during REM sleep is related to processes of memory consolidation. However, the functional role of reactivations during REM sleep for memory stability is still unclear. Here, we reactivated memories during REM sleep and examined its consequences for the stability of declarative memories. After 3 h of early, slow-wave sleep (SWS) rich sleep, 16 healthy young adults learned a 2-D object location task in the presence of a contextual odor. During subsequent REM sleep, participants were either re-exposed to the odor or to an odorless vehicle, in a counterbalanced within subject design. Reactivation was followed by an interference learning task to probe memory stability after awakening. We show that odor-induced memory reactivation during REM sleep does not stabilize memories against future interference. We propose that the beneficial effect of reactivation during sleep on memory stability might be critically linked to processes characterizing SWS including, e.g., slow oscillatory activity, sleep spindles, or low cholinergic tone, which are required for a successful redistribution of memories from medial temporal lobe regions to neocortical long-term stores. PMID:25225474

DCCA cross-correlation coefficients reveals the change of both synchronization and oscillation in EEG of Alzheimer disease patients

NASA Astrophysics Data System (ADS)

Chen, Yingyuan; Cai, Lihui; Wang, Ruofan; Song, Zhenxi; Deng, Bin; Wang, Jiang; Yu, Haitao

2018-01-01

Alzheimer's disease (AD) is a degenerative disorder of neural system that affects mainly the older population. Recently, many researches show that the EEG of AD patients can be characterized by EEG slowing, enhanced complexity of the EEG signals, and EEG synchrony. In order to examine the neural synchrony at multi scales, and to find a biomarker that help detecting AD in diagnosis, detrended cross-correlation analysis (DCCA) of EEG signals is applied in this paper. Several parameters, namely DCCA coefficients in the whole brain, DCCA coefficients at a specific scale, maximum DCCA coefficient over the span of all time scales and the corresponding scale of such coefficients, were extracted to examine the synchronization, respectively. The results show that DCCA coefficients have a trend of increase as scale increases, and decreases as electrode distance increases. Comparing DCCA coefficients in AD patients with healthy controls, a decrease of synchronization in the whole brain, and a bigger scale corresponding to maximum correlation is discovered in AD patients. The change of max-correlation scale may relate to the slowing of oscillatory activities. Linear combination of max DCCA coefficient and max-correlation scale reaches a classification accuracy of 90%. From the above results, it is reasonable to conclude that DCCA coefficient reveals the change of both oscillation and synchrony in AD, and thus is a powerful tool to differentiate AD patients from healthy elderly individuals.

Scalp-recorded slow EEG responses generated in response to hemodynamic changes in the human brain.

PubMed

Vanhatalo, S; Tallgren, P; Becker, C; Holmes, M D; Miller, J W; Kaila, K; Voipio, J

2003-09-01

To study whether hemodynamic changes in human brain generate scalp-EEG responses. Direct current EEG (DC-EEG) was recorded from 12 subjects during 5 non-invasive manipulations that affect intracranial hemodynamics by different mechanisms: bilateral jugular vein compression (JVC), head-up tilt (HUT), head-down tilt (HDT), Valsalva maneuver (VM), and Mueller maneuver (MM). DC shifts were compared to changes in cerebral blood volume (CBV) measured by near-infrared spectroscopy (NIRS). DC shifts were observed during all manipulations with highest amplitudes (up to 250 microV) at the midline electrodes, and the most pronounced changes (up to 15 microV/cm) in the DC voltage gradient around vertex. In spite of inter-individual variation in both amplitude and polarity, the DC shifts were consistent and reproducible for each subject and they showed a clear temporal correlation with changes in CBV. Our results indicate that hemodynamic changes in human brain are associated with marked DC shifts that cannot be accounted for by intracortical neuronal or glial currents. Instead, the data are consistent with a non-neuronal generator mechanism that is associated with the blood-brain barrier. These findings have direct implications for mechanistic interpretation of slow EEG responses in various experimental paradigms.

Long-Term Monitoring of Brain Dopamine Metabolism In Vivo with Carbon Paste Electrodes

PubMed Central

O'Neill, Robert D.

2005-01-01

This review focuses on the stability of voltammetric signals recorded over periods of months with carbon paste electrodes (CPEs) implanted in the brain. The key interaction underlying this stability is between the pasting oil and brain lipids that are capable of inhibiting the fouling caused by proteins. In brain regions receiving a significant dopaminergic input, a peak due to the methylated metabolites of dopamine, principally homovanillic acid (HVA), is clearly resolved using slow sweep voltammetry. Although a number of factors limit the time resolution for monitoring brain HVA concentration dynamics, the stability of CPEs allows investigations of long-term effects of drugs, as well as behavioral studies, not possible using other in-vivo monitoring techniques.

Pacemaker rate and depolarization block in nigral dopamine neurons: a somatic sodium channel balancing act

PubMed Central

Tucker, Kristal R.; Huertas, Marco A.; Horn, John P.; Canavier, Carmen C.; Levitan, Edwin S.

2012-01-01

Midbrain dopamine (DA) neurons are slow intrinsic pacemakers that undergo depolarization (DP) block upon moderate stimulation. Understanding DP block is important because it has been correlated with the clinical efficacy of chronic antipsychotic drug treatment. Here we describe how voltage-gated sodium (NaV) channels regulate DP block and pacemaker activity in DA neurons of the substantia nigra using rat brain slices. The distribution, density and gating of NaV currents were manipulated by blocking native channels with tetrodotoxin and by creating virtual channels and anti-channels with dynamic clamp. Although action potentials initiate in the axon initial segment (AIS) and NaV channels are distributed in multiple dendrites, selective reduction of NaV channel activity in the soma was sufficient to decrease pacemaker frequency and increase susceptibility to DP block. Conversely, increasing somatic NaV current density raised pacemaker frequency and lowered susceptibility to DP block. Finally, when NaV currents were restricted to the soma, pacemaker activity occurred at abnormally high rates due to excessive local subthreshold NaV current. Together with computational simulations, these data show that both the slow pacemaker rate and the sensitivity to DP block that characterizes DA neurons result from the low density of somatic NaV channels. More generally, we conclude that the somatodendritic distribution of NaV channels is a major determinant of repetitive spiking frequency. PMID:23077037

Role of the sodium pump in pacemaker generation in dog colonic smooth muscle.

PubMed Central

Barajas-López, C; Chow, E; Den Hertog, A; Huizinga, J D

1989-01-01

1. The role of the Na+ pump in the generation of slow wave activity in circular muscle of the dog colon was investigated using a partitioned 'Abe-Tomita' type chamber for voltage control. 2. Blockade of the Na+ pump by omission of extracellular K+, by ouabain, or the combination of 0 mM-Na+ and ouabain, depolarized the membrane up to approximately -40 mV and abolished the slow wave activity. Repolarization back to the control membrane potential by hyperpolarizing current restored the slow wave activity. 3. Slow waves continued to be present in 0 Na+, Li+ HEPES solution. 4. The depolarization induced by the procedures to block Na+ pump activity was associated with an increase in input membrane resistance. 5. Voltage-current relationships show the presence of an inward rectification. 6. Reduction of temperature depolarized the membrane, and decreased the slow wave frequency and amplitude. The slow wave amplitude was restored by repolarization of the membrane. 7. Brief depolarizing pulses evoked premature slow waves. Brief hyperpolarizing pulses terminated the slow waves. 8. We conclude that abolition of slow wave activity by Na+ pump blockade is a direct effect of membrane depolarization and that the Na+ pump is not responsible for the generation of the slow wave. 9. Our results are consistent with the hypothesis that pacemaker activity in smooth muscle is a consequence of membrane conductance changes which are metabolically dependent. PMID:2607455

Cognitive Slowing in Gulf War Illness Predicts Executive Network Hyperconnectivity: Study in a Population-Representative Sample.

PubMed

Turner, Monroe P; Hubbard, Nicholas A; Himes, Lyndahl M; Faghihahmadabadi, Shawheen; Hutchison, Joanna L; Bennett, Ilana J; Motes, Michael A; Haley, Robert W; Rypma, Bart

Cognitive slowing is a prevalent symptom observed in Gulf War Illness (GWI). The present study assessed the extent to which functional connectivity between dorsolateral prefrontal cortex (DLPFC) and other task-relevant brain regions was predictive of GWI-related cognitive slowing. GWI patients (n = 54) and healthy veteran controls (n = 29) were assessed on performance of a processing speed task (the Digit Symbol Substitution Task; DSST) while undergoing functional magnetic resonance imaging (fMRI). GWI patients were slower on the DSST relative to controls. Bilateral DLPFC connectivity with task-relevant nodes was altered in GWI patients compared to healthy controls during DSST performance. Moreover, hyperconnectivity in these networks predicted GWI-related increases in reaction time on the DSST, whereas hypoconnectivity did not. These results suggest that GWI-related cognitive slowing reflects reduced efficiency in cortical networks.

Structured Illumination Diffuse Optical Tomography for Mouse Brain Imaging

NASA Astrophysics Data System (ADS)

Reisman, Matthew David

As advances in functional magnetic resonance imaging (fMRI) have transformed the study of human brain function, they have also widened the divide between standard research techniques used in humans and those used in mice, where high quality images are difficult to obtain using fMRI given the small volume of the mouse brain. Optical imaging techniques have been developed to study mouse brain networks, which are highly valuable given the ability to study brain disease treatments or development in a controlled environment. A planar imaging technique known as optical intrinsic signal (OIS) imaging has been a powerful tool for capturing functional brain hemodynamics in rodents. Recent wide field-of-view implementations of OIS have provided efficient maps of functional connectivity from spontaneous brain activity in mice. However, OIS requires scalp retraction and is limited to imaging a 2-dimensional view of superficial cortical tissues. Diffuse optical tomography (DOT) is a non-invasive, volumetric neuroimaging technique that has been valuable for bedside imaging of patients in the clinic, but previous DOT systems for rodent neuroimaging have been limited by either sparse spatial sampling or by slow speed. My research has been to develop diffuse optical tomography for whole brain mouse neuroimaging by expanding previous techniques to achieve high spatial sampling using multiple camera views for detection and high speed using structured illumination sources. I have shown the feasibility of this method to perform non-invasive functional neuroimaging in mice and its capabilities of imaging the entire volume of the brain. Additionally, the system has been built with a custom, flexible framework to accommodate the expansion to imaging multiple dynamic contrasts in the brain and populations that were previously difficult or impossible to image, such as infant mice and awake mice. I have contributed to preliminary feasibility studies of these more advanced techniques using OIS, which can now be carried out using the structured illumination diffuse optical tomography technique to perform longitudinal, non-invasive studies of the whole volume of the mouse brain.

Caged Naloxone Reveals Opioid Signaling Deactivation Kinetics

PubMed Central

Banghart, Matthew R.; Shah, Ruchir C.; Lavis, Luke D.

2013-01-01

The spatiotemporal dynamics of opioid signaling in the brain remain poorly defined. Photoactivatable opioid ligands provide a means to quantitatively measure these dynamics and their underlying mechanisms in brain tissue. Although activation kinetics can be assessed using caged agonists, deactivation kinetics are obscured by slow clearance of agonist in tissue. To reveal deactivation kinetics of opioid signaling we developed a caged competitive antagonist that can be quickly photoreleased in sufficient concentrations to render agonist dissociation effectively irreversible. Carboxynitroveratryl-naloxone (CNV-NLX), a caged analog of the competitive opioid antagonist NLX, was readily synthesized from commercially available NLX in good yield and found to be devoid of antagonist activity at heterologously expressed opioid receptors. Photolysis in slices of rat locus coeruleus produced a rapid inhibition of the ionic currents evoked by multiple agonists of the μ-opioid receptor (MOR), but not of α-adrenergic receptors, which activate the same pool of ion channels. Using the high-affinity peptide agonist dermorphin, we established conditions under which light-driven deactivation rates are independent of agonist concentration and thus intrinsic to the agonist-receptor complex. Under these conditions, some MOR agonists yielded deactivation rates that are limited by G protein signaling, whereas others appeared limited by agonist dissociation. Therefore, the choice of agonist determines which feature of receptor signaling is unmasked by CNV-NLX photolysis. PMID:23960100

Subjective complaints after acquired brain injury: presentation of the Brain Injury Complaint Questionnaire (BICoQ).

PubMed

Vallat-Azouvi, Claire; Paillat, Cyrille; Bercovici, Stéphanie; Morin, Bénédicte; Paquereau, Julie; Charanton, James; Ghout, Idir; Azouvi, Philippe

2018-04-01

The objective of the present study was to present a new complaint questionnaire designed to assess a wide range of difficulties commonly reported by patients with acquired brain injury. Patients (n =  619) had been referred to a community re-entry service at a chronic stage after brain injury, mainly traumatic brain injury (TBI). The Brain Injury Complaint Questionnaire (BICoQ) includes 25 questions in the following domains: cognition, behavior, fatigue and sleep, mood, and somatic problems. A self and a proxy questionnaire were given. An additional question was given to the relative, about the patient's awareness of his difficulties. The questionnaires had a good internal coherence, as measured with Cronbach's alpha. The most frequent complaints were, in decreasing order, mental slowness, memory troubles, fatigue, concentration difficulties, anxiety, and dual tasking problems. Principal component analysis with varimax rotation yielded six underlying factors explaining 50.5% of total variance: somatic concerns, cognition, and lack of drive, lack of control, psycholinguistic disorders, mood, and mental fatigue/slowness. About 52% of patients reported fewer complaints than their proxy, suggesting lack of awareness. The total complaint scores were not significantly correlated with any injury severity measure, but were significantly correlated with disability and poorer quality of life (Note: only factor 2 [cognition/lack of drive] was significantly related to disability.) The BICoQ is a simple scale that can be used in addition to traditional clinical and cognitive assessment measures, and to assess awareness of everyday life problems. © 2017 Wiley Periodicals, Inc.

Electrical activity of the cingulate cortex. II. Cholinergic modulation.

PubMed

Borst, J G; Leung, L W; MacFabe, D F

1987-03-24

The role of the cholinergic innervation in the modulation of cingulate electrical activity was studied by means of pharmacological manipulations and brain lesions. In the normal rat, an irregular slow activity (ISA) accompanied with EEG-spikes was recorded in the cingulate cortex during immobility as compared to walking. Atropine sulfate, but not atropine methyl nitrate, increased ISA and the frequency of cingulate EEG-spikes. Pilocarpine suppressed ISA and EEG-spikes during immobility, and induced a slow (4-7 Hz) theta rhythm. Unilateral or bilateral lesions of the substantia innominata and ventral globus pallidus area using kainic acid did not significantly change the cingulate EEG or its relation to behavior. Large electrolytic lesions of the medial septal nuclei and vertical limbs of the diagonal band generally decreased or abolished all theta activity in the cingulate cortex and the hippocampus. However, in 5 rats the cingulate theta rhythm increased while the hippocampal theta disappeared after a medial septal lesion. The large, postlesion cingulate theta, accompanied by sharp EEG-spikes during its negative phase, is an unequivocal demonstration of the existence of a theta rhythm in the cingulate cortex, independent of the hippocampal rhythm. Cholinergic afferents from the medial septum and diagonal band nuclei are inferred to be responsible for the behavioral suppression of cingulate EEG-spikes and ISA, and partially for the generation of a local cingulate theta rhythm. However, an atropine-resistant pathway and a theta-suppressing pathway, possibly coming from the medial septum or the hippocampus, may also be important in cingulate theta generation.

Simultaneous Denoising, Deconvolution, and Demixing of Calcium Imaging Data

PubMed Central

Pnevmatikakis, Eftychios A.; Soudry, Daniel; Gao, Yuanjun; Machado, Timothy A.; Merel, Josh; Pfau, David; Reardon, Thomas; Mu, Yu; Lacefield, Clay; Yang, Weijian; Ahrens, Misha; Bruno, Randy; Jessell, Thomas M.; Peterka, Darcy S.; Yuste, Rafael; Paninski, Liam

2016-01-01

SUMMARY We present a modular approach for analyzing calcium imaging recordings of large neuronal ensembles. Our goal is to simultaneously identify the locations of the neurons, demix spatially overlapping components, and denoise and deconvolve the spiking activity from the slow dynamics of the calcium indicator. Our approach relies on a constrained nonnegative matrix factorization that expresses the spatiotemporal fluorescence activity as the product of a spatial matrix that encodes the spatial footprint of each neuron in the optical field and a temporal matrix that characterizes the calcium concentration of each neuron over time. This framework is combined with a novel constrained deconvolution approach that extracts estimates of neural activity from fluorescence traces, to create a spatiotemporal processing algorithm that requires minimal parameter tuning. We demonstrate the general applicability of our method by applying it to in vitro and in vivo multineuronal imaging data, whole-brain light-sheet imaging data, and dendritic imaging data. PMID:26774160

Inflammation and immune system activation in aging: a mathematical approach.

PubMed

Nikas, Jason B

2013-11-19

Memory and learning declines are consequences of normal aging. Since those functions are associated with the hippocampus, I analyzed the global gene expression data from post-mortem hippocampal tissue of 25 old (age ≥ 60 yrs) and 15 young (age ≤ 45 yrs) cognitively intact human subjects. By employing a rigorous, multi-method bioinformatic approach, I identified 36 genes that were the most significant in terms of differential expression; and by employing mathematical modeling, I demonstrated that 7 of the 36 genes were able to discriminate between the old and young subjects with high accuracy. Remarkably, 90% of the known genes from those 36 most significant genes are associated with either inflammation or immune system activation. This suggests that chronic inflammation and immune system over-activity may underlie the aging process of the human brain, and that potential anti-inflammatory treatments targeting those genes may slow down this process and alleviate its symptoms.

Memory improvement via slow-oscillatory stimulation during sleep in older adults.

PubMed

Westerberg, Carmen E; Florczak, Susan M; Weintraub, Sandra; Mesulam, M-Marsel; Marshall, Lisa; Zee, Phyllis C; Paller, Ken A

2015-09-01

We examined the intriguing but controversial idea that disrupted sleep-dependent consolidation contributes to age-related memory decline. Slow-wave activity during sleep may help strengthen neural connections and provide memories with long-term stability, in which case decreased slow-wave activity in older adults could contribute to their weaker memories. One prediction from this account is that age-related memory deficits should be reduced by artificially enhancing slow-wave activity. In young adults, applying transcranial current oscillating at a slow frequency (0.75 Hz) during sleep improves memory. Here, we tested whether this procedure can improve memory in older adults. In 2 sessions separated by 1 week, we applied either slow-oscillatory stimulation or sham stimulation during an afternoon nap in a double-blind, crossover design. Memory tests were administered before and after sleep. A larger improvement in word-pair recall and higher slow-wave activity was observed with slow-oscillatory stimulation than with sham stimulation. This is the first demonstration that this procedure can improve memory in older adults, suggesting that declarative memory performance in older adults is partly dependent on slow-wave activity during sleep. Copyright © 2015 Elsevier Inc. All rights reserved.

Differing Event-Related Patterns of Gamma-Band Power in Brain Waves of Fast- and Slow-Reacting Subjects

DTIC Science & Technology

1994-05-01

Wilhelm Wundt proposed that there are two types of subjects in sim- ple RT experiments: fast-reacting subjects, who respond before they fully...quickly as possible to auditory stimuli. This result appears to confirm long-standing speculations of Wundt that fast- and slow-reacting subjects...accord with the hypothesis of Wundt and others that slower ("sensorial") responders wait to fully perceive a stimulus and then react to their perception

Region-Specific Slowing of Alpha Oscillations is Associated with Visual-Perceptual Abilities in Children Born Very Preterm

PubMed Central

Doesburg, Sam M.; Moiseev, Alexander; Herdman, Anthony T.; Ribary, Urs; Grunau, Ruth E.

2013-01-01

Children born very preterm (≤32 weeks gestational age) without major intellectual or neurological impairments often express selective deficits in visual-perceptual abilities. The alterations in neurophysiological development underlying these problems, however, remain poorly understood. Recent research has indicated that spontaneous alpha oscillations are slowed in children born very preterm, and that atypical alpha-mediated functional network connectivity may underlie selective developmental difficulties in visual-perceptual ability in this group. The present study provides the first source-resolved analysis of slowing of spontaneous alpha oscillations in very preterm children, indicating alterations in a distributed set of brain regions concentrated in areas of posterior parietal and inferior temporal regions associated with visual perception, as well as prefrontal cortical regions and thalamus. We also uniquely demonstrate that slowing of alpha oscillations is associated with selective difficulties in visual-perceptual ability in very preterm children. These results indicate that region-specific slowing of alpha oscillations contribute to selective developmental difficulties prevalent in this population. PMID:24298250

Temperature-dependent regulation of vocal pattern generator.

PubMed

Yamaguchi, Ayako; Gooler, David; Herrold, Amy; Patel, Shailja; Pong, Winnie W

2008-12-01

Vocalizations of Xenopus laevis are generated by central pattern generators (CPGs). The advertisement call of male X. laevis is a complex biphasic motor rhythm consisting of fast and slow trills (a train of clicks). We found that the trill rate of these advertisement calls is sensitive to temperature and that this rate modification of the vocal rhythms originates in the central pattern generators. In vivo the rates of fast and slow trills increased linearly with an increase in temperature. In vitro a similar linear relation between temperature and compound action potential frequency in the laryngeal nerve was found when fictive advertisement calls were evoked in the isolated brain. Temperature did not limit the contractile properties of laryngeal muscles within the frequency range of vocalizations. We next took advantage of the temperature sensitivity of the vocal CPG in vitro to localize the source of the vocal rhythms. We focused on the dorsal tegmental area of the medulla (DTAM), a brain stem nucleus that is essential for vocal production. We found that bilateral cooling of DTAM reduced both fast and slow trill rates. Thus we conclude that DTAM is a source of biphasic vocal rhythms.

Diurnal influences on electrophysiological oscillations and coupling in the dorsal striatum and cerebellar cortex of the anesthetized rat

PubMed Central

Frederick, Ariana; Bourget-Murray, Jonathan; Chapman, C. Andrew; Amir, Shimon; Courtemanche, Richard

2014-01-01

Circadian rhythms modulate behavioral processes over a 24 h period through clock gene expression. What is largely unknown is how these molecular influences shape neural activity in different brain areas. The clock gene Per2 is rhythmically expressed in the striatum and the cerebellum and its expression is linked with daily fluctuations in extracellular dopamine levels and D2 receptor activity. Electrophysiologically, dopamine depletion enhances striatal local field potential (LFP) oscillations. We investigated if LFP oscillations and synchrony were influenced by time of day, potentially via dopamine mechanisms. To assess the presence of a diurnal effect, oscillatory power and coherence were examined in the striatum and cerebellum of rats under urethane anesthesia at four different times of day zeitgeber time (ZT1, 7, 13 and 19—indicating number of hours after lights turned on in a 12:12 h light-dark cycle). We also investigated the diurnal response to systemic raclopride, a D2 receptor antagonist. Time of day affected the proportion of LFP oscillations within the 0–3 Hz band and the 3–8 Hz band. In both the striatum and the cerebellum, slow oscillations were strongest at ZT1 and weakest at ZT13. A 3–8 Hz oscillation was present when the slow oscillation was lowest, with peak 3–8 Hz activity occurring at ZT13. Raclopride enhanced the slow oscillations, and had the greatest effect at ZT13. Within the striatum and with the cerebellum, 0–3 Hz coherence was greatest at ZT1, when the slow oscillations were strongest. Coherence was also affected the most by raclopride at ZT13. Our results suggest that neural oscillations in the cerebellum and striatum, and the synchrony between these areas, are modulated by time of day, and that these changes are influenced by dopamine manipulation. This may provide insight into how circadian gene transcription patterns influence network electrophysiology. Future experiments will address how these network alterations are linked with behavior. PMID:25309348

Right inferior frontal gyrus activation is associated with memory improvement in patients with left frontal low-grade glioma resection.

PubMed

Miotto, Eliane C; Balardin, Joana B; Vieira, Gilson; Sato, Joao R; Martin, Maria da Graça M; Scaff, Milberto; Teixeira, Manoel J; Junior, Edson Amaro

2014-01-01

Patients with low-grade glioma (LGG) have been studied as a model of functional brain reorganization due to their slow-growing nature. However, there is no information regarding which brain areas are involved during verbal memory encoding after extensive left frontal LGG resection. In addition, it remains unknown whether these patients can improve their memory performance after instructions to apply efficient strategies. The neural correlates of verbal memory encoding were investigated in patients who had undergone extensive left frontal lobe (LFL) LGG resections and healthy controls using fMRI both before and after directed instructions were given for semantic organizational strategies. Participants were scanned during the encoding of word lists under three different conditions before and after a brief period of practice. The conditions included semantically unrelated (UR), related-non-structured (RNS), and related-structured words (RS), allowing for different levels of semantic organization. All participants improved on memory recall and semantic strategy application after the instructions for the RNS condition. Healthy subjects showed increased activation in the left inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during encoding for the RNS condition after the instructions. Patients with LFL excisions demonstrated increased activation in the right IFG for the RNS condition after instructions were given for the semantic strategies. Despite extensive damage in relevant areas that support verbal memory encoding and semantic strategy applications, patients that had undergone resections for LFL tumor could recruit the right-sided contralateral homologous areas after instructions were given and semantic strategies were practiced. These results provide insights into changes in brain activation areas typically implicated in verbal memory encoding and semantic processing.

Subcortical roles in lexical task processing: Inferences from thalamic and subthalamic event-related potentials.

PubMed

Tiedt, Hannes O; Ehlen, Felicitas; Krugel, Lea K; Horn, Andreas; Kühn, Andrea A; Klostermann, Fabian

2017-01-01

Subcortical functions for language capacities are poorly defined, but may be investigated in the context of deep brain stimulation. Here, we studied event-related potentials recorded from electrodes in the subthalamic nucleus (STN) and the thalamic ventral intermediate nucleus (VIM) together with surface-EEG. Participants completed a lexical decision task (LDT), which required the differentiation of acoustically presented words from pseudo-words by button press. Target stimuli were preceded by prime-words. In recordings from VIM, a slow potential shift apparent at the lower electrode contacts persisted during target stimulus presentation (equally for words and pseudo-words). In contrast, recordings from STN electrodes showed a short local activation on prime-words but not target-stimuli. In both depth-recording regions, further components related to contralateral motor responses to target words were evident. On scalp level, mid-central activations on (pseudo)lexical stimuli were obtained, in line with the expression of N400 potentials. The prolonged activity recorded from VIM, exclusively accompanying the relevant LDT phase, is in line with the idea of thalamic "selective engagement" for supporting the realization of the behavioral focus demanded by the task. In contrast, the phasic prime related activity rather indicates "procedural" STN functions, for example, for trial sequencing or readiness inhibition of prepared target reactions. Hum Brain Mapp 38:370-383, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Extracellular levels of lactate, but not oxygen, reflect sleep homeostasis in the rat cerebral cortex.

PubMed

Dash, Michael B; Tononi, Giulio; Cirelli, Chiara

2012-07-01

It is well established that brain metabolism is higher during wake and rapid eye movement (REM) sleep than in nonrapid eye movement (NREM) sleep. Most of the brain's energy is used to maintain neuronal firing and glutamatergic transmission. Recent evidence shows that cortical firing rates, extracellular glutamate levels, and markers of excitatory synaptic strength increase with time spent awake and decline throughout NREM sleep. These data imply that the metabolic cost of each behavioral state is not fixed but may reflect sleep-wake history, a possibility that is investigated in the current report. Chronic (4d) electroencephalographic (EEG) recordings in the rat cerebral cortex were coupled with fixed-potential amperometry to monitor the extracellular concentration of oxygen ([oxy]) and lactate ([lac]) on a second-by-second basis across the spontaneous sleep-wake cycle and in response to sleep deprivation. Basic sleep research laboratory. Wistar Kyoto (WKY) adult male rats. N/A. Within 30-60 sec [lac] and [oxy] progressively increased during wake and REM sleep and declined during NREM sleep (n = 10 rats/metabolite), but with several differences. [Oxy], but not [lac], increased more during wake with high motor activity and/or elevated EEG high-frequency power. Meanwhile, only the NREM decline of [lac] reflected sleep pressure as measured by slow-wave activity, mirroring previous results for cortical glutamate. The observed state-dependent changes in cortical [lac] and [oxy] are consistent with higher brain metabolism during waking and REM sleep in comparison with NREM sleep. Moreover, these data suggest that glycolytic activity, most likely through its link with glutamatergic transmission, reflects sleep homeostasis.

Annotation: neurofeedback - train your brain to train behaviour.

PubMed

Heinrich, Hartmut; Gevensleben, Holger; Strehl, Ute

2007-01-01

Neurofeedback (NF) is a form of behavioural training aimed at developing skills for self-regulation of brain activity. Within the past decade, several NF studies have been published that tend to overcome the methodological shortcomings of earlier studies. This annotation describes the methodical basis of NF and reviews the evidence base for its clinical efficacy and effectiveness in neuropsychiatric disorders. In NF training, self-regulation of specific aspects of electrical brain activity is acquired by means of immediate feedback and positive reinforcement. In frequency training, activity in different EEG frequency bands has to be decreased or increased. Training of slow cortical potentials (SCPs) addresses the regulation of cortical excitability. NF studies revealed paradigm-specific effects on, e.g., attention and memory processes and performance improvements in real-life conditions, in healthy subjects as well as in patients. In several studies it was shown that children with attention-deficit hyperactivity disorder (ADHD) improved behavioural and cognitive variables after frequency (e.g., theta/beta) training or SCP training. Neurophysiological effects could also be measured. However, specific and unspecific training effects could not be disentangled in these studies. For drug-resistant patients with epilepsy, significant and long-lasting decreases of seizure frequency and intensity through SCP training were documented in a series of studies. For other child psychiatric disorders (e.g., tic disorders, anxiety, and autism) only preliminary investigations are available. There is growing evidence for NF as a valuable treatment module in neuropsychiatric disorders. Further, controlled studies are necessary to establish clinical efficacy and effectiveness and to learn more about the mechanisms underlying successful training.

Large-scale recording of thalamocortical circuits: in vivo electrophysiology with the two-dimensional electronic depth control silicon probe.

PubMed

Fiáth, Richárd; Beregszászi, Patrícia; Horváth, Domonkos; Wittner, Lucia; Aarts, Arno A A; Ruther, Patrick; Neves, Hercules P; Bokor, Hajnalka; Acsády, László; Ulbert, István

2016-11-01

Recording simultaneous activity of a large number of neurons in distributed neuronal networks is crucial to understand higher order brain functions. We demonstrate the in vivo performance of a recently developed electrophysiological recording system comprising a two-dimensional, multi-shank, high-density silicon probe with integrated complementary metal-oxide semiconductor electronics. The system implements the concept of electronic depth control (EDC), which enables the electronic selection of a limited number of recording sites on each of the probe shafts. This innovative feature of the system permits simultaneous recording of local field potentials (LFP) and single- and multiple-unit activity (SUA and MUA, respectively) from multiple brain sites with high quality and without the actual physical movement of the probe. To evaluate the in vivo recording capabilities of the EDC probe, we recorded LFP, MUA, and SUA in acute experiments from cortical and thalamic brain areas of anesthetized rats and mice. The advantages of large-scale recording with the EDC probe are illustrated by investigating the spatiotemporal dynamics of pharmacologically induced thalamocortical slow-wave activity in rats and by the two-dimensional tonotopic mapping of the auditory thalamus. In mice, spatial distribution of thalamic responses to optogenetic stimulation of the neocortex was examined. Utilizing the benefits of the EDC system may result in a higher yield of useful data from a single experiment compared with traditional passive multielectrode arrays, and thus in the reduction of animals needed for a research study. Copyright © 2016 the American Physiological Society.

Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity.

PubMed

Chéreau, Ronan; Saraceno, G Ezequiel; Angibaud, Julie; Cattaert, Daniel; Nägerl, U Valentin

2017-02-07

Axons convey information to nearby and distant cells, and the time it takes for action potentials (APs) to reach their targets governs the timing of information transfer in neural circuits. In the unmyelinated axons of hippocampus, the conduction speed of APs depends crucially on axon diameters, which vary widely. However, it is not known whether axon diameters are dynamic and regulated by activity-dependent mechanisms. Using time-lapse superresolution microscopy in brain slices, we report that axons grow wider after high-frequency AP firing: synaptic boutons undergo a rapid enlargement, which is mostly transient, whereas axon shafts show a more delayed and progressive increase in diameter. Simulations of AP propagation incorporating these morphological dynamics predicted bidirectional effects on AP conduction speed. The predictions were confirmed by electrophysiological experiments, revealing a phase of slowed down AP conduction, which is linked to the transient enlargement of the synaptic boutons, followed by a sustained increase in conduction speed that accompanies the axon shaft widening induced by high-frequency AP firing. Taken together, our study outlines a morphological plasticity mechanism for dynamically fine-tuning AP conduction velocity, which potentially has wide implications for the temporal transfer of information in the brain.

Hypothermia for the treatment of ischemic and hemorrhagic stroke.

PubMed

Linares, Guillermo; Mayer, Stephan A

2009-07-01

Hypothermia is considered nature's "gold standard" for neuroprotection, and its efficacy for improving outcome in patients with hypoxic-ischemic brain injury as a result of cardiac arrest is well-established. Hypothermia reduces brain edema and intracranial pressure in patients with traumatic brain injury. By contrast, only a few small pilot studies have evaluated hypothermia as a treatment for acute ischemic stroke, and no controlled trials of hypothermia for hemorrhagic stroke have been performed. Logistic challenges present an important barrier to the widespread application of hypothermia for stroke, most importantly the need for high-quality critical care to start immediately in the emergency department. Rapid induction of hypothermia within 3 to 6 hrs of onset has been hampered by slow cooling rates, but is feasible. Delayed cooling for the treatment of cytotoxic brain edema does not provide definitive or lasting treatment for intracranial mass effect, and should not be used as an alternative to hemicraniectomy. Sustained fever control is feasible in patients with intracerebral and subarachnoid hemorrhage, but has yet to be tested in a phase III study. Important observations from studies investigating the use of hypothermia for stroke to date include the necessity for proactive antishivering therapy for successful cooling, the importance of slow controlled rewarming to avoid rebound brain edema, and the high risk for infectious and cardiovascular complications in this patient population. More research is clearly needed to bring us closer to the successful application of hypothermia in the treatment for stroke.

Variable outcome for epilepsy after neonatal hypoglycaemia.

PubMed

Fong, Choong Yi; Harvey, A Simon

2014-11-01

To evaluate the electroclinical features of epilepsy secondary to neonatal hypoglycaemia. This was a retrospective study of children who had seizures beyond infancy after neonatal hypoglycaemia treated at The Royal Children's Hospital, Melbourne between 1996 and 2012. Patients with perinatal asphyxia were excluded. Clinical details were obtained from medical records. Digital electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were reviewed. Eleven patients met the inclusion criteria (six males, five females; mean age 10y 5mo, range 4-18y at the time of review). Age at seizure onset ranged from 4 months to 5 years. Seizures were focal occipital in nine and generalized tonic in two patients. MRI showed gliosis with or without cortical atrophy in the occipital lobe with or without parietal lobe in all. Predominant EEG findings were stereotyped occipital sharp-slow discharges in five, polymorphic occipital spike-wave or paroxysmal fast activity in three, and generalized slow spike-wave and fast activity in two. Seizures were infrequent or remitted in six of the nine children with focal occipital seizures, and frequent and refractory in both children with generalized seizures. Despite the common antecedent and bilateral occipital lobe injury, the seizure manifestations and course of epilepsy after neonatal hypoglycaemia were variable, with mild occipital, refractory occipital, and symptomatic generalized epilepsy recognized. © 2014 Mac Keith Press.

Cortical activity during cued picture naming predicts individual differences in stuttering frequency

PubMed Central

Mock, Jeffrey R.; Foundas, Anne L.; Golob, Edward J.

2016-01-01

Objective Developmental stuttering is characterized by fluent speech punctuated by stuttering events, the frequency of which varies among individuals and contexts. Most stuttering events occur at the beginning of an utterance, suggesting neural dynamics associated with stuttering may be evident during speech preparation. Methods This study used EEG to measure cortical activity during speech preparation in men who stutter, and compared the EEG measures to individual differences in stuttering rate as well as to a fluent control group. Each trial contained a cue followed by an acoustic probe at one of two onset times (early or late), and then a picture. There were two conditions: a speech condition where cues induced speech preparation of the picture’s name and a control condition that minimized speech preparation. Results Across conditions stuttering frequency correlated to cue-related EEG beta power and auditory ERP slow waves from early onset acoustic probes. Conclusions The findings reveal two new cortical markers of stuttering frequency that were present in both conditions, manifest at different times, are elicited by different stimuli (visual cue, auditory probe), and have different EEG responses (beta power, ERP slow wave). Significance The cue-target paradigm evoked brain responses that correlated to pre-experimental stuttering rate. PMID:27472545

Cortical activity during cued picture naming predicts individual differences in stuttering frequency.

PubMed

Mock, Jeffrey R; Foundas, Anne L; Golob, Edward J

2016-09-01

Developmental stuttering is characterized by fluent speech punctuated by stuttering events, the frequency of which varies among individuals and contexts. Most stuttering events occur at the beginning of an utterance, suggesting neural dynamics associated with stuttering may be evident during speech preparation. This study used EEG to measure cortical activity during speech preparation in men who stutter, and compared the EEG measures to individual differences in stuttering rate as well as to a fluent control group. Each trial contained a cue followed by an acoustic probe at one of two onset times (early or late), and then a picture. There were two conditions: a speech condition where cues induced speech preparation of the picture's name and a control condition that minimized speech preparation. Across conditions stuttering frequency correlated to cue-related EEG beta power and auditory ERP slow waves from early onset acoustic probes. The findings reveal two new cortical markers of stuttering frequency that were present in both conditions, manifest at different times, are elicited by different stimuli (visual cue, auditory probe), and have different EEG responses (beta power, ERP slow wave). The cue-target paradigm evoked brain responses that correlated to pre-experimental stuttering rate. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Practical Designs of Brain-Computer Interfaces Based on the Modulation of EEG Rhythms

NASA Astrophysics Data System (ADS)

Wang, Yijun; Gao, Xiaorong; Hong, Bo; Gao, Shangkai

A brain-computer interface (BCI) is a communication channel which does not depend on the brain's normal output pathways of peripheral nerves and muscles [1-3]. It supplies paralyzed patients with a new approach to communicate with the environment. Among various brain monitoring methods employed in current BCI research, electroencephalogram (EEG) is the main interest due to its advantages of low cost, convenient operation and non-invasiveness. In present-day EEG-based BCIs, the following signals have been paid much attention: visual evoked potential (VEP), sensorimotor mu/beta rhythms, P300 evoked potential, slow cortical potential (SCP), and movement-related cortical potential (MRCP). Details about these signals can be found in chapter "Brain Signals for Brain-Computer Interfaces". These systems offer some practical solutions (e.g., cursor movement and word processing) for patients with motor disabilities.

Astrocyte-derived adenosine is central to the hypnogenic effect of glucose

PubMed Central

Scharbarg, Emeric; Daenens, Marion; Lemaître, Frédéric; Geoffroy, Hélène; Guille-Collignon, Manon; Gallopin, Thierry; Rancillac, Armelle

2016-01-01

Sleep has been hypothesised to maintain a close relationship with metabolism. Here we focus on the brain structure that triggers slow-wave sleep, the ventrolateral preoptic nucleus (VLPO), to explore the cellular and molecular signalling pathways recruited by an increase in glucose concentration. We used infrared videomicroscopy on ex vivo brain slices to establish that glucose induces vasodilations specifically in the VLPO via the astrocytic release of adenosine. Real-time detection by in situ purine biosensors further revealed that the adenosine level doubles in response to glucose, and triples during the wakefulness period. Finally, patch-clamp recordings uncovered the depolarizing effect of adenosine and its A2A receptor agonist, CGS-21680, on sleep-promoting VLPO neurons. Altogether, our results provide new insights into the metabolically driven release of adenosine. We hypothesise that adenosine adjusts the local energy supply to local neuronal activity in response to glucose. This pathway could contribute to sleep-wake transition and sleep intensity. PMID:26755200

Distinct cortical codes and temporal dynamics for conscious and unconscious percepts

PubMed Central

Salti, Moti; Monto, Simo; Charles, Lucie; King, Jean-Remi; Parkkonen, Lauri; Dehaene, Stanislas

2015-01-01

The neural correlates of consciousness are typically sought by comparing the overall brain responses to perceived and unperceived stimuli. However, this comparison may be contaminated by non-specific attention, alerting, performance, and reporting confounds. Here, we pursue a novel approach, tracking the neuronal coding of consciously and unconsciously perceived contents while keeping behavior identical (blindsight). EEG and MEG were recorded while participants reported the spatial location and visibility of a briefly presented target. Multivariate pattern analysis demonstrated that considerable information about spatial location traverses the cortex on blindsight trials, but that starting ≈270 ms post-onset, information unique to consciously perceived stimuli, emerges in superior parietal and superior frontal regions. Conscious access appears characterized by the entry of the perceived stimulus into a series of additional brain processes, each restricted in time, while the failure of conscious access results in the breaking of this chain and a subsequent slow decay of the lingering unconscious activity. DOI: http://dx.doi.org/10.7554/eLife.05652.001 PMID:25997100

High Plasticity of New Granule Cells in the Aging Hippocampus.

PubMed

Trinchero, Mariela F; Buttner, Karina A; Sulkes Cuevas, Jessica N; Temprana, Silvio G; Fontanet, Paula A; Monzón-Salinas, M Cristina; Ledda, Fernanda; Paratcha, Gustavo; Schinder, Alejandro F

2017-10-31

During aging, the brain undergoes changes that impair cognitive capacity and circuit plasticity, including a marked decrease in production of adult-born hippocampal neurons. It is unclear whether development and integration of those new neurons are also affected by age. Here, we show that adult-born granule cells (GCs) in aging mice are scarce and exhibit slow development, but they display a remarkable potential for structural plasticity. Retrovirally labeled 3-week-old GCs in middle-aged mice were small, underdeveloped, and disconnected. Neuronal development and integration were accelerated by voluntary exercise or environmental enrichment. Similar effects were observed via knockdown of Lrig1, an endogenous negative modulator of neurotrophin receptors. Consistently, blocking neurotrophin signaling by Lrig1 overexpression abolished the positive effects of exercise. These results demonstrate an unparalleled degree of plasticity in the aging brain mediated by neurotrophins, whereby new GCs remain immature until becoming rapidly recruited to the network by activity. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Sleep confers a benefit for retention of statistical language learning in 6.5month old infants.

PubMed

Simon, Katharine N S; Werchan, Denise; Goldstein, Michael R; Sweeney, Lucia; Bootzin, Richard R; Nadel, Lynn; Gómez, Rebecca L

2017-04-01

Infants show robust ability to track transitional probabilities within language and can use this information to extract words from continuous speech. The degree to which infants remember these words across a delay is unknown. Given well-established benefits of sleep on long-term memory retention in adults, we examine whether sleep similarly facilitates memory in 6.5month olds. Infants listened to an artificial language for 7minutes, followed by a period of sleep or wakefulness. After a time-matched delay for sleep and wakefulness dyads, we measured retention using the head-turn-preference procedure. Infants who slept retained memory for the extracted words that was prone to interference during the test. Infants who remained awake showed no retention. Within the nap group, retention correlated with three electrophysiological measures (1) absolute theta across the brain, (2) absolute alpha across the brain, and (3) greater fronto-central slow wave activity (SWA). Copyright © 2016 Elsevier Inc. All rights reserved.

Imbalance of Hsp70 family variants fosters tau accumulation.

PubMed

Jinwal, Umesh K; Akoury, Elias; Abisambra, Jose F; O'Leary, John C; Thompson, Andrea D; Blair, Laura J; Jin, Ying; Bacon, Justin; Nordhues, Bryce A; Cockman, Matthew; Zhang, Juan; Li, Pengfei; Zhang, Bo; Borysov, Sergiy; Uversky, Vladimir N; Biernat, Jacek; Mandelkow, Eckhard; Gestwicki, Jason E; Zweckstetter, Markus; Dickey, Chad A

2013-04-01

Dysfunctional tau accumulation is a major contributing factor in tauopathies, and the heat-shock protein 70 (Hsp70) seems to play an important role in this accumulation. Several reports suggest that Hsp70 proteins can cause tau degradation to be accelerated or slowed, but how these opposing activities are controlled is unclear. Here we demonstrate that highly homologous variants in the Hsp70 family can have opposing effects on tau clearance kinetics. When overexpressed in a tetracycline (Tet)-based protein chase model, constitutive heat shock cognate 70 (Hsc70) and inducible Hsp72 slowed or accelerated tau clearance, respectively. Tau synergized with Hsc70, but not Hsp72, to promote microtubule assembly at nearly twice the rate of either Hsp70 homologue in reconstituted, ATP-regenerating Xenopus extracts supplemented with rhodamine-labeled tubulin and human recombinant Hsp72 and Hsc70. Nuclear magnetic resonance spectroscopy with human recombinant protein revealed that Hsp72 had greater affinity for tau than Hsc70 (I/I0 ratio difference of 0.3), but Hsc70 was 30 times more abundant than Hsp72 in human and mouse brain tissue. This indicates that the predominant Hsp70 variant in the brain is Hsc70, suggesting that the brain environment primarily supports slower tau clearance. Despite its capacity to clear tau, Hsp72 was not induced in the Alzheimer's disease brain, suggesting a mechanism for age-associated onset of the disease. Through the use of chimeras that blended the domains of Hsp72 and Hsc70, we determined that the reason for these differences between Hsc70 and Hsp72 with regard to tau clearance kinetics lies within their C-terminal domains, which are essential for their interactions with substrates and cochaperones. Hsp72 but not Hsc70 in the presence of tau was able to recruit the cochaperone ubiquitin ligase CHIP, which is known to facilitate the ubiquitination of tau, describing a possible mechanism of how the C-termini of these homologous Hsp70 variants can differentially regulate tau triage. Thus, efforts to promote Hsp72 expression and inhibit Hsc70 could be therapeutically relevant for tauopathies.

Pharmacology of the Nav1.1 domain IV voltage sensor reveals coupling between inactivation gating processes.

PubMed

Osteen, Jeremiah D; Sampson, Kevin; Iyer, Vivek; Julius, David; Bosmans, Frank

2017-06-27

The Na v 1.1 voltage-gated sodium channel is a critical contributor to excitability in the brain, where pathological loss of function leads to such disorders as epilepsy, Alzheimer's disease, and autism. This voltage-gated sodium (Na v ) channel subtype also plays an important role in mechanical pain signaling by primary afferent somatosensory neurons. Therefore, pharmacologic modulation of Na v 1.1 represents a potential strategy for treating excitability disorders of the brain and periphery. Inactivation is a complex aspect of Na v channel gating and consists of fast and slow components, each of which may involve a contribution from one or more voltage-sensing domains. Here, we exploit the Hm1a spider toxin, a Na v 1.1-selective modulator, to better understand the relationship between these temporally distinct modes of inactivation and ask whether they can be distinguished pharmacologically. We show that Hm1a inhibits the gating movement of the domain IV voltage sensor (VSDIV), hindering both fast and slow inactivation and leading to an increase in Na v 1.1 availability during high-frequency stimulation. In contrast, ICA-121431, a small-molecule Na v 1.1 inhibitor, accelerates a subsequent VSDIV gating transition to accelerate entry into the slow inactivated state, resulting in use-dependent block. Further evidence for functional coupling between fast and slow inactivation is provided by a Na v 1.1 mutant in which fast inactivation removal has complex effects on slow inactivation. Taken together, our data substantiate the key role of VSDIV in Na v channel fast and slow inactivation and demonstrate that these gating processes are sequential and coupled through VSDIV. These findings provide insight into a pharmacophore on VSDIV through which modulation of inactivation gating can inhibit or facilitate Na v 1.1 function.

Low Activity Microstates During Sleep.

PubMed

Miyawaki, Hiroyuki; Billeh, Yazan N; Diba, Kamran

2017-06-01

To better understand the distinct activity patterns of the brain during sleep, we observed and investigated periods of diminished oscillatory and population spiking activity lasting for seconds during non-rapid eye movement (non-REM) sleep, which we call "LOW" activity sleep. We analyzed spiking and local field potential (LFP) activity of hippocampal CA1 region alongside neocortical electroencephalogram (EEG) and electromyogram (EMG) in 19 sessions from four male Long-Evans rats (260-360 g) during natural wake/sleep across the 24-hr cycle as well as data from other brain regions obtained from http://crcns.org.1,2. LOW states lasted longer than OFF/DOWN states and were distinguished by a subset of "LOW-active" cells. LOW activity sleep was preceded and followed by increased sharp-wave ripple activity. We also observed decreased slow-wave activity and sleep spindles in the hippocampal LFP and neocortical EEG upon LOW onset, with a partial rebound immediately after LOW. LOW states demonstrated activity patterns consistent with sleep but frequently transitioned into microarousals and showed EMG and LFP differences from small-amplitude irregular activity during quiet waking. Their likelihood decreased within individual non-REM epochs yet increased over the course of sleep. By analyzing data from the entorhinal cortex of rats,1 as well as the hippocampus, the medial prefrontal cortex, the postsubiculum, and the anterior thalamus of mice,2 obtained from http://crcns.org, we confirmed that LOW states corresponded to markedly diminished activity simultaneously in all of these regions. We propose that LOW states are an important microstate within non-REM sleep that provide respite from high-activity sleep and may serve a restorative function. © Sleep Research Society 2017. Published by Oxford University Press [on behalf of the Sleep Research Society].

Targeting the Circadian Clock to Treat Cancer

Cancer.gov

Two compounds that target components of the circadian clock killed several types of cancer cells in the lab and slowed the growth of brain cancer in mice without harming healthy cells, as this Cancer Currents post reports.

Patient-Derived Antibody Targets Tumor Cells

Cancer.gov

An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

Facilitation of epileptic activity during sleep is mediated by high amplitude slow waves

PubMed Central

von Ellenrieder, Nicolás; Ferrari-Marinho, Taissa; Avoli, Massimo; Dubeau, François; Gotman, Jean

2015-01-01

Epileptic discharges in focal epilepsy are frequently activated during non-rapid eye movement sleep. Sleep slow waves are present during this stage and have been shown to include a deactivated (‘down’, hyperpolarized) and an activated state (‘up’, depolarized). The ‘up’ state enhances physiological rhythms, and we hypothesize that sleep slow waves and particularly the ‘up’ state are the specific components of non-rapid eye movement sleep that mediate the activation of epileptic activity. We investigated eight patients with pharmaco-resistant focal epilepsies who underwent combined scalp-intracerebral electroencephalography for diagnostic evaluation. We analysed 259 frontal electroencephalographic channels, and manually marked 442 epileptic spikes and 8487 high frequency oscillations during high amplitude widespread slow waves, and during matched control segments with low amplitude widespread slow waves, non-widespread slow waves or no slow waves selected during the same sleep stages (total duration of slow wave and control segments: 49 min each). During the slow waves, spikes and high frequency oscillations were more frequent than during control segments (79% of spikes during slow waves and 65% of high frequency oscillations, both P ∼ 0). The spike and high frequency oscillation density also increased for higher amplitude slow waves. We compared the density of spikes and high frequency oscillations between the ‘up’ and ‘down’ states. Spike and high frequency oscillation density was highest during the transition from the ‘up’ to the ‘down’ state. Interestingly, high frequency oscillations in channels with normal activity expressed a different peak at the transition from the ‘down’ to the ‘up’ state. These results show that the apparent activation of epileptic discharges by non-rapid eye movement sleep is not a state-dependent phenomenon but is predominantly associated with specific events, the high amplitude widespread slow waves that are frequent, but not continuous, during this state of sleep. Both epileptic spikes and high frequency oscillations do not predominate, like physiological activity, during the ‘up’ state but during the transition from the ‘up’ to the ‘down’ state of the slow wave, a period of high synchronization. Epileptic discharges appear therefore more associated with synchronization than with excitability. Furthermore, high frequency oscillations in channels devoid of epileptic activity peak differently during the slow wave cycle from those in channels with epileptic activity. This property may allow differentiating physiological from pathological high frequency oscillations, a problem that is unresolved until now. PMID:25792528

Computerized measures of finger tapping: reliability, malingering and traumatic brain injury.

PubMed

Hubel, Kerry A; Yund, E William; Herron, Timothy J; Woods, David L

2013-01-01

We analyzed computerized finger tapping metrics in four experiments. Experiment 1 showed tapping-rate differences associated with hand dominance, digits, sex, and fatigue that replicated those seen in a previous, large-scale community sample. Experiment 2 revealed test-retest correlations (r = .91) that exceeded those reported in previous tapping studies. Experiment 3 investigated subjects simulating symptoms of traumatic brain injury (TBI); 62% of malingering subjects produced abnormally slow tapping rates. A tapping-rate malingering index, based on rate-independent tapping patterns, provided confirmatory evidence of malingering in 48% of the subjects with abnormal tapping rates. Experiment 4 compared tapping in 24 patients with mild TBI (mTBI) and a matched control group; mTBI patients showed slowed tapping without evidence of malingering. Computerized finger tapping measures are reliable measures of motor speed, useful in detecting subjects performing with suboptimal effort, and are sensitive to motor abnormalities following mTBI.

Circadian regulation of slow waves in human sleep: Topographical aspects

PubMed Central

Lazar, Alpar S.; Lazar, Zsolt I.; Dijk, Derk-Jan

2015-01-01

Slow waves (SWs, 0.5–4 Hz) in field potentials during sleep reflect synchronized alternations between bursts of action potentials and periods of membrane hyperpolarization of cortical neurons. SWs decline during sleep and this is thought to be related to a reduction of synaptic strength in cortical networks and to be central to sleep's role in maintaining brain function. A central assumption in current concepts of sleep function is that SWs during sleep, and associated recovery processes, are independent of circadian rhythmicity. We tested this hypothesis by quantifying all SWs from 12 EEG derivations in 34 participants in whom 231 sleep periods were scheduled across the circadian cycle in a 10-day forced-desynchrony protocol which allowed estimation of the separate circadian and sleep-dependent modulation of SWs. Circadian rhythmicity significantly modulated the incidence, amplitude, frequency and the slope of the SWs such that the peaks of the circadian rhythms in these slow-wave parameters were located during the biological day. Topographical analyses demonstrated that the sleep-dependent modulation of SW characteristics was most prominent in frontal brain areas whereas the circadian effect was similar to or greater than the sleep-dependent modulation over the central and posterior brain regions. The data demonstrate that circadian rhythmicity directly modulates characteristics of SWs thought to be related to synaptic plasticity and that this modulation depends on topography. These findings have implications for the understanding of local sleep regulation and conditions such as ageing, depression, and neurodegeneration which are associated with changes in SWs, neural plasticity and circadian rhythmicity. PMID:25979664

Advanced Glycation End-Products and Their Receptor-Mediated Roles: Inflammation and Oxidative Stress

PubMed Central

Younessi, Parisa; Yoonessi, Ali

2011-01-01

Glycation is a protein modification, which results in a change in a protein structure. Glycation is believed to be the etiology of various age-related diseases such as diabetes mellitus and Alzheimer’s disease (AD). Activation of microglia and resident macrophages in the brain by glycated proteins with subsequent oxidative stress and cytokine release may be an important factor in the progression of AD. It is also suggested that interaction between an advanced glycation end product (AGE) and its receptor (RAGE) results in glial activation as well as cytokine release and reactive oxygen species release. The use of antioxidants, receptor mediated compounds and reactive oxygen species scavenging enzyme produce an opportunity to intervene with AGE-RAGE signaling pathway, and thereby to slow down the progression of aging-related diseases. PMID:23358382

To select or to wait? The importance of criterion setting in debates of competitive lexical selection.

PubMed

Nozari, Nazbanou; Hepner, Christopher R

2018-06-05

Competitive accounts of lexical selection propose that the activation of competitors slows down the selection of the target. Non-competitive accounts, on the other hand, posit that target response latencies are independent of the activation of competing items. In this paper, we propose a signal detection framework for lexical selection and show how a flexible selection criterion affects claims of competitive selection. Specifically, we review evidence from neurotypical and brain-damaged speakers and demonstrate that task goals and the state of the production system determine whether a competitive or a non-competitive selection profile arises. We end by arguing that there is conclusive evidence for a flexible criterion in lexical selection, and that integrating criterion shifts into models of language production is critical for evaluating theoretical claims regarding (non-)competitive selection.

Proactive Control: Neural Oscillatory Correlates of Conflict Anticipation and Response Slowing.

PubMed

Chang, Andrew; Ide, Jaime S; Li, Hsin-Hung; Chen, Chien-Chung; Li, Chiang-Shan R

2017-01-01

Proactive control allows us to anticipate environmental changes and adjust behavioral strategy. In the laboratory, investigators have used a number of different behavioral paradigms, including the stop-signal task (SST), to examine the neural processes of proactive control. Previous functional MRI studies of the SST have demonstrated regional responses to conflict anticipation-the likelihood of a stop signal or P(stop) as estimated by a Bayesian model-and reaction time (RT) slowing and how these responses are interrelated. Here, in an electrophysiological study, we investigated the time-frequency domain substrates of proactive control. The results showed that conflict anticipation as indexed by P(stop) was positively correlated with the power in low-theta band (3-5 Hz) in the fixation (trial onset)-locked interval, and go-RT was negatively correlated with the power in delta-theta band (2-8 Hz) in the go-locked interval. Stimulus prediction error was positively correlated with the power in the low-beta band (12-22 Hz) in the stop-locked interval. Further, the power of the P(stop) and go-RT clusters was negatively correlated, providing a mechanism relating conflict anticipation to RT slowing in the SST. Source reconstruction with beamformer localized these time-frequency activities close to brain regions as revealed by functional MRI in earlier work. These are the novel results to show oscillatory electrophysiological substrates in support of trial-by-trial behavioral adjustment for proactive control.

Asynchronous Rate Chaos in Spiking Neuronal Circuits

PubMed Central

Harish, Omri; Hansel, David

2015-01-01

The brain exhibits temporally complex patterns of activity with features similar to those of chaotic systems. Theoretical studies over the last twenty years have described various computational advantages for such regimes in neuronal systems. Nevertheless, it still remains unclear whether chaos requires specific cellular properties or network architectures, or whether it is a generic property of neuronal circuits. We investigate the dynamics of networks of excitatory-inhibitory (EI) spiking neurons with random sparse connectivity operating in the regime of balance of excitation and inhibition. Combining Dynamical Mean-Field Theory with numerical simulations, we show that chaotic, asynchronous firing rate fluctuations emerge generically for sufficiently strong synapses. Two different mechanisms can lead to these chaotic fluctuations. One mechanism relies on slow I-I inhibition which gives rise to slow subthreshold voltage and rate fluctuations. The decorrelation time of these fluctuations is proportional to the time constant of the inhibition. The second mechanism relies on the recurrent E-I-E feedback loop. It requires slow excitation but the inhibition can be fast. In the corresponding dynamical regime all neurons exhibit rate fluctuations on the time scale of the excitation. Another feature of this regime is that the population-averaged firing rate is substantially smaller in the excitatory population than in the inhibitory population. This is not necessarily the case in the I-I mechanism. Finally, we discuss the neurophysiological and computational significance of our results. PMID:26230679

Examining the impact of grape consumption on brain metabolism and cognitive function in patients with mild decline in cognition: A double-blinded placebo controlled pilot study.

PubMed

Lee, Jooyeon; Torosyan, Nare; Silverman, Daniel H

2017-01-01

Natural compounds in grapes such as resveratrol are known for their antioxidant and anti-inflammatory properties. Some studies have shown a potential role for grapes or wine in slowing cognitive decline and other effects of aging. However, well-controlled experimental data obtained in human subjects are still in need of further development. Here we aimed to systematically assess effects of grapes on regional cerebral metabolism. Ten subjects with mild decline in cognition (mean, 72.2±4.7years; 50% female) were included in this analysis. Participants were randomized into an active grape formulation arm or a placebo arm which consumed a formulation free of polyphenols for six months. Cognitive performance was measured through neuropsychological assessments performed at baseline and 6months after initiation of therapy. Changes in brain metabolism occurring with each therapy regimen were assessed by brain PET scans with the radiotracer [F-18] fluorodeoxyglucose (FDG), obtained during initial evaluation and 6months later. Standardized volumes of interest (sVOI) and statistical parametric mapping (SPM) methods were applied to FDG-PET scans to identify significant regional cerebral metabolic changes. In contrast to participants taking the active grape formulation, who displayed no significant decline in metabolism, the placebo arm underwent significant metabolic decline in sVOI's of the right posterior cingulate cortex (p=0.01), and left superior posterolateral temporal cortex (p=0.04). SPM analyses also found significant declines in the placebo group, particularly in left prefrontal, cingulate, and left superior posterolateral temporal cortex (p<0.01) with stable brain metabolism in the active formulation arm. No significant differences were seen in scores on the neuropsychological battery of tests between the two groups. However, metabolism in right superior parietal cortex and left inferior anterior temporal cortex was correlated with improvements in attention/working memory, as measured with WAIS-III Digital Span within the active formulation group (r=-0.69, p=0.04). The placebo arm had declines in regions of the brain known to be significantly affected in the early stages of Alzheimer's disease, while the active formulation group was spared such decline. This suggests a protective effect of grapes against early pathologic metabolic decline. Copyright © 2016 Elsevier Inc. All rights reserved.

Integrating Health Promotion Into Physical Therapy Practice to Improve Brain Health and Prevent Alzheimer Disease.

PubMed

McGough, Ellen; Kirk-Sanchez, Neva; Liu-Ambrose, Teresa

2017-07-01

Alzheimer disease is the most common cause of dementia, and brain pathology appears years before symptoms are evident. Primary prevention through health promotion can incorporate lifestyle improvement across the lifespan. Risk factor assessment and identifying markers of disease might also trigger preventive measures needed for high-risk individuals and groups. Many potential risk factors are modifiable through exercise, and may be responsive to early intervention strategies to reduce the downward slope toward disability. Through the use of common clinical tests to identify cognitive and noncognitive functional markers of disease, detection and intervention can occur at earlier stages, including preclinical stages of disease. Physical activity and exercise interventions to address modifiable risk factors and impairments can play a pivotal role in the prevention and delay of functional decline, ultimately reducing the incidence of dementia. This article discusses prevention, prediction, plasticity, and participation in the context of preserving brain health and preventing Alzheimer disease and related dementias in aging adults. Rehabilitation professionals have opportunities to slow disease progression through research, practice, and education initiatives. From a clinical perspective, interventions that target brain health through lifestyle changes and exercise interventions show promise for preventing stroke and associated neurovascular diseases in addition to dementia. Physical therapists are well positioned to integrate primary health promotion into practice for the prevention of dementia and other neurological conditions in older adults.

Encephalopathy Associated with Influenza B in a Healthy Young Man.

PubMed

Shimamoto, Masaki; Okada, Satoshi; Terashima, Takeshi

2017-01-01

A 19-year-old man presented with a fever, convulsions, and loss of consciousness at our hospital. The patient had a Glasgow Coma Scale score of 12. Influenza B virus infection was diagnosed using the rapid test kit, and an eight-fold increase in the serum levels of anti-influenza B virus antibody was confirmed using the complement fixation test. Brain magnetic resonance imaging showed multifocal high-signal lesions, and an electroencephalogram showed diffuse slowing of the background activity, indicating acute encephalopathy. After treatment with peramivir and methylprednisolone for 3 days, the patient was discharged without any neurological impairment. This was a case of influenza B infection associated with acute encephalopathy in a healthy young man.

Concussion management in collegiate student-athletes: return-to-academics recommendations.

PubMed

Hall, Eric E; Ketcham, Caroline J; Crenshaw, Cayce R; Baker, Martin H; McConnell, Jodi M; Patel, Kirtida

2015-05-01

Concussions in collegiate athletics can affect student-athletes both on the field and in the classroom. As policies are made to outline return-to-play decisions and timelines, this article will make the case that return-to-academics should also be included and follow a step-wise protocol. Complete cognitive rest is a cornerstone of concussion recovery and slow reintroduction to academics should precede return-to-play. The college structure allows for student-athletes to begin small doses of cognitive activity after the recommended complete cognitive rest. It is recommended that return-to-academics involves a team approach to help the student-athlete navigate the responsibilities of course work while healing from a brain injury.

[Biofeedback treatment for epilepsy].

PubMed

Nagai, Yoko

2014-05-01

Pharmacological treatment is the mainstay for the treatment of epilepsy. However concerns regarding long-term side effects of drugs are increasingly voiced. Behavioral treatments including biofeedback, represents an alternative management option for the control of epilepsy. Biofeedback is a non-invasive bio-behavioral procedure through which patients can learn to gain psychophysiological control over seizures. This article will first overview seizure precipitation from a psychological perspective, and then introduce three major biofeedback treatments. Sensory motor rhythm (SMR) and slow cortical potential(SCP) biofeedback uses electroencephalographic parameters and are categorized as neurofeedback. Electrodermal activity (EDA) biofeedback focuses on modulation of peripheral sympathetic tone. The neural mechanisms underlying biofeedback treatment will be discussed in relation to thalamo-cortical regulation(of neural excitability across brain networks).

Update of sleep alterations in depression

PubMed Central

Medina, Andrés Barrera; Lechuga, DeboraYoaly Arana; Escandón, Oscar Sánchez; Moctezuma, Javier Velázquez

2014-01-01

Sleep disturbances in depression are up to 70%. Patients frequently have difficulty in falling asleep, frequent awakenings during the night and non-restorative sleep. Sleep abnormalities in depression are mainly characterized by increased rapid eye movement (REM) sleep and reduced slow wave sleep. Among the mechanisms of sleep disturbances in depression are hyperactivation of the hypothalamic-pituitary-adrenal axis, CLOCK gene polymorphism and primary sleep disorders. The habenula is a structure regulating the activities of monoaminergic neurons in the brain. The hyperactivation of the habenula has also been implicated, together with sleep disturbances, in depression. The presence of depression in primary sleep disorders is common. Sleep disturbances treatment include pharmacotherapy or Cognitive Behavioral Therapy. PMID:26483922

Can passive mobilization provide clinically-relevant brain stimulation? A pilot EEG and NIRS study on healthy subjects.

PubMed

Pittaccio, Simone; Garavaglia, Lorenzo; Molteni, Erika; Guanziroli, Eleonora; Zappasodi, Filippo; Beretta, Elena; Strazzer, Sandra; Molteni, Franco; Villa, Elena; Passaretti, Francesca

2013-01-01

Lower limb rehabilitation is a fundamental part of post-acute care in neurological disease. Early commencement of active workout is often prevented by paresis, thus physical treatment may be delayed until patients regain some voluntary command of their muscles. Passive mobilization of the affected joints is mostly delivered in order to safeguard tissue properties and shun circulatory problems. The present paper investigates the potential role of early passive motion in stimulating cortical areas of the brain devoted to the control of the lower limb. An electro-mechanical mobilizer for the ankle joint (Toe-Up!) was implemented utilizing specially-designed shape-memory-alloy-based actuators. This device was constructed to be usable by bedridden subjects. Besides, the slowness and gentleness of the imparted motion, make it suitable for patients in a very early stage of their recovery. The mobilizer underwent technical checks to confirm reliability and passed the required safety tests for electric biomedical devices. Four healthy volunteers took part in the pre-clinical phase of the study. The protocol consisted in measuring of brain activity by EEG and NIRS in four different conditions: rest, active dorsiflexion of the ankle, passive mobilization of the ankle, and assisted motion of the same joint. The acquired data were processed to obtain maps of cortical activation, which were then compared. The measurements collected so far show that there is a similar pattern of activity between active and passive/assisted particularly in the contralateral premotor areas. This result, albeit based on very few observations, might suggest that passive motion provides somatosensory afferences that are processed in a similar manner as for voluntary control. Should this evidence be confirmed by further trials on healthy individuals and neurological patients, it could form a basis for a clinical use of early passive exercise in supporting central functional recovery.

Endocannabinoids in Liver Disease

PubMed Central

Tam, Joseph; Liu, Jie; Mukhopadhyay, Bani; Cinar, Resat; Godlewski, Grzegorz; Kunos, George

2010-01-01

Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana. The endocannabinoid system (ECS) consists of CB receptors, endocannabinoids, and the enzymes involved in their biosynthesis and degradation, and is present both in brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases, which contributes to the underlying pathologies. In cirrhosis of various etiologies, activation of vascular and cardiac CB1 receptors by macrophage- and platelet-derived endocannabinoids contribute to the vasodilated state and cardiomyopathy, which can be reversed by CB1 blockade. In mouse models of liver fibrosis, activation of CB1 receptors on hepatic stellate cells is fibrogenic, and CB1 blockade slows the progression of fibrosis. Fatty liver induced by high-fat diets or chronic alcohol feeding depend on activation of peripheral, including hepatic CB1 receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB1 blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB1 antagonists. PMID:21254182

Dementia

MedlinePlus

... elderly people, it is not part of normal aging. Many different diseases can cause dementia, including Alzheimer's disease and stroke. Drugs are available to treat some of these diseases. While these drugs cannot cure dementia or repair brain damage, they may improve symptoms or slow down ...

Effects of Different Correlation Metrics and Preprocessing Factors on Small-World Brain Functional Networks: A Resting-State Functional MRI Study

PubMed Central

Liang, Xia; Wang, Jinhui; Yan, Chaogan; Shu, Ni; Xu, Ke; Gong, Gaolang; He, Yong

2012-01-01

Graph theoretical analysis of brain networks based on resting-state functional MRI (R-fMRI) has attracted a great deal of attention in recent years. These analyses often involve the selection of correlation metrics and specific preprocessing steps. However, the influence of these factors on the topological properties of functional brain networks has not been systematically examined. Here, we investigated the influences of correlation metric choice (Pearson's correlation versus partial correlation), global signal presence (regressed or not) and frequency band selection [slow-5 (0.01–0.027 Hz) versus slow-4 (0.027–0.073 Hz)] on the topological properties of both binary and weighted brain networks derived from them, and we employed test-retest (TRT) analyses for further guidance on how to choose the “best” network modeling strategy from the reliability perspective. Our results show significant differences in global network metrics associated with both correlation metrics and global signals. Analysis of nodal degree revealed differing hub distributions for brain networks derived from Pearson's correlation versus partial correlation. TRT analysis revealed that the reliability of both global and local topological properties are modulated by correlation metrics and the global signal, with the highest reliability observed for Pearson's-correlation-based brain networks without global signal removal (WOGR-PEAR). The nodal reliability exhibited a spatially heterogeneous distribution wherein regions in association and limbic/paralimbic cortices showed moderate TRT reliability in Pearson's-correlation-based brain networks. Moreover, we found that there were significant frequency-related differences in topological properties of WOGR-PEAR networks, and brain networks derived in the 0.027–0.073 Hz band exhibited greater reliability than those in the 0.01–0.027 Hz band. Taken together, our results provide direct evidence regarding the influences of correlation metrics and specific preprocessing choices on both the global and nodal topological properties of functional brain networks. This study also has important implications for how to choose reliable analytical schemes in brain network studies. PMID:22412922

Cholinergic left-right asymmetry in the habenulo-interpeduncular pathway.

PubMed

Hong, Elim; Santhakumar, Kirankumar; Akitake, Courtney A; Ahn, Sang Jung; Thisse, Christine; Thisse, Bernard; Wyart, Claire; Mangin, Jean-Marie; Halpern, Marnie E

2013-12-24

The habenulo-interpeduncular pathway, a highly conserved cholinergic system, has emerged as a valuable model to study left-right asymmetry in the brain. In larval zebrafish, the bilaterally paired dorsal habenular nuclei (dHb) exhibit prominent left-right differences in their organization, gene expression, and connectivity, but their cholinergic nature was unclear. Through the discovery of a duplicated cholinergic gene locus, we now show that choline acetyltransferase and vesicular acetylcholine transporter homologs are preferentially expressed in the right dHb of larval zebrafish. Genes encoding the nicotinic acetylcholine receptor subunits α2 and β4 are transcribed in the target interpeduncular nucleus (IPN), suggesting that the asymmetrical cholinergic pathway is functional. To confirm this, we activated channelrhodopsin-2 specifically in the larval dHb and performed whole-cell patch-clamp recording of IPN neurons. The response to optogenetic or electrical stimulation of the right dHb consisted of an initial fast glutamatergic excitatory postsynaptic current followed by a slow-rising cholinergic current. In adult zebrafish, the dHb are divided into discrete cholinergic and peptidergic subnuclei that differ in size between the left and right sides of the brain. After exposing adults to nicotine, fos expression was activated in subregions of the IPN enriched for specific nicotinic acetylcholine receptor subunits. Our studies of the newly identified cholinergic gene locus resolve the neurotransmitter identity of the zebrafish habenular nuclei and reveal functional asymmetry in a major cholinergic neuromodulatory pathway of the vertebrate brain.

Functional and Structural Correlates of Motor Speed in the Cerebellar Anterior Lobe

PubMed Central

Wenzel, Uwe; Taubert, Marco; Ragert, Patrick; Krug, Jürgen; Villringer, Arno

2014-01-01

In athletics, motor performance is determined by different abilities such as technique, endurance, strength and speed. Based on animal studies, motor speed is thought to be encoded in the basal ganglia, sensorimotor cortex and the cerebellum. The question arises whether there is a unique structural feature in the human brain, which allows “power athletes” to perform a simple foot movement significantly faster than “endurance athletes”. We acquired structural and functional brain imaging data from 32 track-and-field athletes. The study comprised of 16 “power athletes” requiring high speed foot movements (sprinters, jumpers, throwers) and 16 endurance athletes (distance runners) which in contrast do not require as high speed foot movements. Functional magnetic resonance imaging (fMRI) was used to identify speed specific regions of interest in the brain during fast and slow foot movements. Anatomical MRI scans were performed to assess structural grey matter volume differences between athletes groups (voxel based morphometry). We tested maximum movement velocity of plantarflexion (PF-Vmax) and acquired electromyographical activity of the lateral and medial gastrocnemius muscle. Behaviourally, a significant difference between the two groups of athletes was noted in PF-Vmax and fMRI indicates that fast plantarflexions are accompanied by increased activity in the cerebellar anterior lobe. The same region indicates increased grey matter volume for the power athletes compared to the endurance counterparts. Our results suggest that speed-specific neuro-functional and -structural differences exist between power and endurance athletes in the peripheral and central nervous system. PMID:24800742

Muscle fiber type specific induction of slow myosin heavy chain 2 gene expression by electrical stimulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crew, Jennifer R.; Falzari, Kanakeshwari; DiMario, Joseph X., E-mail: joseph.dimario@rosalindfranklin.edu

Vertebrate skeletal muscle fiber types are defined by a broad array of differentially expressed contractile and metabolic protein genes. The mechanisms that establish and maintain these different fiber types vary throughout development and with changing functional demand. Chicken skeletal muscle fibers can be generally categorized as fast and fast/slow based on expression of the slow myosin heavy chain 2 (MyHC2) gene in fast/slow muscle fibers. To investigate the cellular and molecular mechanisms that control fiber type formation in secondary or fetal muscle fibers, myoblasts from the fast pectoralis major (PM) and fast/slow medial adductor (MA) muscles were isolated, allowed tomore » differentiate in vitro, and electrically stimulated. MA muscle fibers were induced to express the slow MyHC2 gene by electrical stimulation, whereas PM muscle fibers did not express the slow MyHC2 gene under identical stimulation conditions. However, PM muscle fibers did express the slow MyHC2 gene when electrical stimulation was combined with inhibition of inositol triphosphate receptor (IP3R) activity. Electrical stimulation was sufficient to increase nuclear localization of expressed nuclear-factor-of-activated-T-cells (NFAT), NFAT-mediated transcription, and slow MyHC2 promoter activity in MA muscle fibers. In contrast, both electrical stimulation and inhibitors of IP3R activity were required for these effects in PM muscle fibers. Electrical stimulation also increased levels of peroxisome-proliferator-activated receptor-{gamma} co-activator-1 (PGC-1{alpha}) protein in PM and MA muscle fibers. These results indicate that MA muscle fibers can be induced by electrical stimulation to express the slow MyHC2 gene and that fast PM muscle fibers are refractory to stimulation-induced slow MyHC2 gene expression due to fast PM muscle fiber specific cellular mechanisms involving IP3R activity.« less

Looking for a precursor of spontaneous Sleep Slow Oscillations in human sleep: The role of the sigma activity

PubMed Central

Allegrini, Paolo; Bedini, Remo; Bergamasco, Massimo; Laurino, Marco; Sebastiani, Laura; Gemignani, Angelo

2016-01-01

Sleep Slow Oscillations (SSOs), paradigmatic EEG markers of cortical bistability (alternation between cellular downstates and upstates), and sleep spindles, paradigmatic EEG markers of thalamic rhythm, are two hallmarks of sleeping brain. Selective thalamic lesions are reportedly associated to reductions of spindle activity and its spectrum ~14 Hz (sigma), and to alterations of SSO features. This apparent, parallel behavior suggests that thalamo-cortical entrainment favors cortical bistability. Here we investigate temporally-causal associations between thalamic sigma activity and shape, topology, and dynamics of SSOs. We recorded sleep EEG and studied whether spatio-temporal variability of SSO amplitude, negative slope (synchronization in downstate falling) and detection rate are driven by cortical-sigma-activity expression (12–18 Hz), in 3 consecutive 1 s-EEG-epochs preceding each SSO event (Baselines). We analyzed: (i) spatial variability, comparing maps of baseline sigma power and of SSO features, averaged over the first sleep cycle; (ii) event-by-event shape variability, computing for each electrode correlations between baseline sigma power and amplitude/slope of related SSOs; (iii) event-by-event spreading variability, comparing baseline sigma power in electrodes showing an SSO event with the homologous ones, spared by the event. The scalp distribution of baseline sigma power mirrored those of SSO amplitude and slope; event-by-event variability in baseline sigma power was associated with that in SSO amplitude in fronto-central areas; within each SSO event, electrodes involved in cortical bistability presented higher baseline sigma activity than those free of SSO. In conclusion, spatio-temporal variability of thalamocortical entrainment, measured by background sigma activity, is a reliable estimate of the cortical proneness to bistability. PMID:26003553

Transcranial oscillatory direct current stimulation during sleep improves declarative memory consolidation in children with attention-deficit/hyperactivity disorder to a level comparable to healthy controls.

PubMed

Prehn-Kristensen, Alexander; Munz, Manuel; Göder, Robert; Wilhelm, Ines; Korr, Katharina; Vahl, Wiebke; Wiesner, Christian D; Baving, Lioba

2014-01-01

Slow oscillations (<1 Hz) during slow wave sleep (SWS) promote the consolidation of declarative memory. Children with attention-deficit/hyperactivity disorder (ADHD) have been shown to display deficits in sleep-dependent consolidation of declarative memory supposedly due to dysfunctional slow brain rhythms during SWS. Using transcranial oscillating direct current stimulation (toDCS) at 0.75 Hz, we investigated whether an externally triggered increase in slow oscillations during early SWS elevates memory performance in children with ADHD. 12 children with ADHD underwent a toDCS and a sham condition in a double-blind crossover study design conducted in a sleep laboratory. Memory was tested using a 2D object-location task. In addition, 12 healthy children performed the same memory task in their home environment. Stimulation enhanced slow oscillation power in children with ADHD and boosted memory performance to the same level as in healthy children. These data indicate that increasing slow oscillation power during sleep by toDCS can alleviate declarative memory deficits in children with ADHD. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Vasovagal Syncope

MedlinePlus

... Combined, the drop in blood pressure and slowed heart rate quickly reduce blood flow to your brain, and you faint. Sometimes there is no classical vasovagal syncope trigger, but common triggers include: Standing for long periods of time Heat exposure Seeing blood Having blood drawn Fear of ...

Consciousness and Complexity during Unresponsiveness Induced by Propofol, Xenon, and Ketamine.

PubMed

Sarasso, Simone; Boly, Melanie; Napolitani, Martino; Gosseries, Olivia; Charland-Verville, Vanessa; Casarotto, Silvia; Rosanova, Mario; Casali, Adenauer Girardi; Brichant, Jean-Francois; Boveroux, Pierre; Rex, Steffen; Tononi, Giulio; Laureys, Steven; Massimini, Marcello

2015-12-07

A common endpoint of general anesthetics is behavioral unresponsiveness, which is commonly associated with loss of consciousness. However, subjects can become disconnected from the environment while still having conscious experiences, as demonstrated by sleep states associated with dreaming. Among anesthetics, ketamine is remarkable in that it induces profound unresponsiveness, but subjects often report "ketamine dreams" upon emergence from anesthesia. Here, we aimed at assessing consciousness during anesthesia with propofol, xenon, and ketamine, independent of behavioral responsiveness. To do so, in 18 healthy volunteers, we measured the complexity of the cortical response to transcranial magnetic stimulation (TMS)--an approach that has proven helpful in assessing objectively the level of consciousness irrespective of sensory processing and motor responses. In addition, upon emergence from anesthesia, we collected reports about conscious experiences during unresponsiveness. Both frontal and parietal TMS elicited a low-amplitude electroencephalographic (EEG) slow wave corresponding to a local pattern of cortical activation with low complexity during propofol anesthesia, a high-amplitude EEG slow wave corresponding to a global, stereotypical pattern of cortical activation with low complexity during xenon anesthesia, and a wakefulness-like, complex spatiotemporal activation pattern during ketamine anesthesia. Crucially, participants reported no conscious experience after emergence from propofol and xenon anesthesia, whereas after ketamine they reported long, vivid dreams unrelated to the external environment. These results are relevant because they suggest that brain complexity may be sensitive to the presence of disconnected consciousness in subjects who are considered unconscious based on behavioral responses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Brain perfusion imaging using a Reconstruction-of-Difference (RoD) approach for cone-beam computed tomography

NASA Astrophysics Data System (ADS)

Mow, M.; Zbijewski, W.; Sisniega, A.; Xu, J.; Dang, H.; Stayman, J. W.; Wang, X.; Foos, D. H.; Koliatsos, V.; Aygun, N.; Siewerdsen, J. H.

2017-03-01

Purpose: To improve the timely detection and treatment of intracranial hemorrhage or ischemic stroke, recent efforts include the development of cone-beam CT (CBCT) systems for perfusion imaging and new approaches to estimate perfusion parameters despite slow rotation speeds compared to multi-detector CT (MDCT) systems. This work describes development of a brain perfusion CBCT method using a reconstruction of difference (RoD) approach to enable perfusion imaging on a newly developed CBCT head scanner prototype. Methods: A new reconstruction approach using RoD with a penalized-likelihood framework was developed to image the temporal dynamics of vascular enhancement. A digital perfusion simulation was developed to give a realistic representation of brain anatomy, artifacts, noise, scanner characteristics, and hemo-dynamic properties. This simulation includes a digital brain phantom, time-attenuation curves and noise parameters, a novel forward projection method for improved computational efficiency, and perfusion parameter calculation. Results: Our results show the feasibility of estimating perfusion parameters from a set of images reconstructed from slow scans, sparse data sets, and arc length scans as short as 60 degrees. The RoD framework significantly reduces noise and time-varying artifacts from inconsistent projections. Proper regularization and the use of overlapping reconstructed arcs can potentially further decrease bias and increase temporal resolution, respectively. Conclusions: A digital brain perfusion simulation with RoD imaging approach has been developed and supports the feasibility of using a CBCT head scanner for perfusion imaging. Future work will include testing with data acquired using a 3D-printed perfusion phantom currently and translation to preclinical and clinical studies.

Metabolism and possible health effects of aluminum.

PubMed Central

Ganrot, P O

1986-01-01

Literature regarding the biochemistry of aluminum and eight similar ions is reviewed. Close and hitherto unknown similarities were found. A hypothetical model is presented for the metabolism, based on documented direct observations of Al3+ and analogies from other ions. Main characteristics are low intestinal absorption, rapid urinary excretion, and slow tissue uptake, mostly in skeleton and reticuloendothelial cells. Intracellular Al3+ is probably first confined in the lysosomes but then slowly accumulates in the cell nucleus and chromatin. Large, long-lived cells, e.g., neurons, may be the most liable to this accumulation. In heterochromatin, Al3+ levels can be found comparable to those used in leather tannage. It is proposed that an accumulation may take place at a subcellular level without any significant increase in the corresponding tissue concentration. The possible effects of this accumulation are discussed. As Al3+ is neurotoxic, the brain metabolism is most interesting. The normal and the lethally toxic brain levels of Al3+ are well documented and differ only by a factor of 3-10. The normal brain uptake of Al3+ is estimated from data on intestinal uptake of Al3+ and brain uptake of radionuclides of similar ions administered intravenously. The uptake is very slow, 1 mg in 36 years, and is consistent with an assumption that Al3+ taken up by the brain cannot be eliminated and is therefore accumulated. The possibility that Al3+ may cause or contribute to some specific diseases, most of them related to aging, is discussed with the proposed metabolic picture in mind. PMID:2940082

AMPK activation protects from neuronal dysfunction and vulnerability across nematode, cellular and mouse models of Huntington's disease

PubMed Central

Vázquez-Manrique, Rafael P.; Farina, Francesca; Cambon, Karine; Dolores Sequedo, María; Parker, Alex J.; Millán, José María; Weiss, Andreas; Déglon, Nicole; Neri, Christian

2016-01-01

The adenosine monophosphate activated kinase protein (AMPK) is an evolutionary-conserved protein important for cell survival and organismal longevity through the modulation of energy homeostasis. Several studies suggested that AMPK activation may improve energy metabolism and protein clearance in the brains of patients with vascular injury or neurodegenerative disease. However, in Huntington's disease (HD), AMPK may be activated in the striatum of HD mice at a late, post-symptomatic phase of the disease, and high-dose regiments of the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide may worsen neuropathological and behavioural phenotypes. Here, we revisited the role of AMPK in HD using models that recapitulate the early features of the disease, including Caenorhabditis elegans neuron dysfunction before cell death and mouse striatal cell vulnerability. Genetic and pharmacological manipulation of aak-2/AMPKα shows that AMPK activation protects C. elegans neurons from the dysfunction induced by human exon-1 huntingtin (Htt) expression, in a daf-16/forkhead box O-dependent manner. Similarly, AMPK activation using genetic manipulation and low-dose metformin treatment protects mouse striatal cells expressing full-length mutant Htt (mHtt), counteracting their vulnerability to stress, with reduction of soluble mHtt levels by metformin and compensation of cytotoxicity by AMPKα1. Furthermore, AMPK protection is active in the mouse brain as delivery of gain-of-function AMPK-γ1 to mouse striata slows down the neurodegenerative effects of mHtt. Collectively, these data highlight the importance of considering the dynamic of HD for assessing the therapeutic potential of stress-response targets in the disease. We postulate that AMPK activation is a compensatory response and valid approach for protecting dysfunctional and vulnerable neurons in HD. PMID:26681807

Neural complexity in patients with poststroke depression: A resting EEG study.

PubMed

Zhang, Ying; Wang, Chunfang; Sun, Changcheng; Zhang, Xi; Wang, Yongjun; Qi, Hongzhi; He, Feng; Zhao, Xin; Wan, Baikun; Du, Jingang; Ming, Dong

2015-12-01

Poststroke depression (PSD) is one of the most common emotional disorders affecting post-stroke patients. However, the neurophysiological mechanism remains elusive. This study was aimed to study the relationship between complexity of neural electrical activity and PSD. Resting state eye-closed electroencephalogram (EEG) signals of 16 electrodes were recorded in 21 ischemic poststroke depression (PSD) patients, 22 ischemic poststroke non-depression (PSND) patients and 15 healthy controls (CONT). Lempel-Ziv Complexity (LZC) was used to evaluate changes in EEG complexity in PSD patients. Statistical analysis was performed to explore difference among different groups and electrodes. Correlation between the severity of depression (HDRS) and EEG complexity was determined with pearson correlation coefficients. Receiver operating characteristic (ROC) and binary logistic regression analysis were conducted to estimate the discriminating ability of LZC for PSD in specificity, sensitivity and accuracy. PSD patients showed lower neural complexity compared with PSND and CONT subjects in the whole brain regions. There was no significant difference among different brain regions, and no interactions between group and electrodes. None of the LZC significantly correlated with overall depression severity or differentiated symptom severity of 7 items in PSD patients, but in stroke patients, significant correlation was found between HDRS and LZC in the whole brain regions, especially in frontal and temporal. LZC parameters used for PSD recognition possessed more than 85% in specificity, sensitivity and accuracy, suggesting the feasibility of LZC to serve as screening indicators for PSD. Increased slow wave rhythms were found in PSD patients and clearly correlation was confirmed between neuronal complexity and spectral power of the four EEG rhythms. Lesion location of stroke patients in the study distributed in different brain regions, and most of the PSD patients were mild or moderate in depressive severity. Compared with conventional spectral analysis, complexity of neural activity using LZC was more sensitive and stationary in the measurement of abnormal brain activity in PSD patients and may offer a potential approach to facilitate clinical screening of this disease. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Astrocyte-Mediated Neuronal Synchronization Properties Revealed by False Gliotransmitter Release

PubMed Central

Pirttimaki, Tiina M.; Sims, Robert E.; Saunders, Gregory; Antonio, Serena A.; Codadu, Neela Krushna

2017-01-01

Astrocytes spontaneously release glutamate (Glut) as a gliotransmitter (GT), resulting in the generation of extrasynaptic NMDAR-mediated slow inward currents (SICs) in neighboring neurons, which can increase local neuronal excitability. However, there is a deficit in our knowledge of the factors that control spontaneous astrocyte GT release and the extent of its influence. We found that, in rat brain slices, increasing the supply of the physiological transmitter Glut increased the frequency and signaling charge of SICs over an extended period. This phenomenon was replicated by exogenous preexposure to the amino acid D-aspartate (D-Asp). Using D-Asp as a “false” GT, we determined the extent of local neuron excitation by GT release in ventrobasal thalamus, CA1 hippocampus, and somatosensory cortex. By analyzing synchronized neuronal NMDAR-mediated excitation, we found that the properties of the excitation were conserved in different brain areas. In the three areas, astrocyte-derived GT release synchronized groups of neurons at distances of >;200 μm. Individual neurons participated in more than one synchronized population, indicating that individual neurons can be excited by more than one astrocyte and that individual astrocytes may determine a neuron's synchronized network. The results confirm that astrocytes can act as excitatory nodes that can influence neurons over a significant range in a number of brain regions. Our findings further suggest that chronic elevation of ambient Glut levels can lead to increased GT Glut release, which may be relevant in some pathological states. SIGNIFICANCE STATEMENT Astrocytes spontaneously release glutamate (Glut) and other gliotransmitters (GTs) that can modify neuronal activity. Exposing brain slices to Glut and D-aspartate (D-Asp) before recording resulted in an increase in frequency of GT-mediated astrocyte–neuron signaling. Using D-Asp, it was possible to investigate the effects of specific GT release at neuronal NMDARs. Calcium imaging showed synchronized activity in groups of neurons in cortex, hippocampus, and thalamus. The size of these populations was similar in all areas and some neurons were involved in more than one synchronous group. The findings show that GT release is supply dependent and that the properties of the signaling and activated networks are largely conserved between different brain areas. PMID:28899919

Slow Bursting Neurons of Mouse Cortical Layer 6b Are Depolarized by Hypocretin/Orexin and Major Transmitters of Arousal

PubMed Central

Wenger Combremont, Anne-Laure; Bayer, Laurence; Dupré, Anouk; Mühlethaler, Michel; Serafin, Mauro

2016-01-01

Neurons firing spontaneously in bursts in the absence of synaptic transmission have been previously recorded in different layers of cortical brain slices. It has been suggested that such neurons could contribute to the generation of alternating UP and DOWN states, a pattern of activity seen during slow-wave sleep. Here, we show that in layer 6b (L6b), known from our previous studies to contain neurons highly responsive to the wake-promoting transmitter hypocretin/orexin (hcrt/orx), there is a set of neurons, endowed with distinct intrinsic properties, which displayed a strong propensity to fire spontaneously in rhythmic bursts. In response to small depolarizing steps, they responded with a delayed firing of action potentials which, upon higher depolarizing steps, invariably inactivated and were followed by a depolarized plateau potential and a depolarizing afterpotential. These cells also displayed a strong hyperpolarization-activated rectification compatible with the presence of an Ih current. Most L6b neurons with such properties were able to fire spontaneously in bursts. Their bursting activity was of intrinsic origin as it persisted not only in presence of blockers of ionotropic glutamatergic and GABAergic receptors but also in a condition of complete synaptic blockade. However, a small number of these neurons displayed a mix of intrinsic bursting and synaptically driven recurrent UP and DOWN states. Most of the bursting L6b neurons were depolarized and excited by hcrt/orx through a direct postsynaptic mechanism that led to tonic firing and eventually inactivation. Similarly, they were directly excited by noradrenaline, histamine, dopamine, and neurotensin. Finally, the intracellular injection of these cells with dye and their subsequent Neurolucida reconstruction indicated that they were spiny non-pyramidal neurons. These results lead us to suggest that the propensity for slow rhythmic bursting of this set of L6b neurons could be directly impeded by hcrt/orx and other wake-promoting transmitters. PMID:27379007

The role of serotonin and norepinephrine in sleep-waking activity.

PubMed

Morgane, P J; Stern, W C

1975-11-01

A critical review of the evidences relating the biogenic amines serotonin and norepinephrine to the states of slow-wave and rapid eye movement (REM) sleep is presented. Various alternative explanations for specific chemical regulation of the individual sleep states, including the phasic events of REM sleep, are evaluated within the overall framework of the monoamine theory of sleep. Several critical neuropsychopharmacological studies relating to metabolsim of the amines in relation to sleep-waking behavior are presented. Models of the chemical neuronal circuitry involved in sleep-waking activity are derived and interactions between several brainstem nuclei, particularly the raphé complex and locus coeruleus, are discussed. Activity in these aminergic systems in relation to oscillations in the sleep-waking cycles is evaluated. In particular, the assessment of single cell activity in specific chemical systems in relations to chemical models of sleep is reviewed. Overall, it appears that the biogenic amines, especially serotonin and norepinephrine, play key roles in the generation and maintenance of the sleep states. These neurotransmitters participate in some manner in the "triggering" processes necessary for actuating each sleep phase and in regulating the transitions from sleep to waking activity. The biogenic amines are, however, probably not "sleep factors" or direct inducers of the sleep states. Rather, they appear to be components of a multiplicity of interacting chemical circuitry in the brain whose activity maintains various chemical balances in different brain regions. Shifts in these balances appear to be involved in the triggering and maintenance of the various states comprising the vigilance continuum.

Fast fMRI can detect oscillatory neural activity in humans.

PubMed

Lewis, Laura D; Setsompop, Kawin; Rosen, Bruce R; Polimeni, Jonathan R

2016-10-25

Oscillatory neural dynamics play an important role in the coordination of large-scale brain networks. High-level cognitive processes depend on dynamics evolving over hundreds of milliseconds, so measuring neural activity in this frequency range is important for cognitive neuroscience. However, current noninvasive neuroimaging methods are not able to precisely localize oscillatory neural activity above 0.2 Hz. Electroencephalography and magnetoencephalography have limited spatial resolution, whereas fMRI has limited temporal resolution because it measures vascular responses rather than directly recording neural activity. We hypothesized that the recent development of fast fMRI techniques, combined with the extra sensitivity afforded by ultra-high-field systems, could enable precise localization of neural oscillations. We tested whether fMRI can detect neural oscillations using human visual cortex as a model system. We detected small oscillatory fMRI signals in response to stimuli oscillating at up to 0.75 Hz within single scan sessions, and these responses were an order of magnitude larger than predicted by canonical linear models. Simultaneous EEG-fMRI and simulations based on a biophysical model of the hemodynamic response to neuronal activity suggested that the blood oxygen level-dependent response becomes faster for rapidly varying stimuli, enabling the detection of higher frequencies than expected. Accounting for phase delays across voxels further improved detection, demonstrating that identifying vascular delays will be of increasing importance with higher-frequency activity. These results challenge the assumption that the hemodynamic response is slow, and demonstrate that fMRI has the potential to map neural oscillations directly throughout the brain.

Effects of Acanthopanax senticosus on Brain Injury Induced by Simulated Spatial Radiation in Mouse Model Based on Pharmacokinetics and Comparative Proteomics

PubMed Central

Cheng, Cuilin; Baranenko, Denis; Wang, Jiaping; Li, Yongzhi; Lu, Weihong

2018-01-01

The active compounds in Acanthopanax senticosus (AS) have different pharmacokinetic characteristics in mouse models. Cmax and AUC of Acanthopanax senticosus polysaccharides (ASPS) were significantly reduced in radiation-injured mice, suggesting that the blood flow of mouse was blocked or slowed, due to the pathological state of ischemia and hypoxia, which are caused by radiation. In contrast, the ability of various metabolizing enzymes to inactivate, capacity of biofilm transport decrease, and lessening of renal blood flow accounts for radiation, resulting in the accumulation of syringin and eleutheroside E in the irradiated mouse. Therefore, there were higher pharmacokinetic parameters—AUC, MRT, and t1/2 of the two compounds in radiation-injured mouse, when compared with normal mouse. In order to investigate the intrinsic mechanism of AS on radiation injury, AS extract’s protective effects on brain, the main part of mouse that suffered from radiation, were explored. The function of AS extract in repressing expression changes of radiation response proteins in prefrontal cortex (PFC) of mouse brain included tubulin protein family (α-, β-tubulin subunits), dihydropyrimidinase-related protein 2 (CRMP2), γ-actin, 14-3-3 protein family (14-3-3ζ, ε), heat shock protein 90β (HSP90β), and enolase 2. The results demonstrated the AS extract had positive effects on nerve cells’ structure, adhesion, locomotion, fission, and phagocytosis, through regulating various action pathways, such as Hippo, phagosome, PI3K/Akt (phosphatidylinositol 3 kinase/protein kinase B), Neurotrophin, Rap1 (Ras-related protein RAP-1A), gap junction glycolysis/gluconeogenesis, and HIF-1 (Hypoxia-inducible factor 1) signaling pathways to maintain normal mouse neurological activity. All of the results indicated that AS may be a promising alternative medicine for the treatment of radiation injury in mouse brain. It would be tested that whether the bioactive ingredients of AS could be effective through the blood–brain barrier in the future. PMID:29342911

GABA homeostasis contributes to the developmental programming of anxiety-related behavior.

PubMed

Depino, Amaicha Mara; Tsetsenis, Theodoros; Gross, Cornelius

2008-05-19

During development, when inhibitory and excitatory synapses are formed and refined, homeostatic mechanisms act to adjust inhibitory input in order to maintain neural activity within a normal range. As the brain matures, synaptogenesis slows and a relatively stable level of inhibition is achieved. Deficits in inhibitory neurotransmission are associated with increased anxiety-related behavior and drugs that potentiate GABA function, the major inhibitory neurotransmitter in the brain, are effective anxiolytics. These observations raise the possibility that transient perturbations in the activity of neural circuits during development might induce compensatory changes in inhibition that could persist into adulthood and contribute to changes in anxiety-related behavior. To test this hypothesis, we treated mice continuously during the major period of forebrain synaptogenesis (P14-28) with the GABA-A receptor positive modulator diazepam and assessed anxiety-related behavior in adulthood. Control experiments confirmed anxiolytic effects of the drug following one day of treatment and the development of tolerance following two weeks of treatment. When tested in adulthood, one month after the end of treatment, diazepam-treated mice exhibited significantly increased behavioral inhibition in the open-field, elevated-plus maze, and novel object behavioral paradigms. Levels of benzodiazepine binding sites in amygdala and frontal cortex were specifically decreased in diazepam-treated mice demonstrating that homeostatic adjustments in GABA function persist into adulthood. Our results show that increased GABAergic activity can affect the developmental programming of anxiety-related behavior.

Changes in Resting State Effective Connectivity in the Motor Network Following Rehabilitation of Upper Extremity Poststroke Paresis

PubMed Central

James, G. Andrew; Lu, Zhong-Lin; VanMeter, John W.; Sathian, K.; Hu, Xiaoping P.; Butler, Andrew J.

2013-01-01

Background A promising paradigm in human neuroimaging is the study of slow (<0.1 Hz) spontaneous fluctuations in the hemodynamic response measured by functional magnetic resonance imaging (fMRI). Spontaneous activity (i.e., resting state) refers to activity that cannot be attributed to specific inputs or outputs, that is, activity intrinsically generated by the brain. Method This article presents pilot data examining neural connectivity in patients with poststroke hemiparesis before and after 3 weeks of upper extremity rehabilitation in the Accelerated Skill Acquisition Program (ASAP). Resting-state fMRI data acquired pre and post therapy were analyzed using an exploratory adaptation of structural equation modeling (SEM) to evaluate therapy-related changes in motor network effective connectivity. Results Each ASAP patient showed behavioral improvement. ASAP patients also showed increased influence of the affected hemisphere premotor cortex (a-PM) upon the unaffected hemisphere premotor cortex (u-PM) following therapy. The influence of a-PM on affected hemisphere primary motor cortex (a-M1) also increased with therapy for 3 of 5 patients, including those with greatest behavioral improvement. Conclusions Our findings suggest that network analyses of resting-state fMRI constitute promising tools for functional characterization of functional brain disorders, for intergroup comparisons, and potentially for assessing effective connectivity within single subjects; all of which have important implications for stroke rehabilitation. PMID:19740732

Cerebral blood flow relationships associated with a difficult tone recognition task in trained normal volunteers.

PubMed

Holcomb, H H; Medoff, D R; Caudill, P J; Zhao, Z; Lahti, A C; Dannals, R F; Tamminga, C A

1998-09-01

Tone recognition is partially subserved by neural activity in the right frontal and primary auditory cortices. First we determined the brain areas associated with tone perception and recognition. This study then examined how regional cerebral blood flow (rCBF) in these and other brain regions correlates with the behavioral characteristics of a difficult tone recognition task. rCBF changes were assessed using H2(15)O positron emission tomography. Subtraction procedures were used to localize significant change regions and correlational analyses were applied to determine how response times (RT) predicted rCBF patterns. Twelve trained normal volunteers were studied in three conditions: REST, sensory motor control (SMC) and decision (DEC). The SMC-REST contrast revealed bilateral activation of primary auditory cortices, cerebellum and bilateral inferior frontal gyri. DEC-SMC produced significant clusters in the right middle and inferior frontal gyri, insula and claustrum; the anterior cingulate gyrus and supplementary motor area; the left insula/claustrum; and the left cerebellum. Correlational analyses, RT versus rCBF from DEC scans, showed a positive correlation in right inferior and middle frontal cortex; rCBF in bilateral auditory cortices and cerebellum exhibited significant negative correlations with RT These changes suggest that neural activity in the right frontal, superior temporal and cerebellar regions shifts back and forth in magnitude depending on whether tone recognition RT is relatively fast or slow, during a difficult, accurate assessment.

Oxidative Stress, Amyloid-β Peptide, and Altered Key Molecular Pathways in the Pathogenesis and Progression of Alzheimer’s Disease

PubMed Central

Butterfield, D. Allan; Boyd-Kimball, Debra

2018-01-01

Oxidative stress is implicated in the pathogenesis and progression of Alzheimer’s disease (AD) and its earlier stage, amnestic mild cognitive impairment (aMCI). One source of oxidative stress in AD and aMCI brains is that associated with amyloid-β peptide, Aβ1-42 oligomers. Our laboratory first showed in AD elevated oxidative stress occurred in brain regions rich in Aβ1-42, but not in Aβ1-42-poor regions, and was among the first to demonstrate Aβ peptides led to lipid peroxidation (indexed by HNE) in AD and aMCI brains. Oxidatively modified proteins have decreased function and contribute to damaged key biochemical and metabolic pathways in which these proteins normally play a role. Identification of oxidatively modified brain proteins by the methods of redox proteomics was pioneered in the Butterfield laboratory. Four recurring altered pathways secondary to oxidative damage in brain from persons with AD, aMCI, or Down syndrome with AD are interrelated and contribute to neuronal death. This “Quadrilateral of Neuronal Death” includes altered: glucose metabolism, mTOR activation, proteostasis network, and protein phosphorylation. Some of these pathways are altered even in brains of persons with preclinical AD. We opine that targeting these pathways pharmacologically and with lifestyle changes potentially may provide strategies to slow or perhaps one day, prevent, progression or development of this devastating dementing disorder. This invited review outlines both in vitro and in vivo studies from the Butterfield laboratory related to Aβ1-42 and AD and discusses the importance and implications of some of the major achievements of the Butterfield laboratory in AD research. PMID:29562527

Mechanical versus humoral determinants of brain death-induced lung injury

PubMed Central

Dewachter, Laurence; Rorive, Sandrine; Remmelink, Myriam; Weynand, Birgit; Melot, Christian; Hupkens, Emeline; Dewachter, Céline; Creteur, Jacques; Mc Entee, Kathleen; Naeije, Robert; Rondelet, Benoît

2017-01-01

Background The mechanisms of brain death (BD)-induced lung injury remain incompletely understood, as uncertainties persist about time-course and relative importance of mechanical and humoral perturbations. Methods Brain death was induced by slow intracranial blood infusion in anesthetized pigs after randomization to placebo (n = 11) or to methylprednisolone (n = 8) to inhibit the expression of pro-inflammatory mediators. Pulmonary artery pressure (PAP), wedged PAP (PAWP), pulmonary vascular resistance (PVR) and effective pulmonary capillary pressure (PCP) were measured 1 and 5 hours after Cushing reflex. Lung tissue was sampled to determine gene expressions of cytokines and oxidative stress molecules, and pathologically score lung injury. Results Intracranial hypertension caused a transient increase in blood pressure followed, after brain death was diagnosed, by persistent increases in PAP, PCP and the venous component of PVR, while PAWP did not change. Arterial PO2/fraction of inspired O2 (PaO2/FiO2) decreased. Brain death was associated with an accumulation of neutrophils and an increased apoptotic rate in lung tissue together with increased pro-inflammatory interleukin (IL)-6/IL-10 ratio and increased heme oxygenase(HO)-1 and hypoxia inducible factor(HIF)-1 alpha expression. Blood expressions of IL-6 and IL-1β were also increased. Methylprednisolone pre-treatment was associated with a blunting of increased PCP and PVR venous component, which returned to baseline 5 hours after BD, and partially corrected lung tissue biological perturbations. PaO2/FiO2 was inversely correlated to PCP and lung injury score. Conclusions Brain death-induced lung injury may be best explained by an initial excessive increase in pulmonary capillary pressure with increased pulmonary venous resistance, and was associated with lung activation of inflammatory apoptotic processes which were partially prevented by methylprednisolone. PMID:28753621

EKG-based detection of deep brain stimulation in fMRI studies.

PubMed

Fiveland, Eric; Madhavan, Radhika; Prusik, Julia; Linton, Renee; Dimarzio, Marisa; Ashe, Jeffrey; Pilitsis, Julie; Hancu, Ileana

2018-04-01

To assess the impact of synchronization errors between the assumed functional MRI paradigm timing and the deep brain stimulation (DBS) on/off cycling using a custom electrocardiogram-based triggering system METHODS: A detector for measuring and predicting the on/off state of cycling deep brain stimulation was developed and tested in six patients in office visits. Three-electrode electrocardiogram measurements, amplified by a commercial bio-amplifier, were used as input for a custom electronics box (e-box). The e-box transformed the deep brain stimulation waveforms into transistor-transistor logic pulses, recorded their timing, and propagated it in time. The e-box was used to trigger task-based deep brain stimulation functional MRI scans in 5 additional subjects; the impact of timing accuracy on t-test values was investigated in a simulation study using the functional MRI data. Following locking to each patient's individual waveform, the e-box was shown to predict stimulation onset with an average absolute error of 112 ± 148 ms, 30 min after disconnecting from the patients. The subsecond accuracy of the e-box in predicting timing onset is more than adequate for our slow varying, 30-/30-s on/off stimulation paradigm. Conversely, the experimental deep brain stimulation onset prediction accuracy in the absence of the e-box, which could be off by as much as 4 to 6 s, could significantly decrease activation strength. Using this detector, stimulation can be accurately synchronized to functional MRI acquisitions, without adding any additional hardware in the MRI environment. Magn Reson Med 79:2432-2439, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Electroencephalographic slow waves prior to sleepwalking episodes.

PubMed

Perrault, Rosemarie; Carrier, Julie; Desautels, Alex; Montplaisir, Jacques; Zadra, Antonio

2014-12-01

Recent studies have suggested that the onset of sleepwalking episodes may be preceded by fluctuations in slow-wave sleep electroencephalographic characteristics. However, whether or not such fluctuations are specific to sleepwalking episodes or generalized to all sleep-wake transitions in sleepwalkers remains unknown. The goal of this study was to compare spectral power for delta (1-4 Hz) and slow delta (0.5-1 Hz) as well as slow oscillation density before the onset of somnambulistic episodes versus non-behavioral awakenings recorded from the same group of sleepwalkers. A secondary aim was to describe the time course of observed changes in slow-wave activity and slow oscillations during the 3 min immediately preceding the occurrence of somnambulistic episodes. Twelve adult sleepwalkers were investigated polysomnographically during the course of one night. Slow-wave activity and slow oscillation density were significantly greater prior to patients' somnambulistic episodes as compared with non-behavioral awakenings. However, there was no evidence for a gradual increase over the 3 min preceding the episodes. Increased slow-wave activity and slow oscillation density appear to be specific to sleepwalking episodes rather than generalized to all sleep-wake transitions in sleepwalkers. Copyright © 2014 Elsevier B.V. All rights reserved.

Activated-Lignite-Based Super Large Granular Slow-Release Fertilizers Improve Apple Tree Growth: Synthesis, Characterizations, and Laboratory and Field Evaluations.

PubMed

Tang, Yafu; Wang, Xinying; Yang, Yuechao; Gao, Bin; Wan, Yongshan; Li, Yuncong C; Cheng, Dongdong

2017-07-26

In this work, lignite, a low-grade coal, was modified using the solid-phase activation method with the aid of a Pd/CeO 2 nanoparticle catalyst to improve its pore structure and nutrient absorption. Results indicate that the adsorption ability of the activated lignite to NO 3 - , NH 4 + , H 2 PO 4 - , and K + was significantly higher than that of raw lignite. The activated lignite was successfully combined with the polymeric slow-release fertilizer, which exhibits typical slow-release behavior, to prepare the super large granular activated lignite slow-release fertilizer (SAF). In addition to the slow-release ability, the SAF showed excellent water-retention capabilities. Soil column leaching experiments further confirmed the slow-release characteristics of the SAF with fertilizer nutrient loss greatly reduced in comparison to traditional and slow-release fertilizers. Furthermore, field tests of the SAF in an orchard showed that the novel SAF was better than other tested fertilizers in improve the growth of young apple trees. Findings from this study suggest that the newly developed SAF has great potential to be used in apple cultivation and production systems in the future.

Interneuron-mediated inhibition synchronizes neuronal activity during slow oscillation.

PubMed

Chen, Jen-Yung; Chauvette, Sylvain; Skorheim, Steven; Timofeev, Igor; Bazhenov, Maxim

2012-08-15

The signature of slow-wave sleep in the electroencephalogram (EEG) is large-amplitude fluctuation of the field potential, which reflects synchronous alternation of activity and silence across cortical neurons. While initiation of the active cortical states during sleep slow oscillation has been intensively studied, the biological mechanisms which drive the network transition from an active state to silence remain poorly understood. In the current study, using a combination of in vivo electrophysiology and thalamocortical network simulation, we explored the impact of intrinsic and synaptic inhibition on state transition during sleep slow oscillation. We found that in normal physiological conditions, synaptic inhibition controls the duration and the synchrony of active state termination. The decline of interneuron-mediated inhibition led to asynchronous downward transition across the cortical network and broke the regular slow oscillation pattern. Furthermore, in both in vivo experiment and computational modelling, we revealed that when the level of synaptic inhibition was reduced significantly, it led to a recovery of synchronized oscillations in the form of seizure-like bursting activity. In this condition, the fast active state termination was mediated by intrinsic hyperpolarizing conductances. Our study highlights the significance of both intrinsic and synaptic inhibition in manipulating sleep slow rhythms.

Interneuron-mediated inhibition synchronizes neuronal activity during slow oscillation

PubMed Central

Chen, Jen-Yung; Chauvette, Sylvain; Skorheim, Steven; Timofeev, Igor; Bazhenov, Maxim

2012-01-01

The signature of slow-wave sleep in the electroencephalogram (EEG) is large-amplitude fluctuation of the field potential, which reflects synchronous alternation of activity and silence across cortical neurons. While initiation of the active cortical states during sleep slow oscillation has been intensively studied, the biological mechanisms which drive the network transition from an active state to silence remain poorly understood. In the current study, using a combination of in vivo electrophysiology and thalamocortical network simulation, we explored the impact of intrinsic and synaptic inhibition on state transition during sleep slow oscillation. We found that in normal physiological conditions, synaptic inhibition controls the duration and the synchrony of active state termination. The decline of interneuron-mediated inhibition led to asynchronous downward transition across the cortical network and broke the regular slow oscillation pattern. Furthermore, in both in vivo experiment and computational modelling, we revealed that when the level of synaptic inhibition was reduced significantly, it led to a recovery of synchronized oscillations in the form of seizure-like bursting activity. In this condition, the fast active state termination was mediated by intrinsic hyperpolarizing conductances. Our study highlights the significance of both intrinsic and synaptic inhibition in manipulating sleep slow rhythms. PMID:22641778

16 CFR 1303.5 - Findings.

Code of Federal Regulations, 2012 CFR

2012-01-01

... designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability, withdrawal... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

16 CFR 1303.5 - Findings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability, withdrawal... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

16 CFR 1303.5 - Findings.

Code of Federal Regulations, 2011 CFR

2011-01-01

... designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability, withdrawal... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

16 CFR 1303.5 - Findings.

Code of Federal Regulations, 2014 CFR

2014-01-01

... designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability, withdrawal... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

Expression of multiple slow myosin heavy chain genes reveals a diversity of zebrafish slow twitch muscle fibres with differing requirements for Hedgehog and Prdm1 activity.

PubMed

Elworthy, Stone; Hargrave, Murray; Knight, Robert; Mebus, Katharina; Ingham, Philip W

2008-06-01

The zebrafish embryo develops a series of anatomically distinct slow twitch muscle fibres that characteristically express genes encoding lineage-specific isoforms of sarcomeric proteins such as MyHC and troponin. We show here that different subsets of these slow fibres express distinct members of a tandem array of slow MyHC genes. The first slow twitch muscle fibres to differentiate, which are specified by the activity of the transcription factor Prdm1 (also called Ubo or Blimp1) in response to Hedgehog (Hh) signalling, express the smyhc1 gene. Subsequently, secondary slow twitch fibres differentiate in most cases independently of Hh activity. We find that although some of these later-forming fibres also express smyhc1, others express smyhc2 or smyhc3. We show that the smyhc1-positive fibres express the ubo (prdm1) gene and adopt fast twitch fibre characteristics in the absence of Prdm1 activity, whereas those that do not express smyhc1 can differentiate independently of Prdm1 function. Conversely, some smyhc2-expressing fibres, although independent of Prdm1 function, require Hh activity to form. The adult trunk slow fibres express smyhc2 and smyhc3, but lack smyhc1 expression. The different slow fibres in the craniofacial muscles variously express smyhc1, smyhc2 and smyhc3, and all differentiate independently of Prdm1.

In vitro characterization of pralidoxime transport and acetylcholinesterase reactivation across MDCK cells and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs).

PubMed

Gallagher, Erin; Minn, Il; Chambers, Janice E; Searson, Peter C

2016-07-11

Current therapies for organophosphate poisoning involve administration of oximes, such as pralidoxime (2-PAM), that reactivate the enzyme acetylcholinesterase. Studies in animal models have shown a low concentration in the brain following systemic injection. To assess 2-PAM transport, we studied transwell permeability in three Madin-Darby canine kidney (MDCKII) cell lines and stem cell-derived human brain microvascular endothelial cells (BC1-hBMECs). To determine whether 2-PAM is a substrate for common brain efflux pumps, experiments were performed in the MDCKII-MDR1 cell line, transfected to overexpress the P-gp efflux pump, and the MDCKII-FLuc-ABCG2 cell line, transfected to overexpress the BCRP efflux pump. To determine how transcellular transport influences enzyme reactivation, we developed a modified transwell assay where the inhibited acetylcholinesterase enzyme, substrate, and reporter are introduced into the basolateral chamber. Enzymatic activity was inhibited using paraoxon and parathion. The permeability of 2-PAM is about 2 × 10(-6) cm s(-1) in MDCK cells and about 1 × 10(-6) cm s(-1) in BC1-hBMECs. Permeability is not influenced by pre-treatment with atropine. In addition, 2-PAM is not a substrate for the P-gp or BCRP efflux pumps. The low permeability explains poor brain penetration of 2-PAM and therefore the slow enzyme reactivation. This elucidates one of the reasons for the necessity of sustained intravascular (IV) infusion in response to organophosphate poisoning.

Valeriana wallichii root extract improves sleep quality and modulates brain monoamine level in rats.

PubMed

Sahu, Surajit; Ray, Koushik; Yogendra Kumar, M S; Gupta, Shilpa; Kauser, Hina; Kumar, Sanjeev; Mishra, Kshipra; Panjwani, Usha

2012-07-15

The present study was performed to investigate the effects of Valeriana wallichi (VW) aqueous root extract on sleep-wake profile and level of brain monoamines on Sprague-Dawley rats. Electrodes and transmitters were implanted to record EEG and EMG in freely moving condition and the changes were recorded telemetrically after oral administration of VW in the doses of 100, 200 and 300 mg/kg body weight. Sleep latency was decreased and duration of non-rapid eye movement (NREM) sleep was increased in a dose dependent manner. A significant decrease of sleep latency and duration of wakefulness were observed with VW at doses of 200 and 300 mg/kg. Duration of NREM sleep as well as duration of total sleep was increased significantly after treatment with VW at the doses of 200 and 300 mg/kg. VW also increased EEG slow wave activity during NREM sleep at the doses of 200 and 300 mg/kg. Level of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT) and hydroxy indole acetic acid (HIAA) were measured in frontal cortex and brain stem after VW treatment at the dose of 200mg/kg. NE and 5HT level were decreased significantly in both frontal cortex and brain stem. DA and HIAA level significantly decreased only in cortex. DOPAC level was not changed in any brain region studied. In conclusion it can be said that VW water extract has a sleep quality improving effect which may be dependent upon levels of monoamines in cortex and brainstem. Copyright © 2012 Elsevier GmbH. All rights reserved.

Functional connectivity of the rodent brain using optical imaging

NASA Astrophysics Data System (ADS)

Guevara Codina, Edgar

The aim of this thesis is to apply functional connectivity in a variety of animal models, using several optical imaging modalities. Even at rest, the brain shows high metabolic activity: the correlation in slow spontaneous fluctuations identifies remotely connected areas of the brain; hence the term "functional connectivity". Ongoing changes in spontaneous activity may provide insight into the neural processing that takes most of the brain metabolic activity, and so may provide a vast source of disease related changes. Brain hemodynamics may be modified during disease and affect resting-state activity. The thesis aims to better understand these changes in functional connectivity due to disease, using functional optical imaging. The optical imaging techniques explored in the first two contributions of this thesis are Optical Imaging of Intrinsic Signals and Laser Speckle Contrast Imaging, together they can estimate the metabolic rate of oxygen consumption, that closely parallels neural activity. They both have adequate spatial and temporal resolution and are well adapted to image the convexity of the mouse cortex. In the last article, a depth-sensitive modality called photoacoustic tomography was used in the newborn rat. Optical coherence tomography and laminar optical tomography were also part of the array of imaging techniques developed and applied in other collaborations. The first article of this work shows the changes in functional connectivity in an acute murine model of epileptiform activity. Homologous correlations are both increased and decreased with a small dependence on seizure duration. These changes suggest a potential decoupling between the hemodynamic parameters in resting-state networks, underlining the importance to investigate epileptic networks with several independent hemodynamic measures. The second study examines a novel murine model of arterial stiffness: the unilateral calcification of the right carotid. Seed-based connectivity analysis showed a decreasing trend of homologous correlation in the motor and cingulate cortices. Graph analyses showed a randomization of the cortex functional networks, suggesting a loss of connectivity, more specifically in the motor cortex ipsilateral to the treated carotid; however these changes are not reflected in differentiated metabolic estimates. Confounds remain due to the fact that carotid rigidification gives rise to neural decline in the hippocampus as well as unilateral alteration of vascular pulsatility; however the results support the need to look at several hemodynamic parameters when imaging the brain after arterial remodeling. The third article of this thesis studies a model of inflammatory injury on the newborn rat. Oxygen saturation and functional connectivity were assessed with photoacoustic tomography. Oxygen saturation was decreased in the site of the lesion and on the cortex ipsilateral to the injury; however this decrease is not fully explained by hypovascularization revealed by histology. Seed-based functional connectivity analysis showed that inter-hemispheric connectivity is not affected by inflammatory injury.

Dendritic Slow Dynamics Enables Localized Cortical Activity to Switch between Mobile and Immobile Modes with Noisy Background Input

PubMed Central

Kurashige, Hiroki; Câteau, Hideyuki

2011-01-01

Mounting lines of evidence suggest the significant computational ability of a single neuron empowered by active dendritic dynamics. This motivates us to study what functionality can be acquired by a network of such neurons. The present paper studies how such rich single-neuron dendritic dynamics affects the network dynamics, a question which has scarcely been specifically studied to date. We simulate neurons with active dendrites networked locally like cortical pyramidal neurons, and find that naturally arising localized activity – called a bump – can be in two distinct modes, mobile or immobile. The mode can be switched back and forth by transient input to the cortical network. Interestingly, this functionality arises only if each neuron is equipped with the observed slow dendritic dynamics and with in vivo-like noisy background input. If the bump activity is considered to indicate a point of attention in the sensory areas or to indicate a representation of memory in the storage areas of the cortex, this would imply that the flexible mode switching would be of great potential use for the brain as an information processing device. We derive these conclusions using a natural extension of the conventional field model, which is defined by combining two distinct fields, one representing the somatic population and the other representing the dendritic population. With this tool, we analyze the spatial distribution of the degree of after-spike adaptation and explain how we can understand the presence of the two distinct modes and switching between the modes. We also discuss the possible functional impact of this mode-switching ability. PMID:21931635

Effects of radiofrequency radiation emitted by cellular telephones on the cognitive functions of humans.

PubMed

Eliyahu, Ilan; Luria, Roy; Hareuveny, Ronen; Margaliot, Menachem; Meiran, Nachshon; Shani, Gad

2006-02-01

The present study examined the effects of exposure to Electromagnetic Radiation emitted by a standard GSM phone at 890 MHz on human cognitive functions. This study attempted to establish a connection between the exposure of a specific area of the brain and the cognitive functions associated with that area. A total of 36 healthy right-handed male subjects performed four distinct cognitive tasks: spatial item recognition, verbal item recognition, and two spatial compatibility tasks. Tasks were chosen according to the brain side they are assumed to activate. All subjects performed the tasks under three exposure conditions: right side, left side, and sham exposure. The phones were controlled by a base station simulator and operated at their full power. We have recorded the reaction times (RTs) and accuracy of the responses. The experiments consisted of two sections, of 1 h each, with a 5 min break in between. The tasks and the exposure regimes were counterbalanced. The results indicated that the exposure of the left side of the brain slows down the left-hand response time, in the second-later-part of the experiment. This effect was apparent in three of the four tasks, and was highly significant in only one of the tests. The exposure intensity and its duration exceeded the common exposure of cellular phone users.

Chaotic time series analysis of vision evoked EEG

NASA Astrophysics Data System (ADS)

Zhang, Ningning; Wang, Hong

2010-01-01

To investigate the human brain activities for aesthetic processing, beautiful woman face picture and ugly buffoon face picture were applied. Twelve subjects were assigned the aesthetic processing task while the electroencephalogram (EEG) was recorded. Event-related brain potential (ERP) was required from the 32 scalp electrodes and the ugly buffoon picture produced larger amplitudes for the N1, P2, N2, and late slow wave components. Average ERP from the ugly buffoon picture were larger than that from the beautiful woman picture. The ERP signals shows that the ugly buffoon elite higher emotion waves than the beautiful woman face, because some expression is on the face of the buffoon. Then, chaos time series analysis was carried out to calculate the largest Lyapunov exponent using small data set method and the correlation dimension using G-P algorithm. The results show that the largest Lyapunov exponents of the ERP signals are greater than zero, which indicate that the ERP signals may be chaotic. The correlations dimensions coming from the beautiful woman picture are larger than that from the ugly buffoon picture. The comparison of the correlations dimensions shows that the beautiful face can excite the brain nerve cells. The research in the paper is a persuasive proof to the opinion that cerebrum's work is chaotic under some picture stimuli.

Resting EEG deficits in accused murderers with schizophrenia.

PubMed

Schug, Robert A; Yang, Yaling; Raine, Adrian; Han, Chenbo; Liu, Jianghong; Li, Liejia

2011-10-31

Empirical evidence continues to suggest a biologically distinct violent subtype of schizophrenia. The present study examined whether murderers with schizophrenia would demonstrate resting EEG deficits distinguishing them from both non-violent schizophrenia patients and murderers without schizophrenia. Resting EEG data were collected from five diagnostic groups (normal controls, non-murderers with schizophrenia, murderers with schizophrenia, murderers without schizophrenia, and murderers with psychiatric conditions other than schizophrenia) at a brain hospital in Nanjing, China. Murderers with schizophrenia were characterized by increased left-hemispheric fast-wave EEG activity relative to non-violent schizophrenia patients, while non-violent schizophrenia patients instead demonstrated increased diffuse slow-wave activity compared to all other groups. Results are discussed within the framework of a proposed left-hemispheric over-processing hypothesis specific to violent individuals with schizophrenia, involving left hemispheric hyperarousal deficits, which may lead to a homicidally violent schizophrenia outcome. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Cortical firing and sleep homeostasis.

PubMed

Vyazovskiy, Vladyslav V; Olcese, Umberto; Lazimy, Yaniv M; Faraguna, Ugo; Esser, Steve K; Williams, Justin C; Cirelli, Chiara; Tononi, Giulio

2009-09-24

The need to sleep grows with the duration of wakefulness and dissipates with time spent asleep, a process called sleep homeostasis. What are the consequences of staying awake on brain cells, and why is sleep needed? Surprisingly, we do not know whether the firing of cortical neurons is affected by how long an animal has been awake or asleep. Here, we found that after sustained wakefulness cortical neurons fire at higher frequencies in all behavioral states. During early NREM sleep after sustained wakefulness, periods of population activity (ON) are short, frequent, and associated with synchronous firing, while periods of neuronal silence are long and frequent. After sustained sleep, firing rates and synchrony decrease, while the duration of ON periods increases. Changes in firing patterns in NREM sleep correlate with changes in slow-wave activity, a marker of sleep homeostasis. Thus, the systematic increase of firing during wakefulness is counterbalanced by staying asleep.

Dynamic Balance of Excitation and Inhibition in Human and Monkey Neocortex

NASA Astrophysics Data System (ADS)

Dehghani, Nima; Peyrache, Adrien; Telenczuk, Bartosz; Le van Quyen, Michel; Halgren, Eric; Cash, Sydney S.; Hatsopoulos, Nicholas G.; Destexhe, Alain

2016-03-01

Balance of excitation and inhibition is a fundamental feature of in vivo network activity and is important for its computations. However, its presence in the neocortex of higher mammals is not well established. We investigated the dynamics of excitation and inhibition using dense multielectrode recordings in humans and monkeys. We found that in all states of the wake-sleep cycle, excitatory and inhibitory ensembles are well balanced, and co-fluctuate with slight instantaneous deviations from perfect balance, mostly in slow-wave sleep. Remarkably, these correlated fluctuations are seen for many different temporal scales. The similarity of these computational features with a network model of self-generated balanced states suggests that such balanced activity is essentially generated by recurrent activity in the local network and is not due to external inputs. Finally, we find that this balance breaks down during seizures, where the temporal correlation of excitatory and inhibitory populations is disrupted. These results show that balanced activity is a feature of normal brain activity, and break down of the balance could be an important factor to define pathological states.

Gap junctions mediate large-scale Turing structures in a mean-field cortex driven by subcortical noise

NASA Astrophysics Data System (ADS)

Steyn-Ross, Moira L.; Steyn-Ross, D. A.; Wilson, M. T.; Sleigh, J. W.

2007-07-01

One of the grand puzzles in neuroscience is establishing the link between cognition and the disparate patterns of spontaneous and task-induced brain activity that can be measured clinically using a wide range of detection modalities such as scalp electrodes and imaging tomography. High-level brain function is not a single-neuron property, yet emerges as a cooperative phenomenon of multiply-interacting populations of neurons. Therefore a fruitful modeling approach is to picture the cerebral cortex as a continuum characterized by parameters that have been averaged over a small volume of cortical tissue. Such mean-field cortical models have been used to investigate gross patterns of brain behavior such as anesthesia, the cycles of natural sleep, memory and erasure in slow-wave sleep, and epilepsy. There is persuasive and accumulating evidence that direct gap-junction connections between inhibitory neurons promote synchronous oscillatory behavior both locally and across distances of some centimeters, but, to date, continuum models have ignored gap-junction connectivity. In this paper we employ simple mean-field arguments to derive an expression for D2 , the diffusive coupling strength arising from gap-junction connections between inhibitory neurons. Using recent neurophysiological measurements reported by Fukuda [J. Neurosci. 26, 3434 (2006)], we estimate an upper limit of D2≈0.6cm2 . We apply a linear stability analysis to a standard mean-field cortical model, augmented with gap-junction diffusion, and find this value for the diffusive coupling strength to be close to the critical value required to destabilize the homogeneous steady state. Computer simulations demonstrate that larger values of D2 cause the noise-driven model cortex to spontaneously crystalize into random mazelike Turing structures: centimeter-scale spatial patterns in which regions of high-firing activity are intermixed with regions of low-firing activity. These structures are consistent with the spatial variations in brain activity patterns detected with the BOLD (blood oxygen-level-dependent) signal detected with magnetic resonance imaging, and may provide a natural substrate for synchronous gamma-band rhythms observed across separated EEG (electroencephalogram) electrodes.

Modulating NMDA Receptor Function with D-Amino Acid Oxidase Inhibitors: Understanding Functional Activity in PCP-Treated Mouse Model

PubMed Central

Sershen, Henry; Hashim, Audrey; Dunlop, David S.; Suckow, Raymond F.; Cooper, Tom B.; Javitt, Daniel C.

2016-01-01

Deficits in N-methyl-D-aspartate receptor (NMDAR) function are increasingly linked to persistent negative symptoms and cognitive deficits in schizophrenia. Accordingly, clinical studies have been targeting the modulatory site of the NMDA receptor, based on the decreased function of NMDA receptor, to see whether increasing NMDA function can potentially help treat the negative and cognitive deficits seen in the disease. Glycine and D-serine are endogenous ligands to the NMDA modulatory site, but since high doses are needed to affect brain levels, related compounds are being developed, for example glycine transport (GlyT) inhibitors to potentially elevate brain glycine or targeting enzymes, such as D-amino acid oxidase (DAAO) to slow the breakdown and increase the brain level of D-serine. In the present study we further evaluated the effect of DAAO inhibitors 5-chloro-benzo[d]isoxazol-3-ol (CBIO) and sodium benzoate (NaB) in a phencyclidine (PCP) rodent mouse model to see if the inhibitors affect PCP-induced locomotor activity, alter brain D-serine level, and thereby potentially enhance D-serine responses. D-Serine dose-dependently reduced the PCP-induced locomotor activity at doses above 1000 mg/kg. Acute CBIO (30 mg/kg) did not affect PCP-induced locomotor activity, but appeared to reduce locomotor activity when given with D-serine (600 mg/kg); a dose that by itself did not have an effect. However, the effect was also present when the vehicle (Trappsol®) was tested with D-serine, suggesting that the reduction in locomotor activity was not related to DAAO inhibition, but possibly reflected enhanced bioavailability of D-serine across the blood brain barrier related to the vehicle. With this acute dose of CBIO, D-serine level in brain and plasma were not increased. Another weaker DAAO inhibitor sodium benzoate (NaB) (400 mg/kg), and NaB plus D-serine also significantly reduced PCP-induced locomotor activity, but without affecting plasma or brain D-serine level, arguing against a DAAO-mediated effect. However, NaB reduced plasma L-serine and based on reports that NaB also elevates various plasma metabolites, for example aminoisobutyric acid (AIB), a potential effect via the System A amino acid carrier may be involved in the regulation of synaptic glycine level to modulate NMDAR function needs to be investigated. Acute ascorbic acid (300 mg/kg) also inhibited PCP-induced locomotor activity, which was further attenuated in the presence of D-serine (600 mg/kg). Ascorbic acid may have an action at the dopamine membrane carrier and/or altering redox mechanisms that modulate NMDARs, but this needs to be further investigated. The findings support an effect of D-serine on PCP-induced hyperactivity. They also offer suggestions on an interaction of NaB via an unknown mechanism, other than DAAO inhibition, perhaps through metabolomic changes, and find unexpected synergy between D-serine and ascorbic acid that supports combined NMDA glycine- and redox-site intervention. Although mechanisms of these specific agents need to be determined, overall it supports continued glutamatergic drug development. PMID:26857796

Tetrapentylammonium block of chloramine-T and veratridine modified rat brain type IIA sodium channels

PubMed Central

Ghatpande, A S; Rao, S; Sikdar, S K

2001-01-01

Tetrapentylammonium (TPeA) block of rat brain type IIA sodium channel α subunit was studied using whole cell patch clamp. Results indicate that TPeA blocks the inactivating brain sodium channel in a potential and use-dependent manner similar to that of the cardiac sodium channel. Removal of inactivation using chloramine-T (CT) unmasks a time-dependent block by TPeA consistent with slow blocking kinetics. On the other hand, no time dependence is observed when inactivation is abolished by modification with veratridine. TPeA does not bind in a potential-dependent fashion to veratridine-modified channels and does not significantly affect gating of veratridine-modified channels suggesting that high affinity binding of TPeA to the brain sodium channel is lost after veratridine modification. PMID:11309247

The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism

PubMed Central

Sonsalla, Patricia K.; Coleman, Christal; Wong, Lai-Yoong; Harris, Suzan L.; Richardson, Jason R.; Gadad, Bharathi S.; Li, Wenhao; German, Dwight C.

2013-01-01

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by a prominent loss of nigrostriatal dopamine (DA) neurons with an accompanying neuroinflammation. The peptide angiotensin II (AngII) plays a role in oxidative-stress induced disorders and is thought to mediate its detrimental actions via activation of AngII AT1 receptors. The brain renin-angiotensin system is implicated in neurodegenerative disorders including PD. Blockade of the angiotensin converting enzyme or AT1 receptors provides protection in acute animal models of parkinsonism. We demonstrate here that treatment of mice with the angiotensin converting enzyme inhibitor captopril protects the striatum from acutely administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP), and that chronic captopril protects the nigral DA cell bodies from degeneration in a progressive rat model of parkinsonism created by the chronic intracerebral infusion of 1-methyl-4-phenylpyridinium (MPP+). The accompanying activation of microglia in the substantia nigra of MPP+-treated rats was reduced by the chronic captopril treatment. These findings indicate that captopril is neuroprotective for nigrostriatal DA neurons in both acute and chronic rodent PD models. Targeting the brain AngII pathway may be a feasible approach to slowing neurodegeneration in PD. PMID:24184050

Opioid system of the brain and ethanol.

PubMed

Gogichadze, M; Mgaloblishvili-Nemsadze, M; Oniani, N; Emukhvary, N; Basishvili, T

2009-04-01

Influence of blocking of opioid receptors with concomitant intraperitoneal injections of Naloxone (20 mg/kg) (non-selective antagonist of opioid system) on the outcomes of anesthetic dose of ethanol (4,25 ml /kg 25% solution) was investigated in the rats. The sleep-wakefulness cycle (SWC) was used as a model for identification of the effects. Alterations of the SWC structure adequately reflect the neuro-chemical changes, which may develop during pharmacological and non-pharmacological impact. Administration of anesthetic dose of ethanol evoked considerable modification of spontaneous EEG activity of the neocortex. The EEG activity was depressed and full inhibition of spinal reflexes and somatic muscular relaxation did occur. During EEG depression regular SWC did not develop. All phases of SWC were reduced. The disturbances of SWC, such as decrease of slow wave sleep and paradoxical sleep duration and increase of wakefulness, remained for several days. At concomitant administration of Naloxone and ethanol, duration of EEG depression decreased significantly. Generation of normal SWC was observed on the same experimental day. However, it should be noted that complete abolishment of ethanol effects by Naloxone was not observed. The results obtained suggest that Naloxone partially blocks ethanol depressogenic effects and duration of this effect is mediated by GABA-ergic system of the brain.

Hierarchical Heteroclinics in Dynamical Model of Cognitive Processes: Chunking

NASA Astrophysics Data System (ADS)

Afraimovich, Valentin S.; Young, Todd R.; Rabinovich, Mikhail I.

Combining the results of brain imaging and nonlinear dynamics provides a new hierarchical vision of brain network functionality that is helpful in understanding the relationship of the network to different mental tasks. Using these ideas it is possible to build adequate models for the description and prediction of different cognitive activities in which the number of variables is usually small enough for analysis. The dynamical images of different mental processes depend on their temporal organization and, as a rule, cannot be just simple attractors since cognition is characterized by transient dynamics. The mathematical image for a robust transient is a stable heteroclinic channel consisting of a chain of saddles connected by unstable separatrices. We focus here on hierarchical chunking dynamics that can represent several cognitive activities. Chunking is the dynamical phenomenon that means dividing a long information chain into shorter items. Chunking is known to be important in many processes of perception, learning, memory and cognition. We prove that in the phase space of the model that describes chunking there exists a new mathematical object — heteroclinic sequence of heteroclinic cycles — using the technique of slow-fast approximations. This new object serves as a skeleton of motions reflecting sequential features of hierarchical chunking dynamics and is an adequate image of the chunking processing.

Slow Cortical Dynamics and the Accumulation of Information over Long Timescales

PubMed Central

Honey, Christopher J.; Thesen, Thomas; Donner, Tobias H.; Silbert, Lauren J.; Carlson, Chad E.; Devinsky, Orrin; Doyle, Werner K.; Rubin, Nava; Heeger, David J.; Hasson, Uri

2012-01-01

SUMMARY Making sense of the world requires us to process information over multiple timescales. We sought to identify brain regions that accumulate information over short and long timescales and to characterize the distinguishing features of their dynamics. We recorded electrocorticographic (ECoG) signals from individuals watching intact and scrambled movies. Within sensory regions, fluctuations of high-frequency (64–200 Hz) power reliably tracked instantaneous low-level properties of the intact and scrambled movies. Within higher order regions, the power fluctuations were more reliable for the intact movie than the scrambled movie, indicating that these regions accumulate information over relatively long time periods (several seconds or longer). Slow (<0.1 Hz) fluctuations of high-frequency power with time courses locked to the movies were observed throughout the cortex. Slow fluctuations were relatively larger in regions that accumulated information over longer time periods, suggesting a connection between slow neuronal population dynamics and temporally extended information processing. PMID:23083743

16 CFR § 1303.5 - Findings.

Code of Federal Regulations, 2013 CFR

2013-01-01

... regulation is designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents in the hippocampus.

PubMed Central

Isaacson, J S; Nicoll, R A

1991-01-01

Aniracetam is a nootropic drug that has been shown to selectively enhance quisqualate receptor-mediated responses in Xenopus oocytes injected with brain mRNA and in hippocampal pyramidal cells [Ito, I., Tanabe, S., Kohda, A. & Sugiyama, H. (1990) J. Physiol. (London) 424, 533-544]. We have used patch clamp recording techniques in hippocampal slices to elucidate the mechanism for this selective action. We find that aniracetam enhances glutamate-evoked currents in whole-cell recordings and, in outside-out patches, strongly reduces glutamate receptor desensitization. In addition, aniracetam selectively prolongs the time course and increases the peak amplitude of fast synaptic currents. These findings indicate that aniracetam slows the kinetics of fast synaptic transmission and are consistent with the proposal [Trussell, L. O. & Fischbach, G. D. (1989) Neuron 3, 209-218; Tang, C.-M., Dichter, M. & Morad, M. (1989) Science 243, 1474-1477] that receptor desensitization governs the strength of fast excitatory synaptic transmission in the brain. PMID:1660156

Aniracetam reduces glutamate receptor desensitization and slows the decay of fast excitatory synaptic currents in the hippocampus.

PubMed

Isaacson, J S; Nicoll, R A

1991-12-01

Aniracetam is a nootropic drug that has been shown to selectively enhance quisqualate receptor-mediated responses in Xenopus oocytes injected with brain mRNA and in hippocampal pyramidal cells [Ito, I., Tanabe, S., Kohda, A. & Sugiyama, H. (1990) J. Physiol. (London) 424, 533-544]. We have used patch clamp recording techniques in hippocampal slices to elucidate the mechanism for this selective action. We find that aniracetam enhances glutamate-evoked currents in whole-cell recordings and, in outside-out patches, strongly reduces glutamate receptor desensitization. In addition, aniracetam selectively prolongs the time course and increases the peak amplitude of fast synaptic currents. These findings indicate that aniracetam slows the kinetics of fast synaptic transmission and are consistent with the proposal [Trussell, L. O. & Fischbach, G. D. (1989) Neuron 3, 209-218; Tang, C.-M., Dichter, M. & Morad, M. (1989) Science 243, 1474-1477] that receptor desensitization governs the strength of fast excitatory synaptic transmission in the brain.

Age-related delay in visual and auditory evoked responses is mediated by white- and grey-matter differences.

PubMed

Price, D; Tyler, L K; Neto Henriques, R; Campbell, K L; Williams, N; Treder, M S; Taylor, J R; Henson, R N A

2017-06-09

Slowing is a common feature of ageing, yet a direct relationship between neural slowing and brain atrophy is yet to be established in healthy humans. We combine magnetoencephalographic (MEG) measures of neural processing speed with magnetic resonance imaging (MRI) measures of white and grey matter in a large population-derived cohort to investigate the relationship between age-related structural differences and visual evoked field (VEF) and auditory evoked field (AEF) delay across two different tasks. Here we use a novel technique to show that VEFs exhibit a constant delay, whereas AEFs exhibit delay that accumulates over time. White-matter (WM) microstructure in the optic radiation partially mediates visual delay, suggesting increased transmission time, whereas grey matter (GM) in auditory cortex partially mediates auditory delay, suggesting less efficient local processing. Our results demonstrate that age has dissociable effects on neural processing speed, and that these effects relate to different types of brain atrophy.

Age-related delay in visual and auditory evoked responses is mediated by white- and grey-matter differences

PubMed Central

Price, D.; Tyler, L. K.; Neto Henriques, R.; Campbell, K. L.; Williams, N.; Treder, M.S.; Taylor, J. R.; Brayne, Carol; Bullmore, Edward T.; Calder, Andrew C.; Cusack, Rhodri; Dalgleish, Tim; Duncan, John; Matthews, Fiona E.; Marslen-Wilson, William D.; Rowe, James B.; Shafto, Meredith A.; Cheung, Teresa; Davis, Simon; Geerligs, Linda; Kievit, Rogier; McCarrey, Anna; Mustafa, Abdur; Samu, David; Tsvetanov, Kamen A.; van Belle, Janna; Bates, Lauren; Emery, Tina; Erzinglioglu, Sharon; Gadie, Andrew; Gerbase, Sofia; Georgieva, Stanimira; Hanley, Claire; Parkin, Beth; Troy, David; Auer, Tibor; Correia, Marta; Gao, Lu; Green, Emma; Allen, Jodie; Amery, Gillian; Amunts, Liana; Barcroft, Anne; Castle, Amanda; Dias, Cheryl; Dowrick, Jonathan; Fair, Melissa; Fisher, Hayley; Goulding, Anna; Grewal, Adarsh; Hale, Geoff; Hilton, Andrew; Johnson, Frances; Johnston, Patricia; Kavanagh-Williamson, Thea; Kwasniewska, Magdalena; McMinn, Alison; Norman, Kim; Penrose, Jessica; Roby, Fiona; Rowland, Diane; Sargeant, John; Squire, Maggie; Stevens, Beth; Stoddart, Aldabra; Stone, Cheryl; Thompson, Tracy; Yazlik, Ozlem; Barnes, Dan; Dixon, Marie; Hillman, Jaya; Mitchell, Joanne; Villis, Laura; Henson, R. N. A.

2017-01-01

Slowing is a common feature of ageing, yet a direct relationship between neural slowing and brain atrophy is yet to be established in healthy humans. We combine magnetoencephalographic (MEG) measures of neural processing speed with magnetic resonance imaging (MRI) measures of white and grey matter in a large population-derived cohort to investigate the relationship between age-related structural differences and visual evoked field (VEF) and auditory evoked field (AEF) delay across two different tasks. Here we use a novel technique to show that VEFs exhibit a constant delay, whereas AEFs exhibit delay that accumulates over time. White-matter (WM) microstructure in the optic radiation partially mediates visual delay, suggesting increased transmission time, whereas grey matter (GM) in auditory cortex partially mediates auditory delay, suggesting less efficient local processing. Our results demonstrate that age has dissociable effects on neural processing speed, and that these effects relate to different types of brain atrophy. PMID:28598417

Mammalian brain development and our grandmothering life history.

PubMed

Hawkes, Kristen; Finlay, Barbara L

2018-05-02

Among mammals, including humans, adult brain size and the relative size of brain components depend precisely on the duration of a highly regular process of neural development. Much wider variation is seen in rates of body growth and the state of neural maturation at life history events like birth and weaning. Large brains result from slow maturation, which in humans is accompanied by weaning early with respect to both neural maturation and longevity. The grandmother hypothesis proposes this distinctive combination of life history features evolved as ancestral populations began to depend on foods that just weaned juveniles couldn't handle. Here we trace possible reciprocal connections between brain development and life history, highlighting the resulting extended neural plasticity in a wider cognitive ecology of allomaternal care that distinguishes human ontogeny with consequences for other peculiarities of our lineage. Copyright © 2018 Elsevier Inc. All rights reserved.

Event-related potentials in homosexual and heterosexual men and women: sex-dimorphic patterns in verbal asymmetries and mental rotation.

PubMed

Wegesin, D J

1998-02-01

To elucidate neurobiological factors related to gender and sexual orientation, event-related brain potentials of 20 heterosexual (HT) men, 20 HT women, 20 homosexual (HM) men, and 20 HM women were examined for neurophysiological differences. Cognitive tasks which typically elicit sex differences were administered. A mental rotation (MR) task assessed spatial ability, and a divided-visual-field lexical-decision/semantic monitoring task (LD/SM) assessed verbal ability and relative degrees of language lateralization. Slow wave activity recorded during MR was greater for HT men than for HT women and gay men. N400 asymmetries recorded during the LD/SM task revealed differences between men and women, but no intrasex differences. Copyright 1998 Academic Press.

The biology of brain metastases—translation to new therapies

PubMed Central

Eichler, April F.; Chung, Euiheon; Kodack, David P.; Loeffler, Jay S.; Fukumura, Dai; Jain, Rakesh K.

2012-01-01

Brain metastases are a serious obstacle in the treatment of patients with solid tumors and contribute to the morbidity and mortality of these cancers. It is speculated that the frequency of brain metastasis is increasing for several reasons, including improved systemic therapy and survival, and detection of metastases in asymptomatic patients. The lack of preclinical models that recapitulate the clinical setting and the exclusion of patients with brain metastases from most clinical trials have slowed progress. Molecular factors contributing to brain metastases are being elucidated, such as genes involved in cell adhesion, extravasation, metabolism, and cellular signaling. Furthermore, the role of the unique brain microenvironment is beginning to be explored. Although the presence and function of the blood–brain barrier in metastatic tumors is still poorly understood, it is likely that some tumor cells are protected from therapeutics by the blood–tumor barrier, creating a sanctuary site. This Review discusses what is known about the biology of brain metastases, what preclinical models are available to study the disease, and which novel therapeutic strategies are being studied in patients. PMID:21487419

Cytoplasm-to-myonucleus ratios and succinate dehydrogenase activities in adult rat slow and fast muscle fibers

NASA Technical Reports Server (NTRS)

Tseng, B. S.; Kasper, C. E.; Edgerton, V. R.

1994-01-01

The relationship between myonuclear number, cellular size, succinate dehydrogenase activity, and myosin type was examined in single fiber segments (n = 54; 9 +/- 3 mm long) mechanically dissected from soleus and plantaris muscles of adult rats. One end of each fiber segment was stained for DNA before quantitative photometric analysis of succinate dehydrogenase activity; the other end was double immunolabeled with fast and slow myosin heavy chain monoclonal antibodies. Mean +/- S.D. cytoplasmic volume/myonucleus ratio was higher in fast and slow plantaris fibers (112 +/- 69 vs. 34 +/- 21 x 10(3) microns3) than fast and slow soleus fibers (40 +/- 20 vs. 30 +/- 14 x 10(3) microns3), respectively. Slow fibers always had small volumes/myonucleus, regardless of fiber diameter, succinate dehydrogenase activity, or muscle of origin. In contrast, smaller diameter (< 70 microns) fast soleus and plantaris fibers with high succinate dehydrogenase activity appeared to have low volumes/myonucleus while larger diameter (> 70 microns) fast fibers with low succinate dehydrogenase activity always had large volume/myonucleus. Slow soleus fibers had significantly greater numbers of myonuclei/mm than did either fast soleus or fast plantaris fibers (116 +/- 51 vs. 55 +/- 22 and 44 +/- 23), respectively. These data suggest that the myonuclear domain is more limited in slow than fast fibers and in the fibers with a high, compared to a low, oxidative metabolic capability.