Distinctive time-lagged resting-state networks revealed by simultaneous EEG-fMRI.

PubMed

Feige, Bernd; Spiegelhalder, Kai; Kiemen, Andrea; Bosch, Oliver G; Tebartz van Elst, Ludger; Hennig, Jürgen; Seifritz, Erich; Riemann, Dieter

2017-01-15

Functional activation as evidenced by blood oxygen level-dependent (BOLD) functional MRI changes or event-related EEG is known to closely follow patterns of stimulation or self-paced action. Any lags are compatible with axonal conduction velocities and neural integration times. The important analysis of resting state networks is generally based on the assumption that these principles also hold for spontaneous fluctuations in brain activity. Previous observations using simultaneous EEG and fMRI indicate that slower processes, with delays in the seconds range, determine at least part of the relationship between spontaneous EEG and fMRI. To assess this relationship systematically, we used deconvolution analysis of EEG-fMRI during the resting state, assessing the relationship between EEG frequency bands and fMRI BOLD across the whole brain while allowing for time lags of up to 10.5s. Cluster analysis, identifying similar BOLD time courses in relation to EEG band power peaks, showed a clear segregation of functional subsystems of the brain. Our analysis shows that fMRI BOLD increases commonly precede EEG power increases by seconds. Most zero-lag correlations, on the other hand, were negative. This indicates two main distinct neuromodulatory mechanisms: an "idling" mechanism of simultaneous electric and metabolic network anticorrelation and a "regulatory" mechanism in which metabolic network activity precedes increased EEG power by some seconds. This has to be taken into consideration in further studies which address the causal and functional relationship of metabolic and electric brain activity patterns. Copyright © 2016 Elsevier Inc. All rights reserved.

Time delay between cardiac and brain activity during sleep transitions

NASA Astrophysics Data System (ADS)

Long, Xi; Arends, Johan B.; Aarts, Ronald M.; Haakma, Reinder; Fonseca, Pedro; Rolink, Jérôme

2015-04-01

Human sleep consists of wake, rapid-eye-movement (REM) sleep, and non-REM (NREM) sleep that includes light and deep sleep stages. This work investigated the time delay between changes of cardiac and brain activity for sleep transitions. Here, the brain activity was quantified by electroencephalographic (EEG) mean frequency and the cardiac parameters included heart rate, standard deviation of heartbeat intervals, and their low- and high-frequency spectral powers. Using a cross-correlation analysis, we found that the cardiac variations during wake-sleep and NREM sleep transitions preceded the EEG changes by 1-3 min but this was not the case for REM sleep transitions. These important findings can be further used to predict the onset and ending of some sleep stages in an early manner.

The Brain Circuitry Underlying the Temporal Evolution of Nausea in Humans

PubMed Central

Sheehan, James D.; Kim, Jieun; LaCount, Lauren T.; Park, Kyungmo; Kaptchuk, Ted J.; Rosen, Bruce R.; Kuo, Braden

2013-01-01

Nausea is a universal human experience. It evolves slowly over time, and brain mechanisms underlying this evolution are not well understood. Our functional magnetic resonance imaging (fMRI) approach evaluated brain activity contributing to and arising from increasing motion sickness. Subjects rated transitions to increasing nausea, produced by visually induced vection within the fMRI environment. We evaluated parametrically increasing brain activity 1) precipitating increasing nausea and 2) following transition to stronger nausea. All subjects demonstrated visual stimulus–associated activation (P < 0.01) in primary and extrastriate visual cortices. In subjects experiencing motion sickness, increasing phasic activity preceding nausea was found in amygdala, putamen, and dorsal pons/locus ceruleus. Increasing sustained response following increased nausea was found in a broader network including insular, anterior cingulate, orbitofrontal, somatosensory and prefrontal cortices. Moreover, sustained anterior insula activation to strong nausea was correlated with midcingulate activation (r = 0.87), suggesting a closer linkage between these specific regions within the brain circuitry subserving nausea perception. Thus, while phasic activation in fear conditioning and noradrenergic brainstem regions precipitates transition to strong nausea, sustained activation following this transition occurs in a broader interoceptive, limbic, somatosensory, and cognitive network, reflecting the multiple dimensions of this aversive commonly occurring symptom. PMID:22473843

The brain circuitry underlying the temporal evolution of nausea in humans.

PubMed

Napadow, Vitaly; Sheehan, James D; Kim, Jieun; Lacount, Lauren T; Park, Kyungmo; Kaptchuk, Ted J; Rosen, Bruce R; Kuo, Braden

2013-04-01

Nausea is a universal human experience. It evolves slowly over time, and brain mechanisms underlying this evolution are not well understood. Our functional magnetic resonance imaging (fMRI) approach evaluated brain activity contributing to and arising from increasing motion sickness. Subjects rated transitions to increasing nausea, produced by visually induced vection within the fMRI environment. We evaluated parametrically increasing brain activity 1) precipitating increasing nausea and 2) following transition to stronger nausea. All subjects demonstrated visual stimulus-associated activation (P < 0.01) in primary and extrastriate visual cortices. In subjects experiencing motion sickness, increasing phasic activity preceding nausea was found in amygdala, putamen, and dorsal pons/locus ceruleus. Increasing sustained response following increased nausea was found in a broader network including insular, anterior cingulate, orbitofrontal, somatosensory and prefrontal cortices. Moreover, sustained anterior insula activation to strong nausea was correlated with midcingulate activation (r = 0.87), suggesting a closer linkage between these specific regions within the brain circuitry subserving nausea perception. Thus, while phasic activation in fear conditioning and noradrenergic brainstem regions precipitates transition to strong nausea, sustained activation following this transition occurs in a broader interoceptive, limbic, somatosensory, and cognitive network, reflecting the multiple dimensions of this aversive commonly occurring symptom.

Dissociable neural effects of stimulus valence and preceding context during the inhibition of responses to emotional faces.

PubMed

Schulz, Kurt P; Clerkin, Suzanne M; Halperin, Jeffrey M; Newcorn, Jeffrey H; Tang, Cheuk Y; Fan, Jin

2009-09-01

Socially appropriate behavior requires the concurrent inhibition of actions that are inappropriate in the context. This self-regulatory function requires an interaction of inhibitory and emotional processes that recruits brain regions beyond those engaged by either processes alone. In this study, we isolated brain activity associated with response inhibition and emotional processing in 24 healthy adults using event-related functional magnetic resonance imaging (fMRI) and a go/no-go task that independently manipulated the context preceding no-go trials (ie, number of go trials) and the valence (ie, happy, sad, and neutral) of the face stimuli used as trial cues. Parallel quadratic trends were seen in correct inhibitions on no-go trials preceded by increasing numbers of go trials and associated activation for correct no-go trials in inferior frontal gyrus pars opercularis, pars triangularis, and pars orbitalis, temporoparietal junction, superior parietal lobule, and temporal sensory association cortices. Conversely, the comparison of happy versus neutral faces and sad versus neutral faces revealed valence-dependent activation in the amygdala, anterior insula cortex, and posterior midcingulate cortex. Further, an interaction between inhibition and emotion was seen in valence-dependent variations in the quadratic trend in no-go activation in the right inferior frontal gyrus and left posterior insula cortex. These results suggest that the inhibition of response to emotional cues involves the interaction of partly dissociable limbic and frontoparietal networks that encode emotional cues and use these cues to exert inhibitory control over the motor, attention, and sensory functions needed to perform the task, respectively. 2008 Wiley-Liss, Inc.

Physical activity and trial-by-trial adjustments of response conflict.

PubMed

Kamijo, Keita; Takeda, Yuji

2013-08-01

The relationship of physical activity to trial-by-trial adjustments of response conflict was assessed using behavioral task performance, the N2 event-related brain potential component, and phase-locking values (PLVs) in a lower gamma band during a perceptual conflict task. Nineteen physically active and 19 inactive young adults (mean age = 21.3 years) performed a Navon task, using a global letter made up of local letters of either the same kind (congruent trials) or a different kind (incongruent trials). Findings revealed that active individuals exhibited smaller N2 amplitudes and greater PLVs on incongruent trials that were preceded by incongruent trials compared with those preceded by congruent trials. Such phenomena were not observed for inactive individuals. These results suggest that greater physical activity is associated with larger trial-by-trial adjustments of response conflict, which we attribute to upregulation of top-down cognitive control and reductions in response conflict.

Temporal orienting precedes intersensory attention and has opposing effects on early evoked brain activity.

PubMed

Keil, Julian; Pomper, Ulrich; Feuerbach, Nele; Senkowski, Daniel

2017-03-01

Intersensory attention (IA) describes the process of directing attention to a specific modality. Temporal orienting (TO) characterizes directing attention to a specific moment in time. Previously, studies indicated that these two processes could have opposite effects on early evoked brain activity. The exact time-course and processing stages of both processes are still unknown. In this human electroencephalography study, we investigated the effects of IA and TO on visuo-tactile stimulus processing within one paradigm. IA was manipulated by presenting auditory cues to indicate whether participants should detect visual or tactile targets in visuo-tactile stimuli. TO was manipulated by presenting stimuli block-wise at fixed or variable inter-stimulus intervals. We observed that TO affects evoked activity to visuo-tactile stimuli prior to IA. Moreover, we found that TO reduces the amplitude of early evoked brain activity, whereas IA enhances it. Using beamformer source-localization, we observed that IA increases neural responses in sensory areas of the attended modality whereas TO reduces brain activity in widespread cortical areas. Based on these findings we derive an updated working model for the effects of temporal and intersensory attention on early evoked brain activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Feature precedence in processing multifeature visual information in the human brain: an event-related potential study.

PubMed

Liu, B; Meng, X; Wu, G; Huang, Y

2012-05-17

In this article, we aimed to study whether feature precedence existed in the cognitive processing of multifeature visual information in the human brain. In our experiment, we paid attention to two important visual features as follows: color and shape. In order to avoid the presence of semantic constraints between them and the resulting impact, pure color and simple geometric shape were chosen as the color feature and shape feature of visual stimulus, respectively. We adopted an "old/new" paradigm to study the cognitive processing of color feature, shape feature and the combination of color feature and shape feature, respectively. The experiment consisted of three tasks as follows: Color task, Shape task and Color-Shape task. The results showed that the feature-based pattern would be activated in the human brain in processing multifeature visual information without semantic association between features. Furthermore, shape feature was processed earlier than color feature, and the cognitive processing of color feature was more difficult than that of shape feature. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia

PubMed Central

Deb, Ishani; Manhas, Namratta; Poddar, Ranjana; Rajagopal, Sathyanarayanan; Allan, Andrea M.; Lombroso, Paul J.; Rosenberg, Gary A.; Candelario-Jalil, Eduardo

2013-01-01

The striatal-enriched phosphatase (STEP) is a component of the NMDA-receptor-mediated excitotoxic signaling pathway, which plays a key role in ischemic brain injury. Using neuronal cultures and a rat model of ischemic stroke, we show that STEP plays an initial role in neuroprotection, during the insult, by disrupting the p38 MAPK pathway. Degradation of active STEP during reperfusion precedes ischemic brain damage and is associated with secondary activation of p38 MAPK. Application of a cell-permeable STEP-derived peptide that is resistant to degradation and binds to p38 MAPK protects cultured neurons from hypoxia-reoxygenation injury and reduces ischemic brain damage when injected up to 6 h after the insult. Conversely, genetic deletion of STEP in mice leads to sustained p38 MAPK activation and exacerbates brain injury and neurological deficits after ischemia. Administration of the STEP-derived peptide at the onset of reperfusion not only prevents the sustained p38 MAPK activation but also reduces ischemic brain damage in STEP KO mice. The findings indicate a neuroprotective role of STEP and suggest a potential role of the STEP-derived peptide in stroke therapy. PMID:24198371

Establishing the functional connectivity of the frontotemporal network in pre-attentive change detection with Transcranial Magnetic Stimulation and event-related optical signal.

PubMed

Tse, Chun-Yu; Long-Yin, Yip; Lui, Troby Ka-Yan; Xiao, Xue-Zhen; Wang, Yang; Chu, Winnie Chiu Wing; Parks, Nathan Allen; Chan, Sandra Sau-Man; Neggers, Sebastiaan Franciscus Wijnandus

2018-06-18

Current theories of pre-attentive deviant detection postulate that before the Superior Temporal Cortex (STC) detects a change, the Inferior Frontal Cortex (IFC) engages in stimulus analysis, which is particularly critical for ambiguous deviations (e.g., deviant preceded by a short train of standards). These theories rest on the assumption that IFC and STC are functionally connected, which has only been supported by correlational brain imaging studies. We examined this functional connectivity assumption by applying Transcranial Magnetic Stimulation (TMS) to disrupt IFC function, while measuring the later STC mismatch response with the event-related optical signal (EROS). EROS can localize brain activity in both spatial and temporal dimensions via measurement of optical property changes associated with neuronal activity, and is inert to the electromagnetic interference produced by TMS. Specifically, the STC mismatch response at 120-180 ms elicited by a deviant preceded by a short standard train when IFC TMS was applied at 80 ms was compared with the STC mismatch responses in temporal control (TMS with 200 ms delay), spatial control (sham TMS at vertex), auditory control (TMS pulse noise only), and cognitive control (deviant preceded by a long standard train) conditions. The STC mismatch response to deviants preceded by the short train was abolished by TMS of the IFC at 80 ms, while the STC responses remained intact in all other control conditions. These results confirm the involvement of the IFC in the STC mismatch response and support a functional connection between IFC and STC. Copyright © 2018. Published by Elsevier Inc.

Aversive emotional interference impacts behavior and prefronto-striatal activity during increasing attentional control.

PubMed

Papazacharias, Apostolos; Taurisano, Paolo; Fazio, Leonardo; Gelao, Barbara; Di Giorgio, Annabella; Lo Bianco, Luciana; Quarto, Tiziana; Mancini, Marina; Porcelli, Annamaria; Romano, Raffaella; Caforio, Grazia; Todarello, Orlando; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

2015-01-01

Earlier studies have demonstrated that emotional stimulation modulates attentional processing during goal-directed behavior and related activity of a brain network including the inferior frontal gyrus (IFG) and the caudate nucleus. However, it is not clear how emotional interference modulates behavior and brain physiology during variation in attentional control, a relevant question for everyday life situations in which both emotional stimuli and cognitive load vary. The aim of this study was to investigate the impact of negative emotions on behavior and activity in IFG and caudate nucleus during increasing levels of attentional control. Twenty two healthy subjects underwent event-related functional magnetic resonance imaging while performing a task in which neutral or fearful facial expressions were displayed before stimuli eliciting increasing levels of attentional control processing. Results indicated slower reaction time (RT) and greater right IFG activity when fearful compared with neutral facial expressions preceded the low level of attentional control. On the other hand, fearful facial expressions preceding the intermediate level of attentional control elicited faster behavioral responses and greater activity in the right and left sides of the caudate. Finally, correlation analysis indicated a relationship between behavioral correlates of attentional control after emotional interference and right IFG activity. All together, these results suggest that the impact of negative emotions on attentional processing is differentially elicited at the behavioral and physiological levels as a function of cognitive load.

Aversive emotional interference impacts behavior and prefronto-striatal activity during increasing attentional control

PubMed Central

Papazacharias, Apostolos; Taurisano, Paolo; Fazio, Leonardo; Gelao, Barbara; Di Giorgio, Annabella; Lo Bianco, Luciana; Quarto, Tiziana; Mancini, Marina; Porcelli, Annamaria; Romano, Raffaella; Caforio, Grazia; Todarello, Orlando; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

2015-01-01

Earlier studies have demonstrated that emotional stimulation modulates attentional processing during goal-directed behavior and related activity of a brain network including the inferior frontal gyrus (IFG) and the caudate nucleus. However, it is not clear how emotional interference modulates behavior and brain physiology during variation in attentional control, a relevant question for everyday life situations in which both emotional stimuli and cognitive load vary. The aim of this study was to investigate the impact of negative emotions on behavior and activity in IFG and caudate nucleus during increasing levels of attentional control. Twenty two healthy subjects underwent event-related functional magnetic resonance imaging while performing a task in which neutral or fearful facial expressions were displayed before stimuli eliciting increasing levels of attentional control processing. Results indicated slower reaction time (RT) and greater right IFG activity when fearful compared with neutral facial expressions preceded the low level of attentional control. On the other hand, fearful facial expressions preceding the intermediate level of attentional control elicited faster behavioral responses and greater activity in the right and left sides of the caudate. Finally, correlation analysis indicated a relationship between behavioral correlates of attentional control after emotional interference and right IFG activity. All together, these results suggest that the impact of negative emotions on attentional processing is differentially elicited at the behavioral and physiological levels as a function of cognitive load. PMID:25954172

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection

PubMed Central

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments. PMID:28928987

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection.

PubMed

Phillips, Cristy

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments.

Heating and eating: brown adipose tissue thermogenesis precedes food ingestion as part of the ultradian basic rest-activity cycle in rats.

PubMed

Blessing, William; Mohammed, Mazher; Ootsuka, Youichirou

2012-02-28

Laboratory rats, throughout the 24 hour day, alternate between behaviorally active and non active episodes that Kleitman called the basic rest-activity cycle (BRAC). We previously demonstrated that brown adipose tissue (BAT), body and brain temperatures and arterial pressure and heart rate increase in an integrated manner during behaviorally active phases. Studies show that eating is preceded by increases in body and brain temperature, but whether eating is integrated into the BRAC has not been investigated. In the present study of chronically instrumented, unrestrained Sprague-Dawley rats, peaks in BAT temperature occurred every 96 ± 7 and 162 ± 16 min (mean ± SE, n=14 rats) in dark and light periods respectively, with no apparent underlying regularity. With food available ad libitum, eating was integrated into the BRAC in a temporally precise manner. Eating occurred only after an increase in BAT temperature, commencing 15 ± 1 min (mean ± SE) after the onset of an increase, with no difference between dark and light phases. There were either no or weak preprandial and postprandial relations between intermeal interval and amount eaten during a given meal. Remarkably, with no food available the rat still disturbed the empty food container 16 ± 1 min (p>0.05 versus ad libitum food) after the onset of increases in BAT temperature, and not at other times. Rather than being triggered by changes in levels of body fuels or other meal-associated factors, in sedentary laboratory rats with ad libitum access to food eating commences as part of the ultradian BRAC, a manifestation of intrinsic brain activity. Copyright © 2011 Elsevier Inc. All rights reserved.

Pre-seizure state identified by diffuse optical tomography

PubMed Central

Zhang, Tao; Zhou, Junli; Jiang, Ruixin; Yang, Hao; Carney, Paul R.; Jiang, Huabei

2014-01-01

In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Here we demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking such brain activities with high spatiotemporal resolution. We detected early hemodynamic responses with heterogeneous patterns, along with intracranial electroencephalogram gamma power changes, several minutes preceding the electroencephalographic seizure onset, supporting the presence of a “pre-seizure” state. We also observed the decoupling between local hemodynamic and neural activities. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways. PMID:24445927

Brain potentials show rapid activation of implicit attitudes towards young and old people.

PubMed

van der Lugt, Arie H; Banfield, Jane F; Osinsky, Roman; Münte, Thomas F

2012-01-06

While previous behavioural research suggests that attitudes, for example towards elderly people, may be activated automatically, this type of research does not provide information about the detailed time-course of such processing in the brain. We investigated the impact of age related attitude information in a Go/NoGo association task that paired photographs of elderly or young faces with positive or negative words. Event related brain potentials showed an N200 (NoGo) component, which appeared earlier in runs which required similar responses for congruent stimulus pairings (e.g. respond to pictures of elderly faces or negative words) than for incongruent pairings (e.g. respond to elderly faces or positive words). As information processing leading to a certain attitude must precede differential brain activity according to the congruence of the paired words and faces, we show that this type of information is activated almost immediately following the structural encoding of the face, between 170 and 230 ms after onset of the face. Copyright © 2011. Published by Elsevier B.V.

Sleepwalking episodes are preceded by arousal-related activation in the cingulate motor area: EEG current density imaging.

PubMed

Januszko, Piotr; Niemcewicz, Szymon; Gajda, Tomasz; Wołyńczyk-Gmaj, Dorota; Piotrowska, Anna Justyna; Gmaj, Bartłomiej; Piotrowski, Tadeusz; Szelenberger, Waldemar

2016-01-01

To investigate local arousal fluctuations in adults who received ICSD-2 diagnosis of somnambulism. EEG neuroimaging (eLORETA) was utilized to compare current density distribution for 4s epochs immediately preceding sleepwalking episode (from -4.0 s to 0 s) to the distribution during earlier 4s epochs (from -8.0 s to -4.0 s) in 20 EEG segments from 15 patients. Comparisons between eLORETA images revealed significant (t>4.52; p<0.05) brain activations before onset of sleepwalking, with greater current density within beta 3 frequency range (24-30 Hz) in Brodmann areas 33 and 24. Sleepwalking motor events are associated with arousal-related activation of cingulate motor area. These results support the notion of blurred boundaries between wakefulness and NREM sleep in sleepwalking. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction.

PubMed

Stanyer, Lee; Jorgensen, Wenche; Hori, Osamu; Clark, John B; Heales, Simon J R

2008-09-01

The accumulation of oxidatively modified proteins has been shown to be a characteristic feature of many neurodegenerative disorders and its regulation requires efficient proteolytic processing. One component of the mitochondrial proteolytic system is Lon, an ATP-dependent protease that has been shown to degrade oxidatively modified aconitase in vitro and may thus play a role in defending against the accumulation of oxidized matrix proteins in mitochondria. Using an assay system that allowed us to distinguish between basal and ATP-stimulated Lon protease activity, we have shown in isolated non-synaptic rat brain mitochondria that Lon protease is highly susceptible to oxidative inactivation by peroxynitrite (ONOO(-)). This susceptibility was more pronounced with regard to ATP-stimulated activity, which was inhibited by 75% in the presence of a bolus addition of 1mM ONOO(-), whereas basal unstimulated activity was inhibited by 45%. Treatment of mitochondria with a range of peroxynitrite concentrations (10-1000 microM) revealed that a decline in Lon protease activity preceded electron transport chain (ETC) dysfunction (complex I, II-III and IV) and that ATP-stimulated activity was approximately fivefold more sensitive than basal Lon protease activity. Furthermore, supplementation of mitochondrial matrix extracts with reduced glutathione, following ONOO(-) exposure, resulted in partial restoration of basal and ATP-stimulated activity, thus suggesting possible redox regulation of this enzyme complex. Taken together these findings suggest that Lon protease may be particularly vulnerable to inactivation in conditions associated with GSH depletion and elevated oxidative stress.

The Primary Visual Cortex Is Differentially Modulated by Stimulus-Driven and Top-Down Attention

PubMed Central

Bekisz, Marek; Bogdan, Wojciech; Ghazaryan, Anaida; Waleszczyk, Wioletta J.; Kublik, Ewa; Wróbel, Andrzej

2016-01-01

Selective attention can be focused either volitionally, by top-down signals derived from task demands, or automatically, by bottom-up signals from salient stimuli. Because the brain mechanisms that underlie these two attention processes are poorly understood, we recorded local field potentials (LFPs) from primary visual cortical areas of cats as they performed stimulus-driven and anticipatory discrimination tasks. Consistent with our previous observations, in both tasks, we found enhanced beta activity, which we have postulated may serve as an attention carrier. We characterized the functional organization of task-related beta activity by (i) cortical responses (EPs) evoked by electrical stimulation of the optic chiasm and (ii) intracortical LFP correlations. During the anticipatory task, peripheral stimulation that was preceded by high-amplitude beta oscillations evoked large-amplitude EPs compared with EPs that followed low-amplitude beta. In contrast, during the stimulus-driven task, cortical EPs preceded by high-amplitude beta oscillations were, on average, smaller than those preceded by low-amplitude beta. Analysis of the correlations between the different recording sites revealed that beta activation maps were heterogeneous during the bottom-up task and homogeneous for the top-down task. We conclude that bottom-up attention activates cortical visual areas in a mosaic-like pattern, whereas top-down attentional modulation results in spatially homogeneous excitation. PMID:26730705

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.

Can the Brain-Dead Be Harmed or Wronged?: On the Moral Status of Brain Death and its Implications for Organ Transplantation.

PubMed

Nair-Collins, Michael

2017-01-01

The majority of transplantable human organs are retrieved from patients declared dead by neurological criteria, or "brain-dead." Since brain death is considered to be sufficient for death, the procurement of vital organs is not considered to harm or wrong such patients. In this essay I argue that this is not the case. After distinguishing welfare, experiential, and investment interests, and defining precedent autonomy and surviving interests, I argue that brain-dead patients can be, and many are, harmed and wronged by organ procurement as currently practiced. Indeed, with respect to precedent autonomy and surviving investment interests, the brain-dead are morally equivalent to patients with severe dementia, and thus can be harmed and wronged if and only if, and to the extent that, patients with severe dementia can. The "bright line" that separates brain death from all other conditions for clinical and legal purposes is not justified by any morally relevant distinctions.

Brain Responses during the Anticipation of Dyspnea

PubMed Central

Stoeckel, M. Cornelia; Esser, Roland W.; Büchel, Christian

2016-01-01

Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea. PMID:27648309

Brain Responses during the Anticipation of Dyspnea.

PubMed

Stoeckel, M Cornelia; Esser, Roland W; Gamer, Matthias; Büchel, Christian; von Leupoldt, Andreas

2016-01-01

Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea.

Fluctuations in central and peripheral temperatures associated with feeding behavior in rats

PubMed Central

Smirnov, Michael S.; Kiyatkin, Eugene A.

2008-01-01

We examined the pattern of temperature fluctuations in the nucleus accumbens (NAcc), temporal muscle, and skin, along with locomotion in food-deprived and nondeprived rats following the presentation of an open or closed food container and during subsequent eating or food-seeking behavior without eating. Although rats in food-deprived, quiet resting conditions had more than twofold lower spontaneous locomotion and lower temperature values than in nondeprived conditions, after presentation of a container, they consistently displayed food-seeking behavior, showing much larger and longer temperature changes. When the container was open, rats rapidly retrieved food and consumed it. Food consumption was preceded and accompanied by gradual increases in brain and muscle temperatures (∼1.5°C) and a weaker, delayed increase in skin temperature (∼0.8°C). All temperatures began to rapidly fall immediately after eating was completed, but NAcc and muscle temperatures returned to baseline after ∼35 min. When the container was closed and rats were unable to obtain food, they continued food-seeking activity during the entire period of presentation. Similar to eating, this activity was preceded and accompanied by gradual temperature increases in the brain and muscle, which were somewhat smaller than those during eating (∼1.2°C), with no changes in skin temperature. In contrast to trials with eating, NAcc and muscle temperatures continued to increase for ∼10 min after the container was removed from the cage and the rat continued food-seeking behavior, with a return to baselines after ∼50 min. These temperature fluctuations are discussed with respect to alterations in metabolic brain activity associated with feeding behavior, depending upon deprivation state and food availability. PMID:18799633

Antecedent descriptions change brain reactivity to emotional stimuli: a functional magnetic resonance imaging study of an extrinsic and incidental reappraisal strategy.

PubMed

Mocaiber, I; Sanchez, T A; Pereira, M G; Erthal, F S; Joffily, M; Araujo, D B; Volchan, E; de Oliveira, L

2011-10-13

In the present study we investigated whether individuals would take advantage of an extrinsic and incidental reappraisal strategy by giving them precedent descriptions to attenuate the emotional impact of unpleasant pictures. In fact, precedent descriptions have successfully promoted down-regulation of electrocortical activity and physiological responses to unpleasant pictures. However, the neuronal substrate underlying this effect remains unclear. Particularly, we investigated whether amygdala and insula responses, brain regions consistently implicated in emotional processing, would be modulated by this strategy. To achieve this, highly unpleasant pictures were shown in two contexts in which a prior description presented them as taken from movie scenes (fictitious) or real scenes. Results showed that the fictitious condition was characterized by down-regulation of amygdala and insula responses. Thus, the present study provides new evidence on reappraisal strategies to down-regulate emotional reactions and suggest that amygdala and insula responses to emotional stimuli are adaptive and highly flexible. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Developmental Modulation of the Temporal Relationship Between Brain and Behavior

PubMed Central

Crandall, Shane R.; Aoki, Naoya; Nick, Teresa A.

2008-01-01

Humans and songbirds shape learned vocalizations during a sensorimotor sensitive period or “babbling” phase. The brain mechanisms that underlie the shaping of vocalizations by sensory feedback are not known. We examined song behavior and brain activity in zebra finches during singing as they actively shaped their song toward a tutor model. We now show that the temporal relationship of behavior and activity in the premotor area HVC changes with the development of song behavior. During sensorimotor learning, HVC bursting activity both preceded and followed learned vocalizations by hundreds of milliseconds. Correspondingly, the duration of bursts that occurred during ongoing song motif behavior was prolonged in juveniles, as compared with adults, and was inversely correlated with song maturation. Multielectrode single-unit recording in juveniles revealed that single fast-spiking neurons were active both before and after vocalization. These same neurons responded to auditory stimuli. Collectively, these data indicate that a key aspect of sensory critical periods—prolonged bursting—also applies to sensorimotor development. In addition, prolonged motor discharge and sensory input coincide in single neurons of the developing song system, providing the necessary cellular elements for sensorimotor shaping through activity-dependent mechanisms. PMID:17079340

Brain Hyperglycemia Induced by Heroin: Association with Metabolic Neural Activation.

PubMed

Solis, Ernesto; Bola, R Aaron; Fasulo, Bradley J; Kiyatkin, Eugene A

2017-02-15

Glucose enters the brain extracellular space from arterial blood, and its proper delivery is essential for metabolic activity of brain cells. By using enzyme-based biosensors coupled with high-speed amperometry in freely moving rats, we previously showed that glucose levels in the nucleus accumbens (NAc) display high variability, increasing rapidly following exposure to various arousing stimuli. In this study, the same technology was used to assess NAc glucose fluctuations induced by intravenous heroin. Heroin passively injected at a low dose optimal for maintaining self-administration behavior (100 μg/kg) induces a rapid but moderate glucose rise (∼150-200 μM or ∼15-25% over resting baseline). When the heroin dose was doubled and tripled, the increase became progressively larger in magnitude and longer in duration. Heroin-induced glucose increases also occurred in other brain structures (medial thalamus, lateral striatum, hippocampus), suggesting that brain hyperglycemia is a whole-brain phenomenon but changes were notably distinct in each structure. While local vasodilation appears to be the possible mechanism underlying the rapid rise in extracellular glucose levels, the driving factor for this vasodilation (central vs peripheral) remains to be clarified. The heroin-induced NAc glucose increases positively correlated with increases in intracerebral heat production determined in separate experiments using multisite temperature recordings (NAc, temporal muscle and skin). However, glucose levels rise very rapidly, preceding much slower increases in brain heat production, a measure of metabolic activation associated with glucose consumption.

FMRI investigation of cross-modal interactions in beat perception: Audition primes vision, but not vice versa

PubMed Central

Grahn, Jessica A.; Henry, Molly J.; McAuley, J. Devin

2011-01-01

How we measure time and integrate temporal cues from different sensory modalities are fundamental questions in neuroscience. Sensitivity to a “beat” (such as that routinely perceived in music) differs substantially between auditory and visual modalities. Here we examined beat sensitivity in each modality, and examined cross-modal influences, using functional magnetic resonance imaging (fMRI) to characterize brain activity during perception of auditory and visual rhythms. In separate fMRI sessions, participants listened to auditory sequences or watched visual sequences. The order of auditory and visual sequence presentation was counterbalanced so that cross-modal order effects could be investigated. Participants judged whether sequences were speeding up or slowing down, and the pattern of tempo judgments was used to derive a measure of sensitivity to an implied beat. As expected, participants were less sensitive to an implied beat in visual sequences than in auditory sequences. However, visual sequences produced a stronger sense of beat when preceded by auditory sequences with identical temporal structure. Moreover, increases in brain activity were observed in the bilateral putamen for visual sequences preceded by auditory sequences when compared to visual sequences without prior auditory exposure. No such order-dependent differences (behavioral or neural) were found for the auditory sequences. The results provide further evidence for the role of the basal ganglia in internal generation of the beat and suggest that an internal auditory rhythm representation may be activated during visual rhythm perception. PMID:20858544

Cerebral complexity preceded enlarged brain size and reduced olfactory bulbs in Old World monkeys

PubMed Central

Gonzales, Lauren A.; Benefit, Brenda R.; McCrossin, Monte L.; Spoor, Fred

2015-01-01

Analysis of the only complete early cercopithecoid (Old World monkey) endocast currently known, that of 15-million-year (Myr)-old Victoriapithecus, reveals an unexpectedly small endocranial volume (ECV) relative to body size and a large olfactory bulb volume relative to ECV, similar to extant lemurs and Oligocene anthropoids. However, the Victoriapithecus brain has principal and arcuate sulci of the frontal lobe not seen in the stem catarrhine Aegyptopithecus, as well as a distinctive cercopithecoid pattern of gyrification, indicating that cerebral complexity preceded encephalization in cercopithecoids. Since larger ECVs, expanded frontal lobes, and reduced olfactory bulbs are already present in the 17- to 18-Myr-old ape Proconsul these features evolved independently in hominoids (apes) and cercopithecoids and much earlier in the former. Moreover, the order of encephalization and brain reorganization was apparently different in hominoids and cercopithecoids, showing that brain size and cerebral organization evolve independently. PMID:26138795

Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response.

PubMed

Nitschke, Jack B; Sarinopoulos, Issidoros; Oathes, Desmond J; Johnstone, Tom; Whalen, Paul J; Davidson, Richard J; Kalin, Ned H

2009-03-01

The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder.

Anticipatory Activation in the Amygdala and Anterior Cingulate in Generalized Anxiety Disorder and Prediction of Treatment Response

PubMed Central

Nitschke, Jack B.; Sarinopoulos, Issidoros; Oathes, Desmond J.; Johnstone, Tom; Whalen, Paul J.; Davidson, Richard J.; Kalin, Ned H.

2009-01-01

Objective The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. Method Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. Results Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. Conclusions These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder. PMID:19122007

Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury

PubMed Central

Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I.

2015-01-01

Abstract Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3–only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI. PMID:25419789

Anticipating epileptic seizures: from mathematics to clinical applications.

PubMed

Le Van Quyen, Michel

2005-02-01

The study of dynamical changes in the neural activity preceding an epileptic seizure allows the characterization of a preictal state several minutes prior to seizure onset. This opens new perspectives for studying the mechanisms of ictogenesis as well as for possible therapeutic interventions that represent a major breakthrough. In this review we present and discuss the results from our group in this domain using nonlinear analysis of brain signals, as well as its limitation and open questions.

Impact of transient emotions on functional connectivity during subsequent resting state: a wavelet correlation approach.

PubMed

Eryilmaz, Hamdi; Van De Ville, Dimitri; Schwartz, Sophie; Vuilleumier, Patrik

2011-02-01

The functional properties of resting brain activity are poorly understood, but have generally been related to self-monitoring and introspective processes. Here we investigated how emotionally positive and negative information differentially influenced subsequent brain activity at rest. We acquired fMRI data in 15 participants during rest periods following fearful, joyful, and neutral movies. Several brain regions were more active during resting than during movie-watching, including posterior/anterior cingulate cortices (PCC, ACC), bilateral insula and inferior parietal lobules (IPL). Functional connectivity at different frequency bands was also assessed using a wavelet correlation approach and small-world network analysis. Resting activity in ACC and insula as well as their coupling were strongly enhanced by preceding emotions, while coupling between ventral-medial prefrontal cortex and amygdala was selectively reduced. These effects were more pronounced after fearful than joyful movies for higher frequency bands. Moreover, the initial suppression of resting activity in ACC and insula after emotional stimuli was followed by a gradual restoration over time. Emotions did not affect IPL average activity but increased its connectivity with other regions. These findings reveal specific neural circuits recruited during the recovery from emotional arousal and highlight the complex functional dynamics of default mode networks in emotionally salient contexts. Copyright © 2010 Elsevier Inc. All rights reserved.

Spatio-Temporal Information Analysis of Event-Related BOLD Responses

PubMed Central

Alpert, Galit Fuhrmann; Handwerker, Dan; Sun, Felice T.; D’Esposito, Mark; Knight, Robert T.

2009-01-01

A new approach for analysis of event related fMRI (BOLD) signals is proposed. The technique is based on measures from information theory and is used both for spatial localization of task related activity, as well as for extracting temporal information regarding the task dependent propagation of activation across different brain regions. This approach enables whole brain visualization of voxels (areas) most involved in coding of a specific task condition, the time at which they are most informative about the condition, as well as their average amplitude at that preferred time. The approach does not require prior assumptions about the shape of the hemodynamic response function (HRF), nor about linear relations between BOLD response and presented stimuli (or task conditions). We show that relative delays between different brain regions can also be computed without prior knowledge of the experimental design, suggesting a general method that could be applied for analysis of differential time delays that occur during natural, uncontrolled conditions. Here we analyze BOLD signals recorded during performance of a motor learning task. We show that during motor learning, the BOLD response of unimodal motor cortical areas precedes the response in higher-order multimodal association areas, including posterior parietal cortex. Brain areas found to be associated with reduced activity during motor learning, predominantly in prefrontal brain regions, are informative about the task typically at significantly later times. PMID:17188515

Segmentation precedes face categorization under suboptimal conditions.

PubMed

Van Den Boomen, Carlijn; Fahrenfort, Johannes J; Snijders, Tineke M; Kemner, Chantal

2015-01-01

Both categorization and segmentation processes play a crucial role in face perception. However, the functional relation between these subprocesses is currently unclear. The present study investigates the temporal relation between segmentation-related and category-selective responses in the brain, using electroencephalography (EEG). Surface segmentation and category content were both manipulated using texture-defined objects, including faces. This allowed us to study brain activity related to segmentation and to categorization. In the main experiment, participants viewed texture-defined objects for a duration of 800 ms. EEG results revealed that segmentation-related responses precede category-selective responses. Three additional experiments revealed that the presence and timing of categorization depends on stimulus properties and presentation duration. Photographic objects were presented for a long and short (92 ms) duration and evoked fast category-selective responses in both cases. On the other hand, presentation of texture-defined objects for a short duration only evoked segmentation-related but no category-selective responses. Category-selective responses were much slower when evoked by texture-defined than by photographic objects. We suggest that in case of categorization of objects under suboptimal conditions, such as when low-level stimulus properties are not sufficient for fast object categorization, segmentation facilitates the slower categorization process.

Segmentation precedes face categorization under suboptimal conditions

PubMed Central

Van Den Boomen, Carlijn; Fahrenfort, Johannes J.; Snijders, Tineke M.; Kemner, Chantal

2015-01-01

Both categorization and segmentation processes play a crucial role in face perception. However, the functional relation between these subprocesses is currently unclear. The present study investigates the temporal relation between segmentation-related and category-selective responses in the brain, using electroencephalography (EEG). Surface segmentation and category content were both manipulated using texture-defined objects, including faces. This allowed us to study brain activity related to segmentation and to categorization. In the main experiment, participants viewed texture-defined objects for a duration of 800 ms. EEG results revealed that segmentation-related responses precede category-selective responses. Three additional experiments revealed that the presence and timing of categorization depends on stimulus properties and presentation duration. Photographic objects were presented for a long and short (92 ms) duration and evoked fast category-selective responses in both cases. On the other hand, presentation of texture-defined objects for a short duration only evoked segmentation-related but no category-selective responses. Category-selective responses were much slower when evoked by texture-defined than by photographic objects. We suggest that in case of categorization of objects under suboptimal conditions, such as when low-level stimulus properties are not sufficient for fast object categorization, segmentation facilitates the slower categorization process. PMID:26074838

Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson's Disease.

PubMed

Harrington, Deborah L; Shen, Qian; Castillo, Gabriel N; Filoteo, J Vincent; Litvan, Irene; Takahashi, Colleen; French, Chelsea

2017-01-01

Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI) are common in Parkinson's disease (PD), but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN) and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF) and regional homogeneity (ReHo), a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex), sensorimotor cortex (primary motor, pre/post-central gyrus), basal ganglia (putamen, caudate), and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a pathological, rather than compensatory influence on cognitive abilities tested in this study. Receiver operating curve analyses demonstrated excellent sensitivity (≥90%) of rsfMRI variables in distinguishing patients from controls, but poor accuracy for brain volume and cognitive variables. Altogether these results provide new insights into the topology, cognitive relevance, and sensitivity of aberrant intrinsic activity and connectivity that precedes clinically significant cognitive impairment. Longitudinal studies are needed to determine if these neurocognitive associations presage the development of future mild cognitive impairment or dementia.

[See the thinking brain: a story about water].

PubMed

Le Bihan, D

2008-01-01

Among the astonishing Einstein's papers from 1905, there is one which unexpectedly gave birth to a powerful method to explore the brain. Molecular diffusion was explained by Einstein on the basis of the random translational motion of molecules which results from their thermal energy. In the mid 1980s it was shown that water diffusion in the brain could be imaged using MRI. During their random displacements water molecules probe tissue structure at a microscopic scale, interacting with cell membranes and, thus, providing unique information on the functional architecture of tissues. A dramatic application of diffusion MRI has been brain ischemia, following the discovery that water diffusion drops immediately after the onset of an ischemic event, when brain cells undergo swelling through cytotoxic edema. On the other hand, water diffusion is anisotropic in white matter, because axon membranes limit molecular movement perpendicularly to the fibers. This feature can be exploited to map out the orientation in space of the white matter tracks and image brain connections. More recently, it has been shown that diffusion MRI could accurately detect cortical activation. As the diffusion response precedes by several seconds the hemodynamic response captured by BOLD fMRI, it has been suggested that water diffusion could reflect early neuronal events, such as the transient swelling of activated cortical cells. If confirmed, this discovery will represent a significant breakthrough, allowing non invasive access to a direct physiological marker of brain activation. This approach will bridge the gap between invasive optical imaging techniques in neuronal cell cultures, and current functional neuroimaging approaches in humans, which are based on indirect and remote blood flow changes.

Central Nervous System Fibrosis Is Associated with Fibrocyte-Like Infiltrates

PubMed Central

Aldrich, Amy; Kielian, Tammy

2011-01-01

Fibrotic wall formation is essential for limiting pathogen dissemination during brain abscess development. However, little is known about the regulation of fibrotic processes in the central nervous system (CNS). Most CNS injury responses are associated with hypertrophy of resident astrocytes, a process termed reactive gliosis. Studies of fibrosis outside the CNS have identified two bone marrow–derived cell types, fibrocytes and alternatively activated M2 macrophages, as key mediators of fibrosis. The current study used bone marrow chimeras generated from green fluorescent protein transgenic mice to evaluate the appearance of these cell types and whether bone marrow–derived cells were capable of acquiring fibrotic characteristics during brain abscess development. Immunofluorescence staining revealed partial overlap between green fluorescent protein, α-smooth muscle actin, and procollagen, suggesting that a population of cells forming the brain abscess capsule originate from a bone marrow precursor. In addition, the influx of fibrocyte-like cells into brain abscesses immediately preceded the onset of fibrotic encapsulation. Fibrotic wall formation was also associated with increased numbers of alternatively activated M2 microglia and macrophages. To our knowledge, this is the first study demonstrating that bone marrow–derived infiltrates are capable of expressing fibrotic molecules during CNS inflammation. PMID:22015460

Upregulation of Neurotrophic Factors Selectively in Frontal Cortex in Response to Olfactory Discrimination Learning

PubMed Central

Naimark, Ari; Barkai, Edi; Matar, Michael A.; Kaplan, Zeev; Kozlovsky, Nitzan; Cohen, Hagit

2007-01-01

We have previously shown that olfactory discrimination learning is accompanied by several forms of long-term enhancement in synaptic connections between layer II pyramidal neurons selectively in the piriform cortex. This study sought to examine whether the previously demonstrated olfactory-learning-task-induced modifications are preceded by suitable changes in the expression of mRNA for neurotrophic factors and in which brain areas this occurs. Rats were trained to discriminate positive cues in pair of odors for a water reward. The relationship between the learning task and local levels of mRNA for brain-derived neurotrophic factor, tyrosine kinase B, nerve growth factor, and neurotrophin-3 in the frontal cortex, hippocampal subregions, and other regions were assessed 24 hours post olfactory learning. The olfactory discrimination learning activated production of endogenous neurotrophic factors and induced their signal transduction in the frontal cortex, but not in other brain areas. These findings suggest that different brain areas may be preferentially involved in different learning/memory tasks. PMID:17710248

Preparation breeds success: Brain activity predicts remembering.

PubMed

Herron, Jane E; Evans, Lisa H

2018-05-09

Successful retrieval of episodic information is thought to involve the adoption of memory states that ensure that stimulus events are treated as episodic memory cues (retrieval mode) and which can bias retrieval toward specific memory contents (retrieval orientation). The neural correlates of these memory states have been identified in many neuroimaging studies, yet critically there is no direct evidence that they facilitate retrieval success. We cued participants before each test item to prepare to complete an episodic (retrieve the encoding task performed on the item at study) or a non-episodic task. Our design allowed us to separate event-related potentials (ERPs) elicited by the preparatory episodic cue according to the accuracy of the subsequent memory judgment. We predicted that a correlate of retrieval orientation should be larger in magnitude preceding correct source judgments than that preceding source errors. This hypothesis was confirmed. Preparatory ERPs at bilateral frontal sites were significantly more positive-going when preceding correct source judgments than when preceding source errors or correct responses in a non-episodic baseline task. Furthermore this effect was not evident prior to recognized items associated with incorrect source judgments. This pattern of results indicates a direct contribution of retrieval orientation to the recovery of task-relevant information and highlights the value of separating preparatory neural activity at retrieval according to subsequent memory accuracy. Moreover, at a more general level this work demonstrates the important role of pre-stimulus processing in ecphory, which has remained largely neglected to date. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer's disease.

PubMed

Streit, Wolfgang J; Braak, Heiko; Xue, Qing-Shan; Bechmann, Ingo

2009-10-01

The role of microglial cells in the pathogenesis of Alzheimer's disease (AD) neurodegeneration is unknown. Although several works suggest that chronic neuroinflammation caused by activated microglia contributes to neurofibrillary degeneration, anti-inflammatory drugs do not prevent or reverse neuronal tau pathology. This raises the question if indeed microglial activation occurs in the human brain at sites of neurofibrillary degeneration. In view of the recent work demonstrating presence of dystrophic (senescent) microglia in aged human brain, the purpose of this study was to investigate microglial cells in situ and at high resolution in the immediate vicinity of tau-positive structures in order to determine conclusively whether degenerating neuronal structures are associated with activated or with dystrophic microglia. We used a newly optimized immunohistochemical method for visualizing microglial cells in human archival brain together with Braak staging of neurofibrillary pathology to ascertain the morphology of microglia in the vicinity of tau-positive structures. We now report histopathological findings from 19 humans covering the spectrum from none to severe AD pathology, including patients with Down's syndrome, showing that degenerating neuronal structures positive for tau (neuropil threads, neurofibrillary tangles, neuritic plaques) are invariably colocalized with severely dystrophic (fragmented) rather than with activated microglial cells. Using Braak staging of Alzheimer neuropathology we demonstrate that microglial dystrophy precedes the spread of tau pathology. Deposits of amyloid-beta protein (Abeta) devoid of tau-positive structures were found to be colocalized with non-activated, ramified microglia, suggesting that Abeta does not trigger microglial activation. Our findings also indicate that when microglial activation does occur in the absence of an identifiable acute central nervous system insult, it is likely to be the result of systemic infectious disease. The findings reported here strongly argue against the hypothesis that neuroinflammatory changes contribute to AD dementia. Instead, they offer an alternative hypothesis of AD pathogenesis that takes into consideration: (1) the notion that microglia are neuron-supporting cells and neuroprotective; (2) the fact that development of non-familial, sporadic AD is inextricably linked to aging. They support the idea that progressive, aging-related microglial degeneration and loss of microglial neuroprotection rather than induction of microglial activation contributes to the onset of sporadic Alzheimer's disease. The results have far-reaching implications in terms of reevaluating current treatment approaches towards AD.

Annual Research Review: Progress in Using Brain Morphometry as a Clinical Tool for Diagnosing Psychiatric Disorders

ERIC Educational Resources Information Center

Haubold, Alexander; Peterson, Bradley S.; Bansal, Ravi

2012-01-01

Brain morphometry in recent decades has increased our understanding of the neural bases of psychiatric disorders by localizing anatomical disturbances to specific nuclei and subnuclei of the brain. At least some of these disturbances precede the overt expression of clinical symptoms and possibly are endophenotypes that could be used to diagnose an…

Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice.

PubMed

Akundi, Ravi S; Huang, Zhenyu; Eason, Joshua; Pandya, Jignesh D; Zhi, Lianteng; Cass, Wayne A; Sullivan, Patrick G; Büeler, Hansruedi

2011-01-13

PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice. Purified brain mitochondria of Pink1⁻/⁻ mice showed impaired Ca²+ storage capacity, resulting in increased Ca²+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1⁻/⁻ mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1⁻/⁻ mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1⁻/⁻ mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1⁻/⁻ embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1⁻/⁻ mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. Increased mitochondrial Ca²+ sensitivity and JNK activity are early defects in Pink1⁻/⁻ mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1⁻/⁻ mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1⁻/⁻ mice to inflammation and injury-induced cell death.

New levels of language processing complexity and organization revealed by granger causation.

PubMed

Gow, David W; Caplan, David N

2012-01-01

Granger causation analysis of high spatiotemporal resolution reconstructions of brain activation offers a new window on the dynamic interactions between brain areas that support language processing. Premised on the observation that causes both precede and uniquely predict their effects, this approach provides an intuitive, model-free means of identifying directed causal interactions in the brain. It requires the analysis of all non-redundant potentially interacting signals, and has shown that even "early" processes such as speech perception involve interactions of many areas in a strikingly large network that extends well beyond traditional left hemisphere perisylvian cortex that play out over hundreds of milliseconds. In this paper we describe this technique and review several general findings that reframe the way we think about language processing and brain function in general. These include the extent and complexity of language processing networks, the central role of interactive processing dynamics, the role of processing hubs where the input from many distinct brain regions are integrated, and the degree to which task requirements and stimulus properties influence processing dynamics and inform our understanding of "language-specific" localized processes.

Calcium-dependent molecular fMRI using a magnetic nanosensor.

PubMed

Okada, Satoshi; Bartelle, Benjamin B; Li, Nan; Breton-Provencher, Vincent; Lee, Jiyoung J; Rodriguez, Elisenda; Melican, James; Sur, Mriganka; Jasanoff, Alan

2018-06-01

Calcium ions are ubiquitous signalling molecules in all multicellular organisms, where they mediate diverse aspects of intracellular and extracellular communication over widely varying temporal and spatial scales 1 . Though techniques to map calcium-related activity at a high resolution by optical means are well established, there is currently no reliable method to measure calcium dynamics over large volumes in intact tissue 2 . Here, we address this need by introducing a family of magnetic calcium-responsive nanoparticles (MaCaReNas) that can be detected by magnetic resonance imaging (MRI). MaCaReNas respond within seconds to [Ca 2+ ] changes in the 0.1-1.0 mM range, suitable for monitoring extracellular calcium signalling processes in the brain. We show that the probes permit the repeated detection of brain activation in response to diverse stimuli in vivo. MaCaReNas thus provide a tool for calcium-activity mapping in deep tissue and offer a precedent for the development of further nanoparticle-based sensors for dynamic molecular imaging with MRI.

Calcium-dependent molecular fMRI using a magnetic nanosensor

NASA Astrophysics Data System (ADS)

Okada, Satoshi; Bartelle, Benjamin B.; Li, Nan; Breton-Provencher, Vincent; Lee, Jiyoung J.; Rodriguez, Elisenda; Melican, James; Sur, Mriganka; Jasanoff, Alan

2018-06-01

Calcium ions are ubiquitous signalling molecules in all multicellular organisms, where they mediate diverse aspects of intracellular and extracellular communication over widely varying temporal and spatial scales1. Though techniques to map calcium-related activity at a high resolution by optical means are well established, there is currently no reliable method to measure calcium dynamics over large volumes in intact tissue2. Here, we address this need by introducing a family of magnetic calcium-responsive nanoparticles (MaCaReNas) that can be detected by magnetic resonance imaging (MRI). MaCaReNas respond within seconds to [Ca2+] changes in the 0.1-1.0 mM range, suitable for monitoring extracellular calcium signalling processes in the brain. We show that the probes permit the repeated detection of brain activation in response to diverse stimuli in vivo. MaCaReNas thus provide a tool for calcium-activity mapping in deep tissue and offer a precedent for the development of further nanoparticle-based sensors for dynamic molecular imaging with MRI.

Prediction of activation patterns preceding hallucinations in patients with schizophrenia using machine learning with structured sparsity.

PubMed

de Pierrefeu, Amicie; Fovet, Thomas; Hadj-Selem, Fouad; Löfstedt, Tommy; Ciuciu, Philippe; Lefebvre, Stephanie; Thomas, Pierre; Lopes, Renaud; Jardri, Renaud; Duchesnay, Edouard

2018-04-01

Despite significant progress in the field, the detection of fMRI signal changes during hallucinatory events remains difficult and time-consuming. This article first proposes a machine-learning algorithm to automatically identify resting-state fMRI periods that precede hallucinations versus periods that do not. When applied to whole-brain fMRI data, state-of-the-art classification methods, such as support vector machines (SVM), yield dense solutions that are difficult to interpret. We proposed to extend the existing sparse classification methods by taking the spatial structure of brain images into account with structured sparsity using the total variation penalty. Based on this approach, we obtained reliable classifying performances associated with interpretable predictive patterns, composed of two clearly identifiable clusters in speech-related brain regions. The variation in transition-to-hallucination functional patterns not only from one patient to another but also from one occurrence to the next (e.g., also depending on the sensory modalities involved) appeared to be the major difficulty when developing effective classifiers. Consequently, second, this article aimed to characterize the variability within the prehallucination patterns using an extension of principal component analysis with spatial constraints. The principal components (PCs) and the associated basis patterns shed light on the intrinsic structures of the variability present in the dataset. Such results are promising in the scope of innovative fMRI-guided therapy for drug-resistant hallucinations, such as fMRI-based neurofeedback. © 2018 Wiley Periodicals, Inc.

Empathic control through coordinated interaction of amygdala, theory of mind and extended pain matrix brain regions.

PubMed

Bruneau, Emile G; Jacoby, Nir; Saxe, Rebecca

2015-07-01

Brain regions in the "pain matrix", can be activated by observing or reading about others in physical pain. In previous research, we found that reading stories about others' emotional suffering, by contrast, recruits a different group of brain regions mostly associated with thinking about others' minds. In the current study, we examined the neural circuits responsible for deliberately regulating empathic responses to others' pain and suffering. In Study 1, a sample of college-aged participants (n=18) read stories about physically painful and emotionally distressing events during functional magnetic resonance imaging (fMRI), while either actively empathizing with the main character or trying to remain objective. In Study 2, the same experiment was performed with professional social workers, who are chronically exposed to human suffering (n=21). Across both studies activity in the amygdala was associated with empathic regulation towards others' emotional pain, but not their physical pain. In addition, psychophysiological interaction (PPI) analysis and Granger causal modeling (GCM) showed that amygdala activity while reading about others' emotional pain was preceded by and positively coupled with activity in the theory of mind brain regions, and followed by and negatively coupled with activity in regions associated with physical pain and bodily sensations. Previous work has shown that the amygdala is critically involved in the deliberate control of self-focused distress - the current results extend the central importance of amygdala activity to the control of other-focused empathy, but only when considering others' emotional pain. Copyright © 2015 Elsevier Inc. All rights reserved.

Decoding the dynamic representation of musical pitch from human brain activity.

PubMed

Sankaran, N; Thompson, W F; Carlile, S; Carlson, T A

2018-01-16

In music, the perception of pitch is governed largely by its tonal function given the preceding harmonic structure of the music. While behavioral research has advanced our understanding of the perceptual representation of musical pitch, relatively little is known about its representational structure in the brain. Using Magnetoencephalography (MEG), we recorded evoked neural responses to different tones presented within a tonal context. Multivariate Pattern Analysis (MVPA) was applied to "decode" the stimulus that listeners heard based on the underlying neural activity. We then characterized the structure of the brain's representation using decoding accuracy as a proxy for representational distance, and compared this structure to several well established perceptual and acoustic models. The observed neural representation was best accounted for by a model based on the Standard Tonal Hierarchy, whereby differences in the neural encoding of musical pitches correspond to their differences in perceived stability. By confirming that perceptual differences honor those in the underlying neuronal population coding, our results provide a crucial link in understanding the cognitive foundations of musical pitch across psychological and neural domains.

Escherichia coli K1 invasion increases human brain microvascular endothelial cell monolayer permeability by disassembling vascular-endothelial cadherins at tight junctions.

PubMed

Sukumaran, Sunil K; Prasadarao, Nemani V

2003-11-01

We investigated the permeability changes that occur in the human brain microvascular endothelial cell (HBMEC) monolayer, an in vitro model of the blood-brain barrier, during Escherichia coli K1 infection. An increase in permeability of HBMECs and a decrease in transendothelial electrical resistance were observed. These permeability changes occurred only when HBMECs were infected with E. coli expressing outer membrane protein A (OmpA) and preceded the traversal of bacteria across the monolayer. Activated protein kinase C (PKC)-alpha interacts with vascular-endothelial cadherins (VECs) at the tight junctions of HBMECs, resulting in the dissociation of beta-catenins from VECs and leading to the increased permeability of the HBMEC monolayer. Overexpression of a dominant negative form of PKC-alpha in HBMECs blocked the E. coli-induced increase in permeability of HBMECs. Anti-OmpA and anti-OmpA receptor antibodies exerted inhibition of E. coli-induced permeability of HBMEC monolayers. This inhibition was the result of the absence of PKC-alpha activation in HBMECs treated with the antibodies.

Functional brain microstate predicts the outcome in a visuospatial working memory task.

PubMed

Muthukrishnan, Suriya-Prakash; Ahuja, Navdeep; Mehta, Nalin; Sharma, Ratna

2016-11-01

Humans have limited capacity of processing just up to 4 integrated items of information in the working memory. Thus, it is inevitable to commit more errors when challenged with high memory loads. However, the neural mechanisms that determine the accuracy of response at high memory loads still remain unclear. High temporal resolution of Electroencephalography (EEG) technique makes it the best tool to resolve the temporal dynamics of brain networks. EEG-defined microstate is the quasi-stable scalp electrical potential topography that represents the momentary functional state of brain. Thus, it has been possible to assess the information processing currently performed by the brain using EEG microstate analysis. We hypothesize that the EEG microstate preceding the trial could determine its outcome in a visuospatial working memory (VSWM) task. Twenty-four healthy participants performed a high memory load VSWM task, while their brain activity was recorded using EEG. Four microstate maps were found to represent the functional brain state prior to the trials in the VSWM task. One pre-trial microstate map was found to determine the accuracy of subsequent behavioural response. The intracranial generators of the pre-trial microstate map that determined the response accuracy were localized to the visuospatial processing areas at bilateral occipital, right temporal and limbic cortices. Our results imply that the behavioural outcome in a VSWM task could be determined by the intensity of activation of memory representations in the visuospatial processing brain regions prior to the trial. Copyright © 2016 Elsevier B.V. All rights reserved.

Astrocyte activation and wound healing in intact-skull mouse after focal brain injury.

PubMed

Suzuki, Takayuki; Sakata, Honami; Kato, Chiaki; Connor, John A; Morita, Mitsuhiro

2012-12-01

Localised brain tissue damage activates surrounding astrocytes, which significantly influences subsequent long-term pathological processes. Most existing focal brain injury models in rodents employ craniotomy to localise mechanical insults. However, the craniotomy procedure itself induces gliosis. To investigate perilesional astrocyte activation under conditions in which the skull is intact, we created focal brain injuries using light exposure through a cranial window made by thinning the skull without inducing gliosis. The lesion size was maximal at ~ 12 h and showed substantial recovery over the subsequent 30 days. Two distinct types of perilesional reactive astrocyte, identified by GFAP upregulation and hypertrophy, were found. In proximal regions the reactive astrocytes proliferated and expressed nestin, whereas in regions distal to the injury core the astrocytes showed increased GFAP expression but did not proliferate, lacked nestin expression, and displayed different morphology. Simply making the window did not induce any of these changes. There were also significant numbers of neurons in the recovering cortical tissue. In the recovery region, reactive astrocytes radially extended processes which appeared to influence the shapes of neuronal nuclei. The proximal reactive astrocytes also formed a cell layer which appeared to serve as a protective barrier, blocking the spread of IgG deposition and migration of microglia from the lesion core to surrounding tissue. The recovery was preceded by perilesional accumulation of leukocytes expressing vascular endothelial growth factor. These results suggest that, under intact skull conditions, focal brain injury is followed by perilesional reactive astrocyte activities that foster cortical tissue protection and recovery. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Postischemic dementia with Alzheimer phenotype: selectively vulnerable versus resistant areas of the brain and neurodegeneration versus β-amyloid peptide.

PubMed

Pluta, Ryszard; Jabłoński, Mirosław; Czuczwar, Stanisław J

2012-01-01

The road to clarity for postischemic dementia mechanisms has been one fraught with a wide range of complications and numerous revisions with a lack of a final solution. Importantly, brain ischemia is a leading cause of death and cognitive impairment worldwide. However, the mechanisms of progressive cognitive decline following brain ischemia are not yet certain. Data from animal models and clinical pioneering studies of brain ischemia have demonstrated an increase in expression and processing of amyloid precursor protein to a neurotoxin oligomeric β-amyloid peptide. Functional and memory brain restoration after ischemic brain injury is delayed and incomplete due to a lesion related increase in the amount of the neurotoxin amyloid protein. Moreover, ischemic injury is strongly accelerated by aging, too. In this review, we will present our current thinking about biogenesis of amyloid from the amyloid precursor protein in ischemic brain injury, and how this factor presents etiological, therapeutic and diagnostic targets that are now under consideration. Progressive injury of the ischemic brain parenchyma may be caused not only by degeneration of selectively vulnerable neurons destroyed during ischemia but also by acute and chronic damage of resistant areas of the brain and progressive damage in the blood-brain barrier. We propose that in postischemic dementia an initial ischemic injury precedes the cerebrovascular and brain parenchyma accumulation of Alzheimer disease related neurotoxin β-amyloid peptide, which in turn amplifies the neurovascular dysfunction triggering focal ischemic episodes as a vicious cycle preceding final neurodegenerative pathology. Persistent ischemic blood-brain barrier insufficiency with accumulation of neurotoxin β-amyloid protein in the brain tissue, especially in extracellular perivascular space and blood-brain barrier microvessels, may gradually, over a lifetime, progress to brain atrophy and to full-blown ischemic dementia with Alzheimer phenotype.

Neurological evidence linguistic processes precede perceptual simulation in conceptual processing.

PubMed

Louwerse, Max; Hutchinson, Sterling

2012-01-01

There is increasing evidence from response time experiments that language statistics and perceptual simulations both play a role in conceptual processing. In an EEG experiment we compared neural activity in cortical regions commonly associated with linguistic processing and visual perceptual processing to determine to what extent symbolic and embodied accounts of cognition applied. Participants were asked to determine the semantic relationship of word pairs (e.g., sky - ground) or to determine their iconic relationship (i.e., if the presentation of the pair matched their expected physical relationship). A linguistic bias was found toward the semantic judgment task and a perceptual bias was found toward the iconicity judgment task. More importantly, conceptual processing involved activation in brain regions associated with both linguistic and perceptual processes. When comparing the relative activation of linguistic cortical regions with perceptual cortical regions, the effect sizes for linguistic cortical regions were larger than those for the perceptual cortical regions early in a trial with the reverse being true later in a trial. These results map upon findings from other experimental literature and provide further evidence that processing of concept words relies both on language statistics and on perceptual simulations, whereby linguistic processes precede perceptual simulation processes.

Neurological Evidence Linguistic Processes Precede Perceptual Simulation in Conceptual Processing

PubMed Central

Louwerse, Max; Hutchinson, Sterling

2012-01-01

There is increasing evidence from response time experiments that language statistics and perceptual simulations both play a role in conceptual processing. In an EEG experiment we compared neural activity in cortical regions commonly associated with linguistic processing and visual perceptual processing to determine to what extent symbolic and embodied accounts of cognition applied. Participants were asked to determine the semantic relationship of word pairs (e.g., sky – ground) or to determine their iconic relationship (i.e., if the presentation of the pair matched their expected physical relationship). A linguistic bias was found toward the semantic judgment task and a perceptual bias was found toward the iconicity judgment task. More importantly, conceptual processing involved activation in brain regions associated with both linguistic and perceptual processes. When comparing the relative activation of linguistic cortical regions with perceptual cortical regions, the effect sizes for linguistic cortical regions were larger than those for the perceptual cortical regions early in a trial with the reverse being true later in a trial. These results map upon findings from other experimental literature and provide further evidence that processing of concept words relies both on language statistics and on perceptual simulations, whereby linguistic processes precede perceptual simulation processes. PMID:23133427

Uncertainty during Anticipation Modulates Neural Responses to Aversion in Human Insula and Amygdala

PubMed Central

Sarinopoulos, I.; Grupe, D. W.; Mackiewicz, K. L.; Herrington, J. D.; Lor, M.; Steege, E. E.

2010-01-01

Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which uncertain cues are followed by negative outcomes, an example of covariation bias. Using functional magnetic resonance imaging, we found that uncertainty-related expectations modulated neural responses to aversion. Insula and amygdala responses to aversive pictures were larger after an uncertain cue (that preceded aversive or neutral pictures) than a certain cue (that always preceded aversive pictures). Anticipatory anterior cingulate cortex (ACC) activity elicited by the cues was inversely associated with the insula and amygdala responses to aversive pictures following the cues. Nearly 75% of subjects overestimated the frequency of aversive pictures following uncertain cues, and ACC and insula activity predicted this uncertainty-related covariation bias. Findings provide the first evidence of the brain mechanisms of covariation bias and highlight the temporal dynamics of ACC, insula, and amygdala recruitment for processing aversion in the context of uncertainty. PMID:19679543

Glial degeneration with oxidative damage drives neuronal demise in MPSII disease

PubMed Central

Zalfa, Cristina; Verpelli, Chiara; D'Avanzo, Francesca; Tomanin, Rosella; Vicidomini, Cinzia; Cajola, Laura; Manara, Renzo; Sala, Carlo; Scarpa, Maurizio; Vescovi, Angelo Luigi; De Filippis, Lidia

2016-01-01

Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression. PMID:27512952

Glial degeneration with oxidative damage drives neuronal demise in MPSII disease.

PubMed

Zalfa, Cristina; Verpelli, Chiara; D'Avanzo, Francesca; Tomanin, Rosella; Vicidomini, Cinzia; Cajola, Laura; Manara, Renzo; Sala, Carlo; Scarpa, Maurizio; Vescovi, Angelo Luigi; De Filippis, Lidia

2016-08-11

Mucopolysaccharidosis type II (MPSII) is a lysosomal storage disorder due to the deficit of the iduronate 2-sulfatase (IDS) enzyme, causing progressive neurodegeneration in patients. Neural stem cells (NSCs) derived from the IDS-ko mouse can recapitulate MPSII pathogenesis in vitro. In differentiating IDS-ko NSCs and in the aging IDS-ko mouse brain, glial degeneration precedes neuronal degeneration. Here we show that pure IDS-ko NSC-derived astrocytes are selectively able to drive neuronal degeneration when cocultured with healthy neurons. This phenotype suggests concurrent oxidative damage with metabolic dysfunction. Similar patterns were observed in murine IDS-ko animals and in human MPSII brains. Most importantly, the mutant phenotype of IDS-ko astrocytes was reversed by low oxygen conditions and treatment with vitamin E, which also reversed the toxic effect on cocultured neurons. Moreover, at very early stages of disease we detected in vivo the development of a neuroinflammatory background that precedes astroglial degeneration, thus suggesting a novel model of MPSII pathogenesis, with neuroinflammation preceding glial degeneration, which is finally followed by neuronal death. This hypothesis is also consistent with the progression of white matter abnormalities in MPSII patients. Our study represents a novel breakthrough in the elucidation of MPSII brain pathogenesis and suggests the antioxidant molecules as potential therapeutic tools to delay MPSII onset and progression.

Voluntary control over prestimulus activity related to encoding

PubMed Central

Gruber, Matthias J.; Otten, Leun J.

2010-01-01

A new development in our understanding of human long-term memory is that effective memory formation relies on neural activity just before an event. It is unknown whether such prestimulus activity is under voluntary control or a reflection of random fluctuations over time. In the present study, we addressed two issues: (i) whether prestimulus activity is influenced by an individual's motivation to encode, and (ii) at what point in time encoding-related activity emerges. Electrical brain activity was recorded while healthy male and female adults memorized series of words. Each word was preceded by a cue, which indicated the monetary reward that would be received if the following word was later remembered. Memory was tested after a short delay with a five-way recognition task to separate different sources of recognition. Electrical activity elicited by the reward cue predicted later memory of a word. Crucially, however, this was only observed when the incentive to memorize a word was high. Encoding-related activity preceded high reward words that were later recollected. This activity started shortly after cue onset and persisted until word onset. Prestimulus activity thus not only signals cue-related processing, but also an ensuing preparatory state. In contrast, reward-related activity was limited to the time period immediately following the reward cue. These findings indicate that engaging neural activity that benefits the encoding of an upcoming event is under voluntary control, reflecting a strategic preparatory state in anticipation of processing an event. PMID:20660262

Functional definition of the N450 event-related brain potential marker of conflict processing: a numerical stroop study

PubMed Central

2012-01-01

Background Several conflict processing studies aimed to dissociate neuroimaging phenomena related to stimulus and response conflict processing. However, previous studies typically did not include a paradigm-independent measure of either stimulus or response conflict. Here we have combined electro-myography (EMG) with event-related brain potentials (ERPs) in order to determine whether a particularly robust marker of conflict processing, the N450 ERP effect usually related to the activity of the Anterior Cingulate Cortex (ACC), is related to stimulus- or to response-conflict processing. EMG provided paradigm-independent measure of response conflict. In a numerical Stroop paradigm participants compared pairs of digits and pressed a button on the side where they saw the larger digit. 50% of digit-pairs were preceded by an effective cue which provided accurate information about the required response. 50% of trials were preceded by a neutral cue which did not communicate the side of response. Results EMG showed that response conflict was significantly larger in neutrally than in effectively cued trials. The N450 was similar when response conflict was high and when it was low. Conclusions We conclude that the N450 is related to stimulus or abstract, rather than to response conflict detection/resolution. Findings may enable timing ACC conflict effects. PMID:22452924

Functional definition of the N450 event-related brain potential marker of conflict processing: a numerical stroop study.

PubMed

Szűcs, Dénes; Soltész, Fruzsina

2012-03-27

Several conflict processing studies aimed to dissociate neuroimaging phenomena related to stimulus and response conflict processing. However, previous studies typically did not include a paradigm-independent measure of either stimulus or response conflict. Here we have combined electro-myography (EMG) with event-related brain potentials (ERPs) in order to determine whether a particularly robust marker of conflict processing, the N450 ERP effect usually related to the activity of the Anterior Cingulate Cortex (ACC), is related to stimulus- or to response-conflict processing. EMG provided paradigm-independent measure of response conflict. In a numerical Stroop paradigm participants compared pairs of digits and pressed a button on the side where they saw the larger digit. 50% of digit-pairs were preceded by an effective cue which provided accurate information about the required response. 50% of trials were preceded by a neutral cue which did not communicate the side of response. EMG showed that response conflict was significantly larger in neutrally than in effectively cued trials. The N450 was similar when response conflict was high and when it was low. We conclude that the N450 is related to stimulus or abstract, rather than to response conflict detection/resolution. Findings may enable timing ACC conflict effects.

Increased Expression of the Chemokines CXCL1 and MIP-1a by Resident Brain Cells Precedes Neutrophil Infiltration in the Brain Following Prolonged Soman-Induced Status Epilepticus in Rats

DTIC Science & Technology

2011-05-01

brain cytokine concentrations. J Neuroinflammation 2010, 7:40. 12. Manley NC, Bertrand AA, Kinney KS, Hing TC, Sapolsky RM: Characterization of monocyte...neurodegeneration. J Neurosci 2007, 27:9301-9309. 16. Wolpe SD, Davatelis G, Sherry B, Beutler B, Hesse DG, Nguyen HT, Moldawer LL , Nathan CF, Lowry SF

Intermittently-visual Tracking Experiments Reveal the Roles of Error-correction and Predictive Mechanisms in the Human Visual-motor Control System

NASA Astrophysics Data System (ADS)

Hayashi, Yoshikatsu; Tamura, Yurie; Sase, Kazuya; Sugawara, Ken; Sawada, Yasuji

Prediction mechanism is necessary for human visual motion to compensate a delay of sensory-motor system. In a previous study, “proactive control” was discussed as one example of predictive function of human beings, in which motion of hands preceded the virtual moving target in visual tracking experiments. To study the roles of the positional-error correction mechanism and the prediction mechanism, we carried out an intermittently-visual tracking experiment where a circular orbit is segmented into the target-visible regions and the target-invisible regions. Main results found in this research were following. A rhythmic component appeared in the tracer velocity when the target velocity was relatively high. The period of the rhythm in the brain obtained from environmental stimuli is shortened more than 10%. The shortening of the period of rhythm in the brain accelerates the hand motion as soon as the visual information is cut-off, and causes the precedence of hand motion to the target motion. Although the precedence of the hand in the blind region is reset by the environmental information when the target enters the visible region, the hand motion precedes the target in average when the predictive mechanism dominates the error-corrective mechanism.

Blood-Brain Barrier Permeability and Monocyte Infiltration in Experimental Allergic Encephalomyelitis

ERIC Educational Resources Information Center

Floris, S.; Blezer, E. L. A.; Schreibelt, G.; Dopp, E.; van der Pol, S. M. A.; Schadee-Eestermans, I. L.; Nicolay, K.; Dijkstra, C. D.; de Vries, H. E.

2004-01-01

Enhanced cerebrovascular permeability and cellular infiltration mark the onset of early multiple sclerosis lesions. So far, the precise sequence of these events and their role in lesion formation and disease progression remain unknown. Here we provide quantitative evidence that blood-brain barrier leakage is an early event and precedes massive…

Stabilization of superoxide dismutase by acetyl-l-carnitine in human brain endothelium during alcohol exposure: novel protective approach.

PubMed

Haorah, James; Floreani, Nicholas A; Knipe, Bryan; Persidsky, Yuri

2011-10-15

Oxidative damage of the endothelium disrupts the integrity of the blood-brain barrier (BBB). We have shown before that alcohol exposure increases the levels of reactive oxygen species (ROS; superoxide and hydroxyl radical) and nitric oxide (NO) in brain endothelial cells by activating NADPH oxidase and inducible nitric oxide synthase. We hypothesize that impairment of antioxidant systems, such as a reduction in catalase and superoxide dismutase (SOD) activity, by ethanol exposure may elevate the levels of ROS/NO in endothelium, resulting in BBB damage. This study examines whether stabilization of antioxidant enzyme activity results in suppression of ROS levels by anti-inflammatory agents. To address this idea, we determined the effects of ethanol on the kinetic profile of SOD and catalase activity and ROS/NO generation in primary human brain endothelial cells (hBECs). We observed an enhanced production of ROS and NO levels due to the metabolism of ethanol in hBECs. Similar increases were found after exposure of hBECs to acetaldehyde, the major metabolite of ethanol. Ethanol simultaneously augmented ROS generation and the activity of antioxidative enzymes. SOD activity was increased for a much longer period of time than catalase activity. A decline in SOD activity and protein levels preceded elevation of oxidant levels. SOD stabilization by the antioxidant and mitochondria-protecting agent acetyl-L-carnitine (ALC) and the anti-inflammatory agent rosiglitazone suppressed ROS levels, with a marginal increase in NO levels. Mitochondrial membrane protein damage and decreased membrane potential after ethanol exposure indicated mitochondrial injury. These changes were prevented by ALC. Our findings suggest the counteracting mechanisms of oxidants and antioxidants during alcohol-induced oxidative stress at the BBB. The presence of enzymatic stabilizers favors the ROS-neutralizing antioxidant redox of the BBB, suggesting an underlying protective mechanism of NO for brain vascular tone and vasodilation. Published by Elsevier Inc.

Lingering representations of stimuli influence recall organization

PubMed Central

Chan, Stephanie C.Y.; Applegate, Marissa C.; Morton, Neal W; Polyn, Sean M.; Norman, Kenneth A.

2017-01-01

Several prominent theories posit that information about recent experiences lingers in the brain and organizes memories for current experiences, by forming a temporal context that is linked to those memories at encoding. According to these theories, if the thoughts preceding an experience X resemble the thoughts preceding an experience Y, then X and Y should show an elevated probability of being recalled together. We tested this prediction by using multi-voxel pattern analysis (MVPA) of fMRI data to measure neural evidence for lingering processing of preceding stimuli. As predicted, memories encoded with similar lingering thoughts about the category of preceding stimuli were more likely to be recalled together. Our results demonstrate that the “fading embers” of previous stimuli help to organize recall, confirming a key prediction of computational models of episodic memory. PMID:28132858

Specific EEG frequencies at specific brain areas and performance.

PubMed

Fernández, T; Harmony, T; Silva-Pereyra, J; Fernández-Bouzas, A; Gersenowies, J; Galán, L; Carbonell, F; Marosi, E; Otero, G; Valdés, S I

2000-08-21

In this study it was shown that in adults, the frequency characteristics of EEG preceding stimuli that were followed by incorrect responses were different from the characteristics of EEG preceding stimuli that were followed by correct responses. In the recording during three different tasks that explore different neuronal networks, higher values of current preceding incorrect performance in those areas directly related to the task were found in frequencies within the delta (1.56 and 3.12 Hz) and beta bands (13.26, 14.04, 14.82, 15.6, 17.16 and 17.94 Hz), suggesting that these frequencies signal inhibition. Frequencies within the alpha band (9.36 and 12.48 Hz) showed greater energy preceding correct responses in task-specific areas, supporting previous results observed in children.

The motivation for very early intervention for infants at high risk for autism spectrum disorders.

PubMed

Webb, Sara Jane; Jones, Emily J H; Kelly, Jean; Dawson, Geraldine

2014-02-01

The first Autism Research Matrix (IACC, 2003) listed the identification of behavioural and biological markers of risk for autism as a top priority. This emphasis was based on the hypothesis that intervention with infants at-risk, at an early age when the brain is developing and before core autism symptoms have emerged, could significantly alter the developmental trajectory of children at risk for the disorder and impact long-range outcome. Research has provided support for specific models of early autism intervention (e.g., Early Start Denver Model) for improving outcomes in young children with autism, based on both behavioural and brain activity measures. Although great strides have been made in ability to identify risk markers for autism in younger infant/toddler samples, how and when to intervene during the prodromal state remains a critical question. Emerging evidence suggests that abnormal brain circuitry in autism precedes altered social behaviours; thus, an intervention designed to promote early social engagement and reciprocity potentially could steer brain development back toward the normal trajectory and remit or reduce the expression of symptoms.

Detection of early seizures by diffuse optical tomography

NASA Astrophysics Data System (ADS)

Zhang, Tao; Hajihashemi, M. Reza; Zhou, Junli; Carney, Paul R.; Jiang, Huabei

2015-03-01

In epilepsy it has been challenging to detect early changes in brain activity that occurs prior to seizure onset and to map their origin and evolution for possible intervention. Besides, preclinical seizure experiments need to be conducted in awake animals with images reconstructed and displayed in real-time. We demonstrate using a rat model of generalized epilepsy that diffuse optical tomography (DOT) provides a unique functional neuroimaging modality for noninvasively and continuously tracking brain activities with high spatiotemporal resolution. We developed methods to conduct seizure experiments in fully awake rats using a subject-specific helmet and a restraining mechanism. For the first time, we detected early hemodynamic responses with heterogeneous patterns several minutes preceding the electroencephalographic seizure onset, supporting the presence of a "pre-seizure" state both in anesthetized and awake rats. Using a novel time-series analysis of scattering images, we show that the analysis of scattered diffuse light is a sensitive and reliable modality for detecting changes in neural activity associated with generalized seizure. We found widespread hemodynamic changes evolving from local regions of the bilateral cortex and thalamus to the entire brain, indicating that the onset of generalized seizures may originate locally rather than diffusely. Together, these findings suggest DOT represents a powerful tool for mapping early seizure onset and propagation pathways.

Pregnant serum induces neuroinflammation and seizure activity via TNFα.

PubMed

Cipolla, Marilyn J; Pusic, Aya D; Grinberg, Yelena Y; Chapman, Abbie C; Poynter, Matthew E; Kraig, Richard P

2012-04-01

Preeclampsia is a hypertensive disorder of pregnancy that affects many organs including the brain. Neurological complications occur during preeclampsia, the most serious of which is seizure known as eclampsia. Although preeclampsia can precede the eclamptic seizure, it often occurs during normal pregnancy, suggesting that processes associated with normal pregnancy can promote neuronal excitability. Here we investigated whether circulating inflammatory mediators that are elevated late in gestation when seizure also occurs are hyperexcitable to neuronal tissue. Evoked field potentials were measured in hippocampal slices in which control horse serum that slices are normally grown in, was replaced with serum from nonpregnant or late-pregnant Wistar rats for 48 h. We found that serum from pregnant, but not nonpregnant rats, caused hyperexcitability to hippocampal neurons and seizure activity that was abrogated by inhibition of tumor necrosis factor alpha (TNFα) signaling. Additionally, application of TNFα mimicked this increased excitability. Pregnant serum also caused morphological changes in microglia characteristic of activation, and increased TNFα mRNA expression that was not seen with exposure to nonpregnant serum. However, TNFα protein was not found to be elevated in pregnant serum itself, suggesting that other circulating factors during pregnancy caused activation of hippocampal slice cells to produce a TNFα-mediated increase in neuronal excitability. Lastly, although pregnant serum caused neuroinflammation and hyperexcitability of hippocampal slices, it did not increase blood-brain barrier permeability, nor were pregnant rats from which the serum was taken undergoing seizure. Thus, the BBB has an important role in protecting the brain from circulating neuroinflammatory mediators that are hyperexcitable to the brain during pregnancy. These studies provide novel insight into the underlying cause of eclampsia without elevated blood pressure and the protective role of the BBB that prevents exposure of the brain to hyperexcitable factors. Copyright © 2012 Elsevier Inc. All rights reserved.

Cortisol Excess and the Brain.

PubMed

Resmini, Eugenia; Santos, Alicia; Webb, Susan M

2016-01-01

Until the last decade, little was known about the effects of chronic hypercortisolism on the brain. In the last few years, new data have arisen thanks to advances in imaging techniques; therefore, it is now possible to investigate brain activity in vivo. Memory impairments are present in patients with Cushing's syndrome (CS) and are related to hippocampal damage; functional dysfunctions would precede structural abnormalities as detected by brain imaging. Earlier diagnosis and rapid normalization of hypercortisolism could stop the progression of hippocampal damage and memory impairments. Impairments of executive functions (including decision-making) and other functions such as visuoconstructive skills, language, motor functions and information processing speed are also present in CS patients. There is controversy concerning the reversibility of brain impairment. It seems that longer disease duration and older age are associated with less recovery of brain functioning. Conversely, earlier diagnosis and rapid normalization of hypercortisolism appear to stop progression of brain damage and functional impairments. Moreover, brain tissue functioning and neuroplasticity can be influenced by many factors. Currently available studies appear to be complementary, evaluating the same phenomenon from different points of view, but are often not directly comparable. Finally, CS patients have a high prevalence of psychopathology, such as depression and anxiety which do not completely revert after cure. Thus, psychological or psychiatric evaluation could be recommended in CS patients, so that treatment may be prescribed if required. © 2016 S. Karger AG, Basel.

Loss of Activity-Induced Phosphorylation of MeCP2 Enhances Synaptogenesis, LTP, and Spatial Memory

PubMed Central

Li, Hongda; Zhong, Xiaofen; Chau, Kevin Fongching; Williams, Emily Cunningham; Chang, Qiang

2012-01-01

DNA methylation-dependent epigenetic mechanisms underlie the development and function of the mammalian brain. MeCP2 expresses highly in neurons, and functions as a molecular linker between DNA methylation, chromatin remodeling and transcription regulation. Previous in vitro studies showed neuronal activity-induced phosphorylation (NAIP) of MeCP2 precedes its release from the Bdnf promoter and the ensuing Bdnf transcription. However, the in vivo function of this phosphorylation event remains elusive. We generated knockin mice that lack NAIP of MeCP2, and show here the Mecp2 phospho-mutant mice perform better in hippocampus-dependent memory tests, present enhanced LTP at two synapses in the hippocampus, and show increased excitatory synaptogenesis. At the molecular level, the phospho-mutant MeCP2 protein binds more tightly to several MeCP2 target gene promoters and alters the expression of these genes. Our results supply the first genetic evidence that NAIP of MeCP2 is required in modulating dynamic functions of the adult mouse brain. PMID:21765426

Visual encoding and fixation target selection in free viewing: presaccadic brain potentials

PubMed Central

Nikolaev, Andrey R.; Jurica, Peter; Nakatani, Chie; Plomp, Gijs; van Leeuwen, Cees

2013-01-01

In scrutinizing a scene, the eyes alternate between fixations and saccades. During a fixation, two component processes can be distinguished: visual encoding and selection of the next fixation target. We aimed to distinguish the neural correlates of these processes in the electrical brain activity prior to a saccade onset. Participants viewed color photographs of natural scenes, in preparation for a change detection task. Then, for each participant and each scene we computed an image heat map, with temperature representing the duration and density of fixations. The temperature difference between the start and end points of saccades was taken as a measure of the expected task-relevance of the information concentrated in specific regions of a scene. Visual encoding was evaluated according to whether subsequent change was correctly detected. Saccades with larger temperature difference were more likely to be followed by correct detection than ones with smaller temperature differences. The amplitude of presaccadic activity over anterior brain areas was larger for correct detection than for detection failure. This difference was observed for short “scrutinizing” but not for long “explorative” saccades, suggesting that presaccadic activity reflects top-down saccade guidance. Thus, successful encoding requires local scanning of scene regions which are expected to be task-relevant. Next, we evaluated fixation target selection. Saccades “moving up” in temperature were preceded by presaccadic activity of higher amplitude than those “moving down”. This finding suggests that presaccadic activity reflects attention deployed to the following fixation location. Our findings illustrate how presaccadic activity can elucidate concurrent brain processes related to the immediate goal of planning the next saccade and the larger-scale goal of constructing a robust representation of the visual scene. PMID:23818877

Subjective memory complaints are associated with brain activation supporting successful memory encoding.

PubMed

Hayes, Jessica M; Tang, Lingfei; Viviano, Raymond P; van Rooden, Sanneke; Ofen, Noa; Damoiseaux, Jessica S

2017-12-01

Subjective memory complaints, the perceived decline in cognitive abilities in the absence of clinical deficits, may precede Alzheimer's disease. Individuals with subjective memory complaints show differential brain activation during memory encoding; however, whether such differences contribute to successful memory formation remains unclear. Here, we investigated how subsequent memory effects, activation which is greater for hits than misses during an encoding task, differed between healthy older adults aged 50 to 85 years with (n = 23) and without (n = 41) memory complaints. Older adults with memory complaints, compared to those without, showed lower subsequent memory effects in the occipital lobe, superior parietal lobe, and posterior cingulate cortex. In addition, older adults with more memory complaints showed a more negative subsequent memory effects in areas of the default mode network, including the posterior cingulate cortex, precuneus, and ventromedial prefrontal cortex. Our findings suggest that for successful memory formation, older adults with subjective memory complaints rely on distinct neural mechanisms which may reflect an overall decreased task-directed attention. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of aging on value-directed modulation of semantic network activity during verbal learning

PubMed Central

Cohen, Michael S.; Rissman, Jesse; Suthana, Nanthia A.; Castel, Alan D.; Knowlton, Barbara J.

2015-01-01

While impairments in memory recall are apparent in aging, older adults show a remarkably preserved ability to selectively remember information deemed valuable. Here, we use fMRI to compare brain activation in healthy older and younger adults during encoding of high and low value words to determine whether there are differences in how older adults achieve value-directed memory selectivity. We find that memory selectivity in older adults is associated with value-related changes in activation during word presentation in left hemisphere regions that are involved in semantic processing, similar to young adults. However, highly selective young adults show a relatively greater increase in semantic network activity during encoding of high-value items, whereas highly selective older adults show relatively diminished activity during encoding of low-value items. Additionally, only younger adults showed value-related increases in activity in semantic and reward processing regions during presentation of the value cue preceding each to-be-remembered word. Young adults therefore respond to cue value more proactively than do older adults, yet the magnitude of value-related differences in cue period brain activity did not predict individual differences in memory selectivity. Thus, our data also show that age-related reductions in prestimulus activity do not always lead to inefficient performance. PMID:26244278

An fMRI investigation into the effect of preceding stimuli during visual oddball tasks.

PubMed

Fajkus, Jiří; Mikl, Michal; Shaw, Daniel Joel; Brázdil, Milan

2015-08-15

This study investigates the modulatory effect of stimulus sequence on neural responses to novel stimuli. A group of 34 healthy volunteers underwent event-related functional magnetic resonance imaging while performing a three-stimulus visual oddball task, involving randomly presented frequent stimuli and two types of infrequent stimuli - targets and distractors. We developed a modified categorization of rare stimuli that incorporated the type of preceding rare stimulus, and analyzed the event-related functional data according to this sequence categorization; specifically, we explored hemodynamic response modulation associated with increasing rare-to-rare stimulus interval. For two consecutive targets, a modulation of brain function was evident throughout posterior midline and lateral temporal cortex, while responses to targets preceded by distractors were modulated in a widely distributed fronto-parietal system. As for distractors that follow targets, brain function was modulated throughout a set of posterior brain structures. For two successive distractors, however, no significant modulation was observed, which is consistent with previous studies and our primary hypothesis. The addition of the aforementioned technique extends the possibilities of conventional oddball task analysis, enabling researchers to explore the effects of the whole range of rare stimuli intervals. This methodology can be applied to study a wide range of associated cognitive mechanisms, such as decision making, expectancy and attention. Copyright © 2015 Elsevier B.V. All rights reserved.

Brain-gut-microbiota axis in Parkinson's disease.

PubMed

Mulak, Agata; Bonaz, Bruno

2015-10-07

Parkinson's disease (PD) is characterized by alpha-synucleinopathy that affects all levels of the brain-gut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gut-microbiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.

Increased Mitochondrial Calcium Sensitivity and Abnormal Expression of Innate Immunity Genes Precede Dopaminergic Defects in Pink1-Deficient Mice

PubMed Central

Akundi, Ravi S.; Huang, Zhenyu; Eason, Joshua; Pandya, Jignesh D.; Zhi, Lianteng; Cass, Wayne A.; Sullivan, Patrick G.; Büeler, Hansruedi

2011-01-01

Background PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca2+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1−/− mice. Methods and Findings Purified brain mitochondria of Pink1−/− mice showed impaired Ca2+ storage capacity, resulting in increased Ca2+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1−/− mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1−/− mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1−/− mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1−/− embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1−/− mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. Conclusions Increased mitochondrial Ca2+ sensitivity and JNK activity are early defects in Pink1−/− mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1−/− mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1−/− mice to inflammation and injury-induced cell death. PMID:21249202

Lingering representations of stimuli influence recall organization.

PubMed

Chan, Stephanie C Y; Applegate, Marissa C; Morton, Neal W; Polyn, Sean M; Norman, Kenneth A

2017-03-01

Several prominent theories posit that information about recent experiences lingers in the brain and organizes memories for current experiences, by forming a temporal context that is linked to those memories at encoding. According to these theories, if the thoughts preceding an experience X resemble the thoughts preceding an experience Y, then X and Y should show an elevated probability of being recalled together. We tested this prediction by using multi-voxel pattern analysis (MVPA) of fMRI data to measure neural evidence for lingering processing of preceding stimuli. As predicted, memories encoded with similar lingering thoughts about the category of preceding stimuli were more likely to be recalled together. Our results demonstrate that the "fading embers" of previous stimuli help to organize recall, confirming a key prediction of computational models of episodic memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

Altered expression of zonula occludens-2 precedes increased blood-brain barrier permeability in a murine model of fulminant hepatic failure.

PubMed

Shimojima, Naoki; Eckman, Christopher B; McKinney, Michael; Sevlever, Daniel; Yamamoto, Satoshi; Lin, Wenlang; Dickson, Dennis W; Nguyen, Justin H

2008-01-01

Brain edema secondary to increased blood-brain barrier (BBB) permeability is a lethal complication in fulminant hepatic failure (FHF). Intact tight junctions (TJ) between brain capillary endothelial cells are critical for normal BBB function. However, the role of TJ in FHF has not been explored. We hypothesized that alterations in the composition of TJ proteins would result in increased BBB permeability in FHF. In this study, FHF was induced in C57BL/6J mice by using azoxymethane. BBB permeability was assessed with sodium fluorescein. Expression of TJ proteins was determined by Western blot, and their cellular distribution was examined using immunofluorescent microscopy. Comatose FHF mice had significant cerebral sodium fluorescein extravasation compared with control and precoma FHF mice, indicating increased BBB permeability. Western blot analysis showed a significant decrease in zonula occludens (ZO)-2 expression starting in the precoma stage. Immunofluorescent microscopy showed a significantly altered distribution pattern of ZO-2 in isolated microvessels from precoma FHF mice. These changes were more prominent in comatose FHF animals. Significant alterations in ZO-2 expression and distribution in the tight junctions preceded the increased BBB permeability in FHF mice. These results suggest that ZO-2 may play an important role in the pathogenesis of brain edema in FHF.

Prestimulus default mode activity influences depth of processing and recognition in an emotional memory task.

PubMed

Soravia, Leila M; Witmer, Joëlle S; Schwab, Simon; Nakataki, Masahito; Dierks, Thomas; Wiest, Roland; Henke, Katharina; Federspiel, Andrea; Jann, Kay

2016-03-01

Low self-referential thoughts are associated with better concentration, which leads to deeper encoding and increases learning and subsequent retrieval. There is evidence that being engaged in externally rather than internally focused tasks is related to low neural activity in the default mode network (DMN) promoting open mind and the deep elaboration of new information. Thus, reduced DMN activity should lead to enhanced concentration, comprehensive stimulus evaluation including emotional categorization, deeper stimulus processing, and better long-term retention over one whole week. In this fMRI study, we investigated brain activation preceding and during incidental encoding of emotional pictures and on subsequent recognition performance. During fMRI, 24 subjects were exposed to 80 pictures of different emotional valence and subsequently asked to complete an online recognition task one week later. Results indicate that neural activity within the medial temporal lobes during encoding predicts subsequent memory performance. Moreover, a low activity of the default mode network preceding incidental encoding leads to slightly better recognition performance independent of the emotional perception of a picture. The findings indicate that the suppression of internally-oriented thoughts leads to a more comprehensive and thorough evaluation of a stimulus and its emotional valence. Reduced activation of the DMN prior to stimulus onset is associated with deeper encoding and enhanced consolidation and retrieval performance even one week later. Even small prestimulus lapses of attention influence consolidation and subsequent recognition performance. © 2015 Wiley Periodicals, Inc.

Methylphenidate attenuates limbic brain inhibition after cocaine-cues exposure in cocaine abusers.

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

Volkow, N.D.; Wang, G.; Volkow, N.D.

Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and {sup 18}FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo andmore » once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2-5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction.« less

Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

PubMed Central

Volkow, Nora D.; Wang, Gene-Jack; Tomasi, Dardo; Telang, Frank; Fowler, Joanna S.; Pradhan, Kith; Jayne, Millard; Logan, Jean; Goldstein, Rita Z.; Alia-Klein, Nelly; Wong, Christopher

2010-01-01

Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2–5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction. PMID:20634975

Visual-gustatory interaction: orbitofrontal and insular cortices mediate the effect of high-calorie visual food cues on taste pleasantness.

PubMed

Ohla, Kathrin; Toepel, Ulrike; le Coutre, Johannes; Hudry, Julie

2012-01-01

Vision provides a primary sensory input for food perception. It raises expectations on taste and nutritional value and drives acceptance or rejection. So far, the impact of visual food cues varying in energy content on subsequent taste integration remains unexplored. Using electrical neuroimaging, we assessed whether high- and low-calorie food cues differentially influence the brain processing and perception of a subsequent neutral electric taste. When viewing high-calorie food images, participants reported the subsequent taste to be more pleasant than when low-calorie food images preceded the identical taste. Moreover, the taste-evoked neural activity was stronger in the bilateral insula and the adjacent frontal operculum (FOP) within 100 ms after taste onset when preceded by high- versus low-calorie cues. A similar pattern evolved in the anterior cingulate (ACC) and medial orbitofrontal cortex (OFC) around 180 ms, as well as, in the right insula, around 360 ms. The activation differences in the OFC correlated positively with changes in taste pleasantness, a finding that is an accord with the role of the OFC in the hedonic evaluation of taste. Later activation differences in the right insula likely indicate revaluation of interoceptive taste awareness. Our findings reveal previously unknown mechanisms of cross-modal, visual-gustatory, sensory interactions underlying food evaluation.

Cumulative activation during positive and negative events and state anxiety predicts subsequent inertia of amygdala reactivity

PubMed Central

Miendlarzewska, Ewa A.; Eryilmaz, Hamdi; Vuilleumier, Patrik

2015-01-01

Inertia, together with intensity and valence, is an important component of emotion. We tested whether positive and negative events generate lingering changes in subsequent brain responses to unrelated threat stimuli and investigated the impact of individual anxiety. We acquired fMRI data while participants watched positive or negative movie-clips and subsequently performed an unrelated task with fearful and neutral faces. We quantified changes in amygdala reactivity to fearful faces as a function of the valence of preceding movies and cumulative neural activity evoked during them. We demonstrate that amygdala responses to emotional movies spill over to subsequent processing of threat information in a valence-specific manner: negative movies enhance later amygdala activation whereas positive movies attenuate it. Critically, the magnitude of such changes is predicted by a measure of cumulative amygdala responses to the preceding positive or negative movies. These effects appear independent of overt attention, are regionally limited to amygdala, with no changes in functional connectivity. Finally, individuals with higher state anxiety displayed stronger modulation of amygdala reactivity by positive movies. These results suggest that intensity and valence of emotional events as well as anxiety levels promote local changes in amygdala sensitivity to threat, highlighting the importance of past experience in shaping future affective reactivity. PMID:24603023

Visual-Gustatory Interaction: Orbitofrontal and Insular Cortices Mediate the Effect of High-Calorie Visual Food Cues on Taste Pleasantness

PubMed Central

Ohla, Kathrin; Toepel, Ulrike; le Coutre, Johannes; Hudry, Julie

2012-01-01

Vision provides a primary sensory input for food perception. It raises expectations on taste and nutritional value and drives acceptance or rejection. So far, the impact of visual food cues varying in energy content on subsequent taste integration remains unexplored. Using electrical neuroimaging, we assessed whether high- and low-calorie food cues differentially influence the brain processing and perception of a subsequent neutral electric taste. When viewing high-calorie food images, participants reported the subsequent taste to be more pleasant than when low-calorie food images preceded the identical taste. Moreover, the taste-evoked neural activity was stronger in the bilateral insula and the adjacent frontal operculum (FOP) within 100 ms after taste onset when preceded by high- versus low-calorie cues. A similar pattern evolved in the anterior cingulate (ACC) and medial orbitofrontal cortex (OFC) around 180 ms, as well as, in the right insula, around 360 ms. The activation differences in the OFC correlated positively with changes in taste pleasantness, a finding that is an accord with the role of the OFC in the hedonic evaluation of taste. Later activation differences in the right insula likely indicate revaluation of interoceptive taste awareness. Our findings reveal previously unknown mechanisms of cross-modal, visual-gustatory, sensory interactions underlying food evaluation. PMID:22431974

Brain electric microstates and momentary conscious mind states as building blocks of spontaneous thinking: I. Visual imagery and abstract thoughts.

PubMed

Lehmann, D; Strik, W K; Henggeler, B; Koenig, T; Koukkou, M

1998-06-01

Prompted reports of recall of spontaneous, conscious experiences were collected in a no-input, no-task, no-response paradigm (30 random prompts to each of 13 healthy volunteers). The mentation reports were classified into visual imagery and abstract thought. Spontaneous 19-channel brain electric activity (EEG) was continuously recorded, viewed as series of momentary spatial distributions (maps) of the brain electric field and segmented into microstates, i.e. into time segments characterized by quasi-stable landscapes of potential distribution maps which showed varying durations in the sub-second range. Microstate segmentation used a data-driven strategy. Different microstates, i.e. different brain electric landscapes must have been generated by activity of different neural assemblies and therefore are hypothesized to constitute different functions. The two types of reported experiences were associated with significantly different microstates (mean duration 121 ms) immediately preceding the prompts; these microstates showed, across subjects, for abstract thought (compared to visual imagery) a shift of the electric gravity center to the left and a clockwise rotation of the field axis. Contrariwise, the microstates 2 s before the prompt did not differ between the two types of experiences. The results support the hypothesis that different microstates of the brain as recognized in its electric field implement different conscious, reportable mind states, i.e. different classes (types) of thoughts (mentations); thus, the microstates might be candidates for the 'atoms of thought'.

Behavioral and neural indices of affective coloring for neutral social stimuli

PubMed Central

Schaefer, Stacey M; Lapate, Regina C; Schoen, Andrew J; Gresham, Lauren K; Mumford, Jeanette A; Davidson, Richard J

2018-01-01

Abstract Emotional processing often continues beyond the presentation of emotionally evocative stimuli, which can result in affective biasing or coloring of subsequently encountered events. Here, we describe neural correlates of affective coloring and examine how individual differences in affective style impact the magnitude of affective coloring. We conducted functional magnetic resonance imaging in 117 adults who passively viewed negative, neutral and positive pictures presented 2 s prior to neutral faces. Brain responses to neutral faces were modulated by the valence of preceding pictures, with greater activation for faces following negative (vs positive) pictures in the amygdala, dorsomedial and lateral prefrontal cortex, ventral visual cortices, posterior superior temporal sulcus, and angular gyrus. Three days after the magnetic resonance imaging scan, participants rated their memory and liking of previously encountered neutral faces. Individuals higher in trait positive affect and emotional reappraisal rated faces as more likable when preceded by emotionally arousing (negative or positive) pictures. In addition, greater amygdala responses to neutral faces preceded by positively valenced pictures were associated with greater memory for these faces 3 days later. Collectively, these results reveal individual differences in how emotions spill over onto the processing of unrelated social stimuli, resulting in persistent and affectively biased evaluations of such stimuli. PMID:29447377

Brain State Before Error Making in Young Patients With Mild Spastic Cerebral Palsy.

PubMed

Hakkarainen, Elina; Pirilä, Silja; Kaartinen, Jukka; van der Meere, Jaap J

2015-10-01

In the present experiment, children with mild spastic cerebral palsy and a control group carried out a memory recognition task. The key question was if errors of the patient group are foreshadowed by attention lapses, by weak motor preparation, or by both. Reaction times together with event-related potentials associated with motor preparation (frontal late contingent negative variation), attention (parietal P300), and response evaluation (parietal error-preceding positivity) were investigated in instances where 3 subsequent correct trials preceded an error. The findings indicated that error responses of the patient group are foreshadowed by weak motor preparation in correct trials directly preceding an error. © The Author(s) 2015.

Streptococcus sanguinis brain abscess as complication of subclinical endocarditis: emphasizing the importance of prompt diagnosis.

PubMed

Kassis, Hayah; Marnejon, Thomas; Gemmel, David; Cutrona, Anthony; Gottimukkula, Rajashree

2010-06-01

A 19-year-old male patient was diagnosed with S. sanguinis brain abscess of unknown etiopathology as a complication of subclinical endocarditis. While viridans streptococci are implicated in dental seeding to the heart, S. sanguinis brain abscesses are rare. Six previous cases of S. sanguinis brain abscess in the literature reported dental procedures and maxillofacial trauma. In our patient, there was no obvious source of infective endocarditis preceding the development of brain abscess. This demonstrates the importance of prompt diagnosis and initiation of antimicrobial therapy given the potential for long-term sequelae such as focal deficits and seizures.

Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia.

PubMed

Cox-Limpens, Kimberly E M; Vles, Johan S H; LA van den Hove, Daniel; Zimmermann, Luc J I; Gavilanes, Antonio W D

2014-05-29

Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of brain preconditioning. Unraveling mechanisms of this endogenous neuroprotection, activated by preconditioning, is an important step towards new clinical strategies for treating asphyctic neonates.Therefore, we investigated whole-genome transcriptional changes in the brain of rats which underwent perinatal asphyxia (PA), and rats where PA was preceded by fetal asphyctic preconditioning (FAPA). Offspring were sacrificed 6 h and 96 h after birth, and whole-genome transcription was investigated using the Affymetrix Gene1.0ST chip. Microarray data were analyzed with the Bioconductor Limma package. In addition to univariate analysis, we performed Gene Set Enrichment Analysis (GSEA) in order to derive results with maximum biological relevance. We observed minimal, 25% or less, overlap of differentially regulated transcripts across different experimental groups which leads us to conclude that the transcriptional phenotype of these groups is largely unique. In both the PA and FAPA group we observe an upregulation of transcripts involved in cellular stress. Contrastingly, transcripts with a function in the cell nucleus were mostly downregulated in PA animals, while we see considerable upregulation in the FAPA group. Furthermore, we observed that histone deacetylases (HDACs) are exclusively regulated in FAPA animals. This study is the first to investigate whole-genome transcription in the neonatal brain after PA alone, and after perinatal asphyxia preceded by preconditioning (FAPA). We describe several genes/pathways, such as ubiquitination and proteolysis, which were not previously linked to preconditioning-induced neuroprotection. Furthermore, we observed that the majority of upregulated genes in preconditioned animals have a function in the cell nucleus, including several epigenetic players such as HDACs, which suggests that epigenetic mechanisms are likely to play a role in preconditioning-induced neuroprotection.

Fetal asphyctic preconditioning alters the transcriptional response to perinatal asphyxia

PubMed Central

2014-01-01

Background Genomic reprogramming is thought to be, at least in part, responsible for the protective effect of brain preconditioning. Unraveling mechanisms of this endogenous neuroprotection, activated by preconditioning, is an important step towards new clinical strategies for treating asphyctic neonates. Therefore, we investigated whole-genome transcriptional changes in the brain of rats which underwent perinatal asphyxia (PA), and rats where PA was preceded by fetal asphyctic preconditioning (FAPA). Offspring were sacrificed 6 h and 96 h after birth, and whole-genome transcription was investigated using the Affymetrix Gene1.0ST chip. Microarray data were analyzed with the Bioconductor Limma package. In addition to univariate analysis, we performed Gene Set Enrichment Analysis (GSEA) in order to derive results with maximum biological relevance. Results We observed minimal, 25% or less, overlap of differentially regulated transcripts across different experimental groups which leads us to conclude that the transcriptional phenotype of these groups is largely unique. In both the PA and FAPA group we observe an upregulation of transcripts involved in cellular stress. Contrastingly, transcripts with a function in the cell nucleus were mostly downregulated in PA animals, while we see considerable upregulation in the FAPA group. Furthermore, we observed that histone deacetylases (HDACs) are exclusively regulated in FAPA animals. Conclusions This study is the first to investigate whole-genome transcription in the neonatal brain after PA alone, and after perinatal asphyxia preceded by preconditioning (FAPA). We describe several genes/pathways, such as ubiquitination and proteolysis, which were not previously linked to preconditioning-induced neuroprotection. Furthermore, we observed that the majority of upregulated genes in preconditioned animals have a function in the cell nucleus, including several epigenetic players such as HDACs, which suggests that epigenetic mechanisms are likely to play a role in preconditioning-induced neuroprotection. PMID:24885038

[Brain Organization of the Preparation for Visual Recognition in Preadolescent Children].

PubMed

Farber, D A; Kurganskii, A V; Petrenko, N E

2015-01-01

The brain organization of the process of preparation for the perception of incomplete images fragmented to different extents. The functional connections of ventrolateral and dorsoventral cortical zones with other zones in 10-11-year-old and 11-12-year-old children were studied at three successive stages of the preparation for the perception of incomplete images. These data were compared with those obtained for adults. In order to reveal the effect of preparatory processes on the image recognition, we also analyzed the regional event-related potentials. In adults, the functional interaction between dorsolateral and ventrolateral prefrontal cortex and other cortical zones of the right hemisphere was found to be enhanced at the stage of waiting for not-yet-recognizable image, while in the left hemisphere the links became stronger shortly before the successful recognition of a stimulus. In children the stage-related changes in functional interactions are similar in both hemispheres, with peak of interaction activity.at the stage preceding the successful recognition. It was found that in 11-12-year-old children the ventrolateral cortex is involved in both preparatory stage and recognition processes to a smaller extent as compared with adults and 10-11-year-old children. At the same time, the group of 11-12-year-old children had more mature pattern of the dorsolateral cortex involvement, which provided more effective recognition of incomplete images in this group as compared with 10-11-year-old children. It is suggested that the features of the brain organization of visual recognition and preceding preparatory processes in 11-12-year-old children are caused by multidirectional effects of sex hormones on the functioning of different zones of the prefrontal cortex at early stages of sexual maturation.

Conveying the concept of movement in music: An event-related brain potential study.

PubMed

Zhou, Linshu; Jiang, Cunmei; Wu, Yingying; Yang, Yufang

2015-10-01

This study on event-related brain potential investigated whether music can convey the concept of movement. Using a semantic priming paradigm, natural musical excerpts were presented to non-musicians, followed by semantically congruent or incongruent pictures that depicted objects either in motion or at rest. The priming effects were tested in object decision and implicit recognition tasks to distinguish the effects of automatic conceptual activation from response competition. Results showed that in both tasks, pictures that were incongruent to preceding musical excerpts elicited larger N400 than congruent pictures, suggesting that music can prime the representations of movement concepts. Results of the multiple regression analysis showed that movement expression could be well predicted by specific acoustic and musical features, indicating the associations between music per se and the processing of iconic musical meaning. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gene inactivation of Na+/H+ exchanger isoform 1 attenuates apoptosis and mitochondrial damage following transient focal cerebral ischemia

PubMed Central

Wang, Yanping; Luo, Jing; Chen, Xinzhi; Chen, Hai; Cramer, Sam W.; Sun, Dandan

2010-01-01

We investigated mechanisms underlying the Na+/H+ exchanger isoform 1 (NHE1)-mediated neuronal damage in transient focal ischemia. Physiological parameters, body and tympanic temperatures, and regional cerebral blood flow during 30 min middle cerebral artery occlusion (MCAO) were similar in wild-type NHE1 (NHE1+/+) and NHE1 heterozygous (NHE1+/−) mice. NHE1+/+ mice developed infarct volume of 57.3 ± 8.8 mm3 at 24 h reperfusion (Rp), which progressed to 86.1 ± 10.0 mm3 at 72 h Rp. This delayed cell death was preceded by release of mitochondrial cytochrome c (Cyt. C), nuclear translocation of apoptosis-inducing factor (AIF), activation of caspase-3, and TUNEL-positive staining and chromatin condensation in the ipsilateral hemispheres of NHE1+/+ brains. In contrast, NHE1+/− mice had a significantly smaller infarct volume and improved neurological function. A similar neuroprotection was obtained with NHE1 inhibitor HOE 642. The number of apoptotic cells, release of AIF and Cyt. C or levels of active caspase-3 was significantly reduced in NHE1+/− brains. These data imply that NHE1 activity may contribute to ischemic apoptosis. Ischemic brains did not exhibit changes of NHE1 protein expression. In contrast, up-regulation of NHE1 expression was found in NHE1+/+ neurons after in vitro ischemia. These data suggest that NHE1 activation following cerebral ischemia contributes to mitochondrial damage and ischemic apoptosis. PMID:18662334

Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer's mouse brain: implication for bioenergetic intervention.

PubMed

Ding, Fan; Yao, Jia; Rettberg, Jamaica R; Chen, Shuhua; Brinton, Roberta Diaz

2013-01-01

We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3-15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6-9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential targets for preventing shifts to less efficient bioenergetic fuels and transition to the ketogenic phenotype of the Alzheimer's brain.

The time course of activity in dorsolateral prefrontal cortex and anterior cingulate cortex during top-down attentional control.

PubMed

Silton, Rebecca Levin; Heller, Wendy; Towers, David N; Engels, Anna S; Spielberg, Jeffrey M; Edgar, J Christopher; Sass, Sarah M; Stewart, Jennifer L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

2010-04-15

A network of brain regions has been implicated in top-down attentional control, including left dorsolateral prefrontal cortex (LDLPFC) and dorsal anterior cingulate cortex (dACC). The present experiment evaluated predictions of the cascade-of-control model (Banich, 2009), which predicts that during attentionally-demanding tasks, LDLPFC imposes a top-down attentional set which precedes late-stage selection performed by dACC. Furthermore, the cascade-of-control model argues that dACC must increase its activity to compensate when top-down control by LDLPFC is poor. The present study tested these hypotheses using fMRI and dense-array ERP data collected from the same 80 participants in separate sessions. fMRI results guided ERP source modeling to characterize the time course of activity in LDLPFC and dACC. As predicted, dACC activity subsequent to LDLPFC activity distinguished congruent and incongruent conditions on the Stroop task. Furthermore, when LDLPFC activity was low, the level of dACC activity was related to performance outcome. These results demonstrate that dACC responds to attentional demand in a flexible manner that is dependent on the level of LDLPFC activity earlier in a trial. Overall, results were consistent with the temporal course of regional brain function proposed by the cascade-of-control model. Copyright 2009 Elsevier Inc. All rights reserved.

Lasting impact of regret and gratification on resting brain activity and its relation to depressive traits.

PubMed

Eryilmaz, Hamdi; Van De Ville, Dimitri; Schwartz, Sophie; Vuilleumier, Patrik

2014-06-04

Obtaining lower gains than rejected alternatives during decision making evokes feelings of regret, whereas higher gains elicit gratification. Although decision-related emotions produce lingering effects on mental state, neuroscience research has generally focused on transient brain responses to positive or negative events, but ignored more sustained consequences of emotional episodes on subsequent brain states. We investigated how spontaneous brain activity and functional connectivity at rest are modulated by postdecision regret and gratification in 18 healthy human subjects using a gambling task in fMRI. Differences between obtained and unobtained outcomes were manipulated parametrically to evoke different levels of regret or gratification. We investigated how individual personality traits related to depression and rumination affected these responses. Medial and ventral prefrontal areas differentially responded to favorable and unfavorable outcomes during the gambling period. More critically, during subsequent rest, rostral anterior and posterior cingulate cortex, ventral striatum, and insula showed parametric response to the gratification level of preceding outcomes. Functional coupling of posterior cingulate with striatum and amygdala was also enhanced during rest after high gratification. Regret produced distinct changes in connectivity of subgenual cingulate with orbitofrontal cortex and thalamus. Interestingly, individual differences in depressive traits and ruminations correlated with activity of the striatum after gratification and orbitofrontal cortex after regret, respectively. By revealing lingering effects of decision-related emotions on key nodes of resting state networks, our findings illuminate how such emotions may influence self-reflective processing and subsequent behavioral adjustment, but also highlight the malleability of resting networks in emotional contexts. Copyright © 2014 the authors 0270-6474/14/347825-11$15.00/0.

Biasing the brain's attentional set: I. cue driven deployments of intersensory selective attention.

PubMed

Foxe, John J; Simpson, Gregory V; Ahlfors, Seppo P; Saron, Clifford D

2005-10-01

Brain activity associated with directing attention to one of two possible sensory modalities was examined using high-density mapping of human event-related potentials. The deployment of selective attention was based on visually presented symbolic cue-words instructing subjects on a trial-by-trial basis, which sensory modality to attend. We measured the spatio-temporal pattern of activation in the approximately 1 second period between the cue-instruction and a subsequent compound auditory-visual imperative stimulus. This allowed us to assess the flow of processing across brain regions involved in deploying and sustaining inter-sensory selective attention, prior to the actual selective processing of the compound audio-visual target stimulus. Activity over frontal and parietal areas showed sensory specific increases in activation during the early part of the anticipatory period (~230 ms), probably representing the activation of fronto-parietal attentional deployment systems for top-down control of attention. In the later period preceding the arrival of the "to-be-attended" stimulus, sustained differential activity was seen over fronto-central regions and parieto-occipital regions, suggesting the maintenance of sensory-specific biased attentional states that would allow for subsequent selective processing. Although there was clear sensory biasing in this late sustained period, it was also clear that both sensory systems were being prepared during the cue-target period. These late sensory-specific biasing effects were also accompanied by sustained activations over frontal cortices that also showed both common and sensory specific activation patterns, suggesting that maintenance of the biased state includes top-down inputs from generators in frontal cortices, some of which are sensory-specific regions. These data support extensive interactions between sensory, parietal and frontal regions during processing of cue information, deployment of attention, and maintenance of the focus of attention in anticipation of impending attentionally relevant input.

Spatiotemporal Neural Dynamics of Word Understanding in 12- to 18-Month-Old-Infants

PubMed Central

Leonard, Matthew K.; Brown, Timothy T.; Hagler, Donald J.; Curran, Megan; Dale, Anders M.; Elman, Jeffrey L.; Halgren, Eric

2011-01-01

Learning words is central in human development. However, lacking clear evidence for how or where language is processed in the developing brain, it is unknown whether these processes are similar in infants and adults. Here, we use magnetoencephalography in combination with high-resolution structural magnetic resonance imaging to noninvasively estimate the spatiotemporal distribution of word-selective brain activity in 12- to 18-month-old infants. Infants watched pictures of common objects and listened to words that they understood. A subset of these infants also listened to familiar words compared with sensory control sounds. In both experiments, words evoked a characteristic event-related brain response peaking ∼400 ms after word onset, which localized to left frontotemporal cortices. In adults, this activity, termed the N400m, is associated with lexico-semantic encoding. Like adults, we find that the amplitude of the infant N400m is also modulated by semantic priming, being reduced to words preceded by a semantically related picture. These findings suggest that similar left frontotemporal areas are used for encoding lexico-semantic information throughout the life span, from the earliest stages of word learning. Furthermore, this ontogenetic consistency implies that the neurophysiological processes underlying the N400m may be important both for understanding already known words and for learning new words. PMID:21209121

Brain indices of disagreement with one’s social values predict EU referendum voting behavior

PubMed Central

Sirota, Miroslav; Materassi, Maurizio; Zaninotto, Francesca; Terry, Philip

2017-01-01

Abstract Pre-electoral surveys typically attempt, and sometimes fail, to predict voting behavior on the basis of explicit measures of agreement or disagreement with a candidate or political position. Here, we assessed whether a specific brain signature of disagreement with one’s social values, the event-related potential component N400, could be predictive of voting behavior. We examined this possibility in the context of the EU referendum in the UK. In the 5 weeks preceding the referendum, we recorded the N400 while participants with different vote intentions expressed their agreement or disagreement with pro- and against-EU statements. We showed that the N400 responded to statements incongruent with one’s view regarding the EU. Crucially, this effect predicted actual voting behavior in decided as well as undecided voters. The N400 was a better predictor of voting choice than an explicit index of preference based on the behavioral responses. Our findings demonstrate that well-defined patterns of brain activity can forecast future voting behavior. PMID:28981799

Mitochondrial dysfunction precedes neurodegeneration in mahogunin (Mgrn1) mutant mice

PubMed Central

Sun, Kaihua; Johnson, Brian S.; Gunn, Teresa M.

2007-01-01

Oxidative stress, ubiquitination defects and mitochondrial dysfunction are commonly associated with neurodegeneration. Mice lacking mahogunin ring finger-1 (MGRN1) or attractin (ATRN) develop age-dependent spongiform neurodegeneration through an unknown mechanism. It has been suggested that they act in a common pathway. As MGRN1 is an E3 ubiquitin ligase, proteomic analysis of Mgrn1 mutant and control brains was performed to explore the hypothesis that loss of MGRN1 causes neurodegeneration via accumulation of its substrates. Many mitochondrial proteins were reduced in Mgrn1 mutants. Subsequent assays confirmed significantly reduced mitochondrial complex IV expression and activity as well as increased oxidative stress in mutant brains. Mitochondrial dysfunction was obvious many months before onset of vacuolation, implicating this as a causative factor. Compatible with the hypothesis that ATRN and MGRN1 act in the same pathway, mitochondrial dysfunction and increased oxidative stress were also observed in the brains of Atrn mutants. Our results suggest that the study of Mgrn1 and Atrn mutant mice will provide insight into a causative molecular mechanism common to many neurodegenerative disorders. PMID:17720281

Loss of activity-induced phosphorylation of MeCP2 enhances synaptogenesis, LTP and spatial memory.

PubMed

Li, Hongda; Zhong, Xiaofen; Chau, Kevin Fongching; Williams, Emily Cunningham; Chang, Qiang

2011-07-17

DNA methylation-dependent epigenetic mechanisms underlie the development and function of the mammalian brain. MeCP2 is highly expressed in neurons and functions as a molecular linker between DNA methylation, chromatin remodeling and transcription regulation. Previous in vitro studies have shown that neuronal activity-induced phosphorylation (NAIP) of methyl CpG-binding protein 2 (MeCP2) precedes its release from the Bdnf promoter and the ensuing Bdnf transcription. However, the in vivo function of this phosphorylation event remains elusive. We generated knock-in mice that lack NAIP of MeCP2 and found that they performed better in hippocampus-dependent memory tests, presented enhanced long-term potentiation at two synapses in the hippocampus and showed increased excitatory synaptogenesis. At the molecular level, the phospho-mutant MeCP2 protein bound more tightly to several MeCP2 target gene promoters and altered the expression of these genes. Our results suggest that NAIP of MeCP2 is required for modulating dynamic functions of the adult mouse brain.

Phonation takes precedence over articulation in development as well as evolution of language.

PubMed

Oller, D Kimbrough

2014-12-01

Early human vocal development is characterized first by emerging control of phonation and later by prosodic and supraglottal articulation. The target article has missed the opportunity to use these facts in the characterization of evolution in language-specific brain mechanisms. Phonation appears to be the initial human-specific brain change for language, and it was presumably a key target of selection in early hominin evolution.

DYSFUNCTIONAL KYNURENINE PATHWAY METABOLISM IN THE R6/2 MOUSE MODEL OF HUNTINGTON’S DISEASE

PubMed Central

Sathyasaikumar, Korrapati V.; Stachowski, Erin K.; Amori, Laura; Guidetti, Paolo; Muchowski, Paul J.; Schwarcz, Robert

2013-01-01

Elevated concentrations of neurotoxic metabolites of the kynurenine pathway (KP) of tryptophan degradation may play a causative role in Huntington’s disease (HD). The brain levels of one of these compounds, 3-hydroxykynurenine (3-HK), are increased in both HD and several mouse models of the disease. In the present study, we examined this impairment in greater detail using the R6/2 mouse, a well-established animal model of HD. Initially, mutant and age-matched wild-type mice received an intrastriatal injection of 3H-tryptophan to assess the acute, local de novo production of kynurenine, the immediate bioprecursor of 3-HK, in vivo. No effect of genotype was observed between 4 and 12 weeks of age. In contrast, intrastriatally applied 3H-kynurenine resulted in significantly increased neosynthesis of 3H-3-HK, but not other tritiated KP metabolites, in the R6/2 striatum. Subsequent ex vivo studies in striatal, cortical and cerebellar tissue revealed substantial increases in the activity of the biosynthetic enzyme of 3-HK, kynurenine 3-monooxygenase (KMO) and significant reductions in the activity of its degradative enzyme, kynureninase, in HD mice starting at 4 weeks of age. Decreased kynureninase activity was most evident in the cortex and preceded the increase in KMO activity. The activity of other KP enzymes showed no consistent brain abnormalities in the mutant mice. These findings suggest that impairments in its immediate metabolic enzymes jointly account for the abnormally high brain levels of 3-HK in the R6/2 model of HD. PMID:20236387

Microwave & Magnetic (M2) Proteomics Reveals CNS-Specific Protein Expression Waves that Precede Clinical Symptoms of Experimental Autoimmune Encephalomyelitis

NASA Astrophysics Data System (ADS)

Raphael, Itay; Mahesula, Swetha; Purkar, Anjali; Black, David; Catala, Alexis; Gelfond, Jonathon A. L.; Forsthuber, Thomas G.; Haskins, William E.

2014-09-01

Central nervous system-specific proteins (CSPs), transported across the damaged blood-brain-barrier (BBB) to cerebrospinal fluid (CSF) and blood (serum), might be promising diagnostic, prognostic and predictive protein biomarkers of disease in individual multiple sclerosis (MS) patients because they are not expected to be present at appreciable levels in the circulation of healthy subjects. We hypothesized that microwave & magnetic (M2) proteomics of CSPs in brain tissue might be an effective means to prioritize putative CSP biomarkers for future immunoassays in serum. To test this hypothesis, we used M2 proteomics to longitudinally assess CSP expression in brain tissue from mice during experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Confirmation of central nervous system (CNS)-infiltrating inflammatory cell response and CSP expression in serum was achieved with cytokine ELISPOT and ELISA immunoassays, respectively, for selected CSPs. M2 proteomics (and ELISA) revealed characteristic CSP expression waves, including synapsin-1 and α-II-spectrin, which peaked at day 7 in brain tissue (and serum) and preceded clinical EAE symptoms that began at day 10 and peaked at day 20. Moreover, M2 proteomics supports the concept that relatively few CNS-infiltrating inflammatory cells can have a disproportionally large impact on CSP expression prior to clinical manifestation of EAE.

Do animals and furniture items elicit different brain responses in human infants?

PubMed

Jeschonek, Susanna; Marinovic, Vesna; Hoehl, Stefanie; Elsner, Birgit; Pauen, Sabina

2010-11-01

One of the earliest categorical distinctions to be made by preverbal infants is the animate-inanimate distinction. To explore the neural basis for this distinction in 7-8-month-olds, an equal number of animal and furniture pictures was presented in an ERP-paradigm. The total of 118 pictures, all looking different from each other, were presented in a semi-randomized order for 1000ms each. Infants' brain responses to exemplars from both categories differed systematically regarding the negative central component (Nc: 400-600ms) at anterior channels. More specifically, the Nc was enhanced for animals in one subgroup of infants, and for furniture items in another subgroup of infants. Explorative analyses related to categorical priming further revealed category-specific differences in brain responses in the late time window (650-1550ms) at right frontal channels: Unprimed stimuli (preceded by a different-category item) elicited a more positive response as compared to primed stimuli (preceded by a same-category item). In sum, these findings suggest that the infant's brain discriminates exemplars from both global domains. Given the design of our task, we conclude that processes of category identification are more likely to account for our findings than processes of on-line category formation during the experimental session. Copyright © 2009 Elsevier B.V. All rights reserved.

Geomagnetic activity and enhanced mortality in rats with acute (epileptic) limbic lability

NASA Astrophysics Data System (ADS)

Bureau, Yves R. J.; Persinger, M. A.

1992-12-01

Presumably unrelated behaviors (e.g. psychiatric admissions, seizures, heart failures) have been correlated with increased global geomagnetic activity. We have suggested that all of these behaviors share a common source of variance. They are evoked by transient, dopamine-mediated paroxysmal electrical patterns that are generated within the amygdala and the hippocampus of the temporal lobes. Both the probability and the propagation of these discharges to distal brain regions are facilitated when nocturnal melatonin levels are suppressed by increased geomagnetic activity. In support of this hypothesis, the present study demonstrated a significant correlation of Pearson r=0.60 between mortality during the critical 4-day period that followed induction of libic seizures in rats and the ambient geomagnetic activity during the 3 to 4 days that preceded death; the risk increased when the 24 h geomagnetic indices exceeded 20 nT for more than 1 to 2 days.

Blood-brain barrier hyperpermeability precedes demyelination in the cuprizone model.

PubMed

Berghoff, Stefan A; Düking, Tim; Spieth, Lena; Winchenbach, Jan; Stumpf, Sina K; Gerndt, Nina; Kusch, Kathrin; Ruhwedel, Torben; Möbius, Wiebke; Saher, Gesine

2017-12-01

In neuroinflammatory disorders such as multiple sclerosis, the physiological function of the blood-brain barrier (BBB) is perturbed, particularly in demyelinating lesions and supposedly secondary to acute demyelinating pathology. Using the toxic non-inflammatory cuprizone model of demyelination, we demonstrate, however, that the onset of persistent BBB impairment precedes demyelination. In addition to a direct effect of cuprizone on endothelial cells, a plethora of inflammatory mediators, which are mainly of astroglial origin during the initial disease phase, likely contribute to the destabilization of endothelial barrier function in vivo. Our study reveals that, at different time points of pathology and in different CNS regions, the level of gliosis correlates with the extent of BBB hyperpermeability and edema. Furthermore, in mutant mice with abolished type 3 CXC chemokine receptor (CXCR3) signaling, inflammatory responses are dampened and BBB dysfunction ameliorated. Together, these data have implications for understanding the role of BBB permeability in the pathogenesis of demyelinating disease.

Cumulative activation during positive and negative events and state anxiety predicts subsequent inertia of amygdala reactivity.

PubMed

Pichon, Swann; Miendlarzewska, Ewa A; Eryilmaz, Hamdi; Vuilleumier, Patrik

2015-02-01

Inertia, together with intensity and valence, is an important component of emotion. We tested whether positive and negative events generate lingering changes in subsequent brain responses to unrelated threat stimuli and investigated the impact of individual anxiety. We acquired fMRI data while participants watched positive or negative movie-clips and subsequently performed an unrelated task with fearful and neutral faces. We quantified changes in amygdala reactivity to fearful faces as a function of the valence of preceding movies and cumulative neural activity evoked during them. We demonstrate that amygdala responses to emotional movies spill over to subsequent processing of threat information in a valence-specific manner: negative movies enhance later amygdala activation whereas positive movies attenuate it. Critically, the magnitude of such changes is predicted by a measure of cumulative amygdala responses to the preceding positive or negative movies. These effects appear independent of overt attention, are regionally limited to amygdala, with no changes in functional connectivity. Finally, individuals with higher state anxiety displayed stronger modulation of amygdala reactivity by positive movies. These results suggest that intensity and valence of emotional events as well as anxiety levels promote local changes in amygdala sensitivity to threat, highlighting the importance of past experience in shaping future affective reactivity. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Effects of motivation on reward and attentional networks: an fMRI study.

PubMed

Ivanov, Iliyan; Liu, Xun; Clerkin, Suzanne; Schulz, Kurt; Friston, Karl; Newcorn, Jeffrey H; Fan, Jin

2012-11-01

Existing evidence suggests that reward and attentional networks function in concert and that activation in one system influences the other in a reciprocal fashion; however, the nature of these influences remains poorly understood. We therefore developed a three-component task to assess the interaction effects of reward anticipation and conflict resolution on the behavioral performance and the activation of brain reward and attentional systems. Sixteen healthy adult volunteers aged 21-45 years were scanned with functional magnetic resonance imaging (fMRI) while performing the task. A two-way repeated measures analysis of variance (ANOVA) with cue (reward vs. non-reward) and target (congruent vs. incongruent) as within-subjects factors was used to test for main and interaction effects. Neural responses to anticipation, conflict, and reward outcomes were tested. Behaviorally there were main effects of both reward cue and target congruency on reaction time. Neuroimaging results showed that reward anticipation and expected reward outcomes activated components of the attentional networks, including the inferior parietal and occipital cortices, whereas surprising non-rewards activated the frontoinsular cortex bilaterally and deactivated the ventral striatum. In turn, conflict activated a broad network associated with cognitive control and motor functions. Interaction effects showed decreased activity in the thalamus, anterior cingulated gyrus, and middle frontal gyrus bilaterally when difficult conflict trials (e.g., incongruent targets) were preceded by reward cues; in contrast, the ventral striatum and orbitofrontal cortex showed greater activation during congruent targets preceded by reward cues. These results suggest that reward anticipation is associated with lower activation in attentional networks, possibly due to increased processing efficiency, whereas more difficult, conflict trials are associated with lower activity in regions of the reward system, possibly because such trials are experienced as less rewarding.

Externalizing proneness and brain response during pre-cuing and viewing of emotional pictures

PubMed Central

Foell, Jens; Brislin, Sarah J.; Strickland, Casey M.; Seo, Dongju; Sabatinelli, Dean

2016-01-01

Externalizing proneness, or trait disinhibition, is a concept relevant to multiple high-impact disorders involving impulsive-aggressive behavior. Its mechanisms remain disputed: major models posit hyperresponsive reward circuitry or heightened threat-system reactivity as sources of disinhibitory tendencies. This study evaluated alternative possibilities by examining relations between trait disinhibition and brain reactivity during preparation for and processing of visual affective stimuli. Forty females participated in a functional neuroimaging procedure with stimuli presented in blocks containing either pleasurable or aversive pictures interspersed with neutral, with each picture preceded by a preparation signal. Preparing to view elicited activation in regions including nucleus accumbens, whereas visual regions and bilateral amygdala were activated during viewing of emotional pictures. High disinhibition predicted reduced nucleus accumbens activation during preparation within pleasant/neutral picture blocks, along with enhanced amygdala reactivity during viewing of pleasant and aversive pictures. Follow-up analyses revealed that the augmented amygdala response was related to reduced preparatory activation. Findings indicate that participants high in disinhibition are less able to process implicit cues and mentally prepare for upcoming stimuli, leading to limbic hyperreactivity during processing of actual stimuli. This outcome is helpful for integrating findings from studies suggesting reward-system hyperreactivity and others suggesting threat-system hyperreactivity as mechanisms for externalizing proneness. PMID:26113614

Separate encoding of model-based and model-free valuations in the human brain.

PubMed

Beierholm, Ulrik R; Anen, Cedric; Quartz, Steven; Bossaerts, Peter

2011-10-01

Behavioral studies have long shown that humans solve problems in two ways, one intuitive and fast (System 1, model-free), and the other reflective and slow (System 2, model-based). The neurobiological basis of dual process problem solving remains unknown due to challenges of separating activation in concurrent systems. We present a novel neuroeconomic task that predicts distinct subjective valuation and updating signals corresponding to these two systems. We found two concurrent value signals in human prefrontal cortex: a System 1 model-free reinforcement signal and a System 2 model-based Bayesian signal. We also found a System 1 updating signal in striatal areas and a System 2 updating signal in lateral prefrontal cortex. Further, signals in prefrontal cortex preceded choices that are optimal according to either updating principle, while signals in anterior cingulate cortex and globus pallidus preceded deviations from optimal choice for reinforcement learning. These deviations tended to occur when uncertainty regarding optimal values was highest, suggesting that disagreement between dual systems is mediated by uncertainty rather than conflict, confirming recent theoretical proposals. Copyright © 2011 Elsevier Inc. All rights reserved.

PHONATION TAKES PRECEDENCE IN DEVELOPMENT AS WELL AS EVOLUTION OF LANGUAGE

PubMed Central

Oller, D. Kimbrough

2014-01-01

Early development of vocalization in humans is characterized by emerging control of phonation, rather than of prosody or supraglottal articulation. This fact offers an opportunity to the authors of the target article to enrich their characterization of the evolution of differential brain mechanisms in human and non-human primates. Phonation, I suggest, is the initial target of human-specific brain changes in sound-making capability upon which language is founded. PMID:25514957

Self-reference modulates the processing of emotional stimuli in the absence of explicit self-referential appraisal instructions

PubMed Central

Pauli, Paul; Herbert, Beate M.

2011-01-01

Self-referential evaluation of emotional stimuli has been shown to modify the way emotional stimuli are processed. This study aimed at a new approach by investigating whether self-reference alters emotion processing in the absence of explicit self-referential appraisal instructions. Event-related potentials were measured while subjects spontaneously viewed a series of emotional and neutral nouns. Nouns were preceded either by personal pronouns (‘my’) indicating self-reference or a definite article (‘the’) without self-reference. The early posterior negativity, a brain potential reflecting rapid attention capture by emotional stimuli was enhanced for unpleasant and pleasant nouns relative to neutral nouns irrespective of whether nouns were preceded by personal pronouns or articles. Later brain potentials such as the late positive potential were enhanced for unpleasant nouns only when preceded by personal pronouns. Unpleasant nouns were better remembered than pleasant or neutral nouns when paired with a personal pronoun. Correlation analysis showed that this bias in favor of self-related unpleasant concepts can be explained by participants’ depression scores. Our results demonstrate that self-reference acts as a first processing filter for emotional material to receive higher order processing after an initial rapid attention capture by emotional content has been completed. Mood-congruent processing may contribute to this effect. PMID:20855295

Self-reference modulates the processing of emotional stimuli in the absence of explicit self-referential appraisal instructions.

PubMed

Herbert, Cornelia; Pauli, Paul; Herbert, Beate M

2011-10-01

Self-referential evaluation of emotional stimuli has been shown to modify the way emotional stimuli are processed. This study aimed at a new approach by investigating whether self-reference alters emotion processing in the absence of explicit self-referential appraisal instructions. Event-related potentials were measured while subjects spontaneously viewed a series of emotional and neutral nouns. Nouns were preceded either by personal pronouns ('my') indicating self-reference or a definite article ('the') without self-reference. The early posterior negativity, a brain potential reflecting rapid attention capture by emotional stimuli was enhanced for unpleasant and pleasant nouns relative to neutral nouns irrespective of whether nouns were preceded by personal pronouns or articles. Later brain potentials such as the late positive potential were enhanced for unpleasant nouns only when preceded by personal pronouns. Unpleasant nouns were better remembered than pleasant or neutral nouns when paired with a personal pronoun. Correlation analysis showed that this bias in favor of self-related unpleasant concepts can be explained by participants' depression scores. Our results demonstrate that self-reference acts as a first processing filter for emotional material to receive higher order processing after an initial rapid attention capture by emotional content has been completed. Mood-congruent processing may contribute to this effect.

A change of heart and a change of mind? Technology and the redefinition of death in 1968.

PubMed

Giacomini, M

1997-05-01

In 1968, an ad hoc committee of Harvard faculty publicly redefined death as "brain death". What interests and issues compelled the redefinition of death, and formed the "spirit" of this precedent-setting policy? This paper reports on an historical study of the files of the Harvard ad hoc committee, the proceedings of an international conference on ethical issues in organ transplantation, and a review of the medical literature and media in the decades preceding the redefinition of death. This analysis of the technological and professional forces involved in the redefinition of death in 1968 questions two common theses: that technological "progress", primarily in the areas of life support and electroencephalography, literally created brain-dead bodies and dictated their defining features (respectively), and that Harvard's definition of brain death by committee constituted a net loss of autonomy for medicine. In fact, medical researchers through the 1960s disputed and negotiated many features of the brain death syndrome, and transplantation interests-perhaps more kidney than heart-played a particularly influential role in tailoring the final criteria put forth by Harvard in 1968. It is also doubtful whether Harvard's definition of brain death by multidisciplinary committee undermined medical privilege and autonomy. The Harvard Ad Hoc Committee may not have succeeded in establishing definitive, indisputable brain death criteria and ensuring their consistent application to all clinical cases of brain death. However, it did gain significant ground for transplant and other medical interests by (1) establishing brain death as a technical "fact" and the definition of brain death as an exercise for medical theorists, (2) involving non-medical ethics and humanities experts in supporting the technical redefinition of death, and, (3) successfully involving transplant surgeons in the redefinition of death and attempting (albeit unsuccessfully) not to exclude them from the actual diagnosis of death in individual cases.

Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution.

PubMed

Calderón-Garcidueñas, Lilian; Reed, William; Maronpot, Robert R; Henríquez-Roldán, Carlos; Delgado-Chavez, Ricardo; Calderón-Garcidueñas, Ana; Dragustinovis, Irma; Franco-Lira, Maricela; Aragón-Flores, Mariana; Solt, Anna C; Altenburg, Michael; Torres-Jardón, Ricardo; Swenberg, James A

2004-01-01

Air pollution is a complex mixture of gases (e.g., ozone), particulate matter, and organic compounds present in outdoor and indoor air. Dogs exposed to severe air pollution exhibit chronic inflammation and acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by pollutants. We investigated whether residency in cities with high levels of air pollution is associated with human brain inflammation. Expression of cyclooxygenase-2 (COX2), an inflammatory mediator, and accumulation of the 42-amino acid form of beta-amyloid (Abeta42), a cause of neuronal dysfunction, were measured in autopsy brain tissues of cognitively and neurologically intact lifelong residents of cities having low (n:9) or high (n:10) levels of air pollution. Genomic DNA apurinic/apyrimidinic sites, nuclear factor-kappaB activation and apolipoprotein E genotype were also evaluated. Residents of cities with severe air pollution had significantly higher COX2 expression in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of Abeta42 compared to residents in low air pollution cities. Increased COX2 expression and Abeta42 accumulation were also observed in the olfactory bulb. These findings suggest that exposure to severe air pollution is associated with brain inflammation and Abeta42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.

Associations between coherent neural activity in the brain's value system during antismoking messages and reductions in smoking.

PubMed

Cooper, Nicole; Tompson, Steven; O'Donnell, Matthew B; Vettel, Jean M; Bassett, Danielle S; Falk, Emily B

2018-04-01

Worldwide, tobacco use is the leading cause of preventable death and illness. One common strategy for reducing the prevalence of cigarette smoking and other health risk behaviors is the use of graphic warning labels (GWLs). This has led to widespread interest from the perspective of health psychology in understanding the mechanisms of GWL effectiveness. Here we investigated differences in how the brain responds to negative, graphic warning label-inspired antismoking ads and neutral control ads, and we probed how this response related to future behavior. A group of smokers (N = 45) viewed GWL-inspired and control antismoking ads while undergoing fMRI, and their smoking behavior was assessed before and one month after the scan. We examined neural coherence between two regions in the brain's valuation network, the medial prefrontal cortex (MPFC) and ventral striatum (VS). We found that greater neural coherence in the brain's valuation network during GWL ads (relative to control ads) preceded later smoking reduction. Our results suggest that the integration of information about message value may be key for message influence. Understanding how the brain responds to health messaging and relates to future behavior could ultimately contribute to the design of effective messaging campaigns, as well as more broadly to theories of message effects and persuasion across domains. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Dissociable neural mechanisms underlying response-based and familiarity-based conflict in working memory.

PubMed

Nelson, James K; Reuter-Lorenz, Patricia A; Sylvester, Ching-Yune C; Jonides, John; Smith, Edward E

2003-09-16

Cognitive control requires the resolution of interference among competing and potentially conflicting representations. Such conflict can emerge at different points between stimulus input and response generation, with the net effect being that of compromising performance. The goal of this article was to dissociate the neural mechanisms underlying different sources of conflict to elucidate the architecture of the neural systems that implement cognitive control. By using functional magnetic resonance imaging and a verbal working memory task (item recognition), we examined brain activity related to two kinds of conflict with comparable behavioral consequences. In a trial of our item-recognition task, participants saw four letters, followed by a retention interval, and a probe letter that did or did not match one of the letters held in working memory (positive probe and negative probe, respectively). On some trials, conflict arose solely because of the current negative probe having a high familiarity, due to its membership in the immediately preceding trial's target set. On other trials, additional conflict arose because of the current negative probe having also been a positive probe on the immediately preceding trial, producing response-level conflict. Consistent with previous work, conflict due to high familiarity was associated with left prefrontal activation, but not with anterior cingulate activation. The response-conflict condition, when compared with high-familiarity conflict trials, was associated with anterior cingulate cortex activation, but with no additional left prefrontal activation. This double dissociation points to differing contributions of specific cortical areas to cognitive control, which are based on the source of conflict.

Forecasting Alzheimer's Disease.

ERIC Educational Resources Information Center

Fackelmann, Kathleen

1996-01-01

Suggests that doctors may one day be able to identify healthy people who will develop Alzheimer's disease. Discusses recent studies in which characteristics of a person's writing early in life appear to predict the disease, and brain scans can highlight changes that may precede dementia. (CCM)

Ventral striatum and the evaluation of memory retrieval strategies.

PubMed

Badre, David; Lebrecht, Sophie; Pagliaccio, David; Long, Nicole M; Scimeca, Jason M

2014-09-01

Adaptive memory retrieval requires mechanisms of cognitive control that facilitate the recovery of goal-relevant information. Frontoparietal systems are known to support control of memory retrieval. However, the mechanisms by which the brain acquires, evaluates, and adapts retrieval strategies remain unknown. Here, we provide evidence that ventral striatal activation tracks the success of a retrieval strategy and correlates with subsequent reliance on that strategy. Human participants were scanned with fMRI while performing a lexical decision task. A rule was provided that indicated the likely semantic category of a target word given the category of a preceding prime. Reliance on the rule improved decision-making, as estimated within a drift diffusion framework. Ventral striatal activation tracked the benefit that relying on the rule had on decision-making. Moreover, activation in ventral striatum correlated with a participant's subsequent reliance on the rule. Taken together, these results support a role for ventral striatum in learning and evaluating declarative retrieval strategies.

The Neural Signature of Subliminal Visuomotor Priming: Brain Activity and Functional Connectivity Profiles.

PubMed

Ulrich, Martin; Kiefer, Markus

2016-06-01

Unconscious visuomotor priming defined as the advantage in reaction time (RT) or accuracy for target shapes mapped to the same (congruent condition) when compared with a different (incongruent condition) motor response as a preceding subliminally presented prime shape has been shown to modulate activity within a visuomotor network comprised of parietal and frontal motor areas in previous functional magnetic resonance imaging (fMRI) studies. The present fMRI study investigated whether, in addition to changes in brain activity, unconscious visuomotor priming results in a modulation of functional connectivity profiles. Activity associated with congruent compared with incongruent trials was lower in the bilateral inferior and medial superior frontal gyri, in the inferior parietal lobules, and in the right caudate nucleus and adjacent portions of the thalamus. Functional connectivity increased under congruent relative to incongruent conditions between ventral visual stream areas (e.g., calcarine, fusiform, and lingual gyri), the precentral gyrus, the supplementary motor area, posterior parietal areas, the inferior frontal gyrus, and the caudate nucleus. Our findings suggest that an increase in coupling between visuomotor regions, reflecting higher efficiency of processing, is an important neural mechanism underlying unconscious visuomotor priming, in addition to changes in the magnitude of activation. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Regional oligodendrocytopathy and astrocytopathy precede myelin loss and blood-brain barrier disruption in a murine model of osmotic demyelination syndrome.

PubMed

Bouchat, Joanna; Couturier, Bruno; Marneffe, Catherine; Gankam-Kengne, Fabrice; Balau, Benoît; De Swert, Kathleen; Brion, Jean-Pierre; Poncelet, Luc; Gilloteaux, Jacques; Nicaise, Charles

2018-03-01

The osmotic demyelination syndrome (ODS) is a non-primary inflammatory disorder of the central nervous system myelin that is often associated with a precipitous rise of serum sodium concentration. To investigate the physiopathology of ODS in vivo, we generated a novel murine model based on the abrupt correction of chronic hyponatremia. Accordingly, ODS mice developed impairments in brainstem auditory evoked potentials and in grip strength. At 24 hr post-correction, oligodendrocyte markers (APC and Cx47) were downregulated, prior to any detectable demyelination. Oligodendrocytopathy was temporally and spatially correlated with the loss of astrocyte markers (ALDH1L1 and Cx43), and both with the brain areas that will develop demyelination. Oligodendrocytopathy and astrocytopathy were confirmed at the ultrastructural level and culminated with necroptotic cell death, as demonstrated by pMLKL immunoreactivity. At 48 hr post-correction, ODS brains contained pathognomonic demyelinating lesions in the pons, mesencephalon, thalamus and cortical regions. These damages were accompanied by blood-brain barrier (BBB) leakages. Expression levels of IL-1β, FasL, TNFRSF6 and LIF factors were significantly upregulated in the ODS lesions. Quiescent microglial cells type A acquired an activated type B morphology within 24 hr post-correction, and reached type D at 48 hr. In conclusion, this murine model of ODS reproduces the CNS demyelination observed in human pathology and indicates ambiguous causes that is regional vulnerability of oligodendrocytes and astrocytes, while it discards BBB disruption as a primary cause of demyelination. This study also raises new queries about the glial heterogeneity in susceptible brain regions as well as about the early microglial activation associated with ODS. © 2017 Wiley Periodicals, Inc.

Dynamics of alpha control: Preparatory suppression of posterior alpha oscillations by frontal modulators revealed with combined EEG and event-related optical signal (EROS)

PubMed Central

Mathewson, Kyle E.; Beck, Diane M.; Ro, Tony; Maclin, Edward L.; Low, Kathy A.; Fabiani, Monica; Gratton, Gabriele

2015-01-01

We investigated the dynamics of brain processes facilitating conscious experience of external stimuli. Previously we proposed that alpha (8-12 Hz) oscillations, which fluctuate with both sustained and directed attention, represent a pulsed inhibition of ongoing sensory brain activity. Here we tested the prediction that inhibitory alpha oscillations in visual cortex are modulated by top-down signals from frontoparietal attention networks. We measured modulations in phase-coherent alpha oscillations from superficial frontal, parietal, and occipital cortices using the event-related optical signal (EROS), a measure of neuronal activity affording high spatiotemporal resolution, along with concurrently-recorded electroencephalogram (EEG), while subjects performed a visual target-detection task. The pre-target alpha oscillations measured with EEG and EROS from posterior areas were larger for subsequently undetected targets, supporting alpha's inhibitory role. Using EROS, we localized brain correlates of these awareness-related alpha oscillations measured at the scalp to the cuneus and precuneus. Crucially, EROS alpha suppression correlated with posterior EEG alpha power across subjects. Sorting the EROS data based on EEG alpha power quartiles to investigate alpha modulators revealed that suppression of posterior alpha was preceded by increased activity in regions of the dorsal attention network, and decreased activity in regions of the cingulo-opercular network. Cross-correlations revealed the temporal dynamics of activity within these preparatory networks prior to posterior alpha modulation. The novel combination of EEG and EROS afforded localization of the sources and correlates of alpha oscillations and their temporal relationships, supporting our proposal that top-down control from attention networks modulates both posterior alpha and awareness of visual stimuli. PMID:24702458

Outcome Uncertainty and Brain Activity Aberrance in the Insula and Anterior Cingulate Cortex Are Associated with Dysfunctional Impulsivity in Borderline Personality Disorder

PubMed Central

Mortensen, Jørgen Assar; Evensmoen, Hallvard Røe; Klensmeden, Gunilla; Håberg, Asta Kristine

2016-01-01

Uncertainty is recognized as an important component in distress, which may elicit impulsive behavior in patients with borderline personality disorder (BPD). These patients are known to be both impulsive and distress intolerant. The present study explored the connection between outcome uncertainty and impulsivity in BPD. The prediction was that cue primes, which provide incomplete information of subsequent target stimuli, led BPD patients to overrate the predictive value of these cues in order to reduce distress related to outcome uncertainty. This would yield dysfunctional impulsive behavior detected as commission errors to incorrectly primed targets. We hypothesized that dysfunctional impulsivity would be accompanied by aberrant brain activity in the right insula and anterior cingulate cortex (ACC), previously described to be involved in uncertainty processing, attention-/cognitive control and BPD pathology. 14 female BPD patients and 14 healthy matched controls (HCs) for comparison completed a Posner task during fMRI at 3T. The task was modified to limit the effect of spatial orientation and enhance the effect of conscious expectations. Brain activity was monitored in the priming phase where the effects of cue primes and neutral primes were compared. As predicted, the BPD group made significantly more commission errors to incorrectly primed targets than HCs. Also, the patients had faster reaction times to correctly primed targets relative to targets preceded by neutral primes. The BPD group had decreased activity in the right mid insula and increased activity in bilateral dorsal ACC during cue primes. The results indicate that strong expectations induced by cue primes led to reduced uncertainty, increased response readiness, and ultimately, dysfunctional impulsivity in BPD patients. We suggest that outcome uncertainty may be an important component in distress related impulsivity in BPD. PMID:27199724

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.

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.

Semantic brain areas are involved in gesture comprehension: An electrical neuroimaging study.

PubMed

Proverbio, Alice Mado; Gabaro, Veronica; Orlandi, Andrea; Zani, Alberto

2015-08-01

While the mechanism of sign language comprehension in deaf people has been widely investigated, little is known about the neural underpinnings of spontaneous gesture comprehension in healthy speakers. Bioelectrical responses to 800 pictures of actors showing common Italian gestures (e.g., emblems, deictic or iconic gestures) were recorded in 14 persons. Stimuli were selected from a wider corpus of 1122 gestures. Half of the pictures were preceded by an incongruent description. ERPs were recorded from 128 sites while participants decided whether the stimulus was congruent. Congruent pictures elicited a posterior P300 followed by late positivity, while incongruent gestures elicited an anterior N400 response. N400 generators were investigated with swLORETA reconstruction. Processing of congruent gestures activated face- and body-related visual areas (e.g., BA19, BA37, BA22), the left angular gyrus, mirror fronto/parietal areas. The incongruent-congruent contrast particularly stimulated linguistic and semantic brain areas, such as the left medial and the superior temporal lobe. Copyright © 2015 Elsevier Inc. All rights reserved.

Self-organizing path integration using a linked continuous attractor and competitive network: path integration of head direction.

PubMed

Stringer, Simon M; Rolls, Edmund T

2006-12-01

A key issue is how networks in the brain learn to perform path integration, that is update a represented position using a velocity signal. Using head direction cells as an example, we show that a competitive network could self-organize to learn to respond to combinations of head direction and angular head rotation velocity. These combination cells can then be used to drive a continuous attractor network to the next head direction based on the incoming rotation signal. An associative synaptic modification rule with a short term memory trace enables preceding combination cell activity during training to be associated with the next position in the continuous attractor network. The network accounts for the presence of neurons found in the brain that respond to combinations of head direction and angular head rotation velocity. Analogous networks in the hippocampal system could self-organize to perform path integration of place and spatial view representations.

Early Decline in Glucose Transport and Metabolism Precedes Shift to Ketogenic System in Female Aging and Alzheimer's Mouse Brain: Implication for Bioenergetic Intervention

PubMed Central

Ding, Fan; Yao, Jia; Rettberg, Jamaica R.; Chen, Shuhua; Brinton, Roberta Diaz

2013-01-01

We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3–15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6–9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential targets for preventing shifts to less efficient bioenergetic fuels and transition to the ketogenic phenotype of the Alzheimer's brain. PMID:24244584

The PI3K/Akt pathway is required for LPS activation of microglial cells.

PubMed

Saponaro, Concetta; Cianciulli, Antonia; Calvello, Rosa; Dragone, Teresa; Iacobazzi, Francesco; Panaro, Maria Antonietta

2012-10-01

Upregulation of inflammatory responses in the brain is associated with a number of neurodegenerative diseases. Microglia are activated in neurodegenerative diseases, producing pro-inflammatory mediators. Critically, lipopolysaccharide (LPS)-induced microglial activation causes dopaminergic neurodegeneration in vitro and in vivo. The signaling mechanisms triggered by LPS to stimulate the release of pro-inflammatory mediators in microglial cells are still incompletely understood. To further explore the mechanisms of LPS-mediated inflammatory response of microglial cells, we studied the role of phosphatidylinositol 3-kinase (PI3K)/Akt signal transduction pathways known to be activated by toll-like receptor-4 signaling through LPS. In the current study, we report that the activation profile of LPS-induced pAkt activation preceded those of LPS-induced NF-κB activation, suggesting a role for PI3K/Akt in the pathway activation of NF-κB-dependent inflammatory responses of activated microglia. These results, providing the first evidence that PI3K dependent signaling is involved in the inflammatory responses of microglial cells following LPS stimulation, may be useful in preventing inflammatory based neurodegenerative processes.

Encouraging expressions affect the brain and alter visual attention.

PubMed

Martín-Loeches, Manuel; Sel, Alejandra; Casado, Pilar; Jiménez, Laura; Castellanos, Luis

2009-06-17

Very often, encouraging or discouraging expressions are used in competitive contexts, such as sports practice, aiming at provoking an emotional reaction on the listener and, consequently, an effect on subsequent cognition and/or performance. However, the actual efficiency of these expressions has not been tested scientifically. To fill this gap, we studied the effects of encouraging, discouraging, and neutral expressions on event-related brain electrical activity during a visual selective attention task in which targets were determined by location, shape, and color. Although the expressions preceded the attentional task, both encouraging and discouraging messages elicited a similar long-lasting brain emotional response present during the visuospatial task. In addition, encouraging expressions were able to alter the customary working pattern of the visual attention system for shape selection in the attended location, increasing the P1 and the SP modulations while simultaneously fading away the SN. This was interpreted as an enhancement of the attentional processes for shape in the attended location after an encouraging expression. It can be stated, therefore, that encouraging expressions, as those used in sport practice, as well as in many other contexts and situations, do seem to be efficient in exerting emotional reactions and measurable effects on cognition.

A designated odor-language integration system in the human brain.

PubMed

Olofsson, Jonas K; Hurley, Robert S; Bowman, Nicholas E; Bao, Xiaojun; Mesulam, M-Marsel; Gottfried, Jay A

2014-11-05

Odors are surprisingly difficult to name, but the mechanism underlying this phenomenon is poorly understood. In experiments using event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI), we investigated the physiological basis of odor naming with a paradigm where olfactory and visual object cues were followed by target words that either matched or mismatched the cue. We hypothesized that word processing would not only be affected by its semantic congruency with the preceding cue, but would also depend on the cue modality (olfactory or visual). Performance was slower and less precise when linking a word to its corresponding odor than to its picture. The ERP index of semantic incongruity (N400), reflected in the comparison of nonmatching versus matching target words, was more constrained to posterior electrode sites and lasted longer on odor-cue (vs picture-cue) trials. In parallel, fMRI cross-adaptation in the right orbitofrontal cortex (OFC) and the left anterior temporal lobe (ATL) was observed in response to words when preceded by matching olfactory cues, but not by matching visual cues. Time-series plots demonstrated increased fMRI activity in OFC and ATL at the onset of the odor cue itself, followed by response habituation after processing of a matching (vs nonmatching) target word, suggesting that predictive perceptual representations in these regions are already established before delivery and deliberation of the target word. Together, our findings underscore the modality-specific anatomy and physiology of object identification in the human brain. Copyright © 2014 the authors 0270-6474/14/3414864-10$15.00/0.

The electrophysiological underpinnings of processing gender stereotypes in language.

PubMed

Siyanova-Chanturia, Anna; Pesciarelli, Francesca; Cacciari, Cristina

2012-01-01

Despite the widely documented influence of gender stereotypes on social behaviour, little is known about the electrophysiological substrates engaged in the processing of such information when conveyed by language. Using event-related brain potentials (ERPs), we examined the brain response to third-person pronouns (lei "she" and lui "he") that were implicitly primed by definitional (passeggera(FEM) "passenger", pensionato(MASC) "pensioner"), or stereotypical antecedents (insegnante "teacher", conducente "driver"). An N400-like effect on the pronoun emerged when it was preceded by a definitionally incongruent prime (passeggera(FEM)--lui; pensionato(MASC)--lei), and a stereotypically incongruent prime for masculine pronouns only (insegnante--lui). In addition, a P300-like effect was found when the pronoun was preceded by definitionally incongruent primes. However, this effect was observed for female, but not male participants. Overall, these results provide further evidence for on-line effects of stereotypical gender in language comprehension. Importantly, our results also suggest a gender stereotype asymmetry in that male and female stereotypes affected the processing of pronouns differently.

CaMKII-dependent endoplasmic reticulum fission by whisker stimulation and during cortical spreading depolarization.

PubMed

Kucharz, Krzysztof; Lauritzen, Martin

2018-04-01

Cortical spreading depolarization waves, the cause underlying migraine aura, are also the markers and mechanism of pathology in the acutely injured human brain. Propagation of spreading depolarization wave uniquely depends on the interaction between presynaptic and postsynaptic glutamate N-methyl-d-aspartate receptors (NMDARs). In the normally perfused brain, even a single wave causes a massive depolarization of neurons and glia, which results in transient loss of neuronal function and depression of the ongoing electrocorticographic activity. Endoplasmic reticulum is the cellular organelle of particular importance for modulation of neurotransmission. Neuronal endoplasmic reticulum structure is assumed to be persistently continuous in neurons, but is rapidly lost within 1 to 2 min of global cerebral ischaemia, i.e. the organelle disintegrates by fission. This phenomenon appears to be timed with the cardiac arrest-induced cortical spreading depolarizations, rather than ensuing cell death. To what extent NMDAR-dependent processes may trigger neuronal endoplasmic reticulum fission and whether fission is reversible in the normally perfused brain is unknown. We used two-photon microscopy to examine neuronal endoplasmic reticulum structural dynamics during whisker stimulation and cortical spreading depolarizations in vivo. Somatosensory stimulation triggered loss of endoplasmic reticulum continuity, a likely outcome of constriction and fission, in dendritic spines within less than 10 s of stimulation, which was spontaneously reversible and recovery to normal took 5 min. The endoplasmic reticulum fission was inhibited by blockade of NMDAR and Ca2+/calmodulin-dependent protein kinase II (CaMKII) activated downstream of the NMDARs, whereas inhibition of guanosine triphosphate hydrolases hindered regain of endoplasmic reticulum continuity, i.e. fusion. In contrast to somatosensory stimulation, endoplasmic reticulum fission during spreading depolarization was widespread and present in dendrites and spines, and was preceded by dramatic rise in intracellular Ca2+. The endoplasmic reticulum fission during spreading depolarization was more persistent, as 1 h after the depolarization cortical neurons still exhibited loss of endoplasmic reticulum continuity. Notably, endoplasmic reticulum fission was accompanied with loss of electrocorticographic activity, whereas subsequent regain of synaptic function paralleled the organelle fusion. Furthermore, blocking CaMKII activity partly rescued endoplasmic reticulum fission and markedly shortened the recovery time of brain spontaneous activity. Thus, prevention of endoplasmic reticulum fission with CaMKII inhibitors may be a novel strategy to rescue brain function in patients with migraine and a promising therapeutic avenue in the acutely injured brain.

ERPS to Monitor Non-conscious Mentation

NASA Technical Reports Server (NTRS)

Donchin, E.

1984-01-01

Event Related Brain Potentials (or ERPs) are extracted from the EEG that can be recorded between a pair of electrodes placed on a person's scalp. The EEG is recorded as a continual fluctuation in voltage. It is the results of the integration of the potential fields generated by a multitude of neuronal ensembles that are active as the brain goes about its business. Within this ongoing signal it is possible to distinguish voltage fluctuations that are triggered in neural structures by the occurrence of specific events. This activity, evoked as it is by an external event, is known as the Evoked, or Event Related, Potential. The ERPs provide a unique opportunity to monitor non-conscious mentation. The inferences that can be based on ERP data are described and the limits of these inferences are emphasized. This, however, will not be an exhaustive review of the use of ERPs in Engineering Psychology. The application, its scope, and its limitations will be illustrated by means of one example. This example is preceded by a brief technical introduction to the methodology used in the study of ERPs. The manner in which ERPs are used to study cognition is described.

[The evoked activity of the lateral hypothalamus during extinction and differential inhibition].

PubMed

Vanetsian, G L

1995-01-01

Character of interaction between symmetric points of the cat's auditory cortex (A1) and the lateral hypothalamus (HL) was determined by calculating Spearman correlation coefficients between averaged summed sound-evoked activity (AEP) of the structures before, during elaboration, extinction and restoration, as well as differentiation of food-procuring conditioned reflex and in the eating full. Close mutual co-tuning between the cortex and hypothalamus characteristic for stable conditioned reflex was found to disrupted during its extinction, elaboration of differentiation and fullness eat inhibition due to entire reduction of hypothalamic AEP and disappearance of correlated with negativity of HL AEP "doubling" of the first positive wave of A1 AEP. Hyperactivity stage, expressed at the beginning of extinction and at the end of differentiation, preceded inactivation of hypothalamic afferents during elaboration of conditioned inhibition. The stage of hyperactivity, initiated by the elevated emotional state of the animal, testifies to an important role of emotional brain structures in the process of internal inhibition. The stage of HL and A1 hyperactivity initiated by emotional stress of the animal and following HL inactivation during inhibition of the conditioned response point to an important role of emotional subcortical brain structures in the mechanisms of inhibitory conditioning.

Randomised prior feedback modulates neural signals of outcome monitoring.

PubMed

Mushtaq, Faisal; Wilkie, Richard M; Mon-Williams, Mark A; Schaefer, Alexandre

2016-01-15

Substantial evidence indicates that decision outcomes are typically evaluated relative to expectations learned from relatively long sequences of previous outcomes. This mechanism is thought to play a key role in general learning and adaptation processes but relatively little is known about the determinants of outcome evaluation when the capacity to learn from series of prior events is difficult or impossible. To investigate this issue, we examined how the feedback-related negativity (FRN) is modulated by information briefly presented before outcome evaluation. The FRN is a brain potential time-locked to the delivery of decision feedback and it is widely thought to be sensitive to prior expectations. We conducted a multi-trial gambling task in which outcomes at each trial were fully randomised to minimise the capacity to learn from long sequences of prior outcomes. Event-related potentials for outcomes (Win/Loss) in the current trial (Outcomet) were separated according to the type of outcomes that occurred in the preceding two trials (Outcomet-1 and Outcomet-2). We found that FRN voltage was more positive during the processing of win feedback when it was preceded by wins at Outcomet-1 compared to win feedback preceded by losses at Outcomet-1. However, no influence of preceding outcomes was found on FRN activity relative to the processing of loss feedback. We also found no effects of Outcomet-2 on FRN amplitude relative to current feedback. Additional analyses indicated that this effect was largest for trials in which participants selected a decision different to the gamble chosen in the previous trial. These findings are inconsistent with models that solely relate the FRN to prediction error computation. Instead, our results suggest that if stable predictions about future events are weak or non-existent, then outcome processing can be determined by affective systems. More specifically, our results indicate that the FRN is likely to reflect the activity of positive affective systems in these contexts. Importantly, our findings indicate that a multifactorial explanation of the nature of the FRN is necessary and such an account must incorporate affective and motivational factors in outcome processing. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Randomised prior feedback modulates neural signals of outcome monitoring

PubMed Central

Mushtaq, Faisal; Wilkie, Richard M.; Mon-Williams, Mark A.; Schaefer, Alexandre

2016-01-01

Substantial evidence indicates that decision outcomes are typically evaluated relative to expectations learned from relatively long sequences of previous outcomes. This mechanism is thought to play a key role in general learning and adaptation processes but relatively little is known about the determinants of outcome evaluation when the capacity to learn from series of prior events is difficult or impossible. To investigate this issue, we examined how the feedback-related negativity (FRN) is modulated by information briefly presented before outcome evaluation. The FRN is a brain potential time-locked to the delivery of decision feedback and it is widely thought to be sensitive to prior expectations. We conducted a multi-trial gambling task in which outcomes at each trial were fully randomised to minimise the capacity to learn from long sequences of prior outcomes. Event-related potentials for outcomes (Win/Loss) in the current trial (Outcomet) were separated according to the type of outcomes that occurred in the preceding two trials (Outcomet-1 and Outcomet-2). We found that FRN voltage was more positive during the processing of win feedback when it was preceded by wins at Outcomet-1 compared to win feedback preceded by losses at Outcomet-1. However, no influence of preceding outcomes was found on FRN activity relative to the processing of loss feedback. We also found no effects of Outcomet-2 on FRN amplitude relative to current feedback. Additional analyses indicated that this effect was largest for trials in which participants selected a decision different to the gamble chosen in the previous trial. These findings are inconsistent with models that solely relate the FRN to prediction error computation. Instead, our results suggest that if stable predictions about future events are weak or non-existent, then outcome processing can be determined by affective systems. More specifically, our results indicate that the FRN is likely to reflect the activity of positive affective systems in these contexts. Importantly, our findings indicate that a multifactorial explanation of the nature of the FRN is necessary and such an account must incorporate affective and motivational factors in outcome processing. PMID:26497268

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.

Externalizing proneness and brain response during pre-cuing and viewing of emotional pictures.

PubMed

Foell, Jens; Brislin, Sarah J; Strickland, Casey M; Seo, Dongju; Sabatinelli, Dean; Patrick, Christopher J

2016-07-01

Externalizing proneness, or trait disinhibition, is a concept relevant to multiple high-impact disorders involving impulsive-aggressive behavior. Its mechanisms remain disputed: major models posit hyperresponsive reward circuitry or heightened threat-system reactivity as sources of disinhibitory tendencies. This study evaluated alternative possibilities by examining relations between trait disinhibition and brain reactivity during preparation for and processing of visual affective stimuli. Forty females participated in a functional neuroimaging procedure with stimuli presented in blocks containing either pleasurable or aversive pictures interspersed with neutral, with each picture preceded by a preparation signal. Preparing to view elicited activation in regions including nucleus accumbens, whereas visual regions and bilateral amygdala were activated during viewing of emotional pictures. High disinhibition predicted reduced nucleus accumbens activation during preparation within pleasant/neutral picture blocks, along with enhanced amygdala reactivity during viewing of pleasant and aversive pictures. Follow-up analyses revealed that the augmented amygdala response was related to reduced preparatory activation. Findings indicate that participants high in disinhibition are less able to process implicit cues and mentally prepare for upcoming stimuli, leading to limbic hyperreactivity during processing of actual stimuli. This outcome is helpful for integrating findings from studies suggesting reward-system hyperreactivity and others suggesting threat-system hyperreactivity as mechanisms for externalizing proneness. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Impact of tocilizumab on N-terminal pro-brain natriuretic peptide levels in patients with active rheumatoid arthritis without cardiac symptoms.

PubMed

Yokoe, I; Kobayashi, H; Kobayashi, Y; Giles, J T; Yoneyama, K; Kitamura, N; Takei, M

2018-05-28

To prospectively investigate the effect of tocilizumab (TCZ) on the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), as a predictor of congestive heart failure (CHF) in patients with active rheumatoid arthritis (RA). Seventy patients with RA (median age 59 years, 86% female) free of cardiovascular disease were treated with TCZ and followed for 24 weeks. The NT-proBNP levels were measured at baseline and week 24. Thirty healthy controls were included for comparison of normal NT-proBNP levels with those of RA patients. The NT-proBNP level was significantly higher in patients with RA than in controls (median 42.5 pg/mL vs 109.0 pg/mL, p < 0.001). NT-proBNP levels decreased by 63% over the 24 weeks of TCZ treatment. Multiple linear regression analysis indicated that the percentage change in the NT-proBNP level was significantly associated with that of the Simplified Disease Activity Index (β = 0.356, p = 0.014), even after adjusting for the levels of rheumatoid factor, duration of RA, age, and anti-cyclic citrullinated peptide antibody. TCZ decreased the NT-proBNP level in patients with RA without preceding cardiovascular disease and CHF. TCZ may have a cardioprotective effect in those with active RA.

Alcohol Alters the Activation of ERK1/2, a Functional Regulator of Binge Alcohol Drinking in Adult C57BL/6J Mice

PubMed Central

Agoglia, Abigail E.; Sharko, Amanda C.; Psilos, Kelly E.; Holstein, Sarah E.; Reid, Grant T.; Hodge, Clyde W.

2014-01-01

Background Binge alcohol drinking is a particularly risky pattern of alcohol consumption that often precedes alcohol dependence and addiction. The transition from binge alcohol drinking to alcohol addiction likely involves mechanisms of synaptic plasticity and learning in the brain. The mitogen-activated protein kinase (MAPK) signaling cascades have been shown to be involved in learning and memory, as well as the response to drugs of abuse, but their role in binge alcohol drinking remains unclear. The present experiments were designed to determine the effects of acute alcohol on extracellular signaling related kinases (ERK1/2) expression and activity, and to determine whether ERK1/2 activity functionally regulates binge-like alcohol drinking. Methods Adult male C57BL/6J mice were injected with ethanol (3.0 mg/kg, IP) 10, 30 or 90 minutes prior to brain tissue collection. Next, mice that were brought to freely consume unsweetened ethanol in a binge-like access procedure were pretreated with the MEK1/2 inhibitor SL327 or the p38 MAP kinase inhibitor SB239063. Results Acute ethanol increased pERK1/2 immunoreactivity relative to vehicle in brain regions known to be involved in drug reward and addiction, including the central amygdala and prefrontal cortex. However, ethanol decreased pERK1/2 immunoreactivity relative to vehicle in the nucleus accumbens core. SB239063 pretreatment significantly decreased ethanol consumption only at doses that also produced nonspecific locomotor effects. SL327 pretreatment significantly increased ethanol, but not sucrose, consumption without inducing generalized locomotor effects. Conclusions These findings indicate that ERK1/2MAPK signaling regulates binge-like alcohol drinking. Since alcohol increased pERK1/2 immunoreactivity relative to vehicle in brain regions known to regulate drug self-administration, SL327 may have blocked this direct pharmacological effect of alcohol and thereby inhibited the termination of binge-like drinking. PMID:25703719

Endocranial morphology of Palaeocene Plesiadapis tricuspidens and evolution of the early primate brain.

PubMed

Orliac, Maeva J; Ladevèze, Sandrine; Gingerich, Philip D; Lebrun, Renaud; Smith, Thierry

2014-04-22

Expansion of the brain is a key feature of primate evolution. The fossil record, although incomplete, allows a partial reconstruction of changes in primate brain size and morphology through time. Palaeogene plesiadapoids, closest relatives of Euprimates (or crown-group primates), are crucial for understanding early evolution of the primate brain. However, brain morphology of this group remains poorly documented, and major questions remain regarding the initial phase of euprimate brain evolution. Micro-CT investigation of the endocranial morphology of Plesiadapis tricuspidens from the Late Palaeocene of Europe--the most complete plesiadapoid cranium known--shows that plesiadapoids retained a very small and simple brain. Plesiadapis has midbrain exposure, and minimal encephalization and neocorticalization, making it comparable with that of stem rodents and lagomorphs. However, Plesiadapis shares a domed neocortex and downwardly shifted olfactory-bulb axis with Euprimates. If accepted phylogenetic relationships are correct, then this implies that the euprimate brain underwent drastic reorganization during the Palaeocene, and some changes in brain structure preceded brain size increase and neocortex expansion during evolution of the primate brain.

Similar Cerebral Motor Plans for Real and Virtual Actions

PubMed Central

Bozzacchi, Chiara; Giusti, Maria Assunta; Pitzalis, Sabrina; Spinelli, Donatella; Di Russo, Francesco

2012-01-01

A simple movement, such as pressing a button, can acquire different meanings by producing different consequences, such as starting an elevator or switching a TV channel. We evaluated whether the brain activity preceding a simple action is modulated by the expected consequences of the action itself. To further this aim, the motor-related cortical potentials were compared during two key-press actions that were identical from the kinematics point of view but different in both meaning and consequences. In one case (virtual grasp), the key-press started a video clip showing a hand moving toward a cup and grasping it; in the other case, the key-press did not produce any consequence (key-press). A third condition (real grasp) was also compared, in which subjects actually grasped the cup, producing the same action presented in the video clip. Data were collected from fifteen subjects. The results showed that motor preparation for virtual grasp (starting 3 s before the movement onset) was different from that of the key-press and similar to the real grasp preparation–as if subjects had to grasp the cup in person. In particular, both virtual and real grasp presented a posterior parietal negativity preceding activity in motor and pre-motor areas. In summary, this finding supports the hypothesis that motor preparation is affected by the meaning of the action, even when the action is only virtual. PMID:23112847

Reward processing in the value-driven attention network: reward signals tracking cue identity and location.

PubMed

Anderson, Brian A

2017-03-01

Through associative reward learning, arbitrary cues acquire the ability to automatically capture visual attention. Previous studies have examined the neural correlates of value-driven attentional orienting, revealing elevated activity within a network of brain regions encompassing the visual corticostriatal loop [caudate tail, lateral occipital complex (LOC) and early visual cortex] and intraparietal sulcus (IPS). Such attentional priority signals raise a broader question concerning how visual signals are combined with reward signals during learning to create a representation that is sensitive to the confluence of the two. This study examines reward signals during the cued reward training phase commonly used to generate value-driven attentional biases. High, compared with low, reward feedback preferentially activated the value-driven attention network, in addition to regions typically implicated in reward processing. Further examination of these reward signals within the visual system revealed information about the identity of the preceding cue in the caudate tail and LOC, and information about the location of the preceding cue in IPS, while early visual cortex represented both location and identity. The results reveal teaching signals within the value-driven attention network during associative reward learning, and further suggest functional specialization within different regions of this network during the acquisition of an integrated representation of stimulus value. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Spatial Attention Modulates the Precedence Effect

ERIC Educational Resources Information Center

London, Sam; Bishop, Christopher W.; Miller, Lee M.

2012-01-01

Communication and navigation in real environments rely heavily on the ability to distinguish objects in acoustic space. However, auditory spatial information is often corrupted by conflicting cues and noise such as acoustic reflections. Fortunately the brain can apply mechanisms at multiple levels to emphasize target information and mitigate such…

Brain electrical activity and subjective experience during altered states of consciousness: ganzfeld and hypnagogic states.

PubMed

Wackermann, Jiri; Pütz, Peter; Büchi, Simone; Strauch, Inge; Lehmann, Dietrich

2002-11-01

Manifestations of experimentally induced altered states of consciousness in the brain's electrical activity as well as in subjective experience were explored via the hypnagogic state at sleep onset, and the state induced by exposure to an unstructured perceptual field (ganzfeld). Twelve female paid volunteers participated in sessions involving sleep onset, ganzfeld, and eyes-closed relaxed waking, and were repeatedly prompted for recall of their momentary mentation, according to a predefined schedule. Nineteen channel EEG, two channels EOG and EMG were recorded simultaneously. The mentation reports were followed by the subjects' ratings of their experience on a number of ordinal scales. Two-hundred and forty-one mentation reports were collected. EEG epochs immediately preceding the mentation reports were FFT-analysed and the spectra compared between states. The ganzfeld EEG spectrum, showing no signs of decreased vigilance, was very similar to the EEG spectrum of waking states, even showed a minor acceleration of alpha activity. The subjective experience data were reduced to four principal components: Factor I represented the subjective vigilance dimension, as confirmed by correlations with EEG spectral indices. Only Factor IV, the 'absorption' dimension, differentiated between the ganzfeld state (more absorption) and other states. In waking states and in ganzfeld, the subjects estimated elapsed time periods significantly shorter than in states at sleep onset. The results did not support the assumption of a hypnagogic nature of the ganzfeld imagery. Dream-like imagery can occur in various global functional states of the brain; hypnagogic and ganzfeld-induced states should be conceived as special cases of a broader class of 'hypnagoid' phenomena.

Near-death experience: arising from the borderlands of consciousness in crisis.

PubMed

Nelson, Kevin R

2014-11-01

Brain activity explains the essential features of near-death experience, including the perceptions of envelopment by light, out-of-body, and meeting deceased loved ones or spiritual beings. To achieve their fullest expression, such near-death experiences require a confluence of events and draw upon more than a single physiological or biochemical system, or one anatomical structure. During impaired cerebral blood flow from syncope or cardiac arrest that commonly precedes near-death, the boundary between consciousness and unconsciousness is often indistinct and a person may enter a borderland and be far more aware than is appreciated by others. Consciousness can also come and go if blood flow rises and falls across a crucial threshold. During crisis the brain's prime biologic purpose to keep itself alive lies at the heart of many spiritual experiences and inextricably binds them to the primal brain. Brain ischemia can disrupt the physiological balance between conscious states by leading the brainstem to blend rapid eye movement (REM) and waking into another borderland of consciousness during near-death. Evidence converges from many points to support this notion, including the observation that the majority of people with a near-death experience possess brains predisposed to fusing REM and waking consciousness into an unfamiliar reality, and are as likely to have out-of-body experience while blending REM and waking consciousness as they are to have out-of-body experience during near-death. © 2014 New York Academy of Sciences.

Acute stress promotes post-injury brain regeneration in fish.

PubMed

Sinyakov, Michael S; Haimovich, Amihai; Avtalion, Ramy R

2017-12-01

The central nervous system and the immune system, the two major players in homeostasis, operate in the ongoing bidirectional interaction. Stress is the third player that exerts strong effect on these two 'supersystems'; yet, its impact is studied much less. In this work employing carp model, we studied the influence of preliminary stress on neural and immune networks involved in post-injury brain regeneration. The relevant in vivo models of air-exposure stress and precisely directed cerebellum injury have been developed. Neuronal regeneration was evaluated by using specific tracers of cell proliferation and differentiation. Involvement of immune networks was accessed by monitoring the expression of selected T cells markers. Contrast difference between acute and chronic stress manifested in the fact that chronically stressed fish did not survive the brain injury. Neuronal regeneration appeared as a biphasic process whereas involvement of immune system proceeded as a monophasic route. In stressed fish, immune response was fast and accompanied or even preceded neuronal regeneration. In unstressed subjects, immune response took place on the second phase of neuronal regeneration. These findings imply an intrinsic regulatory impact of acute stress on neuronal and immune factors involved in post-injury brain regeneration. Stress activates both neuronal and immune defense mechanisms and thus contributes to faster regeneration. In this context, paradoxically, acute preliminary stress might be considered a distinct asset in speeding up the following post-injury brain regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Anticipating words and their gender: an event-related brain potential study of semantic integration, gender expectancy, and gender agreement in Spanish sentence reading.

PubMed

Wicha, Nicole Y Y; Moreno, Eva M; Kutas, Marta

2004-09-01

Recent studies indicate that the human brain attends to and uses grammatical gender cues during sentence comprehension. Here, we examine the nature and time course of the effect of gender on word-by-word sentence reading. Event-related brain potentials were recorded to an article and noun, while native Spanish speakers read medium- to high-constraint Spanish sentences for comprehension. The noun either fit the sentence meaning or not, and matched the preceding article in gender or not; in addition, the preceding article was either expected or unexpected based on prior sentence context. Semantically anomalous nouns elicited an N400. Gender-disagreeing nouns elicited a posterior late positivity (P600), replicating previous findings for words. Gender agreement and semantic congruity interacted in both the N400 window--with a larger negativity frontally for double violations--and the P600 window--with a larger positivity for semantic anomalies, relative to the prestimulus baseline. Finally, unexpected articles elicited an enhanced positivity (500-700 msec post onset) relative to expected articles. Overall, our data indicate that readers anticipate and attend to the gender of both articles and nouns, and use gender in real time to maintain agreement and to build sentence meaning.

Anticipating Words and Their Gender: An Event-related Brain Potential Study of Semantic Integration, Gender Expectancy, and Gender Agreement in Spanish Sentence Reading

PubMed Central

Wicha, Nicole Y. Y.; Moreno, Eva M.; Kutas, Marta

2012-01-01

Recent studies indicate that the human brain attends to and uses grammatical gender cues during sentence comprehension. Here, we examine the nature and time course of the effect of gender on word-by-word sentence reading. Event-related brain potentials were recorded to an article and noun, while native Spanish speakers read medium- to high-constraint Spanish sentences for comprehension. The noun either fit the sentence meaning or not, and matched the preceding article in gender or not; in addition, the preceding article was either expected or unexpected based on prior sentence context. Semantically anomalous nouns elicited an N400. Gender-disagreeing nouns elicited a posterior late positivity (P600), replicating previous findings for words. Gender agreement and semantic congruity interacted in both the N400 window—with a larger negativity frontally for double violations—and the P600 window—with a larger positivity for semantic anomalies, relative to the prestimulus baseline. Finally, unexpected articles elicited an enhanced positivity (500–700 msec post onset) relative to expected articles. Overall, our data indicate that readers anticipate and attend to the gender of both articles and nouns, and use gender in real time to maintain agreement and to build sentence meaning. PMID:15453979

Event-related brain potentials preceding speech and nonspeech oral movements of varying complexity.

PubMed

Wohlert, A B

1993-10-01

Cortical preparation for movement is reflected in the readiness potential (RP) waveform preceding voluntary limb movements. In the case of oral movements, the RP may be affected by the complexity or linguistic nature of the tasks. In this experiment, EEG potentials before a nonspeech task (lip pursing), a speech-like task (lip rounding), and single word production were recorded from scalp electrodes placed at the cranial vertex (Cz) and over the left and right motor strips (C3' and C4'). Seven right-handed female subjects produced at least 70 repetitions of the three tasks, in each of five repeated sessions. EEG records were averaged with respect to EMG onset at the lip. The word task, as opposed to the other tasks, was associated with greater negative amplitude in the RP waveform at the vertex site. Differences between the waveforms recorded at the right- and left-hemisphere sites were insignificant. Although intersubject variability was high, individuals had relatively stable patterns of response across sessions. Results suggest that the RP recorded at the vertex site is sensitive to changes in task complexity. The RP did not reflect lateralized activity indicative of hemispheric dominance.

Vasculo-Neuronal Coupling: Retrograde Vascular Communication to Brain Neurons.

PubMed

Kim, Ki Jung; Ramiro Diaz, Juan; Iddings, Jennifer A; Filosa, Jessica A

2016-12-14

Continuous cerebral blood flow is essential for neuronal survival, but whether vascular tone influences resting neuronal function is not known. Using a multidisciplinary approach in both rat and mice brain slices, we determined whether flow/pressure-evoked increases or decreases in parenchymal arteriole vascular tone, which result in arteriole constriction and dilation, respectively, altered resting cortical pyramidal neuron activity. We present evidence for intercellular communication in the brain involving a flow of information from vessel to astrocyte to neuron, a direction opposite to that of classic neurovascular coupling and referred to here as vasculo-neuronal coupling (VNC). Flow/pressure increases within parenchymal arterioles increased vascular tone and simultaneously decreased resting pyramidal neuron firing activity. On the other hand, flow/pressure decreases evoke parenchymal arteriole dilation and increased resting pyramidal neuron firing activity. In GLAST-CreERT2; R26-lsl-GCaMP3 mice, we demonstrate that increased parenchymal arteriole tone significantly increased intracellular calcium in perivascular astrocyte processes, the onset of astrocyte calcium changes preceded the inhibition of cortical pyramidal neuronal firing activity. During increases in parenchymal arteriole tone, the pyramidal neuron response was unaffected by blockers of nitric oxide, GABA A , glutamate, or ecto-ATPase. However, VNC was abrogated by TRPV4 channel, GABA B , as well as an adenosine A 1 receptor blocker. Differently to pyramidal neuron responses, increases in flow/pressure within parenchymal arterioles increased the firing activity of a subtype of interneuron. Together, these data suggest that VNC is a complex constitutive active process that enables neurons to efficiently adjust their resting activity according to brain perfusion levels, thus safeguarding cellular homeostasis by preventing mismatches between energy supply and demand. We present evidence for vessel-to-neuron communication in the brain slice defined here as vasculo-neuronal coupling. We showed that, in response to increases in parenchymal arteriole tone, astrocyte intracellular Ca 2+ increased and cortical neuronal activity decreased. On the other hand, decreasing parenchymal arteriole tone increased resting cortical pyramidal neuron activity. Vasculo-neuronal coupling was partly mediated by TRPV4 channels as genetic ablation, or pharmacological blockade impaired increased flow/pressure-evoked neuronal inhibition. Increased flow/pressure-evoked neuronal inhibition was blocked in the presence of adenosine A1 receptor and GABA B receptor blockade. Results provide evidence for the concept of vasculo-neuronal coupling and highlight the importance of understanding the interplay between basal CBF and resting neuronal activity. Copyright © 2016 the authors 0270-6474/16/3612624-16$15.00/0.

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].

Therapist activities preceding setbacks in the assimilation process.

PubMed

Gabalda, Isabel Caro; Stiles, William B; Pérez Ruiz, Sergio

2016-11-01

This study examined the therapist activities immediately preceding assimilation setbacks in the treatment of a good-outcome client treated with linguistic therapy of evaluation (LTE). Setbacks (N = 105) were defined as decreases of one or more assimilation stages from one passage to the next dealing with the same theme. The therapist activities immediately preceding those setbacks were classified using two kinds of codes: (a) therapist interventions and (b) positions the therapist took toward the client's internal voices. Preceding setbacks to early assimilation stages, where the problem was unformulated, the therapist was more often actively listening, and the setbacks were more often attributable to pushing a theme beyond the client's working zone. Preceding setbacks to later assimilation stages, where the problem was at least formulated, the therapist was more likely to be directing clients to consider alternatives, following the LTE agenda, and setbacks were more often attributable to the client following these directives shifting attention to less assimilated (but nevertheless formulated) aspects of the problem. At least in this case, setbacks followed systematically different therapist activities depending on the problem's stage of assimilation. Possible implications for the assimilation model's account of setbacks and for practice are discussed.

Ultra-fast magnetic resonance encephalography of physiological brain activity – Glymphatic pulsation mechanisms?

PubMed Central

Wang, Xindi; Korhonen, Vesa; Keinänen, Tuija; Tuovinen, Timo; Autio, Joonas; LeVan, Pierre; Keilholz, Shella; Zang, Yu-Feng; Hennig, Jürgen; Nedergaard, Maiken

2015-01-01

The theory on the glymphatic convection mechanism of cerebrospinal fluid holds that cardiac pulsations in part pump cerebrospinal fluid from the peri-arterial spaces through the extracellular tissue into the peri-venous spaces facilitated by aquaporin water channels. Since cardiac pulses cannot be the sole mechanism of glymphatic propulsion, we searched for additional cerebrospinal fluid pulsations in the human brain with ultra-fast magnetic resonance encephalography. We detected three types of physiological mechanisms affecting cerebral cerebrospinal fluid pulsations: cardiac, respiratory, and very low frequency pulsations. The cardiac pulsations induce a negative magnetic resonance encephalography signal change in peri-arterial regions that extends centrifugally and covers the brain in ≈1 Hz cycles. The respiratory ≈0.3 Hz pulsations are centripetal periodical pulses that occur dominantly in peri-venous areas. The third type of pulsation was very low frequency (VLF 0.001–0.023 Hz) and low frequency (LF 0.023–0.73 Hz) waves that both propagate with unique spatiotemporal patterns. Our findings using critically sampled magnetic resonance encephalography open a new view into cerebral fluid dynamics. Since glymphatic system failure may precede protein accumulations in diseases such as Alzheimer's dementia, this methodological advance offers a novel approach to image brain fluid dynamics that potentially can enable early detection and intervention in neurodegenerative diseases. PMID:26690495

Ultra-fast magnetic resonance encephalography of physiological brain activity - Glymphatic pulsation mechanisms?

PubMed

Kiviniemi, Vesa; Wang, Xindi; Korhonen, Vesa; Keinänen, Tuija; Tuovinen, Timo; Autio, Joonas; LeVan, Pierre; Keilholz, Shella; Zang, Yu-Feng; Hennig, Jürgen; Nedergaard, Maiken

2016-06-01

The theory on the glymphatic convection mechanism of cerebrospinal fluid holds that cardiac pulsations in part pump cerebrospinal fluid from the peri-arterial spaces through the extracellular tissue into the peri-venous spaces facilitated by aquaporin water channels. Since cardiac pulses cannot be the sole mechanism of glymphatic propulsion, we searched for additional cerebrospinal fluid pulsations in the human brain with ultra-fast magnetic resonance encephalography. We detected three types of physiological mechanisms affecting cerebral cerebrospinal fluid pulsations: cardiac, respiratory, and very low frequency pulsations. The cardiac pulsations induce a negative magnetic resonance encephalography signal change in peri-arterial regions that extends centrifugally and covers the brain in ≈1 Hz cycles. The respiratory ≈0.3 Hz pulsations are centripetal periodical pulses that occur dominantly in peri-venous areas. The third type of pulsation was very low frequency (VLF 0.001-0.023 Hz) and low frequency (LF 0.023-0.73 Hz) waves that both propagate with unique spatiotemporal patterns. Our findings using critically sampled magnetic resonance encephalography open a new view into cerebral fluid dynamics. Since glymphatic system failure may precede protein accumulations in diseases such as Alzheimer's dementia, this methodological advance offers a novel approach to image brain fluid dynamics that potentially can enable early detection and intervention in neurodegenerative diseases. © The Author(s) 2015.

Are Depictive Gestures like Pictures? Commonalities and Differences in Semantic Processing

ERIC Educational Resources Information Center

Wu, Ying Choon; Coulson, Seana

2011-01-01

Conversation is multi-modal, involving both talk and gesture. Does understanding depictive gestures engage processes similar to those recruited in the comprehension of drawings or photographs? Event-related brain potentials (ERPs) were recorded from neurotypical adults as they viewed spontaneously produced depictive gestures preceded by congruent…

Auditory cortical activity after intracortical microstimulation and its role for sensory processing and learning.

PubMed

Deliano, Matthias; Scheich, Henning; Ohl, Frank W

2009-12-16

Several studies have shown that animals can learn to make specific use of intracortical microstimulation (ICMS) of sensory cortex within behavioral tasks. Here, we investigate how the focal, artificial activation by ICMS leads to a meaningful, behaviorally interpretable signal. In natural learning, this involves large-scale activity patterns in widespread brain-networks. We therefore trained gerbils to discriminate closely neighboring ICMS sites within primary auditory cortex producing evoked responses largely overlapping in space. In parallel, during training, we recorded electrocorticograms (ECoGs) at high spatial resolution. Applying a multivariate classification procedure, we identified late spatial patterns that emerged with discrimination learning from the ongoing poststimulus ECoG. These patterns contained information about the preceding conditioned stimulus, and were associated with a subsequent correct behavioral response by the animal. Thereby, relevant pattern information was mainly carried by neuron populations outside the range of the lateral spatial spread of ICMS-evoked cortical activation (approximately 1.2 mm). This demonstrates that the stimulated cortical area not only encoded information about the stimulation sites by its focal, stimulus-driven activation, but also provided meaningful signals in its ongoing activity related to the interpretation of ICMS learned by the animal. This involved the stimulated area as a whole, and apparently required large-scale integration in the brain. However, ICMS locally interfered with the ongoing cortical dynamics by suppressing pattern formation near the stimulation sites. The interaction between ICMS and ongoing cortical activity has several implications for the design of ICMS protocols and cortical neuroprostheses, since the meaningful interpretation of ICMS depends on this interaction.

Localizing epileptic seizure onsets with Granger causality

NASA Astrophysics Data System (ADS)

Adhikari, Bhim M.; Epstein, Charles M.; Dhamala, Mukesh

2013-09-01

Accurate localization of the epileptic seizure onset zones (SOZs) is crucial for successful surgery, which usually depends on the information obtained from intracranial electroencephalography (IEEG) recordings. The visual criteria and univariate methods of analyzing IEEG recordings have not always produced clarity on the SOZs for resection and ultimate seizure freedom for patients. Here, to contribute to improving the localization of the SOZs and to understanding the mechanism of seizure propagation over the brain, we applied spectral interdependency methods to IEEG time series recorded from patients during seizures. We found that the high-frequency (>80 Hz) Granger causality (GC) occurs before the onset of any visible ictal activity and causal relationships involve the recording electrodes where clinically identifiable seizures later develop. These results suggest that high-frequency oscillatory network activities precede and underlie epileptic seizures, and that GC spectral measures derived from IEEG can assist in precise delineation of seizure onset times and SOZs.

75 FR 62498 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-12

... activity levels and performance. If the information were not collected it would disrupt budget planning and... SNAP operations during the preceding fiscal year and a Program Activity Statement (FNS-366B), which provides program activity data for the preceding fiscal year. Need and Use of the Information: FNS will...

The Role of Glucose Transporters in Brain Disease: Diabetes and Alzheimer’s Disease

PubMed Central

Shah, Kaushik; DeSilva, Shanal; Abbruscato, Thomas

2012-01-01

The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and Alzheimer’s diseases. However, the preceding mechanism to altered glucose metabolism has not been well understood. Glucose enters the brain via glucose transporters primarily present at the blood-brain barrier. Any changes in glucose transporter function and expression dramatically affects brain glucose homeostasis and function. In the brains of both diabetic and Alzheimer’s disease patients, changes in glucose transporter function and expression have been observed, but a possible link between the altered glucose transporter function and disease progress is missing. Future recognition of the role of new glucose transporter isoforms in the brain may provide a better understanding of brain glucose metabolism in normal and disease states. Elucidation of clinical pathological mechanisms related to glucose transport and metabolism may provide common links to the etiology of these two diseases. Considering these facts, in this review we provide a current understanding of the vital roles of a variety of glucose transporters in the normal, diabetic and Alzheimer’s disease brain. PMID:23202918

Time course of EEG background activity level before spontaneous awakening in infants.

PubMed

Zampi, Chiara; Fagioli, Igino; Salzarulo, Piero

2002-12-01

This research aimed to investigate the time course of the cortical activity level preceding spontaneous awakening as a function of age and state. Two groups of infants (1-4 and 9-14 weeks of age) were continuously monitored by polygraphic recording and behavioural observation during the night. The electroencephalographic (EEG) activity recorded by the C3-O1 lead was analysed through an automatic analysis method which provides, for each 30-s epoch, a single measure, time domain based, of the EEG synchronization. The EEG parameter values were computed in the 6 min preceding each awakening out of non-rapid eye movement (NREM) sleep and out of rapid eye movement (REM) sleep. The EEG background activity level did not change in the minutes preceding awakening out of REM sleep. Awakening out of NREM sleep was preceded by a change of EEG activity level in the direction of higher activation with different time course according to the age. Both REM and NREM sleep results suggest that a high level of EEG activity is a prerequisite for the occurrence of a spontaneous awakening.

Mitochondrial dysfunction precedes depression of AMPK/AKT signaling in insulin resistance induced by high glucose in primary cortical neurons.

PubMed

Peng, Yunhua; Liu, Jing; Shi, Le; Tang, Ying; Gao, Dan; Long, Jiangang; Liu, Jiankang

2016-06-01

Recent studies have demonstrated brain insulin signaling impairment and mitochondrial dysfunction in diabetes. Hyperinsulinemia and hyperlipidemia arising from diabetes have been linked to neuronal insulin resistance, and hyperglycemia induces peripheral sensory neuronal impairment and mitochondrial dysfunction. However, how brain glucose at diabetic conditions elicits cortical neuronal insulin signaling impairment and mitochondrial dysfunction remains unknown. In the present study, we cultured primary cortical neurons with high glucose levels and investigated the neuronal mitochondrial function and insulin response. We found that mitochondrial function was declined in presence of 10 mmol/L glucose, prior to the depression of AKT signaling in primary cortical neurons. We further demonstrated that the cerebral cortex of db/db mice exhibited both insulin resistance and loss of mitochondrial complex components. Moreover, we found that adenosine monophosphate-activated protein kinase (AMPK) inactivation is involved in high glucose-induced mitochondrial dysfunction and insulin resistance in primary cortical neurons and neuroblastoma cells, as well as in cerebral cortex of db/db mice, and all these impairments can be rescued by mitochondrial activator, resveratrol. Taken together, our results extend the finding that high glucose (≥10 mmol/L) comparable to diabetic brain extracellular glucose level leads to neuronal mitochondrial dysfunction and resultant insulin resistance, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central nerves system. We found that high glucose (≥10 mmol/L), comparable to diabetic brain extracellular glucose level, leads to neuronal mitochondrial dysfunction and resultant insulin resistance in an AMPK-dependent manner, and targeting mitochondria-AMPK signaling might be a promising strategy to protect against diabetes-related neuronal impairment in central nerves system. © 2016 International Society for Neurochemistry.

R6/2 Huntington's disease mice develop early and progressive abnormal brain metabolism and seizures.

PubMed

Cepeda-Prado, Efrain; Popp, Susanna; Khan, Usman; Stefanov, Dimitre; Rodríguez, Jorge; Menalled, Liliana B; Dow-Edwards, Diana; Small, Scott A; Moreno, Herman

2012-05-09

A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [(14)C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.

Greater Risk-Sensitivity of Dorsolateral Prefrontal Cortex in Young Smokers than in Nonsmokers

PubMed Central

Galván, Adriana; Schonberg, Tom; Mumford, Jeanette; Kohno, Milky; Poldrack, Russell A.; London, Edythe D.

2013-01-01

Rationale Despite a national reduction in the prevalence of cigarette smoking, ~19% of the adult U.S. population persists in this behavior, with the highest prevalence among 18–25-year-olds. Given that the choice to smoke imposes a known health risk, clarification of brain function related to decision-making, particularly involving risk-taking, in smokers may inform prevention and smoking cessation strategies. Objectives This study aimed to compare brain function related to decision-making in young smokers and nonsmokers. Methods The Balloon Analogue Risk Task (BART) is a computerized risky decision-making task in which participants pump virtual balloons, each pump associated with an incremental increase in potential payoff on a given trial but also with greater risk of balloon explosion and loss of payoff. We used this task to compare brain activation associated with risky decision-making in smokers (n=18) and nonsmokers (n=25) while they performed the BART during functional magnetic resonance imaging (fMRI). The participants were young men and women, 17–21 years of age. Results Risk level (number of pumps) modulated brain activation in the right dorsolateral and ventrolateral prefrontal cortices more in smokers than in nonsmokers; and smoking severity (Heaviness of Smoking Index) was positively related to this modulation in an adjacent frontal region. Conclusions Given evidence for involvement of the right dorsolateral and ventrolateral prefrontal cortices in inhibitory control, these findings suggest that young smokers have a different contribution of prefrontal cortical substrates to risky decision-making than nonsmokers. Future studies are warranted to determine whether the observed neurobiological differences precede or result from smoking. PMID:23644912

Impaired cortical mitochondrial function following TBI precedes behavioral changes

PubMed Central

Watson, William D.; Buonora, John E.; Yarnell, Angela M.; Lucky, Jessica J.; D’Acchille, Michaela I.; McMullen, David C.; Boston, Andrew G.; Kuczmarski, Andrew V.; Kean, William S.; Verma, Ajay; Grunberg, Neil E.; Cole, Jeffrey T.

2014-01-01

Traumatic brain injury (TBI) pathophysiology can be attributed to either the immediate, primary physical injury, or the delayed, secondary injury which begins minutes to hours after the initial injury and can persist for several months or longer. Because these secondary cascades are delayed and last for a significant time period post-TBI, they are primary research targets for new therapeutics. To investigate changes in mitochondrial function after a brain injury, both the cortical impact site and ipsilateral hippocampus of adult male rats 7 and 17 days after a controlled cortical impact (CCI) injury were examined. State 3, state 4, and uncoupler-stimulated rates of oxygen consumption, respiratory control ratios (RCRs) were measured and membrane potential quantified, and all were significantly decreased in 7 day post-TBI cortical mitochondria. By contrast, hippocampal mitochondria at 7 days showed only non-significant decreases in rates of oxygen consumption and membrane potential. NADH oxidase activities measured in disrupted mitochondria were normal in both injured cortex and hippocampus at 7 days post-CCI. Respiratory and phosphorylation capacities at 17 days post-CCI were comparable to naïve animals for both cortical and hippocampus mitochondria. However, unlike oxidative phosphorylation, membrane potential of mitochondria in the cortical lining of the impact site did not recover at 17 days, suggesting that while diminished cortical membrane potential at 17 days does not adversely affect mitochondrial capacity to synthesize ATP, it may negatively impact other membrane potential-sensitive mitochondrial functions. Memory status, as assessed by a passive avoidance paradigm, was not significantly impaired until 17 days after injury. These results indicate pronounced disturbances in cortical mitochondrial function 7 days after CCI which precede the behavioral impairment observed at 17 days. PMID:24550822

Brain structural correlates of sensory phenomena in patients with obsessive–compulsive disorder

PubMed Central

Subirà, Marta; Sato, João R.; Alonso, Pino; do Rosário, Maria C.; Segalàs, Cinto; Batistuzzo, Marcelo C.; Real, Eva; Lopes, Antonio C.; Cerrillo, Ester; Diniz, Juliana B.; Pujol, Jesús; Assis, Rachel O.; Menchón, José M.; Shavitt, Roseli G.; Busatto, Geraldo F.; Cardoner, Narcís; Miguel, Euripedes C.; Hoexter, Marcelo Q.; Soriano-Mas, Carles

2015-01-01

Background Sensory phenomena (SP) are uncomfortable feelings, including bodily sensations, sense of inner tension, “just-right” perceptions, feelings of incompleteness, or “urge-only” phenomena, which have been described to precede, trigger or accompany repetitive behaviours in individuals with obsessive–compulsive disorder (OCD). Sensory phenomena are also observed in individuals with tic disorders, and previous research suggests that sensorimotor cortex abnormalities underpin the presence of SP in such patients. However, to our knowledge, no studies have assessed the neural correlates of SP in patients with OCD. Methods We assessed the presence of SP using the University of São Paulo Sensory Phenomena Scale in patients with OCD and healthy controls from specialized units in São Paulo, Brazil, and Barcelona, Spain. All participants underwent a structural magnetic resonance examination, and brain images were examined using DARTEL voxel-based morphometry. We evaluated grey matter volume differences between patients with and without SP and healthy controls within the sensorimotor and premotor cortices. Results We included 106 patients with OCD and 87 controls in our study. Patients with SP (67% of the sample) showed grey matter volume increases in the left sensorimotor cortex in comparison to patients without SP and bilateral sensorimotor cortex grey matter volume increases in comparison to controls. No differences were observed between patients without SP and controls. Limitations Most patients were medicated. Participant recruitment and image acquisition were performed in 2 different centres. Conclusion We have identified a structural correlate of SP in patients with OCD involving grey matter volume increases within the sensorimotor cortex; this finding is in agreement with those of tic disorder studies showing that abnormal activity and volume increases within this region are associated with the urges preceding tic onset. PMID:25652753

Salient sounds activate human visual cortex automatically.

PubMed

McDonald, John J; Störmer, Viola S; Martinez, Antigona; Feng, Wenfeng; Hillyard, Steven A

2013-05-22

Sudden changes in the acoustic environment enhance perceptual processing of subsequent visual stimuli that appear in close spatial proximity. Little is known, however, about the neural mechanisms by which salient sounds affect visual processing. In particular, it is unclear whether such sounds automatically activate visual cortex. To shed light on this issue, this study examined event-related brain potentials (ERPs) that were triggered either by peripheral sounds that preceded task-relevant visual targets (Experiment 1) or were presented during purely auditory tasks (Experiments 2-4). In all experiments the sounds elicited a contralateral ERP over the occipital scalp that was localized to neural generators in extrastriate visual cortex of the ventral occipital lobe. The amplitude of this cross-modal ERP was predictive of perceptual judgments about the contrast of colocalized visual targets. These findings demonstrate that sudden, intrusive sounds reflexively activate human visual cortex in a spatially specific manner, even during purely auditory tasks when the sounds are not relevant to the ongoing task.

Salient sounds activate human visual cortex automatically

PubMed Central

McDonald, John J.; Störmer, Viola S.; Martinez, Antigona; Feng, Wenfeng; Hillyard, Steven A.

2013-01-01

Sudden changes in the acoustic environment enhance perceptual processing of subsequent visual stimuli that appear in close spatial proximity. Little is known, however, about the neural mechanisms by which salient sounds affect visual processing. In particular, it is unclear whether such sounds automatically activate visual cortex. To shed light on this issue, the present study examined event-related brain potentials (ERPs) that were triggered either by peripheral sounds that preceded task-relevant visual targets (Experiment 1) or were presented during purely auditory tasks (Experiments 2, 3, and 4). In all experiments the sounds elicited a contralateral ERP over the occipital scalp that was localized to neural generators in extrastriate visual cortex of the ventral occipital lobe. The amplitude of this cross-modal ERP was predictive of perceptual judgments about the contrast of co-localized visual targets. These findings demonstrate that sudden, intrusive sounds reflexively activate human visual cortex in a spatially specific manner, even during purely auditory tasks when the sounds are not relevant to the ongoing task. PMID:23699530

Ventral Striatum and the Evaluation of Memory Retrieval Strategies

PubMed Central

Badre, David; Lebrecht, Sophie; Pagliaccio, David; Long, Nicole M.; Scimeca, Jason M.

2015-01-01

Adaptive memory retrieval requires mechanisms of cognitive control that facilitate the recovery of goal-relevant information. Frontoparietal systems are known to support control of memory retrieval. However, the mechanisms by which the brain acquires, evaluates, and adapts retrieval strategies remain unknown. Here, we provide evidence that ventral striatal activation tracks the success of a retrieval strategy and correlates with subsequent reliance on that strategy. Human participants were scanned with fMRI while performing a lexical decision task. A rule was provided that indicated the likely semantic category of a target word given the category of a preceding prime. Reliance on the rule improved decision-making, as estimated within a drift diffusion framework. Ventral striatal activation tracked the benefit that relying on the rule had on decision-making. Moreover, activation in ventral striatum correlated with a participant’s subsequent reliance on the rule. Taken together, these results support a role for ventral striatum in learning and evaluating declarative retrieval strategies. PMID:24564466

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

On the Antecedents of an Electrophysiological Signature of Retrieval Mode.

PubMed

Williams, Angharad N; Evans, Lisa H; Herron, Jane E; Wilding, Edward L

2016-01-01

It has been proposed that people employ a common set of sustained operations (retrieval mode) when preparing to remember different kinds of episodic information. In two experiments, however, there was no evidence for the pattern of brain activity commonly assumed to index these operations. In both experiments event-related potentials (ERPs) were recorded time-locked to alternating preparatory cues signalling that participants should prepare for different retrieval tasks. One cue signalled episodic retrieval: remember the location where the object was presented in a prior study phase. The other signalled semantic retrieval: identify the location where the object is most commonly found (Experiment 1) or identify the typical size of the object (Experiment 2). In both experiments, only two trials of the same task were completed in succession. This enabled ERP contrasts between 'repeat' trials (the cue on the preceding trial signalled the same retrieval task), and 'switch' trials (the cue differed from the preceding trial). There were differences between the ERPs elicited by the preparatory task cues in Experiment 1 only: these were evident only on switch trials and comprised more positive-going activity over right-frontal scalp for the semantic than for the episodic task. These findings diverge from previous outcomes where the activity differentiating cues signalling preparation for episodic or semantic retrieval has been restricted to right-frontal scalp sites, comprising more positive-going activity for the episodic than for the semantic task. While these findings are consistent with the view that there is not a common set of operations engaged when people prepare to remember different kinds of episodic information, an alternative account is offered here, which is that these outcomes are a consequence of structural and temporal components of the experiment designs.

Mind, Languages, and Literacy.

ERIC Educational Resources Information Center

Debes, John L., III

For the past 100 years we have been acting as if education in school was of words, by words, and for words, but in fact verbal literacy was preceded by visual literacy when humans communicated with body language before they had speech. American educators have been concentrating efforts on the left hemisphere of the brain in which the verbal…

Psychological Problems in Mental Deficiency.

ERIC Educational Resources Information Center

Sarason, Seymour B.; Doris, John

A statement of goals and the rationale for organization precede a historical discussion of mental deficiency and society. The problem of labels like IQ and brain injured and the consequences of the diagnostic process are illustrated by case histories; case studies are also used to examine the criteria used to decide who is retarded and to discuss…

Prefrontal Cortex Is Critical for Contextual Processing: Evidence from Brain Lesions

ERIC Educational Resources Information Center

Fogelson, Noa; Shah, Mona; Scabini, Donatella; Knight, Robert T.

2009-01-01

We investigated the role of prefrontal cortex (PFC) in local contextual processing using a combined event-related potentials and lesion approach. Local context was defined as the occurrence of a short predictive series of visual stimuli occurring before delivery of a target event. Targets were preceded by either randomized sequences of standards…

Value-based modulation of memory encoding involves strategic engagement of fronto-temporal semantic processing regions

PubMed Central

Cohen, Michael S.; Rissman, Jesse; Suthana, Nanthia A.; Castel, Alan D.; Knowlton, Barbara J.

2014-01-01

A number of prior fMRI studies have focused on the ways in which the midbrain dopaminergic reward system co-activates with hippocampus to potentiate memory for valuable items. However, another means by which people could selectively remember more valuable to-be-remembered items is to be selective in their use of effective but effortful encoding strategies. To broadly examine the neural mechanisms of value on subsequent memory, we used fMRI to examine how differences in brain activity at encoding as a function of value relate to subsequent free recall for words. Each word was preceded by an arbitrarily assigned point value, and participants went through multiple study-test cycles with feedback on their point total at the end of each list, allowing for sculpting of cognitive strategies. We examined the correlation between value-related modulation of brain activity and participants’ selectivity index, a measure of how close participants were to their optimal point total given the number of items recalled. Greater selectivity scores were associated with greater differences in activation of semantic processing regions, including left inferior frontal gyrus and left posterior lateral temporal cortex, during encoding of high-value words relative to low-value words. Although we also observed value-related modulation within midbrain and ventral striatal reward regions, our fronto-temporal findings suggest that strategic engagement of deep semantic processing may be an important mechanism for selectively encoding valuable items. PMID:24683066

Neural Correlates of Automatic Mood Regulation in Girls at High Risk for Depression

PubMed Central

Joormann, Jutta; Cooney, Rebecca E.; Henry, Melissa L.; Gotlib, Ian H.

2012-01-01

Daughters of depressed mothers are at significantly elevated risk for developing a depressive disorder themselves. We have little understanding, however, of the specific factors that contribute to this risk. The ability to regulate negative affect effectively is critical to emotional and physical health and may play an important role in influencing risk for depression. We examined whether never-disordered daughters whose mothers have experienced recurrent episodes of depression during their daughters’ lifetime differ from never-disordered daughters of never-disordered mothers in their patterns of neural activation during a negative mood induction and during automatic mood regulation. Sad mood was induced in daughters through the use of film clips; daughters then recalled positive autobiographical memories, a procedure shown previously to repair negative affect. During the mood induction, high-risk girls exhibited greater activation than did low-risk daughters in brain areas that have frequently been implicated in the experience of negative affect, including the amygdala and ventrolateral prefrontal cortex. In contrast, during automatic mood regulation, low-risk daughters exhibited greater activation than did their high-risk counterparts in brain areas that have frequently been associated with top-down regulation of emotion, including the dorsolateral prefrontal cortex and dorsal anterior cingulate cortex. These findings indicate that girls at high and low risk for depression differ in their patterns of neural activation both while experiencing, and while repairing negative affect, and suggest that anomalies in neural functioning precede the onset of a depressive episode. PMID:21895344

Brain Regional Blood Flow and Working Memory Performance Predict Change in Blood Pressure Over 2 Years.

PubMed

Jennings, J Richard; Heim, Alicia F; Sheu, Lei K; Muldoon, Matthew F; Ryan, Christopher; Gach, H Michael; Schirda, Claudiu; Gianaros, Peter J

2017-12-01

Hypertension is a presumptive risk factor for premature cognitive decline. However, lowering blood pressure (BP) does not uniformly reverse cognitive decline, suggesting that high BP per se may not cause cognitive decline. We hypothesized that essential hypertension has initial effects on the brain that, over time, manifest as cognitive dysfunction in conjunction with both brain vascular abnormalities and systemic BP elevation. Accordingly, we tested whether neuropsychological function and brain blood flow responses to cognitive challenges among prehypertensive individuals would predict subsequent progression of BP. Midlife adults (n=154; mean age, 49; 45% men) with prehypertensive BP underwent neuropsychological testing and assessment of regional cerebral blood flow (rCBF) response to cognitive challenges. Neuropsychological performance measures were derived for verbal and logical memory (memory), executive function, working memory, mental efficiency, and attention. A pseudo-continuous arterial spin labeling magnetic resonance imaging sequence compared rCBF responses with control and active phases of cognitive challenges. Brain areas previously associated with BP were grouped into composites for frontoparietal, frontostriatal, and insular-subcortical rCBF areas. Multiple regression models tested whether BP after 2 years was predicted by initial BP, initial neuropsychological scores, and initial rCBF responses to cognitive challenge. The neuropsychological composite of working memory (standardized beta, -0.276; se=0.116; P =0.02) and the frontostriatal rCBF response to cognitive challenge (standardized beta, 0.234; se=0.108; P =0.03) significantly predicted follow-up BP. Initial BP failed to significantly predict subsequent cognitive performance or rCBF. Changes in brain function may precede or co-occur with progression of BP toward hypertensive levels in midlife. © 2017 American Heart Association, Inc.

Early Alterations of Brain Cellular Energy Homeostasis in Huntington Disease Models*

PubMed Central

Mochel, Fanny; Durant, Brandon; Meng, Xingli; O'Callaghan, James; Yu, Hua; Brouillet, Emmanuel; Wheeler, Vanessa C.; Humbert, Sandrine; Schiffmann, Raphael; Durr, Alexandra

2012-01-01

Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/2 mice. ATP and phosphocreatine concentrations were inversely correlated with the number of CAG repeats. Conversely, in mice injected with 3-nitroproprionic acid, an acute model of brain energy deficit, both ATP and phosphocreatine were significantly reduced. Increased creatine and phosphocreatine in R6/2 mice was associated with decreased guanidinoacetate N-methyltransferase and creatine kinase, both at the protein and RNA levels, and increased phosphorylated AMP-dependent protein kinase (pAMPK) over AMPK ratio. In addition, in 4-month-old knock-in HdhQ111/+ mice, the earliest metabolic alterations consisted of increased phosphocreatine in the frontal cortex and increased the pAMPK/AMPK ratio. Altogether, this study provides the first direct evidence of chronic alteration in homeostasis of high energy phosphates in HD models in the earliest stages of the disease, indicating possible reduced utilization of the brain phosphocreatine pool. PMID:22123819

An event-related brain potential study of schizotypal personality and associative semantic processing

PubMed Central

Kiang, Michael; Prugh, Jocelyn; Kutas, Marta

2009-01-01

To examine whether schizotypal personality is associated with the degree to which concepts activate each other in semantic memory, event-related brain potentials (ERPs) were recorded during a delayed lexical decision task from healthy volunteers rated for schizotypy. Each target word was directly, indirectly, or not at all related to a prime word preceding it at a 300- or 750-ms stimulus-onset asynchrony (SOA). Overall, N400 amplitudes were largest for unrelated targets, smallest for directly related targets, and intermediate for indirectly related targets. Higher total Schizotypal Personality Questionnaire (SPQ) scores correlated with smaller N400 indirect priming effects (i.e., smaller N400 amplitude differences between unrelated and indirectly related targets) at both SOAs. In addition, schizotypal subscale scores were differentially associated with N400 effects. Higher SPQ Cognitive-Perceptual scores correlated with smaller N400 direct priming effects (smaller N400 amplitude differences between unrelated and directly related targets) at both SOAs, and with smaller N400 indirect priming effects at the shorter SOA. These correlations are consistent with the hypothesis that decreased use of meaningful context to activate related concepts in general, and/or to inhibit unrelated concepts, may play some role in the development of unusual beliefs. PMID:19818815

Simulated self-motion in a visual gravity field: sensitivity to vertical and horizontal heading in the human brain.

PubMed

Indovina, Iole; Maffei, Vincenzo; Pauwels, Karl; Macaluso, Emiliano; Orban, Guy A; Lacquaniti, Francesco

2013-05-01

Multiple visual signals are relevant to perception of heading direction. While the role of optic flow and depth cues has been studied extensively, little is known about the visual effects of gravity on heading perception. We used fMRI to investigate the contribution of gravity-related visual cues on the processing of vertical versus horizontal apparent self-motion. Participants experienced virtual roller-coaster rides in different scenarios, at constant speed or 1g-acceleration/deceleration. Imaging results showed that vertical self-motion coherent with gravity engaged the posterior insula and other brain regions that have been previously associated with vertical object motion under gravity. This selective pattern of activation was also found in a second experiment that included rectilinear motion in tunnels, whose direction was cued by the preceding open-air curves only. We argue that the posterior insula might perform high-order computations on visual motion patterns, combining different sensory cues and prior information about the effects of gravity. Medial-temporal regions including para-hippocampus and hippocampus were more activated by horizontal motion, preferably at constant speed, consistent with a role in inertial navigation. Overall, the results suggest partially distinct neural representations of the cardinal axes of self-motion (horizontal and vertical). Copyright © 2013 Elsevier Inc. All rights reserved.

Posterior reversible encephalopathy syndrome in Korean patients with systemic lupus erythematosus: risk factors and clinical outcome.

PubMed

Jung, S M; Moon, S-J; Kwok, S-K; Ju, J H; Park, K-S; Park, S-H; Kim, H-Y

2013-08-01

Posterior reversible encephalopathy syndrome (PRES) is an uncommon neurologic condition associated with systemic lupus erythematosus (SLE). This study aimed to demonstrate the risk factors and clinical outcome of PRES in patients with SLE. Fifteen patients with SLE were diagnosed with PRES by characteristic clinical manifestations and magnetic resonance imaging (MRI) features from 2000 to 2012. Clinical profiles and outcomes were assessed for this study population. Additionally, 48 SLE patients with neurologic symptoms who underwent brain MRI were included for comparative analyses. The median age and duration of SLE in patients with PRES was 27 and 6.1 years, respectively. Comparison between patients with and without PRES revealed significant differences in the presentation of hypertension and seizure, lupus nephritis with renal insufficiency, treatment with high-dose steroid and cyclophosphamide, recent transfusion, and lupus activity measured by SLE disease activity index. Renal failure was the single independent factor with a high odds ratio of 129.250 by multivariate analysis. Of 15 patients, four experienced relapse and two died of sepsis during hospitalization. Our results suggest that lupus nephritis with renal dysfunction and other related clinical conditions can precede the occurrence of PRES in patients with SLE. It is important to perform early brain imaging for a timely diagnosis of PRES when clinically suspected.

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.

Neural Correlates of Semantic Prediction and Resolution in Sentence Processing.

PubMed

Grisoni, Luigi; Miller, Tally McCormick; Pulvermüller, Friedemann

2017-05-03

Most brain-imaging studies of language comprehension focus on activity following meaningful stimuli. Testing adult human participants with high-density EEG, we show that, already before the presentation of a critical word, context-induced semantic predictions are reflected by a neurophysiological index, which we therefore call the semantic readiness potential (SRP). The SRP precedes critical words if a previous sentence context constrains the upcoming semantic content (high-constraint contexts), but not in unpredictable (low-constraint) contexts. Specific semantic predictions were indexed by SRP sources within the motor system-in dorsolateral hand motor areas for expected hand-related words (e.g., "write"), but in ventral motor cortex for face-related words ("talk"). Compared with affirmative sentences, negated ones led to medial prefrontal and more widespread motor source activation, the latter being consistent with predictive semantic computation of alternatives to the negated expected concept. Predictive processing of semantic alternatives in negated sentences is further supported by a negative-going event-related potential at ∼400 ms (N400), which showed the typical enhancement to semantically incongruent sentence endings only in high-constraint affirmative contexts, but not to high-constraint negated ones. These brain dynamics reveal the interplay between semantic prediction and resolution (match vs error) processing in sentence understanding. SIGNIFICANCE STATEMENT Most neuroscientists agree on the eminent importance of predictive mechanisms for understanding basic as well as higher brain functions. This contrasts with a sparseness of brain measures that directly reflects specific aspects of prediction, as they are relevant in the processing of language and thought. Here we show that when critical words are strongly expected in their sentence context, a predictive brain response reflects meaning features of these anticipated symbols already before they appear. The granularity of the semantic predictions was so fine grained that the cortical sources in sensorimotor and medial prefrontal cortex even distinguished between predicted face- or hand-related action words (e.g., the words "lick" or "pick") and between affirmative and negated sentence meanings. Copyright © 2017 Grisoni et al.

Neural Correlates of Semantic Prediction and Resolution in Sentence Processing

PubMed Central

2017-01-01

Most brain-imaging studies of language comprehension focus on activity following meaningful stimuli. Testing adult human participants with high-density EEG, we show that, already before the presentation of a critical word, context-induced semantic predictions are reflected by a neurophysiological index, which we therefore call the semantic readiness potential (SRP). The SRP precedes critical words if a previous sentence context constrains the upcoming semantic content (high-constraint contexts), but not in unpredictable (low-constraint) contexts. Specific semantic predictions were indexed by SRP sources within the motor system—in dorsolateral hand motor areas for expected hand-related words (e.g., “write”), but in ventral motor cortex for face-related words (“talk”). Compared with affirmative sentences, negated ones led to medial prefrontal and more widespread motor source activation, the latter being consistent with predictive semantic computation of alternatives to the negated expected concept. Predictive processing of semantic alternatives in negated sentences is further supported by a negative-going event-related potential at ∼400 ms (N400), which showed the typical enhancement to semantically incongruent sentence endings only in high-constraint affirmative contexts, but not to high-constraint negated ones. These brain dynamics reveal the interplay between semantic prediction and resolution (match vs error) processing in sentence understanding. SIGNIFICANCE STATEMENT Most neuroscientists agree on the eminent importance of predictive mechanisms for understanding basic as well as higher brain functions. This contrasts with a sparseness of brain measures that directly reflects specific aspects of prediction, as they are relevant in the processing of language and thought. Here we show that when critical words are strongly expected in their sentence context, a predictive brain response reflects meaning features of these anticipated symbols already before they appear. The granularity of the semantic predictions was so fine grained that the cortical sources in sensorimotor and medial prefrontal cortex even distinguished between predicted face- or hand-related action words (e.g., the words “lick” or “pick”) and between affirmative and negated sentence meanings. PMID:28411271

Arterial Stiffening Precedes Systolic Hypertension in Diet-induced Obesity

PubMed Central

Weisbrod, Robert M.; Shiang, Tina; Sayah, Leona Al; Fry, Jessica L.; Bajpai, Saumendra; Reinhart-King, Cynthia A.; Lob, Heinrich E.; Santhanam, Lakshmi; Mitchell, Gary; Cohen, Richard A.; Seta, Francesca

2014-01-01

Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs such as the heart, brain and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension, although the mechanisms contributing to hypertension are unknown. Here we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within one month of the initiation of the diet and precedes the development of hypertension by five months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss returned arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause, rather than a consequence of hypertension. PMID:24060894

Arterial stiffening precedes systolic hypertension in diet-induced obesity.

PubMed

Weisbrod, Robert M; Shiang, Tina; Al Sayah, Leona; Fry, Jessica L; Bajpai, Saumendra; Reinhart-King, Cynthia A; Lob, Heinrich E; Santhanam, Lakshmi; Mitchell, Gary; Cohen, Richard A; Seta, Francesca

2013-12-01

Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs, such as the heart, brain, and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension although the mechanisms underlying hypertension are unknown. Here, we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within 1 month of the initiation of the diet and precedes the development of hypertension by 5 months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss resulted in return of arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause rather than a consequence of hypertension.

Functional Hubs in Mild Cognitive Impairment

NASA Astrophysics Data System (ADS)

Navas, Adrián; Papo, David; Boccaletti, Stefano; Del-Pozo, F.; Bajo, Ricardo; Maestú, Fernando; Martínez, J. H.; Gil, Pablo; Sendiña-Nadal, Irene; Buldú, Javier M.

We investigate how hubs of functional brain networks are modified as a result of mild cognitive impairment (MCI), a condition causing a slight but noticeable decline in cognitive abilities, which sometimes precedes the onset of Alzheimer's disease. We used magnetoencephalography (MEG) to investigate the functional brain networks of a group of patients suffering from MCI and a control group of healthy subjects, during the execution of a short-term memory task. Couplings between brain sites were evaluated using synchronization likelihood, from which a network of functional interdependencies was constructed and the centrality, i.e. importance, of their nodes was quantified. The results showed that, with respect to healthy controls, MCI patients were associated with decreases and increases in hub centrality respectively in occipital and central scalp regions, supporting the hypothesis that MCI modifies functional brain network topology, leading to more random structures.

Act quickly, decide later: long-latency visual processing underlies perceptual decisions but not reflexive behavior.

PubMed

Jolij, Jacob; Scholte, H Steven; van Gaal, Simon; Hodgson, Timothy L; Lamme, Victor A F

2011-12-01

Humans largely guide their behavior by their visual representation of the world. Recent studies have shown that visual information can trigger behavior within 150 msec, suggesting that visually guided responses to external events, in fact, precede conscious awareness of those events. However, is such a view correct? By using a texture discrimination task, we show that the brain relies on long-latency visual processing in order to guide perceptual decisions. Decreasing stimulus saliency leads to selective changes in long-latency visually evoked potential components reflecting scene segmentation. These latency changes are accompanied by almost equal changes in simple RTs and points of subjective simultaneity. Furthermore, we find a strong correlation between individual RTs and the latencies of scene segmentation related components in the visually evoked potentials, showing that the processes underlying these late brain potentials are critical in triggering a response. However, using the same texture stimuli in an antisaccade task, we found that reflexive, but erroneous, prosaccades, but not antisaccades, can be triggered by earlier visual processes. In other words: The brain can act quickly, but decides late. Differences between our study and earlier findings suggesting that action precedes conscious awareness can be explained by assuming that task demands determine whether a fast and unconscious, or a slower and conscious, representation is used to initiate a visually guided response.

Physical activity level and medial temporal health in youth at ultra high-risk for psychosis.

PubMed

Mittal, Vijay A; Gupta, Tina; Orr, Joseph M; Pelletier-Baldelli, Andrea; Dean, Derek J; Lunsford-Avery, Jessica R; Smith, Ashley K; Robustelli, Briana L; Leopold, Daniel R; Millman, Zachary B

2013-11-01

A growing body of evidence suggests that moderate to vigorous activity levels can affect quality of life, cognition, and brain structure in patients diagnosed with schizophrenia. However, physical activity has not been systematically studied during the period immediately preceding the onset of psychosis. Given reports of exercise-based neurogenesis in schizophrenia, understanding naturalistic physical activity levels in the prodrome may provide valuable information for early intervention efforts. The present study examined 29 ultra high-risk (UHR) and 27 matched controls to determine relationships between physical activity level, brain structure (hippocampus and parahippocampal gyrus), and symptoms. Participants were assessed with actigraphy for a 5-day period, MRI, and structured clinical interviews. UHR participants showed a greater percentage of time in sedentary behavior while healthy controls spent more time engaged in light to vigorous activity. There was a strong trend to suggest the UHR group showed less total physical activity. The UHR group exhibited smaller medial temporal volumes when compared with healthy controls. Total level of physical activity in the UHR group was moderately correlated with parahippocampal gyri bilaterally (right: r = .44, left: r = .55) and with occupational functioning (r = -.36; of negative symptom domain), but not positive symptomatology. Results suggest that inactivity is associated with medial temporal lobe health. Future studies are needed to determine if symptoms are driving inactivity, which in turn may be affecting the health of the parahippocampal structure and progression of illness. Although causality cannot be determined from the present design, these findings hold important implications for etiological conceptions and suggest promise for an experimental trial. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing.

PubMed

Fusar-Poli, Paolo; Crippa, José A; Bhattacharyya, Sagnik; Borgwardt, Stefan J; Allen, Paul; Martin-Santos, Rocio; Seal, Marc; Surguladze, Simon A; O'Carrol, Colin; Atakan, Zerrin; Zuardi, Antonio W; McGuire, Philip K

2009-01-01

Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown. To investigate the effects of 2 main psychoactive constituents of Cannabis sativa (Delta9-tetrahydrocannabinol [Delta9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing. Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design. Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life. Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety. Delta9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas. Delta9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta9-THC may be related to effects in other brain regions.

A Long-Term BCI Study With ECoG Recordings in Freely Moving Rats.

PubMed

Costecalde, Thomas; Aksenova, Tetiana; Torres-Martinez, Napoleon; Eliseyev, Andriy; Mestais, Corinne; Moro, Cecile; Benabid, Alim Louis

2018-02-01

Brain Computer Interface (BCI) studies are performed in an increasing number of applications. Questions are raised about electrodes, data processing and effectors. Experiments are needed to solve these issues. To develop a simple BCI set-up to easier studies for improving the mathematical tools to process the ECoG to control an effector. We designed a simple BCI using transcranial electrodes (17 screws, three mechanically linked to create a common reference, 14 used as recording electrodes) to record Electro-Cortico-Graphic (ECoG) neuronal activities in rodents. The data processing is based on an online self-paced non-supervised (asynchronous) BCI paradigm. N-way partial least squares algorithm together with Continuous Wavelet Transformation of ECoG recordings detect signatures related to motor activities. Signature detection in freely moving rats may activate external effectors during a behavioral task, which involved pushing a lever to obtain a reward. After routine training, we showed that peak brain activity preceding a lever push (LP) to obtain food reward was located mostly in the cerebellar cortex with a higher correlation coefficient, suggesting a strong postural component and also in the occipital cerebral cortex. Analysis of brain activities provided a stable signature in the high gamma band (∼180Hz) occurring within 1500 msec before the lever push approximately around -400 msec to -500 msec. Detection of the signature from a single cerebellar cortical electrode triggers the effector with high efficiency (68% Offline and 30% Online) and rare false positives per minute in sessions about 30 minutes and up to one hour (∼2 online and offline). In summary, our results are original as compared to the rest of the literature, which involves rarely rodents, a simple BCI set-up has been developed in rats, the data show for the first time long-term, up to one year, unsupervised online control of an effector. © 2017 International Neuromodulation Society.

Uncertainty in anticipation of uncomfortable rectal distension is modulated by the autonomic nervous system--a fMRI study in healthy volunteers.

PubMed

Rubio, Amandine; Van Oudenhove, Lukas; Pellissier, Sonia; Ly, Huynh Giao; Dupont, Patrick; Lafaye de Micheaux, Hugo; Tack, Jan; Dantzer, Cécile; Delon-Martin, Chantal; Bonaz, Bruno

2015-02-15

The human brain responds both before and during the application of aversive stimuli. Anticipation allows the organism to prepare its nociceptive system to respond adequately to the subsequent stimulus. The context in which an uncomfortable stimulus is experienced may also influence neural processing. Uncertainty of occurrence, timing and intensity of an aversive event may lead to increased anticipatory anxiety, fear, physiological arousal and sensory perception. We aimed to identify, in healthy volunteers, the effects of uncertainty in the anticipation of uncomfortable rectal distension, and the impact of the autonomic nervous system (ANS) activity and anxiety-related psychological variables on neural mechanisms of anticipation of rectal distension using fMRI. Barostat-controlled uncomfortable rectal distensions were preceded by cued uncertain or certain anticipation in 15 healthy volunteers in a fMRI protocol at 3T. Electrocardiographic data were concurrently registered by MR scanner. The low frequency (LF)-component of the heart rate variability (HRV) time-series was extracted and inserted as a regressor in the fMRI model ('LF-HRV model'). The impact of ANS activity was analyzed by comparing the fMRI signal in the 'standard model' and in the 'LF-HRV model' across the different anticipation and distension conditions. The scores of the psychological questionnaires and the rating of perceived anticipatory anxiety were included as covariates in the fMRI data analysis. Our experiments led to the following key findings: 1) the subgenual anterior cingulate cortex (sgACC) is the only activation site that relates to uncertainty in healthy volunteers and is directly correlated to individual questionnaire score for pain-related anxiety; 2) uncertain anticipation of rectal distension involved several relevant brain regions, namely activation of sgACC and medial prefrontal cortex and deactivation of amygdala, insula, thalamus, secondary somatosensory cortex, supplementary motor area and cerebellum; 3) most of the brain activity during anticipation, but not distension, is associated with activity of the central autonomic network. This approach could be applied to study the ANS impact on brain activity in various pathological conditions, namely in patients with chronic digestive conditions characterized by visceral discomfort and ANS imbalance such as irritable bowel syndrome or inflammatory bowel diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Brain responses to filled gaps.

PubMed

Hestvik, Arild; Maxfield, Nathan; Schwartz, Richard G; Shafer, Valerie

2007-03-01

An unresolved issue in the study of sentence comprehension is whether the process of gap-filling is mediated by the construction of empty categories (traces), or whether the parser relates fillers directly to the associated verb's argument structure. We conducted an event-related potentials (ERP) study that used the violation paradigm to examine the time course and spatial distribution of brain responses to ungrammatically filled gaps. The results indicate that the earliest brain response to the violation is an early left anterior negativity (eLAN). This ERP indexes an early phase of pure syntactic structure building, temporally preceding ERPs that reflect semantic integration and argument structure satisfaction. The finding is interpreted as evidence that gap-filling is mediated by structurally predicted empty categories, rather than directly by argument structure operations.

STAT3 precedes HIF1α transcriptional responses to oxygen and oxygen and glucose deprivation in human brain pericytes.

PubMed

Carlsson, Robert; Özen, Ilknur; Barbariga, Marco; Gaceb, Abderahim; Roth, Michaela; Paul, Gesine

2018-01-01

Brain pericytes are important to maintain vascular integrity of the neurovascular unit under both physiological and ischemic conditions. Ischemic stroke is known to induce an inflammatory and hypoxic response due to the lack of oxygen and glucose in the brain tissue. How this early response to ischemia is molecularly regulated in pericytes is largely unknown and may be of importance for future therapeutic targets. Here we evaluate the transcriptional responses in in vitro cultured human brain pericytes after oxygen and/or glucose deprivation. Hypoxia has been widely known to stabilise the transcription factor hypoxia inducible factor 1-alpha (HIF1α) and mediate the induction of hypoxic transcriptional programs after ischemia. However, we find that the transcription factors Jun Proto-Oncogene (c-JUN), Nuclear Factor Of Kappa Light Polypeptide Gene Enhancer In B-Cells (NFκB) and signal transducer and activator of transcription 3 (STAT3) bind genes regulated after 2hours (hs) of omitted glucose and oxygen before HIF1α. Potent HIF1α responses require 6hs of hypoxia to substantiate transcriptional regulation comparable to either c-JUN or STAT3. Phosphorylated STAT3 protein is at its highest after 5 min of oxygen and glucose (OGD) deprivation, whereas maximum HIF1α stabilisation requires 120 min. We show that STAT3 regulates angiogenic and metabolic pathways before HIF1α, suggesting that HIF1α is not the initiating trans-acting factor in the response of pericytes to ischemia.

Sulfoglucuronosyl paragloboside promotes endothelial cell apoptosis in inflammation: elucidation of a novel glycosphingolipid-signaling pathway.

PubMed

Dasgupta, Somsankar; Wang, Guanghu; Yu, Robert K

2011-11-01

Sulfoglucuronosyl paragloboside (SGPG), a minor glycosphingolipid of endothelial cells, is a ligand for L-selectin and has been implicated in neuro-inflammatory diseases, such as Guillian-Barré syndrome. Inflammatory cytokines, such as TNFα and IL-1β, up-regulate SGPG expression by stimulating gene expression for glucuronosyltransferases, both P and S forms (GlcATp and GlcATs), and the human natural killer antigen (HNK-1) sulfotransferase (HNK-1 ST). Transfection of a human cerebromicrovascular endothelial cell (SV-HCEC) line with HNK-1 ST siRNA down-regulated SGPG expression, inhibited cytokine-stimulated T-cell adhesion, and offered protection against apoptosis. However, the precise mechanisms of SGPG elevation in endothelial cell apoptosis and the maintenance of blood-brain or blood-nerve barrier integrity in inflammation have not been elucidated. Blocking SGPG expression inhibited cytokine-mediated stimulation of NF-κB activity but stimulated MAP kinase activity. Furthermore, elevation of SGPG by over-expression of GlcATp and GlcATs triggered endothelial cell apoptosis, with GlcATs being more potent than GlcATp. Although SGPG-mediated endothelial cell apoptosis was preceded by inhibiting the intracellular NF-κB activity, interfering with Akt and ERK activation and stimulating caspase 3 in SV-HCECs, HNK-1ST siRNA transfection also interfered with IκB phosphorylation but stimulated ERK activation. Our data indicate that SGPG is a critical regulatory molecule for maintaining endothelial cell survival and blood-brain or blood-nerve barrier function. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Generalized event knowledge activation during online sentence comprehension

PubMed Central

Metusalem, Ross; Kutas, Marta; Urbach, Thomas P.; Hare, Mary; McRae, Ken; Elman, Jeffrey L.

2012-01-01

Recent research has demonstrated that knowledge of real-world eventsplays an important role inguiding online language comprehension. The present study addresses the scope of event knowledge activation during the course of comprehension, specifically investigating whether activation is limited to those knowledge elements that align with the local linguistic context.The present study addresses this issue by analyzing event-related brain potentials (ERPs) recorded as participants read brief scenariosdescribing typical real-world events. Experiment 1 demonstratesthat a contextually anomalous word elicits a reduced N400 if it is generally related to the described event, even when controlling for the degree of association of this word with individual words in the preceding context and with the expected continuation. Experiment 2 shows that this effect disappears when the discourse context is removed.These findings demonstrate that during the course of incremental comprehension, comprehenders activate general knowledge about the described event, even at points at which this knowledge would constitute an anomalous continuation of the linguistic stream. Generalized event knowledge activationcontributes to mental representations of described events, is immediately available to influence language processing, and likely drives linguistic expectancy generation. PMID:22711976

Grand minima of solar activity and sociodynamics of culture

NASA Astrophysics Data System (ADS)

Vladimirsky, B. M.

2012-12-01

Indices of creative productivity introduced by C. Murrey were used to verify S. Ertel's conclusion about a global increase in creative productivity during the prolonged minimum of solar activity in 1640-1710. It was found that these indices for mathematicians, philosophers, and scientists increase in the Maunder era by factor of 1.6 in comparison with intervals of the same length before and after the minimum. A similar effect was obtained for mathematicians and philosophers for five earlier equitype minima in total (an increase by a factor of 1.9). The regularity that is revealed is confirmed by the fact that the most important achievements of high-ranking mathematicians and philosophers during the whole time period (2300 years) considered in this study fall on epochs of reduced levels of solar activity. The rise in the probability of the generation of rational ideas during grand minima is reflected also in the fact that they precede the appearance of written language and farming. Ultra-low-frequency electromagnetic fields appear to serve as a physical agent stimulating the activity of the brain's left hemisphere during the epochs of minima.

Autism Spectrum Disorders and Childhood-Onset Schizophrenia: Clinical and Biological Contributions to a Relation Revisited

ERIC Educational Resources Information Center

Rapopart, Judith; Chavez, Alex; Greenstein, Deanna; Addington, Anjene; Gogtay, Nitin

2009-01-01

Clinical, demographic, and brain development data on childhood-onset schizophrenia (COS) and family, imaging and genetic data from studies of autism were reviewed. It is found that COS is preceded by and comorbid with autism/pervasive developmental disorder and schizophrenia in 30 to 50 percent of cases based on two large studies.

Reciprocal inhibition of p53 and nuclear factor-kappaB transcriptional activities determines cell survival or death in neurons.

PubMed

Culmsee, Carsten; Siewe, Jan; Junker, Vera; Retiounskaia, Marina; Schwarz, Stephanie; Camandola, Simonetta; El-Metainy, Shahira; Behnke, Hagen; Mattson, Mark P; Krieglstein, Josef

2003-09-17

The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses, and activation of p53 precedes apoptosis in many cell types. Controversial reports exist on the role of the transcription factor nuclear factor-kappaB (NF-kappaB) in p53-mediated apoptosis, depending on the cell type and experimental conditions. Therefore, we sought to elucidate the role of NF-kappaB in p53-mediated neuron death. In cultured neurons DNA damaging compounds induced activation of p53, whereas NF-kappaB activity declined significantly. The p53 inhibitor pifithrin-alpha (PFT) preserved NF-kappaB activity and protected neurons against apoptosis. Immunoprecipitation experiments revealed enhanced p53 binding to the transcriptional cofactor p300 after induction of DNA damage, whereas binding of p300 to NF-kappaB was reduced. In contrast, PFT blocked the interaction of p53 with the cofactor, whereas NF-kappaB binding to p300 was enhanced. Most interestingly, similar results were observed after oxygen glucose deprivation in cultured neurons and in ischemic brain tissue. Ischemia-induced repression of NF-kappaB activity was prevented and brain damage was reduced by the p53 inhibitor PFT in a dose-dependent manner. It is concluded that a balanced competitive interaction of p53 and NF-kappaB with the transcriptional cofactor p300 exists in neurons. Exposure of neurons to lethal stress activates p53 and disrupts NF-kappaB binding to p300, thereby blocking NF-kappaB-mediated survival signaling. Inhibitors of p53 provide pronounced neuroprotective effects because they block p53-mediated induction of cell death and concomitantly enhance NF-kappaB-induced survival signaling.

N400 and the activation of prejudice against rural migrant workers in China.

PubMed

Wang, Lei; Ma, Qingguo; Song, Zhaofeng; Shi, Yisi; Wang, Yi; Pfotenhauer, Lydia

2011-02-23

Rural migrant workers (RMWs) are a special social group under the household registration system in China. Although RMWs work in the city, they are not issued a permanent city resident card, and are hardly integrated into the city life. City residents harbour strong negative stereotypes about RMWs. Facing a word-pair comprising a status noun (RMWs vs. Unban workers) followed by an adjective, 16 young participants were required to classify the adjective as being either negative or positive, while the event-related brain potentials (ERPs) were recorded. An ERP component identified as the N400 was found, and was studied with the question whether its amplitude reflected the effects of prejudice against RMWs. The reaction times to identify the positive adjectives preceded by the nouns pertaining to RMWs were significantly longer than to those preceded by nouns denoting Urban workers. The amplitude of the N400 evoked in RMW-Positive adjective condition was significantly larger than in Urban worker-Positive adjective condition, possibly reflecting the higher conflict when participants identified the adjectives as positive primed by RMWs. These findings revealed that negative stereotypes about RMWs still exist today, although Chinese mainstream media has disseminated positive messages about the RMWs for decades. Copyright © 2010 Elsevier B.V. All rights reserved.

Cortical Local Field Potential Power Is Associated with Behavioral Detection of Near-threshold Stimuli in the Rat Whisker System: Dissociation between Orbitofrontal and Somatosensory Cortices.

PubMed

Rickard, Rachel E; Young, Andrew M J; Gerdjikov, Todor V

2018-01-01

There is growing evidence that ongoing brain oscillations may represent a key regulator of attentional processes and as such may contribute to behavioral performance in psychophysical tasks. OFC appears to be involved in the top-down modulation of sensory processing; however, the specific contribution of ongoing OFC oscillations to perception has not been characterized. Here we used the rat whiskers as a model system to further characterize the relationship between cortical state and tactile detection. Head-fixed rats were trained to report the presence of a vibrotactile stimulus (frequency = 60 Hz, duration = 2 sec, deflection amplitude = 0.01-0.5 mm) applied to a single vibrissa. We calculated power spectra of local field potentials preceding the onset of near-threshold stimuli from microelectrodes chronically implanted in OFC and somatosensory cortex. We found a dissociation between slow oscillation power in the two regions in relation to detection probability: Higher OFC but not somatosensory delta power was associated with increased detection probability. Furthermore, coherence between OFC and barrel cortex was reduced preceding successful detection. Consistent with the role of OFC in attention, our results identify a cortical network whose activity is differentially modulated before successful tactile detection.

The Effect of Play on the Creativity of Young Children during Subsequent Activity.

ERIC Educational Resources Information Center

Howard-Jones, Paul A.; Taylor, Jayne R.; Sutton, Lesley

2002-01-01

Investigated whether experiencing 25 minutes of unstructured play in a preceding task influenced the creativity of 6- and 7-year-olds in a subsequent activity. Found that there was a positive effect of a preceding salt-dough play activity upon the creativity and range of colors used in creating a collage with a controlled range of materials.…

A neuroimaging study of emotion-cognition interaction in schizophrenia: the effect of ziprasidone treatment.

PubMed

Stip, Emmanuel; Cherbal, Adel; Luck, David; Zhornitsky, Simon; Bentaleb, Lahcen Ait; Lungu, Ovidiu

2017-04-01

Functional and structural brain changes associated with the cognitive processing of emotional visual stimuli were assessed in schizophrenic patients after 16 weeks of antipsychotic treatment with ziprasidone. Forty-five adults aged 18 to 40 were recruited: 15 schizophrenia patients (DSM-IV criteria) treated with ziprasidone (mean daily dose = 120 mg), 15 patients treated with other antipsychotics, and 15 healthy controls who did not receive any medication. Functional and structural neuroimaging data were acquired at baseline and 16 weeks after treatment initiation. In each session, participants selected stimuli, taken from standardized sets, based on their emotional valence. After ziprasidone treatment, several prefrontal regions, typically involved in cognitive control (anterior cingulate and ventrolateral prefrontal cortices), were significantly activated in patients in response to positive versus negative stimuli. This effect was greater whenever they had to select negative compared to positive stimuli, indicating an asymmetric effect of cognitive treatment of emotionally laden information. No such changes were observed for patients under other antipsychotics. In addition, there was an increase in the brain volume commonly recruited by healthy controls and patients under ziprasidone, in response to cognitive processing of emotional information. The structural analysis showed no significant changes in the density of gray and white matter in ziprasidone-treated patients compared to patients receiving other antipsychotic treatments. Our results suggest that functional changes in brain activity after ziprasidone medication precede structural and clinical manifestations, as markers that the treatment is efficient in restoring the functionality of prefrontal circuits involved in processing emotionally laden information in schizophrenia.

Reactivation, Replay, and Preplay: How It Might All Fit Together

PubMed Central

Buhry, Laure; Azizi, Amir H.; Cheng, Sen

2011-01-01

Sequential activation of neurons that occurs during “offline” states, such as sleep or awake rest, is correlated with neural sequences recorded during preceding exploration phases. This so-called reactivation, or replay, has been observed in a number of different brain regions such as the striatum, prefrontal cortex, primary visual cortex and, most prominently, the hippocampus. Reactivation largely co-occurs together with hippocampal sharp-waves/ripples, brief high-frequency bursts in the local field potential. Here, we first review the mounting evidence for the hypothesis that reactivation is the neural mechanism for memory consolidation during sleep. We then discuss recent results that suggest that offline sequential activity in the waking state might not be simple repetitions of previously experienced sequences. Some offline sequential activity occurs before animals are exposed to a novel environment for the first time, and some sequences activated offline correspond to trajectories never experienced by the animal. We propose a conceptual framework for the dynamics of offline sequential activity that can parsimoniously describe a broad spectrum of experimental results. These results point to a potentially broader role of offline sequential activity in cognitive functions such as maintenance of spatial representation, learning, or planning. PMID:21918724

Cross-modal and modality-specific expectancy effects between pain and disgust

PubMed Central

Sharvit, Gil; Vuilleumier, Patrik; Delplanque, Sylvain; Corradi-Dell’ Acqua, Corrado

2015-01-01

Pain sensitivity increases when a noxious stimulus is preceded by cues predicting higher intensity. However, it is unclear whether the modulation of nociception by expectancy is sensory-specific (“modality based”) or reflects the aversive-affective consequence of the upcoming event (“unpleasantness”), potentially common with other negative events. Here we compared expectancy effects for pain and disgust by using different, but equally unpleasant, nociceptive (thermal) and olfactory stimulations. Indeed both pain and disgust are aversive, associated with threat to the organism, and processed in partly overlapping brain networks. Participants saw cues predicting the unpleasantness (high/low) and the modality (pain/disgust) of upcoming thermal or olfactory stimulations, and rated the associated unpleasantness after stimuli delivery. Results showed that identical thermal stimuli were perceived as more unpleasant when preceded by cues threatening about high (as opposed to low) pain. A similar expectancy effect was found for olfactory disgust. Critically, cross-modal expectancy effects were observed on inconsistent trials when thermal stimuli were preceded by high-disgust cues or olfactory stimuli preceded by high-pain cues. However, these effects were stronger in consistent than inconsistent conditions. Taken together, our results suggest that expectation of an unpleasant event elicits representations of both its modality-specific properties and its aversive consequences. PMID:26631975

Bilirubin induces a calcium-dependent inhibition of multifunctional Ca2+/calmodulin-dependent kinase II activity in vitro.

PubMed

Churn, S B; DeLorenzo, R J; Shapiro, S M

1995-12-01

Excessive bilirubin levels in newborn infants result in long-term neurologic deficits that remain after bilirubin levels return to normal. Much of the observed neurologic deficits can be attributed to bilirubin-induced, delayed neuronal cell death. Inhibition of calcium/calmodulin-dependent kinase II (CaM kinase II) activity that precedes cell death is observed in conditions such as seizure activity, stroke, and glutamate excitotoxicity. Because neonatal bilirubin exposure results in neuronal loss in developing brain systems, we tested whether bilirubin exposure would induce an immediate inhibition of CaM activity, in vitro. P-81 filtration assay of basal and calcium-stimulated kinase activity was performed under standard kinase assay conditions. Bilirubin and/or albumin was added to the reaction vessels to determine the effect of these agents on kinase activity. Bilirubin exposure resulted in a concentration-dependent inhibition of CaM kinase II activity (IC50 = 16.78 microM). At concentrations above 50 microM, bilirubin exposure resulted in a 71 +/- 8% (mean +/- SD) inhibition of kinase activity (p < 0.001, t test, n = 10). Bilirubin exposure did not result in kinase inhibition if excessive bilirubin was removed by albumin binding before stimulation of kinase activity (106.9 +/- 9.6% control activity, n = 5). However, removal of bilirubin by binding with albumin after calcium addition did not restore kinase activity. (36.1 +/- 3.8% control activity, n = 5). Thus, once inhibition was observed, the activity could not be restored by addition of albumin. The data suggest that bilirubin exposure resulted in a calcium-dependent inhibition of CaM kinase II activity that, once induced, was not reversible by removing bilirubin by the addition of albumin. Because inhibition of CaM kinase II activity has been correlated with delayed neuronal cell death in many neuropathologic conditions, bilirubin-induced inhibition of this enzyme may be a cellular mechanism by which bilirubin exposure results in delayed neuronal cell death in developing brain.

Glycogen Supercompensation in the Rat Brain After Acute Hypoglycemia is Independent of Glucose Levels During Recovery.

PubMed

Duarte, João M N; Morgenthaler, Florence D; Gruetter, Rolf

2017-06-01

Patients with diabetes display a progressive decay in the physiological counter-regulatory response to hypoglycemia, resulting in hypoglycemia unawareness. The mechanism through which the brain adapts to hypoglycemia may involve brain glycogen. We tested the hypothesis that brain glycogen supercompensation following hypoglycemia depends on blood glucose levels during recovery. Conscious rats were submitted to hypoglycemia of 2 mmol/L for 90 min and allowed to recover at different glycemia, controlled by means of i.v. glucose infusion. Brain glycogen concentration was elevated above control levels after 24 h of recovery in the cortex, hippocampus and striatum. This glycogen supercompensation was independent of blood glucose levels in the post-hypoglycemia period. In the absence of a preceding hypoglycemia insult, brain glycogen concentrations were unaltered after 24 h under hyperglycemia. In the hypothalamus, which controls peripheral glucose homeostasis, glycogen levels were unaltered. Overall, we conclude that post-hypoglycemia glycogen supercompensation occurs in several brain areas and its magnitude is independent of plasma glucose levels. By supporting brain metabolism during recurrent hypoglycemia periods, glycogen may have a role in the development of hypoglycemia unawareness.

42 CFR 438.358 - Activities related to external quality review.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Validation of performance improvement projects required by the State to comply with requirements set forth in § 438.240(b)(1) and that were underway during the preceding 12 months. (2) Validation of MCO or PIHP... derived during the preceding 12 months from the following optional activities: (1) Validation of encounter...

42 CFR 438.358 - Activities related to external quality review.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Validation of performance improvement projects required by the State to comply with requirements set forth in § 438.240(b)(1) and that were underway during the preceding 12 months. (2) Validation of MCO or PIHP... derived during the preceding 12 months from the following optional activities: (1) Validation of encounter...

42 CFR 438.358 - Activities related to external quality review.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Validation of performance improvement projects required by the State to comply with requirements set forth in § 438.240(b)(1) and that were underway during the preceding 12 months. (2) Validation of MCO or PIHP... derived during the preceding 12 months from the following optional activities: (1) Validation of encounter...

42 CFR 438.358 - Activities related to external quality review.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Validation of performance improvement projects required by the State to comply with requirements set forth in § 438.240(b)(1) and that were underway during the preceding 12 months. (2) Validation of MCO or PIHP... derived during the preceding 12 months from the following optional activities: (1) Validation of encounter...

Intrapartum fetal heart rate patterns preceding terminal bradycardia in infants (>34 weeks) with poor neurological outcome: A regional population-based study in Japan.

PubMed

Kodama, Yuki; Sameshima, Hiroshi; Yamashita, Rie; Oohashi, Masanao; Ikenoue, Tsuyomu

2015-11-01

Intrapartum fetal bradycardia necessitates immediate operative delivery. Our aim was to investigate the hypothesis that some non-reassuring fetal heart rate (FHR) patterns were present before the onset of terminal bradycardia in infants who developed subsequent brain damage. From a population-based study of 65,197 deliveries, 190 stillbirths, 115 neonatal deaths, and 136 neurologically high-risk infants were registered by the Miyazaki Perinatal Conference. There were 15 cases of neurologically high-risk infants born at >34 weeks of gestation exhibiting intrapartum terminal bradycardia. Focusing on the brain-damaged infants, we retrospectively analyzed FHR patterns for at least 1 h prior to the bradycardia. Brain damage (cerebral palsy [n = 11] and mental retardation [n = 2]) was diagnosed at 2 years old in 13 out of 15 neurologically high-risk infants. Two infants had bradycardia on admission. In the remaining 11 infants, FHR patterns were reassuring in six (55%) and non-reassuring in five (45%), including late decelerations (n = 4) and variable decelerations (n = 2). Clinically relevant factors in the non-reassuring group included intrauterine infection (n = 3), malpresentation with umbilical cord coiling (n = 1), and unknown causes (n = 1). Clinically relevant features in the reassuring group included cord prolapse (n = 1), vaginal breech delivery (n = 1), shoulder dystocia (n = 1), rupture of membranes (n = 1), and unknown causes (n = 2). More than half of the brain-damaged infants born at >34 weeks of gestation who exhibited intrapartum terminal bradycardia had unremarkable FHR patterns before abrupt-onset bradycardia. For those with non-reassuring patterns preceding bradycardia, intrauterine infection was the major sentinel event. © 2015 Japan Society of Obstetrics and Gynecology.

Sustained Attention in Real Classroom Settings: An EEG Study.

PubMed

Ko, Li-Wei; Komarov, Oleksii; Hairston, W David; Jung, Tzyy-Ping; Lin, Chin-Teng

2017-01-01

Sustained attention is a process that enables the maintenance of response persistence and continuous effort over extended periods of time. Performing attention-related tasks in real life involves the need to ignore a variety of distractions and inhibit attention shifts to irrelevant activities. This study investigates electroencephalography (EEG) spectral changes during a sustained attention task within a real classroom environment. Eighteen healthy students were instructed to recognize as fast as possible special visual targets that were displayed during regular university lectures. Sorting their EEG spectra with respect to response times, which indicated the level of visual alertness to randomly introduced visual stimuli, revealed significant changes in the brain oscillation patterns. The results of power-frequency analysis demonstrated a relationship between variations in the EEG spectral dynamics and impaired performance in the sustained attention task. Across subjects and sessions, prolongation of the response time was preceded by an increase in the delta and theta EEG powers over the occipital region, and decrease in the beta power over the occipital and temporal regions. Meanwhile, implementation of the complex attention task paradigm into a real-world classroom setting makes it possible to investigate specific mutual links between brain activities and factors that cause impaired behavioral performance, such as development and manifestation of classroom mental fatigue. The findings of the study set a basis for developing a system capable of estimating the level of visual attention during real classroom activities by monitoring changes in the EEG spectra.

Sustained Attention in Real Classroom Settings: An EEG Study

PubMed Central

Ko, Li-Wei; Komarov, Oleksii; Hairston, W. David; Jung, Tzyy-Ping; Lin, Chin-Teng

2017-01-01

Sustained attention is a process that enables the maintenance of response persistence and continuous effort over extended periods of time. Performing attention-related tasks in real life involves the need to ignore a variety of distractions and inhibit attention shifts to irrelevant activities. This study investigates electroencephalography (EEG) spectral changes during a sustained attention task within a real classroom environment. Eighteen healthy students were instructed to recognize as fast as possible special visual targets that were displayed during regular university lectures. Sorting their EEG spectra with respect to response times, which indicated the level of visual alertness to randomly introduced visual stimuli, revealed significant changes in the brain oscillation patterns. The results of power-frequency analysis demonstrated a relationship between variations in the EEG spectral dynamics and impaired performance in the sustained attention task. Across subjects and sessions, prolongation of the response time was preceded by an increase in the delta and theta EEG powers over the occipital region, and decrease in the beta power over the occipital and temporal regions. Meanwhile, implementation of the complex attention task paradigm into a real-world classroom setting makes it possible to investigate specific mutual links between brain activities and factors that cause impaired behavioral performance, such as development and manifestation of classroom mental fatigue. The findings of the study set a basis for developing a system capable of estimating the level of visual attention during real classroom activities by monitoring changes in the EEG spectra. PMID:28824396

Modulation of α power and functional connectivity during facial affect recognition.

PubMed

Popov, Tzvetan; Miller, Gregory A; Rockstroh, Brigitte; Weisz, Nathan

2013-04-03

Research has linked oscillatory activity in the α frequency range, particularly in sensorimotor cortex, to processing of social actions. Results further suggest involvement of sensorimotor α in the processing of facial expressions, including affect. The sensorimotor face area may be critical for perception of emotional face expression, but the role it plays is unclear. The present study sought to clarify how oscillatory brain activity contributes to or reflects processing of facial affect during changes in facial expression. Neuromagnetic oscillatory brain activity was monitored while 30 volunteers viewed videos of human faces that changed their expression from neutral to fearful, neutral, or happy expressions. Induced changes in α power during the different morphs, source analysis, and graph-theoretic metrics served to identify the role of α power modulation and cross-regional coupling by means of phase synchrony during facial affect recognition. Changes from neutral to emotional faces were associated with a 10-15 Hz power increase localized in bilateral sensorimotor areas, together with occipital power decrease, preceding reported emotional expression recognition. Graph-theoretic analysis revealed that, in the course of a trial, the balance between sensorimotor power increase and decrease was associated with decreased and increased transregional connectedness as measured by node degree. Results suggest that modulations in α power facilitate early registration, with sensorimotor cortex including the sensorimotor face area largely functionally decoupled and thereby protected from additional, disruptive input and that subsequent α power decrease together with increased connectedness of sensorimotor areas facilitates successful facial affect recognition.

Temporal dynamics of the knowledge-mediated visual disambiguation process in humans: a magnetoencephalography study.

PubMed

Urakawa, Tomokazu; Ogata, Katsuya; Kimura, Takahiro; Kume, Yuko; Tobimatsu, Shozo

2015-01-01

Disambiguation of a noisy visual scene with prior knowledge is an indispensable task of the visual system. To adequately adapt to a dynamically changing visual environment full of noisy visual scenes, the implementation of knowledge-mediated disambiguation in the brain is imperative and essential for proceeding as fast as possible under the limited capacity of visual image processing. However, the temporal profile of the disambiguation process has not yet been fully elucidated in the brain. The present study attempted to determine how quickly knowledge-mediated disambiguation began to proceed along visual areas after the onset of a two-tone ambiguous image using magnetoencephalography with high temporal resolution. Using the predictive coding framework, we focused on activity reduction for the two-tone ambiguous image as an index of the implementation of disambiguation. Source analysis revealed that a significant activity reduction was observed in the lateral occipital area at approximately 120 ms after the onset of the ambiguous image, but not in preceding activity (about 115 ms) in the cuneus when participants perceptually disambiguated the ambiguous image with prior knowledge. These results suggested that knowledge-mediated disambiguation may be implemented as early as approximately 120 ms following an ambiguous visual scene, at least in the lateral occipital area, and provided an insight into the temporal profile of the disambiguation process of a noisy visual scene with prior knowledge. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Value-based modulation of memory encoding involves strategic engagement of fronto-temporal semantic processing regions.

PubMed

Cohen, Michael S; Rissman, Jesse; Suthana, Nanthia A; Castel, Alan D; Knowlton, Barbara J

2014-06-01

A number of prior fMRI studies have focused on the ways in which the midbrain dopaminergic reward system coactivates with hippocampus to potentiate memory for valuable items. However, another means by which people could selectively remember more valuable to-be-remembered items is to be selective in their use of effective but effortful encoding strategies. To broadly examine the neural mechanisms of value on subsequent memory, we used fMRI to assess how differences in brain activity at encoding as a function of value relate to subsequent free recall for words. Each word was preceded by an arbitrarily assigned point value, and participants went through multiple study-test cycles with feedback on their point total at the end of each list, allowing for sculpting of cognitive strategies. We examined the correlation between value-related modulation of brain activity and participants' selectivity index, which measures how close participants were to their optimal point total, given the number of items recalled. Greater selectivity scores were associated with greater differences in the activation of semantic processing regions, including left inferior frontal gyrus and left posterior lateral temporal cortex, during the encoding of high-value words relative to low-value words. Although we also observed value-related modulation within midbrain and ventral striatal reward regions, our fronto-temporal findings suggest that strategic engagement of deep semantic processing may be an important mechanism for selectively encoding valuable items.

Implications of oxidative stress in the brain plasticity originated by fasting: a BOLD-fMRI study.

PubMed

Belaïch, Rachida; Boujraf, Saïd; Benzagmout, Mohammed; Magoul, Rabia; Maaroufi, Mustapha; Tizniti, Siham

2017-11-01

The goal of this study was assessing the intermittent fasting effect on brain plasticity and oxidative stress (OS) using blood-oxygenation-level dependent (BOLD)-functional magnetic resonance image (fMRI) approach. Evidences of physiological and molecular phenomena involved in this process are discussed and compared to reported literature. Six fully healthy male non-smokers volunteered in this study. All volunteers were right handed, and have an equilibrated, consistent and healthy daily nutritional habit, and a healthy lifestyle. Participants were allowed consuming food during evening and night time while fasting with self-prohibiting food and liquids during 14 hours/day from sunrise to sunset. All participants underwent identical brain BOLD-fMRI protocol. The images were acquired in the Department of Radiology and Clinical Imaging of the University Hospital of Fez, Fez, Morocco. The anatomical brain and BOLD-fMRIs were acquired using a 1.5-Tesla scanner (Signa, General Electric, Milwaukee, United States). BOLD-fMRI image acquisition was done using single-shot gradient echo echo-planer imaging sequence. BOLD-fMRI paradigm consisted of the motor task where volunteers were asked to perform finger taping of the right hand. Two BOLD-fMRI scan sessions were performed, the first one between the 5th and 10th days preceding the start of fasting and the second between days 25th and 28th of the fasting month. All sessions were performed between 3:30 PM and 5:30 PM. Although individual maps were originated from different individual participants, they cover the same anatomic area in each case. Image processing and statistical analysis were conducted with Statistical Parameter Mapping version 8 (2008, Welcome Department of Cognitive Neurology, London UK). The maximal BOLD signal changes were calculated for each subject in the motor area M1; Activation maps were calculated and overlaid on the anatomical images. Group analysis of the data was performed, and the average volume and the maximum intensity of BOLD signal in the activated area M1 was determined for all studied volunteers. The current study allowed measuring regional brain volumes and neural network activity before and during an extended period of fasting using BOLD-fMRI. This demonstrated and confirmed the impact of fasting on human brain structure and function. Further studies are required to elucidate mechanisms and enable direct inference of a diet-induced OS effect on the brain.

Local cortical dynamics of burst suppression in the anaesthetized brain.

PubMed

Lewis, Laura D; Ching, Shinung; Weiner, Veronica S; Peterfreund, Robert A; Eskandar, Emad N; Cash, Sydney S; Brown, Emery N; Purdon, Patrick L

2013-09-01

Burst suppression is an electroencephalogram pattern that consists of a quasi-periodic alternation between isoelectric 'suppressions' lasting seconds or minutes, and high-voltage 'bursts'. It is characteristic of a profoundly inactivated brain, occurring in conditions including hypothermia, deep general anaesthesia, infant encephalopathy and coma. It is also used in neurology as an electrophysiological endpoint in pharmacologically induced coma for brain protection after traumatic injury and during status epilepticus. Classically, burst suppression has been regarded as a 'global' state with synchronous activity throughout cortex. This assumption has influenced the clinical use of burst suppression as a way to broadly reduce neural activity. However, the extent of spatial homogeneity has not been fully explored due to the challenges in recording from multiple cortical sites simultaneously. The neurophysiological dynamics of large-scale cortical circuits during burst suppression are therefore not well understood. To address this question, we recorded intracranial electrocorticograms from patients who entered burst suppression while receiving propofol general anaesthesia. The electrodes were broadly distributed across cortex, enabling us to examine both the dynamics of burst suppression within local cortical regions and larger-scale network interactions. We found that in contrast to previous characterizations, bursts could be substantially asynchronous across the cortex. Furthermore, the state of burst suppression itself could occur in a limited cortical region while other areas exhibited ongoing continuous activity. In addition, we found a complex temporal structure within bursts, which recapitulated the spectral dynamics of the state preceding burst suppression, and evolved throughout the course of a single burst. Our observations imply that local cortical dynamics are not homogeneous, even during significant brain inactivation. Instead, cortical and, implicitly, subcortical circuits express seemingly different sensitivities to high doses of anaesthetics that suggest a hierarchy governing how the brain enters burst suppression, and emphasize the role of local dynamics in what has previously been regarded as a global state. These findings suggest a conceptual shift in how neurologists could assess the brain function of patients undergoing burst suppression. First, analysing spatial variation in burst suppression could provide insight into the circuit dysfunction underlying a given pathology, and could improve monitoring of medically-induced coma. Second, analysing the temporal dynamics within a burst could help assess the underlying brain state. This approach could be explored as a prognostic tool for recovery from coma, and for guiding treatment of status epilepticus. Overall, these results suggest new research directions and methods that could improve patient monitoring in clinical practice.

Functional connectivity and information flow of the respiratory neural network in chronic obstructive pulmonary disease.

PubMed

Yu, Lianchun; De Mazancourt, Marine; Hess, Agathe; Ashadi, Fakhrul R; Klein, Isabelle; Mal, Hervé; Courbage, Maurice; Mangin, Laurence

2016-08-01

Breathing involves a complex interplay between the brainstem automatic network and cortical voluntary command. How these brain regions communicate at rest or during inspiratory loading is unknown. This issue is crucial for several reasons: (i) increased respiratory loading is a major feature of several respiratory diseases, (ii) failure of the voluntary motor and cortical sensory processing drives is among the mechanisms that precede acute respiratory failure, (iii) several cerebral structures involved in responding to inspiratory loading participate in the perception of dyspnea, a distressing symptom in many disease. We studied functional connectivity and Granger causality of the respiratory network in controls and patients with chronic obstructive pulmonary disease (COPD), at rest and during inspiratory loading. Compared with those of controls, the motor cortex area of patients exhibited decreased connectivity with their contralateral counterparts and no connectivity with the brainstem. In the patients, the information flow was reversed at rest with the source of the network shifted from the medulla towards the motor cortex. During inspiratory loading, the system was overwhelmed and the motor cortex became the sink of the network. This major finding may help to understand why some patients with COPD are prone to acute respiratory failure. Network connectivity and causality were related to lung function and illness severity. We validated our connectivity and causality results with a mathematical model of neural network. Our findings suggest a new therapeutic strategy involving the modulation of brain activity to increase motor cortex functional connectivity and improve respiratory muscles performance in patients. Hum Brain Mapp 37:2736-2754, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Multiple asynchronous stimulus- and task-dependent hierarchies (STDH) within the visual brain's parallel processing systems.

PubMed

Zeki, Semir

2016-10-01

Results from a variety of sources, some many years old, lead ineluctably to a re-appraisal of the twin strategies of hierarchical and parallel processing used by the brain to construct an image of the visual world. Contrary to common supposition, there are at least three 'feed-forward' anatomical hierarchies that reach the primary visual cortex (V1) and the specialized visual areas outside it, in parallel. These anatomical hierarchies do not conform to the temporal order with which visual signals reach the specialized visual areas through V1. Furthermore, neither the anatomical hierarchies nor the temporal order of activation through V1 predict the perceptual hierarchies. The latter shows that we see (and become aware of) different visual attributes at different times, with colour leading form (orientation) and directional visual motion, even though signals from fast-moving, high-contrast stimuli are among the earliest to reach the visual cortex (of area V5). Parallel processing, on the other hand, is much more ubiquitous than commonly supposed but is subject to a barely noticed but fundamental aspect of brain operations, namely that different parallel systems operate asynchronously with respect to each other and reach perceptual endpoints at different times. This re-assessment leads to the conclusion that the visual brain is constituted of multiple, parallel and asynchronously operating task- and stimulus-dependent hierarchies (STDH); which of these parallel anatomical hierarchies have temporal and perceptual precedence at any given moment is stimulus and task related, and dependent on the visual brain's ability to undertake multiple operations asynchronously. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Brain injury expands the numbers of neural stem cells and progenitors in the SVZ by enhancing their responsiveness to EGF

PubMed Central

Alagappan, Dhivyaa; Lazzarino, Deborah A; Felling, Ryan J; Balan, Murugabaskar; Kotenko, Sergei V; Levison, Steven W

2009-01-01

There is an increase in the numbers of neural precursors in the SVZ (subventricular zone) after moderate ischaemic injuries, but the extent of stem cell expansion and the resultant cell regeneration is modest. Therefore our studies have focused on understanding the signals that regulate these processes towards achieving a more robust amplification of the stem/progenitor cell pool. The goal of the present study was to evaluate the role of the EGFR [EGF (epidermal growth factor) receptor] in the regenerative response of the neonatal SVZ to hypoxic/ischaemic injury. We show that injury recruits quiescent cells in the SVZ to proliferate, that they divide more rapidly and that there is increased EGFR expression on both putative stem cells and progenitors. With the amplification of the precursors in the SVZ after injury there is enhanced sensitivity to EGF, but not to FGF (fibroblast growth factor)-2. EGF-dependent SVZ precursor expansion, as measured using the neurosphere assay, is lost when the EGFR is pharmacologically inhibited, and forced expression of a constitutively active EGFR is sufficient to recapitulate the exaggerated proliferation of the neural stem/progenitors that is induced by hypoxic/ischaemic brain injury. Cumulatively, our results reveal that increased EGFR signalling precedes that increase in the abundance of the putative neural stem cells and our studies implicate the EGFR as a key regulator of the expansion of SVZ precursors in response to brain injury. Thus modulating EGFR signalling represents a potential target for therapies to enhance brain repair from endogenous neural precursors following hypoxic/ischaemic and other brain injuries. PMID:19570028

Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis: a quantitative MRI study.

PubMed

Floris, S; Blezer, E L A; Schreibelt, G; Döpp, E; van der Pol, S M A; Schadee-Eestermans, I L; Nicolay, K; Dijkstra, C D; de Vries, H E

2004-03-01

Enhanced cerebrovascular permeability and cellular infiltration mark the onset of early multiple sclerosis lesions. So far, the precise sequence of these events and their role in lesion formation and disease progression remain unknown. Here we provide quantitative evidence that blood-brain barrier leakage is an early event and precedes massive cellular infiltration in the development of acute experimental allergic encephalomyelitis (EAE), the animal correlate of multiple sclerosis. Cerebrovascular leakage and monocytes infiltrates were separately monitored by quantitative in vivo MRI during the course of the disease. Magnetic resonance enhancement of the contrast agent gadolinium diethylenetriaminepentaacetate (Gd-DTPA), reflecting vascular leakage, occurred concomitantly with the onset of neurological signs and was already at a maximal level at this stage of the disease. Immunohistochemical analysis also confirmed the presence of the serum-derived proteins such as fibrinogen around the brain vessels early in the disease, whereas no cellular infiltrates could be detected. MRI further demonstrated that Gd-DTPA leakage clearly preceded monocyte infiltration as imaged by the contrast agent based on ultra small particles of iron oxide (USPIO), which was maximal only during full-blown EAE. Ultrastructural and immunohistochemical investigation revealed that USPIOs were present in newly infiltrated macrophages within the inflammatory lesions. To validate the use of USPIOs as a non-invasive tool to evaluate therapeutic strategies, EAE animals were treated with the immunomodulator 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitor, lovastatin, which ameliorated clinical scores. MRI showed that the USPIO load in the brain was significantly diminished in lovastatin-treated animals. Data indicate that cerebrovascular leakage and monocytic trafficking into the brain are two distinct processes in the development of inflammatory lesions during multiple sclerosis, which can be monitored on-line with MRI using USPIOs and Gd-DTPA as contrast agents. These studies also implicate that USPIOs are a valuable tool to visualize monocyte infiltration in vivo and quantitatively assess the efficacy of new therapeutics like lovastatin.

Sox2 is required for embryonic development of the ventral telencephalon through the activation of the ventral determinants Nkx2.1 and Shh.

PubMed

Ferri, Anna; Favaro, Rebecca; Beccari, Leonardo; Bertolini, Jessica; Mercurio, Sara; Nieto-Lopez, Francisco; Verzeroli, Cristina; La Regina, Federico; De Pietri Tonelli, Davide; Ottolenghi, Sergio; Bovolenta, Paola; Nicolis, Silvia K

2013-03-01

The Sox2 transcription factor is active in stem/progenitor cells throughout the developing vertebrate central nervous system. However, its conditional deletion at E12.5 in mouse causes few brain developmental problems, with the exception of the postnatal loss of the hippocampal radial glia stem cells and the dentate gyrus. We deleted Sox2 at E9.5 in the telencephalon, using a Bf1-Cre transgene. We observed embryonic brain defects that were particularly severe in the ventral, as opposed to the dorsal, telencephalon. Important tissue loss, including the medial ganglionic eminence (MGE), was detected at E12.5, causing the subsequent impairment of MGE-derived neurons. The defect was preceded by loss of expression of the essential ventral determinants Nkx2.1 and Shh, and accompanied by ventral spread of dorsal markers. This phenotype is reminiscent of that of mice mutant for the transcription factor Nkx2.1 or for the Shh receptor Smo. Nkx2.1 is known to mediate the initial activation of ventral telencephalic Shh expression. A partial rescue of the normal phenotype at E14.5 was obtained by administration of a Shh agonist. Experiments in Medaka fish indicate that expression of Nkx2.1 is regulated by Sox2 in this species also. We propose that Sox2 contributes to Nkx2.1 expression in early mouse development, thus participating in the region-specific activation of Shh, thereby mediating ventral telencephalic patterning induction.

BAX channel activity mediates lysosomal disruption linked to Parkinson disease.

PubMed

Bové, Jordi; Martínez-Vicente, Marta; Dehay, Benjamin; Perier, Celine; Recasens, Ariadna; Bombrun, Agnes; Antonsson, Bruno; Vila, Miquel

2014-05-01

Lysosomal disruption is increasingly regarded as a major pathogenic event in Parkinson disease (PD). A reduced number of intraneuronal lysosomes, decreased levels of lysosomal-associated proteins and accumulation of undegraded autophagosomes (AP) are observed in PD-derived samples, including fibroblasts, induced pluripotent stem cell-derived dopaminergic neurons, and post-mortem brain tissue. Mechanistic studies in toxic and genetic rodent PD models attribute PD-related lysosomal breakdown to abnormal lysosomal membrane permeabilization (LMP). However, the molecular mechanisms underlying PD-linked LMP and subsequent lysosomal defects remain virtually unknown, thereby precluding their potential therapeutic targeting. Here we show that the pro-apoptotic protein BAX (BCL2-associated X protein), which permeabilizes mitochondrial membranes in PD models and is activated in PD patients, translocates and internalizes into lysosomal membranes early following treatment with the parkinsonian neurotoxin MPTP, both in vitro and in vivo, within a time-frame correlating with LMP, lysosomal disruption, and autophagosome accumulation and preceding mitochondrial permeabilization and dopaminergic neurodegeneration. Supporting a direct permeabilizing effect of BAX on lysosomal membranes, recombinant BAX is able to induce LMP in purified mouse brain lysosomes and the latter can be prevented by pharmacological blockade of BAX channel activity. Furthermore, pharmacological BAX channel inhibition is able to prevent LMP, restore lysosomal levels, reverse AP accumulation, and attenuate mitochondrial permeabilization and overall nigrostriatal degeneration caused by MPTP, both in vitro and in vivo. Overall, our results reveal that PD-linked lysosomal impairment relies on BAX-induced LMP, and point to small molecules able to block BAX channel activity as potentially beneficial to attenuate both lysosomal defects and neurodegeneration occurring in PD.

Representation of the verb's argument-structure in the human brain

PubMed Central

Assadollahi, Ramin; Rockstroh, Brigitte S

2008-01-01

Background A verb's argument structure defines the number and relationships of participants needed for a complete event. One-argument (intransitive) verbs require only a subject to make a complete sentence, while two- and three-argument verbs (transitives and ditransitives) normally take direct and indirect objects. Cortical responses to verbs embedded into sentences (correct or with syntactic violations) indicate the processing of the verb's argument structure in the human brain. The two experiments of the present study examined whether and how this processing is reflected in distinct spatio-temporal cortical response patterns to isolated verbs and/or verbs presented in minimal context. Results The magnetoencephalogram was recorded while 22 native German-speaking adults saw 130 German verbs, presented one at a time for 150 ms each in experiment 1. Verb-evoked electromagnetic responses at 250 – 300 ms after stimulus onset, analyzed in source space, were higher in the left middle temporal gyrus for verbs that take only one argument, relative to two- and three-argument verbs. In experiment 2, the same verbs (presented in different order) were preceded by a proper name specifying the subject of the verb. This produced additional activation between 350 and 450 ms in or near the left inferior frontal gyrus, activity being larger and peaking earlier for one-argument verbs that required no further arguments to form a complete sentence. Conclusion Localization of sources of activity suggests that the activation in temporal and frontal regions varies with the degree by which representations of an event as a part of the verbs' semantics are completed during parsing. PMID:18644141

Functional Connectivity in Frequency-Tagged Cortical Networks During Active Harm Avoidance

PubMed Central

Miskovic, Vladimir; Príncipe, José C.; Keil, Andreas

2015-01-01

Abstract Many behavioral and cognitive processes are grounded in widespread and dynamic communication between brain regions. Thus, the quantification of functional connectivity with high temporal resolution is highly desirable for capturing in vivo brain function. However, many of the commonly used measures of functional connectivity capture only linear signal dependence and are based entirely on relatively simple quantitative measures such as mean and variance. In this study, the authors used a recently developed algorithm, the generalized measure of association (GMA), to quantify dynamic changes in cortical connectivity using steady-state visual evoked potentials (ssVEPs) measured in the context of a conditioned behavioral avoidance task. GMA uses a nonparametric estimator of statistical dependence based on ranks that are efficient and capable of providing temporal precision roughly corresponding to the timing of cognitive acts (∼100–200 msec). Participants viewed simple gratings predicting the presence/absence of an aversive loud noise, co-occurring with peripheral cues indicating whether the loud noise could be avoided by means of a key press (active) or not (passive). For active compared with passive trials, heightened connectivity between visual and central areas was observed in time segments preceding and surrounding the avoidance cue. Viewing of the threat stimuli also led to greater initial connectivity between occipital and central regions, followed by heightened local coupling among visual regions surrounding the motor response. Local neural coupling within extended visual regions was sustained throughout major parts of the viewing epoch. These findings are discussed in a framework of flexible synchronization between cortical networks as a function of experience and active sensorimotor coupling. PMID:25557925

Mast cell activation and neutrophil recruitment promotes early and robust inflammation in the meninges in EAE.

PubMed

Christy, Alison L; Walker, Margaret E; Hessner, Martin J; Brown, Melissa A

2013-05-01

The meninges are often considered inert tissues that house the CSF and provide protection for the brain and spinal cord. Yet emerging data demonstrates that they are also active sites of immune responses. Furthermore, the blood-CSF barrier surrounding meningeal blood vessels, together with the blood-brain barrier (BBB), is postulated to serve as a gateway for the pathological infiltration of immune cells into the CNS in multiple sclerosis (MS). Our previous studies using mast cell-deficient (Kit(W/Wv)) mice demonstrated that mast cells resident in the dura mater and pia mater exacerbate experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, by facilitating CNS inflammatory cell influx. Here we examined the underlying mechanisms that mediate these effects. We demonstrate that there are dramatic alterations in immune associated gene expression in the meninges in pre-clinical disease, including those associated with mast cell and neutrophil function. Meningeal mast cells are activated within 24 h of disease induction, but do not directly compromise CNS vascular integrity. Rather, through production of TNF, mast cells elicit an early influx of neutrophils, cells known to alter vascular permeability, into the meninges. These data add to the growing evidence that inflammation in the meninges precedes CNS immune cell infiltration and establish that mast cells are among the earliest participants in these disease-initiating events. We hypothesize that mast cell-dependent neutrophil recruitment and activation in the meninges promotes early breakdown of the local BBB and CSF-blood barrier allowing initial immune cell access to the CNS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Staff-reported antecedents to aggression in a post-acute brain injury treatment programme: What are they and what implications do they have for treatment?

PubMed Central

Giles, Gordon Muir; Scott, Karen; Manchester, David

2013-01-01

Research in psychiatric settings has found that staff attribute the majority of inpatient aggression to immediate environmental stressors. We sought to determine if staff working with persons with brain injury-related severe and chronic impairment make similar causal attributions. If immediate environmental stressors precipitate the majority of aggressive incidents in this client group, it is possible an increased focus on the management of factors that initiate client aggression may be helpful. The research was conducted in a low-demand treatment programme for individuals with chronic cognitive impairment due to acquired brain injury. Over a six-week period, 63 staff and a research assistant reported on 508 aggressive incidents. Staff views as to the causes of client aggression were elicited within 72 hours of observing an aggressive incident. Staff descriptions of causes were categorised using qualitative methods and analysed both qualitatively and quantitatively. Aggression towards staff was predominantly preceded by (a) actions that interrupted or redirected a client behaviour, (b) an activity demand, or (c) a physical intrusion. The majority of aggressive incidents appeared hostile/angry in nature and were not considered by staff to be pre-meditated. Common treatment approaches can be usefully augmented by a renewed focus on interventions aimed at reducing antecedents that provoke aggression. Possible approaches for achieving this are considered. PMID:23782342

Dendritic Degeneration, Neurovascular Defects, and Inflammation Precede Neuronal Loss in a Mouse Model for Tau-Mediated Neurodegeneration

PubMed Central

Jaworski, Tomasz; Lechat, Benoit; Demedts, David; Gielis, Lies; Devijver, Herman; Borghgraef, Peter; Duimel, Hans; Verheyen, Fons; Kügler, Sebastian; Van Leuven, Fred

2011-01-01

Adeno-associated virus (AAV)–mediated expression of wild-type or mutant P301L protein tau produces massive degeneration of pyramidal neurons without protein tau aggregation. We probed this novel model for genetic and structural factors and early parameters of pyramidal neurodegeneration. In yellow fluorescent protein–expressing transgenic mice, intracerebral injection of AAV-tauP301L revealed early damage to apical dendrites of CA1 pyramidal neurons, whereas their somata remained normal. Ultrastructurally, more and enlarged autophagic vacuoles were contained in degenerating dendrites and manifested as dark, discontinuous, vacuolated processes surrounded by activated astrocytes. Dendritic spines were lost in AAV-tauP301L–injected yellow fluorescent protein–expressing transgenic mice, and ultrastructurally, spines appeared dark and degenerating. In CX3CR1EGFP/EGFP-deficient mice, microglia were recruited early to neurons expressing human tau. The inflammatory response was accompanied by extravasation of plasma immunoglobulins. α2-Macroglobulin, but neither albumin nor transferrin, became lodged in the brain parenchyma. Large proteins, but not Evans blue, entered the brain of mice injected with AAV-tauP301L. Ultrastructurally, brain capillaries were constricted and surrounded by swollen astrocytes with extensions that contacted degenerating dendrites and axons. Together, these data corroborate the hypothesis that neuroinflammation participates essentially in tau-mediated neurodegeneration, and the model recapitulates early dendritic defects reminiscent of “dendritic amputation” in Alzheimer's disease. PMID:21839061

Staff-reported antecedents to aggression in a post-acute brain injury treatment programme: what are they and what implications do they have for treatment?

PubMed

Giles, Gordon Muir; Scott, Karen; Manchester, David

2013-01-01

Research in psychiatric settings has found that staff attribute the majority of in-patient aggression to immediate environmental stressors. We sought to determine if staff working with persons with brain injury-related severe and chronic impairment make similar causal attributions. If immediate environmental stressors precipitate the majority of aggressive incidents in this client group, it is possible an increased focus on the management of factors that initiate client aggression may be helpful. The research was conducted in a low-demand treatment programme for individuals with chronic cognitive impairment due to acquired brain injury. Over a six-week period, 63 staff and a research assistant reported on 508 aggressive incidents. Staff views as to the causes of client aggression were elicited within 72 hours of observing an aggressive incident. Staff descriptions of causes were categorised using qualitative methods and analysed both qualitatively and quantitatively. Aggression towards staff was predominantly preceded by (a) actions that interrupted or redirected a client behaviour, (b) an activity demand, or (c) a physical intrusion. The majority of aggressive incidents appeared hostile/angry in nature and were not considered by staff to be pre-meditated. Common treatment approaches can be usefully augmented by a renewed focus on interventions aimed at reducing antecedents that provoke aggression. Possible approaches for achieving this are considered.

Large-scale replication study reveals a limit on probabilistic prediction in language comprehension.

PubMed

Nieuwland, Mante S; Politzer-Ahles, Stephen; Heyselaar, Evelien; Segaert, Katrien; Darley, Emily; Kazanina, Nina; Von Grebmer Zu Wolfsthurn, Sarah; Bartolozzi, Federica; Kogan, Vita; Ito, Aine; Mézière, Diane; Barr, Dale J; Rousselet, Guillaume A; Ferguson, Heather J; Busch-Moreno, Simon; Fu, Xiao; Tuomainen, Jyrki; Kulakova, Eugenia; Husband, E Matthew; Donaldson, David I; Kohút, Zdenko; Rueschemeyer, Shirley-Ann; Huettig, Falk

2018-04-03

Do people routinely pre-activate the meaning and even the phonological form of upcoming words? The most acclaimed evidence for phonological prediction comes from a 2005 Nature Neuroscience publication by DeLong, Urbach and Kutas, who observed a graded modulation of electrical brain potentials (N400) to nouns and preceding articles by the probability that people use a word to continue the sentence fragment ('cloze'). In our direct replication study spanning 9 laboratories ( N =334), pre-registered replication-analyses and exploratory Bayes factor analyses successfully replicated the noun-results but, crucially, not the article-results. Pre-registered single-trial analyses also yielded a statistically significant effect for the nouns but not the articles. Exploratory Bayesian single-trial analyses showed that the article-effect may be non-zero but is likely far smaller than originally reported and too small to observe without very large sample sizes. Our results do not support the view that readers routinely pre-activate the phonological form of predictable words. © 2018, Nieuwland et al.

A Primary Role for Nucleus Accumbens and Related Limbic Network in Vocal Tics.

PubMed

McCairn, Kevin W; Nagai, Yuji; Hori, Yukiko; Ninomiya, Taihei; Kikuchi, Erika; Lee, Ju-Young; Suhara, Tetsuya; Iriki, Atsushi; Minamimoto, Takafumi; Takada, Masahiko; Isoda, Masaki; Matsumoto, Masayuki

2016-01-20

Inappropriate vocal expressions, e.g., vocal tics in Tourette syndrome, severely impact quality of life. Neural mechanisms underlying vocal tics remain unexplored because no established animal model representing the condition exists. We report that unilateral disinhibition of the nucleus accumbens (NAc) generates vocal tics in monkeys. Whole-brain PET imaging identified prominent, bilateral limbic cortico-subcortical activation. Local field potentials (LFPs) developed abnormal spikes in the NAc and the anterior cingulate cortex (ACC). Vocalization could occur without obvious LFP spikes, however, when phase-phase coupling of alpha oscillations were accentuated between the NAc, ACC, and the primary motor cortex. These findings contrasted with myoclonic motor tics induced by disinhibition of the dorsolateral putamen, where PET activity was confined to the ipsilateral sensorimotor system and LFP spikes always preceded motor tics. We propose that vocal tics emerge as a consequence of dysrhythmic alpha coupling between critical nodes in the limbic and motor networks. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

Large-scale replication study reveals a limit on probabilistic prediction in language comprehension

PubMed Central

Politzer-Ahles, Stephen; Heyselaar, Evelien; Segaert, Katrien; Darley, Emily; Kazanina, Nina; Von Grebmer Zu Wolfsthurn, Sarah; Bartolozzi, Federica; Kogan, Vita; Ito, Aine; Mézière, Diane; Barr, Dale J; Rousselet, Guillaume A; Ferguson, Heather J; Busch-Moreno, Simon; Fu, Xiao; Tuomainen, Jyrki; Kulakova, Eugenia; Husband, E Matthew; Donaldson, David I; Kohút, Zdenko; Rueschemeyer, Shirley-Ann; Huettig, Falk

2018-01-01

Do people routinely pre-activate the meaning and even the phonological form of upcoming words? The most acclaimed evidence for phonological prediction comes from a 2005 Nature Neuroscience publication by DeLong, Urbach and Kutas, who observed a graded modulation of electrical brain potentials (N400) to nouns and preceding articles by the probability that people use a word to continue the sentence fragment (‘cloze’). In our direct replication study spanning 9 laboratories (N=334), pre-registered replication-analyses and exploratory Bayes factor analyses successfully replicated the noun-results but, crucially, not the article-results. Pre-registered single-trial analyses also yielded a statistically significant effect for the nouns but not the articles. Exploratory Bayesian single-trial analyses showed that the article-effect may be non-zero but is likely far smaller than originally reported and too small to observe without very large sample sizes. Our results do not support the view that readers routinely pre-activate the phonological form of predictable words. PMID:29631695

Modulation of attention network activation under antidepressant agents in healthy subjects.

PubMed

Graf, Heiko; Abler, Birgit; Hartmann, Antonie; Metzger, Coraline D; Walter, Martin

2013-07-01

While antidepressants are supposed to exert similar effects on mood and drive via various mechanisms of action, diverging effects are observed regarding side-effects and accordingly on neural correlates of motivation, emotion, reward and salient stimuli processing as a function of the drugs impact on neurotransmission. In the context of erotic stimulation, a unidirectional modulation of attentional functioning despite opposite effects on sexual arousal has been suggested for the selective serotonin reuptake-inhibitor (SSRI) paroxetine and the selective dopamine and noradrenaline reuptake-inhibitor (SDNRI) bupropion. To further elucidate the effects of antidepressant-related alterations of neural attention networks, we investigated 18 healthy males under subchronic administration (7 d) of paroxetine (20 mg), bupropion (150 mg) and placebo within a randomized placebo-controlled cross-over double-blind functional magnetic resonance imaging (fMRI) design during an established preceding attention task. Neuropsychological effects beyond the fMRI-paradigm were assessed by measuring alertness and divided attention. Comparing preceding attention periods of salient vs. neutral pictures, we revealed congruent effects of both drugs vs. placebo within the anterior midcingulate cortex, dorsolateral prefrontal cortex, anterior prefrontal cortex, superior temporal gyrus, anterior insula and the thalamus. Relatively decreased activation in this network was paralleled by slower reaction times in the divided attention task in both verum conditions compared to placebo. Our results suggest similar effects of antidepressant treatments on behavioural and neural attentional functioning by diverging neurochemical pathways. Concurrent alterations of brain regions within a fronto-parietal and cingulo-opercular attention network for top-down control could point to basic neural mechanisms of antidepressant action irrespective of receptor profiles.

Memory timeline: Brain ERP C250 (not P300) is an early biomarker of short-term storage.

PubMed

Chapman, Robert M; Gardner, Margaret N; Mapstone, Mark; Dupree, Haley M; Antonsdottir, Inga M

2015-04-16

Brain event-related potentials (ERPs) offer a quantitative link between neurophysiological activity and cognitive performance. ERPs were measured while young adults performed a task that required storing a relevant stimulus in short-term memory. Using principal components analysis, ERP component C250 (maximum at 250 ms post-stimulus) was extracted from a set of ERPs that were separately averaged for various task conditions, including stimulus relevancy and stimulus sequence within a trial. C250 was more positive in response to task-specific stimuli that were successfully stored in short-term memory. This relationship between C250 and short-term memory storage of a stimulus was confirmed by a memory probe recall test where the behavioral recall of a stimulus was highly correlated with its C250 amplitude. ERP component P300 (and its subcomponents of P3a and P3b, which are commonly thought to represent memory operations) did not show a pattern of activation reflective of storing task-relevant stimuli. C250 precedes the P300, indicating that initial short-term memory storage may occur earlier than previously believed. Additionally, because C250 is so strongly predictive of a stimulus being stored in short-term memory, C250 may provide a strong index of early memory operations. Copyright © 2015 Elsevier B.V. All rights reserved.

Sustained and transient attentional processes modulate neural predictors of memory encoding in consecutive time periods

PubMed Central

Padovani, Tullia; Koenig, Thomas; Eckstein, Doris; Perrig, Walter J

2013-01-01

Memory formation is commonly thought to rely on brain activity following an event. Yet, recent research has shown that even brain activity previous to an event can predict later recollection (subsequent memory effect, SME). In order to investigate the attentional sources of the SME, event-related potentials (ERPs) elicited by task cues preceding target words were recorded in a switched task paradigm that was followed by a surprise recognition test. Stay trials, that is, those with the same task as the previous trial, were contrasted with switch trials, which included a task switch compared to the previous trial. The underlying assumption was that sustained attention would be dominant in stay trials and that transient attentional reconfiguration processes would be dominant in switch trials. To determine the SME, local and global statistics of scalp electric fields were used to identify differences between subsequently remembered and forgotten items. Results showed that the SME in stay trials occurred in a time window from 2 to 1 sec before target onset, whereas the SME in switch trials occurred subsequently, in a time window from 1 to 0 sec before target onset. Both SMEs showed a frontal negativity resembling the topography of previously reported effects, which suggests that sustained and transient attentional processes contribute to the prestimulus SME in consecutive time periods. PMID:24381815

A single dual-stream framework for syntactic computations in music and language.

PubMed

Musso, Mariacristina; Weiller, Cornelius; Horn, Andreas; Glauche, Volkmer; Umarova, Roza; Hennig, Jürgen; Schneider, Albrecht; Rijntjes, Michel

2015-08-15

This study is the first to compare in the same subjects the specific spatial distribution and the functional and anatomical connectivity of the neuronal resources that activate and integrate syntactic representations during music and language processing. Combining functional magnetic resonance imaging with functional connectivity and diffusion tensor imaging-based probabilistic tractography, we examined the brain network involved in the recognition and integration of words and chords that were not hierarchically related to the preceding syntax; that is, those deviating from the universal principles of grammar and tonal relatedness. This kind of syntactic processing in both domains was found to rely on a shared network in the left hemisphere centered on the inferior part of the inferior frontal gyrus (IFG), including pars opercularis and pars triangularis, and on dorsal and ventral long association tracts connecting this brain area with temporo-parietal regions. Language processing utilized some adjacent left hemispheric IFG and middle temporal regions more than music processing, and music processing also involved right hemisphere regions not activated in language processing. Our data indicate that a dual-stream system with dorsal and ventral long association tracts centered on a functionally and structurally highly differentiated left IFG is pivotal for domain-general syntactic competence over a broad range of elements including words and chords. Copyright © 2015 Elsevier Inc. All rights reserved.

Dynamic Cross-Entropy.

PubMed

Aur, Dorian; Vila-Rodriguez, Fidel

2017-01-01

Complexity measures for time series have been used in many applications to quantify the regularity of one dimensional time series, however many dynamical systems are spatially distributed multidimensional systems. We introduced Dynamic Cross-Entropy (DCE) a novel multidimensional complexity measure that quantifies the degree of regularity of EEG signals in selected frequency bands. Time series generated by discrete logistic equations with varying control parameter r are used to test DCE measures. Sliding window DCE analyses are able to reveal specific period doubling bifurcations that lead to chaos. A similar behavior can be observed in seizures triggered by electroconvulsive therapy (ECT). Sample entropy data show the level of signal complexity in different phases of the ictal ECT. The transition to irregular activity is preceded by the occurrence of cyclic regular behavior. A significant increase of DCE values in successive order from high frequencies in gamma to low frequencies in delta band reveals several phase transitions into less ordered states, possible chaos in the human brain. To our knowledge there are no reliable techniques able to reveal the transition to chaos in case of multidimensional times series. In addition, DCE based on sample entropy appears to be robust to EEG artifacts compared to DCE based on Shannon entropy. The applied technique may offer new approaches to better understand nonlinear brain activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Sustained and transient attentional processes modulate neural predictors of memory encoding in consecutive time periods.

PubMed

Padovani, Tullia; Koenig, Thomas; Eckstein, Doris; Perrig, Walter J

2013-07-01

Memory formation is commonly thought to rely on brain activity following an event. Yet, recent research has shown that even brain activity previous to an event can predict later recollection (subsequent memory effect, SME). In order to investigate the attentional sources of the SME, event-related potentials (ERPs) elicited by task cues preceding target words were recorded in a switched task paradigm that was followed by a surprise recognition test. Stay trials, that is, those with the same task as the previous trial, were contrasted with switch trials, which included a task switch compared to the previous trial. The underlying assumption was that sustained attention would be dominant in stay trials and that transient attentional reconfiguration processes would be dominant in switch trials. To determine the SME, local and global statistics of scalp electric fields were used to identify differences between subsequently remembered and forgotten items. Results showed that the SME in stay trials occurred in a time window from 2 to 1 sec before target onset, whereas the SME in switch trials occurred subsequently, in a time window from 1 to 0 sec before target onset. Both SMEs showed a frontal negativity resembling the topography of previously reported effects, which suggests that sustained and transient attentional processes contribute to the prestimulus SME in consecutive time periods.

Activation of Ras-ERK Signaling and GSK-3 by Amyloid Precursor Protein and Amyloid Beta Facilitates Neurodegeneration in Alzheimer's Disease.

PubMed

Kirouac, Lisa; Rajic, Alexander J; Cribbs, David H; Padmanabhan, Jaya

2017-01-01

It is widely accepted that amyloid β (Aβ) generated from amyloid precursor protein (APP) oligomerizes and fibrillizes to form neuritic plaques in Alzheimer's disease (AD), yet little is known about the contribution of APP to intracellular signaling events preceding AD pathogenesis. The data presented here demonstrate that APP expression and neuronal exposure to oligomeric Aβ42 enhance Ras/ERK signaling cascade and glycogen synthase kinase 3 (GSK-3) activation. We find that RNA interference (RNAi)-directed knockdown of APP in B103 rat neuroblastoma cells expressing APP inhibits Ras-ERK signaling and GSK-3 activation, indicating that APP acts upstream of these signal transduction events. Both ERK and GSK-3 are known to induce hyperphosphorylation of tau and APP at Thr668, and our findings suggest that aberrant signaling by APP facilitates these events. Supporting this notion, analysis of human AD brain samples showed increased expression of Ras, activation of GSK-3, and phosphorylation of APP and tau, which correlated with Aβ levels in the AD brains. Furthermore, treatment of primary rat neurons with Aβ recapitulated these events and showed enhanced Ras-ERK signaling, GSK-3 activation, upregulation of cyclin D1, and phosphorylation of APP and tau. The finding that Aβ induces Thr668 phosphorylation on APP, which enhances APP proteolysis and Aβ generation, denotes a vicious feedforward mechanism by which APP and Aβ promote tau hyperphosphorylation and neurodegeneration in AD. Based on these results, we hypothesize that aberrant proliferative signaling by APP plays a fundamental role in AD neurodegeneration and that inhibition of this would impede cell cycle deregulation and neurodegeneration observed in AD.

Adolescents' Neural Processing of Risky Decisions: Effects of Sex and Behavioral Disinhibition.

PubMed

Crowley, Thomas J; Dalwani, Manish S; Mikulich-Gilbertson, Susan K; Young, Susan E; Sakai, Joseph T; Raymond, Kristen M; McWilliams, Shannon K; Roark, Melissa J; Banich, Marie T

2015-01-01

Accidental injury and homicide, relatively common among adolescents, often follow risky behaviors; those are done more by boys and by adolescents with greater behavioral disinhibition (BD). Neural processing during adolescents' risky decision-making will differ in youths with greater BD severity, and in males vs. females, both before cautious behaviors and before risky behaviors. 81 adolescents (PATIENTS with substance and conduct problems, and comparison youths (Comparisons)), assessed in a 2 x 2 design ( Comparisons x Male:Female) repeatedly decided between doing a cautious behavior that earned 1 cent, or a risky one that either won 5 or lost 10 cents. Odds of winning after risky responses gradually decreased. Functional magnetic resonance imaging captured brain activity during 4-sec deliberation periods preceding responses. Most neural activation appeared in known decision-making structures. PATIENTS, who had more severe BD scores and clinical problems than Comparisons, also had extensive neural hypoactivity. Comparisons' greater activation before cautious responses included frontal pole, medial prefrontal cortex, striatum, and other regions; and before risky responses, insula, temporal, and parietal regions. Males made more risky and fewer cautious responses than females, but before cautious responses males activated numerous regions more than females. Before risky behaviors female-greater activation was more posterior, and male-greater more anterior. Neural processing differences during risky-cautious decision-making may underlie group differences in adolescents' substance-related and antisocial risk-taking. Patients reported harmful real-life decisions and showed extensive neural hypoactivity during risky-or-cautious decision-making. Males made more risky responses than females; apparently biased toward risky decisions, males (compared with females) utilized many more neural resources to make and maintain cautious decisions, indicating an important risk-related brain sexual dimorphism. The results suggest new possibilities for prevention and management of excessive, dangerous adolescent risk-taking.

The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

PubMed Central

Carhart-Harris, Robin L.; Leech, Robert; Hellyer, Peter J.; Shanahan, Murray; Feilding, Amanda; Tagliazucchi, Enzo; Chialvo, Dante R.; Nutt, David

2014-01-01

Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state. PMID:24550805

The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs.

PubMed

Carhart-Harris, Robin L; Leech, Robert; Hellyer, Peter J; Shanahan, Murray; Feilding, Amanda; Tagliazucchi, Enzo; Chialvo, Dante R; Nutt, David

2014-01-01

Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of "primary states" is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit "criticality," i.e., the property of being poised at a "critical" point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.

Pericytes as Inducers of Rapid, Matrix Metalloproteinase-9-Dependent Capillary Damage during Ischemia

PubMed Central

Underly, Robert G.; Levy, Manuel; Hartmann, David A.; Grant, Roger I.; Watson, Ashley N.

2017-01-01

Blood–brain barrier disruption (BBB) and release of toxic blood molecules into the brain contributes to neuronal injury during stroke and other cerebrovascular diseases. While pericytes are builders and custodians of the BBB in the normal brain, their impact on BBB integrity during ischemia remains unclear. We imaged pericyte-labeled transgenic mice with in vivo two-photon microscopy to examine the relationship between pericytes and blood plasma leakage during photothrombotic occlusion of cortical capillaries. Upon cessation of capillary flow, we observed that plasma leakage occurred with three times greater frequency in regions where pericyte somata adjoined the endothelium. Pericyte somata covered only 7% of the total capillary length in cortex, indicating that a disproportionate amount of leakage occurred from a small fraction of the capillary bed. Plasma leakage was preceded by rapid activation of matrix metalloproteinase (MMP) at pericyte somata, which was visualized at high resolution in vivo using a fluorescent probe for matrix metalloproteinase-2/9 activity, fluorescein isothiocyanate (FITC)-gelatin. Coinjection of an MMP-9 inhibitor, but not an MMP-2 inhibitor, reduced pericyte-associated FITC-gelatin fluorescence and plasma leakage. These results suggest that pericytes contribute to rapid and localized proteolytic degradation of the BBB during cerebral ischemia. SIGNIFICANCE STATEMENT Pericytes are a key component of the neurovascular unit and are essential for normal BBB function. However, during acute ischemia, we find that pericytes are involved in creating rapid and heterogeneous BBB disruption in the capillary bed. The mechanism by which pericytes contribute to BBB damage warrants further investigation, as it may yield new therapeutic targets for acute stroke injury and other neurological diseases involving capillary flow impairment. PMID:28053036

Cerebral amyloid-beta protein accumulation with aging in cotton-top tamarins: a model of early Alzheimer's disease?

PubMed

Lemere, Cynthia A; Oh, Jiwon; Stanish, Heather A; Peng, Ying; Pepivani, Imelda; Fagan, Anne M; Yamaguchi, Haruyasu; Westmoreland, Susan V; Mansfield, Keith G

2008-04-01

Alzheimer's disease (AD) is the most common progressive form of dementia in the elderly. Two major neuropathological hallmarks of AD include cerebral deposition of amyloid-beta protein (Abeta) into plaques and blood vessels, and the presence of neurofibrillary tangles in brain. In addition, activated microglia and reactive astrocytes are often associated with plaques and tangles. Numerous other proteins are associated with plaques in human AD brain, including Apo E and ubiquitin. The amyloid precursor protein and its shorter fragment, Abeta, are homologous between humans and non-human primates. Cerebral Abeta deposition has been reported previously for rhesus monkeys, vervets, squirrel monkeys, marmosets, lemurs, cynomologous monkeys, chimpanzees, and orangutans. Here we report, for the first time, age-related neuropathological changes in cotton-top tamarins (CTT, Saguinus oedipus), an endangered non-human primate native to the rainforests of Colombia and Costa Rica. Typical lifespan is 13-14 years of age in the wild and 15-20+ years in captivity. We performed detailed immunohistochemical analyses of Abeta deposition and associated pathogenesis in archived brain sections from 36 tamarins ranging in age from 6-21 years. Abeta plaque deposition was observed in 16 of the 20 oldest tamarins (>12 years). Plaques contained mainly Abeta42, and in the oldest animals, were associated with reactive astrocytes, activated microglia, Apo E, and ubiquitin-positive dystrophic neurites, similar to human plaques. Vascular Abeta was detected in 14 of the 20 aged tamarins; Abeta42 preceded Abeta40 deposition. Phospho-tau labeled dystrophic neurites and tangles, typically present in human AD, were absent in the tamarins. In conclusion, tamarins may represent a model of early AD pathology.

Calcium dysregulation and Cdk5-ATM pathway involved in a mouse model of fragile X-associated tremor/ataxia syndrome.

PubMed

Robin, Gaëlle; López, José R; Espinal, Glenda M; Hulsizer, Susan; Hagerman, Paul J; Pessah, Isaac N

2017-07-15

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurological disorder that affects premutation carriers with 55-200 CGG-expansion repeats (preCGG) in FMR1, presenting with early alterations in neuronal network formation and function that precede neurodegeneration. Whether intranuclear inclusions containing DNA damage response (DDR) proteins are causally linked to abnormal synaptic function, neuronal growth and survival are unknown. In a mouse that harbors a premutation CGG expansion (preCGG), cortical and hippocampal FMRP expression is moderately reduced from birth through adulthood, with greater FMRP reductions in the soma than in the neurite, despite several-fold elevation of Fmr1 mRNA levels. Resting cytoplasmic calcium concentration ([Ca2+]i) in cultured preCGG hippocampal neurons is chronically elevated, 3-fold compared to Wt; elevated ROS and abnormal glutamatergic responses are detected at 14 DIV. Elevated µ-calpain activity and a higher p25/p35 ratio in the cortex of preCGG young adult mice indicate abnormal Cdk5 regulation. In support, the Cdk5 substrate, ATM, is upregulated by 1.5- to 2-fold at P0 and 6 months in preCGG brain, as is p-Ser1981-ATM. Bax:Bcl-2 is 30% higher in preCGG brain, indicating a greater vulnerability to apoptotic activation. Elevated [Ca2+]i, ROS, and DDR signals are normalized with dantrolene. Chronic [Ca2+]i dysregulation amplifies Cdk5-ATM signaling, possibly linking impaired glutamatergic signaling and DDR to neurodegeneration in preCGG brain. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

EEG Functional Connectivity Prior to Sleepwalking: Evidence of Interplay Between Sleep and Wakefulness

PubMed Central

Desjardins, Marie-Ève; Carrier, Julie; Lina, Jean-Marc; Fortin, Maxime; Gosselin, Nadia; Montplaisir, Jacques

2017-01-01

Abstract Study Objectives: Although sleepwalking (somnambulism) affects up to 4% of adults, its pathophysiology remains poorly understood. Sleepwalking can be preceded by fluctuations in slow-wave sleep EEG signals, but the significance of these pre-episode changes remains unknown and methods based on EEG functional connectivity have yet to be used to better comprehend the disorder. Methods: We investigated the sleep EEG of 27 adult sleepwalkers (mean age: 29 ± 7.6 years) who experienced a somnambulistic episode during slow-wave sleep. The 20-second segment of sleep EEG immediately preceding each patient’s episode was compared with the 20-second segment occurring 2 minutes prior to episode onset. Results: Results from spectral analyses revealed increased delta and theta spectral power in the 20 seconds preceding the episodes’ onset as compared to the 20 seconds occurring 2 minutes before the episodes. The imaginary part of the coherence immediately prior to episode onset revealed (1) decreased delta EEG functional connectivity in parietal and occipital regions, (2) increased alpha connectivity over a fronto-parietal network, and (3) increased beta connectivity involving symmetric inter-hemispheric networks implicating frontotemporal, parietal and occipital areas. Conclusions: Taken together, these modifications in EEG functional connectivity suggest that somnambulistic episodes are preceded by brain processes characterized by the co-existence of arousal and deep sleep. PMID:28204773

BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE

PubMed Central

Cunnane, SC; Nugent, S; Roy, M; Courchesne-Loyer, A; Croteau, E; Tremblay, S; Castellano, A; Pifferi, F; Bocti, C; Paquet, N; Begdouri, H; Bentourkia, M; Turcotte, E; Allard, M; Barberger-Gateau, P; Fulop, T; Rapoport, S

2012-01-01

Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may include defects in glucose transport at the blood-brain barrier, glycolysis, and/or mitochondrial function. Methodological issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization which, in turn, may increase the risk of declining brain glucose uptake, at least in some regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e. that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and, hence, reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to – (i) improve insulin sensitivity by improving systemic glucose utilization, or (ii) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia. PMID:21035308

Predictive Factors of Regular Physical Activity among Middle-Aged Women in the West of Iran, Hamadan: Application of PRECEDE Model.

PubMed

Emdadi, Shohreh; Hazavehie, Seyed Mohammad Mehdi; Soltanian, Alireza; Bashirian, Saeed; Heidari Moghadam, Rashid

2015-01-01

Regular physical activity is important for midlife women. Models and theories help better understanding this behavior among middle-aged women and better planning for change behavior in target group. This study aimed to investigate predictive factors of regular physical activity among middle-aged women based on PRECEDE model as a theoretical framework. This descriptive-analytical study was performed on 866 middle-aged women of Hamadan City western Iran, recruited with a proportional stratified sampling method in 2015. The participants completed a self-administered questionnaire including questions on demographic characteristics and PRECEDE model constructs and IPAQ questionnaire. Data were then analyzed by SPSS-16 and AMOS-16 using the Pearson correlation test and the pathway analysis method. Overall, 57% of middle-aged women were inactive (light level) or not sufficiently active. With SEM (Structural Equation Modeling) analysis, knowledge b=0.84, P<0.001, attitude b=0.799, P<0.001, self-efficacy b=0.633, P<0.001 as predisposing factor and social support as reinforcing factor b=0.2, P<0.001 were the most important predictors for physical activity among middle-aged women in Hamadan. The framework of the PRECEDE model is useful in understanding regular physical activity among middle-aged women. Furthermore, results showed the importance of predisposing and reinforcing factors when planning educational interventions.

Predictive Coding or Evidence Accumulation? False Inference and Neuronal Fluctuations

PubMed Central

Friston, Karl J.; Kleinschmidt, Andreas

2010-01-01

Perceptual decisions can be made when sensory input affords an inference about what generated that input. Here, we report findings from two independent perceptual experiments conducted during functional magnetic resonance imaging (fMRI) with a sparse event-related design. The first experiment, in the visual modality, involved forced-choice discrimination of coherence in random dot kinematograms that contained either subliminal or periliminal motion coherence. The second experiment, in the auditory domain, involved free response detection of (non-semantic) near-threshold acoustic stimuli. We analysed fluctuations in ongoing neural activity, as indexed by fMRI, and found that neuronal activity in sensory areas (extrastriate visual and early auditory cortex) biases perceptual decisions towards correct inference and not towards a specific percept. Hits (detection of near-threshold stimuli) were preceded by significantly higher activity than both misses of identical stimuli or false alarms, in which percepts arise in the absence of appropriate sensory input. In accord with predictive coding models and the free-energy principle, this observation suggests that cortical activity in sensory brain areas reflects the precision of prediction errors and not just the sensory evidence or prediction errors per se. PMID:20369004

Withholding response in the face of a smile: age-related differences in prefrontal sensitivity to Nogo cues following happy and angry faces.

PubMed

Todd, Rebecca M; Lee, Wayne; Evans, Jennifer W; Lewis, Marc D; Taylor, Margot J

2012-07-01

The modulation of control processes by stimulus salience, as well as associated neural activation, changes over development. We investigated age-related differences in the influence of facial emotion on brain activation when an action had to be withheld, focusing on a developmental period characterized by rapid social-emotional and cognitive change. Groups of kindergarten and young school-aged children and a group of young adults performed a modified Go/Nogo task. Response cues were preceded by happy or angry faces. After controlling for task performance, left orbitofrontal regions discriminated trials with happy vs. angry faces in children but not in adults when a response was withheld, and this effect decreased parametrically with age group. Age-related changes in prefrontal responsiveness to facial expression were not observed when an action was required, nor did this region show age-related activation changes with the demand to withhold a response in general. Such results reveal age-related differences in prefrontal activation that are specific to stimulus valence and depend on the action required. Copyright © 2012 Elsevier Ltd. All rights reserved.

MRimaging findings after ventricular puncture in patients with SAH.

PubMed

Tominaga, J; Shimoda, M; Oda, S; Kumasaka, A; Yamazaki, K; Tsugane, R

2001-11-01

Using magnetic resonance (MR) imaging, we studied brain injury from ventricular puncture performed during craniotomy in the acute stage of subarachnoid hemorrhage (SAH). 80 patients underwent craniotomy for aneurysm obliteration within 48 hr after SAH, ventricular puncture for drainage of cerebrospinal fluid (CSF) was performed to reduce intracranial pressure. MR imaging was performed within 3 days following surgery to measure the size of the lesion, and was repeated on postoperative days 14 and 30. Of the 80 patients with ventricular puncture preceding craniotomy, 65 (81%) showed MR evidence of brain injury from the puncture. Overall, 149 lesions were detected. According to coronal images, cortical injuries (54 cases), penetrating injury to tracts along the ventricular tube (55 cases), caudate injury (25 cases), and corpus callosum injury (15 cases). Brain injuries from ventricular puncture did not correlate significantly to patient outcome. While ventricular puncture and drainage of CSF can readily be performed to decrease brain volume at the time of craniotomy in acute-stage SAH, neurosurgeons should be aware of a surprisingly high incidence of brain injury complicating puncture.

Non-invasive fluorescent imaging of gliosis in transgenic mice for profiling developmental neurotoxicity

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

Ho, Gideon; Zhang Chunyan; Zhuo Lang

2007-05-15

Gliosis is a universal response of Brain to almost all types of neural insults, including neurotoxicity, neurodegeneration, viral infection, and stroke. A hallmark of gliotic reaction is the up-regulation of the astrocytic biomarker GFAP (glial fibrillary acidic protein), which often precedes the anatomically apparent damages in Brain. In this study, neonatal transgenic mice at postnatal day (PD) 4 expressing GFP (green fluorescent protein) under the control of a widely used 2.2-kb human GFAP promoter in Brain are treated with two model neurotoxicants, 1-methyl-4(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH{sub 3}-MPTP), and kainic acid (KA), respectively, to induce gliosis. Here we show that the neurotoxicant-induced acutemore » gliosis can be non-invasively imaged and quantified in Brain of conscious (un-anesthetized) mice in real-time, at 0, 2, 4, 6, and 8 h post-toxicant dosing. Therefore the current methodology could be a useful tool for studying the developmental aspects of neuropathies and neurotoxicity.« less

Spatiotemporal neurodynamics of automatic temporal expectancy in 9-month old infants.

PubMed

Mento, Giovanni; Valenza, Eloisa

2016-11-04

Anticipating events occurrence (Temporal Expectancy) is a crucial capacity for survival. Yet, there is little evidence about the presence of cortical anticipatory activity from infancy. In this study we recorded the High-density electrophysiological activity in 9 month-old infants and adults undergoing an audio-visual S1-S2 paradigm simulating a lifelike "Peekaboo" game inducing automatic temporal expectancy of smiling faces. The results indicate in the S2-preceding Contingent Negative Variation (CNV) an early electrophysiological signature of expectancy-based anticipatory cortical activity. Moreover, the progressive CNV amplitude increasing across the task suggested that implicit temporal rule learning is at the basis of expectancy building-up over time. Cortical source reconstruction suggested a common CNV generator between adults and infants in the right prefrontal cortex. The decrease in the activity of this area across the task (time-on-task effect) further implied an early, core role of this region in implicit temporal rule learning. By contrast, a time-on-task activity boost was found in the supplementary motor area (SMA) in adults and in the temporoparietal regions in infants. Altogether, our findings suggest that the capacity of the human brain to translate temporal predictions into anticipatory neural activity emerges ontogenetically early, although the underlying spatiotemporal cortical dynamics change across development.

Functional response in ventral temporal cortex differentiates mild cognitive impairment from normal aging

PubMed Central

Gold, Brian T.; Jiang, Yang; Jicha, Greg A.; Smith, Charles D.

2010-01-01

The present study sought to identify altered brain activation patterns in amnestic mild cognitive impairment (MCI) that could precede frank task impairment and neocortical atrophy. A high accuracy lexical decision (LD) task was therefore employed. Both MCI and normal senior (NS) groups completed the LD task while functional magnetic resonance imaging (fMRI) was performed. Accuracy on the LD task was high (≥ 89% correct for both groups), and both groups activated a network of occipitotemporal regions and inferior frontal cortex. However, compared to the NS group, the MCI group showed reduced fMRI activation in these regions and increased activation in bilateral portions of anterior cingluate cortex. Results from a voxel-based morphometry analysis indicate that altered activations in the MCI group were not within regions of atrophy. Receiver operating characteristic curves demonstrate that reduced fMRI response in the left and right mid-fusiform gyri accurately discriminate MCI from NS. When activation magnitude in both fusiform gyri were included in a single logistic regression model, group classification accuracy was very high (area under the curve = 0.93). These results show that a disrupted functional response in the ventral temporal lobe accurately distinguishes individuals with MCI from normal seniors, a finding which may have implications for identifying seniors at risk for cognitive decline. PMID:20063353

Echoes of the spoken past: how auditory cortex hears context during speech perception

PubMed Central

Skipper, Jeremy I.

2014-01-01

What do we hear when someone speaks and what does auditory cortex (AC) do with that sound? Given how meaningful speech is, it might be hypothesized that AC is most active when other people talk so that their productions get decoded. Here, neuroimaging meta-analyses show the opposite: AC is least active and sometimes deactivated when participants listened to meaningful speech compared to less meaningful sounds. Results are explained by an active hypothesis-and-test mechanism where speech production (SP) regions are neurally re-used to predict auditory objects associated with available context. By this model, more AC activity for less meaningful sounds occurs because predictions are less successful from context, requiring further hypotheses be tested. This also explains the large overlap of AC co-activity for less meaningful sounds with meta-analyses of SP. An experiment showed a similar pattern of results for non-verbal context. Specifically, words produced less activity in AC and SP regions when preceded by co-speech gestures that visually described those words compared to those words without gestures. Results collectively suggest that what we ‘hear’ during real-world speech perception may come more from the brain than our ears and that the function of AC is to confirm or deny internal predictions about the identity of sounds. PMID:25092665

Pupillometric evidence for the decoupling of attention from perceptual input during offline thought.

PubMed

Smallwood, Jonathan; Brown, Kevin S; Tipper, Christine; Giesbrecht, Barry; Franklin, Michael S; Mrazek, Michael D; Carlson, Jean M; Schooler, Jonathan W

2011-03-25

Accumulating evidence suggests that the brain can efficiently process both external and internal information. The processing of internal information is a distinct "offline" cognitive mode that requires not only spontaneously generated mental activity; it has also been hypothesized to require a decoupling of attention from perception in order to separate competing streams of internal and external information. This process of decoupling is potentially adaptive because it could prevent unimportant external events from disrupting an internal train of thought. Here, we use measurements of pupil diameter (PD) to provide concrete evidence for the role of decoupling during spontaneous cognitive activity. First, during periods conducive to offline thought but not during periods of task focus, PD exhibited spontaneous activity decoupled from task events. Second, periods requiring external task focus were characterized by large task evoked changes in PD; in contrast, encoding failures were preceded by episodes of high spontaneous baseline PD activity. Finally, high spontaneous PD activity also occurred prior to only the slowest 20% of correct responses, suggesting high baseline PD indexes a distinct mode of cognitive functioning. Together, these data are consistent with the decoupling hypothesis, which suggests that the capacity for spontaneous cognitive activity depends upon minimizing disruptions from the external world.

Neurotoxicity of carbonyl sulfide in F344 rats following inhalation exposure for up to 12 weeks.

PubMed

Morgan, Daniel L; Little, Peter B; Herr, David W; Moser, Virginia C; Collins, Bradley; Herbert, Ronald; Johnson, G Allan; Maronpot, Robert R; Harry, G Jean; Sills, Robert C

2004-10-15

Carbonyl sulfide (COS), a high-priority Clean Air Act chemical, was evaluated for neurotoxicity in short-term studies. F344 rats were exposed to 75-600 ppm COS 6 h per day, 5 days per week for up to 12 weeks. In rats exposed to 500 or 600 ppm for up to 4 days, malacia and microgliosis were detected in numerous neuroanatomical regions of the brain by conventional optical microscopy and magnetic resonance microscopy (MRM). After a 2-week exposure to 400 ppm, rats were evaluated using a functional observational battery. Slight gait abnormality was detected in 50% of the rats and hypotonia was present in all rats exposed to COS. Decreases in motor activity, and forelimb and hindlimb grip strength were also detected. In rats exposed to 400 ppm for 12 weeks, predominant lesions were in the parietal cortex area 1 (necrosis) and posterior colliculus (neuronal loss, microgliosis, hemorrhage), and occasional necrosis was present in the putamen, thalamus, and anterior olivary nucleus. Carbonyl sulfide specifically targeted the auditory system including the olivary nucleus, nucleus of the lateral lemniscus, and posterior colliculus. Consistent with these findings were alterations in the amplitude of the brainstem auditory evoked responses (BAER) for peaks N3, P4, N4, and N5 that represented changes in auditory transmission between the anterior olivary nucleus to the medial geniculate nucleus in animals after exposure for 2 weeks to 400 ppm COS. A concentration-related decrease in cytochrome oxidase activity was detected in the posterior colliculus and parietal cortex of exposed rats as early as 3 weeks. Cytochrome oxidase activity was significantly decreased at COS concentrations that did not cause detectable lesions, suggesting that disruption of the mitochondrial respiratory chain may precede these brain lesions. Our studies demonstrate that this environmental air contaminant has the potential to cause a wide spectrum of brain lesions that are dependent on the degree and duration of exposure.

Ventral tegmental area neurons are either excited or inhibited by cocaine’s actions in the peripheral nervous system

PubMed Central

Mejías-Aponte, Carlos A.; Kiyatkin, Eugene A.

2012-01-01

Cocaine’s multiple pharmacological substrates are ubiquitously present in the peripheral and central nervous system. Thus, upon its administration, cocaine acts in the periphery before directly acting in the brain. We determined whether cocaine alters ventral tegmental area (VTA) neuronal activity via peripheral actions, and whether this precedes its central actions. In urethane-anesthetized rats, we recorded VTA neurons responses to intravenous injections of two cocaine analogs: cocaine-hydrochloride (HCl, 0.25 mg/kg) that readily cross the blood-brain barrier (BBB) and cocaine-methiodide (MI, 0.33 mg/kg) that does not cross the BBB. Both cocaine analogs produced sustained changes in discharge rates that began 5s after the initiation of a 10s drug infusion. Within the first 90s post-injection the magnitudes of neuronal responsive of both cocaine analogs were comparable, but later in time the effects of cocaine-HCl were stronger and persisted longer than those of cocaine-MI. The proportion of neurons responsive to cocaine-HCl was twice to that of cocaine-MI (74% and 35% respectively). Both analogs also differed in the response onsets. Cocaine-MI rarely evoked responses after 1 min whereas cocaine-HCl continued to evoke responses within 3 min post-injection. VTA neurons were either excited or inhibited by both cocaine analogs. Most units responsive to cocaine-MI, regardless of excitation or inhibition, had electrophysiological characteristics of putative DA neurons. Units inhibited by cocaine-HCl also had characteristic of DA neurons whereas excited neurons had widely varying action potential durations and discharge rates. Cocaine-MI and cocaine-HCl each produced changes in VTA neuron activity under full DA receptor blockade. However, the duration of inhibition was shortened, the number of excitations increased, and they occurred with an earlier onset during DA receptor blockade. These findings indicate that cocaine acts peripherally with a short latency and alters the activity of VTA neurons prior to its well-known direct actions in the brain. PMID:22300980

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

Chronic hyperperfusion and angiogenesis follow subacute hypoperfusion in the thalamus of rats with focal cerebral ischemia

PubMed Central

Hayward, Nick MEA; Yanev, Pavel; Haapasalo, Annakaisa; Miettinen, Riitta; Hiltunen, Mikko; Gröhn, Olli; Jolkkonen, Jukka

2011-01-01

Cerebral blood flow (CBF) is disrupted after focal ischemia in rats. We examined long-term hemodynamic and cerebrovascular changes in the rat thalamus after focal cerebral ischemia. Cerebral blood flow quantified by arterial spin labeling magnetic resonance imaging was decreased in the ipsilateral and contralateral thalamus 2 days after cerebral ischemia. Partial thalamic CBF recovery occurred by day 7, then the ipsilateral thalamus was chronically hyperperfused at 30 days and 3 months compared with its contralateral side. This contrasted with permanent hypoperfusion in the ipsilateral cortex. Angiogenesis was indicated by endothelial cell (RECA-1) immunohistochemistry that showed increased blood vessel branching in the ipsilateral thalamus at the end of the 3-month follow-up. Only transient thalamic IgG extravasation was observed, indicating that the blood–brain barrier was intact after day 2. Angiogenesis was preceded by transiently altered expression levels of cadherin family adhesion molecules, cadherin-7, protocadherin-1, and protocadherin-17. In conclusion, thalamic pathology after focal cerebral ischemia involved long-term hemodynamic changes and angiogenesis preceded by altered expression of vascular adhesion factors. Postischemic angiogenesis in the thalamus represents a novel type of remote plasticity, which may support removal of necrotic brain tissue and aid functional recovery. PMID:21081957

Colour Terms Affect Detection of Colour and Colour-Associated Objects Suppressed from Visual Awareness

PubMed Central

Forder, Lewis; Taylor, Olivia; Mankin, Helen; Scott, Ryan B.; Franklin, Anna

2016-01-01

The idea that language can affect how we see the world continues to create controversy. A potentially important study in this field has shown that when an object is suppressed from visual awareness using continuous flash suppression (a form of binocular rivalry), detection of the object is differently affected by a preceding word prime depending on whether the prime matches or does not match the object. This may suggest that language can affect early stages of vision. We replicated this paradigm and further investigated whether colour terms likewise influence the detection of colours or colour-associated object images suppressed from visual awareness by continuous flash suppression. This method presents rapidly changing visual noise to one eye while the target stimulus is presented to the other. It has been shown to delay conscious perception of a target for up to several minutes. In Experiment 1 we presented greyscale photos of objects. They were either preceded by a congruent object label, an incongruent label, or white noise. Detection sensitivity (d’) and hit rates were significantly poorer for suppressed objects preceded by an incongruent label compared to a congruent label or noise. In Experiment 2, targets were coloured discs preceded by a colour term. Detection sensitivity was significantly worse for suppressed colour patches preceded by an incongruent colour term as compared to a congruent term or white noise. In Experiment 3 targets were suppressed greyscale object images preceded by an auditory presentation of a colour term. On congruent trials the colour term matched the object’s stereotypical colour and on incongruent trials the colour term mismatched. Detection sensitivity was significantly poorer on incongruent trials than congruent trials. Overall, these findings suggest that colour terms affect awareness of coloured stimuli and colour- associated objects, and provide new evidence for language-perception interaction in the brain. PMID:27023274

Colour Terms Affect Detection of Colour and Colour-Associated Objects Suppressed from Visual Awareness.

PubMed

Forder, Lewis; Taylor, Olivia; Mankin, Helen; Scott, Ryan B; Franklin, Anna

2016-01-01

The idea that language can affect how we see the world continues to create controversy. A potentially important study in this field has shown that when an object is suppressed from visual awareness using continuous flash suppression (a form of binocular rivalry), detection of the object is differently affected by a preceding word prime depending on whether the prime matches or does not match the object. This may suggest that language can affect early stages of vision. We replicated this paradigm and further investigated whether colour terms likewise influence the detection of colours or colour-associated object images suppressed from visual awareness by continuous flash suppression. This method presents rapidly changing visual noise to one eye while the target stimulus is presented to the other. It has been shown to delay conscious perception of a target for up to several minutes. In Experiment 1 we presented greyscale photos of objects. They were either preceded by a congruent object label, an incongruent label, or white noise. Detection sensitivity (d') and hit rates were significantly poorer for suppressed objects preceded by an incongruent label compared to a congruent label or noise. In Experiment 2, targets were coloured discs preceded by a colour term. Detection sensitivity was significantly worse for suppressed colour patches preceded by an incongruent colour term as compared to a congruent term or white noise. In Experiment 3 targets were suppressed greyscale object images preceded by an auditory presentation of a colour term. On congruent trials the colour term matched the object's stereotypical colour and on incongruent trials the colour term mismatched. Detection sensitivity was significantly poorer on incongruent trials than congruent trials. Overall, these findings suggest that colour terms affect awareness of coloured stimuli and colour- associated objects, and provide new evidence for language-perception interaction in the brain.

An FMRI study of self-regulatory control and conflict resolution in adolescents with bulimia nervosa.

PubMed

Marsh, Rachel; Horga, Guillermo; Wang, Zhishun; Wang, Pengwei; Klahr, Kristin W; Berner, Laura A; Walsh, B Timothy; Peterson, Bradley S

2011-11-01

The authors examined functional activity in the frontostriatal systems that mediate self-regulatory capacities and conflict resolution in adolescents with bulimia nervosa. Functional magnetic resonance imaging was used to compare blood-oxygen-level-dependent response in 18 female adolescents with bulimia nervosa and 18 healthy female age-matched subjects during performance on a Simon spatial incompatibility task. Bayesian analyses were used to compare the two groups on patterns of brain activation during correct responses to conflict stimuli and to explore the effects of antecedent stimulus context on group differences in self-regulation and conflict resolution. Adolescents with and without bulimia nervosa performed similarly on the task. During correct responses in conflict trials, frontostriatal circuits-including the right inferolateral and dorsolateral prefrontal cortices and putamen-failed to activate to the same degree in adolescents with bulimia nervosa as in healthy comparison subjects. Instead, deactivation was seen in the left inferior frontal gyrus as well as a neural system encompassing the posterior cingulate cortex and superior frontal gyrus. Group differences in cortical and striatal regions were driven by the differential responses to stimuli preceded by conflict and nonconflict stimuli, respectively. When engaging the self-regulatory control processes necessary to resolve conflict, adolescents with bulimia nervosa displayed abnormal patterns of activation in frontostriatal and default-mode systems. Their abnormal processing of the antecedent stimulus context conditioned their brain response to conflict differently from that of healthy comparison subjects, specifically in frontal regions. It is suspected that functional disturbances in frontal portions of frontostriatal systems may release feeding behaviors from regulatory control, thereby perpetuating the conflicting desires to consume fattening foods and avoid weight gain that characterize bulimia nervosa.

An fMRI Study of Self-Regulatory Control and Conflict Resolution in Adolescents With Bulimia Nervosa

PubMed Central

Marsh, Rachel; Horga, Guillermo; Wang, Zhishun; Wang, Pengwei; Klahr, Kristin W.; Berner, Laura A.; Walsh, B. Timothy; Peterson, Bradley S.

2012-01-01

Objective The authors examined functional activity in the frontostriatal systems that mediate self-regulatory capacities and conflict resolution in adolescents with bulimia nervosa. Method Functional magnetic resonance imaging was used to compare blood-oxygen-level-dependent response in 18 female adolescents with bulimia nervosa and 18 healthy female age-matched subjects during performance on a Simon spatial incompatibility task. Bayesian analyses were used to compare the two groups on patterns of brain activation during correct responses to conflict stimuli and to explore the effects of antecedent stimulus context on group differences in self-regulation and conflict resolution. Results Adolescents with and without bulimia nervosa performed similarly on the task. During correct responses in conflict trials, frontostriatal circuits—including the right inferolateral and dorsolateral prefrontal cortices and putamen—failed to activate to the same degree in adolescents with bulimia nervosa as in healthy comparison subjects. Instead, deactivation was seen in the left inferior frontal gyrus as well as a neural system encompassing the posterior cingulate cortex and superior frontal gyrus. Group differences in cortical and striatal regions were driven by the differential responses to stimuli preceded by conflict and nonconflict stimuli, respectively. Conclusions When engaging the self-regulatory control processes necessary to resolve conflict, adolescents with bulimia nervosa displayed abnormal patterns of activation in frontostriatal and default-mode systems. Their abnormal processing of the antecedent stimulus context conditioned their brain response to conflict differently from that of healthy comparison subjects, specifically in frontal regions. It is suspected that functional disturbances in frontal portions of frontostriatal systems may release feeding behaviors from regulatory control, thereby perpetuating the conflicting desires to consume fattening foods and avoid weight gain that characterize bulimia nervosa. PMID:21676991

Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

NASA Astrophysics Data System (ADS)

Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

2010-02-01

Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

Brain aromatase (Cyp19A2) and estrogen receptors, in larvae and adult pejerrey fish Odontesthes bonariensis: Neuroanatomical and functional relations

USGS Publications Warehouse

Strobl-Mazzulla, P. H.; Lethimonier, C.; Gueguen, M.M.; Karube, M.; Fernandino, J.I.; Yoshizaki, G.; Patino, R.; Strussmann, C.A.; Kah, O.; Somoza, G.M.

2008-01-01

Although estrogens exert many functions on vertebrate brains, there is little information on the relationship between brain aromatase and estrogen receptors. Here, we report the cloning and characterization of two estrogen receptors, ?? and ??, in pejerrey. Both receptors' mRNAs largely overlap and were predominantly expressed in the brain, pituitary, liver, and gonads. Also brain aromatase and estrogen receptors were up-regulated in the brain of estradiol-treated males. In situ hybridization was performed to study in more detail, the distribution of the two receptors in comparison with brain aromatase mRNA in the brain of adult pejerrey. The estrogen receptors' mRNAs exhibited distinct but partially overlapping patterns of expression in the preoptic area and the mediobasal hypothalamus, as well as in the pituitary gland. Moreover, the estrogen receptor ??, but not ??, were found to be expressed in cells lining the preoptic recess, similarly as observed for brain aromatase. Finally, it was shown that the onset expression of brain aromatase and both estrogen receptors in the head of larvae preceded the morphological differentiation of the gonads. Because pejerrey sex differentiation is strongly influenced by temperature, brain aromatase expression was measured during the temperature-sensitive window and was found to be significantly higher at male-promoting temperature. Taken together these results suggest close neuroanatomical and functional relationships between brain aromatase and estrogen receptors, probably involved in the sexual differentiation of the brain and raising interesting questions on the origin (central or peripheral) of the brain aromatase substrate. ?? 2008 Elsevier Inc.

Reactive recruitment of attentional control in math anxiety: an ERP study of numeric conflict monitoring and adaptation.

PubMed

Suárez-Pellicioni, Macarena; Núñez-Peña, María Isabel; Colomé, Àngels

2014-01-01

This study uses event-related brain potentials (ERPs) to investigate the electrophysiological correlates of numeric conflict monitoring in math-anxious individuals, by analyzing whether math anxiety is related to abnormal processing in early conflict detection (as shown by the N450 component) and/or in a later, response-related stage of processing (as shown by the conflict sustained potential; Conflict-SP). Conflict adaptation effects were also studied by analyzing the effect of the previous trial's congruence in current interference. To this end, 17 low math-anxious (LMA) and 17 high math-anxious (HMA) individuals were presented with a numerical Stroop task. Groups were extreme in math anxiety but did not differ in trait or state anxiety or in simple math ability. The interference effect of the current trial (incongruent-congruent) and the interference effect preceded by congruence and by incongruity were analyzed both for behavioral measures and for ERPs. A greater interference effect was found for response times in the HMA group than in the LMA one. Regarding ERPs, the LMA group showed a greater N450 component for the interference effect preceded by congruence than when preceded by incongruity, while the HMA group showed greater Conflict-SP amplitude for the interference effect preceded by congruence than when preceded by incongruity. Our study showed that the electrophysiological correlates of numeric interference in HMA individuals comprise the absence of a conflict adaptation effect in the first stage of conflict processing (N450) and an abnormal subsequent up-regulation of cognitive control in order to overcome the conflict (Conflict-SP). More concretely, our study shows that math anxiety is related to a reactive and compensatory recruitment of control resources that is implemented only when previously exposed to a stimuli presenting conflicting information.

Reactive Recruitment of Attentional Control in Math Anxiety: An ERP Study of Numeric Conflict Monitoring and Adaptation

PubMed Central

Suárez-Pellicioni, Macarena; Núñez-Peña, María Isabel; Colomé, Àngels

2014-01-01

This study uses event-related brain potentials (ERPs) to investigate the electrophysiological correlates of numeric conflict monitoring in math-anxious individuals, by analyzing whether math anxiety is related to abnormal processing in early conflict detection (as shown by the N450 component) and/or in a later, response-related stage of processing (as shown by the conflict sustained potential; Conflict-SP). Conflict adaptation effects were also studied by analyzing the effect of the previous trial’s congruence in current interference. To this end, 17 low math-anxious (LMA) and 17 high math-anxious (HMA) individuals were presented with a numerical Stroop task. Groups were extreme in math anxiety but did not differ in trait or state anxiety or in simple math ability. The interference effect of the current trial (incongruent-congruent) and the interference effect preceded by congruence and by incongruity were analyzed both for behavioral measures and for ERPs. A greater interference effect was found for response times in the HMA group than in the LMA one. Regarding ERPs, the LMA group showed a greater N450 component for the interference effect preceded by congruence than when preceded by incongruity, while the HMA group showed greater Conflict-SP amplitude for the interference effect preceded by congruence than when preceded by incongruity. Our study showed that the electrophysiological correlates of numeric interference in HMA individuals comprise the absence of a conflict adaptation effect in the first stage of conflict processing (N450) and an abnormal subsequent up-regulation of cognitive control in order to overcome the conflict (Conflict-SP). More concretely, our study shows that math anxiety is related to a reactive and compensatory recruitment of control resources that is implemented only when previously exposed to a stimuli presenting conflicting information. PMID:24918584

VHF discharges in storm cells producing microbursts

NASA Technical Reports Server (NTRS)

Laroche, P.; Malherbe, C.; Bondiou, A.; Weber, M.; Engholm, C.; Coel, V.

1991-01-01

An experiment was carried out in which 3-D mapping of VHF sources was compared to a 3-D description of the reflectivity and dynamics of associated cloud cells observed by a radar network. Data from 61 microbursts were analyzed and it was found that, in 93 pct. of the cases, electrical activity precedes outflow development. The results confirm that the peak in intracloud activity precedes the maximum value of the outflow.

Controlling amyloid-beta peptide(1-42) oligomerization and toxicity by fluorinated nanoparticles.

PubMed

Saraiva, Ana M; Cardoso, Isabel; Pereira, M Carmo; Coelho, Manuel A N; Saraiva, Maria João; Möhwald, Helmuth; Brezesinski, Gerald

2010-09-03

The amyloid-beta peptide (Abeta) is a major fibrillar component of neuritic plaques in Alzheimer's disease brains and is related to the pathogenesis of the disease. Soluble oligomers that precede fibril formation have been proposed as the main neurotoxic species that contributes to neurodegeneration and dementia. We hypothesize that oligomerization and cytotoxicity can be repressed by nanoparticles (NPs) that induce conformational changes in Abeta42. We show here that fluorinated and hydrogenated NPs with different abilities to change Abeta42 conformation influence oligomerization as assessed by atomic force microscopy, immunoblot and SDS-PAGE. Fluorinated NPs, which promote an increase in alpha-helical content, exert an antioligomeric effect, whereas hydrogenated analogues do not and lead to aggregation. Cytotoxicity assays confirmed our hypothesis by indicating that the conformational conversion of Abeta42 into an alpha-helical-enriched secondary structure also has antiapoptotic activity, thereby increasing the viability of cells treated with oligomeric species.

Seizures induced by music.

PubMed

Ogunyemi, A O; Breen, H

1993-01-01

Musicogenic epilepsy is a rare disorder. Much remains to be learned about the electroclinical features. This report describes a patient who has been followed at our institution for 17 years, and was investigated with long-term telemetered simultaneous video-EEG recordings. She began to have seizures at the age of 10 years. She experienced complex partial seizures, often preceded by elementary auditory hallucination and complex auditory illusion. The seizures occurred in relation to singing, listening to music or thinking about music. She also had occasional generalized tonic clonic seizures during sleep. There was no significant antecedent history. The family history was negative for epilepsy. The physical examination was unremarkable. CT and MRI scans of the brain were normal. During long-term simultaneous video-EEG recordings, clinical and electrographic seizure activities were recorded in association with singing and listening to music. Mathematical calculation, copying or viewing geometric patterns and playing the game of chess failed to evoke seizures.

Direct brain recordings reveal hippocampal rhythm underpinnings of language processing.

PubMed

Piai, Vitória; Anderson, Kristopher L; Lin, Jack J; Dewar, Callum; Parvizi, Josef; Dronkers, Nina F; Knight, Robert T

2016-10-04

Language is classically thought to be supported by perisylvian cortical regions. Here we provide intracranial evidence linking the hippocampal complex to linguistic processing. We used direct recordings from the hippocampal structures to investigate whether theta oscillations, pivotal in memory function, track the amount of contextual linguistic information provided in sentences. Twelve participants heard sentences that were either constrained ("She locked the door with the") or unconstrained ("She walked in here with the") before presentation of the final word ("key"), shown as a picture that participants had to name. Hippocampal theta power increased for constrained relative to unconstrained contexts during sentence processing, preceding picture presentation. Our study implicates hippocampal theta oscillations in a language task using natural language associations that do not require memorization. These findings reveal that the hippocampal complex contributes to language in an active fashion, relating incoming words to stored semantic knowledge, a necessary process in the generation of sentence meaning.

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding.

PubMed

Du, Huiyun; Deng, Wei; Aimone, James B; Ge, Minyan; Parylak, Sarah; Walch, Keenan; Zhang, Wei; Cook, Jonathan; Song, Huina; Wang, Liping; Gage, Fred H; Mu, Yangling

2016-09-13

Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2-expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioral experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Overall, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience.

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

PubMed Central

Du, Huiyun; Deng, Wei; Aimone, James B.; Ge, Minyan; Parylak, Sarah; Walch, Keenan; Zhang, Wei; Cook, Jonathan; Song, Huina; Wang, Liping; Gage, Fred H.; Mu, Yangling

2016-01-01

Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2–expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioral experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Overall, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience. PMID:27573822

Estimation of effective connectivity using multi-layer perceptron artificial neural network.

PubMed

Talebi, Nasibeh; Nasrabadi, Ali Motie; Mohammad-Rezazadeh, Iman

2018-02-01

Studies on interactions between brain regions estimate effective connectivity, (usually) based on the causality inferences made on the basis of temporal precedence. In this study, the causal relationship is modeled by a multi-layer perceptron feed-forward artificial neural network, because of the ANN's ability to generate appropriate input-output mapping and to learn from training examples without the need of detailed knowledge of the underlying system. At any time instant, the past samples of data are placed in the network input, and the subsequent values are predicted at its output. To estimate the strength of interactions, the measure of " Causality coefficient " is defined based on the network structure, the connecting weights and the parameters of hidden layer activation function. Simulation analysis demonstrates that the method, called "CREANN" (Causal Relationship Estimation by Artificial Neural Network), can estimate time-invariant and time-varying effective connectivity in terms of MVAR coefficients. The method shows robustness with respect to noise level of data. Furthermore, the estimations are not significantly influenced by the model order (considered time-lag), and the different initial conditions (initial random weights and parameters of the network). CREANN is also applied to EEG data collected during a memory recognition task. The results implicate that it can show changes in the information flow between brain regions, involving in the episodic memory retrieval process. These convincing results emphasize that CREANN can be used as an appropriate method to estimate the causal relationship among brain signals.

A case of neuromyelitis optica spectrum disorder (NMOSD) with Sjögren's syndrome manifested only brain involvement by preceding parotitis.

PubMed

Furukawa, Takahiro; Matsui, Naoko; Tanaka, Keiko; Izumi, Yuishin; Kaji, Ryuji

2017-02-25

A 33 year-old woman presented with intentional incontinence, motor aphasia, supranuclear gaze palsy, and spasticity after parotitis. Brain magnetic resonance images (MRI) showed abnormal signaling in long corticospinal tract involving internal capsules and cerebral peduncles, middle cerebellar peduncle, and frontal subcortical white matter lesions. She had a long history of dry eye and mouth. Immunoserological study showed that she was positive for anti-SS-A, aquaporin 4 (AQP4), and AQP5 antibodies. She clinically showed not only Sjögren's syndrome but also neuromyelitis optica spectrum disorder (NMOSD) without optic neuritis or myelitis. She responded to steroid followed by plasma exchange dramatically. Thereafter, the relapse of brain lesion was once detected while tapering of steroid, but her symptoms have been stable for several years after administration of immunosuppressant. This case suggested that salivary gland inflammation might be associated with the pathogenesis of NMOSD.

The 5th Annual One Mind Summit: Lessons Learned About "Science Informing Brain Health Policies and Practice".

PubMed

Hicks, Ramona; Johnson, Stephen; Porter, Amy; Zatzick, Douglas F; One Mind Summit Panel Participants, The

2017-03-29

Advances in science frequently precede changes in clinical care by several years or even decades. To better understand the path to translation, we invited experts to share their perspectives at the 5th Annual One Mind Summit: "Science Informing Brain Health Policies and Practice", which was held on May 24-25, 2016 in Crystal City, VA. While the translation of brain research throughout the pipeline - from basic science research to patient care - was discussed, the focus was on the implementation of "best evidence" into patient care. The Summit identified key steps, including the need for professional endorsement and clinical guidelines or policies, acceptance by regulators and payers, dissemination and training for clinicians, patient advocacy, and learning healthcare models. The path to implementation was discussed broadly, as well as in the context of a specific project to implement concussion screening in emergency and urgent care centers throughout the U.S.

Epileptic encephalopathy in children with risk factors for brain damage.

PubMed

Ricardo-Garcell, Josefina; Harmony, Thalía; Porras-Kattz, Eneida; Colmenero-Batallán, Miguel J; Barrera-Reséndiz, Jesús E; Fernández-Bouzas, Antonio; Cruz-Rivero, Erika

2012-01-01

In the study of 887 new born infants with prenatal and perinatal risk factors for brain damage, 11 children with West syndrome that progressed into Lennox-Gastaut syndrome and another 4 children with Lennox-Gastaut syndrome that had not been preceded by West syndrome were found. In this study we present the main findings of these 15 subjects. In all infants multifactor antecedents were detected. The most frequent risk factors were prematurity and severe asphyxia; however placenta disorders, sepsis, and hyperbilirubinemia were also frequent. In all infants MRI direct or secondary features of periventricular leukomalacia were observed. Followup of all infants showed moderate to severe neurodevelopmental delay as well as cerebral palsy. It is concluded that prenatal and perinatal risk factors for brain damage are very important antecedents that should be taken into account to follow up those infants from an early age in order to detect and treat as early as possible an epileptic encephalopathy.

Sleep deprivation alters functioning within the neural network underlying the covert orienting of attention.

PubMed

Mander, Bryce A; Reid, Kathryn J; Davuluri, Vijay K; Small, Dana M; Parrish, Todd B; Mesulam, M-Marsel; Zee, Phyllis C; Gitelman, Darren R

2008-06-27

One function of spatial attention is to enable goal-directed interactions with the environment through the allocation of neural resources to motivationally relevant parts of space. Studies have shown that responses are enhanced when spatial attention is predictively biased towards locations where significant events are expected to occur. Previous studies suggest that the ability to bias attention predictively is related to posterior cingulate cortex (PCC) activation [Small, D.M., et al., 2003. The posterior cingulate and medial prefrontal cortex mediate the anticipatory allocation of spatial attention. Neuroimage 18, 633-41]. Sleep deprivation (SD) impairs selective attention and reduces PCC activity [Thomas, M., et al., 2000. Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity. J. Sleep Res. 9, 335-352]. Based on these findings, we hypothesized that SD would affect PCC function and alter the ability to predictively allocate spatial attention. Seven healthy, young adults underwent functional magnetic resonance imaging (fMRI) following normal rest and 34-36 h of SD while performing a task in which attention was shifted in response to peripheral targets preceded by spatially informative (valid), misleading (invalid), or uninformative (neutral) cues. When rested, but not when sleep-deprived, subjects responded more quickly to targets that followed valid cues than those after neutral or invalid cues. Brain activity during validly cued trials with a reaction time benefit was compared to activity in trials with no benefit. PCC activation was greater during trials with a reaction time benefit following normal rest. In contrast, following SD, reaction time benefits were associated with activation in the left intraparietal sulcus, a region associated with receptivity to stimuli at unexpected locations. These changes may render sleep-deprived individuals less able to anticipate the locations of upcoming events, and more susceptible to distraction by stimuli at irrelevant locations.

Tumor Growth Increases Neuroinflammation, Fatigue and Depressive-like Behavior Prior to Alterations in Muscle Function

PubMed Central

Norden, Diana M.; Bicer, Sabahattin; Clark, Yvonne; Jing, Runfeng; Henry, Christopher J.; Wold, Loren E.; Reiser, Peter J.; Godbout, Jonathan P.; McCarthy, Donna O.

2014-01-01

Cancer patients frequently suffer from fatigue, a complex syndrome associated with loss of muscle mass, weakness, and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, during treatment, and persists for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. Currently there are no effective treatments to reduce CRF. The aim of this study was to use a mouse model of tumor growth and discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that tumor growth increased fatigue- and depressive-like behaviors, and reduced body and muscle mass. Decreased voluntary wheel running activity (VWRA) and increased depressive-like behavior in the forced swim and sucrose preference tests were evident in tumor-bearing mice within the first two weeks of tumor growth and preceded the loss of body and muscle mass. At three weeks, tumor-bearing mice had reduced grip strength but this was not associated with altered expression of myosin isoforms or impaired contractile properties of muscles. These increases in fatigue and depressive-like behaviors were paralleled by increased expression of IL-1β mRNA in the cortex and hippocampus. Minocycline administration reduced tumor-induced expression of IL-1β in the brain, reduced depressive-like behavior, and improved grip strength without altering muscle mass. Taken together, these results indicate that neuroinflammation and depressed mood, rather than muscle wasting, contribute to decreased voluntary activity and precede major changes in muscle contractile properties with tumor growth. PMID:25102452

Tumor growth increases neuroinflammation, fatigue and depressive-like behavior prior to alterations in muscle function.

PubMed

Norden, Diana M; Bicer, Sabahattin; Clark, Yvonne; Jing, Runfeng; Henry, Christopher J; Wold, Loren E; Reiser, Peter J; Godbout, Jonathan P; McCarthy, Donna O

2015-01-01

Cancer patients frequently suffer from fatigue, a complex syndrome associated with loss of muscle mass, weakness, and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, during treatment, and persists for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. Currently there are no effective treatments to reduce CRF. The aim of this study was to use a mouse model of tumor growth and discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that tumor growth increased fatigue- and depressive-like behaviors, and reduced body and muscle mass. Decreased voluntary wheel running activity (VWRA) and increased depressive-like behavior in the forced swim and sucrose preference tests were evident in tumor-bearing mice within the first two weeks of tumor growth and preceded the loss of body and muscle mass. At three weeks, tumor-bearing mice had reduced grip strength but this was not associated with altered expression of myosin isoforms or impaired contractile properties of muscles. These increases in fatigue and depressive-like behaviors were paralleled by increased expression of IL-1β mRNA in the cortex and hippocampus. Minocycline administration reduced tumor-induced expression of IL-1β in the brain, reduced depressive-like behavior, and improved grip strength without altering muscle mass. Taken together, these results indicate that neuroinflammation and depressed mood, rather than muscle wasting, contribute to decreased voluntary activity and precede major changes in muscle contractile properties with tumor growth. Copyright © 2014 Elsevier Inc. All rights reserved.

Blood Brain Barrier and Neuroinflammation Are Critical Targets of IGF-1-Mediated Neuroprotection in Stroke for Middle-Aged Female Rats

PubMed Central

Bake, Shameena; Selvamani, Amutha; Cherry, Jessica; Sohrabji, Farida

2014-01-01

Ischemia-induced cerebral infarction is more severe in older animals as compared to younger animals, and is associated with reduced availability of insulin-like growth factor (IGF)-1. This study determined the effect of post-stroke IGF-1 treatment, and used microRNA profiling to identify mechanisms underlying IGF-1’s neuroprotective actions. Post-stroke ICV administration of IGF-1 to middle-aged female rats reduced infarct volume by 39% when measured 24h later. MicroRNA analyses of ischemic tissue collected at the early post-stroke phase (4h) indicated that 8 out of 168 disease-related miRNA were significantly downregulated by IGF-1. KEGG pathway analysis implicated these miRNA in PI3K-Akt signaling, cell adhesion/ECM receptor pathways and T-and B-cell signaling. Specific components of these pathways were subsequently analyzed in vehicle and IGF-1 treated middle-aged females. Phospho-Akt was reduced by ischemia at 4h, but elevated by IGF-1 treatment at 24h. IGF-1 induced Akt activation was preceded by a reduction of blood brain barrier permeability at 4h post-stroke and global suppression of cytokines including IL-6, IL-10 and TNF-α. A subset of these cytokines including IL-6 was also suppressed by IGF-1 at 24h post-stroke. These data are the first to show that the temporal and mechanistic components of post-stroke IGF-1 treatment in older animals, and that cellular components of the blood brain barrier may serve as critical targets of IGF-1 in the aging brain. PMID:24618563

Analgesia induced by localized injection of opiate peptides into the brain of infant rats.

PubMed

Barr, G A; Wang, S

2013-05-01

Stimulation of a variety of brain sites electrically or by opiates activates descending inhibitory pathways to attenuate noxious input to the spinal cord dorsal horn and produce analgesia. Analgesia induced by electrical stimulation of the periaqueductal grey (PAG) of the midbrain or medial rostral ventral medulla (RVM) matures late, towards the end or past the pre-weaning period. Descending facilitation takes precedence over inhibition. Yet opiates injected intracerebroventricularly or directly into the PAG induce analgesia relatively early in development. Our goal was to re-examine the role of opiates specific to individual receptor types in analgesia at several supraspinal sites. Antinociception was tested following microinjection of DAMGO (μ-opiate agonist), DPDPE (∂-opiate agonist) or U50,488 (κ-opiate agonist) into the PAG, RVM or dorsal lateral pons (DLP) in 3-, 10- and 14-day-old rats. DAMGO produced analgesia at 3 days of age at each brain area; the RVM was the most effective and the dorsal PAG was the least effective site. DPDPE produced modest analgesia at 10 and 14 days of age at the ventral PAG, RVM or DLP, but not the dorsal PAG. U50,488H was ineffective at all sites and all ages. Antinociception could be elicited at all three sites by DAMGO as early as 3 days of age and DPDPE at 10 and 14 days of age. The degree of analgesia increased gradually during the first 2 weeks of life, and likely reflects the maturation of connections within the brain and of descending inhibitory paths from these sites. © 2012 European Federation of International Association for the Study of Pain Chapters.

Correlational analysis of electroencephalographic and end-tidal carbon dioxide signals during breath-hold exercise.

PubMed

Morelli, Maria Sole; Vanello, Nicola; Giannoni, Alberto; Frijia, Francesca; Hartwig, Valentina; Maestri, Michelangelo; Bonanni, Enrica; Carnicelli, Luca; Positano, Vincenzo; Passino, Claudio; Emdin, Michele; Landini, Luigi

2015-01-01

The central mechanism of breathing control is not totally understood. Several studies evaluated the correlation between electroencephalographic (EEG) power spectra and respiratory signals by performing resting state tasks or adopting hypercapnic/hypoxic stimuli. The observation of brain activity during voluntary breath hold tasks, might be an useful approach to highlight the areas involved in mechanism of breath regulation. Nevertheless, studies of brain activity with EEG could present some limitations due to presence of severe artifacts. When artifact rejection methods, as independent component analysis, cannot reliably clean EEG data, it is necessary to exclude noisy segments. In this study, global field power in the delta band and end-tidal CO2 were derived from EEG and CO2 signals respectively in 4 healthy subjects during a breath-hold task. The cross correlation function between the two signals was estimated taking into account the presence of missing samples. The statistical significance of the correlation coefficients at different time lags was assessed using surrogate data. Some simulations are introduced to evaluate the effect of missing data on the correlational analysis and their results are discussed. Results obtained on subjects show a significant correlation between changes in EEG power in the delta band and end-tidal CO2. Moreover, the changes in end-tidal CO2 were found to precede those of global field power. These results might help to better understand the cortical mechanisms involved in the control of breathing.

[Promotion of Occupational Mental Health with Psychiatrists].

PubMed

Tanaka, Katsutoshi

2015-01-01

The promotion of occupational mental health is stipulated by laws and precedents, including the Labor Standards Act, Industrial Safety and Health Act, and Labor Contract Act. These laws and precedents are used to formulate actual mental health activities and responses to individuals with mental health disorders to some extent. Among mental health-related undertakings, the most important role that occupational health staff should play as healthcare professionals is to support business operators' obligations regarding safety. This role is to prevent health problems in the workplace, not to manage corporate risk. However, the health and safety obligations imposed on business operators under the current precedents are far beyond the levels that non-specialists can handle. The active participation of psychiatrists is needed to promote workplace mental health today.

EEG Functional Connectivity Prior to Sleepwalking: Evidence of Interplay Between Sleep and Wakefulness.

PubMed

Desjardins, Marie-Ève; Carrier, Julie; Lina, Jean-Marc; Fortin, Maxime; Gosselin, Nadia; Montplaisir, Jacques; Zadra, Antonio

2017-04-01

Although sleepwalking (somnambulism) affects up to 4% of adults, its pathophysiology remains poorly understood. Sleepwalking can be preceded by fluctuations in slow-wave sleep EEG signals, but the significance of these pre-episode changes remains unknown and methods based on EEG functional connectivity have yet to be used to better comprehend the disorder. We investigated the sleep EEG of 27 adult sleepwalkers (mean age: 29 ± 7.6 years) who experienced a somnambulistic episode during slow-wave sleep. The 20-second segment of sleep EEG immediately preceding each patient's episode was compared with the 20-second segment occurring 2 minutes prior to episode onset. Results from spectral analyses revealed increased delta and theta spectral power in the 20 seconds preceding the episodes' onset as compared to the 20 seconds occurring 2 minutes before the episodes. The imaginary part of the coherence immediately prior to episode onset revealed (1) decreased delta EEG functional connectivity in parietal and occipital regions, (2) increased alpha connectivity over a fronto-parietal network, and (3) increased beta connectivity involving symmetric inter-hemispheric networks implicating frontotemporal, parietal and occipital areas. Taken together, these modifications in EEG functional connectivity suggest that somnambulistic episodes are preceded by brain processes characterized by the co-existence of arousal and deep sleep. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Mapping human preictal and ictal haemodynamic networks using simultaneous intracranial EEG-fMRI

PubMed Central

Chaudhary, Umair J.; Centeno, Maria; Thornton, Rachel C.; Rodionov, Roman; Vulliemoz, Serge; McEvoy, Andrew W.; Diehl, Beate; Walker, Matthew C.; Duncan, John S.; Carmichael, David W.; Lemieux, Louis

2016-01-01

Accurately characterising the brain networks involved in seizure activity may have important implications for our understanding of epilepsy. Intracranial EEG-fMRI can be used to capture focal epileptic events in humans with exquisite electrophysiological sensitivity and allows for identification of brain structures involved in this phenomenon over the entire brain. We investigated ictal BOLD networks using the simultaneous intracranial EEG-fMRI (icEEG-fMRI) in a 30 year-old male undergoing invasive presurgical evaluation with bilateral depth electrode implantations in amygdalae and hippocampi for refractory temporal lobe epilepsy. One spontaneous focal electrographic seizure was recorded. The aims of the data analysis were firstly to map BOLD changes related to the ictal activity identified on icEEG and secondly to compare different fMRI modelling approaches. Visual inspection of the icEEG showed an onset dominated by beta activity involving the right amygdala and hippocampus lasting 6.4 s (ictal onset phase), followed by gamma activity bilaterally lasting 14.8 s (late ictal phase). The fMRI data was analysed using SPM8 using two modelling approaches: firstly, purely based on the visually identified phases of the seizure and secondly, based on EEG spectral dynamics quantification. For the visual approach the two ictal phases were modelled as ‘ON’ blocks convolved with the haemodynamic response function; in addition the BOLD changes during the 30 s preceding the onset were modelled using a flexible basis set. For the quantitative fMRI modelling approach two models were evaluated: one consisting of the variations in beta and gamma bands power, thereby adding a quantitative element to the visually-derived models, and another based on principal components analysis of the entire spectrogram in attempt to reduce the bias associated with the visual appreciation of the icEEG. BOLD changes related to the visually defined ictal onset phase were revealed in the medial and lateral right temporal lobe. For the late ictal phase, the BOLD changes were remote from the SOZ and in deep brain areas (precuneus, posterior cingulate and others). The two quantitative models revealed BOLD changes involving the right hippocampus, amygdala and fusiform gyrus and in remote deep brain structures and the default mode network-related areas. In conclusion, icEEG-fMRI allowed us to reveal BOLD changes within and beyond the SOZ linked to very localised ictal fluctuations in beta and gamma activity measured in the amygdala and hippocampus. Furthermore, the BOLD changes within the SOZ structures were better captured by the quantitative models, highlighting the interest in considering seizure-related EEG fluctuations across the entire spectrum. PMID:27114897

Mapping human preictal and ictal haemodynamic networks using simultaneous intracranial EEG-fMRI.

PubMed

Chaudhary, Umair J; Centeno, Maria; Thornton, Rachel C; Rodionov, Roman; Vulliemoz, Serge; McEvoy, Andrew W; Diehl, Beate; Walker, Matthew C; Duncan, John S; Carmichael, David W; Lemieux, Louis

2016-01-01

Accurately characterising the brain networks involved in seizure activity may have important implications for our understanding of epilepsy. Intracranial EEG-fMRI can be used to capture focal epileptic events in humans with exquisite electrophysiological sensitivity and allows for identification of brain structures involved in this phenomenon over the entire brain. We investigated ictal BOLD networks using the simultaneous intracranial EEG-fMRI (icEEG-fMRI) in a 30 year-old male undergoing invasive presurgical evaluation with bilateral depth electrode implantations in amygdalae and hippocampi for refractory temporal lobe epilepsy. One spontaneous focal electrographic seizure was recorded. The aims of the data analysis were firstly to map BOLD changes related to the ictal activity identified on icEEG and secondly to compare different fMRI modelling approaches. Visual inspection of the icEEG showed an onset dominated by beta activity involving the right amygdala and hippocampus lasting 6.4 s (ictal onset phase), followed by gamma activity bilaterally lasting 14.8 s (late ictal phase). The fMRI data was analysed using SPM8 using two modelling approaches: firstly, purely based on the visually identified phases of the seizure and secondly, based on EEG spectral dynamics quantification. For the visual approach the two ictal phases were modelled as 'ON' blocks convolved with the haemodynamic response function; in addition the BOLD changes during the 30 s preceding the onset were modelled using a flexible basis set. For the quantitative fMRI modelling approach two models were evaluated: one consisting of the variations in beta and gamma bands power, thereby adding a quantitative element to the visually-derived models, and another based on principal components analysis of the entire spectrogram in attempt to reduce the bias associated with the visual appreciation of the icEEG. BOLD changes related to the visually defined ictal onset phase were revealed in the medial and lateral right temporal lobe. For the late ictal phase, the BOLD changes were remote from the SOZ and in deep brain areas (precuneus, posterior cingulate and others). The two quantitative models revealed BOLD changes involving the right hippocampus, amygdala and fusiform gyrus and in remote deep brain structures and the default mode network-related areas. In conclusion, icEEG-fMRI allowed us to reveal BOLD changes within and beyond the SOZ linked to very localised ictal fluctuations in beta and gamma activity measured in the amygdala and hippocampus. Furthermore, the BOLD changes within the SOZ structures were better captured by the quantitative models, highlighting the interest in considering seizure-related EEG fluctuations across the entire spectrum.

Neural correlates of informational cascades: brain mechanisms of social influence on belief updating

PubMed Central

Klucharev, Vasily; Rieskamp, Jörg

2015-01-01

Informational cascades can occur when rationally acting individuals decide independently of their private information and follow the decisions of preceding decision-makers. In the process of updating beliefs, differences in the weighting of private and publicly available social information may modulate the probability that a cascade starts in a decisive way. By using functional magnetic resonance imaging, we examined neural activity while participants updated their beliefs based on the decisions of two fictitious stock market traders and their own private information, which led to a final decision of buying one of two stocks. Computational modeling of the behavioral data showed that a majority of participants overweighted private information. Overweighting was negatively correlated with the probability of starting an informational cascade in trials especially prone to conformity. Belief updating by private information was related to activity in the inferior frontal gyrus/anterior insula, the dorsolateral prefrontal cortex and the parietal cortex; the more a participant overweighted private information, the higher the activity in the inferior frontal gyrus/anterior insula and the lower in the parietal-temporal cortex. This study explores the neural correlates of overweighting of private information, which underlies the tendency to start an informational cascade. PMID:24974396

The Neural Bases of Taxonomic and Thematic Conceptual Relations: An MEG Study

PubMed Central

Lewis, Gwyneth A.; Poeppel, David; Murphy, Gregory L.

2015-01-01

Converging evidence from behavioral and neuroimaging studies of human concepts indicate distinct neural systems for taxonomic and thematic knowledge. A recent study of naming in aphasia found involvement of the anterior temporal lobe (ATL) during taxonomic (feature-based) processing, and involvement of the temporoparietal junction (TPJ) during thematic (function-based) processing. We conducted an online magnetoencephalography (MEG) study to examine the spatio-temporal nature of taxonomic and thematic relations. We measured participants’ brain responses to words preceded by either a taxonomically or thematically related item (e.g., cottage→castle, king→castle). In a separate experiment we collected relatedness ratings of the word pairs from participants. We examined effects of relatedness and relation type on activation in ATL and TPJ regions of interest (ROIs) using permutation t-tests to identify differences in ROI activation between conditions as well as single-trial correlational analyses to examine the millisecond-by-millisecond influence of the stimulus variables on the ROIs. Taxonomic relations strongly predicted ATL activation, and both kinds of relations influenced the TPJ. Our results further strengthen the view of the ATL's importance to taxonomic knowledge. Moreover, they provide a nuanced view of thematic relations as involving taxonomic knowledge. PMID:25582406

Spatial and temporal dynamics of cortical networks engaged in memory encoding and retrieval

PubMed Central

Miller, Brian T.; D'Esposito, Mark

2012-01-01

Memory operations such as encoding and retrieval require the coordinated interplay of cortical regions with distinct functional contributions. The mechanistic nature of these interactions, however, remains unspecified. During the performance of a face memory task during fMRI scanning, we measured the magnitude (a measure of the strength of coupling between areas) and phase (a measure of the relative timing across areas) of coherence between regions of interest and the rest of the brain. The fusiform face area (FFA) showed robust coherence with a distributed network of subregions in the prefrontal cortex (PFC), posterior parietal cortex (PPC), precuneus, and hippocampus across both memory operations. While these findings reveal significant overlap in the cortical networks underlying mnemonic encoding and retrieval, coherence phase analyses revealed context-dependent differences in cortical dynamics. During both encoding and retrieval, PFC and PPC exhibited earlier activity than in the FFA and hippocampus. Also, during retrieval, PFC activity preceded PPC activity. These findings are consistent with prior physiology studies suggesting an early contribution of PFC and PPC in mnemonic control. Together, these findings contribute to the growing literature exploring the spatio-temporal dynamics of basic memory operations. PMID:22557959

Neural correlates of cross-modal affective priming by music in Williams syndrome.

PubMed

Lense, Miriam D; Gordon, Reyna L; Key, Alexandra P F; Dykens, Elisabeth M

2014-04-01

Emotional connection is the main reason people engage with music, and the emotional features of music can influence processing in other domains. Williams syndrome (WS) is a neurodevelopmental genetic disorder where musicality and sociability are prominent aspects of the phenotype. This study examined oscillatory brain activity during a musical affective priming paradigm. Participants with WS and age-matched typically developing controls heard brief emotional musical excerpts or emotionally neutral sounds and then reported the emotional valence (happy/sad) of subsequently presented faces. Participants with WS demonstrated greater evoked fronto-central alpha activity to the happy vs sad musical excerpts. The size of these alpha effects correlated with parent-reported emotional reactivity to music. Although participant groups did not differ in accuracy of identifying facial emotions, reaction time data revealed a music priming effect only in persons with WS, who responded faster when the face matched the emotional valence of the preceding musical excerpt vs when the valence differed. Matching emotional valence was also associated with greater evoked gamma activity thought to reflect cross-modal integration. This effect was not present in controls. The results suggest a specific connection between music and socioemotional processing and have implications for clinical and educational approaches for WS.

Network topology and functional connectivity disturbances precede the onset of Huntington's disease.

PubMed

Harrington, Deborah L; Rubinov, Mikail; Durgerian, Sally; Mourany, Lyla; Reece, Christine; Koenig, Katherine; Bullmore, Ed; Long, Jeffrey D; Paulsen, Jane S; Rao, Stephen M

2015-08-01

Cognitive, motor and psychiatric changes in prodromal Huntington's disease have nurtured the emergent need for early interventions. Preventive clinical trials for Huntington's disease, however, are limited by a shortage of suitable measures that could serve as surrogate outcomes. Measures of intrinsic functional connectivity from resting-state functional magnetic resonance imaging are of keen interest. Yet recent studies suggest circumscribed abnormalities in resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease, despite the spectrum of behavioural changes preceding a manifest diagnosis. The present study used two complementary analytical approaches to examine whole-brain resting-state functional magnetic resonance imaging connectivity in prodromal Huntington's disease. Network topology was studied using graph theory and simple functional connectivity amongst brain regions was explored using the network-based statistic. Participants consisted of gene-negative controls (n = 16) and prodromal Huntington's disease individuals (n = 48) with various stages of disease progression to examine the influence of disease burden on intrinsic connectivity. Graph theory analyses showed that global network interconnectivity approximated a random network topology as proximity to diagnosis neared and this was associated with decreased connectivity amongst highly-connected rich-club network hubs, which integrate processing from diverse brain regions. However, functional segregation within the global network (average clustering) was preserved. Functional segregation was also largely maintained at the local level, except for the notable decrease in the diversity of anterior insula intermodular-interconnections (participation coefficient), irrespective of disease burden. In contrast, network-based statistic analyses revealed patterns of weakened frontostriatal connections and strengthened frontal-posterior connections that evolved as disease burden increased. These disturbances were often related to long-range connections involving peripheral nodes and interhemispheric connections. A strong association was found between weaker connectivity and decreased rich-club organization, indicating that whole-brain simple connectivity partially expressed disturbances in the communication of highly-connected hubs. However, network topology and network-based statistic connectivity metrics did not correlate with key markers of executive dysfunction (Stroop Test, Trail Making Test) in prodromal Huntington's disease, which instead were related to whole-brain connectivity disturbances in nodes (right inferior parietal, right thalamus, left anterior cingulate) that exhibited multiple aberrant connections and that mediate executive control. Altogether, our results show for the first time a largely disease burden-dependent functional reorganization of whole-brain networks in prodromal Huntington's disease. Both analytic approaches provided a unique window into brain reorganization that was not related to brain atrophy or motor symptoms. Longitudinal studies currently in progress will chart the course of functional changes to determine the most sensitive markers of disease progression. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

The linguistic context effects on the processing of body-object interaction words: An ERP study on second language learners.

PubMed

Xue, Jin; Marmolejo-Ramos, Fernando; Pei, Xuna

2015-07-10

Embodied theories of cognition argue that the processing of both concrete and abstract concepts requires the activation of sensorimotor systems. The present study examined the time course for embedding a sensorimotor context in order to elicit sensitivity to the sensorimotor consequences of understanding body-object interaction (BOI) words. In the study, Event-Related Potentials (ERPs) were recorded while subjects performed a sentence acceptability task. Target BOI words were preceded by rich or poor sensorimotor sentential contexts. The behavioural results replicated previous findings in that high BOI words received a response faster than low BOI words. In addition to this, however, there was a context effect in the sensorimotor region as well as a BOI effect in the parietal region (involved in object representation). The results indicate that the sentential sensorimotor context contributes to the subsequent BOI processing and that action-and perception-related language leads to the activation of the same brain areas, which is consistent with the embodiment theory. Copyright © 2015 Elsevier B.V. All rights reserved.

An optimized fluorescent probe for visualizing glutamate neurotransmission.

PubMed

Marvin, Jonathan S; Borghuis, Bart G; Tian, Lin; Cichon, Joseph; Harnett, Mark T; Akerboom, Jasper; Gordus, Andrew; Renninger, Sabine L; Chen, Tsai-Wen; Bargmann, Cornelia I; Orger, Michael B; Schreiter, Eric R; Demb, Jonathan B; Gan, Wen-Biao; Hires, S Andrew; Looger, Loren L

2013-02-01

We describe an intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) with signal-to-noise ratio and kinetics appropriate for in vivo imaging. We engineered iGluSnFR in vitro to maximize its fluorescence change, and we validated its utility for visualizing glutamate release by neurons and astrocytes in increasingly intact neurological systems. In hippocampal culture, iGluSnFR detected single field stimulus-evoked glutamate release events. In pyramidal neurons in acute brain slices, glutamate uncaging at single spines showed that iGluSnFR responds robustly and specifically to glutamate in situ, and responses correlate with voltage changes. In mouse retina, iGluSnFR-expressing neurons showed intact light-evoked excitatory currents, and the sensor revealed tonic glutamate signaling in response to light stimuli. In worms, glutamate signals preceded and predicted postsynaptic calcium transients. In zebrafish, iGluSnFR revealed spatial organization of direction-selective synaptic activity in the optic tectum. Finally, in mouse forelimb motor cortex, iGluSnFR expression in layer V pyramidal neurons revealed task-dependent single-spine activity during running.

The pleasure of revenge: retaliatory aggression arises from a neural imbalance toward reward

PubMed Central

DeWall, C. Nathan

2016-01-01

Most of daily life hums along peacefully but provocations tip the balance toward aggression. Negative feelings are often invoked to explain why people lash out after an insult. Yet people might retaliate because provocation makes aggression hedonically rewarding. To test this alternative hypothesis, 69 participants underwent functional neuroimaging while they completed a behavioral aggression task that repeatedly manipulated whether aggression was preceded by an instance of provocation or not. After provocation, greater activity in the nucleus accumbens (NAcc) (a brain region reliably associated with reward) during aggressive decisions predicted louder noise blasts administered in retaliation. Greater NAcc activation was also associated with participants’ history of real-world violence. Functional connectivity between the NAcc and a regulatory region in the lateral prefrontal cortex related to lower retaliatory aggression. These findings suggest that provocation tips the neural balance towards hedonic reward, which fosters retaliatory aggression. Although such pleasure of inflicting pain may promote retaliatory aggression, self-regulatory processes can keep such aggressive urges at bay. Implications for theory and violence reduction are discussed. PMID:26117504

Appearance of β-dystroglycan precedes the formation of glio-vascular end-feet in developing rat brain

PubMed Central

Kálmán, Mihály; Oszwald, Erzsébet; Adorján, István

2018-01-01

Dystroglycan has an important role in binding of perivascular glial end-feet to the basal lamina. Its β-subunit is localized in the glial end-feet. The investigation period lasted from E(embryonic day)12 to E20. Laminin and β-dystroglycan were detected by immunohistochemistry, the glial localization of the latter one was supported by electron microscopy. The immature glial structures were visualized by the immunostaining of nestin. The β-dystroglycan immunoreactivity appeared at E16 following the laminin of basal lamina but preceding the perivascular processes of radial glia (E18) and astrocyte-like cells (E20). It occurred in cell bodies which attached to the vessels directly but not with vascular processes and end-feet. The presence of β-dystroglycan in such immature cells may promote their differentiation to perivascular astrocytes and influence the formation of the glio-vascular processes.

Brain mechanisms of successful recognition through retrieval of semantic context.

PubMed

Flegal, Kristin E; Marín-Gutiérrez, Alejandro; Ragland, J Daniel; Ranganath, Charan

2014-08-01

Episodic memory is associated with the encoding and retrieval of context information and with a subjective sense of reexperiencing past events. The neural correlates of episodic retrieval have been extensively studied using fMRI, leading to the identification of a "general recollection network" including medial temporal, parietal, and prefrontal regions. However, in these studies, it is difficult to disentangle the effects of context retrieval from recollection. In this study, we used fMRI to determine the extent to which the recruitment of regions in the recollection network is contingent on context reinstatement. Participants were scanned during a cued recognition test for target words from encoded sentences. Studied target words were preceded by either a cue word studied in the same sentence (thus congruent with encoding context) or a cue word studied in a different sentence (thus incongruent with encoding context). Converging fMRI results from independently defined ROIs and whole-brain analysis showed regional specificity in the recollection network. Activity in hippocampus and parahippocampal cortex was specifically increased during successful retrieval following congruent context cues, whereas parietal and prefrontal components of the general recollection network were associated with confident retrieval irrespective of contextual congruency. Our findings implicate medial temporal regions in the retrieval of semantic context, contributing to, but dissociable from, recollective experience.

GERIATRIC PATIENTS IN A MENTAL HOSPITAL

PubMed Central

Ernst, Franklin H.; Oliver, W. A.; Simon, Alexander; Malamud, Nathan

1956-01-01

An intensive study was made of men 55 years of age and over admitted to Napa State Hospital with either senile or arteriosclerotic brain disease. A ward treatment program, combining both the medical and psychiatric approaches, was applied to one-half of such patients admitted to a state hospital, with the aim of determining what, if any, effect this program would have on the course of the illnesses. Special laboratory studies showed: (a) Serial electroencephalograms and hospital adjustment ratings appeared to be positively correlated with the patients' clinical course; (b) In 35 per cent of cases the electrocardiographic tracings at the time of admittance were within normal limits; (c) A “pathological level” of blood bromides was found in only one of 340 consecutive admissions in this age group. Sociopsychiatric study of 100 consecutively admitted patients revealed that: (a) 35 per cent of the patients were from the middle, and 65 per cent from the lower classes of society; (b) Only 59 per cent were admitted because of activities specifically psychotic. (c) 63 per cent needed admittance to this state hospital for observation and diagnosis, but only 44 per cent needed to stay for care and treatment; (d) In 88 per cent, specific emotional stresses were present just preceding and coincident with the clinical appearance of the organic brain syndrome. PMID:13304672

Partial Least Squares for Discrimination in fMRI Data

PubMed Central

Andersen, Anders H.; Rayens, William S.; Liu, Yushu; Smith, Charles D.

2011-01-01

Multivariate methods for discrimination were used in the comparison of brain activation patterns between groups of cognitively normal women who are at either high or low Alzheimer's disease risk based on family history and apolipoprotein-E4 status. Linear discriminant analysis (LDA) was preceded by dimension reduction using either principal component analysis (PCA), partial least squares (PLS), or a new oriented partial least squares (OrPLS) method. The aim was to identify a spatial pattern of functionally connected brain regions that was differentially expressed by the risk groups and yielded optimal classification accuracy. Multivariate dimension reduction is required prior to LDA when the data contains more feature variables than there are observations on individual subjects. Whereas PCA has been commonly used to identify covariance patterns in neuroimaging data, this approach only identifies gross variability and is not capable of distinguishing among-groups from within-groups variability. PLS and OrPLS provide a more focused dimension reduction by incorporating information on class structure and therefore lead to more parsimonious models for discrimination. Performance was evaluated in terms of the cross-validated misclassification rates. The results support the potential of using fMRI as an imaging biomarker or diagnostic tool to discriminate individuals with disease or high risk. PMID:22227352

Polysomnographic and neurometabolic features may mark preclinical autosomal dominant cerebellar ataxia, deafness, and narcolepsy due to a mutation in the DNA (cytosine-5-)-methyltransferase gene, DNMT1.

PubMed

Moghadam, Keivan Kaveh; Pizza, Fabio; Tonon, Caterina; Lodi, Raffaele; Carelli, Valerio; Poli, Francesca; Franceschini, Christian; Barboni, Piero; Seri, Marco; Ferrari, Simona; La Morgia, Chiara; Testa, Claudia; Cornelio, Ferdinando; Liguori, Rocco; Winkelmann, Juliane; Lin, Ling; Mignot, Emmanuel; Plazzi, Giuseppe

2014-05-01

We aimed to report the clinical picture of two asymptomatic daughters of a patient with autosomal dominant cerebellar ataxia, deafness, and narcolepsy (ADCA-DN) due to a mutation in the DNA (cytosine-5-)-methyltransferase gene, DNMT1. Clinical assessment based on history, neurologic examination, sleep recordings, neurophysiologic neuroimaging, and genetic tests was performed. History and neurologic examination in both subjects were unremarkable. Genetic analysis disclosed in both the paternally-inherited heterozygous point mutation in the DNMT1 gene. Sleep recordings found sleep-onset rapid eye movement periods (SOREMPs) and proton magnetic resonance spectroscopy (MRS) revealed increased cerebellar myoinositol (mI) in both subjects. Auditory and ophthalmologic investigations as well as structural brain magnetic resonance imaging (MRI) scans revealed no abnormalities. The two asymptomatic carriers of the heterozygous DNMT1 mutation for ADCA-DN, a late-onset neurodegenerative disease, presented with SOREMPs associated with an increase of mI in the brain, a marker of glial cell activity and density characteristic of early stages of neurodegenerative diseases. Therefore, SOREMPs may precede the clinical picture of ADCA-DN as an early polysomnographic marker of central nervous system involvement detected by MRS. Copyright © 2014 Elsevier B.V. All rights reserved.

No auditory experience, no tinnitus: Lessons from subjects with congenital- and acquired single-sided deafness.

PubMed

Lee, Sang-Yeon; Nam, Dong Woo; Koo, Ja-Won; De Ridder, Dirk; Vanneste, Sven; Song, Jae-Jin

2017-10-01

Recent studies have adopted the Bayesian brain model to explain the generation of tinnitus in subjects with auditory deafferentation. That is, as the human brain works in a Bayesian manner to reduce environmental uncertainty, missing auditory information due to hearing loss may cause auditory phantom percepts, i.e., tinnitus. This type of deafferentation-induced auditory phantom percept should be preceded by auditory experience because the fill-in phenomenon, namely tinnitus, is based upon auditory prediction and the resultant prediction error. For example, a recent animal study observed the absence of tinnitus in cats with congenital single-sided deafness (SSD; Eggermont and Kral, Hear Res 2016). However, no human studies have investigated the presence and characteristics of tinnitus in subjects with congenital SSD. Thus, the present study sought to reveal differences in the generation of tinnitus between subjects with congenital SSD and those with acquired SSD to evaluate the replicability of previous animal studies. This study enrolled 20 subjects with congenital SSD and 44 subjects with acquired SSD and examined the presence and characteristics of tinnitus in the groups. None of the 20 subjects with congenital SSD perceived tinnitus on the affected side, whereas 30 of 44 subjects with acquired SSD experienced tinnitus on the affected side. Additionally, there were significant positive correlations between tinnitus characteristics and the audiometric characteristics of the SSD. In accordance with the findings of the recent animal study, tinnitus was absent in subjects with congenital SSD, but relatively frequent in subjects with acquired SSD, which suggests that the development of tinnitus should be preceded by auditory experience. In other words, subjects with profound congenital peripheral deafferentation do not develop auditory phantom percepts because no auditory predictions are available from the Bayesian brain. Copyright © 2017 Elsevier B.V. All rights reserved.

Primary Sjogren's syndrome with central nervous system involvement.

PubMed

Alhomoud, Iftetah A; Bohlega, Saeed A; Alkawi, Mohammed Z; Alsemari, Abdulaziz M; Omer, Saleh M; Alsenani, Fahmi M

2009-08-01

To describe the clinical, laboratory, and radiological features of Primary Sjogren's syndrome (PSS) with central nervous system (CNS) involvement. A retrospective case series of 12 female patients with PSS and CNS involvement at King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia from 1991-2009. The diagnosis of PSS is defined by the American-European Diagnostic Criteria. We analyzed the clinical, radiological, and immunological features. The mean age was 40 years (range 16-58 years); all patient were females and presented with active neurological symptoms. The neurological involvement preceded the classic sicca symptoms (33%). Eight patients (66%) presented with myelopathy, 9 patients (75%) had optic neuritis, and the rest had variable neurological signs. Immunological tests (anti-Sjogren's syndrome A and anti-Sjogren's syndrome B) were high in 7 patients (58%). Minor salivary gland biopsy revealed inflammatory cell infiltrate in 11 patients (92%). Brain MRI showed scattered white matter changes in 7 patients (58%). Spine MRI showed multiple foci of hyperintensity in T2-weighted image in 6 patients (50%), and long segment of hyperintensity at the cervical spinal cord in 2 patients (16%). Our findings demonstrate that CNS involvements in PSS have great clinical variability and could precede the classic sicca symptoms by years. Primary Sjogren's syndrome can mimic multiple sclerosis (primary progressive multiple sclerosis or relapsing remitting multiple sclerosis), therefore a screening test for PSS should be considered in suspected cases. A well-defined management protocol awaits studies with larger case numbers.

Grammatical markers switch roles and elicit different electrophysiological responses under shallow and deep semantic requirements.

PubMed

Soshi, Takahiro; Nakajima, Heizo; Hagiwara, Hiroko

2016-10-01

Static knowledge about the grammar of a natural language is represented in the cortico-subcortical system. However, the differences in dynamic verbal processing under different cognitive conditions are unclear. To clarify this, we conducted an electrophysiological experiment involving a semantic priming paradigm in which semantically congruent or incongruent word sequences (prime nouns-target verbs) were randomly presented. We examined the event-related brain potentials that occurred in response to congruent and incongruent target words that were preceded by primes with or without grammatical case markers. The two participant groups performed either the shallow (lexical judgment) or deep (direct semantic judgment) semantic tasks. We hypothesized that, irrespective of the case markers, the congruent targets would reduce centro-posterior N400 activities under the deep semantic condition, which induces selective attention to the semantic relatedness of content words. However, the same congruent targets with correct case markers would reduce lateralized negativity under the shallow semantic condition because grammatical case markers are related to automatic structural integration under semantically unattended conditions. We observed that congruent targets (e.g., 'open') that were preceded by primes with congruent case markers (e.g., 'shutter-object case') reduced lateralized negativity under the shallow semantic condition. In contrast, congruent targets, irrespective of case markers, consistently yielded N400 reductions under the deep semantic condition. To summarize, human neural verbal processing differed in response to the same grammatical markers in the same verbal expressions under semantically attended or unattended conditions.

Pediatric respiratory and systemic effects of chronic air pollution exposure: nose, lung, heart, and brain pathology.

PubMed

Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Torres-Jardón, Ricardo; Henriquez-Roldán, Carlos; Barragán-Mejía, Gerardo; Valencia-Salazar, Gildardo; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderón, Rafael; Reed, William

2007-01-01

Exposures to particulate matter and gaseous air pollutants have been associated with respiratory tract inflammation, disruption of the nasal respiratory and olfactory barriers, systemic inflammation, production of mediators of inflammation capable of reaching the brain and systemic circulation of particulate matter. Mexico City (MC) residents are exposed to significant amounts of ozone, particulate matter and associated lipopolysaccharides. MC dogs exhibit brain inflammation and an acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by air pollutants. MC children, adolescents and adults have a significant upregulation of cyclooxygenase-2 (COX2) and interleukin-1beta (IL-1beta) in olfactory bulb and frontal cortex, as well as neuronal and astrocytic accumulation of the 42 amino acid form of beta -amyloid peptide (Abeta 42), including diffuse amyloid plaques in frontal cortex. The pathogenesis of Alzheimer's disease (AD) is characterized by brain inflammation and the accumulation of Abeta 42, which precede the appearance of neuritic plaques and neurofibrillary tangles, the pathological hallmarks of AD. Our findings of nasal barrier disruption, systemic inflammation, and the upregulation of COX2 and IL-1beta expression and Abeta 42 accumulation in brain suggests that sustained exposures to significant concentrations of air pollutants such as particulate matter could be a risk factor for AD and other neurodegenerative diseases.

Benefits of physical exercise on the aging brain: the role of the prefrontal cortex.

PubMed

Berchicci, Marika; Lucci, Giuliana; Di Russo, Francesco

2013-11-01

Motor planning in older adults likely relies on the overengagement of the prefrontal cortex (PFC) and is associated with slowness of movement and responses. Does a physically active lifestyle counteract the overrecruitment of the PFC during action preparation? This study used high-resolution electroencephalography to measure the effect of physical exercise on the executive functions of the PFC preceding a visuomotor discriminative task. A total of 130 participants aged 15-86 were divided into two groups based on physical exercise participation. The response times and accuracy and the premotor activity of the PFC were separately correlated with age for the two groups. The data were first fit with a linear function and then a higher order polynomial function. We observed that after 35-40 years of age, physically active individuals have faster response times than their less active peers and showed no signs of PFC hyperactivity during motor planning. The present findings show that physical exercise could speed up the response of older people and reveal that also in middle-aged people, moderate-to-high levels of physical exercise benefits the planning/execution of a response and the executive functions mediated by the PFC, counteracting the neural overactivity often observed in the elderly adults.

Neuronal Activity in the Subthalamic Cerebrovasodilator Area under Partial-Gravity Conditions in Rats

PubMed Central

Zeredo, Jorge L.; Toda, Kazuo; Kumei, Yasuhiro

2014-01-01

The reduced-gravity environment in space is known to cause an upward shift in body fluids and thus require cardiovascular adaptations in astronauts. In this study, we recorded in rats the neuronal activity in the subthalamic cerebrovasodilator area (SVA), a key area that controls cerebral blood flow (CBF), in response to partial gravity. “Partial gravity” is the term that defines the reduced-gravity levels between 1 g (the unit gravity acceleration on Earth) and 0 g (complete weightlessness in space). Neuronal activity was recorded telemetrically through chronically implanted microelectrodes in freely moving rats. Graded levels of partial gravity from 0.4 g to 0.01 g were generated by customized parabolic-flight maneuvers. Electrophysiological signals in each partial-gravity phase were compared to those of the preceding 1 g level-flight. As a result, SVA neuronal activity was significantly inhibited by the partial-gravity levels of 0.15 g and lower, but not by 0.2 g and higher. Gravity levels between 0.2–0.15 g could represent a critical threshold for the inhibition of neurons in the rat SVA. The lunar gravity (0.16 g) might thus trigger neurogenic mechanisms of CBF control. This is the first study to examine brain electrophysiology with partial gravity as an experimental parameter. PMID:25370031

Determination of proenkephalin products in brain tissue by high-performance liquid chromatography and a modified bioassay procedure.

PubMed

Bailey, C; Kitchen, I

1985-06-01

A method is described for the separation of proenkephalin products using gradient high-performance liquid chromatography preceded by Sep-Pak chromatography. Samples can be assayed simply by use of a modified mouse vas deferens bioassay which is sufficiently sensitive for most applications. The preliminary Sep-Pak chromatography method excludes alpha-neoendorphin and the dynorphins and thus provides a suitable procedure for separation of prodynorphin and proenkephalin products.

Estimation of the velocity and trajectory of three-dimensional reaching movements from non-invasive magnetoencephalography signals

NASA Astrophysics Data System (ADS)

Yeom, Hong Gi; Sic Kim, June; Chung, Chun Kee

2013-04-01

Objective. Studies on the non-invasive brain-machine interface that controls prosthetic devices via movement intentions are at their very early stages. Here, we aimed to estimate three-dimensional arm movements using magnetoencephalography (MEG) signals with high accuracy. Approach. Whole-head MEG signals were acquired during three-dimensional reaching movements (center-out paradigm). For movement decoding, we selected 68 MEG channels in motor-related areas, which were band-pass filtered using four subfrequency bands (0.5-8, 9-22, 25-40 and 57-97 Hz). After the filtering, the signals were resampled, and 11 data points preceding the current data point were used as features for estimating velocity. Multiple linear regressions were used to estimate movement velocities. Movement trajectories were calculated by integrating estimated velocities. We evaluated our results by calculating correlation coefficients (r) between real and estimated velocities. Main results. Movement velocities could be estimated from the low-frequency MEG signals (0.5-8 Hz) with significant and considerably high accuracy (p <0.001, mean r > 0.7). We also showed that preceding (60-140 ms) MEG signals are important to estimate current movement velocities and the intervals of brain signals of 200-300 ms are sufficient for movement estimation. Significance. These results imply that disabled people will be able to control prosthetic devices without surgery in the near future.

Semantic integration of differently asynchronous audio-visual information in videos of real-world events in cognitive processing: an ERP study.

PubMed

Liu, Baolin; Wu, Guangning; Wang, Zhongning; Ji, Xiang

2011-07-01

In the real world, some of the auditory and visual information received by the human brain are temporally asynchronous. How is such information integrated in cognitive processing in the brain? In this paper, we aimed to study the semantic integration of differently asynchronous audio-visual information in cognitive processing using ERP (event-related potential) method. Subjects were presented with videos of real world events, in which the auditory and visual information are temporally asynchronous. When the critical action was prior to the sound, sounds incongruous with the preceding critical actions elicited a N400 effect when compared to congruous condition. This result demonstrates that semantic contextual integration indexed by N400 also applies to cognitive processing of multisensory information. In addition, the N400 effect is early in latency when contrasted with other visually induced N400 studies. It is shown that cross modal information is facilitated in time when contrasted with visual information in isolation. When the sound was prior to the critical action, a larger late positive wave was observed under the incongruous condition compared to congruous condition. P600 might represent a reanalysis process, in which the mismatch between the critical action and the preceding sound was evaluated. It is shown that environmental sound may affect the cognitive processing of a visual event. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Inhibition of choline acetyltransferase as a mechanism for cholinergic dysfunction induced by amyloid-β peptide oligomers.

PubMed

Nunes-Tavares, Nilson; Santos, Luís Eduardo; Stutz, Bernardo; Brito-Moreira, Jordano; Klein, William L; Ferreira, Sérgio T; de Mello, Fernando G

2012-06-01

Dysregulated cholinergic signaling is an early hallmark of Alzheimer disease (AD), usually ascribed to degeneration of cholinergic neurons induced by the amyloid-β peptide (Aβ). It is now generally accepted that neuronal dysfunction and memory deficits in the early stages of AD are caused by the neuronal impact of soluble Aβ oligomers (AβOs). AβOs build up in AD brain and specifically attach to excitatory synapses, leading to synapse dysfunction. Here, we have investigated the possibility that AβOs could impact cholinergic signaling. The activity of choline acetyltransferase (ChAT, the enzyme that carries out ACh production) was inhibited by ~50% in cultured cholinergic neurons exposed to low nanomolar concentrations of AβOs. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, lactate dehydrogenase release, and [(3)H]choline uptake assays showed no evidence of neuronal damage or loss of viability that could account for reduced ChAT activity under these conditions. Glutamate receptor antagonists fully blocked ChAT inhibition and oxidative stress induced by AβOs. Antioxidant polyunsaturated fatty acids had similar effects, indicating that oxidative damage may be involved in ChAT inhibition. Treatment with insulin, previously shown to down-regulate neuronal AβO binding sites, fully prevented AβO-induced inhibition of ChAT. Interestingly, we found that AβOs selectively bind to ~50% of cultured cholinergic neurons, suggesting that ChAT is fully inhibited in AβO-targeted neurons. Reduction in ChAT activity instigated by AβOs may thus be a relevant event in early stage AD pathology, preceding the loss of cholinergic neurons commonly observed in AD brains.

Activity in Face-Responsive Brain Regions is Modulated by Invisible, Attended Faces: Evidence from Masked Priming

PubMed Central

Eger, Evelyn; Dolan, Raymond; Henson, Richard N.

2009-01-01

It is often assumed that neural activity in face-responsive regions of primate cortex correlates with conscious perception of faces. However, whether such activity occurs without awareness is still debated. Using functional magnetic resonance imaging (fMRI) in conjunction with a novel masked face priming paradigm, we observed neural modulations that could not be attributed to perceptual awareness. More specifically, we found reduced activity in several classic face-processing regions, including the “fusiform face area,” “occipital face area,” and superior temporal sulcus, when a face was preceded by a briefly flashed image of the same face, relative to a different face, even when 2 images of the same face differed. Importantly, unlike most previous studies, which have minimized awareness by using conditions of inattention, the present results occurred when the stimuli (the primes) were attended. By contrast, when primes were perceived consciously, in a long-lag priming paradigm, we found repetition-related activity increases in additional frontal and parietal regions. These data not only demonstrate that fMRI activity in face-responsive regions can be modulated independently of perceptual awareness, but also document where such subliminal face-processing occurs (i.e., restricted to face-responsive regions of occipital and temporal cortex) and to what extent (i.e., independent of the specific image). PMID:18400791

Independence Pending: Teacher Behaviors Preceding Learner Problem Solving

ERIC Educational Resources Information Center

Roesler, Rebecca A.

2017-01-01

The purposes of the present study were to identify the teacher behaviors that preceded learners' active participation in solving musical and technical problems and describe learners' roles in the problem-solving process. I applied an original model of problem solving to describe the behaviors of teachers and students in 161 rehearsal frames…

Subthalamic Neural Activity Patterns Anticipate Economic Risk Decisions in Gambling

PubMed Central

Rosa, M.; Carpaneto, J.; Priori, A.

2018-01-01

Abstract Economic decision-making is disrupted in individuals with gambling disorder, an addictive behavior observed in Parkinson’s disease (PD) patients receiving dopaminergic therapy. The subthalamic nucleus (STN) is involved in the inhibition of impulsive behaviors; however, its role in impulse control disorders and addiction is still unclear. Here, we recorded STN local field potentials (LFPs) in PD patients with and without gambling disorder during an economic decision-making task. Reaction times analysis showed that for all patients, the decision whether to risk preceded task onset. We compared then for both groups the STN LFP preceding high- and low-risk economic decisions. We found that risk avoidance in gamblers correlated with larger STN LFP low-frequency (<12-Hz) fluctuations preceding task onset. In particular, the amplitude of low-frequency LFP fluctuations carried significant information about future decisions. Decisions of patients not affected by gambling disorder were instead not correlated with pretask STN LFP. Our results suggest that STN activity preceding task onset affects risk decisions by preemptively inhibiting attraction to high but unlikely rewards in favor of a long-term payoff. PMID:29445770

Two sources of meaning in infant communication: preceding action contexts and act-accompanying characteristics

PubMed Central

Liszkowski, Ulf

2014-01-01

How do infants communicate before they have acquired a language? This paper supports the hypothesis that infants possess social–cognitive skills that run deeper than language alone, enabling them to understand others and make themselves understood. I suggested that infants, like adults, use two sources of extralinguistic information to communicate meaningfully and react to and express communicative intentions appropriately. In support, a review of relevant experiments demonstrates, first, that infants use information from preceding shared activities to tailor their comprehension and production of communication. Second, a series of novel findings from our laboratory shows that in the absence of distinguishing information from preceding routines or activities, infants use accompanying characteristics (such as prosody and posture) that mark communicative intentions to extract and transmit meaning. Findings reveal that before infants begin to speak they communicate in meaningful ways by binding preceding and simultaneous multisensory information to a communicative act. These skills are not only a precursor to language, but also an outcome of social–cognitive development and social experience in the first year of life. PMID:25092662

Involvement of neuronal IL-1β in acquired brain lesions in a rat model of neonatal encephalopathy.

PubMed

Savard, Alexandre; Lavoie, Karine; Brochu, Marie-Elsa; Grbic, Djordje; Lepage, Martin; Gris, Denis; Sebire, Guillaume

2013-09-05

Infection-inflammation combined with hypoxia-ischemia (HI) is the most prevalent pathological scenario involved in perinatal brain damage leading to life-long neurological disabilities. Following lipopolysaccharide (LPS) and/or HI aggression, different patterns of inflammatory responses have been uncovered according to the brain differentiation stage. In fact, LPS pre-exposure has been reported to aggravate HI brain lesions in post-natal day 1 (P1) and P7 rat models that are respectively equivalent - in terms of brain development - to early and late human preterm newborns. However, little is known about the innate immune response in LPS plus HI-induced lesions of the full-term newborn forebrain and the associated neuropathological and neurobehavioral outcomes. An original preclinical rat model has been previously documented for the innate neuroimmune response at different post-natal ages. It was used in the present study to investigate the neuroinflammatory mechanisms that underline neurological impairments after pathogen-induced inflammation and HI in term newborns. LPS and HI exerted a synergistic detrimental effect on rat brain. Their effect led to a peculiar pattern of parasagittal cortical-subcortical infarcts mimicking those in the human full-term newborn with subsequent severe neurodevelopmental impairments. An increased IL-1β response in neocortical and basal gray neurons was demonstrated at 4 h after LPS + HI-exposure and preceded other neuroinflammatory responses such as microglial and astroglial cell activation. Neurological deficits were observed during the acute phase of injury followed by a recovery, then by a delayed onset of profound motor behavior impairment, reminiscent of the delayed clinical onset of motor system impairments observed in humans. Interleukin-1 receptor antagonist (IL-1ra) reduced the extent of brain lesions confirming the involvement of IL-1β response in their pathophysiology. In rat pups at a neurodevelopmental age corresponding to full-term human newborns, a systemic pre-exposure to a pathogen component amplified HI-induced mortality and morbidities that are relevant to human pathology. Neuronal cells were the first cells to produce IL-1β in LPS + HI-exposed full-term brains. Such IL-1β production might be responsible for neuronal self-injuries via well-described neurotoxic mechanisms such as IL-1β-induced nitric oxide production, or IL-1β-dependent exacerbation of excitotoxic damage.

Network topology and functional connectivity disturbances precede the onset of Huntington’s disease

PubMed Central

Harrington, Deborah L.; Rubinov, Mikail; Durgerian, Sally; Mourany, Lyla; Reece, Christine; Koenig, Katherine; Bullmore, Ed; Long, Jeffrey D.; Paulsen, Jane S.

2015-01-01

Cognitive, motor and psychiatric changes in prodromal Huntington’s disease have nurtured the emergent need for early interventions. Preventive clinical trials for Huntington’s disease, however, are limited by a shortage of suitable measures that could serve as surrogate outcomes. Measures of intrinsic functional connectivity from resting-state functional magnetic resonance imaging are of keen interest. Yet recent studies suggest circumscribed abnormalities in resting-state functional magnetic resonance imaging connectivity in prodromal Huntington’s disease, despite the spectrum of behavioural changes preceding a manifest diagnosis. The present study used two complementary analytical approaches to examine whole-brain resting-state functional magnetic resonance imaging connectivity in prodromal Huntington’s disease. Network topology was studied using graph theory and simple functional connectivity amongst brain regions was explored using the network-based statistic. Participants consisted of gene-negative controls (n = 16) and prodromal Huntington’s disease individuals (n = 48) with various stages of disease progression to examine the influence of disease burden on intrinsic connectivity. Graph theory analyses showed that global network interconnectivity approximated a random network topology as proximity to diagnosis neared and this was associated with decreased connectivity amongst highly-connected rich-club network hubs, which integrate processing from diverse brain regions. However, functional segregation within the global network (average clustering) was preserved. Functional segregation was also largely maintained at the local level, except for the notable decrease in the diversity of anterior insula intermodular-interconnections (participation coefficient), irrespective of disease burden. In contrast, network-based statistic analyses revealed patterns of weakened frontostriatal connections and strengthened frontal-posterior connections that evolved as disease burden increased. These disturbances were often related to long-range connections involving peripheral nodes and interhemispheric connections. A strong association was found between weaker connectivity and decreased rich-club organization, indicating that whole-brain simple connectivity partially expressed disturbances in the communication of highly-connected hubs. However, network topology and network-based statistic connectivity metrics did not correlate with key markers of executive dysfunction (Stroop Test, Trail Making Test) in prodromal Huntington’s disease, which instead were related to whole-brain connectivity disturbances in nodes (right inferior parietal, right thalamus, left anterior cingulate) that exhibited multiple aberrant connections and that mediate executive control. Altogether, our results show for the first time a largely disease burden-dependent functional reorganization of whole-brain networks in prodromal Huntington’s disease. Both analytic approaches provided a unique window into brain reorganization that was not related to brain atrophy or motor symptoms. Longitudinal studies currently in progress will chart the course of functional changes to determine the most sensitive markers of disease progression. PMID:26059655

When will a stuttering moment occur? The determining role of speech motor preparation.

PubMed

Vanhoutte, Sarah; Cosyns, Marjan; van Mierlo, Pieter; Batens, Katja; Corthals, Paul; De Letter, Miet; Van Borsel, John; Santens, Patrick

2016-06-01

The present study aimed to evaluate whether increased activity related to speech motor preparation preceding fluently produced words reflects a successful compensation strategy in stuttering. For this purpose, a contingent negative variation (CNV) was evoked during a picture naming task and measured by use of electro-encephalography. A CNV is a slow, negative event-related potential known to reflect motor preparation generated by the basal ganglia-thalamo-cortical (BGTC) - loop. In a previous analysis, the CNV of 25 adults with developmental stuttering (AWS) was significantly increased, especially over the right hemisphere, compared to the CNV of 35 fluent speakers (FS) when both groups were speaking fluently (Vanhoutte et al., (2015) doi: 10.1016/j.neuropsychologia.2015.05.013). To elucidate whether this increase is a compensation strategy enabling fluent speech in AWS, the present analysis evaluated the CNV of 7 AWS who stuttered during this picture naming task. The CNV preceding AWS stuttered words was statistically compared to the CNV preceding AWS fluent words and FS fluent words. Though no difference emerged between the CNV of the AWS stuttered words and the FS fluent words, a significant reduction was observed when comparing the CNV preceding AWS stuttered words to the CNV preceding AWS fluent words. The latter seems to confirm the compensation hypothesis: the increased CNV prior to AWS fluent words is a successful compensation strategy, especially when it occurs over the right hemisphere. The words are produced fluently because of an enlarged activity during speech motor preparation. The left CNV preceding AWS stuttered words correlated negatively with stuttering frequency and severity suggestive for a link between the left BGTC - network and the stuttering pathology. Overall, speech motor preparatory activity generated by the BGTC - loop seems to have a determining role in stuttering. An important divergence between left and right hemisphere is hypothesized. Copyright © 2016 Elsevier Ltd. All rights reserved.

Expected reward modulates encoding-related theta activity before an event.

PubMed

Gruber, Matthias J; Watrous, Andrew J; Ekstrom, Arne D; Ranganath, Charan; Otten, Leun J

2013-01-01

Oscillatory brain activity in the theta frequency range (4-8 Hz) before the onset of an event has been shown to affect the likelihood of successfully encoding the event into memory. Recent work has also indicated that frontal theta activity might be modulated by reward, but it is not clear how reward expectancy, anticipatory theta activity, and memory formation might be related. Here, we used scalp electroencephalography (EEG) to assess the relationship between these factors. EEG was recorded from healthy adults while they memorized a series of words. Each word was preceded by a cue that indicated whether a high or low monetary reward would be earned if the word was successfully remembered in a later recognition test. Frontal theta power between the presentation of the reward cue and the onset of a word was predictive of later memory for the word, but only in the high reward condition. No theta differences were observed before word onset following low reward cues. The magnitude of prestimulus encoding-related theta activity in the high reward condition was correlated with the number of high reward words that were later confidently recognized. These findings provide strong evidence for a link between reward expectancy, theta activity, and memory encoding. Theta activity before event onset seems to be especially important for the encoding of motivationally significant stimuli. One possibility is that dopaminergic activity during reward anticipation mediates frontal theta activity related to memory. Copyright © 2012 Elsevier Inc. All rights reserved.

Being Eager to Prove Oneself: U-Shaped Relationship between Competence Frustration and Intrinsic Motivation in Another Activity.

PubMed

Fang, Hui; He, Bin; Fu, Huijian; Meng, Liang

2017-01-01

Competence frustration has been consistently found to undermine one's intrinsic motivation in the same activity. However, the relationship between competence frustration in a preceding activity and one's intrinsic motivation in a subsequent one remains unclear. In order to explore this relationship, self-reported data were collected from 617 undergraduate students of a large comprehensive university in southern China, who took varied courses immediately before taking a less-demanding one. Results suggested a U-shaped relationship between students' competence frustration in a preceding course and intrinsic motivation in a subsequent one. To be specific, for students whose competence frustration reached the inflection point, a restoration process would be activated if the current course would help restore their competence. Importantly, these students' competence frustration in a preceding course was found to positively predict their intrinsic motivation level in a subsequent course. As far as we are concerned, this is the first study to reveal a potential positive effect of need frustration outside of its primary thwarting context, which complements and extends existing literatures on the dynamics between need frustration and intrinsic motivation.

Intra-seasonal variability of extreme boreal stratospheric polar vortex events and their precursors

NASA Astrophysics Data System (ADS)

Díaz-Durán, Adelaida; Serrano, Encarna; Ayarzagüena, Blanca; Abalos, Marta; de la Cámara, Alvaro

2017-11-01

The dynamical variability of the boreal stratospheric polar vortex has been usually analysed considering the extended winter as a whole or only focusing on December, January and February. Yet recent studies have found intra-seasonal differences in the boreal stratospheric dynamics. In this study, the intra-seasonal variability of anomalous wave activity preceding polar vortex extremes in the Northern Hemisphere is examined using ERA-Interim reanalysis data. Weak (WPV) and strong (SPV) polar vortex events are grouped into early, mid- or late winter sub-periods depending on the onset date. Overall, the strongest (weakest) wave-activity anomalies preceding polar vortex extremes are found in mid- (early) winter. Most of WPV (SPV) events in early winter occur under the influence of east (west) phase of the Quasi-Biennial Oscillation (QBO) and an enhancement (inhibition) of wavenumber-1 wave activity (WN1). Mid- and late winter WPV events are preceded by a strong vortex and an enhancement of WN1 and WN2, but the spatial structure of the anomalous wave activity and the phase of the QBO are different. Prior to mid-winter WPVs the enhancement of WN2 is related to the predominance of La Niña and linked to blockings over Siberia. Mid-winter SPV events show a negative phase of the Pacific-North America pattern that inhibits WN1 injected into the stratosphere. This study suggests that dynamical features preceding extreme polar vortex events in mid-winter should not be generalized to other winter sub-periods.

Enhanced upper respiratory tract airflow and head fanning reduce brain temperature in brain-injured, mechanically ventilated patients: a randomized, crossover, factorial trial.

PubMed

Harris, B A; Andrews, P J D; Murray, G D

2007-01-01

Heat loss from the upper airways and through the skull are physiological mechanisms of brain cooling which have not been fully explored clinically. This randomized, crossover, factorial trial in 12 brain-injured, orally intubated patients investigated the effect of enhanced nasal airflow (high flow unhumidified air with 20 p.p.m. nitric oxide gas) and bilateral head fanning on frontal lobe brain temperature and selective brain cooling. After a 30 min baseline, each patient received the four possible combinations of the interventions--airflow, fanning, both together, no intervention--in randomized order. Each combination was delivered for 30 min and followed by a 30 min washout, the last 5 min of which provided the baseline for the next intervention. The difference in mean brain temperature over the last 5 min of the preceding washout minus the mean over the last 5 min of intervention, was 0.15 degrees C with nasal airflow (P=0.001, 95% CI 0.06-0.23 degrees C) and 0.26 degrees C with head fanning (P<0.001, 95% CI 0.17-0.34 degrees C). The estimate of the combined effect of airflow and fanning on brain temperature was 0.41 degrees C. Selective brain cooling did not occur. Physiologically, this study demonstrates that heat loss through the upper airways and through the skull can reduce parenchymal brain temperature in brain-injured humans and the onset of temperature reduction is rapid. Clinically, in ischaemic stroke, a temperature decrease of 0.27 degrees C may reduce the relative risk of poor outcome by 10-20%. Head fanning may have the potential to achieve a temperature decrease of this order.

Brain Injury in Neonates with Complex Congenital Heart Disease: What Is the Predictive Value of MRI in the Fetal Period?

PubMed

Brossard-Racine, M; du Plessis, A; Vezina, G; Robertson, R; Donofrio, M; Tworetzky, W; Limperopoulos, C

2016-07-01

Brain injury in neonates with congenital heart disease is an important predictor of adverse neurodevelopmental outcome. Impaired brain development in congenital heart disease may have a prenatal origin, but the sensitivity and specificity of fetal brain MR imaging for predicting neonatal brain lesions are currently unknown. We sought to determine the value of conventional fetal MR imaging for predicting abnormal findings on neonatal preoperative MR imaging in neonates with complex congenital heart disease. MR imaging studies were performed in 103 fetuses with confirmed congenital heart disease (mean gestational age, 31.57 ± 3.86 weeks) and were repeated postnatally before cardiac surgery (mean age, 6.8 ± 12.2 days). Each MR imaging study was read by a pediatric neuroradiologist. Brain abnormalities were detected in 17/103 (16%) fetuses by fetal MR imaging and in 33/103 (32%) neonates by neonatal MR imaging. Only 9/33 studies with abnormal neonatal findings were preceded by abnormal findings on fetal MR imaging. The sensitivity and specificity of conventional fetal brain MR imaging for predicting neonatal brain abnormalities were 27% and 89%, respectively. Brain abnormalities detected by in utero MR imaging in fetuses with congenital heart disease are associated with higher risk of postnatal preoperative brain injury. However, a substantial proportion of anomalies on postnatal MR imaging were not present on fetal MR imaging; this result is likely due to the limitations of conventional fetal MR imaging and the emergence of new lesions that occurred after the fetal studies. Postnatal brain MR imaging studies are needed to confirm the presence of injury before open heart surgery. © 2016 by American Journal of Neuroradiology.

Low-Frequency Cortical Oscillations Entrain to Subthreshold Rhythmic Auditory Stimuli

PubMed Central

Schroeder, Charles E.; Poeppel, David; van Atteveldt, Nienke

2017-01-01

Many environmental stimuli contain temporal regularities, a feature that can help predict forthcoming input. Phase locking (entrainment) of ongoing low-frequency neuronal oscillations to rhythmic stimuli is proposed as a potential mechanism for enhancing neuronal responses and perceptual sensitivity, by aligning high-excitability phases to events within a stimulus stream. Previous experiments show that rhythmic structure has a behavioral benefit even when the rhythm itself is below perceptual detection thresholds (ten Oever et al., 2014). It is not known whether this “inaudible” rhythmic sound stream also induces entrainment. Here we tested this hypothesis using magnetoencephalography and electrocorticography in humans to record changes in neuronal activity as subthreshold rhythmic stimuli gradually became audible. We found that significant phase locking to the rhythmic sounds preceded participants' detection of them. Moreover, no significant auditory-evoked responses accompanied this prethreshold entrainment. These auditory-evoked responses, distinguished by robust, broad-band increases in intertrial coherence, only appeared after sounds were reported as audible. Taken together with the reduced perceptual thresholds observed for rhythmic sequences, these findings support the proposition that entrainment of low-frequency oscillations serves a mechanistic role in enhancing perceptual sensitivity for temporally predictive sounds. This framework has broad implications for understanding the neural mechanisms involved in generating temporal predictions and their relevance for perception, attention, and awareness. SIGNIFICANCE STATEMENT The environment is full of rhythmically structured signals that the nervous system can exploit for information processing. Thus, it is important to understand how the brain processes such temporally structured, regular features of external stimuli. Here we report the alignment of slowly fluctuating oscillatory brain activity to external rhythmic structure before its behavioral detection. These results indicate that phase alignment is a general mechanism of the brain to process rhythmic structure and can occur without the perceptual detection of this temporal structure. PMID:28411273

Reconciling findings of emotion-induced memory enhancement and impairment of preceding items

PubMed Central

Knight, Marisa; Mather, Mara

2009-01-01

A large body of work reveals that people remember emotionally arousing information better than neutral information. However, previous research reveals contradictory effects of emotional events on memory for neutral events that precede or follow them: in some studies emotionally arousing items impair memory for immediately preceding or following items and in others arousing items enhance memory for preceding items. By demonstrating both emotion-induced enhancement and impairment, Experiments 1 and 2 clarified the conditions under which these effects are likely to occur. The results suggest that emotion-induced enhancement is most likely to occur for neutral items that: (1) precede (and so are poised to predict the onset of) emotionally arousing items, (2) have high attentional weights at encoding, and (3) are tested after a delay period of a week rather than within the same experiment session. In contrast, emotion-induced impairment is most likely to occur for neutral items near the onset of emotional arousal that are overshadowed by highly activated competing items during encoding. PMID:20001121

Brain structural alterations associated with young women with subthreshold depression

PubMed Central

Li, Haijiang; Wei, Dongtao; Sun, Jiangzhou; Chen, Qunlin; Zhang, Qinglin; Qiu, Jiang

2015-01-01

Neuroanatomical abnormalities in patients with major depression disorder (MDD) have been attracted great research attention. However, the structural alterations associated with subthreshold depression (StD) remain unclear and, therefore, require further investigation. In this study, 42 young women with StD, and 30 matched non-depressed controls (NCs) were identified based on two-time Beck Depression Inventory scores. Whole-brain voxel-based morphometry (VBM) and region of interest method were used to investigate altered gray matter volume (GMV) and white matter volume (WMV) among a non-clinical sample of young women with StD. VBM results indicated that young women with StD showed significantly decreased GMV in the right inferior parietal lobule than NCs; increased GMV in the amygdala, posterior cingulate cortex, and precuneus; and increased WMV in the posterior cingulate cortex and precuneus. Together, structural alterations in specific brain regions, which are known to be involved in the fronto-limbic circuits implicated in depression may precede the occurrence of depressive episodes and influence the development of MDD. PMID:25982857

Flexible establishment of functional brain networks supports attentional modulation of unconscious cognition.

PubMed

Ulrich, Martin; Adams, Sarah C; Kiefer, Markus

2014-11-01

In classical theories of attention, unconscious automatic processes are thought to be independent of higher-level attentional influences. Here, we propose that unconscious processing depends on attentional enhancement of task-congruent processing pathways implemented by a dynamic modulation of the functional communication between brain regions. Using functional magnetic resonance imaging, we tested our model with a subliminally primed lexical decision task preceded by an induction task preparing either a semantic or a perceptual task set. Subliminal semantic priming was significantly greater after semantic compared to perceptual induction in ventral occipito-temporal (vOT) and inferior frontal cortex, brain areas known to be involved in semantic processing. The functional connectivity pattern of vOT varied depending on the induction task and successfully predicted the magnitude of behavioral and neural priming. Together, these findings support the proposal that dynamic establishment of functional networks by task sets is an important mechanism in the attentional control of unconscious processing. © 2014 Wiley Periodicals, Inc.

Clinical trial perspective for adult and juvenile Huntington's disease using genetically-engineered mesenchymal stem cells

PubMed Central

Deng, Peter; Torrest, Audrey; Pollock, Kari; Dahlenburg, Heather; Annett, Geralyn; Nolta, Jan A.; Fink, Kyle D.

2016-01-01

Progress to date from our group and others indicate that using genetically-engineered mesenchymal stem cells (MSC) to secrete brain-derived neurotrophic factor (BDNF) supports our plan to submit an Investigational New Drug application to the Food and Drug Administration for the future planned Phase 1 safety and tolerability trial of MSC/BDNF in patients with Huntington's disease (HD). There are also potential applications of this approach beyond HD. Our biological delivery system for BDNF sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), Alzheimer's disease, and some forms of Parkinson's disease. The MSC/BDNF product could also be considered for studies of regeneration in traumatic brain injury, spinal cord and peripheral nerve injury. This work also provides a platform for our future gene editing studies, since we will again use MSCs to deliver the needed molecules into the central nervous system. PMID:27335539

The 5th Annual One Mind Summit: Lessons Learned About “Science Informing Brain Health Policies and Practice”

PubMed Central

Johnson, Stephen; Porter, Amy C.; Zatzick, Douglas

2017-01-01

Abstract Advances in science frequently precede changes in clinical care by several years or even decades. To better understand the path to translation, we invited experts to share their perspectives at the 5th Annual One Mind Summit: “Science Informing Brain Health Policies and Practice,” which was held on May 24–25, 2016, in Crystal City, VA. While the translation of brain research throughout the pipeline—from basic science research to patient care—was discussed, the focus was on the implementation of “best evidence” into patient care. The Summit identified key steps, including the need for professional endorsement and clinical guidelines or policies, acceptance by regulators and payers, dissemination and training for clinicians, patient advocacy, and learning healthcare models. The path to implementation was discussed broadly, as well as in the context of a specific project to implement concussion screening in emergency and urgent care centers throughout the United States. PMID:28351324

Figure-ground segregation modulates apparent motion.

PubMed

Ramachandran, V S; Anstis, S

1986-01-01

We explored the relationship between figure-ground segmentation and apparent motion. Results suggest that: static elements in the surround can eliminate apparent motion of a cluster of dots in the centre, but only if the cluster and surround have similar "grain" or texture; outlines that define occluding surfaces are taken into account by the motion mechanism; the brain uses a hierarchy of precedence rules in attributing motion to different segments of the visual scene. Being designated as "figure" confers a high rank in this scheme of priorities.

ERP correlates of anticipatory attention: spatial and non-spatial specificity and relation to subsequent selective attention.

PubMed

Dale, Corby L; Simpson, Gregory V; Foxe, John J; Luks, Tracy L; Worden, Michael S

2008-06-01

Brain-based models of visual attention hypothesize that attention-related benefits afforded to imperative stimuli occur via enhancement of neural activity associated with relevant spatial and non-spatial features. When relevant information is available in advance of a stimulus, anticipatory deployment processes are likely to facilitate allocation of attention to stimulus properties prior to its arrival. The current study recorded EEG from humans during a centrally-cued covert attention task. Cues indicated relevance of left or right visual field locations for an upcoming motion or orientation discrimination. During a 1 s delay between cue and S2, multiple attention-related events occurred at frontal, parietal and occipital electrode sites. Differences in anticipatory activity associated with the non-spatial task properties were found late in the delay, while spatially-specific modulation of activity occurred during both early and late periods and continued during S2 processing. The magnitude of anticipatory activity preceding the S2 at frontal scalp sites (and not occipital) was predictive of the magnitude of subsequent selective attention effects on the S2 event-related potentials observed at occipital electrodes. Results support the existence of multiple anticipatory attention-related processes, some with differing specificity for spatial and non-spatial task properties, and the hypothesis that levels of activity in anterior areas are important for effective control of subsequent S2 selective attention.

Timing of ectocranial suture activity in Gorilla gorilla as related to cranial volume and dental eruption

PubMed Central

Cray, James; Cooper, Gregory M; Mooney, Mark P; Siegel, Michael I

2011-01-01

Research has shown that Pan and Homo have similar ectocranial suture synostosis patterns and a similar suture ontogeny (relative timing of suture fusion during the species ontogeny). This ontogeny includes patency during and after neurocranial expansion with a delayed bony response associated with adaptation to biomechanical forces generated by mastication. Here we investigate these relationships for Gorilla by examining the association among ectocranial suture morphology, cranial volume (as a proxy for neurocranial expansion) and dental development (as a proxy for the length of time that it has been masticating hard foods and exerting such strains on the cranial vault) in a large sample of Gorilla gorilla skulls. Two-hundred and fifty-five Gorilla gorilla skulls were examined for ectocranial suture closure status, cranial volume and dental eruption. Regression models were calculated for cranial volumes by suture activity, and Kendall's tau (a non-parametric measure of association) was calculated for dental eruption status by suture activity. Results suggest that, as reported for Pan and Homo, neurocranial expansion precedes suture synostosis activity. Here, Gorilla was shown to have a strong relationship between dental development and suture activity (synostosis). These data are suggestive of suture fusion extending further into ontogeny than brain expansion, similar to Homo and Pan. This finding allows for the possibility that masticatory forces influence ectocranial suture morphology. PMID:21385182

Lower Working Memory Performance in Overweight and Obese Adolescents Is Mediated by White Matter Microstructure

PubMed Central

Alarcón, Gabriela; Ray, Siddharth; Nagel, Bonnie J.

2017-01-01

Objectives Elevated body mass index (BMI) is associated with deficits in working memory, reduced gray matter volume in frontal and parietal lobes, as well as changes in white matter (WM) microstructure. The current study examined whether BMI was related to working memory performance and blood oxygen level dependent (BOLD) activity, as well as WM microstructure during adolescence. Methods Linear regressions with BMI and (1) verbal working memory BOLD signal, (2) spatial working memory BOLD signal, and (3) fractional anisotropy (FA), a measure of WM microstructure, were conducted in a sample of 152 healthy adolescents ranging in BMI. Results BMI was inversely related to IQ and verbal and spatial working memory accuracy; however, there was no significant relationship between BMI and BOLD response for either verbal or spatial working memory. Furthermore, BMI was negatively correlated with FA in the left superior longitudinal fasciculus (SLF) and left inferior longitudinal fasciculus (ILF). ILF FA and IQ significantly mediated the relationship between BMI and verbal working memory performance, whereas SLF FA, but not IQ, significantly mediated the relationship between BMI and accuracy of both verbal and spatial working memory. Conclusions These findings indicate that higher BMI is associated with decreased FA in WM fibers connecting brain regions that support working memory, and that WM microstructural deficits may underlie inferior working memory performance in youth with higher BMI. Of interest, BMI did not show the same relationship with working memory BOLD activity, which may indicate that changes in brain structure precede changes in function. PMID:26708324

cAMP and forskolin decrease gamma-aminobutyric acid-gated chloride flux in rat brain synaptoneurosomes.

PubMed Central

Heuschneider, G; Schwartz, R D

1989-01-01

The effects of the cyclic nucleotide cAMP on gamma-aminobutyric acid-gated chloride channel function were investigated. The membrane-permeant cAMP analog N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate inhibited muscimol-induced 36Cl- uptake into rat cerebral cortical synaptoneurosomes in a concentration-dependent manner (IC50 = 1.3 mM). The inhibition was due to a decrease in the maximal effect of muscimol, with no change in potency. Similar effects were observed with 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate, 8-bromoadenosine 3',5'-cyclic monophosphate, and the phosphodiesterase inhibitor isobutylmethylxanthine. The effect of endogenous cAMP accumulation on the gamma-aminobutyric acid-gated Cl- channel was studied with forskolin, an activator of adenylate cyclase. Under identical conditions, in the intact synaptoneurosomes, forskolin inhibited muscimol-induced 36Cl- uptake and generated cAMP with similar potencies (IC50 = 14.3 microM; EC50 = 6.2 microM, respectively). Surprisingly, 1,9-dideoxyforskolin, which does not activate adenylate cyclase, also inhibited the muscimol response, suggesting that forskolin and its lipophilic derivatives may interact with the Cl- channel directly. Indeed, forskolin inhibition of muscimol-induced 36Cl- uptake was extremely rapid (within 5 sec), preceding the accumulation of sufficient levels of cAMP. After 5 min, a slower phase of inhibition was seen, similar to the time course for cAMP accumulation. The data suggest that gamma-aminobutyric acid (GABAA) receptor function in brain can be regulated by cAMP-dependent phosphorylation. PMID:2468163

Rapid Sensitization of Physiological, Neuronal, and Locomotor Effects of Nicotine: Critical Role of Peripheral Drug Actions

PubMed Central

Lenoir, Magalie; Tang, Jeremy S.; Woods, Amina S.

2013-01-01

Repeated exposure to nicotine and other psychostimulant drugs produces persistent increases in their psychomotor and physiological effects (sensitization), a phenomenon related to the drugs' reinforcing properties and abuse potential. Here we examined the role of peripheral actions of nicotine in nicotine-induced sensitization of centrally mediated physiological parameters (brain, muscle, and skin temperatures), cortical and VTA EEG, neck EMG activity, and locomotion in freely moving rats. Repeated injections of intravenous nicotine (30 μg/kg) induced sensitization of the drug's effects on all these measures. In contrast, repeated injections of the peripherally acting analog of nicotine, nicotine pyrrolidine methiodide (nicotinePM, 30 μg/kg, i.v.) resulted in habituation (tolerance) of the same physiological, neuronal, and behavioral measures. However, after repeated nicotine exposure, acute nicotinePM injections induced nicotine-like physiological responses: powerful cortical and VTA EEG desynchronization, EMG activation, a large brain temperature increase, but weaker hyperlocomotion. Additionally, both the acute locomotor response to nicotine and nicotine-induced locomotor sensitization were attenuated by blockade of peripheral nicotinic receptors by hexamethonium (3 mg/kg, i.v.). These data suggest that the peripheral actions of nicotine, which precede its direct central actions, serve as a conditioned interoceptive cue capable of eliciting nicotine-like physiological and neural responses after repeated nicotine exposure. Thus, by providing a neural signal to the CNS that is repeatedly paired with the direct central effects of nicotine, the drug's peripheral actions play a critical role in the development of nicotine-induced physiological, neural, and behavioral sensitization. PMID:23761889

Rapid sensitization of physiological, neuronal, and locomotor effects of nicotine: critical role of peripheral drug actions.

PubMed

Lenoir, Magalie; Tang, Jeremy S; Woods, Amina S; Kiyatkin, Eugene A

2013-06-12

Repeated exposure to nicotine and other psychostimulant drugs produces persistent increases in their psychomotor and physiological effects (sensitization), a phenomenon related to the drugs' reinforcing properties and abuse potential. Here we examined the role of peripheral actions of nicotine in nicotine-induced sensitization of centrally mediated physiological parameters (brain, muscle, and skin temperatures), cortical and VTA EEG, neck EMG activity, and locomotion in freely moving rats. Repeated injections of intravenous nicotine (30 μg/kg) induced sensitization of the drug's effects on all these measures. In contrast, repeated injections of the peripherally acting analog of nicotine, nicotine pyrrolidine methiodide (nicotine(PM), 30 μg/kg, i.v.) resulted in habituation (tolerance) of the same physiological, neuronal, and behavioral measures. However, after repeated nicotine exposure, acute nicotine(PM) injections induced nicotine-like physiological responses: powerful cortical and VTA EEG desynchronization, EMG activation, a large brain temperature increase, but weaker hyperlocomotion. Additionally, both the acute locomotor response to nicotine and nicotine-induced locomotor sensitization were attenuated by blockade of peripheral nicotinic receptors by hexamethonium (3 mg/kg, i.v.). These data suggest that the peripheral actions of nicotine, which precede its direct central actions, serve as a conditioned interoceptive cue capable of eliciting nicotine-like physiological and neural responses after repeated nicotine exposure. Thus, by providing a neural signal to the CNS that is repeatedly paired with the direct central effects of nicotine, the drug's peripheral actions play a critical role in the development of nicotine-induced physiological, neural, and behavioral sensitization.

Neurophysiological signature of effective anticipatory task-set control: a task-switching investigation.

PubMed

Lavric, Aureliu; Mizon, Guy A; Monsell, Stephen

2008-09-01

Changing between cognitive tasks requires a reorganization of cognitive processes. Behavioural evidence suggests this can occur in advance of the stimulus. However, the existence or detectability of an anticipatory task-set reconfiguration process remains controversial, in part because several neuroimaging studies have not detected extra brain activity during preparation for a task switch relative to a task repeat. In contrast, electrophysiological studies have identified potential correlates of preparation for a task switch, but their interpretation is hindered by the scarcity of evidence on their relationship to performance. We aimed to: (i) identify the brain potential(s) reflecting effective preparation for a task-switch in a task-cuing paradigm that shows clear behavioural evidence for advance preparation, and (ii) characterize this activity by means of temporal segmentation and source analysis. Our results show that when advance preparation was effective (as indicated by fast responses), a protracted switch-related component, manifesting itself as widespread posterior positivity and concurrent right anterior negativity, preceded stimulus onset for approximately 300 ms, with sources primarily in the left lateral frontal, right inferior frontal and temporal cortices. When advance preparation was ineffective (as implied by slow responses), or made impossible by a short cue-stimulus interval (CSI), a similar component, with lateral prefrontal generators, peaked approximately 300 ms poststimulus. The protracted prestimulus component (which we show to be distinct from P3 or contingent negative variation, CNV) also correlated over subjects with a behavioural measure of preparation. Furthermore, its differential lateralization for word and picture cues was consistent with a role for verbal self-instruction in preparatory task-set reconfiguration.

Prenatal Dexamethasone, as Used in Preterm Labor, Worsens the Impact of Postnatal Chlorpyrifos Exposure on Serotonergic Pathways

PubMed Central

Slotkin, Theodore A.; Card, Jennifer; Seidler, Frederic J.

2014-01-01

This study explores how glucocorticoids sensitize the developing brain to the organophosphate pesticide, chlorpyrifos. Pregnant rats received a standard therapeutic dose (0.2 mg/kg) of dexamethasone on gestational days 17–19; pups were given subtoxic doses of chlorpyrifos on postnatal days 1–4, (1 mg/kg, <10% cholinesterase inhibition). We evaluated serotonin (5HT) synaptic function from postnatal day 30 to day 150, assessing the expression of 5HT receptors and the 5HT transporter, along with 5HT turnover (index of presynaptic impulse activity) in brain regions encompassing all the 5HT projections and cell bodies. These parameters are known targets for neurodevelopmental effects of dexamethasone and chlorpyrifos individually. In males, chlorpyrifos evoked overall elevations in the expression of 5HT synaptic proteins, with a progressive increase from adolescence to adulthood; this effect was attenuated by prenatal dexamethasone treatment. The chlorpyrifos-induced upregulation was preceded by deficits in 5HT turnover, indicating that the receptor upregulation was an adaptive response to deficient presynaptic activity. Turnover deficiencies were magnified by dexamethasone pretreatment, worsening the functional impairment caused by chlorpyrifos. In females, chlorpyrifos-induced receptor changes reflected relative sparing of adverse effects compared to males. Nevertheless, prenatal dexamethasone still worsened the 5HT turnover deficits and reduced 5HT receptor expression in females, demonstrating the same adverse interaction. Glucocorticoids are used in 10% of U.S. pregnancies, and are also elevated in maternal stress; accordingly, our results indicate that this group represents a large subpopulation that may have heightened vulnerability to developmental neurotoxicants such as the organophosphates. PMID:24280657

Functional changes in the cortical semantic network in amnestic mild cognitive impairment.

PubMed

Pineault, Jessica; Jolicoeur, Pierre; Grimault, Stephan; Bermudez, Patrick; Brambati, Simona Maria; Lacombe, Jacinthe; Villalpando, Juan Manuel; Kergoat, Marie-Jeanne; Joubert, Sven

2018-05-01

Semantic memory impairment has been documented in individuals with amnestic Mild cognitive impairment (aMCI), who are at risk of developing Alzheimer's disease (AD), yet little is known about the neural basis of this breakdown. The aim of this study was to investigate the brain mechanisms associated with semantic performance in aMCI patients. A group of aMCI patients and a group of healthy controls carried out a semantic categorization task while their brain activity was recorded using magnetoencephalography (MEG). During the task, participants were shown famous faces and had to determine whether each famous person matched a given occupation. The main hypotheses were that (a) semantic processing should be compromised for aMCI patients, and (b) these deficits should be associated with cortical dysfunctions within specific areas of the semantic network. Behavioral results showed that aMCI participants were significantly slower and less accurate than controls at the semantic task. Additionally, relative to controls, a significant pattern of hyperactivation was found in the aMCI group within specific regions of the extended semantic network, including the right anterior temporal lobe (ATL) and fusiform gyrus. Abnormal functional activation within key areas of the semantic network suggests that it is compromised early in the disease process. Moreover, this pattern of right ATL and fusiform gyrus hyperactivation was positively associated with gray matter integrity in specific areas, but was not associated with any pattern of atrophy, suggesting that this pattern of hyperactivation may precede structural alteration of the semantic network in aMCI. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Does neuroinflammation drive the relationship between tau hyperphosphorylation and dementia development following traumatic brain injury?

PubMed

Collins-Praino, Lyndsey E; Corrigan, Frances

2017-02-01

A history of traumatic brain injury (TBI) is linked to an increased risk for the later development of dementia. This encompasses a variety of neurodegenerative diseases including Alzheimer's Disease (AD) and chronic traumatic encephalopathy (CTE), with AD linked to history of moderate-severe TBI and CTE to a history of repeated concussion. Of note, both AD and CTE are characterized by the abnormal accumulation of hyperphosphorylated tau aggregates, which are thought to play an important role in the development of neurodegeneration. Hyperphosphorylation of tau leads to destabilization of microtubules, interrupting axonal transport, whilst tau aggregates are associated with synaptic dysfunction. The exact mechanisms via which TBI may promote the later tauopathy and its role in the later development of dementia are yet to be fully determined. Following TBI, it is proposed that axonal injury may provide the initial perturbation of tau, by promoting its dissociation from microtubules, facilitating its phosphorylation and aggregation. Altered tau dynamics may then be exacerbated by the chronic persistent inflammatory response that has been shown to persist for decades following the initial impact. Importantly, immune activation has been shown to play a role in accelerating disease progression in other tauopathies, with pro-inflammatory cytokines, like IL-1β, shown to activate kinases that promote tau hyperphosphorylation. Thus, targeting the inflammatory response in the sub-acute phase following TBI may represent a promising target to halt the alterations in tau dynamics that may precede overt neurodegeneration and later development of dementia. Copyright © 2016 Elsevier Inc. All rights reserved.

Is Brain Emulation Dangerous?

NASA Astrophysics Data System (ADS)

Eckersley, Peter; Sandberg, Anders

2013-12-01

Brain emulation is a hypothetical but extremely transformative technology which has a non-zero chance of appearing during the next century. This paper investigates whether such a technology would also have any predictable characteristics that give it a chance of being catastrophically dangerous, and whether there are any policy levers which might be used to make it safer. We conclude that the riskiness of brain emulation probably depends on the order of the preceding research trajectory. Broadly speaking, it appears safer for brain emulation to happen sooner, because slower CPUs would make the technology`s impact more gradual. It may also be safer if brains are scanned before they are fully understood from a neuroscience perspective, thereby increasing the initial population of emulations, although this prediction is weaker and more scenario-dependent. The risks posed by brain emulation also seem strongly connected to questions about the balance of power between attackers and defenders in computer security contests. If economic property rights in CPU cycles1 are essentially enforceable, emulation appears to be comparatively safe; if CPU cycles are ultimately easy to steal, the appearance of brain emulation is more likely to be a destabilizing development for human geopolitics. Furthermore, if the computers used to run emulations can be kept secure, then it appears that making brain emulation technologies ―open‖ would make them safer. If, however, computer insecurity is deep and unavoidable, openness may actually be more dangerous. We point to some arguments that suggest the former may be true, tentatively implying that it would be good policy to work towards brain emulation using open scientific methodology and free/open source software codebases

Closed Loop Deep Brain Stimulation for PTSD, Addiction, and Disorders of Affective Facial Interpretation: Review and Discussion of Potential Biomarkers and Stimulation Paradigms

PubMed Central

Bina, Robert W.; Langevin, Jean-Phillipe

2018-01-01

The treatment of psychiatric diseases with Deep Brain Stimulation (DBS) is becoming more of a reality as studies proliferate the indications and targets for therapies. Opinions on the initial failures of DBS trials for some psychiatric diseases point to a certain lack of finesse in using an Open Loop DBS (OLDBS) system in these dynamic, cyclical pathologies. OLDBS delivers monomorphic input into dysfunctional brain circuits with modulation of that input via human interface at discrete time points with no interim modulation or adaptation to the changing circuit dynamics. Closed Loop DBS (CLDBS) promises dynamic, intrinsic circuit modulation based on individual physiologic biomarkers of dysfunction. Discussed here are several psychiatric diseases which may be amenable to CLDBS paradigms as the neurophysiologic dysfunction is stochastic and not static. Post-Traumatic Stress Disorder (PTSD) has several peripheral and central physiologic and neurologic changes preceding stereotyped hyper-activation behavioral responses. Biomarkers for CLDBS potentially include skin conductance changes indicating changes in the sympathetic nervous system, changes in serum and central neurotransmitter concentrations, and limbic circuit activation. Chemical dependency and addiction have been demonstrated to be improved with both ablation and DBS of the Nucleus Accumbens and as a serendipitous side effect of movement disorder treatment. Potential peripheral biomarkers are similar to those proposed for PTSD with possible use of environmental and geolocation based cues, peripheral signs of physiologic arousal, and individual changes in central circuit patterns. Non-substance addiction disorders have also been serendipitously treated in patients with OLDBS for movement disorders. As more is learned about these behavioral addictions, DBS targets and effectors will be identified. Finally, discussed is the use of facial recognition software to modulate activation of inappropriate responses for psychiatric diseases in which misinterpretation of social cues feature prominently. These include Autism Spectrum Disorder, PTSD, and Schizophrenia—all of which have a common feature of dysfunctional interpretation of facial affective clues. Technological advances and improvements in circuit-based, individual-specific, real-time adaptable modulation, forecast functional neurosurgery treatments for heretofore treatment-resistant behavioral diseases. PMID:29780303

Automatic activation of exercise and sedentary stereotypes.

PubMed

Berry, Tanya; Spence, John C

2009-09-01

We examined the automatic activation of "sedentary" and "exerciser" stereotypes using a social prime Stroop task. Results showed significantly slower response times between the exercise words and the exercise control words and between the sedentary words and the exercise control words when preceded by an attractive exerciser prime. Words preceded by a normal-weight exerciser prime showed significantly slower response times for sedentary words over sedentary control words and exercise words. An overweight sedentary prime resulted in significantly slower response times for sedentary words over exercise words and exercise control words. These results highlight the need for increased awareness of how active and sedentary lifestyles are portrayed in the media.

Microglial Dynamics During Human Brain Development

PubMed Central

Menassa, David A.; Gomez-Nicola, Diego

2018-01-01

Microglial cells are thought to colonize the human cerebrum between the 4th and 24th gestational weeks. Rodent studies have demonstrated that these cells originate from yolk sac progenitors though it is not clear whether this directly pertains to human development. Our understanding of microglial cell dynamics in the developing human brain comes mostly from postmortem studies demonstrating that the beginning of microglial colonization precedes the appearance of the vasculature, the blood–brain barrier, astrogliogenesis, oligodendrogenesis, neurogenesis, migration, and myelination of the various brain areas. Furthermore, migrating microglial populations cluster by morphology and express differential markers within the developing brain and according to developmental age. With the advent of novel technologies such as RNA-sequencing in fresh human tissue, we are beginning to identify the molecular features of the adult microglial signature. However, this is may not extend to the much more dynamic and rapidly changing antenatal microglial population and this is further complicated by the scarcity of tissue resources. In this brief review, we first describe the various historic schools of thought that had debated the origin of microglial cells while examining the evidence supporting the various theories. We then proceed to examine the evidence we have accumulated on microglial dynamics in the developing human brain, present evidence from rodent studies on the functional role of microglia during development and finally identify limitations for the used approaches in human studies and highlight under investigated questions. PMID:29881376

Mutual relationship between Tau and central insulin signalling: consequences for AD and Tauopathies ?

PubMed

Gratuze, Maud; Joly-Amado, Aurélie; Vieau, Didier; Buée, Luc; Blum, David

2018-02-13

Alzheimer's disease (AD) is a progressive neurodegenerative disorder mainly characterized by cognitive deficits and neuropathological changes such as Tau lesions and amyloid plaques, but also associated with non-cognitive symptomatology. Metabolic and neuroendocrine abnormalities, such as alterations in body weight, brain insulin impairments and lower brain glucose metabolism, that often precede clinical diagnosis, have been extensively reported in AD patients. However, the origin of these symptoms and their relation to pathology and cognitive impairments remain misunderstood. Insulin is a hormone involved in the control of energy homeostasis both peripherally and centrally, and insulin resistant state has been linked to increased risk of dementia. It is now well established that insulin resistance can exacerbate Tau lesions, mainly by disrupting the balance between Tau kinases and phosphatases. On the other hand, emerging literature indicates that Tau protein can also modulate insulin signalling in the brain, thus creating a detrimental vicious circle. The following review will highlight our current understanding on the role of insulin in the brain and its relation to Tau protein in the context of AD and Tauopathies. Considering that insulin signaling is prone to be pharmacologically targeted at multiple levels, it constitutes an appealing approach to improve both insulin brain sensitivity and mitigate brain pathology with expected positive outcome in term of cognition.
. ©2018S. Karger AG, Basel.

Sex Differences in Brain Thyroid Hormone Levels during Early Post-Hatching Development in Zebra Finch (Taeniopygia guttata).

PubMed

Yamaguchi, Shinji; Hayase, Shin; Aoki, Naoya; Takehara, Akihiko; Ishigohoka, Jun; Matsushima, Toshiya; Wada, Kazuhiro; Homma, Koichi J

2017-01-01

Thyroid hormones are closely linked to the hatching process in precocial birds. Previously, we showed that thyroid hormones in brain had a strong impact on filial imprinting, an early learning behavior in newly hatched chicks; brain 3,5,3'-triiodothyronine (T3) peaks around hatching and imprinting training induces additional T3 release, thus, extending the sensitive period for imprinting and enabling subsequent other learning. On the other hand, blood thyroid hormone levels have been reported to increase gradually after hatching in altricial species, but it remains unknown how the brain thyroid hormone levels change during post-hatching development of altricial birds. Here, we determined the changes in serum and brain thyroid hormone levels of a passerine songbird species, the zebra finch using radioimmunoassay. In the serum, we found a gradual increase in thyroid hormone levels during post-hatching development, as well as differences between male and female finches. In the brain, there was clear surge in the hormone levels during development in males and females coinciding with the time of fledging, but the onset of the surge of thyroxine (T4) in males preceded that of females, whereas the onset of the surge of T3 in males succeeded that of females. These findings provide a basis for understanding the functions of thyroid hormones during early development and learning in altricial birds.

Spatial and temporal relationships of electrocorticographic alpha and gamma activity during auditory processing.

PubMed

Potes, Cristhian; Brunner, Peter; Gunduz, Aysegul; Knight, Robert T; Schalk, Gerwin

2014-08-15

Neuroimaging approaches have implicated multiple brain sites in musical perception, including the posterior part of the superior temporal gyrus and adjacent perisylvian areas. However, the detailed spatial and temporal relationship of neural signals that support auditory processing is largely unknown. In this study, we applied a novel inter-subject analysis approach to electrophysiological signals recorded from the surface of the brain (electrocorticography (ECoG)) in ten human subjects. This approach allowed us to reliably identify those ECoG features that were related to the processing of a complex auditory stimulus (i.e., continuous piece of music) and to investigate their spatial, temporal, and causal relationships. Our results identified stimulus-related modulations in the alpha (8-12 Hz) and high gamma (70-110 Hz) bands at neuroanatomical locations implicated in auditory processing. Specifically, we identified stimulus-related ECoG modulations in the alpha band in areas adjacent to primary auditory cortex, which are known to receive afferent auditory projections from the thalamus (80 of a total of 15,107 tested sites). In contrast, we identified stimulus-related ECoG modulations in the high gamma band not only in areas close to primary auditory cortex but also in other perisylvian areas known to be involved in higher-order auditory processing, and in superior premotor cortex (412/15,107 sites). Across all implicated areas, modulations in the high gamma band preceded those in the alpha band by 280 ms, and activity in the high gamma band causally predicted alpha activity, but not vice versa (Granger causality, p<1e(-8)). Additionally, detailed analyses using Granger causality identified causal relationships of high gamma activity between distinct locations in early auditory pathways within superior temporal gyrus (STG) and posterior STG, between posterior STG and inferior frontal cortex, and between STG and premotor cortex. Evidence suggests that these relationships reflect direct cortico-cortical connections rather than common driving input from subcortical structures such as the thalamus. In summary, our inter-subject analyses defined the spatial and temporal relationships between music-related brain activity in the alpha and high gamma bands. They provide experimental evidence supporting current theories about the putative mechanisms of alpha and gamma activity, i.e., reflections of thalamo-cortical interactions and local cortical neural activity, respectively, and the results are also in agreement with existing functional models of auditory processing. Copyright © 2014 Elsevier Inc. All rights reserved.

The oxidized form of vitamin C, dehydroascorbic acid, regulates neuronal energy metabolism.

PubMed

Cisternas, Pedro; Silva-Alvarez, Carmen; Martínez, Fernando; Fernandez, Emilio; Ferrada, Luciano; Oyarce, Karina; Salazar, Katterine; Bolaños, Juan P; Nualart, Francisco

2014-05-01

Vitamin C is an essential factor for neuronal function and survival, existing in two redox states, ascorbic acid (AA), and its oxidized form, dehydroascorbic acid (DHA). Here, we show uptake of both AA and DHA by primary cultures of rat brain cortical neurons. Moreover, we show that most intracellular AA was rapidly oxidized to DHA. Intracellular DHA induced a rapid and dramatic decrease in reduced glutathione that was immediately followed by a spontaneous recovery. This transient decrease in glutathione oxidation was preceded by an increase in the rate of glucose oxidation through the pentose phosphate pathway (PPP), and a concomitant decrease in glucose oxidation through glycolysis. DHA stimulated the activity of glucose-6-phosphate dehydrogenase, the rate-limiting enzyme of the PPP. Furthermore, we found that DHA stimulated the rate of lactate uptake by neurons in a time- and dose-dependent manner. Thus, DHA is a novel modulator of neuronal energy metabolism by facilitating the utilization of glucose through the PPP for antioxidant purposes. © 2014 International Society for Neurochemistry.

A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington's disease in mice.

PubMed

Acuña, Aníbal I; Esparza, Magdalena; Kramm, Carlos; Beltrán, Felipe A; Parra, Alejandra V; Cepeda, Carlos; Toro, Carlos A; Vidal, René L; Hetz, Claudio; Concha, Ilona I; Brauchi, Sebastián; Levine, Michael S; Castro, Maite A

2013-01-01

Huntington's disease has been associated with a failure in energy metabolism and oxidative damage. Ascorbic acid is a powerful antioxidant highly concentrated in the brain where it acts as a messenger, modulating neuronal metabolism. Using an electrophysiological approach in R6/2 HD slices, we observe an abnormal ascorbic acid flux from astrocytes to neurons, which is responsible for alterations in neuronal metabolic substrate preferences. Here using striatal neurons derived from knock-in mice expressing mutant huntingtin (STHdhQ cells), we study ascorbic acid transport. When extracellular ascorbic acid concentration increases, as occurs during synaptic activity, ascorbic acid transporter 2 (SVCT2) translocates to the plasma membrane, ensuring optimal ascorbic acid uptake for neurons. In contrast, SVCT2 from cells that mimic HD symptoms (dubbed HD cells) fails to reach the plasma membrane under the same conditions. We reason that an early impairment of ascorbic acid uptake in HD neurons could lead to early metabolic failure promoting neuronal death.

Neural networks engaged in short-term memory rehearsal are disrupted by irrelevant speech in human subjects.

PubMed

Kopp, Franziska; Schröger, Erich; Lipka, Sigrid

2004-01-02

Rehearsal mechanisms in human short-term memory are increasingly understood in the light of both behavioural and neuroanatomical findings. However, little is known about the cooperation of participating brain structures and how such cooperations are affected when memory performance is disrupted. In this paper we use EEG coherence as a measure of synchronization to investigate rehearsal processes and their disruption by irrelevant speech in a delayed serial recall paradigm. Fronto-central and fronto-parietal theta (4-7.5 Hz), beta (13-20 Hz), and gamma (35-47 Hz) synchronizations are shown to be involved in our short-term memory task. Moreover, the impairment in serial recall due to irrelevant speech was preceded by a reduction of gamma band coherence. Results suggest that the irrelevant speech effect has its neural basis in the disruption of left-lateralized fronto-central networks. This stresses the importance of gamma band activity for short-term memory operations.

How the Context Matters. Literal and Figurative Meaning in the Embodied Language Paradigm

PubMed Central

Cuccio, Valentina; Ambrosecchia, Marianna; Ferri, Francesca; Carapezza, Marco; Lo Piparo, Franco; Fogassi, Leonardo; Gallese, Vittorio

2014-01-01

The involvement of the sensorimotor system in language understanding has been widely demonstrated. However, the role of context in these studies has only recently started to be addressed. Though words are bearers of a semantic potential, meaning is the product of a pragmatic process. It needs to be situated in a context to be disambiguated. The aim of this study was to test the hypothesis that embodied simulation occurring during linguistic processing is contextually modulated to the extent that the same sentence, depending on the context of utterance, leads to the activation of different effector-specific brain motor areas. In order to test this hypothesis, we asked subjects to give a motor response with the hand or the foot to the presentation of ambiguous idioms containing action-related words when these are preceded by context sentences. The results directly support our hypothesis only in relation to the comprehension of hand-related action sentences. PMID:25531530

A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington’s disease in mice

PubMed Central

Acuña, Aníbal I.; Esparza, Magdalena; Kramm, Carlos; Beltrán, Felipe A.; Parra, Alejandra V.; Cepeda, Carlos; Toro, Carlos A.; Vidal, René L.; Hetz, Claudio; Concha, Ilona I.; Brauchi, Sebastián; Levine, Michael S.; Castro, Maite A.

2013-01-01

Huntington’s disease has been associated with a failure in energy metabolism and oxidative damage. Ascorbic acid is a powerful antioxidant highly concentrated in the brain where it acts as a messenger, modulating neuronal metabolism. Using an electrophysiological approach in R6/2 HD slices, we observe an abnormal ascorbic acid flux from astrocytes to neurons, which is responsible for alterations in neuronal metabolic substrate preferences. Here using striatal neurons derived from knock-in mice expressing mutant huntingtin (STHdhQ cells), we study ascorbic acid transport. When extracellular ascorbic acid concentration increases, as occurs during synaptic activity, ascorbic acid transporter 2 (SVCT2) translocates to the plasma membrane, ensuring optimal ascorbic acid uptake for neurons. In contrast, SVCT2 from cells that mimic HD symptoms (dubbed HD cells) fails to reach the plasma membrane under the same conditions. We reason that an early impairment of ascorbic acid uptake in HD neurons could lead to early metabolic failure promoting neuronal death. PMID:24336051

Neural correlates of time versus money in product evaluation.

PubMed

Lehmann, Sebastian; Reimann, Martin

2012-01-01

The common saying "time is money" reflects the widespread belief in many people's everyday life that time is valuable like money. Psychologically and neurophysiologically, however, these concepts seem to be quite different. This research replicates prior behavioral investigations by showing that merely mentioning "time" (compared to merely mentioning "money") leads participants to evaluate a product more positively. Beyond this finding, the present functional magnetic resonance imaging (fMRI) experiment provides novel insight into the neurophysiological underpinnings of this behavioral effect by showing that more positive product evaluations in the time primes (compared to money primes) are preceded by increased activation in the insula. Our data, therefore, support the idea of a time mindset that is different from a money mindset. Studies on the functional neuroanatomy of the insula have implicated this brain area in distinct but related psychological phenomena such as urging, addiction, loss aversion, and love. These functions imply greater personal connection between the consumer and a target subject or object and, thus, help explain why time-primed consumers rate products more positively.

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

DOE PAGES

Du, Huiyun; Deng, Wei; Aimone, James B.; ...

2016-09-13

Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2–expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioralmore » experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Altogether, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience.« less

A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington’s disease in mice

NASA Astrophysics Data System (ADS)

Acuña, Aníbal I.; Esparza, Magdalena; Kramm, Carlos; Beltrán, Felipe A.; Parra, Alejandra V.; Cepeda, Carlos; Toro, Carlos A.; Vidal, René L.; Hetz, Claudio; Concha, Ilona I.; Brauchi, Sebastián; Levine, Michael S.; Castro, Maite A.

2013-12-01

Huntington’s disease has been associated with a failure in energy metabolism and oxidative damage. Ascorbic acid is a powerful antioxidant highly concentrated in the brain where it acts as a messenger, modulating neuronal metabolism. Using an electrophysiological approach in R6/2 HD slices, we observe an abnormal ascorbic acid flux from astrocytes to neurons, which is responsible for alterations in neuronal metabolic substrate preferences. Here using striatal neurons derived from knock-in mice expressing mutant huntingtin (STHdhQ cells), we study ascorbic acid transport. When extracellular ascorbic acid concentration increases, as occurs during synaptic activity, ascorbic acid transporter 2 (SVCT2) translocates to the plasma membrane, ensuring optimal ascorbic acid uptake for neurons. In contrast, SVCT2 from cells that mimic HD symptoms (dubbed HD cells) fails to reach the plasma membrane under the same conditions. We reason that an early impairment of ascorbic acid uptake in HD neurons could lead to early metabolic failure promoting neuronal death.

Dopaminergic inputs in the dentate gyrus direct the choice of memory encoding

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

Du, Huiyun; Deng, Wei; Aimone, James B.

Rewarding experiences are often well remembered, and such memory formation is known to be dependent on dopamine modulation of the neural substrates engaged in learning and memory; however, it is unknown how and where in the brain dopamine signals bias episodic memory toward preceding rather than subsequent events. Here we found that photostimulation of channelrhodopsin-2–expressing dopaminergic fibers in the dentate gyrus induced a long-term depression of cortical inputs, diminished theta oscillations, and impaired subsequent contextual learning. Computational modeling based on this dopamine modulation indicated an asymmetric association of events occurring before and after reward in memory tasks. In subsequent behavioralmore » experiments, preexposure to a natural reward suppressed hippocampus-dependent memory formation, with an effective time window consistent with the duration of dopamine-induced changes of dentate activity. Altogether, our results suggest a mechanism by which dopamine enables the hippocampus to encode memory with reduced interference from subsequent experience.« less

Early brain development in infants at high risk for autism spectrum disorder

PubMed Central

Hazlett, Heather Cody; Gu, Hongbin; Munsell, Brent C.; Kim, Sun Hyung; Styner, Martin; Wolff, Jason J.; Elison, Jed T.; Swanson, Meghan R.; Zhu, Hongtu; Botteron, Kelly N.; Collins, D. Louis; Constantino, John N.; Dager, Stephen R.; Estes, Annette M.; Evans, Alan C.; Fonov, Vladimir S.; Gerig, Guido; Kostopoulos, Penelope; McKinstry, Robert C.; Pandey, Juhi; Paterson, Sarah; Pruett, John R.; Schultz, Robert T.; Shaw, Dennis W.; Zwaigenbaum, Lonnie; Piven, Joseph

2017-01-01

Summary Brain enlargement has been observed in children with Autism Spectrum Disorder (ASD), but the timing of this phenomenon and its relationship to the appearance of behavioral symptoms is unknown. Retrospective head circumference and longitudinal brain volume studies of 2 year olds followed up at age 4 years, have provided evidence that increased brain volume may emerge early in development.1, 2 Studies of infants at high familial risk for autism can provide insight into the early development of autism and have found that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life3,4. These observations suggest that prospective brain imaging studies of infants at high familial risk for ASD might identify early post-natal changes in brain volume occurring before the emergence of an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that cortical surface area hyper-expansion between 6-12 months of age precedes brain volume overgrowth observed between 12-24 months in the 15 high-risk infants diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep learning algorithm primarily using surface area information from brain MRI at 6 and 12 months of age predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81%, sensitivity of 88%). These findings demonstrate that early brain changes unfold during the period in which autistic behaviors are first emerging. PMID:28202961

Predicting Intracranial Pressure and Brain Tissue Oxygen Crises in Patients With Severe Traumatic Brain Injury.

PubMed

Myers, Risa B; Lazaridis, Christos; Jermaine, Christopher M; Robertson, Claudia S; Rusin, Craig G

2016-09-01

To develop computer algorithms that can recognize physiologic patterns in traumatic brain injury patients that occur in advance of intracranial pressure and partial brain tissue oxygenation crises. The automated early detection of crisis precursors can provide clinicians with time to intervene in order to prevent or mitigate secondary brain injury. A retrospective study was conducted from prospectively collected physiologic data. intracranial pressure, and partial brain tissue oxygenation crisis events were defined as intracranial pressure of greater than or equal to 20 mm Hg lasting at least 15 minutes and partial brain tissue oxygenation value of less than 10 mm Hg for at least 10 minutes, respectively. The physiologic data preceding each crisis event were used to identify precursors associated with crisis onset. Multivariate classification models were applied to recorded data in 30-minute epochs of time to predict crises between 15 and 360 minutes in the future. The neurosurgical unit of Ben Taub Hospital (Houston, TX). Our cohort consisted of 817 subjects with severe traumatic brain injury. Our algorithm can predict the onset of intracranial pressure crises with 30-minute advance warning with an area under the receiver operating characteristic curve of 0.86 using only intracranial pressure measurements and time since last crisis. An analogous algorithm can predict the start of partial brain tissue oxygenation crises with 30-minute advanced warning with an area under the receiver operating characteristic curve of 0.91. Our algorithms provide accurate and timely predictions of intracranial hypertension and tissue hypoxia crises in patients with severe traumatic brain injury. Almost all of the information needed to predict the onset of these events is contained within the signal of interest and the time since last crisis.

Early brain development in infants at high risk for autism spectrum disorder.

PubMed

Hazlett, Heather Cody; Gu, Hongbin; Munsell, Brent C; Kim, Sun Hyung; Styner, Martin; Wolff, Jason J; Elison, Jed T; Swanson, Meghan R; Zhu, Hongtu; Botteron, Kelly N; Collins, D Louis; Constantino, John N; Dager, Stephen R; Estes, Annette M; Evans, Alan C; Fonov, Vladimir S; Gerig, Guido; Kostopoulos, Penelope; McKinstry, Robert C; Pandey, Juhi; Paterson, Sarah; Pruett, John R; Schultz, Robert T; Shaw, Dennis W; Zwaigenbaum, Lonnie; Piven, Joseph

2017-02-15

Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6-12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.

The Role of Animacy and Thematic Relationships in Processing Active English Sentences: Evidence from Event-Related Potentials

ERIC Educational Resources Information Center

Kuperberg, Gina R.; Kreher, Donna A.; Sitnikova, Tatiana; Caplan, David N.; Holcomb, Phillip J.

2007-01-01

Recent event-related potential studies report a P600 effect to incongruous verbs preceded by semantically associated inanimate noun-phrase (NP) arguments, e.g., "eat" in "At breakfast the eggs would eat...". This P600 effect may reflect the processing cost incurred when semantic-thematic relationships between critical verbs and their preceding NP…

Neural correlates of cross-modal affective priming by music in Williams syndrome

PubMed Central

Lense, Miriam D.; Gordon, Reyna L.; Key, Alexandra P. F.; Dykens, Elisabeth M.

2014-01-01

Emotional connection is the main reason people engage with music, and the emotional features of music can influence processing in other domains. Williams syndrome (WS) is a neurodevelopmental genetic disorder where musicality and sociability are prominent aspects of the phenotype. This study examined oscillatory brain activity during a musical affective priming paradigm. Participants with WS and age-matched typically developing controls heard brief emotional musical excerpts or emotionally neutral sounds and then reported the emotional valence (happy/sad) of subsequently presented faces. Participants with WS demonstrated greater evoked fronto-central alpha activity to the happy vs sad musical excerpts. The size of these alpha effects correlated with parent-reported emotional reactivity to music. Although participant groups did not differ in accuracy of identifying facial emotions, reaction time data revealed a music priming effect only in persons with WS, who responded faster when the face matched the emotional valence of the preceding musical excerpt vs when the valence differed. Matching emotional valence was also associated with greater evoked gamma activity thought to reflect cross-modal integration. This effect was not present in controls. The results suggest a specific connection between music and socioemotional processing and have implications for clinical and educational approaches for WS. PMID:23386738

Inducing Negative Affect Increases the Reward Value of Appetizing Foods in Dieters

PubMed Central

Wagner, Dylan D.; Boswell, Rebecca G.; Kelley, William M.; Heatherton, Todd F.

2013-01-01

Experiencing negative affect frequently precedes lapses in self-control for dieters, smokers, and drug addicts. Laboratory research has similarly shown that inducing negative emotional distress increases the consumption of food or drugs. One hypothesis for this finding is that emotional distress sensitizes the brain’s reward system to appetitive stimuli. Using functional neuroimaging, we demonstrate that inducing negative affect in chronic dieters increases activity in brain regions representing the reward value of appetitive stimuli when viewing appetizing food cues. Thirty female chronic dieters were randomly assigned to receive either a negative (n = 15) or neutral mood induction (n = 15) immediately followed by exposure to images of appetizing foods and natural scenes during functional magnetic resonance imaging (fMRI). Compared to chronic dieters in a neutral mood, those receiving a negative mood induction showed increased activity in the orbitofrontal cortex to appetizing food images. In addition, activity to food images in the orbitofrontal cortex and ventral striatum was correlated with individual differences in the degree to which the negative mood induction decreased participants’ self-esteem. These findings suggest that distress sensitizes the brain’s reward system to appetitive cues thereby offering a mechanism for the oft-observed relationship between negative affect and disinhibited eating. PMID:22524295

The role of the anterior cingulate cortex in the affective evaluation of conflict

PubMed Central

Braem, Senne; King, Joseph A.; Korb, Franziska M.; Krebs, Ruth M.; Notebaert, Wim; Egner, Tobias

2017-01-01

An influential theory of anterior cingulate cortex (ACC) function argues that this brain region plays a crucial role in the affective evaluation of performance monitoring and control demands. Specifically, control-demanding processes such as response conflict, are thought to be registered as aversive signals by the ACC, which in turn triggers processing adjustments to support avoidance-learning. In support of conflict being treated as an aversive event, recent behavioural studies demonstrated that incongruent (i.e., conflict-inducing) relative to congruent stimuli can speed up subsequent negative relative to positive affective picture processing. Here, we used functional magnetic resonance imaging (fMRI) to investigate directly whether ACC activity in response to negative versus positive pictures is modulated by preceding control demands, consisting of conflict and task-switching conditions. The results show that negative relative to positive pictures elicited higher ACC activation following congruent relative to incongruent trials, suggesting that the ACC’s response to negative (positive) pictures was indeed affectively primed by incongruent (congruent) trials. Interestingly, this pattern of results was observed on task repetitions, but disappeared on task alternations. Our findings support the proposal that conflict induces negative affect, and are the first to show that this affective signal is reflected in ACC activation. PMID:27575278

Sleep and Learning

NASA Astrophysics Data System (ADS)

Margoliash, Daniel

2010-03-01

The neural basis of cognition represents a grand challenge problem involving multiple disciplines and approaches to the analysis of behavior. Song learning by juvenile songbirds such as zebra finches has proven to have considerable utility for exploring how behavior is represented at multiple levels of brain function. As classically described, young birds are exposed to a ``tutor'' (adult) song and commit that song to memory early in life, then engage in an extended period (weeks) of plastic singing as they slowly learn to match vocal output to the tutor song memory via auditory feedback. In recent years, the role of sleep in learning processes has been actively explored. Young birds isolated from adult songs, then suddenly given access to such songs at circa 40 days of age, show a sudden change in their singing behavior starting on the day following first exposure. Such birds sing songs that have less structure in the mornings than do the songs sung in the afternoons before or after that morning. This fluctuation is directly the result of sleep (not circadian rhythm), and the magnitude of fluctuation is positively correlated with the ultimate similarity to the tutor song. Examining spontaneous neuronal activity in certain brain structures during the night in sleeping adults shows ``replay'' of the patterns of activity the same neurons exhibit during daytime singing, and ``preplay'' of new patterns that will first be incorporated into daytime singing the following day. In experiments on juveniles, nighttime neuronal activity shows dramatic changes associated with song learning, even on the night after the first day of tutor song exposure (preceding changes in singing behavior). Offline processing, especially sleep, has been well documented to participate in memory consolidation in a very broad range of behaviors including in humans. Placing the bird song results in a theoretical framework thereby helps to inform a very broad range of phenomena.

Specific subcortical structures are activated during seizure-induced death in a model of sudden unexpected death in epilepsy (SUDEP): A manganese-enhanced magnetic resonance imaging study.

PubMed

Kommajosyula, Srinivasa P; Randall, Marcus E; Brozoski, Thomas J; Odintsov, Boris M; Faingold, Carl L

2017-09-01

Sudden unexpected death in epilepsy (SUDEP) is a major concern for patients with epilepsy. In most witnessed cases of SUDEP generalized seizures and respiratory failure preceded death, and pre-mortem neuroimaging studies in SUDEP patients observed changes in specific subcortical structures. Our study examined the role of subcortical structures in the DBA/1 mouse model of SUDEP using manganese-enhanced magnetic resonance imaging (MEMRI). These mice exhibit acoustically-evoked generalized seizures leading to seizure-induced respiratory arrest (S-IRA) that results in sudden death unless resuscitation is rapidly instituted. MEMRI data in the DBA/1 mouse brain immediately after acoustically-induced S-IRA were compared to data in C57 (control) mice that were exposed to the same acoustic stimulus that did not trigger seizures. The animals were anesthetized and decapitated immediately after seizure in DBA/1 mice and after an equivalent time in control mice. Comparative T1 weighted MEMRI images were evaluated using a 14T MRI scanner and quantified. We observed significant increases in activity in DBA/1 mice as compared to controls at previously-implicated auditory (superior olivary complex) and sensorimotor-limbic [periaqueductal gray (PAG) and amygdala] networks and also in structures in the respiratory network. The activity at certain raphe nuclei was also increased, suggesting activation of serotonergic mechanisms. These data are consistent with previous findings that enhancing the action of serotonin prevents S-IRA in this SUDEP model. Increased activity in the PAG and the respiratory and raphe nuclei suggest that compensatory mechanisms for apnea may have been activated by S-IRA, but they were not sufficient to prevent death. The present findings indicate that changes induced by S-IRA in specific subcortical structures in DBA/1 mice are consistent with human SUDEP findings. Understanding the changes in brain activity during seizure-induced death in animals may lead to improved approaches directed at prevention of human SUDEP. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of emotionally valenced eye region images on visuocortical processing of surprised faces.

PubMed

Li, Shuaixia; Li, Ping; Wang, Wei; Zhu, Xiangru; Luo, Wenbo

2018-05-01

In this study, we presented pictorial representations of happy, neutral, and fearful expressions projected in the eye regions to determine whether the eye region alone is sufficient to produce a context effect. Participants were asked to judge the valence of surprised faces that had been preceded by a picture of an eye region. Behavioral results showed that affective ratings of surprised faces were context dependent. Prime-related ERPs with presentation of happy eyes elicited a larger P1 than those for neutral and fearful eyes, likely due to the recognition advantage provided by a happy expression. Target-related ERPs showed that surprised faces in the context of fearful and happy eyes elicited dramatically larger C1 than those in the neutral context, which reflected the modulation by predictions during the earliest stages of face processing. There were larger N170 with neutral and fearful eye contexts compared to the happy context, suggesting faces were being integrated with contextual threat information. The P3 component exhibited enhanced brain activity in response to faces preceded by happy and fearful eyes compared with neutral eyes, indicating motivated attention processing may be involved at this stage. Altogether, these results indicate for the first time that the influence of isolated eye regions on the perception of surprised faces involves preferential processing at the early stages and elaborate processing at the late stages. Moreover, higher cognitive processes such as predictions and attention can modulate face processing from the earliest stages in a top-down manner. © 2017 Society for Psychophysiological Research.

Neural Encoding and Integration of Learned Probabilistic Sequences in Avian Sensory-Motor Circuitry

PubMed Central

Brainard, Michael S.

2013-01-01

Many complex behaviors, such as human speech and birdsong, reflect a set of categorical actions that can be flexibly organized into variable sequences. However, little is known about how the brain encodes the probabilities of such sequences. Behavioral sequences are typically characterized by the probability of transitioning from a given action to any subsequent action (which we term “divergence probability”). In contrast, we hypothesized that neural circuits might encode the probability of transitioning to a given action from any preceding action (which we term “convergence probability”). The convergence probability of repeatedly experienced sequences could naturally become encoded by Hebbian plasticity operating on the patterns of neural activity associated with those sequences. To determine whether convergence probability is encoded in the nervous system, we investigated how auditory-motor neurons in vocal premotor nucleus HVC of songbirds encode different probabilistic characterizations of produced syllable sequences. We recorded responses to auditory playback of pseudorandomly sequenced syllables from the bird's repertoire, and found that variations in responses to a given syllable could be explained by a positive linear dependence on the convergence probability of preceding sequences. Furthermore, convergence probability accounted for more response variation than other probabilistic characterizations, including divergence probability. Finally, we found that responses integrated over >7–10 syllables (∼700–1000 ms) with the sign, gain, and temporal extent of integration depending on convergence probability. Our results demonstrate that convergence probability is encoded in sensory-motor circuitry of the song-system, and suggest that encoding of convergence probability is a general feature of sensory-motor circuits. PMID:24198363

Deficient multisensory integration in schizophrenia: an event-related potential study.

PubMed

Stekelenburg, Jeroen J; Maes, Jan Pieter; Van Gool, Arthur R; Sitskoorn, Margriet; Vroomen, Jean

2013-07-01

In many natural audiovisual events (e.g., the sight of a face articulating the syllable /ba/), the visual signal precedes the sound and thus allows observers to predict the onset and the content of the sound. In healthy adults, the N1 component of the event-related brain potential (ERP), reflecting neural activity associated with basic sound processing, is suppressed if a sound is accompanied by a video that reliably predicts sound onset. If the sound does not match the content of the video (e.g., hearing /ba/ while lipreading /fu/), the later occurring P2 component is affected. Here, we examined whether these visual information sources affect auditory processing in patients with schizophrenia. The electroencephalography (EEG) was recorded in 18 patients with schizophrenia and compared with that of 18 healthy volunteers. As stimuli we used video recordings of natural actions in which visual information preceded and predicted the onset of the sound that was either congruent or incongruent with the video. For the healthy control group, visual information reduced the auditory-evoked N1 if compared to a sound-only condition, and stimulus-congruency affected the P2. This reduction in N1 was absent in patients with schizophrenia, and the congruency effect on the P2 was diminished. Distributed source estimations revealed deficits in the network subserving audiovisual integration in patients with schizophrenia. The results show a deficit in multisensory processing in patients with schizophrenia and suggest that multisensory integration dysfunction may be an important and, to date, under-researched aspect of schizophrenia. Copyright © 2013. Published by Elsevier B.V.

Brain mechanisms of successful recognition through retrieval of semantic context

PubMed Central

Flegal, Kristin E.; Marín-Gutiérrez, Alejandro; Ragland, J. Daniel; Ranganath, Charan

2017-01-01

Episodic memory is associated with the encoding and retrieval of context information, and with a subjective sense of re-experiencing past events. The neural correlates of episodic retrieval have been extensively studied using fMRI, leading to the identification of a “general recollection network” including medial temporal, parietal, and prefrontal regions. However, in these studies, it is difficult to disentangle the effects of context retrieval from recollection. In the present study, we used functional magnetic resonance imaging (fMRI) to determine the extent to which the recruitment of regions in the recollection network is contingent on context reinstatement. Participants were scanned during a cued recognition test for target words from encoded sentences. Studied target words were preceded by either a cue word studied in the same sentence (thus congruent with encoding context), or a cue word studied in a different sentence (thus incongruent with encoding context). Converging fMRI results from independently-defined regions of interest and whole-brain analysis showed regional specificity in the recollection network. Activity in hippocampus and parahippocampal cortex was specifically increased during successful retrieval following congruent context cues, whereas parietal and prefrontal components of the general recollection network were associated with confident retrieval irrespective of contextual congruency. Our findings implicate medial temporal regions in the retrieval of semantic context, contributing to, but dissociable from, recollective experience. PMID:24564467

Evidence for Post-Translational Processing of Vascular Endothelial (VE)-Cadherin in Brain Tumors: Towards a Candidate Biomarker

PubMed Central

Vilgrain, Isabelle; Sidibé, Adama; Polena, Helena; Cand, Francine; Mannic, Tiphaine; Arboleas, Mélanie; Boccard, Sandra; Baudet, Antoine; Gulino-Debrac, Danielle; Bouillet, Laurence; Quesada, Jean-Louis; Mendoza, Christophe; Lebas, Jean-François; Pelletier, Laurent; Berger, François

2013-01-01

Vessel abnormalities are among the most important features in malignant glioma. Vascular endothelial (VE)-cadherin is of major importance for vascular integrity. Upon cytokine challenge, VE-cadherin structural modifications have been described including tyrosine phosphorylation and cleavage. The goal of this study was to examine whether these events occurred in human glioma vessels. We demonstrated that VE-cadherin is highly expressed in human glioma tissue and tyrosine phosphorylated at site Y685, a site previously found phosphorylated upon VEGF challenge, via Src activation. In vitro experiments showed that VEGF-induced VE-cadherin phosphorylation, preceded the cleavage of its extracellular adhesive domain (sVE, 90 kDa). Interestingly, metalloproteases (MMPs) secreted by glioma cell lines were responsible for sVE release. Because VEGF and MMPs are important components of tumor microenvironment, we hypothesized that VE-cadherin proteolysis might occur in human brain tumors. Analysis of glioma patient sera prior treatment confirmed the presence of sVE in bloodstream. Furthermore, sVE levels studied in a cohort of 53 glioma patients were significantly predictive of the overall survival at three years (HR 0.13 [0.04; 0.40] p≤0.001), irrespective to histopathological grade of tumors. Altogether, these results suggest that VE-cadherin structural modifications should be examined as candidate biomarkers of tumor vessel abnormalities, with promising applications in oncology. PMID:24358106

Trial-Type Dependent Frames of Reference for Value Comparison

PubMed Central

Hunt, Laurence T.; Woolrich, Mark W.; Rushworth, Matthew F. S.; Behrens, Timothy E. J.

2013-01-01

A central question in cognitive neuroscience regards the means by which options are compared and decisions are resolved during value-guided choice. It is clear that several component processes are needed; these include identifying options, a value-based comparison, and implementation of actions to execute the decision. What is less clear is the temporal precedence and functional organisation of these component processes in the brain. Competing models of decision making have proposed that value comparison may occur in the space of alternative actions, or in the space of abstract goods. We hypothesized that the signals observed might in fact depend upon the framing of the decision. We recorded magnetoencephalographic data from humans performing value-guided choices in which two closely related trial types were interleaved. In the first trial type, each option was revealed separately, potentially causing subjects to estimate each action's value as it was revealed and perform comparison in action-space. In the second trial type, both options were presented simultaneously, potentially leading to comparison in abstract goods-space prior to commitment to a specific action. Distinct activity patterns (in distinct brain regions) on the two trial types demonstrated that the observed frame of reference used for decision making indeed differed, despite the information presented being formally identical, between the two trial types. This provides a potential reconciliation of conflicting accounts of value-guided choice. PMID:24068906

miRNA Expression Profile after Status Epilepticus and Hippocampal Neuroprotection by Targeting miR-132

PubMed Central

Jimenez-Mateos, Eva M.; Bray, Isabella; Sanz-Rodriguez, Amaya; Engel, Tobias; McKiernan, Ross C.; Mouri, Genshin; Tanaka, Katsuhiro; Sano, Takanori; Saugstad, Julie A.; Simon, Roger P.; Stallings, Raymond L.; Henshall, David C.

2011-01-01

When an otherwise harmful insult to the brain is preceded by a brief, noninjurious stimulus, the brain becomes tolerant, and the resulting damage is reduced. Epileptic tolerance develops when brief seizures precede an episode of prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status epilepticus in animals that had previously received either seizure preconditioning (tolerance) or no preconditioning (injury), and mature miRNA levels were measured using TaqMan low-density arrays. Expression of 21 miRNAs was increased, relative to control, after status epilepticus alone, and expression of 12 miRNAs was decreased. Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death. PMID:21945804

Exercise starts and ends in the brain.

PubMed

Kayser, Bengt

2003-10-01

Classically the limit to endurance of exercise is explained in terms of metabolic capacity. Cardio-respiratory capacity and muscle fatigue are thought to set the limit and the majority of studies on factors limiting endurance exercise discuss issues such as maximal oxygen uptake (VO2max), aerobic enzyme capacity, cardiac output, glycogen stores, etc. However, this paradigm does not explain the limitation to endurance exercise with large muscle groups at altitude, when at exhaustion exercise is ended without limb locomotor muscle fatigue and with sub-maximal cardiac output. A simple fact provides a basis for an explanation. Voluntary exercise starts and ends in the brain. It starts with spatial and temporal recruitment of motor units and ends with their de-recruitment. A conscious decision precedes a voluntary effort. The end of effort is again volitional and a forced conscious decision to stop precedes it, but it is unknown what forces the off-switch of recruitment at exhaustion although sensation of exertion certainly plays a role. An alternative model explaining the limitation of exercise endurance thus proposes that the central nervous system integrates input from various sources all related to the exercise and limits the intensity and duration of recruitment of limb skeletal muscle to prevent jeopardizing the integrity of the organism. This model acknowledges the cardio-respiratory and muscle metabolic capacities as prime actors on the performance scene, while crediting the central nervous system for its pivotal role as the ultimate site where exercise starts and ends.

Being Eager to Prove Oneself: U-Shaped Relationship between Competence Frustration and Intrinsic Motivation in Another Activity

PubMed Central

Fang, Hui; He, Bin; Fu, Huijian; Meng, Liang

2017-01-01

Competence frustration has been consistently found to undermine one’s intrinsic motivation in the same activity. However, the relationship between competence frustration in a preceding activity and one’s intrinsic motivation in a subsequent one remains unclear. In order to explore this relationship, self-reported data were collected from 617 undergraduate students of a large comprehensive university in southern China, who took varied courses immediately before taking a less-demanding one. Results suggested a U-shaped relationship between students’ competence frustration in a preceding course and intrinsic motivation in a subsequent one. To be specific, for students whose competence frustration reached the inflection point, a restoration process would be activated if the current course would help restore their competence. Importantly, these students’ competence frustration in a preceding course was found to positively predict their intrinsic motivation level in a subsequent course. As far as we are concerned, this is the first study to reveal a potential positive effect of need frustration outside of its primary thwarting context, which complements and extends existing literatures on the dynamics between need frustration and intrinsic motivation. PMID:29312025

Status epilepticus does not induce acute brain inflammatory response in the Amazon rodent Proechimys, an animal model resistant to epileptogenesis.

PubMed

Scorza, Carla A; Marques, Marcia J G; Gomes da Silva, Sérgio; Naffah-Mazzacoratti, Maria da Graça; Scorza, Fulvio A; Cavalheiro, Esper A

2018-03-06

Mesial temporal lobe epilepsy is a serious brain disorder in adults that is often preceded by an initial brain insult, such as status epilepticus (SE), that after a latent period leads to recurrent seizures. Post-SE models are widely used for studies on epileptogenic processes. Previous findings of our laboratory suggested that the Neotropical rodents Proechimys exhibit endogenous antiepileptogenic mechanisms in post-SE models. Strong body of research supports that SE triggers a rapid and dramatic upregulation of inflammatory mediators and vascular endothelial growth factor (VEGF). In this work we found that, in the epilepsy-resistant Proechimys, hippocampal and cortical levels of inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α) and VEGF remained unchanged 24h after SE, strongly contrasting to the high levels of post-SE changes observed in Wistar rats. Furthermore, substantial differences in the brain baseline levels of these proteins were encountered between animal species studied. Since inflammatory cytokines and VEGF have been recognized as major orchestrators of the epileptogenic process, our results suggest their role in the antiepileptogenic mechanisms previously described in Proechimys. Copyright © 2017 Elsevier B.V. All rights reserved.

Impairment of blood-brain barrier is an early event in R6/2 mouse model of Huntington Disease.

PubMed

Di Pardo, Alba; Amico, Enrico; Scalabrì, Francesco; Pepe, Giuseppe; Castaldo, Salvatore; Elifani, Francesca; Capocci, Luca; De Sanctis, Claudia; Comerci, Laura; Pompeo, Francesco; D'Esposito, Maurizio; Filosa, Stefania; Crispi, Stefania; Maglione, Vittorio

2017-01-24

Blood-brain barrier (BBB) breakdown, due to the concomitant disruption of the tight junctions (TJs), normally required for the maintenance of BBB function, and to the altered transport of molecules between blood and brain and vice-versa, has been suggested to significantly contribute to the development and progression of different brain disorders including Huntington's disease (HD). Although the detrimental consequence the BBB breakdown may have in the clinical settings, the timing of its alteration remains elusive for many neurodegenerative diseases. In this study we demonstrate for the first time that BBB disruption in HD is not confined to established symptoms, but occurs early in the disease progression. Despite the obvious signs of impaired BBB permeability were only detectable in concomitance with the onset of the disease, signs of deranged TJs integrity occur precociously in the disease and precede the onset of overt symptoms. To our perspective this finding may add a new dimension to the horizons of pathological mechanisms underlying this devastating disease, however much remains to be elucidated for understanding how specific BBB drug targets can be approached in the future.

Selective alignment of brain responses by task demands during semantic processing.

PubMed

Baggio, Giosuè

2012-04-01

The way the brain binds together words to form sentences may depend on whether and how the arising cognitive representation is to be used in behavior. The amplitude of the N400 effect in event-related brain potentials is inversely correlated with the degree of fit of a word's meaning into a semantic representation of the preceding discourse. This study reports a double dissociation in the latency characteristics of the N400 effect depending on task demands. When participants silently read words in a sentence context, without issuing a relevant overt response, greater temporal alignment over recording sites occurs for N400 onsets than peaks. If however a behavior is produced - here pressing a button in a binary probe selection task - exactly the opposite pattern is observed, with stronger alignment of N400 peaks than onsets. The peak amplitude of the N400 effect correlates best with the latency characteristic showing less temporal dispersion. These findings suggest that meaning construction in the brain is subtly affected by task demands, and that there is complex functional integration between semantic combinatorics and control systems handling behavioral goals. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Developmental Neuroscience Approach to the Search for Biomarkers in Autism Spectrum Disorder

PubMed Central

Varcin, Kandice J.; Nelson, Charles A.

2016-01-01

Purpose of review The delineation of biomarkers in autism spectrum disorder (ASD) offers a promising approach to inform precision-medicine based approaches to ASD diagnosis and treatment and to move toward a mechanistic description of the disorder. However, biomarkers with sufficient sensitivity or specificity for clinical application in ASD are yet to be realized. Here, we review recent evidence for early, low-level alterations in brain and behavior development that may offer promising avenues for biomarker development in ASD. Recent findings Accumulating evidence suggests that signs associated with ASD may unfold in a manner that maps onto the hierarchical organization of brain development. Genetic and neuroimaging evidence points towards perturbations in brain development early in life, and emerging evidence indicates that sensorimotor development may be amongst the earliest emerging signs associated with ASD, preceding social and cognitive impairment. Summary The search for biomarkers of risk, prediction and stratification in ASD may be advanced through a developmental neuroscience approach that looks outside of the core signs of ASD and considers the bottom-up nature of brain development alongside the dynamic nature of development over time. We provide examples of assays that could be incorporated in studies to target low-level circuits. PMID:26953849

Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods

PubMed Central

Daugherty, Ana M; Raz, Naftali

2015-01-01

Age-related increase in frailty is accompanied by a fundamental shift in cellular iron homeostasis. By promoting oxidative stress, the intracellular accumulation of non-heme iron outside of binding complexes contributes to chronic inflammation and interferes with normal brain metabolism. In the absence of direct non-invasive biomarkers of brain oxidative stress, iron accumulation estimated in vivo may serve as its proxy indicator. Hence, developing reliable in vivo measurements of brain iron content via magnetic resonance imaging (MRI) is of significant interest in human neuroscience. To date, by estimating brain iron content through various MRI methods, significant age differences and age-related increases in iron content of the basal ganglia have been revealed across multiple samples. Less consistent are the findings that pertain to the relationship between elevated brain iron content and systemic indices of vascular and metabolic dysfunction. Only a handful of cross-sectional investigations have linked high iron content in various brain regions and poor performance on assorted cognitive tests. The even fewer longitudinal studies indicate that iron accumulation may precede shrinkage of the basal ganglia and thus predict poor maintenance of cognitive functions. This rapidly developing field will benefit from introduction of higher-field MRI scanners, improvement in iron-sensitive and -specific acquisition sequences and post-processing analytic and computational methods, as well as accumulation of data from long-term longitudinal investigations. This review describes the potential advantages and promises of MRI-based assessment of brain iron, summarizes recent findings and highlights the limitations of the current methodology. PMID:26248580

Electrophysiological evidence for the modulation of retrieval orientation by depth of study processing.

PubMed

Rugg, M D; Allan, K; Birch, C S

2000-07-01

Event-related potentials (ERPs) were employed to investigate whether brain activity elicited by retrieval cues in a memory test varies according to the encoding task undertaken at study. Two recognition memory test blocks were administered, preceded, in one case, by a "shallow" study task (alphabetic judgement) and, in the other case, by a "deep" task (sentence generation). ERPs elicited by the new words in each test block differed, the ERPs elicited in the block following the shallow study task exhibiting the more positive-going waveforms. This finding was taken as evidence that subjects adopt different "retrieval sets" when attempting to retrieve items that had been encoded in terms of alphabetic versus semantic attributes. Differences between the ERPs elicited by correctly classified old and new words (old/new effects) also varied with encoding task. The effects for deeply studied words resembled those found in previous ERP studies of recognition memory, whereas old/new effects for shallowly studied words were confined to a late-onsetting, right frontal positivity. Together, the findings indicate that the depth of study processing influences two kinds of memory-related neural activity, associated with memory search operations, and the processing of retrieved information, respectively.

The role of the right temporo-parietal junction in social decision-making.

PubMed

Bitsch, Florian; Berger, Philipp; Nagels, Arne; Falkenberg, Irina; Straube, Benjamin

2018-03-26

Identifying someone else's noncooperative intentions can prevent exploitation in social interactions. Hence, the inference of another person's mental state might be most pronounced in order to improve social decision-making. Here, we tested the hypothesis that brain regions associated with Theory of Mind (ToM), particularly the right temporo-parietal junction (rTPJ), show higher neural responses when interacting with a selfish person and that the rTPJ-activity as well as cooperative tendencies will change over time. We used functional magnetic resonance imaging (fMRI) and a modified prisoner's dilemma game in which 20 participants interacted with three fictive playing partners who behaved according to stable strategies either competitively, cooperatively or randomly during seven interaction blocks. The rTPJ and the posterior-medial prefrontal cortex showed higher activity during the interaction with a competitive compared with a cooperative playing partner. Only the rTPJ showed a high response during an early interaction phase, which preceded participants increase in defective decisions. Enhanced functional connectivity between the rTPJ and the left hippocampus suggests that social cognition and learning processes co-occur when behavioral adaptation seems beneficial. © 2018 Wiley Periodicals, Inc.

Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand binding.

PubMed

Munck Petersen, C; Nielsen, M S; Jacobsen, C; Tauris, J; Jacobsen, L; Gliemann, J; Moestrup, S K; Madsen, P

1999-02-01

We recently reported the isolation and sequencing of sortilin, a new putative sorting receptor that binds receptor-associated protein (RAP). The luminal N-terminus of sortilin comprises a consensus sequence for cleavage by furin, R41WRR44, which precedes a truncation originally found in sortilin isolated from human brain. We now show that the truncation results from cellular processing. Sortilin is synthesized as a proform which, in late Golgi compartments, is converted to the mature receptor by furin-mediated cleavage of a 44 residue N-terminal propeptide. We further demonstrate that the propeptide exhibits pH-dependent high affinity binding to fully processed sortilin, that the binding is competed for by RAP and the newly discovered sortilin ligand neurotensin, and that prevention of propeptide cleavage essentially prevents binding of RAP and neurotensin. The findings evidence that the propeptide sterically hinders ligands from gaining access to overlapping binding sites in prosortilin, and that cleavage and release of the propeptide preconditions sortilin for full functional activity. Although proteolytic processing is involved in the maturation of several receptors, the described exposure of previously concealed ligand-binding sites after furin-mediated cleavage of propeptide represents a novel mechanism in receptor activation.

Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand binding.

PubMed Central

Munck Petersen, C; Nielsen, M S; Jacobsen, C; Tauris, J; Jacobsen, L; Gliemann, J; Moestrup, S K; Madsen, P

1999-01-01

We recently reported the isolation and sequencing of sortilin, a new putative sorting receptor that binds receptor-associated protein (RAP). The luminal N-terminus of sortilin comprises a consensus sequence for cleavage by furin, R41WRR44, which precedes a truncation originally found in sortilin isolated from human brain. We now show that the truncation results from cellular processing. Sortilin is synthesized as a proform which, in late Golgi compartments, is converted to the mature receptor by furin-mediated cleavage of a 44 residue N-terminal propeptide. We further demonstrate that the propeptide exhibits pH-dependent high affinity binding to fully processed sortilin, that the binding is competed for by RAP and the newly discovered sortilin ligand neurotensin, and that prevention of propeptide cleavage essentially prevents binding of RAP and neurotensin. The findings evidence that the propeptide sterically hinders ligands from gaining access to overlapping binding sites in prosortilin, and that cleavage and release of the propeptide preconditions sortilin for full functional activity. Although proteolytic processing is involved in the maturation of several receptors, the described exposure of previously concealed ligand-binding sites after furin-mediated cleavage of propeptide represents a novel mechanism in receptor activation. PMID:9927419

Interplay Between Conceptual Expectations and Movement Predictions Underlies Action Understanding.

PubMed

Ondobaka, Sasha; de Lange, Floris P; Wittmann, Marco; Frith, Chris D; Bekkering, Harold

2015-09-01

Recent accounts of understanding goal-directed action underline the importance of a hierarchical predictive architecture. However, the neural implementation of such an architecture remains elusive. In the present study, we used functional neuroimaging to quantify brain activity associated with predicting physical movements, as they were modulated by conceptual-expectations regarding the purpose of the object involved in the action. Participants observed object-related actions preceded by a cue that generated both conceptual goal expectations and movement goal predictions. In 2 tasks, observers judged whether conceptual or movement goals matched or mismatched the cue. At the conceptual level, expected goals specifically recruited the posterior cingulate cortex, irrespectively of the task and the perceived movement goal. At the movement level, neural activation of the parieto-frontal circuit, including inferior frontal gyrus and the inferior parietal lobe, reflected unpredicted movement goals. Crucially, this movement prediction error was only present when the purpose of the involved object was expected. These findings provide neural evidence that prior conceptual expectations influence processing of physical movement goals and thereby support the hierarchical predictive account of action processing. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Stimulus sequence context differentially modulates inhibition-related theta and delta band activity in a go/nogo task

PubMed Central

Harper, Jeremy; Malone, Stephen M.; Bachman, Matthew D.; Bernat, Edward M.

2015-01-01

Recent work suggests that dissociable activity in theta and delta frequency bands underlies several common event-related potential (ERP) components, including the nogo N2/P3 complex, which can better index separable functional processes than traditional time-domain measures. Reports have also demonstrated that neural activity can be affected by stimulus sequence context information (i.e., the number and type of preceding stimuli). Stemming from prior work demonstrating that theta and delta index separable processes during response inhibition, the current study assessed sequence context in a Go/Nogo paradigm in which the number of go stimuli preceding each nogo was selectively manipulated. Principal component analysis (PCA) of time-frequency representations revealed differential modulation of evoked theta and delta related to sequence context, where delta increased robustly with additional preceding go stimuli, while theta did not. Findings are consistent with the view that theta indexes simpler initial salience-related processes, while delta indexes more varied and complex processes related to a variety of task parameters. PMID:26751830

Regulation of Ca(2+)/calmodulin-dependent protein kinase kinase alpha by cAMP-dependent protein kinase: II. Mutational analysis.

PubMed

Kitani, T; Okuno, S; Fujisawa, H

2001-10-01

We previously reported that rat brain Ca(2+)/calmodulin-dependent protein kinase (CaM-kinase) IV is inactivated by cAMP-dependent protein kinase (PKA) [Kameshita, I. and Fujisawa, H. (1991) Biochem. Biophys. Res. Commun. 180, 191-196]. In the preceding paper, we demonstrated that changes in the activity of CaM-kinase IV by PKA results from the phosphorylation of CaM-kinase kinase alpha by PKA and identified six phosphorylation sites, Ser(24) for autophosphorylation, and Ser(52), Ser(74), Thr(108), Ser(458), and Ser(475) for phosphorylation by PKA. In the present study, a causal relationship between the phosphorylation and change in the activity toward PKIV peptide has been studied using mutant enzymes with amino acid substitutions at the six phosphorylation sites. The following conclusions can be drawn from the experimental results: (i) Phosphorylation of Ser74 and/or unidentified sites causes an increase in activity; (ii) phosphorylation of Thr(108) or Ser(458) causes a decrease in the activity; (iii) the inhibitory effect of the phosphorylation of Thr(108) is canceled by the stimulatory effect of the phosphorylation, but that of Ser(458) is not; and (iv) the inhibitory effects of Thr(108) and Ser(458) are synergistic. In contrast to the activity toward PKIV peptide, the activity toward CaM-kinase IV appears to be decreased by the phosphorylation of Thr(108), but not significantly affected by the phosphorylation of Ser(458).

Daily Scheduled High Fat Meals Moderately Entrain Behavioral Anticipatory Activity, Body Temperature, and Hypothalamic c-Fos Activation

PubMed Central

Gallardo, Christian M.; Gunapala, Keith M.; King, Oliver D.; Steele, Andrew D.

2012-01-01

When fed in restricted amounts, rodents show robust activity in the hours preceding expected meal delivery. This process, termed food anticipatory activity (FAA), is independent of the light-entrained clock, the suprachiasmatic nucleus, yet beyond this basic observation there is little agreement on the neuronal underpinnings of FAA. One complication in studying FAA using a calorie restriction model is that much of the brain is activated in response to this strong hunger signal. Thus, daily timed access to palatable meals in the presence of continuous access to standard chow has been employed as a model to study FAA in rats. In order to exploit the extensive genetic resources available in the murine system we extended this model to mice, which will anticipate rodent high fat diet but not chocolate or other sweet daily meals (Hsu, Patton, Mistlberger, and Steele; 2010, PLoS ONE e12903). In this study we test additional fatty meals, including peanut butter and cheese, both of which induced modest FAA. Measurement of core body temperature revealed a moderate preprandial increase in temperature in mice fed high fat diet but entrainment due to handling complicated interpretation of these results. Finally, we examined activation patterns of neurons by immunostaining for the immediate early gene c-Fos and observed a modest amount of entrainment of gene expression in the hypothalamus of mice fed a daily fatty palatable meal. PMID:22815954

Relationship between speed and EEG activity during imagined and executed hand movements

NASA Astrophysics Data System (ADS)

Yuan, Han; Perdoni, Christopher; He, Bin

2010-04-01

The relationship between primary motor cortex and movement kinematics has been shown in nonhuman primate studies of hand reaching or drawing tasks. Studies have demonstrated that the neural activities accompanying or immediately preceding the movement encode the direction, speed and other information. Here we investigated the relationship between the kinematics of imagined and actual hand movement, i.e. the clenching speed, and the EEG activity in ten human subjects. Study participants were asked to perform and imagine clenching of the left hand and right hand at various speeds. The EEG activity in the alpha (8-12 Hz) and beta (18-28 Hz) frequency bands were found to be linearly correlated with the speed of imagery clenching. Similar parametric modulation was also found during the execution of hand movements. A single equation relating the EEG activity to the speed and the hand (left versus right) was developed. This equation, which contained a linear independent combination of the two parameters, described the time-varying neural activity during the tasks. Based on the model, a regression approach was developed to decode the two parameters from the multiple-channel EEG signals. We demonstrated the continuous decoding of dynamic hand and speed information of the imagined clenching. In particular, the time-varying clenching speed was reconstructed in a bell-shaped profile. Our findings suggest an application to providing continuous and complex control of noninvasive brain-computer interface for movement-impaired paralytics.

The effect of anticipation and the specificity of sex differences for amygdala and hippocampus function in emotional memory.

PubMed

Mackiewicz, Kristen L; Sarinopoulos, Issidoros; Cleven, Krystal L; Nitschke, Jack B

2006-09-19

Prior research has shown memory is enhanced for emotional events. Key brain areas involved in emotional memory are the amygdala and hippocampus, which are also recruited during aversion and its anticipation. This study investigated whether anticipatory processes signaling an upcoming aversive event contribute to emotional memory. In an event-related functional MRI paradigm, 40 healthy participants viewed aversive and neutral pictures preceded by predictive warning cues. Participants completed a surprise recognition task directly after functional MRI scanning or 2 weeks later. In anticipation of aversive pictures, bilateral dorsal amygdala and anterior hippocampus activations were associated with better immediate recognition memory. Similar associations with memory were observed for activation of those areas in response to aversive pictures. Anticipatory activation predicted immediate memory over and above these associations for picture viewing. Bilateral ventral amygdala activations in response to aversive pictures predicted delayed memory only. We found that previously reported sex differences of memory associations with left amygdala for women and with right amygdala for men were confined to the ventral amygdala during picture viewing and delayed memory. Results support an established animal model elucidating the functional neuroanatomy of the amygdala and hippocampus in emotional memory, highlight the importance of anticipatory processes in such memory for aversive events, and extend neuroanatomical evidence of sex differences for emotional memory.

Brain gene expression during REM sleep depends on prior waking experience.

PubMed

Ribeiro, S; Goyal, V; Mello, C V; Pavlides, C

1999-01-01

In most mammalian species studied, two distinct and successive phases of sleep, slow wave (SW), and rapid eye movement (REM), can be recognized on the basis of their EEG profiles and associated behaviors. Both phases have been implicated in the offline sensorimotor processing of daytime events, but the molecular mechanisms remain elusive. We studied brain expression of the plasticity-associated immediate-early gene (IEG) zif-268 during SW and REM sleep in rats exposed to rich sensorimotor experience in the preceding waking period. Whereas nonexposed controls show generalized zif-268 down-regulation during SW and REM sleep, zif-268 is upregulated during REM sleep in the cerebral cortex and the hippocampus of exposed animals. We suggest that this phenomenon represents a window of increased neuronal plasticity during REM sleep that follows enriched waking experience.

Development of magnitude processing in children with developmental dyscalculia: space, time, and number

PubMed Central

Skagerlund, Kenny; Träff, Ulf

2014-01-01

Developmental dyscalculia (DD) is a learning disorder associated with impairments in a preverbal non-symbolic approximate number system (ANS) pertaining to areas in and around the intraparietal sulcus (IPS). The current study sought to enhance our understanding of the developmental trajectory of the ANS and symbolic number processing skills, thereby getting insight into whether a deficit in the ANS precedes or is preceded by impaired symbolic and exact number processing. Recent work has also suggested that humans are endowed with a shared magnitude system (beyond the number domain) in the brain. We therefore investigated whether children with DD demonstrated a general magnitude deficit, stemming from the proposed magnitude system, rather than a specific one limited to numerical quantity. Fourth graders with DD were compared to age-matched controls and a group of ability-matched second graders, on a range of magnitude processing tasks pertaining to space, time, and number. Children with DD displayed difficulties across all magnitude dimensions compared to age-matched peers and showed impaired ANS acuity compared to the younger, ability-matched control group, while exhibiting intact symbolic number processing. We conclude that (1) children with DD suffer from a general magnitude-processing deficit, (2) a shared magnitude system likely exists, and (3) a symbolic number-processing deficit in DD tends to be preceded by an ANS deficit. PMID:25018746

Development of magnitude processing in children with developmental dyscalculia: space, time, and number.

PubMed

Skagerlund, Kenny; Träff, Ulf

2014-01-01

Developmental dyscalculia (DD) is a learning disorder associated with impairments in a preverbal non-symbolic approximate number system (ANS) pertaining to areas in and around the intraparietal sulcus (IPS). The current study sought to enhance our understanding of the developmental trajectory of the ANS and symbolic number processing skills, thereby getting insight into whether a deficit in the ANS precedes or is preceded by impaired symbolic and exact number processing. Recent work has also suggested that humans are endowed with a shared magnitude system (beyond the number domain) in the brain. We therefore investigated whether children with DD demonstrated a general magnitude deficit, stemming from the proposed magnitude system, rather than a specific one limited to numerical quantity. Fourth graders with DD were compared to age-matched controls and a group of ability-matched second graders, on a range of magnitude processing tasks pertaining to space, time, and number. Children with DD displayed difficulties across all magnitude dimensions compared to age-matched peers and showed impaired ANS acuity compared to the younger, ability-matched control group, while exhibiting intact symbolic number processing. We conclude that (1) children with DD suffer from a general magnitude-processing deficit, (2) a shared magnitude system likely exists, and (3) a symbolic number-processing deficit in DD tends to be preceded by an ANS deficit.

Brain Structural and Vascular Anatomy Is Altered in Offspring of Pre-Eclamptic Pregnancies: A Pilot Study.

PubMed

Rätsep, M T; Paolozza, A; Hickman, A F; Maser, B; Kay, V R; Mohammad, S; Pudwell, J; Smith, G N; Brien, D; Stroman, P W; Adams, M A; Reynolds, J N; Croy, B A; Forkert, N D

2016-05-01

Pre-eclampsia is a serious clinical gestational disorder occurring in 3%-5% of all human pregnancies and characterized by endothelial dysfunction and vascular complications. Offspring born of pre-eclamptic pregnancies are reported to exhibit deficits in cognitive function, higher incidence of depression, and increased susceptibility to stroke. However, no brain imaging reports exist on these offspring. We aimed to assess brain structural and vascular anatomy in 7- to 10-year-old offspring of pre-eclamptic pregnancies compared with matched controls. Offspring of pre-eclamptic pregnancies and matched controls (n = 10 per group) were recruited from an established longitudinal cohort examining the effects of pre-eclampsia. Children underwent MR imaging to identify brain structural and vascular anatomic differences. Maternal plasma samples collected at birth were assayed for angiogenic factors by enzyme-linked immunosorbent assay. Offspring of pre-eclamptic pregnancies exhibited enlarged brain regional volumes of the cerebellum, temporal lobe, brain stem, and right and left amygdalae. These offspring displayed reduced cerebral vessel radii in the occipital and parietal lobes. Enzyme-linked immunosorbent assay analysis revealed underexpression of the placental growth factor among the maternal plasma samples from women who experienced pre-eclampsia. This study is the first to report brain structural and vascular anatomic alterations in the population of offspring of pre-eclamptic pregnancies. Brain structural alterations shared similarities with those seen in autism. Vascular alterations may have preceded these structural alterations. This pilot study requires further validation with a larger population to provide stronger estimates of brain structural and vascular outcomes among the offspring of pre-eclamptic pregnancies. © 2016 by American Journal of Neuroradiology.

Visual stimulation synchronizes or desynchronizes the activity of neuron pairs between the caudate nucleus and the posterior thalamus.

PubMed

Rokszin, Alice; Gombköto, Péter; Berényi, Antal; Márkus, Zita; Braunitzer, Gábor; Benedek, György; Nagy, Attila

2011-10-18

Recent morphological and physiological studies have suggested a strong relationship between the suprageniculate nucleus (Sg) of the posterior thalamus and the input structure of the basal ganglia, the caudate nucleus (CN) of the feline brain. Accordingly, to clarify if there is a real functional relationship between Sg and CN during visual information processing, we investigated the temporal relations of simultaneously recorded neuronal spike trains of these two structures, looking for any significant cross-correlation between the spiking of the simultaneously recorded neurons. For the purposes of statistical analysis, we used the shuffle and jittering resampling methods. Of the recorded 288 Sg-CN neuron pairs, 26 (9.2%) showed significantly correlated spontaneous activity. Nineteen pairs (6.7%) showed correlated activity during stationary visual stimulation, while 21 (7.4%) pairs during stimulus movement. There was no overlap between the neuron pairs that showed cross-correlated spontaneous activity and the pairs that synchronized their activity during visual stimulation. Thus visual stimulation seems to have been able to synchronize, and also, by other neuron pairs, desynchronize the activity of CN and Sg. In about half of the cases, the activation of Sg preceded the activation of CN by a few milliseconds, while in the other half, CN was activated earlier. Our results provide the first piece of evidence for the existence of a functional cooperation between Sg and CN. We argue that either a monosynaptic bidirectional direct connection should exist between these structures, or a common input comprising of parallel pathways synchronizing them. Copyright © 2011 Elsevier B.V. All rights reserved.

The engagement of cortical areas preceding exogenous vergence eye movements.

PubMed

Wojtczak-Kwaśniewska, Monika; Przekoracka-Krawczyk, Anna; Van der Lubbe, Rob H J

2018-01-01

Source analyses on event related potentials (ERPs) derived from the electroencephalogram (EEG) were performed to examine the respective roles of cortical areas preceding exogenously triggered saccades, combined convergences, and combined divergences. All eye movements were triggered by the offset of a central fixation light emitting diode (LED) and the onset of a lateral LED at various depths in an otherwise fully darkened room. Our analyses revealed that three source pairs, two located in the frontal lobe-the frontal eye fields (FEF) and an anterior frontal area-, and one located within the occipital cortex, can account for 99.2% of the observed ERPs. Overall, the comparison between source activities revealed the largest activity in the occipital cortex, while no difference in activity between FEF and the anterior frontal area was obtained. For all sources, increased activity was observed for combined vergences, especially combined convergences, relative to saccades. Behavioral results revealed that onset latencies were longest for combined convergences, intermediate for combined divergences, and the shortest for saccades. Together, these findings fit within a perspective in which both occipital and frontal areas play an important role in retinal disparity detection. In the case of saccades and combined divergences stimulus-locked activity was larger than response-locked activity, while no difference between stimulus- and response-locked activity was observed for combined convergences. These findings seem to imply that the electrophysiological activity preceding exogenous eye movements consists of a sensory-related part that is under cortical control, while subcortical structures may be held responsible for final execution.

Transcriptional regulation of N-acetylaspartate metabolism in the 5xFAD model of Alzheimer's disease: evidence for neuron-glia communication during energetic crisis.

PubMed

Zaroff, Samantha; Leone, Paola; Markov, Vladimir; Francis, Jeremy S

2015-03-01

N-acetylaspartate (NAA) provides a non-invasive clinical index of neuronal metabolic integrity across the entire neurodegenerative spectrum. While NAA function is not comprehensively defined, reductions in the brain are associated with compromised mitochondrial metabolism and are tightly linked to ATP. We have undertaken an analysis of abnormalities in NAA during early stage pathology in the 5xFAD mouse model of familial Alzheimer's disease and show here that dysregulated expression of the gene encoding for the rate-limiting NAA synthetic enzyme (Nat8L) is associated with deficits in mitochondrial oxidative phosphorylation in this model system. Downreguation of Nat8L is particularly pronounced in the 5xFAD hippocampus, and is preceded by a significant upregulation of oligodendrocytic aspartoacylase (aspa), which encodes for the sole known NAA-catabolizing enzyme in the brain. Reductions in 5xFAD NAA and Nat8L cannot be accounted for by discrepancies in either neuron content or activity of the substrate-providing malate-aspartate shuttle, thereby implicating transcriptional regulation in a coordinated response to pathological energetic crisis. A central role for ASPA in this response is supported by a parallel developmental analysis showing highly significant increases in Nat8L expression in an ASPA-null mouse model during a period of early postnatal development normally punctuated by the transcriptional upregulation of aspa. These results provide preliminary evidence of a signaling mechanism in Alzheimer's disease that involves cross talk between neurons and oligodendrocytes, and suggest that ASPA acts to negatively regulate Nat8L expression. This mechanism is proposed to be a fundamental means by which the brain conserves available substrate during energy crises. Copyright © 2015 Elsevier Inc. All rights reserved.

Processing of action- but not stimulus-related prediction errors differs between active and observational feedback learning.

PubMed

Kobza, Stefan; Bellebaum, Christian

2015-01-01

Learning of stimulus-response-outcome associations is driven by outcome prediction errors (PEs). Previous studies have shown larger PE-dependent activity in the striatum for learning from own as compared to observed actions and the following outcomes despite comparable learning rates. We hypothesised that this finding relates primarily to a stronger integration of action and outcome information in active learners. Using functional magnetic resonance imaging, we investigated brain activations related to action-dependent PEs, reflecting the deviation between action values and obtained outcomes, and action-independent PEs, reflecting the deviation between subjective values of response-preceding cues and obtained outcomes. To this end, 16 active and 15 observational learners engaged in a probabilistic learning card-guessing paradigm. On each trial, active learners saw one out of five cues and pressed either a left or right response button to receive feedback (monetary win or loss). Each observational learner observed exactly those cues, responses and outcomes of one active learner. Learning performance was assessed in active test trials without feedback and did not differ between groups. For both types of PEs, activations were found in the globus pallidus, putamen, cerebellum, and insula in active learners. However, only for action-dependent PEs, activations in these structures and the anterior cingulate were increased in active relative to observational learners. Thus, PE-related activity in the reward system is not generally enhanced in active relative to observational learning but only for action-dependent PEs. For the cerebellum, additional activations were found across groups for cue-related uncertainty, thereby emphasising the cerebellum's role in stimulus-outcome learning. Copyright © 2014 Elsevier Ltd. All rights reserved.

Systemic inflammation in early neonatal mice induces transient and lasting neurodegenerative effects.

PubMed

Cardoso, Filipa L; Herz, Jasmin; Fernandes, Adelaide; Rocha, João; Sepodes, Bruno; Brito, Maria A; McGavern, Dorian B; Brites, Dora

2015-04-29

The inflammatory mediator lipopolysaccharide (LPS) has been shown to induce acute gliosis in neonatal mice. However, the progressive effects on the murine neurodevelopmental program over the week that follows systemic inflammation are not known. Thus, we investigated the effects of repeated LPS administration in the first postnatal week in mice, a condition mimicking sepsis in late preterm infants, on the developing central nervous system (CNS). Systemic inflammation was induced by daily intraperitoneal administration (i.p.) of LPS (6 mg/kg) in newborn mice from postnatal day (PND) 4 to PND6. The effects on neurodevelopment were examined by staining the white matter and neurons with Luxol Fast Blue and Cresyl Violet, respectively. The inflammatory response was assessed by quantifying the expression/activity of matrix metalloproteinases (MMP), toll-like receptor (TLR)-4, high mobility group box (HMGB)-1, and autotaxin (ATX). In addition, B6 CX3CR1(gfp/+) mice combined with cryo-immunofluorescence were used to determine the acute, delayed, and lasting effects on myelination, microglia, and astrocytes. LPS administration led to acute body and brain weight loss as well as overt structural changes in the brain such as cerebellar hypoplasia, neuronal loss/shrinkage, and delayed myelination. The impaired myelination was associated with alterations in the proliferation and differentiation of NG2 progenitor cells early after LPS administration, rather than with excessive phagocytosis by CNS myeloid cells. In addition to disruptions in brain architecture, a robust inflammatory response to LPS was observed. Quantification of inflammatory biomarkers revealed decreased expression of ATX with concurrent increases in HMGB1, TLR-4, and MMP-9 expression levels. Acute astrogliosis (GFAP(+) cells) in the brain parenchyma and at the microvasculature interface together with parenchymal microgliosis (CX3CR1(+) cells) were also observed. These changes preceded the migration/proliferation of CX3CR1(+) cells around the vessels at later time points and the subsequent loss of GFAP(+) astrocytes. Collectively, our study has uncovered a complex innate inflammatory reaction and associated structural changes in the brains of neonatal mice challenged peripherally with LPS. These findings may explain some of the neurobehavioral abnormalities that develop following neonatal sepsis.

Human single neuron activity precedes emergence of conscious perception.

PubMed

Gelbard-Sagiv, Hagar; Mudrik, Liad; Hill, Michael R; Koch, Christof; Fried, Itzhak

2018-05-25

Identifying the neuronal basis of spontaneous changes in conscious experience in the absence of changes in the external environment is a major challenge. Binocular rivalry, in which two stationary monocular images lead to continuously changing perception, provides a unique opportunity to address this issue. We studied the activity of human single neurons in the medial temporal and frontal lobes while patients were engaged in binocular rivalry. Here we report that internal changes in the content of perception are signaled by very early (~-2000 ms) nonselective medial frontal activity, followed by selective activity of medial temporal lobe neurons that precedes the perceptual change by ~1000 ms. Such early activations are not found for externally driven perceptual changes. These results suggest that a medial fronto-temporal network may be involved in the preconscious internal generation of perceptual transitions.

Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS)

PubMed Central

George, Mark S; Aston-Jones, Gary

2010-01-01

Although the preceding chapters discuss much of the new knowledge of neurocircuitry of neuropsychiatric diseases, and an invasive approach to treatment, this chapter describes and reviews the noninvasive methods of testing circuit-based theories and treating neuropsychiatric diseases that do not involve implanting electrodes into the brain or on its surface. These techniques are transcranial magnetic stimulation, vagus nerve stimulation, and transcranial direct current stimulation. Two of these approaches have FDA approval as therapies. PMID:19693003

ACTIVE IMMUNIZATION AGAINST POLIOMYELITIS IN MONKEYS.

PubMed

Brodie, M; Goldbloom, A

1931-05-31

1. A combination of poliomyelitis virus and specific human serum is effective for the production of active immunity. 2. For each gram of active virus given intradermally as an emulsion, 6 cc. of human immune serum, injected subcutaneously, was required in our experiments to protect a monkey from paralysis. Some degree of active immunity was induced. 3. Immunity, without symptom of the disease, was secured when the serum was given at the time of inoculation, or within 3 days preceding or following inoculation of the virus. 4. For the production of immunity, virus, preceded by serum administration, is probably less effective than when it is given simultaneously with, or before, the injection of serum. 5. The virus neutralization test is more sensitive than the direct intracerebral test for determining the production of immunity.

Chromatin looping and eRNA transcription precede the transcriptional activation of gene in the β-globin locus

PubMed Central

Kim, Yea Woon; Lee, Sungkung; Yun, Jangmi; Kim, AeRi

2015-01-01

Enhancers are closely positioned with actively transcribed target genes by chromatin looping. Non-coding RNAs are often transcribed on active enhancers, referred to as eRNAs (enhancer RNAs). To explore the kinetics of enhancer–promoter looping and eRNA transcription during transcriptional activation, we induced the β-globin locus by chemical treatment and analysed cross-linking frequency between the β-globin gene and locus control region (LCR) and the amount of eRNAs transcribed on the LCR in a time course manner. The cross-linking frequency was increased after chemical induction but before the transcriptional activation of gene in the β-globin locus. Transcription of eRNAs was increased in concomitant with the increase in cross-linking frequency. These results show that chromatin looping and eRNA transcription precedes the transcriptional activation of gene. Concomitant occurrence of the two events suggests functional relationship between them. PMID:25588787

IGF-1 Protects Dopamine Neurons Against Oxidative Stress: Association with Changes in Phosphokinases

PubMed Central

El Ayadi, Amina; Zigmond, Michael J.; Smith, Amanda D.

2016-01-01

Insulin-like growth factor-1 (IGF-1) is an endogenous peptide transported across the blood brain barrier that is protective in several brain injury models, including an acute animal model of Parkinson’s disease (PD). Motor deficits in PD are due largely to the progressive loss of nigrostriatal dopaminergic neurons. Thus, we examined the neuroprotective potential of IGF-1 in a progressive model of dopamine deficiency in which 6-hydroxydopamine (6-OHDA) is infused into the striatum. Rats received intrastriatal IGF-1 (5 or 50 μg) 6 hrs prior to infusion of 4 μg 6-OHDA into the same site and were sacrificed 1 or 4 wks later. Both concentrations of IGF-1 protected tyrosine hydroxylase (TH) immunoreactive terminals in striatum at 4 wks but not at 1 wk, indicating that IGF-induced restoration of the dopaminergic phenotype occurred over several weeks. TH-immunoreactive cell loss was only attenuated with 50 μg IGF-1. We then examined the effect of striatal IGF-1 on the Ras/ERK1/2 and PI3K/Akt pathways to ascertain if their activation correlated with IGF-1-induced protection. Striatal and nigral levels of phospho-ERK1/2 (pERK1/2) were maximal 6 hrs after IGF-1 infusion and, with the exception of an increase in nigral pERK2 at 48 hrs, returned to basal levels by 7 days. Phospho-Akt (Ser473) was elevated 6–24 hrs post-IGF-1 infusion in both striatum and substantia nigra concomitant with inhibition of pro-death GSK-3β, a downstream target of Akt. These results suggest that IGF-1 can protect the nigrostriatal pathway in a progressive PD model and that this protection is preceded by activation of key pro-survival signaling cascades PMID:26894890

EEG predictors of covert vigilant attention

NASA Astrophysics Data System (ADS)

Martel, Adrien; Dähne, Sven; Blankertz, Benjamin

2014-06-01

Objective. The present study addressed the question whether neurophysiological signals exhibit characteristic modulations preceding a miss in a covert vigilant attention task which mimics a natural environment in which critical stimuli may appear in the periphery of the visual field. Approach. Subjective, behavioural and encephalographic (EEG) data of 12 participants performing a modified Mackworth Clock task were obtained and analysed offline. The stimulus consisted of a pointer performing regular ticks in a clockwise sequence across 42 dots arranged in a circle. Participants were requested to covertly attend to the pointer and press a response button as quickly as possible in the event of a jump, a rare and random event. Main results. Significant increases in response latencies and decreases in the detection rates were found as a function of time-on-task, a characteristic effect of sustained attention tasks known as the vigilance decrement. Subjective sleepiness showed a significant increase over the duration of the experiment. Increased activity in the α-frequency range (8-14 Hz) was observed emerging and gradually accumulating 10 s before a missed target. Additionally, a significant gradual attenuation of the P3 event-related component was found to antecede misses by 5 s. Significance. The results corroborate recent findings that behavioural errors are presaged by specific neurophysiological activity and demonstrate that lapses of attention can be predicted in a covert setting up to 10 s in advance reinforcing the prospective use of brain-computer interface (BCI) technology for the detection of waning vigilance in real-world scenarios. Combining these findings with real-time single-trial analysis from BCI may pave the way for cognitive states monitoring systems able to determine the current, and predict the near-future development of the brain's attentional processes.

The Development of Object Function and Manipulation Knowledge: Evidence from a Semantic Priming Study

PubMed Central

Collette, Cynthia; Bonnotte, Isabelle; Jacquemont, Charlotte; Kalénine, Solène; Bartolo, Angela

2016-01-01

Object semantics include object function and manipulation knowledge. Function knowledge refers to the goal attainable by using an object (e.g., the function of a key is to open or close a door) while manipulation knowledge refers to gestures one has to execute to use an object appropriately (e.g., a key is held between the thumb and the index, inserted into the door lock and then turned). To date, several studies have assessed function and manipulation knowledge in brain lesion patients as well as in healthy adult populations. In patients with left brain damage, a double dissociation between these two types of knowledge has been reported; on the other hand, behavioral studies in healthy adults show that function knowledge is processed faster than manipulation knowledge. Empirical evidence has shown that object interaction in children differs from that in adults, suggesting that the access to function and manipulation knowledge in children might also differ. To investigate the development of object function and manipulation knowledge, 51 typically developing 8-9-10 year-old children and 17 healthy young adults were tested on a naming task associated with a semantic priming paradigm (190-ms SOA; prime duration: 90 ms) in which a series of line drawings of manipulable objects were used. Target objects could be preceded by three priming contexts: related (e.g., knife-scissors for function; key-screwdriver for manipulation), unrelated but visually similar (e.g., glasses-scissors; baseball bat-screwdriver), and purely unrelated (e.g., die-scissors; tissue-screwdriver). Results showed a different developmental pattern of function and manipulation priming effects. Function priming effects were not present in children and emerged only in adults, with faster naming responses for targets preceded by objects sharing the same function. In contrast, manipulation priming effects were already present in 8-year-olds with faster naming responses for targets preceded by objects sharing the same manipulation and these decreased linearly between 8 and 10 years of age, 10-year-olds not differing from adults. Overall, results show that the access to object function and manipulation knowledge changes during development by favoring manipulation knowledge in childhood and function knowledge in adulthood. PMID:27602004

Aggressive behaviour of inpatients with acquired brain injury.

PubMed

Visscher, Ada J M; van Meijel, Berno; Stolker, Joost J; Wiersma, Jan; Nijman, Henk

2011-12-01

To study the prevalence, nature and determinants of aggression among inpatients with acquired brain injury. Patients with acquired brain injury often have difficulty in controlling their aggressive impulses. A prospective observational study design. By means of the Staff Observation Aggression Scale-Revised, the prevalence, nature and severity of aggressive behaviour of inpatients with acquired brain injury was assessed on a neuropsychiatric treatment ward with 45 beds. Additional data on patient-related variables were gathered from the patients' files. In total, 388 aggressive incidents were recorded over 17 weeks. Of a total of 57 patients included, 24 (42%) patients had engaged in aggressive behaviour on one or more occasions. A relatively small proportion of patients (n=8; 14%) was found to be responsible for the majority of incidents (n=332; 86%). The vast majority of aggression incidents (n=270; 70%) were directly preceded by interactions between patients and nursing staff. In line with this, most incidents occurred at times of high contact intensity. Aggressive behaviour was associated with male gender, length of stay at the ward, legal status and hypoxia as the cause of brain injury. Aggression was found to be highly prevalent among inpatients with acquired brain injury. The results suggest that for the prevention of aggression on the ward, it may be highly effective to develop individually tailored interventions for the subgroup with serious aggression problems. Insight into the frequency, nature and determinants of aggressive behaviour in inpatients with acquired brain injury provides nurses with tools for the prevention and treatment of aggressive behaviour. © 2011 Blackwell Publishing Ltd.

Timing of ectocranial suture activity in Gorilla gorilla as related to cranial volume and dental eruption.

PubMed

Cray, James; Cooper, Gregory M; Mooney, Mark P; Siegel, Michael I

2011-05-01

Research has shown that Pan and Homo have similar ectocranial suture synostosis patterns and a similar suture ontogeny (relative timing of suture fusion during the species ontogeny). This ontogeny includes patency during and after neurocranial expansion with a delayed bony response associated with adaptation to biomechanical forces generated by mastication. Here we investigate these relationships for Gorilla by examining the association among ectocranial suture morphology, cranial volume (as a proxy for neurocranial expansion) and dental development (as a proxy for the length of time that it has been masticating hard foods and exerting such strains on the cranial vault) in a large sample of Gorilla gorilla skulls. Two-hundred and fifty-five Gorilla gorilla skulls were examined for ectocranial suture closure status, cranial volume and dental eruption. Regression models were calculated for cranial volumes by suture activity, and Kendall's tau (a non-parametric measure of association) was calculated for dental eruption status by suture activity. Results suggest that, as reported for Pan and Homo, neurocranial expansion precedes suture synostosis activity. Here, Gorilla was shown to have a strong relationship between dental development and suture activity (synostosis). These data are suggestive of suture fusion extending further into ontogeny than brain expansion, similar to Homo and Pan. This finding allows for the possibility that masticatory forces influence ectocranial suture morphology. © 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

Sulfoglucuronosyl paragloboside promotes endothelial cell apoptosis in inflammation: Elucidation of a novel glycosphingolipid-signaling pathway

PubMed Central

Dasgupta, Somsankar; Wang, Guanghu; Yu, Robert K.

2011-01-01

Sulfoglucuronosyl paragloboside (SGPG), a minor glycosphingolipid (GSL) of endothelial cells, is a ligand for L-selectin and has been implicated in neuro-inflammatory diseases, such as Guillian-Barré syndrome. Inflammatory cytokines, such as TNFα and IL-1β, up-regulate SGPG expression by stimulating gene expression for glucuronosyltransferases, both P and S forms (GlcATp and GlcATs), and the HNK-1 sulfotransferase (HNK-1 ST). Transfection of a human cerebromicrovascular endothelial cell (SV-HCEC) line with HNK-1 ST siRNA down-regulated SGPG expression, inhibited cytokine-stimulated T cell adhesion, and offered protection against apoptosis. However, the precise mechanisms of SGPG elevation in endothelial cell death (apoptosis) and the maintenance of blood-brain or blood-nerve barrier (BBB or BNB) integrity in inflammation have not been elucidated. Blocking SGPG expression inhibited cytokine-mediated stimulation of NF-κB activity but stimulated MAP kinase (ERK) activity. Furthermore, elevation of SGPG by over-expression of GlcATp and GlcATs triggered endothelial cell apoptosis, with GlcATs being more potent than GlcATp. While SGPG-mediated endothelial cell apoptosis was preceded by inhibiting the intracellular NF-κB activity, interfering with Akt and ERK activation and stimulating caspase 3 in SV-HCECs, HNK-1ST siRNA transfection also interfered with IKB phosphorylation but stimulated ERK activation. Our data indicate that SGPG is a critical regulatory molecule for maintaining endothelial cell survival and BBB/BNB barrier function. PMID:21916893

Objects Mediate Goal Integration in Ventrolateral Prefrontal Cortex during Action Observation

PubMed Central

Hrkać, Mari; Wurm, Moritz F.; Kühn, Anne B.; Schubotz, Ricarda I.

2015-01-01

Actions performed by others are mostly not observed in isolation, but embedded in sequences of actions tied together by an overarching goal. Therefore, preceding actions can modulate the observer's expectations in relation to the currently perceived action. Ventrolateral prefrontal cortex (vlPFC), and inferior frontal gyrus (IFG) in particular, is suggested to subserve the integration of episodic as well as semantic information and memory, including action scripts. The present fMRI study investigated if activation in IFG varies with the effort to integrate expected and observed action, even when not required by the task. During an fMRI session, participants were instructed to attend to short videos of single actions and to deliver a judgment about the actor’s current goal. We manipulated the strength of goal expectation induced by the preceding action, implementing the parameter "goal-relatedness" between the preceding and the currently observed action. Moreover, since objects point to the probability of certain actions, we also manipulated whether the current and the preceding action shared at least one object or not. We found an interaction between the two factors goal-relatedness and shared object: IFG activation increased the weaker the goal-relatedness between the preceding and the current action was, but only when they shared at least one object. Here, integration of successive action steps was triggered by the re-appearing (shared) object but hampered by a weak goal-relatedness between the actually observed manipulation. These findings foster the recently emerging view that IFG is enhanced by goal-related conflicts during action observation. PMID:26218102

The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine

PubMed Central

Maschio, Marta; Dinapoli, Loredana; Vidiri, Antonello; Pace, Andrea; Fabi, Alessandra; Pompili, Alfredo; Carapella, Maria Carmine; Jandolo, Bruno

2009-01-01

Background Seizure control doesn't represent the only challenging goal in patients with brain tumor-related epilepsy. Side effects have often taken precedence for patients' quality of life. Methods We performed an observational retrospective study on patients with brain tumor-related epilepsy: 35 who had assumed oxcarbazepine monotherapy and 35 patients who had undergone treatment with traditional antiepileptic drugs. Primary variable of efficacy was the mean seizure frequency per month and safety variables were the drop-out for side effects and total incidence of side effects. We applied the Propensity Score technique to minimize selection bias. Results Our results showed a similar efficacy of oxcarbazepine and traditional antiepileptic drugs over time, but the difference in safety and tolerability between the two groups was significant: traditional AEDs caused more side effects, both serious and non serious. Conclusion This study highlights the importance of taking into consideration not only seizure control but also the appearance of side effects when choosing antiepileptic drugs in this patients population. PMID:19419544

Brain metastasis from squamous cell carcinoma of the head and neck: a review of the literature in the genomic era.

PubMed

Barrett, Thomas F; Gill, Corey M; Miles, Brett A; Iloreta, Alfred M C; Bakst, Richard L; Fowkes, Mary; Brastianos, Priscilla K; Bederson, Joshua B; Shrivastava, Raj K

2018-06-01

Squamous cell carcinoma of the head and neck (HNSCC) affects nearly 500,000 individuals globally each year. With the rise of human papillomavirus (HPV) in the general population, clinicians are seeing a concomitant rise in HPV-related HNSCC. Notably, a hallmark of HPV-related HNSCC is a predilection for unique biological and clinical features, which portend a tendency for hematogenous metastasis to distant locations, such as the brain. Despite the classic belief that HNSCC is restricted to local spread via passive lymphatic drainage, brain metastases (BMs) are a rare complication that occurs in less than 1% of all HNSCC cases. Time between initial diagnosis of HNSCC and BM development can vary considerably. Some patients experience more than a decade of disease-free survival, whereas others present with definitive neurological symptoms that precede primary tumor detection. The authors systematically review the current literature on HNSCC BMs and discuss the current understanding of the effect of HPV status on the risk of developing BMs in the modern genomic era.

Brain maps 4.0—Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps

PubMed Central

2018-01-01

Abstract The fourth edition (following editions in 1992, 1998, 2004) of Brain maps: structure of the rat brain is presented here as an open access internet resource for the neuroscience community. One new feature is a set of 10 hierarchical nomenclature tables that define and describe all parts of the rat nervous system within the framework of a strictly topographic system devised previously for the human nervous system. These tables constitute a global ontology for knowledge management systems dealing with neural circuitry. A second new feature is an aligned atlas of bilateral flatmaps illustrating rat nervous system development from the neural plate stage to the adult stage, where most gray matter regions, white matter tracts, ganglia, and nerves listed in the nomenclature tables are illustrated schematically. These flatmaps are convenient for future development of online applications analogous to “Google Maps” for systems neuroscience. The third new feature is a completely revised Atlas of the rat brain in spatially aligned transverse sections that can serve as a framework for 3‐D modeling. Atlas parcellation is little changed from the preceding edition, but the nomenclature for rat is now aligned with an emerging panmammalian neuroanatomical nomenclature. All figures are presented in Adobe Illustrator vector graphics format that can be manipulated, modified, and resized as desired, and freely used with a Creative Commons license. PMID:29277900

Nocturnal Gastroesophageal Reflux Revisited by Impedance-pH Monitoring

PubMed Central

Blondeau, Kathleen; Mertens, Veerle; Tack, Jan; Sifrim, Daniel

2011-01-01

Background/Aims Impedance-pH monitoring allows detailed characterization of gastroesophageal reflux and esophageal activity associated with reflux. We assessed the characteristics of nocturnal reflux and esophageal activity preceding and following reflux. Methods Impedance-pH tracings from 11 healthy subjects and 76 patients with gastroesophageal reflux disease off acid-suppressive therapy were analyzed. Characteristics of nocturnal supine reflux, time distribution and esophageal activity seen on impedance at 2 minute intervals preceding and following reflux were described. Results Patients had more nocturnal reflux events than healthy subjects (8 [4-12] vs 2 [1-5], P = 0.002), with lower proportion of weakly acidic reflux (57% [35-78] vs 80% [60-100], P = 0.044). Nocturnal reflux was mainly liquid (80%) and reached the proximal esophagus more often in patients (6% vs 0%, P = 0.047). Acid reflux predominated in the first 2 hours (66%) and weakly acidic reflux in the last 3 hours (70%) of the night. Most nocturnal reflux was preceded by aboral flows and cleared by short lasting volume clearance. In patients, prolonged chemical clearance was associated with less esophageal activity. Conclusions Nocturnal weakly acidic reflux is as common as acid reflux in patients with gastroesophageal reflux disease, and predominates later in the night. Impedance-pH can predict prolonged chemical clearance after nocturnal acid reflux. PMID:21602991

A pioneer work on electric brain stimulation in psychotic patients. Rudolph Gottfried Arndt and his 1870s studies.

PubMed

Steinberg, Holger

2013-07-01

Today's brain stimulation methods are commonly traced back historically to surgical brain operations. With this one-sided historical approach it is easy to overlook the fact that non-surgical electrical brain-stimulating applications preceded present-day therapies. The first study on transcranial electrical brain stimulation for the treatment of severe mental diseases in a larger group of patients was carried out in the 1870s. Between 1870 and 1878 German psychiatrist Rudolph Gottfried Arndt published the results of his studies in three reports. These are contextualized with contemporary developments of the time, focusing in particular on the (neuro-) sciences. As was common practice at the time, Arndt basically reported individual cases in which electricity was applied to treat severe psychoses with depressive symptoms or even catatonia, hypochondriac delusion and melancholia. Despite their lengthiness, there is frequently a lack of precise physical data on the application of psychological-psychopathological details. Only his 1878 report includes general rules for electrical brain stimulation. Despite their methodological shortcomings and lack of precise treatment data impeding exact understanding, Arndt's studies are pioneering works in the field of electric brain stimulation with psychoses and its positive impacts. Today's transcranial direct current stimulation, and partly vagus nerve stimulation, can be compared with Arndt's methods. Although Arndt's only tangible results were indications for the application of faradic electricity (for inactivity, stupor, weakness and manic depressions) and galvanic current (for affective disorders and psychoses), a historiography of present-day brain stimulation therapies should no longer neglect studies on electrotherapy published in German and international psychiatric and neurological journals and monographs in the 1870s and 1880s. Copyright © 2013 Elsevier Inc. All rights reserved.

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

3-Substituted 1,5-Diaryl-1 H-1,2,4-triazoles as Prospective PET Radioligands for Imaging Brain COX-1 in Monkey. Part 2: Selection and Evaluation of [11C]PS13 for Quantitative Imaging.

PubMed

Shrestha, Stal; Singh, Prachi; Cortes-Salva, Michelle Y; Jenko, Kimberly J; Ikawa, Masamichi; Kim, Min-Jeong; Kobayashi, Masato; Morse, Cheryl L; Gladding, Robert L; Liow, Jeih-San; Zoghbi, Sami S; Fujita, Masahiro; Innis, Robert B; Pike, Victor W

2018-06-13

In our preceding paper (Part 1), we identified three 1,5-bis-diaryl-1,2,4-triazole-based compounds that merited evaluation as potential positron emission tomography (PET) radioligands for selectively imaging cyclooxygenase-1 (COX-1) in monkey and human brain, namely, 1,5-bis(4-methoxyphenyl)-3-(alkoxy)-1 H-1,2,4-triazoles bearing a 3-methoxy (PS1), a 3-(2,2,2-trifluoroethoxy) (PS13), or a 3-fluoromethoxy substituent (PS2). PS1 and PS13 were labeled from phenol precursors by O- 11 C-methylation with [ 11 C]iodomethane and PS2 by O- 18 F-fluoroalkylation with [ 2 H 2 , 18 F]fluorobromomethane. Here, we evaluated these PET radioligands in monkey. All three radioligands gave moderately high uptake in brain, although [ 2 H 2 , 18 F]PS2 also showed undesirable radioactivity uptake in skull. [ 11 C]PS13 was selected for further evaluation, mainly based on more favorable brain kinetics than [ 11 C]PS1. Pharmacological preblock experiments showed that about 55% of the radioactivity uptake in brain was specifically bound to COX-1. An index of enzyme density, V T , was well identified from serial brain scans and from the concentrations of parent radioligand in arterial plasma. In addition, V T values were stable within 80 min, suggesting that brain uptake was not contaminated by radiometabolites. [ 11 C]PS13 successfully images and quantifies COX-1 in monkey brain, and merits further investigation for imaging COX-1 in monkey models of neuroinflammation and in healthy human subjects.

Can Monitoring Fetal Intestinal Inflammation Using Heart Rate Variability Analysis Signal Incipient Necrotizing Enterocolitis of the Neonate?

PubMed

Liu, Hai Lun; Garzoni, Luca; Herry, Christophe; Durosier, Lucien Daniel; Cao, Mingju; Burns, Patrick; Fecteau, Gilles; Desrochers, André; Patey, Natalie; Seely, Andrew J E; Faure, Christophe; Frasch, Martin G

2016-04-01

Necrotizing enterocolitis of the neonate is an acute inflammatory intestinal disease that can cause necrosis and sepsis. Chorioamnionitis is a risk factor of necrotizing enterocolitis. The gut represents the biggest vagus-innervated organ. Vagal activity can be measured via fetal heart rate variability. We hypothesized that fetal heart rate variability can detect fetuses with incipient gut inflammation. Prospective animal study. University research laboratory. Chronically instrumented near-term fetal sheep (n = 21). Animals were surgically instrumented with vascular catheters and electrocardiogram to allow manipulation and recording from nonanesthetized animals. In 14 fetal sheep, inflammation was induced with lipopolysaccharide (IV) to mimic chorioamnionitis. Fetal arterial blood samples were drawn at selected time points over 54 hours post lipopolysaccharide for blood gas and cytokines (interleukin-6 and tumor necrosis factor-α enzymelinked immunosorbent assay). Fetal heart rateV was quantified throughout the experiment. The time-matched fetal heart rate variability measures were correlated to the levels of interleukin-6 and tumor necrosis factor-α. Upon necropsy, ionized calcium binding adaptor molecule 1+ (Iba1+), CD11c+ (M1), CD206+ (M2 macrophages), and occludin (leakiness marker) immunofluorescence in the terminal ileum was quantified along with regional Iba1+ signal in the brain (microglia). Interleukin-6 peaked at 3 hours post lipopolysaccharide accompanied by mild cardiovascular signs of sepsis. At 54 hours, we identified an increase in Iba1+ and, specifically, M1 macrophages in the ileum accompanied by increased leakiness, with no change in Iba1 signal in the brain. Preceding this change on tissue level, at 24 hours, a subset of nine fetal heart rate variability measures correlated exclusively to the Iba+ markers of ileal, but not brain, inflammation. An additional fetal heart rate variability measure, mean of the differences of R-R intervals, correlated uniquely to M1 ileum macrophages increasing due to lipopolysaccharide. We identified a unique subset of fetal heart rate variability measures reflecting 1.5 days ahead of time the levels of macrophage activation and increased leakiness in terminal ileum. We propose that such subset of fetal heart rate variability measures reflects brain-gut communication via the vagus nerve. Detecting such noninvasively obtainable organ-specific fetal heart rate variability signature of inflammation would alarm neonatologists about neonates at risk of developing necrotizing enterocolitis and sepsis. Clinical validation studies are required.

The evolutionary and integrative roles of transthyretin in thyroid hormone homeostasis.

PubMed

Schreiber, G

2002-10-01

In larger mammals, thyroid hormone-binding plasma proteins are albumin, transthyretin (TTR) and thyroxine (T4)-binding globulin. They differ characteristically in affinities and release rates for T4 and triiodothyronine (T3). Together, they form a 'buffering' system counteracting thyroid hormone permeation from aqueous to lipid phases. Evolution led to important differences in the expression pattern of these three proteins in tissues. In adult liver, TTR is only made in eutherians and herbivorous marsupials. During development, it is also made in tadpole and fish liver. More intense TTR synthesis than in liver is found in the choroid plexus of reptilians, birds and mammals, but none in the choroid plexus of amphibians and fish, i.e. species without a neocortex. All brain-made TTR is secreted into the cerebrospinal fluid, where it becomes the major thyroid hormone-binding protein. During ontogeny, the maximum TTR synthesis in the choroid plexus precedes that of the growth rate of the brain and occurs during the period of maximum neuroblast replication. TTR is only one component in a network of factors determining thyroid hormone distribution. This explains why, under laboratory conditions, TTR-knockout mice show no major abnormalities. The ratio of TTR affinity for T4 over affinity for T3 is higher in eutherians than in reptiles and birds. This favors T4 transport from blood to brain providing more substrate for conversion of the biologically less active T4 into the biologically more active T3 by the tissue-specific brain deiodinases. The change in affinity of TTR during evolution involves a shortening and an increase in the hydrophilicity of the N-terminal regions of the TTR subunits. The molecular mechanism for this change is a stepwise shift of the splice site at the intron 1/exon 2 border of the TTR gene. The shift probably results from a sequence of single base mutations. Thus, TTR evolution provides an example for a molecular mechanism of positive Darwinian evolution. The amino acid sequences of fish and amphibian TTRs are very similar to those in mammals, suggesting that substantial TTR evolution occurred before the vertebrate stage. Open reading frames for TTR-like sequences already exist in Caenorhabditis elegans, yeast and Escherichia coli genomes.

Dendritic small conductance calcium-activated potassium channels activated by action potentials suppress EPSPs and gate spike-timing dependent synaptic plasticity.

PubMed

Jones, Scott L; To, Minh-Son; Stuart, Greg J

2017-10-23

Small conductance calcium-activated potassium channels (SK channels) are present in spines and can be activated by backpropagating action potentials (APs). This suggests they may play a critical role in spike-timing dependent synaptic plasticity (STDP). Consistent with this idea, EPSPs in both cortical and hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent manner. In cortical pyramidal neurons EPSP suppression by preceding APs depended on their precise timing as well as the distance of activated synapses from the soma, was dendritic in origin, and involved SK-dependent suppression of NMDA receptor activation. As a result SK channel activation by backpropagating APs gated STDP induction during low-frequency AP-EPSP pairing, with both LTP and LTD absent under control conditions but present after SK channel block. These findings indicate that activation of SK channels in spines by backpropagating APs plays a key role in regulating both EPSP amplitude and STDP induction.

Consistently high sports/exercise activity is associated with better sleep quality, continuity and depth in midlife women: the SWAN sleep study.

PubMed

Kline, Christopher E; Irish, Leah A; Krafty, Robert T; Sternfeld, Barbara; Kravitz, Howard M; Buysse, Daniel J; Bromberger, Joyce T; Dugan, Sheila A; Hall, Martica H

2013-09-01

To examine relationships between different physical activity (PA) domains and sleep, and the influence of consistent PA on sleep, in midlife women. Cross-sectional. Community-based. 339 women in the Study of Women's Health Across the Nation Sleep Study (52.1 ± 2.1 y). None. Sleep was examined using questionnaires, diaries and in-home polysomnography (PSG). PA was assessed in three domains (Active Living, Household/Caregiving, Sports/Exercise) using the Kaiser Physical Activity Survey (KPAS) up to 4 times over 6 years preceding the sleep assessments. The association between recent PA and sleep was evaluated using KPAS scores immediately preceding the sleep assessments. The association between the historical PA pattern and sleep was examined by categorizing PA in each KPAS domain according to its pattern over the 6 years preceding sleep assessments (consistently low, inconsistent/consistently moderate, or consistently high). Greater recent Sports/Exercise activity was associated with better sleep quality (diary "restedness" [P < 0.01]), greater sleep continuity (diary sleep efficiency [SE; P = 0.02]) and depth (higher NREM delta electroencephalographic [EEG] power [P = 0.04], lower NREM beta EEG power [P < 0.05]), and lower odds of insomnia diagnosis (P < 0.05). Consistently high Sports/Exercise activity was also associated with better Pittsburgh Sleep Quality Index scores (P = 0.02) and higher PSG-assessed SE (P < 0.01). Few associations between sleep and Active Living or Household/Caregiving activity (either recent or historical pattern) were noted. Consistently high levels of recreational physical activity, but not lifestyle- or household-related activity, are associated with better sleep in midlife women. Increasing recreational physical activity early in midlife may protect against sleep disturbance in this population.

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

Lung Metabolic Activation as an Early Biomarker of the Acute Respiratory Distress Syndrome and Local Gene Expression Heterogeneity

PubMed Central

Wellman, Tyler J.; de Prost, Nicolas; Tucci, Mauro; Winkler, Tilo; Baron, Rebecca M.; Filipczak, Piotr; Raby, Benjamin; Chu, Jen-hwa; Harris, R. Scott; Musch, Guido; dos Reis Falcao, Luiz F.; Capelozzi, Vera; Venegas, Jose; Melo, Marcos F. Vidal

2016-01-01

Background The acute respiratory distress syndrome (ARDS) is an inflammatory condition comprising diffuse lung edema and alveolar damage. ARDS frequently results from regional injury mechanisms. However, it is unknown whether detectable inflammation precedes lung edema and opacification, and whether topographically differential gene expression consistent with heterogeneous injury occurs in early ARDS. We aimed to determine the temporal relationship between pulmonary metabolic activation and density in a large animal model of early ARDS, and to assess gene expression in differentially activated regions. Methods We produced ARDS in sheep with intravenous LPS (10ng/kg/h) and mechanical ventilation for 20h. Using positron emission tomography, we assessed regional cellular metabolic activation with 2-deoxy-2-[(18)F]fluoro-D-glucose, perfusion and ventilation with 13NN-saline, and aeration using transmission scans. Species-specific micro-array technology was used to assess regional gene expression. Results Metabolic activation preceded detectable increases in lung density (as required for clinical diagnosis) and correlated with subsequent histological injury, suggesting its predictive value for severity of disease progression. Local time-courses of metabolic activation varied, with highly perfused and less aerated dependent lung regions activated earlier than non-dependent regions. These regions of distinct metabolic trajectories demonstrated differential gene expression for known and potential novel candidates for ARDS pathogenesis. Conclusions Heterogeneous lung metabolic activation precedes increases in lung density in the development of ARDS due to endotoxemia and mechanical ventilation. Local differential gene expression occurs in these early stages and reveals molecular pathways relevant to ARDS biology and of potential use as treatment targets. PMID:27611185

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.

A review of Edward Flatau's 1894 Atlas of the Human Brain by the neurologist Sigmund Freud.

PubMed

Triarhou, Lazaros C

2011-01-01

In 1894, the Polish neurologist Edward Flatau (1868-1932), working in Berlin, published an exquisite photographic atlas of the unfixed human brain, preceding by 2 years Das Menschenhirn, the reference work of Gustaf Retzius (1842-1919) in Stockholm. In his early career as a neuroanatomist and neurologist, Sigmund Freud (1856-1939) wrote a review of Flatau's atlas for the Internationale klinische Rundschau, which has not been included in the 'Standard Edition of the Complete Psychological Works'. The aim of the present paper is twofold: to document Freud's review, and to revive the largely forgotten atlas of Flatau. The full text of Freud is presented in translation. Further, one element Flatau, Retzius and Freud had in common is discussed: their early role as protagonists and firm supporters of Ramón y Cajal's neuron theory, the cornerstone of modern neuroscience. Copyright © 2010 S. Karger AG, Basel.

Led into temptation? Rewarding brand logos bias the neural encoding of incidental economic decisions.

PubMed

Murawski, Carsten; Harris, Philip G; Bode, Stefan; Domínguez D, Juan F; Egan, Gary F

2012-01-01

Human decision-making is driven by subjective values assigned to alternative choice options. These valuations are based on reward cues. It is unknown, however, whether complex reward cues, such as brand logos, may bias the neural encoding of subjective value in unrelated decisions. In this functional magnetic resonance imaging (fMRI) study, we subliminally presented brand logos preceding intertemporal choices. We demonstrated that priming biased participants' preferences towards more immediate rewards in the subsequent temporal discounting task. This was associated with modulations of the neural encoding of subjective values of choice options in a network of brain regions, including but not restricted to medial prefrontal cortex. Our findings demonstrate the general susceptibility of the human decision making system to apparently incidental contextual information. We conclude that the brain incorporates seemingly unrelated value information that modifies decision making outside the decision-maker's awareness.

Diphtheric encephalitis and brain neuroimaging features.

PubMed

Foo, Jen Chun; Rahmat, Kartini; Mumin, Nazimah Ab; Koh, Mia Tuang; Gan, Chin Seng; Ramli, Norlisah; Fong, Choong Yi

2017-11-01

We report a rare case of paediatric diphtheria complicated with encephalitis. A 6-year-old boy who did not receive his scheduled diptheria-tetanus-pertusis vaccination presented with one episode of generalised convulsive seizure. His illness was preceded by a 3day history of fever associated with enlarged exudative tonsils with a pseudomembrane. He was commenced on intravenous penicillin and oral erythromycin. However, he developed progressive encephalopathy with focal neurological deficit which required intubation on day 5 of illness. Throat swab polymerase chain reaction for diphtheria toxin A and B were positive and diphtheria antitoxin was given. Magnetic resonance imaging (MRI) of brain showed T2-weighted hyperintensities over the anterior cingulate gyri, insular cortex and cerebellum. This is the first reported MRI finding of diphtheric encephalitis. Our report highlights the importance of neuroimaging in diagnosing diphtheric encephalitis particularly in cases with unremarkable cerebrospinal findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency

PubMed Central

Shen, Siming; Sandoval, Juan; Swiss, Victoria A; Li, Jiadong; Dupree, Jeff; Franklin, Robin J M; Casaccia-Bonnefil, Patrizia

2009-01-01

The efficiency of remyelination decreases with age, but the molecular mechanisms responsible for this decline remain only partially understood. In this study, we show that remyelination is regulated by age-dependent epigenetic control of gene expression. In demyelinated young brains, new myelin synthesis is preceded by downregulation of oligodendrocyte differentiation inhibitors and neural stem cell markers, and this is associated with recruitment of histone deacetylases (HDACs) to promoter regions. In demyelinated old brains, HDAC recruitment is inefficient, and this allows the accumulation of transcriptional inhibitors and prevents the subsequent surge in myelin gene expression. Defective remyelination can be recapitulated in vivo in mice receiving systemic administration of pharmacological HDAC inhibitors during cuprizone treatment and is consistent with in vitro results showing defective differentiation of oligodendrocyte progenitors after silencing specific HDAC isoforms. Thus, we suggest that inefficient epigenetic modulation of the oligodendrocyte differentiation program contributes to the age-dependent decline in remyelination efficiency. PMID:19160500

EXPECTING GENDER: AN EVENT RELATED BRAIN POTENTIAL STUDY ON THE ROLE OF GRAMMATICAL GENDER IN COMPREHENDING A LINE DRAWING WITHIN A WRITTEN SENTENCE IN SPANISH

PubMed Central

Wicha, Nicole Y. Y.; Moreno, Eva M.; Kutas, Marta

2012-01-01

Event-related brain potentials (ERPs) were used to examine the role of grammatical gender in written sentence comprehension. Native Spanish speakers read sentences in which a drawing depicting a target noun was either congruent or incongruent with sentence meaning, and either agreed or disagreed in gender with that of the preceding article. The gender-agreement violation at the drawing was associated with an enhanced negativity between 500 and 700 msec post-stimulus onset. Semantically incongruent drawings elicited a larger N400 than congruent drawings regardless of gender (dis)agreement, indicating little effect of grammatical gender agreement on contextual integration of a picture into a written sentence context. We also observed an enhanced negativity for articles with unexpected relative to expected gender based on prior sentence context indicating that readers generate expectations for specific nouns and their articles. PMID:12870823

Led into Temptation? Rewarding Brand Logos Bias the Neural Encoding of Incidental Economic Decisions

PubMed Central

Murawski, Carsten; Harris, Philip G.; Bode, Stefan; Domínguez D., Juan F.; Egan, Gary F.

2012-01-01

Human decision-making is driven by subjective values assigned to alternative choice options. These valuations are based on reward cues. It is unknown, however, whether complex reward cues, such as brand logos, may bias the neural encoding of subjective value in unrelated decisions. In this functional magnetic resonance imaging (fMRI) study, we subliminally presented brand logos preceding intertemporal choices. We demonstrated that priming biased participants' preferences towards more immediate rewards in the subsequent temporal discounting task. This was associated with modulations of the neural encoding of subjective values of choice options in a network of brain regions, including but not restricted to medial prefrontal cortex. Our findings demonstrate the general susceptibility of the human decision making system to apparently incidental contextual information. We conclude that the brain incorporates seemingly unrelated value information that modifies decision making outside the decision-maker's awareness. PMID:22479547

miRNA Expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132.

PubMed

Jimenez-Mateos, Eva M; Bray, Isabella; Sanz-Rodriguez, Amaya; Engel, Tobias; McKiernan, Ross C; Mouri, Genshin; Tanaka, Katsuhiro; Sano, Takanori; Saugstad, Julie A; Simon, Roger P; Stallings, Raymond L; Henshall, David C

2011-11-01

When an otherwise harmful insult to the brain is preceded by a brief, noninjurious stimulus, the brain becomes tolerant, and the resulting damage is reduced. Epileptic tolerance develops when brief seizures precede an episode of prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status epilepticus in animals that had previously received either seizure preconditioning (tolerance) or no preconditioning (injury), and mature miRNA levels were measured using TaqMan low-density arrays. Expression of 21 miRNAs was increased, relative to control, after status epilepticus alone, and expression of 12 miRNAs was decreased. Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The neural basis of financial risk taking.

PubMed

Kuhnen, Camelia M; Knutson, Brian

2005-09-01

Investors systematically deviate from rationality when making financial decisions, yet the mechanisms responsible for these deviations have not been identified. Using event-related fMRI, we examined whether anticipatory neural activity would predict optimal and suboptimal choices in a financial decision-making task. We characterized two types of deviations from the optimal investment strategy of a rational risk-neutral agent as risk-seeking mistakes and risk-aversion mistakes. Nucleus accumbens activation preceded risky choices as well as risk-seeking mistakes, while anterior insula activation preceded riskless choices as well as risk-aversion mistakes. These findings suggest that distinct neural circuits linked to anticipatory affect promote different types of financial choices and indicate that excessive activation of these circuits may lead to investing mistakes. Thus, consideration of anticipatory neural mechanisms may add predictive power to the rational actor model of economic decision making.

Dissociative part-dependent biopsychosocial reactions to backward masked angry and neutral faces: An fMRI study of dissociative identity disorder.

PubMed

Schlumpf, Yolanda R; Nijenhuis, Ellert R S; Chalavi, Sima; Weder, Ekaterina V; Zimmermann, Eva; Luechinger, Roger; La Marca, Roberto; Reinders, A A T Simone; Jäncke, Lutz

2013-01-01

The Theory of Structural Dissociation of the Personality (TSDP) proposes that dissociative identity disorder (DID) patients are fixed in traumatic memories as "Emotional Parts" (EP), but mentally avoid these as "Apparently Normal Parts" of the personality (ANP). We tested the hypotheses that ANP and EP have different biopsychosocial reactions to subliminally presented angry and neutral faces, and that actors instructed and motivated to simulate ANP and EP react differently. Women with DID and matched healthy female actors (CON) were as ANP and EP (DIDanp, DIDep, CONanp, CONep) consecutively exposed to masked neutral and angry faces. Their brain activation was monitored using functional magnetic resonance imaging. The black-and-white dotted masks preceding and following the faces each had a centered colored dot, but in a different color. Participants were instructed to immediately press a button after a perceived color change. State anxiety was assessed after each run using the STAI-S. Final statistical analyses were conducted on 11 DID patients and 15 controls for differences in neural activity, and 13 DID patients and 15 controls for differences in behavior and psychometric measures. Differences between ANP and EP in DID patients and between DID and CON in the two dissociative parts of the personality were generally larger for neutral than for angry faces. The longest reaction times (RTs) existed for DIDep when exposed to neutral faces. Compared to DIDanp, DIDep was associated with more activation of the parahippocampal gyrus. Following neutral faces and compared to CONep, DIDep had more activation in the brainstem, face-sensitive regions, and motor-related areas. DIDanp showed a decreased activity all over the brain in the neutral and angry face condition. There were neither significant within differences nor significant between group differences in state anxiety. CON was not able to simulate genuine ANP and EP biopsychosocially. DID patients have dissociative part-dependent biopsychosocial reactions to masked neutral and angry faces. As EP, they are overactivated, and as ANP underactivated. The findings support TSDP. Major clinical implications are discussed.

Dissociative part-dependent biopsychosocial reactions to backward masked angry and neutral faces: An fMRI study of dissociative identity disorder☆

PubMed Central

Schlumpf, Yolanda R.; Nijenhuis, Ellert R.S.; Chalavi, Sima; Weder, Ekaterina V.; Zimmermann, Eva; Luechinger, Roger; La Marca, Roberto; Reinders, A.A.T. Simone; Jäncke, Lutz

2013-01-01

Objective The Theory of Structural Dissociation of the Personality (TSDP) proposes that dissociative identity disorder (DID) patients are fixed in traumatic memories as “Emotional Parts” (EP), but mentally avoid these as “Apparently Normal Parts” of the personality (ANP). We tested the hypotheses that ANP and EP have different biopsychosocial reactions to subliminally presented angry and neutral faces, and that actors instructed and motivated to simulate ANP and EP react differently. Methods Women with DID and matched healthy female actors (CON) were as ANP and EP (DIDanp, DIDep, CONanp, CONep) consecutively exposed to masked neutral and angry faces. Their brain activation was monitored using functional magnetic resonance imaging. The black-and-white dotted masks preceding and following the faces each had a centered colored dot, but in a different color. Participants were instructed to immediately press a button after a perceived color change. State anxiety was assessed after each run using the STAI-S. Final statistical analyses were conducted on 11 DID patients and 15 controls for differences in neural activity, and 13 DID patients and 15 controls for differences in behavior and psychometric measures. Results Differences between ANP and EP in DID patients and between DID and CON in the two dissociative parts of the personality were generally larger for neutral than for angry faces. The longest reaction times (RTs) existed for DIDep when exposed to neutral faces. Compared to DIDanp, DIDep was associated with more activation of the parahippocampal gyrus. Following neutral faces and compared to CONep, DIDep had more activation in the brainstem, face-sensitive regions, and motor-related areas. DIDanp showed a decreased activity all over the brain in the neutral and angry face condition. There were neither significant within differences nor significant between group differences in state anxiety. CON was not able to simulate genuine ANP and EP biopsychosocially. Conclusions DID patients have dissociative part-dependent biopsychosocial reactions to masked neutral and angry faces. As EP, they are overactivated, and as ANP underactivated. The findings support TSDP. Major clinical implications are discussed. PMID:24179849

Circadian Rhythms in Diet-Induced Obesity.

PubMed

Engin, Atilla

2017-01-01

The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronizes these with daily cycles, feeding patterns also regulates circadian clocks. The clock genes and adipocytokines show circadian rhythmicity. Dysfunction of these genes are involved in the alteration of these adipokines during the development of obesity. Food availability promotes the stimuli associated with food intake which is a circadian oscillator outside of the suprachiasmatic nucleus (SCN). Its circadian rhythm is arranged with the predictable daily mealtimes. Food anticipatory activity is mediated by a self-sustained circadian timing and its principal component is food entrained oscillator. However, the hypothalamus has a crucial role in the regulation of energy balance rather than food intake. Fatty acids or their metabolites can modulate neuronal activity by brain nutrient-sensing neurons involved in the regulation of energy and glucose homeostasis. The timing of three-meal schedules indicates close association with the plasma levels of insulin and preceding food availability. Desynchronization between the central and peripheral clocks by altered timing of food intake and diet composition can lead to uncoupling of peripheral clocks from the central pacemaker and to the development of metabolic disorders. Metabolic dysfunction is associated with circadian disturbances at both central and peripheral levels and, eventual disruption of circadian clock functioning can lead to obesity. While CLOCK expression levels are increased with high fat diet-induced obesity, peroxisome proliferator-activated receptor (PPAR) alpha increases the transcriptional level of brain and muscle ARNT-like 1 (BMAL1) in obese subjects. Consequently, disruption of clock genes results in dyslipidemia, insulin resistance and obesity. Modifying the time of feeding alone can greatly affect body weight. Changes in the circadian clock are associated with temporal alterations in feeding behavior and increased weight gain. Thus, shift work is associated with increased risk for obesity, diabetes and cardio-vascular diseases as a result of unusual eating time and disruption of circadian rhythm.

Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS.

PubMed

Silva, Mauro Sb; Prescott, Melanie; Campbell, Rebecca E

2018-04-05

Androgen excess is a hallmark of polycystic ovary syndrome (PCOS), a prevalent yet poorly understood endocrine disorder. Evidence from women and preclinical animal models suggests that elevated perinatal androgens can elicit PCOS onset in adulthood, implying androgen actions in both PCOS ontogeny and adult pathophysiology. Prenatally androgenized (PNA) mice exhibit a robust increase of progesterone-sensitive GABAergic inputs to gonadotropin-releasing hormone (GnRH) neurons implicated in the pathogenesis of PCOS. It is unclear when altered GABAergic wiring develops in the brain, and whether these central abnormalities are dependent upon adult androgen excess. Using GnRH-GFP-transgenic mice, we determined that increased GABA input to GnRH neurons occurs prior to androgen excess and the manifestation of reproductive impairments in PNA mice. These data suggest that brain circuit abnormalities precede the postpubertal development of PCOS traits. Despite the apparent developmental programming of circuit abnormalities, long-term blockade of androgen receptor signaling from early adulthood rescued normal GABAergic wiring onto GnRH neurons, improved ovarian morphology, and restored reproductive cycles in PNA mice. Therefore, androgen excess maintains changes in female brain wiring linked to PCOS features and the blockade of androgen receptor signaling reverses both the central and peripheral PNA-induced PCOS phenotype.

White matter structure in young adults with familial risk for psychosis - The Oulu Brain and Mind Study.

PubMed

Koivukangas, Jenni; Björnholm, Lassi; Tervonen, Osmo; Miettunen, Jouko; Nordström, Tanja; Kiviniemi, Vesa; Mäki, Pirjo; Jääskeläinen, Erika; Mukkala, Sari; Moilanen, Irma; Barnett, Jennifer H; Jones, Peter B; Nikkinen, Juha; Veijola, Juha

2015-09-30

According to the disconnectivity model, disruptions in neural connectivity play an essential role in the pathology of schizophrenia. The aim of this study was to determine whether these abnormalities are present in young adults with familial risk (FR) for psychosis in the general population based sample. We used diffusion tensor imaging (DTI) and tract-based spatial statistics to compare whole-brain fractional anisotropy, mean diffusivity, and axial and radial diffusion in 47 (17 males) FR subjects to 51 controls (17 males). All the participants were aged between 20 and 25 years and were members of the Northern Finland Birth Cohort 1986 (Oulu Brain and Mind Study). Region of interest analyses were conducted for 12 tracts. Separately, we analysed whole-brain FA for the subgroup with FR for schizophrenia (n=13) compared with 13 gender-matched controls. Contrary to our expectations there were no differences in any of the DTI measures between FR and control groups. This suggests that white matter abnormalities may not be a genetic feature for risk of psychosis and preceding the onset of a psychotic disorder. Our findings do not support the theory of disconnectivity as a primary sign of psychosis in young adults with FR for the illness. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Anatomical Variations of the Circulus Arteriosus in Cadaveric Human Brains

PubMed Central

Gunnal, S. A.; Farooqui, M. S.; Wabale, R. N.

2014-01-01

Objective. Circulus arteriosus/circle of Willis (CW) is a polygonal anastomotic channel at the base of the brain which unites the internal carotid and vertebrobasilar system. It maintains the steady and constant supply to the brain. The variations of CW are seen often. The Aim of the present work is to find out the percentage of normal pattern of CW, and the frequency of variations of the CW and to study the morphological and morphometric aspects of all components of CW. Methods. Circulus arteriosus of 150 formalin preserved brains were dissected. Dimensions of all the components forming circles were measured. Variations of all the segments were noted and well photographed. The variations such as aplasia, hypoplasia, duplication, fenestrations, and difference in dimensions with opposite segments were noted. The data collected in the study was analyzed. Results. Twenty-one different types of CW were found in the present study. Normal and complete CW was found in 60%. CW with gross morphological variations was seen in 40%. Maximum variations were seen in the PCoA followed by the ACoA in 50% and 40%, respectively. Conclusion. As it confirms high percentage of variations, all surgical interventions should be preceded by angiography. Awareness of these anatomical variations is important in neurovascular procedures. PMID:24891951

Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS

PubMed Central

Silva, Mauro S.B.; Prescott, Melanie; Campbell, Rebecca E.

2018-01-01

Androgen excess is a hallmark of polycystic ovary syndrome (PCOS), a prevalent yet poorly understood endocrine disorder. Evidence from women and preclinical animal models suggests that elevated perinatal androgens can elicit PCOS onset in adulthood, implying androgen actions in both PCOS ontogeny and adult pathophysiology. Prenatally androgenized (PNA) mice exhibit a robust increase of progesterone-sensitive GABAergic inputs to gonadotropin-releasing hormone (GnRH) neurons implicated in the pathogenesis of PCOS. It is unclear when altered GABAergic wiring develops in the brain, and whether these central abnormalities are dependent upon adult androgen excess. Using GnRH-GFP–transgenic mice, we determined that increased GABA input to GnRH neurons occurs prior to androgen excess and the manifestation of reproductive impairments in PNA mice. These data suggest that brain circuit abnormalities precede the postpubertal development of PCOS traits. Despite the apparent developmental programming of circuit abnormalities, long-term blockade of androgen receptor signaling from early adulthood rescued normal GABAergic wiring onto GnRH neurons, improved ovarian morphology, and restored reproductive cycles in PNA mice. Therefore, androgen excess maintains changes in female brain wiring linked to PCOS features and the blockade of androgen receptor signaling reverses both the central and peripheral PNA-induced PCOS phenotype. PMID:29618656

In vitro blood-brain barrier models: current and perspective technologies.

PubMed

Naik, Pooja; Cucullo, Luca

2012-04-01

Even in the 21st century, studies aimed at characterizing the pathological paradigms associated with the development and progression of central nervous system diseases are primarily performed in laboratory animals. However, limited translational significance, high cost, and labor to develop the appropriate model (e.g., transgenic or inbred strains) have favored parallel in vitro approaches. In vitro models are of particular interest for cerebrovascular studies of the blood-brain barrier (BBB), which plays a critical role in maintaining the brain homeostasis and neuronal functions. Because the BBB dynamically responds to many events associated with rheological and systemic impairments (e.g., hypoperfusion), including the exposure of potentially harmful xenobiotics, the development of more sophisticated artificial systems capable of replicating the vascular properties of the brain microcapillaries are becoming a major focus in basic, translational, and pharmaceutical research. In vitro BBB models are valuable and easy to use supporting tools that can precede and complement animal and human studies. In this article, we provide a detailed review and analysis of currently available in vitro BBB models ranging from static culture systems to the most advanced flow-based and three-dimensional coculture apparatus. We also discuss recent and perspective developments in this ever expanding research field. Copyright © 2011 Wiley Periodicals, Inc.

RADVAN: a randomised phase 2 trial of WBRT plus vandetanib for melanoma brain metastases - results and lessons learnt.

PubMed

Gupta, Avinash; Roberts, Corran; Tysoe, Finn; Goff, Matthew; Nobes, Jenny; Lester, James; Marshall, Ernie; Corner, Carie; Wolstenholme, Virginia; Kelly, Charles; Wise, Adelyn; Collins, Linda; Love, Sharon; Woodward, Martha; Salisbury, Amanda; Middleton, Mark R

2016-11-08

Brain metastases occur in up to 75% of patients with advanced melanoma. Most are treated with whole-brain radiotherapy (WBRT), with limited effectiveness. Vandetanib, an inhibitor of vascular endothelial growth factor receptor, epidermal growth factor receptor and rearranged during transfection tyrosine kinases, is a potent radiosensitiser in xenograft models. We compared WBRT with WBRT plus vandetanib in the treatment of patients with melanoma brain metastases. In this double-blind, multi-centre, phase 2 trial patients with melanoma brain metastases were randomised to receive WBRT (30 Gy in 10 fractions) plus 3 weeks of concurrent vandetanib 100 mg once daily or placebo. The primary endpoint was progression-free survival in brain (PFS brain). The main study was preceded by a safety run-in phase to confirm tolerability of the combination. A post-hoc analysis and literature review considered barriers to recruiting patients with melanoma brain metastases to clinical trials. Twenty-four patients were recruited, six to the safety phase and 18 to the randomised phase. The study closed early due to poor recruitment. Median PFS brain was 3.3 months (90% confidence interval (CI): 1.6-5.6) in the vandetanib group and 2.5 months (90% CI: 0.2-4.8) in the placebo group (P=0.34). Median overall survival (OS) was 4.6 months (90% CI: 1.6-6.3) and 2.5 months (90% CI: 0.2-7.2), respectively (P=0.54). The most frequent adverse events were fatigue, alopecia, confusion and nausea. The most common barrier to study recruitment was availability of alternative treatments. The combination of WBRT plus vandetanib was well tolerated. Compared with WBRT alone, there was no significant improvement in PFS brain or OS, although we are unable to provide a definitive result due to poor accrual. A review of barriers to trial accrual identified several factors that affect study recruitment in this difficult disease area.

Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease

PubMed Central

Cunnane, Stephen C.; Courchesne-Loyer, Alexandre; Vandenberghe, Camille; St-Pierre, Valérie; Fortier, Mélanie; Hennebelle, Marie; Croteau, Etienne; Bocti, Christian; Fulop, Tamas; Castellano, Christian-Alexandre

2016-01-01

We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer’s disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain’s main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain’s main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic interventions improve some cognitive outcomes in MCI and AD. We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal. PMID:27458340

Hope, coping skills, and the prefrontal cortex in alcohol use disorder recovery.

PubMed

Bradshaw, Spencer D; Shumway, Sterling T; Dsauza, Cynthia M; Morris, Neli; Hayes, Nicholas D

2017-09-01

Alcohol use disorders adversely affect individual and societal health. These disorders are a chronic brain disease, and protective factors against relapse should be studied. Prefrontal cortex (PFC) dysfunction is evident in alcohol use disorders, and research that explores recovery of the PFC in alcohol use disorders is needed, specifically in regard to how psychological and behavioral factors can augment medicalized treatments and protect against relapse. For example, hope or a belief that recovery is possible is an important cognitive construct-thought to precede behavioral action-that has been associated with relapse. In this study, associations between healthy coping skills and hope (psychological/behavioral factors) and PFC regional activation in response to alcohol cue exposure were examined. It was also examined whether such associations were unique to alcohol cues. Forty-two participants, 32 males and nine females in recovery from an alcohol use disorder (AUD), were administered a subjective hope and coping in recovery measure. They also viewed alcohol, positive, negative, and neutral cues during functional near-infrared spectroscopy (fNIR) PFC assessment. Levels of healthy coping skills positively correlated with activation in the right dorsomedial prefrontal cortex (DMPFC) in response to alcohol cues. This finding was unique to alcohol cues. The association between coping skills and activation of the right DMPFC in response to alcohol cues may reflect greater action restraint and top-down PFC control processing that may protect against relapse.

The influence of context on hemispheric recruitment during metaphor processing

PubMed Central

Diaz, Michele T.; Hogstrom, Larson J.

2011-01-01

Although the left hemisphere's prominence in language is well established, less emphasis has been placed on possible roles for the right hemisphere. Behavioral, patient, and neuroimaging research suggests that the right hemisphere may be involved in processing figurative language. Additionally, research has demonstrated that context can modify language processes and facilitate comprehension. Here we investigated how figurativeness and context influenced brain activation, with a specific interest in right hemisphere function. Previous work in our lab indicated that novel stimuli engaged right inferior frontal gyrus and that both novel and familiar metaphors engaged right inferior frontal gyrus and right temporal pole. The Graded Salience Hypothesis (GSH) proposes that context may lessen integration demands, increase the salience of metaphors, and thereby reduce right hemisphere recruitment for metaphors. In the present study, functional Magnetic Resonance Imaging was used to investigate brain function while participants read literal and metaphoric sentences that were preceded by either a congruent or an incongruent literal sentence. Consistent with prior research, all sentences engaged traditional left hemisphere regions. Differences between metaphors and literal sentences were observed, but only in the left hemisphere. In contrast, a main effect of congruence was found in right inferior frontal gyrus, right temporal pole, and dorsal medial prefrontal cortex. Partially consistent with the GSH, our results highlight the strong influence of context on language, demonstrate the importance of the right hemisphere in discourse, and suggest that in a wider discourse context congruence has a greater influence on right hemisphere recruitment than figurativeness. PMID:21568642

Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation

PubMed Central

Webber, Emily S.; Mankin, David E.

2016-01-01

Abstract The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats (Rattus norvegicus) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility. PMID:27822506

Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

PubMed

Webber, Emily S; Mankin, David E; Cromwell, Howard C

2016-01-01

The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats ( Rattus norvegicus ) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

Early Correlated Network Activity in the Hippocampus: Its Putative Role in Shaping Neuronal Circuits.

PubMed

Griguoli, Marilena; Cherubini, Enrico

2017-01-01

Synchronized neuronal activity occurring at different developmental stages in various brain structures represents a hallmark of developmental circuits. This activity, which differs in its specific patterns among animal species may play a crucial role in de novo formation and in shaping neuronal networks. In the rodent hippocampus in vitro , the so-called giant depolarizing potentials (GDPs) constitute a primordial form of neuronal synchrony preceding more organized forms of activity such as oscillations in the theta and gamma frequency range. GDPs are generated at the network level by the interaction of the neurotransmitters glutamate and GABA which, immediately after birth, exert both a depolarizing and excitatory action on their targets. GDPs are triggered by GABAergic interneurons, which in virtue of their extensive axonal branching operate as functional hubs to synchronize large ensembles of cells. Intrinsic bursting activity, driven by a persistent sodium conductance and facilitated by the low expression of Kv7.2 and Kv7.3 channel subunits, responsible for I M , exerts a permissive role in GDP generation. Here, we discuss how GDPs are generated in a probabilistic way when neuronal excitability within a local circuit reaches a certain threshold and how GDP-associated calcium transients act as coincident detectors for enhancing synaptic strength at emerging GABAergic and glutamatergic synapses. We discuss the possible in vivo correlate of this activity. Finally, we debate recent data showing how, in several animal models of neuropsychiatric disorders including autism, a GDPs dysfunction is associated to morphological alterations of neuronal circuits and behavioral deficits reminiscent of those observed in patients.

The Precedence of Global Features in the Perception of Map Symbols

DTIC Science & Technology

1988-06-01

be continually updated. The present study evaluated the feasibility of a serial model of visual processing. By comparing performance between a symbol...symbols, is based on a " filter - ing" procedure, consisting of a series of passive-to-active or global- to-local stages. Navon (1977, 1981a) has proposed a...packages or segments. This advances the earlier, static feature aggregation ap- proaches to comprise a "figure." According to the global precedence model

Thalamic deactivation at sleep onset precedes that of the cerebral cortex in humans

PubMed Central

Magnin, Michel; Rey, Marc; Bastuji, Hélène; Guillemant, Philippe; Mauguière, François; Garcia-Larrea, Luis

2010-01-01

Thalamic and cortical activities are assumed to be time-locked throughout all vigilance states. Using simultaneous intracortical and intrathalamic recordings, we demonstrate here that the thalamic deactivation occurring at sleep onset most often precedes that of the cortex by several minutes, whereas reactivation of both structures during awakening is synchronized. Delays between thalamus and cortex deactivations can vary from one subject to another when a similar cortical region is considered. In addition, heterogeneity in activity levels throughout the cortical mantle is larger than previously thought during the descent into sleep. Thus, asynchronous thalamo-cortical deactivation while falling asleep probably explains the production of hypnagogic hallucinations by a still-activated cortex and the common self-overestimation of the time needed to fall asleep. PMID:20142493

Plasticity in neuromagnetic cortical responses suggests enhanced auditory object representation

PubMed Central

2013-01-01

Background Auditory perceptual learning persistently modifies neural networks in the central nervous system. Central auditory processing comprises a hierarchy of sound analysis and integration, which transforms an acoustical signal into a meaningful object for perception. Based on latencies and source locations of auditory evoked responses, we investigated which stage of central processing undergoes neuroplastic changes when gaining auditory experience during passive listening and active perceptual training. Young healthy volunteers participated in a five-day training program to identify two pre-voiced versions of the stop-consonant syllable ‘ba’, which is an unusual speech sound to English listeners. Magnetoencephalographic (MEG) brain responses were recorded during two pre-training and one post-training sessions. Underlying cortical sources were localized, and the temporal dynamics of auditory evoked responses were analyzed. Results After both passive listening and active training, the amplitude of the P2m wave with latency of 200 ms increased considerably. By this latency, the integration of stimulus features into an auditory object for further conscious perception is considered to be complete. Therefore the P2m changes were discussed in the light of auditory object representation. Moreover, P2m sources were localized in anterior auditory association cortex, which is part of the antero-ventral pathway for object identification. The amplitude of the earlier N1m wave, which is related to processing of sensory information, did not change over the time course of the study. Conclusion The P2m amplitude increase and its persistence over time constitute a neuroplastic change. The P2m gain likely reflects enhanced object representation after stimulus experience and training, which enables listeners to improve their ability for scrutinizing fine differences in pre-voicing time. Different trajectories of brain and behaviour changes suggest that the preceding effect of a P2m increase relates to brain processes, which are necessary precursors of perceptual learning. Cautious discussion is required when interpreting the finding of a P2 amplitude increase between recordings before and after training and learning. PMID:24314010

Audiovisual Temporal Processing and Synchrony Perception in the Rat.

PubMed

Schormans, Ashley L; Scott, Kaela E; Vo, Albert M Q; Tyker, Anna; Typlt, Marei; Stolzberg, Daniel; Allman, Brian L

2016-01-01

Extensive research on humans has improved our understanding of how the brain integrates information from our different senses, and has begun to uncover the brain regions and large-scale neural activity that contributes to an observer's ability to perceive the relative timing of auditory and visual stimuli. In the present study, we developed the first behavioral tasks to assess the perception of audiovisual temporal synchrony in rats. Modeled after the parameters used in human studies, separate groups of rats were trained to perform: (1) a simultaneity judgment task in which they reported whether audiovisual stimuli at various stimulus onset asynchronies (SOAs) were presented simultaneously or not; and (2) a temporal order judgment task in which they reported whether they perceived the auditory or visual stimulus to have been presented first. Furthermore, using in vivo electrophysiological recordings in the lateral extrastriate visual (V2L) cortex of anesthetized rats, we performed the first investigation of how neurons in the rat multisensory cortex integrate audiovisual stimuli presented at different SOAs. As predicted, rats ( n = 7) trained to perform the simultaneity judgment task could accurately (~80%) identify synchronous vs. asynchronous (200 ms SOA) trials. Moreover, the rats judged trials at 10 ms SOA to be synchronous, whereas the majority (~70%) of trials at 100 ms SOA were perceived to be asynchronous. During the temporal order judgment task, rats ( n = 7) perceived the synchronous audiovisual stimuli to be "visual first" for ~52% of the trials, and calculation of the smallest timing interval between the auditory and visual stimuli that could be detected in each rat (i.e., the just noticeable difference (JND)) ranged from 77 ms to 122 ms. Neurons in the rat V2L cortex were sensitive to the timing of audiovisual stimuli, such that spiking activity was greatest during trials when the visual stimulus preceded the auditory by 20-40 ms. Ultimately, given that our behavioral and electrophysiological results were consistent with studies conducted on human participants and previous recordings made in multisensory brain regions of different species, we suggest that the rat represents an effective model for studying audiovisual temporal synchrony at both the neuronal and perceptual level.

Audiovisual Temporal Processing and Synchrony Perception in the Rat

PubMed Central

Schormans, Ashley L.; Scott, Kaela E.; Vo, Albert M. Q.; Tyker, Anna; Typlt, Marei; Stolzberg, Daniel; Allman, Brian L.

2017-01-01

Extensive research on humans has improved our understanding of how the brain integrates information from our different senses, and has begun to uncover the brain regions and large-scale neural activity that contributes to an observer’s ability to perceive the relative timing of auditory and visual stimuli. In the present study, we developed the first behavioral tasks to assess the perception of audiovisual temporal synchrony in rats. Modeled after the parameters used in human studies, separate groups of rats were trained to perform: (1) a simultaneity judgment task in which they reported whether audiovisual stimuli at various stimulus onset asynchronies (SOAs) were presented simultaneously or not; and (2) a temporal order judgment task in which they reported whether they perceived the auditory or visual stimulus to have been presented first. Furthermore, using in vivo electrophysiological recordings in the lateral extrastriate visual (V2L) cortex of anesthetized rats, we performed the first investigation of how neurons in the rat multisensory cortex integrate audiovisual stimuli presented at different SOAs. As predicted, rats (n = 7) trained to perform the simultaneity judgment task could accurately (~80%) identify synchronous vs. asynchronous (200 ms SOA) trials. Moreover, the rats judged trials at 10 ms SOA to be synchronous, whereas the majority (~70%) of trials at 100 ms SOA were perceived to be asynchronous. During the temporal order judgment task, rats (n = 7) perceived the synchronous audiovisual stimuli to be “visual first” for ~52% of the trials, and calculation of the smallest timing interval between the auditory and visual stimuli that could be detected in each rat (i.e., the just noticeable difference (JND)) ranged from 77 ms to 122 ms. Neurons in the rat V2L cortex were sensitive to the timing of audiovisual stimuli, such that spiking activity was greatest during trials when the visual stimulus preceded the auditory by 20–40 ms. Ultimately, given that our behavioral and electrophysiological results were consistent with studies conducted on human participants and previous recordings made in multisensory brain regions of different species, we suggest that the rat represents an effective model for studying audiovisual temporal synchrony at both the neuronal and perceptual level. PMID:28119580

Stability of Lentiviral Vector-Mediated Transgene Expression in the Brain in the Presence of Systemic Antivector Immune Responses

PubMed Central

ABORDO-ADESIDA, EVELYN; FOLLENZI, ANTONIA; BARCIA, CARLOS; SCIASCIA, SANDRA; CASTRO, MARIA G.; NALDINI, LUIGI; LOWENSTEIN, PEDRO R.

2009-01-01

Lentiviral vectors are promising tools for gene therapy in the CNS. It is therefore important to characterize their interactions with the immune system in the CNS. This work characterizes transgene expression and brain inflammation in the presence or absence of immune responses generated after systemic immunization with lentiviral vectors. We characterized transduction with SIN-LV vectors in the CNS. A dose—response curve using SIN-LV-GFP demonstrated detectable transgene expression in the striatum at a dose of 102, and maximum expression at 106, transducing units of lentiviral vector, with minimal increase in inflammatory markers between the lowest and highest dose of vector injected. Our studies demonstrate that injection of a lentiviral vector into the CNS did not cause a measurable inflammatory response. Systemic immunization after CNS injection, with the lentiviral vector expressing the same transgene as a vector injected into the CNS, caused a decrease in transgene expression in the CNS, concomitantly with an infiltration of inflammatory cells into the CNS parenchyma at the injection site. However, peripheral immunization with a lentiviral vector carrying a different transgene did not diminish transgene expression, or cause CNS inflammation. Systemic immunization preceding injection of lentiviral vectors into the CNS determined that preexisting antilentiviral immunity, regardless of the transgene, did not affect transgene expression. Furthermore, we showed that the transgene, but not the virion or vector components, is responsible for providing antigenic epitopes to the activated immune system, on systemic immunization with lentivirus. Low immunogenicity and prolonged transgene expression in the presence of preexisting lentiviral immunity are encouraging data for the future use of lentiviral vectors in CNS gene therapy. In summary, the lentiviral vectors tested induced undetectable activation of innate immune responses, and stimulation of adaptive immune responses against lentiviral vectors was effective in causing a decrease in transgene expression only if the immune response was directed against the transgene. A systemic immune response against vector components alone did not cause brain inflammation, possibly because vector-derived epitopes were not being presented in the CNS. PMID:15960605

Evaluation of in silico pharmacokinetic properties and in vitro cytotoxic activity of selected newly synthesized N-succinimide derivatives.

PubMed

Milosevic, Natasa P; Kojic, Vesna; Curcic, Jelena; Jakimov, Dimitar; Milic, Natasa; Banjac, Nebojsa; Uscumlic, Gordana; Kaliszan, Roman

2017-04-15

Design of a new drug entity is usually preceded by analysis of quantitative structure activity (properties) relationships, QSA(P)R. Six newly synthesized succinimide derivatives have been determined for (i) in silico physico-chemical descriptors, pharmacokinetic and toxicity predictors, (ii) in vitro biological activity on four different carcinoma cell lines and on normal fetal lung cells and (iii) lipophilicity on liquid chromatography. All compounds observed were predicted for good permeability and solubility, good oral absorption rate and moderate volume of distribution as well as for modest blood brain permeation, followed by acceptable observed toxicity. In silico determined lipophilicity, permeability through jejunum and aqueous solubility were correlated with experimentally obtained lipophilic constants (by use of high pressure liquid chromatography) and linear correlations were obtained. Absorption rate and volume of distribution were predicted by chromatographic lipophilicity measurements while permeation through blood bran barrier was predicted dominantly by molecular size defined with molecular weight. Five compounds have demonstrated antiproliferative activity toward cervix carcinoma HeLa cell lines; three were cytotoxic against breast carcinoma MCF-7 cells, while one inhibited proliferation of colon carcinoma HT-29 cell lines. Only one compound was cytotoxic toward normal cell lines, while other compounds were proven as safe. Antiproliferative potential against HeLa cells was described as exponential function of lipophilicity. Based on obtained results, lead compounds were selected. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered Blood-Brain Barrier Permeability in Patients With Systemic Lupus Erythematosus: A Novel Imaging Approach.

PubMed

Gulati, Gaurav; Jones, Jordan T; Lee, Gregory; Altaye, Mekibib; Beebe, Dean W; Meyers-Eaton, Jamie; Wiley, Kasha; Brunner, Hermine I; DiFrancesco, Mark W

2017-02-01

To evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood-brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile-onset systemic lupus erythematosus (SLE). In this cross-sectional, case-control study, capillary permeability was measured as a marker of blood-brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion-weighted brain MRI. Regional gray matter volume was measured by voxel-based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood-brain barrier integrity among juvenile SLE patients. Formal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P = 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P < 0.05 for all). There is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood-brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood-brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to confirm the findings of this pilot study. © 2016, American College of Rheumatology.

The Role of Gut Microflora and the Cholinergic Anti-inflammatory Neuroendocrine System in Diabetes Mellitus

PubMed Central

Parekh, Parth J.; Nayi, Vipul R.; Johnson, David A.; Vinik, Aaron I.

2016-01-01

The obesity epidemic has drastically impacted the state of health care in the United States. Paralleling this epidemic is the incidence of diabetes mellitus, with a notable shift toward a much younger age of onset. While central to the pathogenesis of diabetes associated with obesity is the role of inflammation attributed to “adiposopathy.” Emerging data suggest that changes in sympathetic/parasympathetic balance regulated by the brain precede changes in the inflammatory cascade. It has now been established that the gut microflora contributes significantly to the activation and inhibition of autonomic control and impact the set of the neuroinflammatory inhibitory reflex mediated by the cholinergic nervous system. There has been a paradigm shift toward further investigating commensal bacteria in the pathogenesis of obesity and diabetes mellitus and its complications, as dysbiosis is thought to play a pivotal role in diabetic-associated disorders. This paper is intended to evaluate the role of intestinal dysbiosis in the pathogenesis of diabetes mellitus and examine the potential for restoration of balance via use of probiotics. PMID:27375553

Neural Correlates of Time Versus Money in Product Evaluation

PubMed Central

Lehmann, Sebastian; Reimann, Martin

2012-01-01

The common saying “time is money” reflects the widespread belief in many people’s everyday life that time is valuable like money. Psychologically and neurophysiologically, however, these concepts seem to be quite different. This research replicates prior behavioral investigations by showing that merely mentioning “time” (compared to merely mentioning “money”) leads participants to evaluate a product more positively. Beyond this finding, the present functional magnetic resonance imaging (fMRI) experiment provides novel insight into the neurophysiological underpinnings of this behavioral effect by showing that more positive product evaluations in the time primes (compared to money primes) are preceded by increased activation in the insula. Our data, therefore, support the idea of a time mindset that is different from a money mindset. Studies on the functional neuroanatomy of the insula have implicated this brain area in distinct but related psychological phenomena such as urging, addiction, loss aversion, and love. These functions imply greater personal connection between the consumer and a target subject or object and, thus, help explain why time-primed consumers rate products more positively. PMID:23162485

Intimate partner violence perpetration corresponds to a dorsal-ventral gradient in medial PFC reactivity to interpersonal provocation.

PubMed

Chester, David S; DeWall, C Nathan

2018-01-22

Intimate partner violence (IPV) perpetration is often preceded by perceived interpersonal provocations such as slights, insults, and rejections. Yet the neural mechanisms that link provocation to IPV remain unclear. In the context of interactions with strangers, the medial prefrontal cortex (MPFC) has been repeatedly shown to respond to provocation, with more dorsal activation associated with more aggressive reactions and more ventral activation associated with less aggressive reactions. We used functional brain imaging to test whether this dorsal-ventral MPFC reactivity gradient would also correlate with greater aggression towards an unexamined target: intimate partners. To do so, 61 undergraduates (27.87% male, age range: 18-22) reported whether they had ever committed various acts of IPV perpetration (e.g., punching, hitting, shoving) and then were repeatedly provoked by a stranger while undergoing functional MRI (fMRI) scanning. Individuals with a disproportionately dorsal, rather than ventral, MPFC response were more likely to have perpetrated IPV and had perpetrated more kinds of IPV, even when controlling for gender. These findings provide further evidence that the dorsal-ventral MPFC gradient is a critical, biological indicator of whether an individual is more or less likely to react aggressively and suggest new avenues for understanding and potentially preventing IPV perpetration.

Complexity analysis of spontaneous brain activity in mood disorders: A magnetoencephalography study of bipolar disorder and major depression.

PubMed

Fernández, Alberto; Al-Timemy, Ali H; Ferre, Francisco; Rubio, Gabriel; Escudero, Javier

2018-04-26

The lack of a biomarker for Bipolar Disorder (BD) causes problems in the differential diagnosis with other mood disorders such as major depression (MD), and misdiagnosis frequently occurs. Bearing this in mind, we investigated non-linear magnetoencephalography (MEG) patterns in BD and MD. Lempel-Ziv Complexity (LZC) was used to evaluate the resting-state MEG activity in a cross-sectional sample of 60 subjects, including 20 patients with MD, 16 patients with BD type-I, and 24 control (CON) subjects. Particular attention was paid to the role of age. The results were aggregated by scalp region. Overall, MD patients showed significantly higher LZC scores than BD patients and CONs. Linear regression analyses demonstrated distinct tendencies of complexity progression as a function of age, with BD patients showing a divergent tendency as compared with MD and CON groups. Logistic regressions confirmed such distinct relationship with age, which allowed the classification of diagnostic groups. The patterns of neural complexity in BD and MD showed not only quantitative differences in their non-linear MEG characteristics but also divergent trajectories of progression as a function of age. Moreover, neural complexity patterns in BD patients resembled those previously observed in schizophrenia, thus supporting preceding evidence of common neuropathological processes. Copyright © 2018 Elsevier Inc. All rights reserved.

Neuronal LRP1 Regulates Glucose Metabolism and Insulin Signaling in the Brain

PubMed Central

Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L.; Kanekiyo, Takahisa

2015-01-01

Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of Aβ in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor β in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. PMID:25855193

Temporal and spatial localization of prediction-error signals in the visual brain.

PubMed

Johnston, Patrick; Robinson, Jonathan; Kokkinakis, Athanasios; Ridgeway, Samuel; Simpson, Michael; Johnson, Sam; Kaufman, Jordy; Young, Andrew W

2017-04-01

It has been suggested that the brain pre-empts changes in the environment through generating predictions, although real-time electrophysiological evidence of prediction violations in the domain of visual perception remain elusive. In a series of experiments we showed participants sequences of images that followed a predictable implied sequence or whose final image violated the implied sequence. Through careful design we were able to use the same final image transitions across predictable and unpredictable conditions, ensuring that any differences in neural responses were due only to preceding context and not to the images themselves. EEG and MEG recordings showed that early (N170) and mid-latency (N300) visual evoked potentials were robustly modulated by images that violated the implied sequence across a range of types of image change (expression deformations, rigid-rotations and visual field location). This modulation occurred irrespective of stimulus object category. Although the stimuli were static images, MEG source reconstruction of the early latency signal (N/M170) localized expectancy violation signals to brain areas associated with motion perception. Our findings suggest that the N/M170 can index mismatches between predicted and actual visual inputs in a system that predicts trajectories based on ongoing context. More generally we suggest that the N/M170 may reflect a "family" of brain signals generated across widespread regions of the visual brain indexing the resolution of top-down influences and incoming sensory data. This has important implications for understanding the N/M170 and investigating how the brain represents context to generate perceptual predictions. Copyright © 2017 Elsevier B.V. All rights reserved.

How cognitive neuroscience could be more biological—and what it might learn from clinical neuropsychology

PubMed Central

Frisch, Stefan

2014-01-01

Three widespread assumptions of Cognitive-affective Neuroscience are discussed: first, mental functions are assumed to be localized in circumscribed brain areas which can be exactly determined, at least in principle (localizationism). Second, this assumption is associated with the more general claim that these functions (and dysfunctions, such as in neurological or mental diseases) are somehow generated inside the brain (internalism). Third, these functions are seen to be “biological” in the sense that they can be decomposed and finally explained on the basis of elementary biological causes (i.e., genetic, molecular, neurophysiological etc.), causes that can be identified by experimental methods as the gold standard (isolationism). Clinical neuropsychology is widely assumed to support these tenets. However, by making reference to the ideas of Kurt Goldstein (1878–1965), one of its most important founders, I argue that none of these assumptions is sufficiently supported. From the perspective of a clinical-neuropsychological practitioner, assessing and treating brain damage sequelae reveals a quite different picture of the brain as well as of us “brain carriers”, making the organism (or person) in its specific environment the crucial reference point. This conclusion can be further elaborated: all experimental and clinical research on humans presupposes the notion of a situated, reflecting, and interacting subject, which precedes all kinds of scientific decomposition, however useful. These implications support the core assumptions of the embodiment approach to brain and mind, and, as I argue, Goldstein and his clinical-neuropsychological observations are part of its very origin, for both theoretical and historical reasons. PMID:25100981

Boosting airway T-regulatory cells by gastrointestinal stimulation as a strategy for asthma control.

PubMed

Strickland, D H; Judd, S; Thomas, J A; Larcombe, A N; Sly, P D; Holt, P G

2011-01-01

The hallmark of atopic asthma is transient airways hyperresponsiveness (AHR) preceded by aeroallergen-induced Th-cell activation. This is preceded by upregulation of CD86 on resident airway dendritic cells (DCs) that normally lack competence in T-cell triggering. Moreover, AHR duration is controlled via T-regulatory (Treg) cells, which can attenuate CD86 upregulation on DC. We show that airway mucosal Treg/DC interaction represents an accessible therapeutic target for asthma control. Notably, baseline airway Treg activity in sensitized rats can be boosted by microbe-derived stimulation of the gut, resulting in enhanced capacity to control CD86 expression on airway DC triggered by aeroallergen and accelerated resolution of AHR.

Preictal Activity of Subicular, CA1, and Dentate Gyrus Principal Neurons in the Dorsal Hippocampus before Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

PubMed Central

Fujita, Satoshi; Toyoda, Izumi; Thamattoor, Ajoy K.

2014-01-01

Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2–4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41–57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. PMID:25505320

Progressive Brain Structural Changes Mapped as Psychosis Develops in ‘At Risk’ Individuals

PubMed Central

Sun, Daqiang; Phillips, Lisa; Velakoulis, Dennis; Yung, Alison; McGorry, Patrick D.; Wood, Stephen J.; van Erp, Theo G. M.; Thompson, Paul M.; Toga, Arthur W.; Cannon, Tyrone D.; Pantelis, Christos

2009-01-01

Background Schizophrenia and related psychoses are associated with brain structural abnormalities. Recent findings in ‘at risk’ populations have identified progressive changes in various brain regions preceding illness onset, while changes especially in prefrontal and superior temporal regions have been demonstrated in first-episode schizophrenia patients. However, the timing of the cortical changes and their regional extent, relative to the emergence of psychosis, has not been clarified. We followed individuals at high-risk for psychosis to determine whether structural changes in the cerebral cortex occur with the onset of psychosis. We hypothesized that progressive volume loss occurs in prefrontal regions during the transition to psychosis. Methods 35 individuals at ultra-high risk (UHR) for developing psychosis, of whom 12 experienced psychotic onset by 1-year follow-up (‘converters’), participated in a longitudinal structural MRI study. Baseline and follow-up T1-weighted MR images were acquired and longitudinal brain surface contractions were assessed using Cortical Pattern Matching. Results Significantly greater brain contraction was found in the right prefrontal region in the ‘converters’ compared with UHR cases who did not develop psychosis (‘non-converters’). Conclusions These findings show cortical volume loss is associated with the onset of psychosis, indicating ongoing pathological processes during the transition stage to illness. The prefrontal volume loss is in line with structural and functional abnormalities in schizophrenia, suggesting a critical role for this change in the development of psychosis. PMID:19138834

Toward a conceptual framework for early brain and behavior development in autism

PubMed Central

Piven, J; Elison, J T; Zylka, M J

2017-01-01

Studies of infant siblings of older autistic probands, who are at elevated risk for autism, have demonstrated that the defining features of autism are not present in the first year of life but emerge late in the first and into the second year. A recent longitudinal neuroimaging study of high-risk siblings revealed a specific pattern of brain development in infants later diagnosed with autism, characterized by cortical surface area hyper-expansion in the first year followed by brain volume overgrowth in the second year that is associated with the emergence of autistic social deficits. Together with new observations from genetically defined autism risk alleles and rodent model, these findings suggest a conceptual framework for the early, post-natal development of autism. This framework postulates that an increase in the proliferation of neural progenitor cells and hyper-expansion of cortical surface area in the first year, occurring during a pre-symptomatic period characterized by disrupted sensorimotor and attentional experience, leads to altered experience-dependent neuronal development and decreased elimination of neuronal processes. This process is linked to brain volume overgrowth and disruption of the refinement of neural circuit connections and is associated with the emergence of autistic social deficits in the second year of life. A better understanding of the timing of developmental brain and behavior mechanisms in autism during infancy, a period which precedes the emergence of the defining features of this disorder, will likely have important implications for designing rational approaches to early intervention. PMID:28937691

Automated detection of brain atrophy patterns based on MRI for the prediction of Alzheimer's disease

PubMed Central

Plant, Claudia; Teipel, Stefan J.; Oswald, Annahita; Böhm, Christian; Meindl, Thomas; Mourao-Miranda, Janaina; Bokde, Arun W.; Hampel, Harald; Ewers, Michael

2010-01-01

Subjects with mild cognitive impairment (MCI) have an increased risk to develop Alzheimer's disease (AD). Voxel-based MRI studies have demonstrated that widely distributed cortical and subcortical brain areas show atrophic changes in MCI, preceding the onset of AD-type dementia. Here we developed a novel data mining framework in combination with three different classifiers including support vector machine (SVM), Bayes statistics, and voting feature intervals (VFI) to derive a quantitative index of pattern matching for the prediction of the conversion from MCI to AD. MRI was collected in 32 AD patients, 24 MCI subjects and 18 healthy controls (HC). Nine out of 24 MCI subjects converted to AD after an average follow-up interval of 2.5 years. Using feature selection algorithms, brain regions showing the highest accuracy for the discrimination between AD and HC were identified, reaching a classification accuracy of up to 92%. The extracted AD clusters were used as a search region to extract those brain areas that are predictive of conversion to AD within MCI subjects. The most predictive brain areas included the anterior cingulate gyrus and orbitofrontal cortex. The best prediction accuracy, which was cross-validated via train-and-test, was 75% for the prediction of the conversion from MCI to AD. The present results suggest that novel multivariate methods of pattern matching reach a clinically relevant accuracy for the a priori prediction of the progression from MCI to AD. PMID:19961938

Brain maps 4.0-Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps.

PubMed

Swanson, Larry W

2018-04-15

The fourth edition (following editions in 1992, 1998, 2004) of Brain maps: structure of the rat brain is presented here as an open access internet resource for the neuroscience community. One new feature is a set of 10 hierarchical nomenclature tables that define and describe all parts of the rat nervous system within the framework of a strictly topographic system devised previously for the human nervous system. These tables constitute a global ontology for knowledge management systems dealing with neural circuitry. A second new feature is an aligned atlas of bilateral flatmaps illustrating rat nervous system development from the neural plate stage to the adult stage, where most gray matter regions, white matter tracts, ganglia, and nerves listed in the nomenclature tables are illustrated schematically. These flatmaps are convenient for future development of online applications analogous to "Google Maps" for systems neuroscience. The third new feature is a completely revised Atlas of the rat brain in spatially aligned transverse sections that can serve as a framework for 3-D modeling. Atlas parcellation is little changed from the preceding edition, but the nomenclature for rat is now aligned with an emerging panmammalian neuroanatomical nomenclature. All figures are presented in Adobe Illustrator vector graphics format that can be manipulated, modified, and resized as desired, and freely used with a Creative Commons license. © 2018 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Mapping social behavior-induced brain activation at cellular resolution in the mouse

PubMed Central

Kim, Yongsoo; Venkataraju, Kannan Umadevi; Pradhan, Kith; Mende, Carolin; Taranda, Julian; Turaga, Srinivas C.; Arganda-Carreras, Ignacio; Ng, Lydia; Hawrylycz, Michael J.; Rockland, Kathleen; Seung, H. Sebastian; Osten, Pavel

2014-01-01

Understanding how brain activation mediates behaviors is a central goal of systems neuroscience. Here we apply an automated method for mapping brain activation in the mouse in order to probe how sex-specific social behaviors are represented in the male brain. Our method uses the immediate early gene c-fos, a marker of neuronal activation, visualized by serial two-photon tomography: the c-fos-GFP-positive neurons are computationally detected, their distribution is registered to a reference brain and a brain atlas, and their numbers are analyzed by statistical tests. Our results reveal distinct and shared female and male interaction-evoked patterns of male brain activation representing sex discrimination and social recognition. We also identify brain regions whose degree of activity correlates to specific features of social behaviors and estimate the total numbers and the densities of activated neurons per brain areas. Our study opens the door to automated screening of behavior-evoked brain activation in the mouse. PMID:25558063

Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration

PubMed Central

Klein, Arno; Andersson, Jesper; Ardekani, Babak A.; Ashburner, John; Avants, Brian; Chiang, Ming-Chang; Christensen, Gary E.; Collins, D. Louis; Gee, James; Hellier, Pierre; Song, Joo Hyun; Jenkinson, Mark; Lepage, Claude; Rueckert, Daniel; Thompson, Paul; Vercauteren, Tom; Woods, Roger P.; Mann, J. John; Parsey, Ramin V.

2009-01-01

All fields of neuroscience that employ brain imaging need to communicate their results with reference to anatomical regions. In particular, comparative morphometry and group analysis of functional and physiological data require coregistration of brains to establish correspondences across brain structures. It is well established that linear registration of one brain to another is inadequate for aligning brain structures, so numerous algorithms have emerged to nonlinearly register brains to one another. This study is the largest evaluation of nonlinear deformation algorithms applied to brain image registration ever conducted. Fourteen algorithms from laboratories around the world are evaluated using 8 different error measures. More than 45,000 registrations between 80 manually labeled brains were performed by algorithms including: AIR, ANIMAL, ART, Diffeomorphic Demons, FNIRT, IRTK, JRD-fluid, ROMEO, SICLE, SyN, and four different SPM5 algorithms (“SPM2-type” and regular Normalization, Unified Segmentation, and the DARTEL Toolbox). All of these registrations were preceded by linear registration between the same image pairs using FLIRT. One of the most significant findings of this study is that the relative performances of the registration methods under comparison appear to be little affected by the choice of subject population, labeling protocol, and type of overlap measure. This is important because it suggests that the findings are generalizable to new subject populations that are labeled or evaluated using different labeling protocols. Furthermore, we ranked the 14 methods according to three completely independent analyses (permutation tests, one-way ANOVA tests, and indifference-zone ranking) and derived three almost identical top rankings of the methods. ART, SyN, IRTK, and SPM's DARTEL Toolbox gave the best results according to overlap and distance measures, with ART and SyN delivering the most consistently high accuracy across subjects and label sets. Updates will be published on the http://www.mindboggle.info/papers/ website. PMID:19195496