Deficits in cortico-striatal synaptic plasticity and behavioral habituation in rats with portacaval anastomosis

Hepatic encephalopathy is characterized by disturbances of motor and cognitive functions involving the basal ganglia. So far no standards for assessment of neuropsychiatric abnormalities (disorders of sleep, mood, anxiety and personality) in subclinical hepatic encephalopathy have been defined. Using an animal model of mild (subclinical) hepatic encephalopathy we investigated now striatum-related behaviors and cortico-striatal synaptic plasticity in rats 2 months after introduction of a portacaval shunt and sham-operated matched controls. In a novel open field portacaval shunt rats displayed less locomotor activity; unlike controls they also showed no habituation to the field and no recall of the field environment after 24 h, indicative of cognitive deficit. The elevated-plus maze test indicated no differences in fear/anxiety in the portacaval shunt animals. Tetanic stimulation of cortical afferents in magnesium-free solution evoked an N-methyl-D-aspartate-dependent long-term potentiation in sham-operated animals. In portacaval shunt animals long-term potentiation was significantly impaired. Histamine, a potent modulator of cortico-striatal transmission, induced a larger long-term depression of field potentials in control compared with portacaval shunt rats. In conclusion, a combination of electrophysiological and behavioral approaches has revealed functional changes in cortico-striatal transmission. These data are relevant for understanding the mechanisms of motor and cognitive dysfunctions in hepatic encephalopathy patients and for the development of precise psychometric tests, evaluating cognitive deficits in subclinical hepatic encephalopathy.     

肝硬化患者的神经心理功能障碍研究

目的：探讨肝硬化患者的神经心理功能障碍及其特征,为诊断亚临床肝性脑病提供科学依据和检测手段。方法：采用几种神经心理检测对６９例肝硬化患者、６５例脑肿瘤患者及６２名正常人进行测试。结果：三组被试各测验组间比较均有显著性差异（Ｐ〈０．００１）;组间两两比较显示,绝大多数测验成绩正常组优于其它两组（Ｐ〈０．０５０;而肝病组和脑病组的成绩相比,只有少数几个变量（相似性测验、第四例外的全误、木图测验）肝病组优于脑病组（Ｐ〈０．０５）,其余测验成绩两组比较无显著性差异（Ｐ〉０．０５）。结论：亚临床肝性脑病存在分析综合、抽象概括、概念化思维、心理灵活性、心理运动速度、知觉－运动协调和视觉空间等神经心理功能障碍,其严重程度的许多方面和脑肿瘤患者无明显差异。     

纳洛酮治疗亚临床型肝性脑病疗效观察

目的探讨纳洛酮治疗亚临床型肝性脑病(SHE)的疗效。方法69例SHE按双盲法随机分为治疗组及对照组二组,分别给予纳洛酮0.4mg、0.9%氯化钠静脉推注,连用5-10天,用药前后分别作数字连接试验(NCT)、数字符号试验(DS)、脑干诱发电位(BAEP),并随访有否发性临床型肝性脑病。结果治疗组治疗后各项指标均较治疗前有明显改善,且随访无一例发生肝性脑病,对照组治疗前后各项指标改善不明显,且随诊有3例发生临床型肝性脑病。结论纳洛酮是一种对SHE治疗有效的药物。     

Biological Rhythms in Arousal Indices: A Potential Confounding Effect in EEG Biofeedback

Several investigators have observed ultradian rhythmicities in physiological indices of arousal. Although EEG biofeedback has been widely explored as a means of auto-regulating cortical arousal, alpha or theta enhancement has not yet been convincingly demonstrated in comparison to continuous baseline controls for the possible effect of endogenous cyclical arousal trends. Diurnal EEG and subjectively appraised arousal measures were recorded from 11 subjects on a 5-min recording, 5-min recovery schedule, continuously over 7 1/2 hrs. Subjects returned to the laboratory for an equal amount of recording during which they attempted to either raise or lower the frequency of their EEG with the aid of biofeedback. Significant ultradian rhythmicity centered at about 200 min/cycle was observed in EEG measures and in subjectively appraised arousal. Although eyes-open frequency-raising and frequency-lowering biofeedback training was efficacious in comparison to long-day baselines, eyes-closed frequency-lowering training was not, lending support to other studies which have failed to achieve overall eyes-closed alpha or theta enhancement even with many hours of training. Because the observed ultradian and circadian EEG rhythmicities could be spuriously interpreted as learning curves under a biofeedback paradigm, it is argued that future designs should incorporate continuous baseline controls.     

A deep learning-based algorithm for detection of cortical arousal during sleep

Study ObjectivesThe frequency of cortical arousals is an indicator of sleep quality. Additionally, cortical arousals are used to identify hypopneic events. However, it is inconvenient to record electroencephalogram (EEG) data during home sleep testing. Fortunately, most cortical arousal events are associated with autonomic nervous system activity that could be observed on an electrocardiography (ECG) signal. ECG data have lower noise and are easier to record at home than EEG. In this study, we developed a deep learning-based cortical arousal detection algorithm that uses a single-lead ECG to detect arousal during sleep.MethodsThis study included 1,547 polysomnography records that met study inclusion criteria and were selected from the Multi-Ethnic Study of Atherosclerosis database. We developed an end-to-end deep learning model consisting of convolutional neural networks and recurrent neural networks which: (1) accepted varying length physiological data; (2) directly extracted features from the raw ECG signal; (3) captured long-range dependencies in the physiological data; and (4) produced arousal probability in 1-s resolution.ResultsWe evaluated the model on a test set (n = 311). The model achieved a gross area under precision-recall curve score of 0.62 and a gross area under receiver operating characteristic curve score of 0.93.ConclusionThis study demonstrated the end-to-end deep learning approach with a single-lead ECG has the potential to be used to accurately detect arousals in home sleep tests.     

Increased EEG sigma and beta power during NREM sleep in primary insomnia

The hyperarousal model of primary insomnia suggests that a deficit of attenuating arousal during sleep might cause the experience of non-restorative sleep. In the current study, we examined EEG spectral power values for standard frequency bands as indices of cortical arousal and sleep protecting mechanisms during sleep in 25 patients with primary insomnia and 29 good sleeper controls. Patients with primary insomnia demonstrated significantly elevated spectral power values in the EEG beta and sigma frequency band during NREM stage 2 sleep. No differences were observed in other frequency bands or during REM sleep. Based on prior studies suggesting that EEG beta activity represents a marker of cortical arousal and EEG sleep spindle (sigma) activity is an index of sleep protective mechanisms, our findings may provide further evidence for the concept that a simultaneous activation of wake-promoting and sleep-protecting neural activity patterns contributes to the experience of non-restorative sleep in primary insomnia.     

Increased EEG sigma and beta power during NREM sleep in primary insomnia

The hyperarousal model of primary insomnia suggests that a deficit of attenuating arousal during sleep might cause the experience of non-restorative sleep. In the current study, we examined EEG spectral power values for standard frequency bands as indices of cortical arousal and sleep protecting mechanisms during sleep in 25 patients with primary insomnia and 29 good sleeper controls. Patients with primary insomnia demonstrated significantly elevated spectral power values in the EEG beta and sigma frequency band during NREM stage 2 sleep. No differences were observed in other frequency bands or during REM sleep. Based on prior studies suggesting that EEG beta activity represents a marker of cortical arousal and EEG sleep spindle (sigma) activity is an index of sleep protective mechanisms, our findings may provide further evidence for the concept that a simultaneous activation of wake-promoting and sleep-protecting neural activity patterns contributes to the experience of non-restorative sleep in primary insomnia.     

Subclinical hepatic encephalopathy: relationship between neuropsychological deficits and standard laboratory tests assessing hepatic status.

A multivariate analysis of the relationship between biochemical measures of hepatic function and neuropsychological assessments of specific cognitive domains was performed on data obtained from 74 patients with chronic liver disease and subclinical hepatic encephalopathy. Biochemical tests of hepatic protein synthesis correlated significantly with measures of impaired language efficiency, perceptual speed, and psychomotor efficiency. Biochemical indices of impaired processing of nitrogenous compounds correlated with visuopractic deficits. Hepatic blood flow indices correlated with language inefficiency. Interestingly, biochemical measures of hepatic injury did not demonstrate a significant association with any neuropsychological parameter assessed. These results suggest that subclinical hepatic encephalopathy is the consequence of a multifactorial hepatic dysfunction, and that acute hepatic injury, as assessed by elevation of aminotransferases, does not appear to be involved in the pathogenesis of subclinical hepatic encephalopathy.     

Cerebral blood flow autoregulation during orthostatic manoeuvre in patients with permanent cardiac pacemaker

Orthostatic test with passive tilting of the upper body was performed in 28 patients with VVI pacemaker. The changes in BP (Riva-Rocci method), CVR and CBF (impedance technique, REG II) as well as in EEG (automatic spectral analysis) observed after tilting, were compared to those in 20 age-matched controls. While in healthy subjects the autoregulation of the CBF was accomplished through a decrease in CVR and resulted in a moderate but significant increase in CBF, in patients the CVR did not change. This event was estimated as a sign of impaired autoregulation, the CBF remained unchanged most probably on account of the increased diastolic and mean BP. Alpha and beta power spectra in the EEG rose significantly after tilting, the shifts being more pronounced in the controls. In the patients there was an increase in theta activity. Cerebral angiopathy due to "subclinical" brain ischaemia during cardiac rhythm disorders preceding pacemaker implantation was accepted as a mechanism underlying the disturbed autoregulation of the cerebral blood flow. For the occurrence of alterations in orthostatic EEG reactivity, a dyscirculatory encephalopathy has been suspected.     

Memory impairment in patients with cirrhosis

BACKGROUND AND AIM: Subclinical hepatic encephalopathy (HE) in cirrhotic patients is usually characterized by memory impairment and psychomotor slowing. Our aim was to investigate memory status in cirrhotic patients with and without clinically overt HE. MATERIAL AND METHODS: Thirty-two cirrhotic patients (10 female and 22 male) aged 49 +/- 17 years and 20 healthy subjects (six female and 14 male) aged 46 +/- 12 years were included in the study. Memory status was defined by Wechsler Memory Scale, verbal memory process and complex memory process tests. RESULTS: Grade-1 HE was detected in 7 (22%) patients with cirrhosis. We detected 36 to 92% decrement in various memory tests in cirrhotic patients without HE as compared to healthy subjects. The scores for all psychometric testing results were significantly lower in cirrhotic patients without HE as compared to healthy subjects. We detected 42.9 to 100% decrement in various memory tests in cirrhotic patients with HE than cirrhotic patients without HE. However, there was no statistical significant difference between cirrhotic patients with and without HE. There was no statistical significant difference in cirrhotic patients with Child-Pugh A, B, and C. CONCLUSION: In conclusion, memory status was influenced in which patients with cirrhosis yet has a normal mental and neurological status to routine clinical examination (subclinical HE). Occasionally, decreased memory performance may adversely affect the satisfaction and lifestyle of these patients. Therefore, subclinical HE is an important social problem.     

Discrimination of Sensorimotor EEG (12–15 Hz) Activity: A Comparison of Response, Production, and No-Feedback Training Conditions

The current study was concerned with the discrimination of 12–15 Hz (15μV) surface cortical EEG, recorded over the dominant hemisphere. This EEG bandwidth is sometimes called the SMR (sensorimotor rhythm), and has been associated with seizure reduction. Thirty-six normal subjects were divided into three groups and exposed to three methods of discrimination training: response feedback, production feedback, and no-feedback control. In the initial assessment session, all subjects were asked to detect the presence of SMR by pressing a response button in the absence of feedback. Over the next 4 training sessions, the control group continued without feedback, while the response feedback group received feedback (tone) for correct discriminations, and the production group received feedback for producing the SMR signal. Discrimination performance was assessed during a 15-min no-feedback test period, following each feedback segment. The final session took place two weeks after training had been completed and was the same as session 1. The results showed that both experimental groups improved discrimination accuracy over baseline, and relative to the control group. Performance of the groups at baseline was not significantly different, ranging between 16% and 29% correct. Peak performance during training showed that both experimental groups improved over baseline and relative to the control group, averaging 17%, 43% and 78% correct for the control, response and production feedback groups, respectively. In the final assessment, all groups deteriorated in performance, but the production group remained significantly above baseline levels. No changes in average SMR time or frontal EMG were noted. However, time spent in the occipital alpha bandwidth 8–13 Hz (25μV) did increase in the best discriminators. This may indicate some discrimination of subjective sensations associated with SMR discrimination training.     

Differential cerebral responses to aversive auditory arousal versus muscle pain: specific EEG patterns are associated with human pain processing

The specificity of electroencephalogram (EEG) activity in relation to processing of human pain needs further elucidation. This study was designed to determine if nociceptive input and general arousal responses to external stimulation exert different effects on EEG activity. Continuous aversive auditory stimuli (90 dB for 2 min) and painful injection of hypertonic saline (5.8%, 0.2 ml) into the left brachioradialis muscle were administered to 12 male subjects during separate sessions in a counterbalanced design. Intensity, arousal and unpleasantness were assessed during the muscle pain and auditory stimulation using a visual analogue scale and arousal-affective scales. The EEG data (32 channels) was acquired before, during and after application of painful and aversive auditory stimuli. Aversive auditory stimulation and intramuscular injection of hypertonic saline induced similar degrees of arousal and unpleasantness associated with a similarity of intensity of sensation of pain and auditory sensation. However, muscle pain induced a significant decrease of alpha-1 activity (8–14 Hz) at T6, PC2, PC6, Pz, P4, O2 and POz sites compared to the baseline, but aversive auditory stimulation did not produce any significant changes in alpah-1 activity compared to baseline. The alpha-1 EEG powers at P3, Pz, P4, PC1, PC2 and POz, and alpha-2 at Pz and POz sites were significantly decreased during muscle pain when compared with aversive noise stimulation. These results indicate that specific EEG patterns are associated with human pain processing. Electronic Publication     

Alpha-contingent EEG feedback reduces SPECT rCBF variability.

EEG feedback methods, which link the occurrence of alpha to the presentation of repeated visual stimuli, reduce the relative variability of subsequent, alpha-blocking event durations. The temporal association between electro-cortical field activation and regional cerebral blood flow (rCBF) led us to investigate whether the reduced variability of alpha-blocking durations with feedback is associated with a reduction in rCBF variability. Reduced variability in the rCBF response domain under EEG feedback control might have methodological implications for future brain-imaging studies. Visual stimuli were randomly presented to seven subjects, contingent upon the occurrence of alpha (alpha-contingent stimulation (ACS)) or alpha-blocking (not-alpha-blocking-contingent stimulation (NACS)) events. We employed a within-subjects design. rCBF was measured from multiple, cortical and sub-cortical regions. The primary dependent variables were the Mean, Standard Deviation and the ratio of Mean/Standard Deviation of: 1) the alpha-blocking response durations and 2) the temporally summated rCBF responses within the Visual Associative regions of interest (ROIs). Additional within-subjects rCBF measures were derived to quantify the variance-reducing effects of ACS across multiple, distributed areas of the brain. Both EEG and rCBF measures demonstrated decreased variability under ACS. This improved control was seen for localized as well as anatomically distributed rCBF measures.     

Common response repertoire of motor cortical neurons in arousal and epicortical activation

Intracellular responses during phasic Electroencephalograph (EEG) arousal were recorded from 229 motor cortical neurons in the cat encéphale isolé preparations. Identified dominant responses were excitatory postsynaptic potentials (EPSPs) in 105 cells (E cells), inhibitory postsynaptic potentials (IPSPs) in 74 cells (I cells), disfacilitation in 48 cells (DF cells), and disinhibition in two cells (DI cells). These responses were comparable with those to near or distant epicortical stimulation (EPICS). thus, most E cells in phasic arousal were EPSP-dominant in response to near (incidence, 104/105) or distant EPICS (51/54), and only a few of the remaining were IPSP-dominant. About two-thirds of I cells were IPSP-dominant (49/74), and the remaining one-third EPSP-dominant (25/74) to near EPICS. However, most I cells became IPSP-dominant (45/49) to distant EPICS. DF and DI cells were initially EPSP- or IPSP-dominant to EPICS, but later responsive with DF in DF cells and DI in DI cells, respectively. In the interaction experiments, the initial negative wave in the direct cortical responses (DCRs) or the EPSPs of dendritic origin elicited by near EPICS and the initial positive wave in DCRs to distant EPICS were all reduced during phasic EEG arousal perhaps due to the occlusion effect. Common response repertoire in EEG arousal and epicortical activation may support the earlier proposed cascade transmission model of phasic EEG arousal, in which the spread of neuronal activities occurs vertically from the superficial to deep cortical layers as well as laterally along various layers.     

An EEG study of visual attention in schizophrenic patients and normal controls

This is a series of experiments examining the EEG, both at rest and in response to visual stimuli of varied complexity, in schizophrenics and normal controls. Subjects attended on several occasions. The resting EEG of patients was more activated than that of normals on all sessions, although only the patients showed diminished activation as a function of visits. The EEG of normals responded systematically on all occasions, but the patients showed similar response only under conditions of instructional set prescribing active stimulus appraisal. For both groups, subsequent stimulus recognition scores were correlated positively with EEG discrimination of stimuli during inspection. Within the patient group, several measures of pathology correlated both with recognition performance and several EEG parameters. Thus the present study draws together data demonstrating attentional deficit, heightened arousal, and reduced cortical variability in schizophrenics. Attention is drawn to methodological difficulties inherent in this type of study.     

LHA self-stimulation effects on EEG and brain temperature in white rats

Neocortical and hippocampal EEG and brain temperature (in sensorimotor cortical area) were recorded in 11 white rats during stimulation and self-stimulation (SS) of the LHA-MFB region and also during stimulation of nonrewarding hypothalamic sites and the midbrain reticular formation (RF). With moderate current intensities, each rewarding train was found to be accompanied by a burst of regular hippocampal synchronized rhythm (in the theta or alpha-band) and by neocortical desynchronization. With higher current intensitites, hippocampal waves appeared only between SS trains while during bar-pressing desynchronization patterns were noted both in hippocampal and neocortical EEG. A slow rise of brain temperature occurred during SS, up to 1.5°C. Sharp phasic elevations of brain temperature (as those during fast asleep) occurred when sudden changes were made in the SS schedule. RF stimulation which caused only EEG arousal (desynchronization) did not evoke any brain temperature shift, or was followed by its slight decrease. Brain temperature increased if RF stimulation led to behavioral arousal with regular hippocampal synchronized rhythm.     

NO在脂多糖诱发的肝硬化大鼠肝性脑病中的作用

目的:探讨一氧化氮(NO)在LPS诱发的肝硬化大鼠肝性脑病中所起的作用。方法:采用复合因素复制肝硬化大鼠模型,于实验8周末开始分别用09%盐水、L-精氨酸(L-arg)和N-亚硝基L-精氨酸(LNNA)给大鼠灌胃2周。在处死大鼠前4h,腹腔内一次性注射LPS3mg/kg,以诱发大鼠肝性脑病。结果:L-arg组大鼠活动灵活且脑电图基本正常,LNNA组出现肝性脑病。L-arg组脑组织NO₂^-/NO₃^-含量明显高于LNNA组(P<0.05),脑组织组胺含量明显低于LNNA组(P<0.05)。脑组织中组胺含量与脑组织中NO₂^-/NO₃^-含量呈负相关。结论:NO能抑制LPS诱发肝硬化大鼠肝性脑病的发生。     

Effect of cognitive arousal on sleep latency, somatic and cortical arousal following partial sleep deprivation

Emerging research has shown that sleepiness, defined as the tendency to fall asleep, is not only determined by sleep pressure and time of day, but also by physiological and cognitive arousal. In this study we evaluated (i) the impact of experimentally induced cognitive arousal on electroencephalogram (EEG) defined sleep latency, and subjective, somatic and cortical arousal, and (ii) whether experimentally induced cognitive arousal enhances performance on a driving simulator test. Twelve healthy sleepers each spent three nights and the following day in the sleep laboratory: an adaptation, a cognitive arousal and a neutral testing day. In the cognitive arousal condition, a visit of a television camera crew took place and subjects were asked to be interviewed. On each testing day, a 5-min heart rate recording, subjective sleepiness and arousal scales, Multiple Sleep Latency Test and a 25-min driving simulator task were scheduled three times at 2-h intervals. Experimentally induced cognitive arousal resulted in significant increases in objective sleep latency. Significantly elevated levels of subjective and somatic arousal--as indexed by a subjective arousal scale and heart rate--were also evidenced following cognitive arousal induction. A marginally significant trend for increased cortical arousal, measured by EEG beta activity, was also found. No effects were found on driving simulator performance. These findings support the concept of cognitive arousal as a significant component in determining sleep latency. In addition, it was illustrated that cognitively induced arousal can provoke increases in somatic and possibly even cortical arousal in normal sleepers. However, this was not accompanied by an enhanced ability to perform adequately on a driving simulator test.     

Habituation of the infant arousal response.

STUDY OBJECTIVES: Arousal is considered to be an important protective response in a sleeping infant and its depression could leave an infant vulnerable to a life threatening stimulus. We found previously that arousal to a non-respiratory (tactile) stimulus occurs in a sequence of events that begins with spinal, followed by brainstem responses, and then a cortical electroencephalographic (EEG) arousal response. We hypothesized that repeated stimuli would depress the arousal responses by habituation and that spinal and brainstem responses would be more resistant to habituation than cortical responses. PARTICIPANTS: We studied 22 normal infants. INTERVENTIONS: The infants underwent polysomnographic monitoring during a daytime nap. Tactile stimuli was applied to the infants foot at 5-second intervals. MEASUREMENTS AND RESULTS: We found that spinal, brainstem, and cortical responses occurred on the first trial of each test. Repeated trials during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep resulted in a decrease in the incidence of each individual response and eventually elimination of the arousal responses. Cortical responses were eliminated first, followed by brainstem responses and finally spinal responses. The elimination of each of the responses occurred more rapidly during REM sleep that during NREM sleep. CONCLUSIONS: Habituation of the infant arousal sequence occurs with repeated tactile stimulation. There is a serial habituation of responses from the cortical to the spinal level, which occurs more rapidly during REM sleep. Rapid habituation to innocuous stimuli is probably beneficial in avoiding detrimental sleep disruptions. However, in situations requiring the protective functions of arousal, such habituation could be detrimental to an infant.     

Effects of sorbent suspension dialysis on plasma amino acid levels in cirrhotic patients with refractory hepatic encephalopathy

In cirrhotic patients, plasma amino acid levels are severely deranged. A decreased ratio of branched-chain to aromatic amino acids (Fischer ratio) has been implicated in the pathogenesis of hepatic encephalopathy. In this prospective study, we investigated the effects of extracorporeal detoxification on amino acid levels using a sorbent suspension dialysis system. Twenty patients with documented cirrhosis and hepatic encephalopathy grade II-III not responding to standard treatment were randomized to receive either six hours of sorbent dialysis and standardized conventional medical treatment or ongoing medical treatment alone. In contrast to previous uncontrolled studies, no significant effect on amino acid levels, Fischer ratio or clinical grade of hepatic encephalopathy was detected in either treatment group. In conclusion, a 6-hour treatment with sorbent dialysis did not significantly influence plasma levels of amino acids and did not ameliorate the clinical grade of hepatic encephalopathy.