Insight into the relationship between brain/behavioral speed and variability in patients with minimal hepatic encephalopathy

ObjectiveIntra-individual variability (IIV) of response reaction times (RTs) and psychomotor slowing were proposed as markers of brain dysfunction in patients with minimal hepatic encephalopathy (MHE), a subclinical disorder of the central nervous system frequently detectable in patients with liver cirrhosis. However, behavioral measures alone do not enable investigations into the neural correlates of these phenomena. The aim of this study was to investigate the electrophysiological correlates of psychomotor slowing and increased IIV of RTs in patients with MHE.MethodsEvent-related potentials (ERPs), evoked by a stimulus–response (S–R) conflict task, were recorded from a sample of patients with liver cirrhosis, with and without MHE, and a group of healthy controls. A recently presented Bayesian approach was used to estimate single-trial P300 parameters.ResultsPatients with MHE, with both psychomotor slowing and higher IIV of RTs, showed higher P300 latency jittering and lower single-trial P300 amplitude compared to healthy controls. In healthy controls, distribution analysis revealed that single-trial P300 latency increased and amplitude decreased as RTs became longer; however, in patients with MHE the linkage between P300 and RTs was weaker or even absent.ConclusionsThese findings suggest that in patients with MHE, the loss of the relationship between P300 parameters and RTs is related to both higher IIV of RTs and psychomotor slowing.SignificanceThis study highlights the utility of investigating the relationship between single-trial ERPs parameters along with RT distributions to explore brain functioning in normal or pathological conditions.     

Early markers of neural dysfunction and compensation: A model from minimal hepatic encephalopathy

ObjectiveThe Inhibitory Control Task (ICT) was used to detect minimal hepatic encephalopathy (MHE). ICT assesses attention, working memory and inhibition by evaluating performance in detect, go and nogo trials, respectively. The event-related potentials (ERPs) elicited by the ICT provide insight into neural mechanisms underlying the cognitive alterations associated with MHE.MethodsThe performance and the ERPs elicited by ICT were measured in 31 patients with cirrhosis (13 with and 18 without MHE) and in 17 controls. The latency and amplitude of the N2, P3a, P3b and nogo-P3 were compared among the groups.ResultsPatients with MHE performed worse in all ICT trials compared to patients without MHE and controls. Cirrhotic patients, both with and without MHE, displayed a reduction in P3a amplitude, selectively in the detect trials. Patients without MHE exhibited greater N2 and nogo-P3 amplitudes compared to patients with MHE and controls.ConclusionsBoth patients with and without MHE displayed neural alterations reflecting attentional deficits (i.e., P3a attenuation). However, patients without MHE coped with such dysfunctions by recruiting compensatory neural mechanisms, as suggested by the enhancement of the nogo-P3 and N2 amplitudes coupled with a normal ICT performance.SignificanceThe study suggests how initial brain dysfunction might be compensated for by recruitment of additional neurocognitive resources.     

Stimulus intensity affects the latency but not the amplitude of the N2pc

The N2pc component of the event-related potential (ERP) is an index of visual-spatial attention. It is not clear whether the N2pc reflects pure top-down attentional activity or an interaction of top-down activity with bottom-up sensory activity. Here, we manipulated stimulus intensity of the items composing the target display. Although the amplitude of the P1 component increased monotonically with increasing stimulus intensity, the amplitude of the N2pc did not vary with stimulus intensity. Instead, the onset latency of the N2pc was delayed for weaker stimuli, suggesting that the strength of the selection cue (target color) influenced the moment at which attention was deployed. The results reveal one way in which early sensory ERP amplitude differences are converted into later latency differences.     

Attention and short-term memory in chronic fatigue syndrome patients: an event-related potential analysis.

We recorded event-related brain potentials (ERPs) from 13 patients with chronic fatigue syndrome (CFS) and 13 matched normal controls. To assess attentional and memory deficits in CFS patients, we used a short-term memory task in which events occurred in different spatial locations and the patients made a rapid-response (RT) when a letter in a relevant location matched a letter in the prememorized set (Attention paradigm). Time-on-task effects on the ERP and behavioral measures were assessed over the 2 1/4-hour duration of this task. Both groups also performed a visual Oddball paradigm, with an RT, before and after the Attention paradigm. The patients' RTs were much more variable and, in nine of 13 cases, slower than the mean RT of the controls in both paradigms. The patients' memory performance was not significantly different from that of the controls and there were no group differences in the overall amplitude, latency, or scalp distribution of the N1, P2, N2, or P300 components of the ERP in either paradigm. The ERP and performance data from both paradigms suggest that perceptual, attentional, and short-term memory processes were unaffected in CFS patients and that the differences were limited to response-related processes.     

The N2pc component and stimulus duration

The N2pc component of the event-related potential is a moment-by-moment index of the deployment of visual-spatial attention. It is not clear whether the N2pc reflects pure top-down attentional activity or a positive interaction of top-down activity with bottom-up sensory activity. Here, we presented a bilateral visual display containing a target and a distractor for a duration of 50, 200, or 350 ms. The N2pc was smaller for the 350 ms duration than for the two shorter durations. These results go against the hypothesis that the N2pc reflects a long-lasting positive interaction of top-down and bottom-up activity, which would have predicted a larger N2pc as stimulus duration increased. Theoretical and practical implications of the results are discussed.     

Brain mechanisms of involuntary visuospatial attention: an event-related potential study

The brain mechanisms mediating visuospatial attention were investigated by recording event-related potentials (ERPs) during a line-orientation discrimination task. Nonpredictive peripheral cues were used to direct participant's attention involuntarily to a spatial location. The earliest attentional modulation was observed in the P1 component (peak latency about 130 ms), with the valid trials eliciting larger P1 than invalid trials. Moreover, the attentional modulations on both the amplitude and latency of the P1 and N1 components had a different pattern as compared to previous studies with voluntary attention tasks. In contrast, the earliest visual ERP component, C1 (peak latency about 80 ms), was not modulated by attention. Low-resolution brain electromagnetic tomography (LORETA) showed that the earliest attentional modulation occurred in extrastriate cortex (middle occipital gyrus, BA 19) but not in the primary visual cortex. Later attention-related reactivations in the primary visual cortex were found at about 110 ms after stimulus onset. The results suggest that involuntary as well as voluntary attention modulates visual processing at the level of extrastriate cortex; however, at least some different processes are involved by involuntary attention compared to voluntary attention. In addition, the possible feedback from higher visual cortex to the primary visual cortex is faster and occurs earlier in involuntary relative to voluntary attention task.     

Top-down and bottom-up visual information processing of non-social stimuli in high-functioning autism spectrum disorder

Individuals with high-functioning autism spectrum disorder (HF-ASD) often show superior performance in simple visual tasks, despite difficulties in the perception of socially important information such as facial expression. The neural basis of visual perception abnormalities associated with HF-ASD is currently unclear. We sought to elucidate the functioning of bottom-up and top-down visual information processing in HF-ASD using event-related potentials (ERPs). Eleven adults with HF-ASD and 11 age-matched normal controls (NC) participated in this study. Visual ERPs were recorded using 128-channel EEG. The P1 and P300 were recorded in response to target stimuli. Visual mismatch negativity (vMMN) potentials were obtained by subtracting responses to standard from those to deviant stimuli. Behaviorally, individuals with HF-ASD showed faster target detection than NCs. However, vMMN amplitude and latency were the same between the two groups. In contrast, P1 and P300 amplitudes were significantly decreased in HF-ASD compared with NCs. In addition, P300 latency was significantly delayed in HF-ASD. Individuals with HF-ASD exhibit altered visual information processing. Intact bottom-up attention (vMMN) may contribute to their superior simple visual task performance in spite of abnormal low-level (P1) and top-down (P300) visual information processing.     

Aberrant stability of brain functional architecture in cirrhotic patients with minimal hepatic encephalopathy

To investigate the stability changes of brain functional architecture and the relationship between stability change and cognitive impairment in cirrhotic patients. Fifty-one cirrhotic patients (21 with minimal hepatic encephalopathy (MHE) and 30 without MHE (NHE)) and 29 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging and neurocognitive assessment using the Psychometric Hepatic Encephalopathy Score (PHES). Voxel-wise functional connectivity density (FCD) was calculated as the sum of connectivity strength between one voxel and others within the entire brain. The sliding window correlation approach was subsequently utilized to calculate the FCD dynamics over time. Functional stability (FS) is measured as the concordance of dynamic FCD. From HCs to the NHE and MHE groups, a stepwise reduction of FS was found in the right supramarginal gyrus (RSMG), right middle cingulate cortex, left superior frontal gyrus, and bilateral posterior cingulate cortex (BPCC), whereas a progressive increment of FS was observed in the left middle occipital gyrus (LMOG) and right temporal pole (RTP). The mean FS values in RSMG/LMOG/RTP (r = 0.470 and P = 0.001; r = −0.458 and P = 0.001; and r = −0.384 and P = 0.005, respectively) showed a correlation with PHES in cirrhotic patients. The FS index in RSMG/LMOG/BPCC/RTP showed moderate discrimination potential between the NHE and MHE groups. Changes in FS may be linked to neuropathological bias of cognitive impairment in cirrhotic patients and could serve as potential biomarkers for MHE diagnosis and monitoring the progression of hepatic encephalopathy.

     

Auditory event-related potentials during a spatial working memory task.

OBJECTIVE: Sensory cortical activity can be jointly governed by bottom-up (e.g. stimulus features) and top-down (e.g. memory, attention) factors. We tested the hypothesis that auditory sensory cortical activity is affected by encoding and retrieval of spatial information. METHODS: Auditory event-related potentials (ERPs) were recorded during working memory and passive listening conditions. Trials contained three noise bursts (two "items" at different locations, followed by a "probe"). In the working memory task subjects determined if the probe matched an item location. The influence of long-term memory was evaluated by training to one location that was always a non-match. Auditory ERPs were analyzed to items and probes (N100, P200, late positive wave-LPW). RESULTS: Reaction times varied significantly among probes (trained non-match相似文献   

Late event-related potentials and movement complexity in young adults with Down syndrome.

OBJECTIVES: Through event-related potential (ERP) recording, to better understand the perceptive-motor slowness in adults with Down syndrome (DS); in particular, to assess whether motor preparation influences the speed of allocation of perceptual attention as reflected by the P3 latency. PATIENTS AND METHODS: ERPs were obtained in adults with and without DS through an auditory oddball paradigm under a passive and two active (simple vs. complex motor response) conditions. Reaction times (RTs) were recorded in the two active conditions. RESULTS: There was no influence of movement complexity on either RT or P3b latency in the control group. In the DS group, RT was delayed under simple vs. complex conditions whereas P3b latency was not affected. N2a and N2b were often missing in DS individuals. CONCLUSION: Motor preparation processes per se rather than interaction with perceptual attention could be defective in individuals with DS when the motor component of the response is minimal.     

Abnormal baseline brain activity in low-grade hepatic encephalopathy: a resting-state fMRI study

Resting-state functional magnetic resonance imaging (fMRI) has been used to detect the alterations of spontaneous neuronal activity in various neuropsychiatric diseases, but rarely in low-grade hepatic encephalopathy (HE), a common neuropsychiatric complication of liver cirrhosis. We conducted a resting-state fMRI in 19 healthy controls, 18 cirrhotic patients without HE, and 22 cirrhotic patients with low-grade HE. The amplitude of low-frequency fluctuations (ALFF) of fMRI signal was computed to measure the spontaneous neuronal activity. Several regions showing significant ALFF differences among three groups were the precuneus, occipital lobe, left frontal lobe and anterior/middle cingulate cortex, and left cerebellum posterior lobe. Compared to controls or patients without HE, patients with low-grade HE showed decreased ALFF in the precuneus and adjacent cuneus, visual cortex, and left cerebellum posterior lobe. Compared to controls, patients with low-grade HE showed higher ALFF in both cortical and subcortical regions, including the right middle cingulate gyrus, and left anterior/middle cingulate gyrus, inferior frontal gyrus, insula lobe, parahippocampal gyrus, middle temporal gyrus and lentiform nucleus; compared to patients without HE, patients with low-grade HE showed higher ALFF in the left medial frontal gyrus and anterior cingulate gyrus, bilateral superior frontal gyrus, and right middle frontal gyrus. Moreover, correlations between ALFF changes and poor neurocognitive performances were found in patients with low-grade HE. These results suggested the existence of aberrant brain activity at the baseline state in low-grade HE, which may be implicated in the neurological pathophysiology underlying HE.     

Predictive value of novel stimuli modifies visual event-related potentials and behavior.

OBJECTIVE: We examined how behavioral context influences novelty processing by varying the degree that a novel event predicted the occurrence of a subsequent target stimulus. METHODS: Visual event-related potentials (ERPs) and reaction times (RTs) were recorded in 3 detection experiments (23 subjects). The predictive value of a novel stimulus on the occurrence of a subsequent target was varied as was novel-target pairing intervals (200-900 ms). In Experiment 1, novel stimuli always preceded a target, in Experiment 2, 40% of novel stimuli were followed by a target, and in Experiment 3, novel stimuli occurred randomly. RESULTS: In Experiment 1, RTs following 100% predictive novels were shortened for targets at all spatial locations and novel-target pairing intervals. Novel stimuli predicting a target generated a central negativity peaking at 300 ms and reduced P3a and P3b ERPs. In Experiments 2 and 3, target RTs were prolonged only when novel and target stimuli were presented in the same spatial location at short ISIs (200 ms). The central novel N2 was smaller in amplitude in comparison to Experiment 1, and novelty P3a and target extrastriate N2 and posterior scalp P3b ERPs were enhanced. CONCLUSIONS: The enhanced N2 for 100% predictive novel stimuli appears to index an alerting system facilitating behavioral detection. The same novel stimuli with no predictive value distract attention and generate a different ERP pattern characterized by increased novelty P3a and target P3b responses. The results indicate that behavioral context determines how novel stimuli are processed and influence behavior.     

3T磁共振波谱分析在轻微型肝性脑病诊断中的应用

目的研究3T场强磁共振MRS对轻微型肝性脑病（MHE）患者的诊断价值。方法对33例MHE患者和46例无轻微型肝性脑病的肝硬化患者采用单体素点分辨自旋回波波谱序列进行扣带回和右侧前额叶的MRS扫描。计算N-乙酰天门冬氨酸（NAA）、肌酐（Cr）、胆碱（Cho）、肌醇（MI）和谷氨酰胺复合物（Glx）的峰下面积,计算NAA／Cr、Cho／Cr、MI／Cr、Glx／Cr,并与30例健康体检者（正常对照组）比较。33例MHE患者在MRS检查前后1周内进行了静脉血氨水平测定。结果与正常对照组相比,MHE患者扣带回和右侧前额叶的Cho／Cr、MI／Cr显著降低（P值分别〈0．01和〈0．001）,Glx／Cr比值显著升高（P〈0．005）。与无MHE的肝硬化患者间Glx／Cr与Cho／Cr有显著性差异（P〈0．01,P〈0．005）,无MHE的肝硬化患者与正常对照组比较MI／Cr有显著性差异（P〈0．001）。扣带回与右侧额叶的Glx／Cr比值与血氨浓度呈正相关,Cho／Cr和MI／Cr的比值与血氨浓度呈负相关。结论3T场强磁共振MRS检查显示MHE患者扣带回和右侧前额叶Cho、MI水平降低,Glx水平升高;扣带回与右侧额叶的MRS指标与血氨之间存在相关关系,3T场强磁共振MRS对MHE的诊断有显著价值;扣带回与右侧前额叶可作为检测肝硬化患者脑改变的敏感部位。     

Involuntary attentional capture is determined by task set: evidence from event-related brain potentials

To find out whether attentional capture by irrelevant but salient visual objects is an exogenous bottom-up phenomenon, or can be modulated by current task set, two experiments were conducted where the N2pc component was measured as an electrophysiological marker of attentional selection in response to spatially uninformative color singleton cues that preceded target arrays. When observers had to report the orientation of a uniquely colored target bar among distractor bars (color task), behavioral spatial cueing effects were accompanied by an early cue-induced N2pc, indicative of rapid attentional capture by color singleton cues. In contrast, when they reported the orientation of target bars presented without distractors (onset task), no behavioral cueing effects were found and no early N2pc was triggered to physically identical cue arrays. Experiment 2 ruled out an alternative interpretation of these N2pc differences in terms of distractor inhibition. These results do not support previous claims that attentional capture is initially unaffected by top-down intention, and demonstrate the central role of task set in involuntary attentional orienting.     

ERPs associated with and without an "orienting reflex" in patients with schizophrenia.

In this study, we measured traditional late components of the Event Related Potential (ERP: N 100, P 200, N 200 and P 300) in a conventional auditory oddball paradigm, but additionally and simultaneously assessed electrodermal "orienting reflexes (ORs)" in 40 patients with schizophrenia and 40 age and gender matched normal controls. The single epoch ERPs that did and did not evoke an OR, were sub-averaged separately. The control subjects (but not the patient group), revealed delayed P 300 latency in the ERP sub-averages without ORs (ERP-OR), compared with ERP sub-averages with ORs (ERP+OR). Between-group analysis showed reduced N 100, N 200 and P 300 amplitudes (as well as delayed P 300 latency) in the ERP+OR sub-average in patients with schizophrenia. In the ERP-OR sub-average, the patient group also had smaller N 100, N 200 and P 300 amplitudes, but larger P 200 amplitude (compared with normal controls). This study shows the potential to tease out physiologically based OR sub-processes, by simultaneous acquisition and analysis of ERPs and autonomic electrodermal activity. Such ERP sub-averages (based on autonomic responses) highlight that multiple processes overlap across the trial, and their delineation may elucidate more specific patterns of disturbance in schizophrenia, than traditional averaged measures.     

Altered transfer of visual motion information to parietal association cortex in untreated first-episode psychosis: implications for pursuit eye tracking

Visual motion processing and its use for pursuit eye movement control represent a valuable model for studying the use of sensory input for action planning. In psychotic disorders, alterations of visual motion perception have been suggested to cause pursuit eye tracking deficits. We evaluated this system in functional neuroimaging studies of untreated first-episode schizophrenia (N=24), psychotic bipolar disorder patients (N=13) and healthy controls (N=20). During a passive visual motion processing task, both patient groups showed reduced activation in the posterior parietal projection fields of motion-sensitive extrastriate area V5, but not in V5 itself. This suggests reduced bottom-up transfer of visual motion information from extrastriate cortex to perceptual systems in parietal association cortex. During active pursuit, activation was enhanced in anterior intraparietal sulcus and insula in both patient groups, and in dorsolateral prefrontal cortex and dorsomedial thalamus in schizophrenia patients. This may result from increased demands on sensorimotor systems for pursuit control due to the limited availability of perceptual motion information about target speed and tracking error. Visual motion information transfer deficits to higher-level association cortex may contribute to well-established pursuit tracking abnormalities, and perhaps to a wider array of alterations in perception and action planning in psychotic disorders.     

Cortical sources of the early components of the visual evoked potential

This study aimed to characterize the neural generators of the early components of the visual evoked potential (VEP) to isoluminant checkerboard stimuli. Multichannel scalp recordings, retinotopic mapping and dipole modeling techniques were used to estimate the locations of the cortical sources giving rise to the early C1, P1, and N1 components. Dipole locations were matched to anatomical brain regions visualized in structural magnetic resonance imaging (MRI) and to functional MRI (fMRI) activations elicited by the same stimuli. These converging methods confirmed previous reports that the C1 component (onset latency 55 msec; peak latency 90-92 msec) was generated in the primary visual area (striate cortex; area 17). The early phase of the P1 component (onset latency 72-80 msec; peak latency 98-110 msec) was localized to sources in dorsal extrastriate cortex of the middle occipital gyrus, while the late phase of the P1 component (onset latency 110-120 msec; peak latency 136-146 msec) was localized to ventral extrastriate cortex of the fusiform gyrus. Among the N1 subcomponents, the posterior N150 could be accounted for by the same dipolar source as the early P1, while the anterior N155 was localized to a deep source in the parietal lobe. These findings clarify the anatomical origin of these VEP components, which have been studied extensively in relation to visual-perceptual processes.     

Where and when the anterior cingulate cortex modulates attentional response: combined fMRI and ERP evidence

Attentional control provides top-down influences that allow task-relevant stimuli and responses to be processed preferentially. The anterior cingulate cortex (ACC) plays an important role in attentional control, but the spatiotemporal dynamics underlying this process is poorly understood. We examined the activation and connectivity of the ACC using functional magnetic resonance imaging (fMRI) along with fMRI-constrained dipole modeling of event-related potentials (ERPs) obtained from subjects who performed auditory and visual oddball attention tasks. Although attention-related responses in the ACC were similar in the two modalities, effective connectivity analyses showed modality-specific effects with increased ACC influences on the Heschl and superior temporal gyri during auditory task and on the striate cortex during visual task. Dipole modeling of ERPs based on source locations determined from fMRI activations showed that the ACC was the major generator of N2b-P3a attention-related components in both modalities, and that primary sensory regions generated a small mismatch signal about 50 msec prior to feedback from the ACC and a large signal 60 msec after feedback from the ACC. Taken together, these results provide converging neuroimaging and electrophysiological evidence for top-down attentional modulation of sensory processing by the ACC. Our findings suggest a model of attentional control based on dynamic bottom-up and top-down interactions between the ACC and primary sensory regions.     

Prolonged P3 latency and decreased brain perfusion in cerebellar degeneration

OBJECTIVES: To clarify the underlying mechanism of cognitive impairments in patients with cerebellar degeneration using event-related potentials (ERPs) and regional brain perfusion measurement. MATERIALS AND METHODS: The P3 latency of ERPs was measured during a visual discrimination task in 15 patients with idiopathic late-onset cerebellar ataxia (ILOCA) and 10 age-matched control subjects. Regional brain perfusion was measured by single photon emission computed tomography using N-isopropyl-p[123I] iodoamphetamine. RESULTS: The mean P3 latency was longer in the patients than in controls. The patients showed lower perfusion in the frontal cortex and in the cerebellum than control subjects. There was a significant correlation between perfusion of the frontal cortex and cerebellum. CONCLUSIONS: The results indicate that patients with ILOCA exhibit slowing of cognitive information processing and suggest that its cognitive slowing may be due to a disruption of neural circuits between the cerebellum and the frontal cortex.     

Event-related-potential low-resolution brain electromagnetic tomography (ERP-LORETA) suggests decreased energetic resources for cognitive processing in narcolepsy

OBJECTIVE: Event-related potentials (ERPs) are sensitive measures of both perceptual and cognitive processes. The aim of the present study was to identify brain regions involved in the processes of cognitive dysfunction in narcolepsy by means of ERP tomography. METHODS: In 17 drug-free patients with narcolepsy and 17 controls, ERPs were recorded (auditory odd-ball paradigm). Latencies, amplitudes and LORETA sources were determined for standard (N1 and P2) and target (N2 and P300) ERP components. Psychometry included measures of mental performance, affect and critical flicker fusion frequency (CFF). RESULTS: In the ERPs patients demonstrated delayed cognitive N2 and P300 components and reduced amplitudes in midline regions, while N1 and P2 components did not differ from controls. LORETA suggested reduced P300 sources bilaterally in the precuneus, the anterior and posterior cingulate gyri, the ventrolateral prefrontal cortex and the parahippocampal gyrus. In psychometry, patients demonstrated deteriorated mood, increased trait anxiety, decreased CFF and a trend toward reduced general verbal memory and psychomotor activity. CONCLUSIONS: Narcoleptic patients showed prolonged information processing, as indexed by N2 and P300 latencies and decreased energetic resources for cognitive processing. SIGNIFICANCE: Electrophysiological aberrations in brain areas related to the 'executive attention network' and the 'limbic system' may contribute to a deterioration in mental performance and mood at the behavioral level.