Central fatigue and attentional processing in Parkinson’s disease: An event-related potentials study

ObjectiveTo verify whether central fatigue in patients with Parkinson’s disease (PD) is associated with the presence of a more severe selective cognitive impairment.MethodsTwenty-four PD patients without fatigue-PDnF, 11 with fatigue-PDF and 32 healthy volunteers underwent a P300 novelty task that elicits both the P3a and the P3b components.ResultsP3b latency was significantly longer in both PDF and PDnF than in controls. P3b amplitudes were comparable between groups. P3a latency and P3a amplitude were respectively significantly longer and lower in PDF than in either PDnF or controls.ConclusionThe ability to discriminate the significant target stimulus, which requires the integrity of the dorsal attentional network and top-down control mechanisms, is compromised in parkinsonian patients irrespective of the presence of fatigue. PDF exhibited a difficulty in attentional orienting to salient novel stimuli, a bottom-up attentional control mechanism that is related to the functioning of the ventral attention network.SignificanceFatigue seems to be specifically related to an impairment in the processing of novel stimuli, which is an essential part of adaptive decision-making behavior.     

Impaired novelty P3 potentials in multiple system atrophy--correlation with orthostatic hypotension

Although neuropsychological tests demonstrate frontal lobe dysfunction in multiple system atrophy (MSA), assessment of frontal function using event-related brain potentials (ERPs) has not been sufficiently performed in MSA. The correlation between frontal lobe dysfunction and orthostatic hypotension (OH), which is known to cause frontal hypoperfusion, remains unclear. Our objectives were to assess frontal lobe dysfunction in MSA patients using ERPs and to elucidate the relevance of OH to changes in ERPs. Nine consecutive patients with MSA and nine age- and gender-matched healthy controls were compared by performance in the Wisconsin Card Sorting Test (WCST) and somatosensory ERPs to target and novel stimuli, namely, parietal maximal P3 (target P3) and fronto-central P3 (novelty P3), respectively. The correlation between novelty P3 and OH was evaluated in the MSA group. The MSA group showed a poorer performance in categories achieved (CA), total errors (TE) and perseverative errors by Nelson's (PEN) method in the WCST compared with the control group (CA and PEN: p<0.01; TE: p<0.02). Novelty and target P3s in the MSA group showed significantly prolonged latency (novelty: p<0.05; target: p<0.01) and reduced amplitude (novelty: p<0.02; target: p<0.01) compared with the control group. There was a significant negative correlation between novelty P3 latency and a drop in systolic blood pressure (r=0.76; p<0.02). Abnormalities of novelty P3 in the MSA group might reflect frontal lobe dysfunction, namely failure of attentional set-shifting, that was identified by the WCST. OH may play a role in the development of frontal lobe dysfunction in MSA.     

Contribution of subregions of human frontal cortex to novelty processing

Novelty processing was studied in patients with lesions centered in either OFC or lateral pFC (LPFC). An auditory novelty oddball ERP paradigm was applied with environmental sounds serving as task irrelevant novel stimuli. Lesions to the LPFC as well as the OFC resulted in a reduction of the frontal Novelty P3 response, supporting a key role of both frontal subdivisions in novelty processing. The posterior P3b to target sounds was unaffected in patients with frontal lobe lesions in either location, indicating intact posterior cortical target detection mechanisms. LPFC patients displayed an enhanced sustained negative slow wave (NSW) to novel sounds not observed in OFC patients, indicating prolonged resource allocation to task-irrelevant stimuli after LPFC damage. Both patient groups displayed an enhanced NSW to targets relative to controls. However, there was no difference in behavior between patients and controls suggesting that the enhanced NSW to targets may index an increased resource allocation to response requirements enabling comparable performance in the frontal lesioned patients. The current findings indicate that the LPFC and OFC have partly shared and partly differential contributions to the cognitive subcomponents of novelty processing.     

Attention in essential tremor: evidence from event-related potentials

Clinically subtle executive dysfunctions have recently been described in essential tremor (ET), though the presence of attentional deficits is still unclear. We investigated the psychophysiological aspects of attention in ET, using event-related potentials (ERPs). Twenty-one non-demented patients with ET and 21 age- and sex-matched healthy controls underwent a psychophysiological evaluation. P300 components and the Contingent Negative Variation (CNV) were recorded. The latencies and amplitudes of the P3a and P3b subcomponents and CNV areas were evaluated. Possible correlations between clinical parameters and ERP data were investigated. P3a latency was significantly longer in the ET group (p < 0.05), while no differences emerged between patients and controls in P3b latency. No differences were observed between the two groups in the CNV parameters. ET patients display a difficulty in the response to novelty and in the recruitment of prefrontal attentive circuits, while the memory context-updating process appears to be spared. This selective cognitive dysfunction does not appear to interfere with the attentional set linked to the expectancy evaluated during a complex choice-reaction time task, which is preserved in ET. This multitask psychophysiological approach reveals the presence of a peculiar attentional deficit in patients with ET, thus expanding the clinical features of this disease.     

Early cortical gray matter loss and cognitive correlates in non-demented Parkinson's patients

BackgroundWhereas the motor dysfunction in Parkinson's disease (PD) has been related to deficits in basal ganglia (BG) structures, neural correlates of cognitive changes remain to be fully defined. This study tested the hypothesis that cognitive changes in non-demented PD may be related to cortical gray matter (GM) loss.MethodsHigh-resolution T1-weighted magnetic resonance images of the brain and comprehensive cognitive function tests were acquired in 40 right-handed, non-demented PD subjects and 40 matched controls. GM changes were assessed using voxel-based morphometry (VBM) in FSL. VBM and cognitive results were compared between PD and controls, and correlation analyses were performed between those brain areas and cognitive domains that showed significant group differences.ResultsPD patients demonstrated significant GM reduction localized predominantly in frontal and parieto-occipital regions. Patients also showed reduced performance in fine motor speed and set-shifting compared to controls. Fine motor speed and set-shifting were associated with GM volume in the frontal cortex in controls, whereas these domains were associated primarily with occipital GM regions in PD patients.ConclusionsNon-demented PD subjects demonstrate cortical structural changes in frontal and parieto-occipital regions compared to controls. The association between typically recognized “frontal lobe” function and occipital lobe volume suggested a compensatory role of occipital lobe to primary fronto-striatal pathology in PD. Further longitudinal study of these changing structure–function relationships is needed to understand the neural bases of symptom progression in PD.     

Frontal and parietal components of a cerebral network mediating voluntary attention to novel events

Despite the important role that attending to novel events plays in human behavior, there is limited information about the neuroanatomical underpinnings of this vital activity. This study investigated the relative contributions of the frontal and posterior parietal lobes to the differential processing of novel and target stimuli under an experimental condition in which subjects actively directed attention to novel events. Event-related potentials were recorded from well-matched frontal patients, parietal patients, and non-brain-injured subjects who controlled their viewing duration (by button press) of line drawings that included a frequent, repetitive background stimulus, an infrequent target stimulus, and infrequent, novel visual stimuli. Subjects also responded to target stimuli by pressing a foot pedal. Damage to the frontal cortex resulted in a much greater disruption of response to novel stimuli than to designated targets. Frontal patients exhibited a widely distributed, profound reduction of the novelty P3 response and a marked diminution of the viewing duration of novel events. In contrast, damage to posterior parietal lobes was associated with a substantial reduction of both target P3 and novelty P3 amplitude; however, there was less disruption of the processing of novel than of target stimuli. We conclude that two nodes of the neuroanatomical network for responding to and processing novelty are the prefrontal and posterior parietal regions, which participate in the voluntary allocation of attention to novel events. Injury to this network is indexed by reduced novelty P3 amplitude, which is tightly associated with diminished attention to novel stimuli. The prefrontal cortex may serve as the central node in determining the allocation of attentional resources to novel events, whereas the posterior parietal lobe may provide the neural substrate for the dynamic process of updating one's internal model of the environment to take into account a novel event.     

Event-related brain potentials in response to novel sounds in dementia.

OBJECTIVE: Non-target, deviant stimuli generate an earlier latency, front-central novelty P3, whereas correctly detected task-relevant stimuli generate a parietal maximal target P3. We examined whether the P3 component to novel stimuli is affected by dementing processes, and is therefore useful for distinguishing Alzheimer's type dementia (AD) from vascular dementia (VD). METHODS: We recorded ERPs to task-relevant stimuli (target P3) and novel task-irrelevant stimuli (novelty P3) in an auditory oddball task in AD (n = 16), VD (n = 16), and age-matched controls (n = 18). The amplitude, latency, and scalp topography of target and novelty P3 were compared among 3 groups using ANOVA. The relationship between P3 measures and intelligence scores were evaluated by correlation analysis. RESULTS: The amplitude, latency and scalp topography of the target P3 were comparably affected by both AD and VD. However, the amplitude of the novelty P3 was markedly reduced in VD, but not in AD, and the scalp topographics were different in the 3 groups. The amplitude was maximal at frontal sites in controls, at central sites in AD, and at parietal sites in VD. The target P3 latency was prolonged in both AD and VD, whereas the novelty P3 latency was only prolonged in VD. AD was discriminated satisfactorily from VD by using the novelty amplitude at Cz and the ratio of the amplitudes at Fz and Pz as independent variables. CONCLUSIONS: These results suggest that the response to novel stimuli is differentially affected by dementia with degenerative and vascular etiology.     

Impaired cognitive performance in Parkinson's disease is related to caudate dopaminergic hypofunction and hippocampal atrophy

Frontal lobe dysfunction and other cognitive deficits have been described in Parkinson's disease (PD), which may lead to dementia. Both striatal dopaminergic deficiency and regional or global brain volume loss have been suggested to contribute to cognitive decline in PD. We therefore performed a neuropsychological evaluation, structural brain MRI and Fdopa PET in patients with PD and healthy elderly volunteers. PD patients had impaired cognitive performance in many neuropsychological tests compared to controls, not limited just to frontal lobe function tests. Caudate Fdopa correlated positively with performance in verbal (immediate and delayed) and visual memory. Patients with PD showed atrophy in the hippocampus and the prefrontal cortex and hippocampal atrophy was related to impaired memory. Our findings suggest that striatal dopaminergic depletion and global brain volume loss contribute to cognitive impairment in non-demented PD patients, but dysfunction of extra-striatal dopaminergic or non-dopaminergic systems probably plays a role especially in more generalized cognitive impairment.     

Cognitive deficits in amyotrophic lateral sclerosis evaluated by event-related potentials

ObjectiveTo determine the cognitive profiles in non-demented, relatively less handicapped patients with early-stage sporadic amyotrophic lateral sclerosis (ALS) by using neuropsychological tests, event-related potentials (ERPs) and clinical scale.MethodsWe recruited 19 patients with sporadic ALS (eight with limb-onset, 11 with bulbar-onset) and 19 controls. In addition to the mini-mental state examination and the Wechsler adult intelligence scale-revised, we assessed the frontal lobe function with Wisconsin card sorting test, Stroop test and trail making test. We used auditory ‘oddball’ counting paradigm for the ERPs under 20-channel electroencephalogram (EEG) recording. Global field power (GFP) was computed, and its peak amplitudes and latencies of N1/N2/P3 were determined. The results of ERP and neuropsychological tests were correlated with respiratory function and clinical scale.ResultsNo global cognitive impairment except for subtle frontal dysfunction was detected, although N1/N2/P3 GFP latencies were significantly prolonged in ALS patients than in the controls. Vital capacity correlated with P3 GFP amplitude, and the relative bulbar functional rating scale correlated with P3 GFP latency.ConclusionsOur findings indicated the presence of sub-clinical cognitive deficits in non-demented, sporadic ALS patients. In addition, clinical sub-types and respiratory function dependently influenced cognitive function in patients with sporadic ALS.SignificanceERP confirmed cognitive impairment in patients with sporadic ALS.     

Hippocampal and prefrontal atrophy in patients with early non-demented Parkinson's disease is related to cognitive impairment

BACKGROUND: Early stage patients with Parkinson's disease (PD) show cognitive impairment in frontal lobe functions and memory tests. Hippocampal atrophy is seen in medicated patients with advanced PD. OBJECTIVES: To examine whether prefrontal or hippocampal atrophy are already present in early stage PD, and whether such atrophy is associated with cognitive impairment. METHODS: Twenty non-medicated, non-demented patients with early stage PD and 22 neurologically healthy age matched controls were studied. All subjects underwent magnetic resonance imaging to study hippocampal and prefrontal atrophy. Atrophy was evaluated by a neuroradiologist using a five point scale. In addition, the patients underwent a neuropsychological test battery sensitive to frontal lobe functions and memory. RESULTS: Patients with PD had atrophy in the right and the left prefrontal cortex. In the right hippocampus, the mean atrophy score was 1.15 in PD and 0.45 in controls. Corresponding figures for the left hippocampus were 1.05 for PD and 0.64 for controls. In PD, the left hippocampus atrophy correlated with verbal memory and prefrontal atrophy correlated with impaired performance in a test measuring vigilance. CONCLUSIONS: Non-medicated, non-demented patients with early stage PD show hippocampal and prefrontal atrophy. Impaired memory is related to hippocampal atrophy, whereas sustained attention is related to prefrontal atrophy.     

The relation of putamen and caudate nucleus 18F-Dopa uptake to motor and cognitive performances in Parkinson's disease.

The contribution of striatal (caudate nucleus-putamen) dopaminergic deficiency to the severity of motor signs is well established in Parkinson's disease (PD), while its role in the occurrence of cognitive and mood changes remains unresolved. We therefore measured in 27 non-demented PD patients and 10 age-matched controls striatal uptake of [18F]-6-fluoro-L-Dopa (F-Dopa) with PET, and mood (Beck depression), memory (Grober-Buschke), frontal executive functions (verbal fluency and Wisconsin card sorting), and attentional processing of sensory stimuli (N2-P3 auditory event-related potentials--ERPs). Locomotor disability of patients was assessed by Hoehn and Yahr score and Unified Parkinson's Disease Rating Scale (UPDRS). ANOVA showed that memory, but neither frontal lobe functions nor ERPs, was significantly altered in PD patients, whereas indices of depression were found only in advanced PD. The F-Dopa rate constant Ki was significantly reduced in the striatum, more in putamen than caudate nucleus, and inversely correlated with disease duration. A significant inverse correlation was found between both putamen and caudate nucleus Ki and Hoehn and Yahr score, and between putamen--but not caudate nucleus Ki --and UPDRS motor score. Principal components analysis (PCA) of PD patients Ki values and mood, cognitive and ERP parameters gave a three-factor solution. Variables contributing to factor 1 were memory score and N2-P3 ERP latencies, those to factor 2 were striatal Ki values, and those to factor 3 frontal executive performances. Depression did not segregate with any variable. Our findings suggest that unlike locomotor disability, cognitive abilities and mood state of non-demented PD patients are for the most part unrelated to striatal dopaminergic depletion and may result from dysfunction of extra-striatal dopaminergic or from non-dopaminergic systems.     

Perseveration for novel stimuli in Parkinson's disease: an evaluation based on event-related potentials topography.

Event-related potential topography produced by novel and target stimuli was used to detect dysfunction of mental switching (perseveration) in nondemented patients with Parkinson's disease. The study participants were 15 patients with Parkinson's disease and 13 age-matched healthy control patients. Ten percent of the novelty tones with pitches of 125 and 500 Hz were added to 20% of the target tones that had a pitch of 1000 Hz. Patients were instructed to count the target tones. The modified Wisconsin Card Sorting Test was used to evaluate frontal lobe function. Patients with Parkinson's disease showed a significant decrease in the achieved categories and an increase in perseverative errors in the Wisconsin Card Sorting Test. These results indicate that the cognitive impairment of patients with Parkinson's disease can be characterized as failure of mental switching related to frontal lobe dysfunction based on basal ganglia disturbance. As compared with the control patients, patients with Parkinson's disease had shorter P3 latencies to the novel stimuli and a more frontal distribution on the P3 map, especially for the 125-Hz stimuli. This characteristic of P3 to novel stimuli in the patients with Parkinson's disease, but not in the control patients, is categorized by P3a (novelty P3). Our findings suggest that decreased mental switching causes lack of novelty P3 habituation in patients with Parkinson's disease and that it is related to learning disabilities based on dysfunction of the frontal lobe and basal ganglia.     

An FMRI auditory oddball study of combined-subtype attention deficit hyperactivity disorder

OBJECTIVE: Studies of attention deficit hyperactivity disorder (ADHD) have reliably found reduced amplitude event-related potentials (ERPs) measuring attention-related brain function, indicating impairment in the brain's ability to automatically orient attention to odd or novel environmental stimuli and to represent that information in working memory. However, the relationship between abnormal neurocognition and dysfunction in specific brain regions in ADHD remains unclear. METHOD: The authors used functional magnetic resonance imaging (fMRI) to identify brain regions with abnormal hemodynamic activity during processing of target and novelty oddball stimuli that engage attention. Forty-six boys 11-18 years of age participated in the study, including 23 diagnosed as having ADHD with hyperactivity and impulsivity (combined type) and 23 demographically matched control subjects. Event-related fMRI data were collected while participants performed a three-stimulus auditory oddball task. Hemodynamic activity was compared between ADHD participants and control subjects in brain regions previously linked to P3 ERPs. RESULTS: Participants with ADHD showed deficits in brain activity elicited by infrequent attentionally engaging stimuli in regions associated with attentional orienting and working-memory cognitive processes. These deficits co-occurred with highly variable and slow task performance. CONCLUSIONS: This study links ADHD attentional orienting and working-memory deficits to dysfunction in specific cortical brain regions. The results indicate that ADHD pathophysiology impairs brain systems that are important for allocating attention and using cognitive representations to guide cognition and behavior. Attention-related neural dysfunction is thus an important factor to consider in neurobiological theories of ADHD.     

Cognition and event-related potentials in adult-onset non-demented myotonic dystrophy type 1

ObjectiveTo clarify the cognitive and event-related potentials (ERPs) profiles of adult-onset genetically-proven non-demented myotonic dystrophy type 1 (DM1).MethodsFourteen DM1 patients and matched 14 normal controls were enrolled. DM1 patients were compared with normal controls, using a variety of neuropsychological tests; an auditory “oddball” counting paradigm for the ERPs, and low-resolution brain electromagnetic tomography (LORETA). For patients, ERPs and neuropsychological parameters were correlated with CTG repeat size, duration of illness, grip strength, and arterial blood gas analysis.ResultsFrontal lobe dysfunction, prolonged N1 latency, and attenuated N2/P3 amplitudes were observed in DM1. Longer CTG repeat size was associated with fewer categories achieved on Wisconsin Card Sorting Test. Greater grip strength was associated with better scores on color-word “interference” of Stroop test. P3 latency was negatively correlated with PaO₂. LORETA revealed significant hypoactivities at the orbitofrontal and medial temporal lobe, cingulate, and insula. There was no correlation between ERPs and CTG expansion.ConclusionsAdult-onset non-demented DM1 presented frontal lobe dysfunction. Absence of correlations between CTG repeat size and objective ERP parameters suggested CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction.SignificanceCTG expansion in lymphocytes does not directly contribute to cognitive dysfunction of adult-onset non-demented DM1.     

额叶肿瘤患者认知功能和事件相关电位P300的研究

目的 探讨额叶肿瘤患者认知功能的损害和事件相关电位P300有关参数的变化特点,了解额叶在认知功能及P300产生中的作用.方法 对31例额叶肿瘤患者(左侧15例、右侧16例)及30例健康对照者分别进行Stroop字色干扰等多项认知神经心理学测试和P300检查.结果 与健康对照组相比,额叶肿瘤组认知功能各项测试指标评分均显著降低(P＜0.05),P300的N2、P3波潜伏期显著延长(P＜0.05),P3波幅显著降低(P＜0.05).进一步研究发现,右额叶肿瘤组患者的各项认知测试指标评分均显著低于健康对照组(P＜0.05),而左额叶肿瘤组只有词语流畅性指标评分显著低于健康对照组(P＜0.05);与健康对照组相比,左、右额叶肿瘤组P300的N2、P3波潜伏期均显著延长(P＜0.05),P3波幅均显著降低(P＜0.05);左、右额叶肿瘤组患者之间的P300比较则无统计学差异(p＞0.05).结论 额叶肿瘤患者认知功能有明显损害,右侧肿瘤患者的认知功能损害更严重:额叶可能与P300发生或传导有关,且左右额叶无明显的差异.     

Task switching and novelty processing activate a common neural network for cognitive control

The abrupt onset of a novel event captures attention away from, and disrupts, ongoing task performance. Less obvious is that intentional task switching compares with novelty-induced behavioral distraction. Here we explore the hypothesis that intentional task switching and attentional capture by a novel distracter both activate a common neural network involved in processing contextual novelty [Barcelo, F., Periá?ez, J. A., & Knight, R. T. Think differently: A brain orienting response to task novelty. NeuroReport, 13, 1887-1892, 2002.]. Event-related potentials were recorded in two task-cueing paradigms while 16 subjects sorted cards following either two (color or shape; two-task condition) or three (color, shape, or number; three-task condition) rules of action. Each card was preceded by a familiar tone cueing the subject either to switch or to repeat the previous rule. Novel sound distracters were interspersed in one of two blocks of trials in each condition. Both novel sounds and task-switch cues impaired responses to the following visual target. Novel sounds elicited novelty P3 potentials with their usual peak latency and frontal-central scalp distribution. Familiar tonal switch cues in the three- and two-task conditions elicited brain potentials with a similar latency and morphology as the novelty P3, but with relatively smaller amplitudes over frontal scalp regions. Covariance and principal component analyses revealed a sustained frontal negative potential that was distorting concurrent novelty P3 activity to the tonal switch cues. When this frontal negativity was statistically removed, P3 potentials to novel sounds and task-switch cues showed similar scalp topographies. The degree of activation in the novelty P3 network seemed to be a function of the information (entropy) conveyed by the eliciting stimulus for response selection, over and above its relative novelty, probability of occurrence, task relevance, or feedback value. We conclude that novelty P3 reflects transient activation in a neural network involved in updating task set information for goal-directed action selection and might thus constitute one key element in a central bottleneck for attentional control.     

Visual attention deficits in Alzheimer's disease: relationship to HMPAO SPECT cortical hypoperfusion

Patients with Alzheimer's disease (AD) display a multiplicity of cognitive deficits in domains such as memory, language, and attention, all of which can be clearly linked to the underlying neuropathological alterations. The typical degenerative changes occur early on in the disease in the temporal-parietal lobes, with other brain regions, such as the frontal cortex, becoming more affected as the disease progresses. In light of the importance of the parietal cortex in mediating visuospatial attentional processing, in the present study, we investigated a deficit in covert orienting of visual attention and its relationship to cortical hypoperfusion in AD. We characterized the visual attentional profile of 21 AD patients, relative to that of 26 matched normal individuals, and then assessed the correspondence between behavior and hypoperfusion, as measured by regional cerebral blood flow using SPECT. Relative to controls, the AD group demonstrated a unilateral attentional deficit, with disproportionate slowing in reorienting attention to targets in the left compared to the right hemispace, especially following an invalid peripheral cue. Furthermore, even in the presence of bilateral pathology typical of AD, there was a positive correlation between this unilateral attentional disorder and the magnitude of the right superior parietal lobe hypoperfusion. The association of the altered attentional processing profile (i.e., greater difficulty disengaging attention from right-sided stimuli) with right-hemisphere-predominant hypoperfusion not only confirms the critical role of the right parietal lobe in covert attentional orienting but, more importantly, identifies a potential locus of the behavioral alterations in visuospatial processing in AD.     

Cognitive impairment in amyotrophic lateral sclerosis: evidence from neuropsychological investigation and event-related potentials

The presence of subclinical cognitive impairment in patients with amyotrophic lateral sclerosis (ALS) is investigated using neuropsychological assessment and event-related potential recordings (ERP). An extensive battery of neuropsychological tests assessing the domains of attention, memory, language, visuo-spatial and executive functions were administered to 20 non-demented patients with sporadic ALS and 13 age- and education-matched healthy control subjects. Mismatch negativity (MMN), P3b, P3a (novelty P300) and contingent negative variation (CNV) were recorded. ALS patients were significantly impaired in tests of working memory, sustained attention, response inhibition, naming, verbal fluency and complex visuo-spatial processing. The memory impairment seemed to be secondary to deficits in forming learning strategies and retrieval. In ERP recordings, P3a and P3b amplitudes of ALS patients were lower compared with the controls, P3a latencies were significantly longer and mean CNV amplitudes were higher. These results indicate subclinical impairment of cognitive functions in patients with ALS. The pattern of cognitive impairment suggests the dysfunction of the frontal network.     

Electrophysiological evidence of abnormal activation of the cerebral network of involuntary attention in alcoholism.

OBJECTIVE: Increased distractibility is a common impairment in alcoholism, but objective evidence has remained elusive. Here, a task designed to investigate with event-related brain potentials (ERPs) the neural mechanism underlying distraction was used to show abnormal involuntary orienting of attention in chronic alcoholism. METHODS: Fifteen alcoholics and 17 matched healthy controls were instructed to ignore auditory stimuli while concentrating in the discrimination of immediately following visual stimuli. The auditory sequences contained repetitive standard tones occasionally replaced by deviant tones of slightly higher frequency, or by complex novel sounds. RESULTS: Deviant tones and novel sounds distracted visual performance, i.e. increased reaction time to visual stimuli, similarly in patients and controls. Compared to controls, however, alcoholics showed ERP abnormalities, i.e. enhanced P3a amplitudes over the left frontal region, and a positive posterior deflection instead of the frontally distributed reorienting negativity (RON). CONCLUSIONS: The enhanced P3a to novelty and subsequent positive wave instead of RON in alcoholics suggests encoding into working memory of task-irrelevant auditory events and provides neurophysiological markers of impaired involuntary attention mechanisms in chronic alcoholism.     

Pathophysiology underlying diminished attention to novel events in patients with early AD

BACKGROUND: Patients with mild to moderate AD often are apathetic and fail to attend to novel aspects of their environment. OBJECTIVE: To investigate the mechanisms underlying these changes by studying the novelty P3 response that measures shifts of attention toward novel events. METHODS: While event-related potentials were recorded, mildly impaired AD patients and matched normal controls (NC) viewed line drawings that included a repetitive background stimulus, an infrequent target stimulus, and infrequent novel stimuli. Subjects controlled how long they viewed each stimulus by pressing a button. This served as a measure of their allocation of attention. They also responded to targets by depressing a foot pedal. Patients did not differ from NC in age, education, estimated IQ, or mood but were judged by informants to be more apathetic. RESULTS: P3 amplitude to novel stimuli was significantly smaller for AD patients than NC. However, P3 amplitude to target stimuli did not differ between groups. For NC, P3 response to novel stimuli was much larger than to background stimuli. In contrast, for patients with AD, there was no difference in P3 response to novel vs background stimuli. Although NC spent more time looking at novel than background stimuli, patients with AD distributed their viewing time evenly. Remarkably, for patients with AD, the amplitude of the novelty P3 response powerfully predicted how long they would spend looking at novel stimuli (R2 = 0.52) and inversely correlated with apathy severity. CONCLUSIONS: The decreased attention to novel events exhibited by patients with AD cannot be explained by a nonspecific reduction in their attentional abilities. The novelty P3 response is markedly diminished in mild AD, at a time when the target P3 response is preserved. The disruption of the novelty P3 response predicts diminished attention to novel stimuli and is associated with the apathy exhibited by patients with AD.