Dopaminergic modulation of novelty repetition in Parkinson’s disease: A study of P3 event-related brain potentials

ObjectiveParkinson’s Disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. Cognitive impairments have been reported using the event-related potential (ERP) technique. Patients show reduced novelty P3 (nP3) amplitudes in oddball experiments, a response to infrequent, surprising stimuli, linked to the orienting response of the brain. The nP3 is thought to depend on dopaminergic neuronal pathways though the effect of dopaminergic medication in PD has not yet been investigated.MethodsTwenty-two patients with PD were examined “on” and “off” their regular dopaminergic medication in a novelty 3-stimulus-oddball task. Thirty-four healthy controls were also examined over two sessions, but received no medication. P3 amplitudes were compared throughout experimental conditions.ResultsAll participants showed sizeable novelty difference ERP effects, i.e. n_dP3 amplitudes, during both testing sessions. An interaction of diagnosis, medication and testing order was also found, indicating that dopaminergic medication modulated n_dP3 in patients with PD across the two testing sessions: We observed enhanced n_dP3 amplitudes from PD patients who were off medication on the second testing session.ConclusionPatients with PD ‘off’ medication showed ERP evidence for repetition-related enhancement of novelty responses. Dopamine depletion in neuronal pathways that are affected by mid-stage PD possibly accounts for this modulation of novelty processing.SignificanceThe data in this study potentially suggest that repetition effects on novelty processing in patients with PD are enhanced by dopaminergic depletion.     

Are effects of emotion in single words non-lexical? Evidence from event-related brain potentials

Emotional meaning impacts word processing. However, it is unclear, at which functional locus this influence occurs and whether and how it depends on word class. These questions were addressed by recording event-related potentials (ERPs) in a lexical decision task with written adjectives, verbs, and nouns of positive, negative, and neutral emotional valence. In addition, word frequency (high vs. low) was manipulated. The early posterior negativity (EPN) in ERPs started earlier for emotional nouns and adjectives than for verbs. Depending on word class, EPN onsets coincided with or followed the lexicality effects. Main ERP effects of emotion overlapped with effects of word frequency between 300 and 550 ms but interacted with them only after 500 ms. These results indicate that in all three word classes examined, emotional evaluation as represented by the EPN has a post-lexical locus, starting already after a minimum of lexical access.     

Attention or memory? Effects of familiarity and novelty on the Nc component of event-related brain potentials in six-month-old infants

This study tested predictions from attentional, expectancy, and memory accounts of the Nc and early NSW components of ERPs in six-month-old infants. Visual stimuli were presented at the extremes of the probability continuum (a repeating stimulus versus novel stimuli) and at intermediate levels of probability (.80/.20 oddball task). Probability effects were found for Nc, early NSW, and visual fixation performance but there were no differences in the ERPs or behavior to familiar or novel stimuli. The results are discussed in terms of attentional and memory based interpretations of the Nc component.     

Visual event-related potentials in subjects with alexithymia: modified processing of emotional aversive information?

OBJECTIVE: A modified autonomous response (e.g., electrodermal activity) in subjects with alexithymia (a reduced ability to identify and communicate emotions) while processing emotional information is well known. However, the functional and neurobiological bases of this impairment are unclear. Do subjects with alexithymia suffer from a primary lack of perception ("emotional blindness"), or is alexithymia based on incomplete information processing due to immature undifferentiated cognitive schemes? The study investigates if subjects with alexithymia show a modified central response as a correlate of classifying emotional aversive stimuli. METHOD: Twenty subjects with high alexithymia and 20 with low alexithymia (selected by the 20-item Toronto Alexithymia Scale) were investigated within a modified odd-ball paradigm. Three different stimulus categories were presented: aversive (probes) and affective neutral pictures (nontargets and instructed targets). Visual event-related EEG potentials and subjective data were recorded. RESULTS: All subjects showed elevated positive amplitudes or mean activity after probe presentation in the latency range: 150-260, 280-450, and 600-1500 msec. Subjects with alexithymia displayed increased positive components (especially P2) of visual event-related potentials after probe presentation than subjects without alexithymia. Subjects without alexithymia more frequently verbalized the emotional impact of these aversive pictures than subjects with alexithymia. CONCLUSIONS: These findings do not support the assumption of a primary lack of perception in alexithymia. Subjects with alexithymia show central correlates of perception and classification of aversive pictures. They may need more effort and cognitive recourses to process emotional information. Nevertheless, spontaneous verbal reference to emotional stimulus aspects is reduced.     

Top–down modulation of prepulse inhibition of the startle reflex in humans and rats

Prepulse inhibition (PPI) is the attenuation of the startle reflex when the sudden intense startling stimulus is shortly preceded by a weaker, non-startling sensory stimulus (prepulse). PPI reflects a protective function of reducing disruptive influences to the processing of prepulse signals and is recognized as a model of sensorimotor gating. In humans, PPI is modulated by both attentional and emotional responses to prepulse, indicating that this early-stage gating is top–down modulated by higher-order cognitive processes. Recent studies have confirmed top–down modulation of PPI in animals, because PPI in rats is enhanced by auditory fear conditioning and perceived separation between fear-conditioned prepulse and masker. This review summarizes recent studies of top–down modulation of PPI conducted in humans and those in rats. Since both baseline PPI and attentional modulation of PPI in patients with schizophrenia are impaired, and both baseline PPI and conditional modulation of PPI in rats with isolation rearing are impaired, this review emphasizes that investigation of top–down modulation of PPI is critical for establishing new animal models for studying both cognitive features and neural bases of schizophrenia. Deficits in either baseline PPI or attentional modulation of PPI in either patients with attention-deficit/hyperactivity disorder (ADHD) or ADHD-modeling rats are also discussed.     

Are there common mechanisms in sensation seeking and reality distortion in schizophrenia? A study using memory event-related potentials

A growing literature suggests that the characteristics of sensation seeking and reality distortion expressed in schizophrenia share several mechanisms. In a previous study, the comparison of patients with high vs. low reality distortion using event-related potentials (ERPs) recorded in a recognition memory task for unfamiliar faces identified neural and cognitive anomalies specifically related to the expression of these symptoms. As a follow-up, this study investigated the ERP correlates of sensation seeking in schizophrenia using the same recognition memory protocol. ERPs have been recorded in controls (N=21) and schizophrenia patients separated into high (HSS; N=13) and low (LSS; N=17) scorers according to Zuckerman's Sensation Seeking Scale. The results show a reduced P2a that was found unrelated to reality distortion in the previous study of reality distortion. It identifies interference inhibition impairment as being specifically related to sensation seeking. On the other hand, HSS scorers display enhanced fronto-central and normal P600 effects also found in high reality distortion patients. These results indicate inappropriate context processing and mnemonic binding common to sensation seeking and reality distortion. LSS scorers also display a reduced temporal N300 similar to that found in low reality distortion patients. This anomaly could reflect the lower reactivity to emotionally significant stimuli that underlies anhedonia symptoms. Finally, the N400 effect and a late frontal effect are found in both HSS and LSS. Since they were unrelated to reality distortion, these indices have been related to basic aspects of schizophrenia, e.g., deficient knowledge integration, or other mechanisms, e.g. anxiety or impulsivity. In summary, the present study examines the strategy of investigating variables, such as temperamental characteristics, in addition to symptoms, to show how discrete impairments may contribute to the expression of the illness.     

Challenge or threat? Cardiovascular indexes of resilience and vulnerability to potential stress in humans

Humans continually face situations that require actions to achieve valued goals with meaningful consequences at stake. Although the pursuit of such goals can be a negatively “stressful” experience, it is not necessarily so. According to the biopsychosocial model of challenge and threat, evaluations of personal resources and situational demands determine to what extent individuals experience a relatively positive (challenge) versus negative (threat) psychological state in this context. Challenge occurs when evaluated resources meet or exceed demands, whereas threat occurs when demands exceed resources. The challenge response thus reflects resilience in the face of potential stress. Because challenge and threat reliably result in distinct patterns of physiological changes, assessing cardiovascular responses in particular can provide valuable insight into underlying psychological processes. Research applying this methodology to individual differences (e.g., self-esteem level and stability and cumulative lifetime exposure to adversity) has implications for understanding how early life experience could contribute to resilience versus vulnerability to potential stress in daily life.     

Relationship of the BOLD signal with VEP for ultrashort duration visual stimuli (0.1 to 5?ms) in humans

There is currently a great interest to combine electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) to study brain function. Earlier studies have shown different EEG components to correlate well with the fMRI signal arguing for a complex relationship between both measurements. In this study, using separate EEG and fMRI measurements, we show that (1) 0.1 ms visual stimulation evokes detectable hemodynamic and visual-evoked potential (VEP) responses, (2) the negative VEP deflection at ∼80 ms (N2) co-varies with stimulus duration/intensity such as with blood oxygenation level-dependent (BOLD) response; the positive deflection at ∼120 ms (P2) does not, and (3) although the N2 VEP–BOLD relationship is approximately linear, deviation is evident at the limit of zero N2 VEP. The latter finding argues that, although EEG and fMRI measurements can co-vary, they reflect partially independent processes in the brain tissue. Finally, it is shown that the stimulus-induced impulse response function (IRF) at 0.1 ms and the intrinsic IRF during rest have different temporal dynamics, possibly due to predominance of neuromodulation during rest as compared with neurotransmission during stimulation. These results extend earlier findings regarding VEP–BOLD coupling and highlight the component- and context-dependency of the relationship between evoked potentials and hemodynamic responses.     

Mislocalization of near‐threshold tactile stimuli in humans: a central or peripheral phenomenon?

Principles of brain function can be disclosed by studying their limits during performance. Tactile stimuli with near-threshold intensities have been used to assess features of somatosensory processing. When stimulating fingers of one hand using near-threshold intensities, localization errors are observed that deviate significantly from responses obtained by guessing - incorrectly located stimuli are attributed more often to fingers neighbouring the stimulated one than to more distant fingers. Two hypotheses to explain the findings are proposed. The 'central hypothesis' posits that the degree of overlap of cortical tactile representations depends on stimulus intensity, with representations less separated for near-threshold stimuli than for suprathreshold stimuli. The 'peripheral hypothesis' assumes that systematic mislocalizations are due to activation of different sets of skin receptors with specific thresholds. The present experiments were designed to decide between the two hypotheses. Taking advantage of the frequency tuning of somatosensory receptors, their contribution to systematic misclocalizations was studied. In the first experiment, mislocalization profiles were investigated using vibratory stimuli with frequencies of 10, 20 and 100 Hz. Unambiguous mislocalization effects were only obtained for the 10-Hz stimulation, precluding the involvement of Pacinian corpuscles in systematic mislocalization. In the second experiment, Pacinian corpuscles were functionally eliminated by applying a constant 100-Hz vibratory masking stimulus together with near-threshold pulses. Despite masking, systematic mislocation patterns were observed rendering the involvement of Pacinian corpuscles unlikely. The results of both experiments are in favor of the 'central hypothesis' assuming that the extent of overlap in somatosensory representations is modulated by stimulus intensity.     

State and trait markers of emotionally charged visual event-related potentials (P300) in drug-naïve schizophrenia

Aim: In the present study, we investigated the changes in P3 component in the emotionally charged visual event‐related potentials (ERP) in 30 drug‐naïve schizophrenic patients for up to 1 year. Methods: Visual oddball event‐related potential was recorded from six recording sites for crying baby or smiling baby photographs. ERP were recorded before the treatment (session 1 [S1]), after 3 months (session 2 [S2]), and after 12 months (session 3 [S3]), as well as in 30 healthy subjects. Results: Before taking medicine, there were no significant differences in the P300 amplitude between viewing photographs of a crying and a smiling baby. The P300 amplitude was significantly larger at S2 and S3 than at S1 for a crying baby, while there was no significant difference among sessions for a smiling baby after medication. A significant difference of the P300 amplitude was only observed between S3 and healthy subjects for a smiling baby. The P300 latency only when viewing a smiling face became significantly longer at S3 than those at S1 and S2. A significant negative correlation was obtained between the P300 amplitude changes upon viewing crying faces and negative syndrome score changes at the Pz site. Conclusion: The P300 amplitude induced by crying‐face stimuli may be a state marker and the P300 amplitude caused by smiling‐face stimuli may be a trait marker during recovery in schizophrenic patients. Atypical antipsychotic medications may be useful and may recover cognitive function reflected by the emotionally charged visual P300 components in schizophrenic patients.     

Mother to infant or infant to mother? Reciprocal regulation of responsiveness to stress in rodents and the implications for humans

Optimal early development in most species is dependent upon a stable relationship between the mother and her infant. The research described here focuses on the reciprocal nature of this dyad in rodents and humans, with respect to the regulation of responsiveness to stress in both mother and offspring. Dietary influences are critical not only to regulate infant growth but also to modulate the response of the neuroendocrine system to stress and, possibly, to influence some aspects of brain development. In particular, we discuss the role of leptin, a protein produced in the adipose tissue and present in maternal milk, that reduces responses to stress in the infant. We suggest that leptin acts on both central (hypothalamus and hippocampus) and peripheral (pituitary, adrenal gland) targets in the infant to reduce exposure to glucocorticoids and enhance hippocampal development during a sensitive period of brain development. There is also evidence to support the reverse regulatory influence, in which maternal state is profoundly affected by stimulation from the young. During the period of lactation, mothers exhibit lower neuroendocrine and behavioural responses to several types of stressors, except possibly those representing a threat to the infant. This ability to "filter" relevant from irrelevant stimuli while caring for their young might be viewed as adaptive for the mother-infant dyad, and the inability to filter adequately stressful stimuli could at least in part be associated with the development of postpartum depression.     

Circadian system — A novel diagnostic and therapeutic target in Parkinson's disease?

The circadian system regulates biological rhythmicity in the human body. The role of the circadian system in neurological disorders is a theme that is attracting an increasing amount of interest from the scientific community. This has arisen, in part, from emerging evidence that disorders such as Parkinson's disease (PD) are multifactorial with many features exhibiting diurnal fluctuations, thereby suggestive of circadian involvement. Although the importance of fluctuating motor and nonmotor manifestations in PD have been well acknowledged, the role of the circadian system has received little attention until recently. It is proposed that intervening with circadian function provides a novel research avenue down which new strategies for improving symptomatic treatment and slowing of the progressive degenerative process can be approached to lessen the burden of PD. In this article we review the literature describing existing circadian research in PD and its experimental models. © 2016 International Parkinson and Movement Disorder Society     

The auditory P200 is both increased and reduced in schizophrenia? A meta-analytic dissociation of the effect for standard and target stimuli in the oddball task

ObjectiveConflicting reports of P200 amplitude and latency in schizophrenia have suggested that this component is increased, reduced or does not differ from healthy subjects. A systematic review and meta-analysis were undertaken to accurately describe P200 deficits in auditory oddball tasks in schizophrenia.MethodsA systematic search identified 20 studies which were meta-analyzed. Effect size (ES) estimates were obtained: P200 amplitude and latency for target and standard tones at midline electrodes.ResultsThe ES obtained for amplitude (Cz) for standard and target stimuli indicate significant effects in opposite directions: standard stimuli elicit smaller P200 in patients (d = ?0.36; 95% CI [?0.26, ?0.08]); target stimuli elicit larger P200 in patients (d = 0.48; 95% CI [0.16, 0.82]). A similar effect occurs for latency at Cz, which is shorter for standards (d = ?0.32; 95% CI [?0.54, ?0.10]) and longer for targets (d = 0.42; 95% CI [0.23, 0.62]). Meta-regression analyses revealed that samples with more males show larger ES for amplitude of target stimuli, while the amount of medication was negatively associated with the ES for the latency of standards.ConclusionsThe results obtained suggest that claims of reduced or augmented P200 in schizophrenia based on the sole examination of standard or target stimuli fail to consider the stimulus effect.SignificanceQuantification of effects for standard and target stimuli is a required first step to understand the nature of P200 deficits in schizophrenia.     

From adaption to death: endoplasmic reticulum stress as a novel target of selective neurodegeneration?

<正>Neurodegenerative disease is a condition in which subpopulations of neuronal cells of the brain and spinal cord are selectively lost.A common event in many neurodegenerative diseases,such as Parkinson’s disease(PD),Alzheimer’s disease(AD),amyotrophic lateral sclerosis(ALS),multiple sclerosis and prion diseases,is the increased level of endoplasmic reticulum(ER)     

What is novel in the novelty oddball paradigm? Functional significance of the novelty P3 event-related potential as revealed by independent component analysis

To better understand whether voluntary attention affects how the brain processes novel events, variants of the auditory novelty oddball paradigm were presented to two different groups of human volunteers. One group of subjects (n=16) silently counted rarely presented 'infrequent' tones (p=0.10), interspersed with 'novel' task-irrelevant unique environmental sounds (p=0.10) and frequently presented 'standard' tones (p=0.80). A second group of subjects (n=17) silently counted the 'novel' environmental sounds, the 'infrequent' tones now serving as the task-irrelevant deviant events. Analysis of event-related potentials (ERPs) recorded from 63 scalp channels suggested a spatiotemporal overlap of fronto-central novelty P3 and centro-parietal P3 (P3b) ERP features in both groups. Application of independent component analysis (ICA) to concatenated single trials revealed two independent component clusters that accounted for portions of the novelty P3 and P3b response features, respectively. The P3b-related ICA cluster contributed to the novelty P3 amplitude response to novel environmental sounds. In contrast to the scalp ERPs, the amplitude of the novelty P3 related cluster was not affected by voluntary attention, that is, by the target/nontarget distinction. This result demonstrates the usefulness of ICA for disentangling spatiotemporally overlapping ERP processes and provides evidence that task irrelevance is not a necessary feature of novelty processing.     

Combined 18F-fluorodeoxyglucose positron emission tomography and event-related potentials study of the cognitive impairment mechanisms in Parkinson’s disease

This study aimed to analyze positron emission tomography with 18F-fluorodeoxyglucose data and event-related potentials in the Go/NoGo paradigm in patients with Parkinson’s disease with and without cognitive impairment. In the group of cognitively impaired patients, glucose metabolism was decreased in the frontal, parietal, cingulate and posterior temporal cortex. Correlations were found between the cognitive scores and cerebral glucose metabolism in those areas. Event-related potentials analysis revealed a decrease in the amplitude of the late positive wave (P300 NoGo wave) in the group of cognitively impaired patients. The analysis revealed that decline in amplitude of P300 wave was accompanied by decreased glucose metabolism in several cortical areas associated with cognitive impairment in Parkinson’s disease. Correlations of glucose metabolism in these areas with event-related potentials amplitude in the NoGo condition confirm the important role of executive functions disorders in the pathogenesis of cognitive impairment in Parkinson’s disease.     

Is motor perseveration in unilateral neglect 'driven' by the presence of neglected left-sided stimuli?

Unilateral spatial neglect refers to a difficulty in detecting or acting on information in a particular region of space. When asked to cross out stimuli distributed across a page, patients with neglect may miss many targets on the left. In addition, they have a tendency to return to, and re-mark, right-sided targets that they have already cancelled. A recent retrospective study has shown this effect to be specific to unilateral neglect rather than a consequence of right hemisphere damage in general. Here, a consecutive group of seven right-hemisphere neglect patients performed five versions of a standard cancellation task, each version differing in the quantity of left-sided information presented. All of the participants showed perseveration on right-sided targets in the basic task. A highly significant and linear reduction in perseverative behaviour was observed as left-sided information was removed. In a second study, left-sided targets were again progressively removed but, in this case, were replaced with an additional distractor item, keeping the total quantity of stimuli presented in each condition constant. Again, a significant reduction in right-sided perseveration was observed, indicating a high degree of selectivity to the effect. The results show that a difficulty in perceiving existing cancellation marks, or a non-spatially specific motoric perseveration, are unlikely to fully account for this behaviour. As the patients omitted almost all targets on the left side of the basic cancellation task, the results suggest a striking influence on apparently intentional behaviour from un-cancelled information within the neglected field.     

Does neuropeptide Y contribute to the modulation of brain stimulation reward by chronic food restriction?

The rewarding effect produced by electrically stimulating particular sites in the lateral hypothalamus (LH) can be enhanced by chronic food restriction and body weight loss. The impact on brain stimulation reward (BSR) of certain hormones involved in the regulation of energy balance, such as leptin and corticotropin-releasing hormone, depends upon the sensitivity of BSR to food restriction. The present investigation assessed the influence of neuropeptide Y (NPY), a potent orexigenic peptide, on BSR generated by stimulating restriction-sensitive and -insensitive sites in the LH. Twelve male Long Evans rats were trained to press a lever for a rewarding train of stimulation. Rate-frequency curves, reflecting the number of rewards earned as a function of the stimulation frequency, were collected during free-feeding and then again following a period of food restriction and 20-25% body weight loss. NPY (4 microg) was administered intraventriculary during the food restriction condition. Alterations in the rewarding effect of the stimulation were assessed by measuring changes in the frequency required to maintain half-maximal rewards earned (M-50). In half of the subjects, food restriction produced significant decreases in M-50 values, indicating that the reward effectiveness of the stimulation was potentiated. In contrast, M-50 values were unaltered by food restriction in the remaining six animals. In most of the subjects in which M-50 values decreased following chronic food restriction, NPY failed to alter BSR. Similarly, BSR was unchanged by NPY administration in most of the rats with restriction-insensitive stimulation sites. These findings suggest that NPY does not take part in the process whereby food restriction and leptin modulate reward circuitry activated by stimulating restriction-sensitive sites.     

Do evoked potentials contribute to the functional follow-up and clinical prognosis of multiple sclerosis?

The clinical variability and complexity of multiple sclerosis (MS) challenges the individual clinical course prognostication. This study aimed to find out whether multimodal evoked potentials (EP) correlate with the motor components of multiple sclerosis functional composite (MSFCm) and predict clinically relevant motor functional deterioration. One hundred MS patients were assessed at baseline (T ₀) and about 7.5 years later (T ₁), with visual, somatosensory and motor EP and rated on the Expanded Disability Status Scale (EDSS) and the MSFCm, including the 9 Hole Peg Test and the Timed 25 Foot Walk (T25FW). The Spearman correlation coefficient (r _S) was used to evaluate the cross-sectional and longitudinal relationship between EP Z scores and clinical findings. The predictive value of baseline electrophysiological data for clinical worsening (EDSS, 9-HPT, T25FW, MSFCm) during follow-up was assessed by logistic regression analysis. Unlike longitudinal correlations, cross-sectional correlations between EP Z scores and clinical outcomes were all significant and ranged between 0.22 and 0.67 (p < 0.05). The global EP Z score was systematically predictive of EDSS and MSFCm worsening over time (all p < 0.05). EP latency was a better predictor than amplitude, although weaker than latency and amplitude aggregation in the global EP Z score. The study demonstrates that EP numerical scores can be used for motor function monitoring and outcome prediction in patients with MS.