Carboxyfullerene neuroprotection postinjury in Parkinsonian nonhuman primates.

OBJECTIVE: We evaluated the efficacy of the potent antioxidant C3 to salvage nigrostriatal neuronal function after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure in nonhuman primates. C3 is a first-in-class functionalized water-soluble fullerene that reduces oxygen radical species associated with neurodegeneration in in vitro studies. However, C3 has not been evaluated as a neuroprotective agent in a Parkinson model in vivo. METHODS: Macaque fascicularis monkeys were used in a double-blind, placebo-controlled study design. MPTP-lesioned primates were given systemic C3 (n = 8) or placebo (n = 7) for 2 months starting 1 week after MPTP. Outcomes included in vivo behavioral measures of motor parkinsonism using a validated nonhuman primate rating scale, kinematic analyses of peak upper extremity velocity, positron emission tomography imaging of 6-[(18) F]fluorodopa (FD; reflects dopa decarboxylase) and [(11) C]dihydrotetrabenazine (DTBZ; reflects vesicular monoamine transporter type 2), ex vivo quantification of striatal dopamine, and stereologic counts of tyrosine hydroxylase-immunostained neurons in substantia nigra. RESULTS: After 2 months, C3 -treated monkeys had significantly improved parkinsonian motor ratings, greater striatal FD and DTBZ uptake, and higher striatal dopamine levels. None of the C3 -treated animals developed any toxicity. INTERPRETATION: Systemic treatment with C3 reduced striatal injury and improved motor function despite administration after the MPTP injury process had begun. These data strongly support further development of C3 as a promising therapeutic agent for Parkinson disease.

Affective recognition memory processing and event-related brain potentials.

Recognition memory was examined for visual affective stimuli using behavioral and event-related brain potential (ERP) measures. Images from the International Affective Picture System (IAPS) that varied systematically in arousal level (low, high) and valence direction (unpleasant, pleasant) were first viewed passively. Then, during a response phase, the original images were intermixed with an equal number of new images and presented, and participants were instructed to press a button to indicate whether each stimulus picture was previously viewed (target) or new (foil). Participants were more sensitive to unpleasant- than to pleasant-valence stimuli and were biased to respond to high-arousal unpleasant stimuli as targets, whether the stimuli were previously viewed or new. Response times (RTs) to target stimuli were systematically affected by valence, whereas RTs to foil stimuli were influenced by arousal level. ERP component amplitudes were generally larger for high than for low arousal levels. The P300 (late positive component) amplitude was largest for high-arousal unpleasant target images. These and other amplitude effects suggest that high-arousal unpleasant stimuli engage a privileged memory-processing route during stimulus processing. Theoretical relationships between affective and memory processes are discussed.

Occipital gamma activation during Vipassana meditation.

Long-term Vipassana meditators sat in meditation vs. a control rest (mind-wandering) state for 21 min in a counterbalanced design with spontaneous EEG recorded. Meditation state dynamics were measured with spectral decomposition of the last 6 min of the eyes-closed silent meditation compared to control state. Meditation was associated with a decrease in frontal delta (1-4 Hz) power, especially pronounced in those participants not reporting drowsiness during meditation. Relative increase in frontal theta (4-8 Hz) power was observed during meditation, as well as significantly increased parieto-occipital gamma (35-45 Hz) power, but no other state effects were found for the theta (4-8 Hz), alpha (8-12 Hz), or beta (12-25 Hz) bands. Alpha power was sensitive to condition order, and more experienced meditators exhibited no tendency toward enhanced alpha during meditation relative to the control task. All participants tended to exhibit decreased alpha in association with reported drowsiness. Cross-experimental session occipital gamma power was the greatest in meditators with a daily practice of 10+ years, and the meditation-related gamma power increase was similarly the strongest in such advanced practitioners. The findings suggest that long-term Vipassana meditation contributes to increased occipital gamma power related to long-term meditational expertise and enhanced sensory awareness.

Binge drinking in young adults: Data, definitions, and determinants.

Binge drinking is an increasingly important topic in alcohol research, but the field lacks empirical cohesion and definitional precision. The present review summarizes findings and viewpoints from the scientific binge-drinking literature. Epidemiological studies quantify the seriousness of alcohol-related problems arising from binge drinking, with a growing incidence reported in college-age men over the last 2 years. Experimental studies have found neurocognitive deficits for frontal lobe processing and working memory operations in binge-drinking compared with nonbinge alcohol drinkers. The findings are organized with the goals of providing a useful binge-drinking definition in the context of the empirical results. Theoretical implications are discussed on how binge drinking may alter neurophysiological and neurocognitive function.

Affective valence, stimulus attributes, and P300: color vs. black/white and normal vs. scrambled images.

Pictures from the International Affective Picture System (IAPS) were selected to manipulate affective valence (unpleasant, neutral, pleasant) while keeping arousal level the same. The pictures were presented in an oddball paradigm, with a visual pattern used as the standard stimulus. Subjects pressed a button whenever a target was detected. Experiment 1 presented normal pictures in color and black/white. Control stimuli were constructed for both the color and black/white conditions by randomly rearranging 1 cm square fragments of each original picture to produce a "scrambled" image. Experiment 2 presented the same normal color pictures with large, medium, and small scrambled condition (2, 1, and 0.5 cm squares). The P300 event-related brain potential demonstrated larger amplitudes over frontal areas for positive compared to negative or neutral images for normal color pictures in both experiments. Attenuated and nonsignificant valence effects were obtained for black/white images. Scrambled stimuli in each study yielded no valence effects but demonstrated typical P300 topography that increased from frontal to parietal areas. The findings suggest that P300 amplitude is sensitive to affective picture valence in the absence of stimulus arousal differences, and that stimulus color contributes to ERP valence effects.

Clinical neurophysiology of aging brain: from normal aging to neurodegeneration.

Physiological brain aging is characterized by a loss of synaptic contacts and neuronal apoptosis that provokes age-dependent decline of sensory processing, motor performance, and cognitive function. Neural redundancy and plastic remodelling of brain networking, also secondary to mental and physical training, promotes maintenance of brain activity in healthy elderly for everyday life and fully productive affective and intellectual capabilities. However, age is the main risk factor for neurodegenerative disorders such as Alzheimer's disease (AD) that impact on cognition. Oscillatory electromagnetic brain activity is a hallmark of neuronal network function in various brain regions. Modern neurophysiological techniques including electroencephalography (EEG), event-related potential (ERP), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS) can accurately index normal and abnormal brain aging to facilitate non-invasive analysis of cortico-cortical connectivity and neuronal synchronization of firing and coherence of rhythmic oscillations at various frequencies. The present review provides a perspective of these issues by assaying different neurophysiological methods and integrating the results with functional brain imaging findings. It is concluded that discrimination between physiological and pathological brain aging clearly emerges at the group level, with applications at the individual level also suggested. Integrated approaches utilizing neurophysiological techniques together with biological markers and structural and functional imaging are promising for large-scale, low-cost and non-invasive evaluation of at-risk populations. Practical implications of the methods are emphasized.

Affective ERP processing in a visual oddball task: arousal, valence, and gender.

OBJECTIVE: To assess affective event-related brain potentials (ERPs) using visual pictures that were highly distinct on arousal level/valence category ratings and a response task. METHODS: Images from the International Affective Pictures System (IAPS) were selected to obtain distinct affective arousal (low, high) and valence (negative, positive) rating levels. The pictures were used as target stimuli in an oddball paradigm, with a visual pattern as the standard stimulus. Participants were instructed to press a button whenever a picture occurred and to ignore the standard. Task performance and response time did not differ across conditions. RESULTS: High-arousal compared to low-arousal stimuli produced larger amplitudes for the N2, P3, early slow wave, and late slow wave components. Valence amplitude effects were weak overall and originated primarily from the later waveform components and interactions with electrode position. Gender differences were negligible. CONCLUSION: The findings suggest that arousal level is the primary determinant of affective oddball processing, and valence minimally influences ERP amplitude. SIGNIFICANCE: Affective processing engages selective attentional mechanisms that are primarily sensitive to the arousal properties of emotional stimuli. The application and nature of task demands are important considerations for interpreting these effects.

Workload assessment of computer gaming using a single-stimulus event-related potential paradigm.

Behavioral and event-related potential (ERP) measures were used to assess cognitive workload from expert computer gamers playing a "first-person shooter" video game. Game difficulty level was manipulated in separate conditions by adjusting the number of enemies (view, easy, medium, and hard). Infrequently presented single-stimulus tones were either ignored or counted across difficulty conditions. Game performance and tone-counting accuracy declined as game difficulty increased. ERP component amplitudes diminished for both the tone ignore and counting conditions as game difficulty increased. The findings suggest that cognitive workload induced by video gaming can be reliably assessed through behavioral and neuroelectric means, and that the single-stimulus paradigm can be a useful tool for evaluating workload in an immersive stimulus environment with less distraction than conventional tools.

Affective picture processing: an integrative review of ERP findings.

The review summarizes and integrates findings from 40 years of event-related potential (ERP) studies using pictures that differ in valence (unpleasant-to-pleasant) and arousal (low-to-high) and that are used to elicit emotional processing. Affective stimulus factors primarily modulate ERP component amplitude, with little change in peak latency observed. Arousal effects are consistently obtained, and generally occur at longer latencies. Valence effects are inconsistently reported at several latency ranges, including very early components. Some affective ERP modulations vary with recording methodology, stimulus factors, as well as task-relevance and emotional state. Affective ERPs have been linked theoretically to attention orientation for unpleasant pictures at earlier components (<300 ms). Enhanced stimulus processing has been associated with memory encoding for arousing pictures of assumed intrinsic motivational relevance, with task-induced differences contributing to emotional reactivity at later components (>300 ms). Theoretical issues, stimulus factors, task demands, and individual differences are discussed.

Affective visual event-related potentials: arousal, valence, and repetition effects for normal and distorted pictures.

Event-related potentials (ERPs) were used to assess arousal (low, high), valence (negative, positive), and stimulus repetition effects for normal and distorted images from the International Affective Pictures System (IAPS). Distorted stimuli were constructed by dividing each image into small squares and rearranging the segments randomly to produce a "scrambled" picture. Event-related potentials (ERPs) were elicited by presenting the normal and scrambled images as target stimuli, with a repeated visual pattern used as the standard stimulus. Participants (N=32) were instructed to press a button to the targets and ignore the standard. Stimulus repetition effects were assessed by presenting each stimulus twice in the normal and scrambled condition. High-arousal stimuli yielded larger late positive components for both the normal and scrambled pictures. No overall valence effects were obtained, but arousal and valence influenced component amplitudes for middle-latency ERPs from the scrambled stimuli. For the normal pictures, stimulus repetition was associated with increased component amplitudes for all potentials and decreased RTs of all affective categories. For the scrambled pictures, no repetition changes were obtained. The findings suggest that stimulus arousal level contributes more than valence to affective ERP measures for normal as well as perceptually distorted pictures. Stimulus repetition engages memory for previous normal picture items but is not influenced by affective category. Theoretical implications are discussed.

Updating P300: an integrative theory of P3a and P3b.

The empirical and theoretical development of the P300 event-related brain potential (ERP) is reviewed by considering factors that contribute to its amplitude, latency, and general characteristics. The neuropsychological origins of the P3a and P3b subcomponents are detailed, and how target/standard discrimination difficulty modulates scalp topography is discussed. The neural loci of P3a and P3b generation are outlined, and a cognitive model is proffered: P3a originates from stimulus-driven frontal attention mechanisms during task processing, whereas P3b originates from temporal-parietal activity associated with attention and appears related to subsequent memory processing. Neurotransmitter actions associating P3a to frontal/dopaminergic and P3b to parietal/norepinephrine pathways are highlighted. Neuroinhibition is suggested as an overarching theoretical mechanism for P300, which is elicited when stimulus detection engages memory operations.

Affective visual event-related potentials: arousal, repetition, and time-on-task.

Affective stimulus pictures that differed in valence (unpleasant, neutral, and pleasant) were repeated as targets in an oddball task to elicit event-related potentials (ERPs) in young female adults. Each picture target was repeated consecutively four times, with picture order counterbalanced and time-on-task influences assessed across subjects. Response time decreased from the first to second stimulus presentation and remained stable. Stimulus repetition was associated with voltage increases for N1, P2, N2, and P3, from initial to subsequent presentations. Arousal effects did not interact with stimulus repetition at any latency range. Time-on-task was associated with decreased voltages for the N2 and P3 potentials but was unaffected by stimulus valence. The findings suggest affective arousal, stimulus repetition, and time-on-task independently modulate ERP outcomes at overlapping time ranges. Theoretical implications are discussed.

Meditation states and traits: EEG, ERP, and neuroimaging studies.

Neuroelectric and imaging studies of meditation are reviewed. Electroencephalographic measures indicate an overall slowing subsequent to meditation, with theta and alpha activation related to proficiency of practice. Sensory evoked potential assessment of concentrative meditation yields amplitude and latency changes for some components and practices. Cognitive event-related potential evaluation of meditation implies that practice changes attentional allocation. Neuroimaging studies indicate increased regional cerebral blood flow measures during meditation. Taken together, meditation appears to reflect changes in anterior cingulate cortex and dorsolateral prefrontal areas. Neurophysiological meditative state and trait effects are variable but are beginning to demonstrate consistent outcomes for research and clinical applications. Psychological and clinical effects of meditation are summarized, integrated, and discussed with respect to neuroimaging data.

P3a from auditory white noise stimuli.

OBJECTIVE: P3a and P3b event-related brain potentials (ERPs) were elicited with an auditory 3-stimulus (target, distracter, standard) paradigm in which subjects responded only to the target. METHODS: Distracter stimuli consisted of white noise, novel sounds, or a high frequency tone, with stimulus characteristics perceptually controlled. Task difficulty was varied as easy and hard by changing the pitch difference between the target and standard stimuli. RESULTS: Error rate was greater and response time longer for the hard task. P3a distracter amplitude was largest for the white noise and novel stimuli, with maximum amplitude over the central recording sites, and larger for the hard discrimination task. P3b target amplitude was unaffected by distracter type, maximum over the parietal recording sites, and smaller and later for the hard task. CONCLUSIONS: The findings indicate that white noise stimuli can produce reliable P3a components. SIGNIFICANCE: White noise can be useful for clinical P3a applications, as it removes the variability of stimulus novelty.

Neuropsychology and neuropharmacology of P3a and P3b.

Perspectives on the P300 event-related brain potential (ERP) are reviewed by outlining the distinction between the P3a and P3b subcomponents. The critical factor for eliciting P3a is how target/standard discrimination difficulty rather than novelty modulates task processing. The neural loci of P3a and P3b generation are sketched and a theoretical model is developed. P3a originates from stimulus-driven disruption of frontal attention engagement during task processing. P3b originates when temporal-parietal mechanisms process the stimulus information for memory storage. The neuropharmacological implications of this view are then outlined by evaluating how acute and chronic use of ethanol, marijuana, and nicotine affect P3a and P3b. The findings suggest that the circuit underlying ERP generation is influenced in a different ways for acute intake and varies between chronic use levels across drugs. Theoretical implications are assessed.

P3a from visual stimuli: task difficulty effects.

The P3a event-related brain potential (ERP) was elicited using a visual three-stimulus oddball paradigm (target, standard, distracter) in which participants responded only to the target. Discrimination task difficulty between the target and the standard was manipulated by varying the size of the standard stimulus circle relative to a constant target stimulus circle across three conditions (easy, medium, hard). A large checkerboard pattern was employed for the distracter stimulus across all tasks. Error rate and response time increased with increases in task difficulty, so that the task difficulty manipulation was successful. Distracter P3a amplitude increased and target P3b decreased somewhat with increases in task difficulty. The findings suggest that increased perceptual discrimination difficulty between the target and standard stimuli increases P3a amplitude. Theoretical implications are discussed.

Heart rate and P300: Integrating peripheral and central indices of cognitive processing.

To assess the integration of peripheral (heart rate, HR) and central (event-related potential, P300) measures of cognition, the present study varied inter-stimulus presentation time (ISI) and employed comparable data reduction methods for the HR and ERP data. Young adults (n=33) performed an auditory oddball count task in which the ISI was varied (short vs. long, to maximize target detection for both measures) and task condition (single stimulus, short-ISI oddball, long-ISI oddball, to assay stimulus presentation condition between HR and P300). The off-line cardiotachometer method parallels signal averaging and was applied to HR data reduction. The main goal was to characterize target vs. standard processing in each measurement type using appropriate recording approaches with respect to differentiating the two stimuli in each task (target vs. silence, target vs. standard short-ISI, target vs. standard long-ISI). Results demonstrated reliable differences between target/standard stimuli for both the biphasic HR (deceleration/acceleration) signal and for P300 amplitude production, with larger amplitudes for target than standard. The short and long ISIs yielded no reliable initial HR deceleration differences, but the late acceleration was observed for the long-ISI condition only. Correlational analysis between HR and P300 measures indicated that people with smaller HR deceleration had larger P300 amplitude suggesting that the larger target/standard differences for HR deceleration and P300 amplitude, observed at an experimental level, are reversed at an individual level. The contributions of simultaneously recording HR and P300 to characterize cognition and theoretical implications are discussed.

Alzheimer's disease and P300: review and evaluation of task and modality.

Early stage Alzheimer disease patients and matched elderly unaffected controls (n = 16/group) were evaluated with the P300 event-related brain potential (ERP). All subjects performed four oddball tasks that varied systematically in task difficulty and were each presented in the auditory and visual modalities. P300 amplitude was smaller and peak latency longer for the Alzheimer patients compared to elderly control subjects across tasks and modalities. P300 differences between Alzheimer patients and controls were largest for the relatively easy tasks, with little influence of stimulus modality observed. The results suggest that the P300 brain potential is sensitive to Alzheimer's disease processes during its early stages, and that easily performed stimulus discrimination tasks are the clinically most useful. Theoretical and practical implications are reviewed.

Alcoholism risk, tobacco smoking, and P300 event-related potential.

OBJECTIVE: The P300 event-related potential (ERP) is sometimes larger for individuals at low- compared to high-risk for alcoholism. These effects are inconsistent, and how P300 is affected by tobacco smoking in the context of alcoholism risk is unknown. The present study used P300 to examine the inter-relationship between alcoholism heritability and smoking status. METHODS: P300 was elicited with a visual discrimination task from young adults at low- and high-risk for alcoholism. Half of the subjects in each risk category reported that they did not smoke cigarettes, and the other half reported that they smoked regularly, with equal numbers of male and female subjects assessed. ERPs were recorded, and subjects were instructed to respond only to an infrequently presented target stimulus that occurred in a series of standard and distracter stimuli. RESULTS: P300 amplitude from the target stimuli was larger for the low-risk compared to high-risk subjects overall. However, smoking status demonstrated even stronger effects, with non-smokers producing consistently larger component amplitudes than smokers and accounting for more variance than alcoholism risk. These group factors also significantly affected P300 scalp topography. No reliable alcoholism risk or smoking group effects were obtained for the ERPs from the other stimuli. CONCLUSIONS: The findings suggest that P300 measures of alcoholism risk in young adults are moderated by smoking status. Theoretical implications are discussed.