Central adaptations to repetitive grasping in healthy aging.

Augmented cortical activity during repetitive grasping mitigates repetition-related decrease in cortical efficiency in young adults. It is unclear if similar processes occur with healthy aging. We recorded movement-related cortical potentials (MRCP) during 150 repetitive handgrip contractions at 70% of maximal voluntary contraction (MVC) in healthy young (n = 10) and old (n = 10) adults. Repetitions were grouped into two Blocks (Block 1 and 2: repetitions 1-60 and 91-150, respectively) and analyzed separately to assess the effects of aging and block. EMG of the flexor digitorum superficialis and handgrip force were also recorded. No changes in EMG or MVC were observed across blocks for either group. Significant interactions (P < 0.05) were observed for MRCPs recorded from mesial (FCz, Cz, CPz) and motor (C1, C3, Cz) electrode sites, with younger adults demonstrating significant increases in MRCP amplitude. Focal MRCP activity in response to repetitive grasping resulted in minimal changes (i.e. Block 1 versus Block 2) in older adults. Central adaptive processes change across the lifespan, showing increasingly less focal activation in older adults during repetitive grasping. Our findings are consistent with previous paradigms demonstrating more diffuse cortical activation during motor tasks in older adults.

Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence.

BACKGROUND: Endophenotypes reflect more proximal effects of genes than diagnostic categories, hence providing a more powerful strategy in searching for genes involved in complex psychiatric disorders. There is strong evidence suggesting the P3 amplitude of the event-related potential (ERP) as an endophenotype for the risk of alcoholism and other disinhibitory disorders. Recent studies demonstrated a crucial role of corticotropin releasing hormone receptor 1 (CRHR1) in the environmental stress response and ethanol self-administration in animal models. The aim of the present study was to test the potential associations between single-nucleotide polymorphisms (SNPs) in the CRHR1 gene and the quantitative trait, P3 amplitude during the processing of visual target signals in an oddball paradigm, as well as alcohol dependence diagnosis. METHODS: We analyzed a sample from the Collaborative Study on the Genetics of Alcoholism (COGA) comprising 1049 Caucasian subjects from 209 families (including 472 alcohol-dependent individuals). Quantitative transmission disequilibrium test (QTDT) and family-based association test (FBAT) were used to test the association, and false discovery rate (FDR) was applied to correct for multiple comparisons. RESULTS: Significant associations (p < 0.05) were found between the P3 amplitude and alcohol dependence with multiple SNPs in the CRHR1 gene. CONCLUSIONS: Our results suggest that CRHR1 may be involved in modulating the P3 component of the ERP during information processing and in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders.

Obesity, smoking, and frontal brain dysfunction.

Obesity, smoking, and conduct problems have all been associated with decrements in brain function. However, their additive and interactive effects have rarely been examined. To address the deficiency, we studied P300a and P300b electroencephalographic potentials in 218 women grouped by the presence versus absence of: (1) a BMI > or = 30 kg/m(2); (2) recent smoking; and (3) > or = 2 childhood conduct problems. Analyses revealed smaller P300a and P300b amplitudes over the posterior scalp among recent smokers versus nonsmokers. No corresponding group differences were found in P300 latencies or frontal scalp amplitudes. The most interesting analysis result was an interaction between conduct problems and obesity limited to the frontally generated P300a component: its latency was significantly greater in women with both attributes than in those with either or neither attribute. An exploratory ANOVA, substituting the genotype of a GABRA2 SNP for conduct problems, also demonstrated an interaction with obesity affecting P300a latency. It is hypothesized that conduct problems, and a conduct-problem-associated GABRA2 genotype, decrease the age-of-onset and/or increase the lifetime duration of obesity. As a result, they may potentiate the adverse effects of obesity on frontal white matter and thereby increase P300a latency. Smoking may affect brain function by a different mechanism to reduce posterior scalp P300a and P300b amplitudes while preserving frontal scalp P300a latency and amplitude.

Resistance training induces supraspinal adaptations: evidence from movement-related cortical potentials.

Early effects of a resistance training program include neural adaptations at multiple levels of the neuraxis, but direct evidence of central changes is lacking. Plasticity exhibited by multiple supraspinal centers following training may alter slow negative electroencephalographic activity, referred to as movement-related cortical potentials (MRCP). The purpose of this study was to determine whether MRCPs are altered in response to resistance training. Eleven healthy participants (24.6 +/- 3.5 years) performed 3 weeks of explosive unilateral leg extensor resistance training. MRCP were assessed during 60 self-paced leg extensions against a constant nominal load before and after training. Resistance training was effective (P < 0.001) in increasing leg extensor peak force (+22%), rate of force production (+32%) as well as muscle activity (iEMG; +47%, P < 0.05). These changes were accompanied by several MRCP effects. Following training, MRCP amplitude was attenuated at several scalp sites overlying motor-related cortical areas (P < 0.05), and the onset of MRCP at the vertex was 28% (561 ms) earlier. In conclusion, the 3-week training protocol in the present study elicited significant strength gains which were accompanied by neural adaptations at the level of the cortex. We interpret our findings of attenuated cortical demand for submaximal voluntary movement as evidence for enhanced neural economy as a result of resistance training.

Priming deficiency in male subjects at risk for alcoholism: the N4 during a lexical decision task.

BACKGROUND: While there is extensive literature on the relationship between the P3 component of event-related potentials (ERPs) and risk for alcoholism, there are few published studies regarding other potentially important ERP components. One important candidate is the N4(00) component in the context of semantic processing, as abnormalities in this component have been reported for adult alcoholics. METHOD: A semantic priming task was administered to nonalcohol dependent male offspring (18 to 25 years) of alcoholic fathers [high risk (HR) n = 23] and nonalcoholic fathers [low risk (LR) n = 28] to study whether the 2 groups differ in terms of the N4 component. Subjects were presented with 150 words and 150 nonwords. Among the words, 50 words (primed) were preceded by their antonyms (prime, n = 50), whereas the remaining 50 words were unprimed. For the analysis, N4 amplitude and latency as well as behavioral measures for the primed and unprimed words were considered. RESULTS: A significant interaction effect was observed between semantic condition and group, where HR subjects did not show N4 attenuation for primed stimuli. CONCLUSION: The lack of N4 attenuation to primed stimuli and/or inability to differentiate between primed and unprimed stimuli, without latency and reaction time being affected, suggest deficits in semantic priming, especially in semantic expectancy and/or postlexical semantic processing in HR male offspring. Further, it indicates that it might be an electrophysiological endophenotype that reflects genetic vulnerability to develop alcoholism.

Effects of Parkinson disease and antiparkinson medication on central adaptations to repetitive grasping.

Cortical activity during motor task performance is attenuated in individuals with Parkinson disease (PD) relative to age-matched adults without PD, and this activity is enhanced with antiparkinson medication. It remains unclear, however, whether the relative change in cortical activity over the duration of the task, i.e., central adaptation, is affected individuals with PD, and if so, whether medication corrects for any unique behaviors. Movement-related cortical potentials (MRCPs) were recorded from scalp electrode sites Cz and C1 during 150 repetitive handgrip contractions at 70% of maximal voluntary contraction, in individuals with PD (n = 10) both ON and OFF of their PD medication, and neurologically normal age- and sex-matched controls (n = 10). Repetitions were divided into two Blocks (Block 1 and 2: repetitions 1-60 and 91-150, respectively), and the composite MRCP slopes were calculated during periods representing movement initiation (-2 s to movement onset) and execution (movement onset to 1 s). No significant interactions were noted for either comparison (PD OFF vs. control; PD OFF vs. PD ON), irrespective of electrode site (Cz or C1) or movement period (initiation or execution). Despite similar MRCP slopes and task performance, PD OFF endorsed greater perceived exertion during task performance than controls. In the present study, we observed attenuated task-related cortical activity among individuals with PD OFF relative to controls, but a similar relative adaptive response to a fatiguing task. Additionally, although antiparkinson medication enhanced cortical activity (PD OFF vs. PD ON), central adaptation was similar.

Heritability of EEG coherence in a large sib-pair population.

The additive genetic heritability of bipolar EEG coherence in a sample of 305 non-twin sibships comprising 690 individuals (age range 7-65) was estimated. Heritabilities were examined in 6 frequency bands for each of 15 coherence pairs, both interhemispheric and intrahemispheric. The heritabilities of the bipolar EEG coherence ranged from 0.22 to 0.63 in 79 of the 90 phenotypes which had coherences high enough to provide meaningful values for the estimation of heritability. Heritabilities were greatest in the low and high alpha frequency bands, while theta and beta bands had comparable heritabilities. Coherences themselves were greatest in the low and high alpha frequency bands, while theta coherences were somewhat larger than beta. Higher heritability values were not associated with higher coherences. The examination of bivariate genetic correlations suggests that there is a difference between theta and alpha bands in genetic control of interhemispheric coherence.

Genetic influences on bipolar EEG power spectra.

The EEG bipolar power spectra provide more localization than spectral measures obtained from monopolar referencing strategies, and have been shown to be useful endophenotypes of psychiatric disorders such as alcoholism. We estimated the additive genetic heritability of resting bipolar EEG power spectra in a large sample of non-twin sibling pairs. The corresponding heritabilities ranged between 0.220 and 0.647 and were highly significant at all 38 electrode pairs for theta (3-7 Hz), low-alpha (7-9 Hz), high-alpha (9-12 Hz), low-beta (12-16 Hz), middle-beta (16-20 Hz) and high-beta (20-28 Hz) frequency bands. The heritabilities were the highest in the high-alpha and low-beta bands at most electrode pairs. The heritabilities were most variable across the head in the three beta bands. Other heritability patterns were also identified within each frequency band. Our results suggest that substantial proportions of the variability in the bipolar EEG measures are explained by genetic factors.

Delta and theta oscillations as risk markers in adolescent offspring of alcoholics.

BACKGROUND: Visual P300 is consistently lower in alcohol-dependent individuals, their offspring and subjects at risk. Delta and theta event-related oscillations (ERO) are the major contributors to the P300 signal. The total and evoked power in delta and theta bands in the 300 to 700 ms post-stimulus window (corresponding to the zone of P300 maxima) was compared between adolescent offspring of alcoholics (high-risk) and age-matched normal controls (low-risk), to assess the utility of the risk markers. METHODS: EEG was recorded during the performance of a visual oddball task. The S-transform algorithm decomposed the EEG signals into different frequency bands and the group differences in total and evoked power in the oscillatory responses during the P300 time window (300 to 700 ms) were analyzed using a multivariate design. Similar analysis was performed on P300 peak amplitude for the target. RESULTS: The high-risk group showed significantly lower parietal post-stimulus evoked and total power in the delta band for targets. A decrease in total power was seen centrally and parietally in the theta band. The P300 peak amplitude in the parietal electrodes was also significantly lower in the high-risk group. CONCLUSIONS: The decreased total theta power and total and evoked delta power for visual targets in high risk individuals may serve as an endophenotypic marker in the development of alcoholism and other disinhibitory disorders. The differences seen between the offspring of alcoholics and controls may have a cholinergic basis. The ERO measures appear to be more robust than the P300 amplitude in differentiating the groups.

Rapid discrimination of visual scene content in the human brain.

The rapid evaluation of complex visual environments is critical for an organism's adaptation and survival. Previous studies have shown that emotionally significant visual scenes, both pleasant and unpleasant, elicit a larger late positive wave in the event-related brain potential (ERP) than emotionally neutral pictures. The purpose of the present study was to examine whether neuroelectric responses elicited by complex pictures discriminate between specific, biologically relevant contents of the visual scene and to determine how early in the picture processing this discrimination occurs. Subjects (n = 264) viewed 55 color slides differing in both scene content and emotional significance. No categorical judgments or responses were required. Consistent with previous studies, we found that emotionally arousing pictures, regardless of their content, produce a larger late positive wave than neutral pictures. However, when pictures were further categorized by content, anterior ERP components in a time window between 200 and 600 ms following stimulus onset showed a high selectivity for pictures with erotic content compared to other pictures regardless of their emotional valence (pleasant, neutral, and unpleasant) or emotional arousal. The divergence of ERPs elicited by erotic and non-erotic contents started at 185 ms post-stimulus in the fronto-central midline region, with a later onset in parietal regions. This rapid, selective, and content-specific processing of erotic materials and its dissociation from other pictures (including emotionally positive pictures) suggests the existence of a specialized neural network for prioritized processing of a distinct category of biologically relevant stimuli with high adaptive and evolutionary significance.

Evoked gamma band response in male adolescent subjects at high risk for alcoholism during a visual oddball task.

This study investigates early evoked gamma band activity in male adolescent subjects at high risk for alcoholism (HR; n=68) and normal controls (LR; n=27) during a visual oddball task. A time-frequency representation method was applied to EEG data in order to obtain stimulus related early evoked (phase-locked) gamma band activity (29-45 Hz) and was analyzed within a 0-150 ms time window range. Significant reduction of the early evoked gamma band response in the frontal and parietal regions during target stimulus processing was observed in HR subjects compared to LR subjects. Additionally, the HR group showed less differentiation between target and non-target stimuli in both frontal and parietal regions compared to the LR group, indicating difficulty in early stimulus processing, probably due to a dysfunctional frontoparietal attentional network. The results indicate that the deficient early evoked gamma band response may precede the development of alcoholism and could be a potential endophenotypic marker of alcoholism risk.

Cardiorespiratory interactions: Noncontact assessment using laser Doppler vibrometry.

The application of a noncontact physiological recording technique, based on the method of laser Doppler vibrometry (LDV), is described. The effectiveness of the LDV method as a physiological recording modality lies in the ability to detect very small movements of the skin, associated with internal mechanophysiological activities. The method is validated for a range of cardiovascular variables, extracted from the contour of the carotid pulse waveform as a function of phase of the respiration cycle. Data were obtained from 32 young healthy participants, while resting and breathing spontaneously. Individual beats were assigned to four segments, corresponding with inspiration and expiration peaks and transitional periods. Measures relating to cardiac and vascular dynamics are shown to agree with the pattern of effects seen in the substantial body of literature based on human and animal experiments, and with selected signals recorded simultaneously with conventional sensors. These effects include changes in heart rate, systolic time intervals, and stroke volume. There was also some evidence for vascular adjustments over the respiration cycle. The effectiveness of custom algorithmic approaches for extracting the key signal features was confirmed. The advantages of the LDV method are discussed in terms of the metrological properties and utility in psychophysiological research. Although used here within a suite of conventional sensors and electrodes, the LDV method can be used on a stand-alone, noncontact basis, with no requirement for skin preparation, and can be used in harsh environments including the MR scanner.

Beta power in the EEG of alcoholics.

BACKGROUND: In this study, the magnitude and spatial distribution of beta power in the resting electroencephalogram (EEG) were examined to address the possibility of an excitation-inhibition imbalance in the central nervous system of alcoholics. METHODS: Log transformed absolute power in the Beta 1 (12.5-16 Hz), Beta 2 (16.5-20 Hz), and Beta 3 (20.5-28 Hz) bands in the eyes-closed EEG of 307 alcohol-dependent subjects and 307 unaffected age- and gender-matched control subjects were compared using a multivariate repeated measures design. Effect of gender, age, and drinking variables was examined separately. RESULTS: Increased Beta 1 (12.5-16 Hz) and Beta 2 (16.5-20 Hz) absolute power was observed in alcohol-dependent subjects at all loci over the scalp. The increase was most prominent in the central region. Increased Beta 3 (20.5-28 Hz) power was frontal in the alcoholics. Age and clinical variables did not influence the increase. Male alcoholics had significantly higher beta power in all three bands. In female alcoholics the increase did not reach statistical significance. CONCLUSIONS: Beta power in all three bands of resting EEG is elevated in alcoholics. This feature is more prominent in male alcoholics. The increased beta power in the resting EEG may be an electrophysiological index of the imbalance in the excitation-inhibition homeostasis in the cortex.

Neurophysiological efficiency in male and female alcoholics.

Chronic alcoholics often exhibit impairment in behavioral indicators of cognitive efficiency. However, potential neurophysiological correlates of this deficit are understudied. To examine this function, semantic expectancy was measured by recording the N400 component of the event-related potential (ERP), which is elicited by incongruent semantic information. Abstinent alcoholics, 21-45 days sober (n = 26; 12 males, 14 females), as well as age and education equated community controls (n = 26; 12 males, 14 females), were instructed to read silently 218 sentences ending with either congruent, related/incongruent, or unrelated/incongruent terminal words. Difference waveforms to the terminal word were derived, and amplitude and latency measures of the most negative peak between 300 and 600 ms were obtained. Electrode sites included the midline sites, Fz, Cz, and Pz; the temporal sites T3 and T4; and parietal sites P3 and P4. Significant group effects in amplitude were observed for the difference waveform under the unrelated/incongruent condition at T3, T4, and P4 (P < or = .05). Measures at P3, Pz, Fz, and Cz approached significance (P < or = .15). Although the overall pattern did not change when regression techniques were used to control for age, only the T4 site retained significance (P < or = .05). Across all electrode sites, alcoholics produced reduced N400 amplitudes relative to community controls. Latency was unaffected. There were no group effects for amplitude or latency measures in the related/incongruent condition. These data are consistent with the hypothesis that alcoholics suffer from a subtle deficiency in neurophysiologically based cognitive efficiency which renders them less likely to respond appropriately to irrelevant information.

Linkage and linkage disequilibrium mapping of ERP and EEG phenotypes.

Linkage analyses of highly heritable electrophysiological phenotypes (EEG, ERP) that can potentially identify individuals at risk for alcoholism were performed on a large sample of families with a high density of alcohol dependence as part of the Collaborative Study on the Genetics of Alcoholism (COGA); these genetic findings are summarized. Quantitative trait loci (QTLs) were identified for several ERP characteristics (P300, N100, N400) and for the beta frequencies of the EEG where we report linkage and linkage disequilibrium at a GABA(A) receptor gene on chromosome 4. Genetic analyses of ERPs suggest that several regions of the human genome contain genetic loci related to the generation of N100, N400 and P300, which are possible candidate loci underlying the functional organization of human neuroelectric activity. The advent of genomics and proteomics and a fuller understanding of gene regulation, will open new horizons on the critical electrical events so essential for human brain function.

Resting EEG in offspring of male alcoholics: beta frequencies.

This study examines the differences in beta (12-28 Hz) band power in offspring of male alcoholics from densely affected alcoholic families. We have attempted to investigate if the increase in beta power is a 'state' or 'trait' marker for alcoholism. This study also explores the gender differences in the expression of this potential risk marker. Absolute beta power in three bands-beta 1(12-16 Hz), beta 2 (16-20 Hz), and beta 3 (20-28 Hz)-in the eyes closed EEG of 171 high risk (HR) subjects who were offspring of male alcoholics and 204 low risk (LR) subjects with no family history of alcoholism, were compared for each gender separately using a repeated measures analysis of variance design. Alcoholic and non-alcoholic subjects within the high risk group were compared using a repeated measures design as a follow-up analysis. The present study demonstrated increased beta power in the resting EEG of offspring of male alcoholics. Male HR subjects had higher beta 1 (12-16 Hz) power and female HR subjects had increased power in beta 2 (16-20 Hz) and beta 3 (20-28 Hz) as compared with low risk participants. Female HR subjects also showed significantly increased beta 2 and beta 3 power if they had two or more alcoholic first-degree relatives when compared with HR females having only an affected father. Risk characteristics are expressed differentially in males and females and may be an index of differential vulnerability to alcoholism. The results indicate that increased EEG beta power can be considered as a likely marker of risk for developing alcoholism and may be used as a predictive endophenotype.

Linkage and linkage disequilibrium of evoked EEG oscillations with CHRM2 receptor gene polymorphisms: implications for human brain dynamics and cognition.

Event-related oscillations (ERO) offer an alternative theoretical and methodological approach to the analysis of event-related EEG responses. The P300 event-related potential (ERP) is elicited through the superposition of the delta (1-3 Hz) and theta (3-7 Hz) band oscillatory responses. The cholinergic neurotransmitter system has a key function in modulating excitatory post-synaptic potentials caused by glutamate, and therefore influences P300 generation and the underlying oscillatory responses. Here we report significant linkage and linkage disequilibrium between target case frontal theta band, visual evoked brain oscillations and a single nucleotide polymorphism (SNP) from the cholinergic muscarinic receptor gene (CHRM2) on chromosome 7. We also demonstrate significant linkage disequilibrium between CHRM2 SNPs and target case parietal delta band visual evoked oscillations (LD P<0.001). These findings were not observed for the equivalent non-target case data, suggesting a role for the CHRM2 gene in higher cognitive processing in humans.

The relationship between two intermediate phenotypes for alcoholism: low voltage alpha EEG and low P300 ERP amplitude.

OBJECTIVE: There is considerable evidence that the amplitude of the heritable P300 event-related potential (ERP) is reduced in alcoholics and their alcohol-naive children. Low voltage alpha (LVA), a heritable resting electroencephalogram (EEG) trait present in 7-14% of the population, has been shown to be associated with alcoholism and anxiety disorders. A few studies have demonstrated a modest correlation between pre-stimulus alpha power and P300 amplitude. We aimed to test this finding in community volunteers, hypothesizing that LVA would be associated with low P300 amplitude. METHOD: Digitized resting EEG was recorded at the central parietal site (Pz) from 85 male and 113 female community volunteers (120 unrelated). ERPs were elicited at Pz by auditory and visual oddball paradigms. All participants were interviewed with the Schedule for Affective Disorders, Lifetime Version (SADS-L) and assigned blind-rated psychiatric diagnoses according to the American Psychiatric Association DSM-III-R criteria. RESULTS: LVA participants (including alcoholics and nonalcoholics) had significantly lower auditory and visual P300 amplitudes. Absolute alpha power was modestly correlated with auditory and visual P300 amplitude and was associated with 9.4% and 4.6% of the variance, respectively. CONCLUSIONS: The association between LVA and low P300 amplitude, two distinct electrophysiological traits, suggests that, at least in individuals with the LVA trait, some aspects of resting, unstimulated brain activity and activated brain function in the form of attentional response may be fundamentally related.

Effects of lifetime ethanol consumption on postural control: a computerized dynamic posturography study.

The relationship between lifetime alcohol consumption and postural control was investigated in 35 subjects with no clinically-detectable neurologic abnormalities, using computerized dynamic posturography (CDP) procedures. The estimated total number of lifetime alcoholic drinks was positively correlated with anteroposterior sway spectral power within the 2-4 Hz and 4-6 Hz frequency bands, in three Sensory Organization Test (SOT) conditions: eyes closed with stable support surface (SOT 2), eyes open with sway-referenced support (SOT 4), and eyes closed with sway-referenced support (SOT 5). All correlations remained significant after controlling for subject age, and were increased after excluding nine drug-abusing subjects. In contrast to the strong findings for frequency-based measures, no correlation was observed using conventional amplitude-based sway measures. These results suggest that 1) alcohol consumption compromises postural control in an exposure-dependent manner, and 2) sway frequency analysis reveals pathological processes not manifested in conventional CDP measures of sway amplitude.

Novel Applications of Laser Doppler Vibration Measurements to Medical Imaging.

Laser Doppler Vibrometry (LDV) has been widely used in engineering applications involving non-contact vibration and sound measurements. This technique has also been used in some biomedical applications including hearing research. The detectable frequencies are in the range of near-DC to 1 GHz or higher. This paper reviews applications of LDV in biomedical engineering and proposes new medical imaging applications based on measuring surface vibrations of tissues and organs. Tests were conducted on human skin using single point and scanning laser vibrometers. These tests suggest that skin vibrations due to the forcing excitation from the heart can be used in imaging of blood flow. The results of these tests illustrate the potential of such vibration measurements in a variety of diagnostic medical imaging applications including blood flow/restrictions, real-time monitoring of blood pressure variations, wound healing, muscle movements, etc. The fact that the measurements can be conducted remotely (non-contact) is an important benefit that adds to the promise of this approach.