Event-related potential correlates of mindfulness meditation competence.

OBJECTIVE: This cross-sectional study evaluated event-related potentials (ERPs) across three groups: naïve, novice, and experienced meditators as potential physiological markers of mindfulness meditation competence. METHODS: Electroencephalographic (EEG) data were collected during a target tone detection task and a Breath Counting task. The Breath Counting task served as the mindfulness meditation condition for the novice and experienced meditator groups. Participants were instructed to respond to target tones with a button press in the first task (Tones), and then ignore the primed tones while Breath Counting. The primary outcomes were ERP responses to target tones, namely the N2 and P3, as markers of stimulus discrimination and attention, respectively. RESULTS: As expected, P3 amplitudes elicited by target tones were attenuated within groups during the Breath Counting task in comparison to the Tones task (p<.001). There was a task by group interaction for P3 (p=.039). Both meditator groups displayed greater change in peak-to-trough P3 amplitudes, with higher amplitudes during the Tones condition and more pronounced reductions in P3 amplitudes during the Breath Counting meditation task in comparison to the naïve group. CONCLUSIONS: Meditators had stronger P3 amplitude responses to target tones when instructed to attend to the tones, and a greater attenuation of P3 amplitudes when instructed to ignore the same tones during the Breath Counting task. This study introduces the idea of identifying ERP markers as a means of measuring mindfulness meditation competence, and results suggest this may be a valid approach. This information has the potential to improve mindfulness meditation interventions by allowing objective assessment of mindfulness meditation quality.

Improved accuracy using recursive bayesian estimation based language model fusion in ERP-based BCI typing systems.

RSVP Keyboard™ is an electroencephalography (EEG) based brain computer interface (BCI) typing system, designed as an assistive technology for the communication needs of people with locked-in syndrome (LIS). It relies on rapid serial visual presentation (RSVP) and does not require precise eye gaze control. Existing BCI typing systems which uses event related potentials (ERP) in EEG suffer from low accuracy due to low signal-to-noise ratio. Henceforth, RSVP Keyboard™ utilizes a context based decision making via incorporating a language model, to improve the accuracy of letter decisions. To further improve the contributions of the language model, we propose recursive bayesian estimation, which relies on non-committing string decisions, and conduct an offline analysis, which compares it with the existing naïve bayesian fusion approach. The results indicate the superiority of the recursive bayesian fusion and in the next generation of RSVP Keyboard™ we plan to incorporate this new approach.

On Visually Evoked Potentials in EEG Induced by Multiple Pseudorandom Binary Sequences for Brain Computer Interface Design.

Visually evoked potentials have attracted great attention in the last two decades for the purpose of brain computer interface design. Visually evoked P300 response is a major signal of interest that has been widely studied. Steady state visual evoked potentials that occur in response to periodically flickering visual stimuli have been primarily investigated as an alternative. There also exists some work on the use of an m-sequence and its shifted versions to induce responses that are primarily in the visual cortex but are not periodic. In this paper, we study the use of multiple m-sequences for intent discrimination in the brain interface, as opposed to a single m-sequence whose shifted versions are to be discriminated from each other. Specifically we used four different m-sequences of length 31. Our main goal is to study if the bit presentation rate of the m-sequences have an impact on classification accuracy and speed. In this initial study, where we compared two basic classifier schemes using EEG data acquired with 15Hz and 30Hz bit presentation rates, our results are mixed; while on one subject, we got promising results indicating bit presentation rate could be increased without decrease in classification accuracy; thus leading to a faster decision-rate in the brain interface, on our second subject, this conclusion is not supported. Further detailed experimental studies as well as signal processing methodology design, especially for information fusion across EEG channels, will be conducted to investigate this question further.

A randomized placebo-controlled trial of Ginkgo biloba for the prevention of cognitive decline.

OBJECTIVE: To assess the feasibility, safety, and efficacy of Ginkgo biloba extract (GBE) on delaying the progression to cognitive impairment in normal elderly aged 85 and older. METHODS: Randomized, placebo-controlled, double-blind, 42-month pilot study with 118 cognitively intact subjects randomized to standardized GBE or placebo. Kaplan-Meier estimation, Cox proportional hazard, and random-effects models were used to compare the risk of progression from Clinical Dementia Rating (CDR) = 0 to CDR = 0.5 and decline in episodic memory function between GBE and placebo groups. RESULTS: In the intention-to-treat analysis, there was no reduced risk of progression to CDR = 0.5 (log-rank test, p = 0.06) among the GBE group. There was no less of a decline in memory function among the GBE group (p = 0.05). In the secondary analysis, where we controlled the medication adherence level, the GBE group had a lower risk of progression from CDR = 0 to CDR = 0.5 (HR = 0.33, p = 0.02), and a smaller decline in memory scores (p = 0.04). There were more ischemic strokes and TIAs in the GBE group (p = 0.01). CONCLUSIONS: In unadjusted analyses, Ginkgo biloba extract (GBE) neither altered the risk of progression from normal to Clinical Dementia Rating (CDR) = 0.5, nor protected against a decline in memory function. Secondary analysis taking into account medication adherence showed a protective effect of GBE on the progression to CDR = 0.5 and memory decline. Results of larger prevention trials taking into account medication adherence may clarify the effectiveness of GBE. More stroke and TIA cases observed among the GBE group requires further study to confirm.

Adherence to yoga and exercise interventions in a 6-month clinical trial.

BACKGROUND: To determine factors that predict adherence to a mind-body intervention in a randomized trial. DESIGN: We analyzed adherence data from a 3-arm trial involving 135 generally healthy seniors 65-85 years of age randomized to a 6-month intervention consisting of: an Iyengar yoga class with home practice, an exercise class with home practice, or a wait-list control group. Outcome measures included cognitive function, mood, fatigue, anxiety, health-related quality of life, and physical measures. Adherence to the intervention was obtained by class attendance and biweekly home practice logs. RESULTS: The drop-out rate was 13%. Among the completers of the two active interventions, average yoga class attendance was 77% and home practice occurred 64% of all days. Average exercise class attendance was 69% and home exercise occurred 54% of all days. There were no clear effects of adherence on the significant study outcomes (quality of life and physical measures). Class attendance was significantly correlated with baseline measures of depression, fatigue, and physical components of health-related quality of life. Significant differences in baseline measures were also found between study completers and drop-outs in the active interventions. Adherence was not related to age, gender, or education level. CONCLUSION: Healthy seniors have good attendance at classes with a physically active intervention. Home practice takes place over half of the time. Decreased adherence to a potentially beneficial intervention has the potential to decrease the effect of the intervention in a clinical trial because subjects who might sustain the greatest benefit will receive a lower dose of the intervention and subjects with higher adherence rates may be functioning closer to maximum ability before the intervention. Strategies to maximize adherence among subjects at greater risk for low adherence will be important for future trials, especially complementary treatments requiring greater effort than simple pill-taking.

Ginkgo biloba for the improvement of cognitive performance in multiple sclerosis: a randomized, placebo-controlled trial.

OBJECTIVES: To determine if Ginkgo biloba (GB) improves the cognitive performance of subjects with multiple sclerosis (MS). METHODS: Randomized, double-blind, placebo-controlled trial of GB, 120 mg twice a day or placebo for 12 weeks. The primary outcomes were: the long delay free recall from the California Verbal Learning Test-II; the Paced Auditory Serial Addition Test; the Controlled Oral Word Association Test; the Symbol Digit Modalities Test; Useful Field of View Test; and the color-word interference condition from the Stroop Color and Word Test. RESULTS: On completion, the GB group (n=20) was 4.5 seconds (95% confidence interval (CI) (7.6, 0.9), P=0.015) faster than the placebo group (n=18) on the color-word interference condition of the Stroop test. Subjects who were more impaired at baseline experienced more improvement with GB (treatment*baseline interaction, F=8.10, P=0.008). We found no differences on the other neuropsychological tests. Subjects on GB reported fewer cognitive difficulties in the Retrospective Memory Scale of the Perceived Deficits Questionnaire than subjects on placebo (1.5 points, 95% CI (2.6, 0.3), P=0.016). No serious drug related side-effects occurred and GB did not alter platelet function assays. CONCLUSION: Overall, GB did not show a statistically significant improvement in cognitive function. A treatment effect trend, limited to the Stroop test, suggests that GB may have an effect on cognitive domains assessed by this test, such as susceptibility to interference and mental flexibility.

Vigilance, alertness, or sustained attention: physiological basis and measurement.

Vigilance is a term with varied definitions but the most common usage is sustained attention or tonic alertness. This usage of vigilance implies both the degree of arousal on the sleep-wake axis and the level of cognitive performance. There are many interacting neural and neurotransmitter systems that affect vigilance. Most studies of vigilance have relied on states where the sleep-wake state is altered, e.g. drowsiness, sleep-deprivation, and CNS-active drugs, but there are factors ranging from psychophysics to motivation that may impact vigilance. While EEG is the most commonly studied physiologic measure of vigilance, various measures of eye movement and of autonomic nervous system activity have also been used. This review paper discusses the underlying neural basis of vigilance and its assessment using physiologic tools. Since, assessment of vigilance requires assessment of cognitive function this aspect is also discussed.

Cortical excitability and age-related volumetric MRI changes.

OBJECTIVE: Normative data on transcranial magnetic stimulation (TMS)-derived measures of cortical excitability in the elderly is sparse. Nevertheless, elderly subjects are included as controls in studies utilizing TMS to investigate disease states. Age-associated increased ventricular cerebrospinal fluid CSF (vCSF) and white matter hyperintensity (WMH) MRI volumes have uncertain significance in non-demented elderly. Information regarding cortical excitability in neurologically intact elderly would augment our understanding of the pathophysiology of aging and assist in the interpretation of TMS studies involving elderly subjects. METHODS: Twenty-four healthy elderly subjects underwent TMS testing to determine outcomes of resting motor threshold (RMT) cortical silent period (cSP) and central motor conduction time for examination in relation to WMH, vCSF, and CNS volumes. RESULTS: Increased vCSF and WMH volumes were associated with decreased right and left hemisphere RMT. Smaller CNS volumes were associated with decreased right hemisphere RMT and shorted cSP. CONCLUSIONS: Commonly observed age-associated MRI changes are associated with findings consistent with increased cortical excitability. SIGNIFICANCE: Age-related MRI findings likely reflect changes at a cellular level, and may influence cognitive and motor integrity in the elderly. Future TMS studies investigating cortical excitability may wish to consider neuroimaging markers of neurodegeneration prior to enrolling elderly subjects as controls.

Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers.

OBJECTIVE: To evaluate the cognitive effects of topiramate (TPM) and gabapentin (GBP). METHODS: Forty healthy volunteers were randomized to a 12-week course of TPM, GBP, or placebo. Doses were gradually escalated over 10 weeks to a maximum of 400 mg/day of TPM or 3,600 mg/day of GBP or to the highest tolerated dose. Subjects were interviewed and examined biweekly. Cognitive testing was performed prior to initiating the drug and again 12 weeks later, at least 2 weeks after achieving plateau dosing. For each subject and cognitive measure, test-retest Z scores were calculated based on regression equations derived from 73 healthy volunteers. Group comparisons utilized the Wilcoxon test. RESULTS: There were significant TPM vs GBP and TPM vs placebo differences in test-retest Z scores for four of six target cognitive measures (Digit Symbol, Story Recall, Selective Reminding, Controlled Oral Word Association), always indicating worse retest performance for subjects receiving TPM. Overall, 12 of 24 cognitive measures were similarly affected. TPM effects were large, and several target measures averaged >2 SD of negative change. One measure was significantly affected by GBP. CONCLUSIONS: Topiramate (TPM) impaired cognitive test performance, whereas gabapentin had minimal effects. The effects of TPM were of sufficient magnitude potentially to affect daily and occupational function.

Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers.

We studied the EEG and cognitive effects of oxcarbazepine (OXC) and phenytoin (PHT) using a double-blind, randomized, parallel-group design. Thirty-two healthy volunteers received a maximum of 1200 mg of OXC or 360 mg of PHT. EEG and cognitive testing were performed at baseline and after 12 weeks of treatment. For each subject and measure, test-retest Z scores were calculated from regression equations derived from 73 healthy controls. Twenty-six subjects completed the study. Both the OXC and PHT groups had significant slowing of the EEG peak frequency and increased relative theta and delta power. Differences between AEDs (antiepileptic drugs) were not significant. Significant cognitive effects were seen on 5 of 20 measures, primarily measures of motor speed and reaction time. Again, there were no significant differences between AEDs. The only significant difference between AEDs was for the POMS-Vigor scale, favoring OXC. The small sample size may have contributed to the lack of significant differences between AEDs.

Randomized controlled trial of yoga and exercise in multiple sclerosis.

OBJECTIVE: To determine the effect of yoga and of aerobic exercise on cognitive function, fatigue, mood, and quality of life in multiple sclerosis (MS). METHODS: Subjects with clinically definite MS and Expanded Disability Status Score less than or equal to 6.0 were randomly assigned to one of three groups lasting 6 months: weekly Iyengar yoga class along with home practice, weekly exercise class using a stationary bicycle along with home exercise, or a waiting-list control group. Outcome assessments performed at baseline and at the end of the 6-month period included a battery of cognitive measures focused on attention, physiologic measures of alertness, Profile of Mood States, State-Trait Anxiety Inventory, Multi-Dimensional Fatigue Inventory (MFI), and Short Form (SF)-36 health-related quality of life. RESULTS: Sixty-nine subjects were recruited and randomized. Twelve subjects did not finish the 6-month intervention. There were no adverse events related to the intervention. There were no effects from either of the active interventions on either of the primary outcome measures of attention or alertness. Both active interventions produced improvement in secondary measures of fatigue compared to the control group: Energy and Fatigue (Vitality) on the SF-36 and general fatigue on the MFI. There were no clear changes in mood related to yoga or exercise. CONCLUSION: Subjects with MS participating in either a 6-month yoga class or exercise class showed significant improvement in measures of fatigue compared to a waiting-list control group. There was no relative improvement of cognitive function in either of the intervention groups.

Localizing acute stroke-related EEG changes: assessing the effects of spatial undersampling.

Because of its sensitivity to metabolic and ionic disturbances related to ischemia, the EEG can be a potentially useful tool for acute stroke detection and for monitoring affected tissue. However, the clinical use of the EEG in detecting stroke is determined in part by how accurately the spatial information is characterized. The purpose of the current study was to determine the effects of spatial undersampling on the distribution and interpretation of the stroke-related topographic EEG. Using a 128-channel sensor montage, EEG was recorded from six stroke patients acutely (between 8 and 36 hours) after symptom onset. The EEG was submitted to a spectral analysis and was compared with patient symptoms and MRI and computed tomographic findings. To determine loss of spatial and clinical information resulting from spatial undersampling, the average-referenced data from the original 128-channel recording montage were subsampled into 64-, 32-, and 19-channel arrays. Furthermore, the analytical findings were compared with a board-certified electroencephalographer's review of the raw EEG using a conventional clinical montage. As predicted, the results showed that accurate description of stroke-related topographic EEG changes is dependent on adequate spatial sampling density. Accurate description of the spatial distribution of the stroke-related EEG was achieved only with the 64- and 128-channel EEG. As the recording density decreases to 32 channels, the distribution of the scalp EEG spectra is distorted, potentially resulting in mislocalization of the affected region. Results of the clinical review by an expert electroencephalographer corroborated the quantitative analyses, and the results also demonstrated the shortcomings of the conventional 10-20 recording density for capturing focal EEG abnormalities in several cases. The EEG provides useful information about the localization of acute cerebral ischemia, but recording densities of 64 channels or higher are required for accurate spatial characterization of focal stroke-related EEG changes.

Methylphenidate increases the motor effects of L-Dopa in Parkinson's disease: a pilot study.

We determined whether methylphenidate, a dopamine transporter blocker, modifies motor, cognitive, or affective responses to L-Dopa in Parkinson's disease (PD). Five patients who reported benefit from L-Dopa/carbidopa and motor fluctuations were admitted and withdrawn from their usual antiparkinsonian medications. On 3 consecutive days in a randomized double-blinded fashion, they took 0.2 mg/kg oral methylphenidate or placebo followed 30 minutes later by a 1-hour intravenous L-Dopa (2 mg/kg per h) or placebo infusion. Vital signs, tapping, walking, dyskinesias, mood, anxiety, concentration, and arousal were monitored every 30 minutes. Cognitive testing was performed before and following the infusion. Methylphenidate combined with L-Dopa led to greater peak right-hand tapping speed than either alone. Dyskinesia severity increased most when methylphenidate and L-Dopa were co-administered. There were no differences between conditions on the Stroop test, digit ordering, simple reaction time, or covert orienting of attention validity effect. Methylphenidate alone led to improvement in choice reaction time. Change in self-assessed analogue ratings of mood, anxiety, arousal, or concentration did not differ between conditions. Methylphenidate increased the motor effects of L-Dopa with minimal effects on cognitive or affective functions, suggesting a physiologic role for the dopamine transporter in patients with PD with motor fluctuations.

Exacerbated physical fatigue and mental fatigue in Parkinson's disease.

OBJECTIVE: To characterize fatigue in Parkinson's disease (PD). BACKGROUND: Fatigue is a recognized problem in PD. Fatigue can be in the physical realm or in the mental realm. Fatigue has not been characterized in PD. METHODS: We characterized fatigue in 39 PD patients and 32 age-matched normal controls using five questionnaires: A. The Multidimensional Fatigue Inventory (MFI), which measures five dimensions of fatigue independently including general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue. B. The Fatigue Severity Inventory (FSI), which quantifies fatigue in general. C. The Profile of Mood States (POMS), which assesses six subjective subscales: tension-anxiety, depression-dejection, anger-hostility, fatigue-inertia, vigor-activity, and confusion-bewilderment. D. Center for Epidemiological Studies-Depression Scale (CES-D). E. Visual Analog linear scale of energy (VA-E). RESULTS: PD patients scored higher in all of the five dimensions of fatigue in the MFI including general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue (P < 0.001 except for mental fatigue P = 0.005). The severity of physical fatigue did not correlate with that of mental fatigue. PD patients scored higher on the FSI, POMS, CES-D, and scored lower on the VA-E. The scores in the FSI correlated with general fatigue, physical fatigue, reduced activity, and reduced motivation but not with mental fatigue in the MFI. Depression correlated with all dimensions of fatigue except physical fatigue in the MFI. Disease severity, as measured by Modified Hoehn and Yahr staging, did not correlate with any of the measures. CONCLUSIONS: PD patients have increased physical fatigue and mental fatigue compared to normals. Physical fatigue and mental fatigue are independent symptoms in PD that need to be assessed and treated separately.

Age-related differences in global-local processing: stability of laterality differences but disproportionate impairment in global processing.

Visual processing of global and local features differentially engages the right and left hemispheres and requires different allocations of spatial attention. To further understand the decline in visual cognition and visual attention with age, we studied the performance of healthy young subjects and healthy elders on a global-local figures task. The results showed that elders processed global images more quickly when presented in the left visual field and local images in the right visual field, similarly to the young controls. However, we did observe a significant impairment in the elders' ability to process global figures compared with local figures, despite there being no overall difference between global and local processing speed among the young. It is thought that this age-related decline in global processing is related to the narrowed attentional field that can be demonstrated in other age-related visual processing declines such as visual search and useful field of view.

The efficacy of Ginkgo biloba on cognitive function in Alzheimer disease.

OBJECTIVE: To determine the effect of treatment with Ginkgo biloba extract on objective measures of cognitive function in patients with Alzheimer disease (AD) based on formal review of the current literature. METHODS: An attempt was made to identify all English and non-English-language articles in which G. biloba extract was given to subjects with dementia or cognitive impairment. Inclusion criteria for the meta-analysis were (1) sufficiently characterized patients such that it was clearly stated there was a diagnosis of AD by either Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, or National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, or there was enough clinical detail to determine this by our review; (2) clearly stated study exclusion criteria, ie, those studies that did not have stated exclusions for depression, other neurologic disease, and central nervous system-active medications were excluded; (3) use of standardized ginkgo extract in any stated dose; (4) randomized, placebo-controlled and double-blind study design; (5) at least 1 outcome measure was an objective assessment of cognitive function; and (6) sufficient statistical information to allow for meta-analysis. RESULTS: Of more than 50 articles identified, the overwhelming majority did not meet inclusion criteria, primarily because of lack of clear diagnoses of dementia and AD. Only 4 studies met all inclusion criteria. In total there were 212 subjects in each of the placebo and ginkgo treatment groups. Overall there was a significant effect size of 0.40 (P<.0001). This modest effect size translated into a 3% difference in the Alzheimer Disease Assessment Scale-cognitive subtest. CONCLUSIONS: Based on a quantitative analysis of the literature there is a small but significant effect of 3- to 6-month treatment with 120 to 240 mg of G. biloba extract on objective measures of cognitive function in AD. The drug has not had significant adverse effects in formal clinical trials but there are 2 case reports of bleeding complications. In AD, there are limited and inconsistent data that preclude determining if there are effects on noncognitive behavioral and functional measures as well as on clinician's global rating scales. Further research in the area will need to determine if there are functional improvements and to determine the best dosage. Additional research will be needed to define which ingredients in the ginkgo extract are producing its effect in individuals with AD.

Motor slowing precedes cognitive impairment in the oldest old.

Eighty-five healthy elderly subjects were prospectively evaluated for 3 years to determine motor differences between those who remain cognitively intact and those who developed cognitive impairment during prospective follow-up. The 18 subjects who developed cognitive impairment had slower finger tapping and took longer to walk 30 feet before or at the time of cognitive impairment. Coordination was more impaired and steps, but not balance, deteriorated more rapidly, independent of other variables.

Verbal fluency task affects gait in Parkinson's disease with motor freezing.

We examined the effects of a simultaneous verbal fluency task on walking in Parkinson's disease (PD) patients with freezing of gait (PD-F) compared to nonfreezing patients (PD-NF) or control subjects (C). Effects of antiparkinsonian medications on gait in PD-F were examined. PD-F patients exhibited a greater increase in the number of steps to complete the walk with verbal fluency, even when the effect of medication was taken into account (mean increase +/- SD): PD-F = 4.2 +/- 4.6, n = 10; PD-NF = 0.1 +/- 1.6, n = 9; C = 1.5 +/- 1.5, n = 19; P = .007. Medications improved walking in PD-F patients by decreasing the number of steps, the time to walk, and freezing. PD-F patients may be more dependent on attention for walking.