Michael E. Smith

Mapping cognitive brain function with modern high-resolution electroencephalography

High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. While electroencephalography (EEG) provides temporal resolution in the millisecond range, which would seem to make it an ideal complement to other imaging modalities, traditional EEG technology and practice provides insufficient spatial detail to identify relationships between brain electrical events and structures and functions that are visualized by magnetic resonance imaging (MRI) or positron emission tomography (PET). Recent advances overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical information from each subjects MRI, and by correcting the distortion that is caused by volume conduction of EEG signals through the skull and scalp. Along with its ability to record how brains think when performing everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

Test-retest reliability of cognitive EEG

OBJECTIVEnTask-related EEG is sensitive to changes in cognitive state produced by increased task difficulty and by transient impairment. If task-related EEG has high test-retest reliability, it could be used as part of a clinical test to assess changes in cognitive function. The aim of this study was to determine the reliability of the EEG recorded during the performance of a working memory (WM) task and a psychomotor vigilance task (PVT).nnnMETHODSnEEG was recorded while subjects rested quietly and while they performed the tasks. Within session (test-retest interval of approximately 1 h) and between session (test-retest interval of approximately 7 days) reliability was calculated for four EEG components: frontal midline theta at Fz, posterior theta at Pz, and slow and fast alpha at Pz.nnnRESULTSnTask-related EEG was highly reliable within and between sessions (r0.9 for all components in WM task, and r0.8 for all components in the PVT). Resting EEG also showed high reliability, although the magnitude of the correlation was somewhat smaller than that of the task-related EEG (r0.7 for all 4 components).nnnCONCLUSIONSnThese results suggest that under appropriate conditions, task-related EEG has sufficient retest reliability for use in assessing clinical changes in cognitive status.

Towards measurement of brain function in operational environments.

In operational environments that demand sustained vigilance or that involve multiple tasks competing for limited attentional resources, continuous monitoring of the mental state of the operator could decrease the potential for serious errors and provide valuable information concerning the ergonomics of the tasks being performed. There is widespread discussion and appreciation of the basic feasibility of utilizing neurophysiological measurements to derive accurate, reliable, rapid and unobtrusive assessments of mental state. However, progress in transitioning this idea into practical applications has been impeded by the fact that at present no convenient, inexpensive and effective means exists to derive a meaningful index of brain activity outside of laboratory settings. In this paper, we review some recent advances in recording technology and signal processing methods that will help overcome this limitation. For example, rapid progress is being made in the engineering of recording systems that are small, rugged, portable and easy-to-use, and thus suitable for deployment in operational environments. Progress is also being made in the development of signal processing algorithms for detecting and correcting recording artifacts and for increasing the amount of useful information that can be derived from brain signals. Finally, results from basic research studies suggest that accurate and reliable inferences about the mental load and alertness of an individual can be derived from neurophysiological measures in a practical fashion. These research and engineering successes suggest that it is reasonable to expect that in the near term a basic enabling technology will be deployed that will permit routine measurement of brain function in operational environments.

Tracking the Cognitive Pharmacodynamics of Psychoactive Substances with Combinations of Behavioral and Neurophysiological Measures

Many common pharmacological treatments have effects on cognitive ability. Psychometric task batteries used to characterize such effects do not provide direct information about treatment-related changes in brain function. Since overt task performance reflects motivation and effort as well as ability, behavioral measures alone may overestimate or underestimate the impact of a pharmacological intervention on brain function. Here we present a method that combines behavioral and neurophysiological measures in an attempt to detect the psychoactive effects of pharmacological treatments with greater sensitivity than that provided by behavioral measures alone. Initial application of the method is made to the data from a double blind, placebo-controlled, crossover study in which caffeine, diphenhydramine, and alcohol were used to alter the mental state of 16 healthy subjects at rest and while they performed low load and high load versions of a working memory task. For each intervention, more sensitive detection of drug or alcohol effects over a four hour period was obtained when EEG variables were included in multivariate analyses than when only behavioral variables were used. These initial results suggest that it can be useful to incorporate neurophysiological measures of brain activity into inferences concerning the acute impact of drugs on mental function, and demonstrate the feasibility of using multivariate combinations of behavioral and neurophysiological measures to sensitively characterize the pharmacodynamics of drug-induced changes in cognition.

Distinct Cognitive Neurophysiologic Profiles for Lamotrigine and Topiramate

Summary:u2002 Purpose: To contrast the effects of lamotrigine (LTG) and topiramate (TPM) on cognitive task‐related and resting‐state EEG and evoked potential (EP) measures.

Task-related EEG and ERP changes without performance impairment following a single dose of phenytoin

OBJECTIVESnThe acute effects of a single, low dose of phenytoin on behavioral and neurophysiological measures of cognitive function were examined in healthy adults.nnnMETHODSnElectroencephalograms (EEGs) were recorded from 7 healthy volunteers while they performed spatial working memory tasks and while they rested quietly. Behavioral measures, EEG power spectra, and event-related potentials (ERPs) were compared between separate sessions in which subjects ingested either 10mg/kg of phenytoin or placebo.nnnRESULTSnPeak serum levels of phenytoin were in the low therapeutic range. Although participants reported subjective effects of the drug, task accuracy and response time were not affected. In the resting EEG, phenytoin decreased power in the alpha band. In the task-related EEG, the frontal midline theta signal was enhanced in response to increased task difficulty following placebo but not following phenytoin. An attention-related augmentation of the N160 ERP to matching stimuli was also reduced by phenytoin.nnnCONCLUSIONSnNeurophysiological measures displayed sensitivity to subtle alterations in attentional processing even in response to a dose of phenytoin too low to produce behavioral impairment. Such results indicate that EEG and ERP measures can provide information about the neurocognitive side effects of medications that cannot be inferred from cognitive task performance measures alone.

Long-term and within-day variability of working memory performance and EEG in individuals

OBJECTIVEnAssess individual-subject long-term and within-day variability of a combined behavioral and EEG test of working memory.nnnMETHODSnEEGs were recorded from 16 adults performing n-back working memory tasks, with 10 tested in morning and afternoon sessions over several years. Participants were also tested after ingesting non-prescription medications or recreational substances. Performance and EEG measures were analyzed to derive an Overall score and three constituent sub-scores characterizing changes in performance, cortical activation, and alertness from each individuals baseline. Long-term and within-day variability were determined for each score; medication effects were assessed by reference to each individuals normal day-to-day variability.nnnRESULTSnOver the several year period, the mean Overall score and sub-scores were approximately zero with standard deviations less than one. Overall scores were lower and their variability higher in afternoon relative to morning sessions. At the group level, alcohol, diphenhydramine and marijuana produced significant effects, but there were large individual differences.nnnCONCLUSIONSnObjective working memory measures incorporating performance and EEG are stable over time and sensitive at the level of individual subjects to interventions that affect neurocognitive function.nnnSIGNIFICANCEnWith further research these measures may be suitable for use in individualized medical care by providing a sensitive assessment of incipient illness and response to treatment.

A cognitive and neurophysiological test of change from an individual’s baseline

OBJECTIVEnAn automated cognitive neurophysiological test is presented that characterizes how an individual was affected by a drug or treatment. The test calculates sub-scores for working memory task performance, cortical activation, and alertness, and combines the sub-scores into an overall score.nnnMETHODSnThe test was applied in a double-blind, placebo-controlled study of alcohol, caffeine, diphenhydramine, and sleep deprivation in 16 healthy adults.nnnRESULTSnThe between- and within-day variability of the sub-scores and overall scores for placebo were all near zero, suggesting that the scores are stable. All treatments affected the overall score, while differential effects on sub-scores highlighted the added value of EEG measures.nnnCONCLUSIONSnThe test is sensitive to relatively mild alterations in cognitive function. Its automation makes it suitable for use in large-scale clinical trials.nnnSIGNIFICANCEnBy combining task performance with EEG brain function measures, the test may prove to have better sensitivity and specificity in detecting changes due to drugs or other treatments than comparable neuropsychological test batteries that do not directly measure brain function signals.

A Method to Combine Cognitive and Neurophysiological Assessments of the Elderly

Background: The development of better treatments for brain diseases of the elderly will necessitate more sensitive and efficient means of repeatedly assessing an individual’s neurocognitive status. Aim: To illustrate the development of an assessment combining episodic memory and working memory tasks with simultaneous electroencephalography and evoked potential (EP) brain function measures. Methods: Data from matched groups of elderly subjects with mildly impaired episodic verbal memory on neuropsychological tests and those with no objective signs of impairment were used for scale development. An exploratory multivariate divergence analysis selected task performance and neurophysiological variables that best recognized impairment. Discriminant validity was then initially assessed on separate impaired and unimpaired groups. Results: Decreased response accuracy and parietal late positive component EP amplitude in the episodic memory task best characterized impaired subjects. Sensitivity in recognizing impairment in the validation analysis was 89% with 79% specificity (area under the curve = 0.94). Retest reliability was 0.89 for the unimpaired and 0.74 for the impaired validation groups. Conclusion: These promising initial results suggest that with further refinement and testing, an assessment combining cognitive task performance with simultaneous neurofunctional measures could eventually provide an important benefit for clinicians and researchers.