On the relationship between EEG and P300: individual differences, aging, and ultradian rhythms (2023)

The immediately-prestimulus electroencephalographic (EEG) brain state influences subsequent event-related processing, dynamically impacting event-related potential (ERP) and behavioural outcomes. Both EEG and ERPs are known to undergo age-related change, yet few have investigated the consistency in their dynamic interrelations in the context of ageing. The present investigation assessed the impact of prestimulus alpha and beta brain states in 20 young (18–26years) and 20 gender-matched healthy older (59–75years) adults who completed an equiprobable auditory Go/NoGo paradigm. Prestimulus alpha and beta band amplitudes in their prominent band topographies were separately used to derive Go and NoGo ERPs at 10 ascending levels of prestimulus activity, and ERP components were derived for these levels using Principal Components Analysis. Prestimulus alpha directly modulated Go/NoGo P3a amplitudes across the groups, while beta inversely modulated the young (cf. older) adult NoGo N1–1, each supporting and extending limited prior research. Several novel effects were also uncovered, most notably an inverse relationship between prestimulus alpha and reaction time. Prestimulus alpha and beta were confirmed as significant determinants of the processing outcomes in this task, and the complex pattern of results provides a normative map in healthy ageing.

Compared with Alzheimer's disease (AD), Parkinson's disease (PD) shows peculiar clinical manifestations related to vigilance (i.e., executive cognitive deficits and visual hallucinations) that may be reflected in resting-state electroencephalographic rhythms. To test this hypothesis, clinical and resting-state electroencephalographic rhythms in age-, sex-, and education-matched PD patients (N= 136) and Alzheimer's disease patients (AD, N= 85), and healthy older participants (Nold, N= 65), were available from an international archive. Electroencephalographic sources were estimated by eLORETA software. The results are as follows: (1) compared to the Nold participants, the AD and PD patients showed higher widespread delta source activities (PD > AD) and lower posterior alpha source activities (AD > PD); (2) the PD patients with the most pronounced motor deficits exhibited very low alpha source activities in widespread cortical regions; (3) the PD patients with the strongest cognitive deficits showed higher alpha source activities in widespread cortical regions; and (4) compared to the PD patients without visual hallucinations, those with visual hallucinations were characterized by higher posterior alpha sources activities. These results suggest that in PD patients resting in quiet wakefulness, abnormalities in cortical neural synchronization at alpha frequencies are differently related to cognitive, motor, and visual hallucinations. Interestingly, parallel PD neuropathological processes may have opposite effects on cortical neural synchronization mechanisms generating cortical alpha rhythms in quiet wakefulness.

The P300 event-related potential (ERP) varies across individuals, and exploring this variability deepens our knowledge of the event, and scope for its potential applications. Previous studies exploring the P300 have relied on either electroencephalography (EEG) or functional magnetic resonance imaging (fMRI). We applied simultaneous event-related EEG-fMRI to investigate how the network structure is updated from rest to the P300 task so as to guarantee information processing in the oddball task. We first identified 14 widely distributed regions of interest (ROIs) that were task-associated, including the inferior frontal gyrus and the middle frontal gyrus, etc. The task-activated network was found to closely relate to the concurrent P300 amplitude, and moreover, the individuals with optimized resting-state brain architectures experienced the pruning of network architecture, i.e. decreasing connectivity, when the brain switched from rest to P300 task. Our present simultaneous EEG-fMRI study explored the brain reconfigurations governing the variability in P300 across individuals, which provided the possibility to uncover new biomarkers to predict the potential for personalized control of brain-computer interfaces.

With the greying population, it is increasingly necessary to establish robust and individualized markers of cognitive decline. This requires the combination of well-established neural mechanisms, and the development of increasingly sensitive methodologies. The P300 event-related potential (ERP) has been one of the most heavily investigated neural markers of attention and cognition, and studies have reliably shown that changes in the amplitude and latency of the P300 ERP index the process of aging. However, it is still not clear whether either the P3a or P3b sub-components additionally index levels of cognitive impairment. Here, we used a traditional visual three-stimulus oddball paradigm to investigate both the P3a and P3b ERP components in sixteen young and thirty-four healthy elderly individuals with varying degrees of cognitive ability. EEG data extraction was enhanced through the use of a novel signal processing method called Functional Source Separation (FSS) that increases signal-to-noise ratio by using a weighted sum of all electrodes rather than relying on a single, or a small sub-set, of EEG channels. Whilst clear differences in both the P3a and P3b ERPs were seen between young and elderly groups, only P3b amplitude differentiated older people with low memory performance relative to IQ from those with consistent memory and IQ. A machine learning analysis showed that P3b amplitude (derived from FSS analysis) could accurately categorise high and low performing elderly individuals (78% accuracy). A comparison of Bayes Factors found that differences in cognitive decline within the elderly group were 87 times more likely to be detected using FSS compared to the best performing single electrode (Cz). In conclusion, we propose that P3b amplitude could be a sensitive marker of early, age-independent, episodic memory dysfunction within a healthy older population. In addition, we advocate for the use of more advanced signal processing methods, such as FSS, for detecting subtle neural changes in clinical populations.

Ongoing EEG activity contributes to ERP outcomes of stimulus processing, and each of these measures is known to undergo (sometimes significant) age-related change. Variation in their relationship across the life-span may thus elucidate mechanisms of normal and pathological ageing. This study assessed the relationships between low-frequency EEG prestimulus brain states, the ERP, and behavioural outcomes in a simple equiprobable auditory Go/NoGo paradigm, comparing these for 20 young (M_age = 20.4 years) and 20 healthy older (M_age = 68.2 years) adults. Prestimulus delta and theta amplitudes were separately assessed; these were each dominant across the midline region, and reduced in the older adults. For each band, (within-subjects) trials were sorted into ten increasing prestimulus EEG levels for which separate ERPs were derived. The set of ten ERPs for each band-sort was then quantified by PCA, independently for each group (young, older adults). Four components were primarily assessed (P1, N1-1, P2/N2b complex, and P3), with each showing age-related change. Mean RT was comparable, but intra-individual RT variability increased in older adults. Prestimulus delta and theta each generally modulated component positivity, indicating broad influence on task processing. Prestimulus delta was primarily associated with the early sensory processes, and theta more with the later stimulus-specific processes; prestimulus theta also inversely modulated intra-individual RT variability across the groups. These prestimulus EEG–ERP dynamics were consistent between the young and older adults in each band for all components except the P2/N2b, suggesting that across the lifespan, Go/NoGo categorisation is differentially affected by prestimulus delta and theta.

International Journal of Psychophysiology, Volume 97, Issue 3, 2015, pp. 189-209

Despite the recognition that the surface Laplacian may counteract adverse effects of volume conduction and recording reference for surface potential data, electrophysiology as a discipline has been reluctant to embrace this approach for data analysis. The reasons for such hesitation are manifold but often involve unfamiliarity with the nature of the underlying transformation, as well as intimidation by a perceived mathematical complexity, and concerns of signal loss, dense electrode array requirements, or susceptibility to noise. We revisit the pitfalls arising from volume conduction and the mandated arbitrary choice of EEG reference, describe the basic principle of the surface Laplacian transform in an intuitive fashion, and exemplify the differences between common reference schemes (nose, linked mastoids, average) and the surface Laplacian for frequently-measured EEG spectra (theta, alpha) and standard event-related potential (ERP) components, such as N1 or P3. We specifically review common reservations against the universal use of the surface Laplacian, which can be effectively addressed by employing spherical spline interpolations with an appropriate selection of the spline flexibility parameter and regularization constant. We argue from a pragmatic perspective that not only are these reservations unfounded but that the continued predominant use of surface potentials poses a considerable impediment on the progress of EEG and ERP research.

Neurobiology of Aging, Volume 71, 2018, pp. 149-155

The individual alpha peak frequency (IAPF) of the human electroencephalography (EEG) typically experiences slowing with increasing age. Despite this hallmark change, studies that investigate modulations of conventional EEG alpha power and connectivity by aging and age-related neuropathology neglect to account for intergroup differences in IAPF. To investigate the relationship of age-related IAPF slowing with EEG power and connectivity, we recorded eyes-closed resting-state EEG in 37 young adults and 32 older adults. We replicated the finding of a slowed IAPF in older adults. IAPF values were significantly correlated with the frequency of maximum global connectivity and the means of their distributions did not differ, suggesting that connectivity was highest at the IAPF. Older adults expressed reduced global EEG power and connectivity at the conventional upper alpha band (10–12Hz) compared with young adults. By contrast, groups had equivalent power and connectivity at the IAPF. The results suggest that conventional spectral boundaries may be biased against older adults or any group with a slowed IAPF. We conclude that investigations of alpha activity in aging and age-related neuropathology should be adapted to the IAPF of the individual and that previous findings should be interpreted with caution. EEG in the dominant alpha range may be unsuitable for examining cortico-cortical connectivity due to its subcortical origins.

Physiology & Behavior, Volume 156, 2016, pp. 106-116

Mammals typically display alternating active and resting phases and, in most species, these rhythms follow a circadian pattern. The active and resting phases often are accompanied by corresponding physiological changes. In humans, blood pressure decreases during the resting phase of the activity cycle, and the magnitude of that “nocturnal dipping” has been used to stratify patients according to the risk for cardiovascular disease. However, in contrast to most mammals, prairie voles (Microtus ochrogaster) have periods of activity and rest that follow an ultradian rhythm with period lengths significantly <24h. While rhythmic changes in blood pressure across a circadian activity cycle have been well-documented, blood pressure patterns in species that display ultradian rhythms in activity are less well-studied. In the current study, we implanted pressure-sensitive radiotelemetry devices in male prairie voles and recorded activity, mean arterial pressure (MAP), and heart rate (HR) continuously for 3days. Visualization of the ultradian rhythms was enhanced using a 1h running average to filter the dataset. Positive correlations were found between activity and MAP and between activity and HR. During the inactive period of the ultradian cycle, blood pressure decreased by about 15%, which parallels the nocturnal dipping pattern seen in healthy humans. Further, the duration of inactivity did not affect any of the cardiovascular measures, so the differences in blood pressure values between the active and inactive periods are likely driven by ultradian oscillations in hormones and autonomic function. Finally, specific behavioral patterns also were examined. Both the instrumented animal and his non-instrumented cagemate appeared to show synchronized activity patterns, with both animals displaying sleep-like behavior for more than 90% of the inactive period. We propose that the prairie vole ultradian rhythm in blood pressure is an analogue for circadian blood pressure variability and can be used to study the long-term effects of commonly prescribed drugs on blood pressure dipping.

Experimental Neurology, Volume 286, 2016, pp. 69-82

Huntington's disease (HD) is a progressive genetic neurodegenerative disorder characterised by motor and cognitive deficits, as well as sleep and circadian abnormalities. In the R6/2 mouse, a fragment model of HD, rest-activity rhythms controlled by the suprachiasmatic nucleus disintegrate completely by 4months of age. Rhythms driven by a second circadian oscillator, the methamphetamine-sensitive circadian oscillator (MASCO), are disrupted even earlier, and cannot be induced after 2months of age. Here, we studied the effect of the HD mutation on the expression of MASCO-driven rhythms in a more slowly developing, genetically relevant mouse model of HD, the Q175 ‘knock-in’ mouse. We induced expression of MASCO output by administering low dose methamphetamine (0.005%) chronically via the drinking water. We measured locomotor activity in constant darkness in wild-type and Q175 mice at 2 (presymptomatic), 6 (early symptomatic), and 12 (symptomatic) months of age. At 2months, all mice expressed MASCO-driven rhythms, regardless of genotype. At older ages, however, there was a progressive gene dose-dependent deficit in MASCO output in Q175 mice. At 6months of age, these rhythms could be observed in only 45% of heterozygous and 15% of homozygous mice. By 1year of age, 90% of homozygous mice had an impaired MASCO output. There was also an age-dependent disruption of MASCO output seen in wild-type mice. The fact that the progressive deficit in MASCO-driven rhythms in Q175 mice is HD gene dose-dependent suggests that, whatever its role in humans, abnormalities in MASCO output may contribute to the HD circadian phenotype.

Expert Systems with Applications, Volume 114, 2018, pp. 532-542

Trends in Cognitive Sciences, Volume 18, Issue 8, 2014, pp. 414-421

Recent advancements in cognitive neuroscience have afforded a description of neural responses in terms of latent algorithmic operations. However, the adoption of this approach to human scalp electroencephalography (EEG) has been more limited, despite the ability of this methodology to quantify canonical neuronal processes. Here, we provide evidence that theta band activities over the midfrontal cortex appear to reflect a common computation used for realizing the need for cognitive control. Moreover, by virtue of inherent properties of field oscillations, these theta band processes may be used to communicate this need and subsequently implement such control across disparate brain regions. Thus, frontal theta is a compelling candidate mechanism by which emergent processes, such as ‘cognitive control’, may be biophysically realized.