Spontaneous cortical dynamics from the first years to the golden years.

In the largest and most expansive lifespan magnetoencephalography (MEG) study to date (n = 434, 6 to 84 y), we provide critical data on the normative trajectory of resting-state spontaneous activity and its temporal dynamics. We perform cutting-edge analyses to examine age and sex effects on whole-brain, spatially-resolved relative and absolute power maps, and find significant age effects in all spectral bands in both types of maps. Specifically, lower frequencies showed a negative correlation with age, while higher frequencies positively correlated with age. These correlations were further probed with hierarchical regressions, which revealed significant nonlinear trajectories in key brain regions. Sex effects were found in absolute but not relative power maps, highlighting key differences between outcome indices that are generally used interchangeably. Our rigorous and innovative approach provides multispectral maps indicating the unique trajectory of spontaneous neural activity across the lifespan, and illuminates key methodological considerations with the widely used relative/absolute power maps of spontaneous cortical dynamics.

Oscillatory activity in bilateral prefrontal cortices is altered by distractor strength during working memory processing.

Working memory (WM) enables the temporary storage of limited information and is a central component of higher order cognitive function. Irrelevant and/or distracting information can have a negative impact on WM processing and suppressing such incoming stimuli is critical to maintaining adequate performance. However, the neural mechanisms and dynamics underlying such distractor inhibition remain poorly understood. In the current study, we enrolled 46 healthy adults (Mage: 27.92, Nfemale: 28) who completed a Sternberg type WM task with high- and low-distractor conditions during magnetoencephalography (MEG). MEG data were transformed into the time-frequency domain and significant task-related oscillatory responses were imaged to identify the underlying anatomical areas. Whole-brain paired t-tests, with cluster-based permutation testing for multiple comparisons correction, were performed to assess differences between the low- and high-distractor conditions for each oscillatory response. Across conditions, we found strong alpha and beta oscillations (i.e., decreases relative to baseline) and increases in theta power throughout the encoding and maintenance periods. Whole-brain contrasts revealed significantly stronger alpha and beta oscillations in bilateral prefrontal regions during maintenance in high- compared to low-distractor trials, with the stronger beta oscillations being centered on the left dorsolateral prefrontal cortex and right inferior frontal gyrus, while those for alpha being within the right anterior prefrontal cortices and the right middle frontal gyrus. These findings suggest that alpha and beta oscillations in the bilateral prefrontal cortices play a major role in the inhibition of distracting information during WM maintenance. Our results also contribute to prior research on cognitive control and functional inhibition, in which prefrontal regions have been widely implicated.

Optimal gamma-band entrainment of visual cortex.

Visual entrainment is a powerful and widely used research tool to study visual information processing in the brain. While many entrainment studies have focused on frequencies around 14-16 Hz, there is renewed interest in understanding visual entrainment at higher frequencies (e.g., gamma-band entrainment). Notably, recent groundbreaking studies have demonstrated that gamma-band visual entrainment at 40 Hz may have therapeutic effects in the context of Alzheimer's disease (AD) by stimulating specific neural ensembles, which utilize GABAergic signaling. Despite such promising findings, few studies have investigated the optimal parameters for gamma-band visual entrainment. Herein, we examined whether visual stimulation at 32, 40, or 48 Hz produces optimal visual entrainment responses using high-density magnetoencephalography (MEG). Our results indicated strong entrainment responses localizing to the primary visual cortex in each condition. Entrainment responses were stronger for 32 and 40 Hz relative to 48 Hz, indicating more robust synchronization of neural ensembles at these lower gamma-band frequencies. In addition, 32 and 40 Hz entrainment responses showed typical patterns of habituation across trials, but this effect was absent for 48 Hz. Finally, connectivity between visual cortex and parietal and prefrontal cortices tended to be strongest for 40 relative to 32 and 48 Hz entrainment. These results suggest that neural ensembles in the visual cortex may resonate at around 32 and 40 Hz and thus entrain more readily to photic stimulation at these frequencies. Emerging AD therapies, which have focused on 40 Hz entrainment to date, may be more effective at lower relative to higher gamma frequencies, although additional work in clinical populations is needed to confirm these findings. PRACTITIONER POINTS: Gamma-band visual entrainment has emerged as a therapeutic approach for eliminating amyloid in Alzheimer's disease, but its optimal parameters are unknown. We found stronger entrainment at 32 and 40 Hz compared to 48 Hz, suggesting neural ensembles prefer to resonate around these relatively lower gamma-band frequencies. These findings may inform the development and refinement of innovative AD therapies and the study of GABAergic visual cortical functions.

Developmental differences in functional organization of multispectral networks.

Assessing brain connectivity during rest has become a widely used approach to identify changes in functional brain organization during development. Generally, previous works have demonstrated that brain activity shifts from more local to more distributed processing from childhood into adolescence. However, the majority of those works have been based on functional magnetic resonance imaging measures, whereas multispectral functional connectivity, as measured using magnetoencephalography (MEG), has been far less characterized. In our study, we examined spontaneous cortical activity during eyes-closed rest using MEG in 101 typically developing youth (9-15 years old; 51 females, 50 males). Multispectral MEG images were computed, and connectivity was estimated in the canonical delta, theta, alpha, beta, and gamma bands using the imaginary part of the phase coherence, which was computed between 200 brain regions defined by the Schaefer cortical atlas. Delta and alpha connectivity matrices formed more communities as a function of increasing age. Connectivity weights predominantly decreased with age in both frequency bands; delta-band differences largely implicated limbic cortical regions and alpha band differences in attention and cognitive networks. These results are consistent with previous work, indicating the functional organization of the brain becomes more segregated across development, and highlight spectral specificity across different canonical networks.

Disturbances in primary visual processing as a function of healthy aging.

For decades, visual entrainment paradigms have been widely used to investigate basic visual processing in healthy individuals and those with neurological disorders. While healthy aging is known to be associated with alterations in visual processing, whether this extends to visual entrainment responses and the precise cortical regions involved is not fully understood. Such knowledge is imperative given the recent surge in interest surrounding the use of flicker stimulation and entrainment in the context of identifying and treating Alzheimer's disease (AD). In the current study, we examined visual entrainment in eighty healthy aging adults using magnetoencephalography (MEG) and a 15 Hz entrainment paradigm, while controlling for age-related cortical thinning. MEG data were imaged using a time-frequency resolved beamformer and peak voxel time series were extracted to quantify the oscillatory dynamics underlying the processing of the visual flicker stimuli. We found that, as age increased, the mean amplitude of entrainment responses decreased and the latency of these responses increased. However, there was no effect of age on the trial-to-trial consistency in phase (i.e., inter-trial phase locking) nor amplitude (i.e., coefficient of variation) of these visual responses. Importantly, we discovered that the relationship between age and response amplitude was fully mediated by the latency of visual processing. These results indicate that aging is associated with robust changes in the latency and amplitude of visual entrainment responses within regions surrounding the calcarine fissure, which should be considered in studies examining neurological disorders such as AD and other conditions associated with increased age.

Alpha oscillations in left perisylvian cortices support semantic processing and predict performance.

Semantic processing is the ability to discern and maintain conceptual relationships among words and objects. While the neural circuits serving semantic representation and controlled retrieval are well established, the neuronal dynamics underlying these processes are poorly understood. Herein, we examined 25 healthy young adults who completed a semantic relation word-matching task during magnetoencephalography (MEG). MEG data were examined in the time-frequency domain and significant oscillatory responses were imaged using a beamformer. Whole-brain statistical analyses were conducted to compare semantic-related to length-related neural oscillatory responses. Time series were extracted to visualize the dynamics and were linked to task performance using structural equation modeling. The results indicated that participants had significantly longer reaction times in semantic compared to length trials. Robust MEG responses in the theta (3-6 Hz), alpha (10-16 Hz), and gamma (64-76 Hz and 64-94 Hz) bands were observed in parieto-occipital and frontal cortices. Whole-brain analyses revealed stronger alpha oscillations in a left-lateralized network during semantically related relative to length trials. Importantly, stronger alpha oscillations in the left superior temporal gyrus during semantic trials predicted faster responses. These data reinforce existing literature and add novel temporal evidence supporting the executive role of the semantic control network in behavior.

Spontaneous sensorimotor beta power and cortical thickness uniquely predict motor function in healthy aging.

BACKGROUND: Spontaneous beta activity in the primary motor cortices has been shown to increase in amplitude with advancing age, and that such increases are tightly coupled to stronger motor-related beta oscillations during movement planning. However, the relationship between these age-related changes in spontaneous beta in the motor cortices, local cortical thickness, and overall motor function remains unclear. METHODS: We collected resting-state magnetoencephalography (MEG), high-resolution structural MRI, and motor function scores using a neuropsychological battery from 126 healthy adults (56 female; age range = 22-72 years). MEG data were source-imaged and a whole-brain vertex-wise regression model was used to assess age-related differences in spontaneous beta power across the cortex. Cortical thickness was computed from the structural MRI data and local beta power and cortical thickness values were extracted from the sensorimotor cortices. To determine the unique contribution of age, spontaneous beta power, and cortical thickness to the prediction of motor function, a hierarchical regression approach was used. RESULTS: There was an increase in spontaneous beta power with age across the cortex, with the strongest increase being centered on the sensorimotor cortices. Sensorimotor cortical thickness was not related to spontaneous beta power, above and beyond age. Interestingly, both cortical thickness and spontaneous beta power in sensorimotor regions each uniquely contributed to the prediction of motor function when controlling for age. DISCUSSION: This multimodal study showed that cortical thickness and spontaneous beta activity in the sensorimotor cortices have dissociable contributions to motor function across the adult lifespan. These findings highlight the complexity of interactions between structure and function and the importance of understanding these interactions in order to advance our understanding of healthy aging and disease.

Eyes-closed versus eyes-open differences in spontaneous neural dynamics during development.

BACKGROUND: Assessing brain activity during rest has become a widely used approach in developmental neuroscience. Extant literature has measured resting brain activity both during eyes-open and eyes-closed conditions, but the difference between these conditions has not yet been well characterized. Studies, limited to fMRI and EEG, have suggested that eyes-open versus -closed conditions may differentially impact neural activity, especially in visual cortices. METHODS: Spontaneous cortical activity was recorded using MEG from 108 typically developing youth (9-15 years-old; 55 female) during separate sessions of eyes-open and eyes-closed rest. MEG source images were computed, and the strength of spontaneous neural activity was estimated in the canonical delta, theta, alpha, beta, and gamma bands, respectively. Power spectral density maps for eyes-open were subtracted from eyes-closed rest, and then submitted to vertex-wise regression models to identify spatially specific differences between conditions and as a function of age and sex. RESULTS: Relative alpha power was weaker in the eyes-open compared to -closed condition, but otherwise eyes-open was stronger in all frequency bands, with differences concentrated in the occipital cortex. Relative theta power became stronger in the eyes-open compared to the eyes-closed condition with increasing age in frontal cortex. No differences were observed between males and females. CONCLUSIONS: The differences in relative power from eyes-closed to -open conditions are consistent with changes observed in task-based visual sensory responses. Age differences occurred in relatively late developing frontal regions, consistent with canonical attention regions, suggesting that these differences could be reflective of developmental changes in attention processes during puberty. Taken together, resting-state paradigms using eyes-open versus -closed produce distinct results and, in fact, can help pinpoint sensory related brain activity.

The neural oscillations serving task switching are altered in cannabis users.

BACKGROUND: Regular cannabis is known to impact higher-order cognitive processes such as attention, but far less is known regarding cognitive flexibility, a component of executive function. Moreover, whether such changes are related to aberrations in the neural oscillatory dynamics serving flexibility remains poorly understood. AIMS: Quantify the neural oscillatory dynamics serving cognitive flexibility by having participants complete a task-switching paradigm during magnetoencephalography (MEG). Probe whole-brain maps to identify alterations in chronic cannabis users relative to nonusers and determine how these alterations relate to the degree of cannabis use involvement. METHODS: In all, 25 chronic cannabis users and 30 demographically matched nonuser controls completed neuropsychological testing, an interview regarding their substance use, a urinalysis, and a task switch paradigm during MEG. Time-frequency windows of interest were identified using a data-driven statistical approach and these were imaged using a beamformer. Whole-brain neural switch cost maps were computed by subtracting the oscillatory maps of the no-switch condition from the switch condition per participant. These were examined for group differences. RESULTS: Cannabis users had weaker theta switch cost responses in the dorsolateral and dorsomedial prefrontal cortices, while nonusers showed the typical pattern of greater recruitment during switch relative to no switch trials. In addition, theta activity in the dorsomedial prefrontal cortex was significantly correlated with cannabis use involvement. CONCLUSIONS: Cannabis users exhibited altered theta switch cost activity compared to nonusers in prefrontal cortical regions, which are critical for cognitive flexibility. This activity scaled with cannabis use involvement, indicating a link between cannabis use and aberrant oscillatory activity underlying cognitive flexibility.

Spontaneous cortical activity is altered in persons with HIV and related to domain-specific cognitive function.

Whilst the average lifespan of persons with HIV now approximates that of the general population, these individuals are at a much higher risk of developing cognitive impairment with ∼35-70% experiencing at least subtle cognitive deficits. Previous works suggest that HIV impacts both low-level primary sensory regions and higher-level association cortices. Notably, multiple neuroHIV studies have reported elevated levels of spontaneous cortical activity during the pre-stimulus baseline period of task-based experiments, but only a few have examined such activity during resting-state conditions. In the current study, we examined such spontaneous cortical activity using magnetoencephalography in 79 persons with HIV and 83 demographically matched seronegative controls and related this neural activity to performance on neuropsychological assessments of cognitive function. Consistent with previous works, persons with HIV exhibited stronger spontaneous gamma activity, particularly in inferior parietal, prefrontal and superior temporal cortices. In addition, serostatus moderated the relationship between spontaneous beta activity and attention, motor and processing speed scores, with controls but not persons with HIV showing stronger beta activity with better performance. The current results suggest that HIV predominantly impacts spontaneous activity in association cortices, consistent with alterations in higher-order brain function, and may be attributable to deficient GABAergic signalling, given its known role in the generation of gamma and beta oscillations. Overall, these effects align with previous studies showing aberrant spontaneous activity in persons with HIV and provide a critical new linkage to domain-specific cognitive dysfunction.

Comprehensive review of task-based neuroimaging studies of cognitive deficits in Alzheimer's disease using electrophysiological methods.

With an aging population, cognitive decline and neurodegenerative disorders are an emerging public health crises with enormous, yet still under-recognized burdens. Alzheimer's disease (AD) is the most common type of dementia, and the number of cases is expected to dramatically rise in the upcoming decades. Substantial efforts have been placed into understanding the disease. One of the primary avenues of research is neuroimaging, and while positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) are most common, crucial recent advancements in electrophysiological methods such as magnetoencephalography (MEG) and electroencephalography (EEG) have provided novel insight into the aberrant neural dynamics at play in AD pathology. In this review, we outline task-based M/EEG studies published since 2010 using paradigms probing the cognitive domains most affected by AD, including memory, attention, and executive functioning. Furthermore, we provide important recommendations for adapting cognitive tasks for optimal use in this population and adjusting recruitment efforts to improve and expand future neuroimaging work.

Sleep quality differentially modulates neural oscillations and proteinopathy in Alzheimer's disease.

BACKGROUND: Alterations in resting-state neural activity have been reported in people with sleep disruptions and in patients with Alzheimer's disease, but the direct impact of sleep quality on Alzheimer's disease-related neurophysiological aberrations is unclear. METHODS: We collected cross-sectional resting-state magnetoencephalography and extensive neuropsychological and clinical data from 38 biomarker-confirmed patients on the Alzheimer's disease spectrum and 20 cognitively normal older control participants. Sleep efficiency was quantified using the Pittsburgh Sleep Quality Index. FINDINGS: Neural activity in the delta frequency range was differentially affected by poor sleep in patients on the Alzheimer's disease spectrum. Such neural changes were related to processing speed abilities and regional amyloid accumulation, and these associations were mediated and moderated, respectively, by sleep quality. INTERPRETATION: Together, our results point to a mechanistic role for sleep disturbances in the widely reported neurophysiological aberrations seen in patients on the Alzheimer's disease spectrum, with implications for basic research and clinical intervention. FUNDING: National Institutes of Health, USA.

Age-related alterations in the oscillatory dynamics serving verbal working memory processing.

Working memory (WM) is a foundational cognitive function involving the temporary storage of information. Unfortunately, WM is also one of the most sensitive cognitive functions to the detrimental effects of aging. Expanding the field's understanding of age-related WM changes is critical to advancing the development of strategies to mitigate age-related WM declines. In the current study, we investigated the neural mechanisms serving WM function in seventy-eight healthy aging adults (range: 20.2-65.2 years) using magnetoencephalography (MEG) and a Sternberg WM task with letter stimuli. Neural activity during the different phases of the WM task (i.e., encoding, maintenance, and retrieval) were imaged using a time-frequency resolved beamformer and whole-brain statistics were performed. We found stronger increases in theta activity and stronger decreases in alpha and beta activity (i.e., more negative relative to baseline) as a function of healthy aging. Specifically, age-related increases in theta activity were detected during the encoding period in the primary visual and left prefrontal cortices. Additionally, alpha and beta oscillations were stronger (i.e., more negative) during both encoding and maintenance in the left prefrontal cortex in older individuals. Finally, alpha and beta oscillations during the retrieval phase were stronger (i.e., more negative) in older participants within the prefrontal, parietal, and temporal cortices. Together, these results indicate that healthy aging strongly modulates the neural oscillatory dynamics serving WM function.