Alterations of Cortical Structure and Neurophysiology in Parkinson's Disease Are Aligned with Neurochemical Systems.

OBJECTIVE: Parkinson's disease (PD) affects the structural integrity and neurophysiological signaling of the cortex. These alterations are related to the motor and cognitive symptoms of the disease. How these changes are related to the neurochemical systems of the cortex is unknown. METHODS: We used T1-weighted magnetic resonance imaging (MRI) and magnetoencephalography (MEG) to measure cortical thickness and task-free neurophysiological activity in patients with idiopathic PD (nMEG = 79, nMRI = 65) and matched healthy controls (nMEG = 65, nMRI = 37). Using linear mixed-effects models, we examined the topographical alignment of cortical structural and neurophysiological alterations in PD with cortical atlases of 19 neurotransmitter receptor and transporter densities. RESULTS: We found that neurophysiological alterations in PD occur primarily in brain regions rich in acetylcholinergic, serotonergic, and glutamatergic systems, with protective implications for cognitive and psychiatric symptoms. In contrast, cortical thinning occurs preferentially in regions rich in noradrenergic systems, and the strength of this alignment relates to motor deficits. INTERPRETATION: This study shows that the spatial organization of neurophysiological and structural alterations in PD is relevant for nonmotor and motor impairments. The data also advance the identification of the neurochemical systems implicated. The approach uses novel nested atlas modeling methodology that is transferrable to research in other neurological and neuropsychiatric diseases and syndromes. ANN NEUROL 2024;95:802-816.

A lateralized alpha-band marker of the interference of exogenous attention over endogenous attention.

Current theories of attention differentiate exogenous from endogenous orienting of visuospatial attention. While both forms of attention orienting engage different functional systems, endogenous and exogenous attention are thought to share resources, as shown by empirical evidence of their functional interactions. The present study aims to uncover the neurobiological basis of how salient events that drive exogenous attention disrupts endogenous attention processes. We hypothesize that interference from exogenous attention over endogenous attention involves alpha-band activity, a neural marker of visuospatial attention. To test this hypothesis, we contrast the effects of endogenous attention across two experimental tasks while we recorded electroencephalography (n = 32, both sexes): a single cueing task where endogenous attention is engaged in isolation, and a double cueing task where endogenous attention is concurrently engaged with exogenous attention. Our results confirm that the concurrent engagement of exogenous attention interferes with endogenous attention processes. We also found that changes in alpha-band activity mediate the relationship between endogenous attention and its effect on task performance, and that the interference of exogenous attention on endogenous attention occurs via the moderation of this indirect effect. Altogether, our results substantiate a model of attention, whereby endogenous and exogenous attentional processes involve the same neurophysiological resources. SIGNIFICANCE STATEMENT: Scientists differentiate top-down from bottom-up visuospatial attention processes. While bottom-up attention is rapidly engaged by emerging demands from the environment, top-down attention in contrast reflects slow voluntary shifts of spatial attention. Several lines of research substantiate the idea that top-down and bottom-up attentional processes involve distinct functional systems. An increasing number of studies, however, argue that both attention systems share brain processing resources. The current study examines how salient visual events that engage bottom-up processes interfere with top-down attentional processes. Using neurophysiological recordings and multivariate pattern classification techniques, the authors show that these patterns of interference occur within the alpha-band of neural activity (8-12 Hz), which implies that bottom-up and top-down attention processes share this narrow-band frequency brain resource. The results further demonstrate that patterns of alpha-band activity explains, in part, the interference between top-down and bottom-up attention at the behavioral level.

Differential and Overlapping Effects between Exogenous and Endogenous Attention Shape Perceptual Facilitation during Visual Processing.

Visuospatial attention is not a monolithic process and can be divided into different functional systems. In this framework, exogenous attention reflects the involuntary orienting of attention resources following a salient event, whereas endogenous attention corresponds to voluntary orienting based on the goals and intentions of individuals. Previous work shows that these attention processes map onto distinct functional systems, yet evidence suggests that they are not fully independent. In the current work, we investigated the differential and overlapping effects of exogenous and endogenous attention on visual processing. We combined spatial cueing of visuospatial attention, EEG, and multivariate pattern analysis to examine where and when the effects of exogenous and endogenous attention were maximally different and maximally similar. Critically, multivariate pattern analysis provided new insights by examining whether classifiers trained to decode the cueing effect for one attention process (e.g., exogenous attention) can successfully decode the cueing effect for the other attention process (e.g., endogenous attention). These analyses uncovered differential and overlapping effects between exogenous and endogenous attention. Next, we combined principal component analyses, single-trial ERPs, and mediation analysis to determine whether these effects facilitate perception, as indexed by the behavioral spatial cueing effects of exogenous and endogenous attention. This approach revealed that three EEG components shape the cueing effects of exogenous and endogenous attention at various times after target onset. Altogether, our study provides a comprehensive account about how overlapping and differential processes of endogenous and exogenous relate to perceptual facilitation in the context of visuospatial attention.

Effects of interocular grouping demands on binocular rivalry.

Binocular rivalry (BR) is a visual phenomenon in which perception alternates between two non-fusible images presented to each eye. Transition periods between dominant and suppressed images are marked by mixed percepts, where participants report fragments of each image being dynamically perceived. Interestingly, BR remains robust even when typical images are subdivided and presented in complementary patches to each eye, a phenomenon termed interocular grouping (IOG). The objective of the present study was to determine if increasing grouping demand in the context of BR changes the perceptual experience of rivalry. In 48 subjects with normal vision, mean dominant and mixed percept durations were recorded for classic BR and IOG conditions with increasing grouping demands from two, four, and six patches. We found that, as grouping demands increased, the duration of mixed periods increased. Indeed, durations of dominant and mixed percepts, as well as percentage of time spent in dominant or mixed state, differed significantly across conditions. However, durations of global dominant percepts remained relatively stable and saturated at about 1.5 seconds, despite the exponential increase in possible mixed combinations. Evidence shows that this saturation followed a nonlinear trend. The data also indicate that grouping across the vertical meridian is slightly more stable than for the horizontal meridian. Finally, individual differences in speed of alternation identified during BR were maintained in all interocular grouping conditions. These results provide new information about binocular visual spatial integration and will be useful for future studies of the underlying neural substrates and models of binocular vision.

Stability of spectral estimates in resting-state magnetoencephalography: Recommendations for minimal data duration with neuroanatomical specificity.

The principle of resting-state paradigms is appealing and practical for collecting data from impaired patients and special populations, especially if data collection times can be minimized. To achieve this goal, researchers need to ensure estimated signal features of interest are robust. In electro- and magnetoencephalography (EEG, MEG) we are not aware of any studies of the minimal length of data required to yield a robust one-session snapshot of the frequency-spectrum derivatives that are typically used to characterize the complex dynamics of the brain's resting-state. We aimed to fill this knowledge gap by studying the stability of common spectral measures of resting-state MEG source time series obtained from large samples of single-session recordings from shared data repositories featuring different recording conditions and instrument technologies (OMEGA: N = 107; Cam-CAN: N = 50). We discovered that the rhythmic and arrhythmic spectral properties of intrinsic brain activity can be robustly estimated in most cortical regions when derived from relatively short segments of 30-s to 120-s of resting-state data, regardless of instrument technology and resting-state paradigm. Using an adapted leave-one-out approach and Bayesian analysis, we also provide evidence that the stability of spectral features over time is unaffected by age, sex, handedness, and general cognitive function. In summary, short MEG sessions are sufficient to yield robust estimates of frequency-defined brain activity during resting-state. This study may help guide future empirical designs in the field, particularly when recording times need to be minimized, such as with patient or special populations.

Difficult Turned Easy: Suggestion Renders a Challenging Visual Task Simple.

Suggestions can cause some individuals to miss or disregard existing visual stimuli, but can they infuse sensory input with nonexistent information? Although several prominent theories of hypnotic suggestion propose that mental imagery can change our perceptual experience, data to support this stance remain sparse. The present study addressed this lacuna, showing how suggesting the presence of physically absent, yet critical, visual information transforms an otherwise difficult task into an easy one. Here, we show how adult participants who are highly susceptible to hypnotic suggestion successfully hallucinated visual occluders on top of moving objects. Our findings support the idea that, at least in some people, suggestions can add perceptual information to sensory input. This observation adds meaningful weight to theoretical, clinical, and applied aspects of the brain and psychological sciences.

Genetic Foundations of Neurophysiological and Behavioural Variability Across the Lifespan.

Neurophysiological brain activity underpins cognitive functions and behavioural traits. Here, we sought to establish to what extent individual neurophysiological traits spontaneously expressed in ongoing brain activity are primarily driven by genetic variation. We also investigated whether changes in such neurophysiological features observed across the lifespan are supported by longitudinal changes in cortical gene expression. We studied the heritability of neurophysiological traits from task-free brain activity of monozygotic and dizygotic twins as well as non-related individuals recorded with magnetoencephalography. We found that these traits were more similar between monozygotic twins compared to dizygotic twins, and that these heritable core dynamical properties of brain activity are predominantly influenced by genes involved in neurotransmission processes. These genes are expressed in the cortex along a topographical gradient aligned with the distribution of major cognitive functions and psychological processes. Our data also show that the impact of these genetic determinants on cognitive and psychological traits increases with age. These findings collectively highlight the persistent genetic influence across the lifespan on neurophysiological brain activity that supports individual cognitive and behavioural traits.

The neurophysiological brain-fingerprint of Parkinson's disease.

BACKGROUND: Research in healthy young adults shows that characteristic patterns of brain activity define individual "brain-fingerprints" that are unique to each person. However, variability in these brain-fingerprints increases in individuals with neurological conditions, challenging the clinical relevance and potential impact of the approach. Our study shows that brain-fingerprints derived from neurophysiological brain activity are associated with pathophysiological and clinical traits of individual patients with Parkinson's disease (PD). METHODS: We created brain-fingerprints from task-free brain activity recorded through magnetoencephalography in 79 PD patients and compared them with those from two independent samples of age-matched healthy controls (N = 424 total). We decomposed brain activity into arrhythmic and rhythmic components, defining distinct brain-fingerprints for each type from recording durations of up to 4 min and as short as 30 s. FINDINGS: The arrhythmic spectral components of cortical activity in patients with Parkinson's disease are more variable over short periods, challenging the definition of a reliable brain-fingerprint. However, by isolating the rhythmic components of cortical activity, we derived brain-fingerprints that distinguished between patients and healthy controls with about 90% accuracy. The most prominent cortical features of the resulting Parkinson's brain-fingerprint are mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also demonstrate that Parkinson's symptom laterality can be decoded directly from cortical neurophysiological activity. Furthermore, our study reveals that the cortical topography of the Parkinson's brain-fingerprint aligns with that of neurotransmitter systems affected by the disease's pathophysiology. INTERPRETATION: The increased moment-to-moment variability of arrhythmic brain-fingerprints challenges patient differentiation and explains previously published results. We outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and symptom laterality of Parkinson's disease. Thus, the proposed definition of a rhythmic brain-fingerprint of Parkinson's disease may contribute to novel, refined approaches to patient stratification. Symmetrically, we discuss how rhythmic brain-fingerprints may contribute to the improved identification and testing of therapeutic neurostimulation targets. FUNDING: Data collection and sharing for this project was provided by the Quebec Parkinson Network (QPN), the Pre-symptomatic Evaluation of Novel or Experimental Treatments for Alzheimer's Disease (PREVENT-AD; release 6.0) program, the Cambridge Centre for Aging Neuroscience (Cam-CAN), and the Open MEG Archives (OMEGA). The QPN is funded by a grant from Fonds de Recherche du Québec - Santé (FRQS). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public-private partnership using funds provided by McGill University, the FRQS, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. The Brainstorm project is supported by funding to SB from the NIH (R01-EB026299-05). Further funding to SB for this study included a Discovery grant from the Natural Sciences and Engineering Research Council of Canada of Canada (436355-13), and the CIHR Canada research Chair in Neural Dynamics of Brain Systems (CRC-2017-00311).

Structural and neurophysiological alterations in Parkinson's disease are aligned with cortical neurochemical systems.

Parkinson's disease (PD) affects cortical structures and neurophysiology. How these deviations from normative variants relate to the neurochemical systems of the cortex in a manner corresponding to motor and cognitive symptoms is unknown. We measured cortical thickness and spectral neurophysiological alterations from structural magnetic resonance imaging and task-free magnetoencephalography in patients with idiopathic PD (NMEG = 79; NMRI = 65), contrasted with similar data from matched healthy controls (NMEG = 65; NMRI = 37). Using linear mixed-effects models and cortical atlases of 19 neurochemical systems, we found that the structural and neurophysiological alterations of PD align with several receptor and transporter systems (acetylcholine, serotonin, glutamate, and noradrenaline) albeit with different implications for motor and non-motor symptoms. Some neurophysiological alignments are protective of cognitive functions: the alignment of broadband power increases with acetylcholinergic systems is related to better attention function. However, neurochemical alignment with structural and other neurophysiological alterations is associated with motor and psychiatric impairments, respectively. Collectively, the present data advance understanding of the association between the nature of neurophysiological and structural cortical alterations in PD and the symptoms that are characteristic of the disease. They also demonstrate the value of a new nested atlas modeling approach to advance research on neurological and neuropsychiatric diseases.

The neurophysiological brain-fingerprint of Parkinson's disease.

In this study, we investigate the clinical potential of brain-fingerprints derived from electrophysiological brain activity for diagnostics and progression monitoring of Parkinson's disease (PD). We obtained brain-fingerprints from PD patients and age-matched healthy controls using short, task-free magnetoencephalographic recordings. The rhythmic components of the individual brain-fingerprint distinguished between patients and healthy participants with approximately 90% accuracy. The most prominent cortical features of the Parkinson's brain-fingerprint mapped to polyrhythmic activity in unimodal sensorimotor regions. Leveraging these features, we also show that Parkinson's disease stages can be decoded directly from cortical neurophysiological activity. Additionally, our study reveals that the cortical topography of the Parkinson's brain-fingerprint aligns with that of neurotransmitter systems affected by the disease's pathophysiology. We further demonstrate that the arrhythmic components of cortical activity are more variable over short periods of time in patients with Parkinson's disease than in healthy controls, making individual differentiation between patients based on these features more challenging and explaining previous negative published results. Overall, we outline patient-specific rhythmic brain signaling features that provide insights into both the neurophysiological signature and clinical staging of Parkinson's disease. For this reason, the proposed definition of a rhythmic brain-fingerprint of Parkinson's disease may contribute to novel, refined approaches to patient stratification and to the improved identification and testing of therapeutic neurostimulation targets.

Adverse and compensatory neurophysiological slowing in Parkinson's disease.

Patients with Parkinson's disease (PD) exhibit multifaceted changes in neurophysiological brain activity, hypothesized to represent a global cortical slowing effect. Using task-free magnetoencephalography and extensive clinical assessments, we found that neurophysiological slowing in PD is differentially associated with motor and non-motor symptoms along a sagittal gradient over the cortical anatomy. In superior parietal regions, neurophysiological slowing reflects an adverse effect and scales with cognitive and motor impairments, while across the inferior frontal cortex, neurophysiological slowing is compatible with a compensatory role. This adverse-to-compensatory gradient is sensitive to individual clinical profiles, such as drug regimens and laterality of symptoms; it is also aligned with the topography of neurotransmitter and transporter systems relevant to PD. We conclude that neurophysiological slowing in patients with PD signals both deleterious and protective mechanisms of the disease, from posterior to anterior regions across the cortex, respectively, with functional and clinical relevance to motor and cognitive symptoms.

The biological role of local and global fMRI BOLD signal variability in human brain organization.

Variability drives the organization and behavior of complex systems, including the human brain. Understanding the variability of brain signals is thus necessary to broaden our window into brain function and behavior. Few empirical investigations of macroscale brain signal variability have yet been undertaken, given the difficulty in separating biological sources of variance from artefactual noise. Here, we characterize the temporal variability of the most predominant macroscale brain signal, the fMRI BOLD signal, and systematically investigate its statistical, topographical and neurobiological properties. We contrast fMRI acquisition protocols, and integrate across histology, microstructure, transcriptomics, neurotransmitter receptor and metabolic data, fMRI static connectivity, and empirical and simulated magnetoencephalography data. We show that BOLD signal variability represents a spatially heterogeneous, central property of multi-scale multi-modal brain organization, distinct from noise. Our work establishes the biological relevance of BOLD signal variability and provides a lens on brain stochasticity across spatial and temporal scales.

Time-resolved parameterization of aperiodic and periodic brain activity.

Macroscopic neural dynamics comprise both aperiodic and periodic signal components. Recent advances in parameterizing neural power spectra offer practical tools for evaluating these features separately. Although neural signals vary dynamically and express non-stationarity in relation to ongoing behaviour and perception, current methods yield static spectral decompositions. Here, we introduce Spectral Parameterization Resolved in Time (SPRiNT) as a novel method for decomposing complex neural dynamics into periodic and aperiodic spectral elements in a time-resolved manner. First, we demonstrate, with naturalistic synthetic data, SPRiNT's capacity to reliably recover time-varying spectral features. We emphasize SPRiNT's specific strengths compared to other time-frequency parameterization approaches based on wavelets. Second, we use SPRiNT to illustrate how aperiodic spectral features fluctuate across time in empirical resting-state EEG data (n=178) and relate the observed changes in aperiodic parameters over time to participants' demographics and behaviour. Lastly, we use SPRiNT to demonstrate how aperiodic dynamics relate to movement behaviour in intracranial recordings in rodents. We foresee SPRiNT responding to growing neuroscientific interests in the parameterization of time-varying neural power spectra and advancing the quantitation of complex neural dynamics at the natural time scales of behaviour.

Investigating how the modularity of visuospatial attention shapes conscious perception using type I and type II signal detection theory.

Attention abilities rest on the coordinated interplay of multiple components. One consequence to this multifaceted account is that selection processes likely intersect with perception at various junctures. Drawing from this overarching view, the current research examines how different forms of visuospatial attention influence various aspects of conscious perception, including signal detection, signal discrimination, visual awareness, and metacognition. In this effort, we combined a double spatial cueing approach, where stimulus- and goal-driven orienting were concurrently engaged via separate cues, with Type I and Type II signal detection theoretic frameworks through five experiments. Consistent with the modular view of visuospatial attention, our comprehensive assessment reveals that stimulus- and goal-driven orienting operate independently of each other for increasing perceptual sensitivity and reducing the decision bound. Conversely, however, our study shows that both forms of orienting hardly influence visual awareness and metacognition once perceptual sensitivity is accounted for. Our results therefore undermine the idea that attention directly interfaces with subjective aspects of perception. Instead, our findings submit a general framework whereby these attention modules indirectly impact visual awareness and metacognition by increasing perceptual evidence and decreasing the decision bound. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Brief segments of neurophysiological activity enable individual differentiation.

Large, openly available datasets and current analytic tools promise the emergence of population neuroscience. The considerable diversity in personality traits and behaviour between individuals is reflected in the statistical variability of neural data collected in such repositories. Recent studies with functional magnetic resonance imaging (fMRI) have concluded that patterns of resting-state functional connectivity can both successfully distinguish individual participants within a cohort and predict some individual traits, yielding the notion of an individual's neural fingerprint. Here, we aim to clarify the neurophysiological foundations of individual differentiation from features of the rich and complex dynamics of resting-state brain activity using magnetoencephalography (MEG) in 158 participants. We show that akin to fMRI approaches, neurophysiological functional connectomes enable the differentiation of individuals, with rates similar to those seen with fMRI. We also show that individual differentiation is equally successful from simpler measures of the spatial distribution of neurophysiological spectral signal power. Our data further indicate that differentiation can be achieved from brain recordings as short as 30 seconds, and that it is robust over time: the neural fingerprint is present in recordings performed weeks after their baseline reference data was collected. This work, thus, extends the notion of a neural or brain fingerprint to fast and large-scale resting-state electrophysiological dynamics.

"When I hear my language, I travel back in time and I feel at home": Intersections of culture with social inclusion and exclusion of persons with dementia and their caregivers.

Individuals with dementia and their carers often experience a rupture of relationships that co-occurs with declining functional and cognitive abilities, leading to their increased social exclusion in both intimate relationships and community settings. While initiatives have been developed to support meaningful interaction and participation in society, they have broadly ignored the significance of how cultural factors influence experiences of inclusion/exclusion of these individuals. An ethnographic study was conducted by an interdisciplinary research team between April 2018 and January 2019 to explore the intersections of culture and social inclusion/exclusion in a culturally diverse group of persons with dementia, caregivers and staff members of a non-profit organization located in a multicultural neighborhood of a bilingual Canadian city. The participants' culture was inextricably linked to their experiences in three overarching themes of social inclusion/exclusion: transformation of the person with dementia and the caregiver; participation in social networks and meaningful relations; and styles of care provision in health and social services. Cultural mandates that prescribe practices of intergenerational care shape the way certain caregivers perceive their role and mitigated experiences of exclusion. Culturally specific notions and views associated with dementia prevalent in certain communities increased experiences of inclusion or exclusion. Engagement with the cultural elements of individuals with dementia was shown to be an effective and underexplored tool for fostering inclusion. The results of this study highlight the value of the ethnographic methods for incorporating the perspective of persons with dementia in research.