Neurochemical organization of cortical proteinopathy and neurophysiology along the Alzheimer's disease continuum.

INTRODUCTION: Despite parallel research indicating amyloid-ß accumulation, alterations in cortical neurophysiological signaling, and multi-system neurotransmitter disruptions in Alzheimer's disease (AD), the relationships between these phenomena remains unclear. METHODS: Using magnetoencephalography, positron emission tomography, and an atlas of 19 neurotransmitters, we studied the alignment between neurophysiological alterations, amyloid-ß deposition, and the neurochemical gradients of the cortex. RESULTS: In patients with mild cognitive impairment and AD, changes in cortical rhythms were topographically aligned with cholinergic, serotonergic, and dopaminergic systems. These alignments correlated with the severity of clinical impairments. Additionally, cortical amyloid-ß plaques were preferentially deposited along neurochemical boundaries, influencing how neurophysiological alterations align with muscarinic acetylcholine receptors. Most of the amyloid-ß-neurochemical and alpha-band neuro-physio-chemical alignments replicated in an independent dataset of individuals with asymptomatic amyloid-ß accumulation. DISCUSSION: Our findings demonstrate that AD pathology aligns topographically with the cortical distribution of chemical neuromodulator systems and scales with clinical severity, with implications for potential pharmacotherapeutic pathways. HIGHLIGHTS: Changes in cortical rhythms in Alzheimer's are organized along neurochemical boundaries. The strength of these alignments is related to clinical symptom severity. Deposition of amyloid-ß (Aß) is aligned with similar neurotransmitter systems. Aß deposition mediates the alignment of beta rhythms with cholinergic systems. Most alignments replicate in participants with pre-clinical Alzheimer's pathology.

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).

Neuromodulatory effects of parietal high-definition transcranial direct-current stimulation on network-level activity serving fluid intelligence.

Fluid intelligence (Gf) involves rational thinking skills and requires the integration of information from different cortical regions to resolve novel complex problems. The effects of non-invasive brain stimulation on Gf have been studied in attempts to improve Gf, but such studies are rare and the few existing have reached conflicting conclusions. The parieto-frontal integration theory of intelligence (P-FIT) postulates that the parietal and frontal lobes play a critical role in Gf. To investigate the suggested role of parietal cortices, we applied high-definition transcranial direct current stimulation (HD-tDCS) to the left and right parietal cortices of 39 healthy adults (age 19-33 years) for 20 min in three separate sessions (left active, right active and sham). After completing the stimulation session, the participants completed a logical reasoning task based on Raven's Progressive Matrices during magnetoencephalography. Significant neural responses at the sensor level across all stimulation conditions were imaged using a beamformer. Whole-brain, spectrally constrained functional connectivity was then computed to examine the network-level activity. Behaviourally, we found that participants were significantly more accurate following left compared to right parietal stimulation. Regarding neural findings, we found significant HD-tDCS montage-related effects in brain networks thought to be critical for P-FIT, including parieto-occipital, fronto-occipital, fronto-parietal and occipito-cerebellar connectivity during task performance. In conclusion, our findings showed that left parietal stimulation improved abstract reasoning abilities relative to right parietal stimulation and support both P-FIT and the neural efficiency hypothesis. KEY POINTS: Abstract reasoning is a critical component of fluid intelligence and is known to be served by multispectral oscillatory activity in the fronto-parietal cortices. Recent studies have aimed to improve abstract reasoning abilities and fluid intelligence overall through behavioural training, but the results have been mixed. High-definition transcranial direct-current stimulation (HD-tDCS) applied to the parietal cortices modulated task performance and neural oscillations during abstract reasoning. Left parietal stimulation resulted in increased accuracy and decreased functional connectivity between occipital regions and frontal, parietal, and cerebellar regions. Future studies should investigate whether HD-tDCS alters abstract reasoning abilities in those who exhibit declines in performance, such as healthy ageing populations.

Alignments between cortical neurochemical systems, proteinopathy and neurophysiological alterations along the Alzheimer's disease continuum.

Two neuropathological hallmarks of Alzheimer's disease (AD) are the accumulation of amyloid-ß (Aß) proteins and alterations in cortical neurophysiological signaling. Despite parallel research indicating disruption of multiple neurotransmitter systems in AD, it has been unclear whether these two phenomena are related to the neurochemical organization of the cortex. We leveraged task-free magnetoencephalography and positron emission tomography, with a cortical atlas of 19 neurotransmitters to study the alignment and interactions between alterations of neurophysiological signaling, Aß deposition, and the neurochemical gradients of the human cortex. In patients with amnestic mild cognitive impairment (N = 18) and probable AD (N = 20), we found that changes in rhythmic, but not arrhythmic, cortical neurophysiological signaling relative to healthy controls (N = 20) are topographically aligned with cholinergic, serotonergic, and dopaminergic neurochemical systems. These neuro-physio-chemical alignments are related to the severity of cognitive and behavioral impairments. We also found that cortical Aß plaques are preferentially deposited along neurochemical boundaries, and mediate how beta-band rhythmic cortical activity maps align with muscarinic acetylcholine receptors. Finally, we show in an independent dataset that many of these alignments manifest in the asymptomatic stages of cortical Aß accumulation (N = 33; N = 71 healthy controls), particularly the Aß-neurochemical alignments (57.1%) and neuro-physio-chemical alignments in the alpha frequency band (62.5%). Overall, the present study demonstrates that the expression of pathology in pre-clinical and clinical AD aligns topographically with the cortical distribution of chemical neuromodulator systems, scaling with clinical severity and with implications for potential pharmacotherapeutic pathways.

Multispectral brain connectivity during visual attention distinguishes controlled from uncontrolled hypertension.

Hypertension-related changes in brain function place individuals at higher risk for cognitive impairment and Alzheimer's disease. The existing functional neuroimaging literature has identified important neural and behavioural differences between normotensive and hypertensive individuals. However, previously-used methods (i.e. magnetic resonance imaging, functional near-infrared spectroscopy) rely on neurovascular coupling, which is a useful but indirect measure of neuronal activity. Furthermore, most studies fail to distinguish between controlled and uncontrolled hypertensive individuals, who exhibit significant behavioural and clinical differences. To partially remedy this gap in the literature, we used magnetoencephalography (MEG) to directly examine neuronal activity that is invariant to neurovascular coupling changes induced by hypertension. Our study included 52 participants (19 healthy controls, 15 controlled hypertensives, 18 uncontrolled hypertensives) who completed a modified flanker attention task during MEG. We identified significant oscillatory neural responses in two frequencies (alpha: 8-14 Hz, gamma: 48-60 Hz) for imaging and used grand-averaged images to determine seeds for whole-brain connectivity analysis. We then conducted Fisher-z tests for each pair of groups, using the relationship between the neural connectivity and behavioural attention effects. This highlighted a distributed network of regions associated with cognitive control and selective attention, including frontal-occipital and interhemispheric occipital connections. Importantly, the inferior frontal cortex exhibited a unique neurobehavioural relationship that distinguished the uncontrolled hypertensive group from the controlled hypertensive and normotensive groups. This is the first investigation of hypertension using MEG and identifies critical whole-brain connectivity differences based on hypertension profiles. KEY POINTS: Structural and functional changes in brain circuitry scale with hypertension severity and increase the risk of cognitive impairment and Alzheimer's disease. We harness the excellent spatiotemporal precision of magnetoencephalography (MEG) to directly quantify dynamic functional connectivity in healthy control, controlled hypertensive and uncontrolled hypertensive groups during a flanker task. In the first MEG study of hypertension, we show that there are neurobehavioural relationships that distinguish the uncontrolled hypertensive group from healthy and controlled hypertensive group in the prefrontal cortex. These results provide novel insights into the differential impact of hypertension on brain dynamics underlying selective attention.

Associations between neuromelanin depletion and cortical rhythmic activity in Parkinson's disease.

Background and Objectives: Parkinson's disease (PD) is marked by the death of neuromelanin-rich dopaminergic and noradrenergic cells in the substantia nigra (SN) and the locus coeruleus (LC), respectively, resulting in motor and cognitive impairments. While SN dopamine dysfunction has clear neurophysiological effects, the impact of reduced LC norepinephrine signaling on brain activity in PD remains to be established. Methods: We used neuromelanin-sensitive T1-weighted MRI (NPD = 58; NHC = 27) and task-free magnetoencephalography (NPD = 58; NHC = 65) to identify neuropathophysiological factors related to the degeneration of the LC and SN in patients with PD. Results: We found pathological increases in rhythmic alpha (8 - 12 Hz) activity in patients with decreased LC neuromelanin, with a stronger association in patients with worse attentional impairments. This negative alpha-LC neuromelanin relationship is also stronger in fronto-motor cortices, which are regions with high densities of norepinephrine transporters in the healthy brain, and where alpha activity is negatively related to attention scores. These observations support a noradrenergic association between LC integrity and alpha band activity. Our data also show that rhythmic beta (15 - 29 Hz) activity in the left somato-motor cortex decreases with lower levels of SN neuromelanin; the same regions where beta activity reflects axial motor symptoms. Discussion: Together, our findings clarify the association of well-documented alterations of rhythmic neurophysiology in PD with cortical and subcortical neurochemical systems. Specifically, attention-related alpha activity reflects dysfunction of the noradrenergic system, and beta activity with relevance to motor impairments reflects dopaminergic dysfunction.

Modulation of movement-related oscillatory signatures by cognitive interference in healthy aging.

Age-related changes in the neurophysiology underlying motor control are well documented, but whether these changes are specific to motor function or more broadly reflect age-related alterations in fronto-parietal circuitry serving attention and other higher-level processes remains unknown. Herein, we collected high-density magnetoencephalography (MEG) in 72 healthy adults (age 28-63 years) as they completed an adapted version of the multi-source interference task that involved two subtypes of cognitive interference (i.e., flanker and Simon) and their integration (i.e., multi-source). All MEG data were examined for age-related changes in neural oscillatory activity using a whole-brain beamforming approach. Our primary findings indicated robust behavioral differences in task performance based on the type of interference, as well as stronger beta oscillations with increasing age in the right dorsolateral prefrontal cortices (flanker and multi-source conditions), left parietal (flanker and Simon), and medial parietal regions (multi-source). Overall, these data indicate that healthy aging is associated with alterations in higher-order association cortices that are critical for attention and motor control in the context of cognitive interference.

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.

Piecing it together: atrophy profiles of hippocampal subfields relate to cognitive impairment along the Alzheimer's disease spectrum.

Introduction: People with Alzheimer's disease (AD) experience more rapid declines in their ability to form hippocampal-dependent memories than cognitively normal healthy adults. Degeneration of the whole hippocampal formation has previously been found to covary with declines in learning and memory, but the associations between subfield-specific hippocampal neurodegeneration and cognitive impairments are not well characterized in AD. To improve prognostic procedures, it is critical to establish in which hippocampal subfields atrophy relates to domain-specific cognitive declines among people along the AD spectrum. In this study, we examine high-resolution structural magnetic resonance imaging (MRI) of the medial temporal lobe and extensive neuropsychological data from 29 amyloid-positive people on the AD spectrum and 17 demographically-matched amyloid-negative healthy controls. Methods: Participants completed a battery of neuropsychological exams including select tests of immediate recollection, delayed recollection, and general cognitive status (i.e., performance on the Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). Hippocampal subfield volumes (CA1, CA2, CA3, dentate gyrus, and subiculum) were measured using a dedicated MRI slab sequence targeting the medial temporal lobe and used to compute distance metrics to quantify AD spectrum-specific atrophic patterns and their impact on cognitive outcomes. Results: Our results replicate prior studies showing that CA1, dentate gyrus, and subiculum hippocampal subfield volumes were significantly reduced in AD spectrum participants compared to amyloid-negative controls, whereas CA2 and CA3 did not exhibit such patterns of atrophy. Moreover, degeneration of the subiculum along the AD spectrum was linked to a significant decline in general cognitive status measured by the MMSE, while degeneration scores of the CA1 and dentate gyrus were more widely associated with declines on the MMSE and tests of learning and memory. Discussion: These findings provide evidence that subfield-specific patterns of hippocampal degeneration, in combination with cognitive assessments, may constitute a sensitive prognostic approach and could be used to better track disease trajectories among individuals on the AD spectrum.

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.

Altered age-related alpha and gamma prefrontal-occipital connectivity serving distinct cognitive interference variants.

The presence of conflicting stimuli adversely affects behavioral outcomes, which could either be at the level of stimulus (Flanker), response (Simon), or both (Multisource). Briefly, flanker interference involves conflicting stimuli requiring selective attention, Simon interference is caused by an incongruity between the spatial location of the task-relevant stimulus and prepotent motor mapping, and multisource is combination of both. Irrespective of the variant, interference resolution necessitates cognitive control to filter irrelevant information and allocate neural resources to task-related goals. Though previously studied in healthy young adults, the direct quantification of changes in oscillatory activity serving such cognitive control and associated inter-regional interactions in healthy aging are poorly understood. Herein, we used an adapted version of the multisource interference task and magnetoencephalography to investigate age-related alterations in the neural dynamics governing both divergent and convergent cognitive interference in 78 healthy participants (age range: 20-66 years). We identified weaker alpha connectivity between bilateral visual and right dorsolateral prefrontal cortices (DLPFC) and left dorsomedial prefrontal cortices (dmPFC), as well as weaker gamma connectivity between bilateral occipital regions and the right dmPFC during flanker interference with advancing age. Further, an age-related decrease in gamma power was observed in the left cerebellum and parietal region for Simon and differential interference effects (i.e., flanker-Simon), respectively. Moreover, the superadditivity model showed decreased gamma power in the right temporoparietal junction (TPJ) with increasing age. Overall, our findings suggest age-related declines in the engagement of top-down attentional control secondary to reduced alpha and gamma coupling between prefrontal and occipital cortices.

Movement-related beta and gamma oscillations indicate parallels and disparities between Alzheimer's disease and HIV-associated neurocognitive disorder.

People with HIV (PWH) often develop HIV-related neurological impairments known as HIV-associated neurocognitive disorder (HAND), but cognitive dysfunction in older PWH may also be due to age-related disorders such as Alzheimer's disease (AD). Discerning these two conditions is challenging since the specific neural characteristics are not well understood and limited studies have probed HAND and AD spectrum (ADS) directly. We examined the neural dynamics underlying motor processing during cognitive interference using magnetoencephalography (MEG) in 22 biomarker-confirmed patients on the ADS, 22 older participants diagnosed with HAND, and 30 healthy aging controls. MEG data were transformed into the time-frequency domain to examine movement-related oscillatory activity and the impact of cognitive interference on distinct stages of motor programming. Both cognitively impaired groups (ADS/HAND) performed significantly worse on the task (e.g., less accurate and slower reaction time) and exhibited reductions in frontal and cerebellar beta and parietal gamma activity relative to controls. Disease-specific aberrations were also detected such that those with HAND exhibited weaker gamma interference effects than those on the ADS in frontoparietal and motor areas. Additionally, temporally distinct beta interference effects were identified, with ADS participants exhibiting stronger beta interference activity in the temporal cortex during motor planning, along with weaker beta interference oscillations dispersed across frontoparietal and cerebellar cortices during movement execution relative to those with HAND. These results indicate both overlapping and distinct neurophysiological aberrations in those with ADS disorders or HAND in key motor and top-down cognitive processing regions during cognitive interference and provide new evidence for distinct neuropathology.

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.

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.

Aberrant neurophysiological signaling associated with speech impairments in Parkinson's disease.

Difficulty producing intelligible speech is a debilitating symptom of Parkinson's disease (PD). Yet, both the robust evaluation of speech impairments and the identification of the affected brain systems are challenging. Using task-free magnetoencephalography, we examine the spectral and spatial definitions of the functional neuropathology underlying reduced speech quality in patients with PD using a new approach to characterize speech impairments and a novel brain-imaging marker. We found that the interactive scoring of speech impairments in PD (N = 59) is reliable across non-expert raters, and better related to the hallmark motor and cognitive impairments of PD than automatically-extracted acoustical features. By relating these speech impairment ratings to neurophysiological deviations from healthy adults (N = 65), we show that articulation impairments in patients with PD are associated with aberrant activity in the left inferior frontal cortex, and that functional connectivity of this region with somatomotor cortices mediates the influence of cognitive decline on speech deficits.

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.

Youth with Cerebral Palsy Display Abnormal Somatosensory Cortical Activity During a Haptic Exploration Task.

There are numerous clinical reports that youth with cerebral palsy (CP) have proprioceptive, stereognosis and tactile discrimination deficits. The growing consensus is that the altered perceptions in this population are attributable to aberrant somatosensory cortical activity seen during stimulus processing. It has been inferred from these results that youth with CP likely do not adequately process ongoing sensory feedback during motor performance. However, this conjecture has not been tested. Herein, we address this knowledge gap using magnetoencephalographic (MEG) brain imaging by applying electrical stimulation to the median nerve of youth with CP (N = 15, Age = 15.8 ± 0.83 yrs, Males = 12, MACS levels I-III) and neurotypical (NT) controls (N = 18, Age = 14.1 ± 2.4 yrs, Males = 9) while at rest (i.e., passive) and during a haptic exploration task. The results illustrated that the somatosensory cortical activity was reduced in the group with CP compared to controls during the passive and haptic conditions. Furthermore, the strength of the somatosensory cortical responses during the passive condition were positively associated with the strength of somatosensory cortical responses during the haptic condition (r = 0.75, P = 0.004). This indicates that the aberrant somatosensory cortical responses seen in youth with CP during rest are a good predictor of the extent of somatosensory cortical dysfunction during the performance of motor actions. These data provide novel evidence that aberrations in somatosensory cortical function in youth with CP likely contribute to the difficulties in sensorimotor integration and the ability to effectively plan and execute motor actions.

Oscillatory markers of neuroHIV-related cognitive impairment and Alzheimer's disease during attentional interference processing.

People with HIV (PWH) frequently experience mild cognitive decline, which is typically attributed to HIV-associated neurocognitive disorder (HAND). However, such declines could also be a sign of early Alzheimer's disease (AD) in older PWH. Distinguishing these two pathologies in PWH is exceedingly difficult, as there is a major knowledge gap regarding their neural and neuropsychological bases. In the current study, we begin to address this knowledge gap by recording magnetoencephalography (MEG) during a flanker interference task in 31 biomarker-confirmed patients on the AD spectrum (ADS), 25 older participants with HAND, and 31 cognitively-normal controls. MEG data was examined in the time-frequency domain using a data-driven approach. Our results indicated that the clinical groups (ADS/HAND) performed significantly worse than controls on the task and exhibited aberrations in interference-related theta and alpha oscillations, some of which were disease-specific. Specifically, patients (ADS/HAND) exhibited weaker interference activity in frontoparietal and cingulate cortices compared to controls, while the ADS group exhibited stronger theta interference than those with HAND in frontoparietal, occipital, and temporal cortices. These results reveal overlapping and distinct patterns of neurophysiological alterations among those with ADS and HAND in attentional processing centers and suggest the existence of unique oscillatory markers of each condition.

Convergent and divergent oscillatory aberrations during visuospatial processing in HIV-related cognitive impairment and Alzheimer's disease.

Adults with HIV frequently develop a form of mild cognitive impairment known as HIV-associated neurocognitive disorder (HAND), but presumably cognitive decline in older persons with HIV could also be attributable to Alzheimer's disease (AD). However, distinguishing these two conditions in individual patients is exceedingly difficult, as the distinct neural and neuropsychological features are poorly understood and most studies to date have only investigated HAND or AD spectrum (ADS) disorders in isolation. The current study examined the neural dynamics underlying visuospatial processing using magnetoencephalography (MEG) in 31 biomarker-confirmed patients on the ADS, 26 older participants who met criteria for HAND, and 31 older cognitively normal controls. MEG data were examined in the time-frequency domain, and a data-driven approach was utilized to identify the neural dynamics underlying visuospatial processing. Both clinical groups (ADS/HAND) were significantly less accurate than controls on the task and exhibited stronger prefrontal theta oscillations compared to controls. Regarding disease-specific alterations, those with HAND exhibited stronger alpha oscillations than those on the ADS in frontoparietal and temporal cortices. These results indicate both common and unique neurophysiological alterations among those with ADS disorders and HAND in regions serving visuospatial processing and suggest the underlying neuropathological features are at least partially distinct.