•During sleep, glymphatic system (GS) activation clears toxins from the brain.•Striatal dopamine modulates clock gene expression and sleep-wake rhythm.•Dopaminergic dysfunction and alpha-synuclein ...aggregations characterize PD.•Disrupted sleep in PD may decrease metabolic clearance with alpha-synuclein buildup.•Non-invasive neuroimaging of the GS may improve diagnostic and interventional tools.
Recent evidence has advanced our understanding of the function of sleep to include removal of neurotoxic protein aggregates via the glymphatic system. However, most research on the glymphatic system utilizes animal models, and the function of waste clearance processes in humans remains unclear. Understanding glymphatic function offers new insight into the development of neurodegenerative diseases that result from toxic protein inclusions, particularly those characterized by neuropathological sleep dysfunction, like Parkinson’s disease (PD). In PD, we propose that glymphatic flow may be compromised due to the combined neurotoxic effects of alpha-synuclein protein aggregates and deteriorated dopaminergic neurons that are linked to altered REM sleep, circadian rhythms, and clock gene dysfunction. This review highlights the importance of understanding the functional role of glymphatic system disturbance in neurodegenerative disorders and the subsequent clinical and neuropathological effects on disease progression. Future research initiatives utilizing noninvasive brain imaging methods in human subjects with PD are warranted, as in vivo identification of functional biomarkers in glymphatic system functioning may improve clinical diagnosis and treatment of PD.
More than 30 years after the human immunodeficiency virus (HIV) epidemic, HIV patients are now aging due to the advances of antiretroviral therapy. With immunosenescence and the susceptibility of ...dopamine-rich basal ganglia regions to HIV-related injury, older HIV patients may show neurofunctional deficits similar to patients with Parkinson's disease (PD). We examined the amplitudes of low frequency fluctuations (ALFF) across different frequency bands of the BOLD signal in 30 older HIV-infected individuals, 33 older healthy controls, and 36 PD patients. Participants underwent resting-state fMRI, neuropsychological testing, and a clinical motor exam. HIV patients mainly showed abnormalities in cortical ALFF with reduced prefrontal amplitudes and enhanced sensorimotor and inferior temporal amplitudes. Frontal hypoactivation was overlapping for HIV and PD groups and different from controls. PD patients further exhibited reduced pallidum amplitudes compared to the other groups. In the HIV group, lower pallidum amplitudes were associated with lower CD4
nadir and CD4
T cell counts. Abnormalities in ALFF dynamics were largely associated with cognitive and motor functioning in HIV and PD groups. The disruption of neurofunctional frequency dynamics in subcortical-cortical circuits could contribute to the development of cognitive and motor dysfunction and serve as a biomarker for monitoring disease progression with immunosenescence. Graphical Abstract.
Critical changes in adolescence involve brain cognitive maturation of inhibitory control processes that are essential for a myriad of adult functions. Cognitive control advances into adulthood as ...there is more flexible integration of component processes, including inhibitory control of conflicting information, overwriting inappropriate response tendencies, and amplifying relevant responses for accurate execution. Using a modified Stroop task with fMRI, we investigated the effects of age, sex, and puberty on brain functional correlates of cognitive and motor control in 87 boys and 91 girls across the adolescent age range. Results revealed dissociable brain systems for cognitive and motor control processes, whereby adolescents flexibly adapted neural responses to control demands. Specifically, when response repetitions facilitated planning-based action selection, frontoparietal-insular regions associated with cognitive control operations were less activated, whereas cortical-pallidal-cerebellar motor regions associated with motor skill acquisition, were more activated. Attenuated middle cingulate cortex activation occurred with older adolescent age for both motor control and cognitive control with automaticity from repetition learning. Sexual dimorphism for control operations occurred in extrastriate cortices involved in visuo-attentional selection: While boys enhanced extrastriate selection processes for motor control, girls activated these regions more for cognitive control. These sex differences were attenuated with more advanced pubertal stage. Together, our findings show that brain cognitive and motor control processes are segregated, demand-specific, more efficient in older adolescents, and differ between sexes relative to pubertal development. Our findings advance our understanding of how distributed brain activity and the neurodevelopment of automaticity enhances cognitive and motor control ability in adolescence.
Abstract Introduction: Motor and cognitive deficits were compared in aging, chronically treated HIV people, people with mild-to-moderate stage Parkinson’s disease (PD) and healthy controls. Methods: ...Groups consisted of 36 people with PD, 28 with HIV infection and 28 healthy controls. Motor function was assessed with the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-III) and a rapid alternating finger tapping (RAFT) task on an engineered keyboard known as Quantitative Digitography (QDG). Executive function, verbal memory and visuospatial processing were assessed using standard neuropsychological tests. Results: HIV demonstrated RAFT deficits similar to PD such as reduced amplitude (P=0.023) and greater amplitude variability (P=0.019) in the index finger when compared to controls. This fine motor disturbance correlated with HIV’s immune health, measured by their CD4+ T cell count (P<0.01). The UPDRS did not yield motor differences between HIV and controls. Executive function and verbal memory were impaired in HIV (P=0.006, P=0.016, respectively), but not in PD; visuospatial processing was similarly impaired in HIV and PD (P <0.05) although motor deficits predominated in PD. Conclusions: Fine motor bradykinesia measured quantitatively by QDG RAFT holds promise as a marker of motor decline related to current immune health in aging HIV patients and may be useful in longitudinal studies regarding mechanisms of immunosenescence versus potential toxicity of cART in this population. Additionally, motor and cognitive networks in HIV may be affected differently as the disease progresses as observed in the differential patterns of impairment between HIV and PD, providing insight into the mechanisms of brain deterioration in HIV.
In adolescents, the relationship between alcohol-related blackouts (ARBs) and distinct cognitive changes lasting beyond intoxication is unclear. We examined ARBs as a predictor of persistent changes ...in the development of learning, memory, and executive function in participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study.
Descriptive analyses of the NCANDA sample (
= 831, 50.9% female, 12-21 years at baseline) identified ARB patterns within participants with an ARB history (
= 106). Latent growth curve modeling evaluated ARB-related performance changes on four neuropsychological measures across five years, excluding baseline data to reduce the magnitude of practice effects over time (
= 790). Measures included the Penn Conditional Exclusion Test (PCET), Penn Letter N-back Test (PLBT), Penn Facial Memory Test immediate (PFMT
), and delayed (PFMT
) recognition trials, and the Rey Complex Figure Test copy (RCFT
), immediate recall (RCFT
), and delayed recall (RCFT
) trials. Multivariate models were fit for raw accuracy scores from each measure, with ARB history (i.e., presence of past-year ARBs) as the main independent variable. Age, sex, race, socioeconomic status, assessment site, and alcohol use (i.e., past-year frequency) were included as covariates. Interaction effects between ARB history and alcohol use frequency were tested.
By year five, 16% of participants had experienced at least one ARB (59% of whom reported > 1 ARB and 57% of whom had an ARB lasting > 1 h). After controlling for demographics and alcohol use, ARB history predicted attenuated PFMT
performance growth at year one. Interaction effects between ARB history and alcohol use frequency predicted attenuated PFMT
performance growth at years one and two. ARB history predicted attenuated RCFT
and RCFT
performance growth by year four, but not PCET or PLBT performance over time. By contrast, greater past-year alcohol use predicted attenuated PFMT
and PFMT
performance growth between years two and four in adolescents without an ARB history.
We found that ARBs predict distinct, lasting changes in learning and memory for visual information, with results suggesting that the developing brain is vulnerable to ARBs during adolescence and emerging adulthood.
Background: Visuospatial ability is a multifactorial process commonly impaired in chronic alcoholism. Identification of which features of visuospatial processing are affected and which are spared in ...alcoholism, however, has not been clearly determined. We used a global–local paradigm to assess component processes of visuospatial ability and MR diffusion tensor imaging (DTI) to examine whether alcoholism‐related microstructural degradation of the corpus callosum contributes to disruption of selective lateralized visuospatial and attention processes.
Methods: A hierarchical letter paradigm was devised, where large global letters were composed of small local letters. The task required identification of target letters among distractors presented at global, local, both, or neither level. Attention was either selectively directed to global or local levels or divided between levels. Participants were 18 detoxified chronic alcoholics and 22 age‐matched healthy controls. DTI provided quantitative assessment of the integrity of corpus callosal white matter microstructure.
Results: Alcoholics generally had longer reaction times than controls but obtained similar accuracy scores. Both groups processed local targets faster than global targets and showed interference from targets at the unattended level. Alcoholics exhibited moderate compromise in selectively attending to the global level when the global stimuli were composed of local targets. Such local interference was less with longer abstinence. Callosal microstructural integrity compromise predicted degree of interference from stimulus incongruency in the alcoholic group. This relationship was not observed for lateral or third ventricular volumes, which are measures of nonspecific cortical volume deficits.
Conclusion: Global–local feature perception was generally spared in abstinent chronic alcoholics, but impairments were observed when directing attention to global features and when global and local information interfered at stimulus or response levels. Furthermore, the interference‐callosal integrity relationship in alcoholics indicates that compromised visuospatial functions include those requiring bilateral integration of information.
The Resting Brain of Alcoholics Müller-Oehring, Eva M; Jung, Young-Chul; Pfefferbaum, Adolf ...
Cerebral cortex (New York, N.Y. 1991),
11/2015, Letnik:
25, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Chronic alcohol consumption affects multiple cognitive processes supported by far-reaching cerebral networks. To identify neurofunctional mechanisms underlying selective deficits, 27 sober alcoholics ...and 26 age-matched controls underwent resting-state functional magnetic resonance imaging and neuropsychological testing. Functional connectivity analysis assessed the default mode network (DMN); integrative executive control (EC), salience (SA), and attention (AT) networks; primary somatosensory, auditory, and visual (VI) input networks; and subcortical reward (RW) and emotion (EM) networks. The groups showed an extensive overlap of intrinsic connectivity in all brain networks examined, suggesting overall integrity of large-scale functional networks. Despite these similar patterns, connectivity analyses identified network-specific differences of weaker within-network connectivity and expanded connectivity to regions outside the main networks in alcoholics compared with controls. For AT and VI networks, better task performance was related to expanded connectivity in alcoholism, supporting the concept of network expansion as a neural mechanism for functional compensation. For default mode, SA, RW, and EC networks, both weaker within-network and expanded outside-network connectivity correlated with poorer performance and mood. Current smoking contributed to some of these abnormalities in connectivity. The observed pattern of resting-state connectivity might reflect neural vulnerability of intrinsic networking in alcoholics and suggests a mechanism to explain signature impairments in EM, RW evaluation, and EC ability.
The current study identified classes of conjoint marijuana and alcohol use in entering college freshmen using latent profile analysis (N = 772; 53% male, 60% White; Mage = 18). Results yielded 4 ...distinct groups: Class 1 (moderate drinking with recent marijuana use: 22% of sample), Class 2 (moderate drinking with no recent marijuana use: 25%), Class 3 (light drinking with no recent marijuana use: 40%) and Class 4 (heavy drinking with recent marijuana use: 14%). Separate pairwise contrasts examined cross-class differences in demographics and drinking behaviors, comparing differences in drinking when current marijuana use was controlled (Class 1 vs. 4) and differences in marijuana use when drinking was held relatively constant (Class 1 vs. 2). Among moderate drinkers, recent marijuana users were more likely to drink more than intended, drink to get drunk, and had more problems (including higher rates of blackouts, physical injury, and DUI) relative to peers who refrained from marijuana. No cross-class differences were found for alcohol expectancies or behavioral motives. Findings from these analyses show the presence of distinct groups of conjoint users with different drinking behaviors and consequence profiles, and suggest that conjoint alcohol-marijuana use may be more problematic overall than single substance involvement and highlight the need for developing campus prevention and intervention programs that address the increased risk from polysubstance involvement.
Objectives: Worry has been shown to have a negative impact on many aspects of neurocognitive performance. Interestingly, research indicates mindfulness both improves aspects of cognitive ability and ...reduces worry symptoms. Yet, the impact of mindfulness on the relationship between worry and cognition has yet to be explored. Based on research discussed herein, we hypothesize that those with higher levels of dispositional mindfulness will have better cognitive performance than those with lower levels of dispositional mindfulness, regardless of worry level. The present study investigated the potential moderating influence of mindfulness on the relationship between worry and cognitive performance.
Methods: The sample included 113 older veterans who were screened at the VA Palo Alto Health Care System in Palo Alto, CA. Cognitive domains of interest included learning and memory, processing speed, attention, working memory, and executive function. Mindfulness was assessed with the Five Facet Mindfulness Questionnaire (FFMQ), and worry symptoms were assessed using the Penn State Worry Questionnaire (PSWQ). Hypotheses were tested with multiple regression analyses using the Hayes (2003) PROCESS macro.
Results: Contrary to what was hypothesized, only mindful awareness significantly moderated the relationship between worry and processing speed.
Conclusion: This finding has important implications for introducing mindfulness techniques into older adults' routines to decrease worry and mitigate its negative effects on processing speed.
Abstract
Objective
The growing multilingual population in the United States calls for culturally adapted norms for neuropsychological tools. Language testing, for example, is paramount in ...pre-surgical assessment in patients with dominant temporal lobe epilepsy. The Boston Naming Test (BNT) and the Auditory Naming Test (ANT) are frequently used in pre-surgical epilepsy evaluations; yet, while bilingual norms exist for the BNT, these are lacking for the ANT. To parse out how much of a bilingual patient’s language performance is accounted for by bilingualism versus language deficits, we studied whether there is a significant difference in ANT performance between bilingual and monolingual English-speaking epilepsy patients.
Method
Our sample of patients with localized epilepsy from the UCSF Epilepsy Center included 22 bilingual (English-dominant; non-dominant languages included Spanish, Arabic, Dutch, Taiwanese, and Japanese) and 61 monolingual English-speakers (39% female, M age = 36.3). All patients took anti-seizure medication and completed the ANT and BNT as part of a pre-surgical neuropsychological assessment.
Results
Compared to monolingual English-speaking patients, bilingual patients had significantly lower scores on the ANT (Bilingual M = −4.03 SD = 5.6, Monolingual M = −0.7 SD = 1.9; t(81) = 3.89, p < 0.001) and BNT (t(77) = 2.76, p = 0.007). This performance difference was significantly greater for the ANT than BNT (F(1,77) = 7.71, p = 0.007).
Conclusion
These results highlight the importance of considering multilingualism in neuropsychological assessments. This is especially needed for pre-surgical language mapping in epilepsy surgical candidates. Future research should establish bilingual normative standards for neuropsychological language-based tests such as the ANT.
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