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Open Access Publications from the University of California

Scholarly Works (61 results)

  • Article
Neurology (2021)
Several studies have shown the promise of cognitive ERP (event-related potential) as a cost-effective and non-invasive modality for monitoring forms of pathological aging such as Alzheimer’s Disease. Specifically, ERP waveforms P600 and N400 have been shown to be sensitive to pathological aging and potentially predictive for development of Alzheimer’s Disease. In collaboration with UCSD, the Olichney Cognitive Electrophysiology and Neuroimaging (CEAN) lab has been conducting a multiyear longitudinal study to better understand and characterize Alzheimer’s Disease progression through ERP biomarker analysis. This study involves recruitment of four patient groups (control, “preclinical” Alzheimer’s Disease, mild cognitive impairment, and mild Alzheimer’s Dementia) that undergo initial ERP testing with repeat testing at 12 months and 24 months. Here, we assess the preliminary changes seen in ERP waveforms P600 and N400 for enrolled patients with AD progression at baseline when compared to a normal aging cohort. By using average z-scores for each patient group, we found that P600 amplitude was reduced significantly in all three AD groups when compared to the normal control. This suggests that P600 may be a sensitive marker of AD progression prior to clinical symptoms showing. We also found that the N400 congruous effect was increased in MCI and AD patients but not preclinical AD, suggesting that N400 changes may occur later in AD progression than P600. Due to small sample size, however, further statistical analysis must be conducted to confirm these trends when enrollment restarts in Spring 2021.
    Cover page: Characterizing Alzheimer’s Disease Progression through Event Related Potential (ERP) Analysis
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (1993)
    The occurrence of blinking during short term memory tasks was analyzed for 32 subjects divided into three groups: 12 memory impaired patients, 10 elderly normals (age-matched to the patients), and 10 young normals. The subjects were participating in a study of brain evoked potentials accompanying memory activities. They were instructed not to blink during the performance of the memory tasks for reasons related to the quality of the recorded potentials. In this context, the withholding of blinking can be considered a secondary task. Blinking during the short term memory tasks was inversely related to performance accuracy (r = -.57). Age, mini-mental score and reaction time were also significantly related to the frequency of blinking. Dividing the memory patients into two groups according to the incidence of blinking, ("high-blinking" and "low-blinking"), revealed a significant difference in overall task accuracy with the high-blinking group performing more poorly than the low-blinking group.
      Cover page: Blinking in Patients with Memory Disorders During Short Term Memory TasksCreative Commons 'BY' version 4.0 license
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2020)
      Current models of language processing do not address mechanisms at the neurotransmitter level, nor how pharmacologic agents may improve language function(s) in seemingly disparate disorders. L-Glutamate, the primary excitatory neurotransmitter in the human brain, is extensively involved in various higher cortical functions. We postulate that the physiologic role of L-Glutamate neurotransmission extends to the regulation of language access, comprehension, and production, and that disorders in glutamatergic transmission and circuitry contribute to the pathogenesis of neurodegenerative diseases and sporadic-onset language disorders such as the aphasic stroke syndromes. We start with a review of basic science data pertaining to various glutamate receptors in the CNS and ways that they may influence the physiological processes of language access and comprehension. We then focus on the dysregulation of glutamate neurotransmission in three conditions in which language dysfunction is prominent: Alzheimer's Disease, Fragile X-associated Tremor/Ataxia Syndrome, and Aphasic Stroke Syndromes. Finally, we review the pharmacologic and electrophysiologic (event related brain potential or ERP) data pertaining to the role glutamate neurotransmission plays in language processing and disorders.
        Cover page: The Role of Glutamate in Language and Language Disorders - Evidence from ERP and Pharmacologic Studies
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2019)

        Objective

        To determine whether free water (FW) content, initially developed to correct metrics derived from diffusion tensor imaging and recently found to be strongly associated with vascular risk factors, may constitute a sensitive biomarker of white matter (WM) microstructural differences associated with cognitive performance but remains unknown.

        Methods

        Five hundred thirty-six cognitively diverse individuals, aged 77 ± 8 years, received yearly comprehensive clinical evaluations and a baseline MRI examination of whom 224 underwent follow-up MRI. WM microstructural measures, including FW, fractional anisotropy, and mean diffusivity corrected for FW and WM hyperintensity burden were computed within WM voxels of each individual. Baseline and change in MRI metrics were then used as independent variables to explain baseline and change in episodic memory (EM), executive function (EF), and Clinical Dementia Rating (CDR) scores using linear, logistic, and Cox proportional-hazards regressions.

        Results

        Higher baseline FW and WM hyperintensity were associated with lower baseline EM and EF, higher baseline CDR, accelerated EF and EM decline, and higher probability to transition to a more severe CDR stage (p values <0.01). Annual change in FW was also found to be associated with concomitant change in cognitive and functional performance (p values <0.01).

        Conclusions

        This study finds cross-sectional and longitudinal associations between FW content and trajectory of cognitive and functional performance in a large sample of cognitively diverse individuals. It supports the need to investigate the pathophysiologic process that manifests increased FW, potentially leading to more severe WM territory injury and promoting cognitive and functional decline.
          Cover page: Cerebral white matter free water: A sensitive biomarker of cognition and function.
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2010)

          BACKGROUND: Trajectories of cognitive decline among elderly individuals are heterogeneous, and markers that have high reliability for predicting cognitive trajectories across a broad spectrum of the elderly population have yet to be identified. METHOD: This study examined the utility of a variety of MRI-based brain measures, obtained at baseline, as predictors of subsequent declines in domain-specific measures of cognitive function in a cohort of 307 community-dwelling elderly individuals with varying degrees of cognitive impairment who were diverse across several relevant demographic variables and were evaluated yearly. Psychometrically matched measures of cognition were used to assess episodic memory, semantic memory, and executive function. Relationships between baseline MRI measures, including the volumes of the brain, hippocampus, and white matter hyperintensities (WMH), and cognitive trajectories were assessed in mixed effects regression models that modeled MRI effects on cognitive performance at baseline and rate of change as well as interindividual variability in cognitive baseline and rate of change. RESULTS: Greater baseline brain volume predicted slower subsequent rate of decline in episodic memory and smaller WMH volume predicted slower subsequent rate of decline in executive function and semantic memory. Baseline hippocampal volume, while strongly related to baseline cognitive function, was not predictive of subsequent change in any of the cognitive domains. CONCLUSIONS: Baseline measures of brain structure and tissue pathology predicted rate of cognitive decline in a diverse and carefully characterized cohort, suggesting that they may provide summary measures of pre-existing neuropathological damage or the capacity of the brain to compensate for the impact of subsequent neuropathology on cognition. Conventional MRI measures may have use for predicting cognitive outcomes in highly heterogeneous elderly populations.

            Cover page: MRI predictors of cognitive change in a diverse and carefully characterized elderly population.
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2020)
            Reliable biomarkers of memory decline are critical for the early detection of Alzheimer's disease. Previous work has found three EEG measures, namely the event-related brain potential P600, suppression of oscillatory activity in the alpha frequency range (∼10 Hz) and cross-frequency coupling between low theta/high delta and alpha/beta activity, each of which correlates strongly with verbal learning and memory abilities in healthy elderly and patients with mild cognitive impairment or prodromal Alzheimer's disease. In the present study, we address the question of whether event-related or oscillatory measures, or a combination thereof, best predict the decline of verbal memory in mild cognitive impairment and Alzheimer's disease. Single-trial correlation analyses show that despite a similarity in their time courses and sensitivities to word repetition, the P600 and the alpha suppression components are minimally correlated with each other on a trial-by-trial basis (generally |r s| < 0.10). This suggests that they are unlikely to stem from the same neural mechanism. Furthermore, event-related brain potentials constructed from bandpass filtered (delta, theta, alpha, beta or gamma bands) single-trial data indicate that only delta band activity (1-4 Hz) is strongly correlated (r = 0.94, P < 0.001) with the canonical P600 repetition effect; event-related potentials in higher frequency bands are not. Importantly, stepwise multiple regression analyses reveal that the three event-related brain potential/oscillatory measures are complementary in predicting California Verbal Learning Test scores (overall R 2 ' s in 0.45-0.63 range). The present study highlights the importance of combining EEG event-related potential and oscillatory measures to better characterize the multiple mechanisms of memory failure in individuals with mild cognitive impairment or prodromal Alzheimer's disease.
              Cover page: Event-related potential and EEG oscillatory predictors of verbal memory in mild cognitive impairment
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2014)

              Background

              Parkinsonian features have been used as a minor diagnostic criterion for fragile X-associated tremor/ataxia syndrome (FXTAS). However, prior studies have examined parkinsonism (defined as having bradykinesia with at least rest tremor or postural instability) mostly in premutation carriers without a diagnosis of FXTAS. The current study was intended to elaborate this important aspect of the FXTAS spectrum, and to quantify the relationships between parkinsonism, FXTAS clinical staging and genetic/molecular measures.

              Methods

              Thirty eight (38) FXTAS patients and 10 age-matched normal controls underwent a detailed neurological examination that included all but one item (i.e. rigidity) of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS).

              Results

              The FXTAS patient group displayed substantially higher prevalence of parkinsonian features including body bradykinesia (57%) and rest tremor (26%), compared to the control group. Furthermore, parkinsonism was identified in 29% of FXTAS patients. Across all patients, body bradykinesia scores significantly correlated with FXTAS clinical stage, FMR1 mRNA level, and ataxic gait of cerebellar origin, while postural instability was associated with intention tremor.

              Interpretation

              Parkinsonian features in FXTAS appear to be characterized as bradykinesia concurrent with cerebellar gait ataxia, postural instability accompanied by intention tremor, and frequent rest tremor, representing distinctive patterns that highlight the need for further clinical studies including genetic testing for the FMR1 premutation. The association between FMR1 mRNA level and bradykinesia implicates pathophysiological mechanisms which may link FMR1 mRNA toxicity, dopamine deficiency and parkinsonism in FXTAS.
                Cover page: Parkinsonism in fragile X-associated tremor/ataxia syndrome (FXTAS): Revisited
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2023)
                We developed the Life Course Sociodemographics and Neighborhood Questionnaire (LSNEQ) to query older adults about perceived neighborhood greenspaces across the life course (i.e., distance to park, number of neighborhood parks/playgrounds, and neighborhood greenness) and about characteristics hypothesized to confound or moderate/mediate greenspace-health associations. Six perceived life course indices are derived from the LSNEQ: neighborhood socioeconomic status, neighborhood walking/biking, urbanicity, neighborhood amenities, neighborhood park access, and neighborhood greenness. Older adults from St. Louis, Missouri, and Sacramento, California, completed the LSNEQ in 2020-2021. The indices demonstrated borderline acceptable to good internal consistency (alpha = 0.60-0.79) and good to excellent test-retest reliability (ICC = 0.71-0.96) and detected different patterns of park access and neighborhood greenness by racialized group and location. Individuals with index scores indicating more neighborhood walking/biking and greater presence of neighborhood amenities over their life course were more likely to report neighborhood-based walking in older age. Overall, the LSNEQ is a reliable instrument to assess perceptions of life course social determinants of health including neighborhood greenspaces.
                  Cover page: Perceptions of greenspace and social determinants of health across the life course: The Life Course Sociodemographics and Neighborhood Questionnaire (LSNEQ)
                  • Article
                  • Peer Reviewed
                  UC Davis Previously Published Works (2013)
                  Minocycline normalizes synaptic connections and behavior in the knockout mouse model of fragile X syndrome (FXS). Human-targeted treatment trials with minocycline have shown benefits in behavioral measures and parent reports. Event-related potentials (ERPs) may provide a sensitive method of monitoring treatment response and changes in coordinated brain activity. Measurement of electrocortical changes due to minocycline was done in a double-blind, placebo-controlled crossover treatment trial in children with FXS. Children with FXS (Meanage 10.5 years) were randomized to minocycline or placebo treatment for 3 months then changed to the other treatment for 3 months. The minocycline dosage ranged from 25-100 mg daily, based on weight. Twelve individuals with FXS (eight male, four female) completed ERP studies using a passive auditory oddball paradigm. Current source density (CSD) and ERP analysis at baseline showed high-amplitude, long-latency components over temporal regions. After 3 months of treatment with minocycline, the temporal N1 and P2 amplitudes were significantly reduced compared with placebo. There was a significant amplitude increase of the central P2 component on minocycline. Electrocortical habituation to auditory stimuli improved with minocycline treatment. Our study demonstrated improvements of the ERP in children with FXS treated with minocycline, and the potential feasibility and sensitivity of ERPs as a cognitive biomarker in FXS treatment trials.
                    Cover page: Electrocortical changes associated with minocycline treatment in fragile X syndrome
                    • Article
                    • Peer Reviewed
                    UC Davis Previously Published Works (2018)

                    Objective

                    Examine how longitudinal cognitive trajectories relate to brain baseline measures and change in lobar volumes in a racially/ethnically and cognitively diverse sample of older adults.

                    Method

                    Participants were 460 older adults enrolled in a longitudinal aging study. Cognitive outcomes were measures of episodic memory, semantic memory, executive function, and spatial ability derived from the Spanish and English Neuropsychological Assessment Scales (SENAS). Latent variable multilevel modeling of the four cognitive outcomes as parallel longitudinal processes identified intercepts for each outcome and a second order global change factor explaining covariance among the highly correlated slopes. We examined how baseline brain volumes (lobar gray matter, hippocampus, and white matter hyperintensity) and change in brain volumes (lobar gray matter) were associated with cognitive intercepts and global cognitive change. Lobar volumes were dissociated into global and specific components using latent variable methods.

                    Results

                    Cognitive change was most strongly associated with brain gray matter volume change, with strong independent effects of global gray matter change and specific temporal lobe gray matter change. Baseline white matter hyperintensity and hippocampal volumes had significant incremental effects on cognitive decline beyond gray matter change. Baseline lobar gray matter was related to cognitive decline, but did not contribute beyond gray matter change.

                    Conclusion

                    Cognitive decline was strongly influenced by gray matter volume change and, especially, temporal lobe change. The strong influence of temporal lobe gray matter change on cognitive decline may reflect involvement of temporal lobe structures that are critical for late life cognitive health but also are vulnerable to diseases of aging. (PsycINFO Database Record
                      Cover page: Brain Volume Change and Cognitive Trajectories in Aging
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