In Parkinson's Disease (PD), hippocampal atrophy is associated with rapid cognitive decline. Hippocampal function is typically assessed using memory tests but current clinical tools (e.g., free recall) also rely on executive functions or use material that is not optimally engaging hippocampal memory networks. Because of the ubiquity of executive dysfunction in PD, our ability to detect true memory deficits is suboptimal. Our previous behavioural and neuroimaging work in other populations suggests that an experimental memory task - Associative Reinstatement Memory (ARM) - may prove useful in investigating hippocampal function in PD. In this study, we investigated whether ARM is compromised in PD and we assessed its convergent and divergent validity by comparing it to standardized measures of memory and of attention and executive functioning in PD, respectively. Using fMRI, we also investigated whether performance in PD relates to degree of hippocampal engagement. Fifteen participants with PD and 13 age-matched healthy controls completed neuropsychological testing as well as an ARM fMRI recognition paradigm in which they were instructed to identify word pairs comprised of two studied words (intact or rearranged pairs) and those containing at least one new word (new or half new pairs). ARM is measured by the differences in hit rates between intact and rearranged pairs. Behaviourally, ARM was poorer in PD relative to controls and was correlated with verbal memory measures, but not with attention or executive functioning in the PD group. Hippocampal activation associated with ARM was reduced in PD relative to controls and covaried with ARM scores in both groups. To conclude, ARM is a sensitive measure of hippocampal memory function that is unaffected by attention or executive dysfunction in PD. Our study highlights the benefit of integrating cognitive neuroscience frameworks and novel experimental tasks to improve the practice of clinical neuropsychology in PD.
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http://dx.doi.org/10.1016/j.neuropsychologia.2016.04.026 | DOI Listing |
Front Neural Circuits
January 2025
Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
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View Article and Find Full Text PDFThe transmembrane protein Synapse Differentiation Induced Gene 4 (SynDIG4) functions as an auxiliary factor of AMPA receptors (AMPARs) and plays a critical role in excitatory synapse plasticity as well as hippocampal-dependent learning and memory. Mice lacking SynDIG4 have reduced surface expression of GluA1 and GluA2 and are impaired in single tetanus-induced long-term potentiation and NMDA receptor (NMDAR)-dependent long-term depression. These findings suggest that SynDIG4 may play an important role in regulating AMPAR distribution through intracellular trafficking mechanisms; however, the precise roles by which SynDIG4 governs AMPAR distribution remain unclear.
View Article and Find Full Text PDFFluorescent reporters for glutamate release and postsynaptic Ca signaling are essential tools for quantifying synapse functional heterogeneity across neurons and circuits. However, leveraging these probes for neuroscience requires scalable experimental frameworks. Here, we devised a high-throughput approach to efficiently collect and analyze hundreds of optical recordings of glutaamate release activity at presynaptic boutons in cultured rat hippocampal neurons.
View Article and Find Full Text PDFUnlabelled: Mild hypoxic-ischemic encephalopathy is common in neonates with no evidence-based therapies, and 30-40% of patients experience adverse outcomes. The nature and progression of mild injury is poorly understood. Thus, we studied the evolution of mild perinatal brain injury using longitudinal two-photon imaging of transgenic fluorescent proteins as a novel readout of neuronal viability and activity at cellular resolution.
View Article and Find Full Text PDFApolipoprotein E4 (APOE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). Individuals with one copy of APOE4 exhibit greater amyloid-beta (Aβ) deposition compared to noncarriers, an effect that is even more pronounced in APOE4 homozygotes. Interestingly, APOE4 carriers not only show more AD pathology but also experience more rapid cognitive decline, particularly in episodic memory.
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