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Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits.

ABSTRACT: BACKGROUND:Type-2 diabetes mellitus (T2DM) accelerates cognitive aging and increases risk of Alzheimer's disease. Rodent models of T2DM show altered synaptic plasticity associated with reduced learning and memory. Humans with T2DM also show cognitive deficits, including reduced learning and memory, but the relationship of these impairments to the efficacy of neuroplastic mechanisms has never been assessed. OBJECTIVE:Our primary objective was to compare mechanisms of cortical plasticity in humans with and without T2DM. Our secondary objective was to relate plasticity measures to standard measures of cognition. METHODS:A prospective cross-sectional cohort study was conducted on 21 adults with T2DM and 15 demographically-similar non-diabetic controls. Long-term potentiation-like plasticity was assessed in primary motor cortex by comparing the amplitude of motor evoked potentials (MEPs) from single-pulse transcranial magnetic stimulation before and after intermittent theta-burst stimulation (iTBS). Plasticity measures were compared between groups and related to neuropsychological scores. RESULTS:In T2DM, iTBS-induced modulation of MEPs was significantly less than controls, even after controlling for potential confounds. Furthermore, in T2DM, modulation of MEPs 10-min post-iTBS was significantly correlated with Rey Auditory Verbal Learning Task (RAVLT) performance. CONCLUSION:Humans with T2DM show abnormal cortico-motor plasticity that is correlated with reduced verbal learning. Since iTBS after-effects and the RAVLT are both NMDA receptor-dependent measures, their relationship in T2DM may reflect brain-wide alterations in the efficacy of NMDA receptors. These findings offer novel mechanistic insights into the brain consequences of T2DM and provide a reliable means to monitor brain health and evaluate the efficacy of clinical interventions.

SUBMITTER: Fried PJ

PROVIDER: S-EPMC5193103 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits.

Fried Peter J PJ Schilberg Lukas L Brem Anna-Katharine AK Saxena Sadhvi S Wong Bonnie B Cypess Aaron M AM Horton Edward S ES Pascual-Leone Alvaro A

Journal of Alzheimer's disease : JAD 20170101 1

<h4>Background</h4>Type-2 diabetes mellitus (T2DM) accelerates cognitive aging and increases risk of Alzheimer's disease. Rodent models of T2DM show altered synaptic plasticity associated with reduced learning and memory. Humans with T2DM also show cognitive deficits, including reduced learning and memory, but the relationship of these impairments to the efficacy of neuroplastic mechanisms has never been assessed.<h4>Objective</h4>Our primary objective was to compare mechanisms of cortical plast ...[more]

PMID: 27636847

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Project description:BACKGROUND:Non-depolarizing magnetic fields, like low frequency-pulsed electromagnetic fields (LF-PEMFs) have shown the ability to modulate living structures, principally by influencing synaptic activity and ion channels on cellular membranes. Recently, the CTU Mega 20 device was presented as a molecular accelerator, using energy up to 200 J and providing high-power (2 Tesla) pulsating fields with a water-repulsive (diamagnetic) action and tissue biostimulation. We tested the hypothesis that LF-PEMFs could modulate long-term corticospinal excitability in healthy brains by applying CTU Mega 20®. Ten healthy subjects without known neurological and/or psychiatric diseases entered the study. A randomized double-blind sham-controlled crossover design was employed, recording TMS parameters (amplitude variation of the motor evoked potential as index of cortical excitability perturbations of the motor system) before (pre) and after (post + 0, + 15, + 30 min) a single CTU Mega 20 session on the corresponding primary right-hand motor area, using a real (magnetic field = 2 Tesla; intensity = 90 J; impulse frequency = 7 Hz; duration = 15 min) or sham device. A two-way repeated measures ANOVA with TIME (pre, post + 0, + 15, + 30 min) and TREATMENT (real vs. sham stimulation) as within-subjects factor was applied. RESULTS:A significant TIME × TREATMENT interaction was found (p < 0.001). Post hoc comparisons showed a significant effect of TIME, with significant differences at + 0, + 15 and + 30 min compared to baseline after real stimulation (all p < 0.05) but not after sham stimulation (all p < 0.05) and significant effects of TREATMENT, with significant differences at + 0, + 15 and + 30 min for real stimulation compared to sham stimulation (all p < 0.005). No significant depolarizing effects were detected throughout the (real) stimulation. CONCLUSIONS:Our proof-of-concept study in healthy subjects supports the idea that non-ionizing LF-PEMFs induced by the CTU Mega 20 diamagnetic acceleration system could represent a new approach for brain neuromodulation. Further studies to optimize protocol parameters for different neurological and psychiatric conditions are warranted. Trial Registration The present work has been retrospectively registered as clinical trial on ClinicalTrials.gov NCT03537469 and publicly released on May 24, 2018.

Dataset Information

Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits.

Publications

Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits.

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