Type 2 Diabetes Mellitus (DM2) is a major cause of disability and death, affecting nearly 26 million people in the US. Nearly three quarters of those affected have DM-related damage to their nervous system that can include behavioral and cognitive deficits, and increase the risk of dementia. We seek to advance our understanding of the neurobiological substrate for these cortical brain consequences of DM2 and develop a reliable assay for their early detection and longitudinal assessment. We hypothesize that cognitive dysfunction in DM2 is associated with alterations in cortical brain plasticity that can b demonstrated by trans-cranial magnetic stimulation (TMS). We propose to apply single- and paired-pulse TMS to evaluate cortical reactivity in individuals with DM2 as compared with matched, healthy controls. Mechanisms of cortical plasticity will be further explored by assessing the modulation of cortical reactivity induced by a specific repetitive TMS protocol known as theta burst stimulation (TBS). The comparison of the motor responses induced by single-pulse TMS before and following TBS provides a noninvasive measure of brain plasticity in humans. Cognitive testing and a motor learning task will be used to demonstrate the behavioral correlates of this measure of plasticity. Magnetic resonance imaging and magnetic resonance spectroscopy will provide further insights into the neurobiological substrates of the neurophysiologic findings. Our pilot studies support the feasibility of our approach and provide supportive evidence for our hypothesis. We thus anticipate that data from the proposed study will address an important need for a rapid, noninvasive, reliable and safe method to diagnose, evaluate and follow cortical brain dysfunction in DM2. If successful, TMS-based measures of cortical reactivity and plasticity will provide a reliable and objective assessment of DM2-associated brain dysfunction, and eventually serve as useful biomarkers to evaluate cognitive dysfunction in DM2, inform the development of effective therapies and assess treatment response in future clinical trials.

Public Health Relevance

Type 2 Diabetes Mellitus (DM2) can affect the central nervous system and lead to cognitive decline and dementia. Using trans-cranial magnetic stimulation, magnetic resonance imaging and magnetic resonance spectroscopy we aim to provide greater insight into the cause for this complication of DM2 and establish a reliable method for its early detection and longitudinal assessment. Such a method will aid in diagnosis of brain affects of DM2, inform the development of effective therapies, and predict treatment response in future clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS082870-02
Application #
8659527
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Babcock, Debra J
Project Start
2013-05-15
Project End
2015-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02215
Corp, Daniel T; Youssef, George J; Clark, Ross A et al. (2018) Reduced motor cortex inhibition and a 'cognitive-first' prioritisation strategy for older adults during dual-tasking. Exp Gerontol 113:95-105
Angius, L; Mauger, A R; Hopker, J et al. (2018) Bilateral extracephalic transcranial direct current stimulation improves endurance performance in healthy individuals. Brain Stimul 11:108-117
Davila-Pérez, Paula; Jannati, Ali; Fried, Peter J et al. (2018) The Effects of Waveform and Current Direction on the Efficacy and Test-Retest Reliability of Transcranial Magnetic Stimulation. Neuroscience 393:97-109
Abellaneda-Pérez, Kilian; Vaqué-Alcázar, Lídia; Vidal-Piñeiro, Dídac et al. (2018) Age-related differences in default-mode network connectivity in response to intermittent theta-burst stimulation and its relationships with maintained cognition and brain integrity in healthy aging. Neuroimage :
Lonergan, Brady; Nguyen, Eliza; Lembo, Cara et al. (2018) Patient- and Technician-Oriented Attitudes Toward Transcranial Magnetic Stimulation Devices. J Neuropsychiatry Clin Neurosci 30:242-245
Manor, Brad; Yu, Wanting; Zhu, Hao et al. (2018) Smartphone App-Based Assessment of Gait During Normal and Dual-Task Walking: Demonstration of Validity and Reliability. JMIR Mhealth Uhealth 6:e36
Leon, Daniel; Cortes, Mar; Elder, Jessica et al. (2017) tDCS does not enhance the effects of robot-assisted gait training in patients with subacute stroke. Restor Neurol Neurosci 35:377-384
Gedankien, Tamara; Fried, Peter J; Pascual-Leone, Alvaro et al. (2017) Intermittent theta-burst stimulation induces correlated changes in cortical and corticospinal excitability in healthy older subjects. Clin Neurophysiol 128:2419-2427
Kaye, Harper L; Gersner, Roman; Boes, Aaron D et al. (2017) Persistent uncrossed corticospinal connections in patients with intractable focal epilepsy. Epilepsy Behav 75:66-71
Madeo, Dario; Talarico, Agostino; Pascual-Leone, Alvaro et al. (2017) An Evolutionary Game Theory Model of Spontaneous Brain Functioning. Sci Rep 7:15978

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