Changes in Theta but not Alpha Modulation Are Associated with Impairment in Working Memory in Alzheimer’s Disease and Mild Cognitive Impairment

Article type: Research Article

Authors: Goodman, Michelle S.^{a; b} | Zomorrodi, Reza^{a; b} | Kumar, Sanjeev^{a; c; d} | Barr, Mera S.^{b; d} | Daskalakis, Zafiris J.^{a; b; d} | Blumberger, Daniel M.^{a; b; c; d} | Fischer, Corinne E.^{d; e} | Flint, Alastair^{d; f} | Mah, Linda^{d; g} | Herrmann, Nathan^{d; h} | Pollock, Bruce G.^{a; c; d} | Bowie, Christopher R.^{a; c} | Mulsant, Benoit H.^{a; c; d} | Rajji, Tarek K.^{a; b; c; d; *} | The PACt-MD Study Group

Collaborators: Mulsant, B.H. | Rajji, T.K. | Herrmann, N. | Pollock, B.G. | Lourenco, L. | Blumberger, D.M. | Bowie, C.R. | Butters, M. | Fischer, C.E. | Flint, A. | Gallagher, D. | Golas, A. | Graff, A. | Kennedy, J.L. | Kumar, S. | Mah, L. | Ovaysikia, S. | Rapoport, M. | Thorpe, K. | Verhoeff, N.P.L.G. | Voineskos, A.N.

Affiliations: [a] Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health, Toronto, Canada | [b] Temerty Centre for Therapeutic Brain Intervention, Centre for Addiction and Mental Health, Toronto, Canada | [c] Geriatric Psychiatry Division, Centre for Addiction and Mental Health, Toronto, Canada | [d] Department of Psychiatry, University of Toronto, Toronto, Canada | [e] Keenan Research Centre for Biomedical Research, St. Michael’s Hospital, Toronto, Canada | [f] Centre for Mental Health, University Health Network, Toronto, Canada | [g] Rotman Research Institute, Baycrest Health Sciences Centre, Toronto, Canada | [h] Sunnybrook Health Sciences Centre, Toronto, Canada

Correspondence: [*] Correspondence to: Tarek K. Rajji, MD, FRCP(C), Associate Professor, Department of Psychiatry, University of Toronto, Chief of Geriatric Psychiatry, Centre for Addiction and Mental Health, 80 Workman Way, Toronto, ON M6J 1H4, Canada. E-mail: [email protected].

Abstract: While several studies have found that neural oscillations play a key role in the functioning of working memory, the nature of aberrant oscillatory activity underlying working memory impairments in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) remains largely unexplored. These individuals often display structural alterations in brain regions and pathways involved in working memory processes and therefore may also display altered oscillatory activity during memory activation. Electroencephalographic (EEG) activity was recorded during the N-back working memory task in three groups: AD (n = 29), MCI (n = 100), and healthy controls (HCs; n = 40). Theta (4–7 Hz) and alpha (7.5–12 Hz) modulation was measured in response to the stimulus presentation during correct and incorrect responses. This modulation represents the change in EEG activity associated with the stimulus onset and was measured as a ratio of post stimulus power to pre stimulus power. We also assessed the relationship between change in oscillatory power and working memory performance. Compared to HCs, the AD group demonstrated the lowest working memory accuracy and a smaller theta ratio for correct responses on the 2-back condition; the MCI group demonstrated a smaller theta ratio for correct responses on the 3-back condition. Finally, we observed that the theta ratio, but not the alpha ratio, was a significant predictor of working memory performance in the three groups for all conditions. Taken together, these behavioral and electrophysiological results suggest that in addition to impairments in working memory performance, modulation of theta, but not alpha power, may be impaired in MCI and AD.

Keywords: Alpha power, Alzheimer’s disease, electroencephalography, mild cognitive impairment, theta power, working memory

DOI: 10.3233/JAD-181195

Journal: Journal of Alzheimer's Disease, vol. 68, no. 3, pp. 1085-1094, 2019