TY - JOUR
T1 - An inverse relationship between cortical plasticity and cognitive inhibition in late-life depression
AU - Lissemore, Jennifer I.
AU - Shanks, Hayley R.C.
AU - Butters, Meryl A.
AU - Bhandari, Apoorva
AU - Zomorrodi, Reza
AU - Rajji, Tarek K.
AU - Karp, Jordan F.
AU - Reynolds, Charles F.
AU - Lenze, Eric J.
AU - Daskalakis, Zafiris J.
AU - Mulsant, Benoit H.
AU - Blumberger, Daniel M.
N1 - Funding Information:
This study was funded in part by a Brain and Behavior Research Foundation New Investigator Award (DMB), the Canadian Institutes of Health Research (CIHR; MOP-123455), and the National Institutes of Health (NIH; R34MH101365). We would also like to acknowledge the Temerty Center and the Canada Foundation for Innovation for providing TMS equipment. TKR has received research support from Brain Canada, Brain and Behavior Research Foundation, BrightFocus Foundation, Canada Foundation for Innovation, Canada Research Chair, CIHR, Center for Aging and Brain Health Innovation, NIH, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, and the Weston Brain Institute. JFK received medication supplies from Indivior to support this investigator-initiated trial. He has also received medication supplies from Pfizer for investigator-initiated work. He receives research funding from the NIH and Patient-Centered Outcomes Research Institute (PCORI). CFR has received research support from the NIH, PCORI, the Center for Medicare and Medicaid Services, the American Foundation for Suicide Prevention, the Brain and Behavior Research Foundation, and the Commonwealth of Pennsylvania. Bristol Meyers Squib and Pfizer have provided pharmaceutical supplies for his NIH sponsored research. EJL reports research funding (current/past) from Janssen, Alkermes, Acadia, Takeda, Lundbeck, Barnes Jewish Foundation, PCORI, and Taylor Family Institute for Innovative Psychiatric Research. In the past 5 years, ZJD has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc. and Magven-ture Inc. His work was supported by the Ontario Mental Health Foundation (OMHF), CIHR, the NIMH, and the Temerty Family and Grant Family and through the CAMH Foundation and the Campbell Institute. BHM currently receives research funding from Brain Canada, the CAMH Foundation, PCORI, and the NIH. During the past 5 years, he also received research funding from CIHR, and support in kind from Capital Solution Design LLC (software used in a study funded by CAMH Foundation), HAPPYneuron (software used in a study funded by Brain Canada), Bristol-Myers Squibb (medications for a NIH-funded clinical trial), Eli-Lilly (medications for a NIH-funded clinical trial), and Pfizer (medications for a NIH-funded clinical trial). He directly owns stocks of General Electric (<$5000). DMB has received research support from CIHR, NIH, Brain Canada. and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He receives research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he is the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. He also receives in-kind equipment support from Magventure for an investigator-initiated study. He receives medication supplies for an investigator-initiated trial from Indivior. The other authors declare no competing interests.
Publisher Copyright:
© 2019, American College of Neuropsychopharmacology.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Executive dysfunction is a common and disabling component of late-life depression (LLD), yet its neural mechanisms remain unclear. In particular, it is not yet known how executive functioning in LLD relates to measures of cortical physiology that may change with age and illness, namely cortical inhibition/excitation and plasticity. Here, we used transcranial magnetic stimulation (TMS) to measure cortical inhibition/excitation (n = 51), and the potentiation of cortical activity following paired associative stimulation, which is thought to reflect long-term potentiation (LTP)-like cortical plasticity (n = 32). We assessed the correlation between these measures of cortical physiology and two measures of executive functioning: cognitive inhibition, assessed using the Delis–Kaplan Executive Function System Color-Word Interference [“Stroop”] Test, and cognitive flexibility, assessed using the Trail Making Test. Correlations with recall memory and processing speed were also performed to assess the specificity of any associations to executive functioning. A significant correlation was found between greater LTP-like cortical plasticity and poorer cognitive inhibition, a core executive function (rp = −0.56, p < 0.001). We did not observe significant associations between cortical inhibition/excitation and executive functioning, or between any neurophysiological measure and cognitive flexibility, memory, or processing speed. Our finding that elevated cortical plasticity is associated with diminished cognitive inhibition emphasizes the importance of balanced synaptic strengthening to healthy cognition. More specifically, our findings suggest that hyper-excitability of cortical circuits following repeated cortical activation may promote inappropriate prepotent responses in LLD. LTP-like cortical plasticity might therefore represent a neural mechanism underlying an inhibitory control cognitive endophenotype of LLD.
AB - Executive dysfunction is a common and disabling component of late-life depression (LLD), yet its neural mechanisms remain unclear. In particular, it is not yet known how executive functioning in LLD relates to measures of cortical physiology that may change with age and illness, namely cortical inhibition/excitation and plasticity. Here, we used transcranial magnetic stimulation (TMS) to measure cortical inhibition/excitation (n = 51), and the potentiation of cortical activity following paired associative stimulation, which is thought to reflect long-term potentiation (LTP)-like cortical plasticity (n = 32). We assessed the correlation between these measures of cortical physiology and two measures of executive functioning: cognitive inhibition, assessed using the Delis–Kaplan Executive Function System Color-Word Interference [“Stroop”] Test, and cognitive flexibility, assessed using the Trail Making Test. Correlations with recall memory and processing speed were also performed to assess the specificity of any associations to executive functioning. A significant correlation was found between greater LTP-like cortical plasticity and poorer cognitive inhibition, a core executive function (rp = −0.56, p < 0.001). We did not observe significant associations between cortical inhibition/excitation and executive functioning, or between any neurophysiological measure and cognitive flexibility, memory, or processing speed. Our finding that elevated cortical plasticity is associated with diminished cognitive inhibition emphasizes the importance of balanced synaptic strengthening to healthy cognition. More specifically, our findings suggest that hyper-excitability of cortical circuits following repeated cortical activation may promote inappropriate prepotent responses in LLD. LTP-like cortical plasticity might therefore represent a neural mechanism underlying an inhibitory control cognitive endophenotype of LLD.
UR - http://www.scopus.com/inward/record.url?scp=85065649670&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065649670&partnerID=8YFLogxK
U2 - 10.1038/s41386-019-0413-9
DO - 10.1038/s41386-019-0413-9
M3 - Article
C2 - 31071718
AN - SCOPUS:85065649670
SN - 0893-133X
VL - 44
SP - 1659
EP - 1666
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 9
ER -