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Neuroimage Clin. 2018 Jul 12;20:110-118. doi: 10.1016/j.nicl.2018.07.010. eCollection 2018.

Hippocampal functional connectivity is related to self-reported cognitive concerns in breast cancer patients undergoing adjuvant therapy.

Author information

1
Division of Clinical Psychology, Northwestern University Feinberg School of Medicine, United States; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, United States. Electronic address: Alexandra.Apple@northwestern.edu.
2
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, United States.
3
Department of Social Sciences and Health Policy, Wake Forest School of Medicine, United States.
4
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, United States; Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, United States; Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, United States.
5
Department of Psychiatry, University of California, San Diego, United States.
6
Division of Clinical Psychology, Northwestern University Feinberg School of Medicine, United States; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, United States.
7
Department of Medical Social Sciences, Northwestern University Feinberg School of Medicine, United States.
8
Division of Clinical Psychology, Northwestern University Feinberg School of Medicine, United States; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, United States; Department of Radiology, Northwestern University Feinberg School of Medicine, United States.

Abstract

Nearly three out of four survivors experience Cancer-Related Cognitive Impairment (CRCI) for months or years following treatment. Both clinical and animal studies point to the hippocampus as a likely brain region affected in CRCI, however no previous study has investigated the functional connectivity of the hippocampus in CRCI. We compared hippocampal connectivity in cancer survivors and healthy controls and tested the relationship between functional connectivity differences and measures of objective and subjective cognition. Exploratory analysis of inflammatory markers was conducted in a small subset of participants as well. FMRI data were acquired during a memory task from 16 breast cancer survivors and 17 controls. The NIH Toolbox was used to assess cognitive performance and Neuro-QoL was used to measure self-reported cognitive concerns. Whole-brain group-level comparisons identified clusters with different connectivity to the hippocampus in survivors versus controls during task. Average connectivity was extracted from clusters of significant difference between the groups and correlated with cognitive performance and subjective report. Survivors performed worse on a test of episodic memory and reported greater cognitive concern than controls. Exploratory analysis found higher IL6 in cancer survivors compared to controls. Cancer survivors demonstrated higher connectivity of hippocampus with left cuneus, left lingual, left precuneus, and right middle prefrontal gyrus compared with controls. In survivors, higher task-related hippocampal-cortical connectivity was related to worse subjective measures of cognitive concern. Of the four significant clusters, higher connectivity of the precuneus with hippocampus was significantly associated with worse cognitive concern in survivors. The observed greater hippocampal-cortical connectivity in survivors compared to controls is the first reported fMRI biomarker of subjective concern, and may represent a compensatory response to cancer and its treatments. This compensation could explain, in part, the subjective feelings of cognitive impairment that were reported by survivors.

PMID:
30094161
PMCID:
PMC6077172
DOI:
10.1016/j.nicl.2018.07.010
[Indexed for MEDLINE]
Free PMC Article

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