Functional Connectivity of the Supplementary and Presupplementary Motor Areas in Postoperative Transition Between Stages of Frailty

Abstract

Background: Frailty is a multietiological geriatric syndrome of run-down physical reserves with high vulnerability to stressors. Transitions between physical robustness and frailty often occur in the context of medical interventions. Studies suggest that neurological disorders contribute to faster progression of frailty. In a previous cross-sectional study we found altered functional connectivity of supplementary motor area (SMA) in (pre)frail compared to robust patients. We analyzed functional connectivity of the SMA and presupplementary motor area (pre-SMA) in patients with postoperative transitions between physical robustness and stages of frailty.

Methods: We investigated 120 cognitively healthy patients (49.2% robust, 47.5% prefrail, 3.3% frail, 37.5% female, median age 71 [65-87] years) undergoing elective surgery from the BioCog project, a multicentric prospective cohort study on postoperative delirium and cognitive dysfunction. Assessments took place 14 days before and 3 months after surgery, comprising assessments of a modified frailty phenotype according to Fried and resting-state functional magnetic resonance imaging at 3 T. The associations between functional connectivity of the SMA and pre-SMA networks, preoperative frailty stages, and postoperative transitions were examined using mixed linear effects models.

Results: Nineteen patients showed physical improvement after surgery, 24 patients progressed to (pre)frailty and in 77 patients no transition was observed. At follow-up, 57 (47.5%) patients were robust, 52 (43.3%) prefrail, and 11 (9.2%) frail. Lower functional connectivity in the pre-SMA network was associated with more unfavorable postoperative transition types. An exploratory analysis suggested that the association was restricted to patients who were prefrail at baseline. There was no association of transition type with SMA functional connectivity in the primary analysis. In an exploratory analysis, transition from prefrailty to robustness was associated with higher functional connectivity and progression in robust patients was associated with higher SMA network segregation.

Conclusions: Our findings implicate that dysfunctions of cortical networks involved in higher cognitive control of motion are associated with postoperative transitions between frailty stages. The pre-SMA may be a target for neurofeedback or brain stimulation in approaches to prevent frailty. Clinical Trials Registration Number: NCT02265263.

Keywords: Frailty; Functional magnetic resonance imaging; Presupplementary motor cortex; Resting-state network; Supplementary motor cortex; Surgery.