Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

TY - JOUR

T1 - Stress-induced brain activity, brain atrophy, and clinical disability in multiple sclerosis

AU - Weygandt, Martin

AU - Meyer-Arndt, Lil

AU - Behrens, Janina Ruth

AU - Wakonig, Katharina

AU - Bellmann-Strobl, Judith

AU - Ritter, Kerstin

AU - Scheel, Michael

AU - Brandt, Alexander U

AU - Labadie, Christian

AU - Hetzer, Stefan

AU - Gold, Stefan

AU - Paul, Friedemann

AU - Haynes, John-Dylan

PY - 2016/11/22

Y1 - 2016/11/22

N2 - Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin–labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was reQ: 12 lated to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, these responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to imQ: 13 pairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy and positively to GM volume in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone.

AB - Prospective clinical studies support a link between psychological stress and multiple sclerosis (MS) disease severity, and peripheral stress systems are frequently dysregulated in MS patients. However, the exact link between neurobiological stress systems and MS symptoms is unknown. To evaluate the link between neural stress responses and disease parameters, we used an arterial-spin–labeling functional MRI stress paradigm in 36 MS patients and 21 healthy controls. Specifically, we measured brain activity during a mental arithmetic paradigm with performance-adaptive task frequency and performance feedback and related this activity to disease parameters. Across all participants, stress increased heart rate, perceived stress, and neural activity in the visual, cerebellar and insular cortex areas compared with a resting condition. None of these responses was reQ: 12 lated to cognitive load (task frequency). Consistently, although performance and cognitive load were lower in patients than in controls, these responses did not differ between groups. Insula activity elevated during stress compared with rest was negatively linked to imQ: 13 pairment of pyramidal and cerebral functions in patients. Cerebellar activation was related negatively to gray matter (GM) atrophy and positively to GM volume in patients. Interestingly, this link was also observed in overlapping areas in controls. Cognitive load did not contribute to these associations. The results show that our task induced psychological stress independent of cognitive load. Moreover, stress-induced brain activity reflects clinical disability in MS. Finally, the link between stress-induced activity and GM volume in patients and controls in overlapping areas suggests that this link cannot be caused by the disease alone.

M3 - SCORING: Journal article

C2 - 27821732

VL - 113

SP - 13444

EP - 13449

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 47

ER -