Neural and physiological responses to a cold pressor challenge in healthy adolescents

Abnormal autonomic function is common in pediatric diseases. Assessment of central mechanisms underlying autonomic challenges may reveal vulnerabilities antecedent to system failure. Our objective was to characterize central markers and physiological responses to a cold pressor challenge in normal children as a critical step for establishing such screening. We performed functional magnetic resonance imaging (fMRI) and collected physiological measures during cold application to the foot in 24 healthy adolescents (15.5 ± 0.4 years, 13 male). The protocol included a 120-sec baseline, 120-sec right-foot cold water immersion (4°C), and 120-sec recovery. Analyses included heart rate (HR) cross-correlations with fMRI signals. Cold application increased HR 13% 5-7 sec after onset, which remained elevated throughout the challenge. Respiratory rate transiently increased (peak 22%), then declined (nadir 12% below baseline), before normalizing at 75 sec. Cold onset rapidly increased somatosensory cortex and medullary signals, which fell after 25 sec. Right anterior insular cortex signals increased early, followed after 20 sec by the left anterior insula, with HR declining 8 sec later. Amygdalae signals also rose, but signals declined in the posterior cingulate cortex, caudate nucleus, hippocampus, and hypothalamus. Declining signals appeared late in the cerebellar fastigial nuclei (60-120 sec), and in the pons and thalamus. Somatosensory cortex, fastigial nuclei, and hypothalamic responses were principally left-sided, with bilateral responses elsewhere. Late left anterior insula responses likely underlie the HR decline; the late cerebellar pattern may modulate recovery. The laterality, timing, and amplitude of normative responses and rostral response differentiation indicate the complex integration of adolescent autonomic processing and provide indices for pathological comparisons.