Effect of Heat Exposure on Cognition in Persons with Higher Cord Lesions

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After spinal cord injury (SCI), particularly cervical and high thoracic injuries, the motor, sensory, and sympathetic pathways necessary for effective thermoregulation are interrupted, resulting in an impaired ability to maintain core body temperature (Tcore) when exposed to challenges in environmental temperature. Control of distal extremity vasoconstriction (heat conservation) and shivering thermogenesis (heat production) are impaired, and the ability to maintain a constant Tcore is compromised. In addition, changes in body composition (loss of lean body mass) and medications commonly prescribed in persons with SCI may lower metabolic rate and further depress Tcore. Persons with tetraplegia often report “feeling cold,” frequently present with subnormal Tcore (35.5-36.5°C), and are particularly vulnerable to hypothermia (Tcore<35°C), even at temperatures that are comfortable for able-bodied (AB) individuals. The deleterious effects of hypothermia are well appreciated in AB persons with documented progressive decline in various aspects of cognitive performance associated with the magnitude of the depression in Tcore. However, the potential beneficial effects of increasing subnormal Tcore to euthermic levels on cognitive function of those with tetraplegia are not known. In our current submission, we are proposing a prospective two-group comparative study to compare the physiological and cognitive responses to warm exposure in persons with SCI who have subnormal Tcore and in AB persons who are euthermic. Twenty subjects with SCI (C3-T4, AIS A & B; Tcore <37°C) and 20 age/gender-matched AB control subjects will be recruited for study. Subjects will be placed in a thermoneutral (27°C) environment for instrumentation. Measurements of Tcore (rectal thermocouple), skin temperature (skin thermocouple), sweat rate (QSweat methodology), and thermal sensitivity (9-point thermal sensation scale) will be made during 15 minutes of baseline (27°C) and during up to 120 minutes of warm (35°C) temperature exposure while in the seated position. Cognitive performance will be assessed twice, at baseline and after Tcore rises 0.5°C or at the end of the warm challenge. The primary dependent variables will be Tcore and cognitive performance. The secondary dependent variables will be measures of autonomic adaption to a warm environment and include distal skin temperature, sweat rate, and thermal sensitivity. Specific Aims: During exposure to a warm environment (35°C) for up to 120 min in the seated position: Primary Specific Aim: To determine if 2 hours of warm exposure will cause a 0.5°C increase in Tcore and favorably effect cognitive performance (attention, working memory, processing speed, and executive function). Primary Hypotheses: Based on our pilot data: (1) Eighty percent of persons with tetraplegia will demonstrate an increase of 0.5°C in Tcore while none of the AB controls will demonstrate such an increase in Tcore; (2) Eighty percent of persons with tetraplegia will have an increase of at least one T-score in Stroop Interference scores (a validated measure of executive function) while none of the AB controls will demonstrate a change in cognitive performance. Secondary Specific Aims: To determine changes in: (1) The average of distal skin temperatures; (2) Sweat rate; and (3) Subjective rating of thermal sensitivity. Secondary Hypotheses: Persons with tetraplegia will have less of a percent change in average distal skin temperatures and sweat rate, and will report blunted ratings of thermal sensitivity compared to that of AB controls. Our proposed study will confirm our preliminary observations in persons with SCI who have subnormal Tcore to demonstrate in a more definitive manner that cognitive function will be improved by raising Tcore to normal. By rapidly and dramatically reversing the impairment in cognitive function by raising Tcore about 0.5°C to euthermic values, we would anticipate greater functional capacity and independence, enhanced reintegration into society, and improved quality of life, albeit these endpoints are beyond the scope of the current proposal.