title: Evolution and resolution of human brain perfusion responses to the stress of induced hypoglycemia.
abstract: The relationship between the human brain response to acute stress and subjective, behavioural and physiological responses is poorly understood. We have examined the human cerebral response to the intense interoceptive stressor of hypoglycemia, controlling plasma glucose at either normal fasting concentrations (5 mmol/l, n=7) or at hypoglycemia (2.7 mmol/l, n=10) for 1 h in healthy volunteers. Hypoglycemia was associated with symptomatic responses, counterregulatory neuroendocrine responses and a sequential pattern of brain regional engagement, mapped as changes in relative cerebral perfusion using [(15)O]-H(2)O water positron emission tomography. The early cerebral response comprised activation bilaterally in anterior cingulate cortex (ACC) and thalamic pulvinar, with deactivation in posterior parahippocampal gyrus. Later responses (>20 min) engaged bilateral anterior insula, ventral striatum and pituitary. Following resolution of hypoglycemia, the majority of responses returned to baseline, save persistent engagement of the ACC and sustained elevation of growth hormone and cortisol. Catecholamine responses correlated with increased perfusion in pulvinar and medial thalamus, ACC and pituitary, while growth hormone and cortisol responses showed no correlation with thalamic activation but did show additional correlation with the hypothalamus and ventral striatum bilaterally. These data demonstrate complex dynamic responses to the stressor of hypoglycemia that would be expected to drive physiological and behavioural changes to remedy the state. Further, these data show that sustained stress and its aftermath engage distinct sets of brain regions, providing a neural substrate for adaptive or 'allostasic' responses to stressors.
authors.affiliation: Diabetes Research Group, King's College Hospital School of Medicine, King's College Hospital Campus, London, UK.
authors.forename: Ming Ming
authors.initials: MM
authors.lastname: Teh
authors.forename: Joel T
authors.initials: JT
authors.lastname: Dunn
authors.forename: Pratik
authors.initials: P
authors.lastname: Choudhary
authors.forename: Yohan
authors.initials: Y
authors.lastname: Samarasinghe
authors.forename: Ian
authors.initials: I
authors.lastname: Macdonald
authors.forename: Michael
authors.initials: M
authors.lastname: O'Doherty
authors.forename: Paul
authors.initials: P
authors.lastname: Marsden
authors.forename: Laurence J
authors.initials: LJ
authors.lastname: Reed
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Amiel
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000502:physiology; D015992:Body Mass Index; D001923:Brain Chemistry / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004837:Epinephrine / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007003:Hypoglycemia / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008297:Male; D049268:Positron-Emission Tomography; D013312:Stress, Physiological / Q000187:drug effects*; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D006854:Hydrocortisone; D004837:Epinephrine