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The Effect of Acute Hypoglycemia on Brain Function and Activation

A Functional Magnetic Resonance Imaging Study

  1. J. Miranda Rosenthal12,
  2. Stephanie A. Amiel1,
  3. Lidia Yágüez23,
  4. Edward Bullmore2,
  5. David Hopkins1,
  6. Mark Evans1,
  7. Andrew Pernet1,
  8. Helen Reid1,
  9. Vincent Giampietro2,
  10. Chris M. Andrew2,
  11. John Suckling2,
  12. Andrew Simmons23 and
  13. Stephen C.R. Williams23
  1. 1Department of Medicine, Guy’s, King’s and St. Thomas’ School of Medicine
  2. 2Institute of Psychiatry, King’s College
  3. 3Maudsley Hospital, London, U.K.

    Abstract

    The authors’ aim was to examine the regional anatomy of brain activation by cognitive tasks commonly used in hypoglycemia research and to assess the effect of acute hypoglycemia on these in healthy volunteers. Eight right-handed volunteers performed a set of cognitive tasks—finger tapping (FT), simple reaction time (SRT), and four-choice reaction time (4CRT)—twice during blood oxygen level–dependent (BOLD) functional magnetic resonance imaging of the brain on two occasions. In study 1 (n = 6), plasma glucose was maintained at euglycemia (5 mmol/l) throughout. In study 2 (n = 6), plasma glucose was reduced to 2.5 mmol/l for the second set. Performance of the tasks resulted in specific group brain activation maps. During hypoglycemia, FT slowed (P = 0.026), with decreased BOLD activation in right premotor cortex and supplementary motor area and left hippocampus and with increased BOLD activation in left cerebellum and right frontal pole. Although there was no significant change in SRT, BOLD activation was reduced in right cerebellum and visual cortex. The 4CRT deteriorated (P = 0.020), with reduction in BOLD activation in motor and visual systems but increased BOLD signal in a large area of the left parietal association cortex, a region involved in planning. Hypoglycemia impairs simple brain functions and is associated with task-specific localized reductions in brain activation. For a task with greater cognitive load, the increased BOLD signal in planning areas is compatible with recruitment of brain regions in an attempt to limit dysfunction. Further investigation of these mechanisms may help devise rational treatment strategies to limit cortical dysfunction during acute iatrogenic hypoglycemia.

    Footnotes

    • Address correspondence and reprint requests to Dr. Jane Miranda Rosenthal, Department of Diabetes, Endocrinology, and Internal Medicine, GKTSM, Denmark Hill Campus, Bessemer Road, London SE5 9PJ, U.K. E-mail: miranda.rosenthal{at}kcl.ac.uk.

      Received for publication 8 May 2000 and accepted in revised form 19 March 2001.

      AC-PC, anterior commisure–posterior commisure; 4CRT, four-choice reaction time; BOLD, blood oxygen level–dependent; fMRI, functional magnetic resonance imaging; FT, finger tapping; MR, magnetic resonance; SRT, simple reaction time; TE, echo time; TI, inversion time; TR, repetition time.

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