The Effect of Acute Hypoglycemia on Brain Function
The Effect of Acute Hypoglycemia on Brain Function
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 tasksfinger tapping (FT), simple reaction time (SRT), and four-choice reaction time (4CRT)twice during blood oxygen leveldependent (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.
The brain is normally dependent on glucose for oxidative metabolism and function. Acute iatrogenic hypoglycemia, occurring as a result of insulin excess during the treatment of type 1 diabetes, can cause clinically significant cognitive impairment. In health, such hypoglycemic cognitive dysfunction does not occur. Endogenous counterregulatory mechanisms are activated in response to a small reduction in circulating glucose, preventing more profound hypoglycemia. In diabetes, the inability to reduce circulating insulin levels , the failure of glucagon responses , sometimes accompanied by defective autonomic and adrenergic responses , can allow plasma glucose levels to fall low enough to result in detectable disturbance of cognitive function, ranging from a subtle slowing of reaction times to coma .
A variety of measures of cognitive function have been used in the investigation of the responses of the brain to acute hypoglycemia, and these show different susceptibilities to hypoglycemia. In health, autonomic activation occurs at arterialized plasma glucose of 3.03.6 mmol/l . Choice reaction times and performance of Stroop interference tests become slower at ~ 3 mmol/l; short-term memory deteriorates at 2.5 mmol/l ; and finger tapping, a simple motor task, slows at ~ 2.3 mmol/l . The glucose level at which some brain functions alter, such as the activation of autonomic counterregulatory responses (a hypothalamic action ) or deterioration of the performance of the Stroop and memory tests , may change according to prior experience of hyper- or hypoglycemia, with higher or lower plasma glucose associated with the onset of change, respectively. Such changes may leave those diabetic patients with prior experience of hypoglycemia at high risk for severe hypoglycemia with no warning hypoglycemia unawareness .
Functional magnetic resonance imaging (fMRI) detects regional changes in brain oxygenation state during activation by a task . This allows exploration of physiological mechanisms underlying cognitive dysfunction during hypoglycemia. This study uses fMRI to test the hypothesis that different functional brain areas are involved in the performance of the different cognitive functions tests used in hypoglycemia research, and these will respond in distinct ways during a single hypoglycemic challenge, depending on the cognitive load of the task.
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 tasksfinger tapping (FT), simple reaction time (SRT), and four-choice reaction time (4CRT)twice during blood oxygen leveldependent (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.
The brain is normally dependent on glucose for oxidative metabolism and function. Acute iatrogenic hypoglycemia, occurring as a result of insulin excess during the treatment of type 1 diabetes, can cause clinically significant cognitive impairment. In health, such hypoglycemic cognitive dysfunction does not occur. Endogenous counterregulatory mechanisms are activated in response to a small reduction in circulating glucose, preventing more profound hypoglycemia. In diabetes, the inability to reduce circulating insulin levels , the failure of glucagon responses , sometimes accompanied by defective autonomic and adrenergic responses , can allow plasma glucose levels to fall low enough to result in detectable disturbance of cognitive function, ranging from a subtle slowing of reaction times to coma .
A variety of measures of cognitive function have been used in the investigation of the responses of the brain to acute hypoglycemia, and these show different susceptibilities to hypoglycemia. In health, autonomic activation occurs at arterialized plasma glucose of 3.03.6 mmol/l . Choice reaction times and performance of Stroop interference tests become slower at ~ 3 mmol/l; short-term memory deteriorates at 2.5 mmol/l ; and finger tapping, a simple motor task, slows at ~ 2.3 mmol/l . The glucose level at which some brain functions alter, such as the activation of autonomic counterregulatory responses (a hypothalamic action ) or deterioration of the performance of the Stroop and memory tests , may change according to prior experience of hyper- or hypoglycemia, with higher or lower plasma glucose associated with the onset of change, respectively. Such changes may leave those diabetic patients with prior experience of hypoglycemia at high risk for severe hypoglycemia with no warning hypoglycemia unawareness .
Functional magnetic resonance imaging (fMRI) detects regional changes in brain oxygenation state during activation by a task . This allows exploration of physiological mechanisms underlying cognitive dysfunction during hypoglycemia. This study uses fMRI to test the hypothesis that different functional brain areas are involved in the performance of the different cognitive functions tests used in hypoglycemia research, and these will respond in distinct ways during a single hypoglycemic challenge, depending on the cognitive load of the task.
