Activation of the Insular Cortex During Dynamic Exercise in Humans

Abstract

The insular cortex has been implicated as a region of cortical cardiovascular control, yet its role during exercise remains undefined. The purpose of the present investigation was to determine whether the insular cortex was activated during volitional dynamic exercise and to evaluate further its role as a site for regulation of autonomic activity. Eight subjects were studied during voluntary active cycling and passively induced cycling. Additionally, four of the subjects underwent passive movement combined with electrical stimulation of the legs. Increases in regional cerebral blood flow (rCBF) distribution were determined for each individual using single‐photon emission‐computed tomography (SPECT) co‐registered with magnetic resonance (MR) images to define exact anatomical sites of cerebral activation during each condition. The rCBF significantly increased in the left insula during active, but not passive cycling. There were no significant changes in rCBF for the right insula. Also, the magnitude of rCBF increase for leg primary motor areas was significantly greater for both active cycling and passive cycling combined with electrical stimulation compared with passive cycling alone. These findings provide the first evidence of insular activation during dynamic exercise in humans, suggesting that the left insular cortex may serve as a site for cortical regulation of cardiac autonomic (parasympathetic) activity. Additionally, findings during passive cycling with electrical stimulation support the role of leg muscle afferent input towards the full activation of leg motor areas.

A prominent role for amygdaloid complexes in the Variability in Heart Rate (VHR) during Rapid Eye Movement (REM) sleep relative to wakefulness

“…In normal humans, rCBF in the right insula covaries with heart rate (Critchley et al, 2000). Functional magnetic resonance imaging (fMRI) recently confirmed the functional links between the insular cortex and the modulation of heart rate (Williamson et al, 1997(Williamson et al, , 1999Critchley et al, 2000). The activity in the left insula increases during dynamic exercise (cycling) but not passive exercise (cycling movement induced by moving pedals independently) (Williamson et al, 1997(Williamson et al, , 1999.…”

“…Intraoperative electrical stimulation of the insula elicits changes in heart rate and blood pressure (Oppenheimer et al, 1992). In normal subjects, functional neuroimaging studies showed that in response to physical exercise (Williamson et al, 1997(Williamson et al, , 1999 and mental stressor tasks (Critchley et al, 2000), both associated with significantly increased heart rate, the activity in both insula covaried with heart rate.…”

“…We determined the brain areas where the regional blood flow (CBF) was more tightly related to the VHR during REMS than during wakefulness, during SWS than during wakefulness or during SWS than during REMS. We focused on a set of target areas identified as critical in autonomous regulation during wakefulness: the insula (Cechetto and Saper, 1987;Oppenheimer et al, 1992;Oppenheimer, 1994;Corfield et al, 1995;Oppenheimer et al, 1996;Williamson et al, 1997;Critchley et al, 2000), the amygdala (Orem and Keeling, 1980;Sei and Morita, 1996;Critchley et al, 2000), the hypothalamus (paraventricular nucleus) (Hopkins and Holstege, 1978;Coote, 1995;Xia and Krukoff, 2003) and the midbrain (Herbert et al, 1990;Chamberlin and Saper, 1992;Henderson et al, 2002). Other areas more occasionally implicated in heart rate regulation were also considered as potential regions of interest: the hippocampus (Rowe et al, 1999;Ribeiro et al, 2002;Pedemonte et al, 2003), the anterior cingulate cortex (Buchanan et al, 1985;Neafsey, 1990), the ventromedial prefrontal cortex (Buchanan et al, 1985;Neafsey, 1990), the motor cortex (Critchley et al, 2000), the neostriatum (Delgado, 1960;Bradley et al, 1987Bradley et al, , 1991Lin and Yang, 1994;Critchley et al, 2000), the cerebellum (Delgado, 1960;Bradley et al, 1987Bradley et al, , 1991Lin and Yang, 1994;Critchley et al, 2000) and the brainstem areas of the pons and medulla …”

Mapping brain function in freely moving subjects

“…Technetium-99m-hexamethyl-proyleneamine oxime (Tc 99m -D,L-HMPAO or exametazime; Ceretec™, radioactive t 1/2 = 6.03 h, NycomedAmersham, Little Chalfont, UK), a commercially available tracer, has been used to study brain activation in freely-moving human subjects during walking [67], during cycling on a stationary bicycle [68], and in nonrestrained subjects during performance of the Wisconsin Card Sorting Test [69]. The 99m Tc complex of HMPAO (but not HMPAO itself) readily passes the intact blood-brain barrier, and brain uptake of Tc 99m -D,L-HMPAO closely reflects regional CBF [70].…”

Mechanisms of Neuroprotection Underlying Physical Exercise in Ischemia - Reperfusion Injury

“…However, in rats preconditioned with physical exercise, brain glucose uptake and metabolism was substantially preserved following reperfusion and was associated with a decrease in infarct volume and functional neurologic deficit. CBF and metabolism also increase during the act of physical exercise, signifying the increased metabolic demand on neuronal cells during training (Hellstrom et al, 1996;Ide and Secher, 2000;Vissing et al, 1996;Williamson et al, 1997) and the likely underlying mechanism through which neuroprotection is obtained. The angiogenic changes that occur following exercise preconditioning provide the brain with an enriched vascular bed with an enhanced ability for proper cerebral blood flow and glucose delivery to neurons, yielding more tolerance to reperfusion injury in the setting of ischemia/reperfusion.…”