The balance between metabolic heat production, heat removal by blood flow, and heat conductance defines local temperature distribution in a living tissue. Disproportional local increases in blood flow as compared with oxygen consumption during functional brain activity disturb this balance, leading to temperature changes. In this article we have developed a theoretical framework that allows analysis of temperature changes during arbitrary functional brain activity. We established theoretical boundaries on temperature changes and explained how these boundaries depend on physiology (blood flow and metabolism) and external (heat exchange with the environment) experimental conditions. We show that, in regions located deep in the brain, task performance should be accompanied by temperature decreases in regions where blood flow increases (activated regions) and by temperature increases in regions where blood flow decreases (deactivated regions). The sign of temperature effect may be reversed for superficial cortex regions, where the baseline brain temperature is lower than the temperature of incoming arterial blood due to the heat exchange with the environment. Importantly, due to heat conductance, the temperature effect is not localized to the activated region but extends to a surrounding tissue at rest over the distances regulated by the temperature-shielding effect of blood flow. This temperature-shielding effect quantifies the means by which cerebral blood flow prevents ''temperature perturbations'' from propagating away from the perturbed regions. For small activated regions, this effect also substantially suppresses the magnitude of the temperature response, making it especially important for small animal brains.brain temperature ͉ cerebral blood flow ͉ cerebral metabolism ͉ functional brain activity B asic mechanisms underlying global temperature regulation in humans and animals have attracted substantial attention from scientists, and considerable progress has been achieved in this area both in health and disease (see, e.g., refs. 1-4). However, information on brain temperature regulation, especially its relationship to function, is conflicting. Indeed, although, numerous experimental studies have demonstrated changes in the brain temperature of humans and animals upon functionally induced changes in brain activity, the magnitude and even sign of reported temperature changes vary substantially. For example, localized temperature variations from 0.01°C to 0.2°C were observed in animal brains (5-13) under different stimuli (visual, auditory, somatic). As reported in ref. 6, the sign of temperature response to visual stimulation in cats depends on the frequency of flashing light; for low frequencies (2-12 Hz), the temperature increases, whereas at high-frequencies (42-62 Hz) the temperature decreased. Negative temperature changes, on average Ϫ0.2°C, were observed in the deep regions of the visual cortex in conscious intact human subjects by a magnetic resonance method (14), whereas positive temperature changes up...