Revisiting the brain activity associated with innocuous and noxious cold exposure.

Humans have a sophisticated set of neural structures for cutaneous thermoception. Sufficiently cold temperatures are thought to evoke pain and motivation to resolve disturbed homeostasis, while cool but not painful temperatures are evaluated as cold but do not cause thermoregulatory behaviour. Brain networks for innocuous and noxious cold temperature have been proposed but a quantitative meta-analysis comparing the two has never been conducted. As a result, we sought to perform activation likelihood estimation analysis of the brain activity associated with innocuous and noxious cold exposure. Combining data from 33 data sets revealed that innocuous cold exposure activates the posterior insular, middle/orbital and posterior parietal cortices while noxious cold activates the thalamus, putamen, and right anterior insula cortex. Both conditions respectively show greater activation in these areas and no areas are common between conditions. Our results confirm the long-standing hypothesis that noxious cold is encoded in the right anterior insula, but contradicts the selective importance of the posterior insula for cool somatosensory processing.