Studies in neuroscience have allowed us to define brain areas involved in laughter Citation 1, 2 in a project that was carried through in collaboration with Dr. E. Wattendorf and Profs. M. Celio and M. Lotze. To our surprise, tickling that was accompanied by laughter showed activation of the lateral hypothalamus, parietal operculum and amygdala, and implies that the hypothalamus is evoking this ticklish laughter reaction. Data that were obtained recently were analyzed to determine the key nodes of the emotional motor system in the anticipation of tickling Citation 3: In analogy to the appreciation of humor, that of tickling is based upon the re-interpretation of an anticipated emotional situation. Hence, two successive conditions, anticipation and tickling, contribute to the final outburst of ticklish laughter Paradigm. To localize the neuronal substrates of these processes, fMRI was conducted on 31 healthy volunteers. The state of anticipation was generated by creating an uncertainty with regard to the onset of the manually provided foot tickles. Anticipation was characterized by an increased fMRI signal in the anterior insula, the hypothalamus, the nucleus accumbens and the ventral tegmental area as well as by an attenuated signal in the internal globus pallidus fMRI. Furthermore, anticipatory activity in the anterior insula correlated positively with the degree of laughter that was produced during tickling fMRI. These findings are consistent with an encoding of the expected emotional consequences of being tickled and suggest that early regulatory mechanisms automatically influence the laughter circuitry at the level of affective and sensory processing. During tickling fMRI, additional brain regions were functionally implicated, including the posterior insula, the anterior cingulate cortex and the periaqueductal gray fMRI. Sequential or combined anticipatory and tickling-related neuronal activities may adjust the emotional- and sensory-motoric pathways in preparation for the impending laughter response.