New insight on the functions organization of the insula of Reil and the inner perisylvian regions: a multidisciplinary approach

Abstract

The insula of Reil is a wide cortical region (~ 160mm² in rhesus monkey) buried in the depth of the sylvian fissure with an incomplete opercularization in non-human primates that reaches a complete opercularization only in the human brain. Researchers attributed to the insula and adjoining perisylvian regions in both monkeys and humans a very wide range of functions including autonomic and visceral functions, emotions, processing of various sensorial modalities (gustatory, olfactory, somatosensory, auditory). Based on these observations, the present research was undertaken in order to assess the eventual role of the insula and inner perisylvian regions in each of these functions. Two complementary approaches were combined: intracortical microstimulation in awake free behaving monkeys and anatomical connection study. The first study investigates the functional organization of the insula and inner perisylvian regions in macaque monkeys in order to assess a possible somatotopic organization. ICMS experiments were carried out on two awake free-moving rhesus monkeys (macaca mulatta). ICMS was performed with 50 Hz biphasic waves (0.2 msec of phase width) lasting from 50 msec up to 3 sec. Intensity was varied in a range up to 4 mA. During experiments, overt behavior and cardiac activity (ECG) evoked by ICMS have been monitored. The results showed that ICMS of inner perisylvian regions evokes a wide range of behavioral responses, which appeared to be roughly somatotopically arranged. In the rostral part a representation of oro-alimentary behaviour is present; responses like chewing, mouthing and deglutition prevail dorsally (frontal operculum and dorsal insula). In the ventral part (anterior ventral insula), strong viscero-motor responses (vomiting) are evoked. In the middle part (fronto-parietal operculum and middle dorsal insula), complex behaviours are evoked. In the dorsal caudal part (parietal operculum and posterior dorsal insula), simple motor responses involving distal and proximal effectors are evoked. Moreover, in the ventral intermediate sector of the insula, ICMS evoked communicative responses: the stimulations induced the monkey to lip-smack only when facing the experimenter. In the ventral insula and the lower bank, a miscellaneous of stereotyped and repetitive responses was also present. For what concerns the effects of ICMS on the autonomic system, a heart rate variability (HRV) analysis was carried out. The results showed different responses (bradycardia and tachycardia) along the rostro-caudal axis: bradycardia was evoked by stimulation of the rostral portion, showing an increase of the effect along the dorso-ventral axis. The posterior part of the studied regions showed a segregation of spots where stimulation induces bradycardia, tachycardia and no-effect. The present results show the involvement of inner perisylvian regions in the control of behavior as well as in the control of autonomic nervous system functions. Moreover, they show that such control obeys to a coarse somatotopically arranged segregation of functions within the explored regions. In the second experiment, we investigated the cortical and subcortical connections of the insular cortex. Three anatomical tracers were injected in three different sites where the functional properties were studied by mean of ICMS. On the one hand, the findings of this experiment are in agreement with what had been reported in the literature. The anterior insulo-orbital regions where oro-alimentary behaviours were evoked are connected with orbito-frontal areas (area 12, 11, 13 and 14), the rostral ventral prefrontal cortex (area 46), the precentral opercular area (PrCO), anterior cingulate areas (24b\c and 24a, 32), temporal pole, superior temporal pole (STP), inferior temporal gyrus (TEm, TEa\d), entorhinal cortex, baso-lateral amygdaloid nuclei, hypothalamus and ventral tegmental area (VTA). The ventral middle insula, where communicative responses were evoked, shows connections with areas 12r\m, 13l\m and 11 of the orbitofrontal cortex, area 45a of the prefrontal cortex, with area 44, area F5c of the premotor cortex, disgranular opercular area (DO), areas 24c and 24b of the cingulate cortex, temporal pole, TEa and TEm of the inferior temporal cortex, IPa and amygdala. Injection in the most medial part of SII, bordering with the posterior dorsal insula, where simple movement of lower limbs were evoked, is connected with area F3 of the premotor cortex, primary motor cortex, posterior cingulate areas (32, 24d, 23c), primary and secondary somatosensory areas, superior parietal cortex (PE, MIP) and inferior parietal lobule (AIP, PFop, PGop). On the other hand, these findings are in agreement with the functional properties of the injected sites, since the connected areas are functionally involved in different aspects of the behaviours evoked by ICMS performed in the injected loci. Taken together, the findings of these two experiments not only confirm a role of the insular cortex and the inner perisylvian regions in a wide range of behaviours and in the control of the autonomic functions, but also improve our understanding of the dynamics of the involvement of the stimulated regions within neural networks responsible of complex behaviours.