Functional connectivity of frontal components of the human mirror system: a PPI study.

Introduction Great attention has been paid to the human mirror system (MNS) in recent years (Caspers et al., 2010; Rizzolatti & Sinigaglia 2010); among the peculiarities of the human MNS, the fact that it responds to action observation even in the absence of a target object (Lui et al., 2008). However, so far few studies have dealt with the functional connectivity of the components of this system (Skippers et al., 2007; Hattori et al., 2009; Xu et al., 2009; Emmorey et al., 2010). With the present work, we aimed at revealing patterns of connectivity of ventral premotor cortex/dorsal BA44 (PMv) and Broca area (BA44/45) during the observation of different types of gestures: Symbolic (SY) and Grasping (GR). Methods Twenty healthy right-handed volunteers (8 males, 12 females; mean age 26.6) took part in this study. An event-related paradigm was adopted. A continuous video was presented, showing some common objects (glasses, cup, scissors, etc.) on a table. At intervals, an actor, of whom only the trunk and arms were visible, performed different kinds of hand movements: a) SY: non-object related symbolic actions (OK, hello, etc.); b) GR: grasping of an object. Three runs were carried out for each subject. Six movements for each class were shown in each run, alternated in pseudorandom order; each single movement was presented only once to each volunteer. Functional imaging was performed on a 3T Philips Intera scanner. Twenty-four axial slices were acquired (in-plane matrix: 64x64; TR: 2515 ms; voxel size: 3.75x3.75x4 mm, with a 0.6 mm gap between contiguous slices). Data analysis was carried out using SPM5. After a conventional GLM analysis, we assessed changes in functional connectivity related to the SY and GR observation tasks, by means of two separate PsychoPhysiologic Interaction (PPI) analyses (Friston et al., 1997). Foci in the right PMv and left BA44/45, identified by the conventional GLM analyses, were the seed regions. Group analyses were performed by random-effect models. Results Activity in right PMv during the observation of SY was positively related to activity in bilateral regions in posterior (occipito-temporo-parietal) cortex and cerebellum; during the observation of GR, the pattern was similar, but an additional correlated focus was present in the right inferior and middle frontal gyri, BA44/45/46 (Fig. 1). Activity in left BA44/45 during the observation of SY was positively related to activity in two foci: a larger focus in the left inferior and middle frontal gyri, mainly in BA45/46/47, and a second focus in the medial and superior frontal gyri, BA6/8, also mostly in the left hemisphere (Fig. 2). During the observation of GR, a very different pattern was present, with extensive bilateral clusters in sensorimotor and premotor cortex (mainly BA3/4/6/7 and BA6/8). Conclusions The present data suggest that right PMv and left Broca area are parts of different functional networks, differentially active during the observation of different meaningful arm-hand actions. The PMv connections to a mainly visual network during the observation of symbolic, intransitive movements are probably related to extracting visuo/spatial features of the observed scene; only during observation of grasping, PMv relates to the inferior frontal gyrus. On the other hand, the left Broca area has a specific pattern of connectivity with premotor regions involved in higher-order motor programming during the observation of symbolic gestures. References Caspers, S. et al. (2010), 'ALE meta-analysis of action observation and imitation in the human brain', NeuroImage, vol. 50, pp. 1148-1167. Emmorey, K. et al. (2010), ‘CNS activation and regional connectivity during pantomime observation: no engagement of the mirror neuron system for deaf signers’, Neuroimage vol. 49, pp. 994-1005. Hattori, N. et al. (2009), ‘Discrete parieto-frontal functional connectivity related to grasping’, Journal of Neurophysiology, vol. 101, pp. 1267-1282. Lui, F. et al. (2008), ‘Neural substrates for observing and imagining non-object-directed actions’, Social Neuroscience, vol. 3, pp.261-275. Rizzolatti, G. & Sinigaglia, C. (2010), ‘The functional role of the parieto-frontal mirror circuit: interpretations and misinterpretations’, Nature Reviews Neuroscience, vol. 11, pp. 264-274. Skipper, J.I. et al. (2007), ‘Speech-associated gestures, Broca's area, and the human mirror system’, Brain and Language, vol. 101, pp. 260-277. Xu, J. et al. (2009), ‘Symbolic gestures and spoken language are processed by a common neural system’, Proceedings of the National Academy of Sciences U S A, vol. 106, pp. 20664-20669.