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Afferent feedback from muscles and skin has been suggested to influence our emotions during the control of facial expressions. Recent imaging studies have shown that imitation of facial expressions is associated with activation in limbic regions such as the amygdala. Yet, the physiological interaction between this limbic activation and facial feedback remains unclear. To study if facial feedback effects on limbic brain responses during intentional imitation of facial expressions, we applied botulinum toxin (BTX)-induced denervation of frown muscles in combination with functional magnetic resonance imaging as a reversible lesion model to minimize the occurrence of afferent muscular and cutaneous input. We show that, during imitation of angry facial expressions, reduced feedback due to BTX treatment attenuates activation of the left amygdala and its functional coupling with brain stem regions implicated in autonomic manifestations of emotional states. These findings demonstrate that facial feedback modulates neural activity within central circuitries of emotion during intentional imitation of facial expressions. Given that people tend to mimic the emotional expressions of others, this could provide a potential physiological basis for the social transfer of emotion.

Previous studies showed cortical dysfunction and impaired sensorimotor integration in primary generalized and focal hand dystonia. We used a whistling task and silent event-related fMRI to investigate functional changes in patients with blepharospasm and patients with a combination of blepharospasm and oromandibular dystonia (Meige's syndrome). Whistling served as a model for a skilful orofacial movement with a high demand on sensorimotor integration. It allowed us to study the oromandibular motor system that is clinically affected in Meige's syndrome but not in isolated blepharospasm. In Meige's syndrome, functional MRI revealed deficient activation of the primary motor and ventral premotor cortex within the mouth representation area during whistling. Compared with healthy controls, both forms of orofacial dystonia had increased activation of bilateral somatosensory areas and the caudal supplementary motor area (SMA) in common. While overactivity of somatosensory areas and caudal SMA in Meige patients was partly reversed by botulinum toxin treatment, impaired motor activation was not. We conclude that impaired motor activation appears to be specific for the clinically affected oromandibular motor system in Meige's syndrome while enhanced somatosensory activation is a common abnormality in both forms of orofacial dystonia independent of the affected motor system. Somatosensory overactivity indicates an altered somatosensory representation in orofacial dystonia while impaired motor activation may be a functional correlate of reduced cortical inhibition during oromandibular motor execution in Meige's syndrome.

Whistling serves as a model for a skilful coordinated orofacial movement with sensorimotor integration of auditory and proprioceptive input. The neural substrate of whistling was investigated by sparse sampling functional MRI (fMRI) where the motor task occurred during a silent interval between successive image acquisitions to minimize task-related imaging artefacts. Whistling recruited a symmetrically represented neural network including primary motor and ventral premotor cortex (PMv), SMA, cingulate gyrus, basal ganglia, primary and secondary somatosensory cortex, amygdala, thalamus and cerebellum. A temporal analysis revealed higher activity of left sensory cortex, right PMv and cerebellum during late execution compared to initiation of whistling. Task-related signal changes in right PMv and right paravermal cerebellum were found to correlate with the amplitude of the whistle sound in a separate correlation analysis. The findings emphasize the role of ventral premotor cortex, cerebellum and somatosensory areas as integrators of afferent input within a distributed orofacial sensorimotor network.

The inability to imitate gestures is an essential feature of apraxia. However, discrepancies exist between clinical studies in apraxic patients and neuroimaging findings on imitation. We therefore aimed to investigate: (1) which areas are recruited during imitation under conditions similar to clinical tests for apraxic deficits; (2) whether there are common lateralized areas subserving imitation irrespective of the acting limb side; and also (3) whether there are differences between hand and finger gestures. We used fMRI in 12 healthy, right handed subjects to investigate the imitation of four types of variable gestures that were presented by video clips (16 different finger and 16 different hand gestures with either the right or the left arm). The respective control conditions consisted of stereotyped gestures (only two gestures presented in pseudorandom order). Subtraction analysis of each type of gesture imitation (variable>stereotyped) revealed a bilateral activation pattern including the inferior parietal cortex Brodmann Area (BA 40), the superior parietal cortex, the inferior frontal cortex (opercular region), the prefrontal motor cortex, the lateral occipito-temporal junction, and the cerebellum. These results were supported by statistical conjunction of all four subtraction analyses and by the common analysis of all four types of gesture imitation. The direct comparison of the right and left hemispheric activation revealed a lateralization to the left only of the inferior parietal cortex. Comparisons between different types of gesture imitation yielded no significant results. In conclusion, gesture imitation recruits bilateral fronto-parietal regions, with significant lateralization of only one area, namely the left inferior parietal cortex. These in vivo data indicate left inferior parietal dominance for gesture imitation in right handers, confirming lesion-based theories of apraxia.

Vesicular monoamine transporters (VMATs) are a prerequisite for the uptake of biogenic amines into intracellular storage organelles, whereas soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs; such as SNAP-25 and syntaxin1) are essential for exocytosis of biogenic amines by neurons and endocrine cells. In this study, we examined whether these proteins exist in high-grade malignant small cell lung carcinomas (SCLCs), large cell carcinomas, adenocarcinomas, and squamous cell carcinomas of the lung. We analyzed two established human SCLC cell lines, one adenocarcinoma cell line, paraffin-embedded tumors (SCLC, n = 25; large cell carcinoma, n = 10; adenocarcinoma, n = 10; squamous cell carcinoma, n = 10), and snap-frozen SCLC samples (n = 2). Using immunocytochemistry, Western blotting, Northern blotting, RT-PCR, and sequencing, we identified VMAT1, VMAT2, SNAP-25, and syntaxin1 in cultured SCLC cells. Immunohistochemistry carried out on paraffin sections revealed that all SCLC tumors express VMAT1, VMAT2, SNAP-25, and syntaxin1. The presence of SNAP-25 and syntaxin1 in SCLC was confirmed by RT-PCR performed with material extracted from paraffin sections. Western blot analysis and RT-PCR carried out with snap-frozen SCLC tumors revealed the presence of SNAREs and VMATs. Immunohistochemistry showed that non-SCLC tumors were negative for SNAREs and VMATs, with the exception of immunostaining for SNAP-25 and syntaxin1 in 3 of 10 adenocarcinomas. Our findings indicate that SCLC cells are endowed with transporters necessary for intracellular storage of biogenic amines and with proteins required for exocytosis of secretory products. These proteins may be used as markers of differentiation of human lung tumors. Moreover, the presence of VMATs provides the basis for a diagnostic application of biogenic amine-derived tracers in positron emission tomography of SCLC tumors.