Christian Dresel

The Link between Facial Feedback and Neural Activity within Central Circuitries of Emotion—New Insights from Botulinum Toxin–Induced Denervation of Frown Muscles

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.

The functional neuroanatomy of coordinated orofacial movements: sparse sampling fMRI of whistling.

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.

A new device for tactile stimulation during fMRI.

Standardized somatosensory stimulation of the face during functional MRI is technically demanding due to the high magnetic field of the MRI scanner and the confined geometry of the head coil. We developed a new computer-controlled MR-compatible stimulation device for mapping somatosensory-evoked brain activations during fMRI. The device employs von Frey-filaments which are commonly used for quantitative sensory testing (QST) to deliver punctate tactile stimuli to the face and other body surfaces with a high spatiotemporal accuracy. Such stimuli were applied to the ipsilateral face and hand of eight volunteers during two different experimental designs to explore the feasibility of the new stimulator for somatosensory mapping. Tactile stimulation activated a distributed neural network including primary (S1) and secondary (S2) somatosensory areas as well as the premotor cortex and the thalamus. An event-related experimental design yielded S1 activation in all subjects despite a smaller total number of stimuli compared to a blocked design where S1 activation was not consistently found in three subjects. In individuals where S1 was significantly activated during both experimental conditions, the punctate tactile stimuli allowed discriminating the face and the hand representation in S1. We conclude that the novel stimulation device appears to be a valuable tool for mapping somatosensory representations. The data suggest that an event-related study design could be beneficial as it better controls for confounding factors such as anticipation, habituation and attention.

Basal ganglia-premotor dysfunction during movement imagination in writer's cramp.

The pathophysiology of idiopathic focal hand dystonia (writers cramp) is characterized by deficient inhibitory basal ganglia function and altered cortical sensorimotor processing. To explore if this is already a primary finding in dystonia for internal movement simulation independent of dystonic motor output or abnormal sensory input, we investigated the neural correlates of movement imagination and observation in patients with writers cramp. Event‐related fMRI was applied during kinesthetic motor imagery of drawing simple geometric figures (imagination task) and passively observing videos of hands drawing identical figures (observation task). Compared with healthy controls, patients with writers cramp showed deficient activation of the left primary sensorimotor cortex, mesial and left dorsal premotor cortex, bilateral putamen, and bilateral thalamus during motor imagery. No significant signal differences between both groups were found during the observation task. We conclude that internal movement simulation and planning as tested during imagination of hand movements appear to be dysfunctional in patients with writers cramp, whereas visual signal processing and observation‐induced activation are unaffected. Deficient basal ganglia–premotor activation could be a correlate of impaired basal ganglia inhibition and focusing during the selection of motor programs in dystonia. This finding seems to be an intrinsic deficit, as it is found during motor imagery in the absence of dystonic symptoms.

Multiple changes of functional connectivity between sensorimotor areas in focal hand dystonia

Background Task-specific focal hand dystonia impairs the control of arm muscles during fine motor skills such as writing (writers cramp (WC)). Functional imaging found abnormal task-related activation of sensorimotor areas in this disorder, but little is known on their functional connectivity (FC). Methods Resting-state fMRI and regions of interest (ROI)-voxel cross-correlation analyses were used for systematically analysing the FC between multiple ROIs within the cerebello-basal ganglia-thalamocortical network in 15 patients with right-sided WC and 15 healthy volunteers. Results Patients with WC showed a lower positive FC of several seed ROIs (left lateral premotor cortex, left thalamus, left/right pallidum) to the symptomatic left primary sensorimotor cortex compared with controls. The FC of the left primary motor cortex to prefrontal areas, pre- supplementary motor area and right somatosensory cortex was reduced and correlated with disease severity. Several cerebellar seed ROIs (right dentate nucleus, right crus I and bilateral crus II) revealed a stronger negative FC to primary and secondary sensorimotor areas. Conclusions An increase of negative cerebello-cortical FC at rest is in line with the hypothesis of a pathogenetic role of the cerebellum in dystonia. The deficit of positive subcortico-cortical FC indicates more generalised changes within the basal ganglia-thalamocortical motor loops beyond primary sensorimotor areas in WC. As patients with WC are asymptomatic during rest, these functional network changes could reflect an underlying abnormality or compensatory neuroplastic changes of network architecture in this disorder.

Rare sequence variants in ANO3 and GNAL in a primary torsion dystonia series and controls

Rare autosomal‐dominant mutations in ANO3 and GNAL have been recently shown to represent novel genetic factors underlying primary torsion dystonia (PTD) with predominantly craniocervical involvement.

Botulinum toxin modulates basal ganglia but not deficient somatosensory activation in orofacial dystonia.

The etiology of idiopathic orofacial dystonia is incompletely understood. Neurophysiological studies indicated that a sensory dysfunction could play a key role in the pathophysiology of focal dystonia. To explore if central sensory processing is abnormal in patients with blepharospasm and Meiges syndrome and to study the effects of botulinum toxin (BTX) treatment, we systematically mapped the somatotopic representations of punctate tactile stimuli in these patients before and after therapy.

Changes in resting‐state connectivity in musicians with embouchure dystonia

Objective: Embouchure dystonia is a highly disabling task‐specific dystonia in professional brass musicians leading to spasms of perioral muscles while playing the instrument. As they are asymptomatic at rest, resting‐state functional magnetic resonance imaging in these patients can reveal changes in functional connectivity within and between brain networks independent from dystonic symptoms.

Neuronal Oscillations in Various Frequency Bands Differ between Pain and Touch

Although humans are generally capable of distinguishing single events of pain or touch, recent research suggested that both modalities activate a network of similar brain regions. By contrast, less attention has been paid to which processes uniquely contribute to each modality. The present study investigated the neuronal oscillations that enable a subject to process pain and touch as well as to evaluate the intensity of both modalities by means of Electroencephalography. Nineteen healthy subjects were asked to rate the intensity of each stimulus at single trial level. By computing Linear mixed effects models (LME) encoding of both modalities was explored by relating stimulus intensities to brain responses. While the intensity of single touch trials is encoded only by theta activity, pain perception is encoded by theta, alpha and gamma activity. Beta activity in the tactile domain shows an on/off like characteristic in response to touch which was not observed in the pain domain. Our results enhance recent findings pointing to the contribution of different neuronal oscillations to the processing of nociceptive and tactile stimuli.

Mutational screening of THAP1 in a German population with primary dystonia.

Dystonia linked to DYT6 locus is a form of primary dystonia with an autosomal dominant inheritance and penetrance of approximately 60% independent of sex. An insertion/deletion founder mutation (134_135insGGGTT; 137_139delAAC) in exon 2 of THAP1 [THAP (Thanatos-associated protein) domaincontaining protein 1] (8p21–8q22) was identified in three Amish-Mennonite families with dystonia linked to DYT6 locus. Furthermore, a missense mutation in exon 2 (241T > C) was identified in another family with partial German ancestry [1]. Novel mutations in THAP1 were identified in sporadic or familial cases with various dystonic phenotypes expanding the genotypic and phenotypic spectrum of mutations in THAP1 (for an overview, see Table 2). THAP1 is a zinc-finger transcription factor and represses TOR1A (DYT1) expression, linking the two forms of primary torsion dystonia (DYT6 and DYT1 loci) on the molecular level [2]. The protein contains a DNA binding domain, which is an atypical zing finger, a coiled coil domain with a nuclear localization signal and a Pro-rich domain. We screened THAP1 in patients with various types of primary dystonia in an attempt to reveal possible novel variants of THAP1 and a putative role of THAP1 mutations in primary focal/segmental dystonia.