"Silent event-related" fMRI reveals reduced sensorimotor activation in laryngeal dystonia.

OBJECTIVE: To study with fMRI the pattern of sensorimotor activation in patients with spasmodic dysphonia (laryngeal dystonia) compared to healthy controls. METHODS: The authors performed fMRI measurements during vocal motor tasks in 12 patients with laryngeal dystonia and compared them with those of 12 healthy volunteers. Patients were scanned before (pre) and after (post) treatment with local injections of botulinum toxin (BTX). They examined two different motor tasks: simple vocalization inducing dystonia and whispering without appearance of dystonic symptoms. To avoid movement artifacts with oral motor tasks, the authors used a silent event-related fMRI approach involving noncontinuous sampling with no data acquisition during task performance. RESULTS: They found reduced activation of primary sensorimotor as well as of premotor and sensory association cortices during vocalization in patients with laryngeal dystonia pre-BTX. This was partly observed also during the asymptomatic whispering task. BTX treatment did not result in reversal of reduced cortical activation. CONCLUSION: fMRI signal is reduced in sensorimotor cortices associated with movement of the affected body part in laryngeal dystonia, supporting a dystonic basis for this voice disorder.

Transmodal sensorimotor networks during action observation in professional pianists.

Audiovisual perception and imitation are essential for musical learning and skill acquisition. We compared professional pianists to musically naive controls with fMRI while observing piano playing finger-hand movements and serial finger-thumb opposition movements both with and without synchronous piano sound. Pianists showed stronger activations within a fronto-parieto-temporal network while observing piano playing compared to controls and contrasted to perception of serial finger-thumb opposition movements. Observation of silent piano playing additionally recruited auditory areas in pianists. Perception of piano sounds coupled with serial finger-thumb opposition movements evoked increased activation within the sensorimotor network. This indicates specialization of multimodal auditory-sensorimotor systems within a fronto-parieto-temporal network by professional musical training. Musical ''language,'' which is acquired by observation and imitation, seems to be tightly coupled to this network in accord with an observation-execution system linking visual and auditory perception to motor performance.

Alexithymia is no risk factor for exacerbation in spasmodic torticollis patients.

OBJECTIVE: To assess whether alexithymia is a risk factor for exacerbation in spasmodic torticollis (ST). METHODS: ST patients (2 x 10) with high vs. low alexithymia scores (mean score on the 20-item Toronto Alexithymia Scale [TAS-20]=69.2 vs. 28.7) were compared on physiological, motor and subjective responses to a cognitive and an emotional laboratory stressor. Changes in sustained abnormal head/shoulder positions and maximum range of motion (ROM) of the cervical spine were kinematically quantified. Skin conductance level (SCL), nonspecific skin conductance fluctuations (NS.SCF), heart rate (HR) and skin temperature (T) were measured. RESULTS: High alexithymia had no effect on the abnormal head posture or movements, but high-alexithymic ST patients showed generally increased levels of autonomic arousal (more NS.SCF, higher SCL; analysis of variance [ANOVA]: P=.016 and P=.051, respectively) under all experimental conditions. When ST symptom severity (TSUI-score) was partialled out, these group differences were somewhat reduced (analysis of covariance [ANCOVA]: P=.052 and P=.143). CONCLUSIONS: High alexithymia did not lead to increased abnormal head movements to stressors, but may result in a subtle increase in tonic level of sympathetic activity.

Neural correlates associated with impaired disgust processing in pre-symptomatic Huntington's disease.

Disturbances in recognizing facial expressions of disgust have been reported previously in pre-symptomatic and manifest Huntington's disease. Given the substantial role of the insula and basal ganglia in the perception of disgust as revealed by functional imaging, lesion studies and intracerebral recordings, we propose dysfunction within the insula and/or basal ganglia as the underlying neural substrate. Using functional MRI (fMRI), we studied a group of nine pre-symptomatic Huntington's disease gene carriers and nine healthy controls, matched for age, gender, intelligence and years of education, while they were viewing disgusted facial expressions. As control conditions, surprised and neutral expressions were presented. Compared with healthy controls, Huntington's disease gene carriers showed reduced responses within the left dorsal anterior insula during processing of disgusted facial expressions. Moreover, processing of disgust was associated with significant activation of the left dorsal anterior insula and putamen in healthy controls, but not in Huntington's disease gene carriers. Furthermore, behavioural assessment revealed a selective impairment in recognizing facial expressions displaying disgust in Huntington's disease gene carriers. Our finding of dysfunctional decreased insula activation in pre-symptomatic Huntington's disease provides an explanation for the clinical deficit in recognizing facial expression of disgust. Furthermore, it underscores the role of the insula in the emotion of disgust.

Facial expression recognition and subthalamic nucleus stimulation.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor signs in Parkinson's disease. However, clinical studies suggest that DBS of the STN may also affect cognitive and emotional functions. OBJECTIVE: To study the impact of STN stimulation in Parkinson's disease on perception of facial expressions. RESULTS: There was a selective reduction in recognition of angry faces, but not other expressions, during STN stimulation. CONCLUSIONS: The findings may have important implications for social adjustment in these patients.

Differential modulation of subcortical target and cortex during deep brain stimulation.

The combination of electrical deep brain stimulation (DBS) with functional imaging offers a unique model for tracing brain circuitry and for testing the modulatory potential of electrical stimulation on a neuronal network in vivo. We therefore applied parametric positron emission tomography (PET) analyses that allow characterization of rCBF responses as linear and nonlinear functions of the experimentally modulated stimulus (variable stimulator setting). In patients with electrodes in the thalamic ventrointermediate nucleus (VIM) for the treatment of essential tremor (ET) here we show that variations in voltage and frequency of thalamic stimulation have differential effects in a thalamo-cortical circuitry. Increasing stimulation amplitude was associated with a linear raise in rCBF at the thalamic stimulation site, but with a nonlinear rCBF response in the primary sensorimotor cortex (M1/S1). The reverse pattern in rCBF changes was observed with increasing stimulation frequency. These results indicate close connectivity between the stimulated nucleus (VIM) and primary sensorimotor cortex. Likewise, stimulation parameter-specific modulation occurs at this simple interface between an electrical and a cerebral system and suggests that the scope of DBS extends beyond an ablation-like on-off effect: DBS could rather allow a gradual tuning of activity within a neuronal circuit.

A H(2)(15)O positron emission tomography study on mental imagery of movement sequences--the effect of modulating sequence length and direction.

Motor imagery is a state of mental rehearsal of single movements or movement patterns and has been shown to recruit motor networks overlapping with those activated during movement execution. We wished to examine whether the brain areas subserving control of sequential processes could be delineated by pure mental imagery, their activation levels reflecting the processing demands of a sequential task. We studied six right-handed volunteers (39.0 +/- 14 years) with H(2)(15)O positron emission tomography (PET) while they continuously mentally pursued with their right hand one of five sequences differing in complexity (i.e., increases in sequence length, single-finger repetitions, and reversals). Conditions were repeated twice, alternating with two rest scans. Each imagined single motor element was paced at a frequency of 1 Hz. Significant activation increases (P < 0.05, corrected) associated with imagination of right finger movement sequences (conditions I to V combined)--compared to the rest condition--were observed in left sensorimotor cortex (M1/S1) and the adjacent inferior parietal cortex. Further activation increases (P < 0.001, uncorrected) occurred in bilateral dorsal premotor (PMd) cortex, left caudal supplementary motor area, bilateral ventral premotor cortex, right M1, left superior parietal cortex, left putamen, and right cerebellum. Activation decreases occurred in bilateral prefrontal and right temporo-occipital cortex. Activation increases that correlated with sequence complexity were observed only in specific areas of the activated network, notably in left PMd, right superior parietal cortex, and right cerebellar vermis (P < 0.05, corrected). In conclusion, our study, by varying the sequence structure of imagined finger movements, identified task-related activity changes in parietopremotor-cerebellar structures, reflecting their role in mediating sequence control.

Subthalamic nucleus stimulation affects striato-anterior cingulate cortex circuit in a response conflict task: a PET study.

The subthalamic nucleus (STN) has generally been considered as a relay station within frontal-subcortical motor control circuitry. Little is known about the influence of the STN on cognitive networks. Clinical observations and studies in animals suggest that the STN participates in non-motor functions which can now be probed in Parkinson's disease patients with deep brain stimulation of the STN, allowing selective and reversible modulation of this nucleus. Using PET, we studied changes in regional cerebral blood flow (rCBF) associated with a response conflict task (Stroop task) in Parkinson's disease patients ON and OFF bilateral STN stimulation. The Stroop task requires subjects to name the font colour of colour words (e.g. "blue") printed in an incongruent colour ink (e.g. yellow). During STN stimulation, impaired task performance (prolonged reaction times) was associated with decreased activation in both right anterior cingulate cortex (ACC) and right ventral striatum. Concomitant increased activation in left angular gyrus indicative of ongoing word processing during stimulation is consistent with an impairment to inhibit habitual responses. ACC and ventral striatum are part of the ACC circuit associated with response conflict tasks. The decreased activation during STN stimulation in the ACC circuit, while response conflict processing worsened, provides direct evidence of STN modulating non-motor basal ganglia-thalamocortical circuitry. Impairment in ACC circuit function could account for the subtle negative effects on cognition induced by STN stimulation.

[Dopaminergic agents, COMT inhibitors or amantadine? Proper treatment for your Parkinson patient]. / Dopaminergika, COMT-Hemmer oder Amantadin? Wie Sie Ihren Parkinsonpatienten richtig behandeln.

Over the last six years, eight new substances for the treatment of idiopathic parkinsonism (IP) have been approved for use: four oral and one parenteral dopamine agonist (apomorphine), two COMT-inhibitors and budipine. The old drug amantadine has experienced a renaissance in the treatment of a complication occurring during long-term treatment of IP, namely levodopa-induced dyskinesia. Deep brain stimulation with programmable pulse generators and stereotactically implanted electrodes are increasingly being used in patients with severe on-off phases and levodopa dyskinesia. The treatment of Parkinson's disease unresponsive to dopaminergic substances and that associated with dementia remains problematical. In combinations of parkinsonism and dementia, the cholinesterase inhibitors are being used in particular for Lewy body dementia.

Service-based survey of dystonia in munich.

We performed a service-based epidemiological study of dystonia in Munich, Germany. Due to favourable referral and treatment patterns in the Munich area, we could provide confident data from dystonia patients seeking botulinum toxin treatment. A total of 230 patients were ascertained, of whom 188 had primary dystonia. Point prevalence ratios were estimated to be 10.1 (95% confidence interval 8.4-11.9) per 100,000 for focal and 0.3 (0.0-0.6) for generalised primary dystonia. The most common focal primary dystonias were cervical dystonia with 5.4 (4.2-6.7) and essential blepharospasm with 3.1 (2.1-4.1) per 100,000 followed by laryngeal dystonia (spasmodic dysphonia) with 1.0 (0.4-1.5) per 100,000.

Social phobia in spasmodic torticollis.

OBJECTIVES: To study the prevalence of psychiatric comorbidity assessed by the use of a structured clinical interview in a large, representative sample of patients with spasmodic torticollis (ST) and to test the hypothesis that social phobia would be highly prevalent. METHODS: In a consecutive cohort of 116 patients with ST treated with botulinum toxin overall psychiatric comorbidity was studied prospectively with the structured clinical interview (SCID) for DSM-IV axis I disorders. Physical disability and psychosocial variables were also assessed with standardised self rating questionnaires. RESULTS: 41.3% of the subjects met DSM-IV clinical criteria A-G for current social phobia as the primary psychiatric diagnosis. This figure rose to 56% including secondary and tertiary psychiatric diagnosis. There was no correlation between severity of disease (Tsui score, severity of pain, body image dissatisfaction score) and psychiatric comorbidity. The only significant predictor of psychiatric comorbidity was depressive coping behaviour (logistic regression analysis, p < 0.01; OR=10.8). Compared with a representative sample of the general adult population, in the patients with ST the prevalence of clinically relevant social phobia is 10-fold, of mood disorders 2.4-fold, and of lifetime psychiatric comorbidity 2.6-fold increased. CONCLUSIONS: A particularly high prevalence of social phobia was found in the cohort of patients with ST. The finding of a high prevalence of social phobia and depressive coping behaviour as the main predictor of psychiatric comorbidity may make a subgroup of patients with ST particularly amenable to specific psychotherapeutic interventions.

Cortical correlates of gesture processing: clues to the cerebral mechanisms underlying apraxia during the imitation of meaningless gestures.

The clinical test of imitation of meaningless gestures is highly sensitive in revealing limb apraxia after dominant left brain damage. To relate lesion locations in apraxic patients to functional brain activation and to reveal the neuronal network subserving gesture representation, repeated H2(15O)-PET measurements were made in seven healthy subjects during a gesture discrimination task. Observing paired images of either meaningless hand or meaningless finger gestures, subjects had to indicate whether they were identical or different. As a control condition subjects simply had to indicate whether two portrayed persons were identical or not. Brain activity during the discrimination of hand gestures was strongly lateralized to the left hemisphere, a prominent peak activation being localized within the inferior parietal cortex (BA40). The discrimination of finger gestures induced a more symmetrical activation and rCBF peaks in the right intraparietal sulcus and in medial visual association areas (BA18/19). Two additional foci of prominent rCBF increase were found. One focus was located at the left lateral occipitotemporal junction (BA 19/37) and was related to both tasks; the other in the pre-SMA was particularly related to hand gestures. The pattern of task-dependent activation corresponds closely to the predictions made from the clinical findings, and underlines the left brain dominance for meaningless hand gestures and the critical involvement of the parietal cortex. The lateral visual association areas appear to support first stages of gesture representation, and the parietal cortex is part of the dorsal action stream. Finger gestures may require in addition precise visual analysis and spatial attention enabled by occipital and right intraparietal activity. Pre-SMA activity during the perception of hand gestures may reflect engagement of a network that is intimately related to gesture execution.

Right lateralized motor cortex activation during volitional blinking.

Using H2 15O positron emission tomography in 6 healthy volunteers, we found that self-initiated and externally cued blinking activated the right primary motor cortex and supplementary motor area (SMA). The left dorsolateral prefrontal cortex (DLPFC) and the rostral SMA showed greater activation during the self-initiated task compared to the externally cued task. This study confirms the hypothesis of right hemispheric lateralization of volitional blinking derived from observations in stroke patients. Furthermore, it underscores the role of DLPFC and rostral SMA in self-initiated movements, which has been found in similar experiments with hand movements.

Evidence-based medicine in botulinum toxin therapy for cervical dystonia.

Early controlled studies of botulinum toxin (BTX) in cervical dystonia were unblinded and indicated that BTX injections are more successful than medication. In this article, the use of botulinum toxin (BTX) in cervical dystonia is reviewed according to evidence-based medicine. To document the efficacy of BTX, there have been a number of prospective, placebo-controlled studies of the use of BTX in cervical dystonia. Most were double-blind, some included videotapes to provide blinded objective assessments. The more recent studies of BTX in cervical dystonia focused on particular issues such as utility of EMG guidance, comparison to anti-cholinergic treatment, BTX serotype B in BTX type A resistant and non-resistant patients and different dosages. Despite the wealth of data generated with prospective placebo-controlled studies on the effectiveness of BTX in cervical dystonia, there is uncertainty on which outcome measures to use to express the efficacy of treatments for cervical dystonia. Disease specific instruments to measure quality of life in cervical dystonia have not been used so far. Data on the use of BTX for cervical dystonia have long been restricted to small series of patients reflecting exclusively the experience of individual specialized centers.

Thalamic stimulation for essential tremor activates motor and deactivates vestibular cortex.

BACKGROUND: The functional effects of deep brain stimulation in the nucleus ventralis intermedius (VIM) of the thalamus on brain circuitry are not well understood. The connectivity of the VIM has so far not been studied functionally. It was hypothesized that VIM stimulation would exert an effect primarily on VIM projection areas, namely motor and parietoinsular vestibular cortex. METHODS: Six patients with essential tremor who had electrodes implanted in the VIM were studied with PET. Regional cerebral blood flow was measured during three experimental conditions: with 130 Hz (effective) and 50 Hz (ineffective) stimulation, and without stimulation. RESULTS: Effective stimulation was associated with regional cerebral blood flow increases in motor cortex ipsilateral to the side of stimulation. Right retroinsular (parietoinsular vestibular) cortex showed regional cerebral blood flow decreases with stimulation. CONCLUSIONS: Beneficial effects of VIM stimulation in essential tremor are associated with increased synaptic activity in motor cortex, possibly due to nonphysiologic activation of thalamofrontal projections or frequency-dependent neuroinhibition. Retroinsular regional cerebral blood flow decreases suggest an interaction of VIM stimulation on vestibular-thalamic-cortical projections that may explain dysequilibrium, a common and reversible stimulation-associated side effect.

Motor imagery in normal subjects and Parkinson's disease patients: an H215O PET study.

Motor imagery paradigms can be used to investigate motor preparation. We used positron emission tomography to compare regional cerebral blood flow (rCBF) in patients with Parkinson's disease and normal controls under three conditions: rest, motor imagery and motor execution. In controls, imagery activated bilateral dorsolateral and mesial frontal cortex, inferior parietal cortex and precuneus. Motor execution additionally activated primary motor cortex (p < 0.001). Between-group, for imagery there was relative reduction in dorsolateral and mesial frontal activation in the patient group (p<0.01). For execution, there was impaired activation of right dorsolateral frontal cortex and basal ganglia (p<0.01). Our results support the notion that underfunctioning of mesial frontal and dorsolateral prefrontal cortex may underlie motor preparation in Parkinson's disease but also suggest that akinesia may occur in the absence of impaired mesial frontal cortex activation.

Event-related functional magnetic resonance imaging in Parkinson's disease before and after levodopa.

Event-related functional MRI (fMRI) was used to study blood oxygen level dependent cortical signal changes associated with volitional limb movements off and on levodopa in Parkinson's disease. Eight patients with early stage akinetic Parkinson's disease and eight healthy volunteers underwent three functional imaging runs (high speed echo planar imaging with 600 scans/run) while performing paced single joystick movements in a freely chosen direction every 7-15 s. The non-magnetic joystick was linked to a monitoring system for on-line registration of performance parameters along with timing of the pacing tones and fMRI-scan acquisition parameters. This allowed correlation of movement onset, i.e. event-onset, to scanning time. We repeated the scanning procedure in the Parkinson's disease patients when akinesia improved 30 min after oral levodopa. Compared with the control group, patients both off and on levodopa showed movement-related impaired activation in the rostral supplementary motor area and increased activation in primary motor cortex (M1) and the lateral premotor cortex bilaterally. Levodopa led to a relative normalization of the impaired activation in the mesial premotor cortex and decreased signal levels in M1, lateral premotor and superior parietal cortex. We conclude that levodopa improves impaired motor initiation in the supplementary motor area and decreases hyperfunction of lateral premotor and M1 associated with Parkinson's disease during simple volitional movements.

Botulinum toxin A for axillary hyperhidrosis (excessive sweating).

BACKGROUND: Treatment of primary focal hyperhidrosis is often unsatisfactory. Botulinum toxin A can stop excessive sweating by blocking the release of acetylcholine, which mediates sympathetic neurotransmission in the sweat glands. METHODS: We conducted a multicenter trial of botulinum toxin A in 145 patients with axillary hyperhidrosis. The patients had rates of sweat production greater than 50 mg per minute and had had primary axillary hyperhidrosis that was unresponsive to topical therapy with aluminum chloride for more than one year. In each patient, botulinum toxin A (200 U) was injected into one axilla, and placebo was injected into the other in a randomized, double-blind manner. (The units of the botulinum toxin A preparation used in this study are not identical to those of other preparations.) Two weeks later, after the treatments were revealed, the axilla that had received placebo was injected with 100 U of botulinum toxin A. Changes in the rates of sweat production were measured by gravimetry. RESULTS: At base line, the mean (+/-SD) rate of sweat production was 192+/-136 mg per minute. Two weeks after the first injections the mean rate of sweat production in the axilla that received botulinum toxin A was 24+/-27 mg per minute, as compared with 144+/-113 mg per minute in the axilla that received placebo (P< 0.001). Injection of 100 U into the axilla that had been treated with placebo reduced the mean rate of sweat production in that axilla to 32+/-39 mg per minute (P<0.001). Twenty-four weeks after the injection of 100 U, the rates of sweat production (in the 136 patients in whom the rates were measured at that time) were still lower than base-line values, at 67+/-66 mg per minute in the axilla that received 200 U and 65+/-64 mg per minute in the axilla that received placebo and 100 U of the toxin. Treatment was well tolerated; 98 percent of the patients said they would recommend this therapy to others. CONCLUSIONS: Intradermal injection of botulinum toxin A is an effective and safe therapy for severe axillary hyperhidrosis.

[Current perspectives of alexithymia]. / Aktuelle Perspektiven der Alexithymie.

Although alexithymia is found in patients with various somatic disorders, it remains unclear whether it is really related to organic disease--as proposed by the founders of the concept.[125]. As the interplay between the experience of emotion and possible adverse effects on health is a fundamental tenet of psychosomatic medicine, alexithymia remains an interesting concept to be further explored, especially concerning (1) possible pathways linking emotion to physical illness and (2) the neurobiologic basis of emotional information processing. Compared to the intense international discussion on the subject, in Germany there are still many doubts concerning alexithymia: while some clinicians question the validity of the whole concept, psychiatric and psychosomatic researchers seem unsure about alexithymia's role in their search for a physiological basis to the link between emotion and physical disease. Our review deals with the empirical literature concerning that possible association and tries to tie in their data with modern, neuro-biologically founded insights into emotional information processing within the brain.