Victor Candia

Prefrontal cortex modulates placebo analgesia.

&NA; Expectations and beliefs modulate the experience of pain, which is particularly evident in placebo analgesia. The dorsolateral prefrontal cortex (DLPFC) has been associated with pain regulation and with the generation, maintenance and manipulation of cognitive representations, consistent with its role in expectation. In a heat‐pain paradigm, we employed non‐invasive low‐frequency repetitive transcranial magnetic stimulation (rTMS) to transiently disrupt left and right DLPFC function or used the TMS device itself as a placebo, before applying an expectation‐induced placebo analgesia. The results demonstrated that placebo significantly increased pain threshold and pain tolerance. While rTMS did not affect pain experience, it completely blocked placebo analgesia. These findings suggest that expectation‐induced placebo analgesia is mediated by symmetric prefrontal cortex function.

Effective behavioral treatment of focal hand dystonia in musicians alters somatosensory cortical organization

New perspectives in neurorehabilitation suggest that behavioral treatments of movement disorders may modify the functional organization of central somatosensory neural networks. On the basis of the assumption that use-dependent reorganization in these networks contributes to the fundamental abnormalities seen in focal dystonia, we treated 10 affected musicians and measured the concomitant somatosensory changes by using whole-head magnetoencephalography. We found that effective treatment, using the method of sensory motor retuning, leads to alterations in the functional organization of the somatosensory cortex. Specifically, before treatment, somatosensory relationships of the individual fingers differ between the affected and unaffected hands, whereas after treatment, finger representations contralateral to the dystonic side become more similar to the less-affected side. Further, somatosensory finger representations are ordered more according to homuncular principles after treatment. In addition, the observed physiologic changes correlated with behavioral data. These results confirm that plastic changes in parallel with emergent neurological dysfunction may be reversed by context-specific, intensive training-based remediation.

Brain activation in response to bladder filling and simultaneous stimulation of the dorsal clitoral nerve—An fMRI study in healthy women

AIMS Using functional magnetic resonance imaging (fMRI) we investigated the cortical and subcortical representations during bladder filling and the effect of simultaneous stimulation of the dorsal clitoral nerve on these cortical and subcortical structures. METHODS After approval of the local ethics committee, 8 healthy females were included. Prior to scanning, subjects were catheterized and the bladder was filled until first desire to void occurred. In a block design protocol we performed repetitive manual bladder filling (FILLING) and emptying of additional 80 ml saline, alternating with rest conditions (REST) of constant bladder volume. The protocol was repeated with simultaneous stimulation of the dorsal clitoral nerve during the filling periods (COMBINED). Activation maps were calculated by means for 3 different contrasts: 1) FILLING>REST, 2) COMBINED>REST and 3) FILLING>COMBINED. RESULTS A group analysis of contrast 1) showed activation of the right prefrontal and orbitofrontal cortices, the insula bilaterally, the left precuneus, the parietal operculum bilaterally, the cerebellum bilaterally (q(FDR)< or =0.001), the right anterior cingulate gyrus (q(FDR)< or =0.005) and the right anterior mid pons (q(FDR)< or =0.05). Contrast 2) showed activation in the right frontal area, the left insula, the parietal operculum bilaterally and the left cerebellum (q(FDR)< or =0.001). Deactivations were found in the middle frontal gyrus bilaterally and the post- and paracentral gyri bilaterally. Contrast 3) revealed stronger activation during FILLING in the bilateral frontal and prefrontal areas, the right anterior cingulated gyrus, and the right putamen (q(FDR)< or =0.05). Only the right insula showed stronger activation during the COMBINED condition. CONCLUSION Simultaneous dorsal clitoral nerve stimulation during bladder filling reduced the activation of certain cortical areas suggesting a neuromodulatory effect of this stimulation on supraspinal centres involved in lower urinary tract control.

Secondary motor disturbances in 101 patients with musician’s dystonia

Objective: Musician’s focal dystonia is usually considered to be task specific but secondary motor disturbances have been reported also. We carried out a detailed evaluation of the incidence of these secondary motor problems in 101 patients. Method: Symptoms were assessed using clinical histories, neurological examinations and observation of instrumental manoeuvres. Results: 53.5% of patients reported secondary motor disturbances in activities other than playing their main instrument, with the onset delayed in some cases by up to 12 years from the awareness of dystonic symptoms. 46.5% suffered from simple, 19.8% from complex and 33.7% from progressive cramps. Plucked string players (guitarists) mainly suffered from simple cramps while keyboardists more frequently displayed the progressive form. In all patients, symptoms were focal, and the type of cramp was unrelated to the severity of the perceived symptoms. Those patients playing a second instrument similar to their main instrument showed symptoms which worsened to a higher degree than those playing either only one instrument or whose second instrument was different. Conclusions: Longer follow-up assessments may reveal secondary motor symptoms that are not visible over shorter examination periods. Therefore, a thorough evaluation of everyday life motor activities should be considered in any clinical and treatment protocol. We speculate that the avoidance of movements that are similar to the main affected task may be of help in limiting symptoms. Consequently, focal dystonia may be considered more movement than task specific.

Changing the Brain through Therapy for Musicians' Hand Dystonia

Abstract: Focal hand dystonia is a disorder in which sensory and motor anomalies emerge that appear to be grounded in maladaptive routes of cortical plasticity. Remodeling cortical networks through sensory‐motor retuning (SMR), we achieved long‐term reduction in the symptoms of focal hand dystonia. Magnetoencephalography confirmed that SMR modified the representational cortex of the fingers, whereby the representation of the affected hand was reorganized so that it resembled more the organization of the non‐affected side. Furthermore, we observed differences in abnormal tactile acuity between patients with musicians cramp and those with writers cramp: Using two‐point finger discrimination, dystonic musicians showed perceptual asymmetry between hands, while writers cramp patients did not. To further evaluate the occurrence of collateral disturbances in focal dystonia, we assessed the clinical histories of 101 affected musicians. An important finding from this study was that dystonic musicians who play a similar first and second instrument reported a continuous worsening of their symptoms. In addition, collateral disturbances appeared with a shorter delay when more than one instrument was played. Taken together, these studies suggest that (1) neurological dysfunction can be reversed by context‐specific training protocols, (2) specific symptomatic and etiological differences among various forms of focal hand dystonia might result from different behavioral experiences and their central representation, and (3) the spread of symptoms might be prevented by avoiding training that implies movement patterns similar to the main affected task, and by reducing the amount of task‐associated movement behavior.

A portable and low-cost fMRI compatible pneumatic system for the investigation of the somatosensensory system in clinical and research environments

There still is a need for devices that allow reproducible stimulation of skin areas of the human body. We constructed a stimulation system and tested it by using brief pneumatic stimulation to the right thumb of nine healthy volunteers. BOLD-signals in response to tactile stimulation with frequencies of 1, 3 and 5 Hz were measured using a 3 T MRI scanner. The stimulation device consists of synthetic membranes connected to plastic tubes capable of carrying compressed air, and an electronic component, which controls the on- and off-switching of an electromagnetic valve. The valve near the MR-scanner did not lower the image quality. Primary somatosensory activation contralateral to the stimulation site was reliably detected in response to a stimulus magnitude of 3.5 bar in all volunteers. 1 Hz stimulation resulted in higher maximal percentage BOLD-signal changes. Our device is an easy-to-construct, low-cost and portable tool suitable for research and clinical environments. It permits passive non-painful stimulation relevant for clinical assessments and is also compatible with magnetoencephalography (MEG) and electroencephalography (EEG). In basic and clinical research, this device therefore contributes to meaningful comparisons between results obtained with different techniques.

REM Sleep Behavior Disorder is not Linked to Postural Instability and Gait Dysfunction in Parkinson

To evaluate a potential association of REM‐sleep behavior disorder (RBD) with gait and postural impairment in Parkinsons disease (PD). Gait difficulties and postural impairment are frequent in PD and are a major cause of disability. Animal studies indicate a key role of the pedunculopontine nucleus (PPN) in gait, postural control, and REM sleep, and also in the pathophysiology of RBD. In humans, such an association has not been investigated. Twenty‐six patients with mild‐to‐moderate PD (13 with polysomnography confirmed and 13 with excluded RBD), and 20 age‐matched healthy controls were prospectively investigated. Gait assessment on a treadmill, and static and dynamic posturography were performed. PD patients with RBD do not differ from those without RBD in gait and postural control. Greater severity of PD or prevalence of gait and postural disturbances in the presence of RBD were not found. RBD was not associated with any particular motor phenotype. We found no association of RBD with gait disturbances and postural impairment. Human gait and postural control and RBD appear to depend upon different neuronal circuits.

The challenge of diagnosing focal hand dystonia in musicians

Background and purpose:  To most clinicians, medical problems in musicians, particularly those concerning focal hand dystonia, constitute an unfamiliar domain difficult to manage. The latter can importantly influence diagnostics and the course of treatment. The purpose of this study was to enlighten the issue and to identify possible problems in diagnosing musicians’ cramp within the Spanish medical community.

Changes in self-perceived role identity modulate pain perception.

Abstract Pain is an experience including physiological and psychological factors. We assume that emotions may be elicited and increased through self‐perceived role identity and that change of role identity alters quality and intensity of pain perception. We used role‐play strategies to assess whether pain can be better tolerated whenever, in an unavoidable and unpleasant context, role identity confers pain a meaningful and thus suitable character. We induced antithetic roles in 21 actors who received heat stimuli on their arms before and after role‐play conditions. Pain tolerance, skin conductance and voice signals were measured. Pain tolerance increased for heroes/heroines and decreased for faint‐hearts. Men showed higher pain tolerance. Heroes/heroines evaluated heat stimuli as more intense. Faint‐hearts found pain stimuli more affectively loaded at lower temperatures. Women showed higher pain ratings. Hence, self‐perception influences pain perception. Role‐play strategies may be of value for new pain management strategies.

Pleasure-related analgesia activates opioid-insensitive circuits.

Recent findings suggest that pain and pleasure share common neurochemical circuits, and studies in animals and humans show that opioid-mediated descending pathways can inhibit or facilitate pain. We explored the role of endogenous opioid neurotransmission in pleasure-related analgesia. μ-Opioidergic activity was blocked with 0.2 mg/kg naloxone to assess its effects on hedonic responses to pleasant emotional pictures (International Affective Picture System) and its modulating effects on heat pain tolerance. Naloxone did not alter subjective and autonomous reactions to pleasure induction or overall mood of participants. In addition, pleasure-related increases in pain tolerance persisted after reversal of endogenous μ-opioidergic neurotransmission. Subjective pain intensity and unpleasantness ratings increased after naloxone administration. These findings suggest that, in addition to opioid-sensitive circuits, mainly opioid-insensitive pain-modulating circuits are activated during pleasure-related analgesia.