Imaging Studies in Focal Dystonias: A Systems Level Approach to Studying a Systems Level Disorder

Focal dystonias are dystonias that affect one part of the body, and are sometimes task-specific. Brain imaging and transcranial magnetic stimulation techniques have been valuable in defining the pathophysiology of dystonias in general, and are particularly amenable to studying focal dystonias. Over the past few years, several common themes have emerged in the imaging literature, and this review summarizes these findings and suggests some ways in which these distinct themes might all point to one common systems-level mechanism for dystonia. These themes include (1) the role of premotor regions in focal dystonia, (2) the role of the sensory system and sensorimotor integration in focal dystonia, (3) the role of decreased inhibition/increased excitation in focal dystonia, and (4) the role of brain imaging in evaluating and guiding treatment of focal dystonias. The data across these themes, together with the features of dystonia itself, are consistent with a hypothesis that all dystonias reflect excessive output of postural control/stabilization systems in the brain, and that the mechanisms for dystonia reflect amplification of an existing functional system, rather than recruitment of the wrong motor programs. Imaging is currently being used to test treatment effectiveness, and to visually guide treatment of dystonia, such as placement of deep brain stimulation electrodes. In the future, it is hoped that imaging may be used to individualize treatments across behavioral, pharmacologic, and surgical domains, thus optimizing both the speed and effectiveness of treatment for any given individual with focal dystonia

Auditory feedback control mechanisms do not contribute to cortical hyperactivity within the voice production network in adductor spasmodic dysphonia

Adductor spasmodic dysphonia (ADSD), the most common form of spasmodic dysphonia, is a debilitating voice disorder characterized by hyperactivity and muscle spasms in the vocal folds during speech. Prior neuroimaging studies have noted excessive brain activity during speech in ADSD participants compared to controls. Speech involves an auditory feedback control mechanism that generates motor commands aimed at eliminating disparities between desired and actual auditory signals. Thus, excessive neural activity in ADSD during speech may reflect, at least in part, increased engagement of the auditory feedback control mechanism as it attempts to correct vocal production errors detected through audition. To test this possibility, functional magnetic resonance imaging was used to identify differences between ADSD participants and age-matched controls in (i) brain activity when producing speech under different auditory feedback conditions, and (ii) resting state functional connectivity within the cortical network responsible for vocalization. The ADSD group had significantly higher activity than the control group during speech (compared to a silent baseline task) in three left-hemisphere cortical regions: ventral Rolandic (sensorimotor) cortex, anterior planum temporale, and posterior superior temporal gyrus/planum temporale. This was true for speech while auditory feedback was masked with noise as well as for speech with normal auditory feedback, indicating that the excess activity was not the result of auditory feedback control mechanisms attempting to correct for perceived voicing errors in ADSD. Furthermore, the ADSD group had significantly higher resting state functional connectivity between sensorimotor and auditory cortical regions within the left hemisphere as well as between the left and right hemispheres, consistent with the view that excessive motor activity frequently co-occurs with increased auditory cortical activity in individuals with ADSD.First author draf

Brain structure can mediate or moderate the relationship of behavior to brain function and transcriptome. A preliminary study

Abnormalities in motor-control behavior, which have been with concussion and head acceleration events (HAE), can be quantified using virtual reality (VR) technologies. Motor-control behavior has been consistently mapped to the brain's somatomotor network (SM) using both structural (sMRI) and functional MRI (fMRI). However, no studies habe integrated HAE, motor-control behavior, sMRI and fMRI measures. Here, brain networks important for motor-control were hypothesized to show changes in tractography-based diffusion weighted imaging [difference in fractional anisotropy (dFA)] and resting-state fMRI (rs-fMRI) measures in collegiate American football players across the season, and that these measures would relate to VR-based motor-control. We firther tested if nine inflammation-related miRNAs were associated with behavior-structure-function variables. Using permutation-based mediation and moderation methods, we found that across-season dFA from the SM structural connectome (SM-dFA) mediated the relationship between across-season VR-based Sensory-motor Reactivity (dSR) and rs-fMRI SM fingerprint similarity (p = 0.007 and Teff = 47%). The interaction between dSR and SM-dFA also predicted (pF = 0.036, pbeta3 = 0.058) across-season levels of dmiRNA-30d through permutation-based moderation analysis. These results suggest (1) that motor-control is in a feedback relationship with brain structure and function, (2) behavior-structure-function can be connected to HAE, and (3) behavior-structure might predict molecular biology measures.Comment: 62 pages, 4 figures, 2 table

White Matter Changes in Cervical Dystonia Relate to Clinical Effectiveness of Botulinum Toxin Treatment

In a previous report showing white matter microstructural hemispheric asymmetries medial to the pallidum in focal dystonias, we showed preliminary evidence that this abnormality was reduced 4 weeks after botulinum toxin (BTX) injections. In the current study we report the completed treatment study in a full-size cohort of CD patients (n = 14). In addition to showing a shift toward normalization of the hemispheric asymmetry, we evaluated clinical relevance of these findings by relating white matter changes to degree of symptom improvement. We also evaluated whether the magnitude of the white matter asymmetry before treatment was related to severity, laterality, duration of dystonia, and/or number of previous BTX injections. Our results confirm the findings of our preliminary report: we observed significant fractional anisotropy (FA) changes medial to the pallidum 4 weeks after BTX in CD participants that were not observed in controls scanned at the same interval. There was a significant relationship between magnitude of hemispheric asymmetry and dystonia symptom improvement, as measured by percent reduction in dystonia scale scores. There was also a trend toward a relationship between magnitude of pre-injection white matter asymmetry and symptom severity, but not symptom laterality, disorder duration, or number of previous BTX injections. Post-hoc analyses suggested the FA changes at least partially reflected changes in pathophysiology, but a dissociation between patient perception of benefit from injections and FA changes suggested the changes did not reflect changes to the primary “driver” of the dystonia. In contrast, there were no changes or group differences in DTI diffusivity measures, suggesting the hemispheric asymmetry in CD does not reflect irreversible white matter tissue loss. These findings support the hypothesis that central nervous system white matter changes are involved in the mechanism by which BTX exerts clinical benefit

Effect of the Planet Health Intervention on Eating Disorder Symptoms in Massachusetts Middle Schools, 2005–2008

Introduction: The Planet Health obesity prevention curriculum has prevented purging and abuse of diet pills (disordered weight control behavior [DWCB]) in middle-school girls in randomized trials, but the effects of Planet Health on DWCB when implemented by schools under dissemination conditions are not known. Methods: Massachusetts Department of Public Health and Blue Cross Blue Shield of Massachusetts disseminated Planet Health as part of the 3-year, Healthy Choices obesity prevention program in middle schools. We conducted an evaluation in 45 schools from fall 2005 to spring 2008. We gathered data from school staff to quantify intervention activities, and we gathered anonymous cross-sectional survey data from students on DWCB at baseline and Year 3 follow-up (n = 16,369). Multivariate logistic analyses with generalized estimating equations examined the effect of intervention activities on odds of students reporting DWCB at follow-up. Results: Students in schools reaching a high number of youth with Planet Health lessons on reducing television viewing had lower odds of DWCB at follow-up (odds ratio [OR], 0.80 per 100 lesson-exposures; 95% confidence interval [CI], 0.74–0.85). In addition, reduced odds of DWCB at follow-up were found in schools with active staff teamwork (OR, 0.76; 95% CI, 0.66–0.86) and the presence of programs addressing television viewing goals with staff (OR, 0.38; 95% CI, 0.28–0.53). Conclusion: Combined evidence from efficacy and effectiveness trials and now from dissemination research indicates that appropriately designed obesity prevention programs can achieve DWCB prevention on a large scale

Effect of the planet health intervention on eating disorder symptoms in Massachusetts middle schools, 2005-2008

INTRODUCTION: The Planet Health obesity prevention curriculum has prevented purging and abuse of diet pills (disordered weight control behavior [DWCB]) in middle-school girls in randomized trials, but the effects of Planet Health on DWCB when implemented by schools under dissemination conditions are not known. METHODS: Massachusetts Department of Public Health and Blue Cross Blue Shield of Massachusetts disseminated Planet Health as part of the 3-year, Healthy Choices obesity prevention program in middle schools. We conducted an evaluation in 45 schools from fall 2005 to spring 2008. We gathered data from school staff to quantify intervention activities, and we gathered anonymous cross-sectional survey data from students on DWCB at baseline and Year 3 follow-up (n = 16,369). Multivariate logistic analyses with generalized estimating equations examined the effect of intervention activities on odds of students reporting DWCB at follow-up. RESULTS: Students in schools reaching a high number of youth with Planet Health lessons on reducing television viewing had lower odds of DWCB at follow-up (odds ratio [OR], 0.80 per 100 lesson-exposures; 95% confidence interval [CI], 0.74-0.85). In addition, reduced odds of DWCB at follow-up were found in schools with active staff teamwork (OR, 0.76; 95% CI, 0.66-0.86) and the presence of programs addressing television viewing goals with staff (OR, 0.38; 95% CI, 0.28-0.53). CONCLUSION: Combined evidence from efficacy and effectiveness trials and now from dissemination research indicates that appropriately designed obesity prevention programs can achieve DWCB prevention on a large scale

Redefining neuromarketing as an integrated science of influence

Multiple transformative forces target marketing, many of which derive from new technologies that allow us to sample thinking in real time (i.e., brain imaging), or to look at large aggregations of decisions (i.e., big data). There has been an inclination to refer to the intersection of these technologies with the general topic of marketing as “neuromarketing”. There has not been a serious effort to frame neuromarketing, which is the goal of this paper. Neuromarketing can be compared to neuroeconomics, wherein neuroeconomics is generally focused on how individuals make “choices”, and represent distributions of choices. Neuromarketing, in contrast, focuses on how a distribution of choices can be shifted or “influenced”, which can occur at multiple “scales” of behavior (e.g., individual, group, or market/society). Given influence can affect choice through many cognitive modalities, and not just that of valuation of choice options, a science of influence also implies a need to develop a model of cognitive function integrating attention, memory, and reward/aversion function. The paper concludes with a brief description of three domains of neuromarketing application for studying influence, and their caveats

Evidence for Altered Basal Ganglia-Brainstem Connections in Cervical Dystonia

Background: There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia. Methodology/Principal Findings: In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients. Conclusions/Significance: These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia