Diffusion weighted and resting state MRI for studying structural and correlated functional sensorimotor connectivity in patients with focal dystonias

• Applicant: Professor Dr. Bernhard Haslinger
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Human Cognitive and Systems Neuroscience
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 260063645

• Final Report Year: 2018

Final Report Abstract

During the funding period, we performed multimodal MRI studies including resting state and diffusion weighted MRI (DTI) and voxel based morphometry (VBM) in patients with different forms of focal dystonia. These included patients with writer’s cramp (WC), blepharospasm/ Meige syndrome, musicians with embouchure dystonia (ED) and a small group of patients with a newly identified form of genetic dystonia (DYT27). ROI based hypothesis driven and data driven (ICA-) analyses of functional connectivity were performed to study a putative dysfunction of sensorimotor networks already in the absence of dystonic symptoms, i.e. at rest. Voxel wise analyses of local diffusivity as well as probabilistic fiber tracking analyses were applied to study changes of white matter architecture within these subcortical-cortical sensorimotor networks, VBM was additionally performed in patients with WC and ED, both methods revealing a potential anatomical basis for the functional abnormalities. Online recordings of facial surface EMG for the first time allowed the acquisition of resting state data in patients with Blepharospasm/Meige syndrome that are controlled for possible artifacts by involuntary movements at rest. Our resting state studies showed alterations of functional connectivity (FC) especially within sensorimotor networks linking basal-ganglia to primary and secondary sensorimotor cortices as well as for connections of the cerebellum in all these different clinical presentations of focal dystonia. In parallel to these functional findings within basal-ganglia-cortical networks, DTI in patients with WC revealed white matter alterations in connections linking lateral premotor cortices to the basal ganglia, in patients with DYT27 dystonia white matter alterations in cerebello-thalamic and thalamo-cortical connections. Grey matter changes were demonstrated in patients with ED in thalamic and primary sensorimotor/premotor areas in WC within the cerebellum. Further DTI analyses in patients with blepharospasm and ED are still pending. Systematic differences of functional/structural connectivity between action induced (WC, ED) or non-action-induced (Blepharospasm, DYT27) dystonias or between different topographic manifestations (orofacial vs. hand) could not been detected so far. Our findings of changes in FC at rest underlines the importance of cerebello-thalamo-cortical sensorimotor networks in dystonia and may constitute a pathophysiological basis for the emergence of dystonic symptoms, e.g. when interacting with a specific task like writing or playing a musical instrument. In parallel, results of altered white matter architecture and grey matter changes especially in cerebello-thalamic networks and connections between thalamus/basal-ganglia and (pre-)motor cortices may represent a structural pathophysiological basis for these findings of altered FC. Together, these data further contribute to the current theory of focal dystonias as a functional “network” disorder and strengthen the important and longtime underestimated contribution of cerebellar networks.

Publications

• (2016). "Altered functional connectivity in patients with blepharospasm/Meige´s syndrome." Movement Disorders: Late breaking abstract, MDS Conference, Berlin
  Jochim, A., Y. Li, G. Gora-Stahlberg, M. Berndt, C. Zimmer, F. Castrop, C. Dresel and B. Haslinger
  
• (2016). "Sensorimotor gray matter changes in professional brass players with and without Embouchure dystonia [abstract]." Movement Disorders 31(Suppl.2): S553
  Mantel, T., C. Dresel, E. Altenmuller, A. Jochim, G. Gora-Stahlberg, C. Zimmer and B. Haslinger
  
• (2016). "Verringerte strukturelle Konnektivität kortiko-subkortikaler Regionen bei Schreibkramp." Clinical Neuroradiology 26 (Suppl.1): S40
  Berndt, M., Y. Li, G. Gora-Stahlberg, C. Zimmer and B. Haslinger
  
• (2017). "Altered functional connectivity in blepharospasm/orofacial dystonia." Brain and Behaviour
  Jochim, A., Y. Li, G. Gora-Stahlberg, T. Mantel, M. Berndt, F. Castrop, C. Dresel and B. Haslinger
  
• (2017). "Changes in resting-state connectivity in musicians with embouchure dystonia." Mov Disord 32(3): 450-458
  Haslinger, B., J. Noe, E. Altenmuller, V. Riedl, C. Zimmer, T. Mantel and C. Dresel
  
• (2018). "Microstructural white matter abnormalities in patients with COL6A3 mutations (DYT27 dystonia)." Parkinsonism Relat Disord. 46:74-78
  Jochim, A., Y. Li, M. Zech, D. Lam, N. Gross, K. Koch, C. Zimmer, J. Winkelmann and B. Haslinger
  
• (2018). "Network-specific resting-state connectivity changes in the premotor-parietal axis in writer's cramp." Neuroimage Clin 17: 137-144
  Mantel, T., T. Meindl, Y. Li, A. Jochim, G. Gora-Stahlberg, J. Kraenbring, M. Berndt, C. Dresel and B. Haslinger