Abnormal Connectivity of the Head Neural Integrator in Cervical Dystonia

Abstract

Background: Cervical dystonia is characterized by abnormal neck and head movements, possibly related to a dysfunction of the interstitial nucleus of Cajal (INC) and the head neural integrator, a system responsible for the control of head and eye movements. However, neuroanatomical evidence of alterations in the head neural integrator in cervical dystonia is sparse.

Objectives: We investigated structural and functional integrity of the INC and its connections in cervical dystonia.

Methods: This cross-sectional, observational study compared 19 cervical dystonia patients and 21 healthy controls, using anatomical, diffusion-weighted, and resting-state functional images. We reconstructed tracts converging on the INC, and involved in the control of head movements. We evaluated group differences in microstructural integrity using fixel-based analysis, and effective connectivity using dynamic causal modeling.

Results: Compared with controls, patients showed microstructural abnormalities within the INC and cerebral peduncle. Effective connectivity showed abnormal self-inhibition in the INC, substantia nigra, and vermis in patients, with decreased excitation from the substantia nigra to the INC, increased inhibition from the deep cerebellar nuclei and primary sensorimotor cortex, and decreased excitation from the INC to the cerebellar vermis.

Conclusions: A dysfunction of the INC might contribute to altered sensorimotor integration in cervical dystonia, and abnormal feedback from its afferent connections could alter its integrative function, resulting in a disturbed head and neck posture. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: brainstem; dynamic casual models; fixel‐based analysis; interstitial nucleus of Cajal.

FIG. 1

Localization of the interstitial nucleus of Cajal (INC). (A) Sagittal view. (B) Axial view at Obex+45. (C) Three‐dimensional (3D) visualization of the INC within the medial longitudinal fasciculus (MLF). The MLF is depicted in dark blue, the medial lemniscus in yellow, and the corticospinal tract in light blue. White crosshairs indicate the INC, and the red box indicates the axial view in 3D. PAG, periaqueductal grey; DK, nucleus of Darkschewitsch; RPC, red parvocellular nucleus; MB, mamillary body. [Color figure can be viewed at wileyonlinelibrary.com]

FIG. 2

Tractography of the interstitial nucleus of Cajal (INC) and definition of the tracts of interest (TOIs). (A) Efferent tract from the bilateral INC to the cerebellar vermis and flocculus. (B) Afferent tracts from the cerebellar dentate and fastigial nuclei to the contralateral INC. (C) Afferent tracts from the frontal eye field (FEF), supplementary motor area (SMA), and neck representation area of the somatosensory cortex to the ipsilateral INC. (D) Afferent tracts from the bilateral substantia nigra to the ipsilateral INC. Crosshairs indicate the INC. Tracts through the right INC are depicted in blue, tracts through the left INC are depicted in red, and climbing fibers from the bilateral olive to the cerebellar flocculus, para‐flocculus, and vermis are depicted in yellow. [Color figure can be viewed at wileyonlinelibrary.com]

FIG. 3

Results of fixel‐based analysis. Reduced FDC (a measure combining fiber density and fiber bundle cross‐section) in patients in the cerebral peduncle, bilaterally. Crosshairs indicate the peak of the significant differences. Clusters represent the P‐values corrected for multiple comparisons with family‐wise error (FWE). [Color figure can be viewed at wileyonlinelibrary.com]

FIG. 4

Results of dynamic casual modeling (DCM) analysis. (A–B). Models with afferent connections to the interstitial nucleus of Cajal (INC). (C–D) Model with efferent connections from the INC. (A) and (C) display the main effect of the connection, from the model averaging over the whole study population. (B) and (D) display the group difference with P > 0.95. Red arrows display positive coupling parameters termed excitatory connections. Blue arrows display negative coupling parameters termed inhibitory connections. The arrow thickness coded for the strength of coupling parameters. For details on the coupling strength see Supplementary Table S2. FEF, frontal eye field; SMA, supplementary motor area; SM1, primary sensorimotor cortex; SN, substantia nigra. [Color figure can be viewed at wileyonlinelibrary.com]