The Role of the Trigeminal Sensory Nuclear Complex in the Pathophysiology of Craniocervical Dystonia

Abstract

Isolated focal dystonia is a neurological disorder that manifests as repetitive involuntary spasms and/or aberrant postures of the affected body part. Craniocervical dystonia involves muscles of the eye, jaw, larynx, or neck. The pathophysiology is unclear, and effective therapies are limited. One mechanism for increased muscle activity in craniocervical dystonia is loss of inhibition involving the trigeminal sensory nuclear complex (TSNC). The TSNC is tightly integrated into functionally connected regions subserving sensorimotor control of the neck and face. It mediates both excitatory and inhibitory reflexes of the jaw, face, and neck. These reflexes are often aberrant in craniocervical dystonia, leading to our hypothesis that the TSNC may play a central role in these particular focal dystonias. In this review, we present a hypothetical extended brain network model that includes the TSNC in describing the pathophysiology of craniocervical dystonia. Our model suggests the TSNC may become hyperexcitable due to loss of tonic inhibition by functionally connected motor nuclei such as the motor cortex, basal ganglia, and cerebellum. Disordered sensory input from trigeminal nerve afferents, such as aberrant feedback from dystonic muscles, may continue to potentiate brainstem circuits subserving craniocervical muscle control. We suggest that potentiation of the TSNC may also contribute to disordered sensorimotor control of face and neck muscles via ascending and cortical descending projections. Better understanding of the role of the TSNC within the extended neural network contributing to the pathophysiology of craniocervical dystonia may facilitate the development of new therapies such as noninvasive brain stimulation.

Anodal Direct Current Stimulation of the Cerebellum Reduces Cerebellar Brain Inhibition but Does Not Influence Afferent Input from the Hand or Face in Healthy Adults

“…Pathophysiological modification of these reflexes has been reported in cervical dystonia [22,60] and other neurological disorders [24,32]. We hypothesised that excitability of these reflexes might be mediated by the cerebellum, as there are direct projections between cerebellum and the trigeminal nuclear complex [4,61]. Our aim was to examine whether cerebellar stimulation would alter TR activity in healthy individuals, to determine if there might be benefits for translation into a neurological population.…”

“…Dysfunction of the cerebellum may, therefore, contribute to motor deficits in movement disorders by defective modulation of its projection targets [2][3][4]. Non-invasive stimulation of the cerebellum can modify the connectivity between the cerebellum and primary motor cortex (M1), by putative polarisation of Purkinje cells in the cerebellar cortex [5,6].…”

“…TRs are evoked by stimulation of trigeminal sensory branches of the face, and responses are recorded in facial and neck muscles using electromyography [30][31][32]. There has been no report of cerebellar modification of TR reflexes although an anatomical pathway exists [4]. Understanding the influence of the cerebellum on SAI and TRs may support non-invasive stimulation of the cerebellum in movement disorders with dysfunction of somatosensory processing, such as dystonia [33,34].…”

Non-invasive cerebellar stimulation in dystonia

“…Pairing [22]. Activity in cerebellar-brainstem circuits cannot be measured directly using TMS in humans and may explain why there was no association between the effect of cerebellar NBS on CBI and handwriting and circle-drawing tasks in our pilot study.…”

“…Effects of non-invasive brain stimulation (NBS) to suppress M1 activity, either directly [13][14][15] or via premotor-M1 connections [16,17] have had mixed results to date. However, evidence of a wide network of brain dysfunction in the pathophysiology of dystonia that include the cerebellum [18][19][20][21][22], opens up the prospect of applying NBS to these novel targets. Furthermore, emerging evidence that the cerebellum is highly involved in moderating certain aspects of cognition [23,24] suggest that stimulating both motor …”