Thesis defense Jorik Nonnekes (Donders Series 188)

2 September 2015

Promotors: Prof.dr. S. Geurts, Prof.dr. B. Bloem, copomotor: Dr. V. Weerdesteyn

Balance and gait in neurodegenerative disease: what startle tells us about motor control

Motor control is the set of processes by which movements in human beings are produced and regulated. Most people are able to make movements without any problems. In contrast, motor control is hampered in patients with a wide variety of neurological diseases. Gait and balance impairments are among the most frequent and debilitating symptoms in these patients. The mechanisms underlying deficits in motor control, and in particular the mechanisms underlying gait and balance impairments, are not well understood. Moreover, symptomatic treatment is limited. To develop improved treatment strategies, more insight is needed into the underlying mechanisms. To this aim, in this thesis, motor control was studied in three different groups: healthy subjects, people with hereditary spastic paraplegia (HSP), and people with Parkinson’s disease (PD). Studies in healthy subjects were essential to investigate unaffected motor control. Studies in HSP and PD were performed to study motor control in two different neurodegenerative disorders that both develop slowly, but that affect different neural structures. In HSP, the corticospinal (pyramidal) tract is affected bilaterally. HSP is therefore termed a ‘pyramidal disease’. In contrast, PD is a typical example of an ‘extrapyramidal disease’, which means that brain structures outside the pyramidal tract are affected.

In particular, the thesis focuses on the role of brainstem reticular formation in impaired motor control. An important method that was used to study the brainstem reticular formation was the startle reflex and the StartReact paradigm, in which reaction times can be accelerated by a startling acoustic stimulus.

The results of the performed studies suggest that dysfunction of the reticular formation likely contributes to gait deficits in extrapyramidal neurodegenerative diseases, but plays a compensatory role in gait and balance impairments in patients with pyramidal diseases. Future studies could evaluate whether this compensatory role can be enhanced, for example by tDCS-induced subcortical facilitation.