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Neuronal correlates of locomotion: understanding the effects of post-stroke neuroplasticity

One of the most important goals for stroke survivors, who have motor impairments, is to walk independently again. Unfortunately, the risk of falling after stroke is higher than for people among the general population. In the general population the risk of hip fracture due to falls is 8 times higher during turning while walking than walking straight (Cumming and Klineberg 1994). Thus, it is not surprising that subjects who had a stroke mostly fall during walking and turning or during transfers. Currently, little is known on how steering of locomotion is organized at the brain level, mostly because of lack of measures to quantify these changes DURING walking. Hence, even less is known on how brain activations for the steering of locomotion are modulated following an injury such as a stroke.

In the HBCL lab, a unique imaging approach to quantify brain activation changes while subjects are walking: 18F-fluorodesoxy-glucose Positron Emission Tomography (18F-FDG PET) imaging. 18F-FDG is a glucose analog taken up by neurons in the same way as normal glucose. The 18F-FDG tracer is injected immediately prior to a gait task and is metabolically trapped by neuronal cells while subjects are actually walking. 18F-FDG concentration in the brain can be imaged with PET before the tracer decays. Therefore, it is only brain regions activated by the motor tasks performed during the 20 minute uptake period that is imaged in the PET scanner. We specifically use this technique to identify brain networks activated during steering of locomotion in subjects with stroke. Finally, non-invasive brain stimulation techniques will be used to stimulate cortical areas measured with 18F-FDG PET.

Objectives

  1. Determine the effects of stroke on the activation of neuronal networks involved in steering of locomotion.
  2. Study the behavioral impact of the non-invasive modulation (inhibition or excitation) of key cortical areas on steering of locomotion in stroke.

Funding  

  


Neuronal correlates of locomotion in normal healthy humans

The long-term objective of this research is to identify brain structures directly involved in the control of posture, locomotion and steering of human locomotion. Quantification of neuronal networks during human locomotion is possible through metabolic trapping with 18F-fluorodesoxy-glucose (18F-FDG PET, as detailed in the previous research project). This technique allows us to compare whole brain activations between real tasks (posture, gait and steering of gait), currently not possible with any other imaging modality. A non-invasive brain stimulation technique is also used to modulate activity in key cortical areas. Finally, we also compare activated areas in natural and laboratory conditions to better understand the universality of these brain activations during posture and locomotion. With this research our goal is to contribute to the fundamental knowledge of how the central nervous system controls human posture and locomotion by revealing the neuronal networks involved in these tasks. Furthermore, by manipulating the various cortical areas involved in steering of locomotion we will significantly improve our knowledge of brain function for the control of whole-body movement. The knowledge acquired from this research program may eventually contribute to the training of posture and locomotor abilities to optimize the performance of athletes and also contribute to the development of preventive programs to compensate for declines in posture and mobility.

Funding 


Improving post-stroke recovery by combining non-invasive brain stimulation with rehabilitation

The human brain has a considerable capacity to adapt its functional networks to acute brain lesions (stroke, trauma): a process summarized as functional neuroplasticity. Although a major driving force for the recovery of function after stroke, neuroplasticity is not always most beneficial for patients. It has been shown that for a satisfactory recovery of motor as well as language functions after stroke, the re-activation of functional networks in the affected hemisphere is more efficient than the recruitment of homologous regions in the intact hemisphere. This favorable re-activation of functional networks in the affected hemisphere is often compromised by a lack of inhibitory activity from the damaged hemisphere onto the intact hemisphere. This transcallosal disinhibition phenomenon causes an increased excitability of the intact hemisphere and thus favors the recruitment of less effective functional networks contralateral to the stroke.

Most recently, non-invasive brain stimulation techniques employing repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) have widely been used to investigate brain plasticity. As new evidence emerges from clinical pilot studies, brain stimulation techniques show great potential to become effective therapeutic tools to re-establish balance in motor cortex excitability between both hemispheres. Yet, it is unknown whether these changes in motor cortex excitability actually translate into long-lasting improvement of motor function or which stimulation techniques are best suited for potential clinical application.

With this project, our aim is to modulate transcallosal inhibition in acute stroke patients using several non-invasive brain stimulation techniques in order to facilitate the recovery of motor networks in the affected hemisphere. Brain stimulation is be given during daily sessions of upper-limb rehabilitation therapy. Three types of non-invasive brain stimulation protocols are compared in a blinded, randomized placebo-controlled design with respect to their potential for suppressing brain activity in the unaffected part of the brain and for facilitating recruitment of motor areas in the affected area, in the early phase of rehabilitation. Clinical scales, fMRI and motor evoked potentials are used to quantify motor improvement, suppression of contra-lateral and facilitation of ipsi-lateral brain activity in the motor system. Assessments take place before and after the 10-day therapy regiment and at 3 and 6 months. The outcome of this study will directly impact the design of future larger scale multi-centre trials on non-invasive brain stimulation and influence our current approach to post-stroke rehabilitation.

Funding  

  


NORTHSTAR: NOninvasive Repeated THerapeutic STimulation for Aphasia Recovery

Aphasia is the inability to communicate by means of written or spoken language. It is a debilitating consequence of stroke that has a major impact on the quality of life of stroke survivors and their caregivers. To date, early focused and intensive speech and language therapy (SLT) seems to be the only effective treatment option for these patients. Emerging evidence from recent studies investigating the effectiveness of such treatments indicates that especially the intensity of treatment within the first weeks after stroke is an important predictor of stroke outcome, independent of initial stroke severity. With NORTHSTAR, we use of two different non-invasive brain stimulation methods: repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) to down regulate the unaffected brain hemisphere in patients suffering from post-stroke aphasia, in order to focus the effect of conventional SLT onto reactivation of language networks in the damaged hemisphere. We hypothesize that patients receiving non-invasive brain stimulation immediately preceding or during conventional SLT sessions will show better aphasia recovery than patients receiving sham stimulation. The NORHTSTAR is as a multicenter study to determine whether rTMS and tDCS are equally effective adjuvant therapies and to identify subgroups of aphasia patients which may respond better to this kind of therapy than others.

Funding  


Future Studies

Several studies are currently being developed:

  • Neuroplastic mechanisms in subjects with Parkinson’s disease to better understand turning difficulties in these subjects.
  • Exercise prescription: type, intensity and frequency to alleviate PD symptoms.
  • Differences in brain structure & function in superior aging: Masters Athletes.
  • Interaction between posture and visuomotor control with aging.