Objective/Rationale:
Direct electrical stimulation of certain areas of the brain is an effective method to treat the motor symptoms of Parkinson’s, but it requires the insertion of electrodes into the brain. We propose an indirect way to deliver stimulation to the brain via its natural input/output structure: the spinal cord. Recent evidence obtained in a pre-clinical model shows that spinal cord stimulation can improve impaired motor function, suggesting this method could eventually become a therapy for PD.
Project Description:
Before testing this method in humans, it is necessary to identify the parameters that yield the most therapeutical benefits. It is also important to know to what extent these benefits exceed the associated side effects and risks of the method. To that end, a pre-clinical model will be induced to a neurological condition similar to that of a Parkinson’s patient, and will be treated with different parameters and devices of spinal cord stimulation. Improvement in motor function will be assessed by evaluating ability to move, climb and grasp objects. The neural activity and neurotransmitter levels of specific brain areas will be recorded and later analyzed to gain further insight on the possible neural mechanisms involved in the therapeutical effect.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
While the efficacy of the pharmacological treatment decreases in the long term, the current criteria used for selecting candidates for deep brain stimulation are very restrictive. These two facts leave a number of patients with a very limited number of therapeutical options. Thus, spinal cord stimulation could provide an additional therapeutical option for patients that for different reasons can not use the classical options. This is important considering that Parkinson’s is a chronic and progressive disease with a variety of motor symptoms that have a differential response to treatments.
Anticipated Outcome:
With this work we expect to confirm that spinal cord stimulation, previously observed to alleviate parkinsonian motor symptoms in a pre-clinical model, is also effective in a more refined pre-clinical model. Such confirmation will allow advancing to the next step that is the clinical validation of the method. Also, with this work we expect to identify what stimulation parameters, such as frequency and electrode configuration, produce the most therapeutical benefits.
Final Outcome
We have used a pre-clinical model of Parkinson's disease to explore spinal cord stimulation as a therapy, and the possible neural mechanisms by which it operates. We observed a striking oscillatory synchrony at 11-14 Hz in the activity of the main neural circuits involved in motor control. This abnormal synchrony is correlated with the symptoms of bradykinesia and rigidity. Electrical stimulation of the spinal cord was effective in alleviating these symptoms, allowing the subjects to engage in normal behavior. Together with the motor improvements, spinal cord stimulation decreased the abnormal synchronous activity of the brain, suggesting, that this could be a mechanism underlying the therapeutic effect. This study will allow, in the close future, to test the efficacy of spinal cord stimulation in Parkinson's patients and has, in addition, provided valuable new insights into certain aspects of the pathophysiology of the disease.
Presentations & Publications
Abstracts
1 - SANTANA, M. B. ; SIMPLICIO, H. ; MORYA, E. ; BRYS, I. ; PEREIRA, A. ; PETERSSON, P. ; FUENTES, R. ; NICOLELIS, M. A. L. . Desenvolvimento de um modelo da Doença Parkinson com injeção estriatal bilateral de 6-Hidroxidopamina em sagui comum (Callithrix jacchus). In: XXVII Reunião Anual da Federação de Sociedades de Biologia Experimental (FeSBE), 2012, Águas de Lindóia. XXVII Reunião Anual da Federação de Sociedades de Biologia Experimental (FeSBE), 2012.
2. FUENTES, R. ; PETERSSON, P. ; SANTANA, M. B. ; SIMPLICIO, H. ; PALMER, T. ; NICOLELIS, M. A. L. . Spinal cord stimulation restores motor function in a primate model of Parkinson s disease. In: The Society for Neuroscience Annual Meeting, 2012, New Orleans. The Society for Neuroscience Annual Meeting, 2012.
3. SANTANA, M. B. ; PALMER, T. ; SIMPLICIO, H. ; PEREIRA, A. ; PETERSSON, P. ; FUENTES, R. ; NICOLELIS, M. A. L. . Quantitative evaluation of motor impairment in the common marmoset after the two-stage injection of 6-hidroxydopamine. In: The Society for Neuroscience Annual Meeting, 2012, New Orleans. The Society for Neuroscience Annual Meeting, 2012.
4. SANTANA, M. B. ; MORYA, E. ; SAVOLDI, R. ; BRYS, I. ; KUNICKI, C. A. ; FUENTES, R. ; NICOLELIS, M. A. L. . Introduction to manual video behavior analysis as a neuroscience trigger to young students. In: The Society for Neuroscience Annual Meeting, 2012, New Orleans. The Society for Neuroscience Annual Meeting,
2012.
5. PALMER, T. ; SANTANA, M. B. ; FUENTES, R. ; PETERSSON, P. . Automated Tracking of Motor Behavior as a Means to Assess Severity of Symptoms in the 6-OHDA Marmoset Model of Parkinson's Disease. In: 21st International Conference on Pattern Recognition, 2012, Tsukuba. 21st International Conference on Pattern Recognition, 2012
Papers
1. Santana M., Halje, P, Simplício H., Richter, U., Petersson, P., Fuentes, R. and Nicolelis MAL. Spinal cord stimulation alleviates symptoms in a primate model of Parkinson’s disease through multi-circuit desynchronization (In Preparation 2013).
2. Santana M, Palmer T, Simplicio H, Nicolelis MAL, Petersson P, Fuentes R. Characterization of long-term motor deficits in the 6-OHDA model of Parkinson’s disease in the common Marmoset (In preparation 2013)