Neuromodulation of deep brain structures (deep brain stimulation) is the current surgical procedure for treatment of Parkinson's disease (PD). Less studied is the stimulation of cortical motor areas to treat PD symptoms, although also known to alleviate motor disturbances in PD. We were able to show that optogenetic activation of secondary (M2) motor cortex improves motor functions in dopamine-depleted male mice. The stimulated M2 cortex harbors glutamatergic pyramidal neurons that project to subcortical structures, critically involved in motor control, and makes synaptic contacts with dopaminergic neurons. Strikingly, optogenetic activation of M2 neurons or axons into the dorsomedial striatum increases striatal levels of dopamine and evokes locomotor activity. We found that dopamine neurotransmission sensitizes the locomotor behavior elicited by activation of M2 neurons. Furthermore, combination of intranigral infusion of glutamatergic antagonists and circuit specific optogenetic stimulation revealed that behavioral response depended on the activity of M2 neurons projecting to SNc. Interestingly, repeated M2 stimulation combined with L-DOPA treatment produced an unanticipated improvement in working memory performance, which was absent in control mice under L-DOPA treatment only. Therefore, the M2-basal ganglia circuit is critical for the assembly of the motor and cognitive function, and this study demonstrates a therapeutic mechanism for cortical stimulation in PD that involves recruitment of long-range glutamatergic projection neurons.

Gamma Knife® radiosurgery (GKRS) for trigeminal neuralgia is an effective treatment with at least a 50% reduction of pain in 75-95% of patients. Objective: To present the first series of patients treated for trigeminal neuralgia using GKRS in Latin America. Methods: Retrospective analysis. Analysis consisted of time to improvement of symptoms, best Barrow Neurological Institute scale (BNI) score after procedure, time without pain, time to recurrence and post-procedural hypoesthesia. Results: Nineteen cases of classical trigeminal neuralgia were analyzed and three cases of symptomatic trigeminal neuralgia were described. Mean time from symptom onset to radiosurgery was 99.6 months, and 78.9% of patients had undergone invasive procedures before treatment. Patients were followed for a mean of 21.7 months. BNI I was achieved in 36.8%, IIIa in 21.1%, IIIb in 21.1%, IV in 5.3% and V in 15.7%. New hypoesthesia developed in 12.1% patients, which was associated with achieving BNI I after the procedure (p < 0.05). Time from diagnosis to GKRS was higher in patients who failed to achieve BNI I (143 vs. 76 months). The distance from the root entry zone in patients who achieved BNI I was greater than patients who did not (1.94 vs. 1.14 mm). Mean distance from the root entry zone in patients with new hypoesthesia was 2.85 mm vs. 1.06 mm (p = 0.06). Conclusion: Clinical response to GKRS is related to the time between diagnosis and procedure, thus its indication should be considered early in the management of these patients.