Continuous high-frequency deep brain stimulation (DBS) is a widely used therapy for advanced Parkinson's disease (PD) management. However, the mechanisms underlying DBS effects remain enigmatic and are the subject of an ongoing debate. Here, we present and test a closed-loop stimulation strategy for PD in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of PD. Application of pallidal closed-loop stimulation leads to dissociation between changes in basal ganglia (BG) discharge rates and patterns, providing insights into PD pathophysiology. Furthermore, cortico-pallidal closed-loop stimulation has a significantly greater effect on akinesia and on cortical and pallidal discharge patterns than standard open-loop DBS and matched control stimulation paradigms. Thus, closed-loop DBS paradigms, by modulating pathological oscillatory activity rather than the discharge rate of the BG-cortical networks, may afford more effective management of advanced PD. Such strategies have the potential to be effective in additional brain disorders in which a pathological neuronal discharge pattern can be recognized.

Midbrain dopaminergic neurons (DANs) typically increase their discharge rate in response to appetitive predictive cues and outcomes, whereas striatal cholinergic tonically active interneurons (TANs) decrease their rate. This may indicate that the activity of TANs and DANs is negatively correlated and that TANs can broaden the basal ganglia reinforcement teaching signal, for instance by encoding worse than predicted events. We studied the activity of 106 DANs and 180 TANs of two monkeys recorded during the performance of a classical conditioning task with cues predicting the probability of food, neutral, and air puff outcomes. DANs responded to all cues with elevations of discharge rate, whereas TANs depressed their discharge rate. Nevertheless, although dopaminergic responses to appetitive cues were larger than their responses to neutral or aversive cues, the TAN responses were more similar. Both TANs and DANs responded faster to an air puff than to a food outcome; however, DANs responded with a discharge elevation, whereas the TAN responses included major negative and positive deflections. Finally, food versus air puff omission was better encoded by TANs. In terms of the activity of single neurons with distinct responses to the different behavioral events, both DANs and TANs were more strongly modulated by reward than by aversive related events and better reflected the probability of reward than aversive outcome. Thus, TANs and DANs encode the task episodes differentially. The DANs encode mainly the cue and outcome delivery, whereas the TANs mainly encode outcome delivery and omission at termination of the behavioral trial episode.

Octopus arms, as well as other muscular hydrostats, are characterized by a very large number of degrees of freedom and a rich motion repertoire. Over the years, several attempts have been made to elucidate the interplay between the biomechanics of these organs and their control systems. Recent developments in electrophysiological recordings from both the arms and brains of behaving octopuses mark significant progress in this direction. The next stage is relating these recordings to the octopus arm movements, which requires an accurate and reliable method of movement description and analysis. Here we describe a semiautomatic computerized system for 3D reconstruction of an octopus arm during motion. It consists of two digital video cameras and a PC computer running custom-made software. The system overcomes the difficulty of extracting the motion of smooth, nonrigid objects in poor viewing conditions. Some of the trouble is explained by the problem of light refraction in recording underwater motion. Here we use both experiments and simulations to analyze the refraction problem and show that accurate reconstruction is possible. We have used this system successfully to reconstruct different types of octopus arm movements, such as reaching and bend initiation movements. Our system is noninvasive and does not require attaching any artificial markers to the octopus arm. It may therefore be of more general use in reconstructing other nonrigid, elongated objects in motion.

-methyl-d-aspartate (NMDA) antagonists are widely used in anesthesia, pain management, and schizophrenia animal model studies, and recently as potential antidepressants. However, the mechanisms underlying their anesthetic, psychotic, cognitive, and emotional effects are still elusive. The basal ganglia (BG) integrate input from different cortical domains through their dopamine-modulated connections to achieve optimal behavior control. NMDA antagonists have been shown to induce gamma oscillations in human EEG recordings and in rodent cortical and BG networks. However, network relations and implications to the primate brain are still unclear. We recorded local field potentials (LFPs) simultaneously from the primary motor cortex (M1) and the external globus pallidus (GPe) of four vervet monkeys (26 sessions, 97 and 76 cortical and pallidal LFPs, respectively) before and after administration of ketamine (NMDA antagonist, 10 mg/kg im). Ketamine induced robust, spontaneous gamma (30-50 Hz) oscillations in M1 and GPe. These oscillations were initially modulated by ultraslow oscillations (~0.3 Hz) and were highly synchronized within and between M1 and the GPe (mean coherence magnitude = 0.76, 0.88, and 0.41 for M1-M1, GPe-GPe, and M1-GPe pairs). Phase differences were distributed evenly around zero with broad and very narrow distribution for the M1-M1 and GPe-GPe pairs (-3.5 ± 31.8° and -0.4 ± 6.0°), respectively. The distribution of M1-GPe phase shift was skewed to the left with a mean of -18.4 ± 20.9°. The increased gamma coherence between M1 and GPe, two central stages in the cortico-BG loops, suggests a global abnormal network phenomenon with a unique spectral signature, which is enabled by the BG funneling architecture. This study is the first to show spontaneous gamma oscillations under NMDA antagonist in nonhuman primates. These oscillations appear in synchrony in the cortex and the basal ganglia. Phase analysis refutes the confounding effects of volume conduction and supports the funneling and amplifying architecture of the cortico-basal ganglia loops. These results suggest an abnormal network phenomenon with a unique spectral signature that could account for pathological mental and neurological states.