Poster Session 1 - B3
1,3Tameem M. Alozzi, 5Luis F. Botero Posada, 5Adriana L. Lopez Rios, 1,2,3,4,5William D. Hutchison
1 Dept. of Physiology, University of Toronto; 2 Dept. of Surgery, University of Toronto; 3 Toronto Western Research Institute; 4 Division of Neurosurgery, Toronto Western Hospital, Toronto, ON, Canada; 5 Hospital Universitario De San Vicente FundaciÓn, MedellÍn, Antioquia, Colombia
The subthalamic nucleus (STN) of the basal ganglia (BG) has been broadly accepted as a subcortical structure that facilitates movement, as evident from its anatomical position in the motor cortico-striatal circuit. Recent anatomic studies however have shown that the STN has connections with other cortical and subcortical regions besides motor cortical areas such as the dorsolateral prefrontal cortex and the anterior cingulate cortex. These connections give rise to associative and limbic circuits, implicating the STN to be involved in higher order cognitive functions such as response selection/inhibition - decision making. These cognitive processes are impaired in Parkinson’s disease (PD). A physiological hallmark of PD is elevated beta oscillations (15 - 30 Hz) throughout the BG circuitry, particularly in the STN. According to an oscillatory model in PD, beta oscillations between the BG and cortex are antikinetic and disruptive to normal motor programming. The role of beta oscillations in cognitive-related motor processes is poorly understood. Previously, go/no-go and stop-signal reaction time tasks have been carried out to study the role of the STN in response inhibition. To further dissect the functional role of beta oscillations in cognitive motor-control and the role of the STN in decision making, we implement a preference-based decision-making task.
STN neuron spiking activity and local field potential (LFP) beta oscillations were simultaneously recorded intraoperatively prior to bilateral implantation of deep brain stimulation (DBS) electrodes for the treatment of PD. Data was recorded from awake patients using two microelectrodes 2mm apart, from both hemispheres. Upon encountering a stable STN cell, the patient engaged in the task designed offline (paradigm). Pictures of 5 animals were presented, two at a time and the patient had to choose one by either right or left clicking mouse buttons. Patients went through 75 trials and each animal was presented 20% of the time in random order. Once a decision has been made and a click was registered, a blank screen was shown for 500ms before the presentation of the next sequence of pictures. After the experiment was done, the patients were asked to rank the animals on a scale of most favorite to least favorite. Results were analyzed offline using Spike2 (CED) for STN neuron spiking activity by constructing peristimulus time histograms aligned to presentation of pictures. LFP signals were band pass Butterworth filtered from 5 – 45 Hz to remove noise artifacts and a fast Fourier transform algorithm was implemented for spectral analysis. LFP was analyzed over the same time epochs for comparison of spike and LFP activities.
Based on our preliminary findings, STN neuron spiking activity followed one of three firing rate patterns during the experiment. When the favorite picture was presented, cell firing was strongly inhibited with shorter latency that correlated with shorter reaction times (58%, n=7/12). Other cells showed a short latency increase in firing rate every time the favorite picture was presented and chosen (n=2/12). Three cells showed no change in firing rate. In 3 cases, cell pairs were recorded 2mm apart and showed firing rate changes in opposite directions. When presented with conflicting animals, the change in spiking activity was less pronounced, irregular and had an overall longer onset latency that correlated with longer reaction times. Beta activity was seen for all patients (n=8) in the 15 Hz – 28 Hz range with a mean of 20.5 Hz across patients. There was a clear modulation of beta activity during the experiment in 2 distinct timeframes. First, we saw a difference in beta power during the whole experiment compared to pre/post, as evident by a decrease in power upon starting the experiment or an immediate beta rebound once the experiment was over. Second, we saw significant beta desynchronization upon presentation of a favorite picture as opposed to a stronger beta synchronization when conflicting animals were presented. Further statistical analysis is currently being conducted.
Results suggest an interaction of STN neuron spiking and beta frequency oscillations during decision making. The different types of STN neuron firing support the dynamic ‘centre-surround’ model proposed for the functioning of the basal ganglia. Our preliminary findings also showed an overall decrease in beta power as patients were engaged in the task. This may be explained by the patient’s mental engagement and preparedness to make a movement, thus a decrease in antikinetic beta oscillations. Also, changes in STN firing seem to be locked to the event-related desynchronizations (ERDs) in beta oscillations that occur immediately after the presentation of the favorite picture. This may be due to the modulatory effect of beta on STN cells. This further supports the notion that the lower beta power seen is a sign of preparing for a movement.