a b s t r a c tBackground: Electrical neuromodulation via implanted electrodes is used in treating numerous neurological disorders, yet our knowledge of how different brain regions respond to varying stimulation parameters is sparse. Objective/Hypothesis: We hypothesized that the neural response to electrical stimulation is both regionspecific and non-linearly related to amplitude and frequency. Methods: We examined evoked neural responses following 400 ms trains of 10e400 Hz electrical stimulation ranging from 0.1 to 10 mA. We stimulated electrodes implanted in cingulate cortex (dorsal anterior cingulate and rostral anterior cingulate) and subcortical regions (nucleus accumbens, amygdala) of nonhuman primates (NHP, N ¼ 4) and patients with intractable epilepsy (N ¼ 15) being monitored via intracranial electrodes. Recordings were performed in prefrontal, subcortical, and temporal lobe locations. Results: In subcortical regions as well as dorsal and rostral anterior cingulate cortex, response waveforms depended non-linearly on frequency (Pearson's linear correlation r < 0.39), but linearly on current (r > 0.58). These relationships between location, and input-output characteristics were similar in homologous brain regions with average Pearson's linear correlation values r > 0.75 between species and linear correlation values between participants r > 0.75 across frequency and current values per brain region. Evoked waveforms could be described by three main principal components (PCs) which allowed us to successfully predict response waveforms across individuals and across frequencies using PC strengths as functions of current and frequency using brain region specific regression models. Conclusions: These results provide a framework for creation of an atlas of input-output relationships which could be used in the principled selection of stimulation parameters per brain region.
Decision making in both animals and humans is influenced by the anticipation of reward and/or punishment. Little is known about how reward and punishment interact in the context of decision making. The Avoidance-Reward Conflict (ARC) Task is a new paradigm that varies the degree of reward and the probability of punishment in a single paradigm that can be used in both non-human primates (NHPs) and humans. This study examined the behavioral pattern in the ARC task in both NHPs and humans. Two adult male NHPs (macaca mulatta) and 20 healthy human volunteers (12 females) participated in the ARC task. NHPs and humans perform similarly on the ARC task. With a high probability of punishment (an aversive air puff to the eye), both NHPs and humans are more likely to forgo reward if it is small or medium magnitude than when it is large. Both NHPs and humans perform similarly on the same behavioral task suggesting the reliability of animal models in predicting human behavior.
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