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.

The motor systems that generate feeding-related behaviors of gastropod mollusks provide exceptional opportunities for increasing our understanding of neural homologies and the evolution of neural networks. This report examines the neural control of feeding in Helisoma trivolvis, a pulmonate snail that ingests food by rasping or scraping material from the substrate, and Aplysia californica, an opisthobranch sea slug that feeds by using a grasping or seizing motion. Two classes of neurons that are present in the buccal ganglia of both species are considered: (1) clusters of peptidergic mechanoafferent cells that transmit sensory information from the tongue-like radula/odontophore complex to the central motor circuit; and (2) sets of octopamine-immunoreactive interneurons that are intrinsic to the feeding network. We review evidence that suggests homology of these cell types and propose that their roles have been largely conserved in the control of food-scraping and food-grasping consummatory behaviors. We also consider significant differences in the feeding systems of Aplysia and Helisoma that are associated with the existence of radular closure in Aplysia, an action that does not occur in Helisoma. It is hypothesized that a major adaptation in the innervation patterns of analogous, possibly homologous muscles could distinguish the food-scraping versus food-grasping species. It appears that although core CPG elements have been largely conserved in this system, the neuromuscular elements that they regulate have been more evolutionarily labile.

Single-neuronal studies remain the gold standard for studying brain function. Here we describe a protocol for studying task-related single-neuronal activity in human subjects during neurosurgical procedures involving microelectrode recordings. This protocol has two phases: a preoperative phase and an intraoperative phase. During the preoperative phase, we discuss informed consent, equipment setup and behavioral testing. During the intraoperative phase, we discuss the procedure for microelectrode recordings. Because patients are often awake during these procedures, this protocol can be performed in conjunction with behavioral tasks for studying a variety of cognitive functions. We describe the protocol in detail and provide two examples of expected results. In addition, we discuss the potential difficulties and pitfalls related to intraoperative studies. This protocol takes ∼1.5 h to complete.

Multifunctional central pattern generators (CPGs) are circuits of neurons that can generate manifold actions from a single effector system. This study examined a bilateral pair of pharyngeal motor neurons, designated B67, that participate in the multifunctional feeding network of Aplysia californica. Fictive buccal motor programs (BMPs) were elicited with four distinct stimulus paradigms to assess the activity of B67 during ingestive versus egestive patterns. In both classes of programs, B67 fired during the phase of radula protraction and received a potent inhibitory postsynaptic potential (IPSP) during fictive radula retraction. When programs were ingestive, the retraction phase IPSP exhibited a depolarizing sag and was followed by a postinhibitory rebound (PIR) that could generate a postretraction phase of impulse activity. When programs were egestive, the depolarizing sag potential and PIR were both diminished or were not present. Examination of the membrane properties of B67 disclosed a cesium-sensitive depolarizing sag, a corresponding Ih-like current, and PIR in its responses to hyperpolarizing pulses. Direct IPSPs originating from the influential CPG retraction phase interneuron B64 were also found to activate the sag potential and PIR of B67. Dopamine, a modulator that can promote ingestive behavior in this system, enhanced the sag potential, Ih-like current, and PIR of B67. Finally, a pharyngeal muscle contraction followed the radula retraction phase of ingestive, but not egestive motor patterns. It is proposed that regulation of the intrinsic properties of this motor neuron can contribute to generating a program-specific phase of motor activity.