Delta/theta-rhythmically interleaved gamma and beta oscillations in striatum: modeling and data analysis

Striatal oscillatory activity associated with movement, reward, and decision-making is observed in several interacting frequency bands. Rodent striatal local field potential recordings show dopamine- and reward-dependent transitions between a 'spontaneous' state involving beta (15-30 Hz) and low gamma (40-60 Hz) and a 'dopaminergic' state involving theta (4-8 Hz) and high gamma (60-100 Hz) activity. The mechanisms underlying these rhythmic dynamics and their functional consequences are not well understood. In this thesis, I construct a biophysical model of striatal microcircuits that comprehensively describes the generation and interaction of these rhythms as well as their modulation by dopamine and rhythmic inputs, and test its predictions using human electroencephalography (EEG) data. Chapter 1 describes the striatal model and its dopaminergic modulation. Building on previous work suggesting striatal projection neuron (SPN) networks can generate beta oscillations, I construct a model network of striatal fast-spiking interneurons (FSIs) capable of generating delta/theta (2-6 Hz) and gamma rhythms. This FSI network produces low gamma oscillations under low (simulated) dopaminergic tone, and high gamma activity nested within a delta/theta oscillation under high dopaminergic tone. In a combined model under high dopaminergic tone SPN network beta oscillations are interrupted by delta/theta-periodic bursts of gamma-frequency FSI inhibition. This high dopamine-induced periodic inhibition may enable switching between beta-rhythmic SPN cell assemblies representing motor programs, suggesting that dopamine facilitates movement in part by allowing for rapid, periodic changes in motor program execution. Chapter 2 describes the model's response to square-wave periodic cortical inputs. Comparing models with and without FSIs reveals that the FSI network: (i) prevents the SPN network's generation of phase-locked beta oscillations in response to beta's harmonic frequencies, ensuring fidelity of transmission of cortical beta rhythms; and (ii) limits or entrains SPN activity in response to certain gamma frequency inputs. Chapter 3 describes an analysis of phase-amplitude coupling at cortical electrodes in human EEG data during a reward task. The alternating rhythms predicted by the model appear in response to positive feedback. While the origins of these rhythms remain unclear, if they represent striatal signals, they provide a direct link between human behavior and striatal cellular function

Noninvasive neurostimulation of left ventral motor cortex enhances sensorimotor adaptation in speech production

Sensorimotor adaptation¬—enduring changes to motor commands due to sensory feedback—allows speakers to match their articulations to intended speech acoustics. How the brain integrates auditory feedback to modify speech motor commands and what limits the degree of these modifications remain unknown. Here, we investigated the role of speech motor cortex in modifying stored speech motor plans. In a within-subjects design, participants underwent separate sessions of sham and anodal transcranial direct current stimulation (tDCS) over speech motor cortex while speaking and receiving altered auditory feedback of the first formant. Anodal tDCS increased the rate of sensorimotor adaptation for feedback perturbation. Computational modeling of our results using the Directions Into Velocities of Articulators (DIVA) framework of speech production suggested that tDCS primarily affected behavior by increasing the feedforward learning rate. This study demonstrates how focal noninvasive neurostimulation can enhance the integration of auditory feedback into speech motor plans.This research was supported by NIDCD of the NIH under award numbers R03DC014045 to TP, and R01DC002852 to FG. TLS was supported by T90DA032484. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Healt

A biophysical model of striatal microcircuits suggests delta/theta - rhythmically interleaved gamma and beta oscillations mediate periodicity in motor control

First author draf