Involvement of the cortico-basal ganglia-thalamocortical loop in developmental stuttering

Stuttering is a complex neurodevelopmental disorder that has to date eluded a clear explication of its pathophysiological bases. In this review, we utilize the Directions Into Velocities of Articulators (DIVA) neurocomputational modeling framework to mechanistically interpret relevant findings from the behavioral and neurological literatures on stuttering. Within this theoretical framework, we propose that the primary impairment underlying stuttering behavior is malfunction in the cortico-basal ganglia-thalamocortical (hereafter, cortico-BG) loop that is responsible for initiating speech motor programs. This theoretical perspective predicts three possible loci of impaired neural processing within the cortico-BG loop that could lead to stuttering behaviors: impairment within the basal ganglia proper; impairment of axonal projections between cerebral cortex, basal ganglia, and thalamus; and impairment in cortical processing. These theoretical perspectives are presented in detail, followed by a review of empirical data that make reference to these three possibilities. We also highlight any differences that are present in the literature based on examining adults versus children, which give important insights into potential core deficits associated with stuttering versus compensatory changes that occur in the brain as a result of having stuttered for many years in the case of adults who stutter. We conclude with outstanding questions in the field and promising areas for future studies that have the potential to further advance mechanistic understanding of neural deficits underlying persistent developmental stuttering.R01 DC007683 - NIDCD NIH HHS; R01 DC011277 - NIDCD NIH HHSPublished versio

Basal ganglia role in learning rewarded actions and executing previously learned choices: Healthy and diseased states

The basal ganglia (BG) is a collection of nuclei located deep beneath the cerebral cortex that is involved in learning and selection of rewarded actions. Here, we analyzed BG mechanisms that enable these functions. We implemented a rate model of a BG-thalamo-cortical loop and simulated its performance in a standard action selection task. We have shown that potentiation of corticostriatal synapses enables learning of a rewarded option. However, these synapses became redundant later as direct connections between prefrontal and premotor cortices (PFC-PMC) were potentiated by Hebbian learning. After we switched the reward to the previously unrewarded option (reversal), the BG was again responsible for switching to the new option. Due to the potentiated direct cortical connections, the system was biased to the previously rewarded choice, and establishing the new choice required a greater number of trials. Guided by physiological research, we then modified our model to reproduce pathological states of mild Parkinson's and Huntington's diseases. We found that in the Parkinsonian state PMC activity levels become extremely variable, which is caused by oscillations arising in the BG-thalamo-cortical loop. The model reproduced severe impairment of learning and predicted that this is caused by these oscillations as well as a reduced reward prediction signal. In the Huntington state, the potentiation of the PFC-PMC connections produced better learning, but altered BG output disrupted expression of the rewarded choices. This resulted in random switching between rewarded and unrewarded choices resembling an exploratory phase that never ended. Along with other computational studies, our results further reconcile the apparent contradiction between the critical involvement of the BG in execution of previously learned actions and yet no impairment of these actions after BG output is ablated by lesions or deep brain stimulation. We predict that the cortico-BG-thalamo-cortical loop conforms to previously learned choice in healthy conditions, but impedes those choices in disease states

The hierarchical organisation of cortical and basal-ganglia systems: a computationally-informed review and integrated hypothesis

To suitably adapt to the challenges posed by reproduction and survival, animals need to learn to select when to perform different behaviours, to have internal criteria for guiding these learning processes, and to perform behaviours efficiently once selected. To implement these processes, their brain must be organised in a suitable hierarchical fashion. Here we briefly review two types of neural/behavioural/computational literatures, focussed respectively on cortex and on sub-cortical areas, and highlight their important limitations. Then we review two computational modelling works of the authors that exemplify the problems, brain areas, experiments, main concepts and limitations of the two research threads. Finally we propose a theoretical integration of the two views, showing how this allows to solve most of the problems found by the two accounts if taken in isolation. The overall picture that emerges is that the cortical and the basal ganglia systems form two highly-organised hierarchical systems working in close synergy and jointly solving all the challenges of choice, selection, and implementation needed to acquire and express adaptive behaviour

Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Cortico-basal ganglia-thalamic (CBT) neural circuits are critical modulators of cognitive and motor function. When compromised, these circuits contribute to neurological and psychiatric disorders, such as Parkinson's disease (PD). In PD, motor deficits correlate with the emergence of exaggerated beta frequency (15-30 Hz) oscillations throughout the CBT network. However, little is known about how specific cell types within individual CBT brain regions support the generation, propagation, and interaction of oscillatory dynamics throughout the CBT circuit or how specific oscillatory dynamics are related to motor function. Here, we investigated the role of striatal cholinergic interneurons (SChIs) in generating beta and gamma oscillations in cortical-striatal circuits and in influencing movement behavior. We found that selective stimulation of SChIs via optogenetics in normal mice robustly and reversibly amplified beta and gamma oscillations that are supported by distinct mechanisms within striatal-cortical circuits. Whereas beta oscillations are supported robustly in the striatum and all layers of primary motor cortex (M1) through a muscarinic-receptor mediated mechanism, gamma oscillations are largely restricted to the striatum and the deeper layers of M1. Finally, SChI activation led to parkinsonian-like motor deficits in otherwise normal mice. These results highlight the important role of striatal cholinergic interneurons in supporting oscillations in the CBT network that are closely related to movement and parkinsonian motor symptoms.DP2 NS082126 - NINDS NIH HHS; R01 NS081716 - NINDS NIH HHS; R21 NS078660 - NINDS NIH HHShttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896681/Published versio

A Sing-Song Way of Vocalizing: Generalization and Specificity in Language and Birdsong.

Spoken languages such as German are extremely discrete, whereas others such as Portuguese are melodic or "sing-song" wherein identifying a word relies on what comes before and after. Perhaps surprisingly, birdsong also exhibits specificity and generalization as articulated by Tian and Brainard (2017)