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

Patients with basal ganglia damage show preserved learning in an economic game.

Both basal ganglia (BG) and orbitofrontal cortex (OFC) have been widely implicated in social and non-social decision-making. However, unlike OFC damage, BG pathology is not typically associated with disturbances in social functioning. Here we studied the behavior of patients with focal lesions to either BG or OFC in a multi-strategy competitive game known to engage these regions. We find that whereas OFC patients are significantly impaired, BG patients show intact learning in the economic game. By contrast, when information about the strategic context is absent, both cohorts are significantly impaired. Computational modeling further shows a preserved ability in BG patients to learn by anticipating and responding to the behavior of others using the strategic context. These results suggest that apparently divergent findings on BG contribution to social decision-making may instead reflect a model where higher-order learning processes are dissociable from trial-and-error learning, and can be preserved despite BG damage

Reading aloud boosts connectivity through the putamen

Functional neuroimaging and lesion studies have frequently reported thalamic and putamen activation during reading and speech production. However, it is currently unknown how activity in these structures interacts with that in other reading and speech production areas. This study investigates how reading aloud modulates the neuronal interactions between visual recognition and articulatory areas, when both the putamen and thalamus are explicitly included. Using dynamic causal modeling in skilled readers who were reading regularly spelled English words, we compared 27 possible pathways that might connect the ventral anterior occipito-temporal sulcus (aOT) to articulatory areas in the precentral cortex (PrC). We focused on whether the neuronal interactions within these pathways were increased by reading relative to picture naming and other visual and articulatory control conditions. The results provide strong evidence that reading boosts the aOT–PrC pathway via the putamen but not the thalamus. However, the putamen pathway was not exclusive because there was also evidence for another reading pathway that did not involve either the putamen or the thalamus. We conclude that the putamen plays a special role in reading but this is likely to vary with individual reading preferences and strategies

Action-based effects on music perception

The classical, disembodied approach to music cognition conceptualizes action and perception as separate, peripheral processes. In contrast, embodied accounts of music cognition emphasize the central role of the close coupling of action and perception. It is a commonly established fact that perception spurs action tendencies. We present a theoretical framework that captures the ways in which the human motor system and its actions can reciprocally influence the perception of music. The cornerstone of this framework is the common coding theory, postulating a representational overlap in the brain between the planning, the execution, and the perception of movement. The integration of action and perception in so-called internal models is explained as a result of associative learning processes. Characteristic of internal models is that they allow intended or perceived sensory states to be transferred into corresponding motor commands (inverse modeling), and vice versa, to predict the sensory outcomes of planned actions (forward modeling). Embodied accounts typically refer to inverse modeling to explain action effects on music perception (Leman, 2007). We extend this account by pinpointing forward modeling as an alternative mechanism by which action can modulate perception. We provide an extensive overview of recent empirical evidence in support of this idea. Additionally, we demonstrate that motor dysfunctions can cause perceptual disabilities, supporting the main idea of the paper that the human motor system plays a functional role in auditory perception. The finding that music perception is shaped by the human motor system and its actions suggests that the musical mind is highly embodied. However, we advocate for a more radical approach to embodied (music) cognition in the sense that it needs to be considered as a dynamical process, in which aspects of action, perception, introspection, and social interaction are of crucial importance

How may the basal ganglia contribute to auditory categorization and speech perception?

Listeners must accomplish two complementary perceptual feats in extracting a message from speech. They must discriminate linguistically-relevant acoustic variability and generalize across irrelevant variability. Said another way, they must categorize speech. Since the mapping of acoustic variability is language-specific, these categories must be learned from experience. Thus, understanding how, in general, the auditory system acquires and represents categories can inform us about the toolbox of mechanisms available to speech perception. This perspective invites consideration of findings from cognitive neuroscience literatures outside of the speech domain as a means of constraining models of speech perception. Although neurobiological models of speech perception have mainly focused on cerebral cortex, research outside the speech domain is consistent with the possibility of significant subcortical contributions in category learning. Here, we review the functional role of one such structure, the basal ganglia. We examine research from animal electrophysiology, human neuroimaging, and behavior to consider characteristics of basal ganglia processing that may be advantageous for speech category learning. We also present emerging evidence for a direct role for basal ganglia in learning auditory categories in a complex, naturalistic task intended to model the incidental manner in which speech categories are acquired. To conclude, we highlight new research questions that arise in incorporating the broader neuroscience research literature in modeling speech perception, and suggest how understanding contributions of the basal ganglia can inform attempts to optimize training protocols for learning non-native speech categories in adulthood

Regional differences in the coupling between resting cerebral blood flow and metabolism may indicate action preparedness as a default state.

Although most functional neuroimaging studies examine task effects, interest intensifies in the "default" resting brain. Resting conditions show consistent regional activity, yet oxygen extraction fraction constancy across regions. We compared resting cerebral metabolic rates of glucose (CMRgl) measured with 18F-labeled 2-fluoro-2-deoxy-D-glucose to cerebral blood flow (CBF) 15O-H2O measures, using the same positron emission tomography scanner in 2 samples (n = 60 and 30) of healthy right-handed adults. Region to whole-brain ratios were calculated for 35 standard regions of interest, and compared between CBF and CMRgl to determine perfusion relative to metabolism. Primary visual and auditory areas showed coupling between CBF and CMRgl, limbic and subcortical regions--basal ganglia, thalamus and posterior fossa structures--were hyperperfused, whereas association cortices were hypoperfused. Hyperperfusion was higher in left than right hemisphere for most cortical and subcallosal limbic regions, but symmetric in cingulate, basal ganglia and somatomotor regions. Hyperperfused regions are perhaps those where activation is anticipated at short notice, whereas downstream cortical modulatory regions have longer "lead times" for deployment. The novel observation of systematic uncoupling of CBF and CMRgl may help elucidate the potential biological significance of the "default" resting state. Whether greater left hemispheric hyperperfusion reflects lateral dominance needs further examination