Cortico-basal Ganglia-thalamo-cortical Loops Research Articles

Modeling Synaptic Integration of Bursty and β Oscillatory Inputs in Ventromedial Motor Thalamic Neurons in Normal and Parkinsonian States.

The ventromedial motor thalamus (VM) is implicated in multiple motor functions and occupies a central position in the cortico-basal ganglia-thalamocortical loop. It integrates glutamatergic inputs from motor cortex (MC) and motor-related subcortical areas, and it is a major recipient of inhibition from basal ganglia. Previous in vitro experiments performed in mice showed that dopamine depletion enhances the excitability of thalamocortical (TC) neurons in VM due to reduced M-type potassium currents. To understand how these excitability changes impact synaptic integration in vivo, we constructed biophysically detailed mouse VM TC model neurons fit to normal and dopamine-depleted conditions, using the NEURON simulator. These models allowed us to assess the influence of excitability changes with dopamine depletion on the integration of synaptic inputs expected in vivo We found that VM neuron models in the dopamine-depleted state showed increased firing rates with the same synaptic inputs. Synchronous bursting in inhibitory input from the substantia nigra pars reticulata (SNR), as observed in parkinsonian conditions, evoked a postinhibitory firing rate increase with a longer duration in dopamine-depleted than control conditions, due to different M-type potassium channel densities. With β oscillations in the inhibitory inputs from SNR and the excitatory inputs from cortex, we observed spike-phase locking in the activity of the models in normal and dopamine-depleted states, which relayed and amplified the oscillations of the inputs, suggesting that the increased β oscillations observed in VM of parkinsonian animals are predominantly a consequence of changes in the presynaptic activity rather than changes in intrinsic properties.

Parkinsonism Is Associated with Altered SMA-Basal Ganglia Structural and Functional Connectivity in Frontotemporal Degeneration

Patients with frontotemporal degeneration (FTD) often manifest parkinsonism, which likely results from cortical and subcortical degeneration of brain structures involved in motor control. We used a multimodal magnetic resonance imaging (MRI) approach to investigate possible structural and/or functional alterations in FTD patients with and without parkinsonism (Park+ and Park-). Thirty FTD patients (12 Park+, 18 Park-) and 30 healthy controls were enrolled and underwent 3T MRI scanning. MRI analyses included: (1) surface-based morphometry; (2) basal ganglia and thalamic volumetry; (3) diffusion-based probabilistic tractography of fiber tracts connecting the supplementary motor area (SMA) and primary motor cortex (M1) to the putamen, globus pallidus, and thalamus; and (4) resting-state functional connectivity (RSFC) between the aforementioned regions. Patients in Park+ and Park- groups showed comparable patterns of cortical thinning in frontotemporal regions and reduced thalamic volume with respect to controls. Only Park+ patients showed reduced putaminal volume and reduced fractional anisotropy of the fibers connecting the SMA to the globus pallidus, putamen, and thalamus, with respect to controls. Park+ patients also showed decreased RSFC between the SMA and putamen with respect to both Park- patients and controls. The present findings support the hypothesis that FTD patients with parkinsonism are characterized by neurodegenerative processes in specific corticobasal ganglia-thalamocortical motor loops.

Intracranial direct electrical mapping reveals the functional architecture of the human basal ganglia

The basal ganglia play a key role in integrating a variety of human behaviors through the cortico–basal ganglia–thalamo–cortical loops. Accordingly, basal ganglia disturbances are implicated in a broad range of debilitating neuropsychiatric disorders. Despite accumulating knowledge of the basal ganglia functional organization, the neural substrates and circuitry subserving functions have not been directly mapped in humans. By direct electrical stimulation of distinct basal ganglia regions in 35 refractory epilepsy patients undergoing stereoelectroencephalography recordings, we here offer currently the most complete overview of basal ganglia functional characterization, extending not only to the expected sensorimotor responses, but also to vestibular sensations, autonomic responses, cognitive and multimodal effects. Specifically, some locations identified responses weren’t predicted by the model derived from large-scale meta-analyses. Our work may mark an important step toward understanding the functional architecture of the human basal ganglia and provide mechanistic explanations of non-motor symptoms in brain circuit disorders.

White matter tract strength correlates with therapy outcome in persistent developmental stuttering.

Persistent stuttering is a prevalent neurodevelopmental speech disorder, which presents with involuntary speech blocks, sound and syllable repetitions, and sound prolongations. Affected individuals often struggle with negative feelings, elevated anxiety, and low self‐esteem. Neuroimaging studies frequently link persistent stuttering with cortical alterations and dysfunctional cortico‐basal ganglia‐thalamocortical loops; dMRI data also point toward connectivity changes of the superior longitudinal fasciculus (SLF) and the frontal aslant tract (FAT). Both tracts are involved in speech and language functions, and the FAT also supports inhibitory control and conflict monitoring. Whether the two tracts are involved in therapy‐associated improvements and how they relate to therapeutic outcomes is currently unknown. Here, we analyzed dMRI data of 22 patients who participated in a fluency‐shaping program, 18 patients not participating in therapy, and 27 fluent control participants, measured 1 year apart. We used diffusion tractography to segment the SLF and FAT bilaterally and to quantify their microstructural properties before and after a fluency‐shaping program. Participants learned to speak with soft articulation, pitch, and voicing during a 2‐week on‐site boot camp and computer‐assisted biofeedback‐based daily training for 1 year. Therapy had no impact on the microstructural properties of the two tracts. Yet, after therapy, stuttering severity correlated positively with left SLF fractional anisotropy, whereas relief from the social–emotional burden to stutter correlated negatively with right FAT fractional anisotropy. Thus, posttreatment, speech motor performance relates to the left dorsal stream, while the experience of the adverse impact of stuttering relates to the structure recently associated with conflict monitoring and action inhibition.

Drug-induced stuttering: A comprehensive literature review.

Drug-induced stuttering (DIS) is a type of neurogenic stuttering (NS). Although DIS has not been reported as frequently as other cases of NS in the literature, it is not a negligible adverse drug reaction (ADR) which can significantly affect the quality of life if not treated. This literature review aims to evaluate the epidemiological and clinical characteristics of DIS and suggests some pathophysiological mechanisms for this ADR. Relevant English-language reports in Google Scholar, PubMed, Web of Science, and Scopus were identified and assessed without time restriction. Finally, a total of 62 reports were included. Twenty-seven drugs caused 86 episodes of stuttering in 82 cases. The most episodes of DIS were related to antipsychotic drugs (57%), mostly including clozapine, followed by central nervous system agents (11.6%) and anticonvulsant drugs (9.3%). The majority of the cases were male and between the ages of 31 and 40 years. Repetitions were the most frequent core manifestations of DIS. In 55.8% of the episodes of DIS, the offending drug was withdrawn to manage stuttering, which resulted in significant improvement or complete relief of stuttering in all cases. Based on the suggested pathophysiological mechanisms for developmental stuttering and neurotransmitters dysfunctions involved in speech dysfluency, it seems that the abnormalities of several neurotransmitters, especially dopamine and glutamate, in different circuits and areas of the brain, including cortico-basal ganglia-thalamocortical loop and white matter fiber tracts, may be engaged in the pathogenesis of DIS.

The mouse cortico\u2013basal ganglia\u2013thalamic network

The cortico–basal ganglia–thalamo–cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1–4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico–basal ganglia–thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico–basal ganglia–thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.

A neurocomputational view of developmental stuttering

An estimated 5% of children go through a period of stuttering around 3–5 years of age, with stuttering persisting into adulthood in approximately 20% of these children. Research into the neural underpinnings of stuttering have identified a number of structural and functional anomalies in various components of the left hemisphere cortico-basal ganglia-thalamocortical motor loop in children and adults who stutter. This talk will present the theoretical view that this loop is heavily involved in the initiation of speech motor programs (rather than encoding sensory-motor transformations that make up the motor programs themselves) and that stuttering is primarily a disorder of speech initiation rather than one of impaired motor programs for speech. Relevant neural and behavioral findings will be reviewed in light of this hypothesis, including findings that seemingly implicate audio-motor transformation difficulties in stuttering. In the current view, these latter findings are interpreted as evidence of difficulty in using auditory information to determine the appropriate time to initiate the next motor program in a speech sequence.

Cortico-Striatal Oscillations Are Correlated to Motor Activity Levels in Both Physiological and Parkinsonian Conditions.

Oscillatory neural activity in the cortico-basal ganglia-thalamocortical (CBGTC) loop is associated with the motor state of a subject, but also with the availability of modulatory neurotransmitters. For example, increased low-frequency oscillations in Parkinson’s disease (PD) are related to decreased levels of dopamine and have been proposed as biomarkers to adapt and optimize therapeutic interventions, such as deep brain stimulation. Using neural oscillations as biomarkers require differentiating between changes in oscillatory patterns associated with parkinsonism vs. those related to a subject’s motor state. To address this point, we studied the correlation between neural oscillatory activity in the motor cortex and striatum and varying degrees of motor activity under normal and parkinsonian conditions. Using rats with bilateral or unilateral 6-hydroxydopamine lesions as PD models, we correlated the motion index (MI)—a measure based on the physical acceleration of the head of rats—to the local field potential (LFP) oscillatory power in the 1–80 Hz range. In motor cortices and striata, we observed a robust correlation between the motion index and the oscillatory power in two main broad frequency ranges: a low-frequency range [5.0–26.5 Hz] was negatively correlated to motor activity, whereas a high-frequency range [35.0–79.9 Hz] was positively correlated. We observed these correlations in both normal and parkinsonian conditions. In addition to these general changes in broad-band power, we observed a more restricted narrow-band oscillation [25–40 Hz] in dopamine-denervated hemispheres. This oscillation, which seems to be selective to the parkinsonian state, showed a linear frequency dependence on the concurrent motor activity level. We conclude that, independently of the parkinsonian condition, changes in broad-band oscillatory activities of cortico-basal ganglia networks (including changes in the relative power of low- and high-frequency bands) are closely correlated to ongoing motions, most likely reflecting he operations of these neural circuits to control motor activity. Hence, biomarkers based on neural oscillations should focus on specific features, such as narrow frequency bands, to allow differentiation between parkinsonian states and physiological movement-dependent circuit modulation.

Mediodorsal Thalamus Contributes to the Timing of Instrumental Actions.

The perception of time is critical to adaptive behavior. While prefrontal cortex and basal ganglia have been implicated in interval timing in the seconds to minutes range, little is known about the role of the mediodorsal thalamus (MD), which is a key component of the limbic cortico-basal ganglia-thalamocortical loop. In this study, we tested the role of the MD in timing, using an operant temporal production task in male mice. In this task, that the expected timing of available rewards is indicated by lever pressing. Inactivation of the MD with muscimol produced rightward shifts in peak pressing on probe trials as well as increases in peak spread, thus significantly altering both temporal accuracy and precision. Optogenetic inhibition of glutamatergic projection neurons in the MD also resulted in similar changes in timing. The observed effects were found to be independent of significant changes in movement. Our findings suggest that the MD is a critical component of the neural circuit for interval timing, without playing a direct role in regulating ongoing performance.SIGNIFICANCE STATEMENT The mediodorsal nucleus (MD) of the thalamus is strongly connected with the prefrontal cortex and basal ganglia, areas which have been implicated in interval timing. Previous work has shown that the MD contributes to working memory and learning of action-outcome contingencies, but its role in behavioral timing is poorly understood. Using an operant temporal production task, we showed that inactivation of the MD significantly impaired timing behavior.

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.

Attentional Reinforcement Learning in the Brain

Recently, attention mechanisms have significantly boosted the performance of natural language processing using deep learning. An attention mechanism can select the information to be used, such as by conducting a dictionary lookup; this information is then used, for example, to select the next utterance word in a sentence. In neuroscience, the basis of the function of sequentially selecting words is considered to be the cortico-basal ganglia-thalamocortical loop. Here, we first show that the attention mechanism used in deep learning corresponds to the mechanism in which the cerebral basal ganglia suppress thalamic relay cells in the brain. Next, we demonstrate that, in neuroscience, the output of the basal ganglia is associated with the action output in the actor of reinforcement learning. Based on these, we show that the aforementioned loop can be generalized as reinforcement learning that controls the transmission of the prediction signal so as to maximize the prediction reward. We call this attentional reinforcement learning (ARL). In ARL, the actor selects the information transmission route according to the attention, and the prediction signal changes according to the context detected by the information source of the route. Hence, ARL enables flexible action selection that depends on the situation, unlike traditional reinforcement learning, wherein the actor must directly select an action.

The role of coupling connections in a model of the cortico-basal ganglia-thalamocortical neural loop for the generation of beta oscillations

Excessive neural synchronization in the cortico-basal ganglia-thalamocortical circuits in the beta (β) frequency range (12–35 Hz) is closely associated with dopamine depletion in Parkinson’s disease (PD) and correlated with movement impairments, but the neural basis remains unclear. In this work, we establish a double-oscillator neural mass model for the cortico-basal ganglia-thalamocortical closed-loop system and explore the impacts of dopamine depletion induced changes in coupling connections within or between the two oscillators on neural activities within the loop. Spectral analysis of the neural mass activities revealed that the power and frequency of their principal components are greatly dependent on the coupling strengths between nuclei. We found that the increased intra-coupling in the basal ganglia-thalamic (BG-Th) oscillator contributes to increased oscillations in the lower β frequency band (12–25 Hz), while increased intra-coupling in the cortical oscillator mainly contributes to increased oscillations in the upper β frequency band (26–35 Hz). Interestingly, pathological upper β oscillations in the cortical oscillator may be another origin of the lower β oscillations in the BG-Th oscillator, in addition to increased intra-coupling strength within the BG-Th network. Lower β oscillations in the BG-Th oscillator can also change the dominant oscillation frequency of a cortical nucleus from the upper to the lower β band. Thus, this work may pave the way towards revealing a possible neural basis underlying the Parkinsonian state.

An open cortico-basal ganglia loop allows limbic control over motor output via the nigrothalamic pathway.

Cortico-basal ganglia-thalamocortical loops are largely conceived as parallel circuits that process limbic, associative, and sensorimotor information separately. Whether and how these functionally distinct loops interact remains unclear. Combining genetic and viral approaches, we systemically mapped the limbic and motor cortico-basal ganglia-thalamocortical loops in rodents. Despite largely closed loops within each functional domain, we discovered a unidirectional influence of the limbic over the motor loop via ventral striatum-substantia nigra (SNr)-motor thalamus circuitry. Slice electrophysiology verifies that the projection from ventral striatum functionally inhibits nigro-thalamic SNr neurons. In vivo optogenetic stimulation of ventral or dorsolateral striatum to SNr pathway modulates activity in medial prefrontal cortex (mPFC) and motor cortex (M1), respectively. However, whereas the dorsolateral striatum-SNr pathway exerts little impact on mPFC, activation of the ventral striatum-SNr pathway effectively alters M1 activity. These results demonstrate an open cortico-basal ganglia loop whereby limbic information could modulate motor output through ventral striatum control of M1.

Real-Time Neuromorphic System for Large-Scale Conductance-Based Spiking Neural Networks.

The investigation of the human intelligence, cognitive systems and functional complexity of human brain is significantly facilitated by high-performance computational platforms. In this paper, we present a real-time digital neuromorphic system for the simulation of large-scale conductance-based spiking neural networks (LaCSNN), which has the advantages of both high biological realism and large network scale. Using this system, a detailed large-scale cortico-basal ganglia-thalamocortical loop is simulated using a scalable 3-D network-on-chip (NoC) topology with six Altera Stratix III field-programmable gate arrays simulate 1 million neurons. Novel router architecture is presented to deal with the communication of multiple data flows in the multinuclei neural network, which has not been solved in previous NoC studies. At the single neuron level, cost-efficient conductance-based neuron models are proposed, resulting in the average utilization of 95% less memory resources and 100% less DSP resources for multiplier-less realization, which is the foundation of the large-scale realization. An analysis of the modified models is conducted, including investigation of bifurcation behaviors and ionic dynamics, demonstrating the required range of dynamics with a more reduced resource cost. The proposed LaCSNN system is shown to outperform the alternative state-of-the-art approaches previously used to implement the large-scale spiking neural network, and enables a broad range of potential applications due to its real-time computational power.

The influence of acetylcholine, dopamine, and GABA on the functioning of the corticostriatal neuronal network in Alzheimer’s and Parkinson’s diseases: A hypothetical mechanism

A proposed model of the functioning of the basal ganglia complements the existing opinions about the complex interaction between cholinergic and dopaminergic systems. A hypothesis is proposed that one of the means of interaction between these systems is the operation of a negative feedback loop. In this loop, a conditioned stimulus evokes the excitation of dopaminergic neurons and GABAergic cells with long axons in the dopaminergic nuclei, which leads to an increase in the influence on dopamine D2 receptors on striatal cholinergic interneurons; an increase in their inhibition can lead to a pause in their responses. In turn, during this pause reduced action on presynaptic nicotinic receptors at axon terminals of dopaminergic neurons results in a decrease in dopamine release. In addition, dopaminergic neurons are under the inhibitory action of GABAergic striatonigral cells in the striosomes of the dorsal striatum and clusters in the ventral striatum. During the pause, stimulation of M2/M4 receptors located on these striatonigral cells weakens, which should promote potentiation of their excitation, subsequent enhancement of the inhibition of dopaminergic cells, and a decrease in the dopamine concentration in the striatum. In addition, a decrease in the stimulation of M1 receptors on striatopallidal cells and M2 receptors on striatonigral cells of the matrix during the pause should promote synergistic disinhibition through the direct and indirect pathways via the basal ganglia of certain groups of thalamic neurons and enhancement of the excitation of neocortical neurons connected with them. This interaction between cholinergic and dopaminergic systems contributes to the normal functioning of the various parallel cortico–basal ganglia–thalamocortical loops, which play a determining role in movement choice, sensory perception, learning, and intentional behavior. The proposed model implies that cholinergic and dopaminergic denervation of different structures, as well as changes in the density and affinity of receptors that are sensitive to acetylcholine, dopamine, and NMDA, which are typical for Alzheimer’s and Parkinson’s diseases, should lead to abnormal functioning of these loops. This may underlie various cognitive and motor disorders.

Inhibitory Control in the Cortico-Basal Ganglia-Thalamocortical Loop: Complex Regulation and Interplay with Memory and Decision Processes

We developed a circuit model of spiking neurons thatincludes multiple pathways in the basal ganglia (BG) and is endowed with feedback mechanisms at three levels: cortical microcircuit, corticothalamic loop, and cortico-BG-thalamocortical system. We focused on executive control in a stop signal task, which is known to depend on BG across species. The model reproduces a range of experimental observations and shows that the newly discovered feedback projection from external globus pallidus to striatum is crucial for inhibitory control. Moreover, stopping process is enhanced by the cortico-subcortical reverberatory dynamics underlying persistent activity, establishing interdependence between working memory and inhibitory control. Surprisingly, the stop signal reaction time (SSRT) can be adjusted by weights of certain connections but is insensitive to other connections in this complex circuit, suggesting novel circuit-based intervention for inhibitory control deficits associated with mental illness. Our model provides a unified framework for inhibitory control, decision making, and working memory.

EP 30. Deep brain stimulation both at 130 Hz and 340 Hz suppresses cortical alpha and beta band activity

Introduction Deep brain stimulation (DBS) is an established therapy to treat motor symptoms in movement disorders such as Parkinson’s disease (PD). However, its mechanisms are still poorly understood. Oscillatory activity,on the other hand, plays a crucial role in the pathophysiology of PD. Investigating the effect of DBS on oscillatory activity can help to clarify the neurophysiological mechanisms of DBS. In this study, we aimed at investigating changes of cortical oscillatory activity using magnetoencephalography (MEG) while stimulating the subthalamic nucleus (STN) at two different stimulation frequencies: 130 Hz as the clinical standard stimulation frequency and 340 Hz as being in the range of high frequency oscillations, which have been reported to be associated with motor improvement ( Ozkurt et al., 2011 ). Methods Seventeen PD patients (13 male, mean age 63.4 ± 9.8 y) clinically selected for DBS participated. Recordings were done with a 306-channel, whole head MEG system (Elekta Oy, Helsinki, Finland) and took place the day after electrode implantation and before implanting the stimulator. STN was stimulated with an external stimulator (OSIRIS, inomed, Emmendingen, Germany) using externalized leads (Medtronic Bakken Research Center, Maastricht, the Netherlands) at the two different stimulation frequencies. All patients were off medication during the recording. Patients were seated comfortably in the MEG chair and asked to rest while keeping their eyes open. Recordings started with 180 s DBS OFF followed by 4 intervals of DBS ON (180 s), which were interleaved by further DBS OFF periods (60 s). When possible, the recording was realized both for stimulation frequencies of 130 Hz and 340 Hz (stimulation amplitude 3 mA; pulse width 60 μs, contralateral to the symptom dominant side, contacts 1 vs. 3). Data from eight patients were discarded due to severe movement artefacts. The DBS artefact was removed from MEG data using a methodology based on the combination of independent component analysis (ICA) and mutual information theory ( Abbasi et al., 2015 ). Results Both 130 Hz and 340 Hz DBS led to a widespread suppression of cortical alpha and beta band activity (8–22 Hz) focused over bilateral sensorimotor cortices ( p Discussion Our finding of a widespread suppression of alpha and beta band activity is particularly interesting as Parkinson’s disease is generally associated with abnormally increased beta band activity in the cortico-basal ganglia thalamocortical loop ( Oswal et al., 2013 ). Previously, it has been shown that DBS suppresses beta activity in the STN and results in a decrease of motor-cortical-STN coherence in the beta band ( Kuhn et al., 2008 ). The modulation of cortical oscillatory activity may be a crucial effect of DBS for relieving motor symptoms in PD and might be achieved at different stimulation frequencies.

Emotion recognition in early Parkinson's disease patients undergoing deep brain stimulation or dopaminergic therapy: a comparison to healthy participants.

Parkinson’s disease (PD) is traditionally regarded as a neurodegenerative movement disorder, however, nigrostriatal dopaminergic degeneration is also thought to disrupt non-motor loops connecting basal ganglia to areas in frontal cortex involved in cognition and emotion processing. PD patients are impaired on tests of emotion recognition, but it is difficult to disentangle this deficit from the more general cognitive dysfunction that frequently accompanies disease progression. Testing for emotion recognition deficits early in the disease course, prior to cognitive decline, better assesses the sensitivity of these non-motor corticobasal ganglia-thalamocortical loops involved in emotion processing to early degenerative change in basal ganglia circuits. In addition, contrasting this with a group of healthy aging individuals demonstrates changes in emotion processing specific to the degeneration of basal ganglia circuitry in PD. Early PD patients (EPD) were recruited from a randomized clinical trial testing the safety and tolerability of deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) in early-staged PD. EPD patients were previously randomized to receive optimal drug therapy only (ODT), or drug therapy plus STN-DBS (ODT + DBS). Matched healthy elderly controls (HEC) and young controls (HYC) also participated in this study. Participants completed two control tasks and three emotion recognition tests that varied in stimulus domain. EPD patients were impaired on all emotion recognition tasks compared to HEC. Neither therapy type (ODT or ODT + DBS) nor therapy state (ON/OFF) altered emotion recognition performance in this study. Finally, HEC were impaired on vocal emotion recognition relative to HYC, suggesting a decline related to healthy aging. This study supports the existence of impaired emotion recognition early in the PD course, implicating an early disruption of fronto-striatal loops mediating emotional function.

Variable universe fuzzy closed-loop control of tremor predominant Parkinsonian state based on parameter estimation

A variable universe fuzzy closed-loop control method based on parameter estimation is proposed for controlling tremor predominant Parkinsonian state. First, the computational model of thalamocortical relay neuron is established to characterize the cortico-basal ganglia-thalamocortical loop behavior in relation to Parkinsonian state. Then, in order to estimate critical parameter which exhibits the different levels of the tremor state, unscented Kalman filter is presented. Finally, an efficient control strategy on Parkinsonian state is designed by using variable universe fuzzy control theory. In the whole strategy, the slow variable that is easily reconstructed from the measured membrane potential is regarded as feedback variable, being vital to excellent control performance and low energy of the control signals. By comparing with simple proportional–integral control algorithm and ordinary fuzzy control method, it can be demonstrated that variable universe fuzzy control can avoid the repeated determinations of the controller׳s parameters, quicken the convergence speed, and improve the robustness of the controlled system, which may become a universal and valid method to alleviate any levels of the tremor state, and its control signals may apply to the current deep brain stimulation.

Model-based iterative learning control of Parkinsonian state in thalamic relay neuron

Although the beneficial effects of chronic deep brain stimulation on Parkinson’s disease motor symptoms are now largely confirmed, the underlying mechanisms behind deep brain stimulation remain unclear and under debate. Hence, the selection of stimulation parameters is full of challenges. Additionally, due to the complexity of neural system, together with omnipresent noises, the accurate model of thalamic relay neuron is unknown. Thus, the iterative learning control of the thalamic relay neuron’s Parkinsonian state based on various variables is presented. Combining the iterative learning control with typical proportional–integral control algorithm, a novel and efficient control strategy is proposed, which does not require any particular knowledge on the detailed physiological characteristics of cortico-basal ganglia-thalamocortical loop and can automatically adjust the stimulation parameters. Simulation results demonstrate the feasibility of the proposed control strategy to restore the fidelity of thalamic relay in the Parkinsonian condition. Furthermore, through changing the important parameter—the maximum ionic conductance densities of low-threshold calcium current, the dominant characteristic of the proposed method which is independent of the accurate model can be further verified.