Role of Individual Basal Ganglia Nuclei in Force Amplitude Generation

The basal ganglia-thalamo-cortical loop is an important neural circuit that regulates motor control. A key parameter that the nervous system regulates is the level of force to exert against an object during tasks such as grasping. Previous studies indicate that the basal ganglia do not exhibit increased activity with increasing amplitude of force, although these conclusions are based mainly on the putamen. The present study used functional magnetic resonance imaging to investigate which regions in the basal ganglia, thalamus, and motor cortex display increased activity when producing pinch-grip contractions of increasing force amplitude. We found that the internal portion of the globus pallidus (GPi) and subthalamic nucleus (STN) had a positive increase in percent signal change with increasing force, whereas the external portion of the globus pallidus, anterior putamen, posterior putamen, and caudate did not. In the thalamus we found that the ventral thalamic regions increase in percent signal change and activation volume with increasing force amplitude. The contralateral and ipsilateral primary motor/somatosensory (M1/S1) cortices had a positive increase in percent signal change and activation volume with increasing force amplitude, and the contralateral M1/S1 had a greater increase in percent signal change and activation volume than the ipsilateral side. We also found that deactivation did not change across force in the motor cortex and basal ganglia, but that the ipsilateral M1/S1 had greater deactivation than the contralateral M1/S1. Our findings provide direct evidence that GPi and STN regulate the amplitude of force output. These findings emphasize the heterogeneous role of individual nuclei of the basal ganglia in regulating specific parameters of motor output.

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Modeling Basal Ganglia for Understanding Parkinsonian Reaching Movements

Neural Computation ◽

10.1162/neco_a_00073 ◽

2011 ◽

Vol 23 (2) ◽

pp. 477-516 ◽

Cited By ~ 30

Author(s):

K. N. Magdoom ◽

D. Subramanian ◽

V. S. Chakravarthy ◽

B. Ravindran ◽

Shun-ichi Amari ◽

...

Keyword(s):

Basal Ganglia ◽

Motor Cortex ◽

Reaching Movements ◽

Substantia Nigra Pars Compacta ◽

Temporal Difference ◽

Indirect Pathway ◽

Dynamical Disease ◽

Exploratory Movements ◽

Dopamine Signal

We present a computational model that highlights the role of basal ganglia (BG) in generating simple reaching movements. The model is cast within the reinforcement learning (RL) framework with correspondence between RL components and neuroanatomy as follows: dopamine signal of substantia nigra pars compacta as the temporal difference error, striatum as the substrate for the critic, and the motor cortex as the actor. A key feature of this neurobiological interpretation is our hypothesis that the indirect pathway is the explorer. Chaotic activity, originating from the indirect pathway part of the model, drives the wandering, exploratory movements of the arm. Thus, the direct pathway subserves exploitation, while the indirect pathway subserves exploration. The motor cortex becomes more and more independent of the corrective influence of BG as training progresses. Reaching trajectories show diminishing variability with training. Reaching movements associated with Parkinson's disease (PD) are simulated by reducing dopamine and degrading the complexity of indirect pathway dynamics by switching it from chaotic to periodic behavior. Under the simulated PD conditions, the arm exhibits PD motor symptoms like tremor, bradykinesia and undershooting. The model echoes the notion that PD is a dynamical disease.

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Basal ganglia and cerebellar contributions to vocal emotion processing: a high resolution fMRI study

10.1101/2020.11.26.399790 ◽

2020 ◽

Author(s):

Leonardo Ceravolo ◽

Sascha Frühholz ◽

Jordan Pierce ◽

Didier Grandjean ◽

Julie Péron

Keyword(s):

Basal Ganglia ◽

High Resolution ◽

Globus Pallidus ◽

Subthalamic Nucleus ◽

Effective Connectivity ◽

Emotion Processing ◽

Brain Regions ◽

Fmri Study ◽

Vocal Emotion

AbstractUntil recently, brain networks underlying emotional voice prosody decoding and processing were focused on modulations in primary and secondary auditory, ventral frontal and prefrontal cortices, and the amygdala. Growing interest for a specific role of the basal ganglia and cerebellum was recently brought into the spotlight. In the present study, we aimed at characterizing the role of such subcortical brain regions in vocal emotion processing, at the level of both brain activation and functional and effective connectivity, using high resolution functional magnetic resonance imaging. Variance explained by low-level acoustic parameters (fundamental frequency, voice energy) was also modelled. Wholebrain data revealed expected contributions of the temporal and frontal cortices, basal ganglia and cerebellum to vocal emotion processing, while functional connectivity analyses highlighted correlations between basal ganglia and cerebellum, especially for angry voices. Seed-to-seed and seed-to-voxel effective connectivity revealed direct connections within the basal ganglia ̶ especially between the putamen and external globus pallidus ̶ and between the subthalamic nucleus and the cerebellum. Our results speak in favour of crucial contributions of the basal ganglia, especially the putamen, external globus pallidus and subthalamic nucleus, and several cerebellar lobules and nuclei for an efficient decoding of and response to vocal emotions.

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Understanding Parkinsonian Handwriting Through a Computational Model of Basal Ganglia

Neural Computation ◽

10.1162/neco.2008.03-07-498 ◽

2008 ◽

Vol 20 (10) ◽

pp. 2491-2525 ◽

Cited By ~ 19

Author(s):

Garipelli Gangadhar ◽

Denny Joseph ◽

V. Srinivasa Chakravarthy

Keyword(s):

Basal Ganglia ◽

Computational Model ◽

Globus Pallidus ◽

Subthalamic Nucleus ◽

Line Contour ◽

Velocity Fluctuations ◽

Signaling Model ◽

Tip Velocity ◽

Handwriting Generation

Handwriting in Parkinson's disease (PD) is typically characterized by micrographia, jagged line contour, and unusual fluctuations in pen tip velocity. Although PD handwriting features have been used for diagnostics, they are not based on a signaling model of basal ganglia (BG). In this letter, we present a computational model of handwriting generation that highlights the role of BG. When PD conditions like reduced dopamine and altered dynamics of the subthalamic nucleus and globus pallidus externa subsystems are simulated, the handwriting produced by the model manifested characteristic PD handwriting distortions like micrographia and velocity fluctuations. Our approach to PD modeling is in tune with the perspective that PD is a dynamic disease.

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Motor cortex can directly drive the globus pallidus neurons in a projection neuron type-dependent manner in the rat

eLife ◽

10.7554/elife.49511 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 7

Author(s):

Fuyuki Karube ◽

Susumu Takahashi ◽

Kenta Kobayashi ◽

Fumino Fujiyama

Keyword(s):

Basal Ganglia ◽

Motor Cortex ◽

Globus Pallidus ◽

Projection Neuron ◽

Excitatory Input ◽

Morphological Observation ◽

Dependent Manner ◽

Motor Behaviors ◽

Connection Probability ◽

Motor Loop

The basal ganglia are critical for the control of motor behaviors and for reinforcement learning. Here, we demonstrate in rats that primary and secondary motor areas (M1 and M2) make functional synaptic connections in the globus pallidus (GP), not usually thought of as an input site of the basal ganglia. Morphological observation revealed that the density of axonal boutons from motor cortices in the GP was 47% and 78% of that in the subthalamic nucleus (STN) from M1 and M2, respectively. Cortical excitation of GP neurons was comparable to that of STN neurons in slice preparations. FoxP2-expressing arkypallidal neurons were preferentially innervated by the motor cortex. The connection probability of cortico-pallidal innervation was higher for M2 than M1. These results suggest that cortico-pallidal innervation is an additional excitatory input to the basal ganglia, and that it can affect behaviors via the cortex-basal ganglia-thalamus motor loop.

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326 Characterization of Synchronization Between Globus Pallidus Neurons and Motor Cortex in Parkinson's Disease

Neurosurgery ◽

10.1093/neuros/nyx417.326 ◽

2017 ◽

Vol 64 (CN_suppl_1) ◽

pp. 271-272

Author(s):

Doris D Wang ◽

Nicki Swann ◽

Coralie de Hemptinne ◽

Philip A Starr

Keyword(s):

Basal Ganglia ◽

Motor Cortex ◽

Globus Pallidus ◽

Field Potentials ◽

Frequency Range ◽

Neuronal Synchronization ◽

Motor Loop ◽

Beta Oscillation ◽

Insight Into

Abstract INTRODUCTION Excessive oscillatory neuronal synchronization throughout the basal ganglia thalamocortical motor loop is a hallmark of the Parkinsonian state. This may manifest as spike-spike correlations, coherence between field potentials, or spike-field interactions within or between structures in the circuit. Globus pallidus occupies a central role in basal ganglia processing, but neither internal (GPi) nor external (GPe) globus pallidus is monosynaptically connected to motor cortex. Understanding patterns of M1-pallidal synchronization will provide insight into the possible different roles of GPi and GPe stimulation, compared to STN stimulation, in ameliorating the excessive neuronal synchronization in PD. METHODS Using subdural electrodes and high resolution electrocorticography (ECoG) contacts temporarily placed over motor cortex during DBS implantation and microelectrode recordings, we evaluate the strength and topography of synchronization between pallidal neurons and cortical ECoG potentials in 16 PD patients. RESULTS >Recording from 59 GPe and 42 GPi cells with cortical ECoG field potentials demonstrated that 17% of GPe and 12% of GPi neurons showed significant interactions associated with cortical recording sites approximately 25 mm from midline. For those pairs with significant interactions, peak of the spike-triggered average potentials occurred within 100ms prior to spike time. GPe neurons showed maximum coherence with M1 in the beta (13-30 Hz) frequency range while GPi neurons had maximum coherence in the alpha (8-12 Hz) range. CONCLUSION Topography of significant M1-pallidal interactions is consistent with tractography findings showing more mesial areas of M1 to dominate cortical-basal ganglia anatomic connectivity. The observation that GPe stimulation is more “prokinetic” than GPi stimulation may be explained by the finding that GPe is more synchronized to the cortex in beta frequencies than GPi, as disruption of beta oscillation is important in ameliorating akinesia.

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Cortico-subthalamic projections send brief stop signals to halt visually-guided locomotion

10.1101/2020.02.05.936443 ◽

2020 ◽

Cited By ~ 2

Author(s):

Elie M. Adam ◽

Taylor Johns ◽

Mriganka Sur

Keyword(s):

Basal Ganglia ◽

Motor Cortex ◽

Subthalamic Nucleus ◽

Behavioral Strategy ◽

Visually Guided ◽

Short Route ◽

Mesencephalic Locomotor Region ◽

Neuronal Control ◽

Control Signals

SummaryGoal-directed locomotion necessitates control signals that propagate from higher-order areas to regulate spinal mechanisms. The cortico-subthalamic hyperdirect pathway offers a short route for cortical information to reach locomotor centers in the brainstem. We developed a task where head-fixed mice run to a visual landmark, then stop and wait to collect reward, and examined the role of secondary motor cortex (M2) projections to the subthalamic nucleus (STN) in controlling locomotion. Our modeled behavioral strategy indicates a switching point in behavior, suggesting a critical neuronal control signal at stop locations. Optogenetic activation of M2 axons in STN leads the animal to stop prematurely. By imaging M2 neurons projecting to STN, we find neurons that are active at the onset of stops, when executed at the landmark but not spontaneously elsewhere. Our results suggest that the M2-STN pathway can be recruited during visually-guided locomotion to rapidly and precisely control the mesencephalic locomotor region through the basal ganglia.

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Basal ganglia and cerebellum contributions to vocal emotion processing as revealed by high-resolution fMRI

Scientific Reports ◽

10.1038/s41598-021-90222-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Leonardo Ceravolo ◽

Sascha Frühholz ◽

Jordan Pierce ◽

Didier Grandjean ◽

Julie Péron

Keyword(s):

Basal Ganglia ◽

High Resolution ◽

Globus Pallidus ◽

Subthalamic Nucleus ◽

Effective Connectivity ◽

Emotion Processing ◽

Brain Regions ◽

Vocal Emotion ◽

Variance Explained

AbstractUntil recently, brain networks underlying emotional voice prosody decoding and processing were focused on modulations in primary and secondary auditory, ventral frontal and prefrontal cortices, and the amygdala. Growing interest for a specific role of the basal ganglia and cerebellum was recently brought into the spotlight. In the present study, we aimed at characterizing the role of such subcortical brain regions in vocal emotion processing, at the level of both brain activation and functional and effective connectivity, using high resolution functional magnetic resonance imaging. Variance explained by low-level acoustic parameters (fundamental frequency, voice energy) was also modelled. Wholebrain data revealed expected contributions of the temporal and frontal cortices, basal ganglia and cerebellum to vocal emotion processing, while functional connectivity analyses highlighted correlations between basal ganglia and cerebellum, especially for angry voices. Seed-to-seed and seed-to-voxel effective connectivity revealed direct connections within the basal ganglia—especially between the putamen and external globus pallidus—and between the subthalamic nucleus and the cerebellum. Our results speak in favour of crucial contributions of the basal ganglia, especially the putamen, external globus pallidus and subthalamic nucleus, and several cerebellar lobules and nuclei for an efficient decoding of and response to vocal emotions.

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Paper 22: Experimental Studies on the Role of the Basal Ganglia in the Control of Movement

Proceedings of the Institution of Mechanical Engineers Conference Proceedings ◽

10.1243/pime_conf_1968_183_190_02 ◽

1968 ◽

Vol 183 (10) ◽

pp. 126-134

Author(s):

E. M. Sedgwick

Keyword(s):

Basal Ganglia ◽

Motor Cortex ◽

Caudate Nucleus ◽

Reticular Formation ◽

Sensory Input ◽

Inferior Olive ◽

Experimental Studies ◽

Sensory Inputs ◽

Influence Activity

When the basal ganglia are damaged by disease processes in man, various disorders of movement occur. In order to control movement the basal ganglia must have a sensory input and in the absence of direct connections to motoneurones or motor cortex they must act through intermediate structures. The experiments, on cats, demonstrate: (1) which sensory inputs reach the caudate nucleus and how they influence activity of the neurones there; (2) the effect of the output from the caudate nucleus and globus pallidus on the neurones of the inferior olive and reticular formation. The results are discussed with respect to the control of movement.

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IDENTIFICATION OF A NOVEL BDNF-SPECIFIC CORTICOSTRIATAL CIRCUITRY

10.1101/2021.08.26.457842 ◽

2021 ◽

Author(s):

Yann Ehinger ◽

Drishti Soneja ◽

Khanhky Phamluong ◽

Dorit Ron

Keyword(s):

Motor Cortex ◽

Orbitofrontal Cortex ◽

Neural Circuit ◽

Dorsal Striatum ◽

Medial Part ◽

Striatal Neurons ◽

Bdnf Expression ◽

Axon Terminals ◽

Bdnf Signaling

BDNF is released from axon terminals originating in the cerebral cortex onto striatal neurons. Here, we characterized BDNF in the corticostriatal circuitry. First, we utilized Bdnf-Cre and Ribotag transgenic mouse lines to label BDNF-positive cells in the cortex, and detected BDNF expression in the motor cortex, medial prefrontal cortex (mPFC) and the orbitofrontal cortex (OFC). Next, we used a retrograde viral tracing strategy, in combination with Bdnf-Cre knockin mice, to map the cortical outputs of BDNF neurons in the dorsal striatum. We found that the BDNF-positive prefrontal regions differentially project to the dorsal striatum. Specifically, BDNF-expressing neurons located in the mPFC project to both dorsolateral striatum (DLS) and dorsomedial striatum (DMS), and those located in the motor cortex project to the DLS. Surprisingly however, the BDNF-expressing OFC neurons differentially target the dorsal striatum depending on their mediolateral location. Specifically, the DMS is mainly innervated by the medial part of the OFC (mOFC) whereas, the DLS receives projections specifically from the ventrolateral region of the OFC (vlOFC). Next, using an anterograde viral tracing strategy, we confirmed the presence of a BDNF-specific vlOFC-DLS circuit. Finally, we show that overexpression of BDNF in the vlOFC activates TrkB signaling specifically in the DLS but not in the DMS demonstrating the functionality of this circuit. Our study uncovers a previously unknown neural circuit composed of BDNF-positive vlOFC neurons projecting to the DLS. These findings could have important implications for the role of BDNF signaling in the OFC as well as in other corticostriatal circuitries.

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Effect of Stimulation of Subthalamic Nucleus onbeta Oscillations and Thalamus Tremor Activity in aComputational Model of Parkinson’s Disease

10.21203/rs.3.rs-125807/v1 ◽

2020 ◽

Author(s):

Seyed-Mojtaba Alavi ◽

Amin Mirzaei ◽

Alireza Valizadeh ◽

Reza Ebrahimpour

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Basal Ganglia ◽

Globus Pallidus ◽

Subthalamic Nucleus ◽

Experimental Studies ◽

Underlying Mechanism ◽

Motor Deficits ◽

Synaptic Coupling

Abstract Parkinson’s disease (PD) is associated with abnormal b band oscillations (13-30 Hz) in the cortico-basal ganglia circuits.Abnormally increased striato-pallidal inhibition and strengthening the synaptic coupling between subthalamic nucleus (STN)and globus pallidus externa (GPe), due to the loss of dopamine, are accounted as the potential sources of b oscillations in thebasal ganglia. Deep brain stimulation (DBS) of the basal ganglia subregions is known as a way to reduce the pathological boscillations and motor deficits related to PD. Despite the success of the DBS, its underlying mechanism is poorly understoodand, there is controversy about the inhibitory or excitatory role of the DBS in the literature. Here, we utilized a computationalnetwork model of basal ganglia which consists STN, GPe, globus pallidus interna (GPi), and thalamus neuronal population.This model can capture healthy and pathological b oscillations as what has been observed in experimental studies. Using thismodel, we investigated the effect of DBS to understand whether its effect is excitatory or inhibitory. Our results show that theexcitatory DBS (EDBS) is able to quench the pathological synchrony and b oscillations, while, applying inhibitory DBS (IDBS)failed to quench the PD signs. In addition, the EDBS ameliorated the thalamic activity related to tremor in the model, while,the IDBS outperformed. However, with the help of the model results, we conclude that the effect of the DBS on its target isexcitatory

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