scholarly journals Globus pallidus dynamics reveal covert strategies for behavioral inhibition

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Bon-Mi Gu ◽  
Robert Schmidt ◽  
Joshua D Berke

Flexible behavior requires restraint of actions that are no longer appropriate. This behavioral inhibition critically relies on frontal cortex - basal ganglia circuits. Within the basal ganglia, the globus pallidus pars externa (GPe) has been hypothesized to mediate selective proactive inhibition: being prepared to stop a specific action, if needed. Here we investigate population dynamics of rat GPe neurons during preparation-to-stop, stopping, and going. Rats selectively engaged proactive inhibition towards specific actions, as shown by slowed reaction times (RTs). Under proactive inhibition, GPe population activity occupied state-space locations farther from the trajectory followed during normal movement initiation. Furthermore, the state-space locations were predictive of distinct types of errors: failures-to-stop, failures-to-go, and incorrect choices. Slowed RTs on correct proactive trials reflected starting bias towards the alternative action, which was overcome before progressing towards action initiation. Our results demonstrate that rats can exert cognitive control via strategic adjustments to their GPe network state.

Author(s):  
Bon-Mi Gu ◽  
Robert Schmidt ◽  
Joshua D. Berke

AbstractFlexible behavior requires restraint or cancellation of actions that are no longer appropriate. This behavioral inhibition critically relies on frontal cortex - basal ganglia circuits. A central node within the basal ganglia, the globus pallidus pars externa (GPe), has been hypothesized to mediate “proactive” inhibition: being prepared to stop an action if needed. Here we investigate the population dynamics of rat GPe neurons during preparation-to-stop, stopping, and going. Rats could selectively engage proactive inhibition towards one specific action, as shown by slowed reaction times (RTs) for that action. While proactive inhibition was engaged, GPe population activity occupied state-space locations farther from the trajectory followed during normal movement initiation. Furthermore, the specific state-space location was predictive of distinct types of errors: failures to stop, failures to go, and incorrect choices. The slowed RTs on correct proactive trials reflected a starting bias towards the alternative action, which was overcome before making progress towards action initiation. Our results demonstrate that rats can exert cognitive control via strategic positioning of their GPe network state.


2008 ◽  
Vol 99 (3) ◽  
pp. 1057-1076 ◽  
Author(s):  
M. Desmurget ◽  
R. S. Turner

To test current hypotheses on the contribution of the basal ganglia (BG) to motor control, we examined the effects of muscimol-induced inactivations in the skeletomotor region of the internal globus pallidus (sGPi) on visually directed reaching. Injections were made in two monkeys trained to perform four out-and-back reaching movements in quick succession toward four randomly selected target locations. Following sGPi inactivations the following occurred. 1) Peak velocity and acceleration were decreased in nearly all sessions, whereas movement duration lengthened inconsistently. 2) Reaction times were unaffected on average, although minor changes were observed in several individual sessions. 3) Outward reaches showed a substantial hypometria that correlated closely with bradykinesia, but directional accuracy was unaffected. 4) Endpoint accuracy was preserved for the slow visually guided return movements. 5) No impairments were found in the rapid chaining of out-and-back movements, in the selection or initiation of four independent reaches in quick succession or in the quick on-line correction of initially misdirected reaches. 6) Inactivation-induced reductions in the magnitude of movement-related muscle activity (EMG) correlated with the severity of slowing and hypometria. There was no evidence for inactivation-induced alterations in the relative timing of EMG bursts, excessive cocontraction, or impaired suppression of antagonist EMG. Therefore disconnecting the BG motor pathway consistently produced bradykinesia and hypometria, but seldom affected movement initiation time, feedback-mediated guidance, the capacity to produce iterative reaches, or the ability to abruptly reverse movement direction. These results are discussed with reference to the idea that the BG motor loop may regulate energetic expenditures during movement (i.e., movement “vigor”).


1984 ◽  
Vol 52 (2) ◽  
pp. 305-322 ◽  
Author(s):  
F. B. Horak ◽  
M. E. Anderson

The effect of changing basal ganglia activity with electrical stimulation in and around the globus pallidus (GP) was studied in monkeys trained to make rapid arm-reaching movements to a visual target in a reaction time task. As was the case following kainic acid (KA) lesions of the globus pallidus (30), stimulation changed movement times (MT) without affecting the pattern of sequential activation of muscles involved in the task or, in most cases, the reaction times (RT). Stimulation in the ventrolateral internal segment of the globus pallidus (GPi) or in the ansa lenticularis reduced movement times, whereas stimulation at many sites in the external pallidal segment (GPe), dorsal GPi, and putamen increased movement times for the contralateral arm. These results are consistent with the hypothesis that arm movements are speeded up when the critical output of GPi is increased and arm movements are slowed down when critical GPi output is reduced, either by an inhibitory process (via stimulation-induced activation of inhibitory elements presynaptic to GPi) or by destroying GPi neurons (via kainic acid). The influence of the basal ganglia on the scaling of electromyographic (EMG) amplitude, as opposed to the spatiotemporal organization of EMG activation, is discussed.


2003 ◽  
Vol 89 (5) ◽  
pp. 2528-2537 ◽  
Author(s):  
Irwin H. Lee ◽  
John A. Assad

To examine the role of basal ganglia-cortical circuits in movement initiation, we trained monkeys to make the same arm movements in two ways—in immediate reaction to a randomly timed external cue (cued movements) and also following a variable delay without an explicit initiation signal (self-timed movements). The two movement types were interleaved and balanced in overall timing to allow a direct comparison of activity before and during the movement. Posterior putaminal neurons generally had phasic, movement-related discharges that were comparable for cued and self-timed movements. On cued movements, neuronal activity increased sharply following cue onset. However, for self-timed movements, there was a slow build-up in activity that preceded the phasic discharge. This slow build-up was time-locked to movement and restricted to a narrow time window hundreds of milliseconds before movement. The difference in premovement activity between cued and self-timed trials was present before the earliest cue-onset times and was not related to any differences in the overall time-to-move between the two types of trials. These features suggest that activity evolving in the basal ganglia-cortical circuitry may drive the initiation of movements by increasing until an activity threshold is exceeded. The activity may increase abruptly in response to an external cue or gradually when the timing of movements is determined by the animals themselves rather than an external cue. In this view, small changes in activity that occur in advance of the much larger perimovement neuronal activity may be an important determinant of when movement occurs. In support of this hypothesis, we found that even for cued movements, faster reaction times were associated with slightly higher levels of activity hundreds of milliseconds before movement.


2021 ◽  
pp. 1-12
Author(s):  
Xi Bai ◽  
Peter Vajkoczy ◽  
Katharina Faust

<b><i>Objective:</i></b> The pathophysiology of dystonia is poorly understood. As opposed to secondary forms of dystonia, primary dystonia has long been believed to lack any neuroanatomical substrate. During trajectory planning for DBS, however, conspicuous T2-hyperinstensive signal alterations (SA) were registered within the target region, even in young patients, where ischemia is rare. <b><i>Methods:</i></b> Fifty MRIs of primary dystonia patients scheduled for DBS were analyzed. Total basal ganglia (BG) volumes, as well as proportionate SA volumes, were measured and compared to 50 age-matched control patients. <b><i>Results:</i></b> There was a 10-fold preponderance of percentaged SA within the globus pallidus (GP) in dystonia patients. The greatest disparity was in young patients &#x3c;25 years. Also, total BG volume differences were observed with larger GP and markedly smaller putamen and caudate in the dystonia group. <b><i>Conclusions:</i></b> BG morphology in primary dystonia differed from a control population. Volume reductions of the putamen and caudate may reflect functional degeneration, while volume increases of the GP may indicate overactivity. T2-hyperintensive SA in the GP of young primary dystonia patients, where microvascular lesions are highly unlikely, are striking. Their pathogenic role remains unclear.


2005 ◽  
Vol 93 (1) ◽  
pp. 519-534 ◽  
Author(s):  
Masayuki Watanabe ◽  
Yasushi Kobayashi ◽  
Yuka Inoue ◽  
Tadashi Isa

To examine the role of competitive and cooperative neural interactions within the intermediate layer of superior colliculus (SC), we elevated the basal SC neuronal activity by locally injecting a cholinergic agonist nicotine and analyzed its effects on saccade performance. After microinjection, spontaneous saccades were directed toward the movement field of neurons at the injection site (affected area). For visually guided saccades, reaction times were decreased when targets were presented close to the affected area. However, when visual targets were presented remote from the affected area, reaction times were not increased regardless of the rostrocaudal level of the injection sites. The endpoints of visually guided saccades were biased toward the affected area when targets were presented close to the affected area. After this endpoint effect diminished, the trajectories of visually guided saccades remained modestly curved toward the affected area. Compared with the effects on endpoints, the effects on reaction times were more localized to the targets close to the affected area. These results are consistent with a model that saccades are triggered by the activities of neurons within a restricted region, and the endpoints and trajectories of the saccades are determined by the widespread population activity in the SC. However, because increased reaction times were not observed for saccades toward targets remote from the affected area, inhibitory interactions in the SC may not be strong enough to shape the spatial distribution of the low-frequency preparatory activities in the SC.


Development ◽  
1998 ◽  
Vol 125 (24) ◽  
pp. 5079-5089 ◽  
Author(s):  
J.D. Kohtz ◽  
D.P. Baker ◽  
G. Corte ◽  
G. Fishell

The cortex and basal ganglia are the major structures of the adult brain derived from the embryonic telencephalon. Two morphologically distinct regions of the basal ganglia are evident within the mature ventral telencephalon, the globus pallidus medially, and the striatum, which is positioned between the globus pallidus and the cortex. Deletion of the Sonic Hedgehog gene in mice indicates that this secreted signaling molecule is vital for the generation of both these ventral telencephalic regions. Previous experiments showed that Sonic Hedgehog induces differentiation of ventral neurons characteristic of the medial ganglionic eminence, the embryonic structure which gives rise to the globus pallidus. In this paper, we show that later in development, Sonic Hedgehog induces ventral neurons with patterns of gene expression characteristic of the lateral ganglionic eminence. This is the embryonic structure from which the striatum is derived. These results suggest that temporally regulated changes in Sonic Hedgehog responsiveness are integral in the sequential induction of basal telencephalic structures.


2019 ◽  
Author(s):  
Xiaosong He ◽  
Ganne Chaitanya ◽  
Burcu Asma ◽  
Lorenzo Caciagli ◽  
Danielle S. Bassett ◽  
...  

AbstractFocal to bilateral tonic-clonic seizures are associated with lower quality of life, higher risk of seizure-related injuries, increased chance of sudden unexpected death, as well as unfavorable treatment outcomes. Achieving greater understanding of its underlying circuitry offers better opportunity to control these particularly serious seizures. Towards this goal, we provide a network science perspective of the interactive pathways among basal ganglia, thalamus and the cortex, to explore the imprinting of secondary seizure generalization on the mesoscale brain network in temporal lobe epilepsy. Specifically, we parameterized the functional organization of both the thalamocortical network and the basal ganglia—thalamus network with resting-state functional magnetic resonance imaging in three groups of patients with different focal to bilateral tonic-clonic seizure histories. Using the participation coefficient to describe the pattern of thalamocortical connections among different cortical networks, we showed that, compared to patients with no previous history, those with positive histories of focal to bilateral tonic-clonic seizures, including both remote (none for over one year) and current (within the past year) histories, presented more uniform distribution patterns of thalamocortical connections in the ipsilateral medial-dorsal thalamic nuclei. As a sign of greater thalamus mediated cortico-cortical communication, this result comports with greater susceptibility to secondary seizure generalization from the epileptogenic temporal lobe to broader brain networks in these patients. Using interregional integration to characterize the functional interaction between basal ganglia and thalamus, we demonstrated that patients with current history presented increased interaction between putamen and globus pallidus internus, and decreased interaction between the latter and the thalamus, compared to the other two patient groups. Importantly, through a series of “disconnection” simulations, we showed that these changes in interactive profiles of the basal ganglia—thalamus network in the current history group mainly depended upon the direct but not the indirect basal ganglia pathway. It is intuitively plausible that such disruption in the striatum modulated tonic inhibition of the thalamus from the globus pallidus internus could lead to an under-suppressed thalamus, which in turn may account for their greater vulnerability to secondary seizure generalization. Collectively, these findings suggest that the broken balance between the basal ganglia inhibition and thalamus synchronization can inform the presence and effective control of focal to bilateral tonic-clonic seizures. The mechanistic underpinnings we uncover may shed light on the development of new treatment strategies for patients with temporal lobe epilepsy.


2009 ◽  
Vol 102 (2) ◽  
pp. 1092-1102 ◽  
Author(s):  
Ana V. Cruz ◽  
Nicolas Mallet ◽  
Peter J. Magill ◽  
Peter Brown ◽  
Bruno B. Averbeck

Dopamine depletion in cortical-basal ganglia circuits in Parkinson's disease (PD) grossly disturbs movement and cognition. Classic models relate Parkinsonian dysfunction to changes in firing rates of basal ganglia neurons. However, disturbances in other dynamics of neural activity are also common. Taking both inappropriate firing rates and other dynamics into account and determining how changes in the properties of these neural circuits that occur during PD impact on information coding are thus imperative. Here, we examined in vivo network dynamics in the external globus pallidus (GPe) of rats before and after chronic dopamine depletion. Dopamine depletion led to decreases in the firing rates of GPe neurons and increases in synchronized network oscillations in the β frequency (13–30 Hz) band. Using logistic regression models, we determined the combined and separate impacts of these factors on network entropy, a measure of the upper bound of information coding capacity. Importantly, changes in these features in dopamine-depleted rats led to a significant decrease in GPe network entropy. Changes in firing rates had the largest impact on entropy, with changes in synchrony also decreasing entropy at the network level. Changes in autocorrelations tended to offset these effects because autocorrelations decreased entropy more in the control animals. Thus it is possible that reduced information coding capacity within basal ganglia networks may contribute to the behavioral deficits accompanying PD.


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