Motor Pathways, Basal Ganglia Physiology, and Pathophysiology

Bergman, Hagai; Katabi, Shiran; Slovik, Maya; Deffains, Marc; Arkadir, David; Israel, Zvi; Eitan, Renana

doi:10.1002/9781118568323.ch3

Cited by 4 publications

(4 citation statements)

References 78 publications

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“…Moreover, not only STN-DBS, but also GPi-DBS suppresses other conditions with phenotypes similar to the SIB seen in some ASD patients, such as Lesch-Nyhan syndrome (Cif et al, 2007;Taira et al, 2003), Tourette's syndrome (Cannon et al, 2012) and OCD (Nair et al, 2014). Taken together, these studies converge on a central idea that the basal ganglia is a behavioral filter, which can be shifted toward conservative or liberal restriction based on sufficient activation or inhibition of key 'no-go' nuclei such as the STN, GPi, and SNr (Bergman et al, 2015). Finally, it is also possible that STN-HFS could be effective in our study because of stimulation of fibers of passage in the neighboring internal capsule and zona incerta.…”

Section: Discussionmentioning

confidence: 80%

High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models

Chang

Berges

Chung

et al. 2015

Neuropsychopharmacol

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Approximately one quarter of individuals with an autism spectrum disorder (ASD) display self-injurious behavior (SIB) ranging from head banging to self-directed biting and punching. Sometimes, these behaviors are extreme and unresponsive to pharmacological and behavioral therapies. We have found electroconvulsive therapy (ECT) can produce life-changing results, with more than 90% suppression of SIB frequency. However, these patients typically require frequent maintenance ECT (mECT), as often as every 5 days, to sustain the improvement gained during the acute course. Long-term consequences of such frequent mECT started as early as childhood in some cases are unknown. Accordingly, there is a need for alternative forms of chronic stimulation for these patients. To explore the feasibility of deep brain stimulation (DBS) for intractable SIB seen in some patients with an ASD, we utilized two genetically distinct mouse models demonstrating excessive self-grooming, namely the Viaat-Mecp2 − /y and Shank3B −/− lines, and administered high-frequency stimulation (HFS) via implanted electrodes at the subthalamic nucleus (STN-HFS). We found that STN-HFS significantly suppressed excessive selfgrooming in both genetic lines. Suppression occurs both acutely when stimulation is switched on, and persists for several days after HFS is stopped. This effect was not explained by a change in locomotor activity, which was unaffected by STN-HFS. Likewise, social interaction deficits were not corrected by STN-HFS. Our data show STN-HFS suppresses excessive self-grooming in two autism-like mouse models, raising the possibility DBS might be used to treat intractable SIB associated with ASDs. Further studies are required to explore the circuitry engaged by STN-HFS, as well as other potential stimulation sites. Such studies might also yield clues about pathways, which could be modulated by non-invasive stimulatory techniques.

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Section: Discussionmentioning

confidence: 80%

High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models

Chang

Berges

Chung

et al. 2015

Neuropsychopharmacol

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“…Disruption of pathological oscillations by DRT (Heimer et al, 2006), the inactivation of the subthalamic nucleus (STN) (Wichmann et al, 1994), or deep brain stimulation (DBS) of the STN (Deuschl et al, 2006) consistently decreases the motor disturbances of PD. This suggests a causal relationship between the pathological oscillations and symptoms of PD (Bergman et al, 2015). The target of the STN stimulation may be the corticostriatal axons (Gradinaru et al, 2009).…”

Section: Parkinson's Diseasementioning

confidence: 96%

Oscillotherapeutics – Time-targeted interventions in epilepsy and beyond

Takeuchi

Berényi

2020

Neuroscience Research

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Oscillatory brain activities support many physiological functions from motor control to cognition. Disruptions of the normal oscillatory brain activities are commonly observed in neurological and psychiatric disorders including epilepsy, Parkinson's disease, Alzheimer's disease, schizophrenia, anxiety/traumarelated disorders, major depressive disorders, and drug addiction. Therefore, these disorders can be considered as common oscillation defects despite having distinct behavioral manifestations and genetic causes. Recent technical advances of neuronal activity recording and analysis have allowed us to study the pathological oscillations of each disorder as a possible biomarker of symptoms. Furthermore, recent advances in brain stimulation technologies enable time-and space-targeted interventions of the pathological oscillations of both neurological disorders and psychiatric disorders as possible targets for regulating their symptoms.

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“…We highlight that the DA levels have a dual role in the network model (Bergman et al. 2015 ; Schultz et al. 1997 ).…”

Section: A Dynamical Model Of the Basal Ganglia-thalamo-cortical Networkmentioning

confidence: 91%

“…We highlight that the DA levels have a dual role in the network model (Bergman et al 2015;Schultz et al 1997). First, the DA interferes with the excitability of the MSNs subtypes in the BG network.…”

Section: Building the Network From Single Neuronsmentioning

confidence: 92%

A dynamical model for the basal ganglia-thalamo-cortical oscillatory activity and its implications in Parkinson’s disease

2020

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We propose to investigate brain electrophysiological alterations associated with Parkinson’s disease through a novel adaptive dynamical model of the network of the basal ganglia, the cortex and the thalamus. The model uniquely unifies the influence of dopamine in the regulation of the activity of all basal ganglia nuclei, the self-organised neuronal interdependent activity of basal ganglia-thalamo-cortical circuits and the generation of subcortical background oscillations. Variations in the amount of dopamine produced in the neurons of the substantia nigra pars compacta are key both in the onset of Parkinson’s disease and in the basal ganglia action selection. We model these dopamine-induced relationships, and Parkinsonian states are interpreted as spontaneous emergent behaviours associated with different rhythms of oscillatory activity patterns of the basal ganglia-thalamo-cortical network. These results are significant because: (1) the neural populations are built upon single-neuron models that have been robustly designed to have eletrophysiologically-realistic responses, and (2) our model distinctively links changes in the oscillatory activity in subcortical structures, dopamine levels in the basal ganglia and pathological synchronisation neuronal patterns compatible with Parkinsonian states, this still remains an open problem and is crucial to better understand the progression of the disease.

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Motor Pathways, Basal Ganglia Physiology, and Pathophysiology

Cited by 4 publications

References 78 publications

High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models

High-Frequency Stimulation at the Subthalamic Nucleus Suppresses Excessive Self-Grooming in Autism-Like Mouse Models

Oscillotherapeutics – Time-targeted interventions in epilepsy and beyond

A dynamical model for the basal ganglia-thalamo-cortical oscillatory activity and its implications in Parkinson’s disease

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