Mechanisms of pallidal deep brain stimulation: Alteration of cortico-striatal synaptic communication in a dystonia animal model

Heerdegen, Marco; Zwar, Monique; Franz, Denise; Hörnschemeyer, Julia; Neubert, Valentin; Plocksties, Franz; Niemann, Christoph; Timmermann, Dirk; Bahls, Christian; Rienen, Ursula van; Paap, Maria; Perl, Stefanie; Lüttig, Anika; Richter, Angelika; Köhling, Rüdiger

doi:10.1016/j.nbd.2021.105341

Cited by 5 publications

(8 citation statements)

References 65 publications

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“… 161 , 162 Modulation of this abnormal plasticity has been proposed to underpin the therapeutic effects of DBS, highlighting the area as key to mediating clinical outcomes. 163 …”

Section: Discussionmentioning

confidence: 99%

A structural magnetic resonance imaging review of clinical motor outcomes from deep brain stimulation in movement disorders

Andrews

Keller

Osman-Farah

et al. 2023

Brain Communications

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Patients with movement disorders treated by deep brain stimulation do not always achieve successful therapeutic alleviation of motor symptoms, even in cases where surgery is without complications. Magnetic resonance imaging (MRI) offers methods to investigate structural brain-related factors that may be predictive for clinical motor outcomes. This review aimed to identify features which have been associated with variability in clinical post-operative motor outcomes in patients with Parkinson’s disease, dystonia, and essential tremor from structural MRI modalities. We performed a literature search for articles published between January 01, 2000, and April 01, 2022, and identified 5197 articles. Following screening through our inclusion criteria, we identified 60 total studies (39 = Parkinson’s disease, 11 = dystonia syndromes and 10 = essential tremor). The review captured a range of structural MRI methods and analysis techniques used to identify factors related to clinical post-operative motor outcomes from deep brain stimulation. Morphometric markers, including volume and cortical thickness were commonly identified in studies focused on patients with Parkinson’s disease and dystonia syndromes. Reduced metrics in basal ganglia, sensorimotor and frontal regions showed frequent associations with reduced motor outcomes. Increased structural connectivity to subcortical nuclei, sensorimotor and frontal regions were also associated with greater motor outcomes. In patients with tremor, increased structural connectivity to the cerebellum and cortical motor regions showed high prevalence across studies for greater clinical motor outcomes. In addition, we highlight conceptual issues for studies assessing clinical response with structural MRI and discuss future approaches towards optimising individualised therapeutic benefits. Although quantitative MRI markers are in their infancy for clinical purposes in movement disorder treatments, structural features obtained from MRI offer powerful potential to identify candidates who are more likely to benefit from deep brain stimulation and provide insight into the complexity of disorder pathophysiology.

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“… 161 , 162 Modulation of this abnormal plasticity has been proposed to underpin the therapeutic effects of DBS, highlighting the area as key to mediating clinical outcomes. 163 …”

Section: Discussionmentioning

confidence: 99%

A structural magnetic resonance imaging review of clinical motor outcomes from deep brain stimulation in movement disorders

Andrews

Keller

Osman-Farah

et al. 2023

Brain Communications

View full text Add to dashboard Cite

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“…Several lines of evidence indicate abnormal cortico-striatal activity in dystonia [ 49 , 72 ], but in addition to the cortical input, MSN receive quantitatively similar glutamatergic inputs through thalamo-striatal synapses [ 6 , 26 , 76 ] (Fig. 2 ).…”

Section: Hypotheses For the Pathophysiology Of Isolated Dystoniamentioning

confidence: 99%

“…The complex mechanisms of synaptic plasticity of MSN reflect the crucial role of granular time-scaled activation of dopamine, acetylcholine, and adenosine receptors. It is widely assumed that plasticity at cortico-striatal synapses underlying motor learning is a critical factor in the pathophysiology of dystonia [ 8 , 49 , 87 , 114 ]. There is evidence from clinical and experimental studies for abnormal synaptic plasticity and a prevailing in LTP, which lead to abnormal sensorimotor integration and consolidation of motor engrams [ 87 ].…”

Section: Hypotheses For the Pathophysiology Of Isolated Dystoniamentioning

confidence: 99%

“…There is evidence from clinical and experimental studies for abnormal synaptic plasticity and a prevailing in LTP, which lead to abnormal sensorimotor integration and consolidation of motor engrams [ 87 ]. The delayed effect of deep brain stimulation (DBS), which, in contrast to PD, could take several days, weeks, or even months, pointed out the abnormal plasticity that may be reorganised by the stimulation [ 10 , 44 , 49 , 63 , 84 , 94 , 124 ].…”

Section: Hypotheses For the Pathophysiology Of Isolated Dystoniamentioning

confidence: 99%

“…Reducing the stimulation frequency incidentally would consume less power in a stimulation system, allowing for longer intervals between charging [ 86 ]. The experiments revealed that, at least for the dt sz mutant hamster, 130 Hz is the most effective frequency for short-term DBS of 3 h. Taking the optimal GPi-DBS parameters as determined by Paap et al (2021), we could show that the frequency of miniature excitatory postsynaptic currents (mEPSC) recorded in MSN of the dt sz mutant hamster is significantly reduced [ 49 ]. Thus, compared to healthy, wild-type tissue, dt sz mutant hamster neurons exhibited more mEPSC, which may reflect increased cortico-striatal excitability.…”

Section: Electrophysiological Data On Dbs In Dystonia Modelsmentioning

confidence: 99%

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Electrophysiological insights into deep brain stimulation of the network disorder dystonia

Franz,

Richter,

Köhling

2023

Pflugers Arch - Eur J Physiol

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Deep brain stimulation (DBS), a treatment for modulating the abnormal central neuronal circuitry, has become the standard of care nowadays and is sometimes the only option to reduce symptoms of movement disorders such as dystonia. However, on the one hand, there are still open questions regarding the pathomechanisms of dystonia and, on the other hand, the mechanisms of DBS on neuronal circuitry. That lack of knowledge limits the therapeutic effect and makes it hard to predict the outcome of DBS for individual dystonia patients. Finding electrophysiological biomarkers seems to be a promising option to enable adapted individualised DBS treatment. However, biomarker search studies cannot be conducted on patients on a large scale and experimental approaches with animal models of dystonia are needed. In this review, physiological findings of deep brain stimulation studies in humans and animal models of dystonia are summarised and the current pathophysiological concepts of dystonia are discussed.

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Short-term stimulations of the entopeduncular nucleus induce cerebellar changes of c-Fos expression in an animal model of paroxysmal dystonia

Lüttig,

Perl,

Zetsche

et al. 2024

Brain Research

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Mechanisms of pallidal deep brain stimulation: Alteration of cortico-striatal synaptic communication in a dystonia animal model

Cited by 5 publications

References 65 publications

A structural magnetic resonance imaging review of clinical motor outcomes from deep brain stimulation in movement disorders

A structural magnetic resonance imaging review of clinical motor outcomes from deep brain stimulation in movement disorders

Electrophysiological insights into deep brain stimulation of the network disorder dystonia

Short-term stimulations of the entopeduncular nucleus induce cerebellar changes of c-Fos expression in an animal model of paroxysmal dystonia

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