Physiological mechanisms of thalamic ventral intermediate nucleus stimulation for tremor suppression

Milosevic, Luka; Kalia, Suneil K.; Hodaie, Mojgan; Lozano, Andrés M.; Popović, Miloš R.; Hutchison, William D.

doi:10.1093/brain/awy139

Cited by 115 publications

(125 citation statements)

References 101 publications

(117 reference statements)

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…Of course, a major question is how this type of stimulation could be changing activity at the level of single cells or local circuits. Indeed, there is evidence that the local GABAergic and excitatory neural populations respond to stimulation differentially depending on frequency, more specifically in the subthalamic nucleus [27,28]. As might be expected, researchers have found some degree of neural plasticity in this region depends on the frequency of the stimulation [27,28].…”

Section: Discussionmentioning

confidence: 84%

Consistent linear and non-linear responses to invasive electrical brain stimulation across individuals and primate species with implanted electrodes

et al. 2019

View full text Add to dashboard Cite

a b s t r a c tBackground: Electrical neuromodulation via implanted electrodes is used in treating numerous neurological disorders, yet our knowledge of how different brain regions respond to varying stimulation parameters is sparse. Objective/Hypothesis: We hypothesized that the neural response to electrical stimulation is both regionspecific and non-linearly related to amplitude and frequency. Methods: We examined evoked neural responses following 400 ms trains of 10e400 Hz electrical stimulation ranging from 0.1 to 10 mA. We stimulated electrodes implanted in cingulate cortex (dorsal anterior cingulate and rostral anterior cingulate) and subcortical regions (nucleus accumbens, amygdala) of nonhuman primates (NHP, N ¼ 4) and patients with intractable epilepsy (N ¼ 15) being monitored via intracranial electrodes. Recordings were performed in prefrontal, subcortical, and temporal lobe locations. Results: In subcortical regions as well as dorsal and rostral anterior cingulate cortex, response waveforms depended non-linearly on frequency (Pearson's linear correlation r < 0.39), but linearly on current (r > 0.58). These relationships between location, and input-output characteristics were similar in homologous brain regions with average Pearson's linear correlation values r > 0.75 between species and linear correlation values between participants r > 0.75 across frequency and current values per brain region. Evoked waveforms could be described by three main principal components (PCs) which allowed us to successfully predict response waveforms across individuals and across frequencies using PC strengths as functions of current and frequency using brain region specific regression models. Conclusions: These results provide a framework for creation of an atlas of input-output relationships which could be used in the principled selection of stimulation parameters per brain region.

show abstract

Section: Discussionmentioning

confidence: 84%

Consistent linear and non-linear responses to invasive electrical brain stimulation across individuals and primate species with implanted electrodes

et al. 2019

View full text Add to dashboard Cite

show abstract

“…During the first surgery, STN activity during HFS (≥50 Hz) was in accordance with the previously reported group data (robustly suppressed); however, the neurons appeared to be more resistant to suppression at high stimulation frequencies in recordings obtained during the second surgery. Neuronal suppression during stimulation at high frequencies has been attributed to synaptic depression [9,[21][22][23][24]; a transient decrease in synaptic strength that is hypothesized to occur by way of vesicle depletion (caused by delivery of subsequent stimuli before replenishment of neurotransmitter vesicles) and/or decreased presynaptic Ca 2+ conductance [21,25]. Thus, an increased resistance to synaptic depression, perhaps in response to chronic stimulation, may be attributable to increased presynaptic Ca 2+ conductance or changes to intracellular Ca 2+ homeostasis [26] or perhaps to adaptation in the rate at which vesicles are replenished.…”

Section: Discussionmentioning

confidence: 99%

Neuronal Activity and Synaptic Plasticity in a Reimplanted STN-DBS Patient with Parkinson’s Disease: Recordings from Two Surgeries

Milosevic

Vloo

Gramer

et al. 2020

Stereotact Funct Neurosurg

Self Cite

View full text Add to dashboard Cite

The authors report the case of an elderly male in his 60s who, after 5 months of efficacious treatment with chronic deep brain stimulation of the subthalamic nucleus (STN-DBS), developed a hardware-related erosion necessitating removal of the complete DBS system. One and a half years following the first implantation, a new STN-DBS system was implanted along an immediately adjacent trajectory, and reproduction of clinical efficacy was reported. Additionally, 2 microstimulation protocols were compared between the 2 surgeries, i.e., one to assess the stimulation frequency response of STN neurons and another to assess inhibitory synaptic plasticity in the substantia nigra pars reticulata (SNr). The spontaneous neuronal firing rates of STN neurons in each hemisphere were also compared between the 2 surgeries. The results suggest that the frequency-sensitivity of STN neurons may have been reduced (i.e., more resistant to neuronal suppression), while the spontaneous baseline firing rates of STN neurons and the plasticity measured in the SNr remained unchanged (2 factors that may be indicative of neurodegenerative processes).

show abstract

“…Theoretically, interference with any of these cerebello-thalamo-cortical nodes should suppress tremor oscillation. The thalamic (VIM) nucleus which receives most of the cerebellar afferent fibers (Asanuma et al, 1983) has been of much interest in tremor research (Pedrosa et al, 2012;Basha et al, 2014;Fang et al, 2016;Milosevic et al, 2018). The VIM also projects to the aforementioned tremor-related motor areas (McFarland and Haber, 2002;Haber and Calzavara, 2009).…”

Section: The Tremor Network and Pattern Of Beneficial Dbs Connectivitymentioning

confidence: 99%

Connectivity profile of thalamic deep brain stimulation to effectively treat essential tremor

Al‐Fatly

Ewert

Kübler

et al. 2019

Preprint

View full text Add to dashboard Cite

Essential tremor is the most prevalent movement disorder and is often refractory to medical treatment. Deep brain stimulation offers a therapeutic approach that can efficiently control tremor symptoms. Several deep brain stimulation targets (ventral intermediate nucleus, zona incerta, posterior subthalamic area) have been discussed for tremor treatment. Effective deep brain stimulation therapy for tremor critically involves optimal targeting to modulate the tremor network. This could potentially become more robust and precise by using state-of-the-art brain connectivity measurements. In the current study, we utilized two normative brain connectomes (structural and functional) to show the pattern of effective deep brain stimulation electrode connectivity in 36 essential tremor patients. Our structural and functional connectivity models were significantly predictive of post-operative tremor improvement in out-of-sample data (p < 0.001 for both structural and functional leave-one-out cross-validation). Additionally, we segregated the somatotopic brain network based on head and hand tremor scores. These resulted in segregations that mapped onto the well-known somatotopic maps of both motor cortex and cerebellum. Crucially, this shows that slightly distinct networks need to be modulated to ameliorate head vs. hand tremor and that those networks could be identified based on somatotopic zones in motor cortex and cerebellum.Finally, we propose a multi-modal connectomic deep brain stimulation sweet spot that may serve as a reference to enhance clinical care, in the future. This spot resided in the posterior subthalamic area, encroaching on the inferior borders of ventral intermediate nucleus and sensory thalamus.Our results underscore the importance of integrating brain connectivity in optimizing deep brain stimulation targeting for essential tremor.

show abstract

Physiological mechanisms of thalamic ventral intermediate nucleus stimulation for tremor suppression

Cited by 115 publications

References 101 publications

Consistent linear and non-linear responses to invasive electrical brain stimulation across individuals and primate species with implanted electrodes

Consistent linear and non-linear responses to invasive electrical brain stimulation across individuals and primate species with implanted electrodes

Neuronal Activity and Synaptic Plasticity in a Reimplanted STN-DBS Patient with Parkinson’s Disease: Recordings from Two Surgeries

Connectivity profile of thalamic deep brain stimulation to effectively treat essential tremor

Contact Info

Product

Resources

About