This scientific commentary refers to ‘Globus pallidus internus deep brain stimulation evokes resonant neural activity in Parkinson’s disease’, by Johnson et al. ...(https://doi.org/10.1093/braincomms/fcad025).
Deep brain stimulation procedures offer an invaluable opportunity to study disease through intracranial recordings from awake patients. Here, we address the relationship between single-neuron and ...aggregate-level (local field potential; LFP) activities in the subthalamic nucleus (STN) and thalamic ventral intermediate nucleus (Vim) of patients with Parkinson's disease (
= 19) and essential tremor (
= 16), respectively. Both disorders have been characterized by pathologically elevated LFP oscillations, as well as an increased tendency for neuronal bursting. Our findings suggest that periodic single-neuron bursts encode both pathophysiological beta (13 to 33 Hz; STN) and tremor (4 to 10 Hz; Vim) LFP oscillations, evidenced by strong time-frequency and phase-coupling relationships between the bursting and LFP signals. Spiking activity occurring outside of bursts had no relationship to the LFP. In STN, bursting activity most commonly preceded the LFP oscillation, suggesting that neuronal bursting generated within STN may give rise to an aggregate-level LFP oscillation. In Vim, LFP oscillations most commonly preceded bursting activity, suggesting that neuronal firing may be entrained by periodic afferent inputs. In both STN and Vim, the phase-coupling relationship between LFP and high-frequency oscillation (HFO) signals closely resembled the relationships between the LFP and single-neuron bursting. This suggests that periodic single-neuron bursting is likely representative of a higher spatial and temporal resolution readout of periodic increases in the amplitude of HFOs, which themselves may be a higher resolution readout of aggregate-level LFP oscillations. Overall, our results may reconcile "rate" and "oscillation" models of Parkinson's disease and shed light on the single-neuron basis and origin of pathophysiological oscillations in movement disorders.
Recently, neuroscience has seen a shift from localist approaches to network-wide investigations of brain function. Neurophysiological signals across different spatial and temporal scales provide ...insight into neural communication. However, additional methodological considerations arise when investigating network-wide brain dynamics rather than local effects. Specifically, larger amounts of data, investigated across a higher dimensional space, are necessary. Here, we present FiNN (
nd
europhysiological
etworks), a novel toolbox for the analysis of neurophysiological data with a focus on functional and effective connectivity. FiNN provides a wide range of data processing methods and statistical and visualization tools to facilitate inspection of connectivity estimates and the resulting metrics of brain dynamics. The Python toolbox and its documentation are freely available as
. We evaluated FiNN against a number of established frameworks on both a conceptual and an implementation level. We found FiNN to require much less processing time and memory than other toolboxes. In addition, FiNN adheres to a design philosophy of easy access and modifiability, while providing efficient data processing implementations. Since the investigation of network-level neural dynamics is experiencing increasing interest, we place FiNN at the disposal of the neuroscientific community as open-source software.
The auditory oddball is a mainstay in research on attention, novelty, and sensory prediction. How this task engages subcortical structures like the subthalamic nucleus and substantia nigra pars ...reticulata is unclear. We administered an auditory OB task while recording single unit activity (35 units) and local field potentials (57 recordings) from the subthalamic nucleus and substantia nigra pars reticulata of 30 patients with Parkinson's disease undergoing deep brain stimulation surgery. We found tone modulated and oddball modulated units in both regions. Population activity differentiated oddball from standard trials from 200 ms to 1000 ms after the tone in both regions. In the substantia nigra, beta band activity in the local field potential was decreased following oddball tones. The oddball related activity we observe may underlie attention, sensory prediction, or surprise-induced motor suppression.
•Population activity and single units in the STN and SNr distinguish infrequent from frequent tones.•OB + TM units distinguish infrequent from frequent tones earlier in time compared to pure OB units.•A model-switching analysis suggests that the population code changes over time.•Beta power decreases following oddball tones in the SNr, but not STN.
Axial symptoms of Parkinson's disease (PD) can be debilitating and are often refractory to conventional therapies such as dopamine replacement therapy and deep brain stimulation (DBS) of the ...subthalamic nuclei (STN).
Evaluate the efficacy of bilateral DBS of the pedunculopontine nucleus area (PPNa) and investigate structural and physiological correlates of clinical response.
A randomized, double-blind, cross-over clinical trial was employed to evaluate the efficacy of bilateral PPNa-DBS on axial symptoms. Lead positions and neuronal activity were evaluated with respect to clinical response. Connectomic cortical activation profiles were generated based on the volumes of tissue activated.
PPNa-DBS modestly improved (p = 0.057) axial symptoms in the medication-off condition, with greatest positive effects on gait symptoms (p = 0.027). Electrode placements towards the anterior commissure (ρ= 0.912; p = 0.011) or foramen caecum (ρ= 0.853; p = 0.031), near the 50% mark of the ponto-mesencephalic junction, yielded better therapeutic responses. Recording trajectories of patients with better therapeutic responses (i.e., more anterior electrode placements) had neurons with lower firing-rates (p = 0.003) and higher burst indexes (p = 0.007). Structural connectomic profiles implicated activation of fibers of the posterior parietal lobule which is involved in orienting behavior and locomotion.
Bilateral PPNa-DBS influenced gait symptoms in patients with PD. Anatomical and physiological information may aid in localization of a favorable stimulation target.
Neuronal loss within the cholinergic nucleus basalis of Meynert (nbM) correlates with cognitive decline in dementing disorders such as Alzheimer's disease and Parkinson's disease (PD). In nonhuman ...primates, the nbM firing pattern (5-40 Hz) has also been correlated with working memory and sustained attention. In this study, authors performed microelectrode recordings of the globus pallidus pars interna (GPi) and the nbM immediately prior to the implantation of bilateral deep brain stimulation (DBS) electrodes in PD patients to treat motor symptoms and cognitive impairment, respectively. Here, the authors evaluate the electrophysiological properties of the nbM in patients with PD.
Five patients (4 male, mean age 66 ± 4 years) with PD and mild cognitive impairment underwent bilateral GPi and nbM DBS lead implantation. Microelectrode recordings were performed through the GPi and nbM along a single trajectory. Firing rates and burst indices were characterized for each neuronal population with the patient at rest and performing a sustained-attention auditory oddball task. Action potential (AP) depolarization and repolarization widths were measured for each neuronal population at rest.
In PD patients off medication, the authors identified neuronal discharge rates that were specific to each area populated by GPi cells (92.6 ± 46.1 Hz), border cells (34 ± 21 Hz), and nbM cells (13 ± 10 Hz). During the oddball task, firing rates of nbM cells decreased (2.9 ± 0.9 to 2.0 ± 1.1 Hz, p < 0.05). During baseline recordings, the burst index for nbM cells (1.7 ± 0.6) was significantly greater than those for GPi cells (1.2 ± 0.2, p < 0.05) and border cells (1.1 ± 0.1, p < 0.05). There was no significant difference in the nbM burst index during the oddball task relative to baseline (3.4 ± 1.7, p = 0.20). With the patient at rest, the width of the depolarization phase of APs did not differ among the GPi cells, border cells, and nbM cells (p = 0.60); however, during the repolarization phase, the nbM spikes were significantly longer than those for GPi high-frequency discharge cells (p < 0.05) but not the border cells (p = 0.20).
Neurons along the trajectory through the GPi and nbM have distinct firing patterns. The profile of nbM activity is similar to that observed in nonhuman primates and is altered during a cognitive task associated with cholinergic activation. These findings will serve to identify these targets intraoperatively and form the basis for further research to characterize the role of the nbM in cognition.
Deep brain stimulation (DBS) is an invasive neuromodulation therapy for management of the motor symptoms of several movement disorders; however, its mechanisms are complex, varied, and remain ...unclear. We employed a dual-microelectrode methodology for intraoperative measurement of neuronal activity and synaptic events, in order to assess the physiological response properties of different subcortical DBS target structures to electrical stimulation at different settings. A total of 50 patients with Parkinson’s disease undergoing DBS surgery of the subthalamic nucleus (STN; n = 40), globus pallidus internus (GPi; n = 8), or ventral intermediate nucleus (Vim; n = 2); and nine patients with essential tremor undergoing DBS surgery of the Vim (n = 9) participated in the studies. We found that the STN required higher frequencies for inhibition during stimulation compared to the substantia nigra par reticulata (SNr), likely due to a higher prevalence of GABAergic terminals on SNr somas; although both structures receive predominantly GABAergic inputs. In the Vim, a structure with predominantly glutamatergic synapses, higher (200Hz) frequencies were required for neuronal inhibition compared to the STN (100Hz) and SNr (50Hz). Additionally, unlike the STN and SNr, a transient period of neuronal excitation occurred prior to inhibition, reflective of the glutamatergic predominance. Thus, the effects of electrical stimulation are site specific and dependent on the weighted composition of inhibitory and excitatory inputs. We furthermore determined that an enhancement of inhibitory synaptic plasticity occurred in the SNr and GPi after continuous high frequency stimulation (HFS) at 100Hz; demonstrated by increased amplitudes of extracellular inhibitory field evoked potentials (fEPs). We found greater plasticity in the GPi compared to SNr, and that intraoperative administration of levodopa had a potent effect on SNr plasticity. Further, we determined that during stimulation at ≥ 30Hz, synaptic depression occurred in the SNr; demonstrated by rapid attenuation of successive fEPs. Clinically, we determined that lower levels of SNr plasticity were related to higher severity axial and global motor symptoms, and that neuronal inhibition in the Vim was necessary for tremor suppression. These findings expand upon the understanding of the physiological stimulation response properties of different brain structures in movement disorders patients, and may have implications for advancing DBS technologies.
Deep brain stimulation (DBS) is an effective treatment for movement disorders, including Parkinson disease and essential tremor. However, the underlying mechanisms of DBS remain elusive. Despite the ...capability of existing models in interpreting experimental data qualitatively, there are very few unified computational models that quantitatively capture the dynamics of the neuronal activity of varying stimulated nuclei-including subthalamic nucleus (STN), substantia nigra pars reticulata (SNr), and ventral intermediate nucleus (Vim)-across different DBS frequencies.
Both synthetic and experimental data were used in the model fitting; the synthetic data were generated by an established spiking neuron model that was reported in our previous work, and the experimental data were provided using single-unit microelectrode recordings (MERs) during DBS (microelectrode stimulation). Based on these data, we developed a novel mathematical model to represent the firing rate of neurons receiving DBS, including neurons in STN, SNr, and Vim-across different DBS frequencies. In our model, the DBS pulses were filtered through a synapse model and a nonlinear transfer function to formulate the firing rate variability. For each DBS-targeted nucleus, we fitted a single set of optimal model parameters consistent across varying DBS frequencies.
Our model accurately reproduced the firing rates observed and calculated from both synthetic and experimental data. The optimal model parameters were consistent across different DBS frequencies.
The result of our model fitting was in agreement with experimental single-unit MER data during DBS. Reproducing neuronal firing rates of different nuclei of the basal ganglia and thalamus during DBS can be helpful to further understand the mechanisms of DBS and to potentially optimize stimulation parameters based on their actual effects on neuronal activity.
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