Journal: The Journal of Neuroscience

Article Title: Direct Activation of Primary Motor Cortex during Subthalamic But Not Pallidal Deep Brain Stimulation

doi: 10.1523/JNEUROSCI.2480-19.2020

Figure Lengend Snippet: Location of Utah array and DBS leads. A, Utah arrays were placed over the arm area of the M1 (top). The image of Subject K was obtained end of study after perfusion; the image of Subject J was obtained intraoperatively. B, DBS lead locations in the STN and GPi with location of DBS leads in the STN and GPi in each subject. Contacts used for therapeutic stimulation shown in yellow. In both animals, we verified that DBS in STN and GPi contacts produced improvements in parkinsonian motor signs (Table 1). Th = thalamus, SN = substantia nigra, GPe = globus pallidus externus.

Article Snippet: Briefly, the location of the target nuclei was confirmed using extracellular microelectrode mapping and each animal was implanted targeting the STN and GPi with an 8-contact scaled-down version of human DBS leads (0.5 mm contact height, 0.5 mm inter-contact spacing, 0.625 mm diameter; NuMed).

Techniques: Produced

Journal: The Journal of Neuroscience

Article Title: Direct Activation of Primary Motor Cortex during Subthalamic But Not Pallidal Deep Brain Stimulation

doi: 10.1523/JNEUROSCI.2480-19.2020

Figure Lengend Snippet: Improvement in parkinsonian motor signs during acute STN and GPi DBS

Article Snippet: Briefly, the location of the target nuclei was confirmed using extracellular microelectrode mapping and each animal was implanted targeting the STN and GPi with an 8-contact scaled-down version of human DBS leads (0.5 mm contact height, 0.5 mm inter-contact spacing, 0.625 mm diameter; NuMed).

Techniques:

Journal: The Journal of Neuroscience

Article Title: Direct Activation of Primary Motor Cortex during Subthalamic But Not Pallidal Deep Brain Stimulation

doi: 10.1523/JNEUROSCI.2480-19.2020

Figure Lengend Snippet: M1 single-unit responses to acute STN and GPi DBS. A, Example recording traces from two channels at the onset of STN DBS. Channel 17 had two isolated cells: 17a decreased firing rate and 17b increased firing rate. Channel 75 had one isolated cell with antidromic firing response. B, Examples of peristimulus time raster plots aligned to DBS (or sham) pulses before, during, and after STN DBS illustrating the four main response categories based on firing rate and pattern: antidromic, suppression, excitation, and no change. C, Examples of peristimulus time raster plots demonstrating suppression, excitation, and no change responses before, during, and after GPi DBS. Antidromic activation of M1 was not observed with GPi DBS. D, Normalized peristimulus time histograms (firing rate relative to the mean pre-DBS period) are shown, illustrating the four response classifications used in this study. E, Pie charts illustrating the percentage of each response type in M1 during acute STN (left) and GPi DBS (right) for each animal. Antidromic firing in M1 was only observed during STN DBS, and in greater proportion in Subject K than in Subject J, whereas similar proportions of excitation and suppression were observed for each animal for either STN or GPi DBS.

Article Snippet: Briefly, the location of the target nuclei was confirmed using extracellular microelectrode mapping and each animal was implanted targeting the STN and GPi with an 8-contact scaled-down version of human DBS leads (0.5 mm contact height, 0.5 mm inter-contact spacing, 0.625 mm diameter; NuMed).

Techniques: Isolation, Activation Assay

Journal: The Journal of Neuroscience

Article Title: Direct Activation of Primary Motor Cortex during Subthalamic But Not Pallidal Deep Brain Stimulation

doi: 10.1523/JNEUROSCI.2480-19.2020

Figure Lengend Snippet: Strength of antidromic firing in M1 diminishes over time. A, Heat map illustrating the time course of the population PSTH of M1 cells that were antidromically activated during the first 50 s of STN DBS for both subjects. Before averaging, the PSTH of each cell was aligned to the time bin in the PSTH where firing was maximal, and firing rate normalized to the firing rate calculated over the first three time bins. Zero on the x-axis represents the time point of peak antidromic firing. PSTH were calculated in 2 s bins and for visualization a 5-point linear interpolation both x and y axes was performed. B, The percentage of cells with significant change in their peak PSTH firing rate [first 10 s vs the last 10 s, Wilcoxon rank sum (WRS) test, p < 0.05]. C, Time course of the population PSTH of cells whose responses to 15 and 80 Hz stimulation were tested in addition to 130 Hz.

Article Snippet: Briefly, the location of the target nuclei was confirmed using extracellular microelectrode mapping and each animal was implanted targeting the STN and GPi with an 8-contact scaled-down version of human DBS leads (0.5 mm contact height, 0.5 mm inter-contact spacing, 0.625 mm diameter; NuMed).

Techniques:

Journal: The Journal of Neuroscience

Article Title: Direct Activation of Primary Motor Cortex during Subthalamic But Not Pallidal Deep Brain Stimulation

doi: 10.1523/JNEUROSCI.2480-19.2020

Figure Lengend Snippet: The strength of antidromic activation of M1 cells was progressively diminished over 4 h of continuous STN. A, C, Composite scores based on the mUPDRS (y-axis) for Subjects K and J, respectively. X-axis represents the time of stimulation. mUPDRS scores are shown for Hours 1–3 but were not taken in Hour 4. Detailed scores for individual motor signs are presented in Table 2. B, D, Time course of cell population PSTH over 4 h of STN DBS in each animal is shown in the heat map (left). The percentage of cells with significant change in their peak PSTH firing rate [DBS onset vs 4 h DBS duration, Wilcoxon rank sum (WRS) test, p < 0.05] is shown in the pie charts (right). PSTH were calculated in 2 s bins and grouped into DBS onset (first 50 s of recording) and 1, 2, 3, and 4 h DBS time bins. Before averaging, the PSTH of each cell was aligned to the time bin in the PSTH where firing was maximal, and firing rate normalized to the firing rate calculated over the first three time bins.

Article Snippet: Briefly, the location of the target nuclei was confirmed using extracellular microelectrode mapping and each animal was implanted targeting the STN and GPi with an 8-contact scaled-down version of human DBS leads (0.5 mm contact height, 0.5 mm inter-contact spacing, 0.625 mm diameter; NuMed).

Techniques: Activation Assay

Journal: The Journal of Neuroscience

Article Title: Direct Activation of Primary Motor Cortex during Subthalamic But Not Pallidal Deep Brain Stimulation

doi: 10.1523/JNEUROSCI.2480-19.2020

Figure Lengend Snippet: Clinical ratings of parkinsonian animals before, during and after subacute STN DBS

Article Snippet: Briefly, the location of the target nuclei was confirmed using extracellular microelectrode mapping and each animal was implanted targeting the STN and GPi with an 8-contact scaled-down version of human DBS leads (0.5 mm contact height, 0.5 mm inter-contact spacing, 0.625 mm diameter; NuMed).

Techniques:

Journal: The Journal of Neuroscience

Article Title: Direct Activation of Primary Motor Cortex during Subthalamic But Not Pallidal Deep Brain Stimulation

doi: 10.1523/JNEUROSCI.2480-19.2020

Figure Lengend Snippet: Interspike interval (ISI) probability histograms illustrate that antidromic-classified cells had highly regular discharge patterns during DBS. A, Spike occurrences during STN DBS in two M1 cells from Subject K are shown in the top (2.5 s duration segment shown, each row = 0.5 s). Corresponding ISI probability histograms from the entire recording block are shown in the bottom, with Off-DBS ISI histograms shown for comparison. Prominent peaks corresponding to one and two times the DBS stimulation interstimulus period (∼7.7 ms) are evident. B, ISI probability histograms from 15 simultaneously recorded cells identified as antidromic (Subject K) displayed as a heat map. C, Proportion of antidromic-classified cells in subacute DBS sessions with ISI probability peaks at one or two times the DBS ISI (or other) based on recordings at early (<0.5 h on-DBS) and late (3–4 h on-DBS) in the on-DBS recording period.

Article Snippet: Briefly, the location of the target nuclei was confirmed using extracellular microelectrode mapping and each animal was implanted targeting the STN and GPi with an 8-contact scaled-down version of human DBS leads (0.5 mm contact height, 0.5 mm inter-contact spacing, 0.625 mm diameter; NuMed).

Techniques: Blocking Assay, Comparison

Journal: The Journal of Neuroscience

Article Title: Direct Activation of Primary Motor Cortex during Subthalamic But Not Pallidal Deep Brain Stimulation

doi: 10.1523/JNEUROSCI.2480-19.2020

Figure Lengend Snippet: Synchronization in populational unit activities decreased with therapeutic STN DBS. A, Spike synchronization scores for all simultaneously recorded M1 cells across multiple 4 h STN DBS stimulation days (color coded) in both animals are shown as mean ± SD. Results of one-way ANOVA test for each session are shown in the tables (top). Following a significant one-way ANOVA test result, Dunnett's test with control = PRE (*p < 0.05) was performed for the sessions that had awake rest data in the PRE-DBS condition (2 for Subject K and 5 for Subject J), showing significant reduction of spike synchronization during STN DBS in each day. B, Combined spike synchronization scores (mean ± SD) from all the stimulation days that had the PRE-DBS condition are reduced during therapeutic STN DBS for both NHPs (mixed-model ANOVA, Subject K: F(6,9966) = 5.2, p = 0.028, 2 d; Subject J: F(6,22780) = 8.1, p < 0.0001, 5 d; followed by Dunnett's test with control = PRE (*p < 0.05). The combined spike synchronization scores for the first and second hours post-DBS returned to the pre-DBS level (Dunnett's test with control = PRE, p > 0.05).

Article Snippet: Briefly, the location of the target nuclei was confirmed using extracellular microelectrode mapping and each animal was implanted targeting the STN and GPi with an 8-contact scaled-down version of human DBS leads (0.5 mm contact height, 0.5 mm inter-contact spacing, 0.625 mm diameter; NuMed).

Techniques: Control

Journal: The Journal of Neuroscience

Article Title: Direct Activation of Primary Motor Cortex during Subthalamic But Not Pallidal Deep Brain Stimulation

doi: 10.1523/JNEUROSCI.2480-19.2020

Figure Lengend Snippet: Pairwise spike synchronization of simultaneously recorded unit activities pre, during and post-therapeutic STN DBS in both NHPs. A, Averaged matrix illustration of the pattern of cell–cell synchronization changes with STN DBS from the first stimulation day in each animal. Matrices were generated based on the synchronization score calculated for each pair of cells. Fourteen (of 54) and four (of 30) antidromic classified neurons were identified in Subjects K and J, respectively, in these examples. Different pairs including antidromic to antidromic (Anti–Anti), antidromic to non-antidromic (Anti–NonAnti), non-antidromic to non-antidromic (NonAnti–NonAnti) neurons are labeled as shown in the left matrix pattern. B, Pairwise spike synchronization from all the stimulation days that had awake rest data in the PRE-DBS condition (2 for Subject K and 5 for Subject J) for different groups (Anti–Anti, Anti–NonAnti and NonAnti–NonAnti) are shown. Anti–NonAnti pairwise spike synchronization was reduced by STN DBS in both subjects, whereas NonAnti–NonAnti spike synchronization was only reduced in Subject K. Anti-Anti spike synchronization did not change except for an increase at the first hour on STN DBS in Subject K. Wilcoxon test followed by Steel's test with control = PRE. *p < 0.05. C, Proportion of cell pairs with increased or decreased cell–cell spike synchronization scores, comparing pre-DBS period to fourth hour on-DBS, in all cell pairs (top) and in different groups (bottom).

Article Snippet: Briefly, the location of the target nuclei was confirmed using extracellular microelectrode mapping and each animal was implanted targeting the STN and GPi with an 8-contact scaled-down version of human DBS leads (0.5 mm contact height, 0.5 mm inter-contact spacing, 0.625 mm diameter; NuMed).

Techniques: Generated, Labeling, Control