13 research outputs found
An Implantable Cranial Window Using a Collagen Membrane for Chronic Voltage-Sensitive Dye Imaging
Incorporating optical methods into implantable neural sensing devices is a challenging approach for brain–machine interfacing. Specifically, voltage-sensitive dye (VSD) imaging is a powerful tool enabling visualization of the network activity of thousands of neurons at high spatiotemporal resolution. However, VSD imaging usually requires removal of the dura mater for dye staining, and thereafter the exposed cortex needs to be protected using an optically transparent artificial dura. This is a major disadvantage that limits repeated VSD imaging over the long term. To address this issue, we propose to use an atelocollagen membrane as the dura substitute. We fabricated a small cranial chamber device, which is a tubular structure equipped with a collagen membrane at one end of the tube. We implanted the device into rats and monitored neural activity in the frontal cortex 1 week following surgery. The results indicate that the collagen membrane was chemically transparent, allowing VSD staining across the membrane material. The membrane was also optically transparent enough to pass light; forelimb-evoked neural activity was successfully visualized through the artificial dura. Because of its ideal chemical and optical manipulation capability, this collagen membrane may be widely applicable in various implantable neural sensors
Neural Activity during Voluntary Movements in Each Body Representation of the Intracortical Microstimulation-Derived Map in the Macaque Motor Cortex
<div><p>In order to accurately interpret experimental data using the topographic body map identified by conventional intracortical microstimulation (ICMS), it is important to know how neurons in each division of the map respond during voluntary movements. Here we systematically investigated neuronal responses in each body representation of the ICMS map during a reach-grasp-retrieval task that involves the movements of multiple body parts. The topographic body map in the primary motor cortex (M1) generally corresponds to functional divisions of voluntary movements; neurons at the recording sites in each body representation with movement thresholds of 10 ÎĽA or less were differentially activated during the task, and the timing of responses was consistent with the movements of the body part represented. Moreover, neurons in the digit representation responded differently for the different types of grasping. In addition, the present study showed that neural activity depends on the ICMS current threshold required to elicit body movements and the location of the recording on the cortical surface. In the ventral premotor cortex (PMv), no correlation was found between the response properties of neurons and the body representation in the ICMS map. Neural responses specific to forelimb movements were often observed in the rostral part of PMv, including the lateral bank of the lower arcuate limb, in which ICMS up to 100 ÎĽA evoked no detectable movement. These results indicate that the physiological significance of the ICMS-derived maps is different between, and even within, areas M1 and PMv.</p></div
Single-unit recordings in M1 and PMv during the motor task.
<p>(A–E) Examples of neurons whose firing rates changed during the task. The timing of responses was consistent with the movements of the body part represented in the recording site. Raster plots and firing rate histograms show examples of neuronal firing during the precision grip task, aligned to the time of HPR (dashed blue lines), in each body representation—digits (A), thumb (B), wrist (C), elbow/shoulder (D), and mouth (E)—of the intracortical microstimulation (ICMS) map in the primary motor cortex (M1). The red crosses, pink asterisks, and green diamonds in the raster plot indicate the times of approaching the target (AP), pulling the target out (PO), and bringing the hand to the mouth (HM), respectively, in each trial. (F–H) Examples of neuronal responses that did not correspond to the body representation on the ICMS map; a neuron in the digit representation that showed no modulation during the task (F), and neurons in the digit and mouth representations showed peak activity in the periods around HM (G) and AP (H), respectively. The higher threshold (HT) neurons shown in (F–H) were located at recording sites with movement thresholds of at least 15μA. (I) A raster plot and firing rate histogram showing examples of neuronal firing during the precision grip task, aligned to the time of HPR, in the ventral premotor cortex (PMv).</p
Difference of neural activity among neurons located at recording sites with different movement thresholds for intracortical microstimulation (ICMS).
<p>(A) Percentage of neurons in the digit representation of the ICMS map in the primary motor cortex (M1) activated during the grasping phase, 0 to +300 ms from the time of approaching the target (AP), of the precision grip task. (B) The median and interquartile range of normalized neuronal activities in the digit representation in the same period as (A). Both the percentage of activated neurons and normalized neuronal activity decreased as the movement threshold increased. The normalized neuronal activities for different movement thresholds were significantly different (<i>P</i> < 0.05, Kruskal–Wallis one-way ANOVA), and Dunn’s multiple comparisons test showed that the normalized neuronal activity for ≤5 μA was significantly greater than that for ≤50 μA (*<i>P</i> < 0.05). The numbers of neurons for ≤5 μA, ≤10 μA, ≤20 μA, ≤30 μA and ≤50 μA were 23, 40, 26, 22, and 22, respectively.</p
Experimental setup and the hand movements of the monkeys.
<p>(A) Sequence of photographs and drawings during a single trial of the reach-grasp-retrieval task. Panels 1, 2, 3, and 4 show the moments at which the monkey released a homepad (HPR), reached toward the target (AP), pulled the target out (PO), and brought its hand to its mouth (HM), respectively. The arrowheads in the photographs indicate the locations of the fingertip. The arrows in the drawings indicate the movement direction of the hand at HPR, AP, and PO, and that of the mouth at HM. (B, C) Schematic illustrations showing the precision grip (B) and power grip (C) tasks. In the precision grip task, the monkey retrieved a disk from a vertical slit aperture of the tube by grasping a small knob (7 × 7 × 7 mm in size), using a precision grip with the tips of its index finger and thumb. In the power grip task, the monkey retrieved a cylindrical apparatus (32 mm in diameter and 30 mm in length), using a power grip. (D) Activity of digit (digits: flexor digitorum superficialis) and shoulder muscles (el/sh: biceps brachii) during the precision (prec) and power (pow) grip tasks, aligned to the time of HPR. EMG was normalized to the maximum level of activity across two grasp types. Activity of proximal forelimb muscles increased around the time of HPR, and that of distal forelimb muscles increased during grasping of the object, 300–500 ms after HPR. The proximal forelimb muscles are more active during retrieval of the object, 500–1000 ms after HPR, than during the preceding period of grasping. (E, F) Sequential activation of the muscles of the forelimb and mouth during task performance. The box and whisker plots show the median, upper and lower quartiles, and 10th and 90th percentiles of the latencies (E) as well as the times of peak activity (F) relative to HPR. Both latency and peak activation time of the mouth muscle were significantly greater than those of the forelimb muscles, and the peak activation time of the digit muscle was significantly greater than that of the elbow/shoulder muscles (*<i>P</i> < 0.01, Mann–Whitney U-test). The black and white triangles indicate the median values of latency and time of peak activity for precision and power grip tasks, respectively.</p
Number of primary motor cortex (M1) neurons analyzed.
<p>Number of primary motor cortex (M1) neurons analyzed.</p
Sequential activation of neurons in each body representation of the ICMS map in M1 during task performance.
<p>(A, B) The box and whisker plots show the median, upper and lower quartiles, and 10th and 90th percentiles of the latencies (A) and the times of peak activity (B) relative to HPR of lower threshold (LT) neurons (located at recording sites with movement thresholds of 10 μA or less). Both latency and peak activation time of the neurons in the mouth representation were significantly greater than those in the forelimb representations, and the latency of the neurons in the digit representation was significantly greater than that in the wrist or elbow/shoulder representation (*<i>P</i> < 0.05, **<i>P</i> < 0.01, Mann–Whitney U-test). (C, D) The box and whisker plots show the median, upper and lower quartiles, and 10th and 90th percentiles of the latencies (C) as well as the times of peak activity (D) relative to HPR of higher threshold (HT) neurons (located at recording sites with movement thresholds of at least 15 μA). Both the latency and peak activation time of the neurons in the mouth representation were significantly greater than those in the forelimb representations (**<i>P</i> < 0.01, Mann–Whitney U-test). The black and white triangles indicate the median values of latency and time of peak activity for precision and power grip tasks, respectively.</p
Normalized neuronal activity for both precision and power grip tasks, aligned to the time of approaching the target (AP), in each body representation in the primary motor cortex (M1).
<p>(A) Digit representation. (B) Thumb representation. (C) Wrist representation. (D) Elbow/shoulder representation. The neuronal firing rate was normalized by subtracting the baseline firing rate and then dividing the resulting value by the maximum level of activity observed across the two grasp types for all periods. The asterisks and lines at the top of the graphs indicate the bins in which the normalized activities of lower threshold (LT) neurons (located at recording sites with movement thresholds of 10 μA or less) for precision grasping were higher than those for power grasping (<i>P</i> < 0.001, Mann–Whitney U-test). In the digit representation, a significant difference in normalized neuronal activity was observed between precision and power gripping during the grasping phase, and the difference was greater when only neurons in the thumb representation were analyzed. LT neurons in the elbow/shoulder representation showed higher normalized neuronal activity than did HT neurons during the period just before grasping (–100 to 0 ms from AP) for both precision and power grip tasks (<i>P</i> < 0.01, Mann–Whitney U-test).</p
Percentage of neurons in each body representation of the intracortical microstimulation (ICMS) map in the primary motor cortex (M1) activated during the course of the task.
<p>(A–D) Precision grip task. (E–H) Power grip task. Neuronal firing rates were aligned to the time of homepad release (HPR: A, E), approaching the target (AP: B, F), pulling the target out (PO: C, G), and bringing the hand to the mouth (HM: D, H). Each line color represents a different body representation, and the solid and dashed lines show the results of lower threshold (LT) and higher threshold (HT) neurons located at recording sites with movement thresholds of 10 μA or less, and at least 15 μA, respectively. The number of neurons in each category is shown in parentheses. Chi-square tests were performed to test the null hypothesis that there is no association between the body representation and percentage of neurons activated, not only among the five body representations—digits, thumb, wrist, elbow/shoulder, and mouth—but also the four forelimb representations, excluding the mouth. The asterisks and solid lines at the top of the graphs indicate bins in which LT neurons in each of five representations were differentially activated (<i>P</i> < 0.01, chi-square test). The red lines indicate the bins in which LT neurons in each forelimb representation (i.e., without the mouth representation) were differentially activated (<i>P</i> < 0.01, chi-square test). Similarly, the black triangles and dashed lines at the bottom of the graphs indicate the 10-ms bins in which HT neurons in each representation including the mouth and each forelimb representation were differentially activated (<i>P</i> < 0.01, chi-square test). This analysis shows that populations of LT neurons in each body representation were differentially activated during reach-grasp-retrieval movements.</p