Implantable microcoils for intracortical magnetic stimulation

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Science Advances  09 Dec 2016:
Vol. 2, no. 12, e1600889
DOI: 10.1126/sciadv.1600889
  • Fig. 1 Micrometer-sized microcoils generate suprathreshold fields.

    (A) Surface (middle) plot of the electric field gradients in the x direction (dEx/dx) arising from the 500-μm square coil on the left (red). Note that the horizontally oriented peaks in the surface plot indicate the peak gradients in a direction normal to the cortical surface, that is, up and down in the cortical column representation on the left. Right: Two-dimensional profile of the gradients in the vertical (dEx/dx, top) and horizontal (dEz/dz, bottom) directions; the “0” on the abscissa corresponds to the bottom right corner of the coil. The horizontal lines indicate estimated threshold levels from earlier studies with much larger coils (see text). Dashed vertical lines indicate the width of the suprathreshold region. (B) Similar to (A), except for a 100-μm trapezoidal coil.

  • Fig. 2 Area of suprathreshold field expands as current amplitude increases.

    (A) Plots of the electric fields (middle) and the field gradients (right) arising from the microcoil (left) in the x direction (dEx/dx) along the x axis for three different vertical cross sections through the coil. The red dashed lines in the gradient plot indicate estimated threshold levels from earlier studies with transcranial magnetic stimulation coils (see text). (B) Plots of the electric fields (middle) and the spatial gradients (bottom) in the x direction (dEx/dx) along the y axis for three horizontal cross sections. (C) Extracted portion of the field gradient profiles for different amplitudes along the x axis for values of x ≥ 0. (D) Similar to (C), but for the field gradients along the y axis for values of y ≤ 0. (E) Contour plots of suprathreshold gradient areas for different current amplitudes.

  • Fig. 3 Microcoils activate cortical PNs in vitro.

    (A) Schematic of the microfabricated coil consisting of a copper trace (red) on a silicon substrate (yellow). (B) Illustration of the bent-wire microcoil. The 50-μm copper wire (red) is surrounded by 5-μm polyurethane/polyamide insulation. (C) Responses to subthreshold (left) and suprathreshold stimulation (right) in the presence of synaptic blockers (top traces) and with TTX added (bottom traces). The blue curves were computed by subtracting the TTX traces from the corresponding traces in the top panels. The asterisk indicates the evoked action potential. (D) Action potentials (APs) could also be extracted without the use of TTX by subtracting a response without a presumed spike (artifact only) from a response with a spike; the black trace is such a spike [different cell from (C)]. A spontaneous spike from the same cell is overlaid (green). (E) Schematic of the in vitro experimental setup. A cell-attached patch electrode was used to record from the soma of an L5 PN in response to stimulation from the microcoil; the long axis of the coil could be positioned either normal to (top) or parallel to the slice surface (bottom). In all cases, the tip of the coil was positioned over the proximal axon. The red dashed and solid horizontal arrows represent weak and strong (respectively) electric fields induced along the length of the axon. AIS, axon initial segment. (F) Typical responses for each orientation. Stimulation was delivered at a rate of 100 Hz; the stimulus artifact indicates the timing of each pulse. The prominent after-hyperpolarizations seen following each pulse in the bottom traces are reliable indicators of elicited spikes. (G) Probability of eliciting an action potential as a function of stimulation current amplitude for control artificial cerebrospinal fluid (aCSF) (left, n = 7 cells) and with synaptic blockers added (right, n = 4 cells). (H) Onset latencies of evoked spikes were plotted for 10 consecutive pulses delivered at 100 Hz in 11 individual neurons. All spikes were elicited within 0.3 to 0.7 ms after onset of the stimulus. (I) Same as (H), but with synaptic blockers added to the perfusion bath (n = 4 cells). (J) Schematic of the experimental setup showing the coil positioned over the apical dendrites in either a perpendicular (top) or a parallel orientation (bottom). (K) Typical responses to apical dendrite stimulation for each orientation. The red horizontal bar indicates the duration over which stimulation was applied.

  • Fig. 4 Comparison of spatial extent of excitation.

    (A) Light microscope photograph of a microelectrode situated over a V1 coronal slice from Thy1-GCaMP6f transgenic mice. The somas of individual neurons from L5 can be observed. (B) The change in fluorescence in response to three different levels of stimulation from an electrode. The tip of the electrode is seen as a downward-pointing triangle at the top of each image. The yellow triangle and the dashed line indicate the approximate orientation of cortical columns. (C) Similar to (A), showing the microcoil implanted over the V1 slice. The approximately semicircular tip of the coil is seen at the top of the image. (D) The change in fluorescence in response to three different levels of magnetic stimulation. (E) A region of interest (ROI) was defined for individual PNs on the basis of the somatic outline and used to calculate the cellular calcium fluorescence transients in each cell. Red neurons show strong calcium transients (ΔF/F >5%); yellow and green neurons indicate moderate (ΔF/F > 3%) and weak calcium transients (ΔF/F > 1%), respectively. Blue neurons indicate no observable increase in calcium fluorescence. (F) Schematic diagram illustrating the region over which PNs are predicted to be activated by stimulation from the coil. The proximal axon of PNs at location A (blue soma) is aligned with the region for which the induced field gradient (along the length of the neuron) is suprathreshold (yellow circular region); the apical dendrites of other neurons (location B, red soma) also extend into the suprathreshold region and become activated as well; and the processes of neurons that do not extend into the strong gradient region (location C, green soma) do not become activated. (G) Average calcium transient responses for the L5 PNs depicted in (F).

  • Fig. 5 Implanted microcoils activate neuronal circuits in vivo.

    (A) Stimulus waveforms consisted of 5 pulses delivered at 10 Hz or 10 pulses delivered at 100 Hz. Each pulse consisted of one full period of a 3-kHz sinusoid with an amplitude of 112 mV. (B) Left: Coils were inserted into the whisker motor cortex (left hemisphere). Ten-hertz stimulation resulted in protraction of whiskers (upward deflections) on the right side (top), whereas 100-Hz stimulation induced retraction (downward deflections) (bottom). (C) Illustration of the approximate location for coil insertion to simulate the whisker sensory cortex. Both 10- and 100-Hz stimulation resulted in whisker retraction (top and bottom panels on the right). (D) Mean amplitudes of peak whisker movements for each stimulus condition. (E) Mean latency for the onset of whisker movements for each stimulus condition.

  • Fig. 6 Continuous stimulation induces whisker movement at reduced power levels.

    (A) Schematic illustration of the repetitive stimulation waveforms. Each “pulse” was a single 3-kHz sinusoid. (B) Averaged whisker movement in response to repetitive stimulation at power levels of 11.2 mV (0.75 mA). (C) Average whisker movements for each waveform (upward denotes protraction; downward indicates retraction).

Supplementary Materials

  • Supplementary Materials

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    • fig. S1. Power consumption levels for microcoils and other stimulation modalities.
    • References (55–58)

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