Microelectrode array stimulation combined with intrinsic optical imaging: A novel tool for functional brain mapping

Abstract

Background: Functional brain mapping via cortical microstimulation is a widely used clinical and experimental tool. However, data are traditionally collected point by point, making the technique very time consuming. Moreover, even in skilled hands, consistent penetration depths are difficult to achieve. Finally, the effects of microstimulation are assessed behaviorally, with no attempt to capture the activity of the local cortical circuits being stimulated.

New method: We propose a novel method for functional brain mapping, which combines the use of a microelectrode array with intrinsic optical imaging. The precise spacing of electrodes allows for fast, accurate mapping of the area of interest in a regular grid. At the same time, the optical window allows for visualization of local neural connections when stimulation is combined with intrinsic optical imaging.

Results: We demonstrate the efficacy of our technique using the primate motor cortex as a sample application, using a combination of microstimulation, imaging and electrophysiological recordings during wakefulness and under anesthesia. Comparison with current method: We find the data collected with our method is consistent with previous data published by others. We believe that our approach enables data to be collected faster and in a more consistent fashion and makes possible a number of studies that would be difficult to carry out with the traditional approach.

Conclusions: Our technique allows for simultaneous modulation and imaging of cortical sensorimotor networks in wakeful subjects over multiple sessions which is highly desirable for both the study of cortical organization and the design of brain machine interfaces.

Keywords: Cortical mapping; Functional tract tracing; Microstimulation; Optical chamber; Utah array.

Fig 1. Utah array within a chronically implanted optical window

(A) Approximate location of array implantation (black square) in the motor region of the macaque monkey brain. Red circle indicates the extent of the chronically implanted optical window. (B) Image of the array after insertion into the motor cortex. The electrodes are numbered as shown (1 to 96). (C) View of the array beneath the silicone optical window, the walls of which are marked with blue arrows. (D) A schematic side view of the imaging chamber. Legend: A- anterior, L-lateral, AS- arcuate sulcus, CS-central sulcus, PS- principal sulcus, M1- primary motor cortex, PMd, dorsal premotor cortex, PMv, ventral premotor cortex.

Fig 2. Somatotopy within motor cortex obtained using Utah array microstimulation

The array was injected in the region outlined by the black square, over monkey motor cortex, covering both the primary (M1) and dorsal pre-motor (PMd) regions. The location of the array was determined by aligning photographs taking before and after the implantation through a surgical microscope, using blood vessel patterns as markers. Colored dots represent the Utah array electrode locations which evoked movements of the contralateral forelimb, with the specific arm regions labeled below. The electrodes are numbered as in Fig. 1. The electrode site circled in red was stimulated during the imaging session shown in Fig. 3 and awake recording session in Fig. 4. The electrode site circled in green was stimulated during imaging session shown in Supplementary Fig. 1. A-anterior, L-lateral.

Fig 3. Imaging of local projections during Utah array stimulation

(A) Blood vessel map of the cortical region containing portions of M1, PMd and PMv. The Utah array was located over M1 and PMd (orange square). The imaging field of view included parts of M1 and PMv (blue square). Images from this field of view are shown in (B), (C) and (D). The array orientation is approximately the same as in Fig.2 but tilted slightly anti-clockwise. Red dot indicates the electrode being stimulated in (C) and (D). (B) Intrinsic optical signal image without stimulation (first frame subtracted) of M1 and PMv located lateral to the Utah array. (C) Blank-subtracted map of activation following stimulation of electrode indicated by red dot (elbow) in (A). Two dark areas, labeled as 1 and 2, show activation following stimulation, while region 3 does not. (D) Same map as (C). Pixels with significant changes in intrinsic optical signal shown in color (p<.05, paired T-test). Each area was isolated and used as a mask for ROI analysis. (E) Time course of average reflectance changes from each of ROI's 1 (blue, PMv), 2 (red, M1), and 3 (green, ROI overlying an area of no activation). Orange bar indicates the period (300 ms) of stimulation.

Fig 4. Awake recording via Utah array during reach and grab task

(A-C) and (E-G). Two examples of color-coded spike rates recorded by the Utah array during an awake reach and grab experiment, with the animal using the arm contralateral to the array. (I-K). An example of spike rates recorded when the animal was using the arm ipsilateral to the array. Three panels with integration times of 0.46 second are shown for each of the three movements, including rest (left), reach (middle) and return to rest (right). (D), (H) and (L) represent raster plots of the electrode outlined by the red square. The distance between each tick mark is one second. Stimulation of this electrode evoked movement of the elbow joint under anesthesia (Fig 2). Lettering below the raster plots indicate the location at which activity maps (A-C), (E-G) and (I-K) were recorded and the period when forelimb movement was observed is highlighted in pink. (M) Electrode sites which demonstrated increased firing rate during the reach and grab task with the contralateral arm (N=8 trials), compared to rest, color coded by levels of significance using a paired T-test.