A method for localizing microelectrode trajectories in the macaque brain using MRI

Abstract

Magnetic resonance imaging (MRI) is often used by electrophysiologists to target specific brain regions for placement of microelectrodes. However, the effectiveness of this technique has been limited by few methods to quantify in three dimensions the relative locations of brain structures, recording chambers and microelectrode trajectories. Here we present such a method. After surgical implantation, recording chambers are fitted with a plastic cylinder that is filled with a high-contrast agent to aid in the segmentation of the cylinder from brain matter in an MRI volume. The resulting images of the filled cylinder correspond to a virtual cylinder that is projected along its long axis - parallel to the trajectories of microelectrodes advanced through the recording chamber - through the three-dimensional image of the brain. This technique, which does not require a stereotaxic coordinate system, can be used to quantify the coverage of an implanted recording chamber relative to anatomical landmarks at any depth or orientation. We have used this technique in conjunction with Caret [Van Essen DC, Drury HA, Dickson J, Harwell J, Hanlon D, Anderson CH. An integrated software suite for surface-based analyses of cerebral cortex. J Am Med Inform Assoc 2001;8:443-59] and AFNI [Cox RW. AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res 1996;29:162-73] brain-mapping software to successfully localize several regions of macaque cortex, including the middle temporal area, the lateral intraparietal area and the frontal eye field, and one subcortical structure, the locus coeruleus, for electrophysiological recordings.

Figure 1

Current qualitative method using MRI to determine recording chamber position relative to desired anatomical target(s). The image is a coronal section of the head and neck of a rhesus macaque (image courtesy MN Shadlen, University of Washington and HHMI). A. Recording chamber and microelectrode grid (1 mm spacing; Crist Instruments, Inc, Hagerstown, MD) filled with saline. B. Intraparietal sulcus. This is the primary anatomical landmark used to identify the location of the lateral intraparietal area (LIP), which is located on the lateral bank of the sulcus. Approximate electrode trajectories can be estimated by extending a particular grid hole ventrally through the image of the brain. However, this technique is limited to orientations within this plane of section.

Figure 2

Recording chamber and plastic cylinder. The cylinder must fit snugly within the recording chamber so that the long axis of the cylinder is parallel to the long axis of the cylinder.

Figure 3

Calculating the three-dimensional projection of the recording chamber. A. Schematic of the cylinder (filled with an aqueous solution of CuSO₄) placed snugly in the recording chamber, shown in a three-dimensional Cartesian coordinate system (red axes). B. The head, recording chamber and cylinder are all imaged together, including multiple planes of section through the cylinder. C. All parallel planes of section that intersect the cylinder contain an image of an identical ellipse (planes that intersect <50% of the cross-sectional area on the ends of the cylinder are discarded). D. These ellipses are projected virtually through the rest of the brain image along a line that connects their center points, representing the central long axis of the recording chamber.

Figure 4

Estimates of error. All errors were stimulated by comparing a high-resolution (0.01 mm isotropic voxels) image of an ellipse of a random aspect ratio (between 1 and 2.5) and orientation (between 0 and 180°) to a sampled, corrupted version of the same ellipse (0.7 mm isotropic voxels; n=100 iterations per condition). A. Box-and-whisker plot (center lines are medians; boxes are interquartile ranges; lines extend to the most extreme values within 1.5 times the interquartile range; crosses are outliers) of coverage (percent of the high-resolution image covered by the sampled image) as a function of the signal-to-noise ratio (SNR) of the sampled image. For these simulations, cylinder diameter=20 mm. B. Box-and-whisker plot of coverage as a function of cylinder diameter; SNR=20. C. Error in the estimate of the center point of the high-resolution ellipse in one dimension (estimated using the sampled image) as a function of SNR; cylinder diameter=20 mm. D. Error in the estimate of the center point of the high-resolution ellipse in one dimension as a function of cylinder diameter; SNR=20. E. Standard deviation of the estimated location of the long axis of the cylinder corresponding to the high-resolution ellipses as a function of depth from the sampled ellipses. Lines correspond to different standard deviations in the estimates of the centers of the sampled ellipses (bottom-to-top are 0 to 0.1 mm in increments of 0.02). F. Standard deviation of the estimated location of the long axis of the high-resolution cylinder as a function of depth from the sampled ellipses. Lines correspond to different numbers of sampled ellipses (bottom-to-top are 2 to 10 in increments of 2). In E and F, errors in the estimates of the centers of the sampled ellipses increase with increasing depth.

Figure 5

Localizing area MT. In each panel, blue indicates cylinder coverage (diameter = 1.65 cm), green crosshairs and red spots in B and C indicate the predicted location of MT determined by registering the images to a publicly available atlas (Lewis and Van Essen, 2000; Van Essen and Dierker, 2007) and color codes shown at bottom indicate the number of recording sites at a given location classified as a “hit” or “miss” of MT based on physiological properties, including tuning for the direction of visual motion and restricted receptive fields in contralateral space (Allman and Kaas, 1971; Dubner and Zeki, 1971; Zeki, 1974). A. Volume render showing external surfaces of the head and recording chamber. B. Surface reconstruction of the left cortical hemisphere. C. Flat map of the left cortical hemisphere. D. Horizontal section. E. Sagittal section. F. Coronal section. G. Section taken perpendicular to the long axis of the recording chamber at a depth corresponding to the location of MT. Circles indicate penetrations that included at least one recording site that was classified as MT based on physiological properties; crosses indicate penetrations with no sites that were classified as MT. B and C were generated using Caret (Van Essen et al., 2001). A and D–G were generated using AFNI (Cox, 1996).

Figure 6

Localizing area LIP. In each panel, orange indicates cylinder coverage (diameter = 1.65 cm), green crosshairs and purple spots in B and C indicate the predicted location of LIP determined by registering the images to a publicly available atlas (Lewis and Van Essen, 2000; Van Essen and Dierker, 2007) and color codes shown at bottom indicate the number of recording sites at a given location classified as a “hit” or “miss” of LIP based on physiological properties, including spatially selective visual, delay and oculomotor responses (Gnadt and Andersen, 1988; Colby et al., 1996). A. Volume render showing external surfaces of the head and recording chamber. B. Surface reconstruction of the left cortical hemisphere. C. Flat map of the left cortical hemisphere. D. Horizontal section. E. Sagittal section. F. Coronal section. G. Section taken perpendicular to the long axis of the recording chamber at a depth corresponding to the location of LIP. Circles indicate penetrations that included at least one recording site that was classified as LIP based on physiological properties; crosses indicate penetrations with no sites that were classified as LIP. B and C were generated using Caret (Van Essen et al., 2001). A and D–G were generated using AFNI (Cox, 1996).

Figure 7

Localizing area FEF. In each panel, green indicates cylinder coverage (diameter = 1.65 cm), green crosshairs and blue spots in B and C indicate the predicted location of FEF determined by registering the images to a publicly available atlas (Lewis and Van Essen, 2000; Van Essen and Dierker, 2007) and color codes shown at bottom indicate the number of recording sites at a given location classified as a “hit” or “miss” of FEF based on physiological properties, including the ability to evoke saccadic eye movements with electrical microstimulation using <50 μA of current (Bruce et al., 1985). A. Volume render showing external surfaces of the head and recording chamber. B. Surface reconstruction of the right cortical hemisphere. C. Flat map of the right cortical hemisphere. D. Horizontal section. E. Sagittal section. F. Coronal section. G. Section taken perpendicular to the long axis of the recording chamber at a depth corresponding to the location of the FEF. Circles indicate penetrations that included at least one recording site that was classified as FEF based on physiological properties; crosses indicate penetrations with no sites that were classified as FEF. B and C were generated using Caret (Van Essen et al., 2001). A and D–G were generated using AFNI (Cox, 1996).

Figure 8

Localizing the LC. In each panel, yellow indicates cylinder coverage (diameter = 1.65 cm), green crosshairs indicate the estimated location of LC determined by physiological properties of neurons recorded at that site, including waveform shape, phasic responses to surprising stimuli, low-frequency continuous discharge and decreased activity during periods of drowsiness (Clayton et al., 2004; Rajkowski et al., 1998; Rajkowski et al., 2004). A. Section taken perpendicular to the long axis of the recording chamber at a depth corresponding to the estimated location of the LC. B. Sagittal section. IC, inferior colliculus; IV, IVth ventricle. C. Coronal section.