Functional near-infrared-spectroscopy-based measurement of changes in cortical activity in macaques during post-infarct recovery of manual dexterity

Figures

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  Figure 1. Experimental design and placement of optodes. (a) The experimental design. After implantation of optode sockets, the animals were trained on the Klüver board task (shown in the image at the right) and the vertical slit task. We first measured hemodynamic responses evoked during the Klüver task with fNIRS before infarction. Focal infarcts were then induced by local injection of endothelin-1 into the posterior limb of the internal capsule. After the recovery of dexterous hand movements with postlesion motor training, the hemodynamic response evoked during a small-object retrieval task (Klüver board or vertical slit) was again measured with fNIRS. A pharmacological inactivation experiment was performed by using muscimol, a gamma-aminobutyric acid receptor agonist. MRI scans were performed to decide on and confirm the arrangement of optode sockets, to decide on the stereotaxic coordinates for the endothelin-1 injection, and to evaluate the size of the infarcts. Finally, the brain damage caused by the infarcts and the locations of the muscimol injections were confirmed histologically in Nissl-stained brain sections. (b) The arrangement of fNIRS optodes on the skull surfaces of the…

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  Figure 2. Hemodynamic responses before infarction. (a,c) Time-course curves of paired t-values of hemodynamic response in Monkeys 1 (a) and 2 (c) before infarction. The t-values for the paired t-test were calculated from the difference in hemodynamics during trials of left-hand and right-hand use in the session, using a food well with a diameter of 10 mm. The t-values of changes in oxygenated (ΔHbO) and deoxygenated (ΔHbR) hemoglobin in each channel (indicated by the numbers in each frame) are drawn with red and blue lines, respectively. The horizontal dotted lines in each frame indicate levels of p = 0.0001. The horizontal axis indicates time from the onset of the retrieval movement (vertical dashed line). The locations of the fNIRS optodes are indicated by gray circles with probe numbers (PR). (b,d) Color-mapping of t-values onto the anatomical MRIs for Monkeys 1 (b) and 2 (d). The t-values for ΔHbO around 5.0 s (for Monkey 1) and 5.5 s (for Monkey 2) after task onset are depicted. Amplitudes of t-values at most channels were maximal at this time. Arrowheads indicate the positions of the “hand knob” in M1 in the left hemisphere.

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  Figure 3. Extent of infarcts and behavioral recovery. (a,e) Axial T2-weighted MR images of the brains of Monkeys 1 (a) and 2 (e), showing the locations of the infarcts 1 month after endothelin-1 injection. The yellow squares indicate the areas shown in (b,f). (b,f) Higher-magnification MR images around the infarcts. The violet dotted lines indicate the anterior two-thirds of the posterior limb of the internal capsule, which contains fibers of the corticospinal tract. The magenta solid lines indicate the hypointense infarct core; T2-hyperintense cystic lesions were also found in Monkey 2. (c,g) Nissl-stained coronal sections made from the anterior two-thirds of the posterior limb of the internal capsule after the completion of the fNIRS measurements and pharmacological inactivation experiment. The area bordered by the violet dotted lines indicates the internal capsule (IC). The magenta solid lines indicate the lesioned area, which is defined as the area of a dense concentration of small cells (5–10 μm in diameter), which presumably include both glial cells and blood cells. The images were acquired with a microscope (BX60, Olympus, Tokyo, Japan) equipped with a 3CCD color video camera…

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  Figure 4. Hemodynamic changes with hand use after recovery. (a,c) Time-course curves of paired t-values of the hemodynamic response in Monkeys 1 (a) and 2 (c) after recovery of dexterous hand movements after infarction. The t-values for the paired t-test were calculated from the difference in hemodynamics during trials of left-hand and right-hand use in the session using a food well with a diameter of 10 mm. The t-values of ΔHbO and ΔHbR in each channel are drawn with red and blue lines, respectively. The horizontal dotted lines in each frame indicate levels of p = 0.0001. The horizontal axis indicates time from the onset of the retrieval movement (vertical dashed line). The locations of fNIRS optodes are shown by gray circles with probe numbers (PR). (b,d) Color-mapping of t-values onto the anatomical MR images of Monkeys 1 (b) and 2 (d). The t-values for ΔHbO around 3.5 s (for Monkey 1) and 2.0 s (for Monkey 2) after task onset are depicted. Amplitudes of t-values at most channels were maximal at these times. Arrows indicate the positions of the PMv in the left (b) and right hemispheres (d).

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  Figure 5. Interaction effects between infarction and hand. (a,c) Two-way MANOVA was applied to the data presented in Figs. 2 and 4 to find interaction effects between infarction (Pre/Post) and the hand used (Left/Right). Time-course curves of the interaction effects in Monkeys 1 (a) and 2 (c) are shown. The F-values of ΔHbO and ΔHbR in each channel are drawn with red and blue lines, respectively. The dotted lines in each frame indicate levels of p = 0.0001. The horizontal axis indicates time from the onset of the retrieval movement (vertical dashed lines). Locations of fNIRS optodes are shown by gray circles with probe numbers (PR). The red-highlighted frames indicate sites with high interaction effects, which we selected for muscimol injection. (b,d) Changes of the interaction effect depending on the size of the food well at channels 8 (red) and 16 (gold) in Monkey 1(b) and at channel 11 in Monkey 2 (d).

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  Figure 6. Effects of inactivating PMv on the performance of dexterous hand movements. (a–c) Muscimol injections into the ipsilesional (left) PMv of Monkey 1 resulted in a significant deficit of the right hand in performing the Klüver board task with well diameters of 11 or 10 mm, but not 20 mm. (d,e) Muscimol injections into the contralesional (right) PMv of Monkey 2 resulted in a significant deficit of the right hand in performing the vertical slit task (d), whereas muscimol injections into the ipsilesional (left) PMv did not significantly change performance for either hand (e). *p < 0.05, **p < 0.01, Fisher’s exact test. (f) Representative Nissl-stained section showing brain microinjection sites in the contralesional PMv of Monkey 2. The dotted lines with arrows indicate the estimated spread of muscimol. The muscimol injection was also confirmed in the ipsilesional PMv of both monkeys in the same manner. The image was acquired with a microscope (BX60, Olympus, Tokyo, Japan) equipped with a 3CCD color video camera (DHC-950, Sony, Tokyo, Japan) and digitized with an image analysis system (version 2019.1.1, Stereo Investigator, MBF Bioscience Inc., Williston, VT, USA. URL…