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

Abstract

Because compensatory changes in brain activity underlie functional recovery after brain damage, monitoring of these changes will help to improve rehabilitation effectiveness. Functional nearinfrared spectroscopy (fNIRS) has the potential to measure brain activity in freely moving subjects. We recently established a macaque model of internal capsule infarcts and an fniRS system for use in the monkey brain. Here, we used these systems to study motor recovery in two macaques, for which focal infarcts of different sizes were induced in the posterior limb of the internal capsule. Immediately after the injection, flaccid paralysis was observed in the hand contralateral to the injected hemisphere. Thereafter, dexterous hand movements gradually recovered over months. After movement recovery, task-evoked hemodynamic responses increased in the ventral premotor cortex (PMv). The response in the PMv of the infarcted (i.e., ipsilesional) hemisphere increased in the monkey that had received less damage. In contrast, the PMv of the non-infarcted (contralesional) hemisphere was recruited in the monkey with more damage. A pharmacological inactivation experiment with muscimol suggested the involvement of these areas in dexterous hand movements during recovery. These results indicate that fNIRS can be used to evaluate brain activity changes crucial for functional recovery after brain damage.Neuronal motor systems have the capacity for functional recovery following brain damage such as that induced by stroke, and functional recovery can be enhanced by postlesion rehabilitative training 1,2 . Compensatory activity changes in the brain areas that remain undamaged are thought to underlie functional recovery 1,3-16 . Therefore, it is important to monitor brain activity during rehabilitative training to determine whether the training is actually inducing appropriate brain activity changes. Clinical studies in human stroke patients, as well as experimental studies in animals in which damage is artificially induced in a specific region in the brain, have helped to elucidate the compensatory changes of brain activity that occur during the course of functional recovery 1,7-10,17 .We previously established a macaque model for inducing artificial damage in brain regions involved in the transduction of motor commands 2,18,19 . The motor cortex and corticospinal tract of macaque monkeys are more comparable to those of humans than are those of other animals used in experimental research (see ref. 20 . for review). This motor system homology with that of humans, in combination with the relatively large macaque brain, makes imaging data obtained in macaque monkeys comparable to data obtained in clinical research. Therefore, studying macaque models of brain damage can facilitate the translation of findings to stroke patients.Brain damage related to hand functionality can greatly affect the quality of human life and is therefore an important area of study. Using H 2 15 O-positron emission tomography (PET) scans in macaque monkeys, we previously showe...

Non-human Primate Models to Explore the Adaptive Mechanisms After Stroke

“…The results of brain imaging studies, in which activity changes during motor recovery and CPSP development are consistent between macaque stroke models and stroke patients as described above (Loubinoux et al, 2007;Horn et al, 2016;Kato et al, 2020b), may indicate the high translational potential of the primate models. Notably, however, the brains of non-human primates are still different from human brains.…”

“…The cortex contralateral to the stroke plays a greater role in recovery when lesions are more severe (E) . Reproduced from Figures 2, 4 of the study by Kato et al (2020b) .…”

“…A recent study used the macaque model of internal capsular infarcts to report compensatory changes in motor cortical activity during voluntary movements ( Figures 1B,C ) ( Kato et al, 2020b ). Similar changes in motor cortical activity have also been reported in stroke patients during motor recovery ( Loubinoux et al, 2007 ; Horn et al, 2016 ); therefore, the macaque internal capsular infarct model is thought to reproduce the plastic neural changes that occur in stroke patients.…”

Contralateral and Ipsilateral Interactions in the Somatosensory Pathway in Healthy Humans

“…Additionally, functional motor representation maps around the damage and remote cortical regions change with rehabilitative motor training after focal damage in the forelimb movement area of the motor cortex (Nudo et al, 1996;Frost et al, 2003;Ramanathan et al, 2006;Barbay et al, 2013). These studies suggest that a pathway normally suppressed and preserved in the course of development may participate in the control of the paretic limb to adapt to changes in the internal environment (Murata et al, 2015;Isa, 2017Isa, , 2019Isa et al, 2019;Yamamoto et al, 2019;Kato et al, 2020).…”

Interaction of the Left–Right Somatosensory Pathways in Patients With Thalamic Hemorrhage: A Case Report

“…In addition, the functional motor representation maps around the damage and remote cortical regions change with rehabilitative motor training after focal damage in the forelimb movement area of the motor cortex ( Nudo et al, 1996 ; Frost et al, 2003 ; Ramanathan et al, 2006 ; Barbay et al, 2013 ). These studies suggest that an unusual neural route is created, which then controls the paretic limb ( Murata et al, 2015 ; Isa, 2017 ; Yamamoto et al, 2019 ; Kato et al, 2020 ). Conversely, no compensatory mechanism for sensory information processing after damage to the somatosensory pathway has been identified.…”