Behavioral and neurophysiological effects of delayed training following a small ischemic infarct in primary motor cortex of squirrel monkeys

Abstract

A focal injury within the cerebral cortex results in functional reorganization within the spared cortex through time-dependent metabolic and physiological reactions. Physiological changes are also associated with specific post-injury behavioral experiences. Knowing how these factors interact can be beneficial in planning rehabilitative intervention after a stroke. The purpose of this study was to assess the functional impact of delaying the rehabilitative behavioral experience upon movement representations within the primary motor cortex (M1) in an established nonhuman primate, ischemic infarct model. Five adult squirrel monkeys were trained on a motor-skill task prior to and 1 month after an experimental ischemic infarct was induced in M1. Movement representations of the hand were derived within M1 using standard electrophysiological procedures prior to the infarct and again one and two months after the infarct. The results of this study show that even though recovery of motor skills was similar to that of a previous study in squirrel monkeys after early training, unlike early training, delayed training did not result in maintenance of the spared hand representation within the M1 peri-infarct hand area. Instead, delaying training resulted in a large decrease in spared hand representation during the spontaneous recovery period that persisted following the delayed training. In addition, delayed training resulted in an increase of simultaneously evoked movements that are typically independent. These results indicate that post-injury behavioral experience, such as motor skill training, may modulate peri-infarct cortical plasticity in different ways in the acute versus chronic stages following stroke.

Figures

Fig. 1

Motor skill performance associated with ICMS maps of hand representations in M1 were acquired for five squirrel monkeys that were trained on a motor skill task prior to an ischemic infarct, after 1 month of spontaneous recovery from the infarct and again after approximately 1 month of training (~2 mos. post-infarct)

Fig. 2

a A magnified digital photograph of the surface of the cerebral cortex of a squirrel monkey brain after ICMS mapping. Each penetration site is marked with a filled, colored circle. Red, digit movements, Green, wrist–forearm movements, Blue, arm movements proximal to the forearm, and Black, non-responsive areas. Intended lesion is outlined within the mapped hand area. b Cortical regions with similar movement representations were delineated on a two dimensional representation of the M1 hand area. Borders were established between adjacent movement representations midway between microelectrode penetration sites using customized software. Color codes are the same as in a plus additional codes: yellow, digit/(wrist–forearm), light blue, digit/proximal and magenta, (wrist–forearm)/proximal

Fig. 3

a Alterations in spared M1 hand area were analyzed 1 month after spontaneous recovery and 1 month after delayed training in the same monkeys. For each movement representation, and in each map, changes in M1 were described as the percentage change in area compared to the baseline condition. After 1 month of spontaneous recovery, total hand and digit representations were significantly reduced compared to baseline (indicated by asterisks). The reduction in hand area persisted after delayed training except for dual response representations that increased compared to spontaneous recovery maps (indicated by S). b Data from Nudo et al. 1996b showing alterations in spared M1 hand area analyzed after 1 month of early training that was implemented within 1 week after a cortical infarct in the M1 hand area. Early training was more beneficial than delayed training for maintaining distal hand area in M1 adjacent to the ischemic infarct, and did not result in a significant increase in dual responses above baseline values

Fig. 4

The minimum stimulus necessary to evoke a movement via ICMS in motor cortex was defined for each movement (stimulus threshold). Stimulus thresholds did not change from baseline after spontaneous recovery or delayed training. Pooled across conditions, the average threshold was below 20 μA, the average dual responses thresholds were significantly lower than average distal hand response thresholds (digit or wrist) or proximal arm thresholds

Fig. 5

Improvements in motor performance associated with the proportion of wrist–forearm dual response representations within the peri–infarct hand area of M1 in post–training maps. Monkeys from both the delayed (present study) and early training (Nudo et al. 1996) studies were combined for a linear regression analysis. A negative correlation is shown between improved performance and increases in wrist–forearm/proximal dual response area (r2=−0.72, P=0.008)

Fig. 6

Average percentage of digit, wrist–forearm and dual responses comprising post-infarct map after delayed training. The average total M1 hand area after delayed training = 4.69 mm2. The average number of penetration sites = 271.8. The average distal hand area is composed of 18.8 digit sites, 35.0 wrist–forearm sites, 3.4 wrist–forearm/proximal sites, 2.8 digit/wrist–forearm sites, and 2.2 digit/proximal sites. The remaining penetration sites included 89.2 proximal sites and 119.8 non-responsive sites