Functional preservation and enhanced capacity for visual restoration in subacute occipital stroke

Abstract

Stroke damage to the primary visual cortex (V1) causes a loss of vision known as hemianopia or cortically-induced blindness. While perimetric visual field improvements can occur spontaneously in the first few months post-stroke, by 6 months post-stroke, the deficit is considered chronic and permanent. Despite evidence from sensorimotor stroke showing that early injury responses heighten neuroplastic potential, to date, visual rehabilitation research has focused on patients with chronic cortically-induced blindness. Consequently, little is known about the functional properties of the post-stroke visual system in the subacute period, nor do we know if these properties can be harnessed to enhance visual recovery. Here, for the first time, we show that 'conscious' visual discrimination abilities are often preserved inside subacute, perimetrically-defined blind fields, but they disappear by ∼6 months post-stroke. Complementing this discovery, we now show that training initiated subacutely can recover global motion discrimination and integration, as well as luminance detection perimetry, just as it does in chronic cortically-induced blindness. However, subacute recovery was attained six times faster; it also generalized to deeper, untrained regions of the blind field, and to other (untrained) aspects of motion perception, preventing their degradation upon reaching the chronic period. In contrast, untrained subacutes exhibited spontaneous improvements in luminance detection perimetry, but spontaneous recovery of motion discriminations was never observed. Thus, in cortically-induced blindness, the early post-stroke period appears characterized by gradual-rather than sudden-loss of visual processing. Subacute training stops this degradation, and is far more efficient at eliciting recovery than identical training in the chronic period. Finally, spontaneous visual improvements in subacutes were restricted to luminance detection; discrimination abilities only recovered following deliberate training. Our findings suggest that after V1 damage, rather than waiting for vision to stabilize, early training interventions may be key to maximize the system's potential for recovery.

Keywords: hemianopia; perceptual learning; rehabilitation; training; vision.

© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1

Baseline Humphrey visual field composite maps, MRIs and testing/training locations in subacute participants. Grey scale denoting Humphrey-derived visual sensitivity is provided under the right-most column. MRI type [T1, diffusion-weighted imaging (DWI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR)] is indicated on radiographic images, which are shown according to radiographic convention (left brain hemisphere on image right). Red circles = CDDI training locations; yellow circles = putative training locations in untrained controls, which were only pre- and post-tested; blue circles = locations tested at baseline in subacutes who were used in a separate training study (designated ‘other’ training type in Table 1).

Figure 2

Baseline Humphrey visual field composite maps, structural (T1) MRI and training locations in chronic participants. Grey scale denoting Humphrey-derived visual sensitivity is provided under right-most column. MRIs are shown according to radiographic convention with left brain hemisphere on image right (L). Red circles = CDDI training locations. Data from these chronic subjects were previously published (Cavanaugh and Huxlin, 2017).

Figure 3

Measuring and retraining vision in subacute and chronic stroke. Trial sequences for psychophysical tasks measuring (A) CDDI, (B) FDD, (C) contrast sensitivity for direction and (D) static orientation discrimination.

Figure 4

Preserved visual discrimination abilities in subacute but not chronic cortically-blind fields. (A) Plot of individual baseline FDD thresholds at blind-field training locations and corresponding, intact-field locations in patients with chronic and subacute cortically-induced blindness. Bars indicate means ± SD. Baseline FDD was unmeasurable in all chronics and two-thirds of subacutes, but measurable in one-third of subacutes. Patient CB15 is included in both subacute categories because of this hemianope’s ability to discriminate FDD in one blind-field quadrant but not the other, illustrating heterogeneity of perception across cortically-blind fields. As a group, subacutes’ baseline FDD thresholds were better than chronics’ [one-sample t-test versus mean of 90°, t(18) = 3.08, P = 0.0064]. However, subacutes with preserved FDD had worse thresholds than in their own intact hemifields [paired t-test, t(6) = 4.09, P = 0.0064]. (B) Plot of baseline CDDI at blind- and corresponding intact-field locations in patients with chronic and subacute cortically-induced blindness, stratified by preservation of blind-field FDD. Three subacutes with preserved blind-field FDD had measurable CDDI thresholds, a phenomenon never observed in chronics. (C) Baseline contrast sensitivity functions for direction discrimination in the blind and intact fields of subacutes (datapoints = mean ± SEM); light blue lines denote contrast sensitivity functions of participants with preserved blind-field sensitivity (significant in n = 5, P < 0.005; in the sixth subject, P = 0.16, see ‘Materials and methods’ section for bootstrap analysis). Group t-tests were performed at each spatial frequency: *P < 0.05, #P < 0.10. There were significant effects for peak contrast sensitivity [t(14) = 2.38, P = 0.016] and total area under the contrast sensitivity function [t(14) = 2.10, P = 0.027] (D) Baseline contrast sensitivity functions for orientation discrimination in subacutes. Labelling conventions as in C. Statistics for peak contrast sensitivity and area under the contrast sensitivity function: t(13) = 1.5, P = 0.079 and t(13) = 1.62, P = 0.065, respectively.

Figure 5

Trained subacutes recover direction integration faster and deeper than chronics. (A) Training data for representative patients with chronic and subacute cortically-induced blindness. (B) Plot of individual CDDI thresholds at training locations pre- and post-testing. Bars indicate mean ± SD. Two-way repeated measures ANOVA for group (chronics, trained subacutes, untrained subacutes) across locations (pre-training blind field, post-training blind field, intact field) was significant: F(4,48) = 37.11, P < 0.0001. Post hoc Tukey’s multiple comparisons tests within group are shown on graph. (C) Plot of the number of training sessions to reach normal CDDI thresholds in the blind field. Bars indicate mean ± SD. Chronics required significantly more training sessions than trained subacutes: unpaired t-test t(20) = 4.98, P < 0.0001. (D) Plot of initial CDDI threshold at location 1° deeper into the blind field than trained/tested location. Bars indicate mean ± SD. Only trained subacutes had measurable thresholds deeper than the trained blind-field location. (E) Plot of degrees of visual angle by which random dot stimulus could be moved deeper into the blind field than the last training/testing location, while still able to attain a measurable CDDI thresholds. All trained subacutes had measurable CDDI thresholds deeper into the blind field, something never observed in chronic or untrained subacutes. Bars indicate mean ± SD. Two trained subacutes were not included because of the extent of recovery exceeding our ability to measure depth in the blind field. One-way ANOVA across groups F(2,22) = 10.69, P < 0.0001.

Figure 6

Subacute training on CDDI improves FDD thresholds and motion contrast sensitivity functions at trained, blind-field locations. (A) Plot of FDD thresholds in participants without baseline FDD, before and after CDDI training. Labelling conventions as in Fig. 4B. CDDI training improved FDD thresholds in most cases, whereas untrained subacutes never improved. A 3participant type × 3visual field location repeated measures ANOVA showed a main effect of participant [F(2,12) = 9.715, P = 0.0031], visual field location [F(1.007,12.09) = 168.6, P < 0.0001, Geisser-Greenhouse ε  =  0.5036], and a significant interaction between the two [F(4,24) = 9.629, P < 0.0001]. Mean recovered FDD thresholds were better in chronic than subacute trained participants (Tukey’s multiple comparisons test: P < 0.01). (B) Plot of FDD thresholds in participants with preserved baseline FDD, before and after CDDI training. No enhancements in FDD thresholds were noted [one-way repeated measures ANOVA: F(2,8) = 3.81, P = 0.12]. When left untrained, FDD thresholds worsened to chance in the one subacute participant in this group. (C) Post-training contrast sensitivity functions for direction in the blind and intact fields of trained subacutes. Labelling conventions as in Fig. 3C except for light green lines denoting individual, post-training contrast sensitivity functions. CDDI training improved contrast sensitivity for motion direction across multiple spatial frequencies in four of seven subacutes (n = 4, P < 0.01, see ‘Materials and methods’ section for bootstrap analysis). Group t-tests were performed at each spatial frequency, with *P < 0.05, #P < 0.10. There were significant effects for peak contrast sensitivity [t(6) = 2.45, P = 0.025] and area under the contrast sensitivity function [t(6) = 2.28, P = 0.032]. (D) Post-training contrast sensitivity functions for orientation in subacute participants showing no improvements after CDDI training (P > 0.2). Labelling conventions as in C.

Figure 7

Subacute CDDI training improves Humphrey perimetry similarly to spontaneous recovery. (A) Composite visual field maps of representative trained subacute participant (Patient CB1) at baseline and post-training, along with a map of the net change in visual sensitivity (red shading), with a threshold for change of 6 dB. Training location indicated by a white circle. (B) Composite visual field maps of representative untrained subacute participant (Patient CB11) at baseline and follow-up, along with a map of net change in visual sensitivity. (C) Plot of changes in the Humphrey-derived perimetric mean deviation (PMD) of individual patients with subacute cortically-induced blindness who were untrained versus CDDI-trained. The PMD is the overall difference in sensitivity between the tested and expected hill of vision for an age-corrected, normal population. Bars indicate means ± SD. No significant differences were observed between groups (independent Student’s t-test: P > 0.05). (D) Plot of change in visual deficit area in the same participants as in C, computed from Humphrey perimetry as previously described (Cavanaugh and Huxlin, 2017). No significant differences were observed between trained and untrained subacutes (independent Student’s t-test: P > 0.05). (E) Plot of the area of the Humphrey visual field that improves by >6 dB (Cavanaugh and Huxlin, 2017) in the same participants as in C and D. No significant differences were observed between trained and untrained subacutes (independent Student’s t-test: P > 0.05). (F) Plot of the area of the Humphrey visual field that worsens by >6 dB (Cavanaugh and Huxlin, 2017) in the same participants as in C–E. No significant differences were observed between trained and untrained subacutes (independent Student’s t-test: P > 0.05).