ABSTRACT
Transcriptional changes involved in neuronal recovery after sports-related concussion (SRC) may be obscured by inter-individual variation in mRNA expression and nonspecific changes related to physical exertion. Using a co-twin study, the objective of this study was to identify important differences in mRNA expression among a single pair of monozygotic (MZ) twins discordant for concussion. A pair of MZ twins were enrolled as part of a larger study of concussion biomarkers among collegiate athletes. During the study, Twin A sustained SRC, allowing comparison of mRNA expression to the nonconcussed Twin B. Twin A clinically recovered by Day 7. mRNA expression was measured pre-injury and at 6 h and 7 days postinjury using Affymetrix HG-U133 Plus 2.0 microarray. Changes in mRNA expression from pre-injury to each postinjury time point were compared between the twins; differences >1.5-fold were considered important. Kyoto Encyclopedia of Genes and Genomes identified biologic networks associated with important transcripts. Among 38,000 analyzed genes, important changes were identified in 153 genes. The ErbB (epidermal growth factor receptor) signaling pathway was identified as the top transcriptional network from pre-injury to 7 days postinjury. Genes in this pathway with important transcriptional changes included epidermal growth factor (2.41), epiregulin (1.73), neuregulin 1 (1.54) and mechanistic target of rapamycin (1.51). In conclusion, the ErbB signaling pathway was identified as a potential regulator of clinical recovery in a MZ twin pair discordant for SRC. A co-twin study design may be a useful method for identifying important gene pathways associated with concussion recovery.
Subject(s)
Sports , Twins, Monozygotic , Athletes , Humans , RNA, Messenger , Signal Transduction/genetics , Twins, Monozygotic/geneticsABSTRACT
PURPOSE OF REVIEW: Homonymous visual field defects are a common sequela of stroke, and are assumed to be permanent within a few weeks of the event. Because consensus about the efficacy of rehabilitation is lacking, visual therapy is rarely prescribed. Here, we review current rehabilitation options and strategies in the translational pipeline that could change these perspectives. RECENT FINDINGS: The mainstays of available therapy for homonymous visual defects are compensation training and substitution, which allow patients to better use their spared vision. However, early clinical studies suggest that vision can partially recover following intensive training inside the blind field. Research into the relative efficacy of different restorative approaches continues, providing insights into neurophysiologic substrates of recovery and its limitations. This, in turn, has led to new work examining the possible benefits of earlier intervention, advanced training procedures, noninvasive brain stimulation, and pharmacological adjuvants, all of which remain to be vetted through properly powered, randomized, clinical trials. SUMMARY: Research has uncovered substantial visual plasticity after occipital strokes, suggesting that rehabilitative strategies for this condition should be more aggressive. For maximal benefit, poststroke vision-restorative interventions should begin early, and in parallel with strategies that optimize everyday use of an expanding field of view.
Subject(s)
Stroke Rehabilitation , Stroke/complications , Vision Disorders/etiology , Vision Disorders/rehabilitation , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Humans , Stroke/physiopathology , Stroke Rehabilitation/methods , Stroke Rehabilitation/trends , Vision, Ocular/physiology , Visual Fields/physiologyABSTRACT
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 â¼6 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.
Subject(s)
Blindness, Cortical/physiopathology , Blindness, Cortical/rehabilitation , Stroke Rehabilitation/methods , Adult , Aged , Blindness, Cortical/etiology , Female , Functional Laterality/physiology , Humans , Learning/physiology , Male , Middle Aged , Motion Perception/physiology , Neuronal Plasticity/physiology , Occipital Lobe/pathology , Stroke/complications , Vision, Ocular/physiology , Visual Cortex/physiopathology , Visual Fields/physiology , Visual Perception/physiologyABSTRACT
Stroke damage to the primary visual cortex (V1) causes severe visual deficits, which benefit from perceptual retraining. However, whereas training with high-contrast stimuli can locally restore orientation and motion direction discrimination abilities at trained locations, it only partially restores luminance contrast sensitivity (CS). Recent work revealed that high-contrast discrimination abilities may be preserved in the blind field of some patients early after stroke. Here, we asked if CS for orientation and direction discrimination is similarly preserved inside the blind field, to what extent, and whether it could benefit from a visual training intervention. Thirteen subacute patients (<3 months post-V1-stroke) and 12 chronic patients (>6 months post-V1-stroke) were pre-tested, then trained to discriminate either orientation or motion direction of Gabor patches of progressively lower contrasts as their performance improved. At baseline, more subacute than chronic participants could correctly discriminate the orientation of high-contrast Gabors in their blind field, but all failed to perform this task at lower contrasts, even when 10Hz flicker or motion direction were added. Training improved CS in a greater portion of subacute than chronic participants, but no-one attained normal CS, even when stimuli contained flicker or motion. We conclude that, unlike the near-complete training-induced restoration of high-contrast orientation and motion direction discrimination abilities, V1 damage in adulthood may severely limit the residual visual system's ability to regain normal CS. Our results support the notion that CS involves different neural substrates and computations than those required for orientation and direction discrimination in V1-damaged visual systems.Significance statement Stroke-induced V1 damage in adult humans induces a rapid and severe impairment of contrast sensitivity for orientation and motion direction discrimination in the affected hemifield, although discrimination of high-contrast stimuli can persist for several months. Adaptive training with Gabor patches of progressively lower contrasts improves contrast sensitivity for both orientation and motion discriminations in the blind-field of subacute (<3 months post-stroke) and chronic (>6 months post-stroke) participants; however, it fails to restore normal contrast sensitivity. Nonetheless, more subacute than chronic stroke participants benefit from such training, particularly when discriminating the orientation of static, non-flickering targets. Thus, contrast sensitivity appears critically dependent on processing within V1, with perceptual training displaying limited potential to fully restore it after V1 damage.
ABSTRACT
Stroke damage to the primary visual cortex (V1) causes severe visual deficits, which benefit from perceptual retraining. However, whereas training with high-contrast stimuli can locally restore orientation and direction discrimination abilities at trained locations, it only partially restores luminance contrast sensitivity (CS). Recent work revealed that high-contrast discrimination abilities may be preserved in the blind field of some patients early after stroke. Here, we asked if CS for orientation and direction discrimination is similarly preserved inside the blind field, to what extent, and whether it could benefit from a visual training intervention. Thirteen subacute (<3 months post-V1-stroke) and 12 chronic (>6 months post-V1-stroke) participants were pre-tested, then trained to discriminate either orientation or motion direction of Gabor patches of progressively lower contrasts. At baseline, more subacute than chronic participants could correctly discriminate the orientation of high-contrast Gabors in their blind field, but all failed to perform this task at lower contrasts, even when 10Hz flicker or motion direction were added. Training improved CS in a greater portion of subacute than chronic participants, but no-one attained normal CS, even when stimuli contained flicker or motion. We conclude that, unlike the near-complete training-induced restoration of high-contrast orientation and direction discrimination, there is limited capacity for restoring CS after V1 damage in adulthood. Our results suggest that CS involves different neural substrates and computations than those required for orientation and direction discrimination in V1-damaged visual systems.
ABSTRACT
Blindness is a common sequela after stroke affecting the primary visual cortex, presenting as a contralesional, homonymous, visual field cut. This can occur unilaterally or, less commonly, bilaterally. While it has been widely assumed that after a brief period of spontaneous improvement, vision loss becomes stable and permanent, accumulating data show that visual training can recover some of the vision loss, even long after the stroke. Here, we review the different approaches to rehabilitation employed in adult-onset cortical blindness (CB), focusing on visual restoration methods. Most of this work was conducted in chronic stroke patients, partially restoring visual discrimination and luminance detection. However, to achieve this, patients had to train for extended periods (usually many months), and the vision restored was not entirely normal. Several adjuvants to training such as noninvasive, transcranial brain stimulation, and pharmacology are starting to be investigated for their potential to increase the efficacy of training in CB patients. However, these approaches are still exploratory and require considerably more research before being adopted. Nonetheless, having established that the adult visual system retains the capacity for restorative plasticity, attention recently turned toward the subacute poststroke period. Drawing inspiration from sensorimotor stroke rehabilitation, visual training was recently attempted for the first time in subacute poststroke patients. It improved vision faster, over larger portions of the blind field, and for a larger number of visual discrimination abilities than identical training initiated more than 6 months poststroke (i.e., in the chronic period). In conclusion, evidence now suggests that visual neuroplasticity after occipital stroke can be reliably recruited by a range of visual training approaches. In addition, it appears that poststroke visual plasticity is dynamic, with a critical window of opportunity in the early postdamage period to attain more rapid, more extensive recovery of a larger set of visual perceptual abilities.