m-Terphenylamines, Acting as Selective COX-1 Inhibitors, Block Microglia Inflammatory Response and Exert Neuroprotective Activity.

Inhibition of cyclooxygenase-2 (COX-2) has been extensively studied as an approach to reduce proinflammatory markers in acute brain diseases, but the anti-neuroinflammatory role of cyclooxygenase-1 (COX-1) inhibition has been rather neglected. We report that m-terphenylamine derivatives are selective COX-1 inhibitors, able to block microglia inflammatory response and elicit a neuroprotective effect. These compounds were synthesized via a three-component reaction of chalcones, ß-ketoesters, and primary amines, followed by hydrolysis/decarboxylation of the ester group. Together with their synthetic intermediates and some urea derivatives, they were studied as inhibitors of COX-1 and COX-2. The m-terphenylamine derivatives, which were selective COX-1 inhibitors, were also analyzed for their ability to block microglia inflammatory and oxidative response. Compound 3b presented an interesting anti-inflammatory and neuroprotective profile by reducing nitrite release, ROS overproduction, and cell death in organotypic hippocampal cultures subjected to LPS. We thus show that COX-1 inhibition is a promising approach to provide enhanced neuroprotection against acute inflammatory processes, which are crucial in the development of a plethora of acute neurodegenerative injuries.

An FMRI investigation of the cortical network underlying detection and categorization abilities in hemianopic patients.

The current study aims to investigate visual scene perception and its neuro-anatomical correlates for stimuli presented in the central visual field of patients with homonymous hemianopia, and thereby to assess the effect of a right or a left occipital lesion on brain reorganization. Fourteen healthy participants, three left brain damaged (LBD) patients with right homonymous hemianopia and five right brain damaged (RBD) patients with left homonymous hemianopia performed a visual detection task (i.e. "Is there an image on the screen?") and a categorization task (i.e. "Is it an image of a highway or a city?") during a block-designed functional magnetic resonance imaging recording session. Cerebral activity analyses of the posterior areas-the occipital lobe in particular-highlighted bi-hemispheric activation during the detection task but more lateralized, left occipital lobe activation during the categorization task in healthy participants. Conversely, in patients, the same network of activity was observed in both tasks. However, LBD patients showed a predominant activation in their right hemisphere (occipital lobe and posterior temporal areas) whereas RBD patients showed a more bilateral activation (in the occipital lobes). Overall, our preliminary findings suggest a specific pattern of cerebral activation depending on the task instruction in healthy participants and cerebral reorganization of the posterior areas following brain injury in hemianopic patients which could depend upon the side of the occipital lesion.

Redox Regulation of Microglial Inflammatory Response: Fine Control of NLRP3 Inflammasome through Nrf2 and NOX4.

The role of inflammation and immunity in the pathomechanism of neurodegenerative diseases has become increasingly relevant within the past few years. In this context, the NOD-like receptor protein 3 (NLRP3) inflammasome plays a crucial role in the activation of inflammatory responses by promoting the maturation and secretion of pro-inflammatory cytokines such as interleukin-1ß and interleukin-18. We hypothesized that the interplay between nuclear factor erythroid 2-related factor 2 (Nrf2) and NADPH oxidase 4 (NOX4) may play a critical role in the activation of the NLRP3 inflammasome and subsequent inflammatory responses. After priming mixed glial cultures with lipopolysaccharide (LPS), cells were stimulated with ATP, showing a significant reduction of IL1-ß release in NOX4 and Nrf2 KO mice. Importantly, NOX4 inhibition using GKT136901 also reduced IL-1ß release, as in NOX4 KO mixed glial cultures. Moreover, we measured NOX4 and NLRP3 expression in wild-type mixed glial cultures following LPS treatment, observing that both increased after TLR4 activation, while 24 h treatment with tert-butylhydroquinone, a potent Nrf2 inducer, significantly reduced NLRP3 expression. LPS administration resulted in significant cognitive impairment compared to the control group. Indeed, LPS also modified the expression of NLRP3 and NOX4 in mouse hippocampus. However, mice treated with GKT136901 after LPS impairment showed a significantly improved discrimination index and recovered the expression of inflammatory genes to normal levels compared with wild-type animals. Hence, we here validate NOX4 as a key player in NLRP3 inflammasome activation, suggesting NOX4 pharmacological inhibition as a potent therapeutic approach in neurodegenerative diseases.

Activation of NLRP3 Is Required for a Functional and Beneficial Microglia Response after Brain Trauma.

Despite the numerous research studies on traumatic brain injury (TBI), many physiopathologic mechanisms remain unknown. TBI is a complex process, in which neuroinflammation and glial cells play an important role in exerting a functional immune and damage-repair response. The activation of the NLRP3 inflammasome is one of the first steps to initiate neuroinflammation and so its regulation is essential. Using a closed-head injury model and a pharmacological (MCC950; 3 mg/kg, pre- and post-injury) and genetical approach (NLRP3 knockout (KO) mice), we defined the transcriptional and behavioral profiles 24 h after TBI. Wild-type (WT) mice showed a strong pro-inflammatory response, with increased expression of inflammasome components, microglia and astrocytes markers, and cytokines. There was no difference in the IL1ß production between WT and KO, nor compensatory mechanisms of other inflammasomes. However, some microglia and astrocyte markers were overexpressed in KO mice, resulting in an exacerbated cytokine expression. Pretreatment with MCC950 replicated the behavioral and blood-brain barrier results observed in KO mice and its administration 1 h after the lesion improved the damage. These findings highlight the importance of NLRP3 time-dependent activation and its role in the fine regulation of glial response.

Synthesis and Pharmacological Evaluation of New N-Sulfonylureas as NLRP3 Inflammasome Inhibitors: Identification of a Hit Compound to Treat Gout.

NLRP3 is involved in the pathophysiology of several inflammatory diseases. Therefore, there is high current interest in the clinical development of new NLRP3 inflammasome small inhibitors to treat these diseases. Novel N-sulfonylureas were obtained by the replacement of the hexahydroindacene moiety of the previously described NLRP3 inhibitor MCC950. These new derivatives show moderate to high potency in inhibiting IL-1ß release in vitro. The greatest effect was observed for compound 4b, which was similar to MCC950. Moreover, compound 4b was able to reduce caspase-1 activation, oligomerization of ASC, and therefore, IL-1ß processing. Additional in silico predictions confirmed the safety profile of compound 4b, and in vitro studies in AML12 hepatic cells confirmed the absence of toxicological effects. Finally, we evaluated in vivo anti-inflammatory properties of compound 4b, which showed a significant anti-inflammatory effect and reduced mechanical hyperalgesia at 3 and 10 mg/kg (i.p.) in an in vivo mouse model of gout.

Time-dependent dual effect of NLRP3 inflammasome in brain ischaemia.

BACKGROUND: Inflammasomes are cytosolic multiprotein complexes which, upon assembly, activate the maturation and secretion of the inflammatory cytokines IL-1ß and IL-18. However, participation of the NLRP3 inflammasome in ischaemic stroke remains controversial. Our aims were to determine the role of NLRP3 in brain ischaemia, and explore the mechanism involved in the potential protective effect of the neurovascular unit. METHODS: WT and NLRP3 knock-out mice were subjected to ischaemia by middle cerebral artery occlusion (60 min) with or without treatment with MCC950 at different time points post-stroke. Brain injury was measured histologically with 2,3,5-triphenyltetrazolium chloride (TTC) staining. RESULTS: We identified a time-dependent dual effect of NLRP3. While neither the pre-treatment with MCC950 nor the genetic approach (NLRP3 KO) proved to be neuroprotective, post-reperfusion treatment with MCC950 significantly reduced the infarct volume in a dose-dependent manner. Importantly, MCC950 improved the neuro-motor function and reduced the expression of different pro-inflammatory cytokines (IL-1ß and TNF-α), NLRP3 inflammasome components (NLRP3 and pro-caspase-1), protease expression (MMP9), and endothelial adhesion molecules (ICAM and VCAM). We observed a marked protection of the blood-brain barrier (BBB), which was also reflected in the recovery of the tight junction proteins (ZO-1 and Claudin-5). Additionally, MCC950 produced a reduction of the CCL2 chemokine in blood serum and in brain tissue, which lead to a reduction in the immune cell infiltration. CONCLUSIONS: These findings suggest that post-reperfusion NLRP3 inhibition may be an effective acute therapy for protecting the blood-brain barrier in cerebral ischaemia with potential clinical translation.

Visual demand and visual field presentation influence natural scene processing.

BACKGROUND: Bottom-up and top-down processes are involved in visual analysis of scenes. Here we examined the influence of top-down visual demand on natural scene processing. METHODS: We measured accuracy and response time in adults performing two stimuli-equivalent tasks. Unfiltered, low or high spatial frequency (SF) natural scenes were presented in central, left, or right visual fields (CVF, LVF, RVF). The tasks differed only by the instructed visual demand. In the detection task, participants had to decide whether a scene was present or not. In the categorization task, they had to decide whether the scene was a city or a forest. RESULTS: Higher accuracy was seen for the LVF in the detection task, but for categorization, greater accuracy was seen for the RVF. The interaction between Task and SF revealed coarse-to-fine processing in the categorization task for both accuracy and reaction time, which nearly disappeared in the detection task. Considering the interaction of Task, VF and SF, a left-hemisphere specialisation (i.e., RVF advantage) was observed for the categorisation of HSF scenes for accuracy alone, whereas a LVF advantage was seen for all SFs in the detection task for both accuracy and reaction time. CONCLUSION: Our results revealed that the nature of top-down visual demand is essential to understanding how visual analysis is achieved in each hemisphere. Moreover, this study examining the effects of visual demand, visual field presentation, and SF content of stimuli through the use of ecological stimuli provides a tool to enrich the clinical examination of visual and neurovisual patients.

Emotional face recognition in autism and in cerebral visual impairments: In search for specificity.

Autism spectrum disorder (ASD) is characterized by difficulties in the social domain, but also by hyper- and hypo-reactivity. Atypical visual behaviours and processing have often been observed. Nevertheless, several similar signs are also identified in other clinical conditions including cerebral visual impairments (CVI). In the present study, we investigated emotional face categorization in groups of children with ASD and CVI by comparing each group to typically developing individuals (TD) in two tasks. Stimuli were either non-filtered or filtered by low- and high-spatial frequencies (LSF and HSF). All participants completed the autism spectrum quotient score (AQ) and a complete neurovisual evaluation. The results show that while both clinical groups presented difficulties in the emotional face recognition tasks and atypical processing of filtered stimuli, they did not differ from one another. Additionally, autistic traits were observed in the CVI group and symmetrically, some visual disturbances were present in the ASD group as measured via the AQ score and a neurovisual evaluation, respectively. The present study suggests the relevance of comparing ASD to CVI by showing that emotional face categorization difficulties should not be solely considered as autism-specific but merit investigation for potential dysfunction of the visual processing neural network. These results are of interest in both clinical and research perspectives, indicating that systematic visual examination is warranted for individuals with ASD.

Serum Amyloid A1/Toll-Like Receptor-4 Axis, an Important Link between Inflammation and Outcome of TBI Patients.

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability worldwide without any validated biomarker or set of biomarkers to help the diagnosis and evaluation of the evolution/prognosis of TBI patients. To achieve this aim, a deeper knowledge of the biochemical and pathophysiological processes triggered after the trauma is essential. Here, we identified the serum amyloid A1 protein-Toll-like receptor 4 (SAA1-TLR4) axis as an important link between inflammation and the outcome of TBI patients. Using serum and mRNA from white blood cells (WBC) of TBI patients, we found a positive correlation between serum SAA1 levels and injury severity, as well as with the 6-month outcome of TBI patients. SAA1 levels also correlate with the presence of TLR4 mRNA in WBC. In vitro, we found that SAA1 contributes to inflammation via TLR4 activation that releases inflammatory cytokines, which in turn increases SAA1 levels, establishing a positive proinflammatory loop. In vivo, post-TBI treatment with the TLR4-antagonist TAK242 reduces SAA1 levels, improves neurobehavioral outcome, and prevents blood-brain barrier disruption. Our data support further evaluation of (i) post-TBI treatment in the presence of TLR4 inhibition for limiting TBI-induced damage and (ii) SAA1-TLR4 as a biomarker of injury progression in TBI patients.

Dissociations between perception and awareness in hemianopia.

The most common visual defect to follow a lesion of the retrochiasmal pathways is homonymous hemianopia (HH), whereby patients are blind to the contralesional visual field of each eye. Homonymous hemianopia has been studied in terms of its deleterious consequences on perceptual, cognitive and motor tasks as well as because it represents an interesting model of vision loss after a unilateral lesion of the occipital lobe. From a behavioral perspective, in addition to exhibiting a severe deficit in their contralesional visual field, HH patients can also exhibit dissociations between perception and awareness. Firstly, HH patients suffering from anosognosia may be unaware of their visual field defect. Secondly, HH patients can present with unconscious visual abilities in the blind hemifield, a phenomenon referred to as blindsight. Thirdly, recent reports demonstrate that HH patients can suffer from a subtle deficit in their ipsilesional visual field that they are unaware of, a condition called sightblindness (i.e. the reverse case of 'blindsight'). Finally, HH patients may also exhibit visual hallucinations in their blind field; however, such patients are not systematically aware that their perceptions are unreal. In this review, we provide an overview of the visual-field losses in HH patients after a left or right unilateral occipital lesion. Furthermore, we explore the implications of these four phenomena for models of visual processing and rehabilitation of visual field defects in HH patients. Finally, in contrast to the traditional view that HH is solely a visual-field defect, we discuss why this deficit is an interesting model for studying the dissociation between perception and awareness.

Neuroanatomic correlates of visual hallucinations in poststroke hemianopic patients.

OBJECTIVES: Homonymous hemianopia (HH) is the most frequent visual-field defect after a stroke. Some of these patients also have visual hallucinations, the origin and frequency of which remain largely unknown. The aims of this work were to determine the occurrence of visual hallucinations among poststroke hemianopic patients in function of the location (Brodmann areas) of the brain lesion, as determined by MRI, and to study the neuroanatomic correlates of these hallucinations by nature, frequency, and type. METHODS: One hundred sixteen patients with HH who had had a stroke in the posterior region, including the occipital lobe, participated in the study. We evaluated the frequency and nature of visual hallucinations with the Questionnaire for Hallucinations in Homonymous Hemianopia. The volume of each patient's brain lesion was modeled in 3 dimensions. RESULTS: Of 116 patients with an HH from a cortical infarction, 85 were excluded due to confounding factors associated with hallucinations. In the final cohort of 31 patients matched for lesion location and etiology, 58% had experienced hallucinations. A significant inverse correlation between lesion size and the frequency of visual hallucinations emerged. The presence of visual hallucinations in poststroke hemianopic patients requires a relatively small lesion that includes, at the very least, loss of the striate cortex but that spares Brodmann area 19, 20, and 37. CONCLUSION: Our results suggest that visual hallucinations might be due to complex interactions between damaged areas and intact areas of the visual cortex. We discuss these findings regarding models of perception and of visual recognition. Our results also have implications for the clinical care of patients with HH who have had a stroke.

Melatonin Reduces NLRP3 Inflammasome Activation by Increasing α7 nAChR-Mediated Autophagic Flux.

Microglia controls the immune system response in the brain. Specifically, the activation and dysregulation of the NLRP3 inflammasome is responsible for the initiation of the inflammatory process through IL-1ß and IL-18 release. In this work, we have focused on studying the effect of melatonin on the regulation of the NLRP3 inflammasome through α7 nicotinic receptor (nAChR) and its relationship with autophagy. For this purpose, we have used pharmacological and genetic approaches in lipopolysaccharide (LPS)-induced inflammation models in both in vitro and in vivo models. In the BV2 cell line, LPS inhibited autophagy, which increased NLRP3 protein levels. However, melatonin promoted an increase in the autophagic flux. Treatment of glial cultures from wild-type (WT) mice with LPS followed by extracellular adenosine triphosphate (ATP) produced the release of IL-1ß, which was reversed by melatonin pretreatment. In cultures from α7 nAChR knock-out (KO) mice, melatonin did not reduce IL-1ß release. Furthermore, melatonin decreased the expression of inflammasome components and reactive oxygen species (ROS) induced by LPS; co-incubation of melatonin with α-bungarotoxin (α-bgt) or luzindole abolished the anti-inflammatory and antioxidant effects. In vivo, melatonin reverted LPS-induced cognitive decline, reduced NLRP3 levels and promoted autophagic flux in the hippocampi of WT mice, whereas in α7 nAChR KO mice melatonin effect was not observed. These results suggest that melatonin may modulate the complex interplay between α7 nAChR and autophagy signaling.

Ipsilesional deficit of selective attention in left homonymous hemianopia and left unilateral spatial neglect.

AIMS: Patients with homonymous hemianopia may present a subtle ipsilesional deficit, recently referred to as 'sightblindness' in addition to the contralesional visual field defect. We recently demonstrated that this deficit could be worse in right brain-damaged patients with left hemianopia than in left brain-damaged patients with right hemianopia, confirming right hemisphere dominance for visuo-spatial and attentional capacities. In the present study we investigate whether this ipsilesional deficit could be attentional in nature and to what extent it is comparable in right brain-damaged (RBD) patients with left hemianopia and in RBD patients with left neglect. The study was also conducted in RBD patients with neither left hemianopia nor left neglect signs in order to test if a right hemisphere lesion per se could be responsible for subtle ipsilesional attentional deficit. To reach this aim, we tested selective attentional capacities in both visual fields of 10 right brain-damaged patients with left neglect (LN), 8 right brain-damaged patients with left homonymous hemianopia (LHH), 8 right brain-damaged patients with no signs of left neglect or left hemianopia (RBD controls), and 17 healthy age-matched participants (Normal controls). METHOD: A lateralized letter-detection task was used to test if right-brain damaged patients with LN or LH may present a deficit of selective attention in their right, ipsilesional visual field, in comparison to Normal and RBD controls. Participants were asked to detect a target letter in either a single large stimulus (low attentional load) or a small stimulus surrounded by flankers (high attentional load). Stimuli were displayed either in the left or in the right visual field. Accuracy and reaction times were recorded. RESULTS: Results on accuracy showed that both LN and LH patients exhibited lower correct responses than Normal controls in their ipsilesional right visual field, suggesting an attentional deficit in their ipsilesional, supposed healthy visual field. More specifically, LH patients exhibited a specific deficit for processing single large stimuli, but not for processing flanked stimuli, relative to normal controls. LN patients exhibited lower correct responses for processing all types of stimulus than normal controls, but also than right brain damaged controls, in both visual fields suggesting a non-lateralized deficit not only due to the right hemisphere lesion. Furthermore, this deficit is more pronounced for flanked small stimuli, requiring higher attentional load. CONCLUSIONS: The present results bring further evidence that patients with left homonymous hemianopia or left unilateral neglect both present a weaker but significant ipsilesional deficit in addition to their well-known massive contralesional deficit. The presence of a specific attentional deficit in the right ipsilesional visual field of left hemianopic and left neglect patients is discussed regarding the hypothesis of hemispheric specialization for selective spatial attention and may have clinical implications for both conditions.

Dissociation between objective and subjective perceptual experiences in a population of hemianopic patients: A new form of blindsight?

After a post-chiasmatic lesion, some patients may retain unconscious visual function, known as blindsight, in their contralesional visual field. Despite the importance of blindsight in the study of consciousness, little is known about the nature of patients' experience in their hemianopic field. To address this knowledge gap, we measured blindsight, and assessed the perceptual experience in the contralesional visual field, of seventeen homonymous hemianopic (HH) patients. To ensure that the stimuli were shown in a "blind" sector of the visual field, we selected a subgroup of eight complete-HH patients, as determined by automatic perimetry. Firstly, we measured blindsight through a forced-choice task in which the patients had to identify letters displayed on a screen. Secondly, we compared the patients' binary responses ("Something was presented" vs "Nothing was presented") to responses on a new, five-level scale, the Sensation Awareness Scale (SAS), which we designed to include visual as well as non-visual answers (e.g., "I felt something"). Interestingly, only one of the eight complete-HH patients met the criteria for blindsight. More importantly, our SAS enabled us to identify a previously unreported dissociation, which we have named blindsense, in four of the eight complete-HH patients. Specifically, these four patients exhibited better-than-chance sensitivity to the presence of a stimulus on the subjective scale, despite being unable to identify the stimulus during the forced-choice task. Our findings highlight the importance of awareness-assessment methods to investigate perceptual experiences in the contralesional visual field and suggest a low incidence of blindsight in post-stroke HH patients.

From blindsight to sight: cognitive rehabilitation of visual field defects.

PURPOSE: Traditionally, post-chiasmatic lesions were believed to result in complete and permanent visual loss in the topographically related areas of the visual field. However, a number of studies with monkeys, and later with humans, have demonstrated spared implicit visual functioning, referred to as 'blindsight'. The present study assessed whether training this phenomenon would induce an objective restoration of conscious vision in the blind field of hemianopic patients. METHODS: For a period of 22 weeks nine patients with unilateral occipital damage participated in several forced-choice visual tasks known to elicit blindsight: pointing to visual targets, letter recognition, visual comparison between the two hemifields, target localization, and letter identification. Before and after rehabilitation, patients were submitted to a behavioral pre- and post-test, including visual detection and letter identification as well as to automated perimetry visual field testing (Humphrey Automated 24-2 Full Threshold). RESULTS: An objective improvement was found in the behavioral tasks for all patients at the post-test stage as well as an objective enlargement of the contralesional visual field for all except one of the nine patients. An overall decrease is seen in the number of undetected points (out of 30) on automated perimetry visual field testing after rehabilitation (F (1, 16)=22.57; p<0.001) for both eyes (Right Eye, RE: T=0; z=2.52; p<0.05; Left Eye, LE: T=0, z=2.37; p<0.05) regardless of lesion side. CONCLUSIONS: The results suggest that explicit (conscious) visual detection can be restored in the blind visual field by using implicit (unconscious) visual capacities. Results are discussed regarding visual field defect rehabilitation, blindsight, attention, and brain plasticity hypotheses.

Behavioral Consequences and Cortical Reorganization in Homonymous Hemianopia.

The most common visual defect to follow a lesion of the retrochiasmal pathways is homonymous hemianopia (HH), whereby, in each eye, patients are blind to the contralesional visual field. From a behavioral perspective, in addition to exhibiting a severe deficit in their contralesional visual field, hemianopic patients can also present implicit residual capacities, now usually referred to collectively as blindsight. It was recently demonstrated that HH patients can also suffer from a subtle deficit in their ipsilesional visual field, called sightblindness (the reverse case of blindsight). Furthermore, the nature of the visual deficit in the contralesional and ipsilesional visual fields, as well as the pattern of functional reorganization in the occipital lobe of HH patients after stroke, all appear to depend on the lesion side. In addition to their contralesional and ipsilesional visual deficits, and to their residual capacities, HH patients can also experience visual hallucinations in their blind field, the physiopathological mechanisms of which remain poorly understood. Herein we review blindsight in terms of its better-known aspects as well as its less-studied clinical signs such as sightblindness, hemispheric specialization and visual hallucinations. We also discuss the implications of recent experimental findings for rehabilitation of visual field defects in hemianopic patients.

Hemisphere-dependent ipsilesional deficits in hemianopia: Sightblindness in the 'intact' visual field.

OBJECTIVES: In addition to exhibiting a severe contralesional deficit, hemianopic patients may also show a subtle ipsilesional visual deficit, called sightblindness (the reverse case of 'blindsight). We have tested for the presence, nature and extent of such an ipsilesional visual field (IVF) deficit in hemianopic patients that we assigned to perform two visual tasks. Namely, we aimed to ascertain any links between this ipsilesional deficit, the lesion side, and the tasks performed or the stimuli used. METHODS: We tested left and right homonymous hemianopic (right brain-damaged RBD and left brain-damaged LBD, respectively) patients and healthy controls. Natural-scene images, either non-filtered or filtered in low or high spatial frequency (LSF or HSF, respectively) were presented in the IVF of each subject. For the two tasks, detection ("Is an image present?") and categorization ("Is the image of a forest or a city?"), accuracy and response time were recorded. RESULTS: In the IVF the RBD (left hemianopes) patients made more errors on the categorization task than did their matched controls, regardless of image type. In contrast, the only task in which the LBD (right hemianopes) patients made more errors than did the controls was the HSF-images task. Furthermore, in both tasks (detection and categorization), the RBD patients performed worse than did the LBD patients. DISCUSSION: Homonymous hemianopic patients do indeed exhibit a specific visual deficit in their IVF, which was previously thought to be unaffected. We have demonstrated that the nature and severity of this ipsilesional deficit is determined by the side of the occipital lesion as well as by the tasks and the stimuli. Our findings corroborate the idea of hemispheric specialization at the occipital level, which might determine the nature and severity of ipsilesional deficits in hemianopic patients.

Rehabilitation of homonymous hemianopia: insight into blindsight.

Strong evidence of considerable plasticity in primary sensory areas in the adult cortex, and of dramatic cross-modal reorganization in visual areas, after short- or long-term visual deprivation has recently been reported. In the context of patient rehabilitation, this scientifically challenging topic takes on urgent clinical relevance, especially given the lack of information about the role of such reorganization on spared or newly emerged visual performance. Amongst the most common visual field defects found upon unilateral occipital damage of the primary visual cortex is homonymous hemianopia (HH), a perfectly symmetric loss of vision in both eyes. Traditionally, geniculostriate lesions were considered to result in complete and permanent visual loss in the topographically related area of the visual field (Huber, 1992). However, numerous studies in monkeys, and later, in humans, have demonstrated that despite destruction of the striate cortex, or even following a hemispherectomy, some patients retain a certain degree of unconscious visual function, known as blindsight. Accordingly, there have recently been attempts to restore visual function in patients by stimulating unconscious preserved blindsight capacities. Herein we review different visual rehabilitation techniques designed for brain-damaged patients with visual field loss. We discuss the hypothesis that explicit (conscious) visual detection can be restored in the blind visual field by harnessing implicit (unconscious) visual capacities. The results that we summarize here underline the need for early diagnosis of cortical visual impairment (CVI), and the urgency in rehabilitating such deficits, in these patients. Based on the research precedent, we explore the link between implicit (unconscious) vision and conscious perception and discuss possible mechanisms of adaptation and plasticity in the visual cortex.

Effects of age and cardiovascular disease on selective attention.

In order to study the effect of normal aging and cardiovascular disease on selective attention, a letter-identification task was proposed to younger and older healthy adults as well as patients with a recent myocardial infarction or a recent coronary artery bypass grafting. Participants had to detect either a big stimulus or a small one surrounded by flanking letters. The stimuli were displayed horizontally, either in the left (LVF) or in the right visual field (RVF). The interaction between the type of stimulus and the hemifield of presentation reached significance in all groups except in patients who underwent a coronary artery bypass. Only young normal adults showed the expected significant RVF advantage when detecting big stimuli and an LVF advantage when detecting small stimuli surrounded by flankers. In older control adults and in patients with myocardial infarction, the RVF advantage for the condition with selective attention vanished. In patients who underwent a coronary artery bypass, reaction times were increased and no hemispheric specialization for selective attention emerged. The results are discussed with regard to the hypothesis of a Hemispheric Asymmetry Reduction in Older Adults (HAROLD model) and to the presence of cognitive dysfunction consecutive to cardiovascular disease.

Specific impairments in visual processing following lesion side in hemianopic patients.

INTRODUCTION: Following unilateral damage of the primary visual cortex one of the most common visual field defects observed is Homonymous Hemianopia (HH), a loss of vision of the contralesional hemifield in each eye. The ipsilesional ("intact") part of the central visual field is often used to compensate for difficulties encountered in the peripheral hemianopic visual field. However, the quality of vision within the central visual field is not well-known. METHODS: To better describe and understand visual processing in hemianopia, two tasks were conducted with 25 healthy controls, six left hemianopes, and five right hemianopes. Filtered (in high, above 6 cycles/degree, or low, below 4 cycles/degree, spatial frequencies - HSF and LSF, respectively) and unfiltered natural scene images (5° of visual angle) were briefly presented (100 msec) centrally on a computer screen. Participants were required either to respond when a natural scene was presented (yes/no detection task) or to indicate if the stimulus was a city or a highway (categorization task). RESULTS: The three groups showed similar accuracy levels but significant differences were observed in response times. More precisely, left hemianopes were impaired both in the detection and in the categorization tasks whereas right hemianopes were only impaired in the categorization task. However, the three groups had similar responses to spatial frequencies: HSF were processed more slowly than LSF. CONCLUSIONS: Overall these results suggest that central vision is not intact in hemianopia. Lesion side selectively affects reaction times (RTs) in the detection and the categorization tasks, but does not seem to determine a specific deficit in spatial frequency processing.