Conserved cysteine residues in Kaposi's sarcoma herpesvirus ORF34 are necessary for viral production and viral pre-initiation complex formation.

Kaposi's sarcoma herpesvirus (KSHV) ORF34 plays a significant role as a component of the viral pre-initiation complex (vPIC), which is indispensable for late gene expression across beta- and gammaherpesviruses. Although the key role of ORF34 within the vPIC and its function as a hub protein have been recognized, further clarification regarding its specific contribution to vPIC functionality and interactions with other components is required. This study employed a deep learning algorithm-assisted structural model of ORF34, revealing highly conserved amino acid residues across human beta- and gammaherpesviruses localized in structured domains. Thus, we engineered ORF34 alanine-scanning mutants by substituting conserved residues with alanine. These mutants were evaluated for their ability to interact with other vPIC factors and restore viral production in cells harboring the ORF34-deficient KSHV-BAC. Our experimental results highlight the crucial role of the four cysteine residues conserved in ORF34: a tetrahedral arrangement consisting of a pair of C-Xn-C consensus motifs. This suggests the potential incorporation of metal cations in interacting with ORF24 and ORF66 vPIC components, facilitating late gene transcription, and promoting overall virus production by capturing metal cations. In summary, our findings underline the essential role of conserved cysteines in KSHV ORF34 for effective vPIC assembly and viral replication, thereby enhancing our understanding of the complex interplay between the vPIC components. IMPORTANCE: The initiation of late gene transcription is universally conserved across the beta- and gammaherpesvirus families. This process employs a viral pre-initiation complex (vPIC), which is analogous to a cellular PIC. Although KSHV ORF34 is a critical factor for viral replication and is a component of the vPIC, the specifics of vPIC formation and the essential domains crucial for its function remain unclear. Structural predictions suggest that the four conserved cysteines (C170, C175, C256, and C259) form a tetrahedron that coordinates the metal cation. We investigated the role of these conserved amino acids in interactions with other vPIC components, late gene expression, and virus production to demonstrate for the first time that these cysteines are pivotal for such functions. This discovery not only deepens our comprehensive understanding of ORF34 and vPIC dynamics but also lays the groundwork for more detailed studies on herpesvirus replication mechanisms in future research.

Continued care and provision of glasses are necessary to improve visual and academic outcomes in children: Experience from a cluster-randomized controlled trial of school-based vision screening.

OBJECTIVE: To assess the effectiveness of a kindergarten vision screening program by randomly assigning schools to receive or not receive vision screening, then following up 1.5 years later. METHODS: Fifty high-needs elementary schools were randomly assigned to participate or not in a vision screening program for children in senior kindergarten (SK; age 5‒6 years). When the children were in Grade 2 (age 6‒7 years), vision screening was conducted at all 50 schools. RESULTS: Contrary to expectations, screened and non-screened schools did not differ in the prevalence of suspected amblyopia in Grade 2 (8.6% vs. 7.5%, p = 0.10), nor prevalence of other visual problems such as astigmatism (45.1% vs. 47.1%, p = 0.51). There was also no difference between screened and non-screened schools in academic outcomes such as the proportion of children below grade level in reading (33% vs. 29%) or math (44% vs. 38%) (p = 0.86). However, more children were wearing glasses in screened than in non-screened schools (10.2% vs. 7.8%, p = 0.05), and more children reported their glasses as missing or broken (8.3% vs. 4.7%, p = 0.01), suggesting that SK screening had identified successfully those in need of glasses. Examination of individual results revealed that 72% of children diagnosed and treated for amblyopia in SK no longer had amblyopia in Grade 2. CONCLUSION: The prevalence of amblyopia and other visual problems was not reduced in Grade 2 by our SK vision screening program, perhaps because of poor treatment compliance and high attrition. The results suggest that a single screening intervention is insufficient to reduce visual problems among young children. However, the data from individuals with amblyopia suggest that continuing vision care and access to glasses benefits children, especially children from lower socioeconomic class.

RéSUMé: OBJECTIF: Évaluer l'efficacité d'un programme de dépistage visuel à l'école maternelle (EM) en assignant aléatoirement des écoles à participer ou non à un tel programme, puis en faisant un suivi un an et demi après. MéTHODES: Cinquante écoles primaires pour étudiants et étudiantes ayant des besoins importants ont été assignées aléatoirement à participer ou non à un programme de dépistage visuel auprès des enfants fréquentant la maternelle (EM; 5‒6 ans). Lorsque ces enfants étaient en 2e année (6‒7 ans), un dépistage visuel a été effectué dans les 50 écoles. RéSULTATS: Contre toute attente, il n'y a pas eu de différence entre les écoles ayant participé ou non au dépistage dans la prévalence de l'amblyopie présumée en 2e année (8,6 % contre 7,5 %, p = 0,10), ni dans la prévalence d'autres problèmes de vision comme l'astigmatisme (45,1 % contre 47,1 %, p = 0,51). Il n'y a pas eu non plus de différence dans les résultats scolaires des deux groupes d'écoles, comme la proportion d'enfants dont le niveau en lecture (33 % contre 29 %) ou en mathématiques (44 % contre 38 %), p = 0,86, ne correspondait pas à leur année d'étude. Cependant, le nombre d'enfants portant des lunettes était plus élevé dans les écoles ayant participé au dépistage que dans les autres écoles (10,2 % contre 7,8 %, p = 0,05), ainsi que le nombre d'enfants disant avoir perdu ou brisé leurs lunettes (8,3 % contre 4,7 %, p = 0,01), ce qui indique que le dépistage en maternelle a identifié avec succès les enfants ayant besoin de lunettes. L'examen des résultats individuels a révélé que 72 % des enfants diagnostiqués et traités pour l'amblyopie en maternelle ne présentaient plus d'amblyopie en 2e année. CONCLUSION: Notre programme de dépistage visuel à l'école maternelle n'a pas réduit la prévalence de l'amblyopie et d'autres problèmes de vision en 2e année, peut-être en raison du manque d'assiduité au traitement et d'une attrition importante. Les résultats indiquent qu'une seule intervention de dépistage ne suffit pas à réduire les problèmes de vision chez les jeunes enfants. Cependant, les données individuelles des sujets présentant une amblyopie indiquent qu'il est avantageux pour les enfants, et surtout ceux de la classe socioéconomique inférieure, de continuer de recevoir des soins de la vue et d'avoir accès à des lunettes.

Conserved cysteine residues in Kaposi's sarcoma herpesvirus ORF34 are necessary for viral production and viral pre-initiation complex formation.

Kaposi's sarcoma herpesvirus (KSHV) ORF34 is a component of the viral pre-initiation complex (vPIC), a highly conserved piece of machinery essential for late gene expression among beta- and gamma-herpes viruses. KSHV ORF34 is also estimated to be a hub protein, associated with the majority of vPIC components. However, the precise mechanisms underlying how the ORF34 molecule contributes to the vPIC function, including the binding manner to other vPIC components, remain unclear. Therefore, we constructed ORF34 alanine-scanning mutants, in which amino-acid residues that were conserved among other herpesviruses had been replaced by alanine. The mutants were analyzed for their binding functions to other vPIC factors, and then were evaluated for their recovering ability of viral production using the cells harboring ORF34-deficient KSHV-BAC. The results demonstrated that at least four cysteines conserved in ORF34 were crucial for binding to other vPIC components, ORF24 and ORF66, virus production, and late gene transcription and expression. Based on the amino acid sequence of ORF34, these four cysteines were expected to constitute a pair of C-Xn-C consensus motifs. An artificial intelligence-predicted structure model revealed that the four cysteines were present tetrahedrally in an intramolecular fashion. Another prediction algorithm indicated the possible capture of metal cations by ORF34. Furthermore, it was experimentally observed that the elimination of cations by a selective chelator resulted in the loss of ORF34's binding ability to other vPIC components. In conclusion, our results suggest the functional importance of KSHV ORF34 conserved cysteines for vPIC components assembly and viral replication.

Eicosapentaenoic acid changes muscle transcriptome and intervenes in aging-related fiber type transition in male mice.

Age-related sarcopenia is associated with a variety of changes in skeletal muscle. These changes are interrelated with each other and associated with systemic metabolism, the details of which, however, are largely unknown. Eicosapentaenoic acid (EPA) is a promising nutrient against sarcopenia and has multifaceted effects on systemic metabolism. In this study, we hypothesized that the aging process in skeletal muscle can be intervened by the administration of EPA. Seventy-five-week-old male mice were assigned to groups fed an EPA-deprived diet (EPA-) or an EPA-enriched diet with 1 wt% EPA (EPA+) for 12 wk. Twenty-four-week-old male mice fed with normal chow were also analyzed. At baseline, the grip strength of the aging mice was lower than that of the young mice. After 12 wk, EPA+ showed similar muscle mass but increased grip strength compared with EPA-. EPA+ displayed higher insulin sensitivity than EPA-. Immunohistochemistry and gene expression analysis of myosin heavy chains (MyHCs) revealed fast-to-slow fiber type transition in aging muscle, which was partially inhibited by EPA. RNA sequencing (RNA-Seq) analysis suggested that EPA supplementation exerts pathway-specific effects in skeletal muscle including the signatures of slow-to-fast fiber type transition. In conclusion, we revealed that aging skeletal muscle in male mice shows lower grip strength and fiber type changes, both of which can be inhibited by EPA supplementation irrespective of muscle mass alteration.NEW & NOTEWORTHY This study demonstrated that the early phenotype of skeletal muscle in aging male mice is characterized by muscle weakness with fast-to-slow fiber type transition, which could be ameliorated by feeding with EPA-enriched diet. EPA induced metabolic changes such as an increase in systemic insulin sensitivity and altered muscle transcriptome in the aging mice. These changes may be related to the fiber type transition and influence muscle quality.

Feasibility of a school-based vision screening program to detect undiagnosed visual problems in kindergarten children in Ontario.

BACKGROUND: Visual problems can negatively affect visual development and learning but often go undetected. We assessed the feasibility of scaling up a school-based screening program to identify and treat kindergarten children with visual problems. METHODS: We conducted a prospective cohort study offering vision screening to junior (JK) and senior kindergarten (SK) children attending 43 schools in 15 Ontario communities. Screening comprised photoscreeners and tests of visual acuity, stereoacuity and eye alignment. Children who failed any test were referred for a comprehensive eye examination, with treatment as needed (e.g., glasses). RESULTS: Using a passive consent model, 89% of children were screened compared with 62% using an active consent model (p < 0.001). Referral rates to an optometrist varied across schools (mean referral rate for children in JK 53%, range 25%-83%; mean referral rate for children in SK 34%, range 12%-61%). Among 4811 children who were screened, a visual problem was detected in 516 (10.7%), including 164 (3.4%) with amblyopia and 324 (6.7%) with clinically significant refractive errors. For 347 (67.2%) of the children with a visual problem, this was their first eye examination. Rescreening in Year 2 did not lead to detection of additional problems among children who passed screening in Year 1. Regardless of location (child's school or optometrist's office), 1563 (68.9%) of children attended the follow-up optometry examination. Most of the children who were surveyed (291 of 322, 90.4%) indicated that they enjoyed vision screening. INTERPRETATION: Many children in Ontario with a visual problem were not being identified by the status quo in 2015-2017. We found that in-school vision screening with follow-up eye examinations is an effective strategy for identifying at-risk children and placing them in eye care before grade 1.

Kaposi's Sarcoma-Associated Herpesvirus ORF66 Is Essential for Late Gene Expression and Virus Production via Interaction with ORF34.

Kaposi's sarcoma-associated herpesvirus (KSHV) is closely associated with B-cell and endothelial cell malignancies. After the initial infection, KSHV retains its viral genome in the nucleus of the host cell and establishes a lifelong latency. During lytic infection, KSHV-encoded lytic-related proteins are expressed in a sequential manner and are classified as immediate early, early, and late (L) gene transcripts. The transcriptional initiation of KSHV late genes is thought to require the complex formation of the viral preinitiation complex (vPIC), which may consist of at least 6 transcription factors (ORF18, -24, -30, -31, -34, and -66). However, the functional role of ORF66 in vPIC during KSHV replication remains largely unclear. Here, we generated ORF66-deficient KSHV using a bacterial artificial chromosome (BAC) system to evaluate its role during viral replication. While ORF66-deficient KSHV demonstrated mainly attenuated late gene expression and decreased virus production, viral DNA replication was unaffected. Chromatin immunoprecipitation analysis showed that ORF66 bound to the promoters of a late gene (K8.1) but did not bind to those of a latent gene (ORF72), an immediate early gene (ORF16), or an early gene (ORF46/47). Furthermore, we found that three highly conserved C-X-X-C sequences and a conserved leucine repeat in the C-terminal region of ORF66 were essential for the interaction with ORF34, the transcription of K8.1, and virus production. The interaction between ORF66 and ORF34 occurred in a zinc-dependent manner. Our data support a model in which ORF66 serves as a critical vPIC component to promote late viral gene expression and virus production.IMPORTANCE KSHV ORF66 is expressed during the early stages of lytic infection, and ORF66 and vPIC are thought to contribute significantly to late gene expression. However, the physiological importance of ORF66 in terms of vPIC formation remains poorly understood. Therefore, we generated an ORF66-deficient BAC clone and evaluated its viral replication. The results showed that ORF66 plays a critical role in virus production and the transcription of L genes. To our knowledge, this is the first report showing the function of ORF66 in virus replication using ORF66-deficient KSHV. We also clarified that ORF66 interacts with the transcription start site of the K8.1 gene, a late gene. Furthermore, we identified the ORF34-binding motifs in the ORF66 C terminus: three C-X-X-C sequences and a leucine-repeat sequence, which are highly conserved among beta- and gammaherpesviruses. Our study provides insights into the regulatory mechanisms of not only the late gene expression of KSHV but also those of other herpesviruses.

Choosing appropriate tools and referral criteria for vision screening of children aged 4-5 years in Canada: a quantitative analysis.

OBJECTIVES: To assess the diagnostic accuracy of five vision screening tools used in a school setting using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). DESIGN: We compared the results of the five best evidence-based screening tools available in 2014 to the results of a comprehensive eye exam with cycloplegic refraction by a licenced optometrist. Screening included Cambridge Crowded Acuity Cards, Plusoptix S12 and Spot photoscreeners, Preschool Randot Stereoacuity Test and the Pediatric Vision Scanner (PVS). Referral criteria followed AAPOS (2013) guidelines and published norms. SETTING: A large school in Toronto, Canada, with 25 split classrooms of junior kindergarten (JK: 4 year olds) and senior kindergarten (SK: 5 year olds) children. PARTICIPANTS: Over 2 years, 1132 eligible children were enrolled at the school. After obtaining parental consent, 832 children were screened. Subsequently, 709 children had complete screening and optometry exam data. MAIN OUTCOME MEASURES: The presence/absence of a visual problem based on optometrist's assessment: amblyopia, amblyopia risk factors (reduced stereoacuity, strabismus and clinically significant refractive errors) and any other ocular problem (eg, nystagmus). RESULTS: Overall, 26.5% of the screened children had a visual problem, including 5.9% with amblyopia. Using all five tools, screening sensitivity=84% (95% CI 78 to 89), specificity=49% (95% CI 44 to 53), PPV=37% (95% CI 33 to 42), and NPV=90% (95% CI 86 to 93). The odds of having a correct screening result in SK (mean age=68.2 months) was 1.5 times those in JK (mean age=55.6 months; 95% CI 1.1 to 2.1), with sensitivity improved to 89% (95% CI 80 to 96) and specificity improved to 57% (95% CI 50 to 64) among SK children. CONCLUSIONS: A school-based screening programme correctly identified 84% of those kindergarten children who were found to have a visual problem by a cyclopleged optometry exam. Additional analyses revealed how accuracy varies with different combinations of screening tools and referral criteria.

Access to Vision Services by Vulnerable Populations in Canada: A Scoping Review.

Vision impairment has a significant impact on quality of life. Seventy percent of existing vision impairment in Canada is estimated to be correctable with prescription glasses. The sizeable proportion of correctable vision impairment appears related to the barriers to access to vision care in Canada. The objective of this scoping review is to determine gaps in the understanding of barriers to accessing vision care for vulnerable populations in Canada. The Arksey and O'Malley methodological framework was adopted. Studies published in English between 2005 and September 2017 on access to primary vision care by vulnerable populations in Canada were reviewed. Electronic databases used included Ovid MEDLINE, Ovid EMBASE, SCOPUS, ProQuest, and CINAHL. The Behavioural Model of Health Services Use was used to elucidate gaps in the literature. To develop relevant policies around vision care, efforts should be made to assess all dimensions of access for vulnerable populations across Canada.

Age-associated increase in mnemonic strategy use is linked to prefrontal cortex development.

Memory functioning undergoes dynamic changes between childhood and adulthood. Spontaneous use of elaborative strategies, which can enhance the recall of information, expands with age and contributes to age-associated improvement in memory functioning. Findings from lesion and neuroimaging studies suggest that the ability to use elaborative strategies is dependent upon intact functioning of the prefrontal cortex (PFC), particularly the dorsolateral PFC region. Because the PFC undergoes protracted maturation, we examined whether age difference in the structure of the PFC is correlated with age-associated increase in strategy use. Here, we investigated the relationship between PFC volume and spontaneous strategy use in a sample of 120 participants aged 5-25 years. We assessed semantic clustering during recall with a standardized word-list recall task (California Verbal Learning Task children's version, CVLT-C) and computed PFC regional volumes from participants' structural brain images. We observed an age-associated increase in the use of semantic clustering and an age-associated decrease in volumes of the PFC. Further, we found that smaller PFC volume was linked to increased use of semantic clustering. Importantly, the volume of the right dorsolateral PFC partially explained the relation between age and the use of semantic clustering. These findings suggest that PFC maturation supports the development of strategy use and lends further support for the notion that brain-behavior relations change across development.

Socioeconomic status and hippocampal volume in children and young adults.

An individual's socioeconomic status (SES) is often viewed as a proxy for a host of environmental influences. SES disparities have been linked to variance in brain structures particularly the hippocampus, a neural substrate of learning and memory. However, it is unclear whether the association between SES and hippocampal volume is similar in children and adults. We investigated the relationship between hippocampal volume and SES in a group of children (n = 31, age 8-12 years) and a group of young adults (n = 32, age 18-25 years). SES was assessed with four indicators that loaded on a single factor, therefore a composite SES scores was used in the main analyses. Hippocampal volume was measured using manual demarcation on high resolution structural images. SES was associated with hippocampal volume in the children, but not in adults, suggesting that in childhood, but not adulthood, SES-related environmental factors influence hippocampal volume. In addition, hippocampal volume, but not SES, was associated with scores on a memory task, suggesting that net effects of postnatal environmental factors, captured by SES, are more distal determinants of memory performance than hippocampal volume. Longitudinal investigation of the association between SES, hippocampal volume and cognitive functioning may further our understanding of the putative neural mechanisms underlying SES-related environmental effects on cognitive development.

Kaposi's sarcoma-associated herpesvirus ORF34 is essential for late gene expression and virus production.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease. KSHV establishes a life-long infection in its host and alternates between a latent and lytic infection state. During lytic infection, lytic-related genes are expressed in a temporal manner and categorized as immediate early, early, and late gene transcripts. ORF34 is an early-late gene that interacts with several viral transcription-associated factors, however its physiological importance remains poorly understood. Here, we investigated the role of ORF34 during KSHV infection by generating ORF34-deficient KSHV, using a bacterial artificial chromosome system. Our results reveal that ORF34-deficient KSHV exhibited significantly attenuated late gene expression and viral production but did not affect viral DNA replication. ORF34 interacted with transcription factors ORF18, ORF24, ORF31, and ORF66, and a novel ORF34-interaction partner, ORF23. The C-terminal region of ORF34 was important for interaction with ORF24 and viral production. Our data support a model, in which ORF34 serves as a hub for recruiting a viral transcription complex to ORF24 to promote late viral gene expression.

Reduced adaptability, but no fundamental disruption, of norm-based face coding following early visual deprivation from congenital cataracts.

Faces are adaptively coded relative to visual norms that are updated by experience, and this adaptive coding is linked to face recognition ability. Here we investigated whether adaptive coding of faces is disrupted in individuals (adolescents and adults) who experience face recognition difficulties following visual deprivation from congenital cataracts in infancy. We measured adaptive coding using face identity aftereffects, where smaller aftereffects indicate less adaptive updating of face-coding mechanisms by experience. We also examined whether the aftereffects increase with adaptor identity strength, consistent with norm-based coding of identity, as in typical populations, or whether they show a different pattern indicating some more fundamental disruption of face-coding mechanisms. Cataract-reversal patients showed significantly smaller face identity aftereffects than did controls (Experiments 1 and 2). However, their aftereffects increased significantly with adaptor strength, consistent with norm-based coding (Experiment 2). Thus we found reduced adaptability but no fundamental disruption of norm-based face-coding mechanisms in cataract-reversal patients. Our results suggest that early visual experience is important for the normal development of adaptive face-coding mechanisms.

Size precedes view: developmental emergence of invariant object representations in lateral occipital complex.

Although object perception involves encoding a wide variety of object properties (e.g., size, color, viewpoint), some properties are irrelevant for identifying the object. The key to successful object recognition is having an internal representation of the object identity that is insensitive to these properties while accurately representing important diagnostic features. Behavioral evidence indicates that the formation of these kinds of invariant object representations takes many years to develop. However, little research has investigated the developmental emergence of invariant object representations in the ventral visual processing stream, particularly in the lateral occipital complex (LOC) that is implicated in object processing in adults. Here, we used an fMR adaptation paradigm to evaluate age-related changes in the neural representation of objects within LOC across variations in size and viewpoint from childhood through early adulthood. We found a dissociation between the neural encoding of object size and object viewpoint within LOC: by age of 5-10 years, area LOC demonstrates adaptation across changes in size, but not viewpoint, suggesting that LOC responses are invariant to size variations, but that adaptation across changes in view is observed in LOC much later in development. Furthermore, activation in LOC was correlated with behavioral indicators of view invariance across the entire sample, such that greater adaptation was correlated with better recognition of objects across changes in viewpoint. We did not observe similar developmental differences within early visual cortex. These results indicate that LOC acquires the capacity to compute invariance specific to different sources of information at different time points over the course of development.

Altered representation of facial expressions after early visual deprivation.

We investigated the effects of early visual deprivation on the underlying representation of the six basic emotions. Using multi-dimensional scaling (MDS), we compared the similarity judgments of adults who had missed early visual input because of bilateral congenital cataracts to control adults with normal vision. Participants made similarity judgments of the six basic emotional expressions, plus neutral, at three different intensities. Consistent with previous studies, the similarity judgments of typical adults could be modeled with four underlying dimensions, which can be interpreted as representing pleasure, arousal, potency and intensity of expressions. As a group, cataract-reversal patients showed a systematic structure with dimensions representing pleasure, potency, and intensity. However, an arousal dimension was not obvious in the patient group's judgments. Hierarchical clustering analysis revealed a pattern in patients seen in typical 7-year-olds but not typical 14-year-olds or adults. There was also more variability among the patients than among the controls, as evidenced by higher stress values for the MDS fit to the patients' data and more dispersed weightings on the four dimensions. The findings suggest an important role for early visual experience in shaping the later development of the representations of emotions. Since the normal underlying structure for emotion emerges postnatally and continues to be refined until late childhood, the altered representation of emotion in adult patients suggests a sleeper effect.

A case of functional (psychogenic) monocular hemianopia analyzed by measurement of hemifield visual evoked potentials.

PURPOSE: Functional monocular hemianopia is an extremely rare condition, for which measurement of hemifield visual evoked potentials (VEPs) has not been previously described. METHODS: A 14-year-old boy with functional monocular hemianopia was followed up with Goldmann perimetry and measurement of hemifield and full-field VEPs. RESULTS: The patient had a history of monocular temporal hemianopia of the right eye following headache, nausea and ague. There was no relative afferent pupillary defect, and a color perception test was normal. Goldmann perimetry revealed a vertical monocular temporal hemianopia of the right eye; the hemianopia on the right was also detected with a binocular visual field test. Computed tomography, magnetic resonance imaging (MRI) and MR angiography of the brain including the optic chiasm as well as orbital MRI revealed no abnormalities. On the basis of these results, we diagnosed the patient's condition as functional monocular hemianopia. Pattern VEPs according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standard were within the normal range. The hemifield pattern VEPs for the right eye showed a symmetrical latency and amplitude for nasal and temporal hemifield stimulation. One month later, the visual field defect of the patient spontaneously disappeared. CONCLUSIONS: The latency and amplitude of hemifield VEPs for a patient with functional monocular hemianopia were normal. Measurement of hemifield VEPs may thus provide an objective tool for distinguishing functional hemianopia from hemifield loss caused by an organic lesion.

Telling one face from another: electrocortical correlates of facial characteristics among individual female faces.

Research investigating the neural correlates of face processing has emphasized differences in neural activity when participants view faces versus other stimulus categories (e.g., houses). Much less is known about the neural mechanisms underlying the discrimination among individual faces. Using a large number of female faces, here we show that the amplitude of the face-sensitive N170 electrocortical component is related to a range of facial characteristics. The right N170 amplitude was related to eye color and face width. The left N170 amplitude was related to eye shape and face proportions, suggesting a functional dissociation between hemispheres. In contrast, the amplitude of the P100 and N250 components was largely unaffected by these facial characteristics. Consistent with recent findings in non-human primates, we identify for the first time evidence of human electrocortical brain potentials that are sensitive to variations in specific facial characteristics, a prerequisite for recognizing the identity of individual faces.

The functional neuroanatomy of object agnosia: a case study.

Cortical reorganization of visual and object representations following neural injury was examined using fMRI and behavioral investigations. We probed the visual responsivity of the ventral visual cortex of an agnosic patient who was impaired at object recognition following a lesion to the right lateral fusiform gyrus. In both hemispheres, retinotopic mapping revealed typical topographic organization and visual activation of early visual cortex. However, visual responses, object-related, and -selective responses were reduced in regions immediately surrounding the lesion in the right hemisphere, and also, surprisingly, in corresponding locations in the structurally intact left hemisphere. In contrast, hV4 of the right hemisphere showed expanded response properties. These findings indicate that the right lateral fusiform gyrus is critically involved in object recognition and that an impairment to this region has widespread consequences for remote parts of cortex. Finally, functional neural plasticity is possible even when a cortical lesion is sustained in adulthood.

Effect of adaptor duration on 8-year-olds' facial identity aftereffects suggests adult-like plasticity of the face norm.

Adapting to a face shifts the perceived identity of a subsequent face in the direction opposite to the adapting face, a phenomenon known as a face identity aftereffect. In the present study, we examined the temporal dynamics of such aftereffects in children at an age when face processing abilities are not yet adult-like. We hypothesized that children's difficulties in face processing may stem from an unstable mental representation of facial identity, which may be especially prone to adaptation aftereffects. Using a novel procedure designed especially for children, we show that both 8-year-olds and adults demonstrate identity aftereffects of similarly small size after just one second of viewing the adapting face, and that the strength of the aftereffect increases logarithmically and similarly with longer adapting durations for both age groups. The findings suggest that the mental representation of facial identity in 8-year-olds is no more malleable than that of adults, at least in response to short-term adaptation.

Probing the face-space of individuals with prosopagnosia.

A useful framework for understanding the mental representation of facial identity is face-space (Valentine, 1991), a multi-dimensional cognitive map in which individual faces are coded relative to the average of previously encountered faces, and in which the distance among faces represents their perceived similarity. We examined whether individuals with prosopagnosia, a disorder characterized by an inability to recognize familiar faces despite normal visual acuity and intellectual abilities, evince behavior consistent with this underlying representational schema. To do so, we compared the performance of 6 individuals with congenital prosopagnosia (CP), with a group of age- and gender-matched control participants in a series of experiments involving judgments of facial identity. We used digital images of male and female faces and morphed them to varying degrees relative to an average face, to create caricatures, anti-caricatures, and anti-faces (i.e. faces of the opposite identity). Across 5 behavioral tasks, CP individuals' performance was similar to that of the control group and consistent with the face-space framework. As a test of the sensitivity of our measures in revealing face processing abnormalities, we also tested a single acquired prosopagnosic (AP) individual, whose performance on the same tasks deviated significantly from the control and CP groups. The findings suggest that, despite an inability to recognize individual identities, CPs perceive faces in a manner consistent with norm-based coding of facial identity, although their representation is likely supported by a feature-based strategy. We suggest that the apparently normal posterior cortical regions, including the fusiform face area, serve as the neural substrate for at least a coarse, feature-based face-space map in CP and that their face recognition impairment arises from the disconnection between these regions and more anterior cortical sites.