Observational cohort study of 100 patients presenting with functional visual loss: clinical characteristics and comparison with other functional neurologic disorders.

OBJECTIVE: Recent research has helped to develop a more detailed understanding of many functional neurologic disorders. The aim of this study was to increase our knowledge of functional visual loss and to compare the findings with those of other functional syndromes. DESIGN: Prospective and retrospective observational cohort study. METHODS: This study took place at neuro-ophthalmology clinics at 3 major hospitals in London, United Kingdom, over a 12-month period. The study population consisted of 157 participants, 100 with functional visual loss, 21 pathologic control subjects with organic visual loss, and 36 healthy nonpathologic control subjects. All participants had their diagnosis confirmed with a full neuro-ophthalmic examination, neuroimaging, and visual electrophysiology. A full assessment of all participants' medical history was obtained from their general practitioner, and all participants completed a series of questionnaires assessing relevant associations. RESULTS: Data were obtained on 157 participants, 100 with functional visual loss, 21 pathologic control subjects with organic visual loss, and 36 healthy nonpathologic control subjects. Participants with functional visual loss were typically female (74%) with a mean age at vision loss of 40.0 ± 16 years. Sixty-four percent of participants had bilateral vision loss; the remainder, unilateral loss. Twenty-six percent of the total cohort had organic visual loss with functional overlay. Fifty percent of participants with functional visual loss had a preexisting psychiatric diagnosis, the most common being a depressive disorder. Sixty-two percent of participants had an ocular history, and 87% had a previously diagnosed medical illness, most commonly neurologic (45%). Thirty-five percent of participants self-reported at least 1 additional functional symptom. CONCLUSIONS: Our population of functional visual loss subjects shares many similarities with the majority of patients with other functional neurologic disorders. They are generally young and female and have a greater than expected rate of psychiatric, medical, and coexisting ocular conditions. We found increased rates of precipitating stressors, clinical depression, and organic eye problems in subjects with functional visual loss.

Psychogenic amnesia: syndromes, outcome, and patterns of retrograde amnesia.

There are very few case series of patients with acute psychogenic memory loss (also known as dissociative/functional amnesia), and still fewer studies of outcome, or comparisons with neurological memory-disordered patients. Consequently, the literature on psychogenic amnesia is somewhat fragmented and offers little prognostic value for individual patients. In the present study, we reviewed the case records and neuropsychological findings in 53 psychogenic amnesia cases (ratio of 3:1, males:females), in comparison with 21 consecutively recruited neurological memory-disordered patients and 14 healthy control subjects. In particular, we examined the pattern of retrograde amnesia on an assessment of autobiographical memory (the Autobiographical Memory Interview). We found that our patients with psychogenic memory loss fell into four distinct groups, which we categorized as: (i) fugue state; (ii) fugue-to-focal retrograde amnesia; (iii) psychogenic focal retrograde amnesia following a minor neurological episode; and (iv) patients with gaps in their memories. While neurological cases were characterized by relevant neurological symptoms, a history of a past head injury was actually more common in our psychogenic cases (P = 0.012), perhaps reflecting a 'learning episode' predisposing to later psychological amnesia. As anticipated, loss of the sense of personal identity was confined to the psychogenic group. However, clinical depression, family/relationship problems, financial/employment problems, and failure to recognize the family were also statistically more common in that group. The pattern of autobiographical memory loss differed between the psychogenic groups: fugue cases showed a severe and uniform loss of memories for both facts and events across all time periods, whereas the two focal retrograde amnesia groups showed a 'reversed' temporal gradient with relative sparing of recent memories. After 3-6 months, the fugue patients had improved to normal scores for facts and near-normal scores for events. By contrast, the two focal retrograde amnesia groups showed less improvement and continued to show a reversed temporal gradient. In conclusion, the outcome in psychogenic amnesia, particularly those characterized by fugue, is better than generally supposed. Findings are interpreted in terms of Markowitsch's and Kopelman's models of psychogenic amnesia, and with respect to Anderson's neuroimaging findings in memory inhibition.

Psychological therapy for psychogenic amnesia: Successful treatment in a single case study.

Psychogenic amnesia is widely understood to be a memory impairment of psychological origin that occurs as a response to severe stress. However, there is a paucity of evidence regarding the effectiveness of psychological therapy approaches in the treatment of this disorder. The current article describes a single case, "Ben", who was treated with formulation-driven psychological therapy using techniques drawn from cognitive behavioural therapy (CBT) and acceptance and commitment therapy (ACT) for psychogenic amnesia. Before treatment, Ben exhibited isolated retrograde and anterograde memory impairments. He received 12 therapy sessions that targeted experiential avoidance followed by two review sessions, six weeks and five months later. Ben's retrograde and anterograde memory impairments improved following therapy to return to within the "average" to "superior" ranges, which were maintained at follow-up. Further experimental single case study designs and larger group studies are required to advance the understanding of the effectiveness and efficacy of psychological therapy for psychogenic amnesia.

Face processing in Williams syndrome is already atypical in infancy.

Face processing is a crucial socio-cognitive ability. Is it acquired progressively or does it constitute an innately-specified, face-processing module? The latter would be supported if some individuals with seriously impaired intelligence nonetheless showed intact face-processing abilities. Some theorists claim that Williams syndrome (WS) provides such evidence since, despite IQs in the 50s, adolescents/adults with WS score in the normal range on standardized face-processing tests. Others argue that atypical neural and cognitive processes underlie WS face-processing proficiencies. But what about infants with WS? Do they start with typical face-processing abilities, with atypicality developing later, or are atypicalities already evident in infancy? We used an infant familiarization/novelty design and compared infants with WS to typically developing controls as well as to a group of infants with Down syndrome matched on both mental and chronological age. Participants were familiarized with a schematic face, after which they saw a novel face in which either the features (eye shape) were changed or just the configuration of the original features. Configural changes were processed successfully by controls, but not by infants with WS who were only sensitive to featural changes and who showed syndrome-specific profiles different from infants with the other neurodevelopmental disorder. Our findings indicate that theorists can no longer use the case of WS to support claims that evolution has endowed the human brain with an independent face-processing module.

A neurogenetics approach to defining differential susceptibility to institutional care.

An individual's neurodevelopmental and cognitive sequelae to negative early experiences may, in part, be explained by genetic susceptibility. We examined whether extreme differences in the early caregiving environment, defined as exposure to severe psychosocial deprivation associated with institutional care compared to normative rearing, interacted with a biologically informed genoset comprising BDNF (rs6265), COMT (rs4680), and SIRT1 (rs3758391) to predict distinct outcomes of neurodevelopment at age 8 (N = 193, 97 males and 96 females). Ethnicity was categorized as Romanian (71%), Roma (21%), unknown (7%), or other (1%). We identified a significant interaction between early caregiving environment (i.e., institutionalized versus never institutionalized children) and the a priori defined genoset for full-scale IQ, two spatial working memory tasks, and prefrontal cortex gray matter volume. Model validation was performed using a bootstrap resampling procedure. Although we hypothesized that the effect of this genoset would operate in a manner consistent with differential susceptibility, our results demonstrate a complex interaction where vantage susceptibility, diathesis stress, and differential susceptibility are implicated.

mHealth and memory aids: levels of smartphone ownership in patients.

BACKGROUND: The use of mobile devices to deliver healthcare has not yet been exploited in neuropsychological rehabilitation. Smartphones have the potential to serve as multi-functional memory aids. AIMS: To investigate whether patients attending a clinic for mixed memory problems own smartphones, to determine whether this could be a widely applicable medium to use as a memory aids device. METHODS: A questionnaire on smartphone ownership was given to an opportunity sample of consecutive patients attending a neuropsychiatry and memory disorders outpatient clinic. Data were collected in 2012 and repeated 12 months later in 2013 to assess changes over time. RESULTS: Ownership of mobile phones was stable between 2012 (81%) and 2013 (85%), but ownership of smartphones showed a significant increase (from 26% to 40%). Age negatively predicted smartphone ownership. CONCLUSION: Despite cognitive or psychiatric problems, our patient group are as likely to own a mobile phone as a member of the general population. Ownership levels are at 40% and likely to increase in the future. Exploring how smartphones and their apps could function as memory aids is likely to be useful for a large enough number of patients to be clinically worthwhile.

The anatomy of the callosal and visual-association pathways in high-functioning autism: a DTI tractography study.

There is increasing recognition that many of the core behavioral impairments that characterize autism potentially emerge from poor neural synchronization across nodes comprising dispersed cortical networks. A likely candidate for the source of this atypical functional connectivity in autism is an alteration in the structural integrity of intra- and inter-hemispheric white matter (WM) tracts that form large-scale cortical networks. To test this hypothesis, in a group of adults with high-functioning autism (HFA) and matched control participants, we used diffusion tensor tractography to compare the structural integrity of three intra-hemispheric visual-association WM tracts, the inferior longitudinal fasciculus (ILF), the inferior fronto-occipito fasciculus (IFOF) and the uncinate fasciculus (UF), with the integrity of three sub-portions of the major inter-hemispheric fiber tract, the corpus callosum. Compared with the control group, the HFA group evinced an increase in the volume of the intra-hemispheric fibers, particularly in the left hemisphere, and a reduction in the volume of the forceps minor (F-Mi) and body of the corpus callosum. The reduction in the volume of the F-Mi also correlated with an increase in repetitive and stereotypical behavior as measured by the Autism Diagnostic Interview. These findings suggest that the abnormalities in the integrity of key inter- and intra-hemispheric WM tracts may underlie the atypical information processing observed in these individuals.

Normal movement selectivity in autism.

It has been proposed that individuals with autism have difficulties understanding the goals and intentions of others because of a fundamental dysfunction in the mirror neuron system. Here, however, we show that individuals with autism exhibited not only normal fMRI responses in mirror system areas during observation and execution of hand movements but also exhibited typical movement-selective adaptation (repetition suppression) when observing or executing the same movement repeatedly. Movement selectivity is a defining characteristic of neurons involved in movement perception, including mirror neurons, and, as such, these findings argue against a mirror system dysfunction in autism.

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.

Reduced structural connectivity in ventral visual cortex in congenital prosopagnosia.

Using diffusion tensor imaging and tractography, we found that a disruption in structural connectivity in ventral occipito-temporal cortex may be the neurobiological basis for the lifelong impairment in face recognition that is experienced by individuals who suffer from congenital prosopagnosia. Our findings suggest that white-matter fibers in ventral occipito-temporal cortex support the integrated function of a distributed cortical network that subserves normal face processing.

Reduction in white matter connectivity, revealed by diffusion tensor imaging, may account for age-related changes in face perception.

An age-related decline in face processing, even under conditions in which learning and memory are not implicated, has been well documented, but the mechanism underlying this perceptual alteration remains unknown. Here, we examine whether this behavioral change may be accounted for by a reduction in white matter connectivity with age. To this end, we acquired diffusion tensor imaging data from 28 individuals aged 18 to 86 years and quantified the number of fibers, voxels, and fractional anisotropy of the two major tracts that pass through the fusiform gyrus, the pre-eminent face processing region in the ventral temporal cortex. We also measured the ability of a subset of these individuals to make fine-grained discriminations between pairs of faces and between pairs of cars. There was a significant reduction in the structural integrity of the inferior fronto-occipital fasciculus (IFOF) in the right hemisphere as a function of age on all dependent measures and there were also some changes in the left hemisphere, albeit to a lesser extent. There was also a clear age-related decrement in accuracy of perceptual discrimination, especially for more challenging perceptual discriminations, and this held to a greater degree for faces than for cars. Of greatest relevance, there was a robust association between the reduction of IFOF integrity in the right hemisphere and the decline in face perception, suggesting that the alteration in structural connectivity between the right ventral temporal and frontal cortices may account for the age-related difficulties in face processing.

Cortical patterns of category-selective activation for faces, places and objects in adults with autism.

Autism is associated with widespread atypicalities in perception, cognition and social behavior. A crucial question concerns how these atypicalities are reflected in the underlying brain activation. One way to examine possible perturbations of cortical organization in autism is to analyze the activation of category-selective ventral visual cortex, already clearly delineated in typical populations. We mapped out the neural correlates of face, place and common object processing, using functional magnetic resonance imaging (fMRI), in a group of high-functioning adults with autism and a typical comparison group, under both controlled and more naturalistic, viewing conditions. There were no consistent group differences in place-related regions. Although there were no significant differences in the extent of the object-related regions, there was more variability for these regions in the autism group. The most marked group differences were in face-selective cortex, with individuals with autism evincing reduced activation, not only in fusiform face area but also in superior temporal sulcus and occipital face area. Ventral visual cortex appears to be organized differently in high-functioning adults with autism, at least for face-selective regions, although subtle differences may also exist for other categories. We propose that cascading developmental effects of low-level differences in neuronal connectivity result in a much more pronounced effect on later developing cortical systems, such as that for face-processing, than earlier maturing systems (those for objects and places).

Visual category-selectivity for faces, places and objects emerges along different developmental trajectories.

The organization of category-selective regions in ventral visual cortex is well characterized in human adults. We investigated a crucial, previously unaddressed, question about how this organization emerges developmentally. We contrasted the developmental trajectories for face-, object-, and place-selective activation in the ventral visual cortex in children, adolescents, and adults. Although children demonstrated adult-like organization in object- and place-related cortex, as a group they failed to show consistent face-selective activation in classical face regions. The lack of a consistent neural signature for faces was attributable to (1) reduced face-selectivity and extent of activation within the regions that will become the FFA, OFA, and STS in adults, and (2) smaller volumes and considerable variability in the locus of face-selective activation in individual children. In contrast, adolescents showed an adult-like pattern of face-selective activation, although it was more right-lateralized. These findings reveal critical age-related differences in the emergence of category-specific functional organization in the visual cortex and support a model of brain development in which specialization emerges from interactions between experience-dependent learning and the maturing brain.

A detailed investigation of facial expression processing in congenital prosopagnosia as compared to acquired prosopagnosia.

Whether the ability to recognize facial expression can be preserved in the absence of the recognition of facial identity remains controversial. The current study reports the results of a detailed investigation of facial expression recognition in three congenital prosopagnosic (CP) participants, in comparison with two patients with acquired prosopagnosia (AP) and a large group of 30 neurologically normal participants, including individually age- and gender-matched controls. Participants completed a fine-grained expression recognition paradigm requiring a six-alternative forced-choice response to continua of morphs of six different basic facial expressions (e.g. happiness and surprise). Accuracy, sensitivity and reaction times were measured. The performance of all three CP individuals was indistinguishable from that of controls, even for the most subtle expressions. In contrast, both individuals with AP displayed pronounced difficulties with the majority of expressions. The results from the CP participants attest to the dissociability of the processing of facial identity and of facial expression. Whether this remarkably good expression recognition is achieved through normal, or compensatory, mechanisms remains to be determined. Either way, this normal level of performance does not extend to include facial identity.

A fine-grained analysis of facial expression processing in high-functioning adults with autism.

It is unclear whether individuals with autism are impaired at recognizing basic facial expressions, and whether, if any impairment exists, it applies to expression processing in general, or to certain expressions, in particular. To evaluate these alternatives, we adopted a fine-grained analysis of facial expression processing in autism. Specifically, we used the 'facial expression megamix' paradigm [Young, A. W., Rowland, D., Calder, A. J, Etcoff, N. L., Seth, A., & Perrett, D. I. (1997). Facial expression megamix: Tests of dimensional and category accounts of emotion recognition Cognition and Emotion, 14, 39-60] in which adults with autism and a typically developing comparison group performed a six alternative forced-choice response to morphs of all possible combinations of the six basic expressions identified by Ekman [Ekman, P. (1972). Universals and cultural differences in facial expressions of emotion. In J. K. Cole (Ed.), Nebraska symposium on motivation: vol. 1971, (pp. 207-283). Lincoln, Nebraska: University of Nebraska Press] (happiness, sadness, disgust, anger, fear and surprise). Clear differences were evident between the two groups, most obviously in the recognition of fear, but also in the recognition of disgust and happiness. A second experiment demonstrated that individuals with autism are able to discriminate between different emotional images and suggests that low-level perceptual difficulties do not underlie the difficulties with emotion recognition.

Using "Bubbles" with babies: a new technique for investigating the informational basis of infant perception.

The 'Bubbles' technique (Gosselin, F. & Schyns, P.G. (2001). Bubbles: A technique to reveal the use of information in recognition tasks. Vision Research, 41, 2261-2271) has been widely used to reveal the information adults use to make perceptual categorizations. We present, for the first time, an adapted form of Bubbles, suitable for use with young infants.

Seeing it differently: visual processing in autism.

Several recent behavioral and neuroimaging studies have documented an impairment in face processing in individuals with Autism Spectrum Disorder (ASD). It remains unknown, however, what underlying mechanism gives rise to this face processing difficulty. One theory suggests that the difficulty derives from a pervasive problem in social interaction and/or motivation. An alternative view proposes that the face-processing problem is not entirely social in nature and that a visual perceptual impairment might also contribute. The focus of this review is on this latter, perceptual perspective, documenting the psychological and neural alterations that might account for the face processing impairment. The available evidence suggests that perceptual alterations are present in ASD, independent of social function.

Configural processing in autism and its relationship to face processing.

Studies of the perceptual performance of individuals with autism have focused, to a large extent, on two domains of visual behavior, one associated with face processing and the other associated with global or holistic processing. Whether autistic individuals differ from neurotypical individuals in these domains is debatable and, moreover, the relationship between the behaviors in these two domains remains unclear. We first compared the face processing ability of 14 adult individuals with autism with that of neurotypical controls and showed that the autistic individuals were slowed in their speed of face discrimination. We then showed that the two groups differed in their ability to derive the global whole in two different tasks, one using hierarchical compound letters and the other using a microgenetic primed matching task with geometric shapes, with the autistic group showing a bias in favor of local information. A significant correlation was also observed between performance on the face task and the configural tasks. We then confirmed the prediction that the ability to derive the global whole is not only critical for faces but also for other objects as well, as the autistic individuals performed more slowly than the control group in discriminating between objects. Taken together, the results suggest that the bias for local processing seen in autistic individuals might have an adverse impact on their ability to process faces and objects.

Exploring the Williams syndrome face-processing debate: the importance of building developmental trajectories.

BACKGROUND: Face processing in Williams syndrome (WS) has been a topic of heated debate over the past decade. Initial claims about a normally developing ('intact') face-processing module were challenged by data suggesting that individuals with WS used a different balance of cognitive processes from controls, even when their behavioural scores fell within the normal range. Measurement of evoked brain potentials also point to atypical processes. However, two recent studies have claimed that people with WS process faces exactly like normal controls. METHOD: In this paper, we examine the details of this continuing debate on the basis of three new face-processing experiments. In particular, for two of our experiments we built task-specific full developmental trajectories from childhood to adolescence/adulthood and plotted the WS data on these trajectories. RESULTS: The first experiment used photos of real faces. While it revealed broadly equivalent accuracy across groups, the WS participants were worse at configural processing when faces were upright and less sensitive than controls to face inversion. In Experiment 2, measuring face processing in a storybook context, the face inversion effect emerged clearly in controls but only weakly in the WS developmental trajectory. Unlike the controls, the Benton Face Recognition Test and the Pattern Construction results were not correlated in WS, highlighting the different developmental patterns in the two groups. Again in contrast to the controls, Experiment 3 with schematic faces and non-face stimuli revealed a configural-processing deficit in WS both with respect to their chronological age (CA) and to their level of performance on the Benton. CONCLUSION: These findings point to both delay and deviance in WS face processing and illustrate how vital it is to build developmental trajectories for each specific task.