Clinicopathological diversity of semantic dementia: Comparisons of patients with early-onset versus late-onset, left-sided versus right-sided temporal atrophy, and TDP-type A versus type C pathology.

Semantic dementia (SD) is a unique clinicopathological entity associated with TDP-type C pathology. We present four cases of SD that illustrate the clinicopathological diversity of TDP-43 pathology, including early-onset cases of TDP-type C with corticospinal tract (CST) and motor neuron pathology and late-onset cases of TDP-type A with combined pathology. Case 1 was a 62-year-old man with semantic variant of primary progressive aphasia (svPPA) with left-predominant temporal atrophy and TDP-type C pathology with low Alzheimer's disease neuropathologic changes (ADNC). Case 2 was a 63-year-old woman with right-predominant temporal atrophy and TDP-type C pathology who had prosopagnosia and personality changes. Phosphorylated(p)-TDP-43-positive long dystrophic neurites (DNs) were observed throughout the cerebral cortex; they were more abundant in the relatively spared cortices and less so in the severely degenerated cortices. We observed CST degeneration with TDP-43 pathology in the upper and lower motor neurons, without apparent motor symptoms, in SD with TDP-type C pathology. Case 3 was a 76-year-old man who had svPPA and personality changes, with left-predominant temporal atrophy and TDP-type A pathology with high ADNC and argyrophilic grain (AG) stage 3. Case 4 was an 82-year-old man who had prosopagnosia and later developed symptoms of dementia with Lewy bodies (DLB) with right-predominant temporal atrophy and TDP-type A pathology with high ADNC, DLB of diffuse neocortical type, and AG stage 3. The distribution of p-TDP-43-positive NCIs and short DNs was localized in the anterior and inferior temporal cortices. An inverse relationship between the extent of TDP pathology and neuronal loss was also observed in SD with TDP-type A pathology. In contrast, the extent of AD, DLB, and AG pathology was greater in severely degenerated regions. CST degeneration was either absent or very mild in SD with TDP-type A. Understanding the clinicopathological diversity of SD will help improve its diagnosis and treatment.

Atypical prosopagnosia following right hemispheric stroke: A 23-year follow-up study with M.T.

Most findings on prosopagnosia to date suggest preserved voice recognition in prosopagnosia (except in cases with bilateral lesions). Here we report a follow-up examination on M.T., suffering from acquired prosopagnosia following a large unilateral right-hemispheric lesion in frontal, parietal, and anterior temporal areas excluding core ventral occipitotemporal face areas. Twenty-three years after initial testing we reassessed face and object recognition skills [Henke, K., Schweinberger, S. R., Grigo, A., Klos, T., & Sommer, W. (1998). Specificity of face recognition: Recognition of exemplars of non-face objects in prosopagnosia. Cortex, 34(2), 289-296]; [Schweinberger, S. R., Klos, T., & Sommer, W. (1995). Covert face recognition in prosopagnosia - A dissociable function? Cortex, 31(3), 517-529] and additionally studied voice recognition. Confirming the persistence of deficits, M.T. exhibited substantial impairments in famous face recognition and memory for learned faces, but preserved face matching and object recognition skills. Critically, he showed substantially impaired voice recognition skills. These findings are congruent with the ideas that (i) prosopagnosia after right anterior temporal lesions can persist over long periods > 20 years, and that (ii) such lesions can be associated with both facial and vocal deficits in person recognition.

Face processing in the temporal lobe.

Face perception is a socially important but complex process with many stages and many facets. There is substantial evidence from many sources that it involves a large extent of the temporal lobe, from the ventral occipitotemporal cortex and superior temporal sulci to anterior temporal regions. While early human neuroimaging work suggested a core face network consisting of the occipital face area, fusiform face area, and posterior superior temporal sulcus, studies in both humans and monkeys show a system of face patches stretching from posterior to anterior in both the superior temporal sulcus and inferotemporal cortex. Sophisticated techniques such as fMRI adaptation have shown that these face-activated regions show responses that have many of the attributes of human face processing. Lesions of some of these regions in humans lead to variants of prosopagnosia, the inability to recognize the identity of a face. Lesion, imaging, and electrophysiologic data all suggest that there is a segregation between identity and expression processing, though some suggest this may be better characterized as a distinction between static and dynamic facial information.

Facial identity and facial speech processing in developmental prosopagnosia.

The neural substrate of acquired prosopagnosia, including its lateralization, remains a matter of investigation. Face processing networks in healthy subjects are right dominant, and acquired prosopagnosia usually results from right or bilateral lesions. Nevertheless, there may be a complementary contribution of the left hemisphere to certain types of face processing. Prior reports suggest that this might be processing faces depicted by line contours, or lip reading. We performed two behavioural studies in seven subjects with developmental prosopagnosia. The first examined their ability to match faces across viewpoint changes, with either unaltered photographs or images that had been reduced to line elements. Prosopagnosic subjects had normal performance with line-contour faces, but failed to show the normal benefit from the additional information in unaltered photographs. The second experiment examined their ability to perceive facial speech patterns. Prosopagnosic subjects could detect, discriminate and identify facial speech patterns, but most showed reduced use of these cues or anomalous audiovisual integration in the McGurk effect, with only one subject performing normally. We conclude that developmental prosopagnosia can be associated with a subtle impairment in lip reading, which in prior studies of acquired lesions has been associated more with left than with right fusiform damage.

Anatomical and neurophysiological basis of face recognition.

Face recognition is a highly developed and efficient human function that involves multiple neural networks. A main pathway links the occipital cortex, where an occipital face area (OFA) has been identified, to a fusiform face area (FFA) in the fusiform gyrus, which plays a critical role in face recognition. This core pathway deals with invariant aspects of the face. Another pathway, including the superior temporal sulcus, is involved in the perception of more changeable aspects of the face such as gaze orientation, face expression and lip movements. It has been defined by some authors as a "third pathway of visual recognition", i.e. a lateral pathway in addition to the "what" and "where" pathways. It deals with sociocognitive aspects of face perception. Many other accessory functional systems are connected to the core system of visual recognition to act in concert with it: the intraparietal sulcus (for the management of spatial attention), the primary auditory cortex (prelexical perception of speech), the amygdala, the insula and the limbic system (perception of emotions), the anterior temporal pole (access to the identity of the individual, his name, biographical information), etc. Functional brain imaging has made remarkable progress in the understanding of face perception, which in the early years was limited to the description of single cases of brain-damaged patients. This progress has made it possible to better analyse the many face recognition disorders, sometimes subtle, other times confusing, observed in human pathology.

[A case suspected of Alzheimer type dementia showing multimodal (face and voice) person recognition disorder from face and voice].

A 90-year-old woman presented with a multimodal (face and voice) person recognition disorder. Although she had moderate general cognitive impairment, her visual cognitive capacity, other than face recognition, was well preserved. She could identify the faces and voices of family members but could not recall the names and voices of relatives whom she met infrequently, famous individuals, or the medical staff. She could remember the first names and some information about prominent individuals when supplied with their surnames. Therefore, we thought that her person-specific semantic memory was intact but she was unable to access it through their faces and voices. MRI revealed predominantly right-sided bilateral anterior temporal lobe and hippocampal atrophy. SPECT images showed decreased blood flow in the bilateral anterior temporal lobes and inferior parietal lobule (heavily and predominantly right-sided), right posterior cingulate gyrus, and precuneus. Progressive person recognition disorder or prosopagnosia has been considered a right temporal variant of frontotemporal lobar degeneration because abnormal behaviors and psychiatric symptoms frequently coexist. However, no such symptoms were observed in this case, therefore we suspected dementia of the Alzheimer type.

The hidden identity of faces: a case of lifelong prosopagnosia.

BACKGROUND: Not being able to recognize a person's face is a highly debilitating condition from which people with developmental prosopagnosia (DP) suffer their entire life. Here we describe the case of J, a 30 year old woman who reports being unable to recognize her parents, her husband, or herself in the mirror. CASE PRESENTATION: We set out to assess the severity of J's prosopagnosia using tests with unfamiliar as well as familiar faces and investigated whether impaired configural processing explains her deficit. To assess the specificity of the impairment, we tested J's performance when evaluating emotions, intentions, and the attractiveness and likability of faces. Detailed testing revealed typical brain activity patterns for faces and normal object recognition skills, and no evidence of any brain injury. However, compared to a group of matched controls, J showed severe deficits in learning new faces, and in recognizing familiar faces when only inner features were available. Her recognition of uncropped faces with blurred features was within the normal range, indicating preserved configural processing when peripheral features are available. J was also unimpaired when evaluating intentions and emotions in faces. In line with healthy controls, J rated more average faces as more attractive. However, she was the only one to rate them as less likable, indicating a preference for more distinctive and easier to recognize faces. CONCLUSIONS: Taken together, the results illustrate both the severity and the specificity of DP in a single case. While DP is a heterogeneous disorder, an inability to integrate the inner features of the face into a whole might be the best explanation for the difficulties many individuals with prosopagnosia experience.

Delayed processing of global shape information is associated with weaker top-down effects in developmental prosopagnosia.

In previous studies we have shown that a group of individuals with developmental prosopagnosia (DP): (i) were impaired at recognizing objects when presented as silhouettes or fragmented forms; stimuli which place particular demands on global shape processing, (ii) that these impairments correlated with their face recognition deficit, (iii) that they showed a reduced global precedence effect in Navon's paradigm, and (iv) that the magnitude of their global precedence effect correlated with their face and object recognition performance. This pattern of deficits points towards a delay in the processing of global shape information; a delay that may weaken top-down influences on recognition performance. Here we show that the DPs show reduced real object superiority effects (faster responses to real objects than nonobjects) compared with controls. Given that real object superiority effects reflect top-down processing, these findings support the notion of impaired global shape based top-down processing in DP.

Decisional space determines saccadic reaction times in healthy observers and acquired prosopagnosia.

Determining the familiarity and identity of a face have been considered as independent processes. Covert face recognition in cases of acquired prosopagnosia, as well as rapid detection of familiarity have been taken to support this view. We tested P.S. a well-described case of acquired prosopagnosia, and two healthy controls (her sister and daughter) in two saccadic reaction time (SRT) experiments. Stimuli depicted their family members and well-matched unfamiliar distractors in the context of binary gender, or familiarity decisions. Observers' minimum SRTs were estimated with Bayesian approaches. For gender decisions, P.S. and her daughter achieved sufficient performance, but displayed different SRT distributions. For familiarity decisions, her daughter exhibited above chance level performance and minimum SRTs corresponding to those reported previously in healthy observers, while P.S. performed at chance. These findings extend previous observations, indicating that decisional space determines performance in both the intact and impaired face processing system.

Identifying Hallmark Symptoms of Developmental Prosopagnosia for Non-Experts.

Developmental prosopagnosia (DP) is characterised by a severe and relatively selective deficit in face recognition, in the absence of neurological injury. Because public and professional awareness of DP is low, many adults and children are not identified for formal testing. This may partly result from the lack of appropriate screening tools that can be used by non-experts in either professional or personal settings. To address this issue, the current study sought to (a) explore when DP can first be detected in oneself and another, and (b) identify a list of the condition's everyday behavioural manifestations. Questionnaires and interviews were administered to large samples of adult DPs, their unaffected significant others, and parents of children with the condition; and data were analysed using inductive content analysis. It was found that DPs have limited insight into their difficulties, with most only achieving realisation in adulthood. Nevertheless, the DPs' reflections on their childhood experiences, together with the parental responses, revealed specific indicators that can potentially be used to spot the condition in early childhood. These everyday hallmark symptoms may aid the detection of individuals who would benefit from objective testing, in oneself (in adults) or another person (for both adults and children).

Altered topology of neural circuits in congenital prosopagnosia.

Using a novel, fMRI-based inter-subject functional correlation (ISFC) approach, which isolates stimulus-locked inter-regional correlation patterns, we compared the cortical topology of the neural circuit for face processing in participants with an impairment in face recognition, congenital prosopagnosia (CP), and matched controls. Whereas the anterior temporal lobe served as the major network hub for face processing in controls, this was not the case for the CPs. Instead, this group evinced hyper-connectivity in posterior regions of the visual cortex, mostly associated with the lateral occipital and the inferior temporal cortices. Moreover, the extent of this hyper-connectivity was correlated with the face recognition deficit. These results offer new insights into the perturbed cortical topology in CP, which may serve as the underlying neural basis of the behavioral deficits typical of this disorder. The approach adopted here has the potential to uncover altered topologies in other neurodevelopmental disorders, as well.

The cognitive and neural basis of developmental prosopagnosia.

Developmental prosopagnosia (DP) is a severe impairment of visual face recognition in the absence of any apparent brain damage. The factors responsible for DP have not yet been fully identified. This article provides a selective review of recent studies investigating cognitive and neural processes that may contribute to the face recognition deficits in DP, focusing primarily on event-related brain potential (ERP) measures of face perception and recognition. Studies that measured the face-sensitive N170 component as a marker of perceptual face processing have shown that the perceptual discrimination between faces and non-face objects is intact in DP. Other N170 studies suggest that faces are not represented in the typical fashion in DP. Individuals with DP appear to have specific difficulties in processing spatial and contrast deviations from canonical upright visual-perceptual face templates. The rapid detection of emotional facial expressions appears to be unaffected in DP. ERP studies of the activation of visual memory for individual faces and of the explicit identification of particular individuals have revealed differences between DPs and controls in the timing of these processes and in the links between visual face memory and explicit face recognition. These observations suggest that the speed and efficiency of information propagation through the cortical face network is altered in DP. The nature of the perceptual impairments in DP suggests that atypical visual experience with the eye region of faces over development may be an important contributing factor to DP.

Altered spontaneous neural activity in the occipital face area reflects behavioral deficits in developmental prosopagnosia.

Individuals with developmental prosopagnosia (DP) exhibit severe difficulties in recognizing faces and to a lesser extent, also exhibit difficulties in recognizing non-face objects. We used fMRI to investigate whether these behavioral deficits could be accounted for by altered spontaneous neural activity. Two aspects of spontaneous neural activity were measured: the intensity of neural activity in a voxel indexed by the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), and the connectivity of a voxel to neighboring voxels indexed by regional homogeneity (ReHo). Compared with normal adults, both the fALFF and ReHo values within the right occipital face area (rOFA) were significantly reduced in DP subjects. Follow-up studies on the normal adults revealed that these two measures indicated further functional division of labor within the rOFA. The fALFF in the rOFA was positively correlated with behavioral performance in recognition of non-face objects, whereas ReHo in the rOFA was positively correlated with processing of faces. When considered together, the altered fALFF and ReHo within the same region (rOFA) may account for the comorbid deficits in both face and object recognition in DPs, whereas the functional division of labor in these two measures helps to explain the relative independency of deficits in face recognition and object recognition in DP.

Localization and patterns of Cerebral dyschromatopsia: A study of subjects with prospagnosia.

OBJECTIVE: Cerebral dyschromatopsia is sometimes associated with acquired prosopagnosia. Given the variability in structural lesions that cause acquired prosopagnosia, this study aimed to investigate the structural correlates of prosopagnosia-associated dyschromatopsia, and to determine if such colour processing deficits could also accompany developmental prosopagnosia. In addition, we studied whether cerebral dyschromatopsia is typified by a consistent pattern of hue impairments. METHODS: We investigated hue discrimination in a cohort of 12 subjects with acquired prosopagnosia and 9 with developmental prosopagnosia, along with 42 matched controls, using the Farnsworth-Munsell 100-hue test. RESULTS: We found impaired hue discrimination in six subjects with acquired prosopagnosia, five with bilateral and one with a unilateral occipitotemporal lesion. Structural MRI analysis showed maximum overlap of lesions in the right and left lingual and fusiform gyri. Fourier analysis of their error scores showed tritanopic-like deficits and blue-green impairments, similar to tendencies displayed by the healthy controls. Three subjects also showed a novel fourth Fourier component, indicating additional peak deficits in purple and green-yellow regions. No subject with developmental prosopagnosia had impaired hue discrimination. CONCLUSIONS: In our subjects with prosopagnosia, dyschromatopsia occurred in those with acquired lesions of the fusiform gyri, usually bilateral but sometimes unilateral. The dyschromatopsic deficit shows mainly an accentuation of normal tritatanopic-like tendencies. These are sometimes accompanied by additional deficits, although these could represent artifacts of the testing procedure.

Temporal lobe contribution to perceptual function: A tale of three patient groups.

There has been growing recognition of the contribution of medial and anterior temporal lobe structures to non-mnemonic functions, such as perception. To evaluate the nature of this contribution, we contrast the perceptual performance of three patient groups, all of whom have a perturbation of these temporal lobe structures. Specifically, we compare the profile of patients with focal hippocampal (HC) lesions, those with more extensive lesions to the medial temporal lobe (MTL) that include HC and perirhinal cortex (PrC), and those with congenital prosopagnosia (CP), whose deficit has been attributed to the disconnection of the anterior temporal lobe from more posterior structures. All participants completed a range of'oddity' tasks in which, on each trial, they determined which of four visual stimuli in a display was the'odd-one-out'. There were five stimulus categories including faces, scenes, objects (high and low ambiguity) and squares of different sizes. Comparisons were conducted separately for the HC, MTL and CP groups against their matched control groups and then the group data were compared to each other directly. The group profiles were easily differentiable. Whereas the HC group stood out for its difficulty in discriminating scenes and the CP group stood out for its disproportionate difficulty in discriminating faces with milder effects for scenes and high ambiguity objects, the MTL group evinced a more general discrimination deficit for faces, scenes and high ambiguity objects. The group differences highlight distinct profiles for each of the three groups and distinguish the signature perceptual impairments following more extended temporal lobe alterations. In the recent reconsideration of the role of the hippocampus and neocortex, Moscovitch and colleagues (Moscovitch et al., 2016) note that the medial temporal lobe structures play a role in non-mnemonic functions, such as perception, problem solving, decision-making and language. Here, we address this exact issue, specifically with respect to perception, and we dedicate this paper to Morris Moscovitch in recognition of his profound contribution to science, to his students and to his colleagues.

Developmental prosopagnosia.

A Quick guide to developmental prosopagnosia, a condition definied by problems in recognising faces that, in contrast with acquired prosopagnosia, develop in the absence of manifest brain injury.

Voice Recognition in Face-Blind Patients.

Right or bilateral anterior temporal damage can impair face recognition, but whether this is an associative variant of prosopagnosia or part of a multimodal disorder of person recognition is an unsettled question, with implications for cognitive and neuroanatomic models of person recognition. We assessed voice perception and short-term recognition of recently heard voices in 10 subjects with impaired face recognition acquired after cerebral lesions. All 4 subjects with apperceptive prosopagnosia due to lesions limited to fusiform cortex had intact voice discrimination and recognition. One subject with bilateral fusiform and anterior temporal lesions had a combined apperceptive prosopagnosia and apperceptive phonagnosia, the first such described case. Deficits indicating a multimodal syndrome of person recognition were found only in 2 subjects with bilateral anterior temporal lesions. All 3 subjects with right anterior temporal lesions had normal voice perception and recognition, 2 of whom performed normally on perceptual discrimination of faces. This confirms that such lesions can cause a modality-specific associative prosopagnosia.