Neural computations in prosopagnosia.

We report an investigation of the neural processes involved in the processing of faces and objects of brain-lesioned patient PS, a well-documented case of pure acquired prosopagnosia. We gathered a substantial dataset of high-density electrophysiological recordings from both PS and neurotypicals. Using representational similarity analysis, we produced time-resolved brain representations in a format that facilitates direct comparisons across time points, different individuals, and computational models. To understand how the lesions in PS's ventral stream affect the temporal evolution of her brain representations, we computed the temporal generalization of her brain representations. We uncovered that PS's early brain representations exhibit an unusual similarity to later representations, implying an excessive generalization of early visual patterns. To reveal the underlying computational deficits, we correlated PS' brain representations with those of deep neural networks (DNN). We found that the computations underlying PS' brain activity bore a closer resemblance to early layers of a visual DNN than those of controls. However, the brain representations in neurotypicals became more akin to those of the later layers of the model compared to PS. We confirmed PS's deficits in high-level brain representations by demonstrating that her brain representations exhibited less similarity with those of a DNN of semantics.

Familiarity enhances functional connectivity between visual and nonvisual regions of the brain during natural viewing.

We explored the neural correlates of familiarity with people and places using a naturalistic viewing paradigm. Neural responses were measured using functional magnetic resonance imaging, while participants viewed a movie taken from Game of Thrones. We compared inter-subject correlations and functional connectivity in participants who were either familiar or unfamiliar with the TV series. Higher inter-subject correlations were found between familiar participants in regions, beyond the visual brain, that are typically associated with the processing of semantic, episodic, and affective information. However, familiarity also increased functional connectivity between face and scene regions in the visual brain and the nonvisual regions of the familiarity network. To determine whether these regions play an important role in face recognition, we measured responses in participants with developmental prosopagnosia (DP). Consistent with a deficit in face recognition, the effect of familiarity was significantly attenuated across the familiarity network in DP. The effect of familiarity on functional connectivity between face regions and the familiarity network was also attenuated in DP. These results show that the neural response to familiarity involves an extended network of brain regions and that functional connectivity between visual and nonvisual regions of the brain plays an important role in the recognition of people and places during natural viewing.

The heterogeneity of holistic processing profiles in developmental prosopagnosia: holistic processing is impaired but not absent.

Although it is generally assumed that face recognition relies on holistic processing, whether face recognition deficits observed in Developmental Prosopagnosics (DPs) can be explained by impaired holistic processing is currently under debate. The mixed findings from past studies could be the consequence of DP's heterogeneous deficit nature and the use of different measures of holistic processing-the inversion, part-whole, and composite tasks-which showed a poor association among each other. The present study aimed to gain further insight into the role of holistic processing in DPs. Groups of DPs and neurotypicals completed three tests measuring holistic face processing and non-face objects (i.e., Navon task). At a group level, DPs showed (1) diminished, but not absent, inversion and part-whole effects, (2) comparable magnitudes of the composite face effect and (3) global precedence effect in the Navon task. However, single-case analyses showed that these holistic processing deficits in DPs are heterogeneous.

Common neural substrates of diverse neurodevelopmental disorders.

Neurodevelopmental disorders are categorized and studied according to their manifestations as distinct syndromes. For instance, congenital prosopagnosia and dyslexia have largely non-overlapping research literatures and clinical pathways for diagnosis and intervention. On the other hand, the high incidence of neurodevelopmental comorbidities or co-existing extreme strengths and weaknesses suggest that transdiagnostic commonalities may be greater than currently appreciated. The core-periphery model holds that brain regions within the stable core perceptual and motor regions are more densely connected to one another compared to regions in the flexible periphery comprising multimodal association regions. This model provides a framework for the interpretation of neural data in normal development and clinical disorders. Considering network-level commonalities reported in studies of neurodevelopmental disorders, variability in multimodal association cortex connectivity may reflect a shared origin of seemingly distinct neurodevelopmental disorders. This framework helps to explain both comorbidities in neurodevelopmental disorders and profiles of strengths and weaknesses attributable to competitive processing between cognitive systems within an individual.

Improving the DSM-5 approach to cognitive impairment: Developmental prosopagnosia reveals the need for tailored diagnoses.

The Diagnostic Statistical Manual of Mental Disorders (DSM-5) recommends diagnosing neurocognitive disorders (i.e., cognitive impairment) when a patient scores beyond - 1 SD below neurotypical norms on two tests. I review how this approach will fail due to cognitive tests' power limitations, validity issues, imperfect reliabilities, and biases, before summarizing their resulting negative consequences. As a proof of concept, I use developmental prosopagnosia, a condition characterized by difficulties recognizing faces, to show the DSM-5 only diagnoses 62-70% (n1 = 61, n2 = 165) versus 100% (n1 = 61) through symptoms alone. Pooling the DSM-5 missed cases confirmed the presence of group-level impairments on objective tests, which were further evidenced through meta-analyses, thus validating their highly atypical symptoms. These findings support a paradigm shift towards bespoke diagnostic approaches for distinct cognitive impairments, including a symptom-based method when validated effective. I reject dogmatic adherence to the DSM-5 approach to neurocognitive disorders, and underscore the importance of a data driven, transdiagnostic approach to understanding patients' subjective cognitive impairments. This will ultimately benefit patients, their families, clinicians, and scientific progress.

Provoked overt recognition in acquired prosopagnosia using multiple different images of famous faces.

Provoked overt recognition refers to the fact that patients with acquired prosopagnosia can sometimes recognize faces when presented in arrays of individuals from the same category (e.g., actors or politicians). We ask whether a prosopagnosic patient might experience recognition when presented with multiple different images of the same face simultaneously. Over two sessions, patient Herschel, a 66-year-old British man with acquired prosopagnosia, viewed face images individually or in arrays. On several occasions he failed to recognize single photos of an individual but successfully identified that person when the same photos were presented together. For example, Herschel failed to recognize any individual images of King Charles or Paul McCartney but recognised both in arrays of the same photos. Like reports based on category membership, overt recognition was transient and inconsistent. These findings are discussed in terms of models of covert recognition, alongside more recent research on within-person variability for face perception.

Acquired prosopagnosia with structurally intact and functional fusiform face area and with face identity-specific configuration processing deficits.

Prosopagnosia or loss of face perception and recognition is still poorly understood and rare single cases of acquired prosopagnosia can provide a unique window on the behavioural and brain basis of normal face perception. The present study of a new case of acquired prosopagnosia with bilateral occipito-temporal lesions but a structurally intact FFA and OFA investigated whether the lesion overlapped with the face network and whether the structurally intact FFA showed a face selective response. We also investigated the behavioral correlates of the neural findings and assessed configural processing in the context of facial and non-facial identity recognition, expression recognition and memory, also focusing on the face-selectivity of each specific deficit. The findings reveal a face-selective response in the FFA, despite lesions in the face perception network. At the behavioural level, the results showed impaired configural processing for facial identity, but not for other stimulus categories and not for facial expression recognition. These findings challenge a critical role of the FFA for face identity processing and support a domain-specific account of configural processing.

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.

No increased prevalence of prosopagnosia in aphantasia: Visual recognition deficits are small and not restricted to faces.

Aphantasia and prosopagnosia are both rare conditions with impairments in visual cognition. While prosopagnosia refers to a face recognition deficit, aphantasics exhibit a lack of mental imagery. Current object recognition theories propose an interplay of perception and mental representations, making an association between recognition performance and visual imagery plausible. While the literature assumes a link between aphantasia and prosopagnosia, other impairments in aphantasia have been shown to be rather global. Therefore, we assumed that aphantasics do not solely exhibit impairments in face recognition but rather in general visual recognition performance, probably moderated by stimulus complexity. To test this hypothesis, 65 aphantasics were compared to 55 controls in a face recognition task, the Cambridge Face Memory Test, and a corresponding object recognition task, the Cambridge Car Memory Test. In both tasks, aphantasics performed worse than controls, indicating mild recognition deficits without face-specificity. Additional correlations between imagery vividness and performance in both tasks were found, suggesting that visual imagery influences visual recognition not only in imagery extremes. Stimulus complexity produced the expected moderation effect but only for the whole imagery-spectrum and only with face stimuli. Overall, the results imply that aphantasia is linked to a general but mild deficit in visual recognition.

Alcohol Use Predicts Face Perception Impairments and Difficulties in Face Recognition.

Background: Risky alcohol use is related to a variety of cognitive impairments, including memory and visuo-perceptual difficulties. Remarkably, no prior work has assessed whether usage of alcohol can predict difficulties perceiving facial identity. Objectives: Therefore, this study aimed to investigate whether riskier alcohol consumption predicted impairments in face perception and self-reported difficulties in face recognition. Results: Participants (N = 239, male = 77) were over 18 years old and had normal or corrected-to-normal vision. Alcohol use was assessed using the Alcohol Use Disorder Identification Test (AUDIT), while face recognition difficulties were determined by the 20-item Prosopagnosia Index questionnaire (PI20). A subsample of participants (N = 126, male = 51) completed the Cambridge Face Perception task (CFPT) to assess their face perception ability. Multiple linear regressions showed significant models of prediction on both face perception and face recognition when considering AUDIT score and age as predictors. Conclusion: This study suggested, for the first time, that risky alcohol use predicts both poorer visuo-perceptual processing for faces and self-reported difficulties in face recognition.

A new approach to diagnosing and researching developmental prosopagnosia: Excluded cases are impaired too.

Developmental prosopagnosia is characterized by severe, lifelong difficulties when recognizing facial identity. Unfortunately, the most common diagnostic assessment (Cambridge Face Memory Test) misses 50-65% of individuals who believe that they have this condition. This results in such excluded cases' absence from scientific knowledge, effect sizes of impairment potentially overestimated, treatment efficacy underrated, and may elicit in them a negative experience of research. To estimate their symptomology and group-level impairments in face processing, we recruited a large cohort who believes that they have prosopagnosia. Matching prior reports, 56% did not meet criteria on the Cambridge Face Memory Test. However, the severity of their prosopagnosia symptoms and holistic perception deficits were comparable to those who did meet criteria. Excluded cases also exhibited face perception and memory impairments that were roughly one standard deviation below neurotypical norms, indicating the presence of objective problems. As the prosopagnosia index correctly classified virtually every case, we propose it should be the primary method for providing a diagnosis, prior to subtype categorization. We present researchers with a plan on how they can analyze these excluded prosopagnosia cases in their future work without negatively impacting their traditional findings. We anticipate such inclusion will enhance scientific knowledge, more accurately estimate effect sizes of impairments and treatments, and identify commonalities and distinctions between these different forms of prosopagnosia. Owing to their atypicalities in visual perception, we recommend that the prosopagnosia index should be used to screen out potential prosopagnosia cases from broader vision research.

Not so fast! Response times in the computerized Benton Face Recognition Test may not reflect face recognition ability.

Response times (RTs) are commonly used to assess cognitive abilities, though it is unclear whether face processing RTs predict recognition ability beyond accuracy. In the current study, we examined accuracy and RT on a widely used face matching assessment modified to collect meaningful RT data, the computerized Benton Facial Recognition Test (BFRT-c), and measured whether RTs predicted face recognition ability and developmental prosopagnosia (DP) vs. control group membership. 62 controls and 36 DPs performed the BFRT-c as well as validated measures of face recognition ability: the Cambridge Face Memory Test (CFMT) and a Famous Faces Memory Test (FFMT). In controls, BFRT-c accuracy robustly predicted CFMT (r = .49, p < .001), FFMT (r = .43, p < .001), and a CFMT-FFMT composite (r = .54, p < .001), whereas BFRT-c RT was not significantly associated with these measures (all r's .21). We also found that BFRT-c accuracy significantly differed between DPs and controls, but RT failed to differentiate the groups.

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.

Prosopamnesia: a case report of amnesia for faces.

Prosopamnesia is a face-selective memory disorder in which face learning is impaired, while face-perception disorder (prosopagnosia) and memory disorders for stimuli other than faces are not present. To date, only two cases of prosopamnesia have been reported in adults - one congenital and one secondary to brain damage. This article reports a case of a 68-year-old woman complaining difficulties recognizing persons she had got to know recently. Neuropsychological examination revealed face-specific anterograde amnesia in the absence of prosopagnosia and other memory impairments. Brain MRI did not present any focal abnormality; PET-scan revealed hypoactivation mostly in the frontotemporal area bilaterally. This patient represents the first case of late-onset primary prosopamnesia.

"This looks like a movie": a case report of post-surgical amnesia.

A 52-year-old male patient with a background of adaptive personality disorder was admitted for mitral valve repair and cardiac ablation for atrial fibrillation. He suffered intraoperative complications with severe mitral insufficiency that suffered ischemia.. Post-operatively, he demonstrated acute loss of retrograde autobiographical memory, prosopagnosia and a loss of public semantic memory. His CT scan was normal and MRI was not possible due to intra-cardiac leads. An initial diagnosis of hypoxic-ischemic encephalopathy was considered. A neuropsychological examination undertaken 20 days after his surgery showed a severe alteration of retrograde autobiographical memory, marked alteration of semantic knowledge and prosopagnosia. He demonstrated an average performance in tasks measuring constructional praxis, visuospatial ability, and executive functions. 34 days after surgery, and after a short nap, the patient "returns" to the day before admission and consequently recovers his memory. Repeat neuropsychological assessment demonstrated performance within the normal range across all previously tested domains. This sudden recovery of memory, together with a normal MRI, led to a rethinking of the diagnosis of dissociative amnesia. This case illustrates the long-standing discussion about the organic or functional origin of some memory disorders, in which, despite advances in neuroimaging techniques, it is still difficult to know their etiology .

Right Fusiform Gyrus Infarct with Acute Prosopagnosia.

A 56-year-old, right-handed man with no known past medical history presented with sudden onset of inability to recognize familiar individuals in person, including his wife and his mother. He also couldn't recognize himself in the mirror. There was no weakness, numbness, visual disturbances, or speech difficulty. Face recognition test, using Warrington Recognition Memory Test (1), showed the presence of complete prosopagnosia. The rest of the neurological and cranial nerves examinations were normal. Magnetic resonance imaging (MRI) of the brain showed restricted diffusion at the right temporal and occipital lobes (the fusiform gyrus) [Figure 1]. Magnetic resonance angiogram (MRA) of the brain was unremarkable. The 24-hours Holter monitoring showed paroxysmal atrial fibrillation. The transthoracic echocardiogram and carotid doppler ultrasound scan were normal. He was then treated with rivaroxaban 20mg daily for secondary stroke prevention in non-valvular atrial fibrillation. Face recognition skill training was started in the ward, which includes compensatory strategies to achieve person recognition by circumventing the face processing impairment, and remediation to enhance mnemonic function for face recognition. His prosopagnosia resolved completely after one week. Prosopagnosia, also known as face blindness, is an impairment in recognizing faces. The core defects are the loss of familiarity with previously known faces and the inability to recognize new faces. Patients with prosopagnosia may present with poor recognition of familiar individuals in person or in the photograph, confusion with plotlines in movies or plays with numerous characters, and difficulty distinguishing individuals wearing a uniform or similar clothing. Stroke is the most common cause of acquired prosopagnosia (2). Other less common aetiologies include traumatic brain injury, carbon monoxide poisoning, temporal lobectomy, and encephalitis. Literature has shown that areas involved in acquired prosopagnosia are the right fusiform gyrus or anterior temporal cortex, or both (3). The fusiform gyrus is part of the lateral temporal lobe and occipital lobe in 'Brodmann area 37' (4). The fusiform gyrus is considered a key structure for functionally specialized computations of high-level vision such as face perception, object recognition, and reading. Individuals with fusiform lesions are more likely to have apperceptive prosopagnosia, while those with anterior temporal lesions have an amnestic variant (5). In summary, prosopagnosia can be the sole presentation for the right fusiform gyrus stroke. It is important to recognize prosopagnosia for early stroke diagnosis and avoid misdiagnosing it as a psychiatric or ocular disorder. Keywords: prosopagnosia, fusiform gyrus, stroke.

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.

Contrasting domain-general and domain-specific accounts in cognitive neuropsychology: An outline of a new approach with developmental prosopagnosia as a case.

The backbone of cognitive neuropsychology is the observation of (double) dissociations in performance between patients, suggesting some degree of independence between cognitive processes (domain specificity). In comparison, observations of associations between disorders/deficits have been deemed less evidential in neuropsychological theorizing about cognitive architecture. The reason is that associations can reflect damage to independent cognitive processes that happen to be mediated by structures commonly affected by the same brain disorder rather than damage to a shared (domain-general) mechanism. Here we demonstrate that it is in principle possible to discriminate between these alternatives by means of a procedure involving large unbiased samples. We exemplify the procedure in the context of developmental prosopagnosia (DP), but the procedure is in principle applicable to all neuropsychological deficits/disorders. A simulation of the procedure on a dataset yields estimates of dissociations/associations that are well in line with existing DP-studies, and also suggests that seemingly selective disorders can reflect damage to both domain-general and domain-specific cognitive processes. However, the simulation also highlights some limitations that should be considered if the procedure is to be applied prospectively. The main advantage of the procedure is that allows for examination of both associations and dissociations in the same sample. Hence, it may help even the balance in the use of associations and dissociations as grounds for neuropsychological theorizing.

An update of the Benton Facial Recognition Test.

The Benton Facial Recognition Test (BFRT) is a paper-and-pen task that is traditionally used to assess face perception skills in neurological, clinical and psychiatric conditions. Despite criticisms of its stimuli, the task enjoys a simple procedure and is rapid to administer. Further, it has recently been computerised (BFRT-c), allowing reliable measurement of completion times and the need for online testing. Here, in response to calls for repeat screening for the accurate detection of face processing deficits, we present the BFRT-Revised (BFRT-r): a new version of the BFRT-c that maintains the task's basic paradigm, but employs new, higher-quality stimuli that reflect recent theoretical advances in the field. An initial validation study with typical participants indicated that the BFRT-r has good internal reliability and content validity. A second investigation indicated that while younger and older participants had comparable accuracy, completion times were longer in the latter, highlighting the need for age-matched norms. Administration of the BFRT-r and BFRT-c to 32 individuals with developmental prosopagnosia resulted in improved sensitivity in diagnostic screening for the BFRT-r compared to the BFRT-c. These findings are discussed in relation to current diagnostic screening protocols for face perception deficits. The BFRT-r is stored in an open repository and is freely available to other researchers.

The Oxford Face Matching Test: A non-biased test of the full range of individual differences in face perception.

Tests of face processing are typically designed to identify individuals performing outside of the typical range; either prosopagnosic individuals who exhibit poor face processing ability, or super recognisers, who have superior face processing abilities. Here we describe the development of the Oxford Face Matching Test (OFMT), designed to identify individual differences in face processing across the full range of performance, from prosopagnosia, through the range of typical performance, to super recognisers. Such a test requires items of varying difficulty, but establishing difficulty is problematic when particular populations (e.g., prosopagnosics, individuals with autism spectrum disorder) may use atypical strategies to process faces. If item difficulty is calibrated on neurotypical individuals, then the test may be poorly calibrated for atypical groups, and vice versa. To obtain items of varying difficulty, we used facial recognition algorithms to obtain face pair similarity ratings that are not biased towards specific populations. These face pairs were used as stimuli in the OFMT, and participants were required to judge whether the face images depicted the same individual or different individuals. Across five studies the OFMT was shown to be sensitive to individual differences in the typical population, and in groups of both prosopagnosic individuals and super recognisers. The test-retest reliability of the task was at least equivalent to the Cambridge Face Memory Test and the Glasgow Face Matching Test. Furthermore, results reveal, at least at the group level, that both face perception and face memory are poor in those with prosopagnosia, and are good in super recognisers.