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Face recognition is important for both visual and social cognition. While prosopagnosia or face blindness has been known for seven decades and face-specific neurons for half a century, the molecular genetic mechanism is not clear. Here we report results after 17 years of research with classic genetics and modern genomics. From a large family with 18 congenital prosopagnosia (CP) members with obvious difficulties in face recognition in daily life, we uncovered a fully cosegregating private mutation in the MCTP2 gene which encodes a calcium binding transmembrane protein expressed in the brain. After screening through cohorts of 6589, we found more CPs and their families, allowing detection of more CP associated mutations in MCTP2. Face recognition differences were detected between 14 carriers with the frameshift mutation S80fs in MCTP2 and 19 noncarrying volunteers. Six families including one with 10 members showed the S80fs-CP correlation. Functional magnetic resonance imaging found association of impaired recognition of individual faces by MCTP2 mutant CPs with reduced repetition suppression to repeated facial identities in the right fusiform face area. Our results have revealed genetic predisposition of MCTP2 mutations in CP, 76 years after the initial report of prosopagnosia and 47 years after the report of the first CP. This is the first time a gene required for a higher form of visual social cognition was found in humans. [ABSTRACT FROM AUTHOR]

Benign paroxysmal positional vertigo (BPPV) is amongst the commonest causes of dizziness and falls in older adults. Diagnosing and treating BPPV can reduce falls, and thereby reduce fall-related morbidity and mortality. Recent World Falls Guidelines recommend formal assessment for BPPV in older adults at risk of falling, but only if they report vertigo. However, this recommendation ignores the data that (i) many older adults with BPPV experience dizziness as vague unsteadiness (rather than vertigo), and (ii) others may experience no symptoms of dizziness at all. BPPV without vertigo is due to an impaired vestibular perception of self-motion, termed 'vestibular agnosia'. Vestibular agnosia is found in ageing, neurodegeneration and traumatic brain injury, and results in dramatically increased missed BPPV diagnoses. Patients with BPPV without vertigo are typically the most vulnerable for negative outcomes associated with this disorder. We thus recommend simplifying the World Falls Guidelines: all older adults (>60 years) with objective or subjective balance problems, irrespective of symptomatic complaint, should have positional testing to examine for BPPV. [ABSTRACT FROM AUTHOR]

Vestibular dysfunction, causing dizziness and imbalance, is a common yet poorly understood feature in patients with TBI. Damage to the inner ear, nerve, brainstem, cerebellum and cerebral hemispheres may all affect vestibular functioning, hence, a multi-level assessment-from reflex to perception-is required. In a previous report, postural instability was the commonest neurological feature in ambulating acute patients with TBI. During ward assessment, we also frequently observe a loss of vertigo sensation in patients with acute TBI, common inner ear conditions and a related vigorous vestibular-ocular reflex nystagmus, suggesting a 'vestibular agnosia'. Patients with vestibular agnosia were also more unbalanced; however, the link between vestibular agnosia and imbalance was confounded by the presence of inner ear conditions. We investigated the brain mechanisms of imbalance in acute TBI, its link with vestibular agnosia, and potential clinical impact, by prospective laboratory assessment of vestibular function, from reflex to perception, in patients with preserved peripheral vestibular function. Assessment included: vestibular reflex function, vestibular perception by participants' report of their passive yaw rotations in the dark, objective balance via posturography, subjective symptoms via questionnaires, and structural neuroimaging. We prospectively screened 918 acute admissions, assessed 146 and recruited 37. Compared to 37 matched controls, patients showed elevated vestibular-perceptual thresholds (patients 12.92°/s versus 3.87°/s) but normal vestibular-ocular reflex thresholds (patients 2.52°/s versus 1.78°/s). Patients with elevated vestibular-perceptual thresholds [3 standard deviations (SD) above controls' average], were designated as having vestibular agnosia, and displayed worse posturography than non-vestibular-agnosia patients, despite no difference in vestibular symptom scores. Only in patients with impaired postural control (3 SD above controls' mean), whole brain diffusion tensor voxel-wise analysis showed elevated mean diffusivity (and trend lower fractional anisotropy) in the inferior longitudinal fasciculus in the right temporal lobe that correlated with vestibular agnosia severity. Thus, impaired balance and vestibular agnosia are co-localized to the inferior longitudinal fasciculus in the right temporal lobe. Finally, a clinical audit showed a sevenfold reduction in clinician recognition of a common peripheral vestibular condition (benign paroxysmal positional vertigo) in acute patients with clinically apparent vestibular agnosia. That vestibular agnosia patients show worse balance, but without increased dizziness symptoms, explains why clinicians may miss treatable vestibular diagnoses in these patients. In conclusion, vestibular agnosia mediates imbalance in traumatic brain injury both directly via white matter tract damage in the right temporal lobe, and indirectly via reduced clinical recognition of common, treatable vestibular diagnoses. [ABSTRACT FROM AUTHOR]

Impairments in reality testing are core features of numerous neuropsychiatric conditions. However, relatively few animal models have been developed to assess this critical facet of neuropsychiatric illness, thus impeding our understanding of the underlying central systems and circuits. Using mice in which dominant-negative Disrupted-in-Schizophrenia-1 is expressed throughout central nervous system circuitry (DN-DISC1-PrP), the capacity for an auditory conditioned stimulus (CS) to evoke perceptual processing of an absent sucrose solution was examined. At test, during CS presentations, DN-DISC1-PrP mice consumed more water and displayed a licking profile that is more typically revealed while ingesting a sweet-tasting solution. DN-DISC1-PrP mice also displayed greater c-fos expression in the insular (gustatory) cortex when consuming water in the presence of the CS. This capacity for the CS to more readily substitute for the taste features of the absent sucrose solution in DN-DISC1-PrP mice was attenuated following systemic treatment with the antipsychotic haloperidol. Conversely, social isolation during adolescence promoted the manifestation of these effects. These results provide strong validation for using associative learning procedures to examine dopamine-mediated reality testing associated with insular cortex activation. [ABSTRACT FROM AUTHOR]

Objective Often, individuals with lower educational attainment and limited proficiency in the English language get misdiagnosed and/or undertreated, which can impact their quality of life and other outcomes. The present case study intends to review and discuss the presentation of a monolingual, Spanish-speaking woman with Semantic Variant Primary Progressive Aphasia (svPPA), who was originally referred for a neuropsychological evaluation to determine the severity of her existing Alzheimer's Disease (AD) diagnosis. Case Description Ms. X, is a 64-year-old, right-handed Hispanic woman with 6 years of education. Symptoms included forgetfulness, restlessness, and insomnia. Her family reported that she was repeating her ideas frequently during conversations and failing to recognize previously acquainted people, including her own relatives. A recent MRI of the brain showed anterior temporal lobe atrophy. Diagnostic Impressions and Outcomes Overall, she showed naming deficits (anomia), impaired verbal fluency, surface dyslexia, and significant problems with comprehension. Executive functioning, sentence repetition, working memory, and attention were generally intact. Qualitatively, her speech was apparently fluent and automatic, yet clearly empty in meaning. In Ms. X's case, collateral reports of word-finding difficulties, tendency to repeat her thoughts incessantly, associative agnosia and prosopagnosia, and spared repetition and motor speech are strongly indicative of svPPA. Discussion svPPA primarily impacts language production and comprehension, and is characterized by severe anomia, word-finding difficulties, impaired single word comprehension, and in some cases, defective recognition of familiar faces. On testing, impairments can be observed in confrontation naming, with motor speech and repetition, working memory, episodic memory, visuospatial skills, and problem-solving skills relatively intact. Language symptoms are thought to stem from deficits of the semantic system. [ABSTRACT FROM AUTHOR]

Objective: Landmark agnosia is a rare type of navigation impairment, for which various definitions have been presented. From a clinical as well as theoretical perspective, consensus on the characteristics of landmark agnosia would be valuable. In the current study we review the literature concerning landmark agnosia and present a new case study. Existing literature highlights the importance of examining familiar as well as novel landmark processing and substantial variation in performance patterns of individual patients. Method: We performed a case study with patient KS, a 53-year-old male, suffering from landmark agnosia, making use of elaborate neuropsychological screening and virtual reality-based tests of navigation ability. Results: Our extensive examination of his impairment shows that landmark agnosia can be very narrow; in KS it is restricted to recognition of newly learned landmarks only. Also, he has no trouble recognizing familiar landmarks that are not part of a navigated route. Conclusions: The literature review shows that the right temporal lobe, and the right hippocampus in particular are the main lesion sites for landmark agnosia. Furthermore, our case study substantiates that this disorder can occur for both familiar and novel landmarks, and can affect novel landmarks in isolation from familiar landmarks. Moreover, it can occur in isolation from problems with processing route information. [ABSTRACT FROM AUTHOR]

Following right-hemisphere damage, a specific disorder of motor awareness can occur called anosognosia for hemiplegia, i.e. the denial of motor deficits contralateral to a brain lesion. The study of anosognosia can offer unique insights into the neurocognitive basis of awareness. Typically, however, awareness is assessed as a first person judgement and the ability of patients to think about their bodies in more 'objective' (third person) terms is not directly assessed. This may be important as right-hemisphere spatial abilities may underlie our ability to take third person perspectives. This possibility was assessed for the first time in the present study. We investigated third person perspective taking using both visuospatial and verbal tasks in right-hemisphere stroke patients with anosognosia (n = 15) and without anosognosia (n = 15), as well as neurologically healthy control subjects (n = 15). The anosognosic group performed worse than both control groups when having to perform the tasks from a third versus a first person perspective. Individual analysis further revealed a classical dissociation between most anosognosic patients and control subjects in mental (but not visuospatial) third person perspective taking abilities. Finally, the severity of unawareness in anosognosia patients was correlated to greater impairments in such third person, mental perspective taking abilities (but not visuospatial perspective taking). In voxel-based lesion mapping we also identified the lesion sites linked with such deficits, including some brain areas previously associated with inhibition, perspective taking and mentalizing, such as the inferior and middle frontal gyri, as well as the supramarginal and superior temporal gyri. These results suggest that neurocognitive deficits in mental perspective taking may contribute to anosognosia and provide novel insights regarding the relation between self-awareness and social cognition. [ABSTRACT FROM AUTHOR]

The clinico-neuroradiological syndrome posterior cortical atrophy is the cardinal 'visual dementia' and most common atypical Alzheimer's disease phenotype, offering insights into mechanisms underlying clinical heterogeneity, pathological propagation and basic visual phenomena (e.g. visual crowding). Given the extensive attention paid to patients' (higher order) perceptual function, it is surprising that there have been no systematic analyses of basic oculomotor function in this population. Here 20 patients with posterior cortical atrophy, 17 patients with typical Alzheimer's disease and 22 healthy controls completed tests of fixation, saccade (including fixation/target gap and overlap conditions) and smooth pursuit eye movements using an infrared pupil-tracking system. Participants underwent detailed neuropsychological and neurological examinations, with a proportion also undertaking brain imaging and analysis of molecular pathology. In contrast to informal clinical evaluations of oculomotor dysfunction frequency (previous studies: 38%, current clinical examination: 33%), detailed eyetracking investigations revealed eye movement abnormalities in 80% of patients with posterior cortical atrophy (compared to 17% typical Alzheimer's disease, 5% controls). The greatest differences between posterior cortical atrophy and typical Alzheimer's disease were seen in saccadic performance. Patients with posterior cortical atrophy made significantly shorter saccades especially for distant targets. They also exhibited a significant exacerbation of the normal gap/overlap effect, consistent with 'sticky fixation'. Time to reach saccadic targets was significantly associated with parietal and occipital cortical thickness measures. On fixation stability tasks, patients with typical Alzheimer's disease showed more square wave jerks whose frequency was associated with lower cerebellar grey matter volume, while patients with posterior cortical atrophy showed large saccadic intrusions whose frequency correlated significantly with generalized reductions in cortical thickness. Patients with both posterior cortical atrophy and typical Alzheimer's disease showed lower gain in smooth pursuit compared to controls. The current study establishes that eye movement abnormalities are near-ubiquitous in posterior cortical atrophy, and highlights multiple aspects of saccadic performance which distinguish posterior cortical atrophy from typical Alzheimer's disease. We suggest the posterior cortical atrophy oculomotor profile (e.g. exacerbation of the saccadic gap/overlap effect, preserved saccadic velocity) reflects weak input from degraded occipito-parietal spatial representations of stimulus location into a superior collicular spatial map for eye movement regulation. This may indicate greater impairment of identification of oculomotor targets rather than generation of oculomotor movements. The results highlight the critical role of spatial attention and object identification but also precise stimulus localization in explaining the complex real world perception deficits observed in posterior cortical atrophy and many other patients with dementia-related visual impairment. [ABSTRACT FROM AUTHOR]

Gerstmann's syndrome includes the clinical tetrad of finger agnosia, agraphia, acalculia, and right–left confusion. Some disagreement remains with regard to the exact localization of the syndrome, but most probable it involves the left angular gyrus with a subcortical extension. Several authors have suggested that a defect in mental spatial rotations could simultaneously account for acalculia, right–left disorientation, and finger agnosia. It has been also suggested that semantic aphasia is always associated with acalculia; as a matter of fact, left angular gyrus has a significant involvement in semantic processing. In this paper, it is proposed that Gerstmann's syndrome should include: acalculia, finger agnosia, right–left disorientation, and semantic aphasia, but not agraphia. When the pathology extends toward the superior parietal gyrus, agraphia can be found. A fundamental defect (i.e., an impairment in verbally mediated spatial operations) could explain these apparently unrelated clinical signs. [ABSTRACT FROM AUTHOR]

Only seven cases of agnosia for mirror stimuli have been reported, always with an extensive lesion. We report a new case of an agnosia for mirror stimuli due to a circumscribed lesion. An extensive battery of neuropsychological tests and a new experimental procedure to assess visual object mirror and orientation discrimination were assessed 10 days after the onset of clinical symptoms, and 5 years later. The performances of our patient were compared with those of four healthy control subjects matched for age. This test revealed an agnosia for mirror stimuli. Brain imaging showed a small right occipitoparietal hematoma, encompassing the extrastriate cortex adjoining the inferior parietal lobe. This new case suggests that: (i) agnosia for mirror stimuli can persist for 5 years after onset and (ii) the posterior part of the right intraparietal sulcus could be critical in the cognitive process of mirror stimuli discrimination. [ABSTRACT FROM PUBLISHER]

A fundamental aspect of visual cognition is our disposition to see the ‘forest before the trees’. However, damage to the posterior parietal cortex, a critical brain region along the dorsal visual pathway, can produce a neurological disorder called simultanagnosia, characterized by a debilitating inability to perceive the ‘forest’ but not the ‘trees’ (i.e. impaired global processing despite intact local processing). This impairment in perceiving the global shape persists even though the ventral visual pathway, the primary recognition pathway, is intact in these patients. Here, we enabled global processing in patients with simultanagnosia using a psychophysical technique, which allowed us to bias stimuli such that they are processed predominantly by the intact ventral visual pathway. Our findings reveal that the impairment in global processing that characterizes simultanagnosia stems from a disruption in the processing of low-spatial frequencies through the dorsal pathway. These findings advance our understanding of the relationship between visuospatial attention and perception and reveal the neural mechanism mediating the disposition to see the ‘forest before the trees’. [ABSTRACT FROM PUBLISHER]

Little is known about the processing of non-verbal sounds in the primary progressive aphasias. Here, we investigated the processing of complex non-verbal sounds in detail, in a consecutive series of 20 patients with primary progressive aphasia [12 with progressive non-fluent aphasia; eight with semantic dementia]. We designed a novel experimental neuropsychological battery to probe complex sound processing at early perceptual, apperceptive and semantic levels, using within-modality response procedures that minimized other cognitive demands and matching tests in the visual modality. Patients with primary progressive aphasia had deficits of non-verbal sound analysis compared with healthy age-matched individuals. Deficits of auditory early perceptual analysis were more common in progressive non-fluent aphasia, deficits of apperceptive processing occurred in both progressive non-fluent aphasia and semantic dementia, and deficits of semantic processing also occurred in both syndromes, but were relatively modality specific in progressive non-fluent aphasia and part of a more severe generic semantic deficit in semantic dementia. Patients with progressive non-fluent aphasia were more likely to show severe auditory than visual deficits as compared to patients with semantic dementia. These findings argue for the existence of core disorders of complex non-verbal sound perception and recognition in primary progressive aphasia and specific disorders at perceptual and semantic levels of cortical auditory processing in progressive non-fluent aphasia and semantic dementia, respectively. [ABSTRACT FROM PUBLISHER]

David Milner and Melvyn Goodale, and the many psychologists and philosophers who have been influenced by their work, claim that ‘the visual system that gives us our visual experience of the world is not the same system that guides our movements in the world’. The arguments that have been offered for this surprising claim place considerable weight on two sources of evidence — visual form agnosia and the reaching behaviour of normal subjects when picking up objects that induce visual illusions. The present article shows that, if we are careful to consider the possibility that a demonstrative gesture can contribute content to a conscious experience, then neither source of evidence is compelling. [ABSTRACT FROM PUBLISHER]

Faces are represented in a more configural or holistic manner than other objects. Substantial evidence indicates that this representation results from face-specific mechanisms, but some have argued that it is produced by configural mechanisms that can be applied to many objects including words. The face-specific hypothesis predicts that non-face configural processes will often be normal in prosopagnosic subjects, whereas the domain-general configural hypothesis predicts they will be deficient on all configural tasks. Although the weight of the evidence favors the face-specific hypothesis, a recent study reopened this issue when it was found that three out of five developmental prosopagnosics showed a larger local processing bias than controls in a global-local task (i.e. a Navon task). To examine this issue more thoroughly we tested a significantly larger sample of prosopagnosics (14 participants) who had severe face memory and face perception deficits. In contrast to the previous report, the developmental prosopagnosics performed normally in the global–local task. Like controls, they showed a typical global advantage and typical global-to-local consistency effects. The results demonstrate that the configural processing required by the Navon task is dissociable from face configural processing. [ABSTRACT FROM PUBLISHER]

Abstract: In addition to memory impairment, deficits in other cognitive processes are common in the advanced stages of Alzheimer's disease (AD). The diagnosis of AD does not consider the relative prevalence of deficits in cognitive areas other than memory. We report on the prevalence of aphasia, apraxia, and other cognitive changes in individuals from a large representative sample of elderly Canadians. The proportion of these symptoms and the relevant neuropsychological test performance were compared in a group of 749 people over 65 years in age with AD and a control group of 563 people without cognitive impairment. Agnosia was less common in both groups than were deficits in complex visuomotor tasks, abstract thinking. aphasia, and constructional defects. The occurrence of all symptoms increased, and levels of performance on relevant neuropsychological tests decreased, with severity of Alzheimer disease. The tests did not, however, distinguish between possible and probable AD. Both these diagnostic groups showed similar levels of performance, which suggests that this distinction is not clinically meaningful. [ABSTRACT FROM PUBLISHER]

The article focuses on Macdonald Critchley's William Gowers lecture concerning Gerstmann's syndrome. The lecture started with an account of the patient described by Josef Gerstmann who is unable to name her fingers and identify her own or the examiner's digits on request. Gerstmann's syndrome includes finger-agnosia, dyscalculia and right-left disorientation. The case of a woman who suffered from complications of eclampsia was described by professor Jules Badal.

This scientific commentary refers to ‘Critical brain regions for tool-related and imitative actions: a componential analysis’, by Buxbaum et al. (doi:10.1093/brain/awu111). [ABSTRACT FROM AUTHOR]