Cognitive decline heralds onset of symptomatic inherited prion disease.

The clinical effectiveness of any disease-modifying treatment for prion disease, as for other neurodegenerative disorders, will depend on early treatment before damage to neural tissue is irrevocable. Thus, there is a need to identify markers that predict disease onset in healthy at-risk individuals. Whilst imaging and neurophysiological biomarkers have shown limited use in this regard, we recently reported progressive neurophysiological changes in individuals with the inherited prion disease mutation P102L. We have also previously demonstrated a signature pattern of fronto-parietal dysfunction in mild prion disease. Here we address whether these cognitive features anticipate the onset of symptoms in a unique sample of patients with inherited prion disease. In the cross-sectional analysis, we analysed the performance of patients at three time points in the course of disease onset: prior to symptoms (n = 27), onset of subjective symptoms without positive clinical findings (n = 8) and symptomatic with positive clinical findings (n = 24). In the longitudinal analysis, we analysed data from 24 patients who were presymptomatic at the time of recruitment and were followed up over a period of up to 17 years, of whom 16 remained healthy and eight converted to become symptomatic. In the cross-sectional analysis, the key finding was that, relative to a group of 25 healthy non-gene carrier controls, patients with subjective symptoms but without positive clinical findings were impaired on a smaller but similar set of tests (Trail Making Test part A, Stroop test, Performance IQ, gesture repetition, figure recall) to those previously found to be impaired in mild prion disease. In the longitudinal analysis, Trail Making Test parts A and B, Stroop test and Performance IQ scores significantly discriminated between patients who remained presymptomatic and those who converted, even before the converters reached criteria for formal diagnosis. Notably, performance on the Stroop test significantly discriminated between presymptomatic patients and converters before the onset of clinical symptoms [area under the curve = 0.83 (95% confidence interval, 0.62-1.00), P = 0.009]. Thus, we report here, for the first time, neuropsychological abnormalities in healthy patients prior to either symptom onset or clinical diagnosis of inherited prion disease. This constitutes an important component of an evolving profile of clinical and biomarker abnormalities in this crucial group for preventive medicine.

Is the Weigl Colour-Form Sorting Test Specific to Frontal Lobe Damage?

OBJECTIVE: The Weigl Colour-Form Sorting Test is a brief, widely used test of executive function. So far, it is unknown whether this test is specific to frontal lobe damage. Our aim was to investigate Weigl performance in patients with focal, unilateral, left or right, frontal, or non-frontal lesions. METHOD: We retrospectively analysed data from patients with focal, unilateral, left or right, frontal (n = 37), or non-frontal (n = 46) lesions who had completed the Weigl. Pass/failure (two correct solutions/less than two correct solutions) and errors were analysed. RESULTS: A greater proportion of frontal patients failed the Weigl than non-frontal patients, which was highly significant (p < 0.001). In patients who failed the test, a significantly greater proportion of frontal patients provided the same solution twice. No significant differences in Weigl performance were found between patients with left versus right hemisphere lesions or left versus right frontal lesions. There was no significant correlation between performance on the Weigl and tests tapping fluid intelligence. CONCLUSIONS: The Weigl is specific to frontal lobe lesions and not underpinned by fluid intelligence. Both pass/failure on this test and error types are informative. Hence, the Weigl is suitable for assessing frontal lobe dysfunction.

The relationship between early post-stroke cognition and longer term activities and participation: A systematic review.

This systematic review examined whether early cognitive impairment after stroke is predictive of outcome within the "activity" and "participation" domains of the International Classification of Functioning, Disability and Health (ICF) at 6-12 months post-injury. Studies were included if cognitive functioning was assessed within 6 weeks of injury and outcome was measured at least 6 months post-injury. PsycINFO, MEDLINE, CINAHL and EMBASE databases were searched and 14 studies were identified. Studies were categorised according to whether "domain-general" or "domain-specific" cognitive assessment was undertaken and whether outcomes measured the ICF activities or participation domains, as determined by three independent raters using previous established linking rules. Quality of studies was assessed using a modified version of Downs and Black's Quality Index. Overall, early cognitive impairment predicted activities and participation 6-12 months post-stroke. This relationship was more consistent when domain-specific cognitive assessment was used. For the domain of activities, visuospatial perception/construction, visual memory, visual neglect, and attention/executive functioning predicted functioning 6-12 months post-stroke. Early domain-specific cognitive assessment may be clinically informative of longer term activities. For the domain of participation, further well-controlled studies are needed to determine the relationship with early post-stroke cognitive impairments.

Super-recognition in development: A case study of an adolescent with extraordinary face recognition skills.

Face recognition abilities vary widely. While face recognition deficits have been reported in children, it is unclear whether superior face recognition skills can be encountered during development. This paper presents O.B., a 14-year-old female with extraordinary face recognition skills: a "super-recognizer" (SR). O.B. demonstrated exceptional face-processing skills across multiple tasks, with a level of performance that is comparable to adult SRs. Her superior abilities appear to be specific to face identity: She showed an exaggerated face inversion effect and her superior abilities did not extend to object processing or non-identity aspects of face recognition. Finally, an eye-movement task demonstrated that O.B. spent more time than controls examining the nose - a pattern previously reported in adult SRs. O.B. is therefore particularly skilled at extracting and using identity-specific facial cues, indicating that face and object recognition are dissociable during development, and that super recognition can be detected in adolescence.

Rehabilitation of face-processing skills in an adolescent with prosopagnosia: Evaluation of an online perceptual training programme.

In this paper we describe the case of EM, a female adolescent who acquired prosopagnosia following encephalitis at the age of eight. Initial neuropsychological and eye-movement investigations indicated that EM had profound difficulties in face perception as well as face recognition. EM underwent 14 weeks of perceptual training in an online programme that attempted to improve her ability to make fine-grained discriminations between faces. Following training, EM's face perception skills had improved, and the effect generalised to untrained faces. Eye-movement analyses also indicated that EM spent more time viewing the inner facial features post-training. Examination of EM's face recognition skills revealed an improvement in her recognition of personally-known faces when presented in a laboratory-based test, although the same gains were not noted in her everyday experiences with these faces. In addition, EM did not improve on a test assessing the recognition of newly encoded faces. One month after training, EM had maintained the improvement on the eye-tracking test, and to a lesser extent, her performance on the familiar faces test. This pattern of findings is interpreted as promising evidence that the programme can improve face perception skills, and with some adjustments, may at least partially improve face recognition skills.

Impaired option generation underpins deficient reasoning in Parkinson's disease patients with apathy.

Apathy is a debilitating neurological syndrome known to be associated with executive dysfunction, particularly affecting abstract reasoning. However, the underlying cognitive mechanism remains unclear. Recently, it has been proposed that one cognitive process disrupted in apathy is option generation. We investigated whether impaired option generation could explain deficient reasoning in apathy. Data was retrospectively analyzed from patients with Parkinson's disease (n = 51) who had completed the Lille Apathy Rating Scale and the Brixton Spatial Anticipation Task (Brixton), a measure of inductive reasoning. A hierarchical regression analysis showed that higher levels of apathy predicted poorer Brixton performance. Detailed analysis of Brixton errors was conducted to investigate the cognitive process underlying this relationship. Additional hierarchical regression analyses showed that apathy specifically predicted Brixton errors associated with a failure to generate either correct or incorrect rules. These findings suggest that deficient reasoning in apathy may be underpinned by impaired option generation.

Is the Brixton Spatial Anticipation Test sensitive to frontal dysfunction? Evidence from patients with frontal and posterior lesions.

INTRODUCTION: The Brixton Spatial Anticipation Test is a widely used neuropsychological test, thought to assess executive functions and to be sensitive to frontal lobe lesions. Our aim was to investigate Brixton performance in patients with focal frontal or posterior lesions and healthy controls. METHOD: We compared performance on the Brixton in a sample of 24 frontal patients, 18 posterior patients and 22 healthy controls. Both overall performance (total number of errors) and error types were analyzed. RESULTS: We found no significant differences between frontal and posterior patients and healthy controls in overall Brixton performance. Moreover, our error analysis showed no difference between frontal patients, posterior patients and healthy controls. The only exception was that posterior patients had a greater tendency to guess and make more errors when following specific rules than healthy controls but this was no longer significant once fluid intelligence was controlled for. We also found no significant difference between the performance of patients with left lateral (n = 11), right lateral (n = 10) or superior medial (n = 18) frontal lesions and healthy controls. CONCLUSIONS: The Brixton test is not sensitive to frontal lobe dysfunction. It is likely that the test draws on a range of cognitive abilities not specific to frontal lobe lesions. Hence, caution should be taken when drawing conclusions about its neural substrates.

Role of clinical neuropsychology in deep brain stimulation: Review of the literature and considerations for clinicians.

Deep Brain Stimulation (DBS) is an effective surgical therapy for several neurological movement disorders. The clinical neuropsychologist has a well-established role in the neuropsychological evaluation and selection of surgical candidates. In this article, we argue that the clinical neuropsychologist's role is much broader, when considered in relation to applied psychologists' core competencies. We consider the role of the clinical neuropsychologist in DBS in relation to: assessment, formulation, evaluation and research, intervention or implementation, and communication. For each competence the relevant evidence-base was reviewed. Clinical neuropsychology has a vital role in presurgical assessment of cognitive functioning and psychological, and emotional and behavioral difficulties. Formulation is central to the selection of surgical candidates and crucial to intervention planning. Clinical neuropsychology has a well-established role in postsurgical assessment of cognitive functioning and psychological, emotional, and behavioral outcomes, which is fundamental to evaluation on an individual and service level. The unique contribution clinical neuropsychology makes to pre- and postsurgical interventions is also highlighted. Finally, we discuss how clinical neuropsychology can promote clear and effective communication with patients and between professionals.

First report of generalized face processing difficulties in möbius sequence.

Reverse simulation models of facial expression recognition suggest that we recognize the emotions of others by running implicit motor programmes responsible for the production of that expression. Previous work has tested this theory by examining facial expression recognition in participants with Möbius sequence, a condition characterized by congenital bilateral facial paralysis. However, a mixed pattern of findings has emerged, and it has not yet been tested whether these individuals can imagine facial expressions, a process also hypothesized to be underpinned by proprioceptive feedback from the face. We investigated this issue by examining expression recognition and imagery in six participants with Möbius sequence, and also carried out tests assessing facial identity and object recognition, as well as basic visual processing. While five of the six participants presented with expression recognition impairments, only one was impaired at the imagery of facial expressions. Further, five participants presented with other difficulties in the recognition of facial identity or objects, or in lower-level visual processing. We discuss the implications of our findings for the reverse simulation model, and suggest that facial identity recognition impairments may be more severe in the condition than has previously been noted.