Mentalizing the body: : spatial and social cognition in anosognosia for hemiplegia

© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] 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.Peer reviewe

"I feel dumb, embarrassed, and frustrated”: A qualitative exploration of the lived experience of acalculia.

Introduction: Acalculia is an acquired disability following stroke or brain injury, which involves difficulty processing numerical information (e.g. phone numbers, measurements) or problems with calculations and understanding quantities. Acalculia is not routinely screened for as part of standard post-stroke assessment. As a result, there is a lack of understanding of the nature and prevalence of poststroke acalculia, and the impact it has on stroke survivors. This qualitative study aimed to explore stroke survivors’ experiences of acalculia. Stroke survivors with a strong interest in acalculia and its rehabilitation initiated the study and contributed to its design. Methods: We explored the impact of acalculia on the lives of 16 stroke/brain injury survivors with acalculia and 7 carers using semi-structured online interviews. Participants ranged in age, gender, time post onset, lesion localisation, country of residence and numeracy level prior to brain injury. Data were analysed using thematic analysis. Results: Three main themes were identified: Awareness and Diagnosis, Emotional and Physical Impact, and Coping Strategies and Independence. Participants and carers repeatedly referred to the lack of awareness and treatment for acalculia and the devastating impact acalculia has had on their lives and independence. Practical impacts included managing money, making appointments, using timetables, organising social activities and employment, and managing medication. Conclusions: Our results highlight the urgent need to develop suitable assessments and interventions for acalculia and the scope for this to be PCPI-led. The data also reveal useful strategies and suggestions regarding effective timing and approaches for intervention

A qualitative exploration of the lived experience of, and quality of professional support for, number processing deficits after brain injury or stroke

Introduction: Acalculia is an acquired disability following brain-injury (hence forth, including stroke) (Ardila & Rosselli, 2002), which involves difficulty processing numerical information (e.g. ‘phone numbers) or problems with calculations and understanding quantities (money, time). While difficulties may result from damage to quantity-processing units in the parietal region, or executive frontal regions, common difficulties are closely related to aphasic symptoms - for example, difficulties articulating numbers, understanding spoken number words, or reading digits or number words. Acalculia is not routinely screened for as part of standard brain-injury assessment, but studies suggest a prevalence of between 35%-60%. Aims: To understand the impact of acalculia on adults with acquired brain-injury, and to explore professional support available for patients with acalculia. Methods: We explored the impact of acalculia on the lives of 16 brain-injury survivors (7 males) with acalculia and 7 carers (4 males), using semi-structured online interviews (mean length of interview = 56min). Interviews investigated participants’ experiences of living with acalculia and the type and quality of professional support they received post brain-injury. Fifteen participants with acalculia also reported aphasic symptoms. Participants ranged in age (mean = 58 years, SD=12.95), time post onset (mean =7.39 years; SD=6.52), lesion localisation, country of residence, severity of aphasic symptoms, and numeracy level prior to brain injury. Data were analysed using thematic analysis. Results: Three main themes were identified: Awareness and Diagnosis, Emotional and Physical Impact, and Coping Strategies and Independence. Participants emphasised that concerns about language and mobility took precedence in the period immediately post brain-injury, and they only became aware of their specific difficulties with numbers later in their recovery. Both participants and carers repeatedly referred to the lack of awareness of, and treatment for, acalculia by all professionals they came across. This contrasted markedly to identification and support given for equally prevalent conditions such as aphasia. Many mentioned the devastating impact acalculia has had on their lives and independence. Practical impacts included managing money or medication, making appointments, using timetables, organising social activities and employment. Conclusions: Our results highlight the urgent need to increase awareness of acalculia amongst patients and professionals involved in post brain-injury care. There is a substantial and presently unmet clinical need to support professionals and patients by developing suitable assessments and interventions for acalculia. Contribution to new knowledge: While a lot is known about numerical cognition, this study highlights the gap between advances in theory and the lack of translational research that positively impact patient care. Implications for practice and/or policy service-user engagement and/or involvement in the study: This study was initiated by stroke survivors with a strong interest in acalculia and its rehabilitation, and the findings are testimony to the contribution of PCPI-led research. Going forward, findings will be used to identify and develop screening tests and interventions, and to increase awareness of acalculia among brain-injury survivors, their carers and professionals

Eating Disorder Examination Questionnaire (EDE-Q) : Norms and psychometric properties in U.K. females and males

The Eating Disorder Examination Questionnaire (EDE-Q) is a widely used assessment of eating disorder psychopathology; however, EDE-Q norms are yet to be provided within a nonclinical U.K. adult sample. Second, there is considerable disagreement regarding the psychometric properties of this measure. Several alternative factor structures have been previously proposed, but very few have subsequently validated their new structure in independent samples and many are often confined to specific subpopulations. Therefore, in the current study, we provide norms of the original four-factor EDE-Q structure, and subsequently assess the psychometric properties of the EDE-Q in females and males using a large nonclinical U.K. sample (total N = 2459). EDE-Q norms were consistently higher in females compared with males across all samples. Initial confirmatory factor analyses (CFA) did not support the original 4-factor structure for females or males (Phase 1). However, subsequent exploratory factor analyses (EFA) revealed a 3-factor structure as being the optimal fit for both females and males, using an 18-item and 16-item model, respectively (Phase 2). For females, the newly proposed 18-item structure was validated within an independent student sample and further validated in an additional nonstudent sample. The 16-item 3-factor male structure was also validated within an independent nonstudent sample, but was marginally below accepted fit indices within an independent student sample (Phase 3). Taken together, the above findings suggest that the EDE-Q factor structure may require further reassessment, with greater focus on the qualitative differences in interpretation of EDE-Q items between females and males. (PsycINFO Database Record (c) 2019 APA, all rights reserved)

The affective modulation of motor awareness in anosognosia for hemiplegia : Behavioural and lesion evidence

© 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).The possible role of emotion in anosognosia for hemiplegia (i.e., denial of motor deficits contralateral to a brain lesion), has long been debated between psychodynamic and neurocognitive theories. However, there are only a handful of case studies focussing on this topic, and the precise role of emotion in anosognosia for hemiplegia requires empirical investigation. In the present study, we aimed to investigate how negative and positive emotions influence motor awareness in anosognosia. Positive and negative emotions were induced under carefully-controlled experimental conditions in right-hemisphere stroke patients with anosognosia for hemiplegia (n = 11) and controls with clinically normal awareness (n = 10). Only the negative, emotion induction condition resulted in a significant improvement of motor awareness in anosognosic patients compared to controls; the positive emotion induction did not. Using lesion overlay and voxel-based lesion-symptom mapping approaches, we also investigated the brain lesions associated with the diagnosis of anosognosia, as well as with performance on the experimental task. Anatomical areas that are commonly damaged in AHP included the right-hemisphere motor and sensory cortices, the inferior frontal cortex, and the insula. Additionally, the insula, putamen and anterior periventricular white matter were associated with less awareness change following the negative emotion induction. This study suggests that motor unawareness and the observed lack of negative emotions about one's disabilities cannot be adequately explained by either purely motivational or neurocognitive accounts. Instead, we propose an integrative account in which insular and striatal lesions result in weak interoceptive and motivational signals. These deficits lead to faulty inferences about the self, involving a difficulty to personalise new sensorimotor information, and an abnormal adherence to premorbid beliefs about the body.Peer reviewedFinal Published versio

Developing infrared spectroscopic detection for stratifying brain tumour patients: glioblastoma multiforme vs. lymphoma

Over a third of brain tumour patients visit their general practitioner more than five times prior to diagnosis in the UK, leading to 62% of patients being diagnosed as emergency presentations. Unfortunately, symptoms are non-specific to brain tumours, and the majority of these patients complain of headaches on multiple occasions before being referred to a neurologist. As there are currently no methods in place for the early detection of brain cancer, the affected patients’ average life expectancy is reduced by 20 years. These statistics indicate that the current pathway is ineffective, and there is a vast need for a rapid diagnostic test. Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy is sensitive to the hallmarks of cancer, as it analyses the full range of macromolecular classes. The combination of serum spectroscopy and advanced data analysis has previously been shown to rapidly and objectively distinguish brain tumour severity. Recently, a novel high-throughput ATR accessory has been developed, which could be cost-effective to the National Health Service in the UK, and valuable for clinical translation. In this study, 765 blood serum samples have been collected from healthy controls and patients diagnosed with various types of brain cancer, contributing to one of the largest spectroscopic studies to date. Three robust machine learning techniques - random forest, partial least squares-discriminant analysis and support vector machine - have all provided promising results. The novel high-throughput technology has been validated by separating brain cancer and non-cancer with balanced accuracies of 90% which is comparable to the traditional fixed diamond crystal methodology. Furthermore, the differentiation of brain tumour type could be useful for neurologists, as some are difficult to distinguish through medical imaging alone. For example, the highly aggressive glioblastoma multiforme and primary cerebral lymphoma can appear similar on magnetic resonance imaging (MRI) scans, thus are often misdiagnosed. Here, we report the ability of infrared spectroscopy to distinguish between glioblastoma and lymphoma patients, at a sensitivity and specificity of 90.1% and 86.3%, respectively. A reliable serum diagnostic test could avoid the need for surgery and speed up time to definitive chemotherapy and radiotherapy

Stratifying Brain Tumour Histological Sub-Types: The Application of ATR-FTIR Serum Spectroscopy in Secondary Care

Patients living with brain tumours have the highest average years of life lost of any cancer, ultimately reducing average life expectancy by 20 years. Diagnosis depends on brain imaging and most often confirmatory tissue biopsy for histology. The majority of patients experience non-specific symptoms, such as headache, and may be reviewed in primary care on multiple occasions before diagnosis is made. Sixty-two per cent of patients are diagnosed on brain imaging performed when they deteriorate and present to the emergency department. Histological diagnosis from invasive surgical biopsy is necessary prior to definitive treatment, because imaging techniques alone have difficulty in distinguishing between several types of brain cancer. However, surgery itself does not necessarily control tumour growth, and risks morbidity for the patient. Due to their similar features on brain scans, glioblastoma, primary central nervous system lymphoma and brain metastases have been known to cause radiological confusion. Non-invasive tests that support stratification of tumour subtype would enhance early personalisation of treatment selection and reduce the delay and risks associated with surgery for many patients. Techniques involving vibrational spectroscopy, such as attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, have previously demonstrated analytical capabilities for cancer diagnostics. In this study, infrared spectra from 641 blood serum samples obtained from brain cancer and control patients have been collected. Firstly, we highlight the capability of ATR-FTIR to distinguish between healthy controls and brain cancer at sensitivities and specificities above 90%, before defining subtle differences in protein secondary structures between patient groups through Amide I deconvolution. We successfully differentiate several types of brain lesions (glioblastoma, meningioma, primary central nervous system lymphoma and metastasis) with balanced accuracies >80%. A reliable blood serum test capable of stratifying brain tumours in secondary care could potentially avoid surgery and speed up the time to definitive therapy, which would be of great value for both neurologists and patients

Academic neurosurgery in the UK: present and future directions.

Academic neurosurgery encompasses basic science and clinical research efforts to better understand and treat diseases of relevance to neurosurgical practice, with the overall aim of improving treatment and outcome for patients. In this article, we provide an overview of the current and future directions of British academic neurosurgery. Training pathways are considered together with personal accounts of experiences of structured integrated clinical academic training and unstructured academic training. Life as an academic consultant is also described. Funding is explored, for the specialty as a whole and at the individual level. UK academic neurosurgical organisations are highlighted. Finally, the UK's international standing is considered

Interrogation of IDH1 Status in Gliomas by Fourier Transform Infrared Spectroscopy

Mutations in the isocitrate dehydrogenase 1 (IDH1) gene are found in a high proportion of diffuse gliomas. The presence of the IDH1 mutation is a valuable diagnostic, prognostic and predictive biomarker for the management of patients with glial tumours. Techniques involving vibrational spectroscopy, e.g., Fourier transform infrared (FTIR) spectroscopy, have previously demonstrated analytical capabilities for cancer detection, and have the potential to contribute to diagnostics. The implementation of FTIR microspectroscopy during surgical biopsy could present a fast, label-free method for molecular genetic classification. For example, the rapid determination of IDH1 status in a patient with a glioma diagnosis could inform intra-operative decision-making between alternative surgical strategies. In this study, we utilized synchrotron-based FTIR microanalysis to probe tissue microarray sections from 79 glioma patients, and distinguished the positive class (IDH1-mutated) from the IDH1-wildtype glioma, with a sensitivity and specificity of 82.4% and 83.4%, respectively. We also examined the ability of attenuated total reflection (ATR)-FTIR spectroscopy in detecting the biomolecular events and global epigenetic and metabolic changes associated with mutations in the IDH1 enzyme, in blood serum samples collected from an additional 72 brain tumour patients. Centrifugal filtration enhanced the diagnostic ability of the classification models, with balanced accuracies up to ~69%. Identification of the molecular status from blood serum prior to biopsy could further direct some patients to alternative treatment strategies

Exploring use of unsupervised clustering to associate signaling profiles of GPCR ligands to clinical response.

Signaling diversity of G protein-coupled (GPCR) ligands provides novel opportunities to develop more effective, better-tolerated therapeutics. Taking advantage of these opportunities requires identifying which effectors should be specifically activated or avoided so as to promote desired clinical responses and avoid side effects. However, identifying signaling profiles that support desired clinical outcomes remains challenging. This study describes signaling diversity of mu opioid receptor (MOR) ligands in terms of logistic and operational parameters for ten different in vitro readouts. It then uses unsupervised clustering of curve parameters to: classify MOR ligands according to similarities in type and magnitude of response, associate resulting ligand categories with frequency of undesired events reported to the pharmacovigilance program of the Food and Drug Administration and associate signals to side effects. The ability of the classification method to associate specific in vitro signaling profiles to clinically relevant responses was corroborated using β2-adrenergic receptor ligands.This research was supported by a research contract from Pfizer Inc. and grants from the Natural Sciences and Engineering Research Council of Canada (Grant 311997 to G.P.) and the Canadian Institutes of Health Research MOP 324876 (to G.P.), MOP 102630 (to M.B. and O.L.) and Foundation grant (FDN-148431) to MB. MB holds a Canada Research Chair in Signal Transduction and Molecular Pharmacology. Dr Lichtarge’s research was supported by National Institutes of Health (NIH 2R01 GM066099; NIH 5R01 GM079656). B.B. was supported by a studentship from Fonds de Recherche en Santé du Québec. P.D. was supported by a MITACS fellowship