Evaluation of LiNES: A New Measure of Trauma, Negative Affect, and Relationship Insecurity Over the Life Span in Persons With FND.

OBJECTIVE: The authors evaluated potential predisposing vulnerabilities and perpetuating factors among individuals with functional neurological disorder (FND) by using the novel Lifespan Negative Experiences Scale (LiNES), which assesses retrospective self-report of interpersonal trauma, negative affect, and relationship insecurity at three developmental stages: childhood, adolescence, and adulthood. METHODS: The LiNES, Childhood Abuse and Trauma Scale (CATS), Relationship Scales Questionnaire (RSQ), and Positive and Negative Affect Schedule (PANAS) were administered to 71 individuals with FND. The reliability and validity of LiNES were examined by correlation with the other measures. FND patients' responses on LiNES were compared with those of 170 healthy control subjects. RESULTS: LiNES scores in the FND group were internally consistent and correlated highly with CATS, RSQ, and PANAS scores. At each developmental stage, LiNES trauma scores were higher among patients with FND, compared with control subjects. The FND subgroup, which comprised patients who also had nonepileptic attack disorder, had higher trauma scores, compared with the FND-only subgroup. Compared with control subjects, patients with FND reported greater negative affect and relationship insecurity in adulthood. Lifetime LiNES scores for interpersonal trauma and relationship insecurity predicted FND group classification with >80% accuracy. CONCLUSIONS: This study provides further support for the links between FND and trauma, negative affect, and insecure attachment. Recognition of these factors is likely to be important for treatment and stratification of important subpopulations in research. These findings provide new insights into the association between the timing of negative experiences and their effect, with LiNES emerging as a potentially useful measure for patients presenting with FND.

Development, reliability, validity, and acceptability of the remote administration of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS).

BACKGROUND: ALS clinical care and research has changed dramatically since the COVID-19 pandemic, accelerating the need for cognitive assessments to be adapted for remote use. OBJECTIVES: To develop the remote administration method of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), and determine its reliability and validity. Methods: The validation process consisted of: (1) Two versions of the ECAS (A and B) were administered, one in-person and one remotely via video call in a randomized order to 27 people without ALS; (2) The ECAS was administered remotely to 24 pwALS, with a second rater independently scoring performance; and (3) Acceptability was assessed by gathering feedback from 17 pwALS and 19 clinicians and researchers about their experience of using the ECAS remotely. RESULTS: In the group without ALS, the remote and in-person ECAS total scores were found to be equivalent, and a Bland-Altman plot showed good agreement between the two administration methods. In pwALS, there was excellent agreement between two raters (ICC = 0.99). Positive feedback was gained from pwALS, researchers and clinicians with regards to ease of process, convenience, time, and the environment. CONCLUSIONS: These findings provide evidence of the reliability and validity of the remote administration of the ECAS for pwALS, with clinicians, researchers and pwALS viewing it as a good alternative to face-to-face administration.

Measuring Health-Related Quality of Life in Amyotrophic Lateral Sclerosis: A Systematic Review and Conceptual Framework.

BACKGROUND AND OBJECTIVES: The assessment of health-related quality of life (HRQoL) in patients with amyotrophic lateral sclerosis (ALS) is heterogeneous and inconsistent. The objectives of this study were (1) to develop a comprehensive conceptual framework of HRQoL in ALS and (2) map the content of existing patient-reported outcome measures (PROMs) used in ALS to this novel framework. METHODS: Our model of HRQoL in ALS (Health-related Quality of life in Amyotrophic Lateral Sclerosis, QuALS) was developed from a systematic literature review and consultative input from key stakeholders (patients, carers, and health care professionals). Five electronic databases were searched in April 2022. Primary studies of any design that assessed HRQoL in ALS by using a multi-item PROM and/or qualitative methods were identified. Using an a priori framework, HRQoL themes were extracted and iteratively modified from the content of each PROM and qualitative study quotations identified in the literature. The conceptual framework was ratified by stakeholders with lived experience and clinical experts. The QuALS framework was used to map the content of identified PROMs and qualitative studies based on thematic coverage. RESULTS: QuALS covers 3 high-level domains of HRQoL (physical, psychological, and social functioning) and consists of 7 themes (Activities; Physical Health; Autonomy; Cognition; Feelings and Emotions; Self-identity; Relationships), characterized by 42 subthemes. Of 8,220 studies identified, 274 were included in the review that informed QuALS. In these studies, 111 PROMs were used to assess at least 1 aspect of HRQoL, and 11 studies used qualitative methods. Of the 3 high-level domains, physical functioning was the most commonly assessed, particularly within ALS-specific PROMs where almost one-quarter of PROMs exclusively assessed physical functioning. None of the PROMs or qualitative studies identified assessed all aspects of HRQoL in the QuALS framework. DISCUSSION: This study presents a new comprehensive conceptual framework of HRQoL in ALS (QuALS), informed by a robust systematic review of existing literature and stakeholder input, incorporating lived experience. QuALS provides a valuable resource for researchers and clinicians interested in taking a holistic approach to assessing and understanding the full impact of ALS on HRQoL and how this may be affected by treatments.

Coherent concepts are computed in the anterior temporal lobes.

In his Philosophical Investigations, Wittgenstein famously noted that the formation of semantic representations requires more than a simple combination of verbal and nonverbal features to generate conceptually based similarities and differences. Classical and contemporary neuroscience has tended to focus upon how different neocortical regions contribute to conceptualization through the summation of modality-specific information. The additional yet critical step of computing coherent concepts has received little attention. Some computational models of semantic memory are able to generate such concepts by the addition of modality-invariant information coded in a multidimensional semantic space. By studying patients with semantic dementia, we demonstrate that this aspect of semantic memory becomes compromised following atrophy of the anterior temporal lobes and, as a result, the patients become increasingly influenced by superficial rather than conceptual similarities.

At the edge of semantic space: the breakdown of coherent concepts in semantic dementia is constrained by typicality and severity but not modality.

Hub-and-spoke models of semantic representation suggest that coherent concepts are formed from the integration of multiple, modality-specific information sources with additional modality-invariant representations-most likely stored in the ventrolateral anterior temporal lobe (vATL). As well as providing the necessary computational mechanisms for the complexities of feature integration, these modality-invariant representations also license a key aspect of semantic memory-semantic-based generalization. Semantic dementia allows us to investigate this aspect of conceptual knowledge because (a) the patients have a selective and progressive semantic degradation and (b) this is associated with profound ventrolateral ATL atrophy. Specifically, the boundaries between concepts become degraded in semantic dementia and, when tested using the appropriate materials, the patients make simultaneous under- and overgeneralization errors. We found that the rate of these errors were a function of typicality and pseudotypicality of the items as well as the severity of the patients' semantic impairment. Following the modality-invariant nature of the vATL hub representation, we also confirmed that the patients were impaired on both verbal- and picture-based versions of the same task.

Psychological interventions for people with motor neuron disease: a scoping review.

OBJECTIVE: Motor neuron disease (MND) is a rapidly progressive neurodegenerative condition with no known cure. MND can affect every aspect of a person's life and has been associated with a wide range of psychological difficulties, which can occur from pre-diagnosis through to the condition's later stages. However, very little research has been conducted on psychological interventions for people with MND (pwMND). This paper aimed to provide the first review specifically targeting psychological interventions in MND and offer potential directions for future research. Methods: A scoping review was carried out across five major databases (PubMed, PsycINFO, CINAHL, Academic Search Ultimate, and Cochrane Library) until 1st of March 2020. Results: From an initial return of 1278 citations, 10 papers were included in the review. These included three randomized controlled trials (RCTs), two quasi-experiments, three uncontrolled pretest-post-test designs, one single case study, and one qualitative secondary analysis. The existing studies focused on a limited number of psychological outcomes and did not take into account site of MND onset or level of depression/anxiety before intervention. Implications for clinical practice are discussed and suggestions for future research are provided. Conclusions: The literature on psychological interventions is still extremely sparse. Mindfulness-based stress reduction (MBSR) and cognitive behavioral therapy (CBT) based on the stress-coping model show promise in RCTs, but require further evaluation. The need for further development and evaluation of psychological interventions to improve the well-being of pwMND cannot be overstated, particularly as the struggle toward the discovery of an effective treatment for MND continues.

Informal Caregivers in Amyotrophic Lateral Sclerosis: A Multi-Centre, Exploratory Study of Burden and Difficulties.

Amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) is a systemic and fatal neurodegenerative condition for which there is currently no cure. Informal caregivers play a vital role in supporting the person with ALS, and it is essential to support their wellbeing. This multi-centre, mixed methods descriptive exploratory study describes the complexity of burden and self-defined difficulties as described by the caregivers themselves. Quantitative and qualitative data were collected during face-to-face interviews with informal caregivers from centres in the Netherlands, England, and Ireland. Standardised measures assessed burden, quality of life, and psychological distress; furthermore, an open-ended question was asked about difficult aspects of caregiving. Most caregivers were female, spouse/partners, and lived with the person with ALS for whom they provided care. Significant differences between national cohorts were identified for burden, quality of life, and anxiety. Among the difficulties described were the practical issues associated with the caregiver role and emotional factors such as witnessing a patient's health decline, relationship change, and their own distress. The mixed-methods approach allows for a more nuanced understanding of the burden and difficulties experienced. It is important to generate an evidence base to support the psychosocial wellbeing and brain health of informal caregivers.

Relearning in semantic dementia reflects contributions from both medial temporal lobe episodic and degraded neocortical semantic systems: evidence in support of the complementary learning systems theory.

When relearning words, patients with semantic dementia (SD) exhibit a characteristic rigidity, including a failure to generalise names to untrained exemplars of trained concepts. This has been attributed to an over-reliance on the medial temporal region which captures information in sparse, non-overlapping and therefore rigid representations. The current study extends previous investigations of SD relearning by re-examining the additional contribution made by the degraded cortical semantic system. The standard relearning protocol was modified by careful selection of foils to show that people with semantic dementia were sometimes able to extend their learning appropriately but that this correct generalisation was minimal (i.e. the patients under-generalised their learning). The revised assessment procedure highlighted the fact that, after relearning, the participants also incorrectly over-generalised the learned label to closely related concepts. It is unlikely that these behaviours would occur if the participants had only formed sparse hippocampal representations. These novel data build on the notion that people with semantic dementia engage both the degraded cortical semantic (neocortex) and the episodic (medial temporal) systems to learn. Because of neocortical damage to the anterior temporal lobes, relearning is disordered with a characteristic pattern of under- and over-generalisation.