Time course of EEG power during creative problem-solving with insight or remote thinking.

Problem-solving often requires creativity and is critical in everyday life. However, the neurocognitive mechanisms underlying creative problem-solving remain poorly understood. Two mechanisms have been highlighted: the formation of new connections among problem elements and insight solving, characterized by sudden realization of a solution. In this study, we investigated EEG activity during a modified version of the remote associates test, a classical insight problem task that requires finding a word connecting three unrelated words. This allowed us to explore the brain correlates associated with the semantic remoteness of connections (by varying the remoteness of the solution word across trials) and with insight solving (identified as a Eurêka moment reported by the participants). Semantic remoteness was associated with power increase in the alpha band (8-12 Hz) in a left parieto-temporal cluster, the beta band (13-30 Hz) in a right fronto-temporal cluster in the early phase of the task, and the theta band (3-7 Hz) in a bilateral frontal cluster just prior to participants' responses. Insight solving was associated with power increase preceding participants' responses in the alpha and gamma (31-60 Hz) bands in a left temporal cluster and the theta band in a frontal cluster. Source reconstructions revealed the brain regions associated with these clusters. Overall, our findings shed new light on some of the mechanisms involved in creative problem-solving.

Could motor blocks be a therapeutic option for treatment-resistant functional dystonia? A case series of three patients.

The diagnosis of functional dystonia is challenging because it is difficult to distinguish functional dystonia from other types of dystonia. After diagnostic explanation, multidisciplinary care is recommended, but some patients are resistant to treatments. We used motor blocks in three patients with severe resistant functional dystonia of the upper limbs to test (i) whether joint contracture was present and (ii) whether motor blocks have a therapeutic effect on functional dystonia. Patient 1 showed a good and sustained therapeutic response, Patient 2 experienced a resolution of the dystonic posture that lasted for 10 days, and Patient 3 experienced no effect. Motor blocks may be a useful therapeutic option in chronic treatment-resistant functional dystonia. The treatment effect might be achieved through the experience of normal positioning and functioning of the limb.

Is the clinical phenotype impact the prognosis in dementia with Lewy bodies?

INTRODUCTION: The first predominant clinical symptoms of dementia with Lewy bodies (DLB) are highly variable; however, the prognosis based on initial predominant symptoms remains poorly understood. METHODS: Multicenter retrospective study in 4 French expert neurological centers. Patients were categorized in 3 groups according to their first more predominant symptoms: cognitive, psychiatric, or motor. RESULTS: Analysis of 310 DLB patients. The mean age was 73.5 years old (SD 7.5) including 32.3% of women. The mean follow-up was 7.25 years (SD 3.6). We observed that the full clinical picture was more frequent in the motor group than in the cognitive group (p = 0.01); male gender and age at onset were associated with a significant excess risk of instantaneous mortality (p = 0.01). CONCLUSION: Initial symptoms may affect the clinical course of patients, but no significant difference in mortality was observed.

Overall comorbidities in functional neurological disorder: A narrative review.

INTRODUCTION: The importance to assess and include the frequent comorbidities in the personalised care management plan of patients with functional neurological disorders (FND) has arisen through the years. FND patients are not only complaining from motor and/or sensory symptoms. They also report some non-specific symptoms that participate to the burden of FND. In this narrative review, we aim to better describe these comorbidities in terms of prevalence, clinical characteristics and their variability depending on the subtype of FND. METHODS: The literature was searched for on Medline and PubMed. The search was narrowed to articles between 2000 and 2022. RESULTS: Fatigue is the most common symptom reported in relation to FND (from 47 to 93%), followed by cognitive symptoms (from 80 to 85%). Psychiatric disorders are reported in 40 to 100% FND patients, depending on the FND subtype (functional motor disorder [FMD], functional dissociative seizures [FDS]…) but also on the type of psychiatric disorder (anxiety disorders being the most frequent, followed by mood disorders and neurodevelopmental disorders). Stress factors such as childhood trauma exposure (emotional neglect and physical abuse predominantly) have also been identified in up to 75% of FND patients, along with maladaptive coping strategies. Organic disorders are commonly reported in FND, such as neurological disorders (including epilepsy in FDS [20%] and FMD in Parkinson's Disease [7%]). Somatic symptom disorders including chronic pain syndromes are frequently associated to FND (about 50%). To be noted, recent data also suggest a high comorbidity between FND and hypermobile Ehlers Danlos Syndrome (about 55%). CONCLUSION: Put together, this narrative review highlights the high burden of FND patients, not only due to somatosensory alterations but also by considering the frequent comorbidities reported. Thus, such comorbidities must be taken into consideration when defining the FND personalised care management strategy for the patients.

Anomalies in the review process and interpretation of the evidence in the NICE guideline for chronic fatigue syndrome and myalgic encephalomyelitis.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

[Validated care programs for patients with functional neurological disorders]. / Modèles de soins validés pour les patients souffrant de troubles neurologiques fonctionnels.

Functional neurological disorder (FND) is a common cause of persistent and disabling neurological symptoms. Diagnostic delay may lead to no treatment, inappropriate treatment or even iatrogenic symptoms. Yet, several treatments significantly reduce physical symptoms and improve functioning in FND patients even though not all patients respond to the currently available treatments. This review aims to describe the range of evidence-based rehabilitative and/or psychological therapeutic approaches available for FND patients. The most effective treatments are multidisciplinary and coordinated; using an outpatient or inpatient setting. Building a network of FND-trained healthcare professionals around the patient is an essential aspect of optimal patient management. Indeed, a supportive environment coupled with a collaborative therapeutic relationship improves understanding of FND and appears to help patients engage in appropriate treatments. Patients need to be invested in their own care and have to understand that recovery may depend on their commitment. The conventional treatment combines psychoeducation, physical rehabilitation and psychotherapy (cognitive and behavioral therapy, hypnosis, psychodynamic interpersonal therapy). Early referral of patients to physical therapy is recommended; however, the optimal parameters of treatment, duration and intensity are unknown and seem to vary with the severity and chronicity of symptoms. The goal is to minimize self-awareness by diverting attention or by stimulating automatically generated movements with non-specific and gradual exercises. The use of compensatory technical aids should be avoided as much as possible. Psychotherapeutic management should encourage self-evaluation of cognitive distortions, emotional reactions and maladaptive behaviors while empowering the patient in managing symptoms. Symptom management can use anchoring strategies to fight against dissociation. The aim is to connect to the immediate environment and to enrich one's sensoriality. The psychological interventions should then be adapted to the individual psychopathology, cognitive style and personality functioning of each patient. There is currently no known curative pharmacological treatment for FND. The pharmacological approach rather consists of progressively discontinuing medication that was introduced by default and that could lead to undesirable side effects. Finally, neurostimulation (transcranial magnetic stimulation, transcranial direct current stimulation) can be effective on motor FND.

[Overview of care management principles in functional neurological disorders]. / Synthèse des principes et schémas de prise en charge dans les troubles neurologiques fonctionnels.

After more than twenty years of academic research on functional neurological disorders (FND) throughout the world, a standardized care management strategy has emerged to allow a more adapted care offer to patients with FND, as close as possible to their experience and their needs. With regard to this special issue on FND in collaboration with L'Encéphale and at the initiative of the Neuropsychiatry section of the AFPBN (French Association of Biological Psychiatry and Neuropsychopharmacology), we would like to suggest a summary of all topics discussed in more detail in each article of this special issue, in order to facilitate its reading. We therefore cover the following themes: the initial contact with a patient with FND, the diagnostic process in favor of a positive diagnosis, the physiological, neural and psychological basis of FND, the diagnostic announcement (and its intangibles), the therapeutic patient education in FND, the general principles of therapeutic management through a personalized and multidisciplinary care program, and the validated therapeutic tools available according to the symptoms identified. This article is designed to be of broad interest on FND, supported by tables and figures showing the key points of all these steps, to keep an educational purpose at most. We hope that through this special issue, each health professional will be able to grasp this knowledge and this framework of care as easily and quickly as possible, in order to participate in the standardization of the care offer.

[Diagnostic criteria, epidemiology and assessment of patients with functional neurological disorders]. / Définitions, épidémiologie et démarche diagnostique clinique dans les troubles neurologiques fonctionnels.

Functional neurological disorders (FND) are symptoms that can affect a variety of functions including motor, sensory and cognitive. These symptoms are genuinely experienced by the patient and are related to a functional disorder rather than a structural one. There is little epidemiological data on these disorders, but their frequency is well established in clinical practice, it is the second most frequent reason for consultation in Neurology. Despite of the frequency of the disorder, general practitioners and specialists are insufficiently trained in the disease, and patients often suffer from stigmatization and/or unnecessary investigations. It is therefore important to be aware of the diagnostic approach to FND, which mostly relies on positive clinical signs. Psychiatric evaluation can help with the characterization of predisposing, precipitating and perpetuating factors of the symptoms (according to the 3P biopsychosocial model related to FND), and guide their management. Finally, diagnosis explanation is a crucial step in the management of the disease, which can in itself have a therapeutic effect, and allow the patient to adhere to the treatments.

[Functional neurological disorders: A clinical anthology]. / Troubles neurologiques fonctionnels : une anthologie clinique.

Functional neurological disorders have a broad phenotypic spectrum and include different clinical syndromes, which are sometimes associated to each other or appear consecutively over the course of the disease. This clinical anthology provides details on the specific and sensitive positive signs that are to be sought in the context of a suspected functional neurological disorder. Beside these positive elements leading to the diagnosis of functional neurological disorder, we should keep in mind the possibility of an associated organic disorder as the combination of both organic and functional disorders is a relatively frequent situation in clinical practice. Here we describe the clinical characteristics of different functional neurological syndromes: motor deficits, abnormal hyperkinetic and hypokinetic movements, voice or speech disorders, sensory disorders, and functional dissociative seizures. The clinical examination and the identification of positive signs play a critical role in the diagnosis of functional neurological disorder. Knowledge of the specific signs associated with each phenotype render possible to make an early diagnosis. For that matter, it contributes to the improvement of patient care management. It allows to a better engagement in an appropriate care pathway, which influence their prognosis. Highlighting and discussing positive signs with patients can also be an interesting step in the process of explaining the disease and its management.

Functional neurological disorder is a feminist issue.

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need.

Impaired social cognition and fine dexterity in patients with Cowden syndrome associated with germline PTEN variants.

PURPOSE: Cowden syndrome (CS) is an autosomal dominant disease related to germline PTEN variants and is characterised by multiple hamartomas, increased risk of cancers and frequent brain alteration. Since the behaviour of patients with CS sometimes appears to be inappropriate, we analysed their neuropsychological functioning. METHODS: This monocentric study was conducted between July 2018 and February 2020. A standardised neuropsychological assessment, including an evaluation of social cognition, executive functions, language and dexterity, as well as a cerebral MRI were systematically proposed to all patients with CS. Moreover, PTEN variants were identified. RESULTS: Fifteen patients from 13 families were included, with six non-sense (40%), three missense (20%), five frameshift (33.3%) and one splice site (6.6%) variant types. Twelve patients (80%) had altered social cognition: 10 patients had an abnormal modified Faux-Pas score and 5 had Ekman's facial emotions recognition impairment. Nearly all patients (93%) had impaired dexterity. Cerebral MRI showed various cerebellar anomalies in seven patients (46.7%). CONCLUSION: Altered social cognition and impaired fine dexterity are frequently associated with CS. Further studies are needed to confirm these results and to determine whether dexterity impairment is due to the effect of germline PTEN variants in the cerebellum.

Video-Based Automated Assessment of Movement Parameters Consistent with MDS-UPDRS III in Parkinson's Disease.

BACKGROUND: Among motor symptoms of Parkinson's disease (PD), including rigidity and resting tremor, bradykinesia is a mandatory feature to define the parkinsonian syndrome. MDS-UPDRS III is the worldwide reference scale to evaluate the parkinsonian motor impairment, especially bradykinesia. However, MDS-UPDRS III is an agent-based score making reproducible measurements and follow-up challenging. OBJECTIVE: Using a deep learning approach, we developed a tool to compute an objective score of bradykinesia based on the guidelines of the gold-standard MDS-UPDRS III. METHODS: We adapted and applied two deep learning algorithms to detect a two-dimensional (2D) skeleton of the hand composed of 21 predefined points, and transposed it into a three-dimensional (3D) skeleton for a large database of videos of parkinsonian patients performing MDS-UPDRS III protocols acquired in the Movement Disorder unit of Avicenne University Hospital. RESULTS: We developed a 2D and 3D automated analysis tool to study the evolution of several key parameters during the protocol repetitions of the MDS-UPDRS III. Scores from 2D automated analysis showed a significant correlation with gold-standard ratings of MDS-UPDRS III, measured with coefficients of determination for the tapping (0.609) and hand movements (0.701) protocols using decision tree algorithms. The individual correlations of the different parameters measured with MDS-UPDRS III scores carry meaningful information and are consistent with MDS-UPDRS III guidelines. CONCLUSION: We developed a deep learning-based tool to precisely analyze movement parameters allowing to reliably score bradykinesia for parkinsonian patients in a MDS-UPDRS manner.

The "Neurospeed" game: a fun tool to learn the neurological semiology.

BACKGROUND: Neurological semiology is often considered by medical students as particularly difficult to learn. Finding alternative teaching methods may improve students' motivation and understanding of this field. METHODS: We developed the "Neurospeed", a game to learn neurological syndromes. We assessed its efficiency on short-term learning of neurological syndromes in third-year medical students, through Multiple Choice Questions (MCQs) before and after the game session. Students' satisfaction was evaluated by a satisfaction survey. RESULTS: Out of the 199 third-year medical students of the Faculty of Medicine Sorbonne Paris Nord, 180 attended the Neurospeed in December 2020, and 148 answered 20 Multiple Choice Questions before and after the game, with significant improvement of their score (p < 0.001). Most of the participants agreed that the game was playful, stimulating, and helpful to learn neurological semiology. CONCLUSIONS: Overall, our results show that the Neurospeed game is an interesting tool as a complement to traditional lectures. Further studies are necessary to compare the efficacy of different types of serious games on short-term and long-term learning of neurological semiology.

Does adding <i>beer</i> to <i>coffee</i> enhance the activation of <i>drinks</i>? An ERP study of semantic category priming.

Categorization - whether of objects, ideas, or events - is a cognitive process that is essential for human thinking, reasoning, and making sense of everyday experiences. Categorization abilities are typically measured by the Wechsler Adult Intelligence Scale (WAIS) similarity subtest, which consists of naming the shared category of two items (e.g., 'How are beer and coffee alike'). Previous studies show that categorization, as measured by similarity tasks, requires executive control functions. However, other theories and studies indicate that semantic memory is organized into taxonomic and thematic categories that can be activated implicitly in semantic priming tasks. To explore whether categories can be primed during a similarity task, we developed a double semantic priming paradigm. We measured the priming effect of two primes on a target word that was taxonomically or thematically related to both primes (double priming) or only one of them (single priming). Our results show a larger and additive priming effect in the double priming condition compared to the single priming condition, as measured by both response times and, more consistently, event-related potentials. Our results support the view that taxonomic and thematic categorization can occur during a double priming task and contribute to improving our knowledge on the organization of semantic memory into categories. These findings show how abstract categories can be activated, which likely shapes the way we think and interact with our environment. Our study also provides a new cognitive tool that could be useful to understand the categorization difficulties of neurological patients.

Treatable Hyperkinetic Movement Disorders Not to Be Missed.

Hyperkinetic movement disorders are characterized by the presence of abnormal involuntary movements, comprising most notably dystonia, chorea, myoclonus, and tremor. Possible causes are numerous, including autoimmune disorders, infections of the central nervous system, metabolic disturbances, genetic diseases, drug-related causes and functional disorders, making the diagnostic process difficult for clinicians. Some diagnoses may be delayed without serious consequences, but diagnosis delays may prove detrimental in treatable disorders, ranging from functional disabilities, as in dopa-responsive dystonia, to death, as in Whipple's disease. In this review, we focus on treatable disorders that may present with prominent hyperkinetic movement disorders.

The Diagnostic Value of a Short Memory Test: The TNI-93.

BACKGROUND: The TNI-93 is a quick memory test designed for all patients regardless of their education level. A significant proportion of patients with Alzheimer's disease (AD) are illiterate or poorly educated, and only a few memory tests are adapted for these patients. OBJECTIVE: In this study we aimed at assessing the diagnostic value of the TNI-93 for diagnosis of patients with biologically confirmed amyloid status. METHODS: We included all patients who had an analysis of AD cerebrospinal fluid biomarkers, a neuropsychological assessment including a TNI-93 and an anatomical brain imaging at Avicenne Hospital between January 2009 and November 2019. We compared the TNI-93 scores in patients with amyloid abnormalities (A+) and patients without amyloid abnormalities (A-) according to the AT(N) diagnostic criteria. RESULTS: 108 patients were included (mean age: 66.9±8.5 years old, mean education level: 8.9±5.2 years). Patients from the A + group (N= 80) were significantly more impaired than patients from the A- group (N= 28) on immediate recall (A+: 5.9±2.8; A-: 7.4±2.6; p = 0.001), free recall (A+: 3.5±2.7; A-: 5.9±2.8; p ≤ 0.001), total recall (A+: 5.7±3.5; A-:7.8±2.8; p ≤ 0.001), and on number of intrusions during the recall phase (A+: 1±1.8; A-: 0.1±0.3; p = 0.002). ROC curves revealed that the best scores to discriminate A + from A- patients were immediate recall (Area under curve (AUC): 0.70), number of encoding trials (AUC: 0.73), free recall (AUC: 0.74), and total recall (AUC: 0.74). CONCLUSION: The TNI-93's immediate, free, and total recalls are valuable tools for the 39 diagnosis of AD.

A single-center series of 482 patients with functional motor disorders.

Functional motor disorders (FMD) are common and disabling. They are known to predominantly affect women and young to middle-aged patients, although they also occur during childhood or in the elderly. Demographic and clinical characteristics of patients with FMD are poorly known, since large series of consecutive patients are scarce. METHODS: In a chart review study, we retrospectively abstracted data from consecutive FMD patients who were referred to the Neurophysiology Department of the Salpêtrière University Hospital between 2008 and 2016 for treatment with repeated transcranial magnetic stimulation. RESULTS: 482 patients were included. Most patients were women (73.7%). Median age at symptoms onset was 35.5 years and symptoms were mostly characterized by acute (47.3%) or subacute (46%) onset. Only 23% of patients were active workers, while 58.3% were unemployed because of FMD. Half of the patients had functional motor weakness (n = 241) whereas the other half had movement disorders (n = 241), mainly with tremor (21.1%) or dystonia (20.5%). Among all patients, 66.4% had psychiatric comorbidity and 82.6% reported a history of trauma in the 6 months before symptoms onset. No difference was found in age or gender according to clinical phenotypes. CONCLUSION: This large series will contribute to better characterize FMDs.

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population.

Functional Motor Symptoms in Parkinson's Disease and Functional Parkinsonism: A Systematic Review.

OBJECTIVE: Whereas functional symptoms are common in Parkinson's disease (PD), a parkinsonian syndrome may occasionally reflect a pure functional disorder (also named functional parkinsonism [FP]). This review aimed to decipher these entities to clarify the link between functional manifestations and PD. METHODS: Following the PRISMA guidelines, the authors performed a systematic literature search of the PubMed and Science Direct databases for the period 1988 to December 2018 to identify studies of patients with either FP or PD associated with functional neurological symptoms. RESULTS: From the 844 articles screened, 22 were retained, including 12 studies of functional neurological symptoms in PD and 16 studies of FP. The studies of functional symptoms in PD included 121 patients-57% were women, and the mean age was 61.3 years. Psychiatric history (mostly depression) and exposure to triggering stressors were frequent: 60% and 82.5%, respectively. The most common symptom was tremor (33.8%), most often located on the side most affected by PD (50%). Studies of FP included a total of 120 patients-62% were women, and the mean age was 50.7 years. The first FP symptoms appeared on average 5 years before diagnosis, with an abrupt onset in half the cases; 67.6% had a psychiatric history, and 46.8% were exposed to triggering stressors, such as physical injury, stress at work, or loss of family or friends. CONCLUSIONS: Findings suggest a possible relationship between PD and FP. Clinicians should keep in mind the possibility of functional symptoms in PD patients.