Transient resting-state salience-limbic co-activation patterns in functional neurological disorders.

BACKGROUND: Functional neurological disorders were historically regarded as the manifestation of a dynamic brain lesion which might be linked to trauma or stress, although this association has not yet been directly tested yet. Analysing large-scale brain network dynamics at rest in relation to stress biomarkers assessed by salivary cortisol and amylase could provide new insights into the pathophysiology of functional neurological symptoms. METHODS: Case-control resting-state functional magnetic resonance imaging study of 79 patients with mixed functional neurological disorders (i.e., functional movement disorders, functional seizures, persistent perceptual-postural dizziness) and 74 age- and sex-matched healthy controls. Using a two-step hierarchical data-driven neuroimaging approach, static functional connectivity was first computed between 17 resting-state networks. Second, dynamic alterations in these networks were examined using co-activation pattern analysis. Using a partial least squares correlation analysis, the multivariate pattern of correlation between altered temporal characteristics and stress biomarkers as well as clinical scores were evaluated. RESULTS: Compared to healthy controls, patients presented with functional aberrancies of the salience-limbic network connectivity. Thus, the insula and amygdala were selected as seed-regions for the subsequent analyses. Insular co-(de)activation patterns related to the salience network, the somatomotor network and the default mode network were detected, which patients entered more frequently than controls. Moreover, an insular co-(de)activation pattern with subcortical regions together with a wide-spread co-(de)activation with diverse cortical networks was detected, which patients entered less frequently than controls. In patients, dynamic alterations conjointly correlated with amylase measures and duration of symptoms. CONCLUSION: The relationship between alterations in insular co-activation patterns, stress biomarkers and clinical data proposes inter-related mechanisms involved in stress regulation and functional (network) integration. In summary, altered functional brain network dynamics were identified in patients with functional neurological disorder supporting previously raised concepts of impaired attentional and interoceptive processing.

Structural and functional changes associated with functional/dissociative seizures: A review of the literature.

INTRODUCTION: The term 'functional/dissociative seizures (FDS)' refers to a paroxysmal, transient clinical manifestation that may include motor, sensory, vegetative, psychological and cognitive signs, similar to the manifestations observed in epileptic seizures. In recent years, there has been an increase of literature in the field of brain imaging research on functional neurological disorders and, more specifically, on FDS. However, most of the studies have been carried out on limited samples. We propose an update of this review work by performing a systematic review of studies performed since 2017 in the field of neuroimaging in patients with FDS. METHODS: We conducted a systematic review of the literature using the PRISMA methodology and reproduced most of the methodological elements of the latest systematic literature review. RESULTS: Our work over the last five years has identified 14 articles. It is still difficult to isolate a distinct structure or network specifically involved in the mechanism of FDS. However, certain structures are recurrently involved in imaging studies, notably the amygdala, the orbitofrontal cortex, and the anterior cingulate cortex. CONCLUSION: The contribution of neuroimaging may allow a more precise explanation of the disorder for patients, avoiding the stigma frequently associated with this diagnosis. as with other 'conversion' phenomena which have traditionally been considered only as 'medically unexplained'. In the longer term and beyond a better understanding of the physiopathology of the disorder, the challenge of this neuroimaging work would be to identify specific imaging biomarkers for a diagnosis of FDS.

Multi-centre classification of functional neurological disorders based on resting-state functional connectivity.

BACKGROUND: Patients suffering from functional neurological disorder (FND) experience disabling neurological symptoms not caused by an underlying classical neurological disease (such as stroke or multiple sclerosis). The diagnosis is made based on reliable positive clinical signs, but clinicians often require additional time- and cost consuming medical tests and examinations. Resting-state functional connectivity (RS FC) showed its potential as an imaging-based adjunctive biomarker to help distinguish patients from healthy controls and could represent a "rule-in" procedure to assist in the diagnostic process. However, the use of RS FC depends on its applicability in a multi-centre setting, which is particularly susceptible to inter-scanner variability. The aim of this study was to test the robustness of a classification approach based on RS FC in a multi-centre setting. METHODS: This study aimed to distinguish 86 FND patients from 86 healthy controls acquired in four different centres using a multivariate machine learning approach based on whole-brain resting-state functional connectivity. First, previously published results were replicated in each centre individually (intra-centre cross-validation) and its robustness across inter-scanner variability was assessed by pooling all the data (pooled cross-validation). Second, we evaluated the generalizability of the method by using data from each centre once as a test set, and the data from the remaining centres as a training set (inter-centre cross-validation). RESULTS: FND patients were successfully distinguished from healthy controls in the replication step (accuracy of 74%) as well as in each individual additional centre (accuracies of 73%, 71% and 70%). The pooled cross validation confirmed that the classifier was robust with an accuracy of 72%. The results survived post-hoc adjustment for anxiety, depression, psychotropic medication intake, and symptom severity. The most discriminant features involved the angular- and supramarginal gyri, sensorimotor cortex, cingular- and insular cortex, and hippocampal regions. The inter-centre validation step did not exceed chance level (accuracy below 50%). CONCLUSIONS: The results demonstrate the applicability of RS FC to correctly distinguish FND patients from healthy controls in different centres and its robustness against inter-scanner variability. In order to generalize its use across different centres and aim for clinical application, future studies should work towards optimization of acquisition parameters and include neurological and psychiatric control groups presenting with similar symptoms.

Understanding conversion disorder: How contemporary brain imaging is shedding light on an early Freudian concept.

Conversion disorder, also called Functional Neurological Symptom Disorder is poorly understood by many in the medical profession and is associated with considerable health care costs. Sigmund Freud, in an early, pre-psychoanalytic period paper, suggested that hysterical motor paralyses arose from a "functional or dynamic lesion" which was no different from an organic one, but rather an altered expression of it. He linked this functional brain disturbance to an excess of affect, a faulty conceptualization on the part of the symptomatic individual of how the affected organ works, and elements of dissociation and dual consciousness. One hundred and thirty years later converging functional imaging studies provide support for the excess affect component of his hypothesis. A small but growing fMRI literature has revealed bottom-up hyperactive neural activity in limbic regions and a potential failure of top-down regulation from prefrontal regions. Aberrant functional connectivity of limbic-motor regions now provides a mechanistic model that sheds light on an early Freudian theory explaining, in part, how symptoms of Conversion Disorder arise.

Neuroradiologic Features Associated With Severe Restriction of Functional Mobility in Children With Cerebral Palsy in North India.

BACKGROUND: Few studies have focused on magnetic resonance imaging (MRI) brain findings associated with functional mobility in cerebral palsy. OBJECTIVE: To determine association between MRI findings and Gross Motor Functional Classification System (GMFCS) levels in cerebral palsy. METHODS: Prospective-observational study conducted in Pediatric Neurology Clinic at a public teaching hospital, Northern India. First 3 new cases of cerebral palsy were enrolled on particular neuro-clinic day per week for 1 year. Functional mobility was classified according to GMFCS. Association between MRI findings, cerebral palsy type, and GMFCS levels were evaluated using χ2 test. RESULTS: A total of 138 cases (mean age 2.71 [SD = 1.91] years; male [64.5%]) were enrolled. Reported types of cerebral palsy were as follows: spastic quadriplegia (47.8%), spastic diplegia (28.35%), spastic hemiplegia (11.6%), extrapyramidal (6.5%), and ataxic/hypotonic (5.8%). GMFCS were classified into level 1 (13%), level 2 (7.2%), level 3 (4.3%), level 4 (10.9%), and level 5 (64.5%). Spastic quadriplegia and extrapyramidal cerebral palsy were significantly associated with higher (severe) levels (IV and V), whereas spastic diplegia and hemiplegia were significantly associated with lower (mild) levels (I-III) of GMFCS. MRI features of periventricular white matter injury, deep gray matter injury, basal ganglia and thalamic changes, and superficial gray matter injury were significantly associated with severe levels of GMFCS (V and IV). MRI was normal in 8 children (5 = mild category, 3 = severe category). CONCLUSION: Severe cerebral palsy is most often associated with spastic quadriplegia, extrapyramidal cerebral palsy, superficial gray matter lesions, deep gray matter lesions, and periventricular white matter injury. This information is useful for anticipating and addressing the needs of children with cerebral palsy and for prognostication.

The neuroimaging evidence of brain abnormalities in functional movement disorders.

Neuroimaging has been pivotal in identifying and reframing our understanding of functional movement disorders. If accessible, it compensates for the limitations of the clinical exam and is especially useful where there is overlap of functional symptoms with classical presentations of disease. Imaging in functional movement disorders has increasingly identified structural and functional abnormalities that implicate hypoactivation of the cortical and subcortical motor pathways and increased modulation by the limbic system. Neurobiological theories suggest an impaired sense of agency, faulty top-down regulation of motor movement and abnormal emotional processing in these individuals. This framework challenges our traditional understanding of functional movement disorders as distinct from the deceptive term of 'organic' diseases and proposes that these conditions are not considered as mutually exclusive. This update summarizes the literature to date and explores the role of imaging in the diagnosis of functional movement disorders and in detecting its underlying molecular network.

Relationship between neural responses to stress and mental health symptoms in psychogenic nonepileptic seizures after traumatic brain injury.

OBJECTIVE: To utilize traumatic brain injury (TBI) as a model for investigating functioning during acute stress experiences in psychogenic nonepileptic seizures (PNES) and to identify neural mechanisms underlying the link between changes in processing of stressful experiences and mental health symptoms in PNES. METHODS: We recruited 94 participants: 50 with TBI only (TBI-only) and 44 with TBI and PNES (TBI + PNES). Participants completed mood (Beck Depression Inventory-II), anxiety (Beck Anxiety Inventory), and posttraumatic stress disorder (PTSD) symptom (PTSD Checklist-Specific Event) assessments before undergoing functional magnetic resonance imaging during an acute psychosocial stress task. Linear mixed-effects analyses identified clusters of significant interactions between group and neural responses to stressful math performance and stressful auditory feedback conditions within limbic brain regions (volume-corrected α = .05). Spearman rank correlation tests compared mean cluster signals to symptom assessments (false discovery rate-corrected α = .05). RESULTS: Demographic and TBI-related measures were similar between groups; TBI + PNES demonstrated worse clinical symptom severity compared to TBI-only. Stressful math performance induced relatively greater reactivity within dorsomedial prefrontal cortex (PFC) and right hippocampal regions and relatively reduced reactivity within left hippocampal and dorsolateral PFC regions for TBI + PNES compared to TBI-only. Stressful auditory feedback induced relatively reduced reactivity within ventral PFC, cingulate, hippocampal, and amygdala regions for TBI + PNES compared to TBI-only. Changes in responses to stressful math within hippocampal and dorsal PFC regions were correlated with increased mood, anxiety, and PTSD symptom severity. SIGNIFICANCE: Corticolimbic functions underlying processing of stressful experiences differ between patients with TBI + PNES and those with TBI-only. Relationships between these neural responses and symptom assessments suggest potential pathophysiologic mechanisms in PNES.

Shared demographics and comorbidities in different functional motor disorders.

INTRODUCTION: Functional motor disorders are often delineated according to the dominant motor symptom. In a large cohort, we aimed to find if there were differences in demographics, mode of onset, pain, fatigue, depression and anxiety and levels of physical functioning, quality of life and social adjustment between patients with different dominant motor symptoms. METHODS: Baseline data from the Self-Help and Education on the Internet for Functional Motor Disorders Trial was used. Patients were divided into dominant motor symptom groups based on the diagnosis of the referring neurologist. Data on the above topics were collected by means of an online questionnaire and compared between groups using parametric and nonparametric statistics. RESULTS: In 160 patients a dominant motor symptom could be determined, 31 had tremor, 45 myoclonus, 23 dystonia, 30 paresis, 31 gait disorder. No statistical differences between groups were detected for demographics, mode of onset and severity of pain, fatigue, depression and anxiety. Physical functioning was worse in the gait disorder group (median 20, IQR 25) compared to tremor (50 (55), p = 0.002) and myoclonus (50 (52), p = 0.001). Work and social adjustment was less impaired in the myoclonus group (median 20, IQR 18) compared to gait disorder (median 30, IQR18, p < 0.001) and paresis (28, IQR 10, p = 0.001). Self-report showed large overlap in motor symptoms. CONCLUSION: No differences were detected between groups of functional motor symptoms, regarding demographics, mode of onset, depression, anxiety, pain and fatigue. The large overlap in symptoms contributes to the hypothesis of shared underlying mechanisms of functional motor disorders.

Modification of both functional neurological symptoms and neuroimaging patterns with a good anatomoclinical concordance: a case report.

BACKGROUND: In the nineteenth century, Jean Martin Charcot explained functional neurological disorder (formerly called conversion disorder) as a "psychodynamic" lesion. Numerous advances in neuroimaging have permitted identification of the neural underpinnings of this disorder. CASE PRESENTATION: Herein we describe a case of functional neurological disorder (FND) with initial left sensorimotor deficit, in-coordinated limb movements, neglect, clouded consciousness, slurred speech and a semiology of visual impairment. A single photon emission computed tomography (SPECT) showed a right thalamic hypoperfusion, which is rather concordant with the initial semiology. Later, the semiology changed, presenting with a predominantly neurovisual complex presentation. The second SPECT showed no more thalamic abnormalities but an hypoperfusion in the right temporo-occipital junction, right inferior parietal lobe and left superior frontal lobe, which is also rather concordant with the changing semiology. CONCLUSIONS: This case illustrates the evolving neuroimaging patterns of FND but also the concordance between semiology and neuroimaging findings in FND supporting Charcot's theory of "dynamic lesion".

The role of the anterior and midcingulate cortex in the neurobiology of functional neurologic disorder.

Functional neurologic disorder (FND)/conversion disorder is a prevalent and disabling condition at the intersection of neurology and psychiatry. Clinicians often report feeling ill-equipped treating patients with FND, perpetuated by a historically limited understanding of neurobiologic disease mechanisms. In this review, we summarize the neuroimaging literature across the spectrum of sensorimotor FND, including functional imaging studies during rest, sensorimotor performance, and emotional-processing tasks as well as structural magnetic resonance imaging findings. Particular attention is given to studies implicating the anterior and middle cingulate cortex and related salience network structures (insula, amygdala, and periaqueductal gray) in the neurobiology of FND. Neuroimaging studies identify cingulo-insular functional alterations during rest, motor performance, and emotion processing in FND populations. The literature also supports that patients with FND exhibit heightened amygdalar and periaqueductal gray reactivity to emotionally valenced stimuli, enhanced coupling between amygdalar and motor control areas, and increased amygdalar volumes. The structural neuroimaging literature also implicates cingulo-insular areas in the pathophysiology of FND, though these findings require replication and clarification. While more research is needed to fully elucidate the pathophysiology of FND, salience network alterations appear present in some FND populations and can be contextualized using biopsychosocial models for FND.

Clinical and neural responses to cognitive behavioral therapy for functional tremor.

OBJECTIVES: To evaluate changes in tremor severity and motor/emotion-processing circuits in response to cognitive behavioral therapy (CBT) delivered as treatment for functional tremor (FT), the most common functional movement disorder in adults. METHODS: Fifteen patients with FT underwent fMRI with motor, basic-emotion, and intense-emotion tasks before and after 12 weeks of CBT. Baseline fMRI was compared to those of 25 healthy controls (HCs). The main clinical endpoint was the tremor score (sum of severity, duration, and incapacitation subscores) adapted from the Rating Scale for Psychogenic Movement Disorders (PMDRS) assessed by a blinded clinician. CBT responders were defined as those with PMDRS score reduction >75%. Anatomic and functional brain images were obtained with a 4T MRI system. Generalized linear model and region-of-interest analyses were used to evaluate before-versus-after treatment-related changes in brain activation. RESULTS: CBT markedly reduced tremor severity (p < 0.01) with remission/near remission achieved in 73.3% of the cohort. Compared to HCs, in those with FT, a functionally defined fMRI region of interest in the anterior cingulate/paracingulate cortex showed increased activation at baseline and decreased activation after CBT during basic-emotion processing (p = 0.012 for CBT responders). Among CBT responders, the change in anterior cingulate/paracingulate was more significant in those with more severe baseline depression (r = 0.75, p < 0.01). CONCLUSIONS: Tremor severity improved significantly after CBT. The improvement was associated with changes in the anterior cingulate/paracingulate activity, which may represent a marker of emotional dysregulation in FT and a predictor of treatment response. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CBT significantly improves tremor severity in patients with functional tremor.

Structural alterations in functional neurological disorder and related conditions: a software and hardware problem?

Functional neurological (conversion) disorder (FND) is a condition at the interface of neurology and psychiatry. A "software" vs. "hardware" analogy describes abnormal neurobiological mechanisms occurring in the context of intact macroscopic brain structure. While useful for explanatory and treatment models, this framework may require more nuanced considerations in the context of quantitative structural neuroimaging findings in FND. Moreover, high co-occurrence of FND and somatic symptom disorders (SSD) as defined in DSM-IV (somatization disorder, somatoform pain disorder, and undifferentiated somatoform disorder; referred to as SSD for brevity in this article) raises the possibility of a partially overlapping pathophysiology. In this systematic review, we use a transdiagnostic approach to review and appraise the structural neuroimaging literature in FND and SSD. While larger sample size studies are needed for definitive characterization, this article highlights that individuals with FND and SSD may exhibit sensorimotor, prefrontal, striatal-thalamic, paralimbic, and limbic structural alterations. The structural neuroimaging literature is contextualized within the neurobiology of stress-related neuroplasticity, gender differences, psychiatric comorbidities, and the greater spectrum of functional somatic disorders. Future directions that could accelerate the characterization of the pathophysiology of FND and DSM-5 SSD are outlined, including "disease staging" discussions to contextualize subgroups with or without structural changes. Emerging neuroimaging evidence suggests that some individuals with FND and SSD may have a "software" and "hardware" problem, although if structural alterations are present the neural mechanisms of functional disorders remain distinct from lesional neurological conditions. Furthermore, it remains unclear whether structural alterations relate to predisposing vulnerabilities or consequences of the disorder.

Functional Neurologic Symptom Disorder in Children: Clinical Features, Diagnostic Investigations, and Outcomes at a Tertiary Care Children's Hospital.

OBJECTIVE: To describe the presenting symptoms and short-term outcomes of children diagnosed with functional neurologic symptom disorder and to compare the demographic and clinical characteristics of children who received neurodiagnostic testing to those who did not. STUDY DESIGN: Single center, retrospective review of 222 children who presented to the emergency department of a children's hospital, and diagnosed with functional neurologic symptom disorder, between 2010 and 2015. RESULTS: Out of 222 visits (females = 156, African Americans = 130, mean age = 13.9 years), neurodiagnostic tests were performed in 102/222 (46%) visits. The most commonly performed investigations were magnetic resonance imaging (MRI) of brain (n = 37) and electroencephalogram (EEG) (n = 56) and were noted to be unremarkable in all instances. Neurodiagnostic tests were more likely to be performed in patients who (1) were non-African American (54% vs 40%; P = .03), (2) presented with new-onset symptoms (55% vs 31%; P < .01), (3) underwent hospitalization (61% vs 17%; P < .01), and (4) were evaluated by a neurologist (59% vs 9%; P < .01) or a psychiatrist (58% vs 28%; P < .01). Common clinical presentations included seizurelike or strokelike symptoms. Short-term follow-up was possible in 20%, with an alternate diagnosis of syncope, noted in only 1 child. CONCLUSIONS: Most children who presented with a functional neurologic symptom disorder in our study were noted to have seizurelike or strokelike presentations and were adolescent females. Caucasians were more likely to undergo neurodiagnostic investigations. Radiologic and neurophysiological tests were more commonly performed when neurology and psychiatry consultations were sought. Such investigations had low diagnostic utility.

Corticolimbic fast-tracking: enhanced multimodal integration in functional neurological disorder.

OBJECTIVE: Some individuals with functional neurological disorder (FND) exhibit motor and affective disturbances, along with limbic hyper-reactivity and enhanced motor-limbic connectivity. Given that the multimodal integration network (insula, dorsal cingulate, temporoparietal junction (TPJ)) is implicated in convergent sensorimotor, affective and interoceptive processing, we hypothesised that patients with FND would exhibit altered motor and amygdalar resting-state propagation to this network. Patient-reported symptom severity and clinical outcome were also hypothesised to map onto multimodal integration areas. METHODS: Between-group differences in primary motor and amygdalar nuclei (laterobasal, centromedial) were examined using graph-theory stepwise functional connectivity (SFC) in 30 patients with motor FND compared with 30 healthy controls. Within-group analyses correlated functional propagation profiles with symptom severity and prospectively collected 6-month outcomes as measured by the Screening for Somatoform Symptoms Conversion Disorder subscale and Patient Health Questionnaire-15 composite score. Findings were clusterwise corrected for multiple comparisons. RESULTS: Compared with controls, patients with FND exhibited increased SFC from motor regions to the bilateral posterior insula, TPJ, middle cingulate cortex and putamen. From the right laterobasal amygdala, the FND cohort showed enhanced connectivity to the left anterior insula, periaqueductal grey and hypothalamus among other areas. In within-group analyses, symptom severity correlated with enhanced SFC from the left anterior insula to the right anterior insula and TPJ; increased SFC from the left centromedial amygdala to the right anterior insula correlated with clinical improvement. Within-group associations held controlling for depression, anxiety and antidepressant use. CONCLUSIONS: These neuroimaging findings suggest potential candidate neurocircuit pathways in the pathophysiology of FND.

Functional neuroimaging of recovery from motor conversion disorder: A case report.

A patient with motor conversion disorder presented with a functional paresis of the left hand. After exclusion of structural brain damage, she was repeatedly examined with whole-brain functional magnetic resonance imaging, while she performed visually paced finger-tapping tasks. The dorsal premotor cortex showed a bilateral deactivation in the acute-subacute phase. Recovery from unilateral hand paresis was associated with a gradual increase in task-based activation of the dorsal premotor cortex bilaterally. The right medial prefrontal cortex displayed the opposite pattern, showing initial task-based activation that gradually diminished with recovery. The inverse dynamics of premotor and medial prefrontal activity over time were found during unimanual finger-tapping with the affected and non-affected hand as well as during bimanual finger-tapping. These observations suggest that reduced premotor and increased medial prefrontal activity reflect an effector-independent cortical dysfunction in conversion paresis which gradually disappears in parallel with clinical remission of paresis. The results link the medial prefrontal and dorsal premotor areas to the generation of intentional actions. We hypothesise that an excessive 'veto' signal generated in medial prefrontal cortex along with decreased premotor activity might constitute the functional substrate of conversion disorder. This notion warrants further examination in a larger group of affected patients.

Cerebellar activation during a motor task in conversion disorder with motor paralysis: A case report and fMRI study.

BACKGROUND: Motor conversion disorders are characterized by movement symptoms without a neurological cause. A psychogenic etiology is presumed for these disorders, but little is known about their underlying neural mechanisms. Functional magnetic resonance imaging (fMRI) has been utilized to understand the mechanisms associated with unexplained motor symptoms. Here, we used fMRI to investigate the cerebral response to motor stimulation in a patient with conversion disorder with motor paralysis to determine the underlying neural mechanisms of this disorder. METHODS: Brain activation induced by movements of the bilateral ankle joints (repeated plantar flexion and dorsiflexion) was recorded using fMRI in a patient with conversion disorder with unexplained motor paralysis. We acquired 2 types of imaging data: (i) data obtained while motor paralysis remained present and (ii) data obtained after motor paralysis had completely improved. We used a within-subject fMRI block design to compare the patient's brain activities during the motor task and at rest. RESULTS: Cerebral motor areas were significantly activated during the motor task relative to at rest, both when motor paralysis remained present and when paralysis had improved (FWE-corrected P < .05), although there was greater activation in motor areas when motor paralysis had improved than when motor paralysis remained. Notably, activation in the cerebellum posterior lobe during the motor task when motor paralysis remained (FWE-corrected P < .05) disappeared after motor paralysis had completely improved. CONCLUSIONS: The cerebellum is a region that is closely associated with voluntary motion. We suggest that complementary abnormal function in the cerebellum might be associated with the neural basis of conversion disorder with motor paralysis.

Metacognition of visuomotor decisions in conversion disorder.

Motor conversion disorder (CD) entails genuine disturbances in the subjective experience of patients who maintain they are unable to perform a motor function, despite lack of apparent neurological damage. Abilities by which individuals assess their own capacities during performance in a task are called metacognitive, and distinctive impairment of such abilities is observed in several disorders of self-awareness such as blindsight and anosognosia. In CD, previous research has focused on the recruitment of motor and emotional brain systems, generally linking symptoms to altered limbic-motor interactions; however, metacognitive function has not been studied to our knowledge. Here we tested ten CD patients and ten age-gender matched controls during a visually-guided motor paradigm, previously employed in healthy controls (HC), allowing us to probe for motor awareness and metacognition. Participants had to draw straight trajectories towards a visual target while, unbeknownst to them, deviations were occasionally introduced in the reaching trajectory seen on the screen. Participants then reported both awareness of deviations and confidence in their response. Activity in premotor and cingulate cortex distinguished between conscious and unconscious movement corrections in controls better than patients. Critically, whereas controls engaged the left superior precuneus and middle temporal region during confidence judgments, CD patients recruited bilateral parahippocampal and amygdalo-hippocampal regions instead. These results reveal that distinct brain regions subserve metacognitive monitoring for HC and CD, pointing to different mechanisms and sources of information used to monitor and form confidence judgments of motor performance. While brain systems involved in sensory-motor integration and vision are more engaged in controls, CD patients may preferentially rely on memory and contextual associative processing, possibly accounting for how affect and memories can imbue current motor experience in these patients.

Self-reference, emotion inhibition and somatosensory disturbance: preliminary investigation of network perturbations in conversion disorder.

BACKGROUND AND PURPOSE: Conversion disorder (CD), or functional neurological disorder, is manifested as a neurological disturbance that is not macroscopically visible on clinical structural neuroimaging and is instead ascribed to underlying psychological stress. Known for many years in neuropsychiatry, a comprehensive explanation of the way in which psychological stress leads to a neurological deficit of a structural-like origin is still lacking. METHODS: We applied whole-brain network-based data-driven analyses on resting-state functional magnetic resonance imaging, recorded in seven patients with acute-onset, stroke-like CD with unilateral paresis and hypoesthesia as compared with 15 age-matched healthy controls. We used a clustering analysis to measure functional connectivity (FC) strength within 10 different brain networks, as well as between these networks. Finally, we tested FC of specific brain regions that are known to be involved in CD. RESULTS: We found a significant increase in FC strength only within the default-mode network (DMN), which manages self-referential processing. Examination of inter-connectivity between networks showed a structure of disturbed connectivity, which included decreased connectivity between the DMN and limbic/salience network, increased connectivity between the limbic/salience network and body-related temporo-parieto-occipital junction network, decreased connectivity between the temporo-parieto-occipital junction and memory-related medial temporal lobe, and decreased connectivity between the medial temporal lobe and sensorimotor network. Region-specific FC analysis showed increased connectivity between the hippocampus and DMN. DISCUSSION: These preliminary results of disturbances in brain networks related to memory, emotions and self-referential processing, and networks involved in motor planning and execution, suggest a role of these cognitive functions in the psychopathology of CD.

Conversion, Factitious Disorder and Malingering: A Distinct Pattern or a Continuum?

This chapter is aimed at highlighting the recent findings concerning physiopathology, diagnosis, and management of conversion, factitious disorder, and malingering. Conversion disorder is the unintentional production of neurological symptom, whereas malingering and factitious disorder represent the voluntary production of symptoms with internal or external incentives. They have a close history and this has been frequently confounded. Practitioners are often confronted to medically unexplained symptoms; they represent almost 30% of neurologist's consultation. The first challenge is to detect them, and recent studies have confirmed the importance of "positive" clinical bedside signs based on incoherence and discordance, such as the Hoover's sign for the diagnosis of conversion disorder. Functional neuroimaging has allowed a better understanding of the pathophysiology, and highlighted abnormal cerebral activation patterns in conversion disorder in relation to motor, emotional, and limbic networks, different from feigners. This supports the theory evoked by Charcot of a "psychodynamic lesion," which is also reflected by the new term introduced in the DSM-5: functional neurological disorder. Multidisciplinary therapy is recommended with behavioral cognitive therapy, antidepressant to treat frequent comorbid anxiety or depression, and physiotherapy. Factitious disorder and malingering should be clearly delineated from conversion disorder. Factitious disorder should be considered as a mental illness and more research on its physiopathology and treatment is needed, when malingering is a non-medical condition encountered in medico-legal cases.