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

ABSTRACT: 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.

SUBMITTER: Diez I

PROVIDER: S-EPMC6625895 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Diez Ibai I Ortiz-Terán Laura L Williams Benjamin B Jalilianhasanpour Rozita R Ospina Juan Pablo JP Dickerson Bradford C BC Keshavan Matcheri S MS LaFrance W Curt WC Sepulcre Jorge J Perez David L DL

Journal of neurology, neurosurgery, and psychiatry 20190308 8

<h4>Objective</h4>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 ne ...[more]

PMID: 30850473

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Project description:BACKGROUND:Insecure attachment and maladaptive coping are important predisposing vulnerabilities for Functional Neurological Disorders (FND)/Conversion Disorder, yet no prior structural neuroimaging studies have investigated biomarkers associated with these risk factors in FND populations. This magnetic resonance imaging study examined cortical thickness and subcortical volumes associated with self-reported attachment and coping styles in patients with FND. We hypothesized that insecure attachment and maladaptive coping would relate to limbic-paralimbic structural alterations. METHODS:FreeSurfer cortical thickness and subcortical volumetric analyses were performed in 26 patients with motor FND (21 women; 5 men) and 27 healthy controls (22 women; 5 men). For between-group comparisons, patients with FND were stratified by Relationship Scales Questionnaire, Ways of Coping Scale-Revised, and Connor-Davidson Resilience Scale scores. Within-group analyses were also performed in patients with FND. All analyses were performed in the complete cohort and separately in women only to evaluate for gender-specific effects. Cortical thickness analyses were whole-brain corrected at the cluster-wise level; subcortical analyses were Bonferroni corrected. RESULTS:In women with FND, dismissing attachment correlated with reduced left parahippocampal cortical thickness. Confrontive coping was associated with reduced right hippocampal volume, while accepting responsibility positively correlated with right precentral gyrus cortical thickness. These findings held adjusting for anti-depressant use. All FND-related findings were within the normal range when compared to healthy women. CONCLUSION:These observations connect individual-differences in limbic-paralimbic and premotor structures to attachment and coping styles in FND. The relationship between parahippocampal thickness and dismissing attachment may indicate aberrant social-emotional and contextual appraisal in women with FND.

Project description:With the creation of the Somatic Symptom and Related Disorders category of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition in 2013, the functional neurological (symptom) disorder diagnostic criteria underwent transformative changes. These included an emphasis on 'rule-in' physical examination signs/semiological features guiding diagnosis and the removal of a required proximal psychological stressor to be linked to symptoms. In addition, the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition somatization disorder, somatoform pain disorder and undifferentiated somatoform disorder conditions were eliminated and collapsed into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition somatic symptom disorder diagnosis. With somatic symptom disorder, emphasis was placed on a cognitive-behavioural (psychological) formulation as the basis for diagnosis in individuals reporting distressing bodily symptoms such as pain and/or fatigue; the need for bodily symptoms to be 'medically unexplained' was removed, and the overall utility of this diagnostic criteria remains debated. A consequence of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition restructuring is that the diagnosis of somatization disorder that encompassed individuals with functional neurological (sensorimotor) symptoms and prominent other bodily symptoms, including pain, was eliminated. This change negatively impacts clinical and research efforts because many patients with functional neurological disorder experience pain, supporting that the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition would benefit from an integrated diagnosis at this intersection. We seek to revisit this with modifications, particularly since pain (and a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition somatization disorder comorbidity, more specifically) is associated with poor clinical prognosis in functional neurological disorder. As a first step, we systematically reviewed the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition somatization disorder literature to detail epidemiologic, healthcare utilization, demographic, diagnostic, medical and psychiatric comorbidity, psychosocial, neurobiological and treatment data. Thereafter, we propose a preliminary revision to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition allowing for the specifier functional neurological disorder 'with prominent pain'. To meet this criterion, core functional neurological symptoms (e.g. limb weakness, gait difficulties, seizures, non-dermatomal sensory loss and/or blindness) would have 'rule-in' signs and pain (>6 months) impairing social and/or occupational functioning would also be present. Two optional secondary specifiers assist in characterizing individuals with cognitive-behavioural (psychological) features recognized to amplify or perpetuate pain and documenting if there is a pain-related comorbidity. The specifier of 'with prominent pain' is etiologically neutral, while secondary specifiers provide additional clarification. We advocate for a similar approach to contextualize fatigue and mixed somatic symptoms in functional neurological disorder. While this preliminary proposal requires prospective data and additional discussion, these revisions offer the potential benefit to readily identify important functional neurological disorder subgroups-resulting in diagnostic, treatment and pathophysiology implications.

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

Publications

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

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