Anterior hippocampal grey matter predicts mental health outcome in functional neurological disorders: an exploratory pilot study

Perez, David L.; Williams, Benjamin; Matin, Nassim; Mello, Julie; Dickerson, Bradford C.; LaFrance, W. Curt; Keshavan, Matcheri S.

doi:10.1136/jnnp-2017-317305

Cited by 13 publications

(19 citation statements)

References 7 publications

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“…This prospective study assessed the hypothesis that PNES in patients with TBI can be conceptualized as a brain network disorder in which mental health symptom expression varies according to alterations in specific motor and limbic regional PNES networks. 7 This hypothesis was formulated based on prior literature demonstrating that changes in structure and function of motor and limbic regions are associated with symptom expression in PNES [8][9][10][11]21 and that PNES are associated with decreased WM integrity within neural projections that connect these brain regions. [13][14][15] To this end, FNSDs including PNES have been conceptualized as a network brain disorder, rather than a focal deficit, in which patient profiles vary, depending on how limbic and motor regions that comprise the specific FNSD network are altered.…”

Section: Discussionmentioning

confidence: 99%

“…Scales were selected based on prior literature on FNSDs demonstrating sensitivity to greater symptom severity compared to healthy controls, as well as relationships between limbic and motor brain regions structure and/or function. 3,[8][9][10][11]21,27 Independent samples t-tests were used to compare TBI and TBI + PNES groups for depressive (Beck Depression Inventory-II, BDI-II), 28 anxious (Beck Anxiety Inventory, BAI), 29 posttraumatic stress (PTSD Checklist-Specific version, PCL-S), 30 psychoticism (Symptom Checklist-90, SCL-90 PSY), somatization (SCL-90 SOM) 31 symptoms, and symptom severity (Global Assessment of Functioning). 32 Corrected degrees of freedom were used for any comparison that violated assumptions for homogeneity of variance between groups.…”

Section: Psychiatric and Behavioral Assessmentsmentioning

confidence: 99%

“…Specifically, based on prior literature, we hypothesized there would be group differences within the uncinate fasciculus (UF; prefrontal cortex-hippocampus-amygdala), fornix/stria terminalis (FST; hippocampus-amygdala-hypothalamus), cingulum (cingulate cortex-dorsal/ventral prefrontal cortex), and corticospinal tract (pre/post central gyrus-spinal cord). 6,[8][9][10][11][21][22][23] In order to further reduce the likelihood of type-I error, volume extent thresholds (mm 3 ) were calculated using AFNI's 3dClustSim based on an algorithm that uses randomization/ permutation simulation to produce 10 000 iterations of noise only generated t-tests and to determine the global cluster-level threshold values for each of the five separate diffusion measures. Only clusters identified by 3dLMEs exceeding 443 mm 3 for FA, 460 mm 3 for MD, 437 mm 3 for ODI, 548 mm 3 for ICVF, and 612 mm 3 for V-ISO were considered statistically significant (uncorrected P < 0.01, cluster threshold a = 0.05).…”

Section: Mri Parameters and Analysismentioning

confidence: 99%

“…Based on prior literature, we hypothesized that increased depressive, anxious, posttraumatic and psychoticism symptoms of PNES would correspond to group differences within the uncinate fasciculus, fornix/stria terminalis, cingulum, whereas increased somatization symptoms would correspond to group differences within the corticospinal tract. 6,[8][9][10][11][21][22][23][24]…”

Section: Introductionmentioning

confidence: 99%

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White matter and neurite morphology differ in psychogenic nonepileptic seizures

Goodman

Allendorfer

Blum

et al. 2020

Ann Clin Transl Neurol

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Objective: To further evaluate the relationship between the clinical profiles and limbic and motor brain regions and their connecting pathways in psychogenic nonepileptic seizures (PNES). Neurite Orientation Dispersion and Density Indices (NODDI) multicompartment modeling was used to test the relationships between tissue alterations in patients with traumatic brain injury (TBI) and multiple psychiatric symptoms. Methods: The sample included participants with prior TBI (TBI; N = 37) but no PNES, and with TBI and PNES (TBI + PNES; N = 34). Participants completed 3T Siemens Prisma MRI high angular resolution imaging diffusion protocol. Statistical maps, including fractional anisotropy (FA), mean diffusivity (MD), neurite dispersion [orientation dispersion index (ODI)] and density [intracellular volume fraction (ICVF), and free water (i.e., isotropic) volume fraction (V-ISO)] signal intensity, were generated for each participant. Linear mixed-effects models identified clusters of between-group differences in indices of white matter changes. Pearson's r correlation tests assessed any relationship between signal intensity and psychiatric symptoms. Results: Compared to TBI, TBI + PNES revealed decreases in FA, ICVF, and V-ISO and increases in MD for clusters within cingulum bundle, uncinate fasciculus, fornix/stria terminalis, and corticospinal tract pathways (cluster threshold a = 0.05). Indices of white matter changes for these clusters correlated with depressive, anxiety, PTSD, psychoticism, and somatization symptom severity (FDR threshold a = 0.05). A follow-up within-group analysis revealed that these correlations failed to reach the criteria for significance in the TBI + PNES group alone. Interpretation: The results expand support for the hypothesis that alterations in pathways comprising the specific PNES network correspond to patient profiles. These findings implicate myelin-specific changes as possible contributors to PNES, thus introducing novel potential treatment targets.

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Section: Discussionmentioning

confidence: 99%

Section: Psychiatric and Behavioral Assessmentsmentioning

confidence: 99%

Section: Mri Parameters and Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

White matter and neurite morphology differ in psychogenic nonepileptic seizures

Goodman

Allendorfer

Blum

et al. 2020

Ann Clin Transl Neurol

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“…Prior to enrolment, patients were diagnosed with FND and the term 'Functional Neurological Disorder' was communicated along with the pertinent motor subtype. 36 FND was presented as common, real and treatable. Patients were introduced to the www.…”

Section: Participants and Questionnairesmentioning

confidence: 99%

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

Diez

Ortiz-Terán

Williams

et al. 2019

J Neurol Neurosurg Psychiatry

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ObjectiveSome 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.MethodsBetween-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.ResultsCompared 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.ConclusionsThese neuroimaging findings suggest potential candidate neurocircuit pathways in the pathophysiology of FND.

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

2019

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Functional neurological disorder (FND) / conversion disorder is a prevalent and disabling condition at the intersection of neurology and psychiatry. Clinicians often report feeling illequipped treating patients with FND, perpetuated by a historically limited understanding of neurobiological disease mechanisms. In this review, we summarize the neuroimaging literature across the spectrum of sensorimotor FND, including functional imaging studies during rest, sensorimotor, and emotional processing tasks as well as structural magnetic resonance imaging findings. 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 affectively valenced stimuli, enhanced coupling between amygdalar and motor control areas, and increased amygdalar volumes. The early-phase structural neuroimaging literature 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.

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Anterior hippocampal grey matter predicts mental health outcome in functional neurological disorders: an exploratory pilot study

Cited by 13 publications

References 7 publications

White matter and neurite morphology differ in psychogenic nonepileptic seizures

White matter and neurite morphology differ in psychogenic nonepileptic seizures

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

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

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