Magnetic resonance imaging histogram analysis of corpus callosum in a functional neurological disorder

Background/aim: The aim of the present study was to examine and compare the corpus callosum (CC) via histogram analysis (HA) on T1-weighted MR images of patients diagnosed with Functional Neurological Disorder (FND) and healthy controls. Materials and methods: The study group included 19 female patients diagnosed with FND, and the control group included 20 healthy subjects. All participants were scanned with a 1.5 T MR scanner. A high-resolution structural image of the entire brain was obtained with sagittal 3D spiral fast spin echo T1-weighted images. Gray level intensity, standard deviation of the histogram, entropy, uniformity, skewness, and kurtosis values were determined with texture analysis. A student's t-test was used to compare the group data. P < 0.05 was accepted as statistically significant. Results: It was determined that the mean gray level intensity, standard deviation of the histogram, entropy calculated by the maximum, median and variance and size M percentage values were higher in patients with FND. Kurtosis and size U percentages values were lower in patients with FND. Conclusion: In the present study, analysis of CC with T1-weighted MR image HA demonstrated significant differences between FND patients and healthy controls. The study findings indicated that HA is a beneficial technique for demonstrating textural variations between the CCs of patients with FND and healthy controls using MR images.

Breakdown of the affective-cognitive network in functional dystonia.

Previous studies suggested that brain regions subtending affective-cognitive processes can be implicated in the pathophysiology of functional dystonia (FD). In this study, the role of the affective-cognitive network was explored in two phenotypes of FD: fixed (FixFD) and mobile dystonia (MobFD). We hypothesized that each of these phenotypes would show peculiar functional connectivity (FC) alterations in line with their divergent disease clinical expressions. Resting state fMRI (RS-fMRI) was obtained in 40 FD patients (12 FixFD; 28 MobFD) and 43 controls (14 young FixFD-age-matched [yHC]; 29 old MobFD-age-matched [oHC]). FC of brain regions of interest, known to be involved in affective-cognitive processes, and independent component analysis of RS-fMRI data to explore brain networks were employed. Compared to HC, all FD patients showed reduced FC between the majority of affective-cognitive seeds of interest and the fronto-subcortical and limbic circuits; enhanced FC between the right affective-cognitive part of the cerebellum and the bilateral associative parietal cortex; enhanced FC of the bilateral amygdala with the subcortical and posterior cortical brain regions; and altered FC between the left medial dorsal nucleus and the sensorimotor and associative brain regions (enhanced in MobFD and reduced in FixFD). Compared with yHC and MobFD patients, FixFD patients had an extensive pattern of reduced FC within the cerebellar network, and between the majority of affective-cognitive seeds of interest and the sensorimotor and high-order function ("cognitive") areas with a unique involvement of dorsal anterior cingulate cortex connectivity. Brain FC within the affective-cognitive network is altered in FD and presented specific features associated with each FD phenotype, suggesting an interaction between brain connectivity and clinical expression of the disease.

Changes in brain glucose metabolism and connectivity in somatoform disorders: an 18F-FDG PET study.

Somatoform disorders (SFD) are defined as a syndrome characterized by somatic symptoms which cannot be explained by organic reasons. Chronic or recurrent forms of somatization lead to heavy emotional and financial burden to the patients and their families. However, the underlying etiology of SFD is largely unknown. The purpose of this study is to investigate the changed brain glucose metabolic pattern in SFD. In this study, 18 SFD patients and 21 matched healthy controls were enrolled and underwent an 18F-FDG PET scan. First, we explored the altered brain glucose metabolism in SFD. Then, we calculated the mean 18F-FDG uptake values for 90 AAL regions, and detected the changed brain metabolic connectivity between the most significantly changed regions and all other regions. In addition, the Pearson coefficients between the neuropsychological scores and regional brain 18F-FDG uptake values were computed for SFD patients. We found that SFD patients showed extensive hypometabolism in bilateral superolateral prefrontal cortex, insula, and regions in bilateral temporal gyrus, right angular gyrus, left gyrus rectus, right fusiform gyrus, right rolandic operculum and bilateral occipital gyrus. The metabolic connectivity between right insula and prefrontal areas, as well as within prefrontal areas was enhanced in SFD. And several brain regions were associated with the somatic symptoms, including insula, putamen, middle temporal gyrus, superior parietal gyrus and orbital part of inferior frontal gyrus. Our study revealed widespread alterations of the brain glucose metabolic pattern in SFD patients. Those findings might elucidate the neuronal mechanisms with glucose metabolism and shed light on the pathology of SFD.

Brain Functional Connectivity in Patients With Somatic Symptom Disorder.

OBJECTIVE: The aim of the study was to evaluate whether individuals with somatic symptom disorder (SSD) display increased resting-state functional connectivity (FC) within and between the sensorimotor network (SMN), default mode network (DMN), salience network, and dorsal attention network (DAN). METHODS: Eighteen patients with SSD and 20 age- and sex-matched healthy control participants underwent resting-state functional magnetic resonance imaging. We used a seed-based correlation approach for the four brain networks. RESULTS: Patients with SSD had higher scores on the Somato-Sensory Amplification Scale (z = 5.22, p < .001) and Symptom Checklist-90-Revised-Somatization (z = 4.94, p < .001) and greater FC within the SMN, DMN, and salience network than healthy control participants. Patients with SSD also had increased FC between the SMN and DMN, SMN and salience network, SMN and DAN, and salience network and DAN (t = 5.10-7.47, all false discovery rate q < .05). The Somato-Sensory Amplification Scale scores correlated with FC between the SMN and salience network and between the SMN and DAN (r = .61-.82, all p < .003). CONCLUSIONS: Based on the results of the FC analysis between the SMN and salience network, we suggest that SSD may be associated with alterations of sensory-discriminative processing of pain and other somatic symptoms, which is influenced by affective processing. Based on the results of the FC analysis of the SMN and DAN, we suggest that patients with SSD have a deficit in attention, leading to misperception of external stimuli and failure to regulate bodily functions aimed at interactions with external stimuli.

The Neuroanatomy of Somatoform Disorders: A Magnetic Resonance Imaging Study.

BACKGROUND: Somatoform disorders (SDs) are a heterogeneous group of psychiatric syndromes characterized by common symptoms, which may mimic a physical condition but they are not explained by a medical condition. Although the biologic nature of this disorder has been widely accepted, the neuroanatomical correlates characterizing SDs are still inconclusive. OBJECTIVE: This study aims to explore gray matter (GM) volume alterations in SD patients compared to healthy controls and their possible association with clinical and cognitive measures. METHOD: We used voxel-based morphometry to examine regional GM volumes in 20 inpatients with SDs and 24-matched healthy controls. Only for SD patients, we employed multiple instruments to assess psychopathology and cognitive functioning, which were then used to explore their association with GM volume deficits. RESULTS: Compared to healthy controls, SD patients showed GM volume reductions in the hypothalamus, left fusiform gyrus, right cuneus, left inferior frontal gyrus, left posterior cingulate, and right amygdala (p < 0.05, cluster Family Wise Error corrected). Additionally, in SD, Symptom Checklist-90-Phobia and Hamilton Depressive Rating Scale scores negatively correlated with specific fronto-temporoparietal regions whereas Symptom Checklist-90-Sleep scores positively correlated with anterior cingulate cortex. Lastly, the Boston Naming Test negatively correlated with fronto-temporoparietal and striatal volumes whereas Free and Cued Selective Reminding Test and Stroop scores positively correlated with superior temporal gyrus and cuneus, respectively (all p < 0.05, cluster Family Wise Error corrected). CONCLUSION: Our results suggest that SDs might be characterized by selective impairments in specific cortico-limbic regions associated to two overlapping circuits, the neuromatrix of pain and the emotion regulation system.

Cortical thickness alterations linked to somatoform and psychological dissociation in functional neurological disorders.

BACKGROUND: Links between dissociation and functional neurological disorder (FND)/conversion disorder are well-established, yet the pathophysiology of dissociation remains poorly understood. This MRI study investigated structural alterations associated with somatoform and psychological dissociation in FND. We hypothesized that multimodal, paralimbic cingulo-insular regions would relate to the severity of somatoform dissociation in patients with FND. METHODS: FreeSurfer cortical thickness and subcortical volumetric analyses were performed in 26 patients with motor FND and 27 matched healthy controls. Patients with high dissociation as measured by the Somatoform Dissociation Questionnaire-20 (SDQ) or Dissociative Experiences Scale (DES) were compared to controls in stratified analyses. Within-group analyses were also performed with SDQ and DES scores in patients with FND. All cortical thickness analyses were whole-brain corrected at the cluster-wise level. RESULTS: Patients with FND and high somatoform dissociation (SDQ > 35) showed reduced left caudal anterior cingulate cortex (ACC) cortical thickness compared to controls. In within-group analyses, SDQ scores inversely correlated with left caudal ACC cortical thickness in patients with FND. Depersonalization/derealization scores positively correlated with right lateral occipital cortical thickness. Both within-group findings remained statistically significant controlling for trait anxiety/depression, borderline personality disorder and post-traumatic stress disorder, adverse life events, and motor FND subtypes in post-hoc analyses. CONCLUSION: Using complementary between-group and within-group analyses, an inverse association between somatoform dissociation and left caudal ACC cortical thickness was observed in patients with FND. A positive relationship was also appreciated between depersonalization/derealization severity and cortical thickness in visual association areas. These findings advance our neuropathobiological understanding of dissociation in FND. Hum Brain Mapp 39:428-439, 2018. © 2017 Wiley Periodicals, Inc.

Diagnosing psychogenic nonepileptic seizures: Video-EEG monitoring, suggestive seizure induction and diagnostic certainty.

Psychogenic nonepileptic seizures (PNES) can remain undiagnosed for many years, leading to unnecessary medication and delayed treatment. A recent report by the International League Against Epilepsy Nonepileptic Seizures Task Force recommends a staged approach to the diagnosis of PNES (LaFrance, et al., 2013). We aimed to investigate its practical utility, and to apply the proposed classification to evaluate the role of long-term video-EEG monitoring (VEEG) and suggestive seizure induction (SSI) in PNES workup. Using electronic medical records, 122 inpatients (mean age 36.0±12.9years; 68% women) who received the diagnosis of PNES at our epilepsy center during a 4.3-year time period were included. There was an 82.8% agreement between diagnostic certainty documented at discharge and that assigned retroactively using the Task Force recommendations. In a minority of cases, having used the Task Force criteria could have encouraged the clinicians to give more certain diagnoses, exemplifying the Task Force report's utility. Both VEEG and SSI were effective at supporting high level diagnostic certainty. Interestingly, about one in four patients (26.2%) had a non-diagnostic ("negative") VEEG but a positive SSI. On average, this subgroup did not have significantly shorter mean VEEG recording times than VEEG-positive patients. However, VEEG-negative/SSI-positive patients had a significantly lower habitual seizure frequency than their counterparts. This finding emphasizes the utility of SSI in ascertaining the diagnosis of PNES in patients who do not have a spontaneous habitual event during VEEG due to, for example, low seizure frequency.

[Factitious disorders]. / Artifizielle Störungen.

Patients with factitious disorders intentionally fabricate, exaggerate or feign physical and/or psychiatric symptoms for various open and covert psychological reasons. There are many issues regarding the diagnostic state and classification of factitious disorders. Both the categorical differentiation of and clinical continuum ranging from somatoform/dissociative disorders to malingering are being controversially debated. Epidemiological studies on the frequency of factitious disorder meet basic methodological difficulties. Reported rates of prevalence and incidence in the professional literature most probably have to be considered underestimations. Illness deception and self-harm as core features of the abnormal illness behaviour in factitious disorder may refer to various highly adverse and traumatic experiences during early development in a subgroup of patients. Chronic courses of illness prevail; however, there are also episodic variants.

Post-epilepsy surgery psychogenic nonepileptic seizures.

OBJECTIVES: We investigated the prevalence of post-epilepsy surgery psychogenic nonepileptic seizures (PNES) in patients with drug-resistant epilepsy and the possible influence of risk factors on these seizures. METHODS: In this retrospective study, we examined data from all patients with a clinical diagnosis of drug-resistant epilepsy who underwent epilepsy surgery at Graduate Hospital and the Jefferson Comprehensive Epilepsy Center between 1986 and 2016. Postsurgical outcome was identified for up to 15 years after surgery. Diagnosis of PNES was verified in the epilepsy monitoring unit with video-electroencephalography (EEG) ictal recording. Potential associated factors were assessed by comparing patients with or without postoperative PNES. RESULTS: A total of 1,105 patients were studied; 697 patients had postoperative seizures, and, of these, 27 patients (3.9%) had documented PNES after surgery. A full-scale intelligence quotient (IQ) <80 was significantly associated with post-epilepsy surgery PNES (odds ratio [OR] 2.89, p = 0.007, 95% confidence interval [CI] 1.33-6.29). A history of a preoperative psychiatric diagnosis was also significantly associated with post-epilepsy surgery PNES (OR 4.67, p = 0.0001, 95% CI 2.01-10.82). Other factors were not significantly associated with post-epilepsy surgery PNES. SIGNIFICANCE: Post-epilepsy surgery PNES should be considered when patients report recurrent seizures after epilepsy surgery. Although these seizures probably occur relatively infrequently, attention to factors such as appearance of new ictal behaviors, a preoperative history of a psychiatric disorder, and a low full-scale IQ should raise suspicion and lead to appropriate diagnostic measures.

Health care utilization following diagnosis of psychogenic nonepileptic seizures.

OBJECTIVES: The long-term outcome of patients with psychogenic nonepileptic seizures (PNES) is of importance given the disabling symptoms and tendency to affect patients early in their productive years. Health care utilization (HCU) is an important outcome measure reflecting overall health status and costs. There is little information regarding long-term HCU following diagnosis of PNES. METHODS: We retrospectively reviewed records of Veterans diagnosed with PNES during epilepsy monitoring unit (EMU) evaluation. For the three-year period following diagnosis of PNES, we reviewed emergency department (ED) visits, hospitalizations, outpatient clinic visits, and radiology procedures. We compared the three years following PNES diagnosis with the three years preceding diagnosis. We also compared patients with PNES and patients with epileptic seizures (ES). RESULTS: Emergency department visits and hospitalizations were more frequent in patients with PNES compared with those in patients with ES (p=0.01). There was no overall improvement in HCU during the three-year interval following diagnosis of PNES. A transient decrease during the year following diagnosis was not sustained over three-year follow-up. Pain complaints rather than seizures were the most common reason for presentation, whereas the opposite was true for patients with ES (p<0.01). There was a sharp decrease in neurology outpatient visits (p<0.001) and a decrease in primary care visits (p<0.05) after PNES was diagnosed. Total outpatient visits were unchanged. CONCLUSIONS: Overall HCU did not improve during the three years following diagnosis of PNES, compared with three years preceding diagnosis. The results add to studies documenting poor seizure outcomes following diagnosis of PNES and underscore the need for more effective and comprehensive treatments, addressing comorbid symptoms.

Early childhood trauma and hippocampal volumes in patients with epileptic and psychogenic seizures.

OBJECTIVE: Exposure to early life childhood trauma has been implicated as resulting in a vulnerability to epileptic and psychogenic nonepileptic seizures (PNES), hippocampal atrophy, and psychiatric disorders. This study aimed to explore the relationships between childhood trauma, epilepsy, PNES, and hippocampal volume in patients admitted to a video-electroencephalogram monitoring (VEM) unit. METHODS: One hundred thirty-one patients were recruited from the Royal Melbourne Hospital VEM unit. The diagnostic breakdown of this group was: temporal lobe epilepsy (TLE) (32), other epilepsy syndromes (35), PNES (47), other nonepileptic syndromes (5), both epilepsy and PNES (6), and uncertain diagnosis (6). All patients completed a questionnaire assessing exposure to childhood trauma, the Childhood Trauma Questionnaire (CTQ), as well as questionnaires assessing psychiatric symptomatology (SCL-90-R), Anxiety and Depression (HADS), quality of life (QOLIE-98) and cognition (NUCOG). Volumetric coronal T1 MRI scans were available for 84 patients. Hippocampal volumes were manually traced by a blinded operator. RESULTS: The prevalence of childhood trauma in patients with PNES was higher than in patients with other diagnoses (p=0.005), and the group with PNES overall scored significantly higher on the CTQ (p=0.002). No association was found between CTQ scores and hippocampal volumes; however, patients with a history of sexual abuse were found to have smaller left hippocampal volumes than patients who had not (p=0.043). Patients reporting having experienced childhood trauma scored lower on measures of quality of life and higher on measures of psychiatric symptomatology. SIGNIFICANCE: Patients with PNES report having experienced significantly more childhood trauma than those with epileptic seizures, and in both groups there was a relationship between a history of having experienced sexual abuse and reduced left hippocampal volume. Patients with PNES and those with epilepsy who have a history of childhood trauma have overall worse quality of life and more psychiatric symptomatology.

Evaluation of the therapeutic response by (99m)Tc-ECD-SPET in a female with non-organic depression, generalized anxiety and heterophobia.

This is the case of a 33 years old female patient who was diagnosed with depression and heterophobia, which progressed to generalized anxiety according to the International Statistical Classification of Diseases and Health Related Problems, 10th Revision (ICD-10), Version for 2010 diagnostic criteria. The clinical symptoms of the patient were significantly improved after effective treatment. The patient underwent before and after treatment 99mTc-ethyl cysteinate dimmer ((99m)Tc-ECD) brain single-photon emission tomography (SPET). A great improvement in regional cerebral blood flow was found after treatment. In conclusion, this case highlights the value of brain perfusion SPET scan in providing objective imaging evidence of diagnosis and treatment evaluation in a patient with non-organic mental disorder.

Relationship between neural activity and immunity in patients with undifferentiated somatoform disorder.

It has been suggested that somatoform disorders are related to both the brain and the immune system, and that immune functions may be influenced by cerebral asymmetry. However, few studies have examined the relationship between brain activity and immune function in somatoform disorders. Thirty-two patients with non-medicated undifferentiated somatoform disorder were enrolled in this study. Blastogenic responses to phytohemagglutinin (PHA) were used to measure immunity. Regional cerebral perfusion was measured by 99m-Tc-ethyl cysteinate dimer single photon emission computed tomography (SPECT). Significant hypoperfusion was found at the left inferior parietal lobule and the left supramarginal gyrus in the more immune-suppressed (MIS) subgroup compared with the less immune-suppressed (LIS) subgroup. However, no regions of significant hyperperfusion were found in the MIS subgroup compared with the LIS subgroup. Decreased cerebral blood flow in the left inferior parietal lobule and the left supramarginal gyrus in the patient group was also significantly associated with reduced blastogenic responses to PHA regardless of sex and age. These results suggest that the left inferior parietal lobule and the left supramarginal gyrus might play an immunomodulating role in patients with undifferentiated somatoform disorder. In addition, these results suggest the role of cerebral asymmetry in altered immunity in the patients.

Structural neuroimaging of somatoform disorders: A systematic review.

Although there has been an increment in neuroimaging research in somatoform disorders (SD), to date little is known about the neural correlates of these diseases. Therefore, in this systematic, review we aimed at summarizing the existing evidence of structural brain alterations in SD as per DSM-IV and DSM-5 criteria. Three electronic databases (Scopus, PubMed and Web of Science) were searched. Only case-control studies using structural neuroimaging were included. Forty-five out of 369 articles fulfilled inclusion criteria and were reviewed. Compared to controls, subjects with SD showed morphological alterations encompassing motor, limbic and somatosensory circuits. Although far from being conclusive, the results suggested that SD are characterized by selective alterations of large-scale brain networks implicated in cognitive control, emotion regulation and processing, stress and somatic-visceral perception. This review highlights the need for further multimodal neuroimaging studies with longitudinal designs, in larger and better-characterized samples, to elucidate the temporal and causal relationship between neuroanatomical changes and SD, which is paramount for informing tailored treatments.

Frequency-specific alterations of the frontal-cerebellar circuit in first-episode, drug-naive somatization disorder.

BACKGROUND: With the development of imaging techniques, evidence of abnormal neural activity has been implicated in patients with somatization disorder (SD). It remains unclear whether abnormal spontaneous neural activities are related to specific frequency bands. In this study, resting-state functional magnetic resonance imaging (fMRI) using the frequency-specific amplitude of low frequency fluctuation (ALFF) approach was applied to investigate changes in spontaneous neural activity in different frequency bands in patients with SD. METHODS: Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex-, education-matched healthy controls (HCs) underwent resting-state fMRI. The ALFF method with the classical low-frequency (0.01 - 0.08 Hz), slow-5 (0.01 - 0.027 Hz) and slow-4 (0.027 - 0.08 Hz) bands was employed to analyze the data. RESULTS: With the classical low-frequency and slow-5 bands, patients with SD showed significantly increased ALFF in the left orbitofrontal cortex (OFC) and reduced ALFF in the right cerebellum compared with HCs. With the slow-4 band, patients with SD exhibited significantly reduced ALFF in the right cerebellum compared with HCs. However, no significant correlation was observed between the ALFF value in the left OFC or right cerebellum and clinical/cognitive variables. CONCLUSIONS: Our findings indicate that there are abnormal regional activities of the left OFC and right cerebellum in first-episode, treatment-naive patients with SD, suggesting that these alterations occur early in the course of the disease and are independent of medication status. Our study provides novel evidence that different regional activities of the frontal-cerebellar circuit may be involved in the pathophysiology of SD.

Regional cerebral blood flow in patients with orally localized somatoform pain disorder: a single photon emission computed tomography study.

AIM: Somatoform pain disorder is characterized by persistent and chronic pain at one or more sites without an associated general medical condition and in which psychological factors are thought to play a role. This study aimed to investigate the pathological features of somatoform pain disorder localized to the oral region by single photon emission computed tomography (SPECT). METHODS: Ten patients (nine females and one male; average age 55.0 ± 14.4 years) having somatoform pain disorder with oral symptoms participated. SPECT was performed using N-isopropyl-4-[(123) I] iodoamphetamine intravenous injections, and regional cerebral blood flow (rCBF) was assessed by three-dimensional stereotactic surface projections. We also selected 12 healthy individuals (seven females and five males; average age 61.8 ± 13.2 years) to act as controls. RESULTS: Both the patient and control groups showed no atrophy or infarction on CT or magnetic resonance imaging. The patient group showed higher rCBF in the subcortical area, especially in the thalamus and cingulate gyri, than the control group. In contrast, the patient group showed lower rCBF in the bilateral frontal and occipital lobes as well as in the left temporal lobe. CONCLUSIONS: These results suggest that the biological process involved in somatoform pain disorder of the oral region is characterized by changes in limbic and cortical functions. The finding that somatoform pain disorder with oral symptoms is associated with brain functional changes will help to develop treatment regimes for this disorder and clarify the underlying pathology.

Abnormal Functional Asymmetry in the Salience and Auditory Networks in First-episode, Drug-naive Somatization Disorder.

Evidence of abnormal functional connectivity (FC) has been implicated in patients with somatization disorder (SD). Although the importance of damage to the functional asymmetry has been established, it remains unclear as to whether abnormal intra- and inter-hemispheric FCs are related to patients with SD. We applied resting-state functional magnetic resonance imaging to first-episode, medication-naive patients with SD (n = 25) and matched healthy controls (HCs) (n = 28). The data were analyzed using parameter of asymmetry (PAS) and support vector machine (SVM). Patients with SD showed significantly lower PAS values in the left inferior temporal gyrus (ITG) and higher PAS values in the right insula compared to HCs. A negative correlation was observed between the higher PAS values in the right insula and the Hamilton Depression Scale (HAMD) sleep subscale scores (r = -0.502, p = 0.011), and positive correlations were found between the lower PAS values in the left ITG and the Hamilton Anxiety Scale (HAMA) somatic anxiety subscale scores (r = 0.443, p = 0.027) and the HAMA total scores (r = 0.456, p = 0.022). Moreover, the increased PAS values in the right insula could distinguish patients with SD from HCs with acceptable accuracy (77.36%). First-episode, treatment-naive patients with SD show disrupted asymmetry of inter- and intra-hemispheric FCs. The pattern of disrupted functional asymmetry occurs early in the course of the disease and is independent of medication status, which suggests that disrupted functional asymmetry of salience and auditory networks may be applied as early biological markers for SD.

Functional neuroimaging in patients presenting with somatoform disorders: A model for investigating persisting symptoms after tick bites and post-treatment Lyme disease syndrome?

Approximately 10% of patients presenting with Lyme disease experience fatigue, musculoskeletal pain, concentration disorders, or short-term memory deficits in the six months following treatment. This entity has been defined as post-Lyme disease syndrome or post-treatment Lyme disease syndrome. The pathophysiology of this syndrome is unknown, but neither persistence of the bacterium nor effectiveness of antibiotics are currently reported in the literature. The French High Council for Public Health (French acronym HCSP) has recently defined a new entity called "persistent polymorphic symptoms after a tick bite" allowing for designing studies to better understand these subjective presentations, for which objective biomarkers are currently lacking. This entity encompasses patients experiencing fatigue and generalized pain in the months following a tick bite and can be associated with several subjective symptoms with major impact on the quality of life. In the field of somatoform disorders, this article reviews functional neuroimaging studies in patients presenting with subjective complaints and discusses potential clinical implications for persisting symptoms after tick bites and post-treatment Lyme disease syndrome.

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.

Regional white matter volume abnormalities in first-episode somatization disorder.

BACKGROUND: Alterations of white matter integrity have been implicated in patients with somatization disorder (SD). However, changes of white matter volume (WMV) remain unclear. This study is designed to examine regional WMV in patients with SD and to investigate the potential relationships between WMV abnormalities and personality traits, cognitive function, and symptom severity. METHODS: We recruited 25 first-episode, drug-naive patients with SD and 28 sex-, age-, and education-matched healthy controls for the study. Personality traits, cognitive function, and symptom severity were assessed for all participants. Data were analyzed with the computational anatomy toolbox (CAT12) methods. RESULTS: Patients with SD exhibited a significantly increased WMV in the right inferior frontal gyrus (IFG) (t = 4.4009) and a significantly decreased WMV in the left inferior longitudinal fasciculus (ILF) (t = -3.4292) relative to healthy controls. No correlation was found between abnormal WMV and clinical/cognitive variables in the patients. CONCLUSIONS: Our findings suggest the presence of significant regional WMV abnormalities in first-episode, drug-naive patients with SD, which might improve understanding the pathophysiology of SD.