Increased Dendritic Orientation Dispersion in the Left Occipital Gyrus is Associated with Atypical Visual Processing in Adults with Autism Spectrum Disorder.

In autism spectrum disorder (ASD), the complexity-specific hypothesis explains that atypical visual processing is attributable to selective functional changes in visual pathways. We investigated dendritic microstructures and their associations with functional connectivity (FC). Participants included 28 individuals with ASD and 29 typically developed persons. We explored changes in neurite orientation dispersion and density imaging (NODDI) and brain areas whose FC was significantly correlated with NODDI parameters in the explored regions of interests. Individuals with ASD showed significantly higher orientation dispersion index (ODI) values in the left occipital gyrus (OG) corresponding to the secondary visual cortex (V2). FC values between the left OG and the left middle temporal gyrus (MTG) were significantly negatively correlated with mean ODI values. The mean ODI values in the left OG were significantly positively associated with low registration of the visual quadrants of the Adolescent/Adult Sensory Profile (AASP), resulting in a significant positive correlation with passive behavioral responses of the AASP visual quadrants; additionally, the FC values between the left OG and the left MTG were significantly negatively associated with reciprocal social interaction. Our results suggest that abnormal V2 dendritic arborization is associated with atypical visual processing by altered intermediation in the ventral visual pathway.

Uncinate fasciculus disruption relates to poor recognition of negative facial emotions in Alzheimer's disease: a cross-sectional diffusion tensor imaging study.

BACKGROUND: Recognising facial emotions involves visual and emotional information processing. Patients with dementia, including dementia of Alzheimer's type (DAT), are known to poorly recognise facial emotions, especially negative facial emotions. In this study, we aimed to assess if DAT patients exhibit poor facial emotional recognition, and to identify a neural basis for how poor facial emotional recognition might occur. METHODS: Magnetic resonance imaging and diffusion tensor imaging (DTI) analysis were conducted in 20 DAT patients and 15 cognitive normal (CN) subjects. The uncinate fasciculus (UF), inferior longitudinal fasciculus, and inferior fronto-occipital fasciculus were delineated by deterministic tractography. DTI parameters were calculated for each fibre. Facial emotion recognition was evaluated with the Facial Emotion Selection Test (FEST). The relationships between FEST scores and DTI parameters in each fibre were measured by partial correlation analyses with age, gender, and the Mini-Mental State Examination as covariates. Group-wise comparisons between DAT and CN subjects were performed for each DTI parameter in each fibre. RESULTS: DAT patients showed lower FEST negative emotion scores than CN subjects (P < 0.05). The score of negative emotion subscale was negatively correlated (r = -0.770, P < 0.001) to mean diffusivity of the left UF in DAT patients. There were no relationships between negative emotion subscale and the other fibre tracts. DAT patients showed no differences in the DTI parameters for each fibre compared to CN subjects. CONCLUSIONS: DAT-related prefrontal-limbic network dysfunction is associated with poor recognition of unpleasant emotions; consequently, worse facial recognition of negative emotion is observed in DAT patients.

Randomized Trial of Thymectomy in Myasthenia Gravis.

BACKGROUND: Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. METHODS: We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. RESULTS: A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, P<0.001); patients in the thymectomy group also had a lower average requirement for alternate-day prednisone (44 mg vs. 60 mg, P<0.001). Fewer patients in the thymectomy group than in the prednisone-only group required immunosuppression with azathioprine (17% vs. 48%, P<0.001) or were hospitalized for exacerbations (9% vs. 37%, P<0.001). The number of patients with treatment-associated complications did not differ significantly between groups (P=0.73), but patients in the thymectomy group had fewer treatment-associated symptoms related to immunosuppressive medications (P<0.001) and lower distress levels related to symptoms (P=0.003). CONCLUSIONS: Thymectomy improved clinical outcomes over a 3-year period in patients with nonthymomatous myasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).

Correction to: Creation of Straight-Chain Cationic Polysaccharide-Based Bile Salt Sequestrants Made from Euglenoid ß-1,3-Glucan as Potential Antidiabetic Agents.

The corresponding author (Motonari Shibakami) inadvertently failed to include his ORCID ID: http://orcid.org/0000-0003-4484-2982 In the published article.

Decreased perfusion of the posterior cingulate gyri shown by a cingulate island score is a possible marker of vulnerability to behavioural and psychological symptoms of Alzheimer's disease: a pilot study.

BACKGROUND: The cingulate island score (CIScore), which indicates the Z-score ratio of the posterior cingulate gyri to the medial occipital area, has been shown to be useful for differentiating dementia with Lewy bodies from Alzheimer's disease (AD). Our aim was to investigate associations between the clinical symptoms of AD and the CIScore as an index of the relative decrease in perfusion of the posterior cingulate gyri that occurs in the early stages of AD. METHODS: Seventeen patients with early-stage AD and 13 patients with amnesic mild cognitive impairment were examined. Z-score maps of technetium-99m ethyl cysteinate dimer single-photon emission computed tomography images acquired from the patients were converted, and the CIScore was determined by using the easy Z-score imaging system. The relationships between the CIScore and clinical symptom scores were tested. RESULTS: A significant correlation was identified between the CIScore and the Neuropsychiatric Inventory Questionnaire score. No significant correlations were identified between the CIScore and other measures of cognitive function. Based on a CIScore of 0.39, we correctly differentiated patients with and without behavioural and psychological symptoms of dementia (BPSD), with a sensitivity of 72.2% and specificity of 75.0%. DISCUSSION: Using technetium-99m ethyl cysteinate dimer single-photon emission computed tomography, we observed that decreased posterior cingulate gyri perfusion, relative to the medial occipital area, in prodromal and early AD was closely associated with behavioural and psychological symptoms of dementia. Therefore, our findings suggest that CIScore is not only useful for discriminating dementia with Lewy bodies from AD, but it can also be clinically used as a specific indicator of the vulnerability to behavioural and psychological symptoms of dementia in the early stages of AD.

Detection of brain amyloid-ß deposits due to the repetitive head trauma in a former karate player.

Head trauma is a well-established epidemiological risk factor for Alzheimer's disease, but a study of early detection of its pathology has not yet been performed in human patients in vivo. To address this issue, we performed 11 C-labelled Pittsburgh compound B-positron emission tomography on a right-handed 30-year-old man with cognitive deterioration after repetitive head trauma during karate matches. Structural magnetic resonance imaging was also performed on this patient. The same positron emission tomography analysis was performed on elderly healthy controls (15 men, mean age: 70.7 ± 6.2 years). To analyze grey matter volume, structural magnetic resonance imaging was performed on age-matched healthy controls (15 men, mean age: 28.5 ± 3.6 years). The cognitive deterioration in our patient was fixed and partially improved in the 10 years after the repetitive head trauma. However, Pittsburgh compound B-non-displaceable binding potential was significantly elevated in the patient. Volume reduction was shown in the medial temporal region, cerebellum, and the basal frontal cortex, while amyloid-ß increase was shown in the bilateral prefrontal cortex. This is the first study to show an early degenerative process due to head trauma in the prefrontal cortex, where structural damage is not yet visible. Early recognition of the degenerative pathology due to repetitive head trauma by amyloid and possibly tau imaging would help clinicians determine how to treat those with early symptoms.

Creation of Straight-Chain Cationic Polysaccharide-Based Bile Salt Sequestrants Made from Euglenoid ß-1,3-Glucan as Potential Antidiabetic Agents.

PURPOSE: Straight-chain polysaccharides have a greater potential of selectively adsorbing hydrophobic bile salts than resin-based bile salt sequesters because of ionic and hydrophobic interactions; hence, they may possess antidiabetic activity. The feasibility of using cationic polysaccharides made from euglenoid ß-1,3-glucan (referred to as paramylon) as potential antidiabetic agents was examined by using in vitro and animal experiments. METHODS: Cationic straight-chain polysaccharides were synthesized from euglenoid polysaccharide and glycidyltrimethylammonium chloride. The effects of administration of the synthetic polysaccharide on metabolic syndrome-related indicators were examined in high-fat diet-induced obesity mice. The degree of adsorption of bile salts by the polysaccharides was evaluated using spectroscopic analysis. RESULTS: Administration of the cationic paramylon derivatives significantly reduced body and mesenteric fat weight in high-fat diet-induced obesity mice. A noteworthy effect was that glucagon-like peptide-1 (GLP-1) secretion was approximately three times higher in diet-induced obesity mice receiving cationic paramylon derivatives than in those receiving cellulose as a control. CONCLUSIONS: Our results indicate that these cationic paramylon derivatives are potential GLP-1 secretagogues suitable for further study.

Physiological characterization of anaerobic ammonium oxidizing bacterium 'Candidatus†Jettenia caeni'.

To date, six candidate genera of anaerobic ammonium-oxidizing (anammox) bacteria have been identified, and numerous studies have been conducted to understand their ecophysiology. In this study, we examined the physiological characteristics of an anammox bacterium in the genus 'Candidatus Jettenia'. Planctomycete KSU-1 was found to be a mesophilic (20-42.5°C) and neutrophilic (pH 6.5-8.5) bacterium with a maximum growth rate of 0.0020 h(-1) . Planctomycete KSU-1 cells showed typical physiological and structural features of anammox bacteria; i.e. (29) N2 gas production by coupling of (15) NH4 (+) and (14) NO2 (-) , accumulation of hydrazine with the consumption of hydroxylamine and the presence of anammoxosome. In addition, the cells were capable of respiratory ammonification with oxidation of acetate. Notably, the cells contained menaquinone-7 as a dominant respiratory quinone. Proteomic analysis was performed to examine underlying core metabolisms, and high expressions of hydrazine synthase, hydrazine dehydrogenase, hydroxylamine dehydrogenase, nitrite/nitrate oxidoreductase and carbon monoxide dehydrogenase/acetyl-CoA synthase were detected. These proteins require iron or copper as a metal cofactor, and both were dominant in planctomycete KSU-1 cells. On the basis of these experimental results, we proposed the name 'Ca. Jettenia caeni' sp. nov. for the bacterial clade of the planctomycete KSU-1.

CD59 Expression in Skeletal Muscles and Its Role in Myasthenia Gravis.

BACKGROUND AND OBJECTIVES: Complement regulatory proteins at the neuromuscular junction (NMJ) could offer protection against complement-mediated damage in myasthenia gravis (MG). However, there is limited information on their expression at the human NMJ. Thus, this study aimed at investigating the expression of the cluster of differentiation 59 (CD59) at the NMJ of human muscle specimens and demonstrating the overexpression of CD59 mRNA and protein in the muscles of patients with MG. METHODS: In this observational study, muscle specimens from 16 patients with MG (9 and 7 patients with and without thymoma, respectively) and 6 nonmyopathy control patients were examined. Immunohistochemical stains, Western blot analysis, and quantitative real-time reverse transcription PCR were used to evaluate the CD59 expression. RESULTS: A strong localized expression of CD59 was observed at the NMJ in both patients with and without MG. Moreover, the CD59/glyceraldehyde-3-phosphate dehydrogenase protein ratio in patients with MG was significantly higher than that in the nonmyopathy controls (MG; n = 16, median 0.16, interquartile range (IQR) 0.08-0.26 and nonmyopathy controls; n = 6, median 0.03, IQR 0.02-0.11, p = 0.01). The proportion of CD59 mRNA expression relative to AChR mRNA expression (ΔCtCD59/AChR) was associated with the quantitative MG score, MG activities of daily living score, and MG of Foundation of America Clinical Classification (r = 0.663, p = 0.01; r = 0.638, p = 0.014; and r = 0.715, p = 0.003, respectively). DISCUSSION: CD59, which acts as a complement regulator, may protect the NMJ from complement attack. Our findings could provide a basis for further research that investigates the underlying pathogenesis in MG and the immunomodulating interactions of the muscle cells.

Association of adverse childhood experiences and cortical neurite density alterations with posttraumatic stress disorder symptoms in autism spectrum disorder.

Background: Posttraumatic stress disorder (PTSD) can be a source of significant social and daily distress in autism spectrum disorder (ASD). Compared to typically developed (TD) individuals, people with ASD are at an increased risk of adverse childhood experiences (ACEs), which can result in abnormal neuronal development. However, whether or how ACEs influence abnormal neural development and PTSD symptoms in ASD has not been fully elucidated. Methods: Thirty-nine TD individuals and 41 individuals with ASD underwent T1-weighted magnetic resonance imaging and neurite orientation dispersion and density imaging (NODDI), with axonal and dendritic densities assessed in terms of the orientation dispersion index and neurite density index (NDI), respectively. Voxel-based analyses were performed to explore the brain regions associated with PTSD symptoms, and the relationships between the severity of ACEs and PTSD symptoms and NODDI parameters in the extracted brain regions were examined. Results: There was a significant positive association between PTSD symptom severity and NDI in the bilateral supplementary motor area; right superior frontal, left supramarginal, and right superior temporal gyrus; and right precuneus in the ASD group, but not in the TD group. ACE severity was significantly associated with NDI in the right superior frontal and left supramarginal gyrus and right precuneus in the ASD group. Moreover, NDI in the right precuneus mainly predicted the severity of PTSD symptoms in the ASD group, but not the TD group. Conclusion: These results suggest that ACE-associated higher neurite density is of clinical importance in the pathophysiology of PTSD symptoms in ASD.

Immunotherapy for ocular myasthenia gravis: an observational study in Japan.

Background: Treatment for ocular myasthenia gravis (OMG) has not yet been well established. Few reports have been published on the clinical practice and outcomes of OMG. Objectives: We investigated treatment of OMG and its outcomes in Japan.We investigated treatment of OMG and its outcomes in Japan. Design: We performed a retrospective cross-sectional survey of OMG patients from eight hospitals in Japan. Methods: Clinical information, including sex, age at onset, initial symptoms, autoantibodies, clinical course, treatment history, complications, and outcomes, was obtained. In addition, we recorded the total number of patients with MG and OMG separately. Results: In total, 135 patients with OMG (67 men, 68 women) were included. Treatment of OMG was not simple and involved various immunotherapeutic strategies. Eight patients went into remission spontaneously without immunotherapy. A total of 117 patients showed improvements after treatment, whereas 10 patients showed refractory responses to treatment. Overall outcomes were good; however, symptoms persisted in 60.7% of patients even after treatment. Among 90 patients who received immunotherapy, only two showed a refractory response. Meanwhile, for 45 patients who did not receive immunotherapy, 8 were refractory. Thus, the rate of refractory disease in the group with immunotherapy was significantly lower (p = 0.001, u-test) than in the group without immunotherapy. The proportion of generalized MG patients among all MG cases was low in medical centers where immunotherapy for OMG was frequently performed. Conclusion: Although the overall prognosis for patients with OMG was good, symptoms remained in more than half of the patients. Immunotherapy, including corticosteroids, may be beneficial for patients with OMG. Plain language summary: Is immunosuppressive therapy beneficial for myasthenia gravis patients with ocular symptoms only? Patients with ocular myasthenia gravis (OMG) have only eye symptoms for more than 2 years. Whether this condition is an initial stage of the disease before eventually progressing to generalized myasthenia gravis (gMG) is still uncertain. Different from gMG, OMG is not life-threatening. But eye symptoms often cause troublesome problems in life. Doctors have treated OMG patients similarly to patients with gMG. There is no standard clinical practice for OMG. In this study, we examined how patients with OMG were treated at eight different specialist centers in Japan. In 135 patients with OMG, 8 patients became symptom free without treatment, 117 patients showed improvements after treatment, whereas 10 patients did not get well. Overall outcomes were good, but symptoms remained in 60.7% of patients even after treatment. Among 90 patients who received one or more immunotherapies, only 2 did not get well. Meanwhile, for 45 patients who did not receive immunotherapy, 8 remained ill. We found that treatment of OMG was not simple and often needed multiple immunotherapies. Administering immunotherapy, including corticosteroids, may be beneficial for patients with OMG.

Nationwide survey of Lambert-Eaton myasthenic syndrome in Japan.

Background: There was no nationwide epidemiological study of Lambert-Eaton myasthenic syndrome (LEMS) in Japan; therefore, we conducted a nationwide survey. Methods: For the first survey, we sent survey sheets to randomly selected medical departments (n=7545) to obtain the number of LEMS who visited medical departments between 1 January 2017 and 31 December 2017. For the second survey, we sent survey sheets to the corresponding medical departments to obtain clinical information on LEMS. Results: We received 2708 responses (recovery rate: 35.9%) to the first survey. We estimated the number of LEMS as 348 (95% CI 247 to 449). The prevalence was 2.7 (95% CI 1.9 to 3.5) in 1 000 000 population. As a result of the second survey, we obtained 30 case records of 16 men and 14 women. Fourteen patients (46.7%) had a tumour, and 10 out of 14 tumours were small-cell lung carcinoma (71.4%). There was a predominance of men in the LEMS with tumour (paraneoplastic LEMS, P-LEMS) (n=11, 78.6%) and women in the LEMS without tumour (a primary autoimmune form of LEMS, AI-LEMS) (n=11, 68.8%) (p=0.0136). The onset age (mean (SD)) for the P-LEMS was 67.1 (9.0), and that for AI-LEMS was 57.8 (11.2) years old (p=0.0103). The disease duration (median) for P-LEMS was 2 years, and for AI-LEMS was 7.5 years (p=0.0134). Conclusions: The prevalence of LEMS in Japan is similar to that in other countries. There are predominances of men in P-LEMS and women in AI-LEMS.

Two-step nationwide epidemiological survey of myasthenia gravis in Japan 2018.

OBJECTIVE: To study the updated prevalence and clinical features of myasthenia gravis (MG) in Japan during 2017. METHODS: We sent survey sheets to the randomly selected medical departments (number = 7,545). First, we asked the number of MG patients who visited medical departments from January 1, 2017, to December 31, 2017. Then, we sent the second survey sheet to the medical departments that answered the first survey to obtain the clinical information of patients who received MG diagnosis between January 1, 2015, and December 31, 2017. RESULTS: The received answer to the first survey were 2,708 (recovery rate: 35.9%). After all, the prevalence of the 100,000 population was estimated as 23.1 (95%CI: 20.5-25.6). As a result of the second survey, we obtained 1,464 case records. After checking the duplications and lacking data, we utilized 1,195 data for further analysis. The median [interquartile range (IQR)] from the onset age of total patients was 59 (43-70) years old. The male-female ratio was 1: 1.15. The onset age [median (IQR)] for female patients was 58 (40-72) years old, and that for male patients was 60 (49-69) years old (Wilcoxon-Mann-Whitney test, p = 0.0299). We divided patients into four categories: 1) anti-acetylcholine receptor antibody (AChRAb) (+) thymoma (Tm) (-), 2) AChRAb(+)Tm(+), 3) anti-muscle-specific kinase antibody (MuSKAb) (+), and AChRAb(-)MuSKAb(-) (double negative; DN). The onset age [median (IQR)] of AChRAb(+)Tm(-) was 64 (48-73) years old, and AChRb(+)Tm(+) was 55 (45-66), MuSKAb(+) was 49 (36-64), DN was 47 (35-60) year old. The multivariate logistic regression analysis using sex, initial symptoms, repetitive nerve stimulation test (RNST), and edrophonium test revealed that sex, ocular symptoms, bulbar symptoms, and RNST were factors to distinguish each category. The myasthenia gravis activities of daily living profile at the severest state were significantly higher in MuSKAb(+). MuSKAb(+) frequently received prednisolone, tacrolimus plasmapheresis, and intravenous immunoglobulin; however, they received less acetylcholine esterase inhibitor. 99.2% of AChRAb(+)Tm(+) and 15.4% of AChRAb(+)Tm(-) received thymectomy. MuSKAb(+) did not receive thymectomy, and only 5.7% of DN received thymectomy. The prognosis was favorable in all categories. CONCLUSION: Our result revealed that the prevalence of Japanese MG doubled from the previous study using the same survey method in 2006. We also found that the onset age shifted to the elderly, and the male-female ratio reached almost even. Classification in four categories; AChRAb(+)Tm(-), AChRAb(+)Tm(+), MuSKAb(+), and DN, well describe the specific clinical features of each category and differences in therapeutic approaches.

Randomised, double-blind, placebo-controlled study of tacrolimus in myasthenia gravis.

OBJECTIVES: To evaluate the ability of tacrolimus to reduce the corticosteroid dose in patients with myasthenia gravis (MG) and the drug's safety in a double-blind, placebo-controlled, parallel group study. METHODS: Patients being treated with oral prednisolone at doses equivalent to 10-20 mg/day, and with stable symptoms, were randomised to tacrolimus or placebo in a 28-week double-blind study. The dose of corticosteroid was tapered with the procedures specified in the protocol. The primary efficacy endpoint was the mean daily prednisolone dose given in the last 12 weeks of the study. RESULTS: Eighty patients received the study drug (40 patients in each group) and were included in the full analysis set. In the full analysis set, there was no significant difference in the primary efficacy endpoint between the two groups (p = 0.078). However, some secondary analyses suggested the steroid-sparing effect of tacrolimus. Tacrolimus was well tolerated, and no safety concerns were noted. CONCLUSIONS: This study suggests that tacrolimus has a potential advantage as a steroid-sparing agent in the treatment of MG patients. CLINICAL TRIAL REGISTRATION NUMBER: NCT00309088. Name of the trial registry: FK506 Phase 3 STUDY: A STUDY for Steroid Non-Resistant MG Patients.

[Usefulness of epidural anesthesia for percutaneous endoscopic lumbar discectomy (PELD)].

BACKGROUND AND METHODS: To study feasibility of epidural anesthesia for percutaneous endoscopic lumbar discectomy (PELD), we made a retrospective comparison of three anesthetic groups (28 cases with epidural anesthesia, 19 cases with local anesthesia, and 28 cases with general anesthesia) undergoing PELD. RESULTS: Three groups matched each other in age, the surgical site, and the duration of surgery; however, the frequency of male patients was significantly greater in the local anesthesia (LA) group. In the epidural anesthesia (EA) group, there was no patient who required a change of the anesthetic technique or analgesics administration during surgery. In EA group, patients received smaller amount of local anesthetic but spent longer time in the operating room compared with those in LA group. EA and GA groups included several cases staying long time in the hospital and presented wide statistical dispersion of the duration of hospitalization. There was no difference in the dose of local anesthetics, the duration of total procedure, or time to discharge between EA and GA groups. CONCLUSIONS: Epidural anesthesia is suggested to be a useful option for anesthetic techniques in patients undergoing PELD.

Adverse Childhood Experience Is Associated With Disrupted White Matter Integrity in Autism Spectrum Disorder: A Diffusion Tensor Imaging Study.

Individuals with autism spectrum disorder (ASD) have an increased risk of adverse childhood experiences (ACEs) than typically developed (TD) children. Since multiple lines of studies have suggested that ACEs are related to myelination in the frontal lobe, an exposure to ACEs can be associated with white matter microstructural disruption in the frontal lobe, which may be implicated in subsequential psychological deficits after the adulthood. In this study, we investigated the relationship between ACEs and microstructural integrity on frontal lobe-related white matter tracts using diffusion tensor imaging in 63 individuals with ASD and 38 TD participants. Using a tractography-based analysis, we delineated the uncinate fasciculus (UF), dorsal cingulum (Ci), and anterior thalamic radiation (ATR), which are involved in the neural pathology of ASD, and estimated each diffusion parameter. Compared to the TD participants, individuals with ASD displayed significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the left ATR. Then, ASD individuals exposed to severe ACEs displayed higher RD than those exposed to mild ACEs and TD participants in the left ATR. Moreover, the severity of ACEs, particularly neglect, correlated with lower FA and higher RD in the left UF and ATR in individuals with ASD, which was not observed in TD participants. These results suggest that an exposure to ACEs is associated with abnormality in the frontal lobe-related white matter in ASD.

Association of adverse childhood experiences and precuneus volume with intrusive reexperiencing in autism spectrum disorder.

Compared to typically developing (TD) children, people with autism spectrum disorder (ASD) have an increased risk of adverse childhood experiences (ACEs). Exposure to ACEs is associated with adult ASD psychological comorbidities, such as posttraumatic stress disorder (PTSD). Occurrence of intrusive event reexperiencing, characteristic of PTSD, often causes social dysfunction in adults with ASD, but its pathological basis is unclear. This study examined brain regions related to the severity of intrusive reexperiencing and explored whether ACE severity was associated with that of intrusive reexperiencing and/or extracted regional gray matter volume. Forty-six individuals with ASD and 41 TD subjects underwent T1-weighted magnetic resonance imaging and evaluation of ACEs and intrusive reexperiencing. Brain regions related to the severity of intrusive reexperiencing in both groups were identified by voxel-based whole brain analyses. Associations among the severity of intrusive reexperiencing, that of ACEs, and gray matter volume were examined in both groups. The severities of intrusive reexperiencing and ACEs were significantly associated with reduced gray matter volume in the right precuneus in individuals with ASD but not in TD subjects. Although the right precuneus gray matter volume was smaller in individuals with ASD and severe ACEs than in those with mild ACEs or TD subjects, it was similar in the latter two groups. However, ACE-dependent gray matter volume reduction in the right precuneus led to intrusive reexperiencing in individuals with ASD. This suggests that exposure to ACEs is associated with right precuneus gray matter reduction, which is critical for intrusive reexperiencing in adults with ASD. LAY SUMMARY: Individuals with autism spectrum disorder (ASD) are at increased risk of adverse childhood experiences (ACEs) and of subsequent manifestation of intrusive reexperiencing of stressful life events. The present study found that reduced gray matter volume in the right precuneus of the brain was associated with more severe intrusive reexperiencing of ACEs by individuals with ASD. These results suggest that ACEs affect neural development in the precuneus, which is the pathological basis of intrusive event reexperiencing in ASD.