Bilateral Frontal Lobes Research Articles

Brain metabolic signatures in patients with genetic and nongenetic amyotrophic lateral sclerosis.

To study the brain metabolic signature in Chinese amyotrophic lateral sclerosis (ALS) patients and compare the difference in brain metabolic patterns between ALS with and without genetic variants. We included 146 patients with ALS and 128 healthy controls (HCs). All patients with ALS underwent genetic testing to screen for ALS related genetic variants and were then divided into genetic (n = 22) and nongenetic ALS (n = 93) subgroups. All participants underwent brain 18 F-FDG-PET scans. Group comparisons were performed using the two-sample t-test model of SPM12. We identified a large of hypometabolic clusters in ALS patients as compared with HCs, especially in the bilateral basal ganglia, midbrain, and cerebellum. Moreover, hypometabolism in the bilateral temporal lobe, precentral gyrus and hypermetabolism in the left anterior cingulate, occipital lobe, and bilateral frontal lobe were also found in ALS patients as compared with HCs. Compared with nongenetic ALS patients, genetic ALS patients showed hypometabolism in the right postcentral gyrus, precuneus, and middle occipital gyrus. The incidence of sensory disturbance in patients with genetic ALS was higher than that in patients with nongenetic ALS (5 of 22 [22.72%] vs. 7 of 93 [7.52%], p = 0.036). Our investigation provided unprecedented evidence of relative hypometabolism in the midbrain and cerebellum in ALS patients. Genetic ALS patients showed a specific signature of brain metabolism and a higher incidence of sensory disturbance, indicating that genetic factors may be an underlying cause affecting the brain metabolism and increasing the risk of sensory disturbance in ALS.

Early recovery of cognition and brain plasticity after surgery in children with low-grade frontal lobe tumors.

Low-grade frontal lobe tumors (LGFLT) can be cured through total resection, but surgical trauma could impair higher-order cognitive function. We aim to characterize the short-term natural cognitive recovery and brain plasticity in surgically-treated pediatric patients with LGFLT. Ten pediatric patients with LGFLT were enrolled. Their cognitive function was assessed before the surgery (S0), in the first month post-surgery (S1), and 3-6 months post-surgery (S2), using the CNS Vital Signs battery. DTI and rs-fMRI were performed during the same time periods. Changes of cognition and image metrics between S1>S0 and S2>S1 were analyzed. The Motor Speed (MotSp) and Reaction Time (RT) scores significantly decreased in S1 and recovered in S2. Rs-fMRI showed decreased functional connectivity (FC) between the bilateral frontal lobes and bilateral caudates, putamina, and pallidi in S1>S0 (voxel threshold , cluster threshold ). In S2>S1, FC recovery was observed in the neighboring frontal cortex areas ( , ). Among them, the FC in the caudates-right inferior frontal gyri was positively correlated to the RT ( ). A DTI Tract-based spatial statistics (TBSS) analysis showed decreased fractional anisotropy and axial diffusivity mainly in the corticospinal tracts, cingulum, internal capsule, and external capsule at 0-6 months post-surgery (TFCE- ). The DTI metrics were not associated with the cognitive data. Processing speed impairment after an LGFLT resection can recover naturally within 3-6 months in school-age children. Rs-fMRI is more sensitive to short-term brain plasticity than DTI TBSS analysis. "Map expansion" plasticity in the frontal-basal ganglia circuit may contribute to the recovery.

Microglial activation in the frontal cortex predicts cognitive decline in frontotemporal dementia.

Frontotemporal dementia is clinically and neuropathologically heterogeneous, but neuroinflammation, atrophy, and cognitive impairment occur in all of its principal syndromes. Across the clinical spectrum of frontotemporal dementia, we assess the predictive value of in vivo neuroimaging measures of microglial activation and grey-matter volume on the rate of future cognitive decline. We hypothesised that inflammation is detrimental to cognitive performance, in addition to the effect of atrophy. Thirty patients with a clinical diagnosis of frontotemporal dementia underwent a baseline multi-modal imaging assessment, including [11C]PK11195 positron emission tomography (PET) to index microglial activation, and structural magnetic resonance imaging (MRI) to quantify grey-matter volume. Ten people had behavioural variant frontotemporal dementia, ten the semantic variant of primary progressive aphasia and ten had the non-fluent agrammatic variant of primary progressive aphasia. Cognition was assessed at baseline and longitudinally with the revised Addenbrooke's Cognitive Examination (ACE-R), at an average of 7-month intervals (for an average of ∼2 years, up to ∼5 years). Regional [11C]PK11195 binding potential and grey-matter volume were determined, and these were averaged within four hypothesis-driven regions of interest: bilateral frontal and temporal lobes. Linear mixed-effect models were applied to the longitudinal cognitive test scores, with [11C]PK11195 binding potentials and grey-matter volumes as predictors of cognitive performance, with age, education and baseline cognitive performance as covariates. Faster cognitive decline was associated with reduced baseline grey-matter volume and increased microglial activation in frontal regions, bilaterally. In frontal regions, microglial activation and grey-matter volume were negatively correlated, but provided independent information, with inflammation the stronger predictor of the rate of cognitive decline. When clinical diagnosis was included as a factor in the models, a significant predictive effect was found for [11C]PK11195 BPND in the left frontal lobe (-0.70, p=0.01), but not for grey-matter volumes (p>0.05), suggesting that inflammation severity in this region relates to cognitive decline regardless of clinical variant. The main results were validated by two-step prediction frequentist and Bayesian estimation of correlations, showing significant associations between the estimated rate of cognitive change (slope) and baseline microglial activation in the frontal lobe. These findings support preclinical models in which neuroinflammation (by microglial activation) accelerates the neurodegenerative disease trajectory. We highlight the potential for immunomodulatory treatment strategies in frontotemporal dementia, in which measures of microglial activation may also improve stratification for clinical trials.

Intraparenchymal and Subarachnoid Hemorrhage in Stereotactic Electroencephalography Caused by Indirect Adjacent Arterial Injury: Illustrative Case

The complication rate of stereotactic electroencephalography (SEEG) is generally low, but various types of postoperative hemorrhage have been reported. We presented an unusual hemorrhagic complication after SEEG placement. A 20-year-old man presented with suspected frontal lobe epilepsy. We implanted 11 SEEG electrodes in the bilateral frontal lobes and the left insula. Computed tomography after implantation showed intraparenchymal hemorrhage in the left temporal lobe and insula and subarachnoid hemorrhage in the left Sylvian cistern. Later, the point of vessel injury was revealed from the identification of a pseudoaneurysm, but this location was not along the planned or actual electrode trajectory. The cause of hemorrhage was suggested to be indirect injury from stretching of the arachnoid trabeculae by the puncture needle.

Brain connectivity dynamics during listening to music and potential impact on task performance.

To analyze brain connectivity dynamics during listening to music and estimate the potential impact on task performance. Fifteen participants (13 males and 2 females) participated in this study based on their interest in Indian classical music. Measurements of the influence of Indian music on task performance were obtained by assessing brain activation using EEG signals. Brain connectivity analysis was performed to visualize the connections between brain regions under various experimental conditions. Visual Go/No Go Stimuli was used to evaluate visual spatial attention during operation by evaluating misses, committed errors, and reaction times. In Task 1 (listening to music only), it was reported that there was a change in the positions of the electrodes (F3, F7) located in the left frontal lobe. The energy of the relative beta component was significantly higher only at F7 during task 1 (p = 0.005). Event-related desynchronization alpha and theta synchronization were significant (p = 0.005) at all electrode sites in the bilateral frontal lobes (F3, F4, F7 and F8) while listening to music and performing tasks (task 2). When the task without music (task 3) was performed, the energy of the relative alpha component was significantly higher at the Fp2 electrode position (p = 0.005). It is noteworthy that the energy of the theta component was significantly lower at the location of the Fp2 electrode (p = 0.005). The frontal asymmetry index score measures were significantly high at F4/F3 and F8/F7 during task 1. The connectivity map of theta synchronization showed a robust association between Fp2 and F8 which was in turn connected to P4 and O2 during Task 2. Results indicated an increased omission and commission errors during Task 3.

A case of behavioral variant frontotemporal dementia presenting with frequent laughter during conversations

We describe a case of behavioral variant frontotemporal dementia (bvFTD) presenting with frequent laughter during conversations. A 72-year-old male patient visited our hospital because of aspontaneity and abnormal behaviors. His medical history revealed epilepsy attacks approximately five years prior, which improved following administration of antiepileptic drugs. At the age of 67 years, the patient began exhibiting aspontaneity and abnormal behaviors, such as leaving a teahouse without paying for his coffee. Neurological examinations indicated moderate dementia and bradykinesia while walking. The patient frequently laughed during conversations with his wife and doctor, creating the impression that he was euphoric. His laughter was neither explosive nor obsessive, and did not involve loss of consciousness or seizures. MRI of the head revealed symmetrical atrophy of the bilateral frontal lobes. SPECT demonstrated decreased cerebral blood flow in the bilateral frontal lobes, particularly in the outer and inner frontal convexities. Based on the patient's clinical history and imaging results, a diagnosis of bvFTD was established. Our literature review identified only one research paper discussing the frequency of laughter in frontotemporal dementia, which suggested that patients with bvFTD laugh less often. However, several reports indicated that patients with FTD exhibit euphoric behaviors more frequently compared to those with other forms of dementia. We hypothesize that euphoric patients with bvFTD may laugh more frequently during conversations, reflecting disorders of emotional expression and a loss of empathy.

¹⁸F-fluorodeoxyglucose-positron emission tomography findings are not related to cognitive functioning in service members with remote history of mild traumatic brain injury.

Determine whether glucose uptake as measured by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging is associated with cognitive performance and cognitive deficits in active duty service members with a history of mild traumatic brain injury (mTBI). 287 patients with a history of mTBI underwent FDG-PET scans at rest and neuropsychological testing at the National Intrepid Center of Excellence at Walter Reed National Military Medical Center. Glucose uptake in the bilateral frontal, parietal, occipital, and temporal lobes, and 58 cortical/cerebellar regions were correlated with seven neuropsychological composite scores, with and without relevant covariates. Perceptual reasoning correlated with bilateral hippocampi glucose uptake (rs = .141-.165, p < .03), processing speed was inversely related to glucose uptake in the left temporal lobe (r = -.134, p = .034), and working memory was related to glucose uptake in the left parietal, temporal, and occipital lobes (rs = .128-.140, p < .05); however, these findings did not survive correction for multiple comparisons. Partial correlations between cognition and the 56 cortical/cerebellar regions of interests were not significant after correction for multiple comparisons. Glucose uptake in the left hippocampus was inversely related to the likelihood of cognitive deficits (OR = .745, p = .041); however, this did not survive correction for multiple comparisons. After correction for multiple comparisons, there was no significant relationship between regional glucose uptake and neurocognitive performance or cognitive deficits. Glucose uptake as measured by FDG-PET is not indicative of cognitive performance in active duty service members with a remote history of mTBI. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A case of non-fluent/agrammatic variant of primary progressive aphasia with logoclonia

We report a case of non-fluent/agrammatic variant of primary progressive aphasia in a 79-year-old right-handed man who was admitted with a 5-year history of non-fluent speech and apraxia of speech. He also presented with agrammatism and logoclonia (the meaningless repetition of the middle or final syllable of a word). Furthermore, brain MRI revealed atrophy of the bilateral frontal and temporal lobes, while N-isopropyl-p-123I-iodoamphetamine single-photon emission computed tomography (SPECT) revealed relative hypoperfusion in the right basal ganglia. In addition, dopamine transporter SPECT revealed a decrease in specific binding ratio values, indicating neural dopamine dysfunction, which led to his diagnosis of progressive non-fluent aphasia with logoclonia. Logoclonia is a severe linguistic dysfunction usually observed in the advanced stages of Alzheimer's disease. However, based on the clinical course and cerebrospinal fluid evaluation results, our patient did not show any features of Alzheimer's disease. Thus, logoclonia might be associated with lesions involving the basal ganglia, right hemisphere, and left frontotemporal lobe.

Effect of Repetitive Transcranial Magnetic Stimulation on Long Coronavirus Disease 2019 with Fatigue and Cognitive Dysfunction.

There is no established treatment for chronic fatigue and various cognitive dysfunctions (brain fog) caused by long coronavirus disease 2019 (COVID-19). We aimed to clarify the effectiveness of repetitive transcranial magnetic stimulation (rTMS) for treating these symptoms. High-frequency rTMS was applied to occipital and frontal lobes in 12 patients with chronic fatigue and cognitive dysfunction 3 months after severe acute respiratory syndrome coronavirus 2 infection. Before and after ten sessions of rTMS, Brief Fatigue Inventory (BFI), Apathy Scale (AS), and Wechsler Adult Intelligence Scale-fourth edition (WAIS4) were determined and N-isopropyl-p-[123I]iodoamphetamine single photon emission computed tomography (SPECT) was performed. Twelve subjects completed ten sessions of rTMS without adverse events. The mean age of the subjects was 44.3 ± 10.7 years, and the mean duration of illness was 202.4 ± 114.5 days. BFI, which was 5.7 ± 2.3 before the intervention, decreased significantly to 1.9 ± 1.8 after the intervention. The AS was significantly decreased after the intervention from 19.2 ± 8.7 to 10.3 ± 7.2. All WAIS4 sub-items were significantly improved after rTMS intervention, and the full-scale intelligence quotient increased from 94.6 ± 10.9 to 104.4 ± 13.0. Hypoperfusion in the bilateral occipital and frontal lobes observed on SPECT improved in extent and severity after ten sessions of rTMS. Although we are still in the early stages of exploring the effects of rTMS, the procedure has the potential for use as a new non-invasive treatment for the symptoms of long COVID.

Spontaneous Heparin-Induced Thrombocytopenia Presenting as Concomitant Bilateral Cerebrovascular Infarction and Acute Coronary Syndrome

Background: Spontaneous heparin-induced thrombocytopenia is a pro-thrombotic syndrome in which anti-heparin antibodies develop without heparin exposure. Case presentation: A 78-year-old man who underwent a successful lumbar laminectomy presented to the hospital 5 days after discharge for stroke-like symptoms and was found to have acute infarcts of the bilateral frontal lobes. The patient was found to be severely thrombocytopenic and was incidentally found to have an inferior wall myocardial infarction. Further investigation led to the diagnosis of bilateral lower extremity deep vein thromboses. His overall clinical presentation prompted a detailed hematologic workup that indicated positivity for heparin-induced thrombocytopenia despite no previous exposure to heparin products. Conclusions: This case illustrates a patient with no prior lifetime heparin exposure who underwent laminectomy with subsequent development of acute infarcts of the bilateral frontal lobes, an inferior wall myocardial infarction, and bilateral lower extremity deep vein thromboses, with concern for sequelae of spontaneous heparin-induced thrombocytopenia.

Contribution of the μ-opioid receptor system to affective disorders in temporal lobe epilepsy: A bidirectional relationship?

Affective disorders are frequent comorbidities of temporal lobe epilepsy (TLE). The endogenous opioid system has been implicated in both epilepsy and affective disorders, and may play a significant role in their bidirectional relationship. In this cross-sectional study, we investigated the association between μ-opioid receptor binding and affective disorders in patients with TLE. Nine patients with TLE and depression/anxiety underwent 11 C-carfentanil positron emission tomography (CFN PET) and neuropsychiatric assessment, including the Hospital Anxiety and Depression Scale and the Positive and Negative Affect Schedule. The normalized CFN PET scans were compared with those of 26 age-matched healthy controls. Correlation analyses with affective symptoms were performed by region of interest-based analysis focusing on the limbic circuit and orbitofrontal cortex. We observed widely reduced CFN binding potential (BP) in bilateral frontal lobes and striata in patients with TLE compared to healthy controls. In the TLE group, more severe anxiety and negative affect were associated with decreased CFN BP in the posterior cingulate gyrus. In patients with TLE, interictally reduced binding in the opioid system was associated with higher levels of anxiety and negative affect. We speculate that seizure-related agonist-driven desensitization and downregulation of opioid receptors could be a potential underlying pathomechanism.

The pathogenesis and treatment of posterior reversible encephalopathy syndrome after neuromyelitis optica spectrum disorder: a case report and literature review

BackgroundPosterior reversible encephalopathy syndrome (PRES) is a rare disease characterized by reversible subcortical vasogenic brain edema. Neuromyelitis optica spectrum disorder (NMOSD) is a frequent neurological autoimmune disease that is rarely reported to complicate PRES.Case presentationHere, we report a case of neuromyelitis optica (NMO) concurrent with PRES. A 50-year-old woman presented with severe impairment of her health visual acuity, with significantly worsening of the motor weakness in both lower limbs during methylprednisolone therapy after her diagnosis of NMO. MRI showed new-onset brain edematous lesions of the bilateral frontal, occipital, and parietal lobes. PRES was considered. Her vision impairment and weakness of the extremities were alleviated after antihypertensive treatment and dehydration. The edema lesions detected by MRI also completely disappeared.ConclusionsWe reviewed 14 cases of NMO with PRES and concluded that the etiology of NMOSD concurrent PRES may be multifactorial, involving pathogenic IgGs against aquaporin-4 (AQP-4) and immunotherapy treatment. Different underlying pathogeneses require different treatment approaches.

Regional activity alterations in Parkinson's disease patients with anxiety disorders: A resting-state functional magnetic resonance imaging study.

Previous studies have revealed alteration of functional connectivity (FC) in Parkinson's disease patients with anxiety (PD-A), but local brain activities associated with anxiety in Parkinson's disease (PD) patients remain to be elucidated. Regional homogeneity (ReHo) analysis was employed to investigate alterations of regional brain activities in PD-A patients. Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 42 PD-A patients, 41 PD patients without anxiety (PD-NA), and 40 age-and gender-matched healthy control (HC) subjects. ReHo analysis was used to investigate the synchronization of neuronal activities in brain regions in the three groups. The relationship between ReHo value and anxiety score in the PD-A group was also investigated. Parkinson's disease patients with anxiety showed increased ReHo values in the bilateral frontal lobes, caudate nucleus, and anterior cingulate gyrus [Gaussian random field (GRF) correction, voxel size p < 0.01, cluster size p < 0.05], compared with PD-NA patients and HC subjects, but the ReHo values of the right cerebellar hemisphere and posterior cerebellar lobe decreased (GRF correction, voxel size p < 0.01, cluster size p < 0.05). The increased ReHo values of the right superior frontal gyrus (r = 0.633, p = 0.001) and anterior cingulate gyrus (r = 0.45, p = 0.01) were positively correlated with anxiety scores in PD-A patients. The development of PD-A may be associated with dysfunctional local activities in multiple brain regions, including the frontal cortex, cerebella, basal ganglia, and limbic system. Abnormal ReHo values in these brain regions may serve as neuroimaging markers for the early diagnosis of PD-A. The results suggest that using ReHo analysis to identify functional changes in core regions may advance our understanding of the pathophysiological mechanisms underlying PD-A.

Characteristic cerebral perfusion pattern in neuronal intranuclear inclusion disease.

Neuronal intranuclear inclusion disease (NIID), which pathogenesis remains largely unclear, is a neurodegenerative disease caused by GGC repeat expansion in NOTCH2NLC gene. As case studies have reported dynamic cortical perfusion changes in NIID, this study aimed to explore the cerebral perfusion pattern in NIID patients. A total of 38 NIID patients and 34 healthy controls (HCs) were recruited, and 2 NIID patients who had had episodic symptoms within 2 months were excluded. Data on demographic characteristics and clinical features were collected. All participants underwent three-dimensional pseudo-continuous arterial spin labeling perfusion magnetic resonance imaging (MRI) scanning. Voxel-based comparisons of cerebral blood flow (CBF) were conducted. NIID patients showed decreased perfusion in the cortex but increased perfusion in the deep brain regions compared with HCs. The regions with significant hypoperfusion were distributed in the bilateral frontal, temporal, parietal, and occipital gyri, with the left frontal gyrus being the most prominent. The regions with significant hyperperfusion included the bilateral basal ganglia, midbrain, pons, para-hippocampal, and parts of the bilateral cerebellum, fusiform, lingual, rectus, orbital, and cingulum anterior gyri, which were adjacent to the midline (all FDR-corrected p <0.05). When comparing the mean CBF value of the whole brain, no significant differences were observed between NIID patients and HCs (28.81 ± 10.1 vs. 27.99 ± 5.68 ml/100 g*min, p = 0.666). Voxel-based analysis showed no significant difference in cerebral perfusion between NIID patients with and without episodic symptoms. The perfusion within the bilateral middle frontal and anterior cingulate gyri showed positive correlations with MMSE and MoCA scores using age, sex, and education as covariates (p <0.005 uncorrected). NIID patients exhibited characteristic cortical hypoperfusion and deep brain hyperperfusion. The perfusion in the bilateral frontal lobe and cingulate gyrus was correlated with the severity of cognitive dysfunction. Cerebral perfusion change may be involved in NIID pathophysiology and serve as a potential indicator for monitoring NIID severity and progression.

Relationship between consciousness level and perfusion computed tomography in patients with prolonged disorders of consciousness.

We assessed the relationship between consciousness level and values of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP) obtained by whole-brain perfusion computed tomography (pCT) in patients with prolonged disorders of consciousness (pDOC). This study included 29 patients in vegetative state (VS), 34 with minimally consciousness state minus (MCS-), and 13 with minimally consciousness state plus (MCS+). All patients were evaluated using the Coma Recovery Scale-Revised (CRS-R), the Glasgow Coma Scale (GCS), and the Full Outline of UnResponsiveness (FOUR). The values of CBF, CBV, MTT, and TTP were obtained from patients who underwent pCT. Differences in CBF, CBV, MTT, and TTP were compared between the three types of pDOC. Correlations between the CRS-R, GCS, and FOUR scores and the pCT results were analyzed. Among the three groups, patients in VS showed a significantly decreased CBF in the bilateral frontal lobe, thalamus, temporal lobe, occipital lobe, brainstem, and damaged part. CBV was significantly reduced in patients with VS in the bilateral frontal lobe, thalamus, temporal lobe, brainstem, and damaged part. The total CRS-R, GCS, and FOUR scores were positively correlated with CBF, CBV, and TTP in almost all regions of interest. Reductions in CBF and CBV calculated with pCT are associated with impaired consciousness and perfusion CT could be a promising tool in evaluating the conscious level in patients with pDOC.

Association of cognitive function and hypoperfusion in Moyamoya disease patients without stroke

The influence of hypoperfusion on cognition in patients with Moyamoya disease (MMD) is unclear. This study investigated cognitive function changes in MMD patients without stroke and illustrated the relationship between cognitive impairment and hypoperfusion. We prospectively performed a structured battery of seven neurocognitive tests on 115 adult MMD patients without stroke and 82 healthy controls. Hemodynamic assessment was performed using dynamic susceptibility contrast-enhanced MRI. The best subset regression (BSR) strategy was used to identify risk factors. Global cognition (MoCA), speed of information processing (TMT-A), executive function (TMT-B), visuospatial function (CDT), and verbal memory (CAVLT) were significantly poorer in MMD patients without stroke than in healthy controls. The TMT-B score significantly correlated with cerebral blood flow (CBF) in the bilateral lateral frontal lobes, centrum semiovale, and temporal lobes. The TMT-A and CAVLT scores significantly correlated with CBF in the left centrum semiovale (L-CSO) and temporal lobes. According to the BSR results, age, education, white matter lesions, and hypoperfusion of the L-CSO were risk factors for cognitive impairment. Hypoperfusion leads to multiple cognitive impairments in MMD patients without stroke. The perfusion of particular areas may help evaluate the cognitive function of MMD patients and guide therapeutic strategies.

Valosin-containing protein Asp395Gly mutation in a patient with frontotemporal dementia: a case report

BackgroundVariants in the valosin-containing protein (VCP) gene were identified as one of the causes for inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia (FTD). Previously identified pathogenic variants in VCP are associated with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) pathologically, but p.Asp395Gly VCP was recently reported to cause familial FTD with tauopathy characterized by neurofibrillary tau tangles (NFT) and not FTLD-TDP. We describe the clinical and genetic findings of a patient with p.Asp395Gly valosin-containing protein (VCP), who was diagnosed with FTD without a family history and in the absence of muscle or bone disease comorbidity.Case presentationThe patient was a 62-year-old man, who developed atypical depression at the age of 37 years. Subsequently, he presented with self-centered behavior at the age of 45 years. The self-centered behavior intensified from around the age of 50 years, which was accompanied by the development of executive dysfunction; therefore, he visited our hospital at 52 years of age. Magnetic resonance imaging revealed bilateral frontal lobe atrophy. Brain perfusion single-photon emission computed tomography revealed bilateral frontal lobe hypoperfusion. The patient fulfilled the diagnostic criteria for behavioral variant of FTD. Ten years after the diagnosis, computed tomography of the trunk and limbs, muscle biopsy, and bone scintigraphy revealed the absence of concomitant muscle and bone disease. The concentrations of cerebrospinal fluid (CSF) total tau and phosphorylated tau proteins were 389 pg/mL and 53.2 pg/mL (cut-off: 50 pg/mL), respectively. Genetic analyses were performed using the whole-exome and Sanger sequencing methods. We identified p.Asp395Gly VCP in this patient with pure FTD.Conclusionsp.Asp395Gly VCP was identified in a patient with likely sporadic FTD without concomitant muscle and bone disease. The CSF analysis suggested that our patient may have FTD due to NFT accumulation similar to the familial FTD patients with p.Asp395Gly VCP recently reported. Our findings suggest that a genetic search for the pathogenic variants of VCP should be considered not only for familial FTD, but also for patients with sporadic FTD, even in the absence of comorbid muscle or bone disease.

Photon vs. Proton Whole Ventricular Radiotherapy for Non-Germinomatous Germ Cell Tumors

<h3>Purpose/Objective(s)</h3> The hypothesis is that dose to normal CNS structures is lower for children treated with proton therapy, as compared to photon therapy for children receiving whole ventricular radiotherapy (WVRT) for non-germinomatous germ cell tumors (NGGCT). We present data from patients enrolled in stratum 1 of the Children's Oncology Group study ACNS1123. <h3>Materials/Methods</h3> Dosimetric data for NGGCT patients on ACNS1123 who received 30.6 Gy WVRT were compared in a post-hoc analysis. Target segmentation was standardized using a contouring atlas as per the study protocol. The PTV was created by creating a 3-5mm geometric expansion from the CTV. Doses to cranial organs-at-risk (OARs) were compared between proton and photon treatments. Clinically relevant dose-volume parameters that were compared included mean dose and dose to 40% of the OAR volume (D40). A subgroup analysis of patients treated with 3 mm PTV margins was performed. Dosimetric comparisons between proton and photons plans were conducted using two-sided Wilcoxon's rank sum test for continuous variables. <h3>Results</h3> Fifty-eight patients had WVRT dosimetry available and were included; 13 (22%) received proton treatment and 45 (78%) received photon treatment. Median age was 10 years old (range 0-21). Mean and D40 doses to the supratentorial brain, cerebellum (see Table), and bilateral temporal, parietal and frontal lobes were statistically significantly lower amongst proton-treated patients compared to photon-treated patients. In a subgroup analysis of patients uniformly treated with a 3 mm planning target volume, patients who received proton therapy continued to have statistically significantly lower doses to brain OARs. <h3>Conclusion</h3> Children treated with proton therapy for WVRT had lower doses to normal brain structures when compared to those treated with photon therapy. Future work will help elucidate whether this dosimetric advantage of proton therapy translates to a reduction in toxicities for these patients.

Computational modeling of electric fields for prefrontal tDCS across patients with schizophrenia and mood disorders

This cross-diagnostic study aims to computationally model electric field (efield) for prefrontal transcranial direct current stimulation in mood disorders and schizophrenia. Enrolled were patients with major depressive disorder (n = 23), bipolar disorder (n = 24), schizophrenia (n = 23), and healthy controls (n = 23). The efield was simulated using SimNIBS software (ver.2.1.1). Electrodes were placed at the left and right prefrontal areas and the current intensity was set to 2 mA intensity. Schizophrenia and major depressive disorder groups showed significantly lower 99.5th percentile efield strength than healthy controls. In voxel-wise analysis, patients with schizophrenia showed a significant reduction of simulated efield strength in the bilateral frontal lobe, cerebellum and brain stem compared with healthy controls. Among the patients with schizophrenia, reduction of simulated efield strength was not significantly correlated with psychiatric symptoms or global functioning. The patients with bipolar disorder showed no significant difference in simulated efield strength compared with healthy controls, and there was no significant difference between the clinical groups. Our results suggest attenuated electrophysiological response to transcranial direct current stimulation to the prefrontal cortex in patients with schizophrenia, and to some extent in patients with major depressive disorder.

Changes in and asymmetry of the proteome in the human fetal frontal lobe during early development

Inherent hemispheric asymmetry is important for cognition, language and other functions. Describing normal brain and asymmetry development during early development will improve our understanding of how different hemispheres prioritize specific functions, which is currently unknown. Here, we analysed developmental changes in and asymmetry of the proteome in the bilateral frontal lobes of three foetal specimens in the late first trimester of pregnancy. We found that during this period, the difference in expression between gestational weeks (GWs) increased, and the difference in asymmetric expression decreased. Changes in the patterns of protein expression differed in the bilateral frontal lobes. Our results show that brain asymmetry can be observed in early development. These findings can guide researchers in further investigations of the mechanisms of brain asymmetry. We propose that both sides of the brain should be analysed separately in future multiomics and human brain mapping studies.