Yuka Matsuo

Differentiation of Brain Tumor Recurrence from Post-Radiotherapy Necrosis with 11C-Methionine PET: Visual Assessment versus Quantitative Assessment

Purpose The aim of this multi-center study was to assess the diagnostic capability of visual assessment in L-methyl-11C-methionine positron emission tomography (MET-PET) for differentiating a recurrent brain tumor from radiation-induced necrosis after radiotherapy, and to compare it to the accuracy of quantitative analysis. Methods A total of 73 brain lesions (glioma: 31, brain metastasis: 42) in 70 patients who underwent MET-PET were included in this study. Visual analysis was performed by comparison of MET uptake in the brain lesion with MET uptake in one of four regions (around the lesion, contralateral frontal lobe, contralateral area, and contralateral cerebellar cortex). The concordance rate and logistic regression analysis were used to evaluate the diagnostic ability of visual assessment. Receiver-operating characteristic curve analysis was used to compare visual assessment with quantitative assessment based on the lesion-to-normal (L/N) ratio of MET uptake. Results Interobserver and intraobserver κ-values were highest at 0.657 and 0.714, respectively, when assessing MET uptake in the lesion compared to that in the contralateral cerebellar cortex. Logistic regression analysis showed that assessing MET uptake in the contralateral cerebellar cortex with brain metastasis was significantly related to the final result. The highest area under the receiver-operating characteristic curve (AUC) with visual assessment for brain metastasis was 0.85, showing no statistically significant difference with L/Nmax of the contralateral brain (AUC = 0.89) or with L/Nmean of the contralateral cerebellar cortex (AUC = 0.89), which were the areas that were the highest in the quantitative assessment. For evaluation of gliomas, no specific candidate was confirmed among the four areas used in visual assessment, and no significant difference was seen between visual assessment and quantitative assessment. Conclusion The visual assessment showed no significant difference from quantitative assessment of MET-PET with a relevant cut-off value for the differentiation of recurrent brain tumors from radiation-induced necrosis.

Fixational saccades reflect volitional action preparation

Human volitional actions are preceded by preparatory processes, a critical mental process of cognitive control for future behavior. Volitional action preparation is regulated by large-scale neural circuits including the cerebral cortex and the basal ganglia. Because volitional action preparation is a covert process, the network dynamics of such neural circuits have been examined by neuroimaging and recording event-related potentials. Here, we examined whether such covert processes can be measured by the overt responses of fixational saccades (including microsaccades), the largest miniature eye movements that occur during eye fixation. We analyzed fixational saccades while adult humans maintained fixation on a central visual stimulus as they prepared to generate a volitional saccade in response to peripheral stimulus appearance. We used the antisaccade paradigm, in which subjects generate a saccade toward the opposite direction of a peripheral stimulus. Appropriate antisaccade performance requires the following two aspects of volitional control: 1) facilitation of saccades away from the stimulus and 2) suppression of inappropriate saccades toward the stimulus. We found that fixational saccades that occurred before stimulus appearance reflected the dual preparatory states of saccade facilitation and suppression and correlated with behavioral outcome (i.e., whether subjects succeeded or failed to cancel inappropriate saccades toward the stimulus). Moreover, fixational saccades explained a large proportion of individual differences in behavioral performance (poor/excellent) across subjects. These results suggest that fixational saccades predict the outcome of future volitional actions and may be used as a potential biomarker to detect people with difficulties in volitional action preparation.

Fixational saccades alter the gap effect

The reaction times of saccadic eye movements have been studied extensively as a probe for cognitive behavior controlled by large‐scale cortical and subcortical neural networks. Recent studies have shown that the reaction times of targeting saccades toward peripheral visual stimuli are prolonged by fixational saccades, the largest miniature eye movements including microsaccades. We have shown previously that the frequency of fixational saccades is decreased by volitional action preparation controlled internally during the antisaccade paradigm (look away from a stimulus). Instead, here we examined whether fixational saccade modulation induced externally by sensory events could also account for targeting saccade facilitation by the same sensory events. When targeting saccades were facilitated by prior fixation stimulus disappearance (gap effect), fixational saccade occurrence was reduced, which could theoretically facilitate targeting saccades. However, such reduction was followed immediately by the rebound of fixational saccade occurrence in some subjects, which could eliminate potential benefits from the previous fixational saccade reduction. These results do not mean that fixational saccades were unrelated to the gap effect because they indeed altered that effect by delaying targeting saccade initiation on trials without the fixation gap more strongly than trials with it. Such changes might be attributed to the disruption of volitional saccade preparation because the frequency of fixational saccades observed in this study was associated with the ability of volitional control over antisaccade behavior. These results suggest that fixational saccades alter the gap effect on targeting saccade reaction times, presumably by disrupting volitional saccade commands.

Gap Effect Abnormalities during a Visually Guided Pro-Saccade Task in Children with Attention Deficit Hyperactivity Disorder

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that starts in early childhood and has a comprehensive impact on psychosocial activity and education as well as general health across the lifespan. Despite its prevalence, the current diagnostic criteria for ADHD are debated. Saccadic eye movements are easy to quantify and may be a quantitative biomarker for a wide variety of neurological and psychiatric disorders, including ADHD. The goal of this study was to examine whether children with ADHD exhibit abnormalities during a visually guided pro-saccadic eye-movement and to clarify the neurophysiological mechanisms associated with their behavioral impairments. Thirty-seven children with ADHD (aged 5–11 years) and 88 typically developing (TD) children (aged 5–11 years) were asked to perform a simple saccadic eye-movement task in which step and gap conditions were randomly interleaved. We evaluated the gap effect, which is the difference in the reaction time between the two conditions. Children with ADHD had a significantly longer reaction time than TD children (p < 0.01) and the gap effect was markedly attenuated (p < 0.01). These results suggest that the measurement of saccadic eye movements may provide a novel method for evaluating the behavioral symptoms and clinical features of ADHD, and that the gap effect is a potential biomarker for the diagnosis of ADHD in early childhood.

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia: A Case With Long-term Follow-up.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a relatively new disease classification first reported in 1992.1 In the 2015 World Health Organization (WHO) classification, DIPNECH was classified as a type of preinvasive lesion, often accompanied by carcinoid and carcinoid tumorlets.2 Because few DIPNECH cases have been reported, the diagnosis, treatment, and prognosis criteria of DIPNECH have not been established. We report a DIPNECH case with a long-term follow-up, and we review the previous DIPNECH reports.

Saccadic eye movements as a neural correlate measure of preparatory set in children with ADHD

O2-7-2-4 The establishment and analysis of 26S proteasome conditional knockout mice for the mechanisms of neurodegenerative diseases Yoshitaka Tashiro 1 , Haruhisa Inoue 2, Maya Yamazaki 3, Manabu Abe 3, Hidehumi Ito 1, Hidemi Misawa 4, Kenji Sakimura 3, Ryosuke Takahashi 1,5 1 Department of Neurology, Kyoto University Graduate School of Medicine 2 Center for iPS Cell Research and Application, Institute for integrated Cell-Material Sciences. Kyoto University 3 Basic Neuroscience Branch, Niigata University Brain Research 4 Department of Pharmacology, School of Medicine, Keio University 5 JST-CREST