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Abstract The progression of neuroinflammation after anti-parkinsonian therapy on the Parkinson’s disease (PD) brain and in vivo evidence of the therapy purporting neuroprotection remain unclear. To elucidate this, we examined changes in microglial activation, nigrostriatal degeneration, and clinical symptoms longitudinally after dopamine replacement therapy in early, optimally-controlled PD patients with and without zonisamide treatment using positron emission tomography (PET). We enrolled sixteen PD patients (Hoehn and Yahr stage 1–2), and age-matched normal subjects. PD patients were randomly divided into two groups: one (zonisamide+) that did and one (zonisamide−) that did not undergo zonisamide therapy. Annual changes in neuroinflammation ([11C]DPA713 PET), dopamine transporter availability ([11C]CFT PET) and clinical severity were examined. Voxelwise differentiations in the binding of [11C]DPA713 (BPND) and [11C]CFT (SUVR) were compared with normal data and between the zonisamide+ and zonisamide− PD groups. The cerebral [11C]DPA713 BPND increased with time predominantly over the parieto-occipital region in PD patients. Comparison of the zonisamide+ group with the zonisamide− group showed lower levels in the cerebral [11C]DPA713 BPND in the zonisamide+ group. While the striatal [11C]CFT SUVR decreased longitudinally, the [11C]CFT SUVR in the nucleus accumbens showed a higher binding in the zonisamide+ group. A significant annual increase in attention score were found in the zonisamide+ group. The current results indicate neuroinflammation proceeds to the whole brain even after anti-parkinsonian therapy, but zonisamide coadministration might have the potential to ameliorate proinflammatory responses, exerting a neuroprotective effect in more damaged nigrostriatal regions with enhanced attention in PD.

Abstract Cough is known as a protective reflex to keep the airway free from harmful substances. Although brain activity during cough was previously examined mainly by functional magnetic resonance imaging (fMRI) with model analysis, this method does not capture real brain activity during cough. To obtain accurate measurements of brain activity during cough, we conducted whole-brain scans during different coughing tasks while correcting for head motion using a restraint-free positron emission tomography (PET) system. Twenty-four healthy right-handed males underwent multiple PET scans with [15O]H2O. Four tasks were performed during scans: “resting”; “voluntary cough (VC)”, which simply repeated spontaneous coughing; “induced cough (IC)”, where participants coughed in response to an acid stimulus in the cough‐inducing method with tartaric acid (CiTA); and “suppressed cough (SC)”, where coughing was suppressed against CiTA. The whole brain analyses of motion-corrected data revealed that VC chiefly activated the cerebellum extending to pons. In contrast, CiTA-related tasks (IC and SC) activated the higher sensory regions of the cerebral cortex and associated brain regions. The present results suggest that brain activity during simple cough is controlled chiefly by infratentorial areas, whereas manipulating cough predominantly requires the higher sensory brain regions to allow top-down control of information from the periphery.

Abstract We propose a new therapeutic strategy for Alzheimer's disease (AD). Brain peptide p3‐Alcβ37 is generated from the neuronal protein alcadein β through cleavage of γ‐secretase, similar to the generation of amyloid β (Aβ) derived from Aβ‐protein precursor/APP. Neurotoxicity by Aβ oligomers (Aβo) is the prime cause prior to the loss of brain function in AD. We found that p3‐Alcβ37 and its shorter peptide p3‐Alcβ9‐19 enhanced the mitochondrial activity of neurons and protected neurons against Aβo‐induced toxicity. This is due to the suppression of the Aβo‐mediated excessive Ca2+ influx into neurons by p3‐Alcβ. Successful transfer of p3‐Alcβ9‐19 into the brain following peripheral administration improved the mitochondrial viability in the brain of AD mice model, in which the mitochondrial activity is attenuated by increasing the neurotoxic human Aβ42 burden, as revealed through brain PET imaging to monitor mitochondrial function. Because mitochondrial dysfunction is common in the brain of AD patients alongside increased Aβ and reduced p3‐Alcβ37 levels, the administration of p3‐Alcβ9‐19 may be a promising treatment for restoring, protecting, and promoting brain functions in patients with AD.

Abstract Purpose While marked reductions in neural activity and mitochondrial function have been reported in Alzheimer’s disease (AD), the degree of mitochondrial activity in mild cognitive impairment (MCI) or early-stage AD remains unexplored. Here, we used positron emission tomography (PET) to examine the direct relationship between mitochondrial activity (18F-BCPP-EF) and β-amyloid (Aβ) deposition (11C-PiB) in the same brains of senescence-accelerated mouse prone 10 (SAMP10) mice, an Aβ-developing neuroinflammatory animal model showing accelerated senescence with deterioration in cognitive functioning similar to that in MCI. Methods Five- to 25-week-old SAMP10 and control SAMR1 mice, were used in the experiments. PET was used to measure the binding levels (standard uptake value ratios; SUVRs) of [18F]2-tert-butyl-4-chloro-5-2H-pyridazin-3-one (18F-BCPP-EF) for mitochondrial complex 1 availability, and 11C-PiB for Aβ deposition, in the same animals, and immunohistochemistry for ATPB (an ATP synthase on the mitochondrial inner membrane) was also performed, to determine changes in mitochondrial activity in relation to amyloid burden during the early stage of cognitive impairment. Results The SUVR of 18F-BCPP-EF was significantly lower and that of 11C-PiB was higher in the 15-week-old SAMP10 mice than in the control and 5-week-old SAMP10 mice. The two parameters were found to negatively correlate with each other. The immunohistochemical analysis demonstrated temporal upregulation of ATPB levels at 15-week-old, but decreased at 25 week-old SAMP10 mice. Conclusion The present results provide in vivo evidence of a decrease in mitochondrial energy production and elevated amyloidosis at an early stage in SAMP10 mice. The inverse correlation between these two phenomena suggests a concurrent change in neuronal energy failure by Aβ-induced elevation of neuroinflammatory responses. Comparison of PET data with histological findings suggests that temporal increase of ATPB level may not be neurofunctionally implicated during neuropathological processes, including Aβ pathology, in an animal model of early-phase AD spectrum disorder.

Abstract The positron emission tomography probes 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and 2-tert-butyl-4-chloro-5-{6-[2-(2-[18F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF) are designed to evaluate glycolysis and oxidative phosphorylation, respectively, and are both used to estimate neuronal activity. However, previous studies have shown a discrepancy in these probes’ accumulation in the compromised region, possibly due to the presence of activated microglia acting like deleterious or neuroprotective phenotypes. Hence, we evaluated lipopolysaccharide (LPS)- and interleukin 4 (IL4)-stimulated microglial uptake of [14C]2DG and [18F]BCPP-EF to give a new insight into the hypothesis that different uptake of [18F]FDG and [18F]BCPP-EF can be ascribed to the different metabolic pathways activated during microglial activation. LPS or IL4 stimulation increased the proinflammatory or anti-inflammatory marker gene expression in microglial cells. In LPS-stimulated cells, [14C]2DG uptake and glycolysis related gene expression were elevated, and [18F]BCPP-EF uptake was reduced. In IL4-stimulated cells, [18F]BCPP-EF uptake was increased, and [14C]2DG uptake was decreased. The expression of genes involved in glycolysis and mitochondrial complex I subunits was not changed by IL4 stimulation. The uptake of [14C]2DG and [18F]BCPP-EF differs in LPS- and IL4-stimulated polarized microglial cells. The present results suggest that the in vivo accumulation of metabolic tracers [18F]FDG and [18F]BCPP-EF can be influenced by the different aspects of neuroinflammation.

Abstract Background Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF. Methods Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed. Results The [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND (R = 0.2679, p = 0.04), but not [11C] PiB SUVR. Conclusions Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.

Background The AT(N) classification was proposed for categorising individuals according to biomarkers. However, AT(N) profiles may vary depending on the markers chosen and the target population.Methods We stratified 177 individuals who participated in the Japanese Alzheimer’s Disease Neuroimaging Initiative by AT(N) classification according to cerebrospinal fluid (CSF) biomarkers. We compared the frequency of AT(N) profiles between the classification using total tau and neurofilament light chain (NfL) as N markers (AT(N)tau and AT(N)NfL). Baseline characteristics, and longitudinal biological and clinical changes were examined between AT(N) profiles.Results We found that 9% of cognitively unimpaired subjects, 49% of subjects with mild cognitive impairment, and 61% of patients with Alzheimer’s disease (AD) dementia had the biological AD profile (ie, A+T+) in the cohort. The frequency of AT(N) profiles substantially differed between the AT(N)tau and AT(N)NfL classifications. When we used t-tau as the N marker (AT(N)tau), those who had T− were more frequently assigned to (N)−, whereas those who had T+were more frequently assigned to (N)+ than when we used NfL as the N marker (AT(N)NfL). During a follow-up, the AD continuum group progressed clinically and biologically compared with the normal biomarker group in both the AT(N)tau and AT(N)NfL classifications. More frequent conversion to dementia was observed in the non-AD pathological change group in the AT(N)tau classification, but not in the AT(N)NfL classification.Conclusions AT(N)tau and AT(N)NfL in CSF may capture different aspects of neurodegeneration and provide a different prognostic value. The AT(N) classification aids in understanding the AD continuum biology in various populations.

This study aimed to investigate the effect of cognitive reserve (CR) on the rate of cognitive decline and cerebral glucose metabolism in amnestic mild cognitive impairment (MCI) using the Study on Diagnosis of Early Alzheimer’s Disease-Japan (SEAD-J) dataset. The patients in SEAD-J underwent cognitive tests and fluorodeoxyglucose-positron emission tomography (FDG-PET). MCI to be studied was classified as amnestic MCI due to Alzheimer’s disease (AD) with neurodegeneration. A total of 57 patients were visually interpreted as having an AD pattern (P1 pattern, Silverman’s classification). The 57 individuals showing the P1 pattern were divided into a high-education group (years of school education ≥13, N = 18) and a low-education group (years of school education ≤12, N = 39). Voxel-based statistical parametric mapping revealed more severe hypometabolism in the high-education group than in the low-education group. Glucose metabolism in the hippocampus and temporoparietal area was inversely associated with the years of school education in the high- and low-education groups (N = 57). General linear mixed model analyses demonstrated that cognitive decline was more rapid in the high-education group during 3-year follow-up. These results suggest that the cerebral glucose metabolism is lower and cognitive function declines faster in patients with high CR of amnestic MCI due to AD defined by FDG-PET.

Background: Transcranial direct current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) hypothetically modulates cognitive functions by facilitating or inhibiting neuronal activities chiefly in the cerebral cortex. The effect of tDCS in the deeper brain region, the basal ganglia-cortical circuit, remains unknown. Objective: To investigate the interaction between γ-aminobutyric acid (GABA) concentrations and dopamine release following tDCS. Method: This study used a randomized, placebo-controlled, double-blind, crossover design. Seventeen healthy male subjects underwent active and sham tDCS (13 min twice at an interval of 20 min) with the anode placed at the left DLPFC and the cathode at the right DLPFC, followed by examinations with [11C]-raclopride positron emission topography (PET) and GABA-magnetic resonance spectroscopy (MRS). MRS voxels were set in the left DLPFC and bilateral striata. Paired t-tests and regression analyses were performed for PET and MRS parameters. Results: MRS data analyses showed elevations in GABA in the left striatum along with moderate reductions in the right striatum and the left DLPFC after active tDCS. PET data analyses showed that reductions in [11C]-raclopride binding potentials (increase in dopamine release) in the right striatum were inversely correlated with those in the left striatum after active tDCS. GABA reductions in the left DLPFC positively correlated with elevations in GABA in the left striatum and with increases in right striatal dopamine release and negatively correlated with increases in left striatal dopamine release. Conclusion: The present results suggest that tDCS to the DLPFC modulates dopamine-GABA functions in the basal ganglia-cortical circuit.

Abstract Background Functional somatic syndrome (FSS) is a disorder characterized by clusters of medically unexplained symptoms. Some women suffer from persistent FSS after human papillomavirus (HPV) vaccination. However, a causal relationship has not been established, and the pathophysiology of FSS remains elusive. Here, we aimed to identify the brain regions showing altered cerebral metabolism and neuroinflammation in patients with FSS and to correlate the measures of positron emission tomography (PET) with clinical data. Twelve women diagnosed with FSS following HPV vaccination (FSS group) underwent both [18F]FDG-PET to measure glucose metabolism and [11C]DPA713-PET to measure neuroinflammation. [18F]FDG standardized uptake value ratio (SUVR) and [11C]DPA713 binding potential (BPND) values were compared voxel-wise between the FSS and control groups (n = 12 for [18F]FDG, n = 16 for [11C]DPA713). A region-of-interest (ROI)-based analysis was performed to correlate PET parameters with clinical scores. Statistical significance was set at p < 0.05 corrected for multiple comparisons. Results Statistical parametric mapping revealed a concomitant significant decrease of [18F]FDG SUVR and increase of [11C]DPA713 BPND in the regions covering the thalamus, mesial temporal area, and brainstem in the FSS group. Correlation analysis revealed that intelligence and memory scores were significantly positively correlated with [18F]FDG SUVR and negatively so with [11C]DPA713 BPND in these regions. A direct comparison between [18F]FDG SUVR and [11C]DPA713 BPND revealed a significant positive correlation in the right hippocampus and amygdala. Conclusions Cerebral hypometabolism with neuroinflammation occurring in the thalamo-limbic-brainstem region may reflect the pathophysiology of FSS.

BackgroundChanges in γ-aminobutyric acid (GABA) function are noted in patients with Parkinson's disease (PD) who have some non-motor impairments. However, dopamine-related GABA function and GABA-related cognitive changes are still unclear.MethodsThirteen drug-naive early-stage PD patients underwent a series of PET scans with [11C]flumazenil(FMZ) and [11C]CFT. The [11C]FMZ binding potential (BPND) derived from a Logan plot analysis was compared between PD patients and age-matched controls. The [11C]CFT radioactivity relative to the cerebellar counterpart was estimated as a semiquantitative value [11C]CFT SUVR. Correlations between [11C]FMZ BPND and [11C]CFT SUVR in the same region of interest were also examined.ResultsIn patients in the PD group, [11C]CFT SUVR was significantly lower in the putamen. The levels of [11C]FMZ BPND in the cerebral cortex (frontal lobe dominancy) and the affected-side putamen were also reduced. In addition, [11C]CFT SUVR was negatively correlated with the [11C]FMZ BPND level in the affected-side putamen. In patients in the PD group, the total frontal assessment battery (FAB) score was positively correlated with the [11C]FMZ BPND in the frontal region.ConclusionGABAergic dysfunction coexists with dopaminergic loss not only in the putamen but also over the extrastriatal region in patients with early PD and is related to frontal dysfunction. The negative correlation of [11C]CFT SUVR with [11C]FMZ BPND in the affected putamen suggests that a greater dopaminergic demise would decelerate GABA release (or an increase in tracer binding), resulting in persistent failure of the GABAergic system in PD patients.

Abstract Background Microglial cells are activated in response to changes in brain homeostasis during aging, dementia, and stroke. Type 2 endocannabinoid receptors (CB2) and translocator protein 18 kD (TSPO) are considered to reflect distinct aspects of microglia-related neuroinflammatory responses in the brain. CB2 activation is considered to relate to the neuroprotective responses that may occur predominantly in the early stage of brain disorders such as Alzheimer’s disease, while an increase in TSPO expression tends to occur later during neuroinflammation, in a proinflammatory fashion. However, this information was deduced from studies with different animal samples under different experimental settings. In this study, we aimed to examine the early microglial status in the inflammation occurring in the brains of senescence-accelerated mouse prone 10 (SAMP10) mice, using positron emission tomography (PET) with CB2 and TSPO tracers, together with immunohistochemistry. Methods Five- and 15-week-old SAMP10 mice that undergo neurodegeneration after 7 months of age were used. The binding levels of the TSPO tracer (R)-[11C]PK11195 and CB2 tracer [11C]NE40 were measured using PET in combination with immunohistochemistry for CB2 and TSPO. To our knowledge, this is the first study to report PET data for CB2 and TSPO at the early stage of cognitive impairment in an animal model. Results The standard uptake value ratios (SUVRs) of [11C]NE40 binding were significantly higher than those of (R)-[11C]PK11195 binding in the cerebral cortical region at 15 weeks of age. At 5 weeks of age, the [11C]NE40 SUVR tended to be higher than the (R)-[11C]PK11195 SUVR. The (R)-[11C]PK11195 SUVR did not significantly differ between 5- and 15-week-old mice. Consistently, immunostaining analysis confirmed the upregulation of CB2, but not TSPO. Conclusions The use of the CB2 tracer [11C]NE40 and/or an immunohistochemical approach allows evaluation of the role of microglia in acute neuroinflammatory processes in the early stage of neurodegeneration. The present results provide in vivo evidence of different responses of two types of microglia to senescence-accelerated neuroinflammation, implying the perturbation of microglial balance by aging. Specific treatment for CB2-positive microglia might help ameliorate senescence-related neuroinflammation and the following neurodegeneration.

Many neuroimaging studies on morality focus on functional brain areas that relate to moral judgment specifically in morally negative situations. To date, there have been few studies on differences in brain activity under conditions of being morally good and bad along a continuum. To explore not only the brain regions involved but also their functional connections during moral judgments, we used magnetoencephalography (MEG), which is superior to other imaging modalities for analyzing time-dependent brain activities; only men were recruited because sex differences might be a confounding factor. While analyses showed that general patterns of brain activation and connectivity were similar between morally good judgments (MGJs) and morally bad judgments (MBJs), activation in brain areas that subserve emotion and “theory of mind” on the right hemisphere was larger in MGJ than MBJ conditions. In the left local temporal region, the connectivity between brain areas related to emotion and reward/punishment was stronger in MBJ than MGJ conditions. The time-frequency analysis showed distinct laterality (left hemisphere dominant) occurring during early moral information processing in MBJ conditions compared to MGJ conditions and phase-dependent differences in the appearance of theta waves between MBJ and MGJ conditions. During MBJs, connections within the hemispheric regions were more robust than those between hemispheric regions. These results suggested that the local temporal region on the left hemisphere is more important in the execution of MBJs during early moral valence processing than in that with MGJs. Shorter neuronal connections within the hemisphere may allow to make MBJs punctual.

To minimize motion-related distortion of reconstructed images, conventional positron emission tomography (PET) measurements of the brain inevitably require a firm and tight head restraint. While such a restraint is now a routine procedure in brain imaging, the physiological and psychological consequences resulting from the restraint have not been elucidated. To address this problem, we developed a restraint-free brain PET system and conducted PET scans under both restrained and non-restrained conditions. We examined whether head restraint during PET scans could alter brain activities such as regional cerebral blood flow (rCBF) and dopamine release along with psychological stress related to head restraint. Under both conditions, 20 healthy male participants underwent [15O]H2O and [11C]Raclopride PET scans during working memory tasks with the same PET system. Before, during, and after each PET scan, we measured physiological and psychological stress responses, including the State-Trait Anxiety Inventory (STAI) scores. Analysis of the [15O]H2O-PET data revealed higher rCBF in regions such as the parahippocampus in the restrained condition. We found the binding potential (BPND) of [11C]Raclopride in the putamen was significantly reduced in the restrained condition, which reflects an increase in dopamine release. Moreover, the restraint-induced change in BPND was correlated with a shift in the state anxiety score of the STAI, indicating that less anxiety accompanied smaller dopamine release. These results suggest that the stress from head restraint could cause unsolicited responses in brain physiology and emotional states. The restraint-free imaging system may thus be a key enabling technology for the natural depiction of the mind.

Abstract Background Upregulated levels of 18-kDa translocator proteins (TSPO) and type 2 endocannabinoid receptors (CB2) are considered to reflect different aspects of microglia-related neuroinflammatory responses in the brain. Relative to the increase in the TSPO expression that occurs slightly later during neuroinflammation in a proinflammatory fashion, CB2 activation is considered to relate to the neuroprotective responses that occurs predominantly at an early stage of brain disorders. These findings, however, were deduced from studies with different animal samples under different experimental settings. Here, we aimed to examined the differences in TSPO binding and CB2 availability at an early stage of stroke in the same animal using positron emission tomography (PET). Methods We used a total of eight Sprague-Dawley rats that underwent photothrombotic stroke surgery. The binding levels of a TSPO tracer [11C](R)PK11195 and a CB2 tracer [11C]NE40 were measured at 24 h after the surgery in the same animal using PET in combination with immunohistochemistry for CB2 and several other markers. A morphological inspection was also performed with X-ray computed tomography for small animals. Results The levels of [11C]NE40 binding potential (BPND) were significantly higher in the cerebral cortical region on the lesion side than those on the non-lesion side, whereas no difference was found in the levels of [11C](R)PK11195 BPND between hemispheres. The tracer influx index (R1) data were all reduced on the lesion side irrespective of tracers. This increase in [11C]NE40 BPND was concomitant with an elevation in CB2 expression mainly within the microglia in the peri-infarct area, as shown by immunohistochemical examinations with Iba-1, CD11b/c+, and NG2+ staining. Conclusions The present results provide in vivo evidence of different responses of microglia occurring in the acute state of stroke. The use of the CB2 tracer [11C]NE40 allows us to evaluate the roles played by the neuroprotective aspect of microglia in acute neuroinflammatory processes.

It has been reported that the cerebellar vermis is equally involved in both motor imagery about axial movement and the actual execution of postural balance in healthy human subjects, but this finding is yet to be explored in Parkinson's disease (PD). We therefore investigated the neuronal responses during observation of standing posture, imagination of standing and the assumption of an upright posture in ten drug-naïve PD patients using positron emission tomography (PET) with [15O]H2O and evaluated dopamine dysfunction by measuring the level of dopamine transporter binding of [11C]CFT. Within-group statistical parametric mapping (SPM) analysis showed similar cerebellar activation during imagination of standing and its real execution between the PD and control groups (12 healthy subjects); i.e., increases in regional cerebral blood flow (rCBF) were observed in the anterior cerebellar vermis during motor imagination and the posterior vermis during standing. A comparison between the groups showed that the motor execution of standing significantly activated the superior part of the posterior vermis (declive VI) and the paracentral sulcus region in the PD patients, while the prefrontal cortices were deactivated during standing (p

The serotonin system has been implicated in the pathophysiology of anorexia nervosa (AN). A recent report proposed that body image distortion (BID), a core symptom of AN, may relate to abnormalities of the serotonin system, especially the serotonin transporter (5HTT). Positron emission tomography (PET) studies of underweight patients with active AN reported alterations in serotonin receptors, but not 5HTT. Here, we aimed to disclose the clinicopathophysiology of AN by focusing on 5HTT and cognitive functions, including BID, in groups with active AN. Twenty-two underweight female patients with AN (12 restricting-type AN (ANR); 10 binge-eating/purging-type AN (ANBP)) and 20 age-matched healthy female subjects underwent PET with a 5HTT radioligand [11C]DASB. The binding potential (BPND) of [11C]DASB was estimated semiquantitatively, and clinical data from Raven's colored progressive matrices for general intelligence, the Stroop test for focused attention, the Iowa gambling task for decision making and a dot-probe task designed for BID were compared with the levels of BPND in different groups. [11C]DASB BPND was significantly decreased in the medial parietal cortex in patients with AN and in the dorsal raphe in patients with ANR compared with healthy subjects (p

Convolutional neural networks (CNNs) demonstrate excellent performance when employed to reconstruct the images obtained by compressed-sensing magnetic resonance imaging (CS-MRI). Our study aimed to enhance image quality by developing a novel iterative reconstruction approach that utilizes image-based CNNs and k-space correction to preserve original k-space data. In the proposed method, CNNs represent a priori information concerning image spaces. First, the CNNs are trained to map zero-filling images onto corresponding full-sampled images. Then, they recover the zero-filled part of the k-space data. Subsequently, k-space corrections, which involve the replacement of unfilled regions by original k-space data, are implemented to preserve the original k-space data. The above-mentioned processes are used iteratively. The performance of the proposed method was validated using a T2-weighted brain-image dataset, and experiments were conducted with several sampling masks. Finally, the proposed method was compared with other noniterative approaches to demonstrate its effectiveness. The aliasing artifacts in the reconstructed images obtained using the proposed approach were reduced compared to those using other state-of-the-art techniques. In addition, the quantitative results obtained in the form of the peak signal-to-noise ratio and structural similarity index demonstrated the effectiveness of the proposed method. The proposed CS-MRI method enhanced MR image quality with high-throughput examinations.

Inhibition of action is involved in stopping a movement, as well as terminating unnecessary movement during performance of a behavior. The inhibition of single actions, known as response inhibition (Inhibition of the urge to respond before or after actions) has been widely investigated using the go/no-go task and stop signal task. However, few studies focused on phase and volition-related inhibition after an action has been initiated. Here, we used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of planning and execution underlying the voluntary inhibition of ongoing action. We collected fMRI data while participants performed a continuous finger-tapping task involving voluntary and involuntary (externally directed) inhibition, and during the initiation of movement. The results revealed areas of significantly greater activation during the preparation of inhibition of an ongoing action during voluntary inhibition, compared with involuntary inhibition, in the supplementary (SMA) and pre-supplementary motor areas, dorsolateral prefrontal cortex, inferior frontal gyrus (IFG), inferior parietal lobe, bilateral globus pallidus/putamen, bilateral insula and premotor cortex. Focusing on the period of execution of inhibition of ongoing actions, an event-related fMRI analysis revealed significant activation in the SMA, middle cingulate cortex, bilateral insula, right IFG and inferior parietal cortex. Additional comparative analyses suggested that brain activation while participants were planning to inhibit an ongoing action was similar to that during planning to start an action, indicating that the same neural substrates of motor planning may be recruited even when an action is ongoing. The present finding that brain activation associated with inhibiting ongoing actions was compatible with that seen in response inhibition (urge to stop before/after actions) suggests that common inhibitory mechanisms for motor movement are involved in both actual and planned motor action, which makes our behavior keep going seamlessly.

PURPOSE: Cognitive processing generally deteriorates as people age. Recent neuroimaging studies have shown that the prefrontal cortex (PFC) is involved in human-specific behavior, such as preparing for future actions and prospective memory; hence, the PFC may be voluntarily activated even during the "resting" condition that precedes task execution. The purpose of the present study was to investigate changes in voluntary pre-task activation as a result of aging using a paradigm that includes a longer intertrial interval (e.g., 30 sec) than has been used in previous studies. METHODS: A total of 120 cognitively normal adults (young: 60, old: 60) participated in this near-infrared spectroscopy (NIRS) study. All subjects performed 6 repetitions of the working memory task, which included a 30 sec resting period and a 28.8 sec task period. The resting period was divided into baseline and pre-task (preT) periods, and the task period was divided into early easy task (eT) and late difficult task (dT) periods. We then normalized the data, analyzed the magnitude of task-related NIRS responses in each period and compared the results between groups using an analysis of variance test. RESULTS: Statistical analyses revealed a significant interaction between group × optode location × period, in which hemodynamic responses in the PFC during the preT period were smaller in the elderly in than young adults. By contrast, during the task period, the hemodynamic responses were higher in the lateral PFC in the elderly than in young adults. Spearman's rank correlation analysis showed a positive correlation between hemodynamic changes during the preT period in the PFC and correct answer ratios in both groups. CONCLUSIONS: These findings suggest that more pre-task activation in the anterior PFC is related to better cognitive performance in humans. Thus, a reduction in this activation might partly explain cognitive decline in the elderly.

BACKGROUND: Numerous associations between brain-reactive antibodies and neurological or psychiatric symptoms have been proposed. Serum autoantibody against the muscarinic cholinergic receptor (mAChR) was increased in some patients with chronic fatigue syndrome (CFS) or psychiatric disease. We examined whether serum autoantibody against mAChR affected the central cholinergic system by measuring brain mAChR binding and acetylcholinesterase activity using positron emission tomography (PET) in CFS patients with positive [CFS(+)] and negative [CFS(-)] autoantibodies. METHODOLOGY: Five CFS(+) and six CFS(-) patients, as well as 11 normal control subjects underwent a series of PET measurements with N-[(11)C]methyl-3-piperidyl benzilate [(11)C](+)3-MPB for the mAChR binding and N-[(11)C]methyl-4-piperidyl acetate [(11)C]MP4A for acetylcholinesterase activity. Cognitive function of all subjects was assessed by neuropsychological tests. Although the brain [(11)C](+)3-MPB binding in CFS(-) patients did not differ from normal controls, CFS(+) patients showed significantly lower [(11)C](+)3-MPB binding than CFS(-) patients and normal controls. In contrast, the [(11)C]MP4A index showed no significant differences among these three groups. Neuropsychological measures were similar among groups. CONCLUSION: The present results demonstrate that serum autoantibody against the mAChR can affect the brain mAChR without altering acetylcholinesterase activity and cognitive functions in CFS patients.

We devised a new computer-aided diagnosis method to segregate dementia using one estimated index (Total Z score) derived from the Brodmann area (BA) sensitivity map on the stereotaxic brain atlas. The purpose of this study is to investigate its accuracy to differentiate patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) from normal adults (NL).We studied 101 adults (NL: 40, AD: 37, MCI: 24) who underwent (18)FDG positron emission tomography (PET) measurement. We divided NL and AD groups into two categories: a training group with (Category A) and a test group without (Category B) clinical information. In Category A, we estimated sensitivity by comparing the standard uptake value per BA (SUVR) between NL and AD groups. Then, we calculated a summated index (Total Z score) by utilizing the sensitivity-distribution maps and each BA z-score to segregate AD patterns. To confirm the validity of this method, we examined the accuracy in Category B. Finally, we applied this method to MCI patients.In Category A, we found that the sensitivity and specificity of differentiation between NL and AD were all 100%. In Category B, those were 100% and 95%, respectively. Furthermore, we found this method attained 88% to differentiate AD-converters from non-converters in MCI group.The present automated computer-aided evaluation method based on a single estimated index provided good accuracy for differential diagnosis of AD and MCI. This good differentiation power suggests its usefulness not only for dementia diagnosis but also in a longitudinal study.

Fatigue is an indispensable bioalarm to avoid exhaustive state caused by overwork or stresses. It is necessary to elucidate the neural mechanism of fatigue sensation for managing fatigue properly. We performed H2O 15 positron emission tomography scans to indicate neural activations while subjects were performing 35-min fatigue-inducing task trials twice. During the positron emission tomography experiment, subjects performed advanced trail-making tests, touching the target circles in sequence located on the display of a touch-panel screen. In order to identify the brain regions associated with fatigue sensation, correlation analysis was performed using statistical parametric mapping method. The brain region exhibiting a positive correlation in activity with subjective sensation of fatigue, measured immediately after each positron emission tomography scan, was located in medial orbitofrontal cortex (Brodmann's area 10/11). Hence, the medial orbitofrontal cortex is a brain region associated with mental fatigue sensation. Our findings provide a new perspective on the neural basis of fatigue.