An one-pot two-step automated synthesis of [18F]T807 injection, its biodistribution in mice and monkeys, and a preliminary study in humans.

[18F]T807 is a potent tau protein imaging agent. In order to fulfill the demand from preclinical and clinical studies, we developed an automated one-pot two-step synthesis of this potent tau imaging agent and studied its stability, and dosimetry in mice and monkeys. We also conducted a preliminary study of this imaging agent in humans. Using this one-pot two-step method, the radiochemical yield (RCY) of [18F]T807 was 20.5 ± 6.1% (n = 15) at the end of bombardment (EOB) in a synthesis time of 70±5 min. The chemical and radiochemical purities were >90% and the specific activities were 151 ± 52 GBq/µmol. The quality of [18F]T807 synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]T807 injection was stable at room temperature for up to 4 h after the end of synthesis (EOS). The estimated effective dose of the [18F]T807 injection extrapolated from monkeys was 19 µSv/MBq (n = 2), while the estimated effective doses of the [18F]T807 injection extrapolated from fasted and non-fasted mice were 123 ± 27 (n = 3) and 94 ± 19 (n = 4) µSv/MBq, respectively. This one-pot two-step automated method produced the [18F]T807 injection with high reproducibility and high quality. PET imaging and radiation dosimetry evaluation in mice and Formosan rock monkeys suggested that the [18F]T807 injection synthesized by this method is suitable for use in human PET imaging studies. Thus, this method could fulfill the demand for the [18F]T807 injection in both preclinical and clinical studies of tauopathies, especially for nearby study sites without cyclotrons.

Task-Switching Performance Improvements After Tai Chi Chuan Training Are Associated With Greater Prefrontal Activation in Older Adults.

Studies have shown that Tai Chi Chuan (TCC) training has benefits on task-switching ability. However, the neural correlates underlying the effects of TCC training on task-switching ability remain unclear. Using task-related functional magnetic resonance imaging (fMRI) with a numerical Stroop paradigm, we investigated changes of prefrontal brain activation and behavioral performance during task-switching before and after TCC training and examined the relationships between changes in brain activation and task-switching behavioral performance. Cognitively normal older adults were randomly assigned to either the TCC or control (CON) group. Over a 12-week period, the TCC group received three 60-min sessions of Yang-style TCC training weekly, whereas the CON group only received one telephone consultation biweekly and did not alter their life style. All participants underwent assessments of physical functions and neuropsychological functions of task-switching, and fMRI scans, before and after the intervention. Twenty-six (TCC, N = 16; CON, N = 10) participants completed the entire experimental procedure. We found significant group by time interaction effects on behavioral and brain activation measures. Specifically, the TCC group showed improved physical function, decreased errors on task-switching performance, and increased left superior frontal activation for Switch > Non-switch contrast from pre- to post-intervention, that were not seen in the CON group. Intriguingly, TCC participants with greater prefrontal activation increases in the switch condition from pre- to post-intervention presented greater reductions in task-switching errors. These findings suggest that TCC training could potentially provide benefits to some, although not all, older adults to enhance the function of their prefrontal activations during task-switching.

Practice Variability Combined with Task-Oriented Electromyographic Biofeedback Enhances Strength and Balance in People with Chronic Stroke.

OBJECTIVES: To investigate the effects of practice variability combined with task-oriented electromyographic biofeedback (EMGBFB) on strength and balance in people with chronic stroke. METHODS: Thirty-three participants were randomly assigned into the constant force EMGBFB tibialis anterior (TA) exercise (constant) group, the variable force EMGBFB tibialis anterior exercise (variable) group, or the upper extremity exercise without EMGBFB (control) group. Subjects in each group received 6 weekly sessions of exercise training (18 sessions, 40 minutes each). Motor outcomes were TA strength, balance (anteroposterior sway amplitude defined by limits of stability test in dynamic posturography), walking speed, Timed Up and Go test (TUGT), and six-minute walk test (6MWT). Data were measured at baseline, 1 day, 2 weeks, and 6 weeks posttraining. RESULTS: TA strength increased significantly in both the constant and variable groups after training. Balance significantly improved only in the variable group. All participants showed improvements in walking speed, TUGT, and 6MWT. CONCLUSIONS: Task-oriented EMGBFB-assisted TA exercise training improved muscle strength in people with chronic stroke. Practicing to reach varying force levels during EMGBFB-assisted tibialis anterior exercises facilitated improvements in the ability to sway in the anteroposterior direction while standing. Our findings highlight the importance of task-oriented and motor learning principles while using the EMGBFB as an adjunct therapy in stroke rehabilitation. This trial was registered with trial registration number NCT01962662.

Classification of schizophrenia using Genetic Algorithm-Support Vector Machine (GA-SVM).

Recently, Event-Related Potential (ERP) has being the most popular method in evaluating brain waves of schizophrenia patients. ERP is one of the electroencephalography (EEG), which is measured the change of brain waves after giving patients certain stimulations instead of resting state. However, with traditional statistical analysis method, both P50 and MMN showed significant difference between controls and patients but not in Gamma band. Gamma band is a 30-50 Hz auditory stimulation which had been suggested may be abnormal in schizophrenia patients. Our data are recruited from 5 schizophrenia patients and 5 controls in National Taiwan University Hospital have been tested with this platform. The results showed that detection rate is 88.24% and we also analyzed the importance of features, including Standard Deviation (SD) and Total Variation (TotalVar) in different stage of wavelet transform. Therefore, this proposed methodology could serve as a valuable clinical decision support for physiologists in evaluating schizophrenia.

Auditory event-related potential of subjects with suspected pre-psychotic state and first-episode psychosis.

BACKGROUND: Recent schizophrenia research exploring the complicated pathogenesis of schizophrenia has focused on the subjects with at-risk mental states in order to exclude the influence of confounding factors. This study explores 3 sets of auditory-related event potentials in subjects with different risk levels of psychosis. METHODS: Subjects were recruited from the SOPRES study in Taiwan. P50 and N100 using an auditory paired-click paradigm and duration MMN were assessed on 32 first-episode psychosis (FEP), 30 ultra-high risk (UHR), 37 E-BARS (early/broad at-risk mental states) participants and 56 controls. RESULTS: MMN was correlated with neither P50 nor N100, whereas many parameters of the latter two were intercorrelated with each other. Compared to healthy controls, MMNs were significantly lower in all 3 clinical groups (E-BARS, UHR and FEP). A gradient of sensory-gating deficits, manifested by increased P50 ratios (S2/S1) and decreased N100 differences, across different levels of clinical severity was suggested by a linear trend. For the UHR subjects, P50 gating ratio, N100 gating ratio, N100 difference, and N100S2 amplitude might be potential indicators to discriminate converters from non-converters. CONCLUSIONS: By including subjects with E-BARS, our results provide new insight regarding pre-attentive auditory event-related potential in subjects across different risk levels of psychotic disorders. Impaired deviance detection shown by MMNs already exists in people at a pre-psychotic state regardless of clinical severity, while sensory-gating deficits shown by P50/N100 varies depending on the risk levels in prodromal period. Further longitudinal research exploring the relationship between ERPs and subjects with a suspected pre-psychotic state is needed.

Changes in dietary folate intake differentially affect oxidised lipid and mitochondrial DNA damage in various brain regions of rats in the absence/presence of intracerebroventricularly injected amyloid ß-peptide challenge.

Accumulating evidence suggests that changes in dietary folate intake may modulate the risks of Alzheimer's disease (AD) through as yet unknown mechanisms. The aims of the present study were to investigate how dietary folate affects the brain folate distribution, levels of oxidised lipid and DNA damage in the absence/presence of ß-amyloid(25-35) (Aß) peptide challenge, a pathogenic hallmark of AD. Male Wistar rats were assigned to diets with folic acid at 0 (folate deprivation; FD), 8 (moderate folate; MF) and 8 mg folic acid/kg diet+0·003 % in drinking-water (folate supplementation; FS) for 4 weeks. A single injection of Aß peptide (1 mg/ml) or the vehicle solution was intracerebroventricularly (icv) administrated to rats a week before killing. Brain folate, a marker of oxidative injury, and neuronal death were assayed. In the absence of an Aß injection, FD rats showed reduced folate levels, and increased 2-thiobarbituric acid-reactive substances and a mitochondrial (mt)DNA 4834 bp large deletion (mtDNA4834 deletion) in the hippocampus compared with the counterpart brains of control rats (P < 0·05). A single icv injection of Aß peptide potentiated lipid peroxidation in the medulla of FD rats, which was ameliorated by feeding FD rats with the MF and FS diets (P < 0·05). Feeding the FS diet to Aß-injected rats enriched brain folate levels and reduced mtDNA4834 deletion in the hippocampal and medullary regions compared with corresponding tissues of Aß+FD rats (P < 0·05). Aß+FS rats had reduced rates of neuronal death in the frontal cortex compared with Aß+FD rats (P < 0·05). Taken together, our data revealed that folate deprivation differentially depleted brain folate levels, and increased lipid peroxidation and mtDNA4834 deletions, particularly, in the hippocampus. Upon Aß challenge, the FS diet may protect various brain regions against lipid peroxidation, mitochondrial genotoxicity and neural death associated with folate deprivation.