Test-retest reliability of the attention network test from the perspective of intrinsic network organization.

The attention network test (ANT), developed based on the triple-network taxonomy by Posner and colleagues, has been widely used to examine the efficacy of alerting, orienting and executive control in clinical and developmental neuroscience studies. Recent research suggests the imperfect reliability of the behavioural ANT and its variants. However, the classical ANT fMRI task's test-retest reliability has received little attention. Moreover, it remains ambiguous whether the attention-related intrinsic network components, especially the dorsal attention, ventral attention and frontoparietal network, manifest acceptable reliability. The present study approaches these issues by utilizing an openly available ANT fMRI dataset for participants with Parkinson's disease and healthy elderly. The reproducibility of group-level activations across sessions and participant groups and the test-retest reliability at the individual level were examined at the voxel, region and network levels. The intrinsic network was defined using the Yeo-Schaefer atlas. Our results reveal three critical facets: (1) the overlapping of the group-level contrast map between sessions and between participant groups was unsatisfactory; (2) the reliability of alerting, orienting and executive, defined as a contrast between conditions, was worse than estimates of specific conditions. (3) Dorsal attention, ventral attention, visual and somatomotor networks showed acceptable reliability for the congruent and incongruent conditions. Our results suggest that specific condition estimates might be used instead of the contrast map for individual or group-difference studies.

Split-half reliability estimates of an online card sorting task in a community sample of young and elderly adults.

Executive function is vital for normal social, cognitive, and motor functions. Executive function decline due to aging increases the risk of disability and falls in older adults, which has become an urgent public health issue. Fast and convenient neuropsychological tools are thus needed to identify high-risk groups as early as possible to conduct a timely intervention. Card sorting tasks, such as Wisconsin Card Sorting Task (WCST) and its variants, are popular tools for measuring executive function. This study investigated the reliability of an open-source, self-administered, online, short-version card sorting task with a sample of young (n = 107, 65 females, age: M = 30.1 years, SD = 5.5 years) and elderly Chinese (n = 113, 53 females, age: M = 64.0 years, SD = 6.7 years). We developed an automated scoring and visualization procedure following the recent recommendations on scoring perseverative responses to make the results comparable to the standardized WCST. Reliability estimates of commonly used measures were calculated using the split-half method. All task indices' reliabilities were reasonably good in both old and young groups except for "failure-to-maintain-set." Elderly Chinese adults showed compromised task performance on all measures compared with the young Chinese adults at the group level. The R script of automated scoring and estimation of reliability is publicly available.

Explainable Alzheimer's Disease Detection Using Linguistic Features from Automatic Speech Recognition.

INTRODUCTION: Alzheimer's disease (AD) is the most prevalent type of dementia and can cause abnormal cognitive function and progressive loss of essential life skills. Early screening is thus necessary for the prevention and intervention of AD. Speech dysfunction is an early onset symptom of AD patients. Recent studies have demonstrated the promise of automated acoustic assessment using acoustic or linguistic features extracted from speech. However, most previous studies have relied on manual transcription of text to extract linguistic features, which weakens the efficiency of automated assessment. The present study thus investigates the effectiveness of automatic speech recognition (ASR) in building an end-to-end automated speech analysis model for AD detection. METHODS: We implemented three publicly available ASR engines and compared the classification performance using the ADReSS-IS2020 dataset. Besides, the SHapley Additive exPlanations algorithm was then used to identify critical features that contributed most to model performance. RESULTS: Three automatic transcription tools obtained mean word error rate texts of 32%, 43%, and 40%, respectively. These automated texts achieved similar or even better results than manual texts in model performance for detecting dementia, achieving classification accuracies of 89.58%, 83.33%, and 81.25%, respectively. CONCLUSION: Our best model, using ensemble learning, is comparable to the state-of-the-art manual transcription-based methods, suggesting the possibility of an end-to-end medical assistance system for AD detection with ASR engines. Moreover, the critical linguistic features might provide insight into further studies on the mechanism of AD.

Early-Onset Micromorphological Changes of Neuronal Fiber Bundles During Radiotherapy.

BACKGROUND: Patients receiving cranial radiation face the risk of delayed brain dysfunction. However, an early medical imaging marker is not available until irreversible morphological changes emerge. PURPOSE: To explore the micromorphological white matter changes during the radiotherapy session by utilizing an along-tract analysis framework. STUDY TYPE: Prospective. POPULATION: Eighteen nasopharyngeal carcinoma (two female) patients receiving cranial radiation. FIELD STRENGTH/SEQUENCE: 3.0 T; Diffusion tensor imaging (DTI) and T1- and T2-weighted images (T1W, T2W); computed tomography (CT). ASSESSMENT: Patients received three DTI imaging scans during the radiotherapy (RT), namely the baseline scan (1-2 days before RT began), the middle scan (the middle of the RT session), and the end scan (1-2 days after RT ended). Twelve fibers were segmented after whole-brain tractography. Then, the fractional anisotropy (FA) values and the cumulative radiation dose received for each fiber streamline were resampled and projected into their center fiber. STATISTICAL TESTS: The contrast among the three scans (P1: middle scan-baseline scan; P2: end scan-middle scan; P3: end scan-baseline scan) were compared using the linear mixed model for each of the 12 center fibers. Then, a dose-responsiveness relationship was performed using Pearson correlation. P < 0.05 was considered statistically significant. RESULTS: Six of the 12 center fibers showed significant changes of FA values during the RT but with heterogeneous patterns. The significant changes along a specific center fiber were associated with their cumulative dose received (Genu: P1 r = -0.6182, P2 r = -0.5907; Splenium: P1 r = 0.4055, P = 0.1063, P2 r = 0.6742; right uncinate fasciculus: P1 r = -0.3865, P2 r = -0.4912, P = 0.0533; right corticospinal tract: P1 r = 0.4273, P = 0.1122, P2 r = -0.6885). DATA CONCLUSION: The along-tract analysis might provide sensitive measures on the early-onset micromorphological changes. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Chronic nicotine exposure impairs uncertainty modulation on reinforcement learning in anterior cingulate cortex and serotonin system.

Deficits in the computational processes of reinforcement learning have been suggested to underlie addiction. Additionally, environmental uncertainty, which is encoded in the anterior cingulate cortex (ACC), modulates reward prediction errors (RPEs) during reinforcement learning and exacerbates addiction. The present study tested whether and how the ACC would have an essential role in drug addiction by failing to use uncertainty to modulate the RPEs during reinforcement learning. In Experiment I, we found that the ACC/medial prefrontal cortex (MPFC) did not modulate RPE learning according to uncertainty in smokers. The effect of uncertainty × RPE in the ACC/MPFC was correlated with the learning rate of RPEs and the duration of nicotine use. Experiment II demonstrated that serotonin, but not dopamine, receptor mRNA expression significantly decreased in the ACC of the nicotine exposed compared to the control rats. Furthermore, there was a positive correlation between learning rate and serotonin receptor mRNA expression in the ACC. Therefore, all present results suggest that impairments in uncertainty modulation in the ACC disrupt reinforcement learning processes in chronic nicotine users and contribute to maladaptive decision-making. These findings support interventions for pathological decision-making in drug addiction that strongly focus on the serotonin system in ACC.

Modeling the association between functional connectivity and lateralization with the activity flow framework.

The human brain is localized and distributed. On the one hand, each cognitive function tends to involve one hemisphere more than the other, also known as the principle of lateralization. On the other hand, interactions among brain regions in the form of functional connectivity (FC) are indispensable for intact function. Recent years have seen growing interest in the association between lateralization and FC. However, FC metrics vary from spurious correlation to causal associations. If lateralization manifests local processing and causal network interactions, more causally valid FC metrics should predict lateralization index (LI) better than FC based on simple correlations. The present study directly investigates this hypothesis within the activity flow framework to compare the association between lateralization and four brain connectivity metrics: correlation-based FC, multiple-regression FC, partial-correlation FC, and combinedFC. We propose two modeling approaches: the one-step approach, which models the relationship between LI and FC directly, and the two-step approach, which predicts the brain activation and calculates the LI. Our results indicated that multiple-regression FC, partial-correlation FC, and combinedFC could significantly improve the model prediction compared to correlation-based FC, which was consistent in a spatial working memory task (typically right-lateralized) and a language task (typically left-lateralized). The one-step and two-step approach yielded similar conclusions. In addition, the finding was replicated in a clinical sample of schizophrenia (SZ), bipolar disorder (BP), and attention deficit hyperactivity disorder (ADHD). The present study suggests that the causal interactions among brain regions help shape the lateralization pattern.

TSP-GNN: a novel neuropsychiatric disorder classification framework based on task-specific prior knowledge and graph neural network.

Neuropsychiatric disorder (ND) is often accompanied by abnormal functional connectivity (FC) patterns in specific task contexts. The distinctive task-specific FC patterns can provide valuable features for ND classification models using deep learning. However, most previous studies rely solely on the whole-brain FC matrix without considering the prior knowledge of task-specific FC patterns. Insight by the decoding studies on brain-behavior relationship, we develop TSP-GNN, which extracts task-specific prior (TSP) connectome patterns and employs graph neural network (GNN) for disease classification. TSP-GNN was validated using publicly available datasets. Our results demonstrate that different ND types show distinct task-specific connectivity patterns. Compared with the whole-brain node characteristics, utilizing task-specific nodes enhances the accuracy of ND classification. TSP-GNN comprises the first attempt to incorporate prior task-specific connectome patterns and the power of deep learning. This study elucidates the association between brain dysfunction and specific cognitive processes, offering valuable insights into the cognitive mechanism of neuropsychiatric disease.

The Cycling Brain in the Workplace: Does Workload Modulate the Menstrual Cycle Effect on Cognition?

Recent decades have witnessed increased research efforts to clarify how the menstrual cycle influence females' cognitive and emotional functions. Despite noticeable progress, the research field faces the challenges of inconsistency and low generalizability of research findings. Females of reproductive ages are a heterogeneous population. Generalizing the results of female undergraduates to women in the workplace might be problematic. Furthermore, the critical cognitive processes for daily life and work deserve additional research efforts for improved ecological validity. Thus, this study investigates cognitive performance across the menstrual cycle using a sample of young nurses with similar duties. We developed a mini-computerized cognitive battery to assess four mental skills critical for nursing work: cognitive flexibility, divided attention, response inhibition, and working memory. Participants completed the cognitive battery at menses, late-follicular, and mid-luteal phases. In addition, they were classified into low- and high workload groups according to their subjective workload ratings. Our results demonstrate a general mid-luteal cognitive advantage. Besides, this study reveals preliminary evidence that workload modulates the menstrual cycle effect on cognition. Only females of low workload manifest the mid-luteal cognitive advantage on divided attention and response inhibition, implying that a suitable workload threshold might be necessary for regular neuro-steroid interactions. Thus, this study advocates the significance of research focusing on the cycling brain under workloads.

The Split-Half Reliability and Construct Validity of the Virtual Reality-Based Path Integration Task in the Healthy Population.

OBJECTIVE: The virtual reality (VR)-based path integration task shows substantial promise in predicting dementia risk. However, the reliability and validity in healthy populations need further exploration. The present study investigates the relationship between task indicators and brain structures in a healthy population using a VR-based navigation task, particularly the entorhinal cortex (EC) and hippocampus. METHODS: Sixty healthy adults were randomly recruited to perform a VR-based path integration task, the digit span task (DST), and an MRI scan. The indicators of the VR-based path integration task were calculated, including the absolute distance error (ADE), degree of angle deviation (DAD), degree of path deviation (DPD), and return time (Time). The reliability of the above indicators was then estimated using the split-half method and Cronbach's alpha. Correlation and regression analyses were then performed to examine the associations between these indicators and age, general cognitive ability (DST), and brain structural measures. RESULTS: ADE, DAD, and DPD showed reasonable split-half reliability estimates (0.84, 0.81, and 0.72) and nice Cronbach's alpha estimates (0.90, 0.86, and 0.96). All indicators correlated with age and DST. ADE and DAD were sensitive predictors of hippocampal volume, and return time was a predictor of EC thickness. CONCLUSION: Our findings demonstrate that the VR-based path integration task exhibits good reliability and validity in the healthy population. The task indicators are age-sensitive, can capture working memory capacity, and are closely related to the integrity of individual EC and hippocampal structures.

A role of the lateral prefrontal cortex in the congruency sequence effect revealed by transcranial direct current stimulation.

Congruency effect is the increase in response time when relevant and irrelevant cues indicate incongruent rather than congruent responses. The congruency effect is smaller in the trial after an incongruent trial than after a congruent trial: this difference is known as the congruency sequence effect (CSE). Psychophysical and neural studies have suggested that the lateral prefrontal cortex (LPFC) and the medial prefrontal cortex are associated with the CSE. In the present study, we applied anodal and cathodal transcranial direct current stimulation, which is thought to result in excitation and inhibition, respectively, on the LPFC, while human participants were performing a flanker task. We found that the CSE was increased under cathodal stimulation (inhibition) of the LPFC. Moreover, the LPFC stimulation modulated the congruency effect after a congruent trial. Further analyses suggested that the results cannot be explained by any of the currently prevailing hypotheses of the CSE, including the conflict monitoring hypothesis, feature integration hypothesis, and temporal learning account. Based on our findings, we propose that a new distinct mechanism might be involved in the CSE. Specifically, the LPFC might contribute to the CSE by maintaining the attention to the task-relevant information, which is an endogenous goal-oriented function and reduces the carry-over of the task-irrelevant information after a congruent trial.

Neural and Psychological Predictors of Cognitive Enhancement and Impairment from Neurostimulation.

Modulating the temporoparietal junction (TPJ), especially the right counterpart, shows promises in enhancing social cognitive ability. However, it is ambiguous whether the functional lateralization of TPJ determines people's responsiveness to brain stimulation. Here, this issue is investigated with an individual difference approach. Forty-five participants attended three sessions of transcranial direct current stimulation (tDCS) experiments and one neuroimaging session. The results support the symmetric mechanism of left and right TPJ stimulation. First, the left and right TPJ stimulation effect are comparable in the group-level analysis. Second, the individual-level analysis reveals that a less right-lateralized TPJ is associated with a higher level of responsiveness. Participants could be classified into positive responders showing cognitive enhancement and negative responders showing cognitive impairment due to stimulation. The positive responders show weaker connectivity between bilateral TPJ and the medial prefrontal cortex, which mediates the prediction of offline responsiveness by the lateralization and the social-related trait. These findings call for a better characterization and predictive models for whom tDCS should be used for, and highlight the necessity and feasibility of prestimulation screening.

Electrical stimulation reduces smokers' craving by modulating the coupling between dorsal lateral prefrontal cortex and parahippocampal gyrus.

Applying electrical stimulation over the prefrontal cortex can help nicotine dependents reduce cigarette craving. However, the underlying mechanism remains ambiguous. This study investigates this issue with functional magnetic resonance imaging. Thirty-two male chronic smokers received real and sham stimulation over dorsal lateral prefrontal cortex (DLPFC) separated by 1 week. The neuroimaging data of the resting state, the smoking cue-reactivity task and the emotion task after stimulation were collected. The craving across the cue-reactivity task was diminished during real stimulation as compared with sham stimulation. The whole-brain analysis on the cue-reactivity task revealed a significant interaction between the stimulation condition (real vs sham) and the cue type (smoking vs neutral) in the left superior frontal gyrus and the left middle frontal gyrus. The functional connectivity between the left DLPFC and the right parahippocampal gyrus, as revealed by both psychophysical interaction analysis and the resting state functional connectivity, is altered by electrical stimulation. Moreover, the craving change across the real and sham condition is predicted by alteration of functional connectivity revealed by psychophysical interaction analysis. The local and long-distance coupling, altered by the electrical stimulation, might be the underlying neural mechanism of craving regulation.

Non-invasive Brain Stimulation for the Treatment of Nicotine Addiction: Potential and Challenges.

Tobacco consumption is one of the leading causes of preventable death worldwide. However, it is difficult to give up smoking by relying on the help of traditional treatments only. Recent years have witnessed emerging positive evidence that non-invasive brain stimulation (NIBS), such as transcranial magnetic stimulation and transcranial direct-current stimulation, can reduce smoking-related behaviors. Although their potential has been implied by advances in research, several methodological issues restrict the clinical application of NIBS to treating nicotine dependence. In this review, we critically evaluate related studies and give suggestions for future research and applications to meet these challenges.

Cue-induced Behavioral and Neural Changes among Excessive Internet Gamers and Possible Application of Cue Exposure Therapy to Internet Gaming Disorder.

Internet gaming disorder (IGD) may lead to many negative consequences in everyday life, yet there is currently no effective treatment for IGD. Cue-reactivity paradigm is commonly used to evaluate craving for substance, food, and gambling; cue exposure therapy (CET) is applied to treating substance use disorders (SUDs) and some other psychological disorders such as pathological gambling (PG). However, no study has explored CET's application to the treatment of IGD except two articles having implied that cues' exposure may have therapeutic effect on IGD. This paper reviews studies on cue-induced behavioral and neural changes in excessive Internet gamers, indicating that behavioral and neural mechanisms of IGD mostly overlap with those of SUD. The CET's effects in the treatment of SUDs and PG are also reviewed. We finally propose an optimized CET paradigm, which future studies should consider and investigate as a probable treatment of IGD.

Early-onset hearing loss reorganizes the visual and auditory network in children without cochlear implantation.

The present study investigates the effect of early-onset hearing loss on the reorganization of visual and auditory networks in children without cochlear implants. Eleven congenitally deaf children and 12 age-matched hearing children were included in the study. Bilateral transverse temporal cortices and bilateral lateral occipital cortices were defined as auditory and visual seeds, respectively (as verified using an independent component analysis). The four seed-based connectivity maps were computed for each participant. As a result, group analysis showed that the primary auditory cortex was less connected with the motor cortex, whereas the visual cortex showed strengthened connectivity with motor and speech cortices in congenitally deaf children compared with the controls. Moreover, we found that the differences in functional connectivity between deaf and control children were not because of morphometric changes. Our results provide neural evidence for the sensorimotor coupling model of speech development.

Electrical stimulation over bilateral occipito-temporal regions reduces N170 in the right hemisphere and the composite face effect.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate cortical excitability. Although the clinical value of tDCS has been advocated, the potential of tDCS in cognitive rehabilitation of face processing deficits is less understood. Face processing has been associated with the occipito-temporal cortex (OT). The present study investigated whether face processing in healthy adults can be modulated by applying tDCS over the OT. Experiment 1 investigated whether tDCS can affect N170, a face-sensitive ERP component, with a face orientation judgment task. The N170 in the right hemisphere was reduced in active stimulation conditions compared with the sham stimulation condition for both upright faces and inverted faces. Experiment 2 further demonstrated that tDCS can modulate the composite face effect, a type of holistic processing that reflects the obligatory attention to all parts of a face. The composite face effect was reduced in active stimulation conditions compared with the sham stimulation condition. Additionally, the current polarity did not modulate the effect of tDCS in the two experiments. The present study demonstrates that N170 can be causally manipulated by stimulating the OT with weak currents. Furthermore, our study provides evidence that obligatory attention to all parts of a face can be affected by the commonly used tDCS parameter setting.

HP-ß-CD-PLGA nanoparticles improve the penetration and bioavailability of puerarin and enhance the therapeutic effects on brain ischemia-reperfusion injury in rats.

It is well known that puerarin attenuates ischemia-reperfusion injury and promotes function recovery of ischemic region. However, due to its reverse physiochemical properties, puerarin does not easily cross the blood-brain barrier. The aim of the present study is to create puerarin nanoparticles which increase and prolong the puerarin concentration in the brain. Using emulsion solvent evaporation techniques, we designed puerarin-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles. Hydroxypropyl beta cyclodextrin (HP-ß-CD) was used to increase the solubility of puerarin and gelatin to enhance viscosity of inner water phase, which improved puerarin entrapment. The drug release kinetics and nanoparticle degradation in phosphate buffered saline (PBS) were analyzed by electronic microscopy and high-performance liquid chromatography. Computerized tomography scans were used to detect the infarction volume and electroencephalogram (EEG) was recorded to estimate the recovery of brain function. The results showed that the combined HP-ß-CD and gelatin significantly improved the entrapment efficiency. The infarction volume was significantly decreased on days 3 and 7 after the administration of puerarin nanoparticles compared with that of control and pure puerarin. EEG was also significantly improved. Puerarin nanoparticles are potentially applicable for the brain injury induced by ischemic-reperfusion.

Gamma Knife irradiation-induced histopathological changes in the trigeminal nerves of rhesus monkeys.

OBJECT: The authors' goal was to observe histopathological changes in the trigeminal nerve after Gamma Knife surgery (GKS) in rhesus monkeys, and to investigate the radiobiological mechanism of GKS for primary trigeminal neuralgia. The nerve length-dosage effect of irradiation is also discussed. METHODS: One of 5 rhesus monkeys randomly served as a control, and the other 4 monkeys were randomly administered a target radiation dose of 60, 70, 80, or 100 Gy (a different dose in each animal). The size of the collimator was 4 mm, and the target point was the trigeminal nerve root. In each experimental monkey, one side was exposed to single-target-point irradiation, and the contralateral side was exposed to double-target-point irradiation. After 6 months, the trigeminal nerve root was examined using light microscopy, transmission electron microscopy, and immunohistochemistry. RESULTS: At each radiation dose, the damage to the nerve tissue by single-target-point irradiation was identical to that caused by double-target-point irradiation. In the trigeminal nerve tissues of the monkeys irradiated with 60 and 70 Gy, there was limited nerve demyelination and degeneration, fragmentation, or loss of axons. In the trigeminal nerve tissue of the monkey irradiated with 80 Gy, the nerve tissue showed a disordered structure. In the trigeminal nerve tissue of the monkey irradiated with 100 Gy, there was severe derangement in the structure of the nerve tissue, and extensive demyelination, fragmentation, and loss of axons. CONCLUSIONS: The target doses of 60 and 70 Gy have very little impact on the structure of the trigeminal nerve. Irradiation at 80 Gy can cause partial degeneration and loss of axons and demyelination. A 100-Gy dose can cause some necrosis of neurons. Comparing the single-target-point with the double-target-point irradiation, the extent of damage to the nerve tissue is identical, and no difference in the nerve length-dosage effect was found.

Diagnostic performance of magnetic resonance venography in the detection of recanalization in patients with chronic cerebral venous sinus thrombus.

BACKGROUND: In the chronic stage of cerebral venous sinus thrombosis (CVST), recanalization can result in disparate MR appearances. We aimed to prospectively investigate the diagnostic accuracy of magnetic resonance venography (MRV) in the evaluation of the recanalization of CVST. METHODS: This study prospectively evaluated the diagnostic performance of 2-dimensional time-of-flight (2D-TOF) MRV in thirty-two consecutive patients during a three- to six-month follow-up for CVST. Both 2D-TOF MRV and digital substraction angiography (DSA) were undertaken. Diagnostic accuracy of 2D-TOF MRV in the detection of recanalized thrombus was evaluated using DSA as the reference standard. RESULTS: MRV and DSA were completed without complications in all 32 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of 2D-TOF MRV for the detection of recanalization on a segmental basis were 91% (62/68), 93% (37/40), 95% (62/65), and 86% (37/43) respectively. CONCLUSION: 2D-TOF MRV provides high sensitivity and specificity for the diagnosis of recanalized CVST segments.

Effect of devazepide reversed antagonism of CCK-8 against morphine on electrical and mechanical activities of rat duodenum in vitro.

AIM:To study the antagonism of cholecystokinin octapeptide (CCK-8) against the effect of morphine and its mechanism.METHODS:The method of simultaneously recording the electrical and mechanical activities of rat duodenum in vitro was adopted.RESULTS:Acetylcholine (ACh) could increase the amplitude and the number of the spike potential (SPA and SPN of rat duodenum in vitro, followed by the increase of the duodenal contraction amplitudes (CA), showing a positive correlation. Morphine, on the contrary, inhibited the potentiation of ACh, showing a negative correlation. CCK-8 could antagonize the effects of morphine, i.e. th SPA and SPN were increased again, followed by the increase of CA. On the basis of the above, CCK-A receptor antagonist Devazepide could reverse the antagonism of CCK-8 to the effect of morphine.CONCLUSION:CCK-8 could antagonize the effect of morphine which inhibited the potentiation of ACh on the duodenal activities in vitro.Furthermore, it was inferred that the antagonistic effect of CCK-8 on morphine was mainly mediated by CCK-A receptor.