bluuebunny/crossref_metadata_2025 huggingface dataset:
18F-THK5351 Positron Emission Tomography Imaging in Neurodegenerative Tauopathies
Authors: Ezura Michinori , Kikuchi Akio , Okamura Nobuyuki , Ishiki Aiko , Hasegawa Takafumi , Harada Ryuichi , Watanuki Shoichi , Funaki Yoshihito , Hiraoka Kotaro , Baba Toru , Sugeno Naoto , Yoshida Shun , Kobayashi Junpei , Kobayashi Michiko , Tano Ohito , Ishiyama Shun , Nakamura Takaaki , Nakashima Ichiro , Mugikura Shunji , Iwata Ren , Taki Yasuyuki , Furukawa Katsutoshi , Arai Hiroyuki , Furumoto Shozo , Tashiro Manabu , Yanai Kazuhiko , Kudo Yukitsuka , Takeda Atsushi , Aoki Masashi
Published: December 2021

Introduction: We aimed to determine whether in vivo tau deposits and monoamine oxidase B (MAO-B) detection using 18F-THK5351 positron emission tomography (PET) can assist in the differential distribution in patients with corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD) and whether 18F-THK5351 retention of lesion sites in CBS and PSP can correlate with clinical parameters.

Methods:18F-THK5351 PET was performed in 35 participants, including 7, 9, and 10 patients with CBS, PSP, and AD, respectively, and 9 age-matched normal controls. In CBS and PSP, cognitive and motor functions were assessed using the Montreal Cognitive Assessment, Addenbrooke’s Cognitive Examination–Revised, and Frontal Assessment Battery, Unified Parkinson’s Disease Rating Scale Motor Score, and PSP Rating Scale.

Results:18F-THK5351 retention was observed in sites susceptible to disease-related pathologies in CBS, PSP, and AD. 18F-THK5351 uptake in the precentral gyrus clearly differentiated patients with CBS from those with PSP and AD. Furthermore, 18F-THK5351 uptake in the inferior temporal gyrus clearly differentiated patients with AD from those with CBS and PSP. Regional 18F-THK5351 retention was associated with the cognitive function in CBS and PSP.

Conclusion: Measurement of the tau deposits and MAO-B density in the brain using 18F-THK5351 may be helpful for the differential diagnosis of tauopathies and for understanding disease stages.
Action Fluency in Parkinson’s Disease: A Mini-Review and Viewpoint
Authors: Gianelli Claudia , Maiocchi Carlotta , Canessa Nicola
Published: December 2021

Increasing evidence shows that the typical motor symptoms of Parkinson’s disease (PD) are often accompanied, if not preceded, by cognitive dysfunctions that are potentially linked to further complications of the disease. Notably, these cognitive dysfunctions appear to have a significant impact in the domain of action processing, as indicated by specific impairments for action-related stimuli in general, and verbs in particular. In this mini-review, we focus on the use of the action fluency test as a tool to investigate action processing, in PD patients. We discuss the current results within the embodied cognition framework and in relation to general action-related impairments in PD, while also providing an outlook on open issues and possible avenues for future research. We argue that jointly addressing action semantic processing and motor dysfunctions in PD patients could pave the way to interventions where the motor deficits are addressed to improve both motor and communicative skills since the early disease stages, with a likely significant impact on quality of life.
Higher-Order Conditioning in the Spatial Domain
Authors: Bouchekioua Youcef , Kosaki Yutaka , Watanabe Shigeru , Blaisdell Aaron P.
Published: November 2021

Spatial learning and memory, the processes through which a wide range of living organisms encode, compute, and retrieve information from their environment to perform goal-directed navigation, has been systematically investigated since the early twentieth century to unravel behavioral and neural mechanisms of learning and memory. Early theories about learning to navigate space considered that animals learn through trial and error and develop responses to stimuli that guide them to a goal place. According to a trial-and error learning view, organisms can learn a sequence of motor actions that lead to a goal place, a strategy referred to as response learning, which contrasts with place learning where animals learn locations with respect to an allocentric framework. Place learning has been proposed to produce a mental representation of the environment and the cartesian relations between stimuli within it—which Tolman coined the cognitive map. We propose to revisit some of the best empirical evidence of spatial inference in animals, and then discuss recent attempts to account for spatial inferences within an associative framework as opposed to the traditional cognitive map framework. We will first show how higher-order conditioning can successfully account for inferential goal-directed navigation in a variety of situations and then how vectors derived from path integration can be integrated via higher-order conditioning, resulting in the generation of higher-order vectors that explain novel route taking. Finally, implications to cognitive map theories will be discussed.
Robotic Exoskeleton Gait Training in Stroke: An Electromyography-Based Evaluation
Authors: Longatelli Valeria , Pedrocchi Alessandra , Guanziroli Eleonora , Molteni Franco , Gandolla Marta
Published: December 2021

The recovery of symmetric and efficient walking is one of the key goals of a rehabilitation program in patients with stroke. The use of overground exoskeletons alongside conventional gait training might help foster rhythmic muscle activation in the gait cycle toward a more efficient gait. About twenty-nine patients with subacute stroke have been recruited and underwent either conventional gait training or experimental training, including overground gait training using a wearable powered exoskeleton alongside conventional therapy. Before and after the rehabilitation treatment, we assessed: (i) gait functionality by means of clinical scales combined to obtain a Capacity Score, and (ii) gait neuromuscular lower limbs pattern using superficial EMG signals. Both groups improved their ability to walk in terms of functional gait, as detected by the Capacity Score. However, only the group treated with the robotic exoskeleton regained a controlled rhythmic neuromuscular pattern in the proximal lower limb muscles, as observed by the muscular activation analysis. Coherence analysis suggested that the control group (CG) improvement was mediated mainly by spinal cord control, while experimental group improvements were mediated by cortical-driven control. In subacute stroke patients, we hypothesize that exoskeleton multijoint powered fine control overground gait training, alongside conventional care, may lead to a more fine-tuned and efficient gait pattern.
Sex-Specific Microglial Activation and SARS-CoV-2 Receptor Expression Induced by Chronic Unpredictable Stress
Authors: Yan Ling , Jayaram Mohan , Chithanathan Keerthana , Zharkovsky Alexander , Tian Li
Published: November 2021

The coronavirus disease 2019 (COVID-19) pandemic has generated a lot of stress and anxiety among not only infected patients but also the general population across the globe, which disturbs cerebral immune homeostasis and potentially exacerbates the SARS-CoV-2 virus-induced neuroinflammation, especially among people susceptible to neuropsychiatric disorders. Here, we used a chronic unpredictable mild stress (CUMS) mouse model to study its effects on glia-mediated neuroinflammation and expression of SARS-CoV2 viral receptors. We observed that female mice showed depressive-like behavior after CUMS, whereas male mice showed enhanced anxiety and social withdrawal. Interestingly, CUMS led to increased amounts of total and MHCII+ microglia in the hippocampi of female mice but not male mice. mRNA levels of SARS-CoV-2 viral receptors angiotensin-converting enzyme 2 (Ace2) and basigin (Bsg) were also upregulated in the prefrontal cortices of stressed female mice but not male mice. Similarly, sex-specific changes in SARS-CoV-2 viral receptors FURIN and neuropilin-1 (NRP1) were also observed in monocytes of human caregivers enduring chronic stress. Our findings provided evidence on detrimental effects of chronic stress on the brain and behavior and implied potential sex-dependent susceptibility to SARS-CoV-2 infection after chronic stress.
The Up-regulation of TNF-α Maintains Trigeminal Neuralgia by Modulating MAPKs Phosphorylation and BKCa Channels in Trigeminal Nucleus Caudalis
Authors: Lu Zhan-ying , Fan Juan , Yu Li-hua , Ma Bei , Cheng Li-ming
Published: December 2021

Trigeminal neuralgia (TN) is a severe chronic neuropathic pain. Despite numerous available medical interventions, the therapeutic effects are not ideal. To control the pain attacks, the need for more contemporary drugs continues to be a real challenge. Our previous study reported that Ca2+-activated K+ channels (BKCa) channels modulated by mitogen-activated protein kinases (MAPKs) in the trigeminal ganglia (TG) neurons play crucial roles in regulating TN, and some research studies demonstrated that inflammatory cytokine tumor necrosis factor alpha (TNF-α) could promote neuropathic pain. Meanwhile, the trigeminal nucleus caudalis (TNC), the first central site of the trigeminal nociceptive pathway, is responsible for processing sensory and pain signals from the peripheral orofacial area. Thus, this study is aimed to further investigate whether TNF-α and MAPKs phosphorylation in the TNC could mediate the pathogenesis of TN by modulating BKCa channels. The results showed that TNF-α of the TNC region is upregulated significantly in the chronic constriction injury of infraorbital nerve (ION-CCI) rats model, which displayed persistent facial mechanical allodynia. The normal rats with target injection of exogenous TNF-α to the fourth brain ventricle behaved just like the ION-CCI model rats, the orofacial mechanical pain threshold decreased clearly. Meanwhile, the exogenous TNF-α increased the action potential frequency and reduced the BKCa currents of TNC neurons significantly, which could be reversed by U0126 and SB203580, the inhibitors of MAPK. In addition, U0126, SB203580, and another MAPK inhibitor SP600125 could relieve the facial mechanical allodynia by being injected into the fourth brain ventricle of ION-CCI model rats, respectively. Taken together, our work suggests that the upregulation of TNF-α in the TNC region would cause the increase of MAPKs phosphorylation and then the negative regulation of BKCa channels, resulting in the TN.
Distinct Patterns of Brain Metabolism in Patients at Risk of Sudden Unexpected Death in Epilepsy
Authors: Whatley Benjamin P. , Winston Joel S. , Allen Luke A. , Vos Sjoerd B. , Jha Ashwani , Scott Catherine A. , Smith April-Louise , Chowdhury Fahmida A. , Bomanji Jamshed B. , Lhatoo Samden D. , Harper Ronald M. , Diehl Beate
Published: November 2021

Objective: To characterize regional brain metabolic differences in patients at high risk of sudden unexpected death in epilepsy (SUDEP), using fluorine-18-fluorodeoxyglucose positron emission tomography (18FDG-PET).

Methods: We studied patients with refractory focal epilepsy at high (n = 56) and low (n = 69) risk of SUDEP who underwent interictal 18FDG-PET as part of their pre-surgical evaluation. Binary SUDEP risk was ascertained by thresholding frequency of focal to bilateral tonic-clonic seizures (FBTCS). A whole brain analysis was employed to explore regional differences in interictal metabolic patterns. We contrasted these findings with regional brain metabolism more directly related to frequency of FBTCS.

Results: Regions associated with cardiorespiratory and somatomotor regulation differed in interictal metabolism. In patients at relatively high risk of SUDEP, fluorodeoxyglucose (FDG) uptake was increased in the basal ganglia, ventral diencephalon, midbrain, pons, and deep cerebellar nuclei; uptake was decreased in the left planum temporale. These patterns were distinct from the effect of FBTCS frequency, where increasing frequency was associated with decreased uptake in bilateral medial superior frontal gyri, extending into the left dorsal anterior cingulate cortex.

Significance: Regions critical to cardiorespiratory and somatomotor regulation and to recovery from vital challenges show altered interictal metabolic activity in patients with frequent FBTCS considered to be at relatively high-risk of SUDEP, and shed light on the processes that may predispose patients to SUDEP.
Clustering of Spontaneous Recurrent Seizures in a Mouse Model of Extended Hippocampal Kindling
Authors: Liu Haiyu , Zhang Liang
Published: November 2021

Acute repetitive seizures or seizure clusters are common in epileptic patients. Seizure clusters are associated with a high risk of developing status epilepticus and increased morbidity and mortality. Seizure clusters are also recognizable in spontaneous recurrent seizures (SRS) that occur in animal models of epilepsy. The electrical kindling of a limbic structure is a commonly used model of temporal lobe epilepsy. Although classic kindling over the course of a few weeks does not generally induce SRS, extended kindling over the course of a few months can induce SRS in several animal species. SRS in kindled cats often occur in clusters, but the existence of seizure clusters in rodent models of extended kindling remains to be demonstrated. We explored the existence of seizure clusters in mice following extended hippocampal kindling. Adult male mice (C57BL/6) experienced twice daily hippocampal stimulations and underwent continuous 24-hour electroencephalogram (EEG)-video monitoring after ≥80 stimulations. SRS events were recognized by EEG discharges and associated motor seizures. Seizure clusters, defined as ≥4 seizures per cluster and intra-cluster inter-seizure intervals ≤ 120 min, were observed in 19 of the 20 kindled mice. Individual mice showed variable seizure clusters in terms of cluster incidence and circadian-like expression patterns. For clusters consisting of 4–7 seizures and intra-seizure intervals ≤ 20 min, no consistent changes in inter-seizure intervals, EEG discharge duration, or motor seizure severity scores were observed approaching cluster termination. These results suggested that seizure clustering represents a prominent feature of SRS in hippocampal kindled mice. We speculate that, despite experimental limitations and confounding factors, systemic homeostatic mechanisms that have yet to be explored may play an important role in governing the occurrence and termination of seizure clusters.
Abnormal Fractional Amplitude of Low-Frequency Fluctuation as a Potential Imaging Biomarker for First-Episode Major Depressive Disorder: A Resting-State fMRI Study and Support Vector Machine Analysis
Authors: Gao Yujun , Wang Xi , Xiong Zhenying , Ren Hongwei , Liu Ruoshi , Wei Yafen , Li Dongbin
Published: December 2021

Objective: Major depressive disorder (MDD) is a psychiatric disorder with serious negative health outcomes; however, there is no reliable method of diagnosis. This study explored the clinical diagnostic value of the fractional amplitude of low-frequency fluctuation (fALFF) based on the support vector machine (SVM) method for the diagnosis of MDD.

Methods: A total of 198 first-episode MDD patients and 234 healthy controls were involved in this study, and all participants underwent resting-state functional magnetic resonance imaging (fMRI) scanning. Imaging data were analyzed with the fALFF and SVM methods.

Results: Compared with the healthy controls, the first-episode MDD patients showed higher fALFF in the left mid cingulum, right precuneus, and left superior frontal gyrus (SFG). The increased fALFF in these three brain regions was positively correlated with the executive control reaction time (ECRT), and the increased fALFF in the left mid cingulum and left SFG was positively correlated with the 17-item Hamilton Rating Scale for Depression (HRSD-17) scores. The SVM results showed that increased fALFF in the left mid cingulum, right precuneus, and left SFG exhibited high diagnostic accuracy of 72.92% (315/432), 71.76% (310/432), and 73.84% (319/432), respectively. The highest diagnostic accuracy of 76.39% (330/432) was demonstrated for the combination of increased fALFF in the right precuneus and left SFG, along with a sensitivity of 84.34% (167/198), and a specificity of 70.51% (165/234).

Conclusion: Increased fALFF in the left mid cingulum, right precuneus, and left SFG may serve as a neuroimaging marker for first-episode MDD. The use of the increased fALFF in the right precuneus and left SFG in combination showed the best diagnostic value.
Neural Processes of Psychological Stress and Relaxation Predict the Future Evolution of Quality of Life in Multiple Sclerosis
Authors: Meyer-Arndt Lil , Schmitz-Hübsch Tanja , Bellmann-Strobl Judith , Brandt Alexander U. , Haynes John-Dylan , Gold Stefan M. , Paul Friedemann , Weygandt Martin
Published: November 2021

Health-related quality of life (HRQoL) is an essential complementary parameter in the assessment of disease burden and treatment outcome in multiple sclerosis (MS) and can be affected by neuropsychiatric symptoms, which in turn are sensitive to psychological stress. However, until now, the impact of neurobiological stress and relaxation on HRQoL in MS has not been investigated. We thus evaluated whether the activity of neural networks triggered by mild psychological stress (elicited in an fMRI task comprising mental arithmetic with feedback) or by stress termination (i.e., relaxation) at baseline (T0) predicts HRQoL variations occurring between T0 and a follow-up visit (T1) in 28 patients using a robust regression and permutation testing. The median delay between T0 and T1 was 902 (range: 363–1,169) days. We assessed HRQoL based on the Hamburg Quality of Life Questionnaire in MS (HAQUAMS) and accounted for the impact of established HRQoL predictors and the cognitive performance of the participants. Relaxation-triggered activity of a widespread neural network predicted future variations in overall HRQoL (t = 3.68, pfamily−wise error [FWE]-corrected = 0.008). Complementary analyses showed that relaxation-triggered activity of the same network at baseline was associated with variations in the HAQUAMS mood subscale on an αFWE = 0.1 level (t = 3.37, pFWE = 0.087). Finally, stress-induced activity of a prefronto-limbic network predicted future variations in the HAQUAMS lower limb mobility subscale (t = −3.62, pFWE = 0.020). Functional neural network measures of psychological stress and relaxation contain prognostic information for future HRQoL evolution in MS independent of clinical predictors.
Transient Ischemic Attacks Preceding Ischemic Stroke and the Possible Preconditioning of the Human Brain: A Systematic Review and Meta-Analysis
Authors: Ghozy Sherief , Kacimi Salah Eddine Oussama , Elfil Mohamed , Sobeeh Mohamed Gomaa , Reda Abdullah , Kallmes Kevin M. , Rabinstein Alejandro A. , Holmes David R. , Brinjikji Waleed , Kadirvel Ramanathan , Kallmes David F.
Published: November 2021

Stroke is a leading cause of mortality and disability worldwide. Transient ischemic attack (TIA) is defined as transient brain ischemia with temporary neurological deficits. In animal models, prior TIA seems to enhance brain ischemic tolerance to withstand further ischemic events, which might be explained by brain preconditioning. Thus, this review aims to formulate evidence of whether TIAs can induce positive preconditioning and enhance the functional outcomes in patients suffering from subsequent ischemic strokes. Five databases were searched (PubMed, Embase, SAGE, Web of Science, and Scopus), and twelve studies were included in the quantitative analysis. Studies were eligible when comparing patients with acute ischemic stroke (AIS) and previous TIA with those with AIS without TIA. Comparisons included the National Institute of Health Stroke Scale (NIHSS) score at admission and 7 days from the stroke event, modified Rankin score (mRS), and Trial of ORG 10,172 in Acute Stroke Treatment (TOAST) classification. Odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) were used to describe our results using the random effect model. Our results revealed that patients with stroke and prior TIAs had lower NIHSS scores at admission than those without prior TIAs. However, the NIHSS score was not significantly different between the two groups at 7 days. Furthermore, there was no statistically significant difference between both groups in terms of mortality. Despite the differences in the admission mRS score groups, patients with prior TIAs had lower mRS scores at discharge.
Circulating microRNAs in Symptomatic and Asymptomatic Carotid Stenosis
Authors: Grosse Gerrit M. , Derda Anselm A. , Stauss Ricarda D. , Neubert Lavinia , Jonigk Danny D. , Kühnel Mark P. , Gabriel Maria M. , Schuppner Ramona , Wilhelmi Mathias , Bär Christian , Bauersachs Johann , Schrimpf Claudia , Thum Thomas , Weissenborn Karin
Published: November 2021

Background: Specific microRNAs (miRs) have been implicated in the pathophysiology of atherosclerosis and may represent interesting diagnostic and therapeutic targets in carotid stenosis. We hypothesized that the levels of specific circulating miRs are altered in patients with symptomatic carotid stenosis (sCS) in comparison to those in patients with asymptomatic carotid stenosis (aCS) planned to undergo carotid endarterectomy (CEA). We also studied whether miR levels are associated with plaque vulnerability and stability over time after CEA.

Methods: Circulating levels of vascular-enriched miR-92a, miR-126, miR-143, miR-145, miR-155, miR-210, miR-221, miR-222, and miR-342-3p were determined in 21 patients with sCS and 23 patients with aCS before CEA and at a 90-day follow-up. Transcranial Doppler ultrasound for detection of microembolic signals (MES) in the ipsilateral middle cerebral artery was performed prior to CEA. Carotid plaques were histologically analyzed.

Results: Mean levels of miRs were not considerably different between groups and were only marginally higher in sCS than aCS concerning miR-92a, miR-210, miR-145, and miR-143 with the best evidence concerning miR-92a. After adjustment for vascular risk factors and statin pre-treatment, the effect sizes remained essentially unchanged. At follow-up, however, these modest differences remained uncorroborated. There were no relevant associations between miR-levels and MES or histological plaque vulnerability features.

Conclusions: This study does not provide evidence for strong associations between specific circulating miRs and symptomatic state in a collective of comprehensively characterized patients with carotid stenosis. Further work is needed to elucidate the role of circulating miRs as targets in advanced carotid atherosclerosis.
Numerosity Comparison, Estimation and Proportion Estimation Abilities May Predict Numeracy and Cognitive Reflection in Adults
Authors: Tokita Midori , Hirota Sumire
Published: November 2021

This study explores whether and how different tasks associated with approximate number system (ANS) ability are related to numeracy and cognitive reflection in adults. We conducted an online experiment using a sample of 300 Japanese adults aged 20–39. Participants were given three ANS tasks (numerosity comparison, numerosity estimation, and proportion estimation) as well as Rasch-based numeracy scale and cognitive reflection test, and we tested the correlation among the measures of these tasks. We explored the hypothesis that the typical measures used to gauge ANS ability, numerosity comparison and numerosity estimation may mediate different cognitive mechanisms in adults. We also introduced a task measuring proportion estimation, added because such estimation requires numerosity perception and the ability to map symbolic numerals. Our findings suggest that there is a weak, but significant correlation among the three ANS-related tasks. Moreover, there is a significant relationship between each of these measures and the numeracy and CRT score, suggesting that the ANS-related ability may be associated with higher cognitive abilities such as numeracy and cognitive reflection. In addition, we found that performances on the numerosity and proportion estimation are more clearly related to CRT score than the numerosity comparison task.
ES-ImageNet: A Million Event-Stream Classification Dataset for Spiking Neural Networks
Authors: Lin Yihan , Ding Wei , Qiang Shaohua , Deng Lei , Li Guoqi
Published: November 2021

With event-driven algorithms, especially spiking neural networks (SNNs), achieving continuous improvement in neuromorphic vision processing, a more challenging event-stream dataset is urgently needed. However, it is well-known that creating an ES-dataset is a time-consuming and costly task with neuromorphic cameras like dynamic vision sensors (DVS). In this work, we propose a fast and effective algorithm termed Omnidirectional Discrete Gradient (ODG) to convert the popular computer vision dataset ILSVRC2012 into its event-stream (ES) version, generating about 1,300,000 frame-based images into ES-samples in 1,000 categories. In this way, we propose an ES-dataset called ES-ImageNet, which is dozens of times larger than other neuromorphic classification datasets at present and completely generated by the software. The ODG algorithm implements image motion to generate local value changes with discrete gradient information in different directions, providing a low-cost and high-speed method for converting frame-based images into event streams, along with Edge-Integral to reconstruct the high-quality images from event streams. Furthermore, we analyze the statistics of ES-ImageNet in multiple ways, and a performance benchmark of the dataset is also provided using both famous deep neural network algorithms and spiking neural network algorithms. We believe that this work shall provide a new large-scale benchmark dataset for SNNs and neuromorphic vision.
Hallucinations: A Functional Network Model of How Sensory Representations Become Selected for Conscious Awareness in Schizophrenia
Authors: Hare Stephanie M.
Published: November 2021

Hallucinations are conscious perception-like experiences that are a common symptom of schizophrenia spectrum disorders (SSD). Current neuroscience evidence suggests several brain areas are involved in the generation of hallucinations including the sensory cortex, insula, putamen, and hippocampus. But how does activity in these regions give rise to aberrant conscious perceptions that seemingly invade ongoing conscious experience? Most existing models assume that sensory representations are sometimes spontaneously activated in the brain, and that these spontaneous activations somehow play a causal role in the generation of hallucinations. Yet, it remains unclear how these representations become selected for conscious processing. No existing theory of hallucinations has specified such a “selection mechanism.” Global Workspace (GW) theorists argue that the brain’s interconnected processors select relevant piece(s) of information for broadcasting to other brain processors, rendering the information accessible to consciousness; this process known as “ignition” is associated with synchronized activity across distributed cortical and subcortical brain regions. Yet, it remains unclear how certain information and representations become selected for conscious processing. While GW theorists maintain that attention plays an important role, they have not delineated a formal “selection mechanism.” This paper specifies a selection mechanism based upon two central hypotheses: (1) a functional network called the “salience network” plays a critical role in selecting sensory representations for conscious broadcast to the GW in normal (healthy) perception; (2) sensory representations become abnormally selected for conscious broadcast to the GW (instead of being filtered out of consciousness) in individuals with SSD that experience hallucinations.
Autistic Traits and Empathy in Children With Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder and Co-occurring Attention Deficit Hyperactivity Disorder/Autism Spectrum Disorder
Authors: Aiello Stefania , Vagni David , Cerasa Antonio , Leonardi Elisa , Carrozza Cristina , Famà Francesca , Campisi Agrippina , Marino Flavia , Siracusano Rosamaria , Alquino Maria Ausilia , Mainiero Francesco , Germano Eva , Tartarisco Gennaro , Pioggia Giovanni , Gagliano Antonella , Ruta Liliana
Published: November 2021

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD) are two of the most represented neurodevelopmental conditions in childhood. The diagnostic shift introduced by the DSM-5, allowing a combined diagnosis of ADHD and ASD, poses different clinical challenges related to diagnostic overshadowing, accuracy of clinical judgment and potential delay in an ASD diagnosis in children presenting with ADHD. Here we tried to disentangle the clinical phenotype and specificity of the two co-occurring conditions in relation to autism traits and empathy, by comparing children with ASD with and without comorbid ADHD with children presenting ADHD only and children with typical development. The child versions of the Autism Quotient (C-AQ) and Empathy Quotient (C-EQ) were administered to a total sample of 198 male children between 6 and 14 years old with age appropriate language skills and normal intelligence. Univariate analysis demonstrated no significant differences in the C-AQ total and subscale scores as well as the C-EQ between children with ASD and children with ASD + ADHD, while children with ADHD alone presented an intermediate phenotype between ASD and TD. Furthermore, a receiver operating characteristic (ROC) analysis was applied to discriminate among the different phenotypes. We found that the C-AQ and C-EQ were accurate at distinguishing with satisfactory reliability between: (a) ASD vs. non- ASD (N-ASD) groups comprising both ADHD and TD children (Area Under the Curve AUC 88% for C-AQ and 81% for C-EQ); (b) ASD and TD (AUC 92% for C-AQ and 95% for C-EQ); (c) ASD and ADHD (AUC 80% for C-AQ and 68% for C-EQ). Our data confirm the reliability of the C-AQ and C-EQ as behavioral markers to differentiate ASD (regardless of comorbid ADHD) from an ADHD condition and TD. Interestingly, in our sample an ADHD condition does not increase the severity of the clinical phenotype in terms of autism traits distribution and empathy, suggesting that the psychological measures detected by the two quantitative instruments are independent of ADHD traits. This evidence will contribute to the translational efforts in developing better tailored treatments and preventive strategies.
Cognitive Development and Brain Gray Matter Susceptibility to Prenatal Adversities: Moderation by the Prefrontal Cortex Brain-Derived Neurotrophic Factor Gene Co-expression Network
Authors: de Mendonça Filho Euclides José , Barth Barbara , Bandeira Denise Ruschel , de Lima Randriely Merscher Sobreira , Arcego Danusa Mar , Dalmaz Carla , Pokhvisneva Irina , Sassi Roberto Britto , Hall Geoffrey B. C. , Meaney Michael J. , Silveira Patricia Pelufo
Published: November 2021

Background:Previous studies focused on the relationship between prenatal conditions and neurodevelopmental outcomes later in life, but few have explored the interplay between gene co-expression networks and prenatal adversity conditions on cognitive development trajectories and gray matter density.

Methods:We analyzed the moderation effects of an expression polygenic score (ePRS) for the Brain-derived Neurotrophic Factor gene network (BDNF ePRS) on the association between prenatal adversity and child cognitive development. A score based on genes co-expressed with the prefrontal cortex (PFC) BDNF was created, using the effect size of the association between the individual single nucleotide polymorphisms (SNP) and the BDNF expression in the PFC. Cognitive development trajectories of 157 young children from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) cohort were assessed longitudinally in 4-time points (6, 12, 18, and 36 months) using the Bayley-II mental scales.

Results:Linear mixed-effects modeling indicated that BDNF ePRS moderates the effects of prenatal adversity on cognitive growth. In children with high BDNF ePRS, higher prenatal adversity was associated with slower cognitive development in comparison with those exposed to lower prenatal adversity. Parallel-Independent Component Analysis (pICA) suggested that associations of expression-based SNPs and gray matter density significantly differed between low and high prenatal adversity groups. The brain IC included areas involved in visual association processes (Brodmann area 19 and 18), reallocation of attention, and integration of information across the supramodal cortex (Brodmann area 10).

Conclusion:Cognitive development trajectories and brain gray matter seem to be influenced by the interplay of prenatal environmental conditions and the expression of an important BDNF gene network that guides the growth and plasticity of neurons and synapses.
Application of Clustering Method to Explore the Correlation Between Dominant Flora and the Autism Spectrum Disorder Clinical Phenotype in Chinese Children
Authors: Chen Biyuan , You Na , Pan Bangquan , He Xueyi , Zou Xiaobing
Published: November 2021

Autism spectrum disorder (ASD) is characterized by deficits in social interactions and repetitive, stereotypic behaviors. Evidence shows that bidirectional communication of the gut-brain axis plays an important role. Here, we recruited 62 patients with ASD in southern China, and performed a cross-sectional study to test the relationship between repeated behavior, gut microbiome composition, and alpha diversity. We divided all participants into two groups based on the clustering results of their microbial compositions and found Veillonella and Ruminococcus as the seed genera in each group. Repetitive behavior differed between clusters, and cluster 2 had milder repetitive symptoms than Cluster 1. Alpha diversity between clusters was significantly different, indicating that cluster 1 had lower alpha diversity and more severe repetitive, stereotypic behaviors. Repetitive behavior had a negative correlation with alpha diversity. We demonstrated that the difference in intestinal microbiome composition and altered alpha diversity can be associated with repetitive, stereotypic behavior in autism. The role of Ruminococcus and Veillonella in ASD is not yet understood.
Subjective Cognitive Complaints in Newly-Diagnosed Parkinson’s Disease With and Without Mild Cognitive Impairment
Authors: Pan Chenxi , Ren Jingru , Hua Ping , Yan Lei , Yu Miao , Wang Yajie , Zhou Gaiyan , Zhang Ronggui , Chen Jiu , Liu Weiguo
Published: November 2021

Background: Subjective cognitive complaints (SCCs) and mild cognitive impairment (MCI) are common among patients with Parkinson’s disease (PD). However, the relationship between SCCs and MCI is not well understood. Herein, we aimed to investigate whether there are any differences in the prevalence and risk factors of SCCs between early PD patients with and without MCI.

Methods: Overall, 108 newly diagnosed, untreated PD patients underwent comprehensive neuropsychological assessments. PD patients with mild cognitive impairment (PD-MCI) were diagnosed according to the MCI level II criteria. Furthermore, SCCs were measured with the Cognitive Complaints Interview (CCI). Logistic regression analysis, after adjusting for confounding variable, was performed in order to investigate risk factors of SCCs in PD-MCI patients and PD patients with normal cognition (PD-NC).

Results: Furthermore, 42 (42.3%) participants reported SCCs and 53 (53.5%) participants were diagnosed with PD-MCI. The prevalence of SCCs in PD-MCI and PD-NC participants was 30.3% and 12.1%, respectively. Logistic regression analyses revealed that the presence of SCCs in PD-MCI group was significantly associated with Non-Motor Symptoms Questionnaire (NMSQ) score (OR = 1.340, 95%CI = 1.115−1.610, p = 0.002), while the presence of SCCs in PD-NC group was significantly associated with time of Stroop Color-Word Test card C (OR = 1.050, 95%CI = 1.009−1.119, p = 0.016).

Conclusion: SCCs are frequent among patients with early PD. The prevalence and risk factor of SCCs are distinct in PD with and without MCI. These findings suggest that SCCs in early PD with different cognitive status appear to have different pathogenicity.
Vector Auto-Regressive Deep Neural Network: A Data-Driven Deep Learning-Based Directed Functional Connectivity Estimation Toolbox
Authors: Okuno Takuto , Woodward Alexander
Published: November 2021

An important goal in neuroscience is to elucidate the causal relationships between the brain’s different regions. This can help reveal the brain’s functional circuitry and diagnose lesions. Currently there are a lack of approaches to functional connectome estimation that leverage the state-of-the-art in deep learning architectures and training methodologies. Therefore, we propose a new framework based on a vector auto-regressive deep neural network (VARDNN) architecture. Our approach consists of a set of nodes, each with a deep neural network structure. These nodes can be mapped to any spatial sub-division based on the data to be analyzed, such as anatomical brain regions from which representative neural signals can be obtained. VARDNN learns to reproduce experimental time series data using modern deep learning training techniques. Based on this, we developed two novel directed functional connectivity (dFC) measures, namely VARDNN-DI and VARDNN-GC. We evaluated our measures against a number of existing functional connectome estimation measures, such as partial correlation and multivariate Granger causality combined with large dimensionality counter-measure techniques. Our measures outperformed them across various types of ground truth data, especially as the number of nodes increased. We applied VARDNN to fMRI data to compare the dFC between 41 healthy control vs. 32 Alzheimer’s disease subjects. Our VARDNN-DI measure detected lesioned regions consistent with previous studies and separated the two groups well in a subject-wise evaluation framework. Summarily, the VARDNN framework has powerful capabilities for whole brain dFC estimation. We have implemented VARDNN as an open-source toolbox that can be freely downloaded for researchers who wish to carry out functional connectome analysis on their own data.
Deep Convolutional Neural Network With a Multi-Scale Attention Feature Fusion Module for Segmentation of Multimodal Brain Tumor
Authors: He Xueqin , Xu Wenjie , Yang Jane , Mao Jianyao , Chen Sifang , Wang Zhanxiang
Published: December 2021

As a non-invasive, low-cost medical imaging technology, magnetic resonance imaging (MRI) has become an important tool for brain tumor diagnosis. Many scholars have carried out some related researches on MRI brain tumor segmentation based on deep convolutional neural networks, and have achieved good performance. However, due to the large spatial and structural variability of brain tumors and low image contrast, the segmentation of MRI brain tumors is challenging. Deep convolutional neural networks often lead to the loss of low-level details as the network structure deepens, and they cannot effectively utilize the multi-scale feature information. Therefore, a deep convolutional neural network with a multi-scale attention feature fusion module (MAFF-ResUNet) is proposed to address them. The MAFF-ResUNet consists of a U-Net with residual connections and a MAFF module. The combination of residual connections and skip connections fully retain low-level detailed information and improve the global feature extraction capability of the encoding block. Besides, the MAFF module selectively extracts useful information from the multi-scale hybrid feature map based on the attention mechanism to optimize the features of each layer and makes full use of the complementary feature information of different scales. The experimental results on the BraTs 2019 MRI dataset show that the MAFF-ResUNet can learn the edge structure of brain tumors better and achieve high accuracy.
Mitochondria Dysfunction in Frontotemporal Dementia/Amyotrophic Lateral Sclerosis: Lessons From Drosophila Models
Authors: Anoar Sharifah , Woodling Nathaniel S. , Niccoli Teresa
Published: November 2021

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by declining motor and cognitive functions. Even though these diseases present with distinct sets of symptoms, FTD and ALS are two extremes of the same disease spectrum, as they show considerable overlap in genetic, clinical and neuropathological features. Among these overlapping features, mitochondrial dysfunction is associated with both FTD and ALS. Recent studies have shown that cells derived from patients’ induced pluripotent stem cells (iPSC)s display mitochondrial abnormalities, and similar abnormalities have been observed in a number of animal disease models. Drosophila models have been widely used to study FTD and ALS because of their rapid generation time and extensive set of genetic tools. A wide array of fly models have been developed to elucidate the molecular mechanisms of toxicity for mutations associated with FTD/ALS. Fly models have been often instrumental in understanding the role of disease associated mutations in mitochondria biology. In this review, we discuss how mutations associated with FTD/ALS disrupt mitochondrial function, and we review how the use of Drosophila models has been pivotal to our current knowledge in this field.
Contribution of Membrane Lipids to Postsynaptic Protein Organization
Authors: Westra Manon , Gutierrez Yolanda , MacGillavry Harold D.
Published: November 2021

The precise subsynaptic organization of proteins at the postsynaptic membrane controls synaptic transmission. In particular, postsynaptic receptor complexes are concentrated in distinct membrane nanodomains to optimize synaptic signaling. However, despite the clear functional relevance of subsynaptic receptor organization to synaptic transmission and plasticity, the mechanisms that underlie the nanoscale organization of the postsynaptic membrane remain elusive. Over the last decades, the field has predominantly focused on the role of protein-protein interactions in receptor trafficking and positioning in the synaptic membrane. In contrast, the contribution of lipids, the principal constituents of the membrane, to receptor positioning at the synapse remains poorly understood. Nevertheless, there is compelling evidence that the synaptic membrane is enriched in specific lipid species and that deregulation of lipid homeostasis in neurons severely affects synaptic functioning. In this review we focus on how lipids are organized at the synaptic membrane, with special emphasis on how current models of membrane organization could contribute to protein distribution at the synapse and synaptic transmission. Finally, we will present an outlook on how novel technical developments could be applied to study the dynamic interplay between lipids and proteins at the postsynaptic membrane.
Types of Consciousness: The Diversity Problem
Authors: Montemayor Carlos
Published: November 2021

Consciousness research has a cognitive-diversity problem. Any view that holds that attention is either necessary for consciousness or that attention precedes conscious awareness confronts the difficulty that the theoretical categorization of attention is as diverse as the categorization of intelligent cognition, but consciousness is typically referred to as a single and unified capacity. On the one hand, we have a multiplicity of kinds of attention. On the other hand, we use a monolithic “phenomenal” notion of consciousness to define the dependency of consciousness on all these diverse kinds of attention. Since attention is defined in terms of a diverse variety of functions, a lot more needs to be said with respect to the claim that attention is either necessary for consciousness or that attentional processing precedes conscious awareness. Is this dependency based on the diverse cognitive functions of attention? If so, why conceive of consciousness as a single informationally unified cognitive capacity? What does the multiplicity of kinds of attention entail for consciousness research? This is the “diversity problem.” This article argues that consciousness should be also considered as a diverse set of capacities, based on the diversity of attention. While we have the intuition that consciousness is a unified perspective, the article shows that consistency demands this diverse approach. Since research on attention distinguishes a wide range of functions and levels of cognitive processing, the dependency of consciousness on attention entails diverse conscious capacities and diverse types of awareness beyond the distinctions between being awake, dreaming, and being minimally conscious.
The Efference Copy Signal as a Key Mechanism for Consciousness
Authors: Vallortigara Giorgio
Published: December 2021

Animals need to distinguish sensory input caused by their own movement from sensory input which is due to stimuli in the outside world. This can be done by an efference copy mechanism, a carbon copy of the movement-command that is routed to sensory structures. Here I tried to link the mechanism of the efference copy with the idea of the philosopher Thomas Reid that the senses would have a double province, to make us feel, and to make us perceive, and that, as argued by psychologist Nicholas Humphrey, the former would identify with the signals from bodily sense organs with an internalized evaluative response, i.e., with phenomenal consciousness. I discussed a possible departure from the classical implementation of the efference copy mechanism that can effectively provide the senses with such a double province, and possibly allow us some progress in understanding the nature of consciousness.
Association Between Obesity and Post-stroke Anxiety in Patients With Acute Ischemic Stroke
Authors: Zhu Bei-Lei , Hu Ai-Yi , Huang Gui-Qian , Qiu Hui-Hua , Hong Xian-Chai , Hu Ping-Lang , Yuan Cheng-Xiang , Ruan Yi-Ting , Yang Bo , He Jin-Cai
Published: November 2021

Post-stroke anxiety (PSA) is serious psychosomatic comorbidity among patients with stroke, but whether obesity could be positively associated with PSA is currently unknown. The purpose of this study was to investigate the potential association between obesity and subsequent anxiety risk in patients with stroke. A total of 441 patients with acute ischemic stroke (AIS) onset were consecutively recruited within 7 days, and PSA and post-stroke depression (PSD) were evaluated by using a 14-item Hamilton anxiety scale (HAMA) and 17-item Hamilton depression scale (HAMD) at the end of 1-month follow-up. The odds ratio (OR) with 95% CI was estimated for the incidental PSA by using logistic regression analysis. The incidence of PSA was 25.85% at the end of 1-month follow-up, with a significant difference between patients with and without abdominal obesity. Relative fat mass (RFM) and abdominal obesity were significantly associated with an elevated risk of PSA, and the crude ORs were 1.04 (95% CI: 1.01–1.08) and 1.93 (95% CI: 1.11–3.34), respectively. Even after adjustment for obesity-related risk factors and PSA-related clinical measurements, the association remained to be pronounced with abdominal obesity. However, RFM (OR = 1.03, 95% CI: 0.99–1.06, P = 0.053) and abdominal obesity (OR = 1.31, 95% CI: 0.80–2.15, P = 0.280) were not significantly associated with an elevated risk of PSD. Abdominal obesity was independently associated with the PSA instead of PSD, which may help predict PSA risk in clinical practice. Further prospective clinical studies with a long follow-up duration are warranted to verify this finding.