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Qiaoting Huang,1 Changzheng Shi,2 Saurabh Sonkusare,3 Congrui Li,1 Valerie Voon,3 Jiyang Pan1 1Department of Psychiatry, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 2Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China; 3Department of Psychiatry, University of Cambridge, Cambridge, UKCorrespondence: Jiyang Pan, Department of Psychiatry, The First Affiliated Hospital of Jinan University, 613 West Huangpu Avenue, Guangzhou, 510630, People’s Republic of China, Tel +86 20 38688651, Email jiypan@163.com Valerie Voon, Department of Psychiatry, University of Cambridge, Box 189, Level E4, Addenbrooke’s Hospital, Cambridge, CB2 0QQ, UK, Tel +44 1223 765088, Email vv247@cam.ac.ukPurpose: Converging evidence implicates the putamen in sleep-wake regulation. However, its role remains unclear. We hypothesized that metabolic abnormalities in the putamen are linked to insomnia disorder, which has not been previously addressed, and investigated putaminal N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) in patients with insomnia disorder compared to healthy controls.Participants and Methods: In the present study, the concentrations of NAA, Cho, and Cr in the putamen of 23 patients with insomnia disorder and 18 healthy controls were determined using proton magnetic resonance spectroscopy. Sociodemographic, psychometric, and polysomnography data were obtained from all participants.Results: We found that the mean NAA/Cr ratio of the right putamen was significantly greater in the insomnia group compared to the control group and also greater than the left putamen within the insomnia group. The NAA/Cr ratio of the right putamen distinguished insomnia disorder from normal sleep with 78.3% sensitivity and 61.1% specificity. Furthermore, this ratio positively correlated with both objective and subjective insomnia severity and sleep quality.Conclusion: Our findings provide critical evidence for the dysfunctional putaminal metabolism of NAA/Cr in insomnia disorder, suggesting that the abnormal NAA/Cr ratio of the right putamen is linked to wakefulness in patients with insomnia disorder and may serve as a potential biomarker of insomnia disorder.Keywords: insomnia disorder, wakefulness, putamen, proton magnetic resonance spectroscopy, NAA/Cr ratio, polysomnography

Background: Glioblastoma (GBM) is the most common primary malignant brain tumor. The aim of this study was to elucidate the role of microenvironment and intrinsic T-type calcium channels (Cav3) in regulating tumor growth and progression., Methods: We grafted syngeneic GBM cells into Cav3.2 knockout mice to assess the role of microenvironment T-Type calcium channels on GBM tumor growth. We performed single-cell RNA-seq (scRNA-seq) of tumors from WT and Cav3.2 KO mice to elucidate the regulation of tumors by the microenvironment. We used neurons from WT and Cav3.2 KO mice in co-culture with GBM stem cells (GSC) to assess the effects of Cav3.2 on neuron/GSC synaptic connections and tumor cell growth., Results: Cav3.2 KO in the microenvironment led to significant reduction of GBM growth and prolongation of animal survival. scRNA-seq showed that microenvironment Cav3.2 regulates neuronal and glial biological processes. Microenvironment Cav3.2 downregulated numerous genes associated with regulating the OPC cell state in GBM tumors such as SOX10 and Olig2. Neuronal Cav3.2 promoted neuron/GSC synaptic connections and GSC growth. Treatment of GSCs with the Cav3 blocker mibefradil downregulated genes associated with neuronal processes. The Cav3 blocker drug mibefradil synergized with temozolomide (TMZ) and radiation to reduce in vivo tumor growth and prolong animal survival., Conclusions: Together these data reveal a role for microenvironment Cav3 in promoting GBM tumor progression through regulating neuronal and glial processes particularly associated with the OPC-cell state. Targeting both intrinsic and microenvironment Cav3 with the inhibitor mibefradil significantly enhanced the anti-GBM effects of TMZ and radiation., Competing Interests: Conflict of Interest The authors have declared that no conflicts of interest exist

Background: Response inhibition - or the ability to withhold a suboptimal response - relies on the efficacy of fronto-striatal networks, and is impaired in neuropsychiatric disorders including addiction. Cortical paired associative stimulation (cPAS) is a form of transcranial magnetic stimulation (TMS) which can strengthen neuronal connections via spike-timing-dependent plasticity mechanisms. Here, we used cPAS targeting the fronto-striatal inhibitory network to modulate performance on a response inhibition measure in chronic alcohol use., Methods: Fifty-five participants (20 patients with a formal alcohol use disorder (AUD) diagnosis (26-74 years, 6[30%] females) and 20 matched healthy controls (HCs) (27-73 years, 6[30%] females) within a larger sample of 35 HCs (23-84 years, 11[31.4%] females) underwent two randomized sessions of cPAS 1-week apart: right inferior frontal cortex stimulation preceding right presupplementary motor area stimulation by either 4 ms (excitation condition) or 100 ms (control condition), and were subsequently administered the Stop Signal Task (SST) in both sessions., Results: HCs showed decreased stop signal reaction time in the excitation condition (t(19) = -3.01, p = 0.007, [CIs]:-35.6 to -6.42); this facilitatory effect was not observed for AUD (F(1,31) = 9.57, p = 0.004, CIs: -68.64 to -14.11). Individually, rates of SST improvement were substantially higher for healthy (72%) relative to AUD (13.6%) groups (OR: 2.33, p = 0.006, CIs:-3.34 to -0.55)., Conclusion: In line with previous findings, cPAS improved response inhibition in healthy adults by strengthening the fronto-striatal network through putative long-term potentiation-like plasticity mechanisms. Furthermore, we identified a possible marker of impaired cortical excitability, and, thus, diminished capacity for cPAS-induced neuroplasticity in AUD with direct implications to a disorder-relevant cognitive process.

Current behavioural treatment of obsessive-compulsive disorder (OCD) is informed by fear conditioning and involves iteratively re-evaluating previously threatening stimuli as safe. However, there is limited research investigating the neurobiological response to conditioning and reversal of threatening stimuli in individuals with OCD. A clinical sample of individuals with OCD (N = 45) and matched healthy controls (N = 45) underwent functional magnetic resonance imaging. While in the scanner, participants completed a well-validated fear reversal task and a resting-state scan. We found no evidence for group differences in task-evoked brain activation or functional connectivity in OCD. Multivariate analyses encompassing all participants in the clinical and control groups suggested that subjective appraisal of threatening and safe stimuli were associated with a larger difference in brain activity than the contribution of OCD symptoms. In particular, we observed a brain-behaviour continuum whereby heightened affective appraisal was related to increased bilateral insula activation during the task (r = 0.39, p FWE  = .001). These findings suggest that changes in conditioned threat-related processes may not be a core neurobiological feature of OCD and encourage further research on the role of subjective experience in fear conditioning., (© 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Numerous environmental contaminants significantly contribute to human disease, affecting climate change and public and individual health, resulting in increased mortality and morbidity. Because of the scarcity of information regarding pollution exposure from less developed nations with inadequate waste management, higher levels of poverty, and limited adoption of new technology, the relationship between pollutants and health effects needs to be investigated more. A similar situation is present in many developed countries, where solutions are only discovered after the harm has already been done and the necessity for safeguards has subsided. The connection between environmental toxins and health needs to be better understood due to difficulties in quantifying exposure levels and a lack of systematic monitoring. Different pollutants are to blame for both chronic and acute disorders. Additionally, research becomes challenging when disease problems are seen after prolonged exposure. This review aims to discuss the present understanding of the association between environmental toxins and human health in bridging this knowledge gap. The genesis of cancer and the impact of various environmental pollutants on the human body's cardiovascular, respiratory, reproductive, prenatal, and neural health are discussed in this overview., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Introduction: Deep brain stimulation (DBS) studies in Parkinson's Disease (PD) targeting the subthalamic nucleus (STN) have characterized its spectral properties across cognitive processes. In emotional evaluation tasks, specific alpha frequency (8-12 Hz) event-related de-synchronization (ERD) (reduced power) has been demonstrated. The time-locked stimulation of STN relative to stimuli onset has shown subjective positive valence shifts with 10 Hz but not with 130 Hz. However, neurophysiological effects of stimulation on power modulation have not been investigated. We aim to investigate effects of acute stimulation of the right STN on concurrent power modulation in the contralateral STN and frontal scalp EEG. From our previous study, we had a strong a priori hypothesis that negative imagery without stimulation would be associated with alpha ERD; negative imagery with 130 Hz stimulation would be also associated with alpha ERD given the lack of its effect on subjective valence ratings; negative imagery with 10 Hz stimulation was to be associated with enhanced alpha power given the shift in behavioral valence ratings., Methods: Twenty-four subjects with STN DBS underwent emotional picture-viewing tasks comprising neutral and negative pictures. In a subset of these subjects, the negative images were associated with time-locked acute stimulation at either 10 or 130 Hz. Power of signals was estimated relative to the baseline and subjected to non-parametric statistical testing., Results: As hypothesized, in 130 Hz stimulation condition, we show a decrease in alpha power to negative vs. neutral images irrespective of stimulation. In contrast, this alpha power decrease was no longer evident in the negative 10 Hz stimulation condition consistent with a predicted increase in alpha power. Greater beta power in the 10 Hz stimulation condition along with correlations between beta power across the 10 Hz stimulation and unstimulated conditions suggest physiological and cognitive generalization effects., Conclusion: Acute alpha-specific frequency stimulation presumably was associated with a loss of this expected decrease or desynchronization in alpha power to negative images suggesting the capacity to facilitate the synchronization of alpha and enhance power. Acute time-locked stimulation has the potential to provide causal insights into the spectral frequencies and temporal dynamics of emotional processing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Muhammad, Sonkusare, Ding, Wang, Mandali, Zhao, Sun, Li and Voon.)

The dynamic integration of sensory and bodily signals is central to adaptive behaviour. Although the anterior cingulate cortex (ACC) and the anterior insular cortex (AIC) play key roles in this process, their context-dependent dynamic interactions remain unclear. Here, we studied the spectral features and interplay of these two brain regions using high-fidelity intracranial-EEG recordings from five patients (ACC: 13 contacts, AIC: 14 contacts) acquired during movie viewing with validation analyses performed on an independent resting intracranial-EEG dataset. ACC and AIC both showed a power peak and positive functional connectivity in the gamma (30-35 Hz) frequency while this power peak was absent in the resting data. We then used a neurobiologically informed computational model investigating dynamic effective connectivity asking how it linked to the movie's perceptual (visual, audio) features and the viewer's heart rate variability (HRV). Exteroceptive features related to effective connectivity of ACC highlighting its crucial role in processing ongoing sensory information. AIC connectivity was related to HRV and audio emphasising its core role in dynamically linking sensory and bodily signals. Our findings provide new evidence for complementary, yet dissociable, roles of neural dynamics between the ACC and the AIC in supporting brain-body interactions during an emotional experience., (© 2023 Massachusetts Institute of Technology.)

The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is lacking, and the mechanistic understanding of these effects is incomplete. To confirm and advance knowledge on changes in frontostriatal functional connectivity in OCD, participants with OCD and matched healthy controls underwent resting-state functional, structural and diffusion neuroimaging. Functional connectivity changes in frontostriatal systems were here replicated in individuals with OCD (n = 52) compared with controls (n = 45). OCD participants showed greater functional connectivity (t = 4.3, PFWE = 0.01) between the nucleus accumbens (NAcc) and the orbitofrontal cortex (OFC) but lower functional connectivity between the dorsal putamen and lateral prefrontal cortex (t = 3.8, PFWE = 0.04) relative to controls. Computational modelling suggests that NAcc-OFC connectivity changes reflect an increased influence of NAcc over OFC activity and reduced OFC influence over NAcc activity (posterior probability, Pp > 0.66). Conversely, dorsal putamen showed reduced modulation over lateral prefrontal cortex activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalizing frontostriatal dynamics in OCD., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The amygdala, orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) form a crucial part of the emotion circuit, yet their emotion induced responses and interactions have been poorly investigated with direct intracranial recordings. Such high-fidelity signals can uncover precise spectral dynamics and frequency differences in valence processing allowing novel insights on neuromodulation. Here, leveraging the unique spatio-temporal advantages of intracranial electroencephalography (iEEG) from a cohort of 35 patients with intractable epilepsy (with 71 contacts in amygdala, 31 in OFC and 43 in mPFC), we assessed the spectral dynamics and interactions between the amygdala, OFC and mPFC during an emotional picture viewing task. Task induced activity showed greater broadband gamma activity in the negative condition compared to positive condition in all the three regions. Similarly, beta activity was increased in the negative condition in the amygdala and OFC while decreased in mPFC. Furthermore, beta activity of amygdala showed significant negative association with valence ratings. Critically, model-based computational analyses revealed unidirectional connectivity from mPFC to the amygdala and bidirectional communication between OFC-amygdala and OFC-mPFC. Our findings provide direct neurophysiological evidence for a much-posited model of top-down influence of mPFC over amygdala and a bidirectional influence between OFC and the amygdala. Altogether, in a relatively large sample size with human intracranial neuronal recordings, we highlight valence-dependent spectral dynamics and dyadic coupling within the amygdala-mPFC-OFC network with implications for potential targeted neuromodulation in emotion processing., (© 2022. The Author(s).)

Introduction: Cervical cancer is the most frequent malignancy among women caused by an unresolved long-term infection with distinct human papillomavirus (HPV) genotypes. It is the fourth most common form of cancer among women worldwide. The two oncogenic genotypes, HPV 16 and 18, are responsible for >70% of all cervical cancers worldwide. Cervical cancer is one of the most successfully preventable and treatable forms of cancer if detected early., Areas Covered: In this review article, we have summarizedsummarised the different approaches used in clinical diagnosis and research laboratories to detect HPV-related changes associated with cervical cancer for a better understanding of the advantages and limitations of these tests., Expert Opinion: Despite the well-known screening strategies for cervical cancer, developing nations lack effective implementation due to various factors. With the current rate of cervical cancer cases, precise and timely identification of HPV can significantly impact the prevention and efficient management of cervical cancer. Cervical cancer is the most common gynecological cancer in developing countries. The primary screening test with cytology and molecular testing of HPV is important for preventing cervical cancer. To address these issues, several point-of-care assays have been developed to facilitate rapid screening of HPV with the least turnaround time.

Management of postpartum perineal pain is essential because untreated pain can interfere with the motherhood experience and might result in various complications. The study aimed to assess postpartum perineal and postpartum pain intensity, pharmacological management and maternal complications after normal vaginal delivery. A prospective observational study was conducted in Obstetrics and Gynaecology among 300 women who underwent normal vaginal delivery. The severity and intensity of the perineal pain in subjects were relatively high, i.e. severe on Day 1, moderate to mild pain on Day 2 and mild pain on Day 3. The overall postpartum pain was mild on all 3 d. Non-steroidal anti-inflammatory drugs (NSAIDs) and analgesic combination drugs were prescribed the most for pain management, which significantly impacted pain reduction. All participants involved in the study had a postpartum haemorrhage and was the most common complication. The study concludes that there was a significant reduction in the overall intensity of pain from Day 1 to Day 3.IMPACT STATEMENT What is already known on this subject? Vaginal delivery is a multidimensional process that causes inflammation of cervical tissue and tears in the birth canal, leading to pain perception. Previous studies reported increased pain intensity on the first day after childbirth and a gradual decrease as the days pass. What do the results of this study add? The well-accepted pain scales, such as faces rating scale (FRS) and verbal numeric scale (VNS) were appropriate for assessing the intensity of perineal pain. Self-developed and validated postpartum pain assessment questionnaire (PPAQ) was beneficial for the assessment of postpartum pain. NSAIDs and analgesics combination was effective in managing the pain. What are the implications of these findings for clinical practice and/future research? Accurate pain assessment is essential for humanising patient care since it helps make a correct plan for required intervention, and its evaluation can help provide appropriate medications and reduce complications. Self-developed and validated PPAQ is easy to use and can be used in clinical studies to assess postpartum pain.

Background: Breast cancer (BC) is the most common cancer of women and the second most common cancer overall globally. Data suggest that the plasma concentration of omega fatty acids (n-3 and n-6) and the impact of the genetic variant are associated with diet-related inflammatory disease, BC. This study was aimed to find an association between genetic variant rs174537 of fatty acid desaturase gene 1(FADS 1) and breast cancer estrogen receptor subtype., Methodology: Hundred and two blood samples from women were quantified for fatty acids by gas chromatography. SNP rs 174537(G > T) showed maximum variability and the strongest genetic determinant in the Genome-wide association study were genotyped using Sanger sequencing., Results: The highest tertile of ALA showed a significantly reduced risk of BC compared to the lowest tertile (OR = 0.2, 95 %CL = 0.1-1.14, P = 0.03). Median values of ALA were higher in GT/TT genotype in ER +ve molecular subtype (P = 0.03) and DPA was higher in GG genotype of ER-ve molecular subtype (P = 0.037). When both the groups were put together the highest tertile of GG tertile showed significantly reduced risk of BC compared with the other lowest tertiles of GG and GT/TT genotypes (OR, 95% CL = 0.45(0.2-0.9)., Conclusion: The high levels of arachidonic acid and low levels of n-3 fatty acids result in a pro-inflammatory milieu and that these pro-inflammatory effects might contribute to BC. We conclude that the individuals with genetically determined lower activity of FADS1(minor allele T) will derive greater advantage from n-3 FAs than those with higher FADS1 activity (G allele) and reduce the BC risk., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The habenula is an epithalamic structure implicated in negative reward mechanisms and plays a downstream modulatory role in regulation of dopaminergic and serotonergic functions. Human and animal studies show its hyperactivity in depression which is curtailed by the antidepressant response of ketamine. Deep brain stimulation of habenula (DBS) for major depression have also shown promising results. However, direct neuronal activity of habenula in human studies have rarely been reported. Here, in a cross-sectional design, we acquired both spontaneous resting state and emotional task-induced neuronal recordings from habenula from treatment resistant depressed patients undergoing DBS surgery. We first characterise the aperiodic component (1/f slope) of the power spectrum, interpreted to signify excitation-inhibition balance, in resting and task state. This aperiodicity for left habenula correlated between rest and task and which was significantly positively correlated with depression severity. Time-frequency responses to the emotional picture viewing task show condition differences in beta and gamma frequencies for left habenula and alpha for right habenula. Notably, alpha activity for right habenula was negatively correlated with depression severity. Overall, from direct habenular recordings, we thus show findings convergent with depression models of aberrant excitatory glutamatergic output of the habenula driving inhibition of monoaminergic systems., (© 2022. The Author(s).)

Facial infra-red imaging (IRI) is a contact-free technique complimenting the traditional psychophysiological measures to characterize physiological profile. However, its full potential in affective research is arguably unmet due to the analytical challenges it poses. Here we acquired facial IRI data, facial expressions and traditional physiological recordings (heart rate and skin conductance) from healthy human subjects whilst they viewed a 20-min-long unedited emotional movie. We present a novel application of motion correction and the results of spatial independent component analysis of the thermal data. Three distinct spatial components are recovered associated with the nose, the cheeks and respiration. We first benchmark this methodology against a traditional nose-tip region-of-interest based technique showing an expected similarity of signals extracted by these methods. We then show significant correlation of all the physiological responses across subjects, including the thermal signals, suggesting common dynamic shifts in emotional state induced by the movie. In sum, this study introduces an innovative approach to analyse facial IRI data and highlights the potential of thermal imaging to robustly capture emotion-related changes induced by ecological stimuli.

This prospective cohort study, "Prospective Imaging Study of Ageing: Genes, Brain and Behaviour" (PISA) seeks to characterise the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer's disease (AD). In particular, we are recruiting midlife and older Australians with high and low genetic risk of dementia to discover biological markers of early neuropathology, identify modifiable risk factors, and establish the very earliest phenotypic and neuronal signs of disease onset. PISA utilises genetic prediction to recruit and enrich a prospective cohort and follow them longitudinally. Online surveys and cognitive testing are used to characterise an Australia-wide sample currently totalling over 3800 participants. Participants from a defined at-risk cohort and positive controls (clinical cohort of patients with mild cognitive impairment or early AD) are invited for onsite visits for detailed functional, structural and molecular neuroimaging, lifestyle monitoring, detailed neurocognitive testing, plus blood sample donation. This paper describes recruitment of the PISA cohort, study methodology and baseline demographics., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Adaptive brain function requires that sensory impressions of the social and natural milieu are dynamically incorporated into intrinsic brain activity. While dynamic switches between brain states have been well characterised in resting state acquisitions, the remodelling of these state transitions by engagement in naturalistic stimuli remains poorly understood. Here, we show that the temporal dynamics of brain states, as measured in fMRI, are reshaped from predominantly bistable transitions between two relatively indistinct states at rest, toward a sequence of well-defined functional states during movie viewing whose transitions are temporally aligned to specific features of the movie. The expression of these brain states covaries with different physiological states and reflects subjectively rated engagement in the movie. In sum, a data-driven decoding of brain states reveals the distinct reshaping of functional network expression and reliable state transitions that accompany the switch from resting state to perceptual immersion in an ecologically valid sensory experience.

The temporal pole (TP) is an associative cortical region required for complex cognitive functions such as social and emotional cognition. However, mapping the TP with functional magnetic resonance imaging is technically challenging and thus understanding its interaction with other key emotional circuitry, such as the amygdala, remains elusive. We exploited the unique advantages of stereo-electroencephalography (sEEG) to assess the responses of the TP and the amygdala during the perception of emotionally salient stimuli of pictures, music and movies. These stimuli consistently elicited high gamma responses (70-140 Hz) in both the TP and the amygdala, accompanied by functional connectivity in the low frequency range (2-12 Hz). Computational analyses suggested that the TP drove this effect in the theta frequency range, modulated by the emotional valence of the stimuli. Notably, cross-frequency analysis indicated the phase of theta oscillations in the TP modulated the amplitude of high gamma activity in the amygdala. These results were reproducible across three types of sensory inputs including naturalistic stimuli. Our results suggest that multimodal emotional stimuli induce a hierarchical influence of the TP over the amygdala., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Cognitive neuroscience has traditionally focused on simple tasks, presented sparsely and using abstract stimuli. While this approach has yielded fundamental insights into functional specialisation in the brain, its ecological validity remains uncertain. Do these tasks capture how brains function 'in the wild', where stimuli are dynamic, multimodal, and crowded? Ecologically valid paradigms that approximate real life scenarios, using stimuli such as films, spoken narratives, music, and multiperson games emerged in response to these concerns over a decade ago. We critically appraise whether this approach has delivered on its promise to deliver new insights into brain function. We highlight the challenges, technological innovations, and clinical opportunities that are required should this field meet its full potential., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Thermal Imaging (Infrared-Imaging-IRI) is a promising new technique for psychophysiological research and application. Unlike traditional physiological measures (like skin conductance and heart rate), it is uniquely contact-free, substantially enhancing its ecological validity. Investigating facial regions and subsequent reliable signal extraction from IRI data is challenging due to head motion artefacts. Exploiting its potential thus depends on advances in analytical methods. Here, we developed a novel semi-automated thermal signal extraction method employing deep learning algorithms for facial landmark identification. We applied this method to physiological responses elicited by a sudden auditory stimulus, to determine if facial temperature changes induced by a stimulus of a loud sound can be detected. We compared thermal responses with psycho-physiological sensor-based tools of galvanic skin response (GSR) and electrocardiography (ECG). We found that the temperatures of selected facial regions, particularly the nose tip, significantly decreased after the auditory stimulus. Additionally, this response was quite rapid at around 4-5 seconds, starting less than 2 seconds following the GSR changes. These results demonstrate that our methodology offers a sensitive and robust tool to capture facial physiological changes with minimal manual intervention and manual pre-processing of signals. Newer methodological developments for reliable temperature extraction promise to boost IRI use as an ecologically-valid technique in social and affective neuroscience.

Human interactions with the world are influenced by memories of recent events. This effect, often triggered by perceptual cues, occurs naturally and without conscious effort. However, the neuroscience of involuntary memory in a dynamic milieu has received much less attention than the mechanisms of voluntary retrieval with deliberate purpose. Here, we investigate the neural processes driven by naturalistic cues that relate to, and presumably trigger the retrieval of recent experiences. Viewing the continuation of recently viewed clips evokes greater bilateral activation in anterior hippocampus, precuneus and angular gyrus than naïve clips. While these regions manifest reciprocal connectivity, continued viewing specifically modulates the effective connectivity from the anterior hippocampus to the precuneus. The strength of this modulation predicts participants' confidence in later voluntary recall of news details. Our study reveals network mechanisms of dynamic, involuntary memory retrieval and its relevance to metacognition in a rich context resembling everyday life.

Current nonsurgical treatments of discogenic lumbar radiculopathy are neither effective nor safe. Our prior studies have suggested that hydroxylated fullerene (fullerol) nanomaterial could attenuate proinflammatory cytokine tumor necrosis factor alpha (TNF-α)-induced neuroinflammation and oxidative stress in mouse dorsal root ganglia (DRG) and primary neurons. Here, we aim to investigate the analgesic effect of fullerol in a clinically relevant lumbar radiculopathy mouse model and to understand its underlying molecular mechanism in mouse DRGs and neurons. Surprisingly, single and local application of fullerol solution (1 μ M, 10 μ L) was sufficient to alleviate ipsilateral paw pain sensation in mice up to 2 weeks postsurgery. In addition, microCT data suggested fullerol potentially promoted disc height recovery following injury-induced disc herniation. Alcian blue/picrosirius red staining also suggested that fullerol promoted regeneration of extracellular matrix proteins visualized by the presence of abundant newly formed collagen and proteoglycan in herniated discs. For in vitro DRG culture, fullerol attenuated TNF-α-elicited expression of transient receptor potential cation channel subfamily V member 1 (TRPV-1) and neuropeptides release (substance P and calcitonin gene-related peptide). In addition, fullerol suppressed TNF-α-stimulated increase in intracellular Ca 2+ concentrations in primary neurons. Moreover, Western blot analysis in DRG revealed that fullerol's beneficial effects against TNF-α might be mediated through protein kinase B (AKT) and extracellular protein-regulated kinase (ERK) pathways. These TNF-α antagonizing and analgesic effects indicated therapeutic potential of fullerol in treating lumbar radiculopathy, providing solid preclinical evidence toward further translational studies., Competing Interests: Notes The authors declare no competing financial interest.

The crucial role of the cerebellum in motor learning and coordination is very well known. Considerable interest has recently shifted toward its contribution to nonmotor tasks, such as working memory, emotion, and language. However, the cognitive role and functional subdivisions of the cerebellum, particularly in dynamic, ecologically realistic contexts, are not yet established. By analyzing functional neuroimaging data acquired while participants viewed a short dramatic movie, we found that posterior and inferior cerebellar regions are reliably engaged in dynamic perceptual and affective processes with no explicit motor component. These cerebellar regions show significant relevance to visual salience and unexpected turning points of the movie. Our results demonstrate that distinct functional subdivisions of the cerebellum are robustly engaged in real-life cognitive processes, playing specific roles through a dynamic interaction with higher order regions in the cerebral cortex., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Semantic retrieval involves both (1) automatic spreading activation between highly related concepts and (2) executive control processes that tailor this activation to suit the current context or goals. Two structures in left temporoparietal cortex, angular gyrus (AG) and posterior middle temporal gyrus (pMTG), are thought to be crucial to semantic retrieval and are often recruited together during semantic tasks; however, they show strikingly different patterns of functional connectivity at rest (coupling with the "default mode network" and "frontoparietal control system," respectively). Here, transcranial magnetic stimulation (TMS) was used to establish a causal yet dissociable role for these sites in semantic cognition in human volunteers. TMS to AG disrupted thematic judgments particularly when the link between probe and target was strong (e.g., a picture of an Alsatian with a bone), and impaired the identification of objects at a specific but not a superordinate level (for the verbal label "Alsatian" not "animal"). In contrast, TMS to pMTG disrupted thematic judgments for weak but not strong associations (e.g., a picture of an Alsatian with razor wire), and impaired identity matching for both superordinate and specific-level labels. Thus, stimulation to AG interfered with the automatic retrieval of specific concepts from the semantic store while stimulation of pMTG impaired semantic cognition when there was a requirement to flexibly shape conceptual activation in line with the task requirements. These results demonstrate that AG and pMTG make a dissociable contribution to automatic and controlled aspects of semantic retrieval., Significance Statement: We demonstrate a novel functional dissociation between the angular gyrus (AG) and posterior middle temporal gyrus (pMTG) in conceptual processing. These sites are often coactivated during neuroimaging studies using semantic tasks, but their individual contributions are unclear. Using transcranial magnetic stimulation and tasks designed to assess different aspects of semantics (item identity and thematic matching), we tested two alternative theoretical accounts. Neither site showed the pattern expected for a "thematic hub" (i.e., a site storing associations between concepts) since stimulation disrupted both tasks. Instead, the data indicated that pMTG contributes to the controlled retrieval of conceptual knowledge, while AG is critical for the efficient automatic retrieval of specific semantic information., (Copyright © 2015 Davey et al.)

Hyperemesis gravidarum is a severe and disabling condition with potentially life-threatening complications. It is likely to have a multifactorial etiology which contributes to the difficulty in treatment. Treatment is supportive with correction of dehydration and electrolyte disturbance, antiemetic therapy, prevention and treatment of complications like Wernicke's encephalopathy, osmotic demyelination syndrome, thromboembolism, and good psychological support. There are abundant data on the safety of antihistamines, phenothiazines, and metoclopromide in early pregnancy and treatment should therefore not be withheld on the basis of teratogenicity concerns. Thiamine replacement is indicated in hyperemesis gravidarum to prevent development of Wernicke's encephalopathy.

To evaluate the perinatal outcome of premature babies according to the mode of delivery. A total of 113 pregnant women and 124 neonates who delivered from 30 to 35 weeks of gestation were enrolled and outcomes of 70 neonates born vaginally were compared to 54 neonates born by caesarean. Neonatal mortality rate was 20 percent for infants in caesarean group as compared to 10 percent for vaginal group. There was no significant difference in the neonatal morbidity among both the groups. Caesarean delivery cannot be routinely recommended, unless there are obstetric indications.

Vomiting in pregnancy is a very common phenomenon, though not well understood. The extreme form, hyperemesis gravidarum can lead to severe complications. Articles published in the last decade in this field were searched and studied. Various aetiological factors were identified, the recent ones being the association of Helicobacter. pylori with hyperemesis, as well as the presence of cell free fetal DNA. The management of the condition involves symptomatic treatment along with antiemetic, pyridoxine and thiamine. Important role of alternative therapies like ginger and P6 acupoint stimulation in the treatment of hyperemesis has been identified.

Calcium influx through long-lasting ("L-type") Ca(2+) channels (Ca(V)) drives excitation-contraction in the normal heart. Dysregulation of this process contributes to Ca(2+) overload, and interventions that reduce expression of the pore-forming alpha(1) subunit may alleviate cytosolic Ca(2+) excess. As a molecular approach to disrupt the assembly of Ca(V)1.2 (alpha(1C)) channels at the cell membrane, we targeted the Ca(2+) channel beta(2) subunit, an intracellular chaperone that interacts with alpha(1C) via its beta interaction domain (BID) to promote Ca(V)1.2 channel expression. Recombinant adenovirus expressing either the full beta(2) subunit (Full-beta(2)) or truncated beta(2) subunit constructs lacking either the C terminus, N terminus, or both (N-BID, C-BID, and BID, respectively) fused to green fluorescent protein were developed as potential decoys and overexpressed in HL-1 cells. Fluorescence microscopy revealed that the localization of Full-beta(2) at the surface membrane was associated with increased Ca(2+) current mainly attributed to Ca(V)1.2 channels. In contrast, truncated N-BID and C-BID constructs showed punctate intracellular expression, and BID showed a diffuse cytosolic distribution. Total expression of the alpha(1C) protein of Ca(V)1.2 channels was similar between groups, but HL-1 cells overexpressing C-BID and BID exhibited reduced Ca(2+) current. C-BID and BID also attenuated Ca(2+) current associated with another L-type Ca(2+) channel, Ca(V)1.3, but they did not reduce transient Ca(2+) currents attributed to Ca(V)3 channels. These results suggest that beta(2) subunit mutants lacking the N terminus may preferentially disrupt the proper localization of L-type Ca(2+) channels in the cell membrane. Cardiac-specific delivery of these decoy molecules in vivo may represent a gene-based treatment for pathologies involving Ca(2+) overload.

The purpose of this study was to study the determinants of self rated health in the low-risk pregnant women of Melaka Tengah in Malaysia. A total of 387 subjects were analysed. The role of mental health, psychosocial stressors, support from husband, coping skills, socio-economic status and pregnancy characteristics in determining self- rated health were studied. Health items were taken from the Duke Health Profile. Bad obstetric history, poor mental health, stress from the family were found to be significantly associated with poor self - rated health whereas good support from the husband was related to good self - rated health.

Long-lasting Ca(2+) (Ca(L)) channels of the Ca(v)1.2 gene family are heteromultimeric structures that are minimally composed of a pore-forming alpha(1C) subunit and regulatory beta and alpha(2)delta subunits in vascular smooth muscle cells. The Ca(L) channels are the primary pathways for voltage-gated Ca(2+) influx that trigger excitation-contraction coupling in small resistance vessels. Notably, vascular smooth muscle cells of hypertensive rats show an increased expression of Ca(L) channel alpha(1C) subunits, which is associated with elevated Ca(2+) influx and the development of abnormal arterial tone. Indeed, blood pressure per se appears to promote Ca(L) channel expression in small arteries, and even short-term rises in pressure may alter channel expression. Membrane depolarization has been shown to be one stimulus associated with elevated blood pressure that promotes Ca(L) channel expression at the plasma membrane. Future studies to define the molecular processes that regulate Ca(L) channel expression in vascular smooth muscle cells will provide a rational basis for designing antihypertensive therapies to normalize Ca(L) channel expression and the development of anomalous vascular tone in hypertensive pathologies.

Intracerebroventricular (ICV) injection of streptozotocin (STZ) causes cognitive impairment in rats. ICV STZ is known to impair cholinergic neurotransmission by decreasing choline acetyltransferase (ChAT) levels, glucose and energy metabolism in brain and synthesis of acetyl CoA. However, no reports are available regarding the cholinesterase inhibitors in this model. In aging brain, reduced energy metabolism increases glutamate release, which is blocked by L-type calcium channel blockers. These calcium channel blockers have shown beneficial effects on learning and memory in various models of cognitive impairment. The present study was designed to investigate the influence of chronic administration of donepezil (cholinesterase inhibitor, 1 and 3 mg/kg) and lercanidipine (L-type calcium channel blocker, 0.3 and 1 mg/kg) on cognitive impairment in male Sprague-Dawley rats injected twice with ICV STZ (3 mg/kg) bilaterally on days 1 and 3. ICV STZ injected rats developed a severe deficit in learning and memory indicated by deficits in passive avoidance paradigm and elevated plus maze as compared to control rats. Cholinesterase activity in brain was significantly increased in ICV STZ injected rats. Donepezil dose-dependently inhibited cholinesterase activity and improved performance in memory tests at both the doses. Lercanidipine (0.3 mg/kg) showed significant improvement in memory. When administered together, the effect of combination of these two drugs on memory and cholinesterase activity was higher than that obtained with either of the drugs when used alone.