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Background: The pathophysiology of Alzheimer's disease (AD) may begin developing years or even decades prior to the manifestation of its first symptoms. The APOE ε4 genotype is a prominent genetic risk for AD that has been found to be associated with brain changes across the lifespan since early adulthood. Thus, studying brain changes that may occur in young adults with an APOE ε4 status is highly relevant. Objective: Examine potential differences in grey matter (GM) and functional connectivity (FC) in brains of cognitively healthy young APOE ε4 carriers and non-carriers, denoted here as ε4(+) and ε4(−), respectively. Methods: Three Tesla magnetic resonance imaging (MRI) brain scans were acquired from cognitively healthy young participants aged approximately 20 years (n = 151). Voxel-based morphometry (VBM) analysis was employed to identify potential structural differences in GM between ε4(+) and ε4(−). In a subsequent seed-based connectivity (SBC) analysis, brain regions that structurally differed in the VBM analysis were considered as seeds and correlated with all the remaining voxels across the brains to then measure the differences in FC between groups. Results: The VBM analysis suggested that ε4(+) (n = 28) had greater GM densities relative to ε4(−) (n = 123) in the left hippocampus and the left posterior insula (puncorr < 0.001). However, the effect did not survive the correction for multiple comparisons, suggesting minimal structural differences in this age range. In contrast, the SBC analysis indicated that ε4(+) exhibited significantly decreased FC between the left hippocampus and areas of the left middle temporal gyrus (n = 27) compared to ε4(−) (n = 102). These results remained significant after multiple comparisons (pFDR < 0.05). Lastly, no statistically significant differences in FC between groups were observed for the left insular seed (pFDR > 0.05). Discussion: These results suggest early structural and functional brain changes associated with the APOE ε4 genotype on young adults. Yet, they must be cautiously interpreted and contrasted with both older adults with genetic risk for AD and patients diagnosed with AD. [ABSTRACT FROM AUTHOR]

Relating brain activity to cognition and behavior is the primary goal of cognitive neuroscience. Neuroscientists are increasingly summarizing the brain dynamics that underlie cognition and behavior in terms of brain states. Brain states have traditionally been defined as specific spatial patterns of activity or functional connectivity. We propose that brain states should be conceptualized as waves – recurring patterns of activity that sequentially propagate with different delay times. This definition emphasizes both the spatial and temporal patterns of brain activity. There is ample evidence of wave-like activity in the brain at multiple scales and levels. This emerging literature supports the broader adoption of a wave perspective of brain activity. Specifically, a brain state can be described as a set of recurring, sequential patterns of propagating brain activity, namely a wave. We examine a collective body of experimental work investigating wave-like properties. Based on these works, we consider brain states as waves using a scale-agnostic framework across time and space. Emphasis is placed on the sequentiality and periodicity associated with brain activity. We conclude by discussing the implications, prospects, and experimental opportunities of this framework. [ABSTRACT FROM AUTHOR]

Isolated rapid-eye-movement behavior disorder (iRBD) often precedes the development of alpha-synucleinopathies such as Parkinson's disease (PD). Magnetic resonance imaging (MRI) studies have revealed structural brain alterations in iRBD partially resembling those observed in PD. However, relatively little is known about whole-brain functional brain alterations in iRBD. Here, we characterize the functional brain connectome of iRBD compared with PD patients and healthy controls (HC) using resting-state functional MRI (rs-fMRI). Eighteen iRBD subjects (67.3 ± 6.6 years), 18 subjects with PD (65.4 ± 5.8 years), and 39 age- and sex-matched HC (64.4 ± 9.2 years) underwent rs-fMRI at 3 T. We applied a graph theoretical approach to analyze the brain functional connectome at the global and regional levels. Data were analyzed using both frequentist and Bayesian statistics. Global connectivity was largely preserved in iRBD and PD individuals. In contrast, both disease groups displayed altered local connectivity mainly in the motor network, temporal cortical regions including the limbic system, and the visual system. There were some group specific alterations, and connectivity changes were pronounced in PD individuals. Overall, however, there was a good agreement of the connectome changes observed in both disease groups. This study provides evidence for widespread functional brain connectivity alterations in iRBD, including motor circuitry, despite normal motor function. Connectome alterations showed substantial resemblance with those observed in PD, underlining a close pathophysiological relationship of iRBD and PD. • Isolated REM-Sleep-behavior-disorder (iRBD) is a prodrome of Parkinson's disease (PD). • IRBD is characterized by wide spread functional brain alterations. • These connectivity changes show remarkable resemblance with those found in PD. • Our work suggests a close pathophysiological relationship of iRBD with PD. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson disease is a neurodegenerative disease that disrupts functional brain networks. Many neurodegenerative disorders are associated with changes in brain communication patterns. Resting-state functional connectivity studies can distinguish the topological structure of Parkinson patients from healthy individuals by analyzing patterns between different regions of the brain. Accordingly, the present study aimed to determine the brain topological features and functional connectivity in patients with Parkinson disease, using a Bayesian approach. Methods: The data of this study were downloaded from the open neuro site. These data include resting-state functional magnetic resonance imaging (rs-fMRI) of 11 healthy individuals and 11 Parkinson patients with mean ages of 64.36 and 63.73, respectively. An advanced nonparametric Bayesian model was used to evaluate topological characteristics, including clustering of brain regions and correlation coefficient of the clusters. The significance of functional relationships based on each edge between the two groups was examined through false discovery rate (FDR) and network-based statistics (NBS) methods. Results: Brain connectivity results showed a major difference in terms of the number of regions in each cluster and the correlation coefficient between the patient and healthy groups. The largest clusters in the patient and control groups were 26 and 53 regions, respectively, with clustering correlation values of 0.36 and 0.26. Although there are 15 common areas across the two clusters, the intensity of the functional relationship between these areas was different in the two groups. Moreover, using NBS and FDR methods, no significant difference was observed for each edge between the patient and healthy groups (P>0.05). Conclusion: The results of this study show a different topological configuration of the brain network between the patient and healthy groups, indicating changes in the functional relationship between a set of areas of the brain. [ABSTRACT FROM AUTHOR]

Abstract Background Studies in animal models of Alzheimer’s disease (AD) have provided valuable insights into the molecular and cellular processes underlying neuronal network dysfunction. Whether and how AD-related neurophysiological alterations translate between mice and humans remains however uncertain. Methods We characterized neurophysiological alterations in mice and humans carrying AD mutations in the APP and/or PSEN1 genes, focusing on early pre-symptomatic changes. Longitudinal local field potential recordings were performed in APP/PS1 mice and cross-sectional magnetoencephalography recordings in human APP and/or PSEN1 mutation carriers. All recordings were acquired in the left frontal cortex, parietal cortex, and hippocampus. Spectral power and functional connectivity were analyzed and compared with wildtype control mice and healthy age-matched human subjects. Results APP/PS1 mice showed increased absolute power, especially at higher frequencies (beta and gamma) and predominantly between 3 and 6 moa. Relative power showed an overall shift from lower to higher frequencies over almost the entire recording period and across all three brain regions. Human mutation carriers, on the other hand, did not show changes in power except for an increase in relative theta power in the hippocampus. Mouse parietal cortex and hippocampal power spectra showed a characteristic peak at around 8 Hz which was not significantly altered in transgenic mice. Human power spectra showed a characteristic peak at around 9 Hz, the frequency of which was significantly reduced in mutation carriers. Significant alterations in functional connectivity were detected in theta, alpha, beta, and gamma frequency bands, but the exact frequency range and direction of change differed for APP/PS1 mice and human mutation carriers. Conclusions Both mice and humans carrying APP and/or PSEN1 mutations show abnormal neurophysiological activity, but several measures do not translate one-to-one between species. Alterations in absolute and relative power in mice should be interpreted with care and may be due to overexpression of amyloid in combination with the absence of tau pathology and cholinergic degeneration. Future studies should explore whether changes in brain activity in other AD mouse models, for instance, those also including tau pathology, provide better translation to the human AD continuum.

The increasing number of MRI studies focused on prodromal Parkinson's Disease (PD) demonstrates a strong interest in identifying early biomarkers capable of monitoring neurodegeneration. In this systematic review, we present the latest information regarding the most promising MRI markers of neurodegeneration in relation to the most specific prodromal symptoms of PD, namely isolated rapid eye movement (REM) sleep behavior disorder (iRBD). We reviewed structural, diffusion, functional, iron-sensitive, neuro-melanin-sensitive MRI, and proton magnetic resonance spectroscopy studies conducted between 2000 and 2023, which yielded a total of 77 relevant papers. Among these markers, iron and neuromelanin emerged as the most robust and promising indicators for early neurodegenerative processes in iRBD. Atrophy was observed in several regions, including the frontal and temporal cortices, limbic cortices, and basal ganglia, suggesting that neurodegenerative processes had been underway for some time. Diffusion and functional MRI produced heterogeneous yet intriguing results. Additionally, reduced glymphatic clearance function was reported. Technological advancements, such as the development of ultra-high field MRI, have enabled the exploration of minute anatomical structures and the detection of previously undetectable anomalies. The race to achieve early detection of neurodegeneration is well underway. [ABSTRACT FROM AUTHOR]

Background and Aims Despite relevance to pain chronicity, disease burden, and treatment, mechanisms of pain perception for different types of acute pain remain incompletely understood in patients with inflammatory bowel disease [IBD]. Building on experimental research across pain modalities, we herein addressed behavioural and neural correlates of visceral versus somatic pain processing in women with quiescent ulcerative colitis [UC] compared to irritable bowel syndrome [IBS] as a patient control group and healthy women [HC]. Methods Thresholds for visceral and somatic pain were assessed with rectal distensions and cutaneous thermal pain, respectively. Using functional magnetic resonance imaging, neural and behavioural responses to individually calibrated and intensity-matched painful stimuli from both modalities were compared. Results Pain thresholds were comparable across groups, but visceral thresholds correlated with gastrointestinal symptom severity and chronic stress burden exclusively within UC. Upon experience of visceral and somatic pain, both control groups demonstrated enhanced visceral pain-induced neural activation and greater perceived pain intensity, whereas UC patients failed to differentiate between pain modalities at both behavioural and neural levels. Conclusions When confronted with acute pain from multiple bodily sites, UC patients' responses are distinctly altered. Their failure to prioritise pain arising from the viscera may reflect a lack of adaptive behavioural flexibility, possibly resulting from long-lasting central effects of repeated intestinal inflammatory insults persisting during remission. The role of psychological factors, particularly chronic stress, in visceral sensitivity and disease-specific alterations in the response to acute pain call for dedicated mechanistic research as a basis for tailoring interventions for intestinal and extraintestinal pain symptoms in IBD. [ABSTRACT FROM AUTHOR]

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Network analysis of functional brain scans acquired with [18F]-fluorodeoxyglucose positron emission tomography (FDG PET, to map cerebral glucose metabolism), or resting-state functional magnetic resonance imaging (rs-fMRI, to map blood oxygen level-dependent brain activity) has increasingly been used to identify and validate reproducible circuit abnormalities associated with neurodegenerative disorders such as Parkinson's disease (PD). In addition to serving as imaging markers of the underlying disease process, these networks can be used singly or in combination as an adjunct to clinical diagnosis and as a screening tool for therapeutics trials. Disease networks can also be used to measure rates of progression in natural history studies and to assess treatment responses in individual subjects. Recent imaging studies in PD subjects scanned before and after treatment have revealed therapeutic effects beyond the modulation of established disease networks. Rather, other mechanisms of action may be at play, such as the induction of novel functional brain networks directly by treatment. To date, specific treatment-induced networks have been described in association with novel interventions for PD such as subthalamic adeno-associated virus glutamic acid decarboxylase (AAV2-GAD) gene therapy, as well as sham surgery or oral placebo under blinded conditions. Indeed, changes in the expression of these networks with treatment have been found to correlate consistently with clinical outcome. In aggregate, these attributes suggest a role for functional brain networks as biomarkers in future clinical trials. [ABSTRACT FROM AUTHOR]

Objectives: NREM parasomnias also known as disorders of arousal (DOA) are characterised by abnormal motor and autonomic activation during arousals primarily from slow wave sleep. Dissociative state between sleep and wake is likely responsible for clinical symptoms of DOA. We therefore investigated potential dissociation outside of parasomnic events by using simultaneous 256-channel EEG (hdEEG) and functional magnetic resonance imaging (fMRI). Methods: Eight DOA patients (3 women, mean age = 27.8; SD = 4.2) and 8 gender and age matched healthy volunteers (3 women, mean age = 26,5; SD = 4.0) were included into the study. They underwent 30–32 h of sleep deprivation followed by hdEEG and fMRI recording. We determined 2 conditions: falling asleep (FA) and arousal (A), that occurred outside of deep sleep and/or parasomnic event. We used multimodal approach using data obtained from EEG, fMRI and EEG-fMRI integration approach. Results: DOA patients showed increase in delta and beta activity over postcentral gyrus and cuneus during awakening period. This group expressed increased connectivity between motor cortex and cingulate during arousals unrelated to parasomnic events in the beta frequency band. They also showed lower connectivity between different portions of cingulum. In contrast, the greater connectivity was found between thalamus and some cortical areas, such as occipital cortex. Conclusion: Our findings suggest a complex alteration in falling asleep and arousal mechanisms at both subcortical and cortical levels in response to sleep deprivation. As this alteration is present also outside of slow wave sleep and/or parasomnic episodes we believe this could be a trait factor of DOA.

Generalized anxiety disorder (GAD) and depressive disorder (DD) are distinct mental disorders, which are characterized by complex and unique neuroelectrophysiological mechanisms in psychiatric neurosciences. The understanding of the brain functional differences between GAD and DD is crucial for the accurate diagnosis and clinical efficacy evaluation. The aim of this study was to reveal the differences in functional brain imaging between GAD and DD based on multidimensional electroencephalogram (EEG) characteristics. To this end, 10 min resting-state EEG signals were recorded from 38 GAD and 34 DD individuals. Multidimensional EEG features were subsequently extracted, which include power spectrum density (PSD), fuzzy entropy (FE), and phase lag index (PLI). Then, a direct statistical analysis (i.e., ANOVA) and three ensemble learning models (i.e., Random Forest (RF), Light Gradient Boosting Machine (LightGBM), eXtreme Gradient Boosting (XGBoost)) were used on these EEG features for the differential recognitions. Our results showed that DD has significantly higher PSD values in the alpha1 and beta band, and a higher FE in the beta band, in comparison with GAD, along with the aberrant functional connections in all four bands between GAD and DD. Moreover, machine learning analysis further revealed that the distinct features predominantly occurred in the beta band and functional connections. Here, we show that DD has higher power and more complex brain activity patterns in the beta band and reorganized brain functional network structures in all bands compared to GAD. In sum, these findings move towards the practical identification of brain functional differences between GAD and DD. [ABSTRACT FROM AUTHOR]

Background: Studies in animal models of Alzheimer's disease (AD) have provided valuable insights into the molecular and cellular processes underlying neuronal network dysfunction. Whether and how AD-related neurophysiological alterations translate between mice and humans remains however uncertain. Methods: We characterized neurophysiological alterations in mice and humans carrying AD mutations in the APP and/or PSEN1 genes, focusing on early pre-symptomatic changes. Longitudinal local field potential recordings were performed in APP/PS1 mice and cross-sectional magnetoencephalography recordings in human APP and/or PSEN1 mutation carriers. All recordings were acquired in the left frontal cortex, parietal cortex, and hippocampus. Spectral power and functional connectivity were analyzed and compared with wildtype control mice and healthy age-matched human subjects. Results: APP/PS1 mice showed increased absolute power, especially at higher frequencies (beta and gamma) and predominantly between 3 and 6 moa. Relative power showed an overall shift from lower to higher frequencies over almost the entire recording period and across all three brain regions. Human mutation carriers, on the other hand, did not show changes in power except for an increase in relative theta power in the hippocampus. Mouse parietal cortex and hippocampal power spectra showed a characteristic peak at around 8 Hz which was not significantly altered in transgenic mice. Human power spectra showed a characteristic peak at around 9 Hz, the frequency of which was significantly reduced in mutation carriers. Significant alterations in functional connectivity were detected in theta, alpha, beta, and gamma frequency bands, but the exact frequency range and direction of change differed for APP/PS1 mice and human mutation carriers. Conclusions: Both mice and humans carrying APP and/or PSEN1 mutations show abnormal neurophysiological activity, but several measures do not translate one-to-one between species. Alterations in absolute and relative power in mice should be interpreted with care and may be due to overexpression of amyloid in combination with the absence of tau pathology and cholinergic degeneration. Future studies should explore whether changes in brain activity in other AD mouse models, for instance, those also including tau pathology, provide better translation to the human AD continuum. [ABSTRACT FROM AUTHOR]

This study examined global resting-state functional connectivity of neural oscillations in individuals with chronic tinnitus and normal and impaired hearing. We tested the hypothesis that distinct neural oscillatory networks are engaged in tinnitus with and without hearing loss. In both tinnitus groups, with and without hearing loss, we identified multiple frequency band-dependent regions of increased and decreased global functional connectivity. We also found that the auditory domain of tinnitus severity, assayed by the Tinnitus Functional Index, was associated with global functional connectivity in both auditory and nonauditory regions. These findings provide candidate biomarkers to target and monitor treatments for tinnitus with and without hearing loss.

Spatial visualization ability (SVA) has been identified as a potential key factor for academic achievement and student retention in Science, Technology, Engineering, and Mathematics (STEM) in higher education, especially for engineering and related disciplines. Prior studies have shown that training using virtual reality (VR) has the potential to enhance learning through the use of more realistic and/or immersive experiences. The aim of this study was to investigate the effect of VR-based training using spatial visualization tasks on participant performance and mental workload using behavioral (i.e., time spent) and functional near infrared spectroscopy (fNIRS) brain-imaging-technology-derived measures. Data were collected from 10 first-year biomedical engineering students, who engaged with a custom-designed spatial visualization gaming application over a six-week training protocol consisting of tasks and procedures that varied in task load and spatial characteristics. Findings revealed significant small (Cohen's d: 0.10) to large (Cohen's d: 2.40) effects of task load and changes in the spatial characteristics of the task, such as orientation or position changes, on time spent and oxygenated hemoglobin (HbO) measures from all the prefrontal cortex (PFC) areas. Transfer had a large (d = 1.37) significant effect on time spent and HbO measures from right anterior medial PFC (AMPFC); while training had a moderate (d = 0.48) significant effect on time spent and HbR measures from left AMPFC. The findings from this study have important implications for VR training, research, and instructional design focusing on enhancing the learning, retention, and transfer of spatial skills within and across various VR-based training scenarios. [ABSTRACT FROM AUTHOR]

Objectives: : Bipolar disorder (BD) is a severe, chronic, affective disorder characterized by recurrent switching between mood states, psychomotor and cognitive symptoms, which can linger in euthymic states as residual symptoms. Hippocampal alterations may play a key role in the neural processing of BD symptoms. However, its dynamic functional connectivity (dFC) remains unclear. Therefore, the present study explores hippocampal dFC in relation to BD symptoms. Methods: : We assessed hippocampus‐based dFC coactivation patterns (CAPs) on resting‐state fMRI data of 25 euthymic BD patients and 25 age‐ and sex‐matched healthy controls (HC). Results: : Bilateral hippocampal dFC with somatomotor networks (SMN) was reduced in BD, compared to HC, while at the same time dFC between the left hippocampus and midcingulo‐insular salience system (SN) was higher in BD. Correlational analysis between CAPs and clinical scores revealed that dFC between the bilateral hippocampus and the default‐like network (DMN) correlated with depression scores in BD. Furthermore, pathological hyperconnectivity between the default mode network (DMN) and SMN and the frontoparietal network (FPN) was modulated by the same depression scores in BD. Conclusions: : Overall, we observed alterations of large‐scale functional brain networks associated with decreased flexibility in cognitive control, salience detection, and emotion processing in BD. Additionally, the present study provides new insights on the neural architecture underlying a self‐centered perspective on the environment in BD patients. dFC markers may improve detection, treatment, and follow‐up of BD patients and of disabling residual depressive symptoms in particular. [ABSTRACT FROM AUTHOR]

Background: Previous research suggests that children with or at risk of probable developmental coordination disorder (pDCD) activate different areas of the brain when performing certain motor skills compared with typically developing (TD) children. This study used functional near-infrared spectroscopy to compare prefrontal cortex (PFC) activity in TD and pDCD during the completion of manual (three-dimensional [3D]) and computerized versions (two-dimensional) of the Tower of Hanoi (ToH) puzzle. Method: A total of 12 children (TD and pDCD; one female/11 male, x ¯ = 10.36 , SD ± 1.52 years) performed the two-dimensional and 3D conditions of the ToH disk tasks, with equivalent executive function but different motor requirements, with functional near-infrared spectroscopy to compare PFC activity. Results: Interestingly, brain oxygenation levels were more apparent in the 3D versus two-dimensional ToH. In the 3D, there were large differences between pairs of discordant sibling sets and this was located to the right medial PFC, with pDCD exhibiting less activation in this region. Conclusion: While only exploratory, we have identified potential differences in the right medial PFC region, which differs within sibling sets with different pDCD status. These results concur with previous studies and are an area that needs to be explored further with a larger cohort of TD and pDCD. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives : Bipolar disorder (BD) is a severe, chronic, affective disorder characterized by recurrent switching between mood states, psychomotor and cognitive symptoms, which can linger in euthymic states as residual symptoms. Hippocampal alterations may play a key role in the neural processing of BD symptoms. However, its dynamic functional connectivity (dFC) remains unclear. Therefore, the present study explores hippocampal dFC in relation to BD symptoms. Methods : We assessed hippocampus‐based dFC coactivation patterns (CAPs) on resting‐state fMRI data of 25 euthymic BD patients and 25 age‐ and sex‐matched healthy controls (HC). Results : Bilateral hippocampal dFC with somatomotor networks (SMN) was reduced in BD, compared to HC, while at the same time dFC between the left hippocampus and midcingulo‐insular salience system (SN) was higher in BD. Correlational analysis between CAPs and clinical scores revealed that dFC between the bilateral hippocampus and the default‐like network (DMN) correlated with depression scores in BD. Furthermore, pathological hyperconnectivity between the default mode network (DMN) and SMN and the frontoparietal network (FPN) was modulated by the same depression scores in BD. Conclusions : Overall, we observed alterations of large‐scale functional brain networks associated with decreased flexibility in cognitive control, salience detection, and emotion processing in BD. Additionally, the present study provides new insights on the neural architecture underlying a self‐centered perspective on the environment in BD patients. dFC markers may improve detection, treatment, and follow‐up of BD patients and of disabling residual depressive symptoms in particular.

Obstructive sleep apnea (OSA) can affect temporal fluctuations in brain activity during rest. Dynamic functional connectivity (dFC) captures the fluctuations in FC during the resting state. This study aimed to investigate differences in dFC between moderate-to-severe OSA patients and healthy controls using resting-state functional magnetic resonance imaging (fMRI) and sliding-window analysis. Thirty-seven consecutive patients with moderate-to-severe OSA and 16 age- and sex-matched controls underwent resting-state fMRI in the morning following overnight polysomnography. The dynamics of aberrant FC between the groups and the correlation between the dynamics and clinical variables were evaluated. dFC analysis revealed two distinct connectivity states: hypoconnected (State I) and hyperconnected (State II). In OSA patients, State I occurred 34% more often than in the controls and the occurrence of State II was proportionally reduced. The time in State I positively correlated with the Pittsburg Sleep Quality Index score in the OSA patients. This study showed dFC alterations in moderate-to-severe OSA patients, which may serve as a novel physiological biomarker for OSA. • Dynamic functional connectivity analysis revealed two distinct connectivity states. • The hypoconnected state occurred more often in OSA patients than in controls. • The hyperconnected state occurred less often in OSA patients than in controls. • The time in the hypoconnected state positively correlated with sleep quality in OSA. [ABSTRACT FROM AUTHOR]

Abstract Assessment of expertise development during training program primarily consists of evaluating interactions between task characteristics, performance, and mental load. Such a traditional assessment framework may lack consideration of individual characteristics when evaluating training on complex tasks, such as driving and piloting, where operators are typically required to execute multiple tasks simultaneously. Studies have already identified individual characteristics arising from intrinsic, context, strategy, personality, and preference as common predictors of performance and mental load. Therefore, this study aims to investigate the effect of individual difference in skill acquisition and transfer using an ecologically valid dual task, behavioral, and brain activity measures. Specifically, we implemented a search and surveillance task (scanning and identifying targets) using a high-fidelity training simulator for the unmanned aircraft sensor operator, acquired behavioral measures (scan, not scan, over scan, and adaptive target find scores) using simulator-based analysis module, and measured brain activity changes (oxyhemoglobin and deoxyhemoglobin) from the prefrontal cortex (PFC) using a portable functional near-infrared spectroscopy (fNIRS) sensor array. The experimental protocol recruited 13 novice participants and had them undergo three easy and two hard sessions to investigate skill acquisition and transfer, respectively. Our results from skill acquisition sessions indicated that performance on both tasks did not change when individual differences were not accounted for. However inclusion of individual differences indicated that some individuals improved only their scan performance (Attention-focused group), while others improved only their target find performance (Accuracy-focused group). Brain activity changes during skill acquisition sessions showed that mental load decreased in the right anterior medial PFC (RAMPFC) in both groups regardless of individual differences. However, mental load increased in the left anterior medial PFC (LAMPFC) of Attention-focused group and decreased in the Accuracy-focused group only when individual differences were included. Transfer results showed no changes in performance regardless of grouping based on individual differences; however, mental load increased in RAMPFC of Attention-focused group and left dorsolateral PFC (LDLPFC) of Accuracy-focused group. Efficiency and involvement results suggest that the Attention-focused group prioritized the scan task, while the Accuracy-focused group prioritized the target find task. In conclusion, training on multitasks results in individual differences. These differences may potentially be due to individual preference. Future studies should incorporate individual differences while assessing skill acquisition and transfer during multitask training.

Acoustically detecting the optical absorption contrast, photoacoustic imaging (PAI) is a highly versatile imaging modality that can provide anatomical, functional, molecular, and metabolic information of biological tissues. PAI is highly scalable and can probe the same biological process at various length scales ranging from single cells (microscopic) to the whole organ (macroscopic). Using hemoglobin as the endogenous contrast, PAI is capable of label-free imaging of blood vessels in the brain and mapping hemodynamic functions such as blood oxygenation and blood flow. These imaging merits make PAI a great tool for studying ischemic stroke, particularly for probing into hemodynamic changes and impaired cerebral blood perfusion as a consequence of stroke. In this narrative review, we aim to summarize the scientific progresses in the past decade by using PAI to monitor cerebral blood vessel impairment and restoration after ischemic stroke, mostly in the preclinical setting. We also outline and discuss the major technological barriers and challenges that need to be overcome so that PAI can play a more significant role in preclinical stroke research, and more importantly, accelerate its translation to be a useful clinical diagnosis and management tool for human strokes. [ABSTRACT FROM AUTHOR]

Objective: Methylphenidate is effective in reducing the clinical symptoms of patients with attention-deficit/hyperactivity disorder (ADHD). ORADUR®-methylphenidate is a new extended-release preparation of methylphenidate. This study aimed at identifying brain regions with activation changes and their correlations with neuropsychological functions after treatment with ORADUR-methylphenidate in children with ADHD. Methods: We recruited drug-naive children with ADHD and age- and sex-matched typically developing (TD) children. They were all scanned with the functional magnetic resonance imaging (fMRI) during the counting Stroop task at baseline, and those with ADHD had the second fMRI assessment after 8-week treatment with ORADUR-methylphenidate. The Rapid Visual Information Processing (RVP) and Conners' Continuous Performance Test (CCPT) were used to assess the attention performance of the ADHD (before and after treatment) and TD groups. Results: ORADUR-methylphenidate significantly decreased inattention (Cohen d = 2.17) and hyperactivity-impulsivity (Cohen d = 0.98) symptoms. We found less activation in the right inferior frontal gyrus (rIFG) in the pre-treatment ADHD children than TD children and greater treatment-induced activation in the dorsal anterior cingulate cortex (dACC) and the right dorsolateral prefrontal cortex (rDLPFC). There was no significant difference between the post-treatment ADHD and TD groups. However, the treatment-related activations in the dACC, rDLPFC, and rIFG were significantly correlated with CCPT and RVP measures. Conclusions: Our findings indicated that ORADUR-methylphenidate increased brain activations in the dACC, rDLPFC, and rIFG in children with ADHD, associated with improved focused attention, reduced impulsivity, and enhanced inhibition control. Activities of these brain regions might be biomarkers for the treatment effectiveness of methylphenidate for ADHD. Clinical Trials Registration: ClinicalTrials.gov number, NCT02450890. [ABSTRACT FROM AUTHOR]

The increasing number of MRI studies focused on prodromal Parkinson’s Disease (PD) demonstrates a strong interest in identifying early biomarkers capable of monitoring neurodegeneration. In this systematic review, we present the latest information regarding the most promising MRI markers of neurodegeneration in relation to the most specific prodromal symptoms of PD, namely isolated rapid eye movement (REM) sleep behavior disorder (iRBD). We reviewed structural, diffusion, functional, iron-sensitive, neuro-melanin-sensitive MRI, and proton magnetic resonance spectroscopy studies conducted between 2000 and 2023, which yielded a total of 77 relevant papers. Among these markers, iron and neuromelanin emerged as the most robust and promising indicators for early neurodegenerative processes in iRBD. Atrophy was observed in several regions, including the frontal and temporal cortices, limbic cortices, and basal ganglia, suggesting that neurodegenerative processes had been underway for some time. Diffusion and functional MRI produced heterogeneous yet intriguing results. Additionally, reduced glymphatic clearance function was reported. Technological advancements, such as the development of ultra-high field MRI, have enabled the exploration of minute anatomical structures and the detection of previously undetectable anomalies. The race to achieve early detection of neurodegeneration is well underway.

Magnetoencephalography (MEG) measures human brain function via assessment of the magnetic fields generated by electrical activity in neurons. Despite providing high-quality spatiotemporal maps of electrophysiological activity, current MEG instrumentation is limited by cumbersome field sensing technologies, resulting in major barriers to utility. Here, we review a new generation of MEG technology that is beginning to lift many of these barriers. By exploiting quantum sensors, known as optically pumped magnetometers (OPMs), 'OPM-MEG' has the potential to dramatically outperform the current state of the art, promising enhanced data quality (better sensitivity and spatial resolution), adaptability to any head size/shape (from babies to adults), motion robustness (participants can move freely during scanning), and a less complex imaging platform (without reliance on cryogenics). We discuss the current state of this emerging technique and describe its far-reaching implications for neuroscience. Magnetoencephalography (MEG) allows noninvasive electrophysiological imaging of human brain activity. However, current MEG technology has significant limitations. Optically pumped magnetometers (OPM)-MEG is a new type of MEG instrumentation, promising several advantages compared with conventional scanners: higher signal sensitivity, better spatial resolution, more uniform coverage, lifespan compliance, free movement of participants during scanning, and lower system complexity. We describe the principles underlying OPM-MEG and its components, including noncryogenic field sensors and magnetic shielding technologies. We discuss how the OPM-MEG technology is impacting neuroscience, enabling researchers to overcome limitations of conventional human imaging techniques and tackle new types of research questions. [ABSTRACT FROM AUTHOR]

In this work, we introduce a deep learning architecture for evaluation on multimodal electroencephalographic (EEG) and functional near-infrared spectroscopy (fNIRS) recordings from 40 epileptic patients. Long short-term memory units and convolutional neural networks are integrated within a multimodal sequence-to-sequence autoencoder. The trained neural network predicts fNIRS signals from EEG, sans a priori, by hierarchically extracting deep features from EEG full spectra and specific EEG frequency bands. Results show that higher frequency EEG ranges are predictive of fNIRS signals with the gamma band inputs dominating fNIRS prediction as compared to other frequency envelopes. Seed based functional connectivity validates similar patterns between experimental fNIRS and our model's fNIRS reconstructions. This is the first study that shows it is possible to predict brain hemodynamics (fNIRS) from encoded neural data (EEG) in the resting human epileptic brain based on power spectrum amplitude modulation of frequency oscillations in the context of specific hypotheses about how EEG frequency bands decode fNIRS signals. [ABSTRACT FROM AUTHOR]

Distracted driving is one of the main causes of traffic accidents. By predicting the attentional state of drivers, it is possible to prevent distractions and promote safe driving. In this study, we developed a model that could predict the degree of distracted driving based on brain activity. Changes in oxyhemoglobin concentrations were measured in drivers while driving a real car using functional near-infrared spectroscopy (fNIRS). A regression model was constructed for each participant using functional connectivity as an explanatory variable and brake reaction time to random beeps while driving as an objective variable. As a result, we were able to construct a prediction model with the mean absolute error of 5.58 × 102 ms for the BRT of the 12 participants. Furthermore, the regression model with the highest prediction accuracy for each participant was analyzed to gain a better understanding of the neural basis of distracted driving. The 11 of 12 models that showed significant accuracy were classified into five clusters by hierarchical clustering based on their functional connectivity edges used in each cluster. The results showed that the combinations of the dorsal attention network (DAN)-sensory-motor network (SMN) and DAN-ventral attention network (VAN) connections were common in all clusters and that these networks were essential to predict the degree of distraction in complex multitask driving. They also confirmed the existence of multiple types of prediction models with different within- and between-network connectivity patterns. These results indicate that it is possible to predict the degree of distracted driving based on the driver's brain activity during actual driving. These results are expected to contribute to the development of safe driving systems and elucidate the neural basis of distracted driving.

Spatial visualization ability (SVA) has been identified as a potential key factor for academic achievement and student retention in Science, Technology, Engineering, and Mathematics (STEM) in higher education, especially for engineering and related disciplines. Prior studies have shown that training using virtual reality (VR) has the potential to enhance learning through the use of more realistic and/or immersive experiences. The aim of this study was to investigate the effect of VR-based training using spatial visualization tasks on participant performance and mental workload using behavioral (i.e., time spent) and functional near infrared spectroscopy (fNIRS) brain-imaging-technology-derived measures. Data were collected from 10 first-year biomedical engineering students, who engaged with a custom-designed spatial visualization gaming application over a six-week training protocol consisting of tasks and procedures that varied in task load and spatial characteristics. Findings revealed significant small (Cohen’s d: 0.10) to large (Cohen’s d: 2.40) effects of task load and changes in the spatial characteristics of the task, such as orientation or position changes, on time spent and oxygenated hemoglobin (HbO) measures from all the prefrontal cortex (PFC) areas. Transfer had a large (d = 1.37) significant effect on time spent and HbO measures from right anterior medial PFC (AMPFC); while training had a moderate (d = 0.48) significant effect on time spent and HbR measures from left AMPFC. The findings from this study have important implications for VR training, research, and instructional design focusing on enhancing the learning, retention, and transfer of spatial skills within and across various VR-based training scenarios.

Alzheimer's disease (AD) is an insidious neurodegenerative disorder representing a serious continuously escalating medico-social problem. The AD-associated progressive dementia is followed by gradual formation of amyloid plaques and neurofibrillary tangles in the brain. Though, converging evidence indicates apparent metabolic dysfunctions as key AD characteristic. In particular, late-onset AD possesses a clear metabolic signature. Considerable brain insulin signaling impairment and a decline in glucose metabolism are common AD attributes. Thus, positron emission tomography (PET) with glucose tracers is a reliable non-invasive tool for early AD diagnosis and treatment efficacy monitoring. Various approaches and agents have been trialed to modulate insulin signaling. Accumulating data point to arginase inhibition as a promising direction to treat AD via diverse molecular mechanisms involving, inter alia, the insulin pathway. Here, we use a transgenic AD mouse model, demonstrating age-dependent brain insulin signaling abnormalities, reduced brain insulin receptor levels, and substantial energy metabolism alterations, to evaluate the effects of arginase inhibition with Norvaline on glucose metabolism. We utilize fluorodeoxyglucose whole-body micro-PET to reveal a significant treatment-associated increase in glucose uptake by the brain tissue in-vivo. Additionally, we apply advanced molecular biology and bioinformatics methods to explore the mechanisms underlying the effects of Norvaline on glucose metabolism. We demonstrate that treatment-associated improvement in glucose utilization is followed by significantly elevated levels of insulin receptor and glucose transporter-3 expression in the mice hippocampi. Additionally, Norvaline diminishes the rate of Tau protein phosphorylation. Our results suggest that Norvaline interferes with AD pathogenesis. These findings open new avenues for clinical evaluation and innovative drug development. [ABSTRACT FROM AUTHOR]

Background: Background: Although increasing evidence indicates that even variations in normal range thyroid function are associated with Alzheimer's disease (AD), the association between serum thyroid hormone levels within the reference range and AD biomarkers remains unclear. This study examined whether variations in thyroid hormones within the reference range are associated with brain amyloid burden and cortical glucose metabolism in older adults without dementia. Methods: One hundred and two non‐demented older adults underwent 11C‐Pittsburgh Compound B positron emission tomography (PiB‐PET), 18F‐fluorodeoxyglucose (FDG)‐PET, and measurement of serum thyroid‐stimulating hormone (TSH), free triiodothyronine (T3), and free thyroxine (T4) levels. The discrimination between PiB‐negative and PiB‐positive subgroup was made on the basis of a subject's cortical uptake value ratio greater than 1.4. The association of serum thyroid hormone levels with global PiB or FDG uptake, and PiB or FDG uptake in each region of interest, including frontal and temporoparietal lobes and posterior cingulate gyrus, was analysed using a multiple regression model with adjustment for covariates, including age, gender, years of education, apolipoprotein E4 status or PiB uptake value. Results: In the PiB‐positive subgroup, the serum TSH levels positively associated with the global FDG uptake (β = 0.471, P = 0.003) and FDG uptake in the frontal and temporoparietal lobes (β = 0.466, P = 0.003, β = 0.394, P = 0.012, respectively); the serum‐free T3 levels negatively associated with the FDG uptake in the temporoparietal lobe and posterior cingulate region (β = −0.351, P = 0.033, β = −0.544, P = 0.002, respectively). The PiB‐negative subgroup showed no significant associations. The serum thyroid hormone levels did not correlate with the global PiB uptake and PiB uptake in each region. Conclusions: The variations in the thyroid hormones within the reference ranges are associated with glucose metabolism, particularly in the specific regions affected by the neuropathologic changes of AD, in non‐demented older adults with brain amyloid burden. [ABSTRACT FROM AUTHOR]

Appropriate training burden monitoring is still a challenge for the support staff, athletes, and coaches. Extensive research has been done in recent years that proposes several external and internal indicators. Among all measurements, the importance of cognitive factors has been indicated but has never been really considered in the training monitoring process. While there is strong evidence supporting the use of cognitive demand indicators in cognitive neuroscience, their importance in training monitoring for multiple sports settings must be better emphasized. The aims of this scoping review are to (1) provide an overview of the cognitive demand concept beside the physical demand in training; (2) highlight the current methods for assessing cognitive demand in an applied setting to sports in part through a neuroergonomics approach; (3) show how cognitive demand metrics can be exploited and applied to our better understanding of fatigue, sport injury, overtraining and individual performance capabilities. This review highlights also the potential new ways of brain imaging approaches for monitoring in situ. While assessment of cognitive demand is still in its infancy in sport, it may represent a very fruitful approach if applied with rigorous protocols and deep knowledge of both the neurobehavioral and cognitive aspects. It is time now to consider the cognitive demand to avoid underestimating the total training burden and its management. [ABSTRACT FROM AUTHOR]

Background: Interoceptive properties of food may influence emotional state and its neural basis, as shown for fatty acids but remains unstudied for carbohydrates. Objectives: To study the effects of fructose and its interaction with sad emotion on brain activity in homeostatic and hedonic regions and investigate whether gut hormone responses can explain effects. Design: In 15 healthy subjects, brain activity for 40min after intragastric infusion of fructose (25g) or water was recorded using a cross-over pharmacological magnetic resonance imaging (phMRI) paradigm. Sad or neutral emotional states were induced by classical music and emotional facial expressions. Emotional state was assessed using the Self-Assessment Manikin. Blood samples were taken to assess gut hormone levels. Brain responses to fructose versus placebo, sad versus neutral emotion, and their interaction were analyzed over time in a single mask of a priori defined regions of interest at a voxel-level threshold of pFWEcorrected <0.05. Effects on emotion and hormones were tested using linear mixed models. Results: No main effects of fructose, emotion, or fructose-by-emotion interaction on emotional ratings were observed. Main effects of fructose, emotion and aninteraction effect were found on brain activity (medulla, midbrain, hypothalamus, basal ganglia, anterior insula, orbitofrontal cortex, anterior cingulate cortex and amygdala). An increase in circulating GLP-1 after fructose in neutral emotion was abolished during sad emotion (fructose-by-emotion-by-time, p=0.041). Ghrelin levels were higher in sad emotion (time-by-emotion, p=0.037). Conclusions: Emotional state interacts with brain and endocrine responses to intragastric infusion of 25 g of fructose, however such an effect was not found at behavioral level. Trial registration: ClinicalTrials.gov identifier: NCT02946983. [ABSTRACT FROM AUTHOR]

Assessment of expertise development during training program primarily consists of evaluating interactions between task characteristics, performance, and mental load. Such a traditional assessment framework may lack consideration of individual characteristics when evaluating training on complex tasks, such as driving and piloting, where operators are typically required to execute multiple tasks simultaneously. Studies have already identified individual characteristics arising from intrinsic, context, strategy, personality, and preference as common predictors of performance and mental load. Therefore, this study aims to investigate the effect of individual difference in skill acquisition and transfer using an ecologically valid dual task, behavioral, and brain activity measures. Specifically, we implemented a search and surveillance task (scanning and identifying targets) using a high-fidelity training simulator for the unmanned aircraft sensor operator, acquired behavioral measures (scan, not scan, over scan, and adaptive target find scores) using simulator-based analysis module, and measured brain activity changes (oxyhemoglobin and deoxyhemoglobin) from the prefrontal cortex (PFC) using a portable functional near-infrared spectroscopy (fNIRS) sensor array. The experimental protocol recruited 13 novice participants and had them undergo three easy and two hard sessions to investigate skill acquisition and transfer, respectively. Our results from skill acquisition sessions indicated that performance on both tasks did not change when individual differences were not accounted for. However inclusion of individual differences indicated that some individuals improved only their scan performance (Attention-focused group), while others improved only their target find performance (Accuracy-focused group). Brain activity changes during skill acquisition sessions showed that mental load decreased in the right anterior medial PFC (RAMPFC) in both groups regardless of individual differences. However, mental load increased in the left anterior medial PFC (LAMPFC) of Attention-focused group and decreased in the Accuracy-focused group only when individual differences were included. Transfer results showed no changes in performance regardless of grouping based on individual differences; however, mental load increased in RAMPFC of Attention-focused group and left dorsolateral PFC (LDLPFC) of Accuracy-focused group. Efficiency and involvement results suggest that the Attention-focused group prioritized the scan task, while the Accuracy-focused group prioritized the target find task. In conclusion, training on multitasks results in individual differences. These differences may potentially be due to individual preference. Future studies should incorporate individual differences while assessing skill acquisition and transfer during multitask training. [ABSTRACT FROM AUTHOR]

BDSM is an abbreviation used to reference the concepts of bondage and discipline, dominance and submission, sadism and masochism, enacted by power exchanges between consensual partners. In recent years, attention has shifted from the idea of BDSM as a pathological and tabooed niche practice towards viewing BDSM as a healthy form of intimacy. This systematic review brings together all existing literature on the biology of BDSM and places it in a broader biological context. A systematic search was conducted on PubMed, Web of Science and PsycARTICLES, of which 10 articles are included and discussed in this systematic review. There is evidence for cortisol changes in submissives as a result of a BDSM interaction, suggesting involvement of the physiological stress system. Endocannabinoid changes implicate the pleasure and reward system. In dominants, this biologically measured pleasure seemed to be dependent on power play rather than pain play. Testosterone and oxytocin are also implicated in BDSM, though their role is less evident. Research into brain region activity patterns related to BDSM interest suggests a role for the parietal operculum and ventral striatum in the context of the pleasure and reward system, the primary and secondary somatosensory cortex in the context of pain perception, empathy-related circuits such as the anterior insula, anterior midcingulate cortex and sensorimotor cortex and the left frontal cortex in the context of social and sexual interactions. Pain thresholds are shown to be higher in submissive individuals and a BDSM interaction may cause pain thresholds to rise in submissives as well. BDSM interactions are complex and influenced by several psychological, social and biological processes. Though research is limited, there is emerging evidence for an interaction between several biological systems involved in these types of interests and activities. This means there is an important role for future research to replicate and supplement current results. Wuyts E, Morrens M. The Biology of BDSM: A Systematic Review. J Sex Med 2022;19:144–157. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT) is a standard treatment for prostate cancer patients, routinely used in the palliative or in the curative setting in association with radiotherapy. Among the systemic long-term side effects of ADT, growing data suggest a potentially increased risk of dementia/Alzheimer's disease in prostate cancer patients treated with hormonal manipulation. While pre-clinical data suggest that androgen ablation may have neurotoxic effects due to Aβ accumulation and increased tau phosphorylation in small animal brains, clinical studies have measured the impact of ADT on long-term cognitive function, with conflicting results, and studies on biological changes after ADT are still lacking. The aim of this review is to report on the current evidence on the association between the ADT use and the risk of cognitive impairment in prostate cancer patients. We will focus on the contribution of Alzheimer's disease biomarkers, namely through imaging, to investigate potential ADT-induced brain modifications. The evidence from these preliminary studies shows brain changes in gray matter volume, cortical activation and metabolism associated with ADT, however with a large variability in biomarker selection, ADT duration and cognitive outcome. Importantly, no study investigated yet biomarkers of Alzheimer's disease pathology, namely amyloid and tau. These preliminary data emphasize the need for larger targeted investigations. [ABSTRACT FROM AUTHOR]

This paper reviews the findings of brain imaging studies related to human parenting behavior. To examine brain function in healthy parenting, we first review the basic findings on the neuroendocrine basis of parenting behavior revealed by animal studies and further investigate the involvement of the cortical networks in human parenting behavior. Next, to examine brain dysfunction due to parenting difficulties, the effects of parental stress on brain function are outlined, including the findings of our previous functional brain imaging study. The effects of clinical psychological interventions for parenting dysfunction on behavior and brain function are also examined. Furthermore, to examine brain function during the preparation stage of parenting, research on changes in the brain function of adolescents who become parents are reviewed. Lastly, we propose a perspective on supporting caregivers based on recent advances in neuroscience research. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT) is a standard treatment for prostate cancer patients, routinely used in the palliative or in the curative setting in association with radiotherapy. Among the systemic long-term side effects of ADT, growing data suggest a potentially increased risk of dementia/Alzheimer’s disease in prostate cancer patients treated with hormonal manipulation. While pre-clinical data suggest that androgen ablation may have neurotoxic effects due to Aβ accumulation and increased tau phosphorylation in small animal brains, clinical studies have measured the impact of ADT on long-term cognitive function, with conflicting results, and studies on biological changes after ADT are still lacking. The aim of this review is to report on the current evidence on the association between the ADT use and the risk of cognitive impairment in prostate cancer patients. We will focus on the contribution of Alzheimer’s disease biomarkers, namely through imaging, to investigate potential ADT-induced brain modifications. The evidence from these preliminary studies shows brain changes in gray matter volume, cortical activation and metabolism associated with ADT, however with a large variability in biomarker selection, ADT duration and cognitive outcome. Importantly, no study investigated yet biomarkers of Alzheimer’s disease pathology, namely amyloid and tau. These preliminary data emphasize the need for larger targeted investigations.

The goal of this study was to estimate venous blood oxygen saturation (SvO2) in the superior sagittal sinus (SSS) in fetal brains with ventriculomegaly (VM) using quantitative susceptibility mapping (QSM). A radiofrequency spoiled gradient echo sequence was used to evaluate data on 19 fetuses with VM (gestational age(GA): median = 29.9 weeks (range 23 to 37.3 weeks)) and 20 healthy fetuses (GA: median = 30.9 (range 22.7 to 38.7 weeks)) at 1.5 T. Susceptibility weighted images encompassing the entire fetal brain were acquired within 1 min. An iterative, geometry constraint-based thresholded k -space division algorithm was used for generating QSM data of the fetal brain. The venous oxygen saturation was calculated using the magnetic susceptibility of the SSS obtained from the QSM data. Mixed-model analysis of variance and interobserver variability assessment were used to analyze the results. The median SvO2 values in the entire VM cohort as well as for second and third trimester fetuses (with interquartile range) were: 67.8% (63.2%, 73.6%), 73.1% (69.1%, 77.3%) and 63.8% (59.4%, 68.1%), respectively. The corresponding median SvO2 value in the healthy control group was: 65.3% (58.3%, 68.2%), 67.5% (61.7%, 69.2%) and 60.8% (53.6%, 68.2%), respectively. However, the difference of SvO2 between VM and control groups was not significant at the p = 0.05 level (p = 0.076). The SvO2 was found decreasing significantly with GA in the healthy control group (p < 0.05). We report for the first time the estimation of cerebral SvO2 in human fetuses with VM using QSM. This measure of oxygen saturation might be beneficial in assessing and monitoring the metabolic status of the fetus in various clinical conditions. [ABSTRACT FROM AUTHOR]

A prominent goal of neuroscience is to improve our understanding of how brain structure and activity interact to produce perception, emotion, behavior, and cognition. The brain’s network activity is inherently organized in distinct spatiotemporal patterns that span scales from nanometer-sized synapses to meter-long nerve fibers and millisecond intervals between electrical signals to decades of memory storage. There is currently no single imaging method that alone can provide all the relevant information, but intelligent combinations of complementary techniques can be effective. Here, we thus present the latest advances in biomedical and biological engineering on photoacoustic neuroimaging in the context of complementary imaging techniques. A particular focus is placed on recent advances in whole-brain photoacoustic imaging in rodent models and its influential role in bridging the gap between fluorescence microscopy and more non-invasive techniques such as magnetic resonance imaging (MRI). We consider current strategies to address persistent challenges, particularly in developing molecular contrast agents, and conclude with an overview of potential future directions for photoacoustic neuroimaging to provide deeper insights into healthy and pathological brain processes.

A prominent goal of neuroscience is to improve our understanding of how brain structure and activity interact to produce perception, emotion, behavior, and cognition. The brain's network activity is inherently organized in distinct spatiotemporal patterns that span scales from nanometer-sized synapses to meter-long nerve fibers and millisecond intervals between electrical signals to decades of memory storage. There is currently no single imaging method that alone can provide all the relevant information, but intelligent combinations of complementary techniques can be effective. Here, we thus present the latest advances in biomedical and biological engineering on photoacoustic neuroimaging in the context of complementary imaging techniques. A particular focus is placed on recent advances in whole-brain photoacoustic imaging in rodent models and its influential role in bridging the gap between fluorescence microscopy and more non-invasive techniques such as magnetic resonance imaging (MRI). We consider current strategies to address persistent challenges, particularly in developing molecular contrast agents, and conclude with an overview of potential future directions for photoacoustic neuroimaging to provide deeper insights into healthy and pathological brain processes. [ABSTRACT FROM AUTHOR]

Stress is associated with numerous chronic diseases, beginning in fetal development with in utero exposures (prenatal stress) impacting offspring's risk for disorders later in life. In previous studies, we demonstrated adverse maternal in utero immune activity on sex differences in offspring neurodevelopment at age seven and adult risk for major depression and psychoses. Here, we hypothesized that in utero exposure to maternal proinflammatory cytokines has sex-dependent effects on specific brain circuitry regulating stress and immune function in the offspring that are retained across the lifespan. Using a unique prenatal cohort, we tested this hypothesis in 80 adult offspring, equally divided by sex, followed from in utero development to midlife. Functional MRI results showed that exposure to proinflammatory cytokines in utero was significantly associated with sex differences in brain activity and connectivity during response to negative stressful stimuli 45 y later. Lower maternal TNF-a levels were significantly associated with higher hypothalamic activity in both sexes and higher functional connectivity between hypothalamus and anterior cingulate only in men. Higher prenatal levels of IL-6 were significantly associated with higher hippocampal activity in women alone. When examined in relation to the anti-inflammatory effects of IL-10, the ratio TNF-a:IL-10 was associated with sex-dependent effects on hippocampal activity and functional connectivity with the hypothalamus. Collectively, results suggested that adverse levels of maternal in utero proinflammatory cytokines and the balance of pro- to anti-inflammatory cytokines impact brain development of offspring in a sexually dimorphic manner that persists across the lifespan. [ABSTRACT FROM AUTHOR]