Functional Brain Imaging Studies Research Articles

Microstructural abnormality of white matter tracts in rheumatoid arthritis

BackgroundStructural and functional brain imaging studies have reported abnormalities of gray matter morphology and functional activities in patients with rheumatoid arthritis (RA). However, it is largely unknown whether patients with RA show alterations of white matter microstructural organization. ObjectivesTo automatically identify alteration of white matter microstructure in patients with RA and further examine how this alteration associates with clinical characteristics. MethodsThis single-institutional prospective study included 66 participants (33 patients with RA [52 ± 9 years, 29 women] and 33 sex/age-matched healthy controls [53 ± 12 years, 27 women]), who underwent diffusion MRI scan from January 2021 to December 2021. The white matter microstructure was assessed using fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Voxelwise analyses were conducted on white matter skeleton using an automated, observer-independent tract-based spatial statistics analysis. The relationship between white matter microstructural alterations and clinical and neuropsychological variables was evaluated using correlation analysis. ResultsCompared with healthy controls, patients with RA exhibited lower fractional anisotropy in several major white matter tracts (threshold-free cluster enhancement at P < 0.05 for multiple comparison correction, permutation test), involving the forceps minor, bilateral inferior fronto-occipital fasciculus, bilateral anterior thalamic radiation, and bilateral uncinate fasciculus. Lower fractional anisotropy values in the patients with RA were significantly associated with pain-related assessments, including tender joint count (r = -0.43, P = 0.015), Clinical Disease Activity Index score (r = -0.36, P = 0.049), pain severity rated through visual analogue scale (r = -0.45, P = 0.012), and Simplified Disease Activity Index score (r = -0.36, P = 0.045). No significant group difference was found in mean diffusivity, axial diffusivity, and radial diffusivity. ConclusionsWe report the first anatomical evidence for aberrant microstructure organization of several major white matter tracts and its associations with pain processing in patients with rheumatoid arthritis.

Changes in Intrinsic Connectivity Networks Topology Across Levels of Dexmedetomidine-Induced Alteration of Consciousness.

Human consciousness is generally thought to emerge from the activity of intrinsic connectivity networks (resting-state networks [RSNs]) of the brain, which have topological characteristics including, among others, graph strength and efficiency. So far, most functional brain imaging studies in anesthetized subjects have compared wakefulness and unresponsiveness, a state considered as corresponding to unconsciousness. Sedation and general anesthesia not only produce unconsciousness but also phenomenological states of preserved mental content and perception of the environment (connected consciousness), and preserved mental content but no perception of the environment (disconnected consciousness). Unresponsiveness may be seen during unconsciousness, but also during disconnectedness. Deep dexmedetomidine sedation is frequently a state of disconnected consciousness. In this study, we were interested in characterizing the RSN topology changes across 4 different and steady-state levels of dexmedetomidine-induced alteration of consciousness, namely baseline (Awake, drug-free state), Mild sedation (drowsy, still responding), Deep sedation (unresponsive), and Recovery, with a focus on changes occurring between a connected consciousness state and an unresponsiveness state. A functional magnetic resonance imaging database acquired in 14 healthy volunteers receiving dexmedetomidine sedation was analyzed using a method combining independent component analysis and graph theory, specifically looking at changes in connectivity strength and efficiency occurring during the 4 above-mentioned dexmedetomidine-induced altered consciousness states. Dexmedetomidine sedation preserves RSN architecture. Unresponsiveness during dexmedetomidine sedation is mainly characterized by a between-networks graph strength alteration and within-network efficiency alteration of lower-order sensory RSNs, while graph strength and efficiency in higher-order RSNs are relatively preserved. The differential dexmedetomidine-induced RSN topological changes evidenced in this study may be the signature of inadequate processing of sensory information by lower-order RSNs, and of altered communication between lower-order and higher-order networks, while the latter remain functional. If replicated in an experimental paradigm distinguishing, in unresponsive subjects, disconnected consciousness from unconsciousness, such changes would sustain the hypothesis that disconnected consciousness arises from altered information handling by lower-order sensory networks and altered communication between lower-order and higher-order networks, while the preservation of higher-order networks functioning allows for an internally generated mental content (or dream).

Intrinsic Functional Connectivity between the Anterior Insular and Retrosplenial Cortex as a Moderator and Consequence of Cocaine Self-Administration in Rats.

While functional brain imaging studies in humans suggest that chronic cocaine use alters functional connectivity (FC) within and between key large-scale brain networks, including the default mode network (DMN), the salience network (SN), and the central executive network (CEN), cross-sectional studies in humans are challenging to obtain brain FC prior to cocaine use. Such information is critical to reveal the relationship between individual's brain FC and the subsequent development of cocaine dependence and brain changes during abstinence. Here, we performed a longitudinal study examining functional magnetic resonance imaging (fMRI) data in male rats (n = 7), acquired before cocaine self-administration (baseline), on 1 d of abstinence following 10 d of cocaine self-administration, and again after 30 d of experimenter-imposed abstinence. Using repeated-measures analysis of variance (ANOVA) with network-based statistics (NBS), significant connectivity changes were found between anterior insular cortex (AI) of the SN, retrosplenial cortex (RSC) of the DMN, somatosensory cortex, and caudate-putamen (CPu), with AI-RSC FC showing the most robust changes between baseline and 1 d of abstinence. Additionally, the level of escalated cocaine intake is associated with AI-RSC and AI-CPu FC changes between 1 d and 30 d of abstinence; further, the subjects' AI-RSC FC prior to cocaine intake is a significant moderator for the AI-RSC changes during abstinence. These results provide novel insights into the roles of AI-RSC FC before and after cocaine intake and suggest this circuit to be a potential target to modulate large-scale network and associated behavioral changes in cocaine use disorders.

Mild Deficits in Fear Learning: Evidence from Humans and Mice with Cerebellar Cortical Degeneration.

Functional brain imaging studies in humans suggest involvement of the cerebellum in fear conditioning but do not allow conclusions about the functional significance. The main aim of the present study was to examine whether patients with cerebellar degeneration show impaired fear conditioning and whether this is accompanied by alterations in cerebellar cortical activations. To this end, a 2 d differential fear conditioning study was conducted in 20 cerebellar patients and 21 control subjects using a 7 tesla (7 T) MRI system. Fear acquisition and extinction training were performed on day 1, followed by recall on day 2. Cerebellar patients learned to differentiate between the CS+ and CS-. Acquisition and consolidation of learned fear, however, was slowed. Additionally, extinction learning appeared to be delayed. The fMRI signal was reduced in relation to the prediction of the aversive stimulus and altered in relation to its unexpected omission. Similarly, mice with cerebellar cortical degeneration (spinocerebellar ataxia type 6, SCA6) were able to learn the fear association, but retrieval of fear memory was reduced. In sum, cerebellar cortical degeneration led to mild abnormalities in the acquisition of learned fear responses in both humans and mice, particularly manifesting postacquisition training. Future research is warranted to investigate the basis of altered fMRI signals related to fear learning.

Protocol for the development of joint attention-based subclassification of autism spectrum disorder and validation using multi-modal data

BackgroundHeterogeneity in clinical manifestation and underlying neuro-biological mechanisms are major obstacles to providing personalized interventions for individuals with autism spectrum disorder (ASD). Despite various efforts to unify disparate data modalities and machine learning techniques for subclassification, replicable ASD clusters remain elusive. Our study aims to introduce a novel method, utilizing the objective behavioral biomarker of gaze patterns during joint attention, to subclassify ASD. We will assess whether behavior-based subgrouping yields clinically, genetically, and neurologically distinct ASD groups.MethodsWe propose a study involving 60 individuals with ASD recruited from a specialized psychiatric clinic to perform joint attention tasks. Through the examination of gaze patterns in social contexts, we will conduct a semi-supervised clustering analysis, yielding two primary clusters: good gaze response group and poor gaze response group. Subsequent comparison will occur across these clusters, scrutinizing neuroanatomical structure and connectivity using structural as well as functional brain imaging studies, genetic predisposition through single nucleotide polymorphism data, and assorted socio-demographic and clinical information.ConclusionsThe aim of the study is to investigate the discriminative properties and the validity of the joint attention-based subclassification of ASD using multi-modality data.Trial registrationClinical trial, KCT0008530, Registered 16 June 2023, https://cris.nih.go.kr/cris/index/index.do.

Transdiagnostic overlap in brain correlates of affective and cognitive theory of mind deficits.

Social cognitive symptoms characterize multiple neurological disorders, including brain tumours and neurodegeneration. Recently, Campanella and colleagues1 investigated deficits in cognitive and affective theory of mind (TOM) in 105 tumour patients using a non-verbal task of 18 stimuli that required patients to select one out of three possible endings of a cartoon story, i.e. the Story-based Empathy Task (SET).2 The SET includes three conditions [Causal Inference (CI), Intention Attribution (IA) and Emotion Attribution (EA)], reflecting the type of inference the items tap into: inference of physical properties, intentions, or characters’ emotional state, respectively. The behavioural results of Campanella’s study revealed specific EA deficits in patients with temporal lobe tumours. Furthermore, the authors used parcel-based lesion-symptom mapping (PLSM) and reported an association between a right anterior temporal cluster and EA performance. Right amygdalar lesions showed a stronger association with EA than with IA. The association between EA deficits and amygdalar volume has also been also reported in behavioural variant frontotemporal dementia (bvFTD),3 a neurodegenerative disorder, characterized by deficits in social cognition, including cognitive and affective TOM. Consistent with the findings of Campanella, we also observed an association between performance on the EA condition and grey matter volume of the right temporal lobe and amygdala3 (Fig. 1). As documented by Campanella and colleagues, such common neural correlates of EA performance largely overlap with a ‘reasoning about emotions’ network derived from a recent meta-analysis of functional brain imaging studies in healthy participants.4 These combined findings converge in supporting a critical role of the right amygdala and temporal lobe in emotion attribution.

Influence of exercise on pain is associated with resting-state functional connections: A cross-sectional functional brain imaging study

Exercise is associated with lower prevalence and severity of pain, and is widely recommended for pain management. However, the mechanisms the exercise effect on pain remain unclear. In this study, we examined the association of exercise with pain and aimed to identify its neurobiological mediators. We utilized a baseline data of a clinical trial for people with low back pain. Participants reported pain intensity and exercise habit, as well as pain-related psychological and emotional assessments. We also obtained brain imaging data using a resting-state functional MRI and performed mediation analyses to identify brain regions mediating the exercise effect on pain. Forty-five people with low back pain (mean pain intensity = 59.6 and mean duration = 9.9 weeks) were included in this study. Participants with an exercise habit (n = 29) showed significant less pain compared to those without an exercise habit (n = 16). Mediation analysis using resting-state functional connectivity identified the left thalamus, right amygdala, and medial prefrontal cortex as statistical mediators of the exercise effect on pain (indirect effect = −0.460, 95% confidence interval = −0.767 to −0.153). In conclusion, our findings suggest that brain function of the specific regions is probably a neuro-mechanism of exercise alleviating pain.

Minocycline alleviates abnormal microglial phagocytosis of synapses in a mouse model of depression

BackgroundAs antidepressants commonly used in the clinic have proved to be problematic, it is urgent to gain an updated understanding of the pathogenesis of depression and find potential therapeutic targets. Since both functional brain imaging studies and autopsy reports indicated that there is indeed a loss of synapses in depressed patients, it is necessary to explore the mechanism of this process. MethodsWe firstly investigated the effect of chronic social defeat stress (CSDS), a mouse model of depression, on behaviors, synapses, microglia, and microglial phagocytosis of synapses in mice. Then, as it is unclear whether microglial phagocytosis leads to synaptic loss, or synaptic loss induces the microglial clearance in CSDS mice, we used minocycline, a microglial activation inhibitor, to inhibit the microglial phagocytosis of synapses and study its effect on synapses and behaviors in CSDS mice. ResultsOur results showed that the expression levels of PSD-95 in the hippocampal dentate gyrus (DG) of CSDS mice were significantly reduced, while the microglia were significantly activated and the Iba1+CD68+ cell (phagocytic microglia) density was increased. We co-labeled the synaptic protein PSD-95 with the microglia marker Iba1 and found that the microglia in the hippocampal DG of CSDS mice contained significantly more PSD-95 engulfed puncta, which revealed that microglia in CSDS mice abnormally phagocytized synapses. Moreover, our results indicated that minocycline treatment dampened microglial activation, decreased the phagocytic microglia density, reduced abnormal microglial phagocytosis of synapses, reversed synaptic loss, and alleviated behavioral impairment in CSDS mice. ConclusionsUnder depressive pathological conditions, the activated microglia may abnormally engulf neuronal synapses causing synaptic loss and behavioral impairments. Thus, microglial phagocytosis may be a novel therapeutic target for the treatment of depression.

P177 Investigating the neural differences in individuals with chronic widespread pain or fibromyalgia and the effect of sleep: a cross-sectional study using data from UK Biobank

Abstract Background/Aims Sleep problems are common in fibromyalgia (FM) and chronic widespread pain (CWP), and may result in similar structural brain changes as those seen in chronic pain. However, the exact neural mechanisms are not fully understood. Studies to date are relatively small and yield conflicting results. The aim of this study is to investigate structural differences in brain regions of interest (ROI) in participants with FM or CWP from UK Biobank, a large-scale biomedical database, compared with healthy controls. We also explore the potential interaction of sleep on the volume of these ROIs, with the hypothesis that low sleep duration with chronic pain amplifies the atrophy seen. Methods Using T1 structural brain imaging data from UK Biobank, we defined cases as those experiencing CWP for 3+ months at the imaging visit or with a diagnosis of FM. Age- and sex-matched controls did not report any pain or chronic pain diagnoses at the imaging visit. Low sleep duration was defined as less than 7 hours of sleep in a 24-hour period in line with the recommended sleep duration of 7-9 hours. 22 brain ROIs were selected based on the existing literature. Pre-processed image-derived phenotype data for grey matter volumes were compared in brain ROIs using 2-way independent ANOVAs in SPSS. Results 429 cases and 429 controls were included: (n = 664/858 [77.4%] female; mean [SD] age 62.0 ± 7.4). The volume of the grey matter in the bilateral insular cortices and anterior parahippocampal gyri, and the volume of the right pallidum, were all significantly smaller in cases compared to controls, p &amp;lt; 0.05. In addition to the significant difference between the controls and cases in the right anterior parahippocampal gyrus, the interaction effect of sleep duration on pain was also significant, p &amp;lt; 0.05. Even though there were no significant differences between the controls and cases in the grey matter volumes of the left posterior division of the cingulate gyrus, bilateral superior frontal gyri, right middle frontal gyrus, left posterior division of the parahippocampal gyrus, right precuneus cortex and left inferior frontal gyrus, pars opercularis, and the volume of the right thalamus, there was a significant interaction effect of sleep duration and pain status on their volumes, p &amp;lt; 0.05. Conclusion This large-scale study confirms differences in grey matter volumes in key brain ROIs in those with chronic pain, highlighting neural changes in individuals suffering from CWP or FM, and a novel interaction of sleep on these areas. Perhaps these changes are due to neurotoxic effects of low sleep duration. Alternatively, low sleep duration and chronic pain may be caused by these structural differences. Evidently, further research is still needed to identify the directionality of these changes and their functional implications through longitudinal functional brain imaging studies, to identify the underlying cause of these structural differences. Disclosure N.W.I.L. Silva: None. A. Soni: None. V. Wanigasekera: None. S. Zhang: None. A.J.W. Wall: None. I. Tracey: None.

State anxiety may not affect memory encoding, retrieval, or recognition in older adults with mood disorders

<h3>Introduction</h3> State-level anxiety can have broad effects on cognition that are both beneficial (e.g., Yerkes-Dodson law) and detrimental. Data from functional brain imaging and physiological studies suggest state anxiety affects memory performance; however, findings have been inconsistent, and any effects likely depend on the specific memory process being examined (e.g., encoding, retrieval, and retention) and sample characteristics (e.g., age, clinical status). In this vein, few studies have examined how state anxiety affects memory in older adults, and even fewer have focused on patients with late life mood disorders. Moreover, the literature in this regard has produced inconsistent and sometimes conflicting findings, with some studies suggesting a detrimental impact on recall and others suggesting no effect or even modest benefit. Further investigation is needed to better understand how different memory processes might be impacted by state anxiety in older adults with mood disorders. This is an important target of investigation, as accounting for affective state is essential to ascertaining the clinical significance of memory deficits observed during neuropsychological evaluations of older adult psychiatric patients. Accordingly, the goal of the current study was to examine if and how state anxiety affects major memory processes in older adults with mood disorders. <h3>Methods</h3> We analyzed cross-sectional data from 44 older adults (25 female) ranging in age from 55-82 years (mean = 66.41 ± 6.65) with diagnoses of either major depressive disorder (n=21) or bipolar spectrum disorder (n=23) who were enrolled in the Geriatric Mood Disorders Database study at McLean Hospital. State anxiety and memory were measured using the Generalized Anxiety Disorder-7 Item Scale (GAD-7) and California Verbal Learning Test (CVLT-II), respectively. Outcomes variables from the CVLT-II corresponded to three major memory processes: Encoding/registration (trial 1-5 total recall), retrieval (long delay free recall), and storage/retention (recognition accuracy). A whole-group correlational analysis (Spearman rank order) was first performed to examine associations between GAD-7 score and each memory process in the entire sample. Linear regressions were then performed separately for each CVLT-II variable using group (depression vs bipolar), GAD-7 score (mean centered), and their interaction term as predictors to determine if the relationship between group and memory performance varied as a function of state-level anxiety. <h3>Results</h3> Groups did not differ in age, sex, or years of education, though a significant group difference was seen in GAD-7 total score [Depression: 4.43 ± 4.78, Bipolar: 8.39 ± 5.70; t(42) = -2.49, p = .017]. In the whole group analysis, no significant correlations were observed between GAD-7 score and any of the CVLT-II outcomes (all ps > .15). Despite the significant group difference in GAD-7 score, regression analyses did not show significant group x GAD-7 interactions on any of the CVLT-II outcomes, nor were there any significant main effects of group or GAD-7 score on those outcomes (all ps > .10). <h3>Conclusions</h3> The current results suggest that state-level anxiety may not affect memory encoding, retrieval, or recognition in older adults with mood disorders. However, it is important to note that the current study examined only one memory measure (CVLT-II), which limited our ability to detect potential effects of state anxiety on other forms of memory (e.g., visuospatial) and other cognitive domains (e.g., attention/executive function). Similarly, the GAD-7 is a relatively brief anxiety measure that focuses on a narrower range of self-reported symptoms. Future research in this area should employ a broader range of state anxiety measures, such as functional neuroimaging and physiological measures. While this study is also limited by a somewhat modest sample size, it is nonetheless a novel contribution to the literature given the paucity of research to date on the effect of state anxiety on memory in older adults with mood disorders. It is also important to note that while our results are not significant this could provide insight into the effect a diagnosis of a mood disorder might have on resilience in older adults. If we consider the emotional growth that comes with learning how to cope with a mood disorder for many years, we could potentially see an improved ability for older adults with mood disorders to cope with their anxiety symptoms compared to those who are more recently diagnosed. This potential emotional resilience may provide a protective buffer to the threat of anxiety's impact on memory. <h3>This research was funded by</h3> This study is funded by the Rogers Family Foundation.

How the motor system copes with aging: a quantitative meta-analysis of the effect of aging on motor function control

Motor cognitive functions and their neurophysiology evolve and degrade along the lifespan in a dramatic fashion. Current models of how the brain adapts to aging remain inspired primarily by studies on memory or language processes. Yet, aging is strongly associated with reduced motor independence and the associated degraded interaction with the environment: accordingly, any neurocognitive model of aging not considering the motor system is, ipso facto, incomplete. Here we present a meta-analysis of forty functional brain-imaging studies to address aging effects on motor control. Our results indicate that motor control is associated with aging-related changes in brain activity, involving not only motoric brain regions but also posterior areas such as the occipito-temporal cortex. Notably, some of these differences depend on the specific nature of the motor task and the level of performance achieved by the participants. These findings support neurocognitive models of aging that make fewer anatomical assumptions while also considering tasks-dependent and performance-dependent manifestations. Besides the theoretical implications, the present data also provide additional information for the motor rehabilitation domain, indicating that motor control is a more complex phenomenon than previously understood, to which separate cognitive operations can contribute and decrease in different ways with aging.

Chapter 11 - Dyspnea

The clinical term dyspnea (a.k.a. breathlessness or shortness of breath) encompasses at least three qualitatively distinct sensations that warn of threats to breathing: air hunger, effort to breathe, and chest tightness. Air hunger is a primal homeostatic warning signal of insufficient alveolar ventilation that can produce fear and anxiety and severely impacts the lives of patients with cardiopulmonary, neuromuscular, psychological, and end-stage disease. The sense of effort to breathe informs of increased respiratory muscle activity and warns of potential impediments to breathing. Most frequently associated with bronchoconstriction, chest tightness may warn of airway inflammation and constriction through activation of airway sensory nerves. This chapter reviews human and functional brain imaging studies with comparison to pertinent neurorespiratory studies in animals to propose the interoceptive networks underlying each sensation. The neural origins of their distinct sensory and affective dimensions are discussed, and areas for future research are proposed. Despite dyspnea's clinical prevalence and impact, management of dyspnea languishes decades behind the treatment of pain. The neurophysiological bases of current therapeutic approaches are reviewed; however, a better understanding of the neural mechanisms of dyspnea may lead to development of novel therapies and improved patient care.

The Role of Occipital Cortex Hyperexcitability in Visual Snow Syndrome

INTRODUCTION Visual snow syndrome (VSS) is an emerging clinical entity, mainly characterized by persistent, bilateral, whole-visual field, disturbing, small flickering dots or pixelation, floaters, palinopsia, nyctalopia, photopsia, and photophobia. Patients with VSS also describe associated symptoms such as tinnitus, concentration difficulty, lethargy, depression, anxiety, and irritability, all of which affect the patients' quality of life. The consistency of these visual and nonvisual symptoms has recently led to proposed criteria for VSS. The diagnosis relies on the exclusion of other ophthalmic or neuropsychiatric disorders. Interestingly, many patients may have a comorbid migraine, and the symptoms were previously attributed as a persistent visual phenomenon in migraine. VSS is listed in the International Classification of Headache Disorders-Third Edition Appendix as a complication of migraine; however, VSS is a new disease entity distinct from persistent migraine aura. Some patients with VSS recall exposure to illicit hallucinogenic drugs, amphetamines, cannabis, or Lysergic acid diethylamide (LSD). The stereotypic clinical characteristics of VSS are currently well defined, and the pathophysiology is under investigation. Due to the subjective perceptual descriptions of patients with VSS, objective electrophysiologic parameters and functional brain imaging studies using magnetic resonance imaging and positron emission tomography are warranted for defining the quantifiable and reliable outcome measures. Patients with migraine, idiopathic occipital epilepsies, patients with Alice in Wonderland syndrome, patients with Charles Bonnet syndrome, visual hallucinations in recovery from cortical blindness, and recreational 3,4-methylenedioxymethamphetamine/ecstasy users have been suggested to have occipital cortex hyperexcitability. VSS is attributed to involving a dysfunctional magnocellular pathway, thalamocortical dysrhythmia, dysfunctional central visual processing, and occipital cortex hyperexcitability as possible underlying mechanisms. This review will focus on the role of occipital cortex hyperexcitability in VSS and hopefully provide insight into its pathophysiology and therapeutic strategies.

Altered Spontaneous Brain Activity in Subjects With Different Cognitive States of Biologically Defined Alzheimer's Disease: A Surface-Based Functional Brain Imaging Study.

Background: Before the apparent cognitive decline, subjects on the course of Alzheimer's disease (AD) can have significantly altered spontaneous brain activity, which could be potentially used for early diagnosis. As previous studies investigating local brain activity may suffer from the problem of cortical signal aliasing during volume-based analysis, we aimed to investigate the cortical functional alterations in the AD continuum using a surface-based approach.Methods: Based on biomarker profile “A/T,” we included 11 healthy controls (HC, A–T–), 22 preclinical AD (CU, A+T+), 33 prodromal AD (MCI, A+T+), and 20 AD with dementia (d-AD, A+T+) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The amplitude of low-frequency fluctuation (ALFF) method was used to evaluate the changes of spontaneous brain activity, which was performed in the classic frequency band (0.01–0.08 Hz), slow-4 (0.027–0.073 Hz) band, and slow-5 (0.01–0.027 Hz) band.Results: Under classic frequency band and slow-4 band, analysis of covariance (ANCOVA) showed that there were significant differences of standardized ALFF (zALFF) in the left posterior cingulate cortex (PCC) among the four groups. The post-hoc analyses showed that under the classic frequency band, the AD group had significantly decreased zALFF compared with the other three groups, and the cognitively unimpaired (CU) group had decreased zALFF compared with the healthy control (HC) group. Under the slow-4 band, more group differences were detected (HC > CU/MCI > d-AD). The accuracy of classifying CU, mild cognitive impairment (MCI), and AD from HC by left PCC activity under the slow-4 band were 0.774, 0.744, and 0.920, respectively. Moreover, the zALFF values of the left PCC had significant correlations with cerebrospinal fluid (CSF) biomarkers and neuropsychological tests.Conclusions: Spontaneous brain activity in the left PCC may decrease in preclinical AD when cognitive functions were relatively normal. The combination of a surfaced-based approach and specific frequency band analysis may increase sensitivity for the identification of preclinical AD subjects.

Neuropathic and Psychogenic Components of Burning Mouth Syndrome: A Systematic Review

The pathophysiology of primary burning mouth syndrome (BMS) has been extensively debated but is poorly understood despite a large number of hypotheses attempting to explain its etiopathogenic mechanisms. The aim of the present work was to systematically review papers that could provide arguments in favour of the neuropathic and psychogenic components of primary BMS for a better understanding of the disease. This systematic review (SR) was registered in PROSPERO (CRD42021224160). The search was limited to articles in English or French from 1990 to 01 December 2020. A total of 113 articles were considered for data extraction. We divided them into four subgroups: pharmacological and nonpharmacological management studies (n = 23); neurophysiological studies (n = 35); biohistopathological studies (n = 25); and questionnaire-based studies (n = 30). Several of these studies have shown neuropathic involvement at various levels of the neuraxis in BMS with the contribution of quantitative sensory testing (QST), functional brain imaging, and biohistopathological or pharmacologic studies. On the other hand, the role of psychological factors in BMS has also been the focus of several studies and has shown a link with psychiatric disorders such as anxiety and/or depression symptoms. Depending on the patient, the neuropathic and psychogenic components may exist simultaneously, with a preponderance of one or the other, or exist individually. These two components cannot be dissociated to define BMS. Consequently, BMS may be considered nociplastic pain.

Utility of SPECT Functional Neuroimaging of Pain

Functional neuroimaging modalities vary in spatial and temporal resolution. One major limitation of most functional neuroimaging modalities is that only neural activation taking place inside the scanner can be imaged. This limitation makes functional neuroimaging in many clinical scenarios extremely difficult or impossible. The most commonly used radiopharmaceutical in Single Photon Emission Tomography (SPECT) functional brain imaging is Technetium 99 m-labeled Ethyl Cysteinate Dimer (ECD). ECD is a lipophilic compound with unique pharmacodynamics. It crosses the blood brain barrier and has high first pass extraction by the neurons proportional to regional brain perfusion at the time of injection. It reaches peak activity in the brain 1 min after injection and is then slowly cleared from the brain following a biexponential mode. This allows for a practical imaging window of 1 or 2 h after injection. In other words, it freezes a snapshot of brain perfusion at the time of injection that is kept and can be imaged later. This unique feature allows for designing functional brain imaging studies that do not require the patient to be inside the scanner at the time of brain activation. Functional brain imaging during severe burn wound care is an example that has been extensively studied using this technique. Not only does SPECT allow for imaging of brain activity under extreme pain conditions in clinical settings, but it also allows for imaging of brain activity modulation in response to analgesic maneuvers whether pharmacologic or non-traditional such as using virtual reality analgesia. Together with its utility in extreme situations, SPECTS is also helpful in investigating brain activation under typical pain conditions such as experimental controlled pain and chronic pain syndromes.

The Neural Processing of Vocal Emotion After Hearing Reconstruction in Prelingual Deaf Children: A Functional Near-Infrared Spectroscopy Brain Imaging Study.

As elucidated by prior research, children with hearing loss have impaired vocal emotion recognition compared with their normal-hearing peers. Cochlear implants (CIs) have achieved significant success in facilitating hearing and speech abilities for people with severe-to-profound sensorineural hearing loss. However, due to the current limitations in neuroimaging tools, existing research has been unable to detail the neural processing for perception and the recognition of vocal emotions during early stage CI use in infant and toddler CI users (ITCI). In the present study, functional near-infrared spectroscopy (fNIRS) imaging was employed during preoperative and postoperative tests to describe the early neural processing of perception in prelingual deaf ITCIs and their recognition of four vocal emotions (fear, anger, happiness, and neutral). The results revealed that the cortical response elicited by vocal emotional stimulation on the left pre-motor and supplementary motor area (pre-SMA), right middle temporal gyrus (MTG), and right superior temporal gyrus (STG) were significantly different between preoperative and postoperative tests. These findings indicate differences between the preoperative and postoperative neural processing associated with vocal emotional stimulation. Further results revealed that the recognition of vocal emotional stimuli appeared in the right supramarginal gyrus (SMG) after CI implantation, and the response elicited by fear was significantly greater than the response elicited by anger, indicating a negative bias. These findings indicate that the development of emotional bias and the development of emotional perception and recognition capabilities in ITCIs occur on a different timeline and involve different neural processing from those in normal-hearing peers. To assess the speech perception and production abilities, the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) and Speech Intelligibility Rating (SIR) were used. The results revealed no significant differences between preoperative and postoperative tests. Finally, the correlates of the neurobehavioral results were investigated, and the results demonstrated that the preoperative response of the right SMG to anger stimuli was significantly and positively correlated with the evaluation of postoperative behavioral outcomes. And the postoperative response of the right SMG to anger stimuli was significantly and negatively correlated with the evaluation of postoperative behavioral outcomes.

Posttraumatic Stress Disorder and Cardiovascular Disease

Posttraumatic stress disorder (PTSD) is characterized by a persistent maladaptive reaction after exposure to severe psychological trauma. Traumatic events that may precipitate PTSD include violent personal assaults, natural and human-made disasters, and exposure to military combat or warfare. There is a growing body of evidence for associations of PTSD with major risk factors for cardiovascular disease (CVD), such as hypertension and diabetes, as well as with major CVD outcomes, such as myocardial infarction and heart failure. However, it is unclear whether these associations are causal or confounded. Furthermore, the biological and behavioral mechanisms underlying these associations are poorly understood. Here, the available evidence on the association of PTSD with CVD from population, basic, and genomic research as well as from clinical and translational research are reviewed, seeking to identify major research gaps, barriers, and opportunities in knowledge acquisition and technology as well as research tools to support and accelerate critical research for near-term and longer-term translational research directions. Large-scale, well-designed prospective studies, capturing diverse and high-risk populations, are warranted that include uniform phenotyping of PTSD as well as broad assessment of biological and behavioral risk factors and CVD outcomes. Available evidence from functional brain imaging studies demonstrates that PTSD pathophysiology includes changes in specific anatomical brain regions and circuits, and studies of immune system function in individuals with PTSD suggest its association with enhanced immune inflammatory activity. However, establishment of animal models and human tissue biobanks is also warranted to elucidate the potential causal connection of PTSD-induced brain changes and/or inflammation with CVD pathophysiology. Emerging large-scale genome-wide association studies of PTSD will provide an opportunity to conduct mendelian randomization studies that test hypotheses regarding the presence, magnitude, and direction of causal associations between PTSD and CVD outcomes. By identifying research gaps in epidemiology and genomics, animal, and human translational research, opportunities to better justify and design future interventional trials are highlighted that may test whether treatment of PTSD or underlying neurobiological or immune dysregulation may improve or prevent CVD risk or outcomes.

Association of Brain Reward Response With Body Mass Index and Ventral Striatal-Hypothalamic Circuitry Among Young Women With Eating Disorders

Eating disorders are severe psychiatric disorders; however, disease models that cross subtypes and integrate behavior and neurobiologic factors are lacking. To assess brain response during unexpected receipt or omission of a salient sweet stimulus across a large sample of individuals with eating disorders and healthy controls and test for evidence of whether this brain response is associated with the ventral striatal-hypothalamic circuitry, which has been associated with food intake control, and whether salient stimulus response and eating disorder related behaviors are associated. In this cross-sectional functional brain imaging study, young adults across the eating disorder spectrum were matched with healthy controls at a university brain imaging facility and eating disorder treatment program. During a sucrose taste classic conditioning paradigm, violations of learned associations between conditioned visual and unconditioned taste stimuli evoked the dopamine-related prediction error. Dynamic effective connectivity during expected sweet taste receipt was studied to investigate hierarchical brain activation between food intake relevant brain regions. The study was conducted from June 2014 to November 2019. Data were analyzed from December 2019 to February 2020. Prediction error brain reward response across insula and striatum; dynamic effective connectivity between hypothalamus and ventral striatum; and demographic and behavior variables and their correlations with prediction error brain response and connectivity edge coefficients. Of 317 female participants (197 with eating disorders and 120 healthy controls), the mean (SD) age was 23.8 (5.6) years and mean (SD) body mass index was 20.8 (5.4). Prediction error response was elevated in participants with anorexia nervosa (Wilks λ, 0.843; P = .001) and in participants with eating disorders inversely correlated with body mass index (left nucleus accumbens: r = -0.291; 95% CI, -0.413 to -0.167; P < .001; right dorsal anterior insula: r = -0.228; 95% CI, -0.366 to -0.089; P = .001), eating disorder inventory-3 binge eating tendency (left nucleus accumbens: r = -0.207; 95% CI, -0.333 to -0.073; P = .004; right dorsal anterior insula: r = -0.220; 95% CI, -0.354 to -0.073; P = .002), and trait anxiety (left nucleus accumbens: r = -0.148; 95% CI, -0.288 to -0.003; P = .04; right dorsal anterior insula: r = -0.221; 95% CI, -0.357 to -0.076; P = .002). Ventral striatal to hypothalamus directed connectivity was positively correlated with ventral striatal prediction error in eating disorders (r = 0.189; 95% CI, 0.045-0.324; P = .01) and negatively correlated with feeling out of control after eating (right side: r = -0.328; 95% CI, -0.480 to -0.164; P < .001; left side: r = -0.297; 95% CI, -0.439 to -0.142; P = .001). The results of this cross-sectional imaging study support that body mass index modulates prediction error and food intake control circuitry in the brain. Once altered, this circuitry may reinforce eating disorder behaviors when paired with behavioral traits associated with overeating or undereating.

Behavioral and biological divergence in monozygotic twin pairs discordant for autism phenotypes: A systematic review.

Non-shared environment (NSE) effects account for around one-third of the etiology of autism spectrum disorder (ASD). However, the knowledge of mechanisms and phenotypic profiles associated with NSE in ASD is scarce. A systematic search was conducted using Embase, MEDLINE, and PsycINFO for studies published in English between 1990 and August 2020 using co-twin control design to compare behavioral and biological phenotypes among monozygotic (MZ) twin pairs concordant/discordant for ASD, clinical autism symptoms, or autistic traits. Risk of bias was assessed through a modified Newcastle-Ottawa Scale. Twenty six articles were included. Differential DNA methylation and gene expression were found among ASD discordant twins; however, genetic results were inconsistent. Neurological disorders and early medical events were associated with ASD and autistic traits, while no within pair differences were found for minor physical anomalies or head circumference. Structural and functional brain imaging studies and research on social and other cognitive/behavioral functions were inconclusive. Risk of bias assessment found that all studies used the same exposure (or outcome) measures to collect data for participants and most used either secure health-related records or structured interviews for ascertainment of exposure; however, only a handful of studies representative of the population from which they were drawn. Formal assessment of risk of publication bias (i.e., funnel plot) was not possible. Our results suggest that NSE in ASD could be associated with heterogeneous postzygotic genetic mechanisms and manifest as a range of biological and behavioral phenotypes. Extant findings were limited by relatively few studies, small sample sizes, and methodological diversity. More research is needed on co-occurring biological and behavioral phenotypes using a consistent format for designing, analyzing, and reporting MZ ASD discordant twin studies in order to further examine the role of NSE in the etiology of ASD.