Brain Hemodynamic Responses Research Articles

Changes in Hemodynamic Response Function Resulting From Chronic Alcohol Consumption.

Functional MRI (fMRI) task-related analyses rely on an estimate of the brain's hemodynamic response function (HRF) to model the brain's response to events. Although changes in the HRF have been found after acute alcohol administration, the effects of heavy chronic alcohol consumption on the HRF have not been explored, and the potential benefits or pitfalls of estimating each individual's HRF on fMRI analyses of chronic alcohol use disorder (AUD) are not known. Participants with AUD and controls (CTL) received structural, functional, and vascular scans. During fMRI, participants were cued to tap their fingers, and averaged responses were extracted from the motor cortex. Curve fitting on these HRFs modeled them as a difference between 2 gamma distributions, and the temporal occurrence of the main peak and undershoot of the HRF was computed from the mean of the first and second gamma distributions, respectively. ANOVA and regression analyses found that the timing of the HRF undershoot increased significantly as a function of total lifetime drinking. Although gray matter volume in the motor cortex decreased with lifetime drinking, this was not sufficient to explain undershoot timing shifts, and vascular factors measured in the motor cortex did not differ among groups. Comparison of random-effects analyses using custom-fitted and canonical HRFs for CTL and AUD groups showed better results throughout the brain for custom-fitted versus canonical HRFs for CTL subjects. For AUD subjects, the same was true except for the basal ganglia. These findings suggest that excessive alcohol consumption is associated with changes in the HRF undershoot. HRF changes could provide a possible biomarker for the effects of lifetime drinking on brain function. Changes in HRF topography affect fMRI activation measures, and subject-specific HRFs generally improve fMRI activation results.

Acute effects of systemic inflammation upon the neuro-glial-vascular unit and cerebrovascular function

Brain health relies on a tightly regulated system known as neurovascular coupling whereby the cellular constituents of the neuro-glial-vascular unit (NGVU) regulate cerebral haemodynamics in accordance with brain metabolic demand. Disruption of neurovascular coupling impairs brain health and is associated with the development of a number for neurological conditions, including Alzheimer’s disease. The NGVU is also a key site of action for neuroinflammatory responses and contributes to the transition of systemic inflammation to neuroinflammatory processes. Thus, systemic inflammatory challenges may cause a shift in NGVU operation towards prioritising neuroinflammatory action and thus altering neurovascular coupling and resultant cerebrovascular changes. To investigate this, rats were injected with lipopolysaccharide (LPS) (2 ​mg/kg) to induce a systemic inflammatory response, or vehicle, and brain haemodynamic responses to sensory and non-sensory (hypercapnia) stimuli were assessed in vivo using optical imaging techniques. Following imaging, animals were perfused and their brains extracted to histologically characterise components of the NGVU to determine the association between underlying cellular changes and in vivo blood flow regulation. LPS-treated animals showed changes in haemodynamic function and cerebrovascular dynamics 6 ​hours after LPS administration. Histological assessment identified a significant increase in astrogliosis, microgliosis and endothelial activation in LPS-treated animals. Our data shows that an acutely induced systemic inflammatory response is able to rapidly alter invivo haemodynamic function and is associated with significant changes in the cellular constituents of the NGVU. We suggest that these effects are initially mediated by endothelial cells, which are directly exposed to the circulating inflammatory stimulus and have been implicated in regulating functional hyperaemia.

The influence of maternal anxiety and depression symptoms on fNIRS brain responses to emotional faces in 5- and 7-month-old infants

Greater relative right (versus left) frontal cortical activation to emotional faces as measured with alpha power in the electroencephalogram (EEG), has been considered a promising neural marker of increased vulnerability to psychopathology and emotional disorders. We set out to explore multichannel fNIRS as a tool to investigate infants’ frontal asymmetry responses (hypothesizing greater right versus left frontal cortex activation) to emotional faces as influenced by maternal anxiety and depression symptoms during the postnatal period. We also explored activation differences in fronto-temporal regions associated with facial emotion processing. Ninety-one typically developing 5- and 7-month-old infants were shown photographs of women portraying happy, fearful and angry expressions. Hemodynamic brain responses were analyzed over two frontopolar and seven bilateral cortical regions subdivided into frontal, temporal and parietal areas, defined by age-appropriate MRI templates. Infants of mothers reporting higher negative affect had greater oxyhemoglobin (oxyHb) activation across all emotions over the left inferior frontal gyrus, a region implicated in emotional communication. Follow-up analyses indicated that associations were driven by maternal depression, but not anxiety symptoms. Overall, we found no support for greater right versus left frontal cortex activation in association with maternal negative affect. Findings point to the potential utility of fNIRS as a method for identifying altered neural substrates associated with exposure to maternal depression in infancy.

Evaluation of the brain hemodynamic response by means of near-infrared spectroscopy (NIRS) monitoring in patients with atherosclerotic carotid disease undergoing endarterectomy.

BackgroundsNear-infrared spectroscopy (NIRS) is non-invasive technique that detects hemodynamic alterations in tissues. It enables continuous monitoring of intracerebral vascular physiologic information. Due to its portable nature, NIRS may be used bedside or in the operating room.ObjectivesTo evaluate use of NIRS for intraoperative monitoring of the brain hemodynamic response, during carotid endarterectomy.Methods10 patients with atherosclerotic carotid disease scheduled for endarterectomy were evaluated. After patients had been selected, they answered a questionnaire on epidemiological data and information about comorbidities and then carotid disease was confirmed with diagnostic methods. NRIS monitoring was used during the surgical procedure. The variables analyzed before, during and after carotid clamping were oxygen saturation (SatO2), total hemoglobin (THb), reduced hemoglobin (RHb), and oxyhemoglobin (OHb). A p value of <0.05 was considered statistically significant.ResultsThe results obtained from NIRS show that RHb and SatO2 vary during the different stages of surgery. RHb levels are higher during clamping, when compared with the other two surgical stages. On the other hand, SatO2 is lower during clamping.ConclusionsDuring carotid endarterectomy, NIRS is a feasible, real-time, and non-invasive intracranial monitoring method that accurately and reliably measures the changes in intracerebral capillary hemodynamic conditions.

Brain correlates of emotional prosodic change detection in autism spectrum disorder

Autism Spectrum Disorder (ASD) is currently diagnosed by the joint presence of social impairments and restrictive, repetitive patterns of behaviors. While the co-occurrence of these two categories of symptoms is at the core of the pathology, most studies investigated only one dimension to understand underlying physiopathology. In this study, we analyzed brain hemodynamic responses in neurotypical adults (CTRL) and adults with autism spectrum disorder during an oddball paradigm allowing to explore brain responses to vocal changes with different levels of saliency (deviancy or novelty) and different emotional content (neutral, angry).Change detection relies on activation of the supratemporal gyrus and insula and on deactivation of the lingual area. The activity of these brain areas involved in the processing of deviancy with vocal stimuli was modulated by saliency and emotion. No group difference between CTRL and ASD was reported for vocal stimuli processing or for deviancy/novelty processing, regardless of emotional content.Findings highlight that brain processing of voices and of neutral/ emotional vocal changes is typical in adults with ASD. Yet, at the behavioral level, persons with ASD still experience difficulties with those cues. This might indicate impairments at latter processing stages or simply show that alterations present in childhood might have repercussions at adult age.

A gift for gratitude and cooperative behavior: brain and cognitive effects.

Recently, different psychological studies have been interested in identifying the factors that regulate the development and maintenance of long-lasting interpersonal and social relationships. Specifically, the present research explored the link between gift exchange, gratitude and cognitive effects. The behavioral performance and neural activity of 32 participants were recorded during a cooperative game to be played before and after gift exchange. Specifically, participants had to perform the task coupled with a dear friend. Half of the couples were asked to exchange a gift before the task performance; the other half was asked to exchange a gift halfway through the task performance. For hemodynamic brain responses, functional near-infrared spectroscopy was used. Results showed that an increase in cognitive performance occurred after the exchange of gifts, with improved accuracy and lower response times in task performance. Regarding hemodynamic responses, an increase in oxygenated hemoglobin was detected, especially in the dorsolateral prefrontal cortex following the gift exchange. Furthermore, it was observed that gift exchange before the beginning of the task increased the performance level. The present study provides a significant contribution to the identification of those factors that enable the increased cognitive performance based on cooperative relationships.

The effects of exercise on mood and prefrontal brain responses to emotional scenes in smokers

The benefits of exercise for smokers attempting to quit are partially dependent on physical activity levels prior to cessation. Mood disturbances can manifest within 30 min of smoking a cigarette and contribute to negative reinforcement of smoking behavior over time, whereas a single bout of aerobic exercise can reduce negative mood states and improve affect on a similar timescale in non-smokers. The acute effects of exercise among non-abstaining smokers immediately after a cigarette are unknown but may have clinical implications for smokers considering cessation. The aim of this study was to examine the concurrent effects of exercise on mood disturbance and prefrontal brain hemodynamic response to emotionally arousing scenes 30 min after smoking a cigarette and to test whether prefrontal brain hemodynamic response was correlated with affective ratings of the scenes. Fifteen cigarette smokers, averaging 47.6 cigarettes/week in the year prior to screening, served as participants. Functional near-infrared spectroscopy was used to measure hemodynamic status over the dorsolateral prefrontal cortex (DLPFC). Participants viewed pleasant, unpleasant, and neutral scenes prior to smoking a cigarette and 30 min later after seated rest or exercise at a preferred intensity. Mood disturbance was assessed by the Profile of Mood States-Brief Form four times: before smoking a cigarette, before and after exercise and rest, and after a post-condition (exercise/rest) exposure to emotionally arousing scenes. Compared to seated rest, cycling after a cigarette reduced mood disturbance (p = =.038) and DLPFC hemodynamic response to unpleasant (p = =.003) and pleasant (p = =.021) scenes relative to neutral scenes. DLPFC hemodynamic response was not related to affective ratings of scenes. We report that cycling for 20 min at a preferred intensity reduces mood disturbances which occur shortly after smoking a cigarette and blunts DLPFC hemodynamic response to emotionally arousing scenes. The findings encourage further investigation of exercise for smokers in the maintenance stage of smoking cessation.

Redefining Noradrenergic Neuromodulation of Behavior: Impacts of a Modular Locus Coeruleus Architecture.

The locus coeruleus (LC) is a seemingly singular and compact neuromodulatory nucleus that is a prominent component of disparate theories of brain function due to its broad noradrenergic projections throughout the CNS. As a diffuse neuromodulatory system, noradrenaline affects learning and decision making, control of sleep and wakefulness, sensory salience including pain, and the physiology of correlated forebrain activity (ensembles and networks) and brain hemodynamic responses. However, our understanding of the LC is undergoing a dramatic shift due to the application of state-of-the-art methods that reveal a nucleus of many modules that provide targeted neuromodulation. Here, we review the evidence supporting a modular LC based on multiple levels of observation (developmental, genetic, molecular, anatomical, and neurophysiological). We suggest that the concept of the LC as a singular nucleus and, alongside it, the role of the LC in diverse theories of brain function must be reconsidered.

Comparison of Brain Hemodynamic Responses to Forward versus Backward Walking among People Post-Stroke

Comparison of Brain Hemodynamic Responses to Forward versus Backward Walking among People Post-Stroke

Decreased cerebral blood flow and hemodynamic parameters during acute hyperglycemia in mice model observed by dual-wavelength speckle imaging.

In this study, we use dual-wavelength optical imaging-based laser speckle technique to assess cerebral blood flow and metabolic parameters in a mouse model of acute hyperglycemia (high blood glucose). The effect of acute glucose levels on physiological processes has been extensively described in multiple organ systems such as retina, kidney, and others. We postulated that hyperglycemia also alters brain function, which in turn can be monitored optically using dual-wavelength laser speckle imaging (DW-LSI) platform. DW-LSI is a wide-field, noncontact optical imaging modality that integrates the principles of laser flowmetry and oximetry to obtain macroscopic information such as hemoglobin concentration and blood flow. A total of eight mice (C57/BL6) were used, randomized into two groups of normoglycemia (control, n = 3) and hyperglycemia (n = 5). Hyperglycemia was induced by intraperitoneal injection of a commonly used anesthetic drug combining ketamine and xylazine (KX combo). We found that this KX combo increases blood glucose (BG) levels from 150 to 350 mg/dL, approximately, when measured 18 minutes post-administration. BG continues to increase throughout the test period, with BG reaching an average of 463 ± 20.34 mg/dL within 60 minutes. BG levels were measured every 10 minutes from tail blood using commercially available glucometer. Experimental results demonstrated reductions in cerebral blood flow (CBF) by 55%, tissue oxygen saturation (SO2 ) by 15%, and cerebral metabolic rate of oxygen (CMRO2 ) by 75% following acute hyperglycemia. The observed decrease in these parameters was consistent with results reported in the literature, measured by a variety of experimental techniques. Measurements with laser Doppler flowmetry (LDF) were also performed which confirmed a reduction in CBF following acute hyperglycemia. In summary, our findings indicate that acute hyperglycemia modified brain hemodynamic response and induced significant changes in blood flow and metabolism. As far as we are aware, the implementation of the DW-LSI to monitor brain hemodynamic and metabolic response to acute hyperglycemia in intact mouse brain has not been previously reported.

FNIRS Evidence for Recognizably Different Positive Emotions.

The behavioral differentiation of positive emotions has recently been studied in terms of their discrete adaptive functions or appraising profiles. Some preliminary neurophysiological evidences have been found with electroencephalography or autonomic nervous system measurements such as heart rate, skin conductance, etc. However, the brain’s hemodynamic responses to different positive emotions remain largely unknown. In the present study, the functional near-infrared spectroscopy (fNIRS) technique was employed. With this tool, we for the first time reported recognizable discrete positive emotions using fNIRS signals. Thirteen participants watched 30 emotional video clips to elicit 10 typical kinds of positive emotions (joy, gratitude, serenity, interest, hope, pride, amusement, inspiration, awe, and love), and their frontal neural activities were simultaneously recorded with a 24-channel fNIRS system. The multidimensional scaling analysis of participants’ subjective ratings on these 10 positive emotions revealed three distinct clusters, which could be interpreted as “playfulness” for amusement, joy, interest, “encouragement” for awe, gratitude, hope, inspiration, pride, and “harmony” for love, serenity. Hemodynamic responses to these three positive emotion clusters showed distinct patterns, and HbO-based individual-level binary classifications between them achieved an averaged accuracy of 73.79 ± 11.49% (77.56 ± 7.39% for encouragement vs. harmony, 73.29 ± 11.87% for playfulness vs. harmony, 70.51 ± 13.96% for encouragement vs. harmony). Benefited from fNIRS’s high portability, low running cost and the relative robustness against motion and electrical artifacts, our findings provided support for implementing a more fine-grained emotion recognition system with subdivided positive emotion categories.

Classification of motor imagery and execution signals with population-level feature sets: implications for probe design in fNIRS based BCI

Objective. The aim of this study was to introduce a novel methodology for classification of brain hemodynamic responses collected via functional near infrared spectroscopy (fNIRS) during rest, motor imagery (MI) and motor execution (ME) tasks which involves generating population-level training sets. Approach. A 48-channel fNIRS system was utilized to obtain hemodynamic signals from the frontal (FC), primary motor (PMC) and somatosensory cortex (SMC) of ten subjects during an experimental paradigm consisting of MI and ME of various right hand movements. Classification accuracies of random forest (RF), support vector machines (SVM), and artificial neural networks (ANN) were computed at the single subject level by training each classifier with subject specific features, and at the group level by training with features from all subjects for ME versus Rest, MI versus Rest and MI versus ME conditions. The performances were also computed for channel data restricted to FC, PMC and SMC regions separately to determine optimal probe location. Main results. RF, SVM and ANN had comparably high classification accuracies for ME versus Rest (%94, %96 and %98 respectively) and for MI versus Rest (%95, %95 and %98 respectively) when fed with group level feature sets. The accuracy performance of each algorithm in localized brain regions were comparable (>%93) to the accuracy performance obtained with whole brain channels (>%94) for both ME versus Rest and MI versus Rest conditions. Significance. By demonstrating the feasibility of generating a population level training set with a high classification performance for three different classification algorithms, the findings pave the path for removing the necessity to acquire subject specific training data and hold promise for a novel, real-time fNIRS based BCI system design which will be most effective for application to disease populations for whom obtaining data to train a classification algorithm is not possible.

Xây dựng ảnh não ba chiều sử dụng phương pháp quang cận hồng ngoại

Functional near-infrared spectroscopy (fNIRS) is a non-invasive technique utilized to measure hemoglobin concentration of human brain signal. Temporal resolution of this method is high (aproximately 1 ms). However, its spatial resolution is limited (approximately 10 mm) compared with other non-invasive techniques. Therefore, in the present study, fNIRS based 32-optodes are utilized to measure human brain hemodynamic response of 5 male participants with arithmetic tasks. Coordinates of 256 voxels are computed based on the optode geometry. Coefficient of differential path-length factor in Beer-Lambert equation is estimated as a distance function to compute absorption coefficients. The mean concentration of Oxy- and deOxy-hemoglobin obtained from absorption coefficients is utilized to reconstruct 3-dimension brain imaging. The experimental results showed that the proposed method can detect the brain activity with higher spatial resolution than that using conventional approach.

The brain’s hemodynamic response function rapidly changes under acute psychosocial stress in association with genetic and endocrine stress response markers

Ample evidence links dysregulation of the stress response to the risk for psychiatric disorders. However, we lack an integrated understanding of mechanisms that are adaptive during the acute stress response but potentially pathogenic when dysregulated. One mechanistic link emerging from rodent studies is the interaction between stress effectors and neurovascular coupling, a process that adjusts cerebral blood flow according to local metabolic demands. Here, using task-related fMRI, we show that acute psychosocial stress rapidly impacts the peak latency of the hemodynamic response function (HRF-PL) in temporal, insular, and prefrontal regions in two independent cohorts of healthy humans. These latency effects occurred in the absence of amplitude effects and were moderated by regulatory genetic variants of KCNJ2, a known mediator of the effect of stress on vascular responsivity. Further, hippocampal HRF-PL correlated with both cortisol response and genetic variants that influence the transcriptional response to stress hormones and are associated with risk for major depression. We conclude that acute stress modulates hemodynamic response properties as part of the physiological stress response and suggest that HRF indices could serve as endophenotype of stress-related disorders.

Interaction Between Parenting Styles and Adrenarcheal Timing Associated With Affective Brain Function in Late Childhood

Parenting and pubertal timing have consistently been associated with internalizing and externalizing symptoms in childhood and adolescence, and there is some evidence that the interaction between these factors may be important in conferring risk. However, few studies have investigated whether neurobiological factors mediate these relationships. The current study examined whether interactions between adrenarcheal timing and parenting styles were associated with affective brain function and, in turn, mental health difficulties. Participants were 88 healthy children (46 female and 42 male, mean age 9.42 years, SD= 1.08 years), with 45 classified as relatively early and 43 as relatively late in adrenarcheal development based upon adrenal hormone levels. Participants completed an affective face functional magnetic resonance imaging task, and parents reported on 5 parenting styles and on child internalizing and externalizing symptoms. Negative parenting styles (corporal punishment and poor monitoring) were associated with brain hemodynamic response while viewing affective faces in several subcortical and lateral prefrontal regions, and adrenarcheal timing and/or sex moderated most of these relationships. Sex differences in associations between corporal punishment and brain activation to affective faces indicated that late females might show less adaptive affective neural function when more exposed to this parenting style. Findings suggest that the interaction between parenting styles and adrenarcheal timing is associated with affective brain function in late childhood, with marked sex differences. Further longitudinal research with larger samples is needed to corroborate and expand upon these findings.

Differential Path-Length Factor's Effect on the Characterization of Brain's Hemodynamic Response Function: A Functional Near-Infrared Study.

Functional near-infrared spectroscopy (fNIRS) has evolved as a neuro-imaging modality over the course of the past two decades. The removal of superfluous information accompanying the optical signal, however, remains a challenge. A comprehensive analysis of each step is necessary to ensure the extraction of actual information from measured fNIRS waveforms. A slight change in shape could alter the features required for fNIRS-BCI applications. In the present study, the effect of the differential path-length factor (DPF) values on the characteristics of the hemodynamic response function (HRF) was investigated. Results were compiled for both simulated data sets and healthy human subjects over a range of DPF values from three to eight. Different sets of activation durations and stimuli were used to generate the simulated signals for further analysis. These signals were split into optical densities under a constrained environment utilizing known values of DPF. Later, different values of DPF were used to analyze the variations of actual HRF. The results, as summarized into four categories, suggest that the DPF can change the main and post-stimuli responses in addition to other interferences. Six healthy subjects participated in this study. Their observed optical brain time-series were fed into an iterative optimization problem in order to estimate the best possible fit of HRF and physiological noises present in the measured signals with free parameters. A series of solutions was derived for different values of DPF in order to analyze the variations of HRF. It was observed that DPF change is responsible for HRF creep from actual values as well as changes in HRF characteristics.

On pacing trials while scanning brain hemodynamics: The case of the SNARC effect.

Experimental designs used to describe psychological effects on overt human behavior are seldom suited to localize their corresponding neural substrates based on the analysis of stimulus-evoked brain hemodynamic responses. This is because stimuli in behavioral studies are usually separated by intertrial intervals (ITIs) in the order of 1 second or so following a behavioral response, which is notoriously too brief a time to detect a corresponding hemodynamic response. In fact, a solution commonly adopted in neuroimaging studies is to prolong the ITI up to several seconds. In doing so, the consequences of ITI variations between behavioral and neuroimaging design variants are either benignly neglected or explicitly assumed to be negligible. Here, we provide a systematic investigation of the consequence of manipulating ITI in a design optimized to study a well-established and highly replicable psychological phenomenon-the spatial numerical association of response codes (SNARC). The present exploration encompassed standard estimates of the SNARC effect (i.e., on reaction times and accuracy), estimates of ITI effects on the emotional state of participants before and after performing the SNARC task, as well as the degree of perceived task difficulty. The results showed that, in striking contrast to the common wisdom about the nil role of ITI, the substantial number of parametric differences observed between the two ITI conditions suggests that ITI plays a critical role in shaping the meaning of hemodynamic correlate of a psychological, at least the SNARC, effect.

Ternary Near-Infrared Spectroscopy Brain-Computer Interface With Increased Information Transfer Rate Using Prefrontal Hemodynamic Changes During Mental Arithmetic, Breath-Holding, and Idle State

The implementation of a multi-class brain-computer interface (BCI) is an efficient way to increase the information transfer rate (ITR) generally expressed in a unit of bits/trial. The improvement of ITR is of specific importance for near-infrared spectroscopy (NIRS)-BCI, because brain hemodynamic responses recorded by NIRS are much slower than the electrophysiological responses of the brain. In this paper, to implement a ternary NIRS-BCI with increased ITR, we used prefrontal cortex (PFC) hemodynamic changes induced by breath-holding (i.e., the voluntary suppression of breathing movements), which have never been used in the field of BCIs. Additionally, we used traditional BCI tasks such as mental arithmetic and idle state to implement ternary NIRS-BCI. As a result, an average offline ternary classification accuracy of 72.6 ± 10.7% could be achieved, which is the best performance of NIRS-BCI based on PFC hemodynamic changes reported to date. Because the number of available input commands was increased and the classification accuracy remained at an acceptable level, the ITR of the ternary BCI (0.51 ± 0.29 bits/trial) was 1.6 times higher than that of the traditional binary BCI (0.31 ± 0.21 bits/trial). Although the hemodynamic changes induced by the breath-holding were not caused by mental state changes, breath-holding proved to be a promising hybrid BCI task for implementing more efficient ternary NIRS-BCI.

Functional Characterization of 5-HT1B Receptor Drugs in Nonhuman Primates Using Simultaneous PET-MR.

In the present study, we used a simultaneous PET-MR experimental design to investigate the effects of functionally different compounds (agonist, partial agonist, and antagonist) on 5-HT1B receptor (5-HT1BR) occupancy and the associated hemodynamic responses. In anesthetized male nonhuman primates (n = 3), we used positron emission tomography (PET) imaging with the radioligand [11C]AZ10419369 administered as a bolus followed by constant infusion to measure changes in 5-HT1BR occupancy. Simultaneously, we measured changes in cerebral blood volume (CBV) as a proxy of drug effects on neuronal activity. The 5-HT1BR partial agonist AZ10419369 elicited a dose-dependent biphasic hemodynamic response that was related to the 5-HT1BR occupancy. The magnitude of the response was spatially overlapping with high cerebral 5-HT1BR densities. High doses of AZ10419369 exerted an extracranial tissue vasoconstriction that was comparable to the less blood-brain barrier-permeable 5-HT1BR agonist sumatriptan. By contrast, injection of the antagonist GR127935 did not elicit significant hemodynamic responses, even at a 5-HT1BR cerebral occupancy similar to the one obtained with a high dose of AZ10419369. Given the knowledge we have of the 5-HT1BR and its function and distribution in the brain, the hemodynamic response informs us about the functionality of the given drug: changes in CBV are only produced when the receptor is stimulated by the partial agonist AZ10419369 and not by the antagonist GR127935, consistent with low basal occupancy by endogenous serotonin.SIGNIFICANCE STATEMENT We here show that combined simultaneous positron emission tomography and magnetic resonance imaging uniquely enables the assessment of CNS active compounds. We conducted a series of pharmacological interventions to interrogate 5-HT1B receptor binding and function and determined blood-brain barrier passage of drugs and demonstrate target involvement. Importantly, we show how the spatial and temporal effects on brain hemodynamics provide information about pharmacologically driven downstream CNS drug effects; the brain hemodynamic response shows characteristic dose-related effects that differ depending on agonistic or antagonistic drug characteristics and on local 5-HT1B receptor density. The technique lends itself to a comprehensive in vivo investigation and understanding of drugs' effects in the brain.

Influence of Visceral Interoceptive Experience on the Brain's Response to Food Images in Anorexia Nervosa.

The aim of the study was to determine how visceral sensations affect responses to food stimuli in anorexia nervosa (AN). Twenty weight-restored, unmedicated adolescent and young adult women with AN and twenty healthy control participants completed an interoceptive attention task during which they focused on sensations from the heart, stomach, and bladder and made ratings of these sensations. They then underwent functional magnetic resonance imaging scanning while viewing pictures of food and nonfood objects. Between-groups t tests were employed to investigate group differences in the relationship between interoceptive sensation ratings and brain hemodynamic response to food pictures and, specifically, to highly palatable foods. In response to food pictures, AN participants exhibited a positive relationship between stomach sensation ratings and posterior insula activation (peak t = 4.30). AN participants displayed negative relationships between stomach sensation ratings and amygdala activation (peak t = -4.05) and heart sensation ratings and ventromedial prefrontal cortex activation (peak t = -3.52). In response to highly palatable foods, AN was associated with positive relationships between stomach sensation ratings and activity in the subgenual anterior cingulate (peak t = 3.88) and amygdala (peak t = 4.83), and negative relationships in the ventral pallidum (peak t = -3.99) and ventral tegmental area (peak t = -4.03). AN participants also exhibited negative relationships between cardiac sensations and activation in response to highly palatable foods in the putamen (peak t = -3.41) and ventromedial prefrontal cortex (peak t = -3.61). Healthy participants exhibited the opposite pattern in all of these regions. Hedonic and interoceptive inferences made by individuals with AN at the sight of food may be influenced by atypical visceral interoceptive experience, which could contribute to restrictive eating.