Level-dependent Functional Magnetic Resonance Imaging Research Articles

Functional magnetic resonance imaging for staging chronic kidney disease: a systematic review and meta-analysis.

The commonly used clinical indicators are not sensitive and comprehensive enough to evaluate the early staging of chronic kidney disease (CKD). This study aimed to evaluate the differences in arterial spin labeling (ASL) and blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-MRI) parameter values among patients at various stages of chronic kidney disease and healthy individuals. Electronic databases PubMed, Web of Science, Cochrane, and Embase were searched from inception to March 29, 2024, to identify relevant studies on ASL and BOLD in CKD. The renal blood flow (RBF) and apparent relaxation rate (R2*) values were obtained from healthy individuals and patients with various stages of CKD. The meta-analysis was conducted using STATA version 12.0. The random-effects model was used to obtain estimates of the effects, and the results were expressed as 95% confidence intervals (CIs) and mean differences (MDs) of continuous variables. A total of 18 published studies were included in this meta-analysis. The cortical RBF and R2* values and medulla RBF values were considerably distinct between patients with various stages of CKD and healthy controls (MD, - 78.162; 95% CI, - 85.103 to - 71.221; MD, 2.440; 95% CI, 1.843 to 3.037; and MD, - 36.787; 95% CI, - 47.107 to - 26.468, respectively). No obvious difference in medulla R2* values was noted between patients with various stages of CKD and healthy controls (MD, - 1.475; 95% CI, - 4.646 to 1.696). ASL and BOLD may provide complementary and distinct information regarding renal function and could potentially be used together to gain a more comprehensive understanding of renal physiology.

Shen Shuai II recipe improves renal hypoxia to attenuate renal injury in 5/6 renal ablation/infarction rats and effect evaluation using blood oxygenation level-dependent functional magnetic resonance imaging

Background: Renal hypoxia plays a key role in the progression of chronic kidney disease (CKD). Shen Shuai II Recipe (SSR) has shown good results in the treatment of CKD as a common herbal formula. This study aimed to explore the effect of SSR on renal hypoxia and injury in CKD rats. Methods: Twenty-five Wistar rats underwent 5/6 renal ablation/infarction (A/I) surgery were randomly divided into three groups: 5/6 (A/I), 5/6 (A/I) + losartan (LOS), and 5/6 (A/I) + SSR groups. Another eight normal rats were used as the Sham group. After 8-week corresponding interventions, blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) was performed to evaluate renal oxygenation in all rats, and biochemical indicators were used to measure kidney and liver function, hemoglobin, and proteinuria. The expression of fibrosis and hypoxia-related proteins was analyzed using immunoblotting examination. Results: Renal oxygenation, evaluated by BOLD-fMRI as cortical and medullary T2* values (COT2* and MET2*), was decreased in 5/6 (A/I) rats, but increased after SSR treatment. SSR also downregulated the expression of hypoxia-inducible factor-1α (HIF-1α) in 5/6 (A/I) kidneys. With the improvement of renal hypoxia, renal function and fibrosis were improved in 5/6 (A/I) rats, accompanied by reduced proteinuria. Furthermore, the COT2* and MET2* were significantly positively correlated with the levels of creatinine clearance rate (Ccr) and hemoglobin, but negatively associated with the levels of serum creatinine (SCr), blood urea nitrogen (BUN), serum cystatin C (CysC), serum uric acid (UA), 24-h urinary protein (24-h Upr), and urinary albumin:creatinine ratio (UACR). Conclusion: The degree of renal oxygenation reduction is correlated with the severity of renal injury in CKD. SSR can improve renal hypoxia to attenuate renal injury in 5/6 (A/I) rats of CKD.

Tracing the development of learned song preferences in the female zebra finch brain with functional magnetic resonance imaging.

In sexually dimorphic zebra finches (Taeniopygia guttata), only males learn to sing their father's song, whereas females learn to recognize the songs of their father or mate but cannot sing themselves. Memory of learned songs is behaviorally expressed in females by preferring familiar songs over unfamiliar ones. Auditory association regions such as the caudomedial mesopallium (CMM; or caudal mesopallium) have been shown to be key nodes in a network that supports preferences for learned songs in adult females. However, much less is known about how song preferences develop during the sensitive period of learning in juvenile female zebra finches. In this study, we used blood-oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to trace the development of a memory-based preference for the father's song in female zebra finches. Using BOLD fMRI, we found that only in adult female zebra finches with a preference for learned song over novel conspecific song, neural selectivity for the father's song was localized in the thalamus (dorsolateral nucleus of the medial thalamus; part of the anterior forebrain pathway, AFP) and in CMM. These brain regions also showed a selective response in juvenile female zebra finches, although activation was less prominent. These data reveal that neural responses in CMM, and perhaps also in the AFP, are shaped during development to support behavioral preferences for learned songs.

Flow-augmentation STA-MCA bypass for acute and subacute ischemic stroke due to internal carotid artery occlusion and the role of advanced neuroimaging with hemodynamic and flow-measurement in the decision-making: preliminary data.

A major clinical challenge is the adequate identification of patients with acute (<1 week) and subacute (1-6 weeks) ischemic stroke due to internal carotid artery (ICA) occlusion who could benefit from a surgical revascularization after a failure of endovascular and/or medical treatment. Recently, two novel quantitative imaging modalities have been introduced: (I) quantitative magnetic resonance angiography (qMRA) with non-invasive optimal vessel analysis (NOVA) for quantification of blood flow in major cerebral arteries (in mL/min), and (II) blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging to assess cerebrovascular reactivity (CVR). The aim of this study is to present our cohort of patients who underwent surgical revascularization in the acute and subacute phase of ischemic stroke as well as to demonstrate the importance of hemodynamic and flow assessment for the decision-making regarding surgical revascularization in patients with acute and subacute stroke and ICA-occlusion. Symptomatic patients with acute and subacute ischemic stroke because of persistent ICA-occlusion despite optimal medical/endovascular recanalization therapy who were treated at the Neuroscience Clinical Center of the University Hospital Zurich underwent both BOLD-CVR and qMRA-NOVA to study the hemodynamic and collateral vessel status. Patients selected for surgical revascularization according to our previously published flowchart were included in this prospective cohort study. Repeated NOVA and BOLD-CVR investigations were done after bypass surgery as follow up as well as clinical follow up. Continuous BOLD-CVR and qMRA-NOVA variables were compared using paired Student t-test. Between May 2019 and September 2022, superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery was performed in 12 patients with acute and subacute stroke because of ICA-occlusion despite of optimal endovascular and/or medical treatment prior to the surgery. Impaired BOLD-CVR in the occluded vascular territory [MCA territory: ipsilateral vs. contralateral: -0.03±0.07 vs. 0.11±0.07 %BOLD/mmHgCO2, P<0.001] as well as reduced hemispheric flow with qMRA-NOVA (ipsilateral vs. contralateral: 228.00±54.62 vs. 384.50±70.99 mL/min, P=0.01) were measured indicating insufficient collateralization. Post-operative qMRA-NOVA showed improved hemispheric flow (via bypass) (pre-bypass vs. post-bypass: 236.60±76.45 vs. 334.20±131.33 mL/min, P=0.02) and the 3-month-follow-up with BOLD-CVR showed improved cerebral hemodynamics (MCA territory: pre-bypass vs. post-bypass: -0.01±0.05 vs. 0.06±0.03 %BOLD/mmHgCO2, P=0.02) in all patients studied. Quantitative assessment with BOLD-CVR and qMRA-NOVA allows us to evaluate the pre- and post-operative cerebral hemodynamics and collateral vessel status in patients with acute/subacute stroke due to ICA occlusion who may benefit from surgical revascularization after failure of endovascular/medical treatment.

Functional Magnetic Resonance Imaging (fMRI) of the Visual Cortex with Wide-View Retinotopic Stimulation.

High-resolution retinotopic blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) with a wide-view presentation can be used to functionally map the peripheral and central visual cortex. This method for measuring functional changes of the visual brain allows for functional mapping of the occipital lobe, stimulating >100° (±50°) or more of the visual field, compared to standard fMRI visual presentation setups which usually cover <30° of the visual field. A simple wide-view stimulation system for BOLD fMRI can be set up using common MR-compatible projectors by placing a large mirror or screen close to the subject's face and using only the posterior half of a standard head coil to provide a wide-viewing angle without obstructing their vision. The wide-view retinotopic fMRI map can then be imaged using various retinotopic stimulation paradigms, and the data can be analyzed to determine the functional activity of visual cortical regions corresponding to central and peripheral vision. This method provides a practical, easy-to-implement visual presentation system that can be used to evaluate changes in the peripheral and central visual cortex due to eye diseases such as glaucoma and the vision loss that may accompany them.

Persistent post-COVID headache is associated with suppression of scale-free functional brain dynamics in non-hospitalized individuals.

Post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) is a growing concern, with headache being a particularly debilitating symptom with high prevalence. The long-term effects of COVID-19 and post-COVID headache on brain function remain poorly understood, particularly among non-hospitalized individuals. This study focused on the power-law scaling behavior of functional brain dynamics, indexed by the Hurst exponent (H). This measure is suppressed during physiological and psychological distress and was thus hypothesized to be reduced in individuals with post-COVID syndrome, with greatest reductions among those with persistent headache. Resting-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data were collected for 57 individuals who had COVID-19 (32 with no headache, 14 with ongoing headache, 11 recovered) and 17 controls who had cold and flu-like symptoms but tested negative for COVID-19. Individuals were assessed an average of 4-5 months after COVID testing, in a cross-sectional, observational study design. No significant differences in H values were found between non-headache COVID-19 and control groups., while those with ongoing headache had significantly reduced H values, and those who had recovered from headache had elevated H values, relative to non-headache groups. Effects were greatest in temporal, sensorimotor, and insular brain regions. Reduced H in these regions was also associated with decreased BOLD activity and local functional connectivity. These findings provide new insights into the neurophysiological mechanisms that underlie persistent post-COVID headache, with reduced BOLD scaling as a potential biomarker that is specific to this debilitating condition.

Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation.

Androgen deprivation therapy (ADT) for prostate cancer is implicated as a possible cause of cognitive impairment (CI). CI in dementia and Alzheimer's disease is associated with neuroinflammation. In this study, we investigated a potential role of neuroinflammation in ADT-related CI. Patients with prostate cancer on ADT for ≥3 months were categorized as having ADT-emergent CI or normal cognition (NC) based on self-report at interview. Neuroinflammation was evaluated using positron emission tomography (PET) with the translocator protein (TSPO) radioligand [11C]-PBR28. [11C]-PBR28 uptake in various brain regions was quantified as standardized uptake value (SUVR, normalized to cerebellum) and related to blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) choice-reaction time task (CRT) activation maps. Eleven patients underwent PET: four with reported CI (rCI), six with reported NC (rNC), and one status unrecorded. PET did not reveal any between-group differences in SUVR regionally or globally. There was no difference between groups on brain activation to the CRT. Regardless of the reported cognitive status, there was strong correlation between PET-TSPO signal and CRT activation in the hippocampus, amygdala, and medial cortex. We found no difference in neuroinflammation measured by PET-TSPO between patients with rCI and rNC. However, we speculate that the strong correlation between TSPO uptake and BOLD-fMRI activation in brain regions involved in memory and known to have high androgen-receptor expression mediating plasticity (hippocampus and amygdala) might reflect inflammatory effects of ADT with compensatory upregulated/increased synaptic functions. Further studies of this imaging readout are warranted to investigate ADT-related CI.

A state-of-the-art review of functional magnetic resonance imaging technique integrated with advanced statistical modeling and machine learning for primary headache diagnosis.

Primary headache is a very common and burdensome functional headache worldwide, which can be classified as migraine, tension-type headache (TTH), trigeminal autonomic cephalalgia (TAC), and other primary headaches. Managing and treating these different categories require distinct approaches, and accurate diagnosis is crucial. Functional magnetic resonance imaging (fMRI) has become a research hotspot to explore primary headache. By examining the interrelationships between activated brain regions and improving temporal and spatial resolution, fMRI can distinguish between primary headaches and their subtypes. Currently the most commonly used is the cortical brain mapping technique, which is based on blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). This review sheds light on the state-of-the-art advancements in data analysis based on fMRI technology for primary headaches along with their subtypes. It encompasses not only the conventional analysis methodologies employed to unravel pathophysiological mechanisms, but also deep-learning approaches that integrate these techniques with advanced statistical modeling and machine learning. The aim is to highlight cutting-edge fMRI technologies and provide new insights into the diagnosis of primary headaches.

A mechanistic computational framework to investigate the hemodynamic fingerprint of the blood oxygenation level-dependent signal.

Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is one of the most used imaging techniques to map brain activity or to obtain clinical information about human cortical vasculature, in both healthy and disease conditions. Nevertheless, BOLD fMRI is an indirect measurement of brain functioning triggered by neurovascular coupling. The origin of the BOLD signal is quite complex, and the signal formation thus depends, among other factors, on the topology of the cortical vasculature and the associated hemodynamic changes. To understand the hemodynamic evolution of the BOLD signal response in humans, it is beneficial to have a computational framework available that virtually resembles the human cortical vasculature, and simulates hemodynamic changes and corresponding MRI signal changes via interactions of intrinsic biophysical and magnetic properties of the tissues. To this end, we have developed a mechanistic computational framework that simulates the hemodynamic fingerprint of the BOLD signal based on a statistically defined, three-dimensional, vascular model that approaches the human cortical vascular architecture. The microvasculature is approximated through a Voronoi tessellation method and the macrovasculature is adapted from two-photon microscopy mice data. Using this computational framework, we simulated hemodynamic changes-cerebral blood flow, cerebral blood volume, and blood oxygen saturation-induced by virtual arterial dilation. Then we computed local magnetic field disturbances generated by the vascular topology and the corresponding blood oxygen saturation changes. This mechanistic computational framework also considers the intrinsic biophysical and magnetic properties of nearby tissue, such as water diffusion and relaxation properties, resulting in a dynamic BOLD signal response. The proposed mechanistic computational framework provides an integrated biophysical model that can offer better insights regarding the spatial and temporal properties of the BOLD signal changes.

Dorsal striatal response to taste is modified by obesity and insulin resistance.

In preclinical models, insulin resistance in the dorsal striatum (DS) contributes to overeating. Although human studies support the concept of central insulin resistance, they have not investigated its effect on consummatory reward-induced brain activity. Taste-induced activation was assessed in the caudate and putamen of the DS with blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Three phenotypically distinct groups were studied: metabolically healthy lean, metabolically healthy obesity, and metabolically unhealthy obesity (MUO; presumed to have central insulin resistance). Participants with MUO also completed a weight loss intervention followed by a second functional magnetic resonance imaging session. The three groups were significantly different at baseline consistent with the design. The metabolically healthy lean group had a primarily positive BOLD response, the MUO group had a primarily negative BOLD response, and the metabolically healthy obesity group had a response in between the two other groups. Food craving was predicted by taste-induced activation. After weight loss in the MUO group, taste-induced activation increased in the DS. These data support the hypothesis that insulin resistance and obesity contribute to aberrant responses to taste in the DS, which is only partially attenuated by weight loss. Aberrant responses to food exposure may be a barrier to weight loss.

Acute psilocybin increased cortical activities in rats.

Psilocybin, a naturally occurring hallucinogenic component of magic mushrooms, has significant psychoactive effects in both humans and rodents. But the underlying mechanisms are not fully understood. Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a useful tool in many preclinical and clinical trials to investigate psilocybin-induced changes of brain activity and functional connectivity (FC) due to its noninvasive nature and widespread availability. However, fMRI effects of psilocybin on rats have not been carefully investigated. This study aimed to explore how psilocybin affects resting-state brain activity and FC, through a combination of BOLD fMRI and immunofluorescence (IF) of EGR1, an immediate early gene (IEG) closely related to depressive symptoms. Ten minutes after psilocybin hydrochloride injection (2.0 mg/kg, i.p.), positive brain activities were observed in the frontal, temporal, and parietal cortex (including the cingulate cortex and retrosplenial cortex), hippocampus, and striatum. And a region-of-interest (ROI) -wise FC analysis matrix suggested increased interconnectivity of several regions, such as the cingulate cortex, dorsal striatum, prelimbic, and limbic regions. Further seed-based analyses revealed increased FC of cingulate cortex within the cortical and striatal areas. Consistently, acute psilocybin increased the EGR1 level throughout the brain, indicating a consistent activation thought the cortical and striatal areas. In conclusion, the psilocybin-induced hyperactive state of rats is congruent to that of humans, and may be responsible for its pharmacological effects.

Altered Neurovascular Coupling for Multidisciplinary Intensive Rehabilitation in Parkinson's Disease.

Effective rehabilitation in Parkinson's disease (PD) is related to brain reorganization with restoration of cortico-subcortical networks and compensation of frontoparietal networks; however, further neural rehabilitation evidence from a multidimensional perspective is needed. To investigate how multidisciplinary intensive rehabilitation treatment affects neurovascular coupling, 31 PD patients (20 female) before and after treatment and 30 healthy controls (17 female) underwent blood oxygenation level-dependent functional magnetic resonance imaging and arterial spin labeling scans. Cerebral blood flow (CBF) was used to measure perfusion, and fractional amplitude of low-frequency fluctuation (fALFF) was used to measure neural activity. The global CBF-fALFF correlation and regional CBF/fALFF ratio were calculated as neurovascular coupling. Dynamic causal modeling (DCM) was used to evaluate treatment-related alterations in the strength and directionality of information flow. Treatment reduced CBF-fALFF correlations. The altered CBF/fALFF exhibited increases in the left angular gyrus and the right inferior parietal gyrus and decreases in the bilateral thalamus and the right superior frontal gyrus. The CBF/fALFF alteration in right superior frontal gyrus showed correlations with motor improvement. Further, DCM indicated increases in connectivity from the superior frontal gyrus and decreases from the thalamus to the inferior parietal gyrus. The benefits of rehabilitation were reflected in the dual mechanism, with restoration of executive control occurring in the initial phase of motor learning and compensation of information integration occurring in the latter phase. These findings may yield multimodal insights into the role of rehabilitation in disease modification and identify the dorsolateral superior frontal gyrus as a potential target for noninvasive neuromodulation in PD.SIGNIFICANCE STATEMENT Although rehabilitation has been proposed as a promising supplemental treatment for PD as it results in brain reorganization, restoring cortico-subcortical networks and eliciting compensatory activation of frontoparietal networks, further multimodal evidence of the neural mechanisms underlying rehabilitation is needed. We measured the ratio of perfusion and neural activity derived from arterial spin labeling and blood oxygenation level-dependent fMRI data and found that benefits of rehabilitation seem to be related to the dual mechanism, restoring executive control in the initial phase of motor learning and compensating for information integration in the latter phase. We also identified the dorsolateral superior frontal gyrus as a potential target for noninvasive neuromodulation in PD patients.

Unsupervised physiological noise correction of functional magnetic resonance imaging data using phase and magnitude information (PREPAIR).

Of the sources of noise affecting blood oxygen level-dependent functional magnetic resonance imaging (fMRI), respiration and cardiac fluctuations are responsible for the largest part of the variance, particularly at high and ultrahigh field. Existing approaches to removing physiological noise either use external recordings, which can be unwieldy and unreliable, or attempt to identify physiological noise from the magnitude fMRI data. Data-driven approaches are limited by sensitivity, temporal aliasing, and the need for user interaction. In the light of the sensitivity of the phase of the MR signal to local changes in the field stemming from physiological processes, we have developed an unsupervised physiological noise correction method using the information carried in the phase and the magnitude of echo-planar imaging data. Our technique, Physiological Regressor Estimation from Phase and mAgnItude, sub-tR (PREPAIR) derives time series signals sampled at the slice TR from both phase and magnitude images. It allows physiological noise to be captured without aliasing, and efficiently removes other sources of signal fluctuations not related to physiology, prior to regressor estimation. We demonstrate that the physiological signal time courses identified with PREPAIR agree well with those from external devices and retrieve challenging cardiac dynamics. The removal of physiological noise was as effective as that achieved with the most used approach based on external recordings, RETROICOR. In comparison with widely used recording-free physiological noise correction tools-PESTICA and FIX, both performed in unsupervised mode-PREPAIR removed significantly more respiratory and cardiac noise than PESTICA, and achieved a larger increase in temporal signal-to-noise-ratio at both 3 and 7T.

Altered cortical thickness, degree centrality, and functional connectivity in middle-age type 2 diabetes mellitus.

This study aimed to investigate the changes in brain structure and function in middle-aged patients with type 2 diabetes mellitus (T2DM) using morphometry and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). A total of 44 middle-aged patients with T2DM and 45 matched healthy controls (HCs) were recruited. Surface-based morphometry (SBM) was used to evaluate the changes in brain morphology. Degree centrality (DC) and functional connectivity (FC) were used to evaluate the changes in brain function. Compared with HCs, middle-aged patients with T2DM exhibited cortical thickness reductions in the left pars opercularis, left transverse temporal, and right superior temporal gyri. Decreased DC values were observed in the cuneus and precuneus in T2DM. Hub-based FC analysis of these regions revealed lower connectivity in the bilateral hippocampus and parahippocampal gyrus, left precuneus, as well as left frontal sup. Cortical thickness, degree centrality, as well as functional connectivity were found to have significant changes in middle-aged patients with T2DM. Our observations provide potential evidence from neuroimaging for analysis to examine diabetes-related brain damage.

Single Center to Evaluate and Compare Anisometropic Amblyopia in Adults Using Blood Oxygenation Level-Dependent Functional Magnetic Resonance Imaging and Diffusion Kurtosis Imaging.

BackgroundAnisometropic amblyopia results from the unequal ability to focus between the right and left eyes. Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) measures the proportion of oxygenated hemoglobin in specific areas. Diffusion kurtosis imaging (DKI) is a method of diffusion tensor imaging that estimates the skewed distribution of water diffusion probability. We aimed to evaluate and compare 11 adult patients with anisometropic amblyopia (AA) with 13 normally sighted healthy controls (HC) using BOLD-fMRI and DKI.Material/MethodsEleven adults with AA (age range 20–49; mean age 29.18±8.089) and 13 HC adults (age range 22–50; mean age 28.00±5.79) were recruited. DKI scanning used a single excitation echo-planar imaging sequence and a region of interest to obtain DKI parameters for optic radiation; the corpus callosum was manually placed, including mean kurtosis (MK), fractional anisotropic (FA), and mean diffusivity (MD) values; and BOLD data used a gradient-echo echo-planar imaging sequence.ResultsThe AA group had lower MK and FA of bilateral optic radiation than the HC group (P=0.008 and P=0.006, respectively) and higher MD than the HC group (P=0.005). The MK of the corpus callosum in the AA group was lower than that of HC group (P=0.012).Compared with the non-dominant eyes of the HC group, the amblyopic eyes in the AA group had less activation range and intensity in Brodmann areas 17, 18, and 19.ConclusionsThe combined use of DKI and BOLD-fMRI detected microstructural changes associated with local visual pathways and identified damage to the visual cortex in patients with amblyopia.

The effect of endovascular baroreflex amplification on central sympathetic nerve circuits and cerebral blood flow in patients with resistant hypertension: A functional MRI study.

Endovascular baroreflex amplification (EVBA) by implantation of the MobiusHD is hypothesized to lower blood pressure by decreasing sympathetic activity through the mechanism of the baroreflex. In the present exploratory study we investigated the impact of MobiusHD implantation on central sympathetic nerve circuits and cerebral blood flow (CBF) in patients with resistant hypertension. In thirteen patients, we performed blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) at rest and during Valsalva maneuvers, before and 3 months after EVBA. Data were analyzed using a whole-brain approach and a brainstem-specific analysis. CBF was assessed using arterial spin labeling MRI. Resting-state fMRI analysis did not reveal significant differences in functional connectivity at 3 months after EVBA. For the Valsalva maneuver data, the whole-brain fMRI analysis revealed significantly increased activation in the posterior and anterior cingulate, the insular cortex, the precuneus, the left thalamus and the anterior cerebellum. The brainstem-specific fMRI analysis showed a significant increase in BOLD activity in the right midbrain 3 months after EVBA. Mean gray matter CBF (partial volume corrected) decreased significantly from 48.9 (9.9) ml/100 gr/min at baseline to 43.4 (13.0) ml/100 gr/min (p = 0.02) at 3 months. This first fMRI pilot study in patients with resistant hypertension treated with EVBA showed a significant increase in BOLD activity during the Valsalva maneuver in brain regions related to sympathetic activity. No notable signal intensity changes were observed in brain areas involved in the baroreflex circuit. Future randomized controlled studies are needed to investigate whether the observed changes are directly caused by EVBA. www.clinicaltrials.gov, identifier: NCT02827032.

Enhanced endogenous oxytocin signaling in the brain modulates neural responses to social misalignment and promotes conformity in humans: A multi-locus genetic profile approach

The neuropeptide oxytocin (OT) is known to promote social conformity. However, the specific neurocognitive mechanisms underlying OT-induced conformity remain unclear. We aimed to address this gap by examining how genetic variation in the oxytocin receptor gene (OXTR) is linked with behavioral conformity and its underlying neural systems. Specifically, we utilized the genotype-tissue expression database (GTEx) to create a novel multi-locus genetic profile score (MPS) that reflects the level of OXTR expression in the human brain. A total of 194 participants (Neuroimaging N = 50, Behavioral N = 144) performed a novel conformity task in which they viewed a series of word pairs depicting various moral values and virtues widely recognized in the United States. In each trial, participants indicated the relative importance of these words and subsequently learned about the majority opinion. Participants later rated the same word pairs a second time. Changes in participants’ ratings between the first and second sessions were measured and analyzed with respect to social feedback, blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals, and OXTR MPS. We found that participants adjusted their ratings in accordance with the majority opinions. Social misalignment between self and others activated brain areas such as the striatum and the posterior medial frontal cortex (pMFC). However, unlike most findings from previous studies, activation in the pMFC during the inconsistent social feedback negatively, rather than positively, predicted behavioral conformity. Notably, those with higher OXTR MPS had reduced pMFC activation in the face of social misalignment, which led to greater conformity. Our findings suggest that OT may promote conformity by dampening the conflict-related signals in the pMFC. They also show that OXTR MPS may be useful for studying the effect of genes on highly complex human social traits, such as conformity.

Brain Activation During Processing of Depression Emotion in College Students With Premenstrual Syndrome in China: Preliminary Findings.

BackgroundThis study aimed to investigate the neural substrates of processing depression emotion in premenstrual syndrome (PMS) and healthy subjects of college students using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI).MethodsDuring BOLD-fMRI scanning, 13 PMS patients and 15 healthy controls (HC) performed a picture visual stimulation task during luteal and follicular phases, in which participants and HC were asked to see pictures containing depression and non-depression emotions. Simultaneously, self-rating depression scales (SDS) were employed to evaluate the emotional status of participants.ResultsCompared to HC, right inferior occipital gyrus, right middle occipital gyrus, right lingual gyrus, right fusiform gyrus, right inferior temporal gyrus, cerebelum_crus1_R, cerebelum_6_R, culmen, the cerebellum anterior lobe, tuber, and cerebellar tonsil of PMS patients showed enhanced activation. In contrast, sub-lobar, sub-gyral, extra-nuclear, right orbit part of superior frontal gyrus, right middle temporal gyrus, right orbit part of inferior frontal gyrus, limbic lobe, right insula, bilateral anterior and adjacent cingulate gyrus, bilateral caudate, caudate head, bilateral putamen, and left globus pallidus exhibited decreased activation.ConclusionThe findings indicate that abnormal functional regulation of brain regions such as occipital lobe and cerebellum leads to abnormal changes in emotional regulation, cognitive ability, and attention distribution in PMS patients, implying significant central pathogenesis.

Brain Responses to Food Choices and Decisions Depend on Individual Hedonic Profiles and Eating Habits in Healthy Young Women.

The way different food consumption habits in healthy normal-weight individuals can shape their emotional and cognitive relationship with food and further disease susceptibility has been poorly investigated. Documenting the individual consumption of Western-type foods (i.e., high-calorie, sweet, fatty, and/or salty) in relation to psychological traits and brain responses to food-related situations can shed light on the early neurocognitive susceptibility to further diseases and disorders. We aimed to explore the relationship between eating habits, psychological components of eating, and brain responses as measured by blood oxygen level-dependent functional magnetic resonance imaging (fMRI) during a cognitive food choice task and using functional connectivity (FC) during resting-state fMRI (rsfMRI) in a population of 50 healthy normal-weight young women. A Food Consumption Frequency Questionnaire (FCFQ) was used to classify them on the basis of their eating habits and preferences by principal component analysis (PCA). Based on the PCA, we defined two eating habit profiles, namely, prudent-type consumers (PTc, N = 25) and Western-type consumers (WTc, N = 25), i.e., low and high consumers of western diet (WD) foods, respectively. The first two PCA dimensions, PCA1 and PCA2, were associated with different psychological components of eating and brain responses in regions involved in reward and motivation (striatum), hedonic evaluation (orbitofrontal cortex, OFC), decision conflict (anterior cingulate cortex, ACC), and cognitive control of eating (prefrontal cortex). PCA1 was inversely correlated with the FC between the right nucleus accumbens and the left lateral OFC, while PCA2 was inversely correlated with the FC between the right insula and the ACC. Our results suggest that, among a healthy population, distinct eating profiles can be detected, with specific correlates in the psychological components of eating behavior, which are also related to a modulation in the reward and motivation system during food choices. We could detect different patterns in brain functioning at rest, with reduced connectivity between the reward system and the frontal brain region in Western-type food consumers, which might be considered as an initial change toward ongoing modified cortico-striatal control.

219-OR: Intranasal Insulin Enhanced Resting-State Functional Connectivity of Medio-Prefrontal Cortex in Type 2 Diabetes: A Substudy of the Memory Advancement with Type 2 Diabetes (MemAID) Randomized Control Trial

Type 2 diabetes mellitus (T2DM) is associated with impairment of resting-state functional connectivity (rsFC) and cognition. Intranasal insulin (INI) has emerged as potential treatment for T2DM-related cognitive decline. INI treatment has increased perfusion and low-frequency fluctuations in medio-prefrontal cortex (mPFC) . We aimed to evaluate the effect of INI treatment on mPFC rsFC.MemAIDs trial consisted of 24-week of treatment with 40 IU of intranasal insulin (Novolin® R, off label use) or placebo (sterile saline) once daily and 24-week follow-up period. Of 244 randomized participants (115 T2DM and 129 controls, &amp;gt; 50 years old) , T2DM participants (eight INI, three placebo, &amp;gt; 50 years old) completed the baseline and end-of-treatment blood oxygen level dependent (BOLD) fMRI scans.INI treatment increased resting state mPFC-postcentral rsFC (p=0.005) and decreased mPFC-cerebellum rsFC (p&amp;lt;0.001) . The mPFC rsFC changes after INI treatment were different from those from placebo (Figure 1) .INI treatment can modulate resting state connectivity between pre-frontal and sensorimotor cortex and cerebellum, indicating its potential effects on decision making and goal-oriented behaviors. These findings warrant further investigation. Disclosure Z.Zhang: None. V.Novak: None. P.Novak: Stock/Shareholder; Moderna, Inc., Novavax, Pfizer Inc., Prothena. C.Mantzoros: Advisory Panel; Novo Nordisk. L.H.Ngo: None. V.Lioutas: None. W.Dai: None. Funding Funded by NIH-NIDDK (1R01DK103902) , FDA (IND#107690) , Novo Nordisk, Inc. (ISS-001063) , Medtronic Inc. (NERP15-0310) and registered on www.clinicaltrials.gov (NCT02415556.)