Functional Imaging Research Articles

Dose-dependent effect of acute THC on extinction memory recall and fear renewal: a randomized, double-blind, placebo-controlled study.

Prior work from our lab and others demonstrates that the endocannabinoid system is a promising avenue for improving fear memory deficits in posttraumatic stress disorder (PTSD). Specifically, 7.5mg of delta-9-tetrahydrocannabinol (THC) decreases fear responding in healthy adults and increases prefrontal cortex activation during extinction learning and fear renewal in adults with PTSD. The present study will determine whether there is a dose-dependent effect of THC on short-term (24h) and long-term (one week) fear learning and memory in adults with PTSD. Using a randomized, double-blind, placebo-controlled design, N = 36 adults with PTSD completed the study and were randomized to receive placebo (PBO, n = 11), 5mg of THC (n = 11), or 10mg of THC (n = 14) prior to fear extinction learning. Participants completed a Pavlovian conditioning paradigm with extinction recall and fear renewal occurring 24h and one week later, where we measured concurrent functional imaging and behavioral responses. Twenty-four hours after drug administration, individuals with PTSD given 5mg of THC exhibited greater anterior cingulate cortex and prefrontal cortex activation during early fear renewal. One week later, individuals given 10mg of THC exhibited greater hippocampus activation during extinction recall and prefrontal cortex activation during fear renewal. These data suggest that dosing and timing are critical for facilitating fear memory processes in PTSD, and that low-dose oral THC prior to extinction learning can affect brain indices of fear learning and memory both acutely and one week after administration.

Performance control during longitudinal activation fMRI studies.

The documentation of performance during functional imaging represents a standard procedure employed to control for compliance, sensorimotor, and cognitive demands. In the case of motor tasks, preciseness, force, and frequency have a significant impact on the magnitude of functional activation. Questionnaires are used in psychological investigations to control for cognitive demand, while psychophysiological documentation is employed to record bodily responses. For longitudinal intervention studies, it is of utmost importance to implement meticulous pre- and post-performance controls and balance to accurately assess changes over time. Any changes in compliance may introduce additional uncontrolled variables, which can hinder the interpretation of functional magnetic resonance imaging (fMRI)-related changes. This narrative review presents strategies for controlling and balancing performance in functional imaging approaches to document neuroplasticity in rehabilitative studies. These strategies include not only motor-related aspects, such as precision, velocity, and force, but also timing aspects, such as the start and stop of movement periods. In addition, it discusses strategies for the modulation and control of movement aspects with visual feedback, as well as for the control of physiological changes during experimental modulation. Although these measures require additional care, which is often more demanding than the neuroimaging part of the study, they are crucial for a relevant interpretation and publication of fMRI studies.

Convergent functional effects of antidepressants in major depressive disorder: a neuroimaging meta-analysis.

Neuroimaging studies have provided valuable insights into the macroscale impacts of antidepressants on brain functions in patients with major depressive disorder. However, the findings of individual studies are inconsistent. Here, we aimed to provide a quantitative synthesis of the literature to identify convergence of the reported findings at both regional and network levels and to examine their associations with neurotransmitter systems. Through a comprehensive search in PubMed and Scopus databases, we reviewed 5258 abstracts and identified 36 eligible functional neuroimaging studies on antidepressant effects in major depressive disorder. Activation likelihood estimation was used to investigate regional convergence of the reported foci of antidepressant effects, followed by functional decoding and connectivity mapping of the convergent clusters. Additionally, utilizing group-averaged data from the Human Connectome Project, we assessed convergent resting-state functional connectivity patterns of the reported foci. Next, we compared the convergent circuit with the circuits targeted by transcranial magnetic stimulation therapy. Last, we studied the association of regional and network-level convergence maps with selected neurotransmitter receptors/transporters maps. No regional convergence was found across foci of treatment-associated alterations in functional imaging. Subgroup analysis in the Treated > Untreated contrast revealed a convergent cluster in the left dorsolateral prefrontal cortex, which was associated with working memory and attention behavioral domains. Moreover, we found network-level convergence of the treatment-associated alterations in a circuit more prominent in the frontoparietal areas. This circuit was co-aligned with circuits targeted by "anti-subgenual" and "Beam F3"transcranial magnetic stimulation therapy. We observed no significant correlations between our meta-analytic findings with the maps of neurotransmitter receptors/transporters. Our findings highlight the importance of the frontoparietal network and the left dorsolateral prefrontal cortex in the therapeutic effects of antidepressants, which may relate to their role in improving executive functions and emotional processing.

Functional connectivity in resting-state networks relates to short-term global cognitive functioning in cardiac arrest survivors.

Long-term cognitive impairment is common in cardiac arrest survivors. Screening to identify patients at risk is recommended. Functional magnetic resonance brain imaging (fMRI) holds potential to contribute to prediction of cognitive outcomes. In this study, we investigated the possible value of early changes in resting-state networks for predicting short and long-term cognitive functioning of cardiac arrest survivors. We performed a prospective multicenter cohort study in cardiac arrest survivors in three Dutch hospitals. Resting-state fMRI scans were acquired within a month after cardiac arrest. We primarily focused on functional connectivity within the default-mode network (DMN) and salience network (SN), and additionally explored functional connectivity in seven other networks. Cognitive outcome was measured using the Montreal Cognitive Assessment (MoCA) during hospital admission and at 3 and 12 months, and by neuropsychological examination (NPE) at 12 months. We tested mixed effects models to evaluate the value of connectivity within the networks for predicting global cognitive outcomes at the three time points, and long-term cognitive outcomes in the memory, attention, and executive functioning domains. We included 80 patients (age 60 ± 11 years, 72 (90%) male). MoCA scores increased significantly between hospital admission and 3 months (ΔMoCAhospital-3M = 2.89, p < 0.01), but not between 3 and 12 months (ΔMoCA3M-12M = 0.38, p = 0.52). Connectivity within the DMN, SN, and dorsal attention network (DAN) was positively related to global cognitive functioning during hospital admission (βDMN = 0.85, p = 0.03; βSN = 1.48, p < 0.01; βDAN = 0.96, p = 0.01), but not at 3 and 12 months. Network connectivity was also unrelated to long-term memory, attention, or executive functioning. Resting-state functional connectivity in the DMN, SN, and DAN measured in the first month after cardiac arrest is related to short-term global, but not long-term global or domain-specific cognitive performance of survivors. These results do not support the value of functional connectivity within these RSNs for prediction of long-term cognitive performance after cardiac arrest.

Network efficiency of functional brain connectomes altered in type 2 diabetes patients with and without mild cognitive impairment

AimTo explore the topological organization alterations of functional connectomes in type 2 diabetes (T2DM) patients with and without mild cognitive impairment (MCI), and compare these with structural connectomes changes.MethodsTwenty-six T2DM patients with MCI (DM-MCI), 26 without cognitive impairment (DM-NC), and 28 healthy controls were included. Diffusion tensor imaging (DTI) and resting-state functional MRI images were acquired. Networks were constructed and graph-theory based network measurements were calculated. The global network parameters and nodal efficiencies were compared across the three groups using one-way ANOVA and a false-discovery rate correction was applied for multiple comparisons. Partial correlation analyses were performed to investigate relationships between network parameters, cognitive performance and clinical variables.ResultsIn the structural connectome, the DM-MCI group exhibited significantly decreased global efficiency (Eglob) and local efficiency (Eloc) compared to the DM-NC and control groups. In the functional connectome, the DM-MCI group exhibited increased Eloc and clustering coefficient (Cp) compared to the controls. No significant differences were found in Eglob, Eloc, or Cp between the DM-NC and the control group, both in structural and functional connectomes. Nodal efficiencies decreased in some brain regions of structural and functional networks in the DM-MCI and DM-NC groups, but increased in five regions in functional network, some of which were involved in the default-mode network.ConclusionUnlike the consistently decreased global properties and nodal efficiencies in the structural connectome of T2DM patients, increases in Eloc, Cp, and nodal efficiencies in the functional connectome may be viewed as a compensatory mechanism due to functional plasticity and reorganization. Altered nodal efficiency can hint at cognitive decrements at an early stage in T2DM patients.

Pain Catastrophizing and Functional Activation During Occlusion in TMD Patients-An Interventional Study.

In temporomandibular disorder (TMD), the effects of standard interventions such as using an occlusal splint and its impact on pain relief and pain catastrophizing are poorly understood. Earlier work pointed to a crucial role of insula activation with changes in pain relief by occlusal splint treatment. We performed a functional imaging study using specially developed splint systems to allow for a placebo-controlled longitudinal design. Using functional MRI we examined 20 TMD patients during repetitive occlusal movements at baseline and over the course of splint therapy and also collected self-reported pain catastrophizing. For balancing performance between baseline and after intervention we used occlusion force measures in an individualized fMRI-splint system. Splint therapy lasted for approximately 7 weeks with one group selected by randomization wearing a palatine placebo splint over the first 3 weeks (delayed start; 11 individuals). As expected, fMRI activation in areas involved in pain processing (insula, primary and secondary somatosensory cortex) decreased with intervention. At baseline a positive correlation between activation of the left anterior insula and pain catastrophizing was present. Both parameters decreased over intervention while associations were primarily observable for patients with rather mild TMD.

Neural Transformation from Retinotopic to Background-Centric Coordinates in the Macaque Precuneus.

Visual information is initially represented in retinotopic coordinates and later in craniotopic coordinates. Psychophysical evidence suggests that visual information is further represented in more general coordinates related to the external world; however, the neural basis of non-egocentric coordinates remains elusive. This study investigates the automatic transformation from egocentric to non-egocentric coordinates in the macaque precuneus (two males, one female), identified by a functional imaging study as a key area for non-egocentric representation. We found that 6.2% of neurons in the precuneus have receptive fields anchored to the background rather than to the retina or the head, while 16% had traditional retinotopic receptive fields. Notably, these two types were not exclusive: many background-centric neurons initially encode a stimulus's position in retinotopic coordinates (up to ∼90 ms from stimulus onset) but later shift to background coordinates, peaking at ∼150 ms. Regarding retinotopic information, the stimulus dominated the initial period, whereas the background dominated the later period. In the absence of a background, there is a dramatic surge in retinotopic information about the stimulus during the later phase, clearly delineating two distinct periods of retinotopic encoding: one focusing on the figure to be attended and another on the background. These findings suggest that the initial retinotopic information of the stimulus is combined with the background retinotopic information in a subsequent stage, yielding a more stable representation of the stimulus relative to the background through time-division multiplexing.Significance Statement According to psychological literature, the location of visual stimuli is automatically positioned against the background of a scene. This representation relative to the background, not being influenced by eye movements, should be important for stabilizing the visual world. A human functional imaging study suggested that the precuneus in the medial cerebral cortex is a strong candidate. This study recorded neural activity from the precuneus of monkeys and demonstrated the existence of background-centered cells with receptive fields fixed relative to the background.

Kilohertz volumetric imaging of in-vivo dynamics using squeezed light field microscopy.

Volumetric functional imaging of transient cellular signaling and motion dynamics poses a significant challenge to current microscopy techniques, primarily due to limitations in hardware bandwidth and the restricted photon budget within short exposure times. In response to this challenge, we present squeezed light field microscopy (SLIM), a computational imaging method that enables rapid detection of high-resolution three-dimensional (3D) light signals using only a single, low-format camera sensor area. SLIM pushes the boundaries of 3D optical microscopy, achieving over one thousand volumes per second across a large field of view of 550 μm in diameter and 300 μm in depth with a spatial resolution of 3.6 μm laterally and 6 μm axially. Using SLIM, we demonstrated blood cell velocimetry across the embryonic zebrafish brain and in a free-moving tail exhibiting high-frequency swinging motion. The millisecond temporal resolution also enables accurate voltage imaging of neural membrane potentials in the leech ganglion, and in the hippocampus of behaving mice. These results collectively establish SLIM as a versatile and robust imaging tool for high-speed microscopy applications.

Bidirectional regulation of motor circuits using magnetogenetic gene therapy.

Here, we report a magnetogenetic system, based on a single anti-ferritin nanobody-TRPV1 receptor fusion protein, which regulated neuronal activity when exposed to magnetic fields. Adeno-associated virus (AAV)-mediated delivery of a floxed nanobody-TRPV1 into the striatum of adenosine-2a receptor-Cre drivers resulted in motor freezing when placed in a magnetic resonance imaging machine or adjacent to a transcranial magnetic stimulation device. Functional imaging and fiber photometry confirmed activation in response to magnetic fields. Expression of the same construct in the striatum of wild-type mice along with a second injection of an AAVretro expressing Cre into the globus pallidus led to similar circuit specificity and motor responses. Last, a mutation was generated to gate chloride and inhibit neuronal activity. Expression of this variant in the subthalamic nucleus in PitX2-Cre parkinsonian mice resulted in reduced c-fos expression and motor rotational behavior. These data demonstrate that magnetogenetic constructs can bidirectionally regulate activity of specific neuronal circuits noninvasively in vivo using clinically available devices.

Highfield imaging of the subgenual anterior cingulate cortex in uni- and bipolar depression.

The subgenual Anterior Cingulate Cortex (sgACC), as a part of the Anterior Cingulate Cortex and the limbic system plays a crucial role in mood regulation. Previous structural and functional brain imaging studies of the sgACC have revealed alterations of Gray Matter (GM) volumes and Blood Oxygenation Level Dependent signals (BOLD) in patients with Major Depressive Disorder (MDD) and Bipolar Disorder (BD), suggesting potential biomarker traits for affective disorders. In this study we investigated the gray matter volume of the sgACC in 3 different patient groups: 40 MDD patients, of which 20 were medicated (MDDm) and 20 were unmedicated (MDDu), and 21 medicated BD patients, and compared them with 23 healthy volunteers. We examined GM volume alteration using high-resolution 7T Magnetic Resonance Imaging (MRI) which produced quantitative maps of the spin-lattice relaxation time (T1). T1 maps provide high contrast between gray and white matter, and at 7 Tesla voxels with submillimeter resolution can be acquired in a reasonable scan time. We developed a semi-automatic segmentation protocol based on refined landmarks derived from previous volumetric studies using quantitative T1 maps as raw input data for automatic tissue segmentation of GM, WM and CSF (cerebrospinal fluid) tissue. The sgACC ROI was then superimposed on these tissue probability maps and traced manually by two independent raters (F.B., M.M.) following our semi-automatic segmentation protocol. Interrater reliability was calculated on a subset of 10 brain scans for each hemisphere, showing an Intra-Class Correlation coefficient (ICC) r = 0.96 for left sgACC and r = 0.84 for right sgACC respectively. In summary, we have developed a reproducible and reliable semi-automatic segmentation protocol to measure gray matter volume in the sgACC. Based on previous findings from meta-analyses on morphometric studies of the sgACC, we hypothesized that patients with MDD would have lower gray matter sgACC volumes compared to healthy subjects. Post-hoc analysis revealed smaller subgenual volumes for the left hemisphere in both the medicated (MDDm) and non-medicated (MDDu) group versus healthy controls (p = .001, p = .008) respectively. For the right hemisphere, the (MDDu) and BD group exhibited significantly lower subgenual volumes than healthy controls (p < .001, p = .004) respectively. To our knowledge, this is the first morphometric MRI study using T1 maps obtained in high-resolution 7 Tesla MRI to compare MDD and BD patients with healthy controls.

Computed tomography perfusion as a predictor of gastric cancer grades

BackgroundGastric cancer stands as one of the most prevalent malignancies globally, conventional endoscopic specimens have been the primary means of diagnosing preoperative gastric histopathology, however, their limitations in capturing intra-tumor heterogeneity compromise their efficacy in evaluating angiogenesis. Perfusion Computed Tomography (P-CT) emerges as a pivotal functional imaging modality, facilitating objective assessment of tissue perfusion, serving as a marker of angiogenesis. So, our research objective was to evaluate the efficacy of CT perfusion imaging in the prediction of histological grades of gastric tumors using quantitative perfusion parameters such as permeability surface (PS), blood flow (BF), mean transient time (MTT), and blood volume (BV), in addition to the qualitative scoring system then comparing the findings with the histopathological results.ResultsPS and BF were statistically significant predictors of the grade of differentiation, their odds ratio (OR) was (1.05, 95% CI 1.02–1.09, for each of them) (P = 0.004, P = 0.009, respectively). MTT also emerged as a significant predictor of the grade of differentiation with an OR of 0.76 (95% CI 0.57–0.93, P = 0.025). Using multivariate logistic regression model, PS was the most potent individual P-CT predictor of differentiation of the grade and the diagnosis of poorly differentiated tumors at ≥ 39 mL/100 g/min cut off point, followed by BF at ≥ 82.2 mL/100 g/min, and MTT at < 8.4 s. Regarding the qualitative scoring system P-CT, poorly differentiated tumors generally received higher scores of PS (P < 0.001), BF (P < 0.001), and BV (P = 0.017), than well and moderately differentiated tumors, however, MTT showed that poorly differentiated tumors were more frequently scored as low compared to well and moderately differentiated tumors (P < 0.001).ConclusionsP-CT is an innovative, non-invasive biomarker for predicting gastric cancer grade by quantitative and qualitative assessment by P-CT parameters (PS, BF and MTT) with particular role of PS as the strongest individual P-CT predictor of differentiation grade followed by BF and MTT at specific cut off points.

Neural activity for complex sounds in the marmoset anterior cingulate cortex

Vocalizations play an important role in the daily life of nonhuman primates and are likely precursors of human language. Recent functional imaging studies in the highly vocal common marmoset (Callithrix jacchus) have suggested that anterior cingulate cortex (ACC) area 32 may be a part of a vocalization-processing network but the response properties of area 32 neurons to auditory stimuli remain unknown. Here we perform electrophysiological recordings in area 32 in marmosets with high-density Neuropixels probes and characterize neuronal responses to a variety of sounds including conspecific vocalizations. Nearly half of the neurons in area 32 respond to conspecific vocalizations and other complex auditory stimuli. These responses exhibit dynamics consisting of an initially non-selective reduction in neural activity, followed by an increase in activity that immediately conveys sound selectivity. Our findings demonstrate that primate ACC area 32 processes species-specific and biologically relevant sounds.

Enhanced efficiency in the bilingual brain through the inter-hemispheric cortico-cerebellar pathway in early second language acquisition

Bilingualism has a profound impact on the structure and function of the brain, but it is not yet well understood how this experience influences brain functional organization. We examine a large sample (151 participants) of monolinguals and bilinguals with varied age of second language acquisition, who underwent resting-state functional magnetic brain imaging. Whole-brain network analyses reveal higher global efficiency in bilingual individuals than monolinguals, indicating enhanced functional integration in the bilingual brain. Moreover, the age at which the second language was acquired correlated with this increased efficiency, suggesting that earlier exposure to a second language has lasting positive effects on brain functional organization. Further investigation using the network-based statistics approach indicates that this effect is primarily driven by heightened functional connectivity between association networks and the cerebellum. These findings show that the timing of bilingual learning experience alters the brain functional organization at both global and local levels.

Diffuse correlation tomography: a technique to characterize tissue blood flow abnormalities in benign and malignant breast lesions

Accurate assessment and quantification of neoangiogenesis associated with breast cancer could be potentially used to improve the sensitivity and specificity of non-invasive diagnosis, as well as predict outcomes and monitor treatment effects. In this study, we adapted an emerging technology, namely diffuse correlation tomography (DCT), to image microvascular blood flow in breast tissues and evaluate the potential for discriminating between benign and malignant lesions. A custom-made DCT system was designed for breast blood flow imaging, with both the source-detector array and reconstruction algorithm optimized to ensure precise imaging of breast blood flow. The global features and local features of three-dimensional blood flow images were extracted from the relative blood flow index (rBFI), which was obtained from most of the breasts targeted to the lesion. A total of 37 women with 19 benign and 18 malignant lesions were included in the study. Significant differences between malignant and benign groups were found in 12 image features. Moreover, when selecting the lesion mean relative blood flow index (MrBFI) as a single indicator, the malignant and benign tumors were discriminated with an accuracy of 89.2%. The blood flow features were found to successfully identify malignant and benign tumors, suggesting that DCT, as an alternate functional imaging modality, has the potential to be translated into clinical practice for diagnosis and assessment of breast cancers. There is potential to reduce the need for biopsy of benign lesions by improving the specificity of diagnostic imaging, as well as monitoring response to breast cancer treatment.

Multi-echo Acquisition and Thermal Denoising Advances Precision Functional Imaging.

The characterization of individual functional brain organization with Precision Functional Mapping has provided important insights in recent years in adults. However, little is known about the ontogeny of inter-individual differences in brain functional organization during human development. Precise characterization of systems organization during periods of high plasticity is likely to be essential for discoveries promoting lifelong health. Obtaining precision fMRI data during development has unique challenges that highlight the importance of establishing new methods to improve data acquisition, processing, and analysis. Here, we investigate two methods that can facilitate attaining this goal: multi-echo (ME) data acquisition and thermal noise removal with Noise Reduction with Distribution Corrected (NORDIC) principal component analysis. We applied these methods to precision fMRI data from adults, children, and newborn infants. In adults, both ME acquisitions and NORDIC increased temporal signal to noise ratio (tSNR) as well as the split-half reliability of functional connectivity matrices, with the combination helping more than either technique alone. The benefits of NORDIC denoising replicated in both our developmental samples. ME acquisitions revealed longer and more variable T2* relaxation times across the brain in infants relative to older children and adults, leading to major differences in the echo weighting for optimally combining ME data. This result suggests ME acquisitions may be a promising tool for optimizing developmental fMRI, albeit application in infants needs further investigation. The present work showcases methodological advances that improve Precision Functional Mapping in adults and developmental populations and, at the same time, highlights the need for further improvements in infant specific fMRI.

Rare benign breast neoplasm masquerading as malignancy on anatomical and functional imaging with contrast-enhanced mammography

We discuss a unique case of a benign breast neoplasm that initially appeared to be an intracystic papillary carcinoma on digital breast tomosynthesis, ultrasound, and contrast-enhanced mammogram. However, subsequent histopathological examination (HPE) revealed it to be a benign adenomyoepithelioma, an uncommon neoplasm in the breast. Understanding this rare condition and confirming it pre-operatively through HPE can prevent unnecessary aggressive treatment.

Exploring the Role of Sigma Receptors in the Treatment of Cancer: A Narrative Review.

This study investigated the association of sigma receptors (SRs) and their selective ligands (because the molecular characteristics of the same SRs, particularly sigma-2 receptor {S2R}, are not completely clear) in carcinogenesis, their potential use as antitumor agents, and their great utility in tumor imaging.The ion channels and transporters enhance the cell's ability to adapt to the metabolic conditions encountered in the tumor tissue. The high expression of SRs in the proliferating cells compared with those at rest indicates that this is a significant clinical biomarker for determining the proliferative status of solid tumors using functional PET imaging techniques. The association of SRs in the pathophysiology of cancer cells is a result of the high concentration of S1R and S2R binding sites observed in various tumor cell lines and tissues. It would also be remarkable to determine if SRs are involved in metastasis and other metastatic cell behaviorssuch as adhesion, secretion, motility, and penetration. An absolute challenge for research in this field is to develop an integrated model that describes the molecular mechanisms of sigma receptors, incorporating their known biological and pathophysiological roles.

Postoperative reorganization of the supplementary motor area complex: A possible latent bihemispheric network

PurposeBrain plasticity after multistep surgery in low-grade glioma is highly variable; the neurosurgical approach must be individualised and functional imaging can be used for this purpose.In supplementary motor area complex (SMAC) tumors, the early and adequate functional recovery of patients raises the possibility of a latent bihemispheric or “mirror” cortico-subcortical network, which would develop depending on the needs of each patient. MethodsFunctional and DTI-MR data from 4 right-handed patients with left frontal low grade gliomas near the SMAC, who were operated at least in two occasions were collected. The time of the reintervention was variable (18 months- 8 years), related to the tumor growth. All patients were evaluated by a neuropsychologist and imaged before each surgery, in a 3 T MR, with a 24 multichanel head coilMotor and expressive language task-fMRI and DTI sequences were obtained to evidence the main cortico-subcortical components of the SMAC. Data were processed with Brainwave (GE Medical Systems) and with an Iplan Fiber Tracking tool (MEDTRONIC), respectively ResultsNone of our patients presented permanent neurological deficits after the first or second functional surgery. Three patients with partial or complete resection of the left middle and / or inferior frontal gyrus, and the left frontal aslant tract evidenced new right hemispherical cortical activity. This right shift were not observed in the patient without left middle gyrus resection, indeed with partial absent of the left frontal aslant tract. ConclusionSMAC is a latent cortico-subcortical bihemispheric network that allows it to reorganize itself in response to specific neurological deficits. We highlight the importance in the cortical reorganization of the left middle frontal gyrus in the SMAC, closely connected with the essential language areas of this region, but also we focused in the potential cortioco-subcortical changes to compensate the functionality of the FAT.

8607 Gender Affirming Hormone Therapy: Influence of Brain Network Connectivity Changes on Affect

Abstract Disclosure: J. Andreano: None. A. Lopez: None. M. Misra: None. Background: Previous research indicates that acute gonadal treatments and fluctuations in ovarian hormone levels over the course of the menstrual cycle can alter patterns of communication between brain regions, as well as producing significant changes in self-reported affect. Recent research from our laboratory indicates changes in both brain connectivity and affect with gender affirming hormone therapy (GAHT). However, the relationship between these changes with GAHT are not well understood. Additionally, it is difficult to separate influences of GAHT and transgender identity in understanding differences in connectvity and affect from cisgender controls. A better understanding of the influence of GAHT on intrinsic network connectivity could point the way towards improved GAHT treatment regimens that minimize affective side effects. Objective: To assess relationships between changes in brain network connectivity and affective changes following GAHT, identifying regions in which changes of connectivity are associated with changes in self-reported affect, and to examine differences in brain network connectivity between transgender participants and cisgender controls. Methods: 14 transgender individuals receiving GAHT (estradiol n =7, testosterone n = 7)) were scanned using functional magnetic imaging (fMRI) at rest at two timepoints: baseline, prior to treatment, and 6 months into GAHT. Additionally, 20 cisgender controls (10 male, 10 female) were scanned once each. The time course of neural activity was computed for each voxel in the brain, then tested for correlation with each other voxel to develop a whole-brain connectome for each participant. Maps of average connectivity to two seeds known to associate with two major networks in the brain (posterior cingulate cortex for Default Mode Network, and anterior insula for Salience Network) were then generated for each participant. Within transgender participants, these maps were then compared between the baseline and 6 month timepoints. Additionally, baseline scans were also compared to scans from cisgender controls corresponding to biological sex. Results: Within-subjects analyses of transgender participants showed diverse associations between changes in seed-based connectivity and changes in self-reported anxiety and depression following GAHT in both the default mode and salience networks. Between subjects comparisons showed significantly higher connectivity within the salience network in trans men relative to cis women, as well as greater inter-network connectivity in this group. In contrast, cis men showed greater connectivity within both default mode and salience networks relative to trans women. Conclusions: Changes in affect following GAHT appear related to GAHT-induced changes in network connectivity; these influences appear independent of differences between cis and transgender individuals. Presentation: 6/2/2024

7698 A case of Pheochromocytoma in a patient with severe aortic stenosis

Abstract Disclosure: C. Lane: None. L.E. Aguirre: None. J. Azocar-Villalobos: None. R.I. Dorin: None. Background: Pheochromocytomas are rare neuroendocrine tumors derived from chromaffin tissue of the adrenal medulla and can secrete catecholamines. Pre-operative management of pheochromocytoma involves initiation of a- followed by b-adrenergic receptor blockade. In critical aortic stenosis (AS), adrenergic blockade may be complicated by decreased cardiac output and hypotension owing to dependence of venous return on maintenance of high afterload (1). We report a case of critical AS and incidentally discovered pheochromocytoma and describe our management strategy, which involved prioritization of aortic valve repair prior to adrenal surgery and multidisciplinary approach to initiation and titration of a- and b-adrenergic blockade prior to cardiac catheterization and transcutaneous aortic valve replacement (TAVR) procedures. Clinical Case: A 75-year-old Caucasian male with past medical history of obstructive sleep apnea, tobacco use, and cocaine use disorder was admitted with progressive dyspnea, decreased exercise tolerance, and involuntary weight loss of 18 kg over 3 months, and community acquired pneumonia. On admission, he was found to have critical aortic stenosis (valve area of 0.59 cm2, mean gradient 83 mmHg) and new HFrEF (EF 40-45%). CT chest demonstrated incidental right adrenal mass (5.6 x 5.0 x 4.7 cm) with central necrosis, HU units &amp;gt;10, and evidence of internal hemorrhage. Subsequent laboratory and functional imaging studies confirmed diagnosis of pheochromocytoma. Pre-procedural a-adrenergic blockade with doxazosin followed by beta-blockade was managed by a multidisciplinary team with ICU admission for monitoring and uncomplicated completion of cardiac catheterization and TAVR. Conclusions: Pre-procedural diagnosis of pheochromocytoma, multidisciplinary management, and intensive care setting for monitoring hemodynamic response to initiation and titration of a and b-adrenergic blockade appeared to be key factors in achieving uncomplicated completion of cardiac interventions prior to surgical resection of pheochromocytoma and critical AS. Successful TAVR was associated with marked improvement in hemodynamic status. Maintenance of b-adrenergic blockade to reduce myocardial contractility was critical to preservation of the prosthetic aortic valve and in preparation for planned robotic resection of the pheochromocytoma.