Blood Oxygen Level-dependent Activity Research Articles

Task-Dependent Brain Activity in Generalized Anxiety Disorder Determined By Bayesian Spatio-Temporal Single Case Model

Introduction: Data obtained from functional magnetic resonance imaging (fMRI) have a complex structure. Considering the special features of this type of data in analyses is of particular importance. Previous studies on generalized anxiety disorder (GAD) as a prevalent mental disorder using functional neuroimaging have had conflicting results. In this study, we apply a Bayesian spatiotemporal model to this type of data which considers both spatial and temporal dependence among regions which is one of the most essential features to consider. Methods: In this single-subject study, we analyze data from a patient with GAD and a healthy participant. Both participants are 24-year-old women who are assigned an emotion reactivity task (matching neutral and negative facial expressions) inside a scanner. The spatial Bayesian variable selection method is used to detect blood oxygen level-dependent activation in fMRI data. Results: Activation areas in neutral and negative facial expressions are provided for both participants by posterior probability map. The results of our study show a greater level of activity in the GAD participant in comparison to the healthy participant in responding to the negative matching task. Conclusion: the GAD patient showed more neural activity in response to negative facial expressions than the healthy participant in brain regions related to emotional response in the areas of the frontal Pole, middle frontal gyrus, insular cortex, and frontal orbital cortex. Moreover, the inferior frontal gyrus in the patient with GAD showed more reaction to negative emotional stimuli.

Thermal stimulus task fMRI in the cervical spinal cord at 7 Tesla.

Although functional magnetic resonance imaging (fMRI) is widely applied in the brain, fMRI of the spinal cord is more technically demanding. Proximity to the vertebral column and lungs results in strong spatial inhomogeneity and temporal fluctuations in B0 . Increasing field strength enables higher spatial resolution and improved sensitivity to blood oxygenation level-dependent (BOLD) signal, but amplifies the effects of B0 inhomogeneity. In this work, we present the first task fMRI in the spinal cord at 7 T. Further, we compare the performance of single-shot and multi-shot 2D echo-planar imaging (EPI) protocols, which differ in sensitivity to spatial and temporal B0 inhomogeneity. The cervical spinal cords of 11 healthy volunteers were scanned at 7 T using single-shot 2D EPI at 0.75 mm in-plane resolution and multi-shot 2D EPI at 0.75 and 0.6 mm in-plane resolutions. All protocols used 3 mm slice thickness. For each protocol, the BOLD response to 13 10-s noxious thermal stimuli applied to the right thumb was acquired in a 10-min fMRI run. Image quality, temporal signal to noise ratio (SNR), and BOLD activation (percent signal change and z-stat) at both individual- and group-level were evaluated between the protocols. Temporal SNR was highest in single-shot and multi-shot 0.75 mm protocols. In group-level analyses, activation clusters appeared in all protocols in the ipsilateral dorsal quadrant at the expected C6 neurological level. In individual-level analyses, activation clusters at the expected level were detected in some, but not all subjects and protocols. Single-shot 0.75 mm generally produced the highest mean z-statistic, while multi-shot 0.60 mm produced the best-localized activation clusters and the least geometric distortion. Larger than expected within-subject segmental variation of BOLD activation along the cord was observed. Group-level sensory task fMRI of the cervical spinal cord is feasible at 7 T with single-shot or multi-shot EPI. The best choice of protocol will likely depend on the relative importance of sensitivity to activation versus spatial localization of activation for a given experiment. PRACTITIONER POINTS: First stimulus task fMRI results in the spinal cord at 7 T. Single-shot 0.75 mm 2D EPI produced the highest mean z-statistic. Multi-shot 0.60 mm 2D EPI provided the best-localized activation and least distortion.

Controlled noninvasive modulation of deep brain regions in humans

Transcranial focused ultrasound provides noninvasive and reversible approaches for precise and personalized manipulations of brain circuits, with the potential to transform our understanding of brain function and treatments of brain dysfunction. However, effective applications in humans have been limited by the human head, which attenuates and distorts ultrasound severely and unpredictably. This has led to uncertain ultrasound intensities delivered into the brain. Here, we address this lingering barrier using a direct measurement approach that can be repeatedly applied to the human brain. The approach uses an ultrasonic scan of the head to measure and compensate for the attenuation of the ultrasound by all obstacles within the ultrasound path. No other imaging modality is required and the method is parameter-free and personalized to each subject. The approach accurately restores operators’ intended intensities inside ex-vivo human skulls. Moreover, the approach is critical for effective modulation of deep brain regions in humans. When applied, the approach modulates fMRI Blood Oxygen Level Dependent (BOLD) activity in disease-relevant deep brain regions. This tool unlocks the potential of emerging approaches based on low-intensity ultrasound for controlled manipulations of neural circuits in humans.

Amygdala-related electrical fingerprint is modulated with neurofeedback training and correlates with deep-brain activation: proof-of-concept in borderline personality disorder.

The modulation of brain circuits of emotion is a promising pathway to treat borderline personality disorder (BPD). Precise and scalable approaches have yet to be established. Two studies investigating the amygdala-related electrical fingerprint (Amyg-EFP) in BPD are presented: one study addressing the deep-brain correlates of Amyg-EFP, and a second study investigating neurofeedback (NF) as a means to improve brain self-regulation. Study 1 combined electroencephalography (EEG) and simultaneous functional magnetic resonance imaging to investigate the replicability of Amyg-EFP-related brain activation found in the reference dataset (N = 24 healthy subjects, 8 female; re-analysis of published data) in the replication dataset (N = 16 female individuals with BPD). In the replication dataset, we additionally explored how the Amyg-EFP would map to neural circuits defined by the research domain criteria. Study 2 investigated a 10-session Amyg-EFP NF training in parallel to a 12-weeks residential dialectical behavior therapy (DBT) program. Fifteen patients with BPD completed the training, N = 15 matched patients served as DBT-only controls. Study 1 replicated previous findings and showed significant amygdala blood oxygenation level dependent activation in a whole-brain regression analysis with the Amyg-EFP. Neurocircuitry activation (negative affect, salience, and cognitive control) was correlated with the Amyg-EFP signal. Study 2 showed Amyg-EFP modulation with NF training, but patients received reversed feedback for technical reasons, which limited interpretation of results. Recorded via scalp EEG, the Amyg-EFP picks up brain activation of high relevance for emotion. Administering Amyg-EFP NF in addition to standardized BPD treatment was shown to be feasible. Clinical utility remains to be investigated.

Poster Session I: Binocular facilitation of the BOLD response to melanopsin stimulation in the suprachiasmatic nucleus.

In a recent analysis of archival data, Spitschan and Cajochen (2019) identify what appears to be substantial binocular facilitation of melatonin suppression due to melanopic light stimulation. This putative effect likely originates in the melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) which project directly to the suprachiasmatic nucleus (SCN) of the hypothalamus. We asked whether we could measure a direct physiological correlate of this binocular facilitation using a binocular, MRI-compatible, 10-primary spectral stimulation device. We present preliminary findings from a functional magnetic resonance imaging (fMRI) study designed to explore the blood oxygen level dependent (BOLD) response to monocular and binocular melanopic light stimulation. The study used a 30 s on/off design with three 'ocularity' conditions (binocular-low, monocular-high, binocular-high) and two classes of targeted photoreceptors (melanopsin and LMS cones). Throughout each scan, subjects (N=18) also responded to brief, cone-directed sinusoidal modulations of varying intensity. We report that binocular vs. monocular melanopsin stimulation induced significant BOLD activation in SCN but that this effect was not seen for cone-directed stimulation. This is consistent with the binocular facilitation effect described by Spitschan and Cajochen (2019) and provides the first direct evidence of melanopsin-driven activation and binocular facilitation in human subcortical nuclei.

Neural correlates of deceased-related attention during acute grief in suicide-related bereavement

BackgroundIndividuals who have lost a loved one to suicide demonstrate an attentional bias to deceased-related stimuli during early grief. Regulating attention toward reminders of the deceased during acute bereavement may be linked to grief trajectory and pathological grief development. Despite the potential prognostic importance, little is known about underlying neural circuitry correlates of deceased-related grief processing. The current study examines neural substrates of deceased-related attentional processing during acute grief in individuals bereaved by suicide. MethodsThirty-seven participants grieving the loss of a first-degree relative or partner to suicide in the prior six months, underwent functional magnetic resonance imaging (fMRI) while performing an emotional Stroop task using words related to the deceased and a living attachment figure, in order to examine neural correlates of deceased-specific attentional processing. Clinical interviews were conducted at baseline. ResultsDeceased-related attentional bias was associated with blood oxygen level-dependent (BOLD) activation in a brain network, including dorsolateral prefrontal cortex (dlPFC), ventrolateral prefrontal cortex (vlPFC), orbitofrontal cortex (OFC), and insula. Greater activation of a bilateral prefrontal cluster during deceased-specific attention was negatively correlated with self-reported grief avoidance behaviors. LimitationsLack of non-suicide grief control and small sample size. ConclusionsThese data, if confirmed, indicate a neural network specific to deceased-related attention, and that cognitive control regions within this network appear to be related to grief avoidance behaviors during acute bereavement.

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.

Is the Brainstem Activation Different Between Healthy Young Male and Female Volunteers at Initiation of Voiding? A High Definition 7-Tesla Magnetic Resonance Imaging Study.

Assessing brainstem function in humans through typical neuroimaging modalities has been challenging. Our objective was to evaluate brain and brainstem activation patterns during initiation of voiding in healthy males and females utilizing a 7 Tesla magnetic resonance imaging (MRI) scanner and a noninvasive brain-bladder functional MRI (fMRI) protocol. Twenty healthy adult volunteers (10 males and 10 females) with no history of urinary symptoms were recruited. Each volunteer underwent a clinic uroflow and postvoid residual assessment and was asked to consume water prior to entering the scanner. Anatomical and diffusion tensor images were obtained first, followed by a blood oxygenation level dependent (BOLD) resting-state fMRI (rs-fMRI) during the empty bladder. Subjects indicated when they felt the urge to void, and a full bladder rs-fMRI was obtained. Once completed, the subjects began 5 voiding cycles, where the first 7.5 seconds of each voiding cycle was identified as "initiation of voiding." BOLD activation maps were generated, and regions of interests with a t-value greater than 2.1 were deemed statistically significant. We present 5 distinct regions within the periaqueductal gray (PAG) and pontine micturition center (PMC) with statistically significant activation associated with an initiation of voiding in both men and women, 3 within the PAG and 2 within the PMC. Several additional areas in the brain also demonstrated activation as well. When comparing males to females, there was an overall lower BOLD activation seen in females throughout all regions, with the exception of the caudate lobe. Our study effectively defines regions within the PAG and PMC involved in initiation of voiding in healthy volunteers. To our knowledge, this is the first study investigating differences between male and female brainstem activation utilizing an ultra-high definition 7T MRI.

Relation ofresting brain signal variability to cognitive andsocioemotional measures inan adult lifespan sample.

Temporal variability of the fMRI-derived blood-oxygen-level-dependent (BOLD) signal during cognitive tasks shows important associations with individual differences in age and performance. Less is known about relations between spontaneous BOLD variability measured at rest and relatively stable cognitive measures, such as IQ or socioemotional function. Here, we examined associations among resting BOLD variability, cognitive/socioemotional scores from the NIH Toolbox and optimal time of day for alertness (chronotype) in a sample of 157 adults from 20 to 86 years of age. To investigate individual differences in these associations independently of age, we regressed age out from both behavioral and BOLD variability scores. We hypothesized that greater BOLD variability would be related to higher fluid cognition scores, more positive scores on socioemotional scales and a morningness chronotype. Consistent with this idea, we found positive correlations between resting BOLD variability, positive socioemotional scores (e.g. self-efficacy) and morning chronotype, as well as negative correlations between variability and negative emotional scores (e.g. loneliness). Unexpectedly, we found negative correlations between BOLD variability and fluid cognition. These results suggest that greater resting brain signal variability facilitates optimal socioemotional function and characterizes those with morning-type circadian rhythms, but individuals with greater fluid cognition may be more likely to show less temporal variability in spontaneous measures of BOLD activity.

Segmented spin-echo echo-planar imaging improves whole-brain BOLD functional MRI in awake pigeon brains.

Functional magnetic resonance imaging (fMRI) in awake small animals such as pigeons or songbirds opens a new window into the neural fundaments of cognitive behavior. However, high-field fMRI in the avian brain is challenging due to strong local magnetic field inhomogeneities caused by air cavities in the skull. A spoiled gradient-echo fMRI sequence has already been used to map the auditory network in songbirds, but due to susceptibility artifacts only 50% of the whole brain could be recorded. Since whole-brain fMRI coverage is vital to reveal whole-brain networks, an MRI sequence that is less susceptible to these artifacts was required. This was recently achieved in various bird species by using a rapid acquisition with relaxation enhancement (RARE) sequence. Weak blood oxygen level-dependent (BOLD) sensitivity, low temporal resolution, and heat caused by the long train of RF refocusing pulses are the main limits of RARE fMRI at high magnetic fields. To go beyond some of these limitations, we here describe the implementation of a two-segmented spin-echo echo-planar imaging (SE-EPI). The proposed sequence covers the whole brain of awake pigeons. The sequence was applied to investigate the auditory network in awake pigeons and assessed the relative merits of this method in comparison with the single-shot RARE sequence. At the same imaging resolution but with a volume acquisition of 3 s versus 4 s for RARE, the two-segmented SE-EPI provided twice the strength of BOLD activity compared with the single-shot RARE sequence, while the image signal-to-noise ratio (SNR) and in particular the temporal SNR were very similar for the two sequences. In addition, the activation patterns in two-segmented SE-EPI data are more symmetric and larger than single-shot RARE results. Two-segmented SE-EPI represents a valid alternative to the RARE sequence in avian fMRI research since it yields more than twice the BOLD sensitivity per unit of time with much less energy deposition and better temporal resolution, particularly for event-related experiments.

Effects of ulotaront on brain circuits of reward, working memory, and emotion processing in healthy volunteers with high or low schizotypy

Ulotaront, a trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptor agonist without antagonist activity at dopamine D2 or the serotonin 5-HT2A receptors, has demonstrated efficacy in the treatment of schizophrenia. Here we report the phase 1 translational studies that profiled the effect of ulotaront on brain responses to reward, working memory, and resting state connectivity (RSC) in individuals with low or high schizotypy (LS or HS). Participants were randomized to placebo (n = 32), ulotaront (50 mg; n = 30), or the D2 receptor antagonist amisulpride (400 mg; n = 34) 2 h prior to functional magnetic resonance imaging (fMRI) of blood oxygen level-dependent (BOLD) responses to task performance. Ulotaront increased subjective drowsiness, but reaction times were impaired by less than 10% and did not correlate with BOLD responses. In the Monetary Incentive Delay task (reward processing), ulotaront significantly modulated striatal responses to incentive cues, induced medial orbitofrontal responses, and prevented insula activation seen in HS subjects. In the N-Back working memory task, ulotaront modulated BOLD signals in brain regions associated with cognitive impairment in schizophrenia. Ulotaront did not show antidepressant-like biases in an emotion processing task. HS had significantly reduced connectivity in default, salience, and executive networks compared to LS participants and both drugs reduced this difference. Although performance impairment may have weakened or contributed to the fMRI findings, the profile of ulotaront on BOLD activations elicited by reward, memory, and resting state is compatible with an indirect modulation of dopaminergic function as indicated by preclinical studies. This phase 1 study supported the subsequent clinical proof of concept trial in people with schizophrenia.Clinical trial registration: Registry# and URL: ClinicalTrials.gov NCT01972711, https://clinicaltrials.gov/ct2/show/NCT01972711

Neural activation of regions involved in food reward and cognitive control in young females with anorexia nervosa and atypical anorexia nervosa versus healthy controls

Anorexia nervosa (AN) and atypical AN (AtypAN) are complex neurobiological illnesses that typically onset in adolescence with an often treatment-refractory and chronic illness trajectory. Aberrant eating behaviors in this population have been linked to abnormalities in food reward and cognitive control, but prior studies have not examined respective contributions of clinical characteristics and metabolic state. Research is needed to identify specific disruptions and inform novel intervention targets to improve outcomes. Fifty-nine females with AN (n = 34) or AtypAN (n = 25), ages 10–22 years, all ≤90% expected body weight, and 34 age-matched healthy controls (HC) completed a well-established neuroimaging food cue paradigm fasting and after a standardized meal, and we used ANCOVA models to investigate main and interaction effects of Group and Appetitive State on blood oxygenation level-dependent (BOLD) activation for the contrast of exposure to high-calorie food images minus objects. We found main effects of Group with greater BOLD activation in the dorsal anterior cingulate cortex (dACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, caudate, and putamen for AN/AtypAN versus HC groups, and in the three-group model including AN, AtypAN, and HC (sub-)groups, where differences were primarily driven by greater activation in the AtypAN subgroup versus HC group. We found a main effect of Appetitive State with increased premeal BOLD activation in the hypothalamus, amygdala, nucleus accumbens, and caudate for models that included AN/AtypAN and HC groups, and in BOLD activation in the nucleus accumbens for the model that included AN, AtypAN, and HC (sub-)groups. There were no interaction effects of Group with Appetitive State for any of the models. Our findings demonstrate robust feeding-state independent group effects reflecting greater neural activation of specific regions typically associated with reward and cognitive control processing across AN and AtypAN relative to healthy individuals in this food cue paradigm. Differential activation of specific brain regions in response to the passive viewing of high-calorie food images may underlie restrictive eating behavior in this clinical population.

Development and validation of an fMRI-informed EEG model of reward-related ventral striatum activation

Reward processing is essential for our mental-health and well-being. In the current study, we developed and validated a scalable, fMRI-informed EEG model for monitoring reward processing related to activation in the ventral-striatum (VS), a significant node in the brain's reward system. To develop this EEG-based model of VS-related activation, we collected simultaneous EEG/fMRI data from 17 healthy individuals while listening to individually-tailored pleasurable music – a highly rewarding stimulus known to engage the VS. Using these cross-modal data, we constructed a generic regression model for predicting the concurrently acquired Blood-Oxygen-Level-Dependent (BOLD) signal from the VS using spectro-temporal features from the EEG signal (termed hereby VS-related-Electrical Finger Print; VS-EFP). The performance of the extracted model was examined using a series of tests that were applied on the original dataset and, importantly, an external validation dataset collected from a different group of 14 healthy individuals who underwent the same EEG/FMRI procedure. Our results showed that the VS-EFP model, as measured by simultaneous EEG, predicted BOLD activation in the VS and additional functionally relevant regions to a greater extent than an EFP model derived from a different anatomical region. The developed VS-EFP was also modulated by musical pleasure and predictive of the VS-BOLD during a monetary reward task, further indicating its functional relevance. These findings provide compelling evidence for the feasibility of using EEG alone to model neural activation related to the VS, paving the way for future use of this scalable neural probing approach in neural monitoring and self-guided neuromodulation.

Relation of BOLD response to food-specific and generic motor response inhibition tasks to body fat gain in adults with overweight and obesity

BackgroundLow inhibitory control has been theorized to contribute to the development and maintenance of obesity. Knowledge on the neurobiological indicators of inhibitory control deficits predicting future weight gain is limited. The current study examined if individual differences in blood-oxygenation-level-dependent (BOLD) activity associated with food-specific and general motor response inhibition predict future body fat change in adults with overweight or obesity. MethodsBOLD activity and behavioral responses of adults with overweight or obesity (N = 160) were recorded while performing a food-specific stop signal task (n = 92) or a generic stop signal task (n = 68). Percent body fat was measured at baseline, posttest, 3-month, and 6-month follow-up. ResultsElevated BOLD activity in somatosensory (postcentral gyrus), and attention (precuneus) regions during successful inhibition in the food-specific stop signal task and elevated BOLD activity in a motor region (anterior cerebellar lobe) in the generic stop signal task predicted greater body fat gain over 6-month follow-up. Elevated BOLD activity in inhibitory control regions (inferior-, middle-, superior frontal gyri) and error monitoring regions (anterior cingulate cortex, insula) during erroneous responses in the generic stop signal task predicted body fat loss. ConclusionsResults suggest that improving motor response inhibition and error monitoring may facilitate weight loss in adults with overweight and obesity.

Influence of Strenuous Physical Activity and Cardiorespiratory Fitness on Age-Related Differences in Brain Activations During Varieties of Cognitive Control

While there is extensive literature on the beneficial effects of physical activity on age differences in cognitive control, limited research exists on comparing the contributions of strenuous physical activity (sPA) and cardiorespiratory fitness (CRF) to fluctuations in the blood oxygen level-dependent (BOLD) signals during varieties of cognitive control. The current study addresses this gap in knowledge by investigating BOLD signal differences between high-fit and low-fit older adults, determined by their sPA or CRF, during a novel fMRI task with a hybrid block and event-related design that included transient activations (during switching, updating and their combination trials) and sustained activations (during proactive and reactive control blocks). fBOLD signals from older (n = 25) were compared to more functionally efficient younger (n = 15) adults. High-sPA old showed higher task accuracy than Low-sPA old and similar accuracy as young. Whole-brain fMRI analyses identified higher BOLD activations (esp. dlPFC/MFG) in high-fit old during updating and combination trials that were similar to young, suggesting maintenance of BOLD signals in higher fit older adults during working memory updating. Additionally, both High-sPA and High-CRF related compensatory overactivation were observed in left parietal and occipital areas during sustained activations, which were positively correlated with older adults' accuracy. These results suggest that physical fitness is a modifier of age-related changes in BOLD signal modulation elicited in response to increasing cognitive control demands, with higher fitness in old contributing to both compensatory overactivations and maintenance of task-related brain activations during cognitive control, whereas lower fitness contributed to maladaptive overactivations during lower cognitive demands.

421. Low Intensity Focused Ultrasound Induces Targeted Subcortical Online Blood Oxygen-Level Dependent Activation in Humans

421. Low Intensity Focused Ultrasound Induces Targeted Subcortical Online Blood Oxygen-Level Dependent Activation in Humans

Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans.

Low intensity, transcranial focused ultrasound (tFUS) is a re-emerging brain stimulation technique with the unique capability of reaching deep brain structures non-invasively. We sought to demonstrate that tFUS can selectively and accurately target and modulate deep brain structures in humans important for emotional functioning as well as learning and memory. We hypothesized that tFUS would result in significant longitudinal changes in perfusion in the targeted brain region as well as selective modulation of BOLD activity and BOLD-based functional connectivity of the target region. In this study, we collected MRI before, simultaneously during, and after tFUS of two deep brain structures on different days in sixteen healthy adults each serving as their own control. Using longitudinal arterial spin labeling (ASL) MRI and simultaneous blood oxygen level dependent (BOLD) functional MRI, we found changes in cerebral perfusion, regional brain activity and functional connectivity specific to the targeted regions of the amygdala and entorhinal cortex (ErC). tFUS selectively increased perfusion in the targeted brain region and not in the contralateral homolog or either bilateral control region. Additionally, tFUS directly affected BOLD activity in a target specific fashion without engaging auditory cortex in any analysis. Finally, tFUS resulted in selective modulation of the targeted functional network connectivity. We demonstrate that tFUS can selectively modulate perfusion, neural activity and connectivity in deep brain structures and connected networks. Lack of auditory cortex findings suggests that the mechanism of tFUS action is not due to auditory or acoustic startle response but rather a direct neuromodulatory process. Our findings suggest that tFUS has the potential for future application as a novel therapy in a wide range of neurological and psychiatric disorders associated with subcortical pathology.

MP52-13 IMPROVED LOWER URINARY TRACT SYMPTOMS AND ASSOCIATED CHANGES IN MICTURITION-ASSOCIATED BRAIN ACTIVITY IN STROKE SURVIVORS FOLLOWING TRANSCUTANEOUS SPINAL CORD STIMULATION

You have accessJournal of UrologyCME1 Apr 2023MP52-13 IMPROVED LOWER URINARY TRACT SYMPTOMS AND ASSOCIATED CHANGES IN MICTURITION-ASSOCIATED BRAIN ACTIVITY IN STROKE SURVIVORS FOLLOWING TRANSCUTANEOUS SPINAL CORD STIMULATION David Chapman, Luis Alejandro Morales Ojeda, Veronica Stefania Montero Arcila, Sarah Ponce, Rita Jen, Nhi Ha, Parag Gad, Reggie Edgerton, David Ginsberg, Aidin Abedi, Kay Jann, and Evgeniy Kreydin David ChapmanDavid Chapman More articles by this author , Luis Alejandro Morales OjedaLuis Alejandro Morales Ojeda More articles by this author , Veronica Stefania Montero ArcilaVeronica Stefania Montero Arcila More articles by this author , Sarah PonceSarah Ponce More articles by this author , Rita JenRita Jen More articles by this author , Nhi HaNhi Ha More articles by this author , Parag GadParag Gad More articles by this author , Reggie EdgertonReggie Edgerton More articles by this author , David GinsbergDavid Ginsberg More articles by this author , Aidin AbediAidin Abedi More articles by this author , Kay JannKay Jann More articles by this author , and Evgeniy KreydinEvgeniy Kreydin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003300.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Stroke survivors often experience lower urinary tract dysfunction that can be difficult to treat and profoundly impacts their quality of life. After a stroke, micturition-associated brain activity (MABA) has been shown to rely on activation of primitive brain regions including the cerebellum and periaqueductal gray with less activation of cortical regions. Transcutaneous Spinal Cord Stimulation (TSCS), a novel technique of neuromodulation, is emerging as a powerful tool with growing clinical evidence in neuro-restoration potential. The objective was to evaluate changes in brain activity using functional MRI (fMRI) and patient reported outcome measures (PROM) following twelve weeks of TSCS. METHODS: Twelve patients with de novo lower urinary tract symptoms following a stroke prospectively underwent TSCS for 24 sessions. Blood oxygen level dependent (BOLD) brain activity changes detected with fMRI were collected during maximum urgency, measured 10 seconds prior to detrusor contraction. Patients completed a voiding diary, ICIQ-OAB questionnaire, and underwent fMRI+UDS before and after TSCS. Descriptive statistics and paired t-test were used when appropriate. RESULTS: Twelve patients (5 males, 7 females) with a mean age of 52.8±9.8 years old completed the study. After completion of TSCS, patients reported a decreased perception of urge per void (1.83±0.34 vs 0.92±0.21: p<0.05), number of urge incontinence episodes (6.96±2.12 vs 4.15±1.58: p><0.05), and an increased number of urge-free voids per 24 hours (0.27±0.09 vs 2.29±0.91; p<0.05). ICIQ-OAB scores were significantly lower post stimulation (9.6 vs 4.1; p=0.001). Functional MRI detected an increase in BOLD signal in the cerebellum, cuneus, and multiple frontal areas including the inferior, medial, and middle frontal gyri following TSCS. CONCLUSIONS: Patients that completed twelve weeks of TSCS experienced a significant reduction in perceived urge per void and urgency incontinence episodes and an increase in urge-free voids per 24 hours. ICIQ-OAB scores were significantly lower in patient’s post-spinal neuromodulation. TSCS resulted in a restoration of activation of several cortical brain regions. Source of Funding: Urology Care Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e707 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information David Chapman More articles by this author Luis Alejandro Morales Ojeda More articles by this author Veronica Stefania Montero Arcila More articles by this author Sarah Ponce More articles by this author Rita Jen More articles by this author Nhi Ha More articles by this author Parag Gad More articles by this author Reggie Edgerton More articles by this author David Ginsberg More articles by this author Aidin Abedi More articles by this author Kay Jann More articles by this author Evgeniy Kreydin More articles by this author Expand All Advertisement PDF downloadLoading ...

Resting-State Functional MRI/PET Profile as a Potential Alternative to Tri-Modality EEG-MR/PET Imaging: An Exploratory Study in Drug-Refractory Epilepsy.

Objective The study explores whether the epileptic networks associate with predetermined seizure onset zone (SOZ) identified from other modalities such as electroencephalogram/video electroencephalogram/structural MRI (EEG/VEEG/sMRI) and with the degree of resting-state functional MRI/positron emission tomography (RS-fMRI/PET) coupling. Here, we have analyzed the subgroup of patients who reported having a seizure on the day of scan as postictal cases and compared the findings with interictal cases (seizure-free interval). Methods We performed independent component analysis (ICA) on RS-fMRI and 20 ICA were hand-labeled as large scale, noise, downstream, and epilepsy networks (Epinets) based on their profile in spatial, time series, and power spectrum domains. We had a total of 43 cases, with 4 cases in the postictal group (100%). Of 39 cases, 14 cases did not yield any Epinet and 25 cases (61%) were analyzed for the final study. The analysis was done patient-wise and correlated with predetermined SOZ. Results The yield of finding Epinets on RS-fMRI is more during the postictal period than in the interictal period, although PET and RS-fMRI spatial, time series, and power spectral patterns were similar in both these subgroups. Overlaps between large-scale and downstream networks were noted, indicating that epilepsy propagation can involve large-scale cognition networks. Lateralization to SOZ was noted as blood oxygen level-dependent activation and correlated with sMRI/PET findings. Postoperative surgical failure cases showed residual Epinet profile. Conclusion RS-fMRI may be a viable option for trimodality imaging to obtain simultaneous physiological information at the functional network and metabolic level.

Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder

The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to low sexual desire; the most prevalent psychological form is hypoactive sexual desire disorder (HSDD), which affects 8% of men but currently has no effective pharmacological treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target, owing to emerging understanding of its role in reproductive behavior. To determine the physiological, behavioral, neural, and hormonal effects of kisspeptin administration in men with HSDD. This double-blind, 2-way crossover, placebo-controlled randomized clinical trial was performed at a single academic research center in the UK. Eligible participants were right-handed heterosexual men with HSDD. Physiological, behavioral, functional magnetic resonance imaging (fMRI), and hormonal analyses were used to investigate the clinical and mechanistic effects of kisspeptin administration in response to visual sexual stimuli (short and long video tasks). The trial was conducted between January 11 and September 15, 2021, and data analysis was performed between October and November 2021. Participants attended 2 study visits at least 7 days apart, in balanced random order, for intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or for administration of a rate-matched placebo. Changes in (1) brain activity on whole-brain analysis, as determined by fMRI blood oxygen level-dependent activity in response to visual sexual stimuli during kisspeptin administration compared with placebo, (2) physiological sexual arousal (penile tumescence), and (3) behavioral measures of sexual desire and arousal. Of the 37 men randomized, 32 completed the trial. Participants had a mean (SD) age of 37.9 (8.6) years and a mean (SD) body mass index of 24.9 (5.4). On viewing sexual videos, kisspeptin significantly modulated brain activity in key structures of the sexual-processing network on whole-brain analysis compared with placebo (mean absolute change [Cohen d] = 0.81 [95% CI, 0.41-1.21]; P = .003). Furthermore, improvements in several secondary analyses were observed, including significant increases in penile tumescence in response to sexual stimuli (by up to 56% more than placebo; mean difference = 0.28 units [95% CI, 0.04-0.52 units]; P = .02) and behavioral measures of sexual desire-most notably, increased happiness about sex (mean difference = 0.63 points [95% CI, 0.10-1.15 points]; P = .02). Collectively, this randomized clinical trial provides the first evidence to date showing that kisspeptin administration substantially modulates sexual brain processing in men with HSDD, with associated increases in penile tumescence and behavioral measures of sexual desire and arousal. These data suggest that kisspeptin has potential as the first pharmacological treatment for men with low sexual desire. isrctn.org Identifier: ISRCTN17271094.