Magnetic Resonance Imaging Blood Oxygen Research Articles

The missing third dimension-Functional correlations of BOLD signals incorporating white matter.

Correlations between magnetic resonance imaging (MRI) blood oxygenation level-dependent (BOLD) signals from pairs of gray matter areas are used to infer their functional connectivity, but they are unable to describe how white matter is engaged in brain networks. Recently, evidence that BOLD signals in white matter are robustly detectable and are modulated by neural activities has accumulated. We introduce a three-way correlation between BOLD signals from pairs of gray matter volumes (nodes) and white matter bundles (edges) to define the communication connectivity through each white matter bundle. Using MRI images from publicly available databases, we show, for example, that the three-way connectivity is influenced by age. By integrating functional MRI signals from white matter as a third component in network analyses, more comprehensive descriptions of brain function may be obtained.

Self-perception and anticipated efficacy of the anti-dementia multimodal program in 100 older adults with mild cognitive impairment.

Effective and sustainable interventions are clearly needed for mild cognitive impairment (MCI) patients. Despite the clinical importance of the multimodal intervention approach, only one study using a multimodal approach demonstrated promising improvements in memory, attention, and executive functions, which also correlated with functional magnetic resonance imaging (MRI) blood oxygenation level dependent (BOLD) changes in cerebral activation in 50 MCI patients. To investigate the self-perception and anticipated efficacy of each element of the BRAIN-FIT multimodal intervention program (robotic-assisted gait training (RAGT), computerized cognitive therapy, music, light, transcranial direct current stimulation (tDCS), and diaphragmatic breathing exercises) and the correlation between memory, concentration, depression, and sleep in older adults with MCI. One hundred participants (mean±standard deviation: 8.63±78.4 years; 47 women) with MCI were recruited from a major university medical center and community dementia relief center. The survey questionnaire comprised four domains with 21 questions, including four pertaining to general demographic characteristics, eight related to exercise and activity, three related to sleep, and nine related to the BRAIN-FIT program. Chi-squared test was used to analyze the Likert scale data. The descriptive frequencies were calculated. Additionally, Spearman's rho statistics measure the rank-order association. The statistical significance was at P < 0.05. A strong correlation was observed between memory and concentration (r = 0.850, P = 0.000), memory and depression (r = 0.540, P = 0.000), memory and sleep (r = 0.502, P = 0.000), concentration and depression (r = 0.602, P = 0.000), concentration and sleep (r = 0.529, P = 0.000) and sleep and depression (r = 0.497, P = 0.000). The correlation between medical services and sleep (r = 0.249, P = 0.012) was moderate. The chi-square test revealed a significant difference in memory and low-intensity duration of exercise (χ2[3,N = 100] = 11.69, P = 0.01), concentration and high-intensity exercise duration (χ2[3,N = 100] = 10.08, P = 0.02), concentration with low-intensity exercise duration (χ2[3,N = 100] = 21.11, P = 0.00), depression with high-intensity (χ2[3,N = 100] = 10.36, P = 0.02), high-intensity duration of exercise (χ2[3,N = 100] = 10.48, P = 0.02); low-intensity (χ2[3,N = 100] = 7.90, P = 0.48), and low-intensity duration of exercise (χ2[3,N = 100] = 9.69, P = 0.02). Additionally, significant differences were observed between sleep and high-intensity (χ2[3, N = 100] = 10.36, P = 0.02), low-intensity (χ2[3, N = 100] = 18.14, P = 0.00), and low-intensity duration of exercise (χ2[3, N = 100] = 18.30, P = 0.00). Among the participants 5% answered RAGT, and 20% responded that they had experienced computerized cognitive therapy. Music therapy (20 %), diaphragmatic breathing exercises (45 %), and light therapy (10 %) were used. No patient had experienced tDCS. Conversely, 11% of the participants answered RAGT for programs they wanted to experience and 21% responded to computerized cognitive therapy. 25% of music therapy, 22% of diaphragmatic breathing exercises, 5% of light therapy, and 16% of tDCS participants said they wanted to experience it. Finally, 63% of the participants wanted to participate in the BRAIN-FIT program. The present study's results provide clinical evidence-based insights into the utilization of BRAIN-FIT in MCI to maximize cognitive score improvement of memory, concentration, depression, and sleep. Therefore, when designing the BRAIN-FIT, six intervention items were set in proportion to the preference based on the survey, to reduce participants' feeling of repulsion. The program was configured according to exercise intensity.

Dynamic Effective Connectivity using Physiologically informed Dynamic Causal Model with Recurrent Units: A functional Magnetic Resonance Imaging simulation study.

Functional MRI (fMRI) is an indirect reflection of neuronal activity. Using generative biophysical model of fMRI data such as Dynamic Causal Model (DCM), the underlying neuronal activities of different brain areas and their causal interactions (i.e., effective connectivity) can be calculated. Most DCM studies typically consider the effective connectivity to be static for a cognitive task within an experimental run. However, changes in experimental conditions during complex tasks such as movie-watching might result in temporal variations in the connectivity strengths. In this fMRI simulation study, we leverage state-of-the-art Physiologically informed DCM (P-DCM) along with a recurrent window approach and discretization of the equations to infer the underlying neuronal dynamics and concurrently the dynamic (time-varying) effective connectivities between various brain regions for task-based fMRI. Results from simulation studies on 3- and 10-region models showed that functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) responses and effective connectivity time-courses can be accurately predicted and distinguished from faulty graphical connectivity models representing cognitive hypotheses. In summary, we propose and validate a novel approach to determine dynamic effective connectivity between brain areas during complex cognitive tasks by combining P-DCM with recurrent units.

Abnormal Spontaneous Blood Oxygenation Level Dependent Fluctuations in Children with Focal Cortical Dysplasias: Initial Findings in Surgically Confirmed Cases.

Focal cortical dysplasias (FCD) are a frequent cause of drug-resistant epilepsy in children but are often undetected on structural magnetic resonance imaging (MRI). We aimed to measure and validate the variation of resting state functional MRI (rs-fMRI) blood oxygenation level dependent (BOLD) metrics in surgically proven FCDs in children, to assess the potential yield for detecting and understanding these lesions. We prospectively included pediatric patients with surgically proven FCD with inconclusive structural MRI and healthy controls, who underwent a ten-minute rs-fMRI acquired at 3T. Rs-fMRI data was pre-processed and maps of values of regional homogeneity (ReHo), degree centrality (DC), amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF) were calculated. The variations of BOLD metrics within the to-be-resected areas were analyzed visually, and quantitatively using lateralization indices. BOLD metrics variations were also analyzed in fluorodeoxyglucose-positron emission tomography (FDG-PET) hypometabolic areas. We included 7 patients (range: 3-15 years) and 6 aged-matched controls (range: 6-17 years). ReHo lateralization indices were positive in the to-be-resected areas in 4/7 patients, and in 6/7 patients in the additional PET hypometabolic areas. These indices were significantly higher compared to controls in 3/7 and 4/7 patients, respectively. Visual analysis revealed a good spatial correlation between high ReHo areas and MRI structural abnormalities (when present) or PET hypometabolic areas. No consistent variation was seen using DC, ALFF, or fALFF. Resting-state fMRI metrics, noticeably increase in ReHo, may have potential to help detect MRI-negative FCDs in combination with other morphological and functional techniques, used in clinical practice and epilepsy-surgery screening.

A Neurobiological Profile Underlying Comorbidity Load and Prospective Increases in Dysphoria in a Focal Fear Sample

BackgroundKnowledge of the neural mechanisms underlying increased disease burden in anxiety disorders that is unaccounted for by individual categorical diagnoses could lead to improved clinical care. Here, we tested the utility of a joint functional magnetic resonance imaging–electroencephalography neurobiological profile characterized by overvaluation of negative stimuli (amygdala) in combination with blunted elaborated processing of these same stimuli (the late positive potential [LPP], an event-related potential) in predicting increased psychopathology across a 2-year period in people with anxiety disorders. MethodsOne hundred ten participants (64 female, 45 male, 1 other) including 78 participants with phobias who varied in the extent of their internalizing comorbidity and 32 participants who were free from psychopathology viewed negative and neutral pictures during separate functional magnetic resonance imaging blood oxygen level–dependent and electroencephalogram recordings. Dysphoria was assessed at baseline and 2 years later. ResultsParticipants with both heightened amygdala activation and blunted LPPs to negative pictures showed the greatest increases in dysphoria 2 years later. Cross-sectionally, participants with higher comorbidity load (≥2 additional diagnoses, n = 34) showed increased amygdala activation to negative pictures compared with participants with lower comorbidity load (≤1 additional diagnosis, n = 44) and compared with participants free from psychopathology. In addition, high comorbid participants showed reduced LPPs to negative pictures compared with low comorbid participants. ConclusionsHeightened amygdala in response to negative stimuli in combination with blunted LPPs could indicate overvaluation of threatening stimuli in the absence of elaborated processing that might otherwise help regulate threat responding. This brain profile could underlie the worsening and maintenance of internalizing psychopathology over time.

Cortical depth profiles of auditory and visual 7T functional MRI responses in human superior temporal areas.

Invasive neurophysiological studies in nonhuman primates have shown different laminar activation profiles to auditory vs. visual stimuli in auditory cortices and adjacent polymodal areas. Means to examine the underlying feedforward vs. feedback type influences noninvasively have been limited in humans. Here, using 1-mm isotropic resolution 3D echo-planar imaging at 7 T, we studied the intracortical depth profiles of functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) signals to brief auditory (noise bursts) and visual (checkerboard) stimuli. BOLD percent-signal-changes were estimated at 11 equally spaced intracortical depths, within regions-of-interest encompassing auditory (Heschl's gyrus, Heschl's sulcus, planum temporale, and posterior superior temporal gyrus) and polymodal (middle and posterior superior temporal sulcus) areas. Effects of differing BOLD signal strengths for auditory and visual stimuli were controlled via normalization and statistical modeling. The BOLD depth profile shapes, modeled with quadratic regression, were significantly different for auditory vs. visual stimuli in auditory cortices, but not in polymodal areas. The different depth profiles could reflect sensory-specific feedforward versus cross-sensory feedback influences, previously shown in laminar recordings in nonhuman primates. The results suggest that intracortical BOLD profiles can help distinguish between feedforward and feedback type influences in the human brain. Further experimental studies are still needed to clarify how underlying signal strength influences BOLD depth profiles under different stimulus conditions.

No-Reference Video Quality Assessment Using Voxel-Wise fMRI Models of the Visual Cortex

The performance of the human visual system is very efficient in many visual tasks such as identifying visual scenes, anticipating future actions based on the past observations, assessing the quality of visual stimuli, etc. A significant amount of effort has been directed towards finding quality aware representations of natural videos to solve the quality prediction task. In this work we present a novel no reference video quality assessment (NR-VQA) algorithm based on the functional Magnetic Resonance Imaging (fMRI) Blood Oxygen Level Dependent (BOLD) signal prediction with voxel-wise encoding models of the human brain. The voxel encoding models are learnt using deep features extracted from the AlexNet model to predict the fMRI response to natural video stimuli. We show that the curvature in the predicted voxel response time series provides good quality discriminability, and forms an important feature for quality prediction. Further, we show that the proposed curvature features in combination with the spatial index, temporal index and NIQE features deliver acceptable performance on the Video Quality Assessment (VQA) task on both synthetic and authentic distortion data-sets.

Low-Dose Augmentation With Buprenorphine for Treatment-Resistant Depression: A Multisite Randomized Controlled Trial With Multimodal Assessment of Target Engagement

BackgroundThe experimental therapeutics approach that combines a placebo-controlled clinical trial with translational neuroscience methods can provide a better understanding of both the clinical and physiological effects of pharmacotherapy. We aimed to test the efficacy and tolerability of low-dose augmentation with buprenorphine (BPN) for treatment-resistant depression, combined with multimodal assessment of target engagement. MethodsIn this multisite randomized clinical trial, 85 participants ≥50 years of age with a major depressive episode that had not responded to venlafaxine extended release were randomized to augmentation with BPN or placebo for 8 weeks. The primary outcome measure was the Montgomery–Åsberg Depression Rating Scale. In addition, three linked experiments were conducted to test target engagement: 1) functional magnetic resonance imaging using the monetary incentive delay task, 2) brain positron emission tomography of healthy participants using a novel kappa opioid receptor antagonist tracer [11C]LY2795050, and 3) transcranial magnetic stimulation measure of cortical transmission after daily BPN administration. ResultsThe mean ± SD dosage of BPN was 0.59 ± 0.33 mg/day. There were no significant differences between the BPN and placebo groups in Montgomery–Åsberg Depression Rating Scale changes over time or adverse effects. BPN administration had minimal effects on functional magnetic resonance imaging blood oxygen level–dependent responses in regions involved in reward anticipation and response, no significant displacement of kappa opioid receptor radioligand in positron emission tomography imaging, and no significant changes in transcranial magnetic stimulation measures of inhibitory and excitatory cortical transmission. ConclusionsOur findings suggest a lack of clinical effect of low-dose BPN augmentation and lack of target engagement with this dosage and physiological probes.

Static versus Functional PET: Making Sense of Metabolic Connectivity.

Recently, Jamadar etal. (2021, Metabolic and hemodynamic resting-state connectivity of the human brain: a high-temporal resolution simultaneous BOLD-fMRI and FDG-fPET multimodality study. Cereb Cortex. 31(6), 2855-2867) compared the patterns of brain connectivity or covariance as obtained from 3 neuroimaging measures: 1) functional connectivity estimated from temporal correlations in the functional magnetic resonance imaging blood oxygen level-dependent signal, metabolic connectivity estimated, 2) from temporal correlations in 16-s frames of dynamic [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), which they designate as functional FDG-PET (fPET), and 3) from intersubject correlations in static FDG-PET images (sPET). Here, we discuss a number of fundamental issues raised by the Jamadar study. These include the choice of terminology, the interpretation of cross-modal findings, the issue of group- to single-subject level inferences, and the meaning of metabolic connectivity as a biomarker. We applaud the methodological approach taken by the authors, but wish to present an alternative perspective on their findings. In particular, we argue that sPET and fPET can both provide valuable information about brain connectivity. Certainly, resolving this conundrum calls for further experimental and theoretical efforts to advance the developing framework of PET-based brain connectivity indices.

Evaluation of Cognitive Behavioral Therapy vs Mindfulness Meditation in Brain Changes During Reappraisal and Acceptance Among Patients With Social Anxiety Disorder

Cognitive behavioral group therapy (CBGT) and mindfulness-based stress reduction (MBSR) are thought to help patients with social anxiety disorder (SAD) via distinct emotion-regulation mechanisms. However, no study has compared the effects of CBGT and MBSR on brain and negative emotion indicators of cognitive reappraisal and acceptance in patients with SAD. To investigate the effects of CBGT and MBSR on reappraisal and acceptance in patients with SAD and to test whether treatment-associated brain changes are associated with social anxiety symptoms 1 year posttreatment. In this randomized clinical trial, a total of 108 unmedicated adults diagnosed with generalized SAD were randomly assigned to 12 weeks of CBGT, MBSR, or waitlist. The final sample included 31 patients receiving CBGT, 32 patients receiving MBSR, and 32 waitlist patients. Data were collected at the psychology department at Stanford University from September 2012 to December 2014. Data were analyzed from February 2019 to December 2020. CBGT and MBSR. Changes in self-reported negative emotion and functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signal within an a priori-defined brain search region mask derived from a meta-analysis of cognitive reappraisal and attention regulation 1 year posttreatment. Of 108 participants, 60 (56%) were female. The mean (SD) age was 32.7 (8.0) years. Self-reported race and ethnicity data were collected to inform the generalizability of the study to the wider population and to satisfy the requirements of the National Institutes of Health. From the categories provided by the National Institutes of Health, 47 participants selected White (43.5%), 42 selected Asian (38.9%) 10 selected Latinx (9.3%), 1 selected Black (1%), 1 selected Native American (1%), and 7 selected more than 1 race (6.5%). CBGT and MBSR were associated with a significant decrease in negative emotion (partial η2 range, 0.38 to 0.53) with no significant between-group differences when reacting (β, -0.04; SE, 0.09; 95% CI, -0.11 to 0.08; t92 = -0.37; P = .71), reappraising (β, -0.15; SE, 0.09; 95% CI, -0.32 to 0.03; t92 = -1.67; P = .10), or accepting (β, -0.05; SE, 0.08; 95% CI, -0.20 to 0.11; t92 = -0.59; P = .56). There was a significant increase in BOLD percentage signal change in cognitive and attention-regulation regions when reappraising (CBGT = 0.031; MBSR = 0.037) and accepting (CBGT = 0.012; MBSR = 0.077) negative self-beliefs. CBGT and MBSR did not differ in decreased negative emotion and increased reappraisal and acceptance BOLD responses. Reappraisal-associated MBSR (vs CBGT) negative emotions and CBGT (vs MBSR) brain responses were associated with social anxiety symptoms 1 year posttreatment. The results of this study suggest that CBGT and MBSR may be effective treatments with long-term benefits for patients with SAD that recruit cognitive and attention-regulation brain networks. Despite contrasting models of therapeutic change, CBT and MBSR may both enhance reappraisal and acceptance emotion regulation strategies. ClinicalTrials.gov Identifier: NCT02036658.

Sensing and seeing associated with overlapping occipitoparietal activation in simultaneous EEG-fMRI.

The presence of a change in a visual scene can influence brain activity and behavior, even in the absence of full conscious report. It may be possible for us to sense that such a change has occurred, even if we cannot specify exactly where or what it was. Despite existing evidence from electroencephalogram (EEG) and eye-tracking data, it is still unclear how this partial level of awareness relates to functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) activation. Using EEG, fMRI, and a change blindness paradigm, we found multi-modal evidence to suggest that sensing a change is distinguishable from being blind to it. Specifically, trials during which participants could detect the presence of a colour change but not identify the location of the change (sense trials), were compared to those where participants could both detect and localise the change (localise or see trials), as well as change blind trials. In EEG, late parietal positivity and N2 amplitudes were larger for localised changes only, when compared to change blindness. However, ERP-informed fMRI analysis found no voxels with activation that significantly co-varied with fluctuations in single-trial late positivity amplitudes. In fMRI, a range of visual (BA17,18), parietal (BA7,40), and mid-brain (anterior cingulate, BA24) areas showed increased fMRI BOLD activation when a change was sensed, compared to change blindness. These visual and parietal areas are commonly implicated as the storage sites of visual working memory, and we therefore argue that sensing may not be explained by a lack of stored representation of the visual display. Both seeing and sensing a change were associated with an overlapping occipitoparietal network of activation when compared to blind trials, suggesting that the quality of the visual representation, rather than the lack of one, may result in partial awareness during the change blindness paradigm.

Determining the impact of age and sex on the psychophysical and neurophysiological response to thermal pain across the adult lifespan.

AimsDetermine sex‐ and age‐associated psychophysical and neurophysiological differences in the processing of pain across the adult lifespan.DesignPreliminary, exploratory, cross‐sectional study.MethodsUsing psychophysics (to measure intensity and unpleasantness) and functional magnetic resonance imaging blood oxygenation level dependent methods (to measure stimulus‐evoked brain activation), we will examine sex‐ and age‐associated differences in thermal pain processing and their underlying neurophysiology in a broad range of healthy adults (ages 30–89). We will acquire resting state functional connectivity data for secondary analyses exploring whether resting state connectivity predicts psychophysical and neurophysiological responses to thermal pain. To examine the effects of altered blood flow, we will acquire resting‐state arterial spin labeling magnetic resonance imaging data to quantify resting cerebral blood flow. We will interpret findings in the context of a proposed neural model of pain, ageing, and sex. Study funding was received in June of 2014. Ethical approval was obtained from the Vanderbilt University IRB prior to study initiation.ConclusionExploring the biological reasons for age‐ and sex‐associated differences in pain processing will increase our understanding of pain in older adults. The paucity of neurobiological evidence to support best practice pain management in older adults places these individuals at risk for poor pain management.ImpactPoorly treated pain in older adults is a critical public health problem associated with a poor quality of life and increased healthcare costs. Understanding how age and sex have an impact on central processing of pain across the lifespan is a critical step toward improving personalized pain medicine.

Greater BOLD Variability is Associated With Poorer Cognitive Function in an Adult Lifespan Sample.

Moment-to-moment fluctuations in brain signal assessed by functional magnetic resonance imaging blood oxygenation level dependent (BOLD) variability is increasingly thought to represent important “signal” rather than measurement-related “noise.” Efforts to characterize BOLD variability in healthy aging have yielded mixed outcomes, demonstrating both age-related increases and decreases in BOLD variability and both detrimental and beneficial associations. Utilizing BOLD mean-squared-successive-differences (MSSD) during a digit n-back working memory (WM) task in a sample of healthy adults (aged 20–94 years; n = 171), we examined effects of aging on whole-brain 1) BOLD variability during task (mean condition MSSD across 0–2–3-4 back conditions), 2) BOLD variability modulation to incrementally increasing WM difficulty (linear slope from 0–2–3-4 back), and 3) the association of age-related differences in variability with in- and out-of-scanner WM performance. Widespread cortical and subcortical regions evidenced increased mean variability with increasing age, with no regions evidencing age-related decrease in variability. Additionally, posterior cingulate/precuneus exhibited increased variability to WM difficulty. Notably, both age-related increases in BOLD variability were associated with significantly poorer WM performance in all but the oldest adults. These findings lend support to the growing corpus suggesting that brain-signal variability is altered in healthy aging; specifically, in this adult lifespan sample, BOLD-variability increased with age and was detrimental to cognitive performance.

Translational Development Strategies for TAK-063, a Phosphodiesterase 10A Inhibitor.

BackgroundTAK-063 is an inhibitor of phosphodiesterase 10A (PDE10A), an enzyme highly expressed in medium spiny neurons of the striatum. PDE10A hydrolyzes both cyclic adenosine monophosphate and cyclic guanosine monophosphate and modulates dopamine signaling downstream of receptor activation in both direct and indirect pathways of the striatum. TAK-063 exhibited antipsychotic-like effects in animal models; however, the translatability of these models to the clinical manifestations of schizophrenia and the meaningfulness for new targets such as PDE10A has not been established.MethodsThe TAK-063 phase 1 program included a comprehensive translational development strategy with the main objective of determining whether the antipsychotic-like pharmacodynamic effects seen in nonclinical models would translate to human subjects. To evaluate this objective, we conducted a single-rising dose study (84 healthy subjects), a positron emission tomography (PET) study (12 healthy subjects), a functional magnetic resonance imaging blood oxygen level-dependent (BOLD) study (27 healthy subjects), and a multiple-rising dose study that included people with schizophrenia (30 healthy Japanese subjects and 47 subjects with stable schizophrenia). In addition, assessments of cognition and electroencephalography (27 healthy subjects and 47 subjects with stable schizophrenia) were included.ResultsPDE10A engagement by TAK-063 was verified with a novel PET radiotracer for use in primates and humans. TAK-063 showed favorable pharmacokinetic and safety profiles in humans, and TAK-063 reduced ketamine-induced changes in electroencephalography and BOLD signaling in animal models and healthy human subjects. In addition, analogous effects on cognition were observed in animal models and human subjects.ConclusionsOverall, the phase 1 results showed some consistent evidence of antipsychotic activity. This translational strategy may be valuable for the future development of novel therapeutic approaches, even when relevant nonclinical models are not available.

Oxytocin reduces the functional connectivity between brain regions involved in eating behavior in men with overweight and obesity.

Background:Oxytocin (OXT), shown to decrease food intake in animal models and men, is a promising novel treatment for obesity. We have shown that in men with overweight and obesity, intranasal (IN) OXT reduced the functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent signal in the ventral tegmental area (VTA), the origin of the mesolimbic dopaminergic reward system, in response to high-calorie food vs. non-food images. Here, we employed functional connectivity fMRI analysis, which measures the synchrony in activation between neural systems in a context-dependent manner. We hypothesized that OXT would attenuate the functional connectivity of the VTA with key food motivation brain areas only when participants viewed high-calorie food stimuli.Methods:This randomized, double-blind, placebo-controlled crossover study of 24 IU IN OXT included 10 men with overweight or obesity (mean±SEM BMI: 28.9±0.8 kg/m2). Following drug administration, subjects completed an fMRI food motivation paradigm including images of high and low-calorie foods, non-food objects, and fixation stimuli. A psychophysiological interaction analysis was performed with the VTA as seed region.Results:Following OXT administration, compared with placebo, participants exhibited significantly attenuated functional connectivity between the VTA and the insula, oral somatosensory cortex, amygdala, hippocampus, operculum, and middle temporal gyrus in response to viewing high-calorie foods (Z≥3.1, cluster-corrected, p<0.05). There was no difference in functional connectivity between VTA and these brain areas when comparing OXT and placebo for low-calorie food, non-food, and fixation images.Conclusion:In men with overweight and obesity, OXT attenuates the functional connectivity between the VTA and food motivation brain regions in response to high-calorie visual food images. These findings could partially explain the observed anorexigenic effect of OXT, providing insight into the mechanism through which OXT ameliorates food cue-induced reward anticipation in patients with obesity. Additional studies are ongoing to further delineate the anorexigenic effect of OXT in obesity.

The Effects of Attentional Focus on Brain Function During a Gross Motor Task.

Although the beneficial effects of using an external focus of attention are well documented in attainment and performance of movement execution, neural mechanisms underlying external focus' benefits are mostly unknown. To assess brain function during a lower-extremity gross motor movement while manipulating an internal and external focus of attention. Cross-over study. Neuroimaging center Participants: A total of 10 healthy subjects (5 males and 5 females) Intervention: Participants completed external and internal focus of attention unilateral left 45° knee extension/flexion movements at a rate of 1.2Hz laying supine in a magnetic resonance imaging scanner for 4 blocks of 30 seconds interspersed with 30-second rest blocks. During the internal condition, participants were instructed to "squeeze their quadriceps." During the external condition, participants were instructed to "focus on a target" positioned above their tibia. T1 brain structural imaging was performed for registration of the functional data. For each condition, 3T functional magnetic resonance imaging blood oxygenation level dependent data representing 90 whole-brain volumes were acquired. During the external relative to internal condition, increased activation was detected in the right occipital pole, cuneal cortex, anterior portion of the lingual gyrus, and intracalcarine cortex (Zmax = 4.5-6.2, P < .001). During the internal relative to external condition, increased activation was detected in the left primary motor cortex, left supplementary motor cortex, and cerebellum (Zmax = 3.4-3.5, P < .001). Current results suggest that an external focus directed toward a visual target produces more brain activity in regions associated with vision and ventral streaming pathways, whereas an internal focus manipulated through instruction increases activation in brain regions that are responsible for motor control. Results from this study serve as baseline information for future prevention and rehabilitation investigations of how manipulating focus of attention can constructively affect neuroplasticity during training and rehabilitation.

Development of the functional connectivity of the frontoparietal mirror neuron network in preschool Children: An investigation under resting state

Previous task-related imaging studies in adults have demonstrated that there is a frontoparietal mirror neuron system (MNS) that preferentially engages in self-recognition. However, the development of the MNS during preschool (age 3–5 years) has not been thoroughly examined. In this study, we investigated the development of the MNS by examining the correlations in spontaneous fluctuations of the functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signal in healthy, 3–5-year-old preschool children (n = 30, 15 in each group). Using a ROI-based (inferior frontal gyrus) functional connectivity analysis, we identified a right lateralized MNS during rest in both groups with a positive correlation between the inferior frontal gyrus and inferior parietal lobule. A significant increase in the functional connectivity of the MNS was observed in the older group. Our results suggest that the spontaneous functional connectivity of the MNS is shaped at as early as 3 years of age and undergoes age-related development within the preschool period.

It's All About the Networks.

Interictal stereotactic-EEG functional connectivity in refractory focal epilepsies Lagarde S, Roehri N, Lambert I, et al. Brain. 2018;141(10):2966-2980. doi:10.1093/brain/awy214Drug-refractory focal epilepsies are network diseases associated with functional connectivity alterations both during ictal and interictal periods. A large majority of studies on the interictal/resting state have focused on functional magnetic resonance imaging (MRI)-based functional connectivity. Few studies have used electrophysiology, despite its high-temporal capacities. In particular, stereotactic-electroencephalogram (EEG) is highly suitable to study functional connectivity because it permits direct intracranial electrophysiological recordings with relative large-scale sampling. Most previous studies in stereotactic-EEG have been directed toward temporal lobe epilepsy, which does not represent the whole spectrum of drug-refractory epilepsies. The present study aims at filling this gap, investigating interictal functional connectivity alterations behind cortical epileptic organization and its association with postsurgical prognosis. To this purpose, we studied a large cohort of 59 patients with malformation of cortical development explored by stereotactic-EEG with a wide spatial sampling (76 distinct brain areas were recorded, median of 13.2 per patient). We computed functional connectivity using nonlinear correlation. We focused on 3 zones defined by stereotactic-EEG ictal activity: the epileptogenic zone (EZ), the propagation zone (PZ), and the noninvolved zone. First, we compared within-zone and between-zones functional connectivity. Second, we analyzed the directionality of functional connectivity between these zones. Third, we measured the associations between functional connectivity measures and clinical variables, especially postsurgical prognosis. Our study confirms that functional connectivity differs according to the zone under investigation. We found: (1) a gradual decrease in the within-zone functional connectivity with higher values for EZ and PZ, and lower for noninvolved zones; (2) preferential coupling between structures of the EZ; (3) preferential coupling between EZ and PZ; and (4) poorer postsurgical outcome in patients with higher functional connectivity of non-involved zone (within-noninvolved zone, between noninvolved zone, and PZ functional connectivity). Our work suggests that, even during the interictal state, functional connectivity is reinforced within epileptic cortices (EZ and PZ) with a gradual organization. Moreover, larger functional connectivity alterations, suggesting more diffuse disease, are associated with poorer postsurgical prognosis. This is consistent with computational studies suggesting that connectivity is crucial in order to model the spatiotemporal dynamics of seizures. Dynamic brain network states in human generalized spike-wave discharges Tangwiriyasakul C, Perani S, Centeno M, et al. Brain. 2018;141(10):2981-2994.Generalized spike-wave discharges in idiopathic generalized epilepsy are conventionally assumed to have abrupt onset and offset. However, in rodent models, discharges emerge during a dynamic evolution of brain network states, extending several seconds before and after the discharge. In human idiopathic generalized epilepsy, simultaneous EEG and functional MRI shows cortical regions may be active before discharges, and network connectivity around discharges may not be normal. Here, in human idiopathic generalized epilepsy, we investigated whether generalized spike-wave discharges emerge during a dynamic evolution of brain network states. Using EEG-functional MRI, we studied 43 patients and 34 healthy control subjects. We obtained 95 discharges from 20 patients. We compared data from patients with discharges with data from patients without discharges and healthy controls. Changes in MRI (blood oxygenation level dependent) signal amplitude in discharge epochs were observed only at and after EEG onset, involving a sequence of parietal and frontal cortical regions then thalamus (P < .01, across all regions and measurement time points). Examining MRI signal phase synchrony as a measure of functional connectivity between each pair of 90 brain regions, we found significant connections (P < .01, across all connections and measurement time points) involving frontal, parietal and occipital cortex during discharges, and for 20 seconds after EEG offset. This network prominent during discharges showed significantly low synchrony (below 99% confidence interval for synchrony in this network in nondischarge epochs in patients) from 16 seconds to 10 seconds before discharges, then ramped up steeply to a significantly high level of synchrony 2 seconds before discharge onset. Significant connections were seen in a sensorimotor network in the minute before discharge onset. This network also showed elevated synchrony in patients without discharges compared to healthy controls (P = .004). During 6 seconds prior to discharges, additional significant connections to this sensorimotor network were observed, involving prefrontal, and precuneus regions. In healthy subjects, significant connections involved a posterior cortical network. In patients with discharges, this posterior network showed significantly low synchrony during the minute prior to discharge onset. In patients without discharges, this network showed the same level of synchrony as in healthy controls. Our findings suggest persistently high sensorimotor network synchrony, coupled with transiently (at least 1 minute) low posterior network synchrony, may be a state predisposing to generalized spike-wave discharge onset. Our findings also show that EEG onset and associated MRI signal amplitude change is embedded in a considerably longer period of evolving brain network states before and after discharge events.

Effects of PDE5 inhibition on dystrophic muscle following an acute bout of downhill running and endurance training.

Lack of sarcolemma-localized neuronal nitric oxide synthase mu (nNOSμ) contributes to muscle damage and fatigue in dystrophic muscle. In this study, we examined the effects of compensating for lack of nNOSμ with a phosphodiesterase type 5 (PDE5) inhibitor in mdx mice following downhill running and endurance training. Dystrophic mice (mdx) were treated with sildenafil citrate and compared with untreated mdx and wild-type mice after an acute bout of downhill running and during a progressive low-intensity treadmill running program (5 days/wk, 4 wk). Magnetic resonance imaging (MRI) and spectroscopy (MRS) transverse relaxation time constant (T2) of hindlimb and forelimb muscles were measured as a marker of muscle damage after downhill running and throughout training. The MRI blood oxygenation level dependence (BOLD) response and 31phosphorus MRS (31P-MRS) data were acquired after stimulated muscle contractions. After downhill running, the increase in T2 was attenuated (P < 0.05) in treated mdx and wild-type mice compared with untreated mdx. During training, resting T2 values did not change in wild-type and mdx mice from baseline values; however, the running distance completed during training was greater (P < 0.05) in treated mdx (>90% of target distance) and wild-type (100%) than untreated mdx (60%). The post-contractile BOLD response was greater (P < 0.05) in treated mdx that trained than untreated mdx, with no differences in muscle oxidative capacity, as measured by 31P-MRS. Our findings indicate that PDE5 inhibition reduces muscle damage after a single bout of downhill running and improves performance during endurance training in dystrophic mice, possibly because of enhanced microvascular function. NEW & NOTEWORTHY This study examined the combined effects of PDE5 inhibition and exercise in dystrophic muscle using high-resolution magnetic resonance imaging and spectroscopy. Our findings demonstrated that sildenafil citrate reduces muscle damage after a single bout of downhill running, improves endurance-training performance, and enhances microvascular function in dystrophic muscle. Collectively, the results support the combination of exercise and PDE5 inhibition as a therapeutic approach in muscular dystrophies lacking nNOSμ.

BRAD: Software for BRain Activity Detection from hemodynamic response

Background and objective: Precise estimation of neuronal activity from neuroimaging data is one of the central challenges of the application of noninvasive neuroimaging methods. One of the widely used methods for studying brain activity is functional magnetic resonance imaging, which is a neuroimaging procedure that measures brain activity based on the blood oxygenation level dependent effect. The blood oxygenation level dependent signal can be modeled as a linear convolution of a hemodynamic response function with an input signal corresponding to the neuronal activity. Estimating such input signals is a complicated problem.Methods: We present a software tool for estimation of brain neuronal activity, which uses a combination of Wiener filtering with deconvolution methods, including the least absolute shrinkage and selection operator, the ordinary least squares method, and the Dantzig selector. The latter two are equipped with both established selection criteria (Akaike and Bayesian information criterion) as well as newly developed mixture criteria for selection of activations.Results: The software tool was tested on two types of data: measurements during basic visual experiments and during complex naturalistic audiovisual stimulation (watching a movie segment). During testing the software showed reasonable results, with the mixture criteria performing well for temporally extended activations.Conclusions: The presented software tool can be used for estimation, visualization, and analysis of brain neuronal activity from functional magnetic resonance imaging blood oxygenation level dependent measurements. The implemented methods provide valid results not only in the sparse activity scenario studied previously but also for temporally extended activations.