Level-dependent Functional Magnetic Resonance Research Articles

Attention-Related Brain Activation Is Altered in Older Adults With White Matter Hyperintensities Using Multi-Echo fMRI.

Cognitive decline is often undetectable in the early stages of accelerated vascular aging. Attentional processes are particularly affected in older adults with white matter hyperintensities (WMH), although specific neurovascular mechanisms have not been elucidated. We aimed to identify differences in attention-related neurofunctional activation and behavior between adults with and without WMH. Older adults with moderate to severe WMH (n = 18, mean age = 70 years), age-matched adults (n = 28, mean age = 72), and healthy younger adults (n = 19, mean age = 25) performed a modified flanker task during multi-echo blood oxygenation level dependent functional magnetic resonance imaging. Task-related activation was assessed using a weighted-echo approach. Healthy older adults had more widespread response and higher amplitude of activation compared to WMH adults in fronto-temporal and parietal cortices. Activation associated with processing speed was absent in the WMH group, suggesting attention-related activation deficits that may be a consequence of cerebral small vessel disease. WMH adults had greater executive contrast activation in the precuneous and posterior cingulate gyrus compared to HYA, despite no performance benefits, reinforcing the network dysfunction theory in WMH.

Modified Xiaoyaosan (MXYS) Exerts Anti-depressive Effects by Rectifying the Brain Blood Oxygen Level-Dependent fMRI Signals and Improving Hippocampal Neurogenesis in Mice.

As the traditional Chinese herbal formula, Xiaoyaosan and its modified formula have been described in many previous studies with definite anti-depressive effects, but its underlying mechanism remains mystery. Previous work in our lab has demonstrated that depression induced by chronic stress could generate brain blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals disorder, accompanied by the impairment of hippocampal neuronal plasticity, decrease of brain-derived neurotrophic factor, and reduction of the number and complexity of adult neurons in the dentate gyrus. We hypothesized that herbal formula based on Xiaoyaosan could exert anti-depressive effects through restoring these neurobiological dysfunctions and rectifying BOLD-fMRI signals. To test this hypothesis, we examined the effect of modified Xiaoyaosan (MXYS) on depressive-like behaviors, as well as hippocampal neurogenesis and BOLD signals in a mice model of chronic unpredictable mild stress (CUMS)-induced depression. MXYS exerted anti-depressant effects on CUMS-induced depression that were similar to the effects of classical antidepressants drug (fluoxetine hydrochloride), with a significant alleviation of depressive-like behaviors, an improvement of hippocampal neurogenesis, and a reversal of activation of BOLD in the limbic system, particularly in the hippocampus. These results suggested that MXYS attenuated CUMS-induced depressive behaviors by rectifying the BOLD signals in the mice hippocampus. These novel results demonstrated that MXYS had anti-depressive effects accompanied by improving BOLD signals and hippocampal neurogenesis, which suggested that BOLD-fMRI signals in brain regions could be a key component for the evaluation of novel antidepressant drugs.

Neural Activity During Mental Rotation in Deaf Signers: The Influence of Long-Term Sign Language Experience.

Mental rotation is the brain's visuospatial understanding of what objects are and where they belong. Previous research indicated that deaf signers showed behavioral enhancement for nonlinguistic visual tasks, including mental rotation. In this study, we investigated the neural difference of mental rotation processing between deaf signers and hearing nonsigners using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). The participants performed a block-designed experiment, consisting of alternating blocks of comparison and rotation periods, separated by a baseline or fixation period. Mental rotation tasks were performed using three-dimensional figures. fMRI images were acquired during the entire experiment, and the fMRI data were analyzed with Analysis of Functional NeuroImages. A factorial design analysis of variance was designed for fMRI analyses. The differences of activation were analyzed for the main effects of group and task, as well as for the interaction of group by task. The study showed differences in activated areas between deaf signers and hearing nonsigners on the mental rotation of three-dimensional figures. Subtracting activations of fixation from activations of rotation, both groups showed consistent activation in bilateral occipital lobe, bilateral parietal lobe, and bilateral posterior temporal lobe. There were different main effects of task (rotation versus comparison) with significant activation clusters in the bilateral precuneus, the right middle frontal gyrus, the bilateral medial frontal gyrus, the right interior frontal gyrus, the right superior frontal gyrus, the right anterior cingulate, and the bilateral posterior cingulate. There were significant interaction effects of group by task in the bilateral anterior cingulate, the right inferior frontal gyrus, the left superior frontal gyrus, the left posterior cingulate, the left middle temporal gyrus, and the right inferior parietal lobe. In simple effects of deaf and hearing groups with rotation minus comparison, deaf signers mainly showed activity in the right hemisphere, while hearing nonsigners showed bilateral activity. In the simple effects of rotation task, decreased activities were shown for deaf signers compared with hearing nonsigners throughout several regions, including the bilateral parahippocampal gyrus, the left posterior cingulate cortex, the right anterior cingulate cortex, and the right inferior parietal lobe. Decreased activations in several brain regions of deaf signers when compared to hearing nonsigners reflected increased neural efficiency and a precise functional circuitry, which was generated through long-term experience with sign language processing. In addition, we inferred tentatively that there may be a lateralization pattern to the right hemisphere for deaf signers when performing mental rotation tasks.

Application of BOLD-MRI in the classification of renal function in chronic kidney disease

PurposeThe purpose of the study was to explore the application of blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-MRI) in classification of chronic kidney disease (CKD).MethodsTwenty-nine cases with CKD and 27 healthy volunteers underwent renal BOLD-MRI. Cases of CKD were divided into two groups according to the estimated glomerular filtration rate (eGFR). The R2* values were measured in renal cortex and medulla, respectively. The difference of R2* between renal cortex and medulla was compared, and the correlations of R2* value in renal cortex and medulla with eGFR were analyzed.ResultsTwenty-nine cases of CKD were divided into two groups, with 13 cases of mild renal impairment and 16 cases of moderate to severe renal impairment. In the control and mild renal impairment group, the R2* of renal cortex was significantly lower than that of medulla (P < 0.001). In the control group, mild renal impairment and moderate to severe renal impairment group, the R2* value of cortex increased, while the R2* value of medulla gradually decreased. The eGFR of patients was positively correlated with R2* of medulla (r = 0.81, P < 0.001), while displayed no correlation with R2* of cortex (r = − 0.32, P > 0.05). When the threshold of R2* of medulla was set at 28.4 Hz, the sensitivity and specificity to distinguish normal and mild renal impairment group were 92.31% and 85.19%, respectively.ConclusionThe change of blood oxygen in renal cortex and medulla could be detected with BOLD-MRI, so as to evaluate the renal function and anoxic injury of CKD.

Physiological and Pathological Brain Activation in the Anesthetized Rat Produces Hemodynamic-Dependent Cortical Temperature Increases That Can Confound the BOLD fMRI Signal.

Anesthetized rodent models are ubiquitous in pre-clinical neuroimaging studies. However, because the associated cerebral morphology and experimental methodology results in a profound negative brain-core temperature differential, cerebral temperature changes during functional activation are likely to be principally driven by local inflow of fresh, core-temperature, blood. This presents a confound to the interpretation of blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data acquired from such models, since this signal is also critically temperature-dependent. Nevertheless, previous investigation on the subject is surprisingly sparse. Here, we address this issue through use of a novel multi-modal methodology in the urethane anesthetized rat. We reveal that sensory stimulation, hypercapnia and recurrent acute seizures induce significant increases in cortical temperature that are preferentially correlated to changes in total hemoglobin concentration (Hbt), relative to cerebral blood flow and oxidative metabolism. Furthermore, using a phantom-based evaluation of the effect of such temperature changes on the BOLD fMRI signal, we demonstrate a robust inverse relationship between both variables. These findings suggest that temperature increases, due to functional hyperemia, should be accounted for to ensure accurate interpretation of BOLD fMRI signals in pre-clinical neuroimaging studies.

Brain structural changes associated with aberrant functional responses to the Valsalva maneuver in heart failure.

Heart failure (HF) patients show inability to regulate autonomic functions in response to autonomic challenges. The autonomic deficits may stem from brain tissue injury in central autonomic regulatory areas, resulting from ischemic and hypoxic processes accompanying the condition. However, the direct evaluation of correlations between brain structural injury and functional timing and magnitude of neural signal patterns within affected areas, which may lead to impaired autonomic outflow, is unclear. In this study, we evaluate neural responses to the Valsalva maneuver with blood oxygen level-dependent functional magnetic resonance imaging in 29 HF patients and 35 control subjects and brain structural changes using diffusion tensor imaging-based mean diffusivity in a subsample of 19 HF and 24 control subjects. HF showed decreased neural activation in multiple autonomic and motor control areas, including cerebellum cortices, vermis, left insular, left putamen, and bilateral postcentral gyrus. Structural brain changes emerged in similar autonomic, as well as cognitive and mood regulation areas. Functional MRI responses in cerebellum and insula in HF subjects are delayed or decreased in magnitude to the challenge. The impaired functional responses of insular and cerebellar sites are correlated with the severity of tissue changes. These results indicate that the functions of insular and cerebellar regions, sites that are involved in autonomic regulation, are compromised, and that autonomic deficits in these areas have brain structural basis for impaired functions. Our study enhanced our understanding of brain structural and functional alterations underlying impaired autonomic regulations in HF subjects.

A combined study of 18F-FDG PET-CT and fMRI for assessing resting cerebral function in patients with major depressive disorder.

The present study investigated changes in the regional cerebral metabolic rates of glucose uptake (rCMRglc) using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and regional homogeneity (ReHo), together with resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), in patients with major depressive disorder (MDD). In total, 18 patients with untreated MDD and 17 healthy control subjects underwent 18F-FDG PET and BOLD-fMRI scanning. The MDD patients' cerebral changes, measured as rCMRglc and ReHo values, were mapped and statistically analyzed. Compared with the control group, the patients with MDD had a decreased rCMRglc in the bilateral superior, middle and inferior frontal gyrus, in the bilateral superior and middle temporal gyrus, in the bilateral anterior cingulate cortex, in the bilateral putamen and caudate, and in the left pallidum, but an increased rCMRglc in the bilateral hippocampus and left thalamus. The ReHo values in the patient group were decreased in the bilateral superior and middle frontal gyrus, left pallidum, bilateral putamen and left anterior cingulate cortex, but increased in the right hippocampus and thalamus. No statistically significant differences were identified between decreased metabolism and ReHo brain regions of MDD patients (χ2=9.16; P=0.90) and between increased metabolism and ReHo brain regions (χ2=3.96; P=0.27), when comparing activated brain regions of PET and MRI. The standardized uptake values (SUV) of the bilateral superior, middle and inferior frontal gyrus, bilateral superior and middle temporal gyrus, bilateral putamen, the left caudate and pallidum, the left anterior cingulate cortex, and the bilateral hippocampus and thalamus were correlated with the ReHo (r=0.51–0.83; P<0.05). However, no correlation was detected between the SUV and ReHo in the right caudate and anterior cingulate cortex (r=0.41 and 0.37, respectively; P>0.05). Taken together, these results demonstrated that patients with MDD displayed characteristic patterns regarding changes of brain glucose uptake and ReHo in the resting state. Furthermore, 18F-FDG PET may be a more sensitive technique compared with BOLD-fMRI for the identification of brain lesions in patients with MDD.

P29. Differential linear and nonlinear brain activation for probabilistic aversive outcomes in pathological gamblers and controls

Objective Functional imaging studies on decision making under uncertain risk of negative (aversive) outcomes are scarce. To get a better understanding of the underlying processes, we tested models of decision making including participants that were gambling regularly despite negative long-term consequences. Primarily, we sought to detect group differences in cortical and subcortical regions involved in decision processes. Also, we wanted to investigate, if current economic decision making models account for observable physiological data. Do we process aversive contingencies of decisions in a linear or a nonlinear manner, or both? Methods We studied 22 pathological and 18 habitual gamblers, as well as 23 control subjects, evaluated by psychologists with a semi-structured interview and self-reported Southern Oaks Gambling Scale. Participants were scanned with blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and engaged in a card game in which un-ambiguous situations of various risk levels for punishment (unpleasant, but not painful electric shocks) were created. Apart from neural responses to punishment, our paradigm allowed us to measure how neural activity during expectation of a punishment is modulated by the probability to be punished (risk) or the certainty of the outcome (certainty). Results Extending previous work and testing our hypothesis, based on economic studies, we modelled expected outcomes according to the prospect theory. Activations differed spatially when situations were modelled according to risk or certainty. With linearly increasing chances of avoiding punishment we found that the BOLD signal increased in the orbitofrontal cortex, caudate nucleus, precuneus, and the posterior cingulate cortex ( Fig. 1 a). Conversely, with increasing certainty of an outcome (U-shaped from most certain punishment to most certain avoidance), we could demonstrate nonlinear activations in medial superior frontal cortex, anterior cingulate cortex, anterior insula and angular gyrus ( Fig. 1 b). Interestingly, we found no group differences in cerebral activation during the task, which dovetailed with ‘offline’ behavioural analyses of decision making in the same groups. Conclusion Our results support the notion that economic decision making contains both linear and nonlinear cognitive processes largely following contingencies for risk and certainty and provide evidence that these cognitive processes are represented in different sets of brain regions. Correlates of the risk for punishment were found in areas known to be involved in dopaminergic reinforcement learning, while regions known to sub serve decision making, conflict monitoring and punishment show correlation with certainty of the outcome. While differences in reward perception in pathological gamblers are frequently described in the literature, we found no evidence for changes in punishment perception.

Impact of short- and long-term mindfulness meditation training on amygdala reactivity to emotional stimuli

Meditation training can improve mood and emotion regulation, yet the neural mechanisms of these affective changes have yet to be fully elucidated. We evaluated the impact of long- and short-term mindfulness meditation training on the amygdala response to emotional pictures in a healthy, non-clinical population of adults using blood-oxygen level dependent functional magnetic resonance imaging. Long-term meditators (N = 30, 16 female) had 9081 h of lifetime practice on average, primarily in mindfulness meditation. Short-term training consisted of an 8-week Mindfulness- Based Stress Reduction course (N = 32, 22 female), which was compared to an active control condition (N = 35, 19 female) in a randomized controlled trial. Meditation training was associated with less amygdala reactivity to positive pictures relative to controls, but there were no group differences in response to negative pictures. Reductions in reactivity to negative stimuli may require more practice experience or concentrated practice, as hours of retreat practice in long-term meditators was associated with lower amygdala reactivity to negative pictures – yet we did not see this relationship for practice time with MBSR. Short-term training, compared to the control intervention, also led to increased functional connectivity between the amygdala and a region implicated in emotion regulation – ventromedial prefrontal cortex (VMPFC) – during affective pictures. Thus, meditation training may improve affective responding through reduced amygdala reactivity, and heightened amygdala–VMPFC connectivity during affective stimuli may reflect a potential mechanism by which MBSR exerts salutary effects on emotion regulation ability.

Brain response to food brands correlates with increased intake from branded meals in children: an fMRI study.

Food branding is ubiquitous, however, not all children are equally susceptible to its effects. The objectives of this study were to 1) determine whether food brands evoke differential response than non-food brands in brain areas related to motivation and inhibitory control using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and 2) determine the association between brain response and energy intake at test-meals presented with or without brands. Twenty-eight 7-10year-old children completed four visits as part of a within-subjects design where they consumed three multi-item test-meals presented with familiar food brands, novel food brand, and no brand. On the fourth visit an fMRI was performed where children passively viewed food brands, non-food brands and control images. A whole-brain analysis was conducted to compare BOLD response between conditions. Pearson's correlations were calculated to determine the association between brain response and meal intake. Relative to non-food brands, food brand images were associated with increased activity in the right lingual gyrus. Relative to control, food and non-food brand images were associated with greater response in bilateral fusiform gyri and decreased response in the cuneus, precuneus, lingual gyrus, and supramarginal gyrus. Less activation in the bilateral fusiform gyrus to both food and non-food brands was associated with greater energy intake of the branded vs unbranded meal. These findings may help explain differences in the susceptibility to the intake-promoting effects of food advertising in children.

Adolescent Hippocampal and Prefrontal Brain Activation During Performance of the Virtual Morris Water Task.

The frontal cortex undergoes substantial structural and functional changes during adolescence and significant developmental changes also occur in the hippocampus. Both of these regions are notably vulnerable to alcohol and other substance use, which is typically initiated during adolescence. Identifying measures of brain function during adolescence, particularly before initiation of drug or alcohol use, is critical to understanding how such behaviors may affect brain development, especially in these vulnerable brain regions. While there is a substantial developmental literature on adolescent working memory, less is known about spatial memory. Thus, a virtual Morris water task (vMWT) was applied to probe function of the adolescent hippocampus. Multiband blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) data were acquired at 3T during task performance. Participants included 32 healthy, alcohol- and drug-naïve adolescents, 13–14 years old, examined at baseline of a 3-year longitudinal MRI study. Significantly greater BOLD activation was observed in the hippocampus and surrounding areas, and in prefrontal regions involved in executive function, during retrieval relative to motor performance. In contrast, significantly greater BOLD activation was observed in components of the default mode network, including frontal medial cortex, during the motor condition (when task demands were minimal) relative to the retrieval condition. Worse performance (longer path length) during retrieval was associated with greater activation of angular gyrus/supramarginal gyrus, whereas worse performance (longer path length/latency) during motor control was associated with less activation of frontal pole. Furthermore, while latency (time to complete task) was greater in females than in males, there were no sex differences in path length (accuracy), suggesting that females required more time to navigate the virtual environment, but did so as effectively as males. These findings demonstrate that performance of the vMWT elicits hippocampal and prefrontal activation patterns in early adolescence, similar to activation observed during spatial memory retrieval in adults. Given that this task is sensitive to hippocampal function, and that the adolescent hippocampus is notably vulnerable to the effects of alcohol and other substances, data acquired using this task during healthy adolescent development may provide a framework for understanding neurobiological impact of later initiation of use.

Cortical Activation Changes in Hirayama Disease After Anterior Cervical Decompression and Fusion

Spinal cord injury may cause cortical reconstruction. We, therefore explored the changes in cortical activation before and after anterior cervical decompression and fusion surgery in patients with Hirayama disease (HD). In total, 17 cases with HD underwent anterior cervical decompression and fusion surgery. Blood oxygenation level-dependent functional magnetic resonance imaging scan was performed preoperatively, 3 months, 6 months, and 1 year after surgery. Activated voxels were compared between both hands after adjusting for head motion, slice timing, spatial normalization, and image smoothing. Grip strength also was tested in both hands. A retrospective review indicated that the grip strength of the asymptomatic hand was significantly stronger than the symptomatic hand at the time point before the surgery, 3 months after surgery, 6 months after surgery, and 1 year after surgery (P < 0.001). The grip strength of both symptomatic and asymptomatic hands continuously increased within 6 months after surgery (P < 0.05), but it stopped at 1 year after the surgery. The symptomatic limb tends to produce bilateral activation in the primary motor area (M1) during motor tasks. Both contralateral and ipsilateral M1 activation were stronger in symptomatic hand tasks preoperatively (P < 0.05). Both contralateral and ipsilateral activation in M1 during symptomatic hand tasks began to reduce after surgery, and statistical significance was observed 6 months after surgery (P<0.05). Contralateral activation was relatively even over 6 months of the surgery (P > 0.05). After surgery, pathologic reconstruction may have occurred in the primary motor cortex. Recovery of motor function in the symptomatic limb was accompanied by decreased ipsilateral and contralateral M1 activation, as well as symptom improvement. These findings suggested that postoperative cortical activation changes may reflect functional recovery in HD.

Converging Evidence From Electrocorticography and BOLD fMRI for a Sharp Functional Boundary in Superior Temporal Gyrus Related to Multisensory Speech Processing.

Although humans can understand speech using the auditory modality alone, in noisy environments visual speech information from the talker’s mouth can rescue otherwise unintelligible auditory speech. To investigate the neural substrates of multisensory speech perception, we compared neural activity from the human superior temporal gyrus (STG) in two datasets. One dataset consisted of direct neural recordings (electrocorticography, ECoG) from surface electrodes implanted in epilepsy patients (this dataset has been previously published). The second dataset consisted of indirect measures of neural activity using blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI). Both ECoG and fMRI participants viewed the same clear and noisy audiovisual speech stimuli and performed the same speech recognition task. Both techniques demonstrated a sharp functional boundary in the STG, spatially coincident with an anatomical boundary defined by the posterior edge of Heschl’s gyrus. Cortex on the anterior side of the boundary responded more strongly to clear audiovisual speech than to noisy audiovisual speech while cortex on the posterior side of the boundary did not. For both ECoG and fMRI measurements, the transition between the functionally distinct regions happened within 10 mm of anterior-to-posterior distance along the STG. We relate this boundary to the multisensory neural code underlying speech perception and propose that it represents an important functional division within the human speech perception network.

Altered somatosensory neurovascular response in patients with Becker muscular dystrophy.

IntroductionPatients with dystrophinopathies show low levels of neuronal nitric oxide synthase (nNOS), due to reduced or absent dystrophin expression, as nNOS is attached to the dystrophin‐associated protein complex. Deficient nNOS function leads to functional ischemia during muscle activity. Dystrophin‐like proteins with nNOS attached have also been identified in the brain. This suggests that a mechanism of cerebral functional ischemia with attenuation of normal activation‐related vascular response may cause changes in brain function.MethodsThe aim of this study was to investigate whether the brain response of patients with Becker muscular dystrophy (BMD) is dysfunctional compared to that of healthy controls. To investigate a potential change in brain activation response in patients with BMD, median nerve somatosensory evoked stimulation, with stimulation durations of 2, 4, and 10 s, was performed while recording electroencephalography and blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging.ResultsResults in 14 male patients with BMD (36.2 ± 9.9 years) were compared with those of 10 healthy controls (34.4 ± 10.9 years). Compared to controls, the patients with BMD showed sustained cortical electrical activity and a significant smaller BOLD activation in contralateral primary somatosensory cortex and bilaterally in secondary somatosensory cortex. In addition, significant activation differences were found after long duration (10 s) stimuli in thalamus.ConclusionAn altered neurovascular response in patients with BMD may increase our understanding of neurovascular coupling and the pathogenesis related to dystrophinopathy and nNOS.

Characterizing the modulation of resting-state fMRI metrics by baseline physiology

The blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal is commonly used to assess functional connectivity across brain regions, particularly in the resting state (rs-fMRI). However, the BOLD fMRI signal is not merely a representation of neural activity, but a combination of neural activity and vascular response. These aspects of the BOLD signal are easily influenced by systemic physiology, potentially biasing BOLD-based functional connectivity measurements. In this work, we focus on the following physiological modulators of the BOLD signal: cerebral blood flow (CBF), venous blood oxygenation, and cerebrovascular reactivity (CVR). We use simulations and experiments to examine the relationship between the physiological parameters and rs-fMRI functional connectivity measurements in three resting-state networks: default mode network, somatosensory network and visual network. By using the general linear model, we demonstrate that physiological modulators significantly impact functional connectivity measurements in these regions, but in a manner that depends on the interplay between signal- and noise-driven correlations. Moreover, we find that the physiological effects vary by brain region and depend on the range of physiological conditions probed; the associations are more complex than previously reported. The results confirm that it is important to account for the effect of physiological modulators when comparing resting-state fMRI metrics. We note that such modulatory effects may be amplified by disease conditions, which will warrant future investigations.

La acupuntura modula la actividad anormal del tronco del encéfalo en pacientes con migraña sin aura

Migraine is a common neurological disease with a high prevalence and unsatisfactory treatment options. The specific pathophysiological mechanisms of migraine remain unclear, which restricts the development of effective treatments for this prevalent disorder. The aims of this study were to 1) compare the spontaneous brain activity differences between migraine without aura (MwoA) patients and healthy controls (HCs), using amplitude of low-frequency fluctuations (ALFF) calculation method, and 2) explore how an effective treatment (verum acupuncture) could modulate the ALFF of MwoA patients. One hundred MwoA patients and 46 matched HCs were recruited. Patients were randomized to 4 weeks’ verum acupuncture, sham acupuncture, and waiting list groups. Patients had resting state blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) scan before and after treatment, while HCs only had resting state BOLD-fMRI scan at baseline. Headache intensity, headache frequency, self-rating anxiety and self-rating depression were used for clinical efficacy evaluation. Compared with HCs, MwoA patients showed increased ALFF in posterior insula and putamen/caudate, and reduced ALFF in rostral ventromedial medulla (RVM)/trigeminocervical complex (TCC). After longitudinal verum acupuncture treatment, the decreased ALFF of the RVM/TCC was normalized in migraine patients. Verum acupuncture and sham acupuncture have different modulation effects on ALFF of RVM/TCC in migraine patients. Our results suggest that impairment of the homeostasis of the trigeminovascular nociceptive pathway is involved in the neural pathophysiology of migraines. Effective treatments, such as verum acupuncture, could help to restore this imbalance.

Heterogenous migraine aura symptoms correlate with visual cortex functional magnetic resonance imaging responses.

Migraine aura is sparsely studied due to the highly challenging task of capturing patients during aura. Cortical spreading depression (CSD) is likely the underlying phenomenon of aura. The possible correlation between the multifaceted phenomenology of aura symptoms and the effects of CSD on the brain has not been ascertained. Five migraine patients were studied during various forms of aura symptoms induced by hypoxia, sham hypoxia, or physical exercise with concurrent photostimulation. The blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal response to visual stimulation was measured in retinotopic mapping-defined visual cortex areas V1 to V4. We found reduced BOLD response in patients reporting scotoma and increased response in patients who only experienced positive symptoms. Furthermore, patients with bilateral visual symptoms had corresponding bihemispherical changes in BOLD response. These findings suggest that different aura symptoms reflect different types of cerebral dysfunction, which correspond to specific changes in BOLD signal reactivity. Furthermore, we provide evidence of bilateral CSD recorded by fMRI during bilateral aura symptoms. Ann Neurol 2017;82:925-939.

Quantitative relations between BOLD responses, cortical energetics, and impulse firing.

The blood oxygen level-dependent (BOLD) functional magnetic resonance imaging signal arises as a consequence of changes in blood flow and oxygen usage that in turn are modulated by changes in neural activity. Much attention has been given to both theoretical and experimental aspects of the energetics but not to the neural activity. Here we identify the best energetic theory for the steady-state BOLD signal on the basis of correct predictions of experimental observations. This theory is then used, together with the recently determined relationship between energetics and neural activity, to predict how the BOLD signal changes with activity. Unlike existing treatments, this new theory incorporates a nonzero baseline activity in a completely consistent way and is thus able to account for both sustained positive and negative BOLD signals. We also show that the increase in BOLD signal for a given increase in activity is significantly smaller the larger the baseline activity, as is experimentally observed. Furthermore, the decline of the positive BOLD signal arising from deeper cortical laminae in response to an increase in neural firing is shown to arise as a consequence of the larger baseline activity in deeper laminae. Finally, we provide quantitative relations integrating BOLD responses, energetics, and impulse firing, which among other predictions give the same results as existing theories when the baseline activity is zero. NEW & NOTEWORTHY We use a recently established relation between energetics and neural activity to give a quantitative account of BOLD dependence on neural activity. The incorporation of a nonzero baseline neural activity accounts for positive and negative BOLD signals, shows that changes in neural activity give BOLD changes that are smaller the larger the baseline, and provides a basis for the observed inverse relation between BOLD responses and the depth of cortical laminae giving rise to them.

Network-level dysconnectivity in patients with nasopharyngeal carcinoma (NPC) early post-radiotherapy: longitudinal resting state fMRI study

In this study, we seek to longitudinally investigate the network-level functional connectivity (FC) alternations and its association with irradiation dose and cognition changes in the early stage post radiotherapy (RT) in nasopharyngeal carcinoma (NPC) patients. We performed independent component analysis (ICA) of resting state blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) from 39 newly diagnosed NPC patients before receiving treatment (baseline), and 3months post-RT. the default mode network (DMN), salience network (SN), and executive control network (ECN) were extracted with well-validated software (GIFT). Inter-network connectivity was assessed using the functional network connectivity (FNC) toolbox. The inter- and intra-network FC was compared between time points, and the z value of FC alternation was correlated with the RT dose value and cognitive changes. Compared with baseline, the FC of the left anterior cingulate cortex (ACC) within the DMN, and the right insular within the SN, significantly reduced 3months post-RT, with greater effects at higher doses in the right insular. Bilateral ECN FC was also significantly lower 3months post-RT compared to the baseline. Chemotherapy was not associated with inter- and intra- network FC change. We found intra- and inter-network FC disruption in NPC patients 3months post-RT, with the right insular showing a dose-dependent effect. Thus, this network-level FC may serve as a potential biomarker of the RT-induced brain functional impairments, and provide valuable targets for further functional recovery treatment.

Astrocytic and neuronal oxidative metabolism are coupled to the rate of glutamate-glutamine cycle in the tree shrew visual cortex.

Astrocytes play an important role in glutamatergic neurotransmission, namely by clearing synaptic glutamate and converting it into glutamine that is transferred back to neurons. The rate of this glutamate-glutamine cycle (VNT ) has been proposed to couple to that of glucose utilization and of neuronal tricarboxylic acid (TCA) cycle. In this study, we tested the hypothesis that glutamatergic neurotransmission is also coupled to the TCA cycle rate in astrocytes. For that we investigated energy metabolism by means of magnetic resonance spectroscopy (MRS) in the primary visual cortex of tree shrews (Tupaia belangeri) under light isoflurane anesthesia at rest and during continuous visual stimulation. After identifying the activated cortical volume by blood oxygenation level-dependent functional magnetic resonance imaging, 1 H MRS was performed to measure stimulation-induced variations in metabolite concentrations. Relative to baseline, stimulation of cortical activity for 20min caused a reduction of glucose concentration by -0.34±0.09µmol/g (p<0.001), as well as a -9%±1% decrease of the ratio of phosphocreatine-to-creatine (p<0.05). Then 13 C MRS during [1,6-13 C]glucose infusion was employed to measure fluxes of energy metabolism. Stimulation of glutamatergic activity, as indicated by a 20% increase of VNT , resulted in increased TCA cycle rates in neurons by 12% ( VTCAn, p<0.001) and in astrocytes by 24% ( VTCAg, p=0.007). We further observed linear relationships between VNT and both VTCAn and VTCAg. Altogether, these results suggest that in the tree shrew primary visual cortex glutamatergic neurotransmission is linked to overall glucose oxidation and to mitochondrial metabolism in both neurons and astrocytes.