Blood Oxygen Level-dependent Activity Research Articles

Predicting the location of the preoptic and anterior hypothalamic region by visualizing the thermoregulatory center on fMRI in craniopharyngioma using cold and warm stimuli.

Hypothalamic nuclei in the preoptic and anterior hypothalamic region (POAH) are critically involved in thermoregulation and neuroendocrine regulation and can be displaced by craniopharyngiomas (CPs). We aimed to locate the POAH by visualizing hypothalamic thermoregulation through task-related functional magnetic resonance imaging (fMRI) to guide hypothalamus protection intraoperatively. Nine adult healthy volunteers (HVs) and thirty-two adult primary CP patients underwent task-related fMRI for POAH localization by warm (60° C) and cold (0° C) cutaneous thermoreceptor stimulation. Approach selection and intraoperative POAH protection were performed based on preoperative POAH localization. In all HVs and patients, significant single positive blood oxygen level-dependent (BOLD) signal changes were located in the POAH. The BOLD activity was significantly greater for cold (P=0.03) and warm (P=0.03) stimuli in patients than in HVs. Gross total resection and near-total resection were achieved in 28 (87.5%) and 4 (12.5%) patients, respectively. New-onset diabetes insipidus and new-onset hypopituitarism occurred in 6 patients (18.8%) and 10 patients (31.3%), respectively. Our findings suggest that cutaneous thermoreceptor stimulation could accurately activate the hypothalamic thermoregulatory center and allow POAH localization through task-related fMRI. Preoperative POAH localization could help neurosurgeons protect hypothalamic function intraoperatively. The CP patients were more sensitive to thermal stimulation.

Improving the sensitivity of spin-echo fMRI at 3T by highly accelerated acquisitions.

Spin-echo (SE) functional MRI (fMRI) can be highly advantageous compared to gradient-echo (GE) fMRI with respect to magnetic field-inhomogeneity artifacts. However, at 3T, the majority of blood oxygenation level-dependent (BOLD) fMRI experiments are performed using -weighted GE sequences because of their superior sensitivity compared to SE-fMRI. The presented SE implementation of a highly accelerated GE pulse sequence therefore aims to improve the sensitivity of SE-fMRI while profiting from a reduction of susceptibility-induced signal dropout. Spin-echo MR encephalography (SE-MREG) is compared with the more conventionally used spin-echo echo-planar imaging (SE-EPI) and spin-echo simultaneous multislice (SE-SMS) at 3T in terms of capability to detect neuronal activations and resting-state functional connectivity. For activation analysis, healthy subjects underwent consecutive SE-MREG (pulse repetition time [TR] = 0.25 seconds), SE-SMS (TR = 1.3 seconds), and SE-EPI (TR = 4.4 seconds) scans in pseudorandomized order applied to a visual block design paradigm for generation of t-statistics maps. For the investigation of functional connectivity, additional resting-state data were acquired for 5 minutes and a seed-based correlation analysis using Stanford's FIND (Functional Imaging in Neuropsychiatric Disorders) atlas was performed. The increased sampling rate of SE-MREG relative to SE-SMS and SE-EPI improves the sensitivity to detect BOLD activation by 33% and 54%, respectively, and increases the capability to extract resting-state networks. Compared with a brain region that is not affected by magnetic field inhomogeneities, SE-MREG shows 2.5 times higher relative signal strength than GE-MREG in mesial temporal structures. SE-MREG offers a viable possibility for whole-brain fMRI with consideration of brain regions that are affected by strong susceptibility-induced magnetic field gradients.

Visual Cortex Alterations in Early and Late Blind Subjects During Tactile Perception

Involvement of visual cortex varies during tactile perception tasks in early blind (EB) and late blind (LB) human subjects. This study explored differences in sensory motor networks associated with tactile task in EB and LB subjects and between children and adolescents. A total of 40 EB subjects, 40 LB subjects, and 30 sighted controls were recruited in two subgroups: children (6-12 years) and adolescents (13-19 years). Data were acquired using a 3T MR scanner. Analyses of blood oxygen level dependent (BOLD), functional connectivity (FC), correlation, and post hoc test for multiple comparisons were carried out. Difference in BOLD activity was observed in EB and LB groups in visual cortex during tactile perception, with increased FC of visual with dorsal attention and sensory motor networks in EB. EB adolescents exhibited increased connectivity with default mode and salience networks when compared with LB. Functional results correlated with duration of training, suggestive of better performance in EB. Alteration in sensory and visual networks in EB and LB correlated with duration of tactile training. Age of onset of blindness has an effect in cross-modal reorganization of visual cortex in EB and multimodal in LB in children and adolescents.

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.

Novelty preferences and cocaine-associated cues influence regions associated with the salience network in juvenile female rats

Preferences for novel environments (novelty-seeking) is a risk factor for addiction, with little known about its underlying circuitry. Exposure to drug cues facilitates addiction maintenance, leading us to hypothesize that exposure to a novel environment activates a shared neural circuitry. Stimulation of the D1 receptor in the prelimbic cortex increases responsivity to drug-associated environments. Here, we use D1 receptor overexpression in the prelimbic cortex to probe brain responses to novelty-preferences (in a free-choice paradigm) and cocaine-associated odors following place conditioning. These same cocaine-conditioned odors were used to study neural circuitry with Blood Oxygen Level Dependent (BOLD) activity. D1 overexpressing females had deactivated BOLD signals related to novelty-preferences within the insula cortex and amygdala and activation in the frontal cortex and dopamine cell bodies. BOLD responses to cocaine cues were also sensitive to D1. Control females demonstrated a place preference for cocaine environments with no significant BOLD response, while D1 overexpressing females demonstrated a place aversion and weak BOLD responses to cocaine-conditioned odor cues within the insula cortex. For comparison, we provide data from an earlier study with juvenile males overexpressing D1 that show a strong preference for cocaine and elevated BOLD responses. The results support the use of a pharmacological manipulation (e.g., D1 overexpression) to probe the neural circuitry downstream from the prelimbic cortex.

Use of Functional MRI to Assess Effects of Deep Brain Stimulation Frequency Changes on Brain Activation in Parkinson Disease.

Models have been developed for predicting ideal contact and amplitude for subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson disease (PD). Pulse-width is generally varied to modulate the size of the energy field produced. Effects of varying frequency in humans have not been systematically evaluated. To examine how altered frequencies affect blood oxygen level-dependent activation in PD. PD subjects with optimized DBS programming underwent functional magnetic resonance imaging (fMRI). Frequency was altered and fMRI scans/Unified Parkinson Disease Rating Scale motor subunit (UPDRS-III) scores were obtained. Analysis using DBS-OFF data was used to determine which regions were activated during DBS-ON. Peak activity utilizing T-values was obtained and compared. At clinically optimized settings (n=14 subjects), thalamic, globus pallidum externa (GPe), and posterior cerebellum activation were present. Activation levels significantly decreased in the thalamus, anterior cerebellum, and the GPe when frequency was decreased (P <.001). Primary somatosensory cortex activation levels significantly decreased when frequency was increased by 30Hz, but not 60Hz. Sex, age, disease/DBS duration, and bilaterality did not significantly affect the data. Retrospective analysis of fMRI activation patterns predicted optimal frequency in 11/14 subjects. We show the first data with fMRI of STN DBS-ON while synchronizing cycling with magnetic resonance scanning. At clinically optimized settings, an fMRI signature of thalamic, GPe, and posterior cerebellum activation was seen. Reducing frequency significantly decreased thalamic, GPe, and anterior cerebellum activation. Current standard-of-care programming can take up to 6 mo using UPDRS-III testing alone. We provide preliminary evidence that using fMRI signature of frequency may have clinical utility and feasibility.

Functional Magnetic Resonance Imaging Correlates of Ventral Striatal Deep Brain Stimulation for Poststroke Pain

ObjectiveDeep brain stimulation (DBS) for pain has largely been implemented in an uncontrolled manner to target the somatosensory component of pain, with research leading to mixed results. We have previously shown that patients with poststroke pain syndrome who were treated with DBS targeting the ventral striatum/anterior limb of the internal capsule (VS/ALIC) demonstrated a significant improvement in measures related to the affective sphere of pain. In this study, we sought to determine how DBS targeting the VS/ALIC modifies brain activation in response to pain. Materials and MethodsFive patients with poststroke pain syndrome who were blinded to DBS status (ON/OFF) and six age- and sex-matched healthy controls underwent functional magnetic resonance imaging (fMRI) measuring blood oxygen level-dependent activation in a block design. In this design, each participant received heat stimuli to the affected or unaffected wrist area. Statistical comparisons were performed using fMRI z-maps. ResultsIn response to pain, patients in the DBS OFF state showed significant activation (p < 0.001) in the same regions as healthy controls (thalamus, insula, and operculum) and in additional regions (orbitofrontal and superior convexity cortical areas). DBS significantly reduced activation of these additional regions and introduced foci of significant inhibitory activation (p < 0.001) in the hippocampi when painful stimulation was applied to the affected side. ConclusionsThese findings suggest that DBS of the VS/ALIC modulates affective neural networks.

A link between synaptic plasticity and reorganization of brain activity in Parkinson's disease

The link between synaptic plasticity and reorganization of brain activity in health and disease remains a scientific challenge. We examined this question in Parkinson's disease (PD) where functional up-regulation of postsynaptic D2 receptors has been documented while its significance at the neural activity level has never been identified. We investigated cortico-subcortical plasticity in PD using the oculomotor system as a model to study reorganization of dopaminergic networks. This model is ideal because this system reorganizes due to frontal-to-parietal shifts in blood oxygen level-dependent (BOLD) activity. We tested the prediction that functional activation plasticity is associated with postsynaptic dopaminergic modifications by combining positron emission tomography/functional magnetic resonance imaging to investigate striatal postsynaptic reorganization of dopamine D2 receptors (using 11C-raclopride) and neural activation in PD. We used covariance (connectivity) statistics at molecular and functional levels to probe striato-cortical reorganization in PD in on/off medication states to show that functional and molecular forms of reorganization are related. D2 binding across regions defined by prosaccades showed increased molecular connectivity between both caudate/putamen and hyperactive parietal eye fields in PD in contrast with frontal eye fields in controls, in line with the shift model. Concerning antisaccades, parietal-striatal connectivity dominated in again in PD, unlike frontal regions. Concerning molecular-BOLD covariance, a striking sign reversal was observed: PD patients showed negative frontal-putamen functional-molecular associations, consistent with the reorganization shift, in contrast with the positive correlations observed in controls. Follow-up analysis in off-medication PD patients confirmed the negative BOLD-molecular correlation. These results provide a link among BOLD responses, striato-cortical synaptic reorganization, and neural plasticity in PD.

Counteracting Effects of Glutathione on the Glutamate-Driven Excitation/Inhibition Imbalance in First-Episode Schizophrenia: A 7T MRS and Dynamic Causal Modeling Study.

Oxidative stress plays a key role in the pathophysiology of schizophrenia. While free radicals produced by glutamatergic excess and oxidative metabolism have damaging effects on brain tissue, antioxidants such as glutathione (GSH) counteract these effects. The interaction between glutamate (GLU) and GSH is centered on N-Methyl-D-aspartate (NMDA) receptors. GSH levels increase during glutamate-mediated excitatory neuronal activity, which serves as a checkpoint to protect neurons from oxidative damage and reduce excitatory overdrive. We studied the possible influence of GSH on the glutamate-mediated dysconnectivity in 19 first-episode schizophrenia (FES) patients and 20 healthy control (HC) subjects. Using ultra-high field (7 Tesla) magnetic resonance spectroscopy (MRS) and resting state functional magnetic resonance imaging (fMRI), we measured GSH and GLU levels in the dorsal anterior cingulate cortex (dACC) and blood-oxygenation level-dependent activity in both the dACC and the anterior insula (AI). Using spectral dynamic causal modeling, we found that when compared to HCs, in FES patients inhibitory activity within the dACC decreased with GLU levels whereas inhibitory activity in both the dACC and AI increased with GSH levels. Our model explains how higher levels of GSH can reverse the downstream pathophysiological effects of a hyperglutamatergic state in FES. This provides an initial insight into the possible mechanistic effect of antioxidant system on the excitatory overdrive in the salience network (dACC-AI).

Enhancement of Sensorimotor Cortical Adaptation after Dental Implantation in Comparison to the Conventional Denture - Demonstration by Functional MRI at 1-5T.

Dental implantation is thought to be associated with enhancement of neuro-cortical sensorimotor activity which has been lost due to an edentulous state. Such changes are either feeble or absent after the placement of a conventional denture. In the present study, we test this hypothesis using blood oxygen level-dependent (BOLD) activity on functional MRI (fMRI) as a bio-surrogate. fMRI was performed in 12 consecutive edentulous subjects (mean age = 59.2 years) after the placement of a conventional complete denture (CD) and subsequently after intraoral dental implantation (IOD). The semi-quantitative data of the BOLD activity was compiled to depict the activation seen in both scenarios in six anatomical regions. Statistical analysis was done to evaluate the significance of enhancement in BOLD activity in these regions in patients having an IOD as compared to those having a CD. The enhancement of BOLD activity on fMRI after placement of an IOD was much more significant as compared to that noted with CD. Using Wilcoxon's signed-rank test the nonparametric data showed a significant positive elevation in global and regional assigned mean ranks of BOLD activity. Intraoral implantation leads to a significant elevation in the BOLD activity of the sensorimotor cortex as compared to the placement of a conventional CD.

Fetal Alcohol Exposure Alters BOLD Activation Patterns in Brain Regions Mediating the Interpretation of Facial Affect.

Although deficits in the interpretation of affective facial expressions have been described clinically and in behavioral studies of fetal alcohol spectrum disorders (FASD), effects of prenatal alcohol exposure on the neural networks that mediate affective appraisal have not previously been examined. We administered a nonverbal event-related fMRI affective appraisal paradigm to 64 children (mean age=12.5years; 18 with fetal alcohol syndrome (FAS) or partial FAS (PFAS), 18 nonsyndromal heavily exposed (HE), and 28 controls). Happy, sad, angry, fearful, and neutral faces and pixelated control images were presented sequentially in a randomized order. The child indicated whether the currently displayed face showed the same or different affect as the previous one. Data from whole-brain analyses showed that all groups activated the appropriate face processing neural networks. Region of interest analyses indicated that, compared to HE and control children, the FAS/PFAS group exhibited greater blood oxygenation level-dependent (BOLD) signal changes when processing neutral faces than pixelated images in 2 regions that form part of the visual sensory social brain network, which plays an important role in the initial processing of facial affect. By contrast, BOLD signal when processing angry faces was weaker for the FAS/PFAS group in a region involved in the processing of facial identity and facial expressions and in a region involved in the recognition and selection of behavioral responses to aggressive behavior. These findings of greater BOLD signal in the FAS/PFAS group in response to neutral faces suggest less efficient neural processing of more difficult to interpret emotions, and the weaker BOLD response to angry faces suggests altered processing of angry stimuli. Although behavioral performance did not differ in this relatively simple affective appraisal task, these data suggest that in children with FAS and PFAS, the appraisal of neutral affect and anger is likely to be more effortful in more challenging and dynamic social contexts.

Comparing hand movement rate dependence of cerebral blood volume and BOLD responses at 7T

Functional magnetic resonance imaging (fMRI) based on the Blood Oxygenation Level Dependent (BOLD) contrast takes advantage of the coupling between neuronal activity and the hemodynamics to allow a non-invasive localisation of the neuronal activity. In general, fMRI experiments assume a linear relationship between neuronal activation and the observed hemodynamics. However, the relationship between BOLD responses, neuronal activity, and behaviour are often nonlinear. In addition, the nonlinearity between BOLD responses and behaviour may be related to neuronal process rather than a neurovascular uncoupling. Further, part of the nonlinearity may be driven by vascular nonlinearity effects in particular from large vessel contributions. fMRI based on cerebral blood volume (CBV), promises a higher microvascular specificity, potentially without vascular nonlinearity effects and reduced contamination of the large draining vessels compared to BOLD. In this study, we aimed to investigate differences in BOLD and VASO-CBV signal changes during a hand movement task over a broad range of movement rates. We used a double readout 3D-EPI sequence at 7T to simultaneously measure VASO-CBV and BOLD responses in the sensorimotor cortex. The measured BOLD and VASO-CBV responses increased very similarly in a nonlinear fashion, plateauing for movement rates larger than 1 Hz. Our findings show a tight relationship between BOLD and VASO-CBV responses, indicating that the overall interplay of CBV and BOLD responses are similar for the assessed range of movement rates. These results suggest that the observed nonlinearity of neuronal origin is already present in VASO-CBV measurements, and consequently shows relatively unchanged BOLD responses.

Oscillatory correlates of auditory working memory examined with human electrocorticography

This work examines how sounds are held in auditory working memory (AWM) in humans by examining oscillatory local field potentials (LFPs) in candidate brain regions. Previous fMRI studies by our group demonstrated blood oxygenation level-dependent (BOLD) response increases during maintenance in auditory cortex, inferior frontal cortex and the hippocampus using a paradigm with a delay period greater than 10s. The relationship between such BOLD changes and ensemble activity in different frequency bands is complex, and the long delay period raised the possibility that long-term memory mechanisms were engaged. Here we assessed LFPs in different frequency bands in six subjects with recordings from all candidate brain regions using a paradigm with a short delay period of 3 s. Sustained delay activity was demonstrated in all areas, with different patterns in the different areas. Enhancement in low frequency (delta) power and suppression across higher frequencies (beta/gamma) were demonstrated in primary auditory cortex in medial Heschl’s gyrus (HG) whilst non-primary cortex showed patterns of enhancement and suppression that altered at different levels of the auditory hierarchy from lateral HG to superior- and middle-temporal gyrus. Inferior frontal cortex showed increasing suppression with increasing frequency. The hippocampus and parahippocampal gyrus showed low frequency increases and high frequency decreases in oscillatory activity. This work demonstrates sustained activity patterns during AWM maintenance, with prominent low-frequency increases in medial temporal lobe regions.

Questioning the role of amygdala and insula in an attentional capture by emotional stimuli task.

Our senses are constantly monitoring the environment for emotionally salient stimuli that are potentially relevant for survival. Because of our limited cognitive resources, emotionally salient distractors prolong reaction times (RTs) as compared to neutral distractors. In addition, many studies have reported fMRI blood oxygen level‐dependent (BOLD) activation of both the amygdala and the anterior insula for similar valence contrasts. However, a direct correlation of trail‐by‐trial BOLD activity with RTs has not been shown, yet, which would be a crucial piece of evidence to relate the two observations. To investigate the role of the above two regions in the context of emotional distractor effects, we study here the correlation between BOLD activity and RTs for a simple attentional capture by emotional stimuli (ACES) choice reaction time task using a general linear subject‐level model with a parametric RT regressor. We found significant regression coefficients in the anterior insula, supplementary motor cortex, medial precentral regions, sensory‐motor areas and others, but not in the amygdala, despite activation of both insula and amygdala in the traditional valence contrast across trials (i.e., negative vs. neutral pictures). In addition, we found that subjects that exhibit a stronger RT distractor effect across trials also show a stronger BOLD valence contrast in the right anterior insula but not in the amygdala. Our results indicate that the current neuroimaging‐based evidence for the involvement of the amygdala in RT slowing is limited. We advocate that models of emotional capture should incorporate both the amygdala and the anterior insula as separate entities.

Regional Brain Correlates of Beta Bursts in Health and Psychosis: A Concurrent Electroencephalography and Functional Magnetic Resonance Imaging Study

BackgroundThere is emerging evidence for abnormal beta oscillations in psychosis. Beta oscillations are likely to play a key role in the coordination of sensorimotor information that is crucial to healthy mental function. Growing evidence suggests that beta oscillations typically manifest as transient beta bursts that increase in probability following a motor response, observable as post-movement beta rebound. Evidence indicates that post-movement beta rebound is attenuated in psychosis, with greater attenuation associated with greater symptom severity and impairment. Delineating the functional role of beta bursts therefore may be key to understanding the mechanisms underlying persistent psychotic illness. MethodsWe used concurrent electroencephalography and functional magnetic resonance imaging to identify blood oxygen level–dependent correlates of beta bursts during the n-back working memory task and intervening rest periods in healthy control participants (n = 30) and patients with psychosis (n = 48). ResultsDuring both task blocks and intervening rest periods, beta bursts phasically activated regions implicated in task-relevant content while suppressing currently tonically active regions. Patients showed attenuated post-movement beta rebound that was associated with persisting disorganization symptoms as well as impairments in cognition and role function. Patients also showed greater task-related reductions in overall beta burst rate and showed greater, more extensive, beta burst–related blood oxygen level–dependent activation. ConclusionsOur evidence supports a model in which beta bursts reactivate latently maintained sensorimotor information and are dysregulated and inefficient in psychosis. We propose that abnormalities in the mechanisms by which beta bursts coordinate reactivation of contextually appropriate content can manifest as disorganization, working memory deficits, and inaccurate forward models and may underlie a core deficit associated with persisting symptoms and impairment.

Patients with anxiety disorders rely on bilateral dlPFC activation during verbal working memory.

One of the hallmarks of anxiety disorders is impaired cognitive control, affecting working memory (WM). The dorsolateral prefrontal cortex (dlPFC) is critical for WM; however, it is still unclear how dlPFC activity relates to WM impairments in patients. Forty-one healthy volunteers and 32 anxiety (general and/or social anxiety disorder) patients completed the Sternberg WM paradigm during safety and unpredictable shock threat. On each trial, a series of letters was presented, followed by brief retention and response intervals. On low- and high-load trials, subjects retained the series (five and eight letters, respectively) in the original order, while on sort trials, subjects rearranged the series (five letters) in alphabetical order. We sampled the blood oxygenation level–dependent activity during retention using a bilateral anatomical dlPFC mask. Compared to controls, patients showed increased reaction time during high-load trials, greater right dlPFC activity and reduced dlPFC activity during threat. These results suggest that WM performance for patients and controls may rely on distinct patterns of dlPFC activity with patients requiring bilateral dlPFC activity. These results are consistent with reduced efficiency of WM in anxiety patients. This reduced efficiency may be due to an inefficient allocation of dlPFC resources across hemispheres or a decreased overall dlPFC capacity.

No effect of a dopaminergic modulation fMRI task by amisulpride and L-DOPA on reward anticipation in healthy volunteers

RationaleDysregulation of dopaminergic neurotransmission, specifically altered reward processing assessed via the reward anticipation in the MID task, plays a central role in the etiopathogenesis of neuropsychiatric disorders.ObjectivesWe hypothesized to find a difference in the activity level of the reward system (measured by the proxy reward anticipation) under drug administration versus placebo, in that amisulpride reduces, and L-DOPA enhances, its activity.MethodsWe studied the influence of dopamine agonist L-DOPA and the antagonist amisulpride on the reward system using functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task in n = 45 healthy volunteers in a randomized, blinded, cross-over study.ResultsThe MID paradigm elicits strong activation in reward-dependent structures (such as ventral striatum, putamen, caudate, anterior insula) during reward anticipation. The placebo effect demonstrated the expected significant blood oxygen level–dependent activity in reward-dependent brain regions. Neither amisulpride nor L-DOPA led to significant changes in comparison with the placebo condition. This was true for whole-brain analysis as well as analysis of a pre-defined nucleus accumbens region-of-interest mask.ConclusionThe present results cast doubt on the sensitivity of reward anticipation contrast in the MID task for assessing dopamine-specific changes in healthy volunteers by pharmaco-fMRI. While our task was not well-suited for detailed analysis of the outcome phase, we provide reasonable arguments that the lack of effect in the anticipation phase is not due to an inefficient task but points to unexpected behavior of the reward system during pharmacological challenge. Group differences of reward anticipation should therefore not be seen as simple representatives of dopaminergic states.

High-amplitude cofluctuations in cortical activity drive functional connectivity

Resting-state functional connectivity is used throughout neuroscience to study brain organization and to generate biomarkers of development, disease, and cognition. The processes that give rise to correlated activity are, however, poorly understood. Here we decompose resting-state functional connectivity using a temporal unwrapping procedure to assess the contributions of moment-to-moment activity cofluctuations to the overall connectivity pattern. This approach temporally resolves functional connectivity at a timescale of single frames, which enables us to make direct comparisons of cofluctuations of network organization with fluctuations in the blood oxygen level-dependent (BOLD) time series. We show that surprisingly, only a small fraction of frames exhibiting the strongest cofluctuation amplitude are required to explain a significant fraction of variance in the overall pattern of connection weights as well as the network's modular structure. These frames coincide with frames of high BOLD activity amplitude, corresponding to activity patterns that are remarkably consistent across individuals and identify fluctuations in default mode and control network activity as the primary driver of resting-state functional connectivity. Finally, we demonstrate that cofluctuation amplitude synchronizes across subjects during movie watching and that high-amplitude frames carry detailed information about individual subjects (whereas low-amplitude frames carry little). Our approach reveals fine-scale temporal structure of resting-state functional connectivity and discloses that frame-wise contributions vary across time. These observations illuminate the relation of brain activity to functional connectivity and open a number of directions for future research.

Reconstructing lost BOLD signal in individual participants using deep machine learning

Signal loss in blood oxygen level-dependent (BOLD) functional neuroimaging is common and can lead to misinterpretation of findings. Here, we reconstructed compromised fMRI signal using deep machine learning. We trained a model to learn principles governing BOLD activity in one dataset and reconstruct artificially compromised regions in an independent dataset, frame by frame. Intriguingly, BOLD time series extracted from reconstructed frames are correlated with the original time series, even though the frames do not independently carry any temporal information. Moreover, reconstructed functional connectivity maps exhibit good correspondence with the original connectivity maps, indicating that the model recovers functional relationships among brain regions. We replicated this result in two healthy datasets and in patients whose scans suffered signal loss due to intracortical electrodes. Critically, the reconstructions capture individual-specific information. Deep machine learning thus presents a unique opportunity to reconstruct compromised BOLD signal while capturing features of an individual’s own functional brain organization.

Functional connectivity during smooth pursuit eye movements.

Smooth pursuit eye movements (SPEM) hold the image of a slowly moving stimulus on the fovea. The neural system underlying SPEM primarily includes visual, parietal, and frontal areas. In the present study, we investigated how these areas are functionally coupled and how these couplings are influenced by target motion frequency. To this end, healthy participants (n = 57) were instructed to follow a sinusoidal target stimulus moving horizontally at two different frequencies (0.2 Hz, 0.4 Hz). Eye movements and blood oxygen level-dependent (BOLD) activity were recorded simultaneously. Functional connectivity of the key areas of the SPEM network was investigated with a psychophysiological interaction (PPI) approach. How activity in five eye movement-related seed regions (lateral geniculate nucleus, V1, V5, posterior parietal cortex, frontal eye fields) relates to activity in other parts of the brain during SPEM was analyzed. The behavioral results showed clear deterioration of SPEM performance at higher target frequency. BOLD activity during SPEM versus fixation occurred in a geniculo-occipito-parieto-frontal network, replicating previous findings. PPI analysis yielded widespread, partially overlapping networks. In particular, frontal eye fields and posterior parietal cortex showed task-dependent connectivity to large parts of the entire cortex, whereas other seed regions demonstrated more regionally focused connectivity. Higher target frequency was associated with stronger activations in visual areas but had no effect on functional connectivity. In summary, the results confirm and extend previous knowledge regarding the neural mechanisms underlying SPEM and provide a valuable basis for further investigations such as in patients with SPEM impairments and known alterations in brain connectivity.NEW & NOTEWORTHY This study provides a comprehensive investigation of blood oxygen level-dependent (BOLD) functional connectivity during smooth pursuit eye movements. Results from a large sample of healthy participants suggest that key oculomotor regions interact closely with each other but also with regions not primarily associated with eye movements. Understanding functional connectivity during smooth pursuit is important, given its potential role as an endophenotype of psychoses.