Blood Oxygen Level-dependent Response Research Articles

MDD patients with early life stress deactivate the frontostriatal network during facial emotion recognition paradigm: A functional MRI study

IntroductionEarly life stress (ELS) is a significant risk factor for major depressive disorder (MDD) in adults. Functional magnetic resonance imaging (fMRI) studies using face emotion processing paradigms have found altered blood-oxygen-level-dependent (BOLD) responses in the cortico-limbic network both in individuals exposed to ELS and in patients with MDD. Thus, early life stress may have a long-lasting impact on brain areas responsible for the processing of socio-affective cues.ObjectivesBy applying a facial emotion recognition (FER) fMRI paradigm, we examined the long-term effect of childhood adversity on brain activity in MDD patients with and without ELS.MethodsMDD patients without ELS (MDD, N=19), those with ELS (MDD+ELS, N=21), and healthy controls (HC, N=21) matched for age, sex, and intelligence quotient underwent fMRI scanning while performing a block design FER task with faces expressing negative emotions. The severity of ELS was assessed with the 28-item Childhood Trauma Questionnaire.Results Both MDD and MDD+ELS patients were slightly impaired in recognizing sad faces. Statistical analysis of brain activity found that MDD+ELS patients had significantly reduced negative BOLD responses in the right anterior paracingulate gyrus, subcallosal cortex accumbens compared to HCs. Moreover, the MDD+ELS group had a significantly increased negative BOLD signal in the right postcentral and precentral gyri relative to the HC group. MDD+ELS patients had reduced negative BOLD response in their anterior paracingulate gyrus compared to the MDD group.Conclusions Our results support that adult MDD patients with significant ELS are impaired in facial emotion recognition and they display functional alterations in the frontostriatal circuits.DisclosureThis work was financially supported by the Hungarian Brain Research Program (2017-1.2.1-NKP-2017-00002)

Evaluating the Abnormality of Bilateral Motor Cortex Activity in Subacute Stroke Patients Executing a Unimanual Motor Task With Increasing Demand on Precision

Abnormal contralesional M1 activity is consistently reported in patients with compromised upper limb and hand function after stroke. The underlying mechanisms and functional implications of this activity are not clear, which hampers the development of treatment strategies targeting this brain area. The goal of the present study was to determine the extent to which contralesional M1 activity can be explained by the demand of a motor task, given recent evidence for increasing ipsilateral M1 activity with increasing demand in healthy age-matched controls. We hypothesized that higher activity in contralesional M1 is related to greater demand on precision in a hand motor task. fMRI data were collected from 19 patients with ischemic stroke affecting hand function in the subacute recovery phase and 31 healthy, right-handed, age-matched controls. The hand motor task was designed to parametrically modulate the demand on movement precision. Electromyography data confirmed strictly unilateral task performance by all participants. Patients showed significant impairment relative to controls in their ability to perform the task in the fMRI scanner. However, patients and controls responded similarly to an increase in demand for precision, with better performance for larger targets and poorer performance for smaller targets. Patients did not show evidence of elevated ipsilesional or contralesional M1 blood oxygenation level-dependent (BOLD) activation relative to healthy controls and mean BOLD activation levels were not elevated for patients with poorer performance relative to patients with better task performance. While both patients and healthy controls showed demand-dependent increases in BOLD activation in both ipsilesional/contralateral and contralesional/ipsilateral hemispheres, patients with stroke were less likely to show evidence of a linear relationship between the demand on precision and BOLD activation in contralesional M1 than healthy controls. Taken together, the findings suggest that task demand affects the BOLD response in contralesional M1 in patients with stroke, though perhaps less strongly than in healthy controls. This has implications for the interpretation of reported abnormal bilateral M1 activation in patients with stroke because in addition to contralesional M1 reorganization processes it could be partially related to a response to the relatively higher demand of a motor task when completed by patients rather than by healthy controls.

A review of Melodic Intonation Therapy (MIT) and pilot of Dynamic Adaptive Speech Reconstruction (DASR) imaging

IntroductionMaking mistakes is at the heart of learning. This principle is central to “re‐learning” how to speak and, when applied with music, can elicit a robust brain activation. As simple as a search for the right note provokes a plastic process in normal language development since it activates the right hemisphere homolog of Broca’s area, which “takes over” language functions. This review and pilot experiment examines language neuroplasticity by observing how Melodic Intonation Therapy (MIT), a treatment modality that combines elements of speech, rhythm, and melody, plays a role in language re‐learning and how its limitations can be overcome with a new tool our lab is developing ‐ Dynamic Adaptive Speech Reconstruction (DASR). MIT’s design in combining task modalities of speaking, singing, and tapping to activate Broca’s area is limited by its well‐intentioned, yet subjective interpretation by speech‐language pathologists. DASR, when fully developed, overcomes subjectivity by using an AI algorithm that incorporates MIT data in real‐time in combination with functional Near‐Infrared Spectroscopy (fNIRS) to observe areas of the brain that are actively recruited when a patient attempts to form phrases. The DASR algorithm objectively analyzes patients’ responses, deconstructs the response, associates it with the fNIRS brain activation, measured as the Blood Oxygenation Level Dependent (BOLD) response, and suggests the next request the therapist should ask of the patient. We tested two aspects of DASR in recruiting the right hemisphere homologue of Broca’s area.MethodsUsing fNIRS in two age‐matched, middle‐aged subjects, we measured activation of Broca’s area in response to a set of randomized repeated phrases. Participants were fitted with an electrode skull cap that measures the BOLD response to the cerebral cortex. Each participant performed a series of 21 tasks (20 seconds each) per trial (420 seconds). Each of the 21 tasks consisted of a recited prompt, which the subject was to repeat as precisely as possible. Subjects were asked to speak, sing, intone with an augmented 4th note (added per DASR protocol), and tap a specific rhythm to “happy birthday to you” and to subsequently more difficult analogs of the phrase: “Hippo birdseed two ewes,” then “Ep say feef now jam bob,” and finally “happy birthday to you.” The set of 21 tasks were repeated in a pseudo‐random order for each subject five times. Block design statistical parametric mapping was used to visualize activation.ResultsBroca’s area showed the greatest activation when task modalities were combined, in particular when singing augmented 4th phrases. It is notable that when tapping is added to singing the augmented 4th, Broca’s area activation appears to decrease, but activation of the right lateral frontal lobe increases with each successive trial. Subjects repeating the phrase, “happy birthday to you”, after going through a series of increasingly complex phrases showed recruitment of the right inferior frontal lobe after the subject completes just one series of trials.DiscussionThis review and pilot study demonstrates that fNIRS can be used to visual brain activation of Broca’s area, particularly in conditions of increasing linguistic complexity, and shows immediate recruitment of the right hemisphere homologue of Broca’s area.

Molecular Effects of Low-Intensity Shock Wave Therapy on L6 Dorsal Root Ganglion/Spinal Cord and Blood Oxygenation Level-Dependent (BOLD) Functional Magnetic Resonance Imaging (fMRI) Changes in Capsaicin-Induced Prostatitis Rat Models.

Neurogenic inflammation and central sensitization play a role in chronic prostatitis/chronic pelvic pain syndrome. We explore the molecular effects of low-intensity shock wave therapy (Li-ESWT) on central sensitization in a capsaicin-induced prostatitis rat model. Male Sprague–Dawley rats underwent intraprostatic capsaicin (10 mM, 0.1 cm3) injections. After injection, the prostate received Li-ESWT twice, one day apart. The L6 dorsal root ganglion (DRG)/spinal cord was harvested for histology and Western blotting on days 3 and 7. The brain blood oxygenation level-dependent (BOLD) functional images were evaluated using 9.4 T fMRI before the Li-ESWT and one day after. Intraprostatic capsaicin injection induced increased NGF-, BDNF-, and COX-2-positive neurons in the L6 DRG and increased COX-2, NGF, BDNF, receptor Trk-A, and TRPV1 protein expression in the L6 DRG and the dorsal horn of the L6 spinal cord, whose effects were significantly downregulated after Li-ESWT on the prostate. Intraprostatic capsaicin injection increased activity of BOLD fMRI responses in brain regions associated with pain-related responses, such as the caudate putamen, periaqueductal gray, and thalamus, whose BOLD signals were reduced after Li-ESWT. These findings suggest a potential mechanism of Li-ESWT on modulation of peripheral and central sensitization for treating CP/CPPS.

Neural cognitive control moderates the longitudinal link between hedonia and substance use across adolescence

Hedonic dysregulation is evident in addiction and substance use disorders, but it is not clearly understood how hedonic processes may interact with brain development related to cognitive control to influence risky decision making and substance use during adolescence. The present study used prospective longitudinal data to clarify the role of cognitive control in the link between hedonic experiences and the development of substance use during adolescence. Participants included 167 adolescents (53% male) assessed at four time points, annually. Adolescents participated in a functional magnetic resonance imaging (fMRI) session where blood-oxygen level dependent (BOLD) response was monitored during the Multi-Source- Interference Task to assess cognitive control. Substance use and hedonia were assessed using self-report. A two-group growth curve model of substance use with hedonia as a time-varying covariate indicated that higher levels of hedonia predicted higher substance use, but only in adolescents with higher activation in the frontoparietal regions and in the rostral anterior cingulate cortex during cognitive control. Results elucidate the moderating effects of neural cognitive control on associations between hedonia and adolescent substance use, suggesting that lower cognitive control functioning in the brain may exacerbate risk for substance use promoted by hedonia.

The Posterior Cingulate Cortex Reflects the Impact of Anxiety on Drift Rates During Cognitive Processing

BackgroundGenerally, anxiety is thought to impair ongoing cognitive operations. Surprisingly, however, anxiety has been shown to improve performance during the Go/NoGo task. Understanding how anxiety can facilitate task performance may shed light on avenues to address the cognitive deficits commonly associated with anxiety. MethodsA total of 39 participants (mean age ± SD = 27.5 ± 7.22 years; 18 women) performed a Go/NoGo task during periods of safety and periods of experimental anxiety, induced using the unpredictable delivery of aversive stimuli. Computational analysis and ultrahigh field (7T) functional magnetic resonance imaging were used to determine how induced anxiety affected computational processes and blood oxygen level–dependent responses during the task. ResultsInduced anxiety improved accuracy during the Go/NoGo task. Induced anxiety was associated with an amplified drift rate process, which is thought to reflect increased informational uptake. In addition, changes in drift rate during the anxiety condition were associated with enhanced blood oxygen level–dependent responses within the posterior cingulate cortex during Go trials. ConclusionsThese results may reflect the impact of induced anxiety on the activity of neurons within the posterior cingulate cortex, whose activity patterns mimic the buildup of evidence accumulation. Collectively, these results shed light on the mechanisms underlying facilitated task performance and suggest that anxiety can improve cognitive processing by enhancing information uptake and increasing activity within the posterior cingulate cortex.

An Anisotropic 4D Filtering Approach to Recover Brain Activation From Paradigm-Free Functional MRI Data.

Functional Magnetic Resonance Imaging (fMRI) is a non-invasive imaging technique that provides an indirect view into brain activity via the blood oxygen level dependent (BOLD) response. In particular, resting-state fMRI poses challenges to the recovery of brain activity without prior knowledge on the experimental paradigm, as it is the case for task fMRI. Conventional methods to infer brain activity from the fMRI signals, for example, the general linear model (GLM), require the knowledge of the experimental paradigm to define regressors and estimate the contribution of each voxel's time course to the task. To overcome this limitation, approaches to deconvolve the BOLD response and recover the underlying neural activations without a priori information on the task have been proposed. State-of-the-art techniques, and in particular the total activation (TA), formulate the deconvolution as an optimization problem with decoupled spatial and temporal regularization and an optimization strategy that alternates between the constraints. In this work, we propose a paradigm-free regularization algorithm named Anisotropic 4D-fMRI (A4D-fMRI) that is applied on the 4D fMRI image, acting simultaneously in the 3D space and 1D time dimensions. Based on the idea that large image variations should be preserved as they occur during brain activations, whereas small variations considered as noise should be removed, the A4D-fMRI applies an anisotropic regularization, thus recovering the location and the duration of brain activations. Using the experimental paradigm as ground truth, the A4D-fMRI is validated on synthetic and real task-fMRI data from 51 subjects, and its performance is compared to the TA. Results show higher correlations of the recovered time courses with the ground truth compared to the TA and lower computational times. In addition, we show that the A4D-fMRI recovers activity that agrees with the GLM, without requiring or using any knowledge of the experimental paradigm.

Effects of Noninvasive Cervical Vagal Nerve Stimulation on Cognitive Performance But Not Brain Activation in Healthy Adults

ObjectivesWhile preliminary evidence suggests that noninvasive vagal nerve stimulation (nVNS) may enhance cognition, to our knowledge, no study has directly assessed the effects of nVNS on brain function and cognitive performance in healthy individuals. The aim of this study was therefore to assess whether nVNS enhances complex visuospatial problem solving in a normative sample. Functional magnetic resonance imaging (fMRI) was used to examine underlying neural substrates. Material and MethodsParticipants received transcutaneous cervical nVNS (N = 15) or sham (N = 15) stimulation during a 3 T fMRI scan. Stimulation lasted for 2 min at 24 V for nVNS and at 4.5 V for sham. Subjects completed a matrix reasoning (MR) task in the scanner and a forced-choice recognition task outside the scanner. An analysis of variance (ANOVA) was used to assess group differences in cognitive performance. And linear mixed effects (LMEs) regression analysis was used to assess main and interaction effects of experimental groups, level of MR task difficulty, and recall accuracy on changes in blood oxygen level-dependent (BOLD) signal. ResultsSubjects who received nVNS showed higher accuracy for both easy (p = 0.017) and hard (p = 0.013) items of the MR task, slower reaction times for hard items (p = 0.014), and fewer false negative errors during the forced-choice recognition task (p = 0.047). MR task difficulty related to increased activation in frontoparietal regions (p < 0.001). No difference between nVNS and sham stimulation was found on BOLD response during performance of the MR task. ConclusionsWe hypothesize that nVNS increased attention compared to sham, and that this effect led to enhanced executive functions, and consequently to better performance on visuospatial reasoning and recognition tasks. Results provide initial support that nVNS may be a low-risk, low-cost treatment for cognitive disorders.

Cerebral hemodynamic response to caffeine: effect of dietary caffeine consumption.

Caffeine has a significant effect on cerebrovascular systems, and the dual action of caffeine on both neural and vascular responses leads to concerns for the interpretation of blood oxygenation level-dependent (BOLD) functional MRI. However, potential differences in the brain response to caffeine with regard to consumption habits have not been fully elucidated, as BOLD responses may vary with the dietary caffeine consumption history. The main aim of this study was to characterize the acute effect of caffeine on cerebral hemodynamic responses in participants with different patterns of caffeine consumption habits. Fifteen non-habitual and 11 habitual volunteers were included in this study. The cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to the breath-hold challenge were measured before and after 200 mg caffeine administration. The non-habitual individuals exhibited a pattern of progressive reduction in CBF with time. The CVR was diminished in the caffeinated condition (P < 0.05). In the habitual group, the pattern of CBF decrease was smaller and homogeneous across the brain, and reached steady state rapidly. The CVR was not affected in the presence of caffeine (P > 0.05). Our results demonstrated that the cerebral hemodynamic response to caffeine was subject to the habitual consumption patterns of the participants. The compromised CVR following caffeine administration in the non-habitual group may partially explain the suppressed BOLD response to a visual stimulation in low-caffeine-level users.

Searching for the Mechanism of Action of Extremely Low Frequency Electromagnetic Field-The Pilot fNIRS Research.

There is an ongoing debate on the benefits of magnetic stimulation in neurological disorders. Objectives: We aimed to evaluate the influence of magnetic stimulation on blood oxygenation of the motor cortex using functional near-infrared spectroscopy (fNIRS). Methods: A total of 16 healthy volunteer participants were subjected to four protocols. In the first two protocols, the participants remained at rest without (and then with) magnetic stimulation. In the next two protocols, motor cortex stimulation was achieved using a finger-tapping task, with and without magnetic stimulation. Changes in blood oxygenation levels within the motor cortex were recorded and analysed. Results: No characteristic changes in the blood oxygenation level-dependent responses were observed in resting participants after magnetic stimulation. No statistically significant difference was observed in the amplitude of the fNIRS signal before and after magnetic stimulation. We observed characteristic blood oxygenation level-dependent responses after the finger-tapping task in the second protocol, but not after magnetic stimulation. Conclusions: Although we did not observe any measurable effect of the magnetic field on the haemodynamic response of the motor cortex, understanding the mechanism(s) of magnetic stimulation may be important. Additional, detailed studies are needed to prove or negate the potential of this medical procedure.

Hybrid fiber optic-fMRI for multimodal cell-specific recording and manipulation of neural activity in rodents.

.SignificanceMultiscale imaging holds particular relevance to neuroscience, where it helps integrate the cellular and molecular biological scale, which is most accessible to interventions, with holistic organ-level evaluations, most relevant with respect to function. Being inextricably interdisciplinary, multiscale imaging benefits substantially from incremental technology adoption, and a detailed overview of the state-of-the-art is vital to an informed application of imaging methods.AimIn this article, we lay out the background and methodological aspects of multimodal approaches combining functional magnetic resonance imaging (fMRI) with simultaneous optical measurement or stimulation.ApproachWe focus on optical techniques as these allow, in conjunction with genetically encoded proteins (e.g. calcium indicators or optical signal transducers), unprecedented read-out and control specificity for individual cell-types during fMRI experiments, while leveraging non-interfering modalities.ResultsA variety of different solutions for optical/fMRI methods has been reported ranging from bulk fluorescence recordings via fiber photometry to high resolution microscopy. In particular, the plethora of optogenetic tools has enabled the transformation of stimulus-evoked fMRI into a cell biological interrogation method. We discuss the capabilities and limitations of these genetically encoded molecular tools in the study of brain phenomena of great methodological and neuropsychiatric interest—such as neurovascular coupling (NVC) and neuronal network mapping. We provide a methodological description of this interdisciplinary field of study, and focus in particular on the limitations of the widely used blood oxygen level dependent (BOLD) signal and how multimodal readouts can shed light on the contributions arising from neurons, astrocytes, or the vasculature.ConclusionWe conclude that information from multiple signaling pathways must be incorporated in future forward models of the BOLD response to prevent erroneous conclusions when using fMRI as a surrogate measure for neural activity. Further, we highlight the potential of direct neuronal stimulation via genetically defined brain networks towards advancing neurophysiological understanding and better estimating effective connectivity.

Distinct cerebral coherence in task-based fMRI hyperscanning: cooperation versus competition.

This study features an functional magnetic resonance imaging (fMRI) hyperscanning experiment from 2 sites, 305km apart. The experiment contains 2 conditions: the dyad collaborated to win and then split the reward in the cooperation condition, whereas the winner took all the reward in the competition condition, thereby resulting in dynamic strategic interactions. To calculate the cerebral coherence in such jittered event-related fMRI tasks, we first iteratively estimated the feedback-related blood oxygenation level-dependent responses of each trial, using 8 finite impulse response functions (16s) and then concatenated the beta volume series. With the right temporal-parietal junction (rTPJ) as the seed, the interpersonal connected brain areas were separately identified: the right superior temporal gyrus (rSTG) (cooperation) and the left precuneus (lPrecuneus) (competition), both peaking at the designated frequency bin (1/16s = 0.0625Hz), but not in permuted pairs. In addition, the extended coherence analyses on shorter and longer concatenated volumes verified that only in the optimal trial frequency did the rTPJ-rSTG and rTPJ-lPrecuneus couplings peak. In sum, our approach both showcases a flexible analysis method that widens the applicability of interpersonal coherence in the rapid event-related fMRI hyperscanning and reveals a context-based inter-brain coupling between interacting pairs during cooperation and during competition.

Stress-sensitive inference of task controllability.

Estimating the controllability of the environment enables agents to better predict upcoming events and decide when to engage controlled action selection. How does the human brain estimate controllability? Trial-by-trial analysis of choices, decision times and neural activity in an explore-and-predict task demonstrate that humans solve this problem by comparing the predictions of an 'actor' model with those of a reduced 'spectator' model of their environment. Neural blood oxygen level-dependent responses within striatal and medial prefrontal areas tracked the instantaneous difference in the prediction errors generated by these two statistical learning models. Blood oxygen level-dependent activity in the posterior cingulate, temporoparietal and prefrontal cortices covaried with changes in estimated controllability. Exposure to inescapable stressors biased controllability estimates downward and increased reliance on the spectator model in an anxiety-dependent fashion. Taken together, these findings provide a mechanistic account of controllability inference and its distortion by stress exposure.

Visual Motion Coherence Responses in Human Visual Cortex.

Random dot kinematograms (RDKs) have recently been used to train subjects with cortical scotomas to perform direction of motion discrimination, partially restoring visual motion perception. To study the recovery of visual perception, it is important to understand how visual areas in normal subjects and subjects with cortical scotomas respond to RDK stimuli. Studies in normal subjects have shown that blood oxygen level-dependent (BOLD) responses in human area hV5/MT+ increase monotonically with coherence, in general agreement with electrophysiology studies in primates. However, RDK responses in prior studies were obtained while the subject was performing fixation, not a motion discrimination condition. Furthermore, BOLD responses were gauged against a baseline condition of uniform illumination or static dots, potentially decreasing the specificity of responses for the spatial integration of local motion signals (motion coherence). Here, we revisit this question starting from a baseline RDK condition of no coherence, thereby isolating the component of BOLD response due specifically to the spatial integration of local motion signals. In agreement with prior studies, we found that responses in the area hV5/MT+ of healthy subjects were monotonically increasing when subjects fixated without performing a motion discrimination task. In contrast, when subjects were performing an RDK direction of motion discrimination task, responses in the area hV5/MT+ remained flat, changing minimally, if at all, as a function of motion coherence. A similar pattern of responses was seen in the area hV5/MT+ of subjects with dense cortical scotomas performing direction of motion discrimination for RDKs presented inside the scotoma. Passive RDK presentation within the scotoma elicited no significant hV5/MT+ responses. These observations shed further light on how visual cortex responses behave as a function of motion coherence, helping to prepare the ground for future studies using these methods to study visual system recovery after injury.

Brain-wide ongoing activity is responsible for significant cross-trial BOLD variability.

A notorious issue of task-based functional magnetic resonance imaging (fMRI) is its large cross-trial variability. To quantitatively characterize this variability, the blood oxygenation level-dependent (BOLD) signal can be modeled as a linear summation of a stimulation-relevant and an ongoing (i.e. stimulation-irrelevant) component. However, systematic investigation on the spatiotemporal features of the ongoing BOLD component and how these features affect the BOLD response is still lacking. Here we measured fMRI responses to light onsets and light offsets in awake rats. The neuronal response was simultaneously recorded with calcium-based fiber photometry. We established that between-region BOLD signals were highly correlated brain-wide at zero time lag, including regions that did not respond to visual stimulation, suggesting that the ongoing activity co-fluctuates across the brain. Removing this ongoing activity reduced cross-trial variability of the BOLD response by ~30% and increased its coherence with the Ca2+ signal. Additionally, the negative ongoing BOLD activity sometimes dominated over the stimulation-driven response and contributed to the post-stimulation BOLD undershoot. These results suggest that brain-wide ongoing activity is responsible for significant cross-trial BOLD variability, and this component can be reliably quantified and removed to improve the reliability of fMRI response. Importantly, this method can be generalized to virtually all fMRI experiments without changing stimulation paradigms.

Neural correlates of negative emotion processing in subthreshold depression.

Subthreshold depression (SD) is regarded as a major risk factor for major depression. However, little is known about the neural mechanism of negative emotion processing in SD. The study aimed to examine the different neural correlates for negative emotion processing in SD and health controls (HCs) and to investigate changes in functional connectivity in SD compared with HC. Blood oxygenation level-dependent (BOLD) responses of SD and HC were captured while performing a passive viewing task, which comprised a negative condition and a masked condition. A total of 42 SD and 32 HC adolescents participated in the study. Between-group comparisons revealed significant reduced activations in the superior frontal gyrus (SFG), middle frontal gyrus and middle cingulate gyrus. Region of interest (ROI) analyses did not find correlations between contrast values of the ROIs and depressive symptoms. In addition, we found a significant increased functional connectivity between the SFG and caudate, pallidum and insula, which was significantly correlated with depressive symptoms in the SD group (P < 0.05). Altered functional connectivity between the SFG and caudate, pallidum and insula may underlie the pathology of SD. This is the first study to investigate neural mechanisms of negative emotion processing in SD using task-based functional magnetic resonance imaging.

Unimanual sensorimotor learning-A simultaneous EEG-fMRI aging study.

Sensorimotor coordination requires orchestrated network activity in the brain, mediated by inter‐ and intra‐hemispheric interactions that may be affected by aging‐related changes. We adopted a theoretical model, according to which intra‐hemispheric inhibition from premotor to primary motor cortex is mandatory to compensate for inter‐hemispheric excitation through the corpus callosum. To test this as a function of age we acquired electroencephalography (EEG) simultaneously with functional magnetic resonance imaging (fMRI) in two groups of healthy adults (younger N = 13: 20–25 year and older N = 14: 59–70 year) while learning a unimanual motor task. On average, quality of performance of older participants stayed significantly below that of the younger ones. Accompanying decreases in motor‐event‐related EEG β‐activity were lateralized toward contralateral motor regions, albeit more so in younger participants. In this younger group, the mean β‐power during motor task execution was significantly higher in bilateral premotor areas compared to the older adults. In both groups, fMRI blood oxygen level dependent (BOLD) signals were positively correlated with source‐reconstructed β‐amplitudes: positive in primary motor and negative in premotor cortex. This suggests that β‐amplitude modulation is associated with primary motor cortex “activation” (positive BOLD response) and premotor “deactivation” (negative BOLD response). Although the latter results did not discriminate between age groups, they underscore that enhanced modulation in primary motor cortex may be explained by a β‐associated excitatory crosstalk between hemispheres.

Individual slow wave events give rise to macroscopic fMRI signatures and drive the strength of the BOLD signal in human resting-state EEG-fMRI recordings

The slow wave state is a general state of quiescence interrupted by sudden bursts of activity or so-called slow wave events (SWEs). Recently, the relationship between SWEs and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals was assessed in rodent models which revealed cortex-wide BOLD activation. However, it remains unclear which macroscopic signature corresponds to these specific neurophysiological events in the human brain. Therefore, we analyzed simultaneous electroencephalographic (EEG)-fMRI data during human non-REM sleep. SWEs individually detected in the EEG data were used as predictors in event-related fMRI analyses to examine the relationship between SWEs and fMRI signals. For all 10 subjects we identified significant changes in BOLD activity associated with SWEs covering substantial parts of the gray matter. As demonstrated in rodents, we observed a direct relation of a neurophysiological event to specific BOLD activation patterns. We found a correlation between the number of SWEs and the spatial extent of these BOLD activation patterns and discovered that the amplitude of the BOLD response strongly depends on the SWE amplitude. As altered SWE propagation has recently been found in neuropsychiatric diseases, it is critical to reveal the brain's physiological slow wave state networks to potentially establish early imaging biomarkers for various diseases long before disease onset.

Effect of vascular amyloid on white matter disease is mediated by vascular dysfunction in cerebral amyloid angiopathy

We postulated that vascular dysfunction mediates the relationship between amyloid load and white matter hyperintensities (WMH) in cerebral amyloid angiopathy (CAA). Thirty-eight cognitively healthy patients with CAA (mean age 70 ± 7.1) were evaluated. WMH was quantified and expressed as percent of total intracranial volume (pWMH) using structural MRI. Mean global cortical Distribution Volume Ratio representing Pittsburgh Compound B (PiB) uptake (PiB-DVR) was calculated from PET scans. Time-to-peak [TTP] of blood oxygen level-dependent response to visual stimulation was used as an fMRI measure of vascular dysfunction. Higher PiB-DVR correlated with prolonged TTP (r = 0.373, p = 0.021) and higher pWMH (r = 0.337, p = 0.039). Prolonged TTP also correlated with higher pWMH (r = 0.485, p = 0.002). In a multivariate linear regression model, TTP remained independently associated with pWMH (p = 0.006) while PiB-DVR did not (p = 0.225). In a bootstrapping model, TTP had a significant indirect effect (ab = 0.97, 95% CI: 0.137–2.461), supporting that the association between PiB-DVR and pWMH is mediated by TTP response. There was no longer a direct effect independent of the hypothesized pathway. Our study suggests that the effect of vascular amyloid load on white matter disease is mediated by vascular dysfunction in CAA. Amyloid lowering strategies might prevent pathophysiological processes leading to vascular dysfunction, therefore limiting ischemic brain injury.

Repeated blast mild traumatic brain injury and oxycodone self-administration produce interactive effects on neuroimaging outcomes.

Traumatic brain injury (TBI) and drug addiction are common comorbidities, but it is unknown if the neurological sequelae of TBI contribute to this relationship. We have previously reported elevated oxycodone seeking after drug self-administration in rats that received repeated blast TBI (rbTBI). TBI and exposure to drugs of abuse can each change structural and functional neuroimaging outcomes, but it is unknown if there are interactive effects of injury and drug exposure. To determine the effects of TBI and oxycodone exposure, we subjected rats to rbTBI and oxycodone self-administration and measured drug seeking and several neuroimaging measures. We found interactive effects of rbTBI and oxycodone on fractional anisotropy (FA) in the nucleus accumbens (NAc) and that FA in the medial prefrontal cortex (mPFC) was correlated with drug seeking. We also found an interactive effect of injury and drug on widespread functional connectivity and regional homogeneity of the blood oxygen level dependent (BOLD) response, and that intra-hemispheric functional connectivity in the infralimbic medial prefrontal cortex positively correlated with drug seeking. In conclusion, rbTBI and oxycodone self-administration had interactive effects on structural and functional magnetic resonance imaging (MRI) measures, and correlational effects were found between some of these measures and drug seeking. These data support the hypothesis that TBI and opioid exposure produce neuroadaptations that contribute to addiction liability.