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Obsessive-compulsive disorder (OCD) is linked with dysfunction in frontal-striatal, fronto-limbic, and visual brain regions. Research using proton magnetic resonance spectroscopy (1H-MRS) suggests that altered neurometabolite levels, like glutamate, may contribute to this dysfunction. However, static neurometabolite levels in OCD patients have shown inconsistent results, likely due to previous studies' limited focus on neurometabolite dynamics. We employ functional MRS (fMRS) and functional magnetic resonance imaging (fMRI) to explore these dynamics and brain activation during OCD symptom provocation. We utilized a combined 7-tesla fMRI-fMRS setup to examine task-related BOLD response and glutamate changes in the lateral occipital cortex (LOC) of 30 OCD participants and 34 matched controls during an OCD-specific symptom provocation task. The study examined main effects and between-group differences in brain activation and glutamate levels during the task. A whole sample task-effects analysis on data meeting predefined quality criteria showed significant glutamate increases (n = 41 (22 OCD, 19 controls), mean change: 3.2 %, z = 3.75, p <.001) and task activation (n = 54 (26 OCD, 28 controls), p <.001) in the LOC during OCD blocks compared to neutral blocks. However, no differences in task-induced glutamate dynamics or activation between groups were found, nor a correlation between glutamate levels and task activation. We were able to measure task-induced increases in glutamate and BOLD levels, emphasizing its feasibility for OCD research. The absence of group differences highlights the need for further exploration to discern to what extent neurometabolite dynamics differ between OCD patients and controls. Once established, future studies can use pre-post intervention fMRS-fMRI to probe the effects of therapies modulating glutamate pathways in OCD. • We used 7 T fMRI-fMRS to assess neurometabolite dynamics and brain activation in OCD. • Revealed significant glutamate increases during symptom provocation without group differences • We found a negative correlation between LOC BOLD response and HAM-A scores in OCD. • We highlighted the potential of fMRS-fMRI for understanding psychiatric disorders. [ABSTRACT FROM AUTHOR]

Objective: Temporal lobe epilepsy (TLE) has a high probability of becoming drug resistant and is frequently considered for surgical intervention. However, 30% of TLE cases have nonlesional magnetic resonance imaging (MRI) scans, which is associated with worse surgical outcomes. Characterizing interactions between temporal and extratemporal structures in these patients may help understand these poor outcomes. Simultaneous intracranial electroencephalography–functional MRI (iEEG‐fMRI) can measure the hemodynamic changes associated with interictal epileptiform discharges (IEDs) recorded directly from the brain. This study was designed to characterize the whole brain patterns of IED‐associated fMRI activation recorded exclusively from the mesial temporal lobes of patients with nonlesional TLE. Methods: Eighteen patients with nonlesional TLE undergoing iEEG monitoring with mesial temporal IEDs underwent simultaneous iEEG‐fMRI at 3 T. IEDs were marked, and statistically significant clusters of fMRI activation were identified. The locations of IED‐associated fMRI activation for each patient were determined, and patients were grouped based on the location and pattern of fMRI activation. Results: Two patterns of IED‐associated fMRI activation emerged: primarily localized (n = 7), where activation was primarily located within the ipsilateral temporal lobe, and primarily diffuse (n = 11), where widespread bilateral extratemporal activation was detected. The primarily diffuse group reported significantly fewer focal to bilateral tonic–clonic seizures and had better postsurgical outcomes. Significance: Simultaneous iEEG‐fMRI can measure the hemodynamic changes associated with focal IEDs not visible on scalp EEG, such as those arising from the mesial temporal lobe. Significant fMRI activation associated with these IEDs was observed in all patients. Two distinct patterns of IED‐associated activation were seen: primarily localized to the ipsilateral temporal lobe and more widespread, bilateral activation. Patients with widespread IED associated‐activation had fewer focal to bilateral tonic–clonic seizures and better postsurgical outcome, which may suggest a neuroprotective mechanism limiting the spread of ictal events. [ABSTRACT FROM AUTHOR]

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

fMRI imaging measures brain activity by detecting changes in the brain that are associated with blood flow and can be used in order to determine the size and location of visual field maps. This study measured BOLD responses in humans to understand spatial summation by showing them spatial contrast pattern images through vertical and horizontal apertures.Nonlinear responses can be computed from the visual field responses, from which the spatial summation ratio is calculated. A ratio of less than one indicates a smaller response to exposure to a full aperture or contrast image than predicted by the linear model. Datasets were analyzed using MATLAB, producing eccentricity maps of the visual cortices from stimuli. BOLD response curves identify the intensity of the maps within a particular voxel. The eccentricity maps can then be overlain on anatomical representations of the brain, characterizing the various visual field cortices. Methods of fMRI data analysis are confirmed with the results of this study.

In this study we assessed the neural correlates of functional vision while varying patterns of light filtration. Four filter conditions used relatively flat filtering across the visible spectrum while one filter was a step filter that selectively absorbed violet light (wavelengths below about 415 nm). Neural effects were quantified by measuring the BOLD response ((T2*-based fMRI) while subjects performed a challenging visual task (judging gap direction in Landolt Cs that randomly varied in size). In general (based on p

Background and Purpose: A number of functional magnetic resonance imaging (fMRI) studies rely on application of anesthetic agents during scanning that can modulate and complicate interpretation of the measured hemodynamic blood oxygenation level‐dependent (BOLD) response. The purpose of the present study was to investigate the effect of general anesthesia on two main components of BOLD signal including neuronal activity and vascular response. Methods: Breath‐holding (BH) fMRI was conducted in wakefulness and under anesthesia states in 9 patients with drug‐resistant epilepsy who needed to get scanned under anesthesia during laser interstitial thermal therapy. BOLD and BOLD cerebrovascular reactivity (BOLD‐CVR) maps were compared using t‐test between two states to assess the effect of anesthesia on neuronal activity and vascular factors (p <.05). Results: Overall, our findings revealed an increase in BOLD‐CVR and decrease in BOLD response under anesthesia in several brain regions. The results proposed that the modulatory mechanism of anesthetics on neuronal and vascular components of BOLD signal may work in different ways. Conclusion: This experiment for the first human study showed that anesthesia may play an important role in dissociation between neuronal and vascular responses contributed to hemodynamic BOLD signal using BH fMRI imaging that may assist the implication of general anesthesia and interpretation of outcomes in clinical setting. [ABSTRACT FROM AUTHOR]

Recent studies on the pathophysiology of alcohol dependence suggest a link between peripheral calcium concentrations and alcohol craving. Here, we investigated the association between plasma calcium concentration, cue-induced brain activation, and alcohol craving. Plasma calcium concentrations were measured at the onset of inpatient detoxification in a sample of N = 115 alcohol-dependent patients. Alcohol cue-reactivity was assessed during early abstinence (mean 11.1 days) using a functional magnetic resonance imaging (fMRI) alcohol cue-reactivity task. Multiple regression analyses and bivariate correlations between plasma calcium concentrations, clinical craving measures and neural alcohol cue-reactivity (CR) were tested. Results show a significant negative correlation between plasma calcium concentrations and compulsive alcohol craving. Higher calcium levels predicted higher alcohol cue-induced brain response in a cluster of frontal brain areas, including the dorsolateral prefrontal cortex (dlPFC), the anterior prefrontal cortex (alPFC), and the inferior (IFG) and middle frontal gyri (MFG). In addition, functional brain activation in those areas correlated negatively with craving for alcohol during fMRI. Higher peripheral calcium concentrations during withdrawal predicted increased alcohol cue-induced brain activation in frontal brain areas, which are associated with craving inhibition and cognitive control functions. This might indicate that higher plasma calcium concentrations at onset of detoxification could modulate craving inhibition during early abstinence. Trial registration number: DRKS00003388; date of registration: 14.12.2011. [ABSTRACT FROM AUTHOR]

Different types of brain injury, such as status epilepticus (SE), trauma, or stroke may initiate the process of epileptogenesis and lead to the development of temporal lobe epilepsy. Epileptogenesis is characterized by an initial latent period during which impaired network communication and synaptic circuit alterations are occurring. Ultimately, these modifications result in the development of spontaneous recurrent seizures (SRS). Current knowledge on the functional connectivity network changes during epileptogenesis and how network alterations relate to seizure is very limited. To investigate these underlying network connectivity modifications, we imaged epileptic and control rats by means of resting-state functional MRI (rsfMRI) during epileptogenesis. A cohort of animals was video-electroencephalography (video-EEG) monitored continuously over 12 weeks to determine disease severity during the course of disease, with the first SRS appearing around 2 weeks post-SE for most of the animals. Epileptic animals displayed a significant wide-spread hyposynchrony at 2 weeks post-SE, followed by a significant increase in network synchronicity from 2 to 4 weeks post-SE. Interestingly, subjects with a delayed epilepsy onset demonstrated significantly lower synchronicity compared to controls and the epileptic group at 4 weeks post-SE. Finally, network connectivity at 4 weeks post-SE was found to correlate with seizure onset (r = 0.858, p

Combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) enables a non-invasive investigation of the human brain function and evaluation of the correlation of these two important modalities of brain activity. This paper explores recent reports on using advanced simultaneous EEG–fMRI methods proposed to map the regions and networks involved in focal epileptic seizure generation. One of the applications of EEG and fMRI combination as a valuable clinical approach is the pre-surgical evaluation of patients with epilepsy to map and localize the precise brain regions associated with epileptiform activity. In the process of conventional analysis using EEG–fMRI data, the interictal epileptiform discharges (IEDs) are visually extracted from the EEG data to be convolved as binary events with a predefined hemodynamic response function (HRF) to provide a model of epileptiform BOLD activity and use as a regressor for general linear model (GLM) analysis of the fMRI data. This review examines the methodologies involved in performing such studies, including techniques used for the recording of EEG inside the scanner, artifact removal, and statistical analysis of the fMRI signal. It then discusses the results reported for patients with primary generalized epilepsy and patients with different types of focal epileptic disorders. An important matter that these results have brought to light is that the brain regions affected by interictal epileptic discharges might not be limited to the ones where they have been generated. The developed methods can help reveal the regions involved in or affected by a seizure onset zone (SOZ). As confirmed by the reviewed literature, EEG–fMRI provides information that comes particularly useful when evaluating patients with refractory epilepsy for surgery.

Combining functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) enables a non-invasive investigation of the human brain function and evaluation of the correlation of these two important modalities of brain activity. This paper explores recent reports on using advanced simultaneous EEG–fMRI methods proposed to map the regions and networks involved in focal epileptic seizure generation. One of the applications of EEG and fMRI combination as a valuable clinical approach is the pre-surgical evaluation of patients with epilepsy to map and localize the precise brain regions associated with epileptiform activity. In the process of conventional analysis using EEG–fMRI data, the interictal epileptiform discharges (IEDs) are visually extracted from the EEG data to be convolved as binary events with a predefined hemodynamic response function (HRF) to provide a model of epileptiform BOLD activity and use as a regressor for general linear model (GLM) analysis of the fMRI data. This review examines the methodologies involved in performing such studies, including techniques used for the recording of EEG inside the scanner, artifact removal, and statistical analysis of the fMRI signal. It then discusses the results reported for patients with primary generalized epilepsy and patients with different types of focal epileptic disorders. An important matter that these results have brought to light is that the brain regions affected by interictal epileptic discharges might not be limited to the ones where they have been generated. The developed methods can help reveal the regions involved in or affected by a seizure onset zone (SOZ). As confirmed by the reviewed literature, EEG–fMRI provides information that comes particularly useful when evaluating patients with refractory epilepsy for surgery. [ABSTRACT FROM AUTHOR]

BackgroundSignificant cortical thinning and neural resource allocation changes emerge during adolescence; however, little is known of how morphometric changes influence neural response to cognitive demands. This study used a novel multimodal imaging registration technique to examine the relationship between brain structure and function during adolescence.Methods156 healthy 12-14 year-olds (44% female) participants underwent structural and functional magnetic resonance imaging. Cortical surface reconstruction was performed via FreeSurfer, and neural activation was measured from a blood oxygen level dependent (BOLD) contrast during visual working memory (VWM) via AFNI. AFNI Surface Mapper aligned segmented volumetric and functional datasets to a common template space. Hierarchical linear regressions determined the effect of cortical thickness on VWM BOLD contrast in brain regions that activated during the VWM task, controlling for age, pubertal development, gender, IQ, and intracranial volume.ResultsPower analyses suggest this study was able to detect small effect sizes. However, in no region was cortical thickness related to BOLD activation (ps>.01; R(2)Δ

High-resolution functional magnetic resonance imaging (fMRI) using blood oxygenation dependent level-dependent (BOLD) signal is an increasingly popular tool to non-invasively examine neuronal processes at the mesoscopic level. However, as the BOLD signal stems from hemodynamic changes, its temporal and spatial properties do not match those of the underlying neuronal activity. In particular, the laminar BOLD response (LBR), commonly measured with gradient-echo (GE) MRI sequence, is confounded by non-local changes in deoxygenated hemoglobin and cerebral blood volume propagated within intracortical ascending veins, leading to a unidirectional blurring of the neuronal activity distribution towards the cortical surface. Here, we present a new cortical depth-dependent model of the BOLD response based on the principle of mass conservation, which takes the effect of ascending (and pial) veins on the cortical BOLD responses explicitly into account. It can be used to dynamically model cortical depth profiles of the BOLD signal as a function of various baseline- and activity-related physiological parameters for any spatiotemporal distribution of neuronal changes. We demonstrate that the commonly observed spatial increase of LBR is mainly due to baseline blood volume increase towards the surface. In contrast, an occasionally observed local maximum in the LBR (i.e. the so-called “bump”) is mainly due to spatially inhomogeneous neuronal changes rather than locally higher baseline blood volume. In addition, we show that the GE-BOLD signal laminar point-spread functions, representing the signal leakage towards the surface, depend on several physiological parameters and on the level of neuronal activity. Furthermore, even in the case of simultaneous neuronal changes at each depth, inter-laminar delays of LBR transients are present due to the ascending vein. In summary, the model provides a conceptual framework for the biophysical interpretation of common experimental observations in high-resolution fMRI data. In the future, the model will allow for deconvolution of the spatiotemporal hemodynamic bias of the LBR and provide an estimate of the underlying laminar excitatory and inhibitory neuronal activity.

Although the fat mass and obesity-associated gene (FTO) correlates with elevated body mass, it is unclear how it contributes to overeating. We tested if individuals with the A allele show greater reward region responsivity to receipt and anticipated receipt of food and money and palatable food images. We also tested if these individuals show greater future weight gain. Initially healthy weight adolescents (Study 1, N  = 162; Study 2, N  = 135) completed different functional magnetic resonance imaging paradigms and had their body mass measured annually over 3 years. Adolescents with the AA or AT genotypes showed less precuneus and superior parietal lobe response and greater cuneus and prefrontal cortex response to milkshake receipt and less putamen response to anticipated milkshake receipt than those with the TT genotype in separate analyses of each sample. Groups did not differ in response to palatable food images, and receipt and anticipated receipt of money, or in weight gain over 3-year follow-up. Results suggest that initially healthy weight adolescents with vs without the FTO A allele show differential responsivity to receipt and anticipated receipt of food but do not differ in neural response to palatable food images and monetary reward and do not show greater future weight gain. [ABSTRACT FROM AUTHOR]

Purpose: The positive BOLD response can vary across brain regions. Here, the positive BOLD responses of motor regions, including the cerebellum, were investigated by fast fMRI acquisition. Methods: The participants were asked to perform an event‐related finger‐tapping task in a 7T MRI scanner during a fast 3D‐EPI controlled aliasing in parallel imaging acquisition protocol (CAIPI; TR = 399 ms). The positive BOLD responses of 6 motor regions were extracted and their timings and shapes measured. Results: Compared with other brain regions, the positive BOLD responses in the cerebellum and secondary somatosensory cortex showed delayed onsets, but no differences were observed for the time to‐peak. Additionally, variations of the undershoot and main peak amplitudes were also observed, and undershoot was quasi‐absent in the cerebellum. Conclusion: This study confirms that care should be taken when drawing conclusions about neuronal activity from the BOLD signal, particularly for the cerebellum. [ABSTRACT FROM AUTHOR]

Abstract Objectives Simultaneous intracranial EEG and functional MRI (icEEG-fMRI) can be used to map the haemodynamic (BOLD) changes associated with the generation of IEDs. Unlike scalp EEG-fMRI, in most patients who undergo icEEG-fMRI, IEDs recorded intracranially are numerous and show variability in terms of field amplitude and morphology. Therefore, visual marking can be highly subjective and time consuming. In this study, we applied an automated spike classification algorithm, Wave_clus (WC), to IEDs marked visually on icEEG data acquired during simultaneous fMRI acquisition. The motivation of this work is to determine whether using a potentially more consistent and unbiased automated approach can produce more biologically meaningful BOLD patterns compared to the BOLD patterns obtained based on the conventional, visual classification. Methods We analysed simultaneous icEEG-fMRI data from eight patients with severe drug resistant epilepsy, and who subsequently underwent resective surgery that resulted in a good outcome: confirmed epileptogenic zone (EZ). For each patient two fMRI analyses were performed: one based on the conventional visual IED classification and the other based on the automated classification. We used the concordance of the IED-related BOLD maps with the confirmed EZ as an indication of their biological meaning, which we compared for the automated and visual classifications for all IED originating in the EZ. Results Across the group, the visual and automated classifications resulted in 32 and 24 EZ IED classes respectively, for which 75% vs 83% of the corresponding BOLD maps were concordant. At the single-subject level, the BOLD maps for the automated approach had greater concordance in four patients, and less concordance in one patient, compared to those obtained using the conventional visual classification, and equal concordance for three remaining patients. These differences did not reach statistical significance. Conclusion We found automated IED classification on icEEG data recorded during fMRI to be feasible and to result in IED-related BOLD maps that may contain similar or greater biological meaning compared to the conventional approach in the majority of the cases studied. We anticipate that this approach will help to gain significant new insights into the brain networks associated with IEDs and in relation to postsurgical outcome. Highlights • IcEEG-fMRI provides a unique insight into the generators of IEDs. • Visual IED marking can be highly subjective and time consuming. • An automated spike classification algorithm, Wave_clus , can minimise subjectivity. • The BOLD maps associated with IEDs classified using Wave_clus may commonly have equal or greater biological meaning than those obtained using conventional, visual classification. [ABSTRACT FROM AUTHOR]

Objectives: Simultaneous scalp EEG-fMRI can identify hemodynamic changes associated with the generation of interictal epileptiform discharges (IEDs), and it has the potential of becoming a standard, non-invasive technique for pre-surgical assessment of patients with medically intractable epilepsy. This study was designed to assess the BOLD response to focal IEDs recorded via simultaneous intracranial EEG-functional MRI (iEEG-fMRI). Methods: Twelve consecutive patients undergoing intracranial video EEG monitoring were recruited for iEEG-fMRI studies at 3 T. Depth, subdural strip, or grid electrodes were implanted according to our standard clinical protocol. Subjects underwent 10–60 min of continuous iEEG-fMRI scanning. IEDs were marked, and the most statistically significant clusters of BOLD signal were identified (Z-score 2.3, p value