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Previous studies showed equivocal findings regarding the efficacy of focused attention and distraction to experimental pain. This study examined the relative efficacy of these strategies on perception of cold pressor pain in 41 chronic back pain patients and 41 healthy control participants. Participants were randomized to the 2 strategies and then completed a 7-minute cold pressor test. Pain intensity and discomfort ratings were obtained during the task. Participants who completed the first task were asked to complete a second cold pressor task without instructions. Pain and discomfort ratings differed by condition across time. In the distraction condition, pain levels started low but continued to rise throughout the cold pressor immersion, whereas in the focused attention condition, pain levels started higher, rose less quickly, and then decreased from the middle of the task. Focused attention was associated with higher pain and lower completion rates in chronic pain patients compared with healthy control subjects. Focused attention might therefore not be an effective intervention strategy for individuals with chronic back pain. Finally, in the second cold pressor test, patients' pain reports rose more rapidly than those of healthy control subjects. The results of this study can be explained in terms of differences in cognitive appraisal between pain patients and healthy control participants. PERSPECTIVE: Marked differences were found between chronic back pain patients and control participants regarding focused attention as compared with distraction as a means of coping with cold pressor-induced pain. These differences underline the importance of taking into account previous experience with pain when recommending strategies to cope with painful procedures. [ABSTRACT FROM AUTHOR]

Abstract Background Pain is a complex experience with sensory, emotional and cognitive aspects. Genetic and environmental factors contribute to pain-related phenotypes such as chronic pain states. Genetic variations in the gene coding for catechol-O-methyltransferase (COMT) have been suggested to affect clinical and experimental pain-related phenotypes including regional μ-opioid system responses to painful stimulation as measured by ligand-PET (positron emission tomography). The functional val158met single nucleotide polymorphism has been most widely studied. However, apart from its impact on pain-induced opioid release the effect of this genetic variation on cerebral pain processing has not been studied with activation measures such as functional magnetic resonance imaging (fMRI), PET or electroencephalography. In the present fMRI study we therefore sought to investigate the impact of the COMT val158met polymorphism on the blood oxygen level-dependent (BOLD) response to painful laser stimulation. Results 57 subjects were studied. We found that subjects homozygous for the met158 allele exhibit a higher BOLD response in the anterior cingulate cortex (ACC), foremost in the mid-cingulate cortex, than carriers of the val158 allele. Conclusion This result is in line with previous studies that reported higher pain sensitivity in homozygous met carriers. It adds to the current literature in suggesting that this behavioral phenotype may be mediated by, or is at least associated with, increased ACC activity. More generally, apart from one report that focused on pain-induced opioid release, this is the first functional neuroimaging study showing an effect of the COMT val158met polymorphism on cerebral pain processing.

Objective . Combining magnetic resonance imaging (MRI) and electroencephalography (EEG) provides a powerful tool for investigating brain function at varying spatial and temporal scales. Simultaneous acquisition of both modalities can provide unique information that a single modality alone cannot reveal. However, current simultaneous EEG-fMRI studies are limited to a small set of MRI sequences due to the image quality and safety limitations of commercially available MR-conditional EEG nets. We tested whether the Inknet2, a high-resistance polymer thick film based EEG net that uses conductive ink, could enable the acquisition of a variety of MR image modalities with minimal artifacts by reducing the radiofrequency-shielding caused by traditional MR-conditional nets. Approach . We first performed simulations to model the effect of the EEG nets on the magnetic field and image quality. We then performed phantom scans to test image quality with a conventional copper EEG net, with the new Inknet2, and without any EEG net. Finally, we scanned five human subjects at 3 Tesla (3 T) and three human subjects at 7 Tesla (7 T) with and without the Inknet2 to assess structural and functional MRI image quality. Main results . Across these simulations, phantom scans, and human studies, the Inknet2 induced fewer artifacts than the conventional net and produced image quality similar to scans with no net present. Significance . Our results demonstrate that high-quality structural and functional multimodal imaging across a variety of MRI pulse sequences at both 3 T and 7 T is achievable with an EEG net made with conductive ink and polymer thick film technology., (Creative Commons Attribution license.)

Magnetic resonance imaging (MRI) and continuous electroencephalogram (EEG) monitoring are essential in the clinical management of neonatal seizures. EEG electrodes, however, can significantly degrade the image quality of both MRI and CT due to substantial metallic artifacts and distortions. Thus, we developed a novel thin film trace EEG net ("NeoNet") for improved MRI and CT image quality without compromising the EEG signal quality. The aluminum thin film traces were fabricated with an ultra-high-aspect ratio (up to 17,000:1, with dimensions 30 nm × 50.8 cm × 100 µm), resulting in a low density for reducing CT artifacts and a low conductivity for reducing MRI artifacts. We also used numerical simulation to investigate the effects of EEG nets on the B 1 transmit field distortion in 3 T MRI. Specifically, the simulations predicted a 65% and 138% B 1 transmit field distortion higher for the commercially available copper-based EEG net ("CuNet", with and without current limiting resistors, respectively) than with NeoNet. Additionally, two board-certified neuroradiologists, blinded to the presence or absence of NeoNet, compared the image quality of MRI images obtained in an adult and two children with and without the NeoNet device and found no significant difference in the degree of artifact or image distortion. Additionally, the use of NeoNet did not cause either: (i) CT scan artifacts or (ii) impact the quality of EEG recording. Finally, MRI safety testing confirmed a maximum temperature rise associated with the NeoNet device in a child head-phantom to be 0.84 °C after 30 min of high-power scanning, which is within the acceptance criteria for the temperature for 1 h of normal operating mode scanning as per the FDA guidelines. Therefore, the proposed NeoNet device has the potential to allow for concurrent EEG acquisition and MRI or CT scanning without significant image artifacts, facilitating clinical care and EEG/fMRI pediatric research.

Simultaneous EEG-fMRI has developed into a mature measurement technique in the past 25 years. During this time considerable technical and analytical advances have been made, enabling valuable scientific contributions to a range of research fields. This review will begin with an introduction to the measurement principles involved in EEG and fMRI and the advantages of combining these methods. The challenges faced when combining the two techniques will then be considered. An overview of the leading application fields where EEG-fMRI has made a significant contribution to the scientific literature and emerging applications in EEG-fMRI research trends is then presented.

Despite the relationship between brain structure and function being of fundamental interest in cognitive neuroscience, the relationship between the brain's white matter, measured using fractional anisotropy (FA), and the functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) response is poorly understood. A systematic review of literature investigating the association between FA and fMRI BOLD response was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed and Web of Knowledge databases were searched up until 22.04.2016 using a predetermined set of search criteria. The search identified 363 papers, 28 of which met the specified inclusion criteria. Positive relationships were mainly observed in studies investigating the primary sensory and motor systems and in resting state data. Both positive and negative relationships were seen in studies using cognitive tasks. This systematic review suggests that there is a relationship between FA and the fMRI BOLD response and that the relationship is task and region dependent. Behavioural and/or clinical variables were shown to be essential in interpreting the relationships between imaging measures. The results highlight the heterogeneity in the methods used across papers in terms of fMRI task, population investigated and data analysis techniques. Further investigation and replication of current findings are required before definitive conclusions can be drawn., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Unlabelled: Despite a fundamental interest in the relationship between structure and function, the relationships between measures of white matter microstructural coherence and functional brain responses to pain are poorly understood. We investigated whether fractional anisotropy (FA) in 2 white matter regions in pathways associated with pain is related to the functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) response to thermal stimulation. BOLD fMRI was measured from 16 healthy male subjects during painful thermal stimulation of the right arm. Diffusion-weighted images were acquired for each subject and FA estimates were extracted from the posterior internal capsule and the cingulum (cingulate gyrus). These values were then included as covariates in the fMRI data analysis. We found BOLD response in the midcingulate cortex (MCC) to be positively related to FA in the posterior internal capsule and negatively related to FA in the cingulum. Our results suggest that the MCC's involvement in processing pain can be further delineated by considering how the magnitude of the BOLD response is related to white matter microstructural coherence and to subjective perception of pain. Considering relationships to white matter microstructural coherence in tracts involved in transmitting information to different parts of the pain network can help interpretation of MCC BOLD activation., Perspective: Relationships between functional brain responses, white matter microstructural coherence, and subjective ratings are crucial for understanding the role of the MCC in pain. These findings provide a basis for investigating the effect of the reduced white matter microstructural coherence observed in some pain disorders on the functional responses to pain., (Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: Cortical acetylcholine released from cells in the basal forebrain facilitates cue detection and improves attentional performance. Cholinergic fibres to the cortex originate from the CH4 cell group, sometimes referred to as the Nucleus basalis of Meynert and the Nucleus subputaminalis of Ayala. The aim of this work was to investigate the effects of volumes of cholinergic nuclei on attention and executive function., Methods: The volumes of CH4 and CH4p subregions were measured in a subgroup of 38 subjects (33.5 ± 11 years, 20 females) from a population-based cohort study of smokers and never-smokers who have undergone additional MR imaging. To define regions of interest, we applied a DARTEL-based procedure implemented in SPM8 and a validated probabilistic map of the basal forebrain. Attention and executive function were measured with Trail-Making Test (TMT A+B) and Stroop-Task., Results: We found a quadratic effect of the left CH4 subregion on performance of the TMT. Extremely small as well as extremely large volumes are associated with poor test performance., Conclusions: Our results indicate that a small CH4 volume predisposes for a hypocholinergic state, whereas an extremely large volume predisposes for a hypercholinergic state. Both extremes have detrimental effects on attention. Comparable nonlinear effects have already been reported in pharmacological studies on the effects cholinergic agonists on attention.

Background: Combining both high temporal and spatial resolution by means of simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) is of relevance to neuroscientists. This combination, however, leads to a distortion of the EEG signal by the so-called cardio-ballistic artefacts. The aim of the present study was developing an approach to restore meaningful physiological EEG data from recordings at different magnetic fields., New Methods: The distortions introduced by the magnetic field were corrected using a combination of concepts from independent component analysis (ICA) and mutual information (MI). Thus, the components were classified as either related to the cardio-ballistic artefacts or to the signals of interest. EEG data from two experimental paradigms recorded at different magnetic field strengths up to 9.4 T were analyzed: (i) spontaneous activity using an eyes-open/eyes-closed alternation, and (ii) responses to auditory stimuli, i.e. auditory evoked potentials., Results: Even at ultra-high magnetic fields up to 9.4 T the proposed artefact rejection approach restored the physiological time-frequency information contained in the signal of interest and the data were suitable for subsequent analyses., Comparison With Existing Methods: Blind source separation (BSS) has been used to retrieve information from EEG data recorded inside the MR scanner in previous studies. After applying the presented method on EEG data recorded at 4 T, 7 T, and 9.4 T, we could retrieve more information than from data cleaned with the BSS method., Conclusions: The present work demonstrates that EEG data recorded at ultra-high magnetic fields can be used for studying neuroscientific research question related to oscillatory activity., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Based on individual daily physiological cycles, humans can be classified as early (EC), late (LC) and intermediate (IC) chronotypes. Recent studies have verified that chronotype-specificity relates to performance on cognitive tasks: participants perform more efficiently when tested in the chronotype-specific optimal time of day than when tested in their non-optimal time. Surprisingly, imaging studies focussing on the underlying neural mechanisms of potential chronotype-specificities are sparse. Moreover, chronotype-specific alterations of language-related semantic processing have been neglected so far., Methods: 16 male, healthy ECs, 16 ICs and 16 LCs participated in a fast event-related functional Magnetic Resonance Imaging (fMRI) paradigm probing semantic priming. Subjects read two subsequently presented words (prime, target) and were requested to determine whether the target word was an existing word or a non-word. Subjects were tested during their individual evening hours when homeostatic sleep pressure and circadian alertness levels are high to ensure equal entrainment., Results: Chronotype-specificity is associated with task-performance and brain activation. First, ECs exhibited slower reaction times than LCs. Second, ECs showed attenuated BOLD responses in several language-related brain areas, e.g. in the left postcentral gyrus, left and right precentral gyrus and in the right superior frontal gyrus. Additionally, increased BOLD responses were revealed for LCs as compared to ICs in task-related areas, e.g. in the right inferior parietal lobule and in the right postcentral gyrus., Conclusions: These findings reveal that even basic language processes are associated with chronotype-specific neuronal mechanisms. Consequently, results might change the way we schedule patient evaluations and/or healthy subjects in e.g. experimental research and adding "chronotype" as a statistical covariate.

Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) allow for a non-invasive investigation of cerebral functions with high temporal and spatial resolution. The main challenge of such integration is the removal of the pulse artefact (PA) that affects EEG signals recorded in the magnetic resonance (MR) scanner. Often applied techniques for this purpose are Optimal Basis Set (OBS) and Independent Component Analysis (ICA). The combination of OBS and ICA is increasingly used, since it can potentially improve the correction performed by each technique separately. The present study is focused on the OBS-ICA combination and is aimed at providing the optimal ICA parameters for PA correction in resting-state EEG data, where the information of interest is not specified in latency and amplitude as in, for example, evoked potential. A comparison between two intervals for ICA calculation and four methods for marking artefactual components was performed. The performance of the methods was discussed in terms of their capability to 1) remove the artefact and 2) preserve the information of interest. The analysis included 12 subjects and two resting-state datasets for each of them. The results showed that none of the signal lengths for the ICA calculation was highly preferable to the other. Among the methods for the identification of PA-related components, the one based on the wavelets transform of each component emerged as the best compromise between the effectiveness in removing PA and the conservation of the physiological neuronal content.

Introduction: Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provides high spatial and temporal resolution. In this study we combined EEG and fMRI to investigate the structures involved in the processing of different sound pressure levels (SPLs)., Methods: EEG data were recorded simultaneously with fMRI from 16 healthy volunteers using MR compatible devices at 3 T. Tones with different SPLs were delivered to the volunteers and the N1/P2 amplitudes were included as covariates in the fMRI data analysis in order to compare the structures activated with high and low SPLs. Analysis of variance (ANOVA) and ROI analysis were also performed. Additionally, source localisation analysis was performed on the EEG data., Results: The integration of averaged ERP parameters into the fMRI analysis showed an extended map of areas exhibiting covariation with the BOLD signal related to the auditory stimuli. The ANOVA and ROI analyses also revealed additional brain areas other than the primary auditory cortex (PAC) which were active with the auditory stimulation at different SPLs. The source localisation analyses showed additional sources apart from the PAC which were active with the high SPLs., Discussion: The PAC and the insula play an important role in the processing of different SPLs. In the fMRI analysis, additional activation was found in the anterior cingulate cortex, opercular and orbito-frontal cortices with high SPLs. A strong response of the visual cortex was also found with the high SPLs, suggesting the presence of cross-modal effects.

As cognitive neuroscience methods develop, established experimental tasks are used with emerging brain imaging modalities. Here transferring a paradigm (the visual oddball task) with a long history of behavioral and electroencephalography (EEG) experiments to a functional magnetic resonance imaging (fMRI) experiment is considered. The aims of this paper are to briefly describe fMRI and when its use is appropriate in cognitive neuroscience; illustrate how task design can influence the results of an fMRI experiment, particularly when that task is borrowed from another imaging modality; explain the practical aspects of performing an fMRI experiment. It is demonstrated that manipulating the task demands in the visual oddball task results in different patterns of blood oxygen level dependent (BOLD) activation. The nature of the fMRI BOLD measure means that many brain regions are found to be active in a particular task. Determining the functions of these areas of activation is very much dependent on task design and analysis. The complex nature of many fMRI tasks means that the details of the task and its requirements need careful consideration when interpreting data. The data show that this is particularly important in those tasks relying on a motor response as well as cognitive elements and that covert and overt responses should be considered where possible. Furthermore, the data show that transferring an EEG paradigm to an fMRI experiment needs careful consideration and it cannot be assumed that the same paradigm will work equally well across imaging modalities. It is therefore recommended that the design of an fMRI study is pilot tested behaviorally to establish the effects of interest and then pilot tested in the fMRI environment to ensure appropriate design, implementation and analysis for the effects of interest.

Background: The feasibility of recording electroencephalography (EEG) at ultra-high static magnetic fields up to 9.4 T was recently demonstrated and is expected to be incorporated into functional magnetic resonance imaging (fMRI) studies at 9.4 T. Correction of the pulse artefact (PA) is a significant challenge since its amplitude is proportional to the strength of the magnetic field in which EEG is recorded., New Method: We conducted a study in which different PA correction methods were applied to EEG data recorded inside a 9.4 T scanner in order to retrieve visual P100 and auditory P300 evoked potentials. We explored different PA reduction methods, including the optimal basis set (OBS) method as well as objective and subjective component rejection using independent component analysis (ICA)., Results: ICA followed by objective rejection of components is optimal for retrieving visual P100 and auditory P300 from EEG data recorded inside the scanner., Comparison With Existing Methods: Previous studies suggest that OBS or OBS followed by ICA are optimal for retrieving evoked potentials at 3T. In our EEG data recorded at 9.4 T OBS performed alone was not fully optimal for the identification of evoked potentials. OBS followed by ICA was partially effective., Conclusions: In this study ICA has been shown to be an important tool for correcting the PA in EEG data recorded at 9.4 T, particularly when automated rejection of components is performed., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Single-trial fluctuations in the EEG signal have been shown to temporally correlate with the fMRI BOLD response and are valuable for modeling trial-to-trial fluctuations in responses. The P1 and N1 components of the visual ERP are sensitive to different attentional modulations, suggesting that different aspects of stimulus processing can be modeled with these ERP parameters. As such, different patterns of BOLD covariation for P1 and N1 informed regressors would be expected; however, current findings are equivocal. We investigate the effects of variations in attention on P1 and N1 informed BOLD activation in a visual oddball task. Simultaneous EEG-fMRI data were recorded from 13 healthy participants during three conditions of a visual oddball task: Passive, Count, and Respond. We show that the P1 and N1 components of the visual ERP can be used in the integration-by-prediction method of EEG-fMRI data integration to highlight brain regions related to target detection and response production. Our data suggest that the P1 component of the ERP reflects changes in sensory encoding of stimulus features and is more informative for the Passive and Count conditions. The N1, on the other hand, was more informative for the Respond condition, suggesting that it can be used to model the processing of stimulus, meaning specifically discriminating one type of stimulus from another, and processes involved in integrating sensory information with response selection. Our results show that an understanding of the underlying electrophysiology is necessary for a thorough interpretation of EEG-informed fMRI analysis.

More than 80 % of patients diagnosed with schizophrenia are nicotine-dependent. Self-medication of cognitive deficits and an increased vulnerability to stress are discussed as promoting factors for the development of nicotine dependence. However, the effects of nicotine on social cognition and subjective stress responses in schizophrenia are largely unexplored. A 2 × 2-factorial design (drug × group) was used to investigate the effects of nicotine versus placebo in smoking schizophrenia patients and healthy controls after 24 h of abstinence from smoking. Participants performed a facial affect recognition task and a semi-standardized role-play task, after which social competence and self-reported stress during social interaction were assessed. Data analysis revealed no significant group differences in the facial affect recognition task. During social interaction, healthy controls showed more non-verbal expressions and a lower subjective stress level than schizophrenia patients. There were no significant effects of nicotine in terms of an enhanced recognition of facial affect, more expressive behaviour or reduced subjective stress during social interaction. While schizophrenia patients unexpectedly recognized facial affect not significantly worse than healthy controls, the observed group differences in subjective stress and non-verbal expression during social interaction in the role-play situation are in line with previous findings. Contrary to expectations derived from the self-medication hypothesis, nicotine showed no significant effects on the dependent variables, perhaps because of the dosage used and the delay between the administration of nicotine and the performance of the role-play.

We investigate the effects of variations in response requirements on BOLD activation in a visual oddball task and consider implications for fMRI task designs. Sixteen healthy subjects completed 3 runs of a visual oddball task: passive, count and respond. Besides expected activation patterns during passive viewing, we identified joint activations, but more importantly crucial differences between the count and respond versions of the task. Middle frontal gyrus activation was seen in the respond but not the count condition suggesting that this region is associated with action execution rather than the decision-making aspect of the task. In addition, activation observed in the central opercular cortex and parietal operculum in the respond (but not count) condition is likely to reflect integration of the sensory, decision and response processes. We also observed activation in the supplementary motor area (SMA) during count as well as respond. Since the count condition requires no motor planning or response our data provide evidence for an SMA involvement in decision-making. Our study clearly shows that the count and respond versions of the visual oddball task result in different patterns of BOLD activation that could both be attributed to 'target detection' if information on the respective other condition was not available. We also show that considering the elements of a complex task is crucial when transferring it from one imaging modality to another and that a motor response is not always necessary in fMRI studies when the task has been set up appropriately., (Copyright © 2013 Elsevier Inc. All rights reserved.)

EPI with Keyhole (EPIK) is a hybrid imaging technique used to improve the performance of EPI in dynamic MRI applications. The method had been previously validated at 1.5 T with both phantom and in vivo images; EPIK was able to provide a higher temporal resolution and less image distortions than single-shot EPI. The data presented here demonstrate that the performance of EPIK can be further improved by accelerating it with the parallel imaging. For this work, this combination was tested at 3 T. After initial evaluation using phantom images, use of the method in functional MRI was verified with visual fMRI measurements as well as MRI simulation results. The results showed that accelerated EPIK had increased temporal resolution with favorable robustness against susceptibility artifacts when compared with EPI or non-accelerated EPIK., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: In parametric fMRI studies the relationship between the amplitude of the hemodynamic response and electrophysiological or behavioral parameters is commonly analyzed using the general linear model (GLM). We examined ways of using single-trial response time (RT) in the analysis of a decision-making task to better isolate task-specific activation., Methods: fMRI and RT data were recorded in twenty-one subjects performing a visual-oddball-task. Four explanatory variables (EVs) were generated for the GLM-analysis: A conventional (constant impulse) EV, a constant epoch EV informed using subjects' average RT, a variable impulse EV and a variable epoch EV both informed using single-trial RT. EVs were tested individually and as orthogonalized pairs., Results: The individual EVs all detected similar extensive patterns of activation, while orthogonalized EVs were mainly correlated with BOLD signal variance in sensorimotor and parietal areas. Orthogonalizing the variable epoch EV to the constant epoch EV isolated cortical regions resembling the "dorsal frontoparietal attention network" from activation detected by the conventional (i.e., constant impulse) analysis., Conclusion: For short event durations, the activation detected by individual EVs is very similar, but orthogonalized, parametrically informed EVs can improve isolation of task-specific BOLD signal change., Significance: Different approaches for integrating parametric timing measures in fMRI analyses can significantly influence outcomes, refining or confounding findings., (Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Multi-modal MR-PET-EEG data acquisition in simultaneous mode confers a number of advantages at 3 T and 9.4 T. The three modalities complement each other well; structural-functional imaging being the domain of MRI, molecular imaging with specific tracers is the strength of PET, and EEG provides a temporal dimension where the other two modalities are weak. The utility of hybrid MR-PET at 3 T in a clinical setting is presented and critically discussed. The potential problems and the putative gains to be accrued from hybrid imaging at 9.4 T, with examples from the human brain, are outlined. Steps on the road to 9.4 T multi-modal MR-PET-EEG are also illustrated. From an MR perspective, the potential for ultra-high resolution structural imaging is discussed and example images of the cerebellum with an isotropic resolution of 320 μm are presented, setting the stage for hybrid imaging at ultra-high field. Further, metabolic imaging is discussed and high-resolution images of the sodium distribution are presented. Examples of tumour imaging on a 3 T MR-PET system are presented and discussed. Finally, the perspectives for multi-modal imaging are discussed based on two on-going studies, the first comparing MR and PET methods for the measurement of perfusion and the second which looks at tumour delineation based on MRI contrasts but the knowledge of tumour extent is based on simultaneously acquired PET data., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The simultaneous acquisition of electroencephalographic (EEG) and functional magnetic resonance imaging (fMRI) data has gained momentum in recent years due to the synergistic effects of the two modalities with regard to temporal and spatial resolution. Currently, only EEG-data recorded in fields of up to 7 T have been reported. We investigated the feasibility of recording EEG inside a 9.4 T static magnetic field, specifically to determine whether meaningful EEG information could be recovered from the data after removal of the cardiac-related artefact. EEG-data were recorded reliably and reproducibly at 9.4 T and the cardiac-related artefact increased in amplitude with increasing B0, as expected. Furthermore, we were able to correct for the cardiac-related artefact and identify auditory event related responses at 9.4 T in 75% of subjects using independent component analysis (ICA). Also by means of ICA we detected event related spectral perturbations (ERSP) in subjects at 9.4 T in response to opening/closing the eyes comparable with the response at 0 T. Overall our results suggest that it is possible to record meaningful EEG data at ultra-high magnetic fields. The simultaneous EEG-fMRI approach at ultra-high-fields opens up the horizon for investigating brain dynamics at a superb spatial resolution and a temporal resolution in the millisecond domain., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Nicotine can have beneficial effects on attention performance and corresponding brain function in both schizophrenia patients and healthy controls, but it remains controversial whether nicotine affects brain function differentially in patients vs. controls. The effects of nicotine on brain activity elicited by attention-requiring oddball-type tasks have not been studied in schizophrenia patients. In this study we sought to investigate the impact of nicotine on the p300 evoked potential component and corresponding fMRI (functional magnetic resonance imaging) activation measures in schizophrenia patients and controls. Applying a double-blind, placebo-controlled cross-over design, the effects of 1mg nasal nicotine on brain activity elicited by a visual oddball-type task in N=14 schizophrenia and N=15 control smokers were studied with simultaneous EEG-fMRI. EEG single trial amplitudes were used to inform the fMRI analysis. We found a nicotine-associated increase in P300-informed fMRI activation in schizophrenia patients and controls, mainly in the anterior cingulate and adjacent medial frontal cortex. No group differences in the response to nicotine were found. Remarkably, averaged EEG and fMRI activation measures considered in isolation were largely unaffected by nicotine. Taken together, the effects of nicotine on P300 amplitude-associated brain activation do not seem to be fundamentally different in schizophrenic smokers and healthy controls., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

In a previous oddball task study, it was shown that the inclusion of electrophysiology (EEG), that is, single-trial P3 ERP parameters, in the analysis of fMRI responses can detect activation that is not apparent with conventional fMRI data modeling strategies [Warbrick, T., Mobascher, A., Brinkmeyer, J., Musso, F., Richter, N., Stoecker, T., et al. Single-trial P3 amplitude and latency informed event-related fMRI models yield different BOLD response patterns to a target detection task. Neuroimage, 47, 1532-1544, 2009]. Given that P3 is modulated by nicotine, including P3 parameters in the fMRI analysis might provide additional information about nicotine effects on brain function. A 1-mg nasal nicotine spray (0.5 mg each nostril) or placebo (pepper) spray was administered in a double-blind, placebo-controlled, within-subject, randomized, cross-over design. Simultaneous EEG-fMRI and behavioral data were recorded from 19 current smokers in response to an oddball-type visual choice RT task. Conventional general linear model analysis and single-trial P3 amplitude informed general linear model analysis of the fMRI data were performed. Comparing the nicotine with the placebo condition, reduced RTs in the nicotine condition were related to decreased BOLD responses in the conventional analysis encompassing the superior parietal lobule, the precuneus, and the lateral occipital cortex. On the other hand, reduced RTs were related to increased BOLD responses in the precentral and postcentral gyri, and ACC in the EEG-informed fMRI analysis. Our results show how integrated analyses of simultaneous EEG-fMRI data can be used to detect nicotine effects that would not have been revealed through conventional analysis of either measure in isolation. This emphasizes the significance of applying multimodal imaging methods to pharmacoimaging.

Structural cerebral deficiencies in smokers have been well characterized by morphometric investigations focussing on cortical and subcortical structures. Although the role of the cerebellum is increasingly noted in mental and addiction disorders, no reports exist regarding cerebellar alterations in smokers employing a methodology specifically designed to assess the cerebellar morphology. We acquired high-resolution MRI scans from 33 heavy smokers and 22 never-smokers and used a voxel-based morphometry (VBM) approach utilizing the Spatially Unbiased Infratentorial (SUIT) toolbox (Diedrichsen 2006) to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with smoking. Relative to never-smokers, smokers showed significant reductions of grey matter volume in the right cerebellum Crus I. The grey matter volume in Crus I correlated negatively with the amount of nicotine dependence as assessed by means of the Fagerström scale. Since Crus I has been identified as the cognitive division of the cerebellum, the structural deficit may in part mediate cognitive deficits previously reported in smokers. Of note, the dependence-related magnitude of the volume deficit may support the notion that the cerebellum is substantially involved in core mechanisms of drug dependence.

Nicotine enhances attentional functions. Since chronic nicotine exposure through smoking induces neuroadaptive changes in the brain at a structural and molecular level, the present functional MRI (fMRI) study aimed at investigating the neural mechanisms underlying visuospatial and sustained attention in smokers and non-smokers. Visuospatial attention was assessed with a location-cueing paradigm, while sustained attention was measured by changes in response speed over time. During invalid trials, neural activity within the basal forebrain was selectively enhanced in smokers and higher basal forebrain activity was associated with increased parietal cortex activation. Moreover, higher levels of expired carbon monoxide in smokers before scanning were associated with higher parietal cortex activation and faster responses to invalidly cued targets. Smokers showed a slowing of responses and additionally recruited an area within the right supramarginal gyrus with increasing time on task. Activity decreases over time were observed in visual areas in smokers. The data provide evidence for altered attentional functions in smokers as compared with non-smokers, which were partly modulated by residual nicotine levels and were observed at a behavioural level for sustained and at a neural level for spatial and sustained attention.

Background: Behavioral and electrophysiological human ketamine models of schizophrenia are used for testing compounds that target the glutamatergic system. However, corresponding functional neuroimaging models are difficult to reconcile with functional imaging and electrophysiological findings in schizophrenia. Resolving the discrepancies between different observational levels is critical to understand the complex pharmacological ketamine action and its usefulness for modeling schizophrenia pathophysiology., Methods: We conducted a within-subject, randomized, placebo-controlled pharmacoimaging study in twenty-four male volunteers. Subjects were given low-dose S-ketamine (bolus prior to functional imaging: 0.1mg/kg during 5min, thereafter continuous infusion: 0.015625mg/kg/min reduced by 10% every ten minutes) or placebo while performing a visual oddball task during simultaneous functional magnetic resonance imaging (fMRI) with continuous recording of event-related potentials (P300) and electrodermal activity (EDA). Before and after intervention, psychopathological status was assessed using the Positive and Negative Syndrome Scale (PANSS) and the Altered State of Consciousness (5D-ASC) Rating Scale., Results: P300 amplitude and corresponding BOLD responses were diminished in the ketamine condition in cortical regions being involved in sensory processing/selective attention. In both measurement modalities separation of drug conditions was achieved with area under the curve (AUC) values of up to 0.8-0.9. Ketamine effects were also observed in the clinical, behavioral and peripheral physiological domains (Positive and Negative Syndrome Scale, reaction hit and false alarm rate, electrodermal activity and heart rate) which were in part related to the P300/fMRI measures., Conclusion: The findings from our ketamine experiment are consistent across modalities and directly related to observations in schizophrenia supporting the validity of the model. Our investigation provides the first prototypic example of a pharmacoimaging study using simultaneously acquired fMRI/EEG., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Considerable variability across individuals has been reported in both the behavioral and fMRI blood oxygen level-dependent (BOLD) response to nicotine. We aimed to investigate (1) whether there is a heterogeneous effect of nicotine on behavioral and BOLD responses across participants and (2) if heterogeneous BOLD responses are associated with behavioral performance measures. In this double-blind, placebo-controlled, cross-over study, 41 healthy participants (19 smokers)--drawn from a larger population-based sample--performed a visual oddball task after acute challenge with 1 mg nasal nicotine. fMRI data and reaction time were recorded during performance of the task. Across the entire group of subjects, we found increased activation in the anterior cingulate cortex, middle frontal gyrus, superior temporal gyrus, post-central gyrus, planum temporal and frontal pole in the nicotine condition compared with the placebo condition. However, follow-up analyses of this difference in activation between the placebo and nicotine conditions revealed that some participants showed an increase in activation while others showed a decrease in BOLD activation from the placebo to the nicotine condition. A reduction of BOLD activation from placebo to nicotine was associated with a decrease in reaction time and reaction time variability and vice versa, suggesting that it is the direction of BOLD response to nicotine which is related to task performance. We conclude that the BOLD response to nicotine is heterogeneous and that the direction of response to nicotine should be taken into account in future pharmaco-fMRI research on the central action of nicotine.

Previous studies on the spatio-temporal dynamics of cortical pain processing using electroencephalography (EEG), magnetoencephalography (MEG), or intracranial recordings point towards a high degree of parallelism, e.g. parallel instead of sequential activation of primary and secondary somatosensory areas or simultaneous activation of somatosensory areas and the mid-cingulate cortex. However, because of the inverse problem, EEG and MEG provide only limited spatial resolution and certainty about the generators of cortical pain-induced electromagnetic activity, especially when multiple sources are simultaneously active. On the other hand, intracranial recordings are invasive and do not provide whole-brain coverage. In this study, we thought to investigate the spatio-temporal dynamics of cortical pain processing in 10 healthy subjects using simultaneous EEG/functional magnetic resonance imaging (fMRI). Voltages of 20 ms segments of the EEG root mean square (a global, largely reference-free measure of event-related EEG activity) in a time window 0-400 ms poststimulus were used to model trial-to-trial fluctuations in the fMRI blood oxygen level dependent (BOLD) signal. EEG-derived regressors explained additional variance in the BOLD signal from 140 ms poststimulus onward. According to this analysis, the contralateral parietal operculum was the first cortical area to become activated upon painful laser stimulation. The activation pattern in BOLD analyses informed by subsequent EEG-time windows suggests largely parallel signal processing in the bilateral operculo-insular and mid-cingulate cortices. In that regard, our data are in line with previous reports. However, the approach presented here is noninvasive and bypasses the inverse problem using only temporal information from the EEG., (© 2010 Wiley-Liss, Inc.)

During the past 20 years there has been much research into the factors that modulate awareness of contralesional information in neurological patients with visual neglect or extinction. However, the potential role of the individual's emotional state in modulating awareness has been largely overlooked. In the current study, we induced a pleasant and positive affective response in patients with chronic visual neglect by allowing them to listen to their pleasant preferred music. We report that the patients showed enhanced visual awareness when tasks were performed under preferred music conditions relative to when tasks were performed either with unpreferred music or in silence. These results were also replicated when positive affect was induced before neglect was tested. Functional MRI data showed enhanced activity in the orbitofrontal cortex and the cingulate gyrus associated with emotional responses when tasks were performed with preferred music relative to unpreferred music. Improved awareness of contralesional (left) targets with preferred music was also associated with a strong functional coupling between emotional areas and attentional brain regions in spared areas of the parietal cortex and early visual areas of the right hemisphere. These findings suggest that positive affect, generated by preferred music, can decrease visual neglect by increasing attentional resources. We discuss the possible roles of arousal and mood in generating these effects.

There are two basic strategies for applying simultaneous EEG-fMRI: either the fMRI data are acquired continuously, or the stimulus is presented during a brief gap in scanning when the EEG data is clear of gradient artefact. The former has the advantage that the protocol for the fMRI data acquisition is not affected by the presence of EEG. This study investigated the effect of these different strategies and the subsequent ballistocardiogram artefact removal methods (Average Artefact Subtraction (AAS) and Optimal Basis Set (OBS)) on EEG data quality recorded in response to a visual stimulus. Continuous scanning generally resulted in VEPs that were no worse, and in some cases were better, than those measured during a gap in scanning. The AAS and OBS methods lead to comparable results at the level of the grand average visual evoked potential (VEP), although when examined at the level of the single trial the OBS method was more effective. The spectral quality of the data was similar across scanning protocols, as demonstrated by the proportion of spectral power in each frequency band, although there was an effect of the artefact removal method on the overall spectral power. Some differences in the VEPs were also noted when a TR of 1.5 s was used relative to a TR of 3 s. The results indicate improved EEG quality when fMRI scanning is continuous and BCG artefacts are removed using the OBS method, confirming that EEG can be added to an fMRI experiment with minimal change to the experimental protocol.

Recent EEG-fMRI studies have suggested a novel method of data fusion which uses single trial (ST) estimates of event-related potentials in the fMRI analysis. This is potentially very powerful, but rests on the assumption that the ST variability observed in EEG is reflected in the fMRI signal. The current study investigated this assumption and compared two different data processing strategies for each modality. Five subjects underwent separate EEG and fMRI sessions with checkerboard stimuli at two contrasts. EEG data were preprocessed using wavelet denoising and independent component analysis (ICA), whilst the general linear model and ICA were used for fMRI. Amplitudes and latencies of the P1 and N2 components of the visual evoked potential (VEP) were calculated for each trial. For fMRI, the amplitudes and latencies of the ST haemodynamic responses (HR) were calculated. Within modality, the results for the two processing methods were significantly correlated in the majority of data sets. Across modality, the average amplitudes of the VEPs and HRs were also significantly correlated. Examination of ST variability demonstrated that the amplitudes of the mean VEPs and HRs are both influenced by the latency variability of the ST responses to a greater extent than the amplitude variability. For high contrast stimuli the latency variability in EEG and fMRI was significantly correlated, with a similar trend seen for the low contrast stimuli. The results confirm the validity of examining both the EEG and fMRI signals on an ST basis and suggest an underlying neuronal origin in both modalities.

The aim of this study was to investigate whether components of pain event-related potentials (ERPs) are modulated by anxiety. Pain ERPs in response to electrical stimulation were collected from 14 healthy individuals in a neutral condition and a condition where pain-related anxiety was induced. The amplitude of the N140 component of the ERP was found to be larger in the anxiety condition than the neutral condition. Arousal, as indicated by alpha power, did not differ between conditions. Differences in valence and focused attention to the painful stimuli may account for the increases in the N140 in the anxiety condition.

In the Thatcher illusion, a face with inverted eyes and mouth looks abnormal when upright but not when inverted. Behavioral studies have shown that thatcherization of an upright face disrupts perceptual processing of the local configuration. We recorded high-density EEG from normal observers to study ERP correlates of the illusion during the perception of faces and nonface objects, to determine whether inversion and thatcherization affect similar neural mechanisms. Observers viewed faces and houses in four conditions (upright vs. inverted, and normal vs. thatcherized) while detecting an oddball category (chairs). Thatcherization delayed the N170 component over occipito-temporal cortex to faces, but not to houses. This modulation matched the illusion as it was larger for upright than inverted faces. The P1 over medial occipital regions was delayed by face inversion but unaffected by thatcherization. Finally, face thatcherization delayed P2 over occipito-temporal but not over parietal regions, while inversion affected P2 across categories. All effects involving thatcherization were face-specific. These results indicate that effects of face inversion and feature inversion (in thatcherized faces) can be distinguished on a functional as well as neural level, and that they affect configural processing of faces in different time windows.