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Investing mental effort is costly, and the investment has to be matched by a reward to make a person engage in task performance. However, the neural structures underlying the continued management of mental effort are not known. Previous work has identified left-lateralized structures, most prominently the left anterior Insular Cortex (aIC) as regions implied in post-hoc evaluation and also anticipation of mental effort investment. We present a study aimed at identifying neural structures that are sensitive to changes in both task load and fatigue-induced state load. Sixteen healthy participants performed an n-back task before and after a fatigue-inducing day in a helicopter simulator or a free day. Subjective mental effort ratings showed an interaction of the effects of both task and state load changes, with a reduced effect of task load during the fatigued state. Testing for the same interaction effect in a whole-brain functional MRI data, we found a left-lateralized group of clusters in aIC, the anterior cingulate cortex, the dorsal striatum and frontal eye field and M1. We discuss the possible role of these areas and also the relevance of our findings in the light of the proposed opportunity cost model of mental effort.

Attention Deficit Hyperactivity Disorder (ADHD) is characterized by poor cognitive control/attention and hypofunctioning of the dorsal anterior cingulate cortex (dACC). In the current study, we investigated for the first time whether real-time fMRI neurofeedback (rt-fMRI) training targeted at increasing activation levels within dACC in adults with ADHD leads to a reduction of clinical symptoms and improved cognitive functioning. An exploratory randomized controlled treatment study with blinding of the participants was conducted. Participants with ADHD (n = 7 in the neurofeedback group, and n = 6 in the control group) attended four weekly MRI training sessions (60-min training time/session), during which they performed a mental calculation task at varying levels of difficulty, in order to learn how to up-regulate dACC activation. Only neurofeedback participants received continuous feedback information on actual brain activation levels within dACC. Before and after the training, ADHD symptoms and relevant cognitive functioning was assessed. Results showed that both groups achieved a significant increase in dACC activation levels over sessions. While there was no significant difference between the neurofeedback and control group in clinical outcome, neurofeedback participants showed stronger improvement on cognitive functioning. The current study demonstrates the general feasibility of the suggested rt-fMRI neurofeedback training approach as a potential novel treatment option for ADHD patients. Due to the study's small sample size, potential clinical benefits need to be further investigated in future studies.ISRCTN12390961.

To design, construct and validate radiofrequency (RF) transmit and receive phased array coils for high-resolution visual cortex imaging at 7 Tesla.A 4 channel transmit and 16 channel receive array was constructed on a conformal polycarbonate former. Transmit field efficiency and homogeneity were simulated and validated, along with the Specific Absorption Rate, using [Formula: see text] mapping techniques and electromagnetic simulations. Receiver signal-to-noise ratio (SNR), temporal SNR (tSNR) across EPI time series, g-factors for accelerated imaging and noise correlations were evaluated and compared with a commercial 32 channel whole head coil. The performance of the coil was further evaluated with human subjects through functional MRI (fMRI) studies at standard and submillimeter resolutions of upto 0.8mm isotropic.The transmit and receive sections were characterized using bench tests and showed good interelement decoupling, preamplifier decoupling and sample loading. SNR for the 16 channel coil was ∼ 1.5 times that of the commercial coil in the human occipital lobe, and showed better g-factor values for accelerated imaging. fMRI tests conducted showed better response to Blood Oxygen Level Dependent (BOLD) activation, at resolutions of 1.2mm and 0.8mm isotropic.The 4 channel phased array transmit coil provides homogeneous excitation across the visual cortex, which, in combination with the dual row 16 channel receive array, makes for a valuable research tool for high resolution anatomical and functional imaging of the visual cortex at 7T.

BackgroundResearch suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder.MethodsResting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology.ResultsThere was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity.DiscussionIncreased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network "connectivity at rest" intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure.

Within vision research retinotopic mapping and the more general receptive field estimation approach constitute not only an active field of research in itself but also underlie a plethora of interesting applications. This necessitates not only good estimation of population receptive fields (pRFs) but also that these receptive fields are consistent across time rather than dynamically changing. It is therefore of interest to maximize the accuracy with which population receptive fields can be estimated in a functional magnetic resonance imaging (fMRI) setting. This, in turn, requires an adequate estimation framework providing the data for population receptive field mapping. More specifically, adequate decisions with regard to stimulus choice and mode of presentation need to be made. Additionally, it needs to be evaluated whether the stimulation protocol should entail mean luminance periods and whether it is advantageous to average the blood oxygenation level dependent (BOLD) signal across stimulus cycles or not. By systematically studying the effects of these decisions on pRF estimates in an empirical as well as simulation setting we come to the conclusion that a bar stimulus presented at random positions and interspersed with mean luminance periods is generally most favorable. Finally, using this optimal estimation framework we furthermore tested the assumption of temporal consistency of population receptive fields. We show that the estimation of pRFs from two temporally separated sessions leads to highly similar pRF parameters.

Brain activity during rest is spatially coherent over functional connectivity networks called resting-state networks. In resting-state functional magnetic resonance imaging, independent component analysis yields spatially distributed network representations reflecting distinct mental processes, such as intrinsic (default) or extrinsic (executive) attention, and sensory inhibition or excitation. These aspects can be related to different treatments or subjective experiences. Among these, exhaustion is a common psychological state induced by prolonged mental performance. Using repeated functional magnetic resonance imaging sessions and spatial independent component analysis, we explored the effect of several hours of sustained cognitive performances on the resting human brain. Resting-state functional magnetic resonance imaging was performed on the same healthy volunteers in two days, with and without, and before, during and after, an intensive psychological treatment (skill training and sustained practice with a flight simulator). After each scan, subjects rated their level of exhaustion and performed an N-back task to evaluate eventual decrease in cognitive performance. Spatial maps of selected resting-state network components were statistically evaluated across time points to detect possible changes induced by the sustained mental performance. The intensive treatment had a significant effect on exhaustion and effort ratings, but no effects on N-back performances. Significant changes in the most exhausted state were observed in the early visual processing and the anterior default mode networks (enhancement) and in the fronto-parietal executive networks (suppression), suggesting that mental exhaustion is associated with a more idling brain state and that internal attention processes are facilitated to the detriment of more extrinsic processes. The described application may inspire future indicators of the level of fatigue in the neural attention system.

The goal of neurofeedback training is to provide participants with relevant information on their ongoing brain processes in order to enable them to change these processes in a meaningful way. Under the assumption of an intrinsic brain-behavior link, neurofeedback can be a tool to guide a participant towards a desired behavioral state, such as a healthier state in the case of patients. Current research in clinical neuroscience regarding the most robust indicators of pathological brain processes in psychiatric and neurological disorders indicates that fMRI-based functional connectivity measures may be among the most important biomarkers of disease. The present study therefore investigated the general potential of providing fMRI neurofeedback based on functional correlations, computed from short-window time course data at the level of single task periods. The ability to detect subtle changes in task performance with block-wise functional connectivity measures was evaluated based on imaging data from healthy participants performing a simple motor task, which was systematically varied along two task dimensions representing two different aspects of task difficulty. The results demonstrate that fMRI-based functional connectivity measures may provide a better indicator for an increase in overall (motor) task difficulty than activation level-based measures. Windowed functional correlations thus seem to provide relevant and unique information regarding ongoing brain processes, which is not captured equally well by standard activation level-based neurofeedback measures. Functional connectivity markers, therefore, may indeed provide a valuable tool to enhance and monitor learning within an fMRI neurofeedback setup.

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE.

The present study was designed to investigate the brain functional architecture that subserves visuo-spatial and motor processing in highly skilled individuals. By using functional magnetic resonance imaging (fMRI), we measured brain activity while eleven Formula racing-car drivers and eleven 'naïve' volunteers performed a motor reaction and a visuo-spatial task. Tasks were set at a relatively low level of difficulty such to ensure a similar performance in the two groups and thus avoid any potential confounding effects on brain activity due to discrepancies in task execution. The brain functional organization was analyzed in terms of regional brain response, inter-regional interactions and blood oxygen level dependent (BOLD) signal variability. While performance levels were equal in the two groups, as compared to naïve drivers, professional drivers showed a smaller volume recruitment of task-related regions, stronger connections among task-related areas, and an increased information integration as reflected by a higher signal temporal variability. In conclusion, our results demonstrate that, as compared to naïve subjects, the brain functional architecture sustaining visuo-motor processing in professional racing-car drivers, trained to perform at the highest levels under extremely demanding conditions, undergoes both 'quantitative' and 'qualitative' modifications that are evident even when the brain is engaged in relatively simple, non-demanding tasks. These results provide novel evidence in favor of an increased 'neural efficiency' in the brain of highly skilled individuals.

Transcranial magnetic stimulation (TMS) allows for non-invasive interference with ongoing neural processing. Applied in a chronometric design over early visual cortex (EVC), TMS has proved valuable in indicating at which particular time point EVC must remain unperturbed for (conscious) vision to be established. In the current study, we set out to examine the effect of EVC TMS across a broad range of time points, both before (pre-stimulus) and after (post-stimulus) the onset of symbolic visual stimuli. Behavioral priming studies have shown that the behavioral impact of a visual stimulus can be independent from its conscious perception, suggesting two independent neural signatures. To assess whether TMS-induced suppression of visual awareness can be dissociated from behavioral priming in the temporal domain, we thus implemented three different measures of visual processing, namely performance on a standard visual discrimination task, a subjective rating of stimulus visibility, and a visual priming task. To control for non-neural TMS effects, we performed electrooculographical recordings, placebo TMS (sham), and control site TMS (vertex). Our results suggest that, when considering the appropriate control data, the temporal pattern of EVC TMS disruption on visual discrimination, subjective awareness and behavioral priming are not dissociable. Instead, TMS to EVC disrupts visual perception holistically, both when applied before and after the onset of a visual stimulus. The current findings are discussed in light of their implications on models of visual awareness and (subliminal) priming.

It is part of basic emotions like fear or anger that they prepare the brain to act adaptively. Hence scenes representing emotional events are normally associated with characteristic adaptive behavior. Normally, face and body representation areas in the brain are modulated by these emotions when presented in the face or body. Here, we provide neuroimaging evidence (using functional magnetic resonance imaging) that the extrastriate body area (EBA) is highly responsive when subjects observe isolated faces presented in emotional scenes. This response of EBA to threatening scenes in which no body is present gives rise to speculation about its function. We discuss the possibility that the brain reacts proactively to the emotional meaning of the scene.

Many patients show no or incomplete responses to current pharmacological or psychological therapies for depression. Here we explored the feasibility of a new brain self-regulation technique that integrates psychological and neurobiological approaches through neurofeedback with functional magnetic resonance imaging (fMRI). In a proof-of-concept study, eight patients with depression learned to upregulate brain areas involved in the generation of positive emotions (such as the ventrolateral prefrontal cortex (VLPFC) and insula) during four neurofeedback sessions. Their clinical symptoms, as assessed with the 17-item Hamilton Rating Scale for Depression (HDRS), improved significantly. A control group that underwent a training procedure with the same cognitive strategies but without neurofeedback did not improve clinically. Randomised blinded clinical trials are now needed to exclude possible placebo effects and to determine whether fMRI-based neurofeedback might become a useful adjunct to current therapies for depression.

Functional magnetic resonance imaging (fMRI) at high magnetic fields has made it possible to investigate the columnar organization of the human brain in vivo with high degrees of accuracy and sensitivity. Until now, these results have been limited to the organization principles of early visual cortex (V1). While the middle temporal area (MT) has been the first identified extra-striate visual area shown to exhibit a columnar organization in monkeys, evidence of MT's columnar response properties and topographic layout in humans has remained elusive. Research using various approaches suggests similar response properties as in monkeys but failed to provide direct evidence for direction or axis of motion selectivity in human area MT. By combining state of the art pulse sequence design, high spatial resolution in all three dimensions (0.8 mm isotropic), optimized coil design, ultrahigh field magnets (7 Tesla) and novel high resolution cortical grid sampling analysis tools, we provide the first direct evidence for large-scale axis of motion selective feature organization in human area MT closely matching predictions from topographic columnar-level simulations.

Communication is an important aspect of human life, allowing us to powerfully coordinate our behaviour with that of others. Boiled down to its mere essentials, communication entails transferring a mental content from one brain to another. Spoken language obviously plays an important role in communication between human individuals. Manual gestures however often aid the semantic interpretation of the spoken message, and gestures may have played a central role in the earlier evolution of communication. Here we used the social game of charades to investigate the neural basis of gestural communication by having participants produce and interpret meaningful gestures while their brain activity was measured using functional magnetic resonance imaging. While participants decoded observed gestures, the putative mirror neuron system (pMNS: premotor, parietal and posterior mid-temporal cortex), associated with motor simulation, and the temporo-parietal junction (TPJ), associated with mentalizing and agency attribution, were significantly recruited. Of these areas only the pMNS was recruited during the production of gestures. This suggests that gestural communication relies on a combination of simulation and, during decoding, mentalizing/agency attribution brain areas. Comparing the decoding of gestures with a condition in which participants viewed the same gestures with an instruction not to interpret the gestures showed that although parts of the pMNS responded more strongly during active decoding, most of the pMNS and the TPJ did not show such significant task effects. This suggests that the mere observation of gestures recruits most of the system involved in voluntary interpretation.