Activation of Visuomotor Systems during Visually Guided Movements: A Functional MRI Study

The dorsal stream is a dominant visuomotor pathway that connects the striate and extrastriate cortices to posterior parietal areas. In turn, the posterior parietal areas send projections to the frontal primary motor and premotor areas. This cortical pathway is hypothesized to be involved in the transformation of a visual input into the appropriate motor output. In this study we used functional magnetic resonance imaging (fMRI) of the entire brain to determine the patterns of activation that occurred while subjects performed a visually guided motor task. In nine human subjects, fMRI data were acquired on a 4-T whole-body MR system equipped with a head gradient coil and a birdcage RF coil using aT^*₂-weighted EPI sequence. Functional activation was determined for three different tasks: (1) a visuomotor task consisting of moving a cursor on a screen with a joystick in relation to various targets, (2) a hand movement task consisting of moving the joystick without visual input, and (3) a eye movement task consisting of moving the eyes alone without visual input. Blood oxygenation level-dependent (BOLD) contrast-based activation maps of each subject were generated using period cross-correlation statistics. Subsequently, each subject's brain was normalized to Talairach coordinates, and the individual maps were compared on a pixel by pixel basis. Significantly activated pixels common to at least four out of six subjects were retained to construct the final functional image. The pattern of activation during visually guided movements was consistent with the flow of information from striate and extrastriate visual areas, to the posterior parietal complex, and then to frontal motor areas. The extensive activation of this network and the reproducibility among subjects is consistent with a role for the dorsal stream in transforming visual information into motor behavior. Also extensively activated were the medial and lateral cerebellar structures, implicating the cortico–ponto–cerebellar pathway in visually guided movements. Thalamic activation, particularly of the pulvinar, suggests that this nucleus is an important subcortical target of the dorsal stream.     

Characterization of BOLD-fMRI signal during a verbal fluency paradigm in patients with intracerebral tumors affecting the frontal lobe

Previous studies have indicated that the BOLD-fMRI signal can be modified by tumor processes in close vicinity to functional brain areas. This effect has been investigated primarily for the perirolandic area but there is only a limited number of studies concerning frontal cortical regions. Therefore, the aim of the current study was to characterize BOLD-fMRI signal and activation patterns in patients with frontal brain tumors while performing a verbal fluency task. Six patients (ages 31-56 years) suffering from frontal (5 left sided and 1 right sided) intracerebral tumors were examined with fMRI while performing a verbal fluency task in a blocked paradigm design. Eight healthy volunteers served as the control group. The patients (5 right and 1 left handed) demonstrated left frontal activation which could be clearly located outside the tumor area and adjacent edema with varying degrees of additional right frontal activation. In the predominant left frontal activation cluster, the mean voxel based z-score and cluster size were not statistically different between patients and controls. The present fMRI study is indicating that language related BOLD signal changes in the frontal cortex of patients with tumors close to functional areas were comparable to the signal in normal controls. Additionally, the temporal hemodynamic response characteristic was comparable in both groups. This is an important finding consistent with PET results and corroborates the feasibility of functional mapping approaches in patients with tumors affecting the frontal lobe. Additional studies investigating alterations of the hemodynamic response depending on tumor location and histology are required in order to further elucidate the association between pathophysiology and BOLD fMRI signal.     

Mirror Observation of Finger Action Enhances Activity in Anterior Intraparietal Sulcus: A Functional Magnetic Resonance Imaging Study

Mirror therapy can be used to promote recovery from paralysis in patients with post-stroke hemiplegia, There are a lot of reports that mirror-image observation of the unilateral moving hand enhanced the excitability of the primary motor area (M1) ipsilateral to the moving hand in healthy subjects. but the neural mechanisms underlying its therapeutic effects are currently unclear. To investigate this issue, we used functional magnetic resonance imaging to measure activity in brain regions related to visual information processing during mirror image movement observation. Thirteen healthy subjects performed a finger-thumb opposition task with the left and right hands separately, with or without access to mirror observation. In the mirror condition, one hand was reflected in a mirror placed above the abdomen in the MRI scanner. In the masked mirror condition, subjects performed the same task but with the mirror obscured. In both conditions, the other hand was held at rest behind the mirror. A between-task comparison (mirror versus masked mirror) revealed significant activation in the ipsilateral hemisphere in the anterior intraparietal sulcus (aIP) while performing all tasks, regardless of which hand was used. The right aIP was significantly activated while moving the right hand. In contrast, in the left aIP, a small number of voxels showed a tendency toward activation during both left and right hand movement. The enhancement of ipsilateral aIP activity by the mirror image observation of finger action suggests that bimodal aIP neurons can be activated by visual information. We propose that activation in the M1 ipsilateral to the moving hand can be induced by information passing through the ventral premotor area from the aIP.     

Low-frequency signal changes reflect differences in functional connectivity between good readers and dyslexics during continuous phoneme mapping

The current fMRI study investigated correlations of low-frequency signal changes in the left inferior frontal gyrus, right inferior frontal gyrus and cerebellum in 13 adult dyslexic and 10 normal readers to examine functional networks associated with these regions. The extent of these networks to regions associated with phonological processing (frontal gyrus, occipital gyrus, angular gyrus, inferior temporal gyrus, fusiform gyrus, supramarginal gyrus and cerebellum) was compared between good and dyslexic readers. Analysis of correlations in low-frequency range showed that regions known to activate during an "on-off" phoneme-mapping task exhibit synchronous signal changes when the task is administered continuously (without any "off" periods). Results showed that three functional networks, which were defined on the basis of documented structural deficits in dyslexics and included regions associated with phonological processing, differed significantly in spatial extent between good readers and dyslexics. The methodological, theoretical and clinical significance of the findings for advancing fMRI research and knowledge of dyslexia are discussed.     

fMRI study of motor cortex activity modulation in early Parkinson's disease

Parkinson's disease is a neurological disorder associated with the disfunction of dopaminergic pathways of the basal ganglia, mainly resulting in a progressive alteration in the execution of voluntary movements. We present a functional magnetic resonance imaging (fMRI) study on cortical activations during simple motor task performance, in six early–stage hemiparkinsonian patients and seven healthy volunteers. We acquired data in three sessions, during which subjects performed the task with right or left hand, or bimanually. We observed consistent bilateral activations in cingulate cortex and dorsolateral prefrontal cortex of Parkinsonian subjects during the execution of the task with the affected hand. In addition, patients showed both larger and stronger activations in motor cortex of the affected hemisphere with respect to the healthy hemisphere. Compared with the control group, patients showed a hyperactivation of the dorsolateral prefrontal cortex of the affected hemisphere. We concluded that a presymptomatic reorganization of the motor system is likely to occur in Parkinson's disease at earlier stages than previously hypothesized. Moreover, our results support fMRI as a sensitive technique for revealing the initial involvement of motor cortex areas at the debut of this degenerative disorder.     

Dissecting cognitive stages with time-resolved fMRI data: a comparison of fuzzy clustering and independent component analysis

In combination with cognitive tasks entailing sequences of sensory and cognitive processes, event-related acquisition schemes allow using functional MRI to examine not only the topography but also the temporal sequence of cortical activation across brain regions (time-resolved fMRI). In this study, we compared two data-driven methods--fuzzy clustering method (FCM) and independent component analysis (ICA)--in the context of time-resolved fMRI data collected during the performance of a newly devised visual imagery task. We analyzed a multisubject fMRI data set using both methods and compared their results in terms of within- and between-subject consistency and spatial and temporal correspondence of obtained maps and time courses. Both FCM and spatial ICA allowed discriminating the contribution of distinct networks of brain regions to the main cognitive stages of the task (auditory perception, mental imagery and behavioural response), with good agreement across methods. Whereas ICA worked optimally on the original time series, averaging with respect to the task onset (and thus introducing some a priori information on the stimulation protocol) was found to be indispensable in the case of FCM. On averaged time series, FCM led to a richer decomposition of the spatio-temporal patterns of activation and allowed a finer separation of the neurocognitive processes subserving the mental imagery task. This study confirms the efficacy of the two examined methods in the data-driven estimation of hemodynamic responses in time-resolved fMRI studies and provides empirical guidelines to their use.     

Activation mapping as a percentage of local excitation: fMRI stability within scans, between scans and across field strengths

Functional magnetic resonance imaging (fMRI) does not typically yield highly reproducible maps of brain activation. Maps can vary significantly even with constant scanning parameters and consistent task performance conditions (Liu et al., Magn. Reson. Med., 2004, 52:751-760). Reproducibility is even more of a problem when comparing fMRI signal magnitude and spatial extent of activation across scans involving different task performance levels, scan durations, pulse sequences or magnetic field strengths. In this report, the consistency of fMRI was reexamined by considering the relative spatial and temporal distribution of fMRI blood oxygen level dependent (BOLD) activation signals separately from the absolute magnitude of the activation signal in each brain area. Subjects repeatedly performed the same simple motor task but under a variety of imaging conditions, using both spiral and standard echo-planar pulse sequences and at 1.5- and 4.0-T magnetic field strengths. The results demonstrate that the absolute amplitude of BOLD statistical activation signals varied significantly across time and scanning conditions, but the relative spatial pattern of BOLD activation was highly reproducible across all conditions. Analysis of realistic simulated fMRI data sets indicates that stability of relative activation patterns could provide a useful tool for assessing the accuracy of fMRI maps.     

Identification of activated regions during a language task

Functional magnetic resonance imaging (fMRI) techniques are based on the assumption that changes in neural activity are accompanied by modulation in the blood-oxygenation-level-dependent (BOLD) signal. In addition to conventional increases in BOLD signals, sustained negative BOLD signal changes are occasionally observed in many fMRI experiments, which show regions of cortex that seem to respond in antiphase with primary stimulus. The existence of this so-called negative BOLD response (NBR) has been observed and investigated in many functional studies. Several theoretical mechanisms have been proposed to account for it, but its origin has never been fully explained. In this study, the variability of fMRI activation, including the sources of the negative BOLD signal, during phonological and semantic language tasks, was investigated in six right-handed healthy subjects. We found significant activations in the brain regions, mainly in the left hemisphere, involved in the language stimuli [prominent in the inferior frontal gyrus, approximately Brodmann Areas (BA)7, BA44, BA45 and BA47, and in the precuneus]. Moreover, we observed activations in motor regions [precentral gyrus and supplementary motor area (SMA)], a result that suggests a specific role of these areas (particularly the SMA) in language processing. Functional analysis have also shown that certain brain regions, including the posterior cingulate cortex and the anterior cingulate cortex, have consistently greater activity during resting states compared to states of performing cognitive tasks. In our study, we observed diffuse NBR at the cortical level and a stronger negative response in correspondence to the main sinuses. These phenomena seem to be unrelated to a specific neural activity, appearing to be expressions of a mechanical variation in hemodynamics. We discussed about the importance of these responses that are anticorrelated with the stimulus. Our data suggest that particular care must be considered in the interpretation of fMRI findings, especially in the case of presurgical studies.     

Neural mechanisms underlying the facilitation of naming in aphasia using a semantic task: an fMRI study

ABSTRACT: BACKGROUND: Previous attempts to investigate the effects of semantic tasks on picture naming in both healthy controls and people with aphasia have typically been confounded by inclusion of the phonological word form of the target item. As a result, it is difficult to isolate any facilitatory effects of a semantically-focused task to either lexical-semantic or phonological processing. This functional magnetic resonance imaging (fMRI) study examined the neurological mechanisms underlying short-term (within minutes) and long-term (within days) facilitation of naming from a semantic task that did not include the phonological word form, in both participants with aphasia and age-matched controls. RESULTS: Behavioral results showed that a semantic task that did not include the phonological word form can successfully facilitate subsequent picture naming in both healthy controls and individuals with aphasia. The whole brain neuroimaging results for control participants identified a repetition enhancement effect in the short-term, with modulation of activity found in regions that have not traditionally been associated with semantic processing, such as the right lingual gyrus (extending to the precuneus) and the left inferior occipital gyrus (extending to the fusiform gyrus). In contrast, the participants with aphasia showed significant differences in activation over both the short- and the long-term for facilitated items, predominantly within either left hemisphere regions linked to semantic processing or their right hemisphere homologues. CONCLUSIONS: For control participants in this study, the short-lived facilitation effects of a prior semantic task that did not include the phonological word form were primarily driven by object priming and episodic memory mechanisms. However, facilitation effects appeared to engage a predominantly semantic network in participants with aphasia over both the short- and the long-term. The findings of the present study also suggest that right hemisphere involvement may be supportive rather than maladaptive, and that a large distributed perisylvian network in both cerebral hemispheres supports the facilitation of naming in individuals with aphasia.     

Correlation between temporal response of fMRI and fast reaction time in a language task

Correlation between behavioral parameters and fMRI responses can provide an advanced understanding of the neuronal processes. A lexical decision task was employed to examine the correlation between the reaction time (RT) and the temporal parameters in event-related BOLD responses. Word frequency was manipulated in the experiment. RTs for high-frequency, low-frequency and pseudowords were measured during fMRI (417 +/- 9 ms, 631 +/- 22 ms and 658 +/- 15 ms, respectively). For high-frequency words, RTs were significantly shorter than that for low-frequency and pseudowords (p < 0.0005). In the left inferior frontal region, the FWHM of the fMRI responses was significantly correlated with RT (p < 0.001), which may correspond to areas with sustained activation during the whole processing.     

Event-related fMRI of auditory and visual oddball tasks

Functional magnetic resonance imaging (fMRI) was used to investigate the spatial distribution of cortical activation in frontal and parietal lobes during auditory and visual oddball tasks in 10 healthy subjects. The purpose of the study was to compare activation within auditory and visual modalities and identify common patterns of activation across these modalities. Each subject was scanned eight times, four times each for the auditory and visual conditions. The tasks consisted of a series of trials presented every 1500 ms of which 4-6% were target trials. Subjects kept a silent count of the number of targets detected during each scan. The data were analyzed by correlating the fMRI signal response of each pixel to a reference hemodynamic response function that modeled expected responses to each target stimulus. The auditory and visual targets produced target-related activation in frontal and parietal cortices with high spatial overlap particularly in the middle frontal gyrus and in the anterior cingulate. Similar convergence zones were detected in parietal cortex. Temporal differences were detected in the onset of the activation in frontal and parietal areas with an earlier onset in parietal areas than in the middle frontal areas. Based on consistent findings with previous event-related oddball tasks, the high degree of spatial overlap in frontal and parietal areas appears to be due to modality independent or amodal processes related to procedural aspects of the tasks that may involve memory updating and non-specific response organization.     

The effect of task block arrangement on the detectability of activation in fMRI

The effect of task block arrangements on the detection of brain activation was investigated. Sessions of functional magnetic resonance imaging (fMRI) including the same number of two different task conditions but with different arrangements were compared. The two task conditions were, A) Ellipse-shaped black and white checkerboard flicker stimulation at 4.2 Hz covering the bilateral visual field, and B) the same flicker stimuli covering only the left visual field. In the rest blocks (0), the subjects looked at a fixation point. Four different task block arrangements were compared, 1) A0 (0A0A0A0) and B0 (0B0B0B0), 2) A0B0 (0A0B0A0B0A0B0), 3) AB0 (0AB0AB0AB0) and 4) AB (0ABABAB). Bilateral V1, V2, V3 and the left V5 were activated by condition A, and the right V1 and V2 by B. The activation in the left visual field by A0 was larger than in the other three conditions. In a differential analysis between conditions A and B, activation in the left V3 and V5 was declined by AB0 or AB. When rest blocks were located in the post-stimulus undershoot phase, the % signal change of the BOLD signal was emphasized, which caused augmented significance in the detection of the activity. It was indicated that the outcome of the activation map was influenced by the arrangement of task blocks, even though the same number of task blocks were repeated within the sessions. In fMRI studies, task conditions should be carefully compared within or across sessions considering the characteristics of hemodynamic response functions.     

Quantitative analysis of asymmetrical cortical activity in motor areas during sequential finger movement

Brain asymmetry is a phenomenon well known for handedness and has been studied in motor cortices. However, few quantitative studies on asymmetrical cortical activity in motor areas have been conducted. In this study, we systematically investigated asymmetrical cortical activity in motor areas during sequential finger movement by quantitatively analyzing functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) responses. The norm of BOLD signal percentage of change was introduced to quantitatively measure the BOLD signal intensity change difference between the left and right motor areas. The results of the data collected from six subjects show that the norm of BOLD signal percentage of change in the right motor area is higher than that in the left motor area for two-hand movement (P=.0059) and single-hand movement (P=.0279) with right-handedness. These results from fMRI show the asymmetry of motor areas and may suggest that the left hemisphere motor area comes into being as an adaptation system that needs few neuron cells only to finish any movement task for right-handedness. The activation intensity in the left motor area is reduced with normal right finger movement. The activation intensity in the right motor area is obviously higher than that in the left motor area.     

Spatially aggregated multiclass pattern classification in functional MRI using optimally selected functional brain areas

In previous works, boosting aggregation of classifier outputs from discrete brain areas has been demonstrated to reduce dimensionality and improve the robustness and accuracy of functional magnetic resonance imaging (fMRI) classification. However, dimensionality reduction and classification of mixed activation patterns of multiple classes remain challenging. In the present study, the goals were (a) to reduce dimensionality by combining feature reduction at the voxel level and backward elimination of optimally aggregated classifiers at the region level, (b) to compare region selection for spatially aggregated classification using boosting and partial least squares regression methods and (c) to resolve mixed activation patterns using probabilistic prediction of individual tasks. Brain activation maps from interleaved visual, motor, auditory and cognitive tasks were segmented into 144 functional regions. Feature selection reduced the number of feature voxels by more than 50%, leaving 95 regions. The two aggregation approaches further reduced the number of regions to 30, resulting in more than 75% reduction of classification time and misclassification rates of less than 3%. Boosting and partial least squares (PLS) were compared to select the most discriminative and the most task correlated regions, respectively. Successful task prediction in mixed activation patterns was feasible within the first block of task activation in real-time fMRI experiments. This methodology is suitable for sparsifying activation patterns in real-time fMRI and for neurofeedback from distributed networks of brain activation.     

Projection screen or video goggles as stimulus modality in functional magnetic resonance imaging

The purpose of this study was to investigate the reliability of functional magnetic resonance imaging (fMRI) by using either a projection screen or video goggles as stimulus modality. A sequence of visual stimuli were presented to the same subject at different occasions. The sequence was optimized with a genetic algorithm. In five sessions the stimuli were presented using a projection screen viewed through a mirror in the head coil and in five sessions using video goggles. Failure to detect visual activation in the medial left hemisphere was observed in sessions using the projection screen as stimulus modality. Decreased thresholds for P values and cluster size resulted in activation outside the occipital lobe and did not significantly increase activated areas in this region. Results in this study indicate that presentation of fMRI tasks with visual routes is more reliable with direct input through video goggles than with the conventional use of projection screens. Failure to detect crucial visual areas has severe consequences for tumor surgery in the visual cortex. Inferior visual impression might also have negative consequences for cognitive tests with high demand on attention and perception.     

A conditional Granger causality model approach for group analysis in functional magnetic resonance imaging

Granger causality model (GCM) derived from multivariate vector autoregressive models of data has been employed to identify effective connectivity in the human brain with functional magnetic resonance imaging (fMRI) and to reveal complex temporal and spatial dynamics underlying a variety of cognitive processes. In the most recent fMRI effective connectivity measures, pair-wise GCM has commonly been applied based on single-voxel values or average values from special brain areas at the group level. Although a few novel conditional GCM methods have been proposed to quantify the connections between brain areas, our study is the first to propose a viable standardized approach for group analysis of fMRI data with GCM. To compare the effectiveness of our approach with traditional pair-wise GCM models, we applied a well-established conditional GCM to preselected time series of brain regions resulting from general linear model (GLM) and group spatial kernel independent component analysis of an fMRI data set in the temporal domain. Data sets consisting of one task-related and one resting-state fMRI were used to investigate connections among brain areas with the conditional GCM method. With the GLM-detected brain activation regions in the emotion-related cortex during the block design paradigm, the conditional GCM method was proposed to study the causality of the habituation between the left amygdala and pregenual cingulate cortex during emotion processing. For the resting-state data set, it is possible to calculate not only the effective connectivity between networks but also the heterogeneity within a single network. Our results have further shown a particular interacting pattern of default mode network that can be characterized as both afferent and efferent influences on the medial prefrontal cortex and posterior cingulate cortex. These results suggest that the conditional GCM approach based on a linear multivariate vector autoregressive model can achieve greater accuracy in detecting network connectivity than the widely used pair-wise GCM, and this group analysis methodology can be quite useful to extend the information obtainable in fMRI.     

Mapping of spikes, slow waves, and motor tasks in a patient with malformation of cortical development using simultaneous EEG and fMRI

We report on the simultaneous and continuous acquisition of EEG and functional MRI data in a patient with a left hemiparesis and focal epilepsy secondary to malformation of cortical development in the right hemisphere. EEG-triggered fMRI localization was previously demonstrated in this patient. In the experiments reported here, 322 spikes maximum at electrode C4 and 126 focal slow waves were identified offline. A hierarchy of models was explored in order to assess the relative contributions of each type of EEG event. Modeling the BOLD response to C4 spikes alone showed an area of activation within the large malformation, adjacent to the area of infolding cortex. However, also modeling slow-waves gave rise to a broader and stronger activation, suggesting that the generators overlap. Motor mapping of the right hand showed activation in the left sensorimotor cortex; left-hand tapping led to a more diffuse area of activation, displaced superiorly into the superior frontal gyrus, and a small area of activation within the lesion. In conclusion, continuous EEG-fMRI is useful to compare the functional mapping of epileptiform activity and eloquent cortices in individual patients.     

以功能性核磁共振造影初探10Hz调制激光针灸刺激所引发人类大脑皮质的活化现象(英文)

使用10 Hz调制的低功率激光针灸刺激探究大脑皮质反应.以功能性核磁共振造影技术探讨当激光针灸刺激左脚涌泉穴(K1)时,大脑可能产生的反应机制.研究发现调制激光针灸所引发显著的大脑活化反应,包括右额叶中央前回、右额叶上回、左额叶中央前回、左顶叶中央后回、左侧下部顶叶、左小脑舌前叶、左海马旁回和左小脑山顶等区域.安慰剂组实验并没有发现在脑部有任何活化反应,大多数反应区域所涉及功能与记忆、注意力及自我意识等有关联.结果显示出调制激光针灸的大脑血液动力学反应,并隐含此反应机制不只是依据传入感觉信息处理,而且还有着随外部刺激的变化而有所改变的血液动力学性质.     

Spinal fMRI investigation of human spinal cord function over a range of innocuous thermal sensory stimuli and study-related emotional influences

Functional magnetic resonance imaging (fMRI) of the human spinal cord has revealed important details of activity involved with innocuous sensory stimuli, including the primary input to ipsilateral dorsal gray matter and activity in bilateral ventral gray matter regions. The latter is hypothesized to reflect descending modulation from the brainstem and cortex. Here, the functions corresponding to these areas of activity are investigated by varying the temperature of innocuous thermal stimuli, and the order they are presented, across repeated fMRI experiments in the spinal cord and brainstem. Group results and connectivity analyses reveal that the ipsilateral dorsal gray matter (dGM), the primary site of sensory input, also receives inhibitory input from the rostral ventromedial medulla and the locus coeruleus, two components of the brainstem opiate analgesia system. Ipsilateral ventral gray matter (vGM) receives input from the ipsilateral dGM and inhibitory input from the pontine reticular formation, which is involved with coordination of movements by modulation of ventral horn cells. Contralateral vGM regions appear to receive input from only the ipsilateral dGM in these studies. These results provide an unprecedented view of details of human spinal cord function and descending modulation, and have important implications for assessment of the effects of spinal cord trauma and disease by means of fMRI.     

Influence of speech stimuli intensity on the activation of auditory cortex investigated with functional magnetic resonance imaging.

Understanding the impact of variations in the acoustic signal is critical for the development of auditory and language fMRI as an experimental tool. We describe the dependence of the BOLD signal and speech intelligibility on the intensity of auditory stimuli. Eighteen subjects were imaged on a 1.5-T MRI scanner. Speech stimuli were English monosyllabic words played at five intensity levels. Intrasubject reproducibility was measured on one subject by presenting the stimulus five times at the same intensity level. Intelligibility was measured during data acquisition as subjects signaled when hearing two targets. Each functional trial consisted of four cycles (30 s off-30 s on). Five oblique slices covering primary and association auditory areas were imaged. Activated voxels were identified by cross-correlation analysis and their percent signal change (delta S) was measured. Intersubject differences in activation extent, asymmetry, and dependence on intensity were striking. Volume of activation was significantly greater in the left than in the right hemisphere. Intrasubject reproducibility for delta S was higher than for volume of activation. delta S and intelligibility showed a similar dependence on intensity suggesting that not only intensity but also intelligibility affect the fMRI signal.