Pain enhances functional connectivity of a brain network evoked by performance of a cognitive task

Experimental and clinical evidence indicates that pain can affect cognitive processes, but the cortical networks involved in pain-cognition interactions are unclear. In this study, we determined the effect of pain on the activity of cortical areas involved in cognition acting as a whole (i.e., a network). Subjects underwent functional magnetic resonance imaging (fMRI) while engaged in an attention-demanding cognitive task (multisource interference task) of varying difficulty and simultaneously receiving painful stimuli at varying intensities. The control (baseline) condition was simple finger tapping that had minimal cognitive demands and without pain. Functional connectivity analysis revealed a cortical network consisting of two anti-correlated parts: a task-negative part (precuneus/posterior cingulate cortex, medial frontal and inferior parietal/temporal) the activity of which correlated negatively with the cognitive task and positively with the control baseline, and a task-positive part (inferior frontal, superior parietal, premotor, and anterior insula cortices) the activity of which correlated positively with the cognitive task and negatively with the baseline. Independent components analysis revealed these opposing networks were operating at a low frequency (0.03-0.08 Hz). The functional connectivity of the task-positive network was increased by cognitive demand and by pain. We suggest this attention-specific network balances the needs of general self-referential and environmental awareness versus focused attention to salient information. We postulate that pain affects cognitive ability by its reliance on this common attention-specific network. These data provide evidence that pain can modulate a network presumed to be involved in focused attention, suggesting a mechanism for the interference of pain on cognitive ability by the consumption of attentional resources.     

Functional imaging of the human lateral geniculate nucleus and pulvinar

In the human brain, little is known about the functional anatomy and response properties of subcortical nuclei containing visual maps such as the lateral geniculate nucleus (LGN) and the pulvinar. Using functional magnetic resonance imaging (fMRI) at 3 tesla (T), collective responses of neural populations in the LGN were measured as a function of stimulus contrast and flicker reversal rate and compared with those obtained in visual cortex. Flickering checkerboard stimuli presented in alternation to the right and left hemifields reliably activated the LGN. The peak of the LGN activation was found to be on average within +/-2 mm of the anatomical location of the LGN, as identified on high-resolution structural images. In all visual areas except the middle temporal (MT), fMRI responses increased monotonically with stimulus contrast. In the LGN, the dynamic response range of the contrast function was larger and contrast gain was lower than in the cortex. Contrast sensitivity was lowest in the LGN and V1 and increased gradually in extrastriate cortex. In area MT, responses were saturated at 4% contrast. Response modulation by changes in flicker rate was similar in the LGN and V1 and occurred mainly in the frequency range between 0.5 and 7.5 Hz; in contrast, in extrastriate areas V4, V3A, and MT, responses were modulated mainly in the frequency range between 7.5 and 20 Hz. In the human pulvinar, no activations were obtained with the experimental designs used to probe response properties of the LGN. However, regions in the mediodorsal right and left pulvinar were found to be consistently activated by bilaterally presented flickering checkerboard stimuli, when subjects attended to the stimuli. Taken together, our results demonstrate that fMRI at 3 T can be used effectively to study thalamocortical circuits in the human brain.     

Development of large-scale functional networks over the lifespan

The development of large-scale functional organization of the human brain across the lifespan is not well understood. Here we used magnetoencephalographic recordings of 53 adults (ages 18-89) to characterize functional brain networks in the resting state. Slow frequencies engage larger networks than higher frequencies and show different development over the lifespan. Networks in the delta (2-4 Hz) frequency range decrease, while networks in the beta/gamma frequency range (> 16 Hz) increase in size with advancing age. Results show that the right frontal lobe and the temporal areas in both hemispheres are important relay stations in the expanding high-frequency networks. Neuropsychological tests confirmed the tendency of cognitive decline with older age. The decrease in visual memory and visuoconstructive functions was strongly associated with the age-dependent enhancement of functional connectivity in both temporal lobes. Using functional network analysis this study elucidates important neuronal principles underlying age-related cognitive decline paving mental deterioration in senescence.     

Isometric force-related activity in sensorimotor cortex measured with functional MRI

Isometric force-related functional magnetic resonance imaging (fMRI) signals from primary sensorimotor cortex were investigated by imaging during a sustained finger flexion task at a number of force levels related to maximum voluntary contraction. With increasing levels of force, there was an increase in the extent along the central sulcus from which a fMRI signal could be detected and an increase in the summed signal across voxels, but these parameters were related in such a way that the signal from each voxel was similar for each level of force. The results suggest that increased neuronal firing and recruitment of corticomotor cells associated with increased voluntary isometric effort are reflected in an expansion of a relatively constant fMRI signal over a greater volume of cortex, rather than an increase in the magnitude of the response in a particular circumscribed region, possibly due to perfusion of an increase in oxygen-enriched blood over a wider region of the cortex. Received: 16 June 1997 / Accepted: 3 November 1998     

Space–time network connectivity and cortical activations preceding spike wave discharges in human absence epilepsy: a MEG study

To describe the spatial and temporal profiles of connectivity networks and sources preceding generalized spike-and-wave discharges (SWDs) in human absence epilepsy. Nonlinear associations of MEG signals and cluster indices obtained within the framework of graph theory were determined, while source localization in the frequency domain was performed in the low frequency bands with dynamic imaging of coherent sources. The results were projected on a three-dimensional surface rendering of the brain using a semi-realistic head model and MRI images obtained for each of the five patients studied. An increase in clustering and a decrease in path length preceding SWD onset and a rhythmic pattern of increasing and decreasing connectivity were seen during SWDs. Beamforming showed a consistent appearance of a low frequency frontal cortical source prior to the first generalized spikes. This source was preceded by a low frequency occipital source. The changes in the connectivity networks with the onset of SWDs suggest a pathologically predisposed state towards synchronous seizure networks with increasing connectivity from interictal to preictal and ictal state, while the occipital and frontal low frequency early preictal sources demonstrate that SWDs are not suddenly arising but gradually build up in a dynamic network.     

原发性失眠患者大脑背外侧前额叶的异常静息态功能连接

目的:利用功能连接方法观察原发性失眠患者静息态下的背外侧前额叶的异常功能连接。方法:采集33 例原 发性失眠患者以及33 例年龄、性别和受教育程度相匹配的健康对照的功能磁共振图像,以背外侧前额叶为感兴趣区 域,与全脑其他体素进行功能连接分析,得到两组之间功能连接的差异脑区,再对异常功能连接脑区与临床的量表分 数做相关分析。结果:与对照组相比,发现失眠患者左侧背外侧前额叶与左侧枕下回、右侧枕下回、右侧枕中回、右侧 颞叶、左侧额中回,左侧额下回以及右侧梭状回之间的功能连接增强（P<0.05,体素簇个数≥100,FDR校正）,与左侧前 扣带皮层、右侧海马旁回、右侧脑岛、右侧背外侧额上回、右侧顶上回、右侧中央后回以及右侧中央前回之间的功能连 接减弱（P<0.05,体素簇个数≥100,FDR校正）。并且左侧背外侧前额叶与左侧枕叶下回的功能连接值与睡眠状况自评 量表分数成正相关（P=0.035）。结论:原发性失眠患者背外侧前额叶与大脑多个脑区出现异常的功能连接,可能为理 解原发性失眠患者的神经机制提供一些新的影像学依据。     

Aging affects medial but not anterior frontal learning-related theta oscillations

Aging induces a decline in the ties that bind anatomical networks centered on the prefrontal cortex, which are critical for reinforcement learning and decision making. At the neurophysiological level, the prefrontal cortex may engage electrophysiological oscillatory synchronization to coordinate other brain systems during learning. We recorded scalp EEG from 21 older (mean age 69 years) and 20 young (mean age 22 years) healthy human adults while they learned stimulus–response mappings by trial-and-error using feedback. In young adults, theta-band (4–8 Hz) oscillatory power over medial frontal and anterior frontal cortex predicted learning after errors. Older adults demonstrated a decrease in the theta-band learning-predictive signals over medial frontal but not anterior frontal cortex. This age-related decrease in task-relevant medial frontal theta power may be related to the more general decrease in medial frontal theta power that we observed during rest. These results demonstrate a shift in cortical networks that support reinforcement learning in older adults, and shed new light on the changes in neurophysiological (oscillatory) mechanisms with neurocognitive aging.     

Relationship between saccadic eye movements and cortical activity as measured by fMRI: quantitative and qualitative aspects

We investigated the quantitative relationship between saccadic activity (as reflected in frequency of occurrence and amplitude of saccades) and blood oxygenation level dependent (BOLD) changes in the cerebral cortex using functional magnetic resonance imaging (fMRI). Furthermore, we investigated quantitative changes in cortical activity associated with qualitative changes in the saccade task for comparable levels of saccadic activity. All experiments required the simultaneous acquisition of eye movement and fMRI data. For this purpose we used a new high-resolution limbus-tracking technique for recording eye movements in the magnetic resonance tomograph. In the first two experimental series we varied both frequency and amplitude of saccade stimuli (target jumps). In the third series we varied task difficulty; subjects performed either pro-saccades or anti-saccades. The brain volume investigated comprised the frontal and supplementary eye fields, parietal as well as striate cortex, and the motion sensitive area of the parieto-occipital cortex. All these regions showed saccade-related BOLD responses. The responses in these regions were highly correlated with saccade frequency, indicating that repeated processing of saccades is integrated over time in the BOLD response. In contrast, there was no comparable BOLD change with variation of saccade amplitude. This finding speaks for a topological rather than activity-dependent coding of saccade amplitudes in most cortical regions. In the experiments comparing pro- vs anti-saccades we found higher BOLD activation in the "anti" task than in the "pro" task. A comparison of saccade parameters revealed that saccade frequency and cumulative amplitude were comparable between the two tasks, whereas reaction times were longer in the "anti" task than the pro task. The latter finding is taken to indicate a more demanding cortical processing in the "anti" task than the "pro" task, which could explain the observed difference in BOLD activation. We hold that a quantitative analysis of saccade parameters (especially saccade frequency and latency) is important for the interpretation of the BOLD changes observed with visual stimuli in fMRI.     

The Effect of Stimulation Frequency and Retinal Stimulus Location on Visual Evoked Potential Topography

The activity of cortical neurons is influenced by retinal stimulus location and temporal modulation. We investigated how reversal frequency of black-and-white checkerboard patterns presented in different parts of the visual field affects evoked potential topography. Visual evoked potentials were recorded from an array of 16 electrodes over the occipital cortex in 12 healthy adults. A checkerboard reversal stimulus (40′ check size) was presented with frequencies between 1.95 reversals/s and 7.81 reversals/s in the center or in the left or right hemiretina. Evoked potential fields displayed the well-known components of pattern reversal evoked activity. Computation of FFT and wavelets displayed electrical brain responses directly related to stimulation frequency. Further analysis showed that both retinal stimulus location and stimulation frequency affected visual evoked activity. Field strength as well as scalp field topography changed significantly with different reversal frequency. In addition, the pattern of lateralization of components also depended on temporal frequency of stimulation.Electrical brain activity elicited by visual stimuli shows globally similar features which are modulated by stimulus location and frequency. Our results indicate that—at least partly—different neuronal assemblies are activated by stimuli of different temporal characteristics.     

The enhanced cortical activation induced by transcranial direct current stimulation during hand movements

The aim of this study is to evaluate whether tDCS applied on the primary motor cortex (M1) in company with hand movements could enhance cortical activation, using functional MRI (fMRI). Twelve right-handed normal subjects were recruited. Real tDCS and sham tDCS with hand movements were applied during fMRI scanning. Subjects performed grasp-release hand movements at a metronome-guided frequency of 1Hz, while direct current with 1.0mA was delivered to the primary motor cortex. The averaged cortical map and the intensity index were compared between real tDCS with hand movements and sham tDCS with hand movements. Our result showed that cortical activation on the primary sensorimotor cortex was observed under both of two conditions; real tDCS with hand movements and sham tDCS with hand movements. Voxel count and peak intensity were 365.10±227.23 and 5.66±1.97, respectively, in the left primary sensorimotor cortex during real tDCS with right hand movements; in contrast, those were 182.20±117.88 and 4.12±0.88, respectively, during sham tDCS with right hand movements. Significant differences in voxel count and peak intensity were observed between real tDCS and sham tDCS (p<0.05). We found that anodal tDCS application during motor task enhanced cortical activation on the underlying targeted motor cortex, compared with the same motor task without tDCS. Therefore, it seemed that tDCS induced more cortical activity and modulated brain function when concurrently applied with motor task.     

A preliminary study of functional connectivity in comorbid adolescent depression

Major depressive disorder (MDD) begins frequently in adolescence and is associated with severe outcomes, but the developmental neurobiology of MDD is not well understood. Research in adults has implicated fronto-limbic neural networks in the pathophysiology of MDD, particularly in relation to the subgenual anterior cingulate cortex (ACC). Developmental changes in brain networks during adolescence highlight the need to examine MDD-related circuitry in teens separately from adults. Using resting state functional magnetic resonance imaging (fMRI), this study examined functional connectivity in adolescents with MDD (n = 12) and healthy adolescents (n = 14). Seed-based connectivity analysis revealed that adolescents with MDD have decreased functional connectivity in a subgenual ACC-based neural network that includes the supragenual ACC (BA 32), the right medial frontal cortex (BA 10), the left inferior (BA 47) and superior frontal cortex (BA 22), superior temporal gyrus (BA 22), and the insular cortex (BA 13). These preliminary data suggest that MDD in adolescence is associated with abnormal connectivity within neural circuits that mediate emotion processing. Future research in larger, un-medicated samples will be necessary to confirm this finding. We conclude that hypothesis-driven, seed-based analyses of resting state fMRI data hold promise for advancing our current understanding of abnormal development of neural circuitry in adolescents with MDD.     

Analysis of the volumetric relationship among human ocular,orbital and fronto‐occipital cortical morphology

Recent research on the visual system has focused on investigating the relationship among eye (ocular), orbital, and visual cortical anatomy in humans. This issue is relevant in evolutionary and medical fields. In terms of evolution, only in modern humans and Neandertals are the orbits positioned beneath the frontal lobes, with consequent structural constraints. In terms of medicine, such constraints can be associated with minor deformation of the eye, vision defects, and patterns of integration among these features, and in association with the frontal lobes, are important to consider in reconstructive surgery. Further study is therefore necessary to establish how these variables are related, and to what extent ocular size is associated with orbital and cerebral cortical volumes. Relationships among these anatomical components were investigated using magnetic resonance images from a large sample of 83 individuals, which also included each subject's body height, age, sex, and uncorrected visual acuity score. Occipital and frontal gyri volumes were calculated using two different cortical parcellation tools in order to provide a better understanding of how the eye and orbit vary in relation to visual cortical gyri, and frontal cortical gyri which are not directly related to visual processing. Results indicated that ocular and orbital volumes were weakly correlated, and that eye volume explains only a small proportion of the variance in orbital volume. Ocular and orbital volumes were also found to be equally and, in most cases, more highly correlated with five frontal lobe gyri than with occipital lobe gyri associated with V1, V2, and V3 of the visual cortex. Additionally, after accounting for age and sex variation, the relationship between ocular and total visual cortical volume was no longer statistically significant, but remained significantly related to total frontal lobe volume. The relationship between orbital and visual cortical volumes remained significant for a number of occipital lobe gyri even after accounting for these cofactors, but was again found to be more highly correlated with the frontal cortex than with the occipital cortex. These results indicate that eye volume explains only a small amount of variation in orbital and visual cortical volume, and that the eye and orbit are generally more structurally associated with the frontal lobes than they are functionally associated with the visual cortex of the occipital lobes. Results also demonstrate that these components of the visual system are highly complex and influenced by a multitude of factors in humans.     

Primary sensorimotor cortex activation with task-performance after fatiguing hand exercise

We have compared functional MRI signals in primary sensorimotor cortex (SM1) during a paced motor task of each hand before and after unimanual (right hand) fatiguing exercise. Our aims were to determine whether the degree of activation is different when a motor task is performed after a fatiguing exercise, and whether there are any differences in activation between movement of the fatigued and non-fatigued hands. There was a significant reduction in the number of voxels activated in SM1 in the hemisphere contralateral to movement of both the fatigued hand (38±5 pre-exercise versus 21±3 post-exercise; P<0.05) and the non-fatigued hand (32±4 pre-exercise vs 18±4 post-exercise; P<0.05). There was no significant difference in the magnitude of the functional magnetic resonance imaging signal before or after exercise, however, the variance increased significantly after exercise (6.0±0.5 pre-exercise vs 7.3±0.6 post-exercise; P<0.01). Reduced functional activation in SM1 may reflect increased variability in the activation rather than a reduction in activation of cortical motor networks after fatigue.     

Cortical Network Analysis in Patients Affected by Schizophrenia

In the present study, we studied the structural changes of the brain functional network in a group of schizophrenic (SCHZ) patients during a 2-back working memory task. Cortical signals were obtained from scalp EEG signals through the high-resolution EEG technique, which relies on realistic head models and linear inverse solutions. Functional networks were estimated by computing the spectral coherence—i.e. a measure of synchronization in the frequency domain—between the time series of all the available cortical sources. To analyze those cortical networks we followed a theoretical graph approach by computing the network density as the total number of links and the node degree as the number of links of each cortical source. The major result suggest that in the Alpha2 frequency band (11–13 Hz) the cortical functional networks of the SCHZ patients present the largest differences when compared with those of a group of control (CTRL) subjects. In particular, the structure of the SCHZ network altered radically during the memory task, as the number of links that were different from the REST condition increased sensibly with respect to the CTRL network. In addition, a compensatory mechanism was found in the SCHZ patients during the correct performance of the memory task where the node degree showed a frontal asymmetry with higher activation of the left frontal lobe—i.e. higher number of connections—in the Alpha2 frequency band.     

Stimulus frequency dependence of blood oxygenation level-dependent functional magnetic resonance imaging signals in the somatosensory cortex of rats

Understanding the mechanism of coupling between neuronal events and hemodynamic responses is important in non-invasive functional imaging of the brain. The stimulus frequency dependence of hemodynamic responses has been studied using a rat somatosensory cortex model; most results for short stimulus durations reveal peak frequencies at which the hemodynamic response is maximized. However, such peak frequencies have not been observed in studies using blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals with long stimulus durations. To clarify whether the stimulus frequency dependence of BOLD signals depends on the stimulus duration, we measured BOLD signals at 7 T with short- and long-stimulus durations for stimulating rat forepaw at 1-10 Hz using spin-echo echo-planar imaging to enhance changes in activation focus. For both these durations, BOLD signals were significantly higher at stimulus frequencies of 3 or 5 Hz in agreement with the results of previous studies using optical techniques. Our results show that stimulus duration has little influence on the stimulus frequency dependence of BOLD signals in the rat somatosensory model. The discrepant results of most previous fMRI studies using gradient-echo sequence may be ascribed to the difference of imaging to enhance activation focus or draining vein.     

Representation of the temporal envelope of sounds in the human brain

The cerebral representation of the temporal envelope of sounds was studied in five normal-hearing subjects using functional magnetic resonance imaging. The stimuli were white noise, sinusoidally amplitude-modulated at frequencies ranging from 4 to 256 Hz. This range includes low AM frequencies (up to 32 Hz) essential for the perception of the manner of articulation and syllabic rate, and high AM frequencies (above 64 Hz) essential for the perception of voicing and prosody. The right lower brainstem (superior olivary complex), the right inferior colliculus, the left medial geniculate body, Heschl's gyrus, the superior temporal gyrus, the superior temporal sulcus, and the inferior parietal lobule were specifically responsive to AM. Global tuning curves in these regions suggest that the human auditory system is organized as a hierarchical filter bank, each processing level responding preferentially to a given AM frequency, 256 Hz for the lower brainstem, 32-256 Hz for the inferior colliculus, 16 Hz for the medial geniculate body, 8 Hz for the primary auditory cortex, and 4-8 Hz for secondary regions. The time course of the hemodynamic responses showed sustained and transient components with reverse frequency dependent patterns: the lower the AM frequency the better the fit with a sustained response model, the higher the AM frequency the better the fit with a transient response model. Using cortical maps of best modulation frequency, we demonstrate that the spatial representation of AM frequencies varies according to the response type. Sustained responses yield maps of low frequencies organized in large clusters. Transient responses yield maps of high frequencies represented by a mosaic of small clusters. Very few voxels were tuned to intermediate frequencies (32-64 Hz). We did not find spatial gradients of AM frequencies associated with any response type. Our results suggest that two frequency ranges (up to 16 and 128 Hz and above) are represented in the cortex by different response types. However, the spatial segregation of these two ranges is not systematic. Most cortical regions were tuned to low frequencies and only a few to high frequencies. Yet, voxels that show a preference for low frequencies were also responsive to high frequencies. Overall, our study shows that the temporal envelope of sounds is processed by both distinct (hierarchically organized series of filters) and shared (high and low AM frequencies eliciting different responses at the same cortical locus) neural substrates. This layout suggests that the human auditory system is organized in a parallel fashion that allows a degree of separate routing for groups of AM frequencies conveying different information and preserves a possibility for integration of complementary features in cortical auditory regions.     

Dominance of the left oblique view in activating the cortical network for face recognition

Faces in portraits are often depicted from the left 3/4 view (an oblique view of the face that is intermediate between the frontal view and left profile). Here, we used functional magnetic resonance imaging (fMRI) to show that, compared with photographs of right 3/4 views of familiar faces, photographs of left 3/4 views of the same faces elicited stronger neural responses in the right middle occipital/inferior parietal cortex, and right inferior frontal gyrus; which are known to be involved in face recognition. By contrast, there was no differential activation in the temporal cortex including the superior temporal sulcus and fusiform gyrus, which are thought to process face-related visual stimuli at a stage that precedes recognition. We suggest that the preference for the left 3/4 view of faces was produced at a later stage of facial information processing that involves attention or memory retrieval.     

Functional connectivity analysis of steady-state visual evoked potentials

In this paper, functional connectivity of steady-state visual evoked potential (SSVEP) was investigated. Directed transfer function (DTF) was applied to cortical signals recorded from electroencephalography (EEG) in order to obtain connectivity patterns. Flow gain was proposed to assess the role of the specific brain region involved in the information transmission process. We found network connections exist in many regions beyond occipital region. Flow gain mapping both in 8–12 Hz and 13–30 Hz showed that parietal region seemed to serve as the sole hub of information transmission. Further studies of flow gain obtained from channel Pz showed two distinct peaks centered at about 12 Hz low frequency and 20 Hz medium frequency respectively. The low frequency region had a larger value of flow gain. The present study introduced functional connectivity into SSVEP. Furthermore, we put forward the concept of flow gain for the first time to explore the exchange and processing of brain information during SSVEP.     

fMRI signal increases and decreases in cortical areas during small-field optokinetic stimulation and central fixation

Small-field optokinetic nystagmus (OKN) was performed in seven healthy volunteers in order to analyze the activation and deactivation patterns of visual motion, ocular motor, and multisensory vestibular cortex areas by means of fMRI during coherent visual motion stimulation. BOLD signal decreases (deactivations) were found in the first and second long insular gyri and retroinsular areas (the human homologue of the parietoinsular vestibular cortex and the visual posterior sylvian area in the monkey) of both hemispheres, extending into the transverse temporal gyrus and inferior-anterior parts of the superior temporal gyrus (BA 22), and the precentral gyri at two separate sites (BA 4 and 6). Further deactivations were found in cranioposterior parts of the superior temporal gyrus (BA 22) and the adjacent inferior parietal lobule (BA 40), anterior cingulate gyrus, hippocampus, and corpus callosum. Most of these BOLD signal decreases involved parts of the "multisensory vestibular cortical circuit". These findings support the concept of a reciprocally inhibitory visual–vestibular interaction that has now been demonstrated not only for large-field visual motion stimulation that induces vection (without eye movements) but also for optokinetically induced eye movements (without vection). The functional significance of this concept may be related to the perception of self-motion, since both large-field visual motion stimulation and optokinetic nystagmus are linked to the visual control of self-motion. With respect to activation of the cortical ocular motor system two separate and distinct areas of activations were delineated in the precentral sulcus of both hemispheres, one ventrolaterally (in BA 9) and the other dorsomedially at the junction of the superior frontal sulcus with the precentral sulcus (in BA 6). Both probably correspond to different subregions of the frontal eye field and the premotor cortex for the ocular motor performance of OKN. Electronic Publication     

Brain activation during dichoptic presentation of optic flow stimuli

The processing of optic flow fields in motion-sensitive areas in human visual cortex was studied with BOLD (blood oxygen level dependent) contrast in functional magnetic resonance imaging (fMRI). Subjects binocularly viewed optic flow fields in plane (monoptic) or in stereo depth (dichoptic) with various degrees of disparity and increasing radial speed. By varying the directional properties of the stimuli (expansion, spiral motion, random), we explored whether the BOLD effect reflected neuronal responses to these different forms of optic flow. The results suggest that BOLD contrast as assessed by fMRI methods reflects the neural processing of optic flow information in motion-sensitive cortical areas. Furthermore, small but replicable disparity-selective responses were found in parts of Brodmann's area 19.