Frontoparietal mechanisms supporting attention to location and intensity of painful stimuli

Attention can profoundly shape the experience of pain. However, little is known about the neural mechanisms that support directed attention to nociceptive information. In the present study, subjects were cued to attend to either the spatial location or the intensity of sequentially presented pairs of painful heat stimuli during a delayed match-to-sample discrimination task. We hypothesized that attention-related brain activation would be initiated after the presentation of the attentional cue and would be sustained through the discrimination task. Conjunction analysis confirmed that bilateral portions of the posterior parietal cortex (intraparietal sulcus [IPS] and superior parietal lobule) exhibited this sustained activity during attention to spatial but not intensity features of pain. Analyses contrasting activation during spatial and intensity attention tasks revealed that the right IPS region of the posterior parietal cortex was consistently more activated across multiple phases of the spatial task. However, attention to either feature of the noxious stimulus was associated with activation of frontoparietal areas (IPS and frontal eye fields) as well as priming of the primary somatosensory cortex. Taken together, these results delineate the neural substrates that support selective amplification of different features of noxious stimuli for utilization in discriminative processes.     

Human brain activity associated with audiovisual perception and attention

Coherent perception of objects in our environment often requires perceptual integration of auditory and visual information. Recent behavioral data suggest that audiovisual integration depends on attention. The current study investigated the neural basis of audiovisual integration using 3-Tesla functional magnetic resonance imaging (fMRI) in 12 healthy volunteers during attention to auditory or visual features, or audiovisual feature combinations of abstract stimuli (simultaneous harmonic sounds and colored circles). Audiovisual attention was found to modulate activity in the same frontal, temporal, parietal and occipital cortical regions as auditory and visual attention. In addition, attention to audiovisual feature combinations produced stronger activity in the superior temporal cortices than attention to only auditory or visual features. These modality-specific areas might be involved in attention-dependent perceptual binding of synchronous auditory and visual events into coherent audiovisual objects. Furthermore, the modality-specific temporal auditory and occipital visual cortical areas showed attention-related modulations during both auditory and visual attention tasks. This result supports the proposal that attention to stimuli in one modality can spread to encompass synchronously presented stimuli in another modality.     

Segregated processing of auditory motion and auditory location: an ERP mapping study

Recent studies have revealed a distinct cortical network activated during the analysis of sounds' spatial properties. Whether common brain regions in this auditory where pathway are involved in both auditory motion and location processing is unresolved. We investigated this question with multichannel auditory evoked potentials (AEPs) in 11 subjects. Stimuli were binaural 500-ms white noise bursts. Interaural time differences (ITD) created the sensation of moving or stationary sounds within each auditory hemifield, and subjects discriminated either their position or direction of motion in a blocked design. Scalp potential distributions (AEP maps) differentiated electric field configurations across stimulus classes. The initial approximately 250-ms poststimulus yielded common topographies for both stimulus classes and hemifields. After approximately 250-ms, moving and stationary sounds engaged distinct cortical networks at two time periods, again with no differences observed between hemifields. The first ( approximately 250- to 350-ms poststimulus onset) was during stimulus presentation, and the second ( approximately 550- to 900-ms poststimulus onset) occurred after stimulus offset. Distributed linear inverse solutions of the maps over the 250- to 350-ms time period revealed not only bilateral inferior frontal activation for both types of auditory spatial processing, but also strong right inferior parietal activation in the case of auditory motion discrimination. During the later 550-to 900-ms time period, right inferior parietal and bilateral inferior frontal activity was again observed for moving sounds, whereas strong bilateral superior frontal activity was seen in the case of stationary sounds. Collectively, the evidence supports the existence of partly segregated networks within the auditory where pathway for auditory location and auditory motion processing.     

Spatiotemporal imaging of electrical activity related to attention to somatosensory stimulation

The aim of the present study was to localize the effects of spatial attention on somatosensory stimulation in EEG. Median and tibial nerve were stimulated at all four limbs in a random order. Subjects were instructed to count the events on either the right median or the right tibial nerve. Attention-induced changes in the somatosensory evoked potentials (SEP) were revealed by subtracting the median nerve SEPs recorded while subjects attended to stimuli applied to the tibial nerve from those obtained during attention to the stimulated hand. In a current density reconstruction approach source maxima in the time range from 30 to 260 ms after median nerve stimulation were localized and the time courses of activation were elaborated by dipole modeling. Six regions were identified which contribute significant source activity related to selective spatial attention: contralateral postcentral gyrus (Brodman area (BA) 3), contralateral mesial frontal gyrus (BA 6), right posterior parietal cortex (BA 7), anterior cingulate gyrus (BA 32), and bilateral middle temporal gyrus (BA 21). Activation started at the right posterior parietal cortex, followed by the contralateral middle temporal gyrus, probably representing SII activity, and the middle frontal and anterior cingulate gyrus. Similar regions of source activation were revealed by tibial nerve SEP, but the effect was less pronounced and restricted almost entirely to activation of the contralateral postcentral gyrus (BA 3), anterior cingulate gyrus (BA 32), and ipsilateral middle temporal gyrus (BA 21). Our data provide evidence for a spatially separated frontal generator within the anterior cingulum, dependent on selective attention in the somatosensory modality.     

Cortical activation during perception of a rotating wide-field acoustic stimulus.

We describe sound stimuli that produce the perception of complete rotation around the head. Such stimuli are analogous to wide-field motion stimuli used in visual research, though auditory stimuli, unlike visual stimuli, can be perceived at any point around the head; they are the only cues for spatial perception behind the subject. Using PET on six subjects, we have compared regional brain activity during the perception of such motion stimuli, with the perception of a control stimulus producing equivalent amplitude changes without rotation. Rotation produced activation of the premotor cortex bilaterally and the right superior parietal cortex. The premotor activation involved the frontal eye fields and ventral premotor areas. The bifrontal and right parietal activation is consistent with previous demonstrations of activation within a frontoparietal network of areas during perception of a linear motion stimulus. The inferior premotor activation in this experiment may reflect preparation for head turning in response to auditory targets that cannot be tracked visually.     

Auditory Selective Attention: An fMRI Investigation

In the present experiment, 25 adult subjects discriminated speech tokens ([ba]/[da]) or made pitch judgments on tone stimuli (rising/falling) under both binaural and dichotic listening conditions. We observed that when listeners performed tasks under the dichotic conditions, during which greater demands are made on auditory selective attention, activation within the posterior (parietal) attention system and at primary processing sites in the superior temporal and inferior frontal regions was increased. The cingulate gyrus within the anterior attention system was not influenced by this manipulation. Hemispheric differences between speech and nonspeech tasks were also observed, both at Broca's Area within the inferior frontal gyrus and in the middle temporal gyrus.     

Spatial and temporal factors during processing of audiovisual speech: a PET study

Speech perception can use not only auditory signals, but also visual information from seeing the speaker's mouth. The relative timing and relative location of auditory and visual inputs are both known to influence crossmodal integration psychologically, but previous imaging studies of audiovisual speech focused primarily on just temporal aspects. Here we used Positron Emission Tomography (PET) during audiovisual speech processing to study how temporal and spatial factors might jointly affect brain activations. In agreement with previous work, synchronous versus asynchronous audiovisual speech yielded increased activity in multisensory association areas (e.g., superior temporal sulcus [STS]), plus in some unimodal visual areas. Our orthogonal manipulation of relative stimulus position (auditory and visual stimuli presented at same location vs. opposite sides) and stimulus synchrony showed that (i) ventral occipital areas and superior temporal sulcus were unaffected by relative location; (ii) lateral and dorsal occipital areas were selectively activated for synchronous bimodal stimulation at the same external location; (iii) right inferior parietal lobule was activated for synchronous auditory and visual stimuli at different locations, that is, in the condition classically associated with the 'ventriloquism effect' (shift of perceived auditory position toward the visual location). Thus, different brain regions are involved in different aspects of audiovisual integration. While ventral areas appear more affected by audiovisual synchrony (which can influence speech identification), more dorsal areas appear to be associated with spatial multisensory interactions.     

fMRI reveals that involuntary visual deviance processing is resource limited

Previous studies suggest that involuntary auditory attention evoked by unattended auditory stimuli is not influenced by the primary focus of attention. However, prior studies from our laboratory have found that processing of unattended auditory deviant tones in the auditory and frontal regions is modulated by top-down attentional demands and resource availability. Whether processing of unattended visual deviant stimuli is altered by the availability of attentional resources has not been established. The goal of the current study was to examine the automaticity of these activations, their modulation by attentional capacity, and the neuroanatomical distribution of any attentional effects upon visual deviance detection. We designed an event-related functional magnetic resonance imaging (fMRI) study during which subjects performed a continuous perceptual-motor-visual tracking task whose difficulty was modulated by changing the control dynamics of a joystick. Changes in the anatomical localization, spatial distribution, and intensity of the blood oxygenation level-dependent (BOLD) response associated with unattended infrequent visual changes were examined during low- and high-difficulty tracking conditions of the primary visual task. Results revealed that the unattended deviants elicited BOLD activation in the visual, fusiform, and parietal regions. In these regions, the intensity and extent of the activation evoked by the deviants decreased as a function of the demands of the primary visual task. These findings suggest that processing of unattended visual deviant stimuli is restricted by the attentional demands of a primary task, as previously demonstrated for unattended auditory deviant tones.     

Anatomic dissociation of selective and suppressive processes in visual attention

Visual spatial attention is associated with activation in parietal regions as well as with modulation of visual activity in ventral occipital cortex. Within the parietal lobe, localisation of activity has been hampered by variation in individual anatomy. Using fMRI within regions of interest derived from individual functional maps, we examined the response of superior parietal lobule, intraparietal sulcus, and ventral occipital cortex in 11 normal adults as attention was directed to the left and right visual hemifields during bilateral visual stimulation. Activation in ventral occipital cortex was augmented contralateral to the attended hemifield (P < 0.006), while intraparietal activation was augmented ipsilaterally (P < 0.009), and superior parietal lobule showed no modulation of activity as a function of attended hemifield. These findings suggest that spatial enhancement of relevant stimuli in ventral occipital cortex is complemented by an intraparietal response associated with suppression of, or preparation of a reflexive shift of attention toward, irrelevant stimuli. The spatial attention system in superior parietal cortex, in contrast, may be driven to equal degrees by currently attended stimuli and by stimuli that are potential targets of attention.     

Functional specificity of superior parietal mediation of spatial shifting

Using event-related functional magnetic resonance imaging (fMRI) we determined how brain activity changes when an attended target shifts its location. In the main experiment, a white square could appear at 10 possible eccentricities along the horizontal meridian. It remained on the screen for a variable period of time and then changed location. At any time the stimulus could dim briefly. Subjects had to press a button when the stimulus dimmed. In order to perform this task attention had to be locked onto the target and shift with it. Half of the runs were performed overtly and half covertly. The event of interest consisted of the shift in the location of the attentional target. The state of maintained attention occurring in between the shifts constituted the baseline. The superior parietal gyrus was activated bilaterally in response to attentional shifts. No other area showed a significant response to shifting. On the left side the amplitude of the superior parietal response correlated positively with the distance of the shift. On the right side a significant correlation was present only for overt shifts. In a separate experiment we compared the maintaining of attention at a single spatial location to passive fixation: the frontal eye fields, anterior cingulate, right dorsolateral prefrontal cortex, and inferior parietal lobule were significantly activated, indicating that the absence of a shift-related response in these areas in the main experiment was due to the fact that they were equally activated by maintaining and shifting attention. The response to spatial shifts and the correlation with the distance between the original and the new location points to a specific role of the superior parietal gyrus in shifting the locus of spatial attention.     

Attention-dependent changes of activation and connectivity in dichotic listening

Functional studies of auditory spatial attention generally report enhanced neural responses in auditory cortical regions. However, activity in regions of the spatial attentional network as described in the visual modality is not consistently observed. Data analysis limitations due to oppositely lateralized activity depending on the side of attentional orientation and heterogeneity of paradigms makes it hard to untangle the possible causes of these various activation patterns. In the present article we present a PET study of auditory spatial attention in which we manipulated orientation of attention, attentional load, and difficulty of the task by means of the dichotic listening paradigm. Moreover, we designed a systematic, voxel-specific, method in order to deal with oppositely lateralized activity. The results show that when listeners are involved in auditory spatial attention tasks an interacting network of frontal, temporal, and parietal regions is activated. Selective orientation toward one side mostly yields activity and connectivity modulations in the hemisphere contralateral to the attended side while in divided attention activity is mostly bilateral. Taken together, our observations are consistent with the idea of a multimodal large-scale attentional network.     

Neural mechanisms of top-down control during spatial and feature attention

Theories of visual selective attention posit that both spatial location and nonspatial stimulus features (e.g., color) are elementary dimensions on which top-down attentional control mechanisms can selectively influence visual processing. Neuropsychological and neuroimaging studies have demonstrated that regions of superior frontal and parietal cortex are critically involved in the control of visual-spatial attention. This frontoparietal control network has also been found to be activated when attention is oriented to nonspatial stimulus features (e.g., motion). To test the generality of the frontoparietal network in attentional control, we directly compared spatial and nonspatial attention in a cuing paradigm. Event-related fMRI methods permitted the isolation of attentional control activity during orienting to a location or to a nonspatial stimulus feature (color). Portions of the frontoparietal network were commonly activated to the spatial and nonspatial cues. However, direct statistical comparisons of cue-related activity revealed subregions of the frontoparietal network that were significantly more active during spatial than nonspatial orienting when all other stimulus, task, and attentional factors were equated. No regions of the frontal-parietal network were more active for nonspatial cues in comparison to spatial cues. These findings support models suggesting that subregions of the frontal-parietal network are highly specific for controlling spatial selective attention.     

Functional anatomy of visual search: regional segregations within the frontal eye fields and effective connectivity of the superior colliculus

The ability to find targets embedded within complex visual environments requires the dynamic programming of visuomotor search behaviors. Functional magnetic resonance imaging was used to image subjects while they visually searched for targets embedded among foils. Visuomotor search activated the posterior parietal cortex and the frontal eye fields. Both regions showed a greater number of activated voxels on the right, consistent with the known pattern of right hemispheric dominance for spatial attention. The superior colliculus showed prominent activation in the search versus eye movement contrast, demonstrating, for the first time in humans, activation of this region specifically related to an exploratory attentional contingency. An analysis of effective connectivity demonstrated that the search-dependent variance in the activity of the superior colliculus was significantly influenced by the activity in a network of cortical regions including the right frontal eye fields and bilateral parietal and occipital cortices. These experiments also revealed the presence of a mosaic of activated sites within the frontal eye field region wherein saccadic eye movements, covert shifts of attention, and visuomotor search elicited overlapping but not identical zones of activation. In contrast to the existing literature on functional imaging, which has focused on covert shifts of spatial attention, this study helps to characterize the functional anatomy of overt spatial exploration.     

What vs. where in touch: an fMRI study

Two streams have been identified in cortical visual processing: a ventral stream for form, color, and features, and a dorsal stream for spatial characteristics and motion. We investigated whether similar "what" and "where" dissociations of function exist for human somatosensory processing. Using identical stimuli and hand movements, subjects either performed tactile object recognition (TOR) and ignored location or performed tactile object localization (LOC) and ignored identity. A matched-movement control task separated activation associated with sensorimotor input from higher-level cognitive contributions. Results confirmed separate processing streams for TOR and LOC. TOR activated the frontal pole as well as bilateral inferior parietal and left prefrontal regions involved in tactile feature integration and naming. LOC activated bilateral superior parietal areas involved in spatial processing. The dissociation of object and spatial processing streams appears to be a modality general organizational principle in the brain.     

A cross-linguistic PET study of tone perception in Mandarin Chinese and English speakers

PET was used in a cross-linguistic study to determine whether neural mechanisms subserving pitch perception differ as a function of linguistic relevance. We compared tone perception in 12 native Mandarin speakers, who use tonal patterns to distinguish lexical meaning, with that of 12 native speakers of a nontone language, English. Subjects were scanned under two conditions: a silent resting baseline and a tonal task involving discrimination of pitch patterns in Mandarin words. Both groups showed common regions of CBF increase, but only Mandarin speakers showed additional activation in frontal, parietal, and parieto-occipital regions of the left hemisphere; this latter finding indicates that language experience may influence brain circuitry in the processing of auditory cues. In contrast, only the English group showed activity in the right inferior frontal cortex, consistent with a right-hemispheric role in pitch perception.     

Parietal disruption alters audiovisual binding in the sound-induced flash illusion

Selective attention and multisensory integration are fundamental to perception, but little is known about whether, or under what circumstances, these processes interact to shape conscious awareness. Here, we used transcranial magnetic stimulation (TMS) to investigate the causal role of attention-related brain networks in multisensory integration between visual and auditory stimuli in the sound-induced flash illusion. The flash illusion is a widely studied multisensory phenomenon in which a single flash of light is falsely perceived as multiple flashes in the presence of irrelevant sounds. We investigated the hypothesis that extrastriate regions involved in selective attention, specifically within the right parietal cortex, exert an influence on the multisensory integrative processes that cause the flash illusion. We found that disruption of the right angular gyrus, but not of the adjacent supramarginal gyrus or of a sensory control site, enhanced participants' veridical perception of the multisensory events, thereby reducing their susceptibility to the illusion. Our findings suggest that the same parietal networks that normally act to enhance perception of attended events also play a role in the binding of auditory and visual stimuli in the sound-induced flash illusion.     

Orbitofrontal contribution to auditory encoding

Having recently demonstrated that the human orbitofrontal cortex is selectively activated during the encoding of visual information, we investigated whether this same frontal region, which is directly connected to medial temporal structures, would be activated during the encoding of auditory stimuli. We measured cerebral blood flow (CBF) with positron emission tomography (PET) during the encoding of nonverbal abstract auditory stimuli in a group of young healthy volunteers. The results demonstrate that the left orbitofrontal cortex, area 11 in particular, is involved in the encoding of auditory information. We suggest that the orbitofrontal cortex is a critical frontal region that can exert top-down regulation of other regions of the brain including the medial temporal structures and the lateral frontal cortex, enabling the further processing of information.     

Continuous ASL perfusion fMRI investigation of higher cognition: quantification of tonic CBF changes during sustained attention and working memory tasks

Arterial spin labeling (ASL) perfusion fMRI is an emerging method in clinical neuroimaging. Its non-invasiveness, absence of low frequency noise, and ability to quantify the absolute level of cerebral blood flow (CBF) make the method ideal for longitudinal designs or low frequency paradigms. Despite the usefulness in the study of cognitive dysfunctions in clinical populations, perfusion activation studies to date have been conducted for simple sensorimotor paradigms or with single-slice acquisition, mainly due to technical challenges. Using our recently developed amplitude-modulated continuous ASL (CASL) perfusion fMRI protocol, we assessed the feasibility of a higher level cognitive activation study in twelve healthy subjects. Taking advantage of the ASL noise properties, we were able to study tonic CBF changes during uninterrupted 6-min continuous performance of working memory and sustained attention tasks. For the visual sustained attention task, regional CBF increases (6-12 ml/100 g/min) were detected in the right middle frontal gyrus, the bilateral occipital gyri, and the anterior cingulate/medial frontal gyri. During the 2-back working memory task, significantly increased activations (7-11 ml/100 g/min) were found in the left inferior frontal/precentral gyri, the left inferior parietal lobule, the anterior cingulate/medial frontal gyri, and the left occipital gyrus. Locations of activated and deactivated areas largely concur with previous PET and BOLD fMRI studies utilizing similar paradigms. These results demonstrate that CASL perfusion fMRI can be successfully utilized for the investigation of the tonic CBF changes associated with high level cognitive operations. Increased applications of the method to the investigation of cognitively impaired populations are expected to follow.     

Neuroanatomic overlap of working memory and spatial attention networks: a functional MRI comparison within subjects

Frontal and posterior parietal activations have been reported in numerous studies of working memory and visuospatial attention. To directly compare the brain regions engaged by these two cognitive functions, the same set of subjects consecutively participated in tasks of working memory and spatial attention while undergoing functional MRI (fMRI). The working memory task required the subject to maintain an on-line representation of foveally displayed letters against a background of distracters. The spatial attention task required the subject to shift visual attention covertly in response to a centrally presented directional cue. The spatial attention task had no working memory requirement, and the working memory task had no covert spatial attention requirement. Subjects' ability to maintain central fixation was confirmed outside the MRI scanner using infrared oculography. According to cognitive conjunction analysis, the set of activations common to both tasks included the intraparietal sulcus, ventral precentral sulcus, supplementary motor area, frontal eye fields, thalamus, cerebellum, left temporal neocortex, and right insula. Double-subtraction analyses yielded additional activations attributable to verbal working memory in premotor cortex, left inferior prefrontal cortex, right inferior parietal lobule, precuneus, and right cerebellum. Additional activations attributable to covert spatial attention included the occipitotemporal junction and extrastriate cortex. The use of two different tasks in the same set of subjects allowed us to provide an unequivocal demonstration that the neural networks subserving spatial attention and working memory intersect at several frontoparietal sites. These findings support the view that major cognitive domains are represented by partially overlapping large-scale neural networks. The presence of this overlap also suggests that spatial attention and working memory share common cognitive features related to the dynamic shifting of attentional resources.     

fMRI during natural sleep as a method to study brain function during early childhood

Many techniques to study early functional brain development lack the whole-brain spatial resolution that is available with fMRI. We utilized a relatively novel method in which fMRI data were collected from children during natural sleep. Stimulus-evoked responses to auditory and visual stimuli as well as stimulus-independent functional networks were examined in typically developing 2-4-year-old children. Reliable fMRI data were collected from 13 children during presentation of auditory stimuli (tones, vocal sounds, and nonvocal sounds) in a block design. Twelve children were presented with visual flashing lights at 2.5 Hz. When analyses combined all three types of auditory stimulus conditions as compared to rest, activation included bilateral superior temporal gyri/sulci (STG/S) and right cerebellum. Direct comparisons between conditions revealed significantly greater responses to nonvocal sounds and tones than to vocal sounds in a number of brain regions including superior temporal gyrus/sulcus, medial frontal cortex and right lateral cerebellum. The response to visual stimuli was localized to occipital cortex. Furthermore, stimulus-independent functional connectivity MRI analyses (fcMRI) revealed functional connectivity between STG and other temporal regions (including contralateral STG) and medial and lateral prefrontal regions. Functional connectivity with an occipital seed was localized to occipital and parietal cortex. In sum, 2-4 year olds showed a differential fMRI response both between stimulus modalities and between stimuli in the auditory modality. Furthermore, superior temporal regions showed functional connectivity with numerous higher-order regions during sleep. We conclude that the use of sleep fMRI may be a valuable tool for examining functional brain organization in young children.