Single-trial EEG-fMRI coupling of the emotional auditory early posterior negativity

Event-related potential (ERP) studies in the visual domain often report an emotion-evoked early posterior negativity (EPN). Studies in the auditory domain have recently shown a similar component. Little source localization has been done on the visual EPN, and no source localization has been done on the auditory EPN. The aim of the current study was to identify the neural generators of the auditory EPN using EEG-fMRI single-trial coupling. Data were recorded from 19 subjects who completed three auditory choice reaction tasks: (1) a control task using neutral tones; (2) a prosodic emotion task involving the categorization of syllables; and (3) a semantic emotion task involving the categorization of words. The waveforms of the emotion tasks diverged from the neutral task over parietal scalp during a very early time window (132-156 ms) and later during a more traditional EPN time window (252-392 ms). In the EEG-fMRI analyses, the variance of the voltage in the earlier time window was correlated with activity in the medial prefrontal cortex, but only in the word task. In the EEG-fMRI analyses of the traditional EPN time window both emotional tasks covaried with activity in the left superior parietal lobule. Our results support previous parietal cortex source localization findings for the visual EPN, and suggest enhanced selective attention to emotional stimuli during the EPN time window.     

Working memory in another dimension: functional imaging of human olfactory working memory

The majority of working memory research has been carried out within the visual and auditory modalities, leaving it unclear how other modalities would map onto currently proposed working memory models. In this study we examined the previously uninvestigated area of olfactory working memory. Our aim was to investigate if olfactory working memory would engage prefrontal regions known to be involved in working memory for other sensory modalities. Using positron emission tomography we measured cerebral blood flow changes in 12 volunteers during an olfactory working memory task and a comparison visual working memory task. Our findings indicate that both olfactory and face working memory engaged dorsolateral and ventrolateral frontal cortex when the task requirements were matched; a conjunction analysis indicated overlap in the distribution of activity in the two tasks. Similarities and differences in activity were noted in parietal lobe regions, with both tasks engaging inferior areas of 40/7, but only visual working memory showing increased activity within left superior parietal cortex. The findings support the idea that working memory processes engage frontal cortical areas independent of the modality of input, but do not rule out the possibility of modality-specific neural populations within dorsolateral or ventrolateral cortex.     

Dynamics of gamma-band activity in human magnetoencephalogram during auditory pattern working memory

Both electrophysiological research in animals and human brain imaging studies have suggested that, similar to the visual system, separate cortical ventral "what" and dorsal "where" processing streams may also exist in the auditory domain. Recently we have shown enhanced gamma-band activity (GBA) over posterior parietal cortex belonging to the putative auditory dorsal pathway during a sound location working memory task. Using a similar methodological approach, the present study assessed whether GBA would be increased over auditory ventral stream areas during an auditory pattern memory task. Whole-head magnetoencephalogram was recorded from N = 12 subjects while they performed a working memory task requiring same-different judgments about pairs of syllables S1 and S2 presented with 0.8-s delays. S1 and S2 could differ either in voice onset time or in formant structure. This was compared with a control task involving the detection of possible spatial displacements in the background sound presented instead of S2. Under the memory condition, induced GBA was enhanced over left inferior frontal/anterior temporal regions during the delay phase and in response to S2 and over prefrontal cortex at the end of the delay period. gamma-Band coherence between left frontotemporal and prefrontal sensors was increased throughout the delay period of the memory task. In summary, the memorization of syllables was associated with synchronously oscillating networks both in frontotemporal cortex, supporting a role of these areas as parts of the putative auditory ventral stream, and in prefrontal, possible executive regions. Moreover, corticocortical connectivity was increased between these structures.     

Functional topography of working memory for face or voice identity

We used functional magnetic resonance imaging (fMRI) to investigate whether the neural systems for nonspatial visual and auditory working memory exhibits a functional dissociation. The subjects performed a delayed recognition task for previously unfamiliar faces and voices and an audiovisual sensorimotor control task. During the initial sample and subsequent test stimulus presentations, activation was greater for the face than for the voice identity task bilaterally in the occipitotemporal cortex and, conversely, greater for voices than for faces bilaterally in the superior temporal sulcus/gyrus (STS/STG). Ventral prefrontal regions were activated by both memory delays in comparison with the control delays, and there was no significant difference in direct voxelwise comparisons between the tasks. However, further analyses showed that there was a subtle difference in the functional topography for two delay types within the ventral prefrontal cortex. Face delays preferentially activate the dorsal part of the ventral prefrontal cortex (BA 44/45) while voice delays preferentially activate the inferior part (BA 45/47), indicating a ventral/dorsal auditory/visual topography within the ventral prefrontal cortex. The results confirm that there is a modality-specific attentional modulation of activity in visual and auditory sensory areas during stimulus presentation. Moreover, within the nonspatial information-type domain, there is a subtle across-modality dissociation within the ventral prefrontal cortex during working memory maintenance of faces and voices.     

Common neural substrates for visual working memory and attention

Humans are severely limited in their ability to memorize visual information over short periods of time. Selective attention has been implicated as a limiting factor. Here we used functional magnetic resonance imaging to test the hypothesis that this limitation is due to common neural resources shared by visual working memory (WM) and selective attention. We combined visual search and delayed discrimination of complex objects and independently modulated the demands on selective attention and WM encoding. Participants were presented with a search array and performed easy or difficult visual search in order to encode one or three complex objects into visual WM. Overlapping activation for attention-demanding visual search and WM encoding was observed in distributed posterior and frontal regions. In the right prefrontal cortex and bilateral insula blood oxygen-level-dependent activation additively increased with increased WM load and attentional demand. Conversely, several visual, parietal and premotor areas showed overlapping activation for the two task components and were severely reduced in their WM load response under the condition with high attentional demand. Regions in the left prefrontal cortex were selectively responsive to WM load. Areas selectively responsive to high attentional demand were found within the right prefrontal and bilateral occipital cortex. These results indicate that encoding into visual WM and visual selective attention require to a high degree access to common neural resources. We propose that competition for resources shared by visual attention and WM encoding can limit processing capabilities in distributed posterior brain regions.     

Sustained attention in a counting task: normal performance and functional neuroanatomy

We examined changes in relative cerebral flood flow (relCBF) using PET during a sustained attention paradigm which included auditory stimulation and different tasks of mental counting. Ten normal volunteers underwent PET (15O water) during a baseline state and under experimental conditions which included listening to clicks, serial counting with auditory stimulation, counting with no auditory stimulation, and an additional component of working memory and time estimation. All subjects performed within normal limits in a battery of neurocognitive tests, which included measures of attention and working memory. Both counting with auditory stimulation and counting with no auditory stimulation engaged motor cortex, putamen, cerebellum, and anterior cingulate. Furthermore, counting with no auditory stimulation relative to counting while listening resulted in significantly increased relCBF in the inferior parietal, dorsolateral prefrontal, and anterior cingulate. The findings obtained in this study support the notion that the parietal and dorsolateral prefrontal cortex are involved when time estimation and working memory are taking part in a task requiring sustained attention.     

Attentional and linguistic interactions in speech perception

The role of attention in speech comprehension is not well understood. We used fMRI to study the neural correlates of auditory word, pseudoword, and nonspeech (spectrally rotated speech) perception during a bimodal (auditory, visual) selective attention task. In three conditions, Attend Auditory (ignore visual), Ignore Auditory (attend visual), and Visual (no auditory stimulation), 28 subjects performed a one-back matching task in the assigned attended modality. The visual task, attending to rapidly presented Japanese characters, was designed to be highly demanding in order to prevent attention to the simultaneously presented auditory stimuli. Regardless of stimulus type, attention to the auditory channel enhanced activation by the auditory stimuli (Attend Auditory>Ignore Auditory) in bilateral posterior superior temporal regions and left inferior frontal cortex. Across attentional conditions, there were main effects of speech processing (word+pseudoword>rotated speech) in left orbitofrontal cortex and several posterior right hemisphere regions, though these areas also showed strong interactions with attention (larger speech effects in the Attend Auditory than in the Ignore Auditory condition) and no significant speech effects in the Ignore Auditory condition. Several other regions, including the postcentral gyri, left supramarginal gyrus, and temporal lobes bilaterally, showed similar interactions due to the presence of speech effects only in the Attend Auditory condition. Main effects of lexicality (word>pseudoword) were isolated to a small region of the left lateral prefrontal cortex. Examination of this region showed significant word>pseudoword activation only in the Attend Auditory condition. Several other brain regions, including left ventromedial frontal lobe, left dorsal prefrontal cortex, and left middle temporal gyrus, showed Attention x Lexicality interactions due to the presence of lexical activation only in the Attend Auditory condition. These results support a model in which neutral speech presented in an unattended sensory channel undergoes relatively little processing beyond the early perceptual level. Specifically, processing of phonetic and lexical-semantic information appears to be very limited in such circumstances, consistent with prior behavioral studies.     

Working Memory of Identification of Emotional Vocal Expressions: An fMRI Study

The distribution of brain activation during working memory processing of emotional vocal expressions was studied using functional magnetic resonance imaging (fMRI) in eight female subjects performing n-back tasks with three load levels (0-back, 1-back, and 2-back tasks). The stimuli in the n-back tasks were the Finnish female name [Saara] uttered in an astonished, angry, frightened, commanding, and scornful mode, and the subjects were instructed to memorize the emotional connotation of the stimuli. Subregions in the prefrontal, parietal, and visual association areas were load-dependently activated during the performance of the n-back tasks. The most consistently activated areas in the prefrontal region were detected in the inferior frontal gyrus corresponding to Brodmann's areas (BAs) 44 and 45 and in the middle and superior frontal gyri (BAs 6/8). Activation was also found in the inferior parietal lobe and intraparietal sulcus (BAs 40/7) and visual association areas including the lingual and fusiform gyri. The results suggest that a distributed neuronal network in occipital, parietal, and frontal areas is involved in working memory processing of emotional content of aurally presented information.     

A parietal-frontal network studied by somatosensory oddball MEG responses, and its cross-modal consistency

Previous studies using functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) of the brain have found that a distributed parietal-frontal neuronal network is activated in normals during both auditory and visual oddball tasks. The common cortical regions in this network are inferior parietal lobule (IPL)/supramarginal gyrus (SMG), anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). It is not clear whether the same network is activated by oddball tasks during somatosensory stimulation. The present study addressed this question by testing healthy adults as they performed a novel median-nerve oddball paradigm while undergoing magnetoencephalography (MEG). An automated multiple dipole analysis technique, the Multi-Start Spatio-Temporal (MSST) algorithm, localized multiple neuronal generators, and identified their time-courses. IPL/SMG, ACC, and DLPFC were reliably localized in the MEG median-nerve oddball responses, with IPL/SMG activation significantly preceding ACC and DLPFC activation. Thus, the same parietal-frontal neuronal network that shows activation during auditory and visual oddball tests is activated in a median-nerve oddball paradigm. Regions uniquely related to somatosensory oddball responses (e.g., primary and secondary somatosensory, dorsal premotor, primary motor, and supplementary motor areas) were also localized. Since the parietal-frontal network supports attentional allocation during performance of the task, this study may provide a novel method, as well as normative baseline data, for examining attention-related deficits in the somatosensory system of patients with neurological or psychiatric disorders.     

Mapping motor inhibition: conjunctive brain activations across different versions of go/no-go and stop tasks

Conjunction analysis methods were used in functional magnetic resonance imaging to investigate brain regions commonly activated in subjects performing different versions of go/no-go and stop tasks, differing in probability of inhibitory signals and/or contrast conditions. Generic brain activation maps highlighted brain regions commonly activated in (a) two different go/no-go task versions, (b) three different stop task versions, and (c) all 5 inhibition task versions. Comparison between the generic activation maps of stop and go/no-go task versions revealed inhibitory mechanisms specific to go/no-go or stop task performance in 15 healthy, right-handed, male adults. In the go/no-go task a motor response had to be selectively executed or inhibited in either 50% or 30% of trials. In the stop task, the motor response to a go-stimulus had to be retracted on either 50 or 30% of trials, indicated by a stop signal, shortly (250 ms) following the go-stimulus. The shared "inhibitory" neurocognitive network by all inhibition tasks comprised mesial, medial, and inferior frontal and parietal cortices. Generic activation of the go/no-go task versions identified bilateral, but more predominantly left hemispheric mesial, medial, and inferior frontal and parietal cortices. Common activation to all stop task versions was in predominantly right hemispheric anterior cingulate, supplementary motor area, inferior prefrontal, and parietal cortices. On direct comparison between generic stop and go/no-go activation maps increased BOLD signal was observed in left hemispheric dorsolateral prefrontal, medial, and parietal cortices during the go/no-go task, presumably reflecting a left frontoparietal specialization for response selection.     

Common and distinct neural substrates of attentional control in an integrated Simon and spatial Stroop task as assessed by event-related fMRI

The purpose of this experiment was to directly examine the neural mechanisms of attentional control involved in the Simon task as compared to a spatial Stroop task using event-related fMRI. The Simon effect typically refers to the interference people experience when there is a stimulus-response conflict. The Stroop effect refers to the interference people experience when two attributes of the same stimulus conflict with each other. Although previous imaging studies have compared the brain activation for each of these tasks performed separately, none had done so in an integrated task that incorporates both types of interference, as was done in the current experiment. Both tasks activated brain regions that serve as a source of attentional control (dorsolateral prefrontal cortex) and posterior regions that are sites of attentional control (the visual processing stream-middle occipital and inferior temporal cortices). In addition, there were also specific brain regions activated to a significantly greater degree by one task and/or only by a single task. The brain regions significantly more activated by the Simon task were those sensitive to detection of response conflict, response selection, and planning (anterior cingulate cortex, supplementary motor areas, and precuneus), and visuospatial-motor association areas. In contrast, the regions significantly more activated by the Stroop task were those involved in biasing the processing toward the task-relevant attribute (inferior parietal cortex). These findings suggest that the interference effects of these two tasks are caused by different types of conflict (stimulus-response conflict for the Simon effect and stimulus-stimulus conflict for the Stroop effect) but both invoke similar sources of top-down modulation.     

Functional MRI BOLD response to Tower of London performance of first-episode schizophrenia patients using cortical pattern matching

Due to its three-dimensional folding pattern, the human neocortex poses a challenge for accurate co-registration of grouped functional brain imaging data. The present study addressed this problem by employing three-dimensional continuum-mechanical image-warping techniques to derive average anatomical representations for co-registration of functional magnetic resonance brain imaging data obtained from 10 male first-episode schizophrenia patients and 10 age-matched male healthy volunteers while they performed a version of the Tower of London task. This novel technique produced an equivalent representation of blood oxygenation level dependent (BOLD) response across hemispheres, cortical regions, and groups, respectively, when compared to intensity average co-registration, using a deformable Brodmann area atlas as anatomical reference. Somewhat closer association of Brodmann area boundaries with primary visual and auditory areas was evident using the gyral pattern average model. Statistically-thresholded BOLD cluster data confirmed predominantly bilateral prefrontal and parietal, right frontal and dorsolateral prefrontal, and left occipital activation in healthy subjects, while patients' hemispheric dominance pattern was diminished or reversed, particularly decreasing cortical BOLD response with increasing task difficulty in the right superior temporal gyrus. Reduced regional gray matter thickness correlated with reduced left-hemispheric prefrontal/frontal and bilateral parietal BOLD activation in patients. This is the first study demonstrating that reduction of regional gray matter in first-episode schizophrenia patients is associated with impaired brain function when performing the Tower of London task, and supports previous findings of impaired executive attention and working memory in schizophrenia.     

Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection

Inhibitory control and error detection are among the highest evolved human self-monitoring functions. Attempts in functional neuroimaging to effectively isolate inhibitory motor control from other cognitive functions have met with limited success. Different brain regions in inferior, mesial, and dorsolateral prefrontal cortices and parietal and temporal lobes have been related to inhibitory control in go/no-go and stop tasks. The widespread activation reflects the fact that the designs used so far have comeasured additional noninhibitory cognitive functions such as selective attention, response competition, decision making, target detection, and inhibition failure. Here we use rapid, mixed trial, event-related functional magnetic resonance imaging to correlate brain activation with an extremely difficult situation of inhibitory control in a challenging stop task that controls for noninhibitory functions. The difficulty of the stop task, requiring withholding of a triggered motor response, was assured by an algorithm that adjusted the task individually so that each subject only succeeded on half of all stop trials, failing on the other half. This design allowed to elegantly separate brain activation related to successful motor response inhibition and to inhibition failure or error detection. Brain activation correlating with successful inhibitory control in 20 healthy volunteers could be isolated in right inferior prefrontal cortex. Failure to inhibit was associated with activation in mesial frontopolar and bilateral inferior parietal cortices, presumably reflecting an attention network for error detection.     

The parietal role in the sense of self-ownership with temporal discrepancy between visual and proprioceptive feedbacks

One hypothesis on how we recognize an image of, for example, an arm as our own is through the co-occurrence of multiple sensory feedbacks, especially visual and proprioceptive feedbacks, in this process. It has been suggested that the parietal lobe is the region where proprioceptive and visual information of one's own body is integrated. This study investigated parietal cortical activity during a visual-proprioceptive synchrony judgment task in which visual feedback of the subjects' own passively moving hand was delayed. The subjects were required to judge whether or not there was a delay between the proprioceptive and visual feedbacks. Parietal cortical activity, which was measured using a 48-channel near-infrared spectroscopy (NIRS) apparatus, appeared to be modulated by the length of the delay between the visual and proprioceptive feedbacks. The bilateral superior/middle parietal areas were involved in experiencing the synchrony between the visual and proprioceptive feedbacks, whereas the right inferior parietal areas were strongly activated when discrepancy between the two feedbacks was detected. We postulate that the superior portion of the parietal lobe is essential for maintaining one's own body image, while the right inferior portion is involved in detecting movements of others.     

Watching social interactions produces dorsomedial prefrontal and medial parietal BOLD fMRI signal increases compared to a resting baseline

Some human brain areas are tonically active in a resting state when subjects are not engaged in any overt task. The activity of these areas decreases when subjects are engaged in a wide variety of laboratory tasks designed to study cognitive operations. It has been suggested that these areas, among them the medial parietal (precyneus) and the dorsomedial prefrontal cortices, may support a "default state" of the human brain. Passive visual observation of laboratory stimuli typically yields no change in activity in these default areas compared to rest. Here we report functional magnetic resonance imaging (fMRI) data on normal subjects watching realistic movie clips depicting everyday social interactions. In contrast with previous findings on default state brain areas, the observation of the relational segment of the movie clip, during which two persons interact, yielded increased activity in the medial parietal (precuneus) and dorsomedial prefrontal cortices, compared to rest and to observation of the segment of the movie clip depicting a single individual engaged in everyday activities. To the best of our knowledge, this is the first report of joint increased activity in medial parietal and dorsomedial prefrontal cortices. We suggest that the default state areas may participate in the processing of social relations in concert with regions previously identified as critical for social cognition that were also activated by our stimuli, including the inferior frontal cortex, the superior temporal cortex, and the fusiform gyrus.     

Attention to action: specific modulation of corticocortical interactions in humans

The prefrontal cortex may exert cognitive control by a general mechanism of attentional selection of neuronal representations. We used functional magnetic resonance imaging to test this hypothesis in the motor system. Normal volunteers were scanned during performance of a simple motor task, with their attention either directed towards their actions, or diverted towards a visual search task, or neither. Attention to action increased activity in prefrontal, premotor and parietal cortex, compared with unattended performance of the same movements. Analysis of cortical activity by structural equation modelling of regional fMRI time series was used to measure effective connectivity among prefrontal, premotor and parietal cortices. Attention to action enhanced effective connectivity between dorsal prefrontal cortex and premotor cortex, whereas non-motor attention diminished it. These effects were not attributable to common inputs from parietal cortex to the prefrontal and premotor cortex. The results suggest a supra-modal role for the dorsal prefrontal cortex in attentional selection, operating within the motor system as well as sensory and mnemonic domains.     

Collaborative activity between parietal and dorso-lateral prefrontal cortex in dynamic spatial working memory revealed by fMRI

Functional MRI was used to determine how the constituents of the cortical network subserving dynamic spatial working memory respond to two types of increases in task complexity. Participants mentally maintained the most recent location of either one or three objects as the three objects moved discretely in either a two- or three-dimensional array. Cortical activation in the dorsolateral prefrontal (DLPFC) and the parietal cortex increased as a function of the number of object locations to be maintained and the dimensionality of the display. An analysis of the response characteristics of the individual voxels showed that a large proportion were activated only when both the variables imposed the higher level of demand. A smaller proportion were activated specifically in response to increases in task demand associated with each of the independent variables. A second experiment revealed the same effect of dimensionality in the parietal cortex when the movement of objects was signaled auditorily rather than visually, indicating that the additional representational demands induced by 3-D space are independent of input modality. The comodulation of activation in the prefrontal and parietal areas by the amount of computational demand suggests that the collaboration between areas is a basic feature underlying much of the functionality of spatial working memory.     

Cognitive control in the posterior frontolateral cortex: evidence from common activations in task coordination, interference control, and working memory

Cognitive control has often been associated with activations of middorsolateral prefrontal cortex. However, recent evidence highlights the importance of a more posterior frontolateral region around the junction of the inferior frontal sulcus and the inferior precentral sulcus (the inferior frontal junction area, IFJ). In the present experiment, we investigated the involvement of the IFJ in a task-switching paradigm, a manual Stroop task, and a verbal n-back task in a within-session within-group design. After computing contrasts for the individual tasks, the resulting z maps were overlaid to identify areas commonly activated by these tasks. Common activations were found in the IFJ, in the pre-SMA extending into mesial BA 8, in the middle frontal gyrus bordering the inferior frontal sulcus, in the anterior insula, and in parietal and thalamic regions. These results indicate the existence of a network of prefrontal, parietal, and subcortical regions mediating cognitive control in task coordination, interference control, and working memory. In particular, the results provide evidence for the assumption that, in the frontolateral cortex, not only the middorsolateral region but also the IFJ plays an important role in cognitive control.     

Chronometry of parietal and prefrontal activations in verbal working memory revealed by transcranial magnetic stimulation

We explored the temporal dynamics of parietal and prefrontal cortex involvement in verbal working memory employing single-pulse transcranial magnetic stimulation (TMS). In six healthy volunteers the left or right inferior parietal and prefrontal cortex was stimulated with the aid of a frameless stereotactic system. TMS was applied at 10 different time points 140-500 ms into the delay period of a two-back verbal working memory task. A choice reaction task was used as a control task. Interference with task accuracy was induced by TMS earlier in the parietal cortex than in the prefrontal cortex and earlier over the right than the left hemisphere. This suggests a propagation of information flow from posterior to anterior cortical sites converging in the left prefrontal cortex. Significant interference with reaction time was observed after 180 ms with left prefrontal cortex stimulation. These effects were not observed in the control task, underlining the task specificity of our results. We propose that the interference with right-sided prefrontal cortex stimulation leads to impaired performance due to disturbed input into the left prefrontal cortex, whereas left-sided TMS interferes directly with the final information processing. Left- and right-sided brain areas might be involved in parallel processing of semantic and object features of the stimuli, respectively.     

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.