Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensity

Neuroimaging studies of painful stimuli in humans have identified a network of brain regions that is more extensive than identified previously in electrophysiological and anatomical studies of nociceptive pathways. This extensive network has been described as a pain matrix of brain regions that mediate the many interrelated aspects of conscious processing of nociceptive input such as perception, evaluation, affective response, and emotional memory. We used functional magnetic resonance imaging in healthy human subjects to distinguish brain regions required for pain sensory encoding from those required for cognitive evaluation of pain intensity. The results suggest that conscious cognitive evaluation of pain intensity in the absence of any sensory stimulation activates a network that includes bilateral anterior insular cortex/frontal operculum, dorsal lateral prefrontal cortex, bilateral medial prefrontal cortex/anterior cingulate cortex, right superior parietal cortex, inferior parietal lobule, orbital prefrontal cortex, and left occipital cortex. Increased activity common to both encoding and evaluation was observed in bilateral anterior insula/frontal operculum and medial prefrontal cortex/anterior cingulate cortex. We hypothesize that these two regions play a crucial role in bridging the encoding of pain sensation and the cognitive processing of sensory input.     

Neural networks of response shifting: influence of task speed and stimulus material

Functional magnetic resonance imaging (fMRI) was used in 14 healthy subjects to measure brain activation, while response shifting was performed. In the activation phase, subjects were asked to shift their attention between two different types of visually presented stimuli. In the baseline phase, subjects were required to attend to one stimulus type only. Subjects responded by pressing a left or right key according to the side of presentation of the target stimuli. In a verbal task, subjects were required to switch between letters and numbers. In a figural task, subjects reacted to round and square shapes. Stimuli were presented for 750 or 1500 ms. Response shifting revealed significantly increased activation compared to non-switching in the bilateral superior parietal cortex, right occipital cortex, left inferior frontal cortex, left and right striatum, and bilateral dorsolateral prefrontal cortex (DLPFC). Superior parietal and occipital cortex activation may be due to spatial analysis during response shifting. Subvocal rehearsal of the task instructions may have led to activation in the left inferior frontal cortex. Activation in the striatum was related to prefrontal activation and may represent the association between basal ganglia and prefrontal activation during executive control. However, the most important brain region involved in the execution of response shifting was the bilateral DLPFC. Higher task speed increased executive top-down attentional control and, therefore, significantly increased activity in the bilateral DLPFC. Brain activation did not differ significantly between verbal and figural stimulus material. This result suggests that brain activation in the present study illustrates the brain regions involved in the basic cognitive mechanisms of response shifting.     

Sustained involvement of a frontal-parietal network for spatial response selection with practice of a spatial choice-reaction task

With practice, performance on a task typically becomes faster, more accurate, and less prone to interference from competing tasks. Some theories of this performance change suggest it reflects a qualitative reorganization of the cognitive processing required for successful task performance. Other theories suggest this change in performance reflects a more quantitative change in the amount of processing required to perform the task. Neuroimaging research results provide some support for both of these broad theories. This inconsistency may reflect the complex nature of the effect of practice on cognitive and neural processing. Our current experiment addresses this issue by investigating the effect of practice of a relatively easy perceptual-motor task on the frontal-parietal brain network for a specific cognitive process (viz. spatial response selection). Participants were scanned during three functional magnetic resonance imaging sessions on separate days within 4 days while they performed a relatively easy spatial perceptual-motor task. We found sustained activity with practice in right dorsal prefrontal cortex; and sustained but decreasing activity in bilateral dorsal premotor, left superior parietal, and precuneus cortices, supporting a quantitative decrease in difficulty of response selection with practice. Conversely, we found a qualitative change in activity with practice in left dorsal prefrontal cortex. This brain region is outside the response selection network for this task and showed activity only during novel task performance. These results suggest that practice produces both qualitative and quantitative changes in processing. The particular effect of practice depends on the cognitive process in question.     

Two qualitatively different impairments in making rotation operations

It is widely recognized that mental rotation is a cognitive process which engages a distributed cortical network including the frontal, premotor and parietal regions. Like other visual-spatial transformations it could require operations on both metric and categorical spatial representations. Previous reports have implicated respectively the right hemisphere being involved in the metric processing and the left hemisphere in the categorical processing. By using a modified version of the Bricolo et al.'s task (2000), we attempted to establish the cortical regions relevant for the categorical and metric aspects of mental rotation transformations. Two groups of patients were found to be impaired in our study, namely the left prefrontal and the right parietal. In particular, whereas the right parietal group made poor use of categorical information, the left prefrontal patients showed a broader mental rotation impairment with a significant number of metric errors. The results are discussed in terms of the model of Kosslyn et al. (1989) about the possible mental transformation impairments following brain lesions.     

Neural interaction of the amygdala with the prefrontal and temporal cortices in the processing of facial expressions as revealed by fMRI.

Some involvement of the human amygdala in the processing of facial expressions has been investigated in neuroimaging studies, although the neural mechanisms underlying motivated or emotional behavior in response to facial stimuli are not yet fully understood. We investigated, using functional magnetic resonance imaging (fMRI) and healthy volunteers, how the amygdala interacts with other cortical regions while subjects are judging the sex of faces with negative, positive, or neutral emotion. The data were analyzed by a subtractive method, then, to clarify possible interaction among regions within the brain, several kinds of analysis (i.e., a correlation analysis, a psychophysiological interaction analysis and a structural equation modeling) were performed. Overall, significant activation was observed in the bilateral fusiform gyrus, medial temporal lobe, prefrontal cortex, and the right parietal lobe during the task. The results of subtraction between the conditions showed that the left amygdala, right orbitofrontal cortex, and temporal cortices were predominantly involved in the processing of the negative expressions. The right angular gyrus was involved in the processing of the positive expressions when the negative condition was subtracted from the positive condition. The correlation analysis showed that activity in the left amygdala positively correlated with activity in the left prefrontal cortex under the negative minus neutral subtraction condition. The psychophysiological interaction revealed that the neural responses in the left amygdala and the right prefrontal cortex underwent the condition-specific changes between the negative and positive face conditions. The right amygdaloid activity also had an interactive effect with activity in the right hippocampus and middle temporal gyrus. These results may suggest that the left and right amygdalae play a differential role in effective processing of facial expressions in collaboration with other cortical or subcortical regions, with the left being related with the bilateral prefrontal cortex, and the right with the right temporal lobe.     

What have Klingon letters and faces in common? An fMRI study on content-specific working memory systems

Neuroimaging studies show that prefrontal, premotor, and parietal cortical regions are part of a working memory network that supports the active retention of information. In two experiments we used fMRI to examine whether prefrontal and posterior cortical areas are organized in a content-specific way for object and spatial working memory. Subjects performed a delayed matching-to-sample task modified to allow the examination of content-specific retention processes, independent of perceptual and decision-related processes. In Experiment 1, either unfamiliar geometrical objects (Klingon letters from an artificial alphabet unknown to the participants) or their spatial locations had to be memorized, whereas in Experiment 2, either unfamiliar faces or biological objects (butterflies) were actively memorized. All tasks activated a similar cortical network including posterior parietal (banks of the intraparietal sulcus), premotor (banks of the inferior precentral sulcus) and prefrontal regions (banks of the inferior frontal sulcus), and the presupplementary motor area (pre-SMA). For geometrical objects and faces for which strategic semantic processing can be assumed, this activation was larger in the left than in the right hemisphere, whereas a bilateral or right dominant distribution was obtained for butterflies and spatial locations. The present results do not support the process-specific or content-specific view of the role of the prefrontal cortex in working memory task. Rather, they suggest that the inferior prefrontal cortex houses nonmemonic strategic processing systems required for response selection and task management that can flexibly be used across a variety of tasks and informational domains.     

Developmental changes in within- and between-network connectivity between late childhood and adulthood

A number of behavioral changes occur between late childhood and adulthood, including maturation of social cognition, reward receptivity, impulsiveness, risk-taking and cognitive control. Although some of these abilities show linear improvements with age, some abilities may temporarily worsen, reflecting both the restructuring and/or strengthening of connections within some brain systems. The current study uses resting state functional connectivity to examine developmental differences between late childhood and adulthood in task positive (TP) regions, which play a role in cognitive control functions, and task negative (TN) regions, which play a role in social cognition, self-referential, and internally-directed thought. Within the TP network, developmental differences in connectivity were found with the left dorsolateral prefrontal cortex. Within the TN network, developmental differences in connectivity were found with a broad area of the medial prefrontal cortex and the right parahippocampal gyrus. Connections between the two networks also showed significant developmental differences. Stronger anticorrelations were found in the TN maps of the adult group for the right anterior insula/inferior frontal gyrus, bilateral anterior inferior parietal lobule, bilateral superior parietal lobule and an anterior portion of the right posterior cingulate cortex. There was a significant brain–behavior relationship between the strength of anticorrelation in these regions and inhibitory control performance on two Go/No-go tasks suggesting that the development of anticorrelations between late childhood and adulthood supports mature inhibitory control. Overall, maturation of these networks occurred in specific regions which are associated with cognitive control of goal-directed behavior, including those involved in working memory, social cognition, and inhibitory control.     

Who comes first? The role of the prefrontal and parietal cortex in cognitive control

Cognitive control processes enable us to adjust our behavior to changing environmental demands. Although neuropsychological studies suggest that the critical cortical region for cognitive control is the prefrontal cortex, neuro-imaging studies have emphasized the interplay of prefrontal and parietal cortices. This raises the fundamental question about the different contributions of prefrontal and parietal areas in cognitive control. It was assumed that the prefrontal cortex biases processing in posterior brain regions. This assumption leads to the hypothesis that neural activity in the prefrontal cortex should precede parietal activity in cognitive control. The present study tested this assumption by combining results from functional magnetic resonance imaging (fMRI) providing high spatial resolution and event-related potentials (ERPs) to gain high temporal resolution. We collected ERP data using a modified task-switching paradigm. In this paradigm, a situation where the same task was indicated by two different cues was compared with a situation where two cues indicated different tasks. Only the latter condition required updating of the task set. Task-set updating was associated with a midline negative ERP deflection peaking around 470 msec. We placed dipoles in regions activated in a previous fMRI study that used the same paradigm (left inferior frontal junction, right inferior frontal gyrus, right parietal cortex) and fitted their directions and magnitudes to the ERP effect. The frontal dipoles contributed to the ERP effect earlier than the parietal dipole, providing support for the view that the prefrontal cortex is involved in updating of general task representations and biases relevant stimulus-response associations in the parietal cortex.     

Brain network dynamics during error commission

Previous studies suggest that the anterior cingulate and other prefrontal brain regions might form a functionally-integrated error detection network in the human brain. This study examined whole brain functional connectivity to both correct and incorrect button presses using independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) data collected from 25 adolescent and 25 adult healthy participants (ages 11-37) performing a visual Go/No-Go task. Correct responses engaged a network comprising left lateral prefrontal cortex, left postcentral gyrus/inferior parietal lobule, striatum, and left cerebellum. In contrast, a similar network was uniquely engaged during errors, but this network was not integrated with activity in regions believed to be engaged for higher-order cognitive control over behavior. A medial/dorsolateral prefrontal-parietal neural network responded to all No-Go stimuli, but with significantly greater activity to errors. ICA analyses also identified a third error-related circuit comprised of anterior temporal lobe, limbic, and pregenual cingulate cortices, possibly representing an affective response to errors. There were developmental differences in error-processing activity within many of these neural circuits, typically reflecting greater hemodynamic activation in adults. These findings characterize the spatial structure of neural networks underlying error commission and identify neurobiological differences between adolescents and adults.     

Neural correlates of switching set as measured in fast, event-related functional magnetic resonance imaging

Attentional switching has shown to involve several prefrontal and parietal brain regions. Most cognitive paradigms used to measure cognitive switching such as the Wisconsin Card Sorting Task (WCST) involve additional cognitive processes besides switching, in particular working memory (WM). It is, therefore, questionable whether prefrontal brain regions activated in these conditions, especially dorsolateral prefrontal cortex (DLPFC), are involved in cognitive switching per se, or are related to WM components involved in switching tasks. Functional magnetic resonance imaging (fMRI) was used to examine neural correlates of pure switching using a paradigm purposely designed to minimize WM functions. The switching paradigm required subjects to switch unpredictably between two spatial dimensions, clearly indicated throughout the task before each trial. Fast, event-related fMRI was used to compare neural activation associated with switch trials to that related to repeat trials in 20 healthy, right-handed, adult males. A large cluster of activation was observed in the right hemisphere, extending from inferior prefrontal and pre- and postcentral gyri to superior temporal and inferior parietal cortices. A smaller and more caudal cluster of homologous activation in the left hemisphere was accompanied by activation of left dorsolateral prefrontal cortex (DLPFC). We conclude that left DLPFC activation is involved directly in cognitive switching, in conjunction with parietal and temporal brain regions. Pre- and postcentral gyrus activation may be related to motor components of switching set.     

Error-related brain activation during a Go/NoGo response inhibition task

Inhibitory control and performance monitoring are critical executive functions of the human brain. Lesion and imaging studies have shown that the inferior frontal cortex plays an important role in inhibition of inappropriate response. In contrast, specific brain areas involved in error processing and their relation to those implicated in inhibitory control processes are unknown. In this study, we used a random effects model to investigate error-related brain activity associated with failure to inhibit response during a Go/NoGo task. Error-related brain activation was observed in the rostral aspect of the right anterior cingulate (BA 24/32) and adjoining medial prefrontal cortex, the left and right insular cortex and adjoining frontal operculum (BA 47) and left precuneus/posterior cingulate (BA 7/31/29). Brain activation related to response inhibition and competition was observed bilaterally in the dorsolateral prefrontal cortex (BA 9/46), pars triangularis region of the inferior frontal cortex (BA 45/47), premotor cortex (BA 6), inferior parietal lobule (BA 39), lingual gyrus and the caudate, as well as in the right dorsal anterior cingulate cortex (BA 24). These findings provide evidence for a distributed error processing system in the human brain that overlaps partially, but not completely, with brain regions involved in response inhibition and competition. In particular, the rostal anterior cingulate and posterior cingulate/precuneus as well as the left and right anterior insular cortex were activated only during error processing, but not during response competition, inhibition, selection, or execution. Our results also suggest that the brain regions involved in the error processing system overlap with brain areas implicated in the formulation and execution of articulatory plans.     

Coordinate and categorical judgements in spatial imagery. An fMRI study

We aimed at verifying whether the hemispheric specialisation for categorical/coordinate spatial judgements also applies to the spatial imagery domain by the use of whole-brain fMRI. In a block-design experiment we used the "coordinate" mental clock test, contrasting it with a "categorical" task applied to the same clock stimuli; as a control task we used a syllable counting task requiring a verbal-phonological judgement on the same material of the two imagery tasks. Our results showed that categorical and coordinate spatial judgements on imagined stimuli rely on the activation of a set of cortical areas, centred upon the superior parietal lobule (SPL) bilaterally. These regions, together with other parietal and prefrontal areas, showed a pattern of relative lateralization, with the left hemisphere being mainly activated during the categorical task and the right in the coordinate task. These data confirm the strong involvement of the SPL in spatial processing. Moreover, our findings suggest that different interconnected neural networks are activated to comply with specific test requirements, giving rise to functional imaging patterns compatible with psychological theories on hemispheric specialization.     

Direct current stimulation over the human sensorimotor cortex modulates the brain's hemodynamic response to tactile stimulation

Tactile stimuli produce afferent signals that activate specific regions of the cerebral cortex. Noninvasive transcranial direct current stimulation (tDCS) effectively modulates cortical excitability. We therefore hypothesised that a single session of tDCS targeting the sensory cortices would alter the cortical response to tactile stimuli. This hypothesis was tested with a block‐design functional magnetic resonance imaging protocol designed to quantify the blood oxygen level‐dependent response to controlled sinusoidal pressure stimulation applied to the right foot sole, as compared with rest, in 16 healthy young adults. Following sham tDCS, right foot sole stimulation was associated with activation bilaterally within the precentral cortex, postcentral cortex, middle and superior frontal gyri, temporal lobe (subgyral) and cingulate gyrus. Activation was also observed in the left insula, middle temporal lobe, superior parietal lobule, supramarginal gyrus and thalamus, as well as the right inferior parietal lobule and claustrum (false discovery rate corrected, P < 0.05). To explore the regional effects of tDCS, brain regions related to somatosensory processing, and cortical areas underneath each tDCS electrode, were chosen as regions of interest. Real tDCS, as compared with sham tDCS, increased the percent signal change associated with foot stimulation relative to rest in the left posterior paracentral lobule. These results indicate that tDCS acutely modulated the cortical responsiveness to controlled foot pressure stimuli in healthy adults. Further study is warranted, in both healthy individuals and patients with sensory impairments, to link tDCS‐induced modulation of the cortical response to tactile stimuli with changes in somatosensory perception.     

Dynamic and strategic aspects of executive processing

Executive cognitive functions have been postulated to include both dynamic behavioral selection and strategic goal-setting or response preparation. To investigate the relation between these aspects of executive processing, we embedded an event-related oddball paradigm within a blocked design. Subjects responded to infrequent targets presented within a series of standard stimuli that required no response; this task alternated with a visually similar nontask condition. Using functional magnetic resonance imaging (fMRI), we found that a set of brain regions including dorsolateral prefrontal cortex (dlPFC), insular cortex, cingular cortex, and the basal ganglia demonstrated transient activation both to target stimuli and to the onset of task blocks. Within the parietal cortex, there was a dissociation such that the supramarginal gyrus exhibited greater activity to the target stimuli than to block onsets, while the converse pattern was observed in the intraparietal sulcus. Sustained positive activity during task blocks was present in the caudate and supplementary motor area, while sustained negative activity was present in the precuneus and medial parietal cortex. We conclude that dlPFC and related brain regions mediate both dynamic and strategic processing, through the preparation and selection of rules for behavior.     

Tactile discrimination of grating orientation: fMRI activation patterns

Grating orientation discrimination is employed widely to test tactile spatial acuity. We used functional magnetic resonance imaging (fMRI) to investigate the neural circuitry underlying performance of this task. Two studies were carried out. In the first study, an extensive set of parietal and frontal cortical areas was activated during covert task performance, relative to a rest baseline. The active regions included the postcentral sulcus bilaterally and foci in the left parietal operculum, left anterior intraparietal sulcus, and bilateral premotor and prefrontal cortex. The second study examined selective recruitment of cortical areas during discrimination of grating orientation (a task with a macrospatial component) compared to discrimination of grating spacing (a purely microspatial task). The foci activated on this contrast were in the left anterior intraparietal sulcus, right postcentral sulcus and gyrus, left parieto-occipital cortex, bilateral frontal eye fields, and bilateral ventral premotor cortex. These findings not only confirm and extend previous studies of the neural processing underlying grating orientation discrimination, but also demonstrate that a distributed network of putatively multisensory areas is involved.     

Processing of auditory motion in inferior parietal lobule: evidence from transcranial magnetic stimulation

The neural substrates of auditory motion processing are, at present, still a matter of debate. It has been hypothesized that motion information is, as in the visual system, processed separately from other aspects of auditory information, such as stationary location. Here we aimed to differentiate the location of auditory motion processing in human cortex using low-frequency repetitive transcranial magnetic stimulation (rTMS) in combination with a psychophysical task of motion discrimination. rTMS was applied offline to right posterior superior temporal gyrus, right inferior parietal lobule, right dorsal premotor cortex, or right primary somatosensory cortex (as reference site). A significant decrease in performance was obtained exclusively for sounds presented in left hemispace after rTMS over the right inferior parietal lobule (BA 40). This finding indicates that the inferior parietal lobule plays a crucial role in the analysis of moving sound, with an apparent contralaterality of cortical processing. Combined with previous studies which have demonstrated effects of rTMS on static sound localization for both inferior parietal and posterior temporal cortices, the results suggest a hierarchical processing of auditory spatial information, with higher-order functions of motion analysis, such as discrimination of motion direction, mainly taking place beyond the temporal lobe.     

Both left and right posterior parietal activations contribute to compensatory processes in normal aging

Older adults often exhibit greater brain activation in prefrontal cortex compared to younger adults, and there is some evidence that this increased activation compensates for age-related neural degradation that would otherwise adversely affect cognitive performance. Less is known about aging and compensatory recruitment in the parietal cortex. In this event-related functional magnetic resonance imaging study, we presented healthy young and old participants with two Stroop-like tasks (number magnitude and physical size). In young, the number magnitude task activated right parietal cortex and the physical size task activated left parietal cortex. In older adults, we observed contralateral parietal recruitment that depended on the task: in the number magnitude task older participants recruited left posterior parietal cortex (in addition to the right parietal activity observed in young) while in the physical size task they recruited right (in addition to left) posterior parietal cortex. In both cases, the additional parietal activity was associated with better performance suggesting that it played a compensatory role. Older adults also recruited left prefrontal cortex during both tasks and this common activation was also associated with better performance. The results provide evidence for task-specific compensatory recruitment in parietal cortex as well as task-independent compensatory recruitment in prefrontal cortex in normal aging.     

Functional connectivity during orthographic,phonological, and semantic processing of Chinese characters identifies distinct visuospatial and phonosemantic networks

While neuroimaging studies have identified brain regions associated with single word reading, its three constituents, namely, orthography, phonology, and meaning, and the functional connectivity of their networks remain underexplored. This study examined the neurocognitive underpinnings of these neural activations and functional connectivity of the identified brain regions using a within‐subject design. Thirty‐one native Mandarin speakers performed orthographic, phonological, and semantic judgment tasks during functional magnetic resonance imaging. The results indicated that the three processes shared a core network consisting of a large region in the left prefrontal cortex, fusiform gyrus, and medial superior frontal gyrus but not the superior temporal gyrus. Orthographic processing more strongly recruited the left dorsolateral prefrontal cortex, left superior parietal lobule and bilateral fusiform gyri; semantic processing more strongly recruited the left inferior frontal gyrus and left middle temporal gyrus, whereas phonological processing more strongly activated the dorsal part of the precentral gyrus. Functional connectivity analysis identified a posterior visuospatial network and a frontal phonosemantic network interfaced by the left middle frontal gyrus. We conclude that reading Chinese recruits cognitive resources that correspond to basic task demands with unique features best explained in connection with the individual reading subprocesses.     

Neural activation during response competition

The flanker task, introduced by Eriksen and Eriksen [Eriksen, B. A., & Eriksen, C. W. (1974). Effects of noise letters upon the identification of a target letter in a nonsearch task. Perception & Psychophysics, 16, 143--149], provides a means to selectively manipulate the presence or absence of response competition while keeping other task demands constant. We measured brain activity using functional magnetic resonance imaging (fMRI) during performance of the flanker task. In accordance with previous behavioral studies, trials in which the flanking stimuli indicated a different response than the central stimulus were performed significantly more slowly than trials in which all the stimuli indicated the same response. This reaction time effect was accompanied by increases in activity in four regions: the right ventrolateral prefrontal cortex, the supplementary motor area, the left superior parietal lobe, and the left anterior parietal cortex. The increases were not due to changes in stimulus complexity or the need to overcome previously learned associations between stimuli and responses. Correspondences between this study and other experiments manipulating response interference suggest that the frontal foci may be related to response inhibition processes whereas the posterior foci may be related to the activation of representations of the inappropriate responses.     

Cortical dysfunction in patients with Huntington's disease during working memory performance

Previous functional neuroimaging studies on executive function suggested multiple functionally aberrant cortical regions in patients with Huntington's disease (HD). However, little is known about the neural mechanisms of working memory (WM) function in this patient population. The objective of this study was to investigate the functional neuroanatomy of WM in HD patients. We used event-related functional magnetic resonance imaging and a parametric verbal WM task to investigate cerebral function during WM performance in 16 healthy control subjects and 12 mild to moderate stage HD patients. We excluded incorrectly performed trials to control for potential accuracy-related activation confounds. Voxel-based morphometry (VBM) was used to control for confounding cortical and subcortical atrophy. We found that HD patients were slower and less accurate than healthy controls across all WM load levels. In addition, HD patients showed lower activation in the left dorso- and ventrolateral prefrontal cortex, the left inferior parietal cortex, the left putamen, and the right cerebellum at high WM load levels only. VBM revealed gray matter differences in the bilateral caudate nucleus and the thalamus, as well as in inferior parietal and right lateral prefrontal regions. However, volumetric abnormalities in the patient group did not affect the activation differences obtained during WM task performance. These findings demonstrate that WM-related functional abnormalities in HD patients involve distinct WM network nodes associated with cognitive control and subvocal rehearsal. Moreover, aberrant cortical function in HD patients may occur in brain regions, which are relatively well preserved in terms of brain atrophy.