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Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Updating beliefs after unexpected events is fundamental for an optimal adaptation to the environment. Previous findings suggested a causal involvement of the right temporoparietal junction (rTPJ) in belief updating in an attention task. We combined offline continuous theta-burst stimulation (cTBS) over rTPJ with functional magnetic resonance imaging (fMRI) to investigate local and remote stimulation effects within the attention and salience networks. In a sham-controlled, within-subject crossover design, 25 participants performed an attentional cueing task during fMRI with true or false information about cue predictability. By estimating learning rates from response times, we characterized participants' belief updating. Model-derived cue predictability entered the fMRI analysis as a parametric regressor to identify the neural correlates of updating. rTPJ-cTBS effects showed high interindividual variability. The expected learning rate reduction with false cue predictability information by cTBS was only observed in participants showing higher updating in false than in true blocks after sham. cTBS modulated the neural signatures of belief updating, both in rTPJ and in nodes of the attention and salience networks. The interindividual variability of the behavioral cTBS effect was related to differential activity and rTPJ connectivity of the right anterior insula. These results demonstrate a crucial interaction between ventral attention and salience networks for belief updating., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although multiple studies characterized the resting-state functional connectivity (rsFC) of the right temporoparietal junction (rTPJ), little is known about the link between rTPJ rsFC and cognitive functions. Given a putative involvement of rTPJ in both reorienting of attention and the updating of probabilistic beliefs, this study characterized the relationship between rsFC of rTPJ with dorsal and ventral attention systems and these two cognitive processes. Twenty-three healthy young participants performed a modified location-cueing paradigm with true and false prior information about the percentage of cue validity to assess belief updating and attentional reorienting. Resting-state fMRI was recorded before and after the task. Seed-based correlation analysis was employed, and correlations of each behavioral parameter with rsFC before the task, as well as with changes in rsFC after the task, were assessed in an ROI-based approach. Weaker rsFC between rTPJ and right intraparietal sulcus before the task was associated with relatively faster updating of the belief that the cue will be valid after false prior information. Moreover, relatively faster belief updating, as well as faster reorienting, were related to an increase in the interhemispheric rsFC between rTPJ and left TPJ after the task. These findings are in line with task-based connectivity studies on related attentional functions and extend results from stroke patients demonstrating the importance of interhemispheric parietal interactions for behavioral performance. The present results not only highlight the essential role of parietal rsFC for attentional functions but also suggest that cognitive processing during a task changes connectivity patterns in a performance-dependent manner.

Healthy aging is accompanied by changes in brain activation patterns in the motor system. In older subjects, unilateral hand movements typically rely on increased recruitment of ipsilateral frontoparietal areas. While the two central concepts of aging-related brain activity changes, "Hemispheric Asymmetry Reduction in Older Adults" (HAROLD), and "Posterior to Anterior Shift in Aging" (PASA), have initially been suggested in the context of cognitive tasks and were attributed to compensation, current knowledge regarding the functional significance of increased motor system activity remains scarce. We, therefore, used online interference transcranial magnetic stimulation in young and older subjects to investigate the role of key regions of the ipsilateral frontoparietal cortex, that is, (a) primary motor cortex (M1), (b) dorsal premotor cortex (dPMC), and (c) anterior intraparietal sulcus (IPS) in the control of hand movements of different motor demands. Our data suggest a change of the functional roles of ipsilateral brain areas in healthy age with a reduced relevance of ipsilateral M1 and a shift of importance toward dPMC for repetitive high-frequency movements. These results support the notion that mechanisms conceptualized in the models of "PASA" and "HAROLD" also apply to the motor system., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Changes in the size of the attentional focus and task difficulty often co-vary. Nevertheless, the neural processes underlying the attentional spotlight process and task difficulty are likely to differ from each other. To differentiate between the two, we parametrically varied the size of the attentional focus in a novel behavioral paradigm while keeping visual processing difficulty either constant or not. A behavioral control experiment proved that the present behavioral paradigm could indeed effectively manipulate the size of the attentional focus per se, rather than affecting purely perceptual processes or surface processing. Imaging results showed that neural activity in a dorsal frontoparietal network, including right superior parietal cortex (SPL), was positively correlated with the size of the attentional spotlight, irrespective of whether task difficulty was constant or varied across different sizes of attentional focus. In contrast, neural activity in the ventral frontoparietal network, including the right inferior parietal cortex (IPL), was positively correlated with increasing task difficulty. Data suggest that sub-regions in parietal cortex are differentially involved in the attentional spotlight process and task difficulty: while SPL was involved in the attentional spotlight process independent of task difficulty, IPL was involved in the effect of task difficulty independent of the attentional spotlight process. Hum Brain Mapp 38:4996-5018, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Generating and updating probabilistic models of the environment is a fundamental modus operandi of the human brain. Although crucial for various cognitive functions, the neural mechanisms of these inference processes remain to be elucidated. Here, we show the causal involvement of the right temporoparietal junction (rTPJ) in updating probabilistic beliefs and we provide new insights into the chronometry of the process by combining online transcranial magnetic stimulation (TMS) with computational modeling of behavioral responses. Female and male participants performed a modified location-cueing paradigm, where false information about the percentage of cue validity (%CV) was provided in half of the experimental blocks to prompt updating of prior expectations. Online double-pulse TMS over rTPJ 300 ms (but not 50 ms) after target appearance selectively decreased participants' updating of false prior beliefs concerning %CV, reflected in a decreased learning rate of a Rescorla-Wagner model. Online TMS over rTPJ also impacted on participants' explicit beliefs, causing them to overestimate %CV. These results confirm the involvement of rTPJ in updating of probabilistic beliefs, thereby advancing our understanding of this area's function during cognitive processing. SIGNIFICANCE STATEMENT Contemporary views propose that the brain maintains probabilistic models of the world to minimize surprise about sensory inputs. Here, we provide evidence that the right temporoparietal junction (rTPJ) is causally involved in this process. Because neuroimaging has suggested that rTPJ is implicated in divergent cognitive domains, the demonstration of an involvement in updating internal models provides a novel unifying explanation for these findings. We used computational modeling to characterize how participants change their beliefs after new observations. By interfering with rTPJ activity through online transcranial magnetic stimulation, we showed that participants were less able to update prior beliefs with TMS delivered at 300 ms after target onset., (Copyright © 2017 the authors 0270-6474/17/375419-10$15.00/0.)

More than two decades ago, the mirror neuron system (MNS) was discovered in non-human primates: Single-cell recordings detected visuo-motor neurons that discharged not only when the monkey performed an action, but also when it observed conspecifics performing the same action. It has been proposed that a fronto-parietal circuitry constitutes the human homolog of the MNS. However, the functional role of a human MNS (i.e., whether it is functionally necessary for imitation or action understanding) to date remains controversial. We here examined how patients with left hemisphere (LH) stroke imitate, recognize, and comprehend intransitive meaningful limb actions. In particular, we investigated whether apraxic patients with lesions affecting key nodes of the putative human MNS show deficits in action imitation, action recognition, and action comprehension to a similar degree - as predicted by the MNS hypothesis. Behavioral results showed that patients with apraxia (n = 18) indeed performed significantly worse in all three motor cognitive tasks compared to non-apraxic patients (n = 26) and healthy controls (n = 19), whose performance did not differ significantly. Lesions of the apraxic (compared to non-apraxic) patients with LH stroke affected more frequently key regions of the putative human MNS, i.e., the left inferior frontal, superior temporal, and supramarginal gyri as well as the inferior parietal lobe (p < .01, false discovery rate - FDR-corrected). Albeit largely overlapping, voxel-based lesion-symptom mapping (VLSM) revealed that deficits in gesture comprehension were mainly associated with lesions of more anterior parts of the MNS, whereas lesions located more posteriorly mainly resulted in gesture imitation deficits (p < .05, FDR-corrected). Our clinical data support key hypotheses derived from the notion of a human MNS: LH lesions to the MNS core regions affected - critically and to a similar extent - the imitation, recognition, and comprehension of meaningful actions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Modelling psychophysical data using the Theory of Visual Attention (TVA) allows for a quantification of attentional sub-processes, such as the resolution of competition amongst multiple stimuli by top-down control signals for target selection (TVA-parameter α). This fMRI study investigated the neural correlates of α by comparing activity differences and changes of effective connectivity between conditions where a target was accompanied by a distractor or by a second target. Twenty-five participants performed a partial report task inside the MRI scanner. The left angular gyrus (ANG), medial frontal, and posterior cingulate cortex showed higher activity when a target was accompanied by a distractor as opposed to a second target. The reverse contrast yielded activation of a bilateral fronto-parietal network, the anterior insula, anterior cingulate cortex, and left inferior occipital gyrus. A psychophysiological interaction analysis revealed that the connectivity between left ANG and the left and right supramarginal gyrus (SMG), left anterior insula, and right putamen was enhanced in the target-distractor condition in participants with worse attentional top-down control. Dynamic causal modelling suggested that the connection from left ANG to right SMG during distractor presence was modulated by α. Our data show that interindividual differences in attentional processing are reflected in changes of effective connectivity without significant differences in activation strength of network nodes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The right temporoparietal junction (rTPJ) has been associated with the ability to reorient attention to unexpected stimuli and the capacity to understand others' mental states (theory of mind [ToM]/false belief). Using activation likelihood estimation meta-analysis we previously unraveled that the anterior rTPJ is involved in both, reorienting of attention and ToM, possibly indicating a more general role in attention shifting. Here, we used neuronavigated transcranial magnetic stimulation to directly probe the role of the rTPJ across attentional reorienting and false belief. Task performance in a visual cueing paradigm and false belief cartoon task was investigated after application of continuous theta burst stimulation (cTBS) over anterior rTPJ (versus vertex, for control). We found that attentional reorienting was significantly impaired after rTPJ cTBS compared with control. For the false belief task, error rates in trials demanding a shift in mental state significantly increased. Of note, a significant positive correlation indicated a close relation between the stimulation effect on attentional reorienting and false belief trials. Our findings extend previous neuroimaging evidence by indicating an essential overarching role of the anterior rTPJ for both cognitive functions, reorienting of attention and ToM. Hum Brain Mapp 37:796-807, 2016. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

The ability to select, within the complexity of sensory input, the information most relevant for our purposes is influenced by both internal settings (i.e., top-down control) and salient features of external stimuli (i.e., bottom-up control). We here investigated using fMRI the neural underpinning of the interaction of top-down and bottom-up processes, as well as their effects on extrastriate areas processing visual stimuli in a category-selective fashion. We presented photos of bodies or buildings embedded into frequency-matched visual noise to the subjects. Stimulus saliency changed gradually due to an altered degree to which photos stood-out in relation to the surrounding noise (hence generating stronger bottom-up control signals). Top-down settings were manipulated via instruction: participants were asked to attend one stimulus category (i.e., "is there a body?" or "is there a building?"). Highly salient stimuli that were inconsistent with participants' attentional top-down template activated the inferior frontal junction and dorsal parietal regions bilaterally. Stimuli consistent with participants' current attentional set additionally activated insular cortex and the parietal operculum. Furthermore, the extrastriate body area (EBA) exhibited increased neural activity when attention was directed to bodies. However, the latter effect was found only when stimuli were presented at intermediate saliency levels, thus suggesting a top-down modulation of this region only in the presence of weak bottom-up signals. Taken together, our results highlight the role of the inferior frontal junction and posterior parietal regions in integrating bottom-up and top-down attentional control signals., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Attention is a complex construct that comprises at least three major subcomponents: alerting, spatial (re-)orienting, and executive functions, all of which have specific neural correlates along frontoparietal networks. Attention deficits are a common consequence of brain damage. Transcranial direct current stimulation (tDCS) has been shown to modulate spatial attention. We investigated whether tDCS of different stimulation targets differentially modulates alerting, spatial (re-)orienting, and executive functions. Twenty-four healthy participants were included in this randomized, double-blinded study, which employed a within-subject design. On four different days, the effects of 1.5 mA anodal tDCS (real and sham) on the left dorsolateral (EEG 10-20 point F3), left parietal (P3) and right parietal cortex (P4) were assessed using a modified attention network test. tDCS of the right parietal cortex enhanced spatial re-orienting, while tDCS of the other cortical targets did not modulate the assessed attention functions. With regard to visual field asymmetries in attentional processing, right parietal tDCS selectively enhanced mean network efficiency for targets presented in the contralateral left visual field. The observed visual field specific tDCS effects on reorienting suggest that systematic investigations into novel approaches for the treatment of patients suffering from spatial neglect patients are warranted., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The right temporoparietal junction (rTPJ) is frequently associated with different capacities that to shift attention to unexpected stimuli (reorienting of attention) and to understand others' (false) mental state [theory of mind (ToM), typically represented by false belief tasks]. Competing hypotheses either suggest the rTPJ representing a unitary region involved in separate cognitive functions or consisting of subregions subserving distinct processes. We conducted activation likelihood estimation (ALE) meta-analyses to test these hypotheses. A conjunction analysis across ALE meta-analyses delineating regions consistently recruited by reorienting of attention and false belief studies revealed the anterior rTPJ, suggesting an overarching role of this specific region. Moreover, the anatomical difference analysis unravelled the posterior rTPJ as higher converging in false belief compared with reorienting of attention tasks. This supports the concept of an exclusive role of the posterior rTPJ in the social domain. These results were complemented by meta-analytic connectivity mapping (MACM) and resting-state functional connectivity (RSFC) analysis to investigate whole-brain connectivity patterns in task-constrained and task-free brain states. This allowed for detailing the functional separation of the anterior and posterior rTPJ. The combination of MACM and RSFC mapping showed that the posterior rTPJ has connectivity patterns with typical ToM regions, whereas the anterior part of rTPJ co-activates with the attentional network. Taken together, our data suggest that rTPJ contains two functionally fractionated subregions: while posterior rTPJ seems exclusively involved in the social domain, anterior rTPJ is involved in both, attention and ToM, conceivably indicating an attentional shifting role of this region.

Although attention deficit hyperactivity disorders (ADHD) and autism spectrum disorders (ASD) share certain neurocognitive characteristics, it has been hypothesized to differentiate the two disorders based on their brain's reward responsiveness to either social or monetary reward. Thus, the present fMRI study investigated neural activation in response to both reward types in age and IQ-matched boys with ADHD versus ASD relative to typically controls (TDC). A significant group by reward type interaction effect emerged in the ventral striatum with greater activation to monetary versus social reward only in TDC, whereas subjects with ADHD responded equally strong to both reward types, and subjects with ASD showed low striatal reactivity across both reward conditions. Moreover, disorder-specific neural abnormalities were revealed, including medial prefrontal hyperactivation in response to social reward in ADHD versus ventral striatal hypoactivation in response to monetary reward in ASD. Shared dysfunction was characterized by fronto-striato-parietal hypoactivation in both clinical groups when money was at stake. Interestingly, lower neural activation within parietal circuitry was associated with higher autistic traits across the entire study sample. In sum, the present findings concur with the assumption that both ASD and ADHD display distinct and shared neural dysfunction in response to reward., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Apraxia, a disorder of higher motor cognition, is a frequent and outcome-relevant sequel of left hemispheric stroke. Deficient pantomiming of object use constitutes a key symptom of apraxia and is assessed when testing for apraxia. To date the neural basis of pantomime remains controversial. We here review the literature and perform a meta-analysis of the relevant structural and functional imaging (fMRI/PET) studies. Based on a systematic literature search, 10 structural and 12 functional imaging studies were selected. Structural lesion studies associated pantomiming deficits with left frontal, parietal and temporal lesions. In contrast, functional imaging studies associate pantomimes with left parietal activations, with or without concurrent frontal or temporal activations. Functional imaging studies that selectively activated parietal cortex adopted the most stringent controls. In contrast to previous suggestions, current analyses show that both lesion and functional studies support the notion of a left-hemispheric fronto-(temporal)-parietal network underlying pantomiming object use. Furthermore, our review demonstrates that the left parietal cortex plays a key role in pantomime-related processes. More specifically, stringently controlled fMRI-studies suggest that in addition to storing motor schemas, left parietal cortex is also involved in activating these motor schemas in the context of pantomiming object use. In addition to inherent differences between structural and functional imaging studies and consistent with the dedifferentiation hypothesis, the age difference between young healthy subjects (typically included in functional imaging studies) and elderly neurological patients (typically included in structural lesion studies) may well contribute to the finding of a more distributed representation of pantomiming within the motor-dominant left hemisphere in the elderly.

Gesture processing deficits constitute a key symptom of apraxia, a disorder of motor cognition frequently observed after left-hemispheric stroke. The clinical relevance of apraxia stands in stark contrast to the paucity of therapeutic options available. Transcranial direct current stimulation (tDCS) is a promising tool for modulating disturbed network function after stroke. Here, we investigate the effect of parietal tDCS on gesture processing in healthy human subjects. Neuropsychological and imaging studies suggest that the imitation and matching of hand gestures involve the left inferior parietal lobe (IPL). Using neuronavigation based on cytoarchitectonically defined anatomical probability maps, tDCS was applied over left IPL-areas PF, PFm, or PG in healthy participants (n = 26). Before and after tDCS, subjects performed a gesture matching task and a person discrimination task for control. Changes in error rates and reaction times were analyzed for the effects of anodal and cathodal tDCS (compared with sham tDCS). Matching of hand gestures was specifically facilitated by anodal tDCS applied over the cytoarchitectonically defined IPL-area PFm, whereas tDCS over IPL-areas PF and PG did not elucidate significant effects. Taking into account tDCS electrode size and the central position of area PFm within IPL, it can be assumed that the observed effect is rather the result of a combined stimulation of the supramarginal and angular gyrus than an isolated PFm stimulation. Our data confirm the pivotal role of the left IPL in gesture processing. Furthermore, anatomically guided tDCS of the left IPL may constitute a promising approach to neurorehabilitation of apraxic patients with gesture processing deficits.

We used fMRI to investigate both common and differential neural mechanisms underlying two distinct types of switching requirements, namely switching between stimulus categorizations (color vs. form) and switching between response modalities (hand vs. foot responses). Both types of switching induced similar behavioral shift costs. However, at the neural level, switching between stimulus categorizations led to left-hemispheric activations including the inferior frontal gyrus as well as the intraparietal sulcus extending to the superior parietal gyrus and the supramarginal gyrus. In contrast, switching between response modalities was associated mainly with left-hemispheric activation of the intraparietal sulcus and the supramarginal gyrus. A conjunction analysis indicated common activation of the left intraparietal sulcus and the supramarginal gyrus for both types of switching. Together, these results qualify previous claims about a general role of the left prefrontal cortex in task control by suggesting that the left inferior frontal gyrus is specifically involved in switching between stimulus categorizations, whereas parietal cortex is more generally implicated in the selection of action rules., (Copyright © 2012 Wiley Periodicals, Inc.)

The right intraparietal sulcus (rIPS) is a key region for the endogenous control of selective visual attention in the human brain. Previous studies suggest that the rIPS is especially involved in top-down control and spatial distribution of attention across both visual hemifields. We further explored these attentional functions using transcranial direct current stimulation (tDCS) of the rIPS to modulate behavioral performance in a partial report task. Performance was analyzed according to the theory of visual attention (TVA) (Bundesen, 1990), which provides a computational framework to investigate different parameters of visuo-attentional processing such as top-down control, attentional weighting, capacity of visual short term memory, and processing speed. We investigated the effects of different tDCS current strengths (1 mA and 2 mA) in two experiments: 1 mA tDCS (anodal, cathodal, sham) did not affect any of the TVA parameters, but cathodal 2 mA stimulation significantly enhanced top-down control as evidenced by a reduction of the α parameter of TVA, regardless of hemifield. This differential impact on the top-down control component of attentional processing suggests that the horizontal rIPS is mainly involved in attentional selection as none of the spatial or resource variables of TVA were altered. Furthermore, the data add evidence to previous work highlighting (1) the importance of using appropriate current strength in stimulation protocols, and (2) that the often reported inhibitory effect of cathodal stimulation in e.g., motor tasks might not extend to cognitive paradigms.

On the basis of double dissociations in clinical symptoms of patients with unilateral visuospatial neglect, neuropsychological research distinguishes between different spatial domains (near vs. far) and different spatial reference frames (egocentric vs. allocentric). In this fMRI study, we investigated the neural interaction between spatial domains and spatial reference frames by constructing a virtual three-dimensional world and asking participants to perform either allocentric or egocentric judgments on an object located in either near or far space. Our results suggest that the parietal-occipital junction (POJ) not only shows a preference for near-space processing but is also involved in the neural interaction between spatial domains and spatial reference frames. Two dissociable streams of visual processing exist in the human brain: a ventral perception-related stream and a dorsal action-related stream. Consistent with the perception-action model, both far-space processing and allocentric judgments draw upon the ventral stream whereas both near-space processing and egocentric judgments draw upon the dorsal stream. POJ showed higher neural activity during allocentric judgments (ventral) in near space (dorsal) and egocentric judgments (dorsal) in far space (ventral) as compared with egocentric judgments (dorsal) in near space (dorsal) and allocentric judgments (ventral) in far space (ventral). Because representations in the dorsal and ventral streams need to interact during allocentric judgments (ventral) in near space (dorsal) and egocentric judgments (dorsal) in far space (ventral), our results imply that POJ is involved in the neural interaction between the two streams. Further evidence for the suggested role of POJ as a neural interface between the dorsal and ventral streams is provided by functional connectivity analysis.

Attentional orientation to a spatial cue and reorientation-after invalid cueing-are mediated by two distinct networks in the human brain. A bilateral dorsal frontoparietal network, comprising the intraparietal sulcus (IPS) and the frontal eye fields (FEF), controls the voluntary deployment of attention and may modulate visual cortex in preparation for upcoming stimulation. In contrast, reorienting attention to invalidly cued targets engages a right-lateralized ventral frontoparietal network comprising the temporoparietal junction (TPJ) and ventral frontal cortex. The present fMRI study investigated the functional architecture of these two attentional systems by characterizing effective connectivity during lateralized orienting and reorienting of attention, respectively. Subjects performed a modified version of Posner's location-cueing paradigm. Dynamic causal modeling (DCM) of regional responses in the dorsal and ventral network, identified in a conventional (SPM) whole-brain analysis, was used to compare different functional architectures. Bayesian model selection showed that top-down connections from left and right IPS to left and right visual cortex, respectively, were modulated by the direction of attention. Moreover, model evidence was highest for a model with directed influences from bilateral IPS to FEF, and reciprocal coupling between right and left FEF. Invalid cueing enhanced forward connections from visual areas to right TPJ, and directed influences from right TPJ to right IPS and IFG (inferior frontal gyrus). These findings shed further light on the functional organization of the dorsal and ventral attentional network and support a context-sensitive lateralization in the top-down (backward) mediation of attentional orienting and the bottom-up (forward) effects of invalid cueing.

Background and Purpose: The present study investigated the lesion anatomy of anosognosia for visuospatial neglect resulting from right hemispheric stroke., Methods: In 63 patients, self-ratings of performance in paper-and-pencil tests were contrasted with external performance ratings. Lesion analysis was conducted on patient subgroups with different degrees of anosognosia but comparable visuospatial impairment., Results: Independent of the severity of visuospatial neglect per se, damage to the right angular and superior temporal gyrus was associated with higher levels of anosognosia., Conclusions: Using a novel assessment of anosognosia for spatial neglect, the present study relates stroke-induced self-awareness deficits to inferior parietal and superior temporal brain damage.

Nicotine enhances attentional functions. Since chronic nicotine exposure through smoking induces neuroadaptive changes in the brain at a structural and molecular level, the present functional MRI (fMRI) study aimed at investigating the neural mechanisms underlying visuospatial and sustained attention in smokers and non-smokers. Visuospatial attention was assessed with a location-cueing paradigm, while sustained attention was measured by changes in response speed over time. During invalid trials, neural activity within the basal forebrain was selectively enhanced in smokers and higher basal forebrain activity was associated with increased parietal cortex activation. Moreover, higher levels of expired carbon monoxide in smokers before scanning were associated with higher parietal cortex activation and faster responses to invalidly cued targets. Smokers showed a slowing of responses and additionally recruited an area within the right supramarginal gyrus with increasing time on task. Activity decreases over time were observed in visual areas in smokers. The data provide evidence for altered attentional functions in smokers as compared with non-smokers, which were partly modulated by residual nicotine levels and were observed at a behavioural level for sustained and at a neural level for spatial and sustained attention.

Objective: Both executive functions and time perception are typically impaired in subjects with attention-deficit/hyperactivity disorder (ADHD). However, the exact neural mechanisms underlying these deficits remain to be investigated., Method: Fourteen subjects with ADHD and 14 age- and IQ-matched controls (aged 9 through 15 years) were assessed with functional magnetic resonance imaging while they performed a combined spatial stimulus-response compatibility (SRC) and time duration discrimination (TD) paradigm using identical stimuli for all experimental conditions., Results: Children with ADHD performed less accurately in the SRC but not in the TD task compared with controls. On the brain level, subjects with ADHD showed significantly reduced neural activity in the left putamen during SRC and reduced fronto-cerebellar activation during TD when compared with the baseline conditions. Compared with subjects with ADHD, control subjects had increased activation in a left-hemispheric fronto-parietal network during the SRC task and in the right superior-frontal gyrus during the TD task. Functional connectivity analyses revealed abnormal fronto-parietal coupling during the SRC task and reduced fronto-cerebellar connectivity during the TD task in the ADHD group compared with controls., Conclusions: Our findings suggest specific but distinct patterns of cerebral dysfunction associated with interference control and TD processing in ADHD, characterized by both reduced neural activation in regions critical for task performance and reduced co-activation of frontal cortex. Group differences on the behavioral level were controlled by several methodological approaches. Nonetheless, given the use of a block design, we cannot rule out the possibility that between-group differences in behavior confounded the neural activation patterns.

Objective: The contribution of the human anterior intraparietal area and the dorsal premotor cortex to arbitrary visuo-motor mapping during grasping were tested., Methods: Trained right-handed subjects reached for and pincer-grasped a cube with the right hand in the absence of visual feedback after the cube location had been displayed for 200ms. During the reaching movements, the colour of the cube changed and visual feedback about the change of colour was provided for 100ms at 500ms after movement onset (at the time of peak grasp aperture). Depending on colour, subjects were instructed to either pincer-grasp the cube in a horizontal or vertical grasp position with the latter necessitating wrist rotation (experiment 1) or to pincer-grasp and transport the cube to either a left or right target position (experiment 2). Within two consecutive 200ms time windows (TMS 1 and 2) starting 500ms and 700ms after movement onset, respectively, double pulses of supra-threshold transcranial magnetic stimulation (inter-stimulus interval: 100ms) were delivered over (i) the left primary motor cortex (90 degrees vertically angulated coil position, control stimulation), (ii) the left dorsal premotor cortex or (ii) the left anterior intraparietal area., Results: Compared to control stimulation, stimulation of the anterior intraparietal area, but not of the dorsal premotor cortex, at TMS 1 delayed the times to wrist rotation (experiment 1) and hand transport (experiment 2). Compared to control stimulation, stimulation of the dorsal premotor cortex, but not of the anterior intraparietal area, at TMS 2 delayed both wrist rotation (experiment 1) and hand transport (experiment 2)., Conclusions: We contend that the anterior intraparietal area and the dorsal premotor cortex are both involved albeit at different phases during the mapping of arbitrary visual cues with goal directed grasp and transport movements., Significance: These data add to the current understanding of how human cortical areas work in concert during manual activities.

Transcranial direct current stimulation is a painless, non-invasive brain stimulation technique that allows one to induce polarity-specific excitability changes in the human brain. Here, we investigated, for the first time in a 'proof of principle' study, the behavioural effect of transcranial direct current stimulation on visuospatial attention in both healthy controls and stroke patients suffering from left visuospatial neglect. We applied anodal, cathoP:dal or sham transcranial direct current stimulation (57 microA/cm(2), 10 min) to the left or right posterior parietal cortex. Using a visual detection task in a group of right-handed healthy individuals (n = 20), we observed that transcranial direct current stimulation enhanced or impaired performance depending on stimulation parameters (i.e. current polarity) and stimulated hemisphere. These results are in good accordance with classic models of reciprocal interhemispheric competition ('rivalry'). In a second experiment, we investigated the potential of transcranial direct current stimulation to ameliorate left visuospatial neglect (n = 10). Interestingly, both the inhibitory effect of cathodal transcranial direct current stimulation applied over the unlesioned posterior parietal cortex and the facilitatory effect of anodal transcranial direct current stimulation applied over the lesioned posterior parietal cortex reduced symptoms of visuospatial neglect. Taken together, our findings suggest that transcranial direct current stimulation applied over the posterior parietal cortex can be used to modulate visuospatial processing and that this effect is exerted by influencing interhemispheric reciprocal networks. These novel findings also suggest that a transcranial direct current stimulation-induced modulation of interhemispheric parietal balance may be used clinically to ameliorate visuospatial attention deficits in neglect patients.

Action understanding and learning are suggested to be mediated, at least in part, by the human mirror neuron system (hMNS). Static images as well as videos of actions with the outcome occluded have been shown to activate the hMNS. However, whether the hMNS preferentially responds to end or means of an action remains to be investigated. We, therefore, presented subjects with videos of intentional actions that were shown from two perspectives (factor 1, perspective: first vs. third person) while subjects directed their attention to the means or the end thereof (factor 2, task: means vs. end). End- or means-related changes in BOLD signal and corticospinal excitability (CSE) were assessed using fMRI and TMS, respectively. Judging the means of an action compared with its end differentially activated bilateral ventral premotor (vPMC) and inferior parietal cortex (IPL), that is, the core regions of the hMNS. The reverse contrast revealed left precuneus and bilateral superior frontal, angular, and middle temporal gyrus activity. In accordance, the two tasks, although identically in stimulus properties, modulated CSE differentially. Although recent studies suggest that the hMNS may prefer the presence of a goal or context, our data show that within the same context, it responds preferentially when attention is directed to the action means. Consequently, in addition to inferring action goals, a key function of the hMNS may be to anticipate the trajectories and dynamics of observed actions, which is a prerequisite for any timely interaction.

In synaesthesia, stimulation of a sensory modality triggers abnormal additional perceptions. Voxel-based morphometry (VBM) was used in 18 grapheme-colour synaesthetes to investigate the neuro-anatomical basis of their abnormal perceptions. More specifically, we tested the hypothesis that in synaesthesia altered connectivity in temporo-occipital and parietal areas may be associated with grey matter (GM) changes. The data reveal increased GM volumes in fusiform and intraparietal cortices. These findings are consistent with the two-stage model of grapheme-colour synaesthesia implying cross-activation at the level of the fusiform gyrus (FG) and 'hyperbinding' at the level of the parietal cortex. The observed structural differences in grapheme-colour synaesthetes with abnormal additional perceptions may also shed some light on the neural bases of abnormal perceptions in neurological and psychiatric disorders.

Within the parietal cortex, the temporo-parietal junction (TPJ) and the intraparietal sulcus (IPS) seem to be involved in both spatial and nonspatial functions: Both areas are activated when misleading information is provided by invalid spatial cues in Posner's location-cueing paradigm, but also when infrequent deviant stimuli are presented within a series of standard events. In the present study, we used functional magnetic resonance imaging to investigate the distinct and shared brain responses to (i) invalidly cued targets requiring attentional reorienting, and (ii) to target stimuli deviating in color and orientation leading to an oddball-like distraction effect. Both unexpected location and feature changes were accompanied by a significant slowing of manual reaction times. Bilateral TPJ and right superior parietal lobe (SPL) activation was observed in response to invalidly as compared to validly cued targets. In contrast, the bilateral inferior occipito-temporal cortex, the left inferior parietal cortex, right frontal areas, and the cerebellum showed stronger activation in response to deviant than to standard targets. Common activations were observed in the right angular gyrus along the IPS and in the right inferior frontal gyrus. We conclude that the superior parietal and temporo-parietal activations observed here as well as previously in location-cueing paradigms do not merely reflect the detection and processing of unexpected stimuli. Furthermore, our data suggest that the right IPS and the inferior frontal gyrus are involved in attentional selection and distractor processing of both spatial and nonspatial features.

Neuropsychological studies suggest that patients with left parietal lesions may show impaired localization of parts of either their own or the examiner's body, despite preserved ability to identify isolated body parts. This deficit, called autotopagnosia, may result from damage to the Body Structural Description (BSD), a representation which codes spatial relationships among body parts. We used functional magnetic resonance imaging to identify the neural mechanisms underlying the BSD. Two human body or building parts (factor: STIMULI) were shown to participants who either identified them or evaluated their distance (factor: TASK). The analysis of the interaction between STIMULI and TASK, which isolates the neural mechanism underlying BSD, revealed an activation of left posterior intraparietal sulcus (IPS) when the distance between body parts was evaluated. The results show that the left IPS processes specifically the information about spatial relationships among body parts and thereby suggest that damage to this area may underlie autotopagnosia.

When lifting objects of different mass but identical visual appearance, we apply grip forces that match the expected mass of the object. Here we study the role of the primary motor cortex (M1), the ventral premotor cortex (PMv) and the anterior intraparietal area (AIP) for predictive and reactive scaling of grip forces. Participants performed a precision grip between the index finger and thumb of the right hand to lift two different masses of identical visual appearance in random order. Neuronavigated single pulse transcranial magnetic stimulation (TMS) over (i) left M1, (ii) left PMv, (iii) left AIP and (iv) the vertex (for control) was applied at two time points of the grasping movement after an unexpected change in mass had occurred: (a) at the time of movement onset and (b) at the time of peak grasp aperture. TMS over the PMv, but not over the vertex, M1 or the AIP, interfered with the predictive scaling of grip forces according to the most recent lift when applied at the time of peak grasp aperture. In contrast, TMS over AIP, but not over the vertex, M1 or PMv, disrupted the reactive adjustment of grip force to the novel mass of the object at hand. The findings highlight the differential involvement of PMv in the predictive scaling of grip force and of AIP in the reactive online adjustment of grip force during object manipulation.

The secondary somatosensory cortex (SII) of nonhuman primates is located on the parietal operculum. In the monkey, electrophysiological and connectivity tracing studies as well as histological investigations provide converging evidence for 3 distinct cortical areas (SII, PV, and VS) within this region, each of which contains a complete somatotopic map. Although the equivalency of the parietal operculum as the location of SII between humans and nonhuman primates is undisputed, the internal organization of the human SII region is still largely unknown. Based on their topography, we have previously argued that the cytoarchitectonic areas OP 1, OP 4, and OP 3 may constitute the human homologues of areas SII, PV, and VS, respectively. To test this hypothesis, we here examined (using functional magnetic resonance imaging) the somatotopic organization of the human parietal operculum by applying tactile stimulation to the skin at 4 different locations on either side of the body (face, hands, trunk, and legs). The locations of the resulting activation foci were then compared with the cytoarchitectonic maps of this region. Data analysis revealed 2 somatotopic body representations on the lateral operculum in areas OP 1 and OP 4. The functional border between these 2 body maps was defined by a mirror reversal in the somatotopic arrangement and coincided with the cytoarchitectonically defined border between these 2 areas. This somatotopic arrangement closely matches that described for SII and PV in nonhuman primates. The data also suggested a third somatotopic map located deeper inside the Sylvian fissure in area OP 3. Based on the observed topographic arrangement and their functional response characteristics, we conclude that cytoarchitectonic areas OP1, OP 4, and OP 3 on the human parietal operculum constitute the human homologues of primate areas SII, PV, and VS, respectively.

Reorienting of visuospatial attention can be investigated by comparing reaction times to validly and invalidly cued targets ("validity effect"). The cholinergic agonist nicotine reduces the validity effect and neural activity in the posterior parietal cortex. Behavioral effects of nicotine in nonsmokers are weak and it has been suggested that differences in baseline behavior before nicotine exposure may influence the effect of nicotine. This study investigates whether individual differences in reorienting-related neural activity under placebo may be used to predict individual nicotine effects. Individual nicotine effects are defined as the behavioral effects under nicotine that cannot be predicted by the behavioral data under placebo. Fifteen nonsmoking subjects were given either placebo or nicotine gum (2 mg) prior to performing a cued target detection task inside a magnetic resonance imaging scanner. The results of a partial least square analysis suggest that neural data under placebo can be used to predict individual behavioral effects of nicotine. Neural activity in the left posterior cingulate cortex, the right superior parietal cortex, the right dorsal medial prefrontal cortex, and the left ventral medial prefrontal cortex significantly contributes to that prediction. We conclude that nicotine effects on reorienting attention depend on individual differences in reorienting-related neural activity under placebo and suggest that functional magnetic resonance imaging data can contribute to the prediction of individual drug effects.

The mechanisms underlying interhemispheric integration (IHI) remain poorly understood, particularly for lateralized cognitive processes. To test competing theories of IHI, we constructed and fitted dynamic causal models to functional magnetic resonance data from two visual tasks that operated on identical stimuli but showed opposite hemispheric dominance. Using a systematic Bayesian model selection procedure, we found that, in the ventral visual stream, which was activated by letter judgments, interhemispheric connections mediated asymmetric information transfer from the nonspecialized right to the specialized left hemisphere when the latter did not have direct access to stimulus information. Notably, this form of IHI did not engage all areas activated by the task but was specific for areas in the lingual and fusiform gyri. In the dorsal stream, activated by spatial judgments, it did not matter which hemisphere received the stimulus: interhemispheric coupling increased bidirectionally, reflecting recruitment of the nonspecialized left hemisphere. Again, not all areas activated by the task were involved in this form of IHI; instead, it was restricted to interactions between areas in the superior parietal gyrus. Overall, our results provide direct neurophysiological evidence, in terms of effective connectivity, for the existence of context-dependent mechanisms of IHI that are implemented by specific visual areas during task-driven lateralization.

The left hemispheric dominance for complex motor behavior is undisputed. Clinical observations of complex motor deficits in patients with right hemispheric lesions, however, suggest an additional contribution of the right hemisphere to higher motor control. We assessed, using functional MRI (fMRI), which brain regions are implicated in processing the spatial aspects of complex, object-related actions. Using a blocked, factorial design, 17 healthy volunteers were asked to detect either spatial or sequential errors (factor ERROR) in complex activities of daily living, presented as video sequences with the appropriate object(s) or as pantomimes (factor STIMULUS). Observing complex actions (irrespective of stimulus type) activated a bilateral frontoparietal network. Observing actions with objects (relative to pantomimes) differentially increased neural activity in the fusiform gyrus and inferior occipital cortex bilaterally. Observing pantomimes, i.e., the same actions but without any object, differentially activated right prefrontal cortex, anterior cingulate cortex, the precuneus, and left cerebellum. The left cingulate cortex was differentially activated when subjects assessed the sequencing of actions. By contrast, assessing the spatial configuration of complex actions differentially increased neural activity in right posterior parietal cortex. A significant interaction of ERROR and STIMULUS was revealed for the right inferior parietal cortex only. These findings suggest a specific role of the right hemisphere, especially of right posterior parietal cortex, in processing spatial aspects of complex actions and thus provide a physiological basis for the observed apraxic motor deficits in patients with right hemispheric damage., ((c) 2006 Wiley-Liss, Inc.)

Parietal brain regions have been implicated in reorienting of visuospatial attention in location-cueing paradigms when misleading advance information is provided in form of a spatially invalid cue. The difference in reaction times to invalidly and validly cued targets is termed the "validity effect" and used as a behavioral measure for attentional reorienting. Behavioral studies suggest that the magnitude of the validity effect depends on the ratio of validly to invalidly cued targets (termed cue validity), i.e., on the amount of top-down information provided. Using fMRI, we investigated the effects of a cue validity manipulation upon the neural mechanisms underlying attentional reorienting using valid and invalid spatial cues in the context of 90% and 60% cue validity, respectively. We hypothesized that increased parietal activation would be elicited when subjects need to reorient their attention in a context of high cue validity. Behaviorally, subjects showed significantly higher validity effects in the high as compared to the low cue validity condition, indicating slower reorienting. The neuroimaging data revealed higher activation of right inferior parietal and right frontal cortex in the 90% than in the 60% cue validity condition. We conclude that the amount of top-down information provided by predictive cues influences the neural correlates of reorienting of visuospatial attention by modulating activation of a right fronto-parietal attentional network.

Traditionally the posterior parietal cortex was believed to be a sensory structure. More recently, however, its important role in sensory-motor integration has been recognized. One of its functions suggested in this context is the forming of intentions, i.e. high-level cognitive plans for movements. The selection and planning of a specific movement defines motor intention. In this study we used rapid event-related functional magnetic resonance imaging of healthy human subjects to investigate the involvement of posterior parietal cortex in motor intention in response to valid imperative cues. Subjects were provided with either neutral, motor or spatial cues. Neutral cues simply alerted, motor cues indicated which hand to use for response, and spatial cues indicated on which side the target would appear. Importantly, identical targets and responses followed these cues. Therefore any differential neural effects observed are independent from the actual movement performed. Differential blood oxygen level dependent signal changes for motor vs. neutral as well as motor vs. spatial cue trials were found in the left supramarginal gyrus, as hypothesized. The results demonstrate that neural activity in the left supramarginal gyrus underlies motor plans independent from the execution of the movement and thus extend previous neuropsychological and functional imaging data on the role of the left supramarginal gyrus in higher motor cognition.

The parieto-insular vestibular cortex (PIVC) plays a central role in the cortical vestibular network. Although this region was first defined and subsequently extensively studied in nonhuman primates, there is also ample evidence for a human analogue in the posterior parietal operculum. In this study, we functionally and anatomically characterize the putative human equivalent to macaque area PIVC by combining functional magnetic resonance imaging (fMRI) of the cortical response to galvanic vestibular stimulation (GVS) with probabilistic cytoarchitectonic maps of the human parietal operculum. Our fMRI data revealed a bilateral cortical response to GVS in posterior parieto-insular cortex. Based on the topographic similarity of these activations to primate area PIVC, we suggest that they constitute the functionally defined human equivalent to macaque area PIVC. The locations of these activations were then compared to the probabilistic cytoarchitectonic maps of the parietal operculum (Eickhoff et al. [2005a]: Cereb Cortex, in press; Eickhoff et al. [2005c]: Cereb Cortex, in press), whereby the functionally defined PIVC matched most closely the cytoarchitectonically defined area OP 2. This activation of OP 2 by vestibular stimulation and its cytoarchitectonic features, which are similar to other primary sensory areas, suggest that area OP 2 constitutes the human equivalent of macaque area PIVC., (2005 Wiley-Liss, Inc.)

Anatomical studies in the macaque cortex and functional imaging studies in humans have demonstrated the existence of different cortical areas within the intraparietal sulcus (IPS). Such functional segregation, however, does not correlate with presently available architectonic maps of the human brain. This is particularly true for the classical Brodmann map, which is still widely used as an anatomical reference in functional imaging studies. The aim of this cytoarchitectonic mapping study was to use previously defined algorithms to determine whether consistent regions and borders can be found within the cortex of the anterior IPS in a population of 10 post-mortem human brains. Two areas, the human intraparietal area 1 (hIP1) and the human intraparietal area 2 (hIP2), were delineated in serial histological sections of the anterior, lateral bank of the human IPS. The region hIP1 is located posterior and medial to hIP2, and the former is always within the depths of the IPS. The latter, on the other hand, sometimes reaches the free surface of the superior parietal lobule. The delineations were registered to standard reference space, and probabilistic maps were calculated, thereby quantifying the intersubject variability in location and extent of both areas. In the future, they can be a tool for analyzing structure-function relationships and a basis for determining degrees of homology in the IPS among anthropoid primates. We conclude that the human IPS has a more finely grained parcellation than shown in Brodmann's map., (J. Comp. Neurol. 495:53-69, 2006. (c) 2006 Wiley-Liss, Inc.)

This functional magnetic resonance imaging study investigates the effects of nicotine in a cued target detection task when changing cue reliability. Fifteen non-smoking volunteers were studied under placebo and nicotine (Nicorette polacrilex gum 1 and 2 mg). Validly and invalidly cued trials were arranged in blocks with high, middle and low cue reliability. Two effects of nicotine were investigated: its influence on i) parietal cortex activity underlying the processing of invalid vs. valid trials (i.e. validity effect) and ii) neural activity in the context of low, middle and high informative value of the cue (i.e. cue reliability effect). Nicotine did not affect behavioral performance. However, nicotine reduced the difference in the blood oxygenation level dependent (BOLD) signal between invalid and valid trials in the right intraparietal sulcus. The reduction of parietal activity in invalid trials was smaller in the low cue reliability condition. The same posterior parietal region exhibited a nicotinic modulation of BOLD activity in valid trials which was dependent on cue reliability: Nicotine specifically enhanced the neural activity during valid trials in the context of low cue reliability, i.e. when subjects are already in a state of low certainty. We speculate that the right intraparietal sulcus might be part of two networks working in parallel: one responsible for reorienting attention and the other for the cholinergic modulation of cue reliability. By reducing the use of the cue, nicotine modulates parietal activity related to reorienting attention in conditions with higher cue certainty. On the other hand, nicotine increases parietal activity in states of low certainty. This enhanced activation might influence brain regions, such as the posterior cingulate, directly involved in the processing of cue reliability.

In macaque monkeys, the posterior parietal cortex (PPC) is concerned with the integration of multimodal information for constructing a spatial representation of the external world (in relation to the macaque's body or parts thereof), and planning and executing object-centred movements. The areas within the intraparietal sulcus (IPS), in particular, serve as interfaces between the perceptive and motor systems for controlling arm and eye movements in space. We review here the latest evidence for the existence of the IPS areas AIP (anterior intraparietal area), VIP (ventral intraparietal area), MIP (medial intraparietal area), LIP (lateral intraparietal area) and CIP (caudal intraparietal area) in macaques, and discuss putative human equivalents as assessed with functional magnetic resonance imaging. The data suggest that anterior parts of the IPS comprising areas AIP and VIP are relatively well preserved across species. By contrast, posterior areas such as area LIP and CIP have been found more medially in humans, possibly reflecting differences in the evolution of the dorsal visual stream and the inferior parietal lobule. Despite interspecies differences in the precise functional anatomy of the IPS areas, the functional relevance of this sulcus for visuomotor tasks comprising target selections for arm and eye movements, object manipulation and visuospatial attention is similar in humans and macaques, as is also suggested by studies of neurological deficits (apraxia, neglect, Bálint's syndrome) resulting from lesions to this region.

Prior studies in animals and humans indicate that reorienting of visuospatial attention is modulated by the cholinergic agonist nicotine. We have previously identified neural correlates of alerting and reorienting attention in humans and found that the parietal cortex is specifically involved in reorienting. This study investigates whether the alerting and reorienting systems, especially in the parietal cortex, are modulated by nicotine. We used event-related functional magnetic resonance imaging (fMRI) and studied 15 nonsmoking volunteers under placebo and nicotine (NICORETTE) polacrilex gum 1 and 2 mg). Subjects performed a cued target detection task with four different types of randomly intermixed trials (no, neutral, valid, and invalid cue trials). Alerting was captured by comparing BOLD activity and reaction times (RTs) in neutrally cued trials with no cue trials. Reorienting was isolated by comparing invalidly with validly cued trials. On the behavioral level, nicotine affected reorienting of attention by speeding RTs in invalidly cued trials; alerting was not affected by nicotine. Neurally, however, nicotine modulated both attentional systems. Pharmacologic effects on alerting-related brain activity were mainly evident as modulation of BOLD responses in the right angular gyrus and right middle frontal gyrus due to a reduction of neural activity in no cue trials. In the reorienting system, effects of nicotine were mainly evident in the left intraparietal sulcus and precuneus and due to a reduction of neural activity in invalidly cued trials. We conclude that nicotine enhances reorienting of attention in visuospatial tasks and that one behavioral correlate of speeded RTs is reduced parietal activity.

The localization of low-frequency sounds mainly relies on the processing of microsecond temporal disparities between the ears, since low frequencies produce little or no interaural energy differences. The overall auditory cortical response to low-frequency sounds is largely symmetrical between the two hemispheres, even when the sounds are lateralized. However, the effects of unilateral lesions in the superior temporal cortex suggest that the spatial information mediated by lateralized sounds is distributed asymmetrically across the hemispheres. This paper describes a functional magnetic resonance imaging experiment, which shows that the interaural temporal processing of lateralized sounds produces an enhanced response in the contralateral planum temporale (PT). The response is stronger and extends further into adjacent regions of the inferior parietal lobe (IPL) when the sound is moving than when it is stationary. This suggests that the interaural temporal information mediated by lateralized sounds is projected along a posterior pathway comprising the PT and IPL of the respective contralateral hemisphere. The differential responses to moving sounds further revealed that the left hemisphere responded predominantly to sound movement within the right hemifield, whereas the right hemisphere responded to sound movement in both hemifields. This rightward asymmetry parallels the asymmetry associated with the allocation of visuo-spatial attention and may underlie unilateral auditory neglect phenomena.

The integration of spatial and temporal information is a prerequisite for skilled movements. Likewise, spatial and temporal information must be integrated to predict the potential collision (or otherwise) of two moving objects. In a previous blocked functional magnetic resonance imaging (fMRI) study [Neuroimage 20 (2003) S82] we showed that collision judgments (relative to size judgments) provoked a significant increase in neural activity in the left inferior parietal cortex (supramarginal gyrus). This result suggests that this region is involved in the integration of perceptual spatiotemporal information in addition to its known involvement in programming skilled actions. To further investigate the impact of the integration of temporal and spatial information on the left parietal cortex we conducted an event-related fMRI study in which we varied the difficulty of the collision (and the size) judgment tasks parametrically. Reaction times and error rates were used as behavioral measures of increasing task demands. There was a significant linear increase in reaction times and error rates during the collision and the size tasks over the four levels of task difficulty. A linear increase of the blood oxygen level-dependent signal in the left inferior parietal cortex was found only for the collision, not for the size, conditions. Neural activation in the left inferior parietal cortex thus paralleled the increasing demands on spatiotemporal integration. This result confirms that the left supramarginal gyrus integrates spatial and temporal information irrespective of motor demands.

In the macaque, the posterior parietal cortex (PPC) integrates multimodal sensory information for planning and coordinating complex movements. In particular, the areas around the intraparietal sulcus (IPS) serve as an interface between the sensory and motor systems to allow for coordinated movements in space. Because recent imaging studies suggest a comparable functional and anatomical organization of human and monkey IPS, we hypothesized that in humans, as in macaques, the medial intraparietal cortex (area MIP) subserves visuomotor transformations. To test this hypothesis, changes of neural activity were measured using functional magnetic resonance imaging (fMRI) while healthy subjects performed a joystick paradigm similar to the ones previously employed in macaques for studying area MIP. As hypothesized, visuomotor coordinate transformation subserving goal-directed hand movements activated superior parietal cortex with the local maximum of increased neural activity lying in the medial wall of IPS. Compared to the respective visuomotor control conditions, goal-directed hand movements under predominantly proprioceptive control activated a more anterior part of medial IPS, whereas posterior medial IPS was more responsive to visually guided hand movements. Contrasting the two coordinate transformation conditions, changing the modality of movement guidance (visual/proprioceptive) did not significantly alter the BOLD signal within IPS but demonstrated differential recruitment of modality specific areas such as V5/MT and sensorimotor cortex/area 5, respectively. The data suggest that the human medial intraparietal cortex subserves visuomotor transformation processes to control goal-directed hand movements independently from the modality-specific processing of visual or proprioceptive information.

Left inferior parietal lobe lesions can cause perturbation of the space-time plans underlying skilled actions. But does the perceptual integration of spatiotemporal information use the same neural substrate or is the role of the left inferior parietal cortex restricted to visuomotor transformations? We use fMRI and a collision judgment paradigm to examine whether the left inferior parietal cortex integrates temporal and spatial variables in situations in which no complex action and no visuomotor transformation is required. We used a perceptual task in which healthy subjects indicated by simple button presses whether two moving objects (of the same or different size) would or would not collide with each other. This task of interest was contrasted with a control task that employed the same stimuli and identical motor responses but in which the size of the two moving objects had to be compared. To assess putative differential eye-movement effects both tasks were performed with and without central fixation. Analysis of the fMRI data (employing a random-effects model and SPM99) showed that collision judgments (relative to size judgments) provoked a significant increase in neural activity in the left inferior parietal cortex (supramarginal gyrus) only. These results show that left inferior parietal cortex is involved in the integration of perceptual spatiotemporal information and thus provide a neural correlate for the use of space-time plans (whose perturbation can lead to apraxia as originally hypothesized by Liepmann). Furthermore, the data suggest that the left supramarginal gyrus combines temporal and spatial variables more widely than previously supposed.

The organization of macaque posterior parietal cortex (PPC) reflects its functional specialization in integrating polymodal sensory information for object recognition and manipulation. Neuropsychological and recent human imaging studies imply equivalencies between human and macaque PPC, and in particular, the cortex buried in the intraparietal sulcus (IPS). Using functional MRI, we tested the hypothesis that an area in human anterior intraparietal cortex is activated when healthy subjects perform a crossmodal visuo-tactile delayed matching-to-sample task with objects. Tactile or visual object presentation (encoding and recognition) both significantly activated anterior intraparietal cortex. As hypothesized, neural activity in this area was further enhanced when subjects transferred object information between modalities (crossmodal matching). Based on both the observed functional properties and the anatomical location, we suggest that this area in anterior IPS is the human equivalent of macaque area AIP.

We investigated whether posterior parietal cortex controls attentional switching when the tasks involve neither spatial nor visual cognition. Normal volunteers were scanned using functional MRI (fMRI). In all conditions, subjects were required to covertly produce words in verbal fluency tasks. They did so at a rate of one every 2 s (with eyes closed) in response to an auditory beep. In the non-switching (NS) trials, subjects responded with a series of items from a prespecified semantic category (SC) (e.g. fruits or cars) and from overlearned sequences (OSs) (days of the week, months of the year or letters of the alphabet). Instructions as to which category items should be drawn from on a given run of trials were presented over fMRI-compatible earphones prior to each run. In the switching (S) trials, subjects produced a series of word triads from three SCs: for example, fruits, cars and furniture (e.g. pear, Mercedes, table.); and from three OSs: days of the week, months of the year and letters of the alphabet (e.g. Monday, January, A.). This design is factorial, with the factors verbal class (SC or OSs) and switching conditions (S or NS). Increases in neural activity (P < 0.05, corrected for multiple comparisons) were observed only in superior posterior parietal cortex bilaterally as a main effect of the S conditions compared with the NS conditions. When SC fluency was compared with OS fluency, significant activations were found in anterior cingulate cortex bilaterally, the left inferior frontal gyrus, the middle frontal gyrus bilaterally, frontal operculum bilaterally and in the cerebellar vermis. These results support the hypothesis that superior posterior parietal cortex is a supramodal area implicated in task switching, even when no visual or spatial component is implicated in the tasks. Task switching, frequently used to examine 'frontal' executive functions, may also be clinically relevant to the assessment of patients with superior posterior parietal lesions.

Manual line bisection and a perceptual variant thereof (the Landmark test) are widely used to assess visuospatial neglect in neurological patients, but little is known about the cognitive strategies involved. In the Landmark test, one could explicitly compare the lengths of the left and right line segments; alternatively, one could compute the centre of mass of the display. We here investigate with functional MRI if these cognitive strategies modulate the neural mechanisms underlying judgements whether pre-transected horizontal lines are correctly bisected (the Landmark test) in normal volunteers. Functional neuroimaging (fMRI) was carried out in 12 healthy volunteers who judged: (a) whether the line segments on either side of the transection mark were of equal length, and (b) whether the transection mark was in the centre of the line. Line centre judgements were made significantly faster than line length comparisons. Increased neural activity common to both strategies was observed in inferior parietal lobes bilaterally and right temporooccipital cortex. Further activations, most likely reflecting general task demands like response selection and motor control, were found in the precentral gyrus bilaterally, supplementary motor area bilaterally, right anterior cingulate, right dorsolateral prefrontal cortex, cerebellar vermis, and right thalamus and right putamen. Explicit length comparisons (relative to line centre judgements) differentially activated left superior posterior parietal cortex, with a tendency toward activation of the equivalent area on the right, while the reverse comparison revealed differential activation in the lingual gyrus bilaterally and anterior cingulate cortex. The activations observed in inferior parietal cortex during task performance using either strategy are consistent with the results of lesion studies. The differential activation of superior posterior parietal cortex following length instructions suggests that explicit comparisons of spatial extent were implicated. The differential activation of bilateral occipital cortex following centre judgements suggests that the centre of a line is extracted at an early stage of visual processing.

Some highlights of the ongoing study of visuospatial cognition from Descartes to the advent of functional neuroimaging are reviewed. We emphasize that parietal cortex contains multiple representations of space, appropriate to the demands of perception and action in near and far space. Converging evidence from the behavioral effects of relatively focal brain lesions on different aspects of spatial cognition and from the locus of maximal physiological activation when normal volunteers perform spatial tasks is described. Clinical pathologies of spatial attention, including visual extinction, simultanagnosia, and unilateral neglect, are examined for the light they cast on the basic functions of brain circuits involving the parietal lobes., (Copyright 2001 Academic Press.)

Functional magnetic resonance imaging (fMRI) was used to localize brain areas that were active during the observation of actions made by another individual. Object- and non-object-related actions made with different effectors (mouth, hand and foot) were presented. Observation of both object- and non-object-related actions determined a somatotopically organized activation of premotor cortex. The somatotopic pattern was similar to that of the classical motor cortex homunculus. During the observation of object-related actions, an activation, also somatotopically organized, was additionally found in the posterior parietal lobe. Thus, when individuals observe an action, an internal replica of that action is automatically generated in their premotor cortex. In the case of object-related actions, a further object-related analysis is performed in the parietal lobe, as if the subjects were indeed using those objects. These results bring the previous concept of an action observation/execution matching system (mirror system) into a broader perspective: this system is not restricted to the ventral premotor cortex, but involves several somatotopically organized motor circuits.