Recent brain imaging research revealed that internally guided actions involve the frontomedian wall, in particular the preSMA and the rostral cingulate zone (RCZ). However, a systematic decomposition of different components of intentional action is still lacking. We propose a new paradigm to dissociate two components of internally guided behavior: Which action to perform (selection component) and when to perform the action (timing component). Our results suggest a neuro-functional dissociation of intentional action timing and intentional action selection. While the RCZ is more strongly activated for the selection component, a part of the superior medial frontal gyrus is more strongly activated for the timing component. However, in a post hoc conducted signal strength analysis we did also observe an interaction between action timing and action selection, indicating that decisional processes concerning action timing and action selection are not completely dissociated but interdependent. Altogether this study challenges the idea of a unitary system supporting voluntary action and instead suggests the existence of different neuroanatomically dissociable subfunctions.

Cognitive deficits following traumatic brain injury (TBI) commonly include difficulties with memory, attention, and executive dysfunction. These deficits are amenable to cognitive rehabilitation, but optimally selecting rehabilitation programs for individual patients remains a challenge. Recent methods for quantifying regional brain morphometry allow for automated quantification of tissue volumes in numerous distinct brain structures. We hypothesized that such quantitative structural information could help identify individuals more or less likely to benefit from memory rehabilitation. Fifty individuals with TBI of all severities who reported having memory difficulties first underwent structural MRI scanning. They then participated in a 12 session memory rehabilitation program emphasizing internal memory strategies (I-MEMS). Primary outcome measures (HVLT, RBMT) were collected at the time of the MRI scan, immediately following therapy, and again at 1-month post-therapy. Regional brain volumes were used to predict outcome, adjusting for standard predictors (e.g., injury severity, age, education, pretest scores). We identified several brain regions that provided significant predictions of rehabilitation outcome, including the volume of the hippocampus, the lateral prefrontal cortex, the thalamus, and several subregions of the cingulate cortex. The prediction range of regional brain volumes were in some cases nearly equal in magnitude to prediction ranges provided by pretest scores on the outcome variable. We conclude that specific cerebral networks including these regions may contribute to learning during I-MEMS rehabilitation, and suggest that morphometric measures may provide substantial predictive value for rehabilitation outcome in other cognitive interventions as well.

In multiple sclerosis (MS) functional changes in connectivity due to cortical reorganization could lead to cognitive impairment (CI), or reflect a re-adjustment to reduce the clinical effects of widespread tissue damage. Such alterations in connectivity could result in changes in neural activation as assayed by executive function tasks. We examined cognitive function in MS patients with mild to moderate CI and age-matched controls. We evaluated brain activity using functional magnetic resonance imaging (fMRI) during the successful performance of the Wisconsin card sorting (WCS) task by MS patients, showing compensatory maintenance of normal function, as measured by response latency and error rate. To assess changes in functional connectivity throughout the brain, we performed a global functional brain network analysis by computing voxel-by-voxel correlations on the fMRI time series data and carrying out a hierarchical cluster analysis. We found that during the WCS task there is a significant reduction in the number of smaller size brain functional networks, and a change in the brain areas representing the nodes of these networks in MS patients compared to age-matched controls. There is also a concomitant increase in the strength of functional connections between brain loci separated at intermediate-scale distances in these patients. These functional alterations might reflect compensatory neuroplastic reorganization underlying maintenance of relatively normal cognitive function in the face of white matter lesions and cortical atrophy produced by MS.

The ability to represent time and size is essential for thought and action. These domains have traditionally been investigated independently. However, the processing of events in time and space is postulated to have considerable anatomical and behavioral overlap. Here we formally tested for associations and dissociations of abilities in these domains. We examined patterns of impairments in temporal order and relative size judgments in 40 patients with unilateral brain lesions and 20 age-matched control participants. While brain damage can impair both size and temporal order judgments (TOJ), we did not find evidence for global hemispheric differences. When patients were analyzed individually compared to control subjects, we found double dissociations in performances on both kinds of judgments. Voxel lesion symptom mapping allowed us to investigate shared and unique contributions of brain damage to deficits in judgments noticing differences in temporal order and in spatial extent. We found that size and temporal order estimations have overlapping cortical vulnerabilities within the left inferior frontal gyrus, left superior temporal cortex, and bilateral inferior parietal lobule. However, vulnerability unique to TOJ occurred with damage predominantly in left lateralized regions involving inferior and middle frontal cortex and inferior parietal lobule. Conversely, vulnerability unique to size judgments occurred with damage predominantly in right lateralized regions in the supramarginal gyrus and superior temporal cortex. These data provide evidence for interactions between the processing of spatial extent and temporal order; however, they do not provide evidence for right lateralized systems.

Recent EEG and fMRI evidence suggests that behavioral errors are foreshadowed by systematic changes in brain activity preceding the outcome by seconds. In order to further characterize this type of error precursor activity, we investigated single-trial event-related EEG activity from 70 participants performing a modified Eriksen flanker task, in particular focusing on the trial-by-trial dynamics of a fronto-central independent component that previously has been associated with error and feedback processing. The stimulus-locked peaks in the N2 and P3 latency range in the event-related averages showed expected compatibility and error-related modulations. In addition, a small pre-stimulus negative slow wave was present at erroneous trials. Significant error-preceding activity was found in local stimulus sequences with decreased conflict in the form of less negativity at the N2 latency (310-350 ms) accumulating across five trials before errors; concomitantly response times were speeding across trials. These results illustrate that error-preceding activity in event-related EEG is associated with the performance monitoring system and we conclude that the dynamics of performance monitoring contribute to the generation of error-prone states in addition to the more remote and indirect effects in ongoing activity such as posterior alpha power in EEG and default mode drifts in fMRI.

The study investigates the relative degree and timing of cortical activation across parietal, temporal, and frontal regions during performance of a continuous visual-word recognition task in children who experience reading difficulties (N = 44, RD) and typical readers (N = 40, NI). Minimum norm estimates of regional neurophysiological activity were obtained from magnetoencephalographic recordings. Children with RD showed bilaterally reduced neurophysiological activity in the superior and middle temporal gyri, and increased activity in rostral middle frontal and ventral occipitotemporal cortices, bilaterally. The temporal profile of activity in the RD group, featured near-simultaneous activity peaks in temporal, inferior parietal, and prefrontal regions, in contrast to a clear temporal progression of activity among these areas in the NI group. These results replicate and extend previous MEG and fMRI results demonstrating atypical, latency-dependent attributes of the brain circuit involved in word reading in children with reading difficulties.

Fluid intelligence is the ability to think flexibly and to understand abstract relations. People with high fluid intelligence (hi-fluIQ) perform better in analogical reasoning tasks than people with average fluid intelligence (ave-fluIQ). Although previous neuroimaging studies reported involvement of parietal and frontal brain regions in geometric analogical reasoning (which is a prototypical task for fluid intelligence), however, neuroimaging findings on geometric analogical reasoning in hi-fluIQ are sparse. Furthermore, evidence on the relation between brain activation and intelligence while solving cognitive tasks is contradictory. The present study was designed to elucidate the cerebral correlates of geometric analogical reasoning in a sample of hi-fluIQ and ave-fluIQ high school students. We employed a geometric analogical reasoning task with graded levels of task difficulty and confirmed the involvement of the parieto-frontal network in solving this task. In addition to characterizing the brain regions involved in geometric analogical reasoning in hi-fluIQ and ave-fluIQ, we found that blood oxygenation level dependency (BOLD) signal changes were greater for hi-fluIQ than for ave-fluIQ in parietal brain regions. However, ave-fluIQ showed greater BOLD signal changes in the anterior cingulate cortex and medial frontal gyrus than hi-fluIQ. Thus, we showed that a similar network of brain regions is involved in geometric analogical reasoning in both groups. Interestingly, the relation between brain activation and intelligence is not mono-directional, but rather, it is specific for each brain region. The negative brain activation-intelligence relationship in frontal brain regions in hi-fluIQ goes along with a better behavioral performance and reflects a lower demand for executive monitoring compared to ave-fluIQ individuals. In conclusion, our data indicate that flexibly modulating the extent of regional cerebral activity is characteristic for fluid intelligence.

The current fMRI study investigated cortical processing of electrically induced painful tooth stimulation of both maxillary canines and central incisors in 21 healthy, right-handed volunteers. A constant current, 150% above tooth specific pain perception thresholds was applied and corresponding online ratings of perceived pain intensity were recorded with a computerized visual analog scale during fMRI measurements. Lateralization of cortical activations was investigated by a region of interest analysis. A wide cortical network distributed over several areas, typically described as the pain or nociceptive matrix, was activated on a conservative significance level. Distinct lateralization patterns of analyzed structures allow functional classification of the dental pain processing system. Namely, certain parts are activated independent of the stimulation site, and hence are interpreted to reflect cognitive emotional aspects. Other parts represent somatotopic processing and therefore reflect discriminative perceptive analysis. Of particular interest is the observed amygdala activity depending on the stimulated tooth that might indicate a role in somatotopic encoding.

Theta oscillations in the local field potential of neural ensembles are considered key mediators of human working memory. Theoretical accounts arising from animal hippocampal recordings propose that the phase of theta oscillations serves to instantiate sequential neuronal firing to form discrete representations of items held online. Human evidence of phase relationships in visual working memory has enhanced this theory, implicating long theta cycles in supporting greater memory capacity. Here we use human magnetoencephalographic recordings to examine a novel, alternative principle of theta functionality. The principle we hypothesize is derived from information theory and predicts that rather than long (low frequency) theta cycles, short (high frequency) theta cycles are best suited to support high information capacity. From oscillatory activity recorded during the maintenance period of a visual working memory task we show that a network of brain regions displays an increase in peak 4-12 Hz frequency with increasing memory load. Source localization techniques reveal that this network comprises bilateral prefrontal and right parietal cortices. Further, the peak of oscillation along this theta-alpha frequency axis is significantly higher in high capacity individuals compared to low capacity individuals. Importantly while we observe the adherence of cortical neuronal oscillations to our novel principle of theta functioning, we also observe the traditional inverse effect of low frequency theta maintaining high loads, where critically this was located in medial temporal regions suggesting parallel, dissociable hippocampal-centric, and prefrontal-centric theta mechanisms.

According to the conflict-monitoring model of cognitive control, the posterior medial frontal cortex (pMFC) plays an important role in detecting conflict between competing motor responses. Consistent with this view, pMFC activity is greater in high-conflict trials (e.g., incongruent trials and errors) than in low-conflict trials (e.g., congruent trials and correct responses) of distractor interference tasks. However, in both low- and high-conflict trials, pMFC activity increases linearly with reaction time (RT). Thus, heightened pMFC activity in high-conflict trials may simply reflect the fact that mean RT is longer in high-conflict than in low-conflict trials. To investigate this hypothesis, we reanalyzed data from a previously published fMRI study in which participants performed an event-related version of the multi-source interference task. Critically, after controlling for conditional differences in mean RT, effects of response congruency on pMFC activity were eliminated; in contrast, effects of response accuracy on pMFC activity remained robust. These findings indicate that effects of response congruency on pMFC activity may index any of several processes whose recruitment increases with time on task (e.g., sustained attention). However, effects of response accuracy reflect processes unique to error trials. We conclude that effects of response accuracy on pMFC activity provide stronger support for the conflict-monitoring model than effects of response congruency.

It has recently been suggested that schizophrenia involves dysfunction in brain connectivity at a neural level, and a dysfunction in reward processing at a behavioral level. The purpose of the present study was to link these two levels of analyses by examining effective connectivity patterns between brain regions mediating reward learning in patients with schizophrenia and healthy, age-matched controls. To this aim, we used functional magnetic resonance imaging and galvanic skin recordings (GSR) while patients and controls performed an appetitive conditioning experiment with visual cues as the conditioned (CS) stimuli, and monetary reward as the appetitive unconditioned stimulus (US). Based on explicit stimulus contingency ratings, conditioning occurred in both groups; however, based on implicit, physiological GSR measures, patients failed to show differences between CS+ and CS- conditions. Healthy controls exhibited increased blood-oxygen-level dependent (BOLD) activity across striatal, hippocampal, and prefrontal regions and increased effective connectivity from the ventral striatum to the orbitofrontal cortex (OFC BA 11) in the CS+ compared to the CS- condition. Compared to controls, patients showed increased BOLD activity across a similar network of brain regions, and increased effective connectivity from the striatum to hippocampus and prefrontal regions in the CS- compared to the CS+ condition. The findings of increased BOLD activity and effective connectivity in response to the CS- in patients with schizophrenia offer insight into the aberrant assignment of motivational salience to non-reinforced stimuli during conditioning that is thought to accompany schizophrenia.

Neural bases of human olfactory memory are poorly understood. Very few studies have examined neural substrates associated with correct odor recognition, and none has tackled neural networks associated with incorrect odor recognition. We investigated the neural basis of task performance during a yes-no odor recognition memory paradigm in young and elderly subjects using event-related functional magnetic resonance imaging. We explored four response categories: correct (Hit) and incorrect false alarm (FA) recognition, as well as correct (CR) and incorrect (Miss) rejection, and we characterized corresponding brain responses using multivariate analysis and linear regression analysis. We hypothesized that areas of the medial temporal lobe were differentially involved depending on the accuracy of odor recognition. In young adults, we found that significant activity in the hippocampus and the parahippocampal gyrus was associated with correct (true) recognition of odors, whereas the perirhinal cortex was associated with FAs and Misses. These findings are consistent with literature regarding hypothetical functional organization for memory processing. We also found that for correct recognition and rejection responses, the involvement of the hippocampus decreased when memory performances improved. In contrast to young individuals, elderly subjects were more prone to false memories and exhibited less specific activation patterns for the four response categories. Activation in the hippocampus and the parahippocampal gyrus was positively correlated with response bias scores for true and false recognition, demonstrating that conservative subjects produced an additional search effort leading to more activation of these two medial temporal lobe regions. These findings demonstrate that correct and incorrect recognition and rejection induce distinct neural signatures.

The role of the two hemispheres in processing metaphoric language is controversial. While some studies have reported a special role of the right hemisphere (RH) in processing metaphors, others indicate no difference in laterality relative to literal language. Some studies have found a role of the RH for novel/unfamiliar metaphors, but not conventional/familiar metaphors. It is not clear, however, whether the role of the RH is specific to metaphor novelty, or whether it reflects processing, reinterpretation or reanalysis of novel/unfamiliar language in general. Here we used functional magnetic resonance imaging (fMRI) to examine the effects of familiarity in both metaphoric and non-metaphoric sentences. A left lateralized network containing the middle and inferior frontal gyri, posterior temporal regions in the left hemisphere (LH), and inferior frontal regions in the RH, was engaged across both metaphoric and non-metaphoric sentences; engagement of this network decreased as familiarity decreased. No region was engaged selectively for greater metaphoric unfamiliarity. An analysis of laterality, however, showed that the contribution of the RH relative to that of LH does increase in a metaphor-specific manner as familiarity decreases. These results show that RH regions, taken by themselves, including commonly reported regions such as the right inferior frontal gyrus (IFG), are responsive to increased cognitive demands of processing unfamiliar stimuli, rather than being metaphor-selective. The division of labor between the two hemispheres, however, does shift towards the right for metaphoric processing. The shift results not because the RH contributes more to metaphoric processing. Rather, relative to its contribution for processing literals, the LH contributes less.

The capacity to learn new information and manipulate it for efficient retrieval has long been studied through reasoning paradigms, which also has applicability to the study of social behavior. Humans can learn about the linear order within groups using reasoning, and the success of such reasoning may vary according to affective state, such as depression. We investigated the neural basis of these latter findings using functional neuroimaging. Using BDI-II criteria, 14 non-depressed (ND) and 12 mildly depressed volunteers took part in a linear-order reasoning task during functional magnetic resonance imaging. The hippocampus, parietal, and prefrontal cortices were activated during the task, in accordance with previous studies. In the learning phase and in the test phase, greater activation of the parietal cortex was found in the depressed group, which may be a compensatory mechanism in order to reach the same behavioral performance as the ND group, or evidence for a different reasoning strategy in the depressed group.

To explore the time course of inhibitory control in high trait anger individuals, we recorded and analyzed ERP data relevant to visual Go/Nogo task in high and low trait anger participants. Compared with low trait anger participants, high trait anger participants revealed faster RTs in the Go/Nogo task. The nogo effect of N2 related to conflict monitoring was similar between two groups. While the P3go was larger in high than low trait anger groups, the P3nogo did not differ between two groups. This induced the smaller nogo effect of P3 in high than that in low trait anger group, which is closely related to the actual inhibition of the motor system. These data suggest the reduced later stage of inhibitory processes in high trait anger individuals, implicating the dysfunction of inhibitory control.

Subjects with autism often show language difficulties, but it is unclear how they relate to neurophysiological anomalies of cortical speech processing. We used combined EEG and fMRI in 13 subjects with autism and 13 control participants and show that in autism, gamma and theta cortical activity do not engage synergistically in response to speech. Theta activity in left auditory cortex fails to track speech modulations, and to down-regulate gamma oscillations in the group with autism. This deficit predicts the severity of both verbal impairment and autism symptoms in the affected sample. Finally, we found that oscillation-based connectivity between auditory and other language cortices is altered in autism. These results suggest that the verbal disorder in autism could be associated with an altered balance of slow and fast auditory oscillations, and that this anomaly could compromise the mapping between sensory input and higher-level cognitive representations.

When a person recognizes an error during a task, an error-related potential (ErrP) can be measured as response. It has been shown that ErrPs can be automatically detected in tasks with time-discrete feedback, which is widely applied in the field of Brain-Computer Interfaces (BCIs) for error correction or adaptation. However, there are only a few studies that concentrate on ErrPs during continuous feedback. With this study, we wanted to answer three different questions: (i) Can ErrPs be measured in electroencephalography (EEG) recordings during a task with continuous cursor control? (ii) Can ErrPs be classified using machine learning methods and is it possible to discriminate errors of different origins? (iii) Can we use EEG to detect the severity of an error? To answer these questions, we recorded EEG data from 10 subjects during a video game task and investigated two different types of error (execution error, due to inaccurate feedback; outcome error, due to not achieving the goal of an action). We analyzed the recorded data to show that during the same task, different kinds of error produce different ErrP waveforms and have a different spectral response. This allows us to detect and discriminate errors of different origin in an event-locked manner. By utilizing the error-related spectral response, we show that also a continuous, asynchronous detection of errors is possible. Although the detection of error severity based on EEG was one goal of this study, we did not find any significant influence of the severity on the EEG.

Detecting one's own errors and appropriately correcting behavior are crucial for efficient goal-directed performance. A correlate of rapid evaluation of behavioral outcomes is the error-related negativity (Ne/ERN) which emerges at the time of the erroneous response over frontal brain areas. However, whether the error monitoring system's ability to distinguish between errors and correct responses at this early time point is a necessary precondition for the subsequent emergence of error awareness remains unclear. The present study investigated this question using error-related brain activity and vocal error signaling responses in seven human patients with lesions in the rostral anterior cingulate cortex (rACC) and adjoining ventromedial prefrontal cortex, while they performed a flanker task. The difference between errors and correct responses was severely attenuated in these patients indicating impaired rapid error monitong, but they showed no impairment in error signaling. However, impaired rapid error monitoring coincided with a failure to increase response accuracy on trials following errors. These results demonstrate that the error monitoring system's ability to distinguish between errors and correct responses at the time of the response is crucial for adaptive post-error adjustments, but not a necessary precondition for error awareness.

Simple and unambiguous visual cues (e.g., an arrow) can be used to trigger covert shifts of visual attention away from the center of gaze. The processing of visual stimuli is enhanced at the attended location. Covert shifts of attention modulate the power of cerebral oscillations in the alpha band over parietal and occipital regions. These modulations are sufficiently robust to be decoded on a single trial basis from electroencephalography (EEG) signals. It is often assumed that covert attention shifts are under voluntary control, and that they also occur in more natural and complex environments, but there is no direct evidence to support this assumption. We address this important issue by using random-dot stimuli to cue one of two opposite locations, where a visual target is presented. We contrast two conditions, one in which the random-dot motion is predictive of the target location, and the other, in which it provides ambiguous information. Behavioral results show attention shifts in anticipation of the visual target, in both conditions. In addition, using the common spatial patterns (CSPs) algorithm, we extract EEG power features in the alpha-band (around 10 Hz) that best discriminate the attended location in single trials. We obtain a significant decoding accuracy in 7/10 subjects using a cross-validation procedure applied in the predictive condition. Interestingly, similar accuracy (significant in 5/10 subjects) is obtained when the CSPs trained in the predictive condition are tested in the ambiguous condition. In agreement with this result, we find that the CSPs show very similar topographies in both conditions. These results shed a new light on the behavioral and EEG correlates of visuospatial attention in complex visual environments. This study demonstrates that alpha-power features could be used in brain-computer interfaces to decode covert attention shifts in an environment containing ambiguous spatial information.

We investigate the theory that the left inferior parietal lobe (IPL) is closely associated with tracking potential differences of perspective. Developmental studies find that perspective tasks are mastered at around 4 years of age. Our first study, meta-analyses of brain imaging studies shows that perspective tasks specifically activate a region in the left IPL and precuneus. These tasks include processing of false belief, visual perspective, and episodic memory. We test the location specificity theory in our second study with an unusual and novel kind of perspective task: identity statements. According to Frege's classical logical analysis, identity statements require appreciation of modes of presentation (perspectives). We show that identity statements, e.g., "the tour guide is also the driver" activate the left IPL in contrast to a control statements, "the tour guide has an apprentice." This activation overlaps with the activations found in the meta-analysis. This finding is confirmed in a third study with different types of statements and different comparisons. All studies support the theory that the left IPL has as one of its overarching functions the tracking of perspective differences. We discuss how this function relates to the bottom-up attention function proposed for the bilateral IPL.