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People at risk of developing clinical depression exhibit attentional biases for emotional faces. To clarify whether such effects occur at an early, automatic, or at a late, deliberate processing stage of emotional processing, the present study used high-density electroencephalography during both covert and overt processing of sad, fearful, happy, and neutral expressions in healthy participants with high dysphoria (

Event-related potentials (ERPs) were used to assess the neural mechanisms underlying visual-spatial attention abnormalities associated with psychopathic personality traits. Sixty-nine undergraduates (56 women, 13 men) completed the Psychopathic Personality Inventory-Revised (PPI-R; Lilienfeld & Widows, 2005) and performed two cognitive tasks in which search displays containing a lateralized singleton encircled a fixation point that changed luminance from trial-to-trial. When searching for the singleton as a target, PPI-R scores were uncorrelated with ERP measures of its salience (Ppc), goal-directed selection (N2pc), and working memory evaluation (negative amplitude CDA). In contrast, when responding to the changes in luminance at fixation and ignoring the lateral singleton as a salient distractor, PPI-R Self-Centered Impulsivity factor scores were positively correlated with a potential indicator of distractor suppression (a sustained positive amplitude CDA). These findings provide support for a neurophysiological interpretation of the changes in visual-spatial attention associated with psychopathic personality traits: normal selection of target information accompanied by greater elimination of distractor information at a later visual working memory stage.

While reward associative learning has been studied extensively across different species, punishment avoidance learning has received far less attention. Of particular interest is how the two types of learning change perceptual processing of the learned stimuli. We designed a task that required participants to learn the association of emotionally neutral images with reward, punishment, and no incentive value outcomes through trial-and-error. During learning, participants received monetary reward, neutral outcomes or avoided punishment by correctly identifying corresponding images. Results showed an early bias in favor of learning reward associations, in the form of higher accuracy and fewer trials needed to reach learning criterion. We subsequently assessed electrophysiological learning effects with a task in which participants viewed the stimuli with no feedback or reinforcement. Critically, we found modulation of two early event-related potential components for reward images: the frontocentral P2 (170 – 230 ms) and the anterior N2/Early Anterior Positivity (N2/EAP; 210 – 310 ms). We suggest that reward associations may change stimuli detection and incentive salience as indexed by P2 and N2/EAP. We also reported, on an exploratory basis, a late negativity with frontopolar distribution enhanced by punishment images.

There has been a great deal of interest in understanding how the human brain processes appetitive food cues, and knowing how such cues elicit craving responses is particularly relevant when current eating behavior trends within Westernized societies are considered. One substance that holds a special place with regard to food preference is chocolate, and studies that used functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) have identified neural regions and electrical signatures that are elicited by chocolate cue presentations. This review will examine fMRI and ERP findings from studies that used high-caloric food and chocolate cues as stimuli, with a focus on responses observed in samples of healthy participants, as opposed to those with eating-related pathology. The utility of using high-caloric and chocolate stimuli as a means of understanding the human reward system will also be highlighted, as these findings may be particularly important for understanding processes related to pathological overeating and addiction to illicit substances. Finally, research from our own lab that focused on chocolate stimulus processing in chocolate cravers and non-cravers will be discussed, as the approach used may help bridge fMRI and ERP findings so that a more complete understanding of appetitive stimulus processing in the temporal and spatial domains may be established.

Behavioral and electrophysiological correlates of attentional bias to cannabis-related cues were investigated in a marijuana dependent group and a non-user group employing a drug Stroop task in which cannabis-related, negative and neutral images were presented. Behaviorally, cannabis users were less accurate during drug-containing blocks than non-users. Electrophysiologically, in chronic marijuana-users, an early positive ERP enhancement over left frontal scalp (EAP, 200-350ms) was present in response to drug-containing blocks relative to negative blocks. This effect was absent in the non-user group. Furthermore, drug-containing blocks gave rise to enhanced voltage of a posterior P300 (300-400ms), and a posterior sustained slow wave (LPP, 400-700ms) relative to negative blocks. However, such effects were similar between cannabis users and non-users. Brain source imaging in cannabis users revealed a generator for the EAP effect to drug stimuli in left ventromedial prefrontal cortex/medial orbitofrontal cortex, a region active in fMRI studies of drug cue-reactivity and a target of the core dopaminergic mesolimbic pathway involved in the processing of substances of abuse. This study identifies the timing and brain localization of an ERP correlate of early attentional capture to drug-related pictures in chronic marijuana users. The EAP to drug cues may identify a new electrophysiological marker with clinical implications for predicting abstinence versus relapse or to evaluate treatment interventions.

Diminished emotional capacity is a core characteristic of psychopathic personality. We examined behavioral and electrophysiological differences in attentional bias to emotional material in 34 healt ...

Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. ClinicalTrials.gov identifier NCT01655706 . Registered July 27, 2012.

BackgroundRecent models of major depressive disorder (MDD) have proposed the rostral anterior cingulate (rACC) and dorsomedial prefrontal cortex (dmPFC) as nexus sites in the dysfunctional regulation of cognitive-affective state. Limited evidence from remitted-state MDD supports these theories by suggesting that aberrant neural activity proximal to the rACC and the dmPFC may play a role in vulnerability to recurrence/relapse within this disorder. Here we present a targeted analysis assessing functional activity within these two regions of interest (ROIs) for groups with identified vulnerability to MDD: first, remitted, high predicted recurrence-risk patients; and second, patients suffering observed 1-year recurrence.MethodBaseline T2* images sensitive to blood oxygen level-dependent (BOLD) contrast were acquired from patients and controls during a Go/No-Go (GNG) task incorporating negative feedback, with 1-year patient follow-up to identify recurrence. BOLD contrast data for error commission (EC) and visual negative feedback (VNF) were used in an ROI analysis based on rACC and dmPFC coordinates from the literature, comparing patientsversuscontrols and recurrenceversusnon-recurrenceversuscontrol groups.ResultsAnalysis of patients (n = 20)versuscontrols (n = 20) showed significant right dmPFC [Brodmann area (BA) 9] hypoactivity within the patient group, co-localized during EC and VNF, with additional significant rACC (BA 32) hypoactivity during EC. The results from the follow-up analysis were undermined by small groups and potential confounders but suggested persistent right dmPFC (BA 9) hypoactivity associated with 1-year recurrence.ConclusionsConvergent hypoactive right dmPFC (BA 9) processing of VNF and EC, possibly impairing adaptive reappraisal of negative experience, was associated most clearly with clinically predicted vulnerability to MDD.

In this follow-up study, self-referential videos of success and failure were used for mood provocation to investigate mood, neural, and endocrine activity among 26 internationally competitive athletes using functional Magnetic Resonance Imaging (fMRI) and salivary hormone measures. The initial sample of 14 athletes who had experienced career-threatening failure was contrasted to 12 athletes with exceptional success. Endocrine data were added to the preliminary report to round

Background: Deficits characteristic of Attention Deficit/Hyperactivity Disorder (ADHD), including poor attention and inhibitory control, are at least partially alleviated by factors that increase engagement of attention, suggesting a hypodopaminergic reward deficit. Lapses of attention are associated with attenuated deactivation of the Default Mode Network (DMN), a distributed brain system normally deactivated during tasks requiring attention to the external world. Task-related DMN deactivation has been shown to be attenuated in ADHD relative to controls. We hypothesised that motivational incentives to balance speed against restraint would increase task engagement during an inhibitory control task, enhancing DMN deactivation in ADHD. We also hypothesised that methylphenidate, an indirect dopamine agonist, would tend to normalise abnormal patterns of DMN deactivation. Method: We obtained functional magnetic resonance images from eighteen methylphenidate-responsive children with ADHD (DSM-IV combined subtype) and 18 pairwise-matched typically developing children aged 9-15 years while they performed a paced Go/No-go task. We manipulated motivational incentive to balance response speed against inhibitory control, and tested children with ADHD both on and off methylphenidate. Results: When children with ADHD were off-methylphenidate and task incentive was low, event-related DMN deactivation was significantly attenuated compared to controls, but the two groups did not differ under high motivational incentives. The modulation of DMN deactivation by incentive in the children with ADHD, off- methylphenidate, was statistically significant, and significantly greater than in typically developing children. When children with ADHD were on-methylphenidate, motivational modulation of event-related DMN deactivation was abolished, and no attenuation relative to their typically developing peers was apparent in either motivational condition. Conclusions: During an inhibitory control task, children with ADHD exhibit a raised motivational threshold at which task-relevant stimuli become sufficiently salient to deactivate the DMN. Treatment with methylphenidate normalises this threshold, rendering their pattern of task-related DMN deactivation indistinguishable from that of typically developing children.

High-density ERPs were recorded in eight adults with persistent developmental stuttering (PERS) and eight matched normally fluent (CONT) control volunteers while participants either repeatedly uttered the vowel 'ah' or listened to their own previously recorded vocalizations. The fronto-central N1 auditory wave was reduced in response to spoken vowels relative to heard vowels (auditory-vocal gating), but no difference in the extent of such modulation was found in the PERS group. Abnormalities in the PERS group were restricted to the LISTEN condition, in the form of early N1 and late N3 amplitude changes. Voltage of the N1 wave was significantly reduced over right inferior temporo-occipital scalp in the PERS group. A laterality index derived from N1 voltage moderately correlated with the PERS group's assessed pre-experiment stuttering frequency. Source localization with sLORETA (Pascual-Marqui, R. D. (2002). Standardized low-resolution brain electromagnetic tomography (sLORETA): Technical details. Methods & Findings in Experimental & Clinical Pharmacology, 24, 5-12.) revealed that at the peak of the N1 the PERS group displayed significantly greater current density in right primary motor cortex than the CONT group, suggesting abnormal early speech-motor activation. Finally, the late N3 wave was reduced in amplitude over inferior temporo-occipital scalp, more so over the right hemisphere. sLORETA revealed that in the time window of the N3 the PERS group showed significantly less current density in right secondary auditory cortex than the CONT group, suggesting abnormal speech sound perception. These results point to a deficit in auditory processing of speech sounds in persistent developmental stuttering, stemming from early increased activation of right rolandic area and late reduced activation in right auditory cortex.

BACKGROUND: Theories of attention-deficit/hyperactivity disorder (ADHD) posit either executive deficits and/or alterations in motivational style and reward processing as core to the disorder. Effects of motivational incentives on electrophysiological correlates of inhibitory control and relationships between motivation and stimulant medication have not been explicitly tested. METHODS: Children (9-15 years) with combined-type ADHD (n = 28) and matched typically developing children (CTRL) (n = 28) performed a go/no-go task. Electroencephalogram data were recorded. Amplitude of two event-related potentials, the N2 and P3 (markers of response conflict and attention), were measured. The ADHD children were all stimulant responders tested on and off their usual dose of methylphenidate; CTRLs were never medicated. All children performed the task under three motivational conditions: reward; response cost; and baseline, in which points awarded/deducted for inhibitory performance varied. RESULTS: There were effects of diagnosis (CTRL > ADHD unmedicated), medication (on > off), and motivation (reward and/or response cost > baseline) on N2 and P3 amplitude, although the N2 diagnosis effect did not reach statistical significance (p = .1). Interactions between motivation and diagnosis/medication were nonsignificant (p > .1). CONCLUSIONS: Motivational incentives increased amplitudes of electrophysiological correlates of response conflict and attention in children with ADHD, towards the baseline (low motivation) amplitudes of control subjects. These results suggest that, on these measures, motivational incentives have similar effects in children with ADHD as typically developing CTRLs and have additive effects with stimulant medication, enhancing stimulus salience and allocation of attentional resources during response inhibition.

Local alpha-band synchronization has been associated with both cortical idling and active inhibition. Recent evidence, however, suggests that long-range alpha synchronization increases functional coupling between cortical regions. We demonstrate increased long-range alpha and beta band phase synchronization during short-term memory retention in children 6–10 years of age. Furthermore, whereas alpha-band synchronization between posterior cortex and other regions is increased during retention, local alpha-band synchronization over posterior cortex is reduced. This constitutes a functional dissociation for alpha synchronization across local and long-range cortical scales. We interpret long-range synchronization as reflecting functional integration within a network of frontal and visual cortical regions. Local desynchronization of alpha rhythms over posterior cortex, conversely, likely arises because of increased engagement of visual cortex during retention.

The acquisition of volitional control depends, in part, on developing the ability to countermand a planned action. Many tasks have been used to tap the efficiency of this process, but few studies have investigated how it may be modulated by participants’ motivation. Multiple mechanisms may be involved in the deliberate exercise of caution when incentives are provided. For example, control may involve modulation of the efficiency of the countermanding process, and/or inhibitory modulation of the impulse to go. One of the most commonly used paradigms to assess control of action is the Stop Signal Task, in which a primary Go stimulus is occasionally followed by a countermanding Stop signal, allowing a Stop Signal Reaction Time (SSRT) to be inferred as the outcome of a “horse race” between the go and countermanding processes. Here, we present a computational model in which high task motivation modulates proactive pre-stimulus inhibition of the go response. This allows responses to be calibrated so as to fall within a time-window that maximizes the probability of success, regardless of trial type, but does not decrease the observed SSRT. We report empirical support for the model from a sample of typically developing children, and discuss the broader implications for operationalizing measures of volitional control.

A sizable literature on the neuroimaging of speech production has reliably shown activations in the orofacial region of the primary motor cortex. These activations have invariably been interpreted as reflecting "mouth" functioning and thus articulation. We used functional magnetic resonance imaging to compare an overt speech task with tongue movement, lip movement, and vowel phonation. The results showed that the strongest motor activation for speech was the somatotopic larynx area of the motor cortex, thus reflecting the significant contribution of phonation to speech production. In order to analyze further the phonatory component of speech, we performed a voxel-based meta-analysis of neuroimaging studies of syllable-singing (11 studies) and compared the results with a previously-published meta-analysis of oral reading (11 studies), showing again a strong overlap in the larynx motor area. Overall, these findings highlight the under-recognized presence of phonation in imaging studies of speech production, and support the role of the larynx motor cortex in mediating the "melodicity" of speech.

Purpose To explore the use of noninvasive functional imaging and “virtual” lesion techniques to study the neural mechanisms underlying motor speech disorders in Parkinson’s disease. Here, we report the use of positron emission tomography (PET) and transcranial magnetic stimulation (TMS) to explain exacerbated speech impairment following subthalamic nucleus deep brain stimulation (STN-DBS) in a patient with Parkinson’s disease. Method Perceptual and acoustic speech measures, as well as cerebral blood flow during speech as measured by PET, were obtained with STN-DBS on and off. TMS was applied to a region in the speech motor network found to be abnormally active during DBS. Speech disruption by TMS was compared both perceptually and acoustically with speech produced with DBS on. Results Speech production was perceptually inferior and acoustically less contrastive during left STN stimulation compared to no stimulation. Increased neural activity in left dorsal premotor cortex (PMd) was observed during DBS on. “Virtual” lesioning of this region resulted in speech characterized by decreased speech segment duration, increased pause duration, and decreased intelligibility. Conclusions This case report provides evidence that impaired speech production accompanying STN-DBS may result from unintended activation of PMd. Clinical application of functional imaging and TMS may lead to optimizing the delivery of STN-DBS to improve outcomes for speech production as well as general motor abilities.

Athletes who fail are susceptible to negative affect (NA) and impaired future performance. Functional magnetic resonance imaging (fMRI) studies have identified prefrontal, anterior cingulate, and limbic activations following negative mood provocation. Little is known about the neural correlates of negative self-reference (SR), especially in athletes. Even less is known about the neural correlates of the effects of cognitive intervention (CI) in modifying negative SR and NA in this population. In an fMRI study, 13 athletes watched a video of their own career-threatening defeat in two controlled blocks. Between fMRI blocks, they received a 20-min CI designed to assist in event reappraisal and planning for future performance. Relative increases post-CI were seen in pre- motor (BA6) and sensorimotor (BA4/1) cortices. Correlated with mood ratings, relatively higher pre-CI levels were seen in the ventromedial prefrontal cortex, the right dorsomedial prefrontal cortex (PFC; BA10), the right dorsolateral PFC (BA45), the anterior cingulate, and the right parahippocam- pus. CI may counteract the detrimental effects of NA and negative SR on premotor and motor activity.

A substantial literature examining the neural correlates of working memory using functional magnetic resonance imaging (fMRI) has revealed the involvement of a predominantly fronto–parietal network in the maintenance and manipulation of information in working memory. However, the temporal dynamics of activity in this system cannot be revealed by fMRI at the sub-second level. We employed magnetoencephalography (n = 12) to investigate the temporal dynamics of spatial working memory in a well-studied task, the n-back. Dynamic imaging of coherent sources (beamforming) was employed to determine the sources of effects evident in temporal spectral evolution analyses. Results indicated the involvement of brain regions traditionally identified in fMRI, predominantly in the beta frequency range 500–1500 ms post-stimulus.

Magnetoencephalography (MEG) was recorded while 5-7 year-old children were performing a visual-spatial memory recognition task. Full-term children showed greater gamma-band (30-50 Hz) amplitude in the right temporal region during the task, than children who were born extremely preterm. These results may represent altered brain processing in extremely preterm children who escape major impairment.

Event-related potential studies in healthy adults and children have shown that stimuli signaling the need to stop elicit a robust, right-frontal-maximal N2 that is strongly reduced in children with attention-deficit hyperactivity disorder. To further investigate the mechanisms of normal response inhibition, the Stop Signal Task was applied to 12 healthy young adults using whole-head magnetoencephalography. The evoked magnetic response to Successful Stops showed an earlier and greater amplitude N2-like peak (mean = 167 ms) relative to Failed Stops. Such success-related modulation had a scalp distribution over frontomedial scalp. Dipole source analysis using BESA and a five-dipole fMRI-constrained solution identified a dACC source as a major contributor to the success-related N2-like modulation, while right DLPFC appears to contribute to differences in early preparatory or orienting mechanisms.

Vocal imitation is a phenotype that is unique to humans among all primate species, and so an understanding of its neural basis is critical in explaining the emergence of both speech and song in human evolution. Two principal neural models of vocal imitation have emerged from a consideration of nonhuman animals. One hypothesis suggests that putative mirror neurons in the inferior frontal gyrus pars opercularis of Broca's area may be important for imitation. An alternative hypothesis derived from the study of songbirds suggests that the corticostriate motor pathway performs sensorimotor processes that are specific to vocal imitation. Using fMRI with a sparse event-related sampling design, we investigated the neural basis of vocal imitation in humans by comparing imitative vocal production of pitch sequences with both nonimitative vocal production and pitch discrimination. The strongest difference between these tasks was found in the putamen bilaterally, providing a striking parallel to the role of the analogous region in songbirds. Other areas preferentially activated during imitation included the orofacial motor cortex, Rolandic operculum, and SMA, which together outline the corticostriate motor loop. No differences were seen in the inferior frontal gyrus. The corticostriate system thus appears to be the central pathway for vocal imitation in humans, as predicted from an analogy with songbirds.

Objective: Difficulty with response inhibition is a cardinal symptom of attention deficit hyperactivity disorder (ADHD), combined type. Prefrontal and cingulate brain regions are known to be involved in inhibitory control. Event-related functional magnetic resonance imaging (fMRI) might establish if these regions differ in their activity in ADHD children relative to healthy comparison subjects. Method: Fifteen healthy comparison subjects and 17 children with ADHD, combined type, completed fMRI studies while performing the Stop Signal Task. Eight ADHD subjects were treatment naive; the remainder had a history of long-term treatment with stimulants, but they were medication free at the time of the fMRI. No subject had a learning disorder or a comorbid psychiatric condition (other than oppositional defiant disorder in the ADHD subjects). Results: Both the ADHD and comparison subjects activated the right dorsolateral prefrontal cortex on “stop” trials relative to “go” trials; this increase was greater in ADHD...

Though social and behavioral effects of TV violence have been studied extensively, the brain systems involved in TV violence viewing in children are, at present, not known. In this study, 8 children viewed televised violent and nonviolent video sequences while brain activity was measured with functional magnetic resonance imaging. Both violent and nonviolent viewing activated regions involved in visual motion, visual object and scenes, and auditory listening. However, viewing TV violence selectively recruited a network of right hemisphere regions including precuneus, posterior cingulate, amygdala, inferior parietal, and prefrontal and premotor cortex. Bilateral activations were apparent in hippocampus, parahippocampus, and pulvinar. TV violence viewing transiently recruits a network of brain regions involved in the regulation of emotion, arousal and attention, episodic memory encoding and retrieval, and motor programming. This pattern of brain activations may explain the behavioral effects observed in man...

In a recent ERP study of inhibitory control using the Stop-Signal Task [Pliszka, S., Liotti, M., Woldorff, M. (2000). Inhibitory control in children with attention-deficit/hyperactivity disorder: Event-related potentials identify the processing component and timing of an impaired right-frontal response-inhibition mechanism. Biological Psychiatry, 48, 238-246], we showed that in normal children (age 10-12 years) the Stop Signals elicited a robust, right-frontal-maximal N200 (latency approximately 200 ms) that was strongly reduced in children with ADHD. To further investigate the mechanisms of response inhibition, this paradigm was applied to 11 healthy young adults. To better distinguish response-inhibition-related activity from early attentional effects, a "Stop-Signal-Irrelevant" condition was added, in which subjects performed the task while ignoring the Stop Signals. In the Stop-Signal-Relevant condition, the right frontal N200 to the Stop Signals was larger for Successful inhibition (SI) than for Failed inhibition (FI) trials. The timing and distribution of this effect was strikingly similar to that of the right-frontal ADHD deficit reported in Pliszka et al. (2000), supporting this activity being related to successful normal inhibitory control processes. In contrast, a posterior N200 was larger for Stop-Relevant than for Stop-Irrelevant trials, likely reflecting enhanced early sensory attention to the Stop Signals when relevant. Two longer-latency failure-specific ERP effects were also observed: a greater frontopolar negative wave (370-450 ms) to Failed than Successful inhibitions, and a greater parietal positive slow wave (450-650 ms) for Failed inhibitions than ignore-stop trials, likely reflecting differential recruitment of error detection and correction mechanisms following Failed attempts to inhibit a response.

Cigarette smoking is still quite prevalent despite public education campaigns, and more understanding about the processes that relate to relapse and abstinence is still needed. In the current study, recent abstinent smokers who were later deemed to be relapsers or abstainers responded to the color of smoking-related and neutral words in a Smoking Stroop Task while high-density EEG was recorded. One-month Abstinent smokers responded more slowly to smoking words relative to control participants who had never smoked, while Relapsers did not show this effect. One-month relapsers displayed greater voltage of the late positive potential (400-600 ms, aLPP) over the left frontal scalp relative to both one-month abstinent smokers and never smokers. Our findings suggest that smoking cues are more salient for abstinent smokers who are prone to relapse, and this ERP activity evoked by cigarette cues may be a potential biomarker for relapse susceptibility. In contrast, successful abstainers may respond to smoking cues by engaging top-down cognitive control mechanisms leading to less aLPP voltage but greater RT interference. This appears to be the first ERP study to use a Smoking Stroop Task and a high-density electrode array to characterize the spatiotemporal dynamics of smoking-related cue reactivity in abstinent smokers who successfully abstained for one month and those who later relapsed within the same period.

OBJECTIVE: Remitted major depressive disorder is a vulnerable clinical state, suggesting persistence of an underlying disease diathesis between episodes. To investigate neural correlates of such risk and to identify potential depression trait markers, euthymic unipolar patients in remission, acutely depressed patients, and never-depressed volunteers were studied before and after transient sad mood challenge. METHOD: Common and differential changes in regional blood flow among the groups relative to the baseline state were examined with [15O]H2O positron emission tomography after provocation of sadness with autobiographical memory scripts. RESULTS: Mood provocation in both depressed groups resulted in regional cerebral blood flow (rCBF) decreases in medial orbitofrontal cortex Brodmann’s area 10/11, which were absent in the healthy group. In the remitted group, mood provocation produced a unique rCBF decrease in pregenual anterior cingulate 24a. The main effects in healthy subjects, an rCBF increase in sub...

In a positron emission tomography (PET) study, a very large visual display was used to simulate continuous observer roll, yaw, and linear movement in depth. A global analysis based on all three experiments identified brain areas that responded to the three conditions' shared characteristic of coherent, wide-field motion versus incoherent motion. Several areas were identified, in the posterior-inferior temporal cortex (Brodmann area 37), paralimbic cortex, pulvinar, and midbrain tegmentum. In addition, occipital region KO was sensitive to roll and expansion but not yaw (i.e., coherent displays containing differential flow). Continuous ambient motion did not activate V5/MT selectively. The network of sites responding specifically to coherent motion contrasted with the extensive, contiguous activation that both coherent and incoherent motion elicited in visual areas V1, V2, and V3. The coherent motion mechanisms, furthermore, extended beyond the traditional dorsal pathway proposed to account for visual motion processing, and included subcortical and limbic structures, which are implicated in polysensory processing, posture regulation, and arousal.

Recent neuroimaging and neurological data implicate cerebellum in nonmotor sensory, cognitive, vegetative, and affective functions. The present study assessed cerebellar responses when the urge to breathe is stimulated by inhaled CO2. Ventilation changes follow arterial blood partial pressure CO2changes sensed by the medullary ventral respiratory group (VRG) and hypothalamus, entraining changes in midbrain, pons, thalamus, limbic, paralimbic, and insular regions. Nearly all these areas are known to connect anatomically with the cerebellum. Using positron emission tomography, we measured regional brain blood flow during acute CO2-induced breathlessness in humans. Separable physiological and subjective effects (air hunger) were assessed by comparisons with various respiratory control conditions. The conjoint physiological effects of hypercapnia and the consequent air hunger produced strong bilateral, near-midline activations of the cerebellum in anterior quadrangular, central, and lingula lobules, and in many areas of posterior quadrangular, tonsil, biventer, declive, and inferior semilunar lobules. The primal emotion of air hunger, dissociated from hypercapnia, activated midline regions of the central lobule. The distributed activity across the cerebellum is similar to that for thirst, hunger, and their satiation. Four possible interpretations of cerebellar function(s) here are that: it subserves implicit intentions to access air; it provides predictive internal models about the consequences of CO2inhalation; it modulates emotional responses; and that while some cerebellar regions monitor sensory acquisition in the VRG (CO2concentration), others influence VRG to adjust respiratory rate to optimize partial pressure CO2, and others still monitor and optimize the acquisition of other sensory data in service of air hunger aroused vigilance.

There are defined medullary, mesencephalic, hypothalamic, and thalamic functions in regulation of respiration, but knowledge of cortical control and the elements subserving the consciousness of breathlessness and air hunger is limited. In nine young adults, air hunger was produced acutely by CO 2 inhalation. Comparisons were made with inhalation of a N 2 /O 2 gas mixture with the same apparatus, and also with paced breathing, and with eyes closed rest. A network of activations in pons, midbrain (mesencephalic tegmentum, parabrachial nucleus, and periaqueductal gray), hypothalamus, limbic and paralimbic areas (amygdala and periamygdalar region) cingulate, parahippocampal and fusiform gyrus, and anterior insula were seen along with caudate nuclei and pulvinar activations. Strong deactivations were seen in dorsal cingulate, posterior cingulate, and prefrontal cortex. The striking response of limbic and paralimbic regions points to these structures having a singular role in the affective sequelae entrained by disturbance of basic respiratory control whereby a process of which we are normally unaware becomes a salient element of consciousness. These activations and deactivations include phylogenetically ancient areas of allocortex and transitional cortex that together with the amygdalar/periamygdalar region may subserve functions of emotional representation and regulation of breathing.

Depressed individuals show impaired performance in tests of attention and concentration. They also exhibit PET resting state abnormalities in dorsal prefrontal cortex and anterior cingulate, regions known to be substrates of attentional processing in healthy individuals. This chapter outlines a strategy to study neuropsychological mechanisms in emotional disorders using functional imaging methods. It reviews evidence strongly implicating the dorsolateral prefrontal cortex, particularly in the right hemisphere, as a key brain structure in emotion/cognition interactions in negative mood states. It will be argued that this neocortical region is a crucial convergence zone, being the substrate of sustained attention to the external environment, and the main target of limbic-cortical influences during changes in mood state across health and disease.

Ambient vision comprises the visual functions that are associated with the maintenance of spatial orientation and that depend on peripheral, preconscious visual inputs. Although a limited number of brain areas appear to be activated by coherent wide-field-of-view (WFOV) motion in more than one axis, a diffuse pattern of lateralized brain activity occurs in response to clockwise or counterclockwise ambient visual roll motion [15]. In the present study involving positron emission tomography (PET), a similar finding was shown for rightward versus leftward yaw stimulation. A total of 18 PET scans were obtained from six subjects in response to either leftward or rightward WFOV motion in a collimated display subtending > 100 ∘ horizontally. Rightward stimulation elicited mainly activation throughout the right hemisphere, whereas leftward stimulation elicited mainly activation throughout the left hemisphere. These findings provide further evidence that the ambient vision signal is either processed or transmitted throughout the entire brain, as befits a visual function that is fundamental to all other perceptual systems.

Background: Affective disorders are associated with comorbidity of depression and anxiety symptoms. Positron emission tomography resting-state studies in affective disorders have generally failed to isolate specific symptom effects. Emotion provocation studies in healthy volunteers have produced variable results, due to differences in experimental paradigm and instructions. Methods: To better delineate the neural correlates of sad mood and anxiety, this study used autobiographical memory scripts in eight healthy women to generate sadness, anxiety, or a neutral relaxed state in a within-subject design. Results: Sadness and anxiety, when contrasted to a neutral emotional state, engaged a set of distinct paralimbic–cortical regions, with a limited number of common effects. Sadness was accompanied by specific activations of the subgenual cingulate area (BA) 25 and dorsal insula, specific deactivation of the right prefrontal cortex BA 9, and more prominent deactivation of the posterior parietal cortex BAs 40/7. Anxiety was associated with specific activations of the ventral insula, the orbitofrontal and anterior temporal cortices, specific deactivation of parahippocampal gyri, and more prominent deactivation of the inferior temporal cortex BAs 20/37. Conclusions: These findings are interpreted within a model in which sadness and anxiety are represented by segregated corticolimbic pathways, where a major role is played by selective dorsal cortical deactivations during sadness, and ventral cortical deactivations in anxiety.

The electrophysiological correlates of the Stroop color-word interference effect were studied in eight healthy subjects using high-density Event-Related Potentials (ERPs). Three response modalities were compared: Overt Verbal, Covert Verbal, and Manual. Both Overt Verbal and Manual versions of the Stroop yielded robust Stroop color-word interference as indexed by longer RT for incongruent than congruent color words. The Incongruent vs Congruent ERP difference wave presented two effects. A first effect was a medial dorsal negativity between 350-500 ms post-stimulus (peak at 410 ms). This effect had a significantly different scalp distribution in the Verbal and Manual Stroop versions, with an anterior-medial focus for overt or covert speech, and a broader medial-dorsal distribution for the manual task. Dipole source analysis suggested two independent generators in anterior cingulate cortex. Later on in time, a prolonged positivity developed between 500-800 ms post-stimulus over left superior temporo-parietal scalp. This effect was present for all the three response modalities. A possible interpretation of these results is that Stroop color-word interference first activates anterior cingulate cortex (350-500 ms post-stimulus), followed by activation of the left temporo-parietal cortex, possibly related to the need of additional processing of word meaning.

The brain areas involved in processing wide field-of-view (FOV) coherent and incoherent visual stimuli were studied using positron emission tomography (PET). The brains of nine subjects were scanned as they viewed texture patterns moving in the roll plane. Five visual conditions were used: (1) coherent clockwise (CW) wide-FOV (>100 degrees) roll motion; (2) coherent counter-clockwise (CCW) wide-FOV roll motion; (3) wide-FOV incoherent motion; (4) CCW motion confined to the central visual field (approximately 55 degrees); and (5) a stationary control texture. The region most activated by the coherent-motion stimulus relative to the static one was the medial-occipital cortex, whereas both the medial- and lateral-occipital cortices were activated by incoherent motion relative to a static texture. Portions of the retroinsular parietal-temporal cortex, superior insula, putamen, and vestibulocerebellum responded specifically to the coherence of the stimulus, whereas a widespread lateralized activation was observed upon subtracting the CW scans from the CCW scans. The results indicate separate neural regions for processing wide-FOV motion versus stimulus coherence.

Many tasks require rapid and fine-tuned adjustment of motor performance based on incoming sensory information. This process of sensorimotor adaptation engages two parallel subcortico–cortical neural circuits, involving the cerebellum and basal ganglia, respectively1,2,3,4,5,6,7,8,9,10. How these distributed circuits are functionally coordinated has not been shown in humans. The cerebellum and basal ganglia show very similar convergence of input–output organization11,12, which presents an ideal neuroimaging model for the study of parallel processing at a systems level13. Here we used functional magnetic resonance imaging to measure the temporal coherence of brain activity during a tactile discrimination task. We found that, whereas the prefrontal cortex maintained a high level of activation, output activities in the cerebellum and basal ganglia showed different phasic patterns. Moreover, cerebellar activity significantly correlated with the activity of the supplementary motor area but not with that of the primary motor cortex; in contrast, basal ganglia activity was more strongly associated with the activity of the primary motor cortex than with that of the supplementary motor area. These results demonstrate temporally partitioned activity in the cerebellum and basal ganglia, implicating functional independence in the parallel subcortical outputs. This further supports the idea of task-related dynamic reconfiguration of large-scale neural networks14,15.

BackgroundPatients in recovery following episodes of major depressive disorder (MDD) remain highly vulnerable to future recurrence. Although psychological determinants of this risk are well established, little is known about associated biological mechanisms. Recent work has implicated the default mode network (DMN) in this vulnerability but specific hypotheses remain untested within the high risk, recovered state of MDD.AimsTo test the hypothesis that there is excessive DMN functional connectivity during task performance within recovered-state MDD and to test for connected DMN cortical gyrification abnormalities.MethodA multimodal structural and functional magnetic resonance imaging (fMRI) study, including task-based functional connectivity and cortical folding analysis, comparing 20 recovered-state patients with MDD with 20 matched healthy controls.ResultsThe MDD group showed significant task-based DMN hyperconnectivity, associated with hypogyrification of key DMN regions (bilateral precuneus).ConclusionsThis is the first evidence of connected structural and functional DMN abnormalities in recovered-state MDD, supporting recent hypotheses on biological-level vulnerability.

Visual event-related potential (ERP) studies show effects due to target detection in the P3 and in earlier negativities over posterior recording sites. The topography of these earlier components suggests contributions from both anterior and posterior neural generators, however these studies were performed with sparse recording arrays and may not have provided a full description of the scalp topography of the visual ERP. The current study employed a high-density recording array (64 channels) and spherical spline interpolated topographic voltage and current density maps to describe the scalp distribution of the major deflections in the visual ERP from a visual oddball paradigm: the P1, N1, N2/P2a (a temporally coincident posterior negativity and anterior positivity) and P3. A modified difference wave analysis was also performed to track the time-course of target detection effects in the ERP. Target detection effects were found in the N2/P2a and P3 components. The scalp distribution of the N2/P2a was consistent with separate frontal and posterior neural generators and this is discussed in reference to human hemodynamic and nonhuman primate studies of neural activity in the inferior temporal visual object recognition system and in frontal systems of selective attention and working memory in visual target detection tasks.

The present study employed high-density ERPs to examine the effect of induced sad mood on the spatiotemporal correlates of conflict monitoring and resolution in a colour-word Stroop interference task. Neuroimaging evidence and dipole modelling implicates the involvement of the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) regions in conflict-laden interference control. On the basis that these structures have been found to mediate emotion-cognition interactions in negative mood states, it was predicted that Stroop-related cognitive control, which relies heavily on anterior neural sources, would be affected by effective sad mood provocation. Healthy participants (N=14) were induced into transient sadness via use of autobiographical sad scripts, a well-validated mood induction technique (Liotti et al., 2000a, 2002). In accord with previous research, interference effects were shown at both baseline and sad states while Stroop conflict was associated with early (N450) and late (Late Positive Component; LPC) electrophysiological modulations at both states. Sad mood induction attenuated the N450 effect in line with our expectation that it would be susceptible to modulation by mood, given its purported anterior limbic source. The LPC effect was displayed at the typical posterior lateral sites but, as predicted, was not affected by sad mood. However, frontocentral LPC activity-presumably generated from an additional anterior limbic source-was affected at sad state, hinting a role in conflict monitoring. Although the neurophysiological underpinnings of interference control are yet to be clarified, this study provided further insight into emotion-cognition interactions as indexed by Stroop conflict-laden processing.

Psychological studies with reaction time methodology show that there is meaningful variability in the performance of cognitive operations when responses are measured in milliseconds. Temporal precision is also required to reveal the rapid neurophysiological events in cortical networks. Sampling the brain's electrical activity at the scalp surface characterizes regional brain function with millisecond temporal resolution. The problem with electroencephalographic (EEG) data is localizing the areas of the cortex that generate the observed scalp fields. Although the eventual goal will be to specify the neural generators of the EEG, we propose that an important first step for functional studies is to examine accurate, time-dynamic maps of the brain's electrical fields at the head surface. Given an adequate spatial sampling of the surface potentials, accurate electrical studies require measures that are independent of the location of the reference sensor. The 2D Laplacian of the potential field may be used to define the local features of the scalp current flow. Because the electrical fields are dynamic, brain mapping with electrical data requires animations rather than static images. © 1994 Wiley-Liss, Inc.

The electrophysiological correlates of conflict processing and cognitive control have been well characterized for the visual modality in paradigms such as the Stroop task. Much less is known about corresponding processes in the auditory modality. Here, electroencephalographic recordings of brain activity were measured during an auditory Stroop task, using three different forms of behavioral response (overt verbal, covert verbal, and manual), that closely paralleled our previous visual Stroop study. As was expected, behavioral responses were slower and less accurate for incongruent than for congruent trials. Neurally, incongruent trials showed an enhanced fronto-central negative polarity wave (N(inc)), similar to the N450 in visual Stroop tasks, with similar variations as a function of behavioral response mode, but peaking ~150 ms earlier, followed by an enhanced positive posterior wave. In addition, sequential behavioral and neural effects were observed that supported the conflict-monitoring and cognitive adjustment hypothesis. Thus, while some aspects of the conflict detection processes, such as timing, may be modality dependent, the general mechanisms would appear to be supramodal.

The spatiotemporal dynamics of the hedonic response to chocolate images was investigated in healthy participants high and low in trait-chocolate craving employing high-density ERPs. There were two sessions: (1) before and (2) after satiety for chocolate. Among cravers, chocolate stimuli evoked a positive amplitude ERP enhancement over the anterior frontal scalp (250–350 ms) that was not modified by satiety and that source localized to the left lateral orbitofrontal cortex. Chocolate stimuli also elicited a later LPP over the posterior scalp (360–560 ms) which was of similar amplitude for high and low chocolate cravers, independent of satiety. Unexpectedly, in non-cravers, chocolate stimuli elicited an earlier (100–250 ms) negative ERP modulation over the frontomedial scalp, which disappeared after eating chocolate to satiety. These results confirm the role of OFC in unrestrained appetitive responses to chocolate in cravers, and suggest top-down influences from cognitive control mechanisms when attempting to restrain the urge to eat chocolate in non-cravers.

The automatic orienting of attention was studied in medicated non-psychotic schizophrenic patients and in matched controls using the Posner paradigm of covert orienting to peripheral cues. This paradigm allows determination of the "benefits" in performance when attention is moved in advance to target location ("valid" trials) and the "costs" in performance when attention has to be reoriented to target location after an incorrect directional cue ("invalid" trials). Compared to normals, schizophrenics showed reduced costs of invalid cueing and increased benefits of valid directional cueing. Schizophrenics did not show selective visual field asymmetries reported in similar studies. The decreased inhibition in the presence of incorrect directional cues may be related to a reduced tone of monoaminergic terminals possibly involved in the regulation of selective attention and arousal regulation.

Deficits characteristic of attention deficit/hyperactivity disorder (ADHD), including poor attention and inhibitory control, are at least partially alleviated by factors that increase engagement of attention, suggesting a hypodopaminergic reward deficit. Lapses of attention are associated with attenuated deactivation of the default mode network (DMN), a distributed brain system normally deactivated during tasks requiring attention to the external world. Task-related DMN deactivation has been shown to be attenuated in ADHD relative to controls. We hypothesised that motivational incentives to balance speed against restraint would increase task engagement during an inhibitory control task, enhancing DMN deactivation in ADHD. We also hypothesised that methylphenidate, an indirect dopamine agonist, would tend to normalise abnormal patterns of DMN deactivation.We obtained functional magnetic resonance images from 18 methylphenidate-responsive children with ADHD (DSM-IV combined subtype) and 18 pairwise-matched typically developing children aged 9-15 years while they performed a paced Go/No-go task. We manipulated motivational incentive to balance response speed against inhibitory control, and tested children with ADHD both on and off methylphenidate.When children with ADHD were off-methylphenidate and task incentive was low, event-related DMN deactivation was significantly attenuated compared to controls, but the two groups did not differ under high motivational incentives. The modulation of DMN deactivation by incentive in the children with ADHD, off-methylphenidate, was statistically significant, and significantly greater than in typically developing children. When children with ADHD were on-methylphenidate, motivational modulation of event-related DMN deactivation was abolished, and no attenuation relative to their typically developing peers was apparent in either motivational condition.During an inhibitory control task, children with ADHD exhibit a raised motivational threshold at which task-relevant stimuli become sufficiently salient to deactivate the DMN. Treatment with methylphenidate normalises this threshold, rendering their pattern of task-related DMN deactivation indistinguishable from that of typically developing children.

Imitation in humans has been attributed to increased activation of the mirror neuron system, but there is no neural model to explain reciprocal communication. In this study, we investigated whether reciprocal, communicative, imitative exchanges activate the same neural system as imitation of simple movements, and whether the neural network subserving communication is lateralized. Fifteen participants were tested using functional magnetic resonance imaging with an online interactive-imitative paradigm while they performed finger movements for three different purposes: (1) to imitate the experimenter, (2) to elicit an imitation from the experimenter, and (3) to simply perform the movement. Subtraction analysis (imitation > movement, initiation > movement) revealed the activation of a strongly lateralized network, where the infra-parietal lobule (IPL) activation was lateralized to the left, while the infero-frontal gyrus (IFG) activation was to the right. It is concluded that imitation in a communicative paradigm recruits a lateralized network, with left fronto- and right parietal activation, that overlaps with a network that subserves understanding of an Other's intentions in relation to the Self. This finding lends plausibility to the suggestion that the neural network for imitation evolved to support interpersonal communication.

Children born very preterm, even with broadly normal IQ, commonly show selective difficulties in visuospatial processing and executive functioning. Very little, however, is known what alterations in cortical processing underlie these deficits. We recorded MEG while eight children born very preterm (≤32 weeks gestational age) and eight full-term controls performed a visual short-term memory task at mean age 7.5 years (range 6.4 – 8.4). Previously, we demonstrated increased long-range alpha and beta band phase synchronization between MEG sensors during STM retention in a group of 17 full-term children age 6–10 years. Here we present preliminary evidence that long-range phase synchronization in very preterm children, relative to controls, is reduced in the alpha-band but increased in the theta-band. In addition, we investigated cortical activation during STM retention employing synthetic aperture magnetometry (SAM) beamformer to localize changes in gamma-band power. Preliminary results indicate sequential activation of occipital, parietal and frontal cortex in control children, as well as reduced activation in very preterm children relative to controls. These preliminary results suggest that children born very preterm exhibit altered inter-regional functional connectivity and cortical activation during cognitive processing.

Several lines of evidence show impaired right hemisphere function in depression. Lateralized simple reaction time tasks show impaired left visual field responses both in normals experiencing a depressed mood and in patients with mild unipolar depression. One interpretation for these findings is that depression impairs right hemisphere function by interfering with right hemisphere arousal and vigilance mechanisms. In order to test this hypothesis, subjects receiving either depression or relaxation mood suggestions performed an uncued reaction time task that has been shown to be sensitive to right posterior brain damage. Level of alertness was varied by contrasting uncued blocks with blocks in which targets were preceded by a warning tone. The results showed the predicted slowing of left visual field responses in the depressed mood, but only in women. The effect was significant only for the uncued blocks. The left visual field impairment was significantly larger during depression than in the relaxation state, but a smaller left visual field slowing was present in women in the relaxed state as well. These results may be consistent with the notion that depression interferes with right hemisphere function in part by influencing right hemisphere arousal mechanisms.

Somatotopy within the orofacial region of the human motor cortex has been a central concept in inter- preting the results of neuroimaging and transcranial magnetic stimulation studies of normal and disor- dered speech. Yet, somatotopy has been challenged by studies showing overlap among the effectors within the homunculus. In order to address this dichotomy, we performed four voxel-based meta-anal- yses of 54 functional neuroimaging studies of non-speech tasks involving respiration, lip movement, tongue movement, and swallowing, respectively. While the centers of mass of the clusters supported the classic homuncular view of the motor cortex, there was significant variability in the locations of the activation-coordinates among studies, resulting in an overlapping arrangement. This ''somatotopy with overlap" might reflect the intrinsic functional interconnectedness of the oral effectors for speech production.

The decoding of visually presented line segments into letters, and letters into words, is critical to fluent reading abilities. Here we investigate the temporal dynamics of visual orthographic processes, focusing specifically on right hemisphere contributions and interactions between the hemispheres involved in the implicit processing of visually presented words, consonants, false fonts, and symbolic strings. High-density EEG was recorded while participants detected infrequent, simple, perceptual targets (dot strings) embedded amongst a of character strings. Beginning at 130ms, orthographic and non-orthographic stimuli were distinguished by a sequence of ERP effects over occipital recording sites. These early latency occipital effects were dominated by enhanced right-sided negative-polarity activation for non-orthographic stimuli that peaked at around 180ms. This right-sided effect was followed by bilateral positive occipital activity for false-fonts, but not symbol strings. Moreover the size of components of this later positive occipital wave was inversely correlated with the right-sided ROcc180 wave, suggesting that subjects who had larger early right-sided activation for non-orthographic stimuli had less need for more extended bilateral (e.g. interhemispheric) processing of those stimuli shortly later. Additional early (130-150ms) negative-polarity activity over left occipital cortex and longer-latency centrally distributed responses (>300ms) were present, likely reflecting implicit activation of the previously reported ‘visual-word-form’ area and N400-related responses, respectively. Collectively, these results provide a close look at some relatively unexplored portions of the temporal flow of information processing in the brain related to the implicit processing of potentially linguistic information and provide valuable information about the interactions between hemispheres supporting visual orthographic processing.

Executive function and working memory deficits are not only present in ADHD, but also in reading disorder (RD). Here, high-density ERPs were recorded during the Stop Signal Task in 53 children and adolescents: An ADHD-combined type group, a group with RD, and a healthy control group. The ADHD-C group displayed unique abnormalities of the frontal N200. Both healthy controls and RD groups showed a success-related right frontal N200 modulation, which was absent in the ADHD group. Second, for Success Inhibition trials, the ADHD-C had smaller right frontal N200 waves relative to healthy controls, while the RD group did not. In contrast, NoGo-P3 abnormalities were present both in the ADHD-C and RD groups. Impaired early response inhibition mechanisms, indexed by the frontal N200, appear to be limited to ADHD-C. In contrast, deficits in later cognitive control and error monitoring mechanisms, indexed by the NoGo-P3, appear to be present in both conditions.

High-density brain electrical activity elicited by physical threat, positive and neutral words were recorded in 33 healthy individuals screened for high or low anxiety sensitivity (AS) during a modified emotional Stroop task. The paradigm allowed the separate assessment of block and mixed-trial effects. In the block analysis, a significant emotional RT slowing was observed along with the modulation of a frontocentral negativity (350-400ms) in the high AS group only. In contrast, the mixed-trial analysis revealed a positive enhancement of the ERP to threat words peaking earlier (200-300ms) over anterior frontal scalp in the absence of RT slowing. This component was preceded by a very early positive modulation (peaking 50ms) in the high AS group only. It is concluded that frontal ERPs to physical threat words can distinguish the contribution of emotional conflict and emotional salience, particularly in individuals with high trait-anxiety.