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Abstract Contextual cues and prior evidence guide human goal-directed behavior. The neurophysiological mechanisms that implement contextual priors to guide subsequent actions in the human brain remain unclear. Using intracranial electroencephalography (iEEG), we demonstrate that increasing uncertainty introduces a shift from a purely oscillatory to a mixed processing regime with an additional ramping component. Oscillatory and ramping dynamics reflect dissociable signatures, which likely differentially contribute to the encoding and transfer of different cognitive variables in a cue-guided motor task. The results support the idea that prefrontal activity encodes rules and ensuing actions in distinct coding subspaces, while theta oscillations synchronize the prefrontal-motor network, possibly to guide action execution. Collectively, our results reveal how two key features of large-scale neural population activity, namely continuous ramping dynamics and oscillatory synchrony, jointly support rule-guided human behavior.

Orbitofrontal cortex (OFC) is classically linked to inhibitory control, emotion regulation, and reward processing. Recent perspectives propose that the OFC also generates predictions about perceptual events, actions, and their outcomes. We tested the role of the OFC in detecting violations of prediction at two levels of abstraction (i.e., hierarchical predictive processing) by studying the event-related potentials (ERPs) of patients with focal OFC lesions (n = 12) and healthy controls (n = 14) while they detected deviant sequences of tones in a local–global paradigm. The structural regularities of the tones were controlled at two hierarchical levels by rules defined at a local (i.e., between tones within sequences) and at a global (i.e., between sequences) level. In OFC patients, ERPs elicited by standard tones were unaffected at both local and global levels compared to controls. However, patients showed an attenuated mismatch negativity (MMN) and P3a to local prediction violation, as well as a diminished MMN followed by a delayed P3a to the combined local and global level prediction violation. The subsequent P3b component to conditions involving violations of prediction at the level of global rules was preserved in the OFC group. Comparable effects were absent in patients with lesions restricted to the lateral PFC, which lends a degree of anatomical specificity to the altered predictive processing resulting from OFC lesion. Overall, the altered magnitudes and time courses of MMN/P3a responses after lesions to the OFC indicate that the neural correlates of detection of auditory regularity violation are impacted at two hierarchical levels of rule abstraction.

Summary: Emerging research supports a role of the insula in human cognition. Here, we used intracranial EEG to investigate the spatiotemporal dynamics in the insula during a verbal working memory (vWM) task. We found robust effects for theta, beta, and high frequency activity (HFA) during probe presentation requiring a decision. Theta band activity showed differential involvement across left and right insulae while sequential HFA modulations were observed along the anteroposterior axis. HFA in anterior insula tracked decision making and subsequent HFA was observed in posterior insula after the behavioral response. Our results provide electrophysiological evidence of engagement of different insula subregions in both decision-making and response monitoring during vWM and expand our knowledge of the role of the insula in complex human behavior.

Information theory is a viable candidate to advance our understanding of how the brain processes information generated in the internal or external environment. With its universal applicability, information theory enables the analysis of complex data sets, is free of requirements about the data structure, and can help infer the underlying brain mechanisms. Information-theoretical metrics such as Entropy or Mutual Information have been highly beneficial for analyzing neurophysiological recordings. However, a direct comparison of the performance of these methods with well-established metrics, such as the t-test, is rare. Here, such a comparison is carried out by evaluating the novel method of Encoded Information with Mutual Information, Gaussian Copula Mutual Information, Neural Frequency Tagging, and t-test. We do so by applying each method to event-related potentials and event-related activity in different frequency bands originating from intracranial electroencephalography recordings of humans and marmoset monkeys. Encoded Information is a novel procedure that assesses the similarity of brain responses across experimental conditions by compressing the respective signals. Such an information-based encoding is attractive whenever one is interested in detecting where in the brain condition effects are present.

Abstract Groove, understood as an enjoyable compulsion to move to musical rhythms, typically varies along an inverted U-curve with increasing rhythmic complexity (e.g., syncopation, pickups). Predictive coding accounts posit that moderate complexity drives us to move to reduce sensory prediction errors and model the temporal structure. While musicologists generally distinguish the effects of pickups (anacruses) and syncopations, their difference remains unexplored in groove. We used pupillometry as an index to noradrenergic arousal while subjects listened to and rated drumbeats varying in rhythmic complexity. We replicated the inverted U-shaped relationship between rhythmic complexity and groove and showed this is modulated by musical ability, based on a psychoacoustic beat perception test. The pupil drift rates suggest that groovier rhythms hold attention longer than ones rated less groovy. Moreover, we found complementary effects of syncopations and pickups on groove ratings and pupil size, respectively, discovering a distinct predictive process related to pickups. We suggest that the brain deploys attention to pickups to sharpen subsequent strong beats, augmenting the predictive scaffolding’s focus on beats that reduce syncopations’ prediction errors. This interpretation is in accordance with groove envisioned as an embodied resolution of precision-weighted prediction error.

The ability to perceive the beat in music is crucial for both music listeners and players with expert musicians being notably skilled at noticing fine deviations in the beat. However, it is unclear whether this beat perception ability is enhanced in trained musicians who continue to practice relative to musicians who no longer play. Thus, we investigated this by comparing active musicians’, inactive musicians’, and nonmusicians’ beat alignment ability scores on the Computerized Adaptive Beat Alignment Test (CA-BAT). 97 adults with diverse musical experience participated in the study, reporting their years of formal musical training, number of instruments played, hours of weekly music playing, and hours of weekly music listening, in addition to their demographic information. While initial tests between groups indicated active musicians outperformed inactive musicians and nonmusicians on the CA-BAT, a generalized linear regression analysis showed that there was no significant difference once differences in musical training had been accounted for. To ensure that our results were not impacted by multicollinearity between music-related variables, nonparametric and nonlinear machine learning regressions were employed and confirmed that years of formal musical training was the only significant predictor of beat alignment ability. These results suggest that expertly perceiving fine differences in the beat is not a use-dependent ability that degrades without regular maintenance through practice or musical engagement. Instead, better beat alignment appears to be associated with more musical training regardless of continued use.

Abstract Introduction Functional networks develop throughout adolescence when anorexia nervosa (AN) normally debuts. In AN, cerebral structural alterations are found in most brain regions and may be related to the observed functional brain changes. Few studies have investigated the functional networks of the brain in adolescent AN patients.. The aim of this explorative study was to investigate multiple functional networks in adolescent AN patients compared to healthy age-matched controls (HC) and the relationship with age, eating disorder symptoms and structural alterations. Methods Included were 29 female inpatients with restrictive AN, and 27 HC. All participants were between the ages of 12 to 18 years. Independent component analysis (ICA) identified 21 functional networks that were analyzed with multivariate and univariate analyses of components and group affiliation (AN vs HC). Age, age × group interaction and AN symptoms were included as covariates. Follow-up correlational analyses of selected components and structural measures (cortical thickness and subcortical volume) were carried out. Results Decreased functional connectivity (FC) in AN patients was found in one cortical network, involving mainly the precuneus, and identified as a default mode network (DMN). Cortical thickness in the precuneus was significantly correlated with functional connectivity in this network. Significant group differences were also found in two subcortical networks involving mainly the hippocampus and the amygdala respectively, and a significant interaction effect of age and group was found in both these networks. There were no significant associations between FC and the clinical measures used in the study. Conclusion The findings from the present study may imply that functional alterations are related to structural alterations in selected regions and that the restricted food intake in AN patients disrupt normal age-related development of functional networks involving the amygdala and hippocampus.

IntroductionIntracranial electrodes are implanted in patients with drug-resistant epilepsy as part of their pre-surgical evaluation. This allows the investigation of normal and pathological brain functions with excellent spatial and temporal resolution. The spatial resolution relies on methods that precisely localize the implanted electrodes in the cerebral cortex, which is critical for drawing valid inferences about the anatomical localization of brain function. Multiple methods have been developed to localize the electrodes, mainly relying on pre-implantation MRI and post-implantation computer tomography (CT) images. However, they are hard to validate because there is no ground truth data to test them and there is no standard approach to systematically quantify their performance. In other words, their validation lacks standardization. Our work aimed to model intracranial electrode arrays and simulate realistic implantation scenarios, thereby providing localization algorithms with new ways to evaluate and optimize their performance.ResultsWe implemented novel methods to model the coordinates of implanted grids, strips, and depth electrodes, as well as the CT artifacts produced by these. We successfully modeled realistic implantation scenarios, including different sizes, inter-electrode distances, and brain areas. In total, ∼3,300 grids and strips were fitted over the brain surface, and ∼850 depth electrode arrays penetrating the cortical tissue were modeled. Realistic CT artifacts were simulated at the electrode locations under 12 different noise levels. Altogether, ∼50,000 thresholded CT artifact arrays were simulated in these scenarios, and validated with real data from 17 patients regarding the coordinates’ spatial deformation, and the CT artifacts’ shape, intensity distribution, and noise level. Finally, we provide an example of how the simulation platform is used to characterize the performance of two cluster-based localization methods.ConclusionWe successfully developed the first platform to model implanted intracranial grids, strips, and depth electrodes and realistically simulate thresholded CT artifacts and their noise. These methods provide a basis for developing more complex models, while simulations allow systematic evaluation of the performance of electrode localization techniques. The methods described in this article, and the results obtained from the simulations, are freely available via open repositories. A graphical user interface implementation is also accessible via the open-source iElectrodes toolbox.

AbstractPrevious research has shown that the autonomic nervous system provides essential constraints over ongoing cognitive function. However, there is currently a relative lack of direct empirical evidence for how this interaction manifests in the brain at the macroscale level. Here, we examine the role of ascending arousal and attentional load on large-scale network dynamics by combining pupillometry, functional MRI, and graph theoretical analysis to analyze data from a visual motion-tracking task with a parametric load manipulation. We found that attentional load effects were observable in measures of pupil diameter and in a set of brain regions that parametrically modulated their BOLD activity and mesoscale network-level integration. In addition, the regional patterns of network reconfiguration were correlated with the spatial distribution of the α2a adrenergic receptor. Our results further solidify the relationship between ascending noradrenergic activity, large-scale network integration, and cognitive task performance.

Cognitive rehabilitation is useful for many after traumatic brain injury (TBI), but we lack critical knowledge about which patients benefit the most from different approaches. Advanced neuroimaging techniques have provided important insight into brain pathology and systems plasticity after TBI, and have potential to inform new practices in cognitive rehabilitation. In this study, we aimed to identify candidate structural brain measures with relevance for rehabilitation of cognitive control (executive) function after TBI. Twenty-eight patients (9 female, mean age 40.5 (SD = 13.04) years) with TBI (>21 months since injury) that participated in a randomized controlled cognitive rehabilitation trial (NCT02692352) were included in the analyses. Regional brain volume was extracted from T1-weighted MRI scans before treatment using tensor-based morphometry. Both positive and negative associations between treatment outcome (everyday cognitive control function) and regional brain volume were observed. The most robust associations between regional brain volume and improvement in function were observed in midline fronto-parietal regions, including the anterior and posterior cingulate cortices. The study provides proof of concept and valuable insight for planning future studies focusing on neuroimaging in cognitive rehabilitation after TBI.

We investigated “musical effort” with an internationally renowned, classical, pianist while playing, listening, and imagining music. We used pupillometry as an objective measure of mental effort and fMRI as an exploratory method of effort with the same musical pieces. We also compared a group of non-professional pianists and non-musicians by the use of pupillometry and a small group of non-musicians with fMRI. This combined approach of psychophysiology and neuroimaging revealed the cognitive work during different musical activities. We found that pupil diameters were largest when “playing” (regardless of whether there was sound produced or not) compared to conditions with no movement (i.e., “listening” and “imagery”). We found positive correlations between pupil diameters of the professional pianist during different conditions with the same piano piece (i.e., normal playing, silenced playing, listen, imagining), which might indicate similar degrees of load on cognitive resources as well as an intimate link between the motor imagery of sound-producing body motions and gestures. We also confirmed that musical imagery had a strong commonality with music listening in both pianists and musically naïve individuals. Neuroimaging provided evidence for a relationship between noradrenergic (NE) activity and mental workload or attentional intensity within the domain of music cognition. We found effort related activity in the superior part of the locus coeruleus (LC) and, similarly to the pupil, the listening and imagery engaged less the LC–NE network than the motor condition. The pianists attended more intensively to the most difficult piece than the non-musicians since they showed larger pupils for the most difficult piece. Non-musicians were the most engaged by the music listening task, suggesting that the amount of attention allocated for the same task may follow a hierarchy of expertise demanding less attentional effort in expert or performers than in novices. In the professional pianist, we found only weak evidence for a commonality between subjective effort (as rated measure-by-measure) and the objective effort gauged with pupil diameter during listening. We suggest that psychophysiological methods like pupillometry can index mental effort in a manner that is not available to subjective awareness or introspection.

Orbitofrontal cortex (OFC) is implicated in multiple cognitive processes, including inhibitory control, context memory, recency judgment, and choice behavior. Despite an emerging understanding of the role of OFC in memory and executive control, its necessity for core working memory (WM) operations remains undefined. Here, we assessed the impact of OFC damage on interference effects in WM using a Recent Probes task based on the Sternberg item-recognition task (1966). Subjects were asked to memorize a set of letters and then indicate whether a probe letter was presented in a particular set. Four conditions were created according to the forthcoming response (“yes”/“no”) and the recency of the probe (presented in the previous trial set or not). We compared behavioral and electroencephalography (EEG) responses between healthy subjects (n = 14) and patients with bilateral OFC damage (n = 14). Both groups had the same recency pattern of slower reaction time (RT) when the probe was presented in the previous trial but not in the current one, reflecting the proactive interference (PI). The within-group electrophysiological results showed no condition difference during letter encoding and maintenance. In contrast, event-related potentials (ERPs) to probes showed distinct within-group condition effects, and condition by group effects. The response and recency effects for controls occurred within the same time window (300–500 ms after probe onset) and were observed in two distinct spatial groups including right centro-posterior and left frontal electrodes. Both clusters showed ERP differences elicited by the response effect, and one cluster was also sensitive to the recency manipulation. Condition differences for the OFC group involved two different clusters, encompassing only left hemisphere electrodes and occurring during two consecutive time windows (345–463 ms and 565–710 ms). Both clusters were sensitive to the response effect, but no recency effect was found despite the behavioral recency effect. Although the groups had different electrophysiological responses, the maintenance of letters in WM, the evaluation of the context of the probe, and the decision to accept or reject a probed letter were preserved in OFC patients. The results suggest that neural reorganization may contribute to intact recency judgment and response after OFC damage.

Insufficient suppression and connectivity of the default mode network (DMN) is a potential mediator of cognitive dysfunctions across various disorders, including attention deficit/hyperactivity disorder (ADHD). However, it remains unclear if alterations in sustained DMN suppression, variability and connectivity during prolonged cognitive engagement are implicated in adult ADHD pathophysiology, and to which degree methylphenidate (MPH) remediates any DMN abnormalities. This randomized, double-blinded, placebo-controlled, cross-over clinical trial of MPH (clinicaltrials.gov/ct2/show/NCT01831622) explored large-scale brain network dynamics in 20 adults with ADHD on and off MPH, compared to 27 healthy controls, while performing a reward based decision-making task. DMN task-related activation, variability, and connectivity were estimated and compared between groups and conditions using independent component analysis, dual regression, and Bayesian linear mixed models. The results show that the DMN exhibited more variable activation patterns in unmedicated patients compared to healthy controls. Group differences in functional connectivity both between and within functional networks were evident. Further, functional connectivity between and within attention and DMN networks was sensitive both to task performance and case-control status. MPH altered within-network connectivity of the DMN and visual networks, but not between-network connectivity or temporal variability. This study thus provides novel fMRI evidence of reduced sustained DMN suppression in adults with ADHD during value-based decision-making, a pattern that was not alleviated by MPH. We infer from multiple analytical approaches further support to the default mode interference hypothesis, in that higher DMN activation variability is evident in adult ADHD and associated with lower task performance. Keywords: Adult ADHD, Dopamine, Reward, Decision-making, fMRI, Functional networks, DMN

Background: In studies employing physiological measures such as magnetic resonance imaging (MRI), it is often hard to distinguish what constitutes risk-resilience factors to posttraumatic stress disorder (PTSD) following trauma exposure and what the effects of trauma exposure and PTSD are. Objective: We aimed to investigate whether there were observable morphological differences in cortical and sub-cortical regions of the brain, 7–8 years after a single potentially traumatic event. Methods: Twenty-four participants, who all directly experienced the 2004 Indian Ocean Tsunami, and 25 controls, underwent structural MRI using a 3T scanner. We generated cortical thickness maps and parcellated sub-cortical volumes for analysis. Results: We observed greater cortical thickness for the trauma-exposed participants relative to controls, in a right lateralized temporal lobe region including anterior fusiform gyrus, and superior, middle, and inferior temporal gyrus. Conclusions: We observed greater thickness in the right temporal lobe which might indicate that the region could be implicated in resilience to the long-term effects of a traumatic event. We hypothesize this is due to altered emotional semantic memory processing. However, several methodological and confounding issues warrant caution in interpretation of the results.

How do we rapidly process incoming streams of information in working memory, a cognitive mechanism central to human behavior? Dominant views of working memory focus on the prefrontal cortex (PFC), but human hippocampal recordings provide a neurophysiological signature distinct from the PFC. Are these regions independent, or do they interact in the service of working memory? We addressed this core issue in behavior by recording directly from frontotemporal sites in humans performing a visuospatial working memory task that operationalizes the types of identity and spatiotemporal information we encounter every day. Theta band oscillations drove bidirectional interactions between the PFC and medial temporal lobe (MTL; including the hippocampus). MTL theta oscillations directed the PFC preferentially during the processing of spatiotemporal information, while PFC theta oscillations directed the MTL for all types of information being processed in working memory. These findings reveal an MTL theta mechanism for processing space and time and a domain-general PFC theta mechanism, providing evidence that rapid, dynamic MTL-PFC interactions underlie working memory for everyday experiences.

Impairments in cognition, pain intolerance, and physical inactivity characterize adolescent chronic fatigue syndrome (CFS), yet little is known about its neurobiology. The right dorsal anterior insular (dAI) connectivity of the salience network provides a motivational context to stimuli. In this study, we examined regional functional connectivity (FC) patterns of the right dAI in adolescent CFS patients and healthy participants. Eighteen adolescent patients with CFS and 18 aged-matched healthy adolescent control participants underwent resting-state functional magnetic resonance imaging. The right dAI region of interest was examined in a seed-to-voxel resting-state FC analysis using SPM and CONN toolbox. Relative to healthy adolescents, CFS patients demonstrated reduced FC of the right dAI to the right posterior parietal cortex (PPC) node of the central executive network. The decreased FC of the right dAI-PPC might indicate impaired cognitive control development in adolescent CFS. Immature FC of the right dAI-PPC in patients also lacked associations with three known functional domains: cognition, pain and physical activity, which were observed in the healthy group. These results suggest a distinct biological signature of adolescent CFS and might represent a fundamental role of the dAI in motivated behavior.

Most studies of neuro-functional patterns in trauma-exposed individuals have been conducted considerable time after the traumatic event. Hence little is known about neurofunctional processing shortly after trauma-exposure. We investigated brain activity patterns in response to trauma reminders as well as neutral and negative stimuli in individuals who had recently (within 3 weeks) been involved in a Road Traffic Accident (RTA).Twenty-three RTA survivors and 17 non-trauma-exposed Healthy Controls (HC) underwent functional MRI while viewing Trauma-specific, Negative and Neutral pictures. Data were analyzed from four a-priori Regions of Interest (ROI), including bilateral amygdala, subcallosal cortex, and medial prefrontal cortex. In addition, we performed a whole brain analysis and functional connectivity analysis during stimulus presentation.For both groups, Negative stimuli elicited more activity in the amygdala bilaterally than did Neutral and Trauma-specific stimuli. The whole brain analysis revealed higher activation in sensory processing related areas (bilateral occipital and temporal cortices and thalamus) as well as frontal and superior parietal areas, for the RTA group compared to HC, for Trauma-specific stimuli contrasted with Neutral stimuli. We also observed higher functional connectivity for Trauma-Specific stimuli, between bilateral amygdala and somatosensory areas, for the RTA group compared to controls, when contrasted with Neutral stimuli. We argue that these results might indicate an attentional sensory processing bias towards Trauma-specific stimuli for trauma exposed individuals, a result in line with findings from the PTSD literature.

This study investigated whether treatment naïve adults with Attention Deficit Hyperactivity Disorder (ADHD; n = 33; 19 female) differed from healthy controls (n = 31; 17 female) in behavioral performance, event-related potential (ERP) indices of preparatory attention (CueP3 and late CNV), and reactive response control (Go P3, NoGo N2, and NoGo P3) derived from a visual cued Go/NoGo task. On several critical measures, Cue P3, late CNV, and NoGo N2, there were no significant differences between the groups. This indicated normal preparatory processes and conflict monitoring in ADHD patients. However, the patients had attenuated Go P3 and NoGoP3 amplitudes relative to controls, suggesting reduced allocation of attentional resources to processes involved in response control. The patients also had a higher rate of Go signal omission errors, but no other performance decrements compared with controls. Reduced Go P3 and NoGo P3 amplitudes were associated with poorer task performance, particularly in the ADHD group. Notably, the ERPs were not associated with self-reported mood or anxiety. The results provide electrophysiological evidence for reduced effortful engagement of attentional resources to both Go and NoGo signals when reactive response control is needed. The absence of group differences in ERP components indexing proactive control points to impairments in specific aspects of cognitive processes in an untreated adult ADHD cohort. The associations between ERPs and task performance provided additional support for the altered electrophysiological responses.

Neural network investigations are currently absent in adolescent chronic fatigue syndrome (CFS). In this study, we examine whether the core intrinsic connectivity networks (ICNs) are altered in adolescent CFS patients. Eighteen adolescent patients with CFS and 18 aged matched healthy adolescent control subjects underwent resting-state functional magnetic resonance imaging (rfMRI). Data was analyzed using dual-regression independent components analysis, which is a data-driven approach for the identification of independent brain networks. Intrinsic connectivity was evaluated in the default mode network (DMN), salience network (SN), and central executive network (CEN). Associations between network characteristics and symptoms of CFS were also explored. Adolescent CFS patients displayed a significant decrease in SN functional connectivity to the right posterior insula compared to healthy comparison participants, which was related to fatigue symptoms. Additionally, there was an association between pain intensity and SN functional connectivity to the left middle insula and caudate that differed between adolescent patients and healthy comparison participants. Our findings of insula dysfunction and its association with fatigue severity and pain intensity in adolescent CFS demonstrate an aberration of the salience network which might play a role in CFS pathophysiology.

[This corrects the article DOI: 10.1371/journal.pone.0159833.].

Both normative and many descriptive theories of decision making under risk are based on the notion that outcomes are weighted by their probability, with subsequent maximization of the (subjective) expected outcome. Numerous investigations from psychology, economics, and neuroscience have produced evidence consistent with this notion. However, this research has typically investigated choices involving relatively affect-poor, monetary outcomes. We compared choice in relatively affect-poor, monetary lottery problems with choice in relatively affect-rich medical decision problems. Computational modeling of behavioral data and model-based neuroimaging analyses provide converging evidence for substantial differences in the respective decision mechanisms. Relative to affect-poor choices, affect-rich choices yielded a more strongly curved probability weighting function of cumulative prospect theory, thus signaling that the psychological impact of probabilities is strongly diminished for affect-rich outcomes. Examining task-dependent brain activation, we identified a region-by-condition interaction indicating qualitative differences of activation between affect-rich and affect-poor choices. Moreover, brain activation in regions that were more active during affect-poor choices (e.g., the supramarginal gyrus) correlated with individual trial-by-trial decision weights, indicating that these regions reflect processing of probabilities. Formal reverse inference Neurosynth meta-analyses suggested that whereas affect-poor choices seem to be based on brain mechanisms for calculative processes, affect-rich choices are driven by the representation of outcomes' emotional value and autobiographical memories associated with them. These results provide evidence that the traditional notion of expectation maximization may not apply in the context of outcomes laden with affective responses, and that understanding the brain mechanisms of decision making requires the domain of the decision to be taken into account.

Perceptual decision making in monkeys relies on decision neurons, which accumulate evidence and maintain choices until a response is given. In humans, several brain regions have been proposed to accumulate evidence, but it is unknown if these regions also maintain choices. To test if accumulator regions in humans also maintain decisions we compared delayed and self-paced responses during a face/house discrimination decision making task. Computational modeling and fMRI results revealed dissociated processes of evidence accumulation and decision maintenance, with potential accumulator activations found in the dorsomedial prefrontal cortex, right inferior frontal gyrus and bilateral insula. Potential maintenance activation spanned the frontal pole, temporal gyri, precuneus and the lateral occipital and frontal orbital cortices. Results of a quantitative reverse inference meta-analysis performed to differentiate the functions associated with the identified regions did not narrow down potential accumulation regions, but suggested that response-maintenance might rely on a verbalization of the response.

We investigated performance-derived measures of executive control, and their relationship with self- and informant reported executive functions in everyday life, in treatment-naive adults with newly diagnosed Attention Deficit Hyperactivity Disorder (ADHD; n = 36) and in healthy controls (n = 35). Sustained attentional control and response inhibition were examined with the Test of Variables of Attention (T.O.V.A.). Delayed responses, increased reaction time variability, and higher omission error rate to Go signals in ADHD patients relative to controls indicated fluctuating levels of attention in the patients. Furthermore, an increment in NoGo commission errors when Go stimuli increased relative to NoGo stimuli suggests reduced inhibition of task-irrelevant stimuli in conditions demanding frequent responding. The ADHD group reported significantly more cognitive and behavioral executive problems than the control group on the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). There were overall not strong associations between task performance and ratings of everyday executive function. However, for the ADHD group, T.O.V.A. omission errors predicted self-reported difficulties on the Organization of Materials scale, and commission errors predicted informant reported difficulties on the same scale. Although ADHD patients endorsed more symptoms of depression and anxiety on the Achenbach System of Empirically Based Assessment (ASEBA) than controls, ASEBA scores were not significantly associated with T.O.V.A. performance scores. Altogether, the results indicate multifaceted alteration of attentional control in adult ADHD, and accompanying subjective difficulties with several aspects of executive function in everyday living. The relationships between the two sets of data were modest, indicating that the measures represent non-redundant features of adult ADHD.

We investigated whether both the contingent negative variation (CNV), an event-related potential index of preparatory brain activity, and event-related oscillatory EEG activity differentiated Go and NoGo trials in a delayed response task. CNV and spectral power (4-100 Hz) were calculated from EEG activity in the preparatory interval in 16 healthy adult participants. As previously reported, CNV amplitudes were higher in Go compared to NoGo trials. In addition, event-related spectral power of the Go condition was reduced in the theta to low gamma range compared to the NoGo condition, confirming that preparing to respond is associated with modulation of event-related spectral activity as well as the CNV. Altogether, the impact of the experimental manipulation on both slow event-related potentials and oscillatory EEG activity may reflect coordinated dynamic changes in the excitability of distributed neural networks involved in preparation.

CONTEXT: Exploring intermediate phenotypes within the human brain's functional and structural circuitry is a promising approach to explain the relative contributions of genetics, complex behaviors and neural mechanisms in the development of major depressive disorder (MDD). The polymorphic region 5-HTTLPR in the serotonin transporter gene (SLC6A4) has been shown to modulate MDD risk, but the neural underpinnings are incompletely understood. OBJECTIVE: 37 right handed healthy women between 21 and 61 years of age were invited to participate in an fMRI modified n-back study. The functional polymorphism 5-HTTLPR located in the promoter region of the SLC6A4 gene was genotyped using polymerase chain reaction (PCR). RESULTS: Short 5-HTTLPR allele carriers showed more blood-oxygen-level-dependent (BOLD) bilateral prefrontal cortex activation in the right [F(2, 30) = 4.8, η(2) = .25, p = .026] and left [F(2, 30) = 4.1, η(2) = .22, p = .015] inferior frontal gyrus pars triangularis with increasing n-back task difficulty relative to long 5-HTTLPR allele carriers. Short 5-HTTLPR allele carriers had inferior task performance on the most difficult n-back condition [F(2, 30) = 4.9, η(2) = .26, p = .014]. CONCLUSIONS: This activation pattern found in healthy at risk individuals resembles an activation pattern that is typically found in patients suffering from acute MDD. Altered function in these areas may reflect intermediate phenotypes and may help explain the increased risk of depression in short 5-HTTLPR allele carriers.

Neurons in the primary visual cortex, V1, are specialized for the processing of elemental features of the visual stimulus, such as orientation and spatial frequency. Recent fMRI evidence suggest that V1 neurons are also recruited in visual perceptual memory; a number of studies using multi-voxel pattern analysis have successfully decoded stimulus-specific information from V1 activity patterns during the delay phase in memory tasks. However, consistent fMRI signal modulations reflecting the memory process have not yet been demonstrated. Here, we report evidence, from three subjects, that the low V1 BOLD activity during retention of low-level visual features is caused by competing interactions between neural populations coding for different values along the spectrum of the dimension remembered. We applied a memory masking paradigm in which the memory representation of a masker stimulus interferes with a delayed spatial frequency discrimination task when its frequency differs from the discriminanda with ±1 octave and found that impaired behavioral performance due to masking is reflected in weaker V1 BOLD signals. This cross-channel inhibition in V1 only occurs with retinotopic overlap between the masker and the sample stimulus of the discrimination task. The results suggest that memory for spatial frequency is a local process in the retinotopically organized visual cortex.