Testing the efficacy of real-time fMRI neurofeedback for training people who smoke daily to upregulate neural responses to nondrug rewards.

Although the use of nondrug rewards (e.g., money) to facilitate smoking cessation is widespread, recent research has found that such rewards may be least effective when people who smoke cigarettes are tempted to do so. Specifically, among people who smoke, the neural response to nondrug rewards appears blunted when access to cigarettes is anticipated, and this blunting is linked to a decrease in willingness to refrain from smoking to earn a monetary incentive. Accordingly, methods to enhance the value of nondrug rewards may be theoretically and clinically important. The current proof-of-concept study tested if real-time fMRI neurofeedback training augments the ability to upregulate responses in reward-related brain areas relative to a no-feedback control condition in people who smoke. Adults (n = 44, age range = 20-44) who reported smoking >5 cigarettes per day completed the study. Those in the intervention group (n = 22, 5 females) were trained to upregulate brain responses using feedback of ongoing striatal activity (i.e., a dynamic "thermometer" that reflected ongoing changes of fMRI signal intensity in the striatum) in a single neurofeedback session with three training runs. The control group (n = 22, 5 females) underwent a nearly identical procedure but received no neurofeedback. Those who received neurofeedback training demonstrated significantly greater increases in striatal BOLD activation while attempting to think about something rewarding compared to controls, but this effect was present only during the first training run. Future neurofeedback research with those who smoke should explore how to make neurofeedback training more effective for the self-regulation of reward-related brain activities.

Pupillometry and the vigilance decrement: Task-evoked but not baseline pupil measures reflect declining performance in visual vigilance tasks.

Baseline and task-evoked pupil measures are known to reflect the activity of the nervous system's central arousal mechanisms. With the increasing availability, affordability and flexibility of video-based eye tracking hardware, these measures may one day find practical application in real-time biobehavioural monitoring systems to assess performance or fitness for duty in tasks requiring vigilant attention. But real-world vigilance tasks are predominantly visual in their nature and most research in this area has taken place in the auditory domain. Here, we explore the relationship between pupil size-both baseline and task-evoked-and behavioural performance measures in two novel vigilance tasks requiring visual target detection: (1) a traditional vigilance task involving prolonged, continuous and uninterrupted performance (n = 28) and (2) a psychomotor vigilance task (n = 25). In both tasks, behavioural performance and task-evoked pupil responses declined as time spent on task increased, corroborating previous reports in the literature of a vigilance decrement with a corresponding reduction in task-evoked pupil measures. Also in line with previous findings, baseline pupil size did not show a consistent relationship with performance measures. Our data offer novel insights into the complex interplay of brain systems involved in vigilant attention and question the validity of the assumption that baseline (prestimulus) pupil size and task-evoked (poststimulus) pupil measures reflect the tonic and phasic firing modes of the locus coeruleus.

Neurochemistry of response inhibition and interference in gambling disorder: a preliminary study of γ-aminobutyric acid (GABA+) and glutamate-glutamine (Glx).

BACKGROUND: Neurobehavioral research on the role of impulsivity in gambling disorder (GD) has produced heterogeneous findings. Impulsivity is multifaceted with different experimental tasks measuring different subprocesses, such as response inhibition and distractor interference. Little is known about the neurochemistry of inhibition and interference in GD. METHODS: We investigated inhibition with the stop signal task (SST) and interference with the Eriksen Flanker task, and related performance to metabolite levels in individuals with and without GD. We employed magnetic resonance spectroscopy (MRS) to record glutamate-glutamine (Glx/Cr) and inhibitory, γ-aminobutyric acid (GABA+/Cr) levels in the dorsal ACC (dACC), right dorsolateral prefrontal cortex (dlPFC), and an occipital control voxel. RESULTS: We found slower processing of complex stimuli in the Flanker task in GD (P < .001, η2p = 0.78), and no group differences in SST performance. Levels of dACC Glx/Cr and frequency of incongruent errors were correlated positively in GD only (r = 0.92, P = .001). Larger positive correlations were found for those with GD between dACC GABA+/Cr and SST Go error response times (z = 2.83, P = .004), as well as between dACC Glx/Cr and frequency of Go errors (z = 2.23, P = .03), indicating general Glx-related error processing deficits. Both groups expressed equivalent positive correlations between posterror slowing and Glx/Cr in the right dlPFC (GD: r = 0.74, P = .02; non-GD: r = .71, P = .01). CONCLUSION: Inhibition and interference impairments are reflected in dACC baseline metabolite levels and error processing deficits in GD.

Component processes in free-viewing visual search: Insights from fixation-aligned pupillary response averaging.

Pupil size changes during a visual search may reflect cognitive processes, such as effort and memory accumulation, but methodological confounds and the general lack of literature in this area leave the reliability of findings open to question. We used a novel synthesis of experimental methods and averaging techniques to explore how cognitive processing unfolds during free-viewing visual search for multiple targets. Twenty-seven participants completed 152 searches across two separate 1-hour sessions. The number of targets present (Targets: 0, 1, 2, and 3) in each trial was the main manipulation and the task was to "find all of the targets" and report the total via mouse-click at the end of the trial. Search time lasted for 10 seconds or until the participant purported to have found all of the targets, in which case they could terminate the search via keypress. Whole-trial pupil analysis revealed a significant effect of button pressing as well as a significant main effect of targets for trials that were not self-terminated via button press. Fixation-aligned pupil responses revealed transient modulations in pupil size following initial fixations on targets but not distractors and refixations on both targets and distractors. Owing to rigorous control over experimental confounds and a detailed analysis and correction of eye-movement-related measurement error, we confidently discuss these findings in terms of task-related processing and underlying brain activity.

Impulsive decision-making and gambling severity: The influence of γ-amino-butyric acid (GABA) and glutamate-glutamine (Glx).

Discounting larger, delayed rewards for smaller, immediate rewards is a stable psychological trait known to be impaired in gambling disorder (GD). Neuroimaging with non-GD populations indicates involvement of anterior cingulate (ACC) and dorsolateral prefrontal cortex (dlPFC) in delay discounting. However, little is known about the role of intrinsic properties of brain functioning, such as neurotransmitter action, in impaired discounting in GD. Here, we used magnetic resonance spectroscopy to assess glutamate-glutamine (Glx) and γ-amino-butyric acid (GABA+) concentrations in the dorsal ACC (dACC), dlPFC and occipital cortex of human males with and without GD. Gambling symptom severity correlated negatively with Glx levels in the dACC and occipital voxels. Discounting of small and medium delayed rewards was negatively associated with GABA+ in the dACC, while the discounting of large delayed rewards was negatively associated with GABA+/Glx ratios in the dlPFC. Additionally, in GD, discounting of large delayed rewards was negatively correlated with occipital GABA+ levels. Overall, these findings show that high gambling symptom severity is associated with low levels of Glx and that dACC (GABA+), right dlPFC (GABA+/Glx), and occipital areas (GABA+) track the magnitude of delayed rewards during discounting.

Response inhibition in the parametric Go/No-Go task in psychopathic offenders.

Previous research on response inhibition in psychopaths has failed to find consistent evidence for aberrant inhibitory ability, despite strong expectations to the contrary. However, previous examinations have utilised inhibition paradigms that suffer from critical shortcomings, such as a lack of ecological validity and overly simplistic response criteria. To assess inhibition under conditions close to the demands of everyday settings, the current study employs a parametric Go/No-go task in male offenders (n77). Additionally, rather than treating psychopathy as a categorical descriptor, a dimensional approach is taken to assess the relationship between individual psychopathic traits and response inhibition performance. Results indicate significant relationships between response inhibition and individual facets of psychopathy as measured by the Psychopathy Checklist: Screening Version. A positive relationship was found between inhibitory ability and interpersonal aspects of psychopathy, reflecting an enhancement of inhibitory functioning for those scoring high on this facet. In addition, a negative association was found between psychopathic lifestyle characteristics and response inhibition. Whereas the negative association mirrors the conceptualisation of the lifestyle facet, the positive association between interpersonal psychopathic aspects and response inhibition might reflect a propensity for adaptive behaviour that enables psychopaths to adequately manipulate their victims and mask their true nature.

Response inhibition in the parametric go/no-go task and its relation to impulsivity and subclinical psychopathy.

The current study utilizes the parametric go/no-go task (PGNG), a task that examines changes in inhibitory performance as executive function load increases, to examine the link between psychopathic traits, impulsivity, and response inhibition in a cohort of healthy participants. The results show that as executive function load increased, inhibitory ability decreased. High scores on the Cognitive Complexity subscale of the Barratt Impulsivity Scale (BIS-11) predict poor inhibitory ability in the PGNG. Similarly, high scores on the Psychopathy Personality Inventory-Revised (PPI-R) Blame Externalization subscale predict response inhibition deficits in the PGNG, which loads more on the executive functions than the standard go/no-go task. The remaining BIS-11 as well as PPI-R subscales did not interact with inhibitory performance in the PGNG highlighting the specificity of associations between aspects of personality and impulsivity with inhibitory performance as cognitive load is increased. These data point towards the sensitivity of the PGNG in studying response inhibition in the context of highly impulsive populations and its utility as a measure of impulsivity.

Cathodal tDCS improves task performance in participants high in Coldheartedness.

OBJECTIVE: It is investigated whether personality-related inter-individual differences modulate tDCS effects on response inhibition. Psychopathic personality traits have been associated with a reduced ability to inhibit prepotent responses and as such it is likely that these traits may modulate the effect tDCS has on response inhibition. This study represents the first investigation into the effect of psychopathic traits on tDCS effects in the context of response inhibition, and based on previous research, the psychopathic traits Blame Externalization and Coldheartedness were elected as potential candidates for modulating tDCS effects to right dorsolateral prefrontal cortex. METHODS: Eighteen healthy participants underwent tDCS stimulation (sham, anodal, cathodal) before completing a response inhibition task, the parametric Go/No-go task. This task measures response inhibition under conditions of low and high cognitive load. TDCS stimulation was applied to F4 (international 10-20 system), corresponding to right dorsolateral prefrontal cortex, for 20min with an intensity of 1.5mA. Analysis of covariance was performed to assess how changes in response inhibition performance across difficulty level and stimulation condition were related to individual differences in psychopathy scores as measured via the Psychopathic Personality Inventory-Revised questionnaire. RESULTS: A positive relationship was found between greater scores on the Psychopathic Personality Inventory-Revised subscale of Coldheartedness and improvement in Go/No-go task performance after application of cathodal tDCS. This effect specifically related to the high load condition of the Go/No-go task. CONCLUSION: The psychopathic personality trait Coldheartedness may represent an imbalance of excitatory and inhibitory inputs to dlPFC. Improvement in functioning on inhibitory tasks after cathodal tDCS may be a result of a shift of excitatory glutamate levels to a more optimal level. SIGNIFICANCE: The current results demonstrate the utility of tDCS as a tool to assess how differences in cortical responsivity are associated with specific personality traits. Additionally, this study represents the first investigation into the influence of psychopathic traits on tDCS effects on dlPFC, and we observed beneficial changes in response inhibition as a result of, especially, cathodal stimulation in participants scoring high on Coldheartedness.

Domain General Sequence Operations Contribute to Pre-SMA Involvement in Visuo-spatial Processing.

This study used 3T MRI to elucidate the functional role of supplementary motor area (SMA) in relation to visuo-spatial processing. A localizer task contrasting sequential number subtraction and repetitive button pressing was used to functionally delineate non-motor sequence processing in pre-SMA, and activity in SMA-proper associated with motor sequencing. Patterns of BOLD responses in these regions were then contrasted to those from two tasks of visuo-spatial processing. In one task participants performed Mental Rotation (MR) in which recognition memory judgments were made to previously memorized 2D novel patterns across image-plane rotations. The other task involved abstract grid navigation (GN) in which observers computed a series of imagined location shifts in response to directional (arrow) cues around a mental grid. The results showed overlapping activation in pre-SMA for sequential subtraction and both visuo-spatial tasks. These results suggest that visuo-spatial processing is supported by non-motor sequence operations that involve pre-SMA. More broadly, these data further highlight the functional heterogeneity of pre-SMA, and show that its role extends to processes beyond the planning and online control of movement.

"No level up!": no effects of video game specialization and expertise on cognitive performance.

Previous research into the effects of action video gaming on cognition has suggested that long term exposure to this type of game might lead to an enhancement of cognitive skills that transfer to non-gaming cognitive tasks. However, these results have been controversial. The aim of the current study was to test the presence of positive cognitive transfer from action video games to two cognitive tasks. More specifically, this study investigated the effects that participants' expertise and genre specialization have on cognitive improvements in one task unrelated to video gaming (a flanker task) and one related task (change detection task with both control and genre-specific images). This study was unique in three ways. Firstly, it analyzed a continuum of expertise levels, which has yet to be investigated in research into the cognitive benefits of video gaming. Secondly, it explored genre-specific skill developments on these tasks by comparing Action and Strategy video game players (VGPs). Thirdly, it used a very tight experiment design, including the experimenter being blind to expertise level and genre specialization of the participant. Ninety-two university students aged between 18 and 30 (M = 21.25) were recruited through opportunistic sampling and were grouped by video game specialization and expertise level. While the results of the flanker task were consistent with previous research (i.e., effect of congruence), there was no effect of expertise, and the action gamers failed to outperform the strategy gamers. Additionally, contrary to expectation, there was no interaction between genre specialization and image type in the change detection task, again demonstrating no expertise effect. The lack of effects for game specialization and expertise goes against previous research on the positive effects of action video gaming on other cognitive tasks.

Impaired visuospatial transformation but intact sequence processing in Parkinson disease.

OBJECTIVE: We examined whether visuospatial deficits in Parkinson disease (PD) can be explained by a domain-general, nonspatial impairment in the sequencing or serial chaining of mental operations. BACKGROUND: PD has been shown to be associated with impaired visuospatial processing, but the mechanisms of this impairment remain unclear. METHODS: Thirteen patients with PD and 20 age-matched, neurologically normal controls performed a visuospatial grid navigation task requiring sequential spatial transformations. The participants also performed a control task of serial number subtraction designed to assess their nonvisuospatial sequencing. The tasks were matched in structure and difficulty. RESULTS: The patients were impaired on the visuospatial task but not in serial number subtraction. This finding suggests that visuospatial processing impairments in PD do not derive from a general impairment affecting sequencing or serial chaining. CONCLUSIONS: We argue that visuospatial deficits in PD result from impairments to spatial transformation routines involved in the computation of mappings between spatial locations. These routines are mediated by dopaminergic pathways linking the basal ganglia, prefrontal cortex, supplementary motor area, and parietal cortex.

ZNF804A genotype modulates neural activity during working memory for faces.

BACKGROUND: Genetic susceptibility to schizophrenia (SZ) has been suggested to influence the cortical systems supporting working memory (WM) and face processing. Genetic imaging studies link the SZ risk variant rs1344706 on the ZNF804A gene to psychosis via alterations in functional brain connectivity during WM, but no work has looked at the effects of ZNF804A on WM with face-processing components. METHODS: We therefore investigated healthy controls that were genotyped for rs1344706 with a face WM task during functional magnetic resonance imaging. We suggested that variation at the rs1344706 locus would be associated with similar alterations as patients previously tested using the same WM task for faces. RESULTS: The rs1344706 risk allele was indeed associated with altered activation in the right dorsolateral prefrontal (rDLPFC) cortex. We established that the rDLPFC was activated in a task-dependent manner, suggesting that the differences in activation between rs1344706 genotype groups reflected alterations in task processing. Furthermore, we demonstrated that the rDLPFC region showed significant volumetric overlap with the rDLPFC which had previously been reported to be altered during task processing for patients with SZ. CONCLUSIONS: The findings support an association between rs1344706 and alterations in DLPFC activity during WM for faces. We further suggest that WM for faces may be a useful intermediate phenotype in the investigation of genetic susceptibility to psychosis.

Real-time self-regulation of emotion networks in patients with depression.

Many patients show no or incomplete responses to current pharmacological or psychological therapies for depression. Here we explored the feasibility of a new brain self-regulation technique that integrates psychological and neurobiological approaches through neurofeedback with functional magnetic resonance imaging (fMRI). In a proof-of-concept study, eight patients with depression learned to upregulate brain areas involved in the generation of positive emotions (such as the ventrolateral prefrontal cortex (VLPFC) and insula) during four neurofeedback sessions. Their clinical symptoms, as assessed with the 17-item Hamilton Rating Scale for Depression (HDRS), improved significantly. A control group that underwent a training procedure with the same cognitive strategies but without neurofeedback did not improve clinically. Randomised blinded clinical trials are now needed to exclude possible placebo effects and to determine whether fMRI-based neurofeedback might become a useful adjunct to current therapies for depression.

Eye movement patterns during the recognition of three-dimensional objects: preferential fixation of concave surface curvature minima.

This study used eye movement patterns to examine how high-level shape information is used during 3D object recognition. Eye movements were recorded while observers either actively memorized or passively viewed sets of novel objects, and then during a subsequent recognition memory task. Fixation data were contrasted against different algorithmically generated models of shape analysis based on: (1) regions of internal concave or (2) convex surface curvature discontinuity or (3) external bounding contour. The results showed a preference for fixation at regions of internal local features during both active memorization and passive viewing but also for regions of concave surface curvature during the recognition task. These findings provide new evidence supporting the special functional status of local concave discontinuities in recognition and show how studies of eye movement patterns can elucidate shape information processing in human vision.

Functional imaging reveals working memory and attention interact to produce the attentional blink.

If two centrally presented visual stimuli occur within approximately half a second of each other, the second target often fails to be reported correctly. This effect, called the attentional blink (AB; Raymond, J. E., Shapiro, K. L., & Arnell, K. M. Temporary suppression of visual processing in an RSVP task: An attentional blink? Journal of Experimental Psychology, Human Perception and Performance, 18, 849-860, 1992], has been attributed to a resource "bottleneck," likely arising as a failure of attention during encoding into or retrieval from visual working memory (WM). Here we present participants with a hybrid WM-AB study while they undergo fMRI to provide insight into the neural underpinnings of this bottleneck. Consistent with a WM-based bottleneck account, fronto-parietal brain areas exhibited a WM load-dependent modulation of neural responses during the AB task. These results are consistent with the view that WM and attention share a capacity-limited resource and provide insight into the neural structures that underlie resource allocation in tasks requiring joint use of WM and attention.

Neural hyperactivation in carriers of the Alzheimer's risk variant on the clusterin gene.

Recent GWAS identified a risk variant for Alzheimer's disease (AD) at a locus (rs11136000) of the clusterin gene (CLU). Here we use functional magnetic resonance imaging (fMRI) during working memory to probe the effect of the risk variant on brain activation in healthy individuals. Participants with the CLU risk genotype had higher activity than participants with the protective allele in frontal and posterior cingulate cortex and the hippocampus, particularly during high memory demand. These results inform pathophysiological models of the preclinical progression of AD.

The brain's voices: comparing nonclinical auditory hallucinations and imagery.

Although auditory verbal hallucinations are often thought to denote mental illness, the majority of voice hearers do not satisfy the criteria for a psychiatric disorder. Here, we report the first functional imaging study of such nonclinical hallucinations in 7 healthy voice hearers comparing them with auditory imagery. The human voice area in the superior temporal sulcus was activated during both hallucinations and imagery. Other brain areas supporting both hallucinations and imagery included fronto temporal language areas in the left hemisphere and their contralateral homologues and the supplementary motor area (SMA). Hallucinations are critically distinguished from imagery by lack of voluntary control. We expected this difference to be reflected in the relative timing of prefrontal and sensory areas. Activity of the SMA indeed preceded that of auditory areas during imagery, whereas during hallucinations, the 2 processes occurred instantaneously. Voluntary control was thus represented in the relative timing of prefrontal and sensory activation, whereas the sense of reality of the sensory experience may be a product of the voice area activation. Our results reveal mechanisms of the generation of sensory experience in the absence of external stimulation and suggest new approaches to the investigation of the neurobiology of psychopathology.

Random subspace ensembles for FMRI classification.

Classification of brain images obtained through functional magnetic resonance imaging (fMRI) poses a serious challenge to pattern recognition and machine learning due to the extremely large feature-to-instance ratio. This calls for revision and adaptation of the current state-of-the-art classification methods. We investigate the suitability of the random subspace (RS) ensemble method for fMRI classification. RS samples from the original feature set and builds one (base) classifier on each subset. The ensemble assigns a class label by either majority voting or averaging of output probabilities. Looking for guidelines for setting the two parameters of the method-ensemble size and feature sample size-we introduce three criteria calculated through these parameters: usability of the selected feature sets, coverage of the set of "important" features, and feature set diversity. Optimized together, these criteria work toward producing accurate and diverse individual classifiers. RS was tested on three fMRI datasets from single-subject experiments: the Haxby data (Haxby, 2001.) and two datasets collected in-house. We found that RS with support vector machines (SVM) as the base classifier outperformed single classifiers as well as some of the most widely used classifier ensembles such as bagging, AdaBoost, random forest, and rotation forest. The closest rivals were the single SVM and bagging of SVM classifiers. We use kappa-error diagrams to understand the success of RS.

Neural correlates of enhanced visual short-term memory for angry faces: an FMRI study.

BACKGROUND: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities. METHODOLOGY/PRINCIPAL FINDINGS: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load. CONCLUSIONS/SIGNIFICANCE: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.