dlPFC Activity Research Articles

Does Change in Attention Control Mediate the Impact of tDCS on Attentional Bias for Threat? Limited Evidence from a Double-blind Sham-controlled Experiment in an Unselected Sample.

Neurocognitive models of attentional bias for threat posit that attentional bias may result from a decreased activation of the left prefrontal cortex, and especially of its dorsolateral part (dlPFC), resulting in an impaired attention control. Consequently, a transient increase of neural activity within the left dlPFC via non-invasive brain stimulation reduces attentional bias among both anxious and nonanxious participants. Yet, it is still unclear whether the impact of dlPFC activation on attentional bias is mediated by improvement in attention control. In this experiment, we sought to test this hypothesis in an unselected sample (n = 20). Accordingly, we adopted a double-blind within-subject protocol in which we delivered a single-session of anodal versus sham transcranial Direct Current Stimulation (tDCS) over the left dlPFC during the completion of a task assessing attention control. We also assessed its subsequent impact on attentional bias. Neither attention control nor attentional bias did significantly improve following anodal tDCS. Although our results do not support our main hypothesis, we believe the present null results to be particularly useful for future meta-research in the field. We also formulated a series of methodological recommendations for future research aiming at testing the tDCS-induced modification of attentional bias.

Catecholaminergic modulation of indices of cognitive flexibility: A pharmaco-tDCS study

BackgroundDopaminergic activity within the dorsolateral prefrontal cortex (dlPFC) has been implicated in the control of cognitive flexibility. Much of the evidence for a causative relationship between cognitive flexibility and dopamine has come from animal studies, whilst human data have largely been correlational.Objective/Hypothesis:The current study examines whether changes in dopamine levels through tyrosine administration and suppression of dlPFC activity via cathodal tDCS could be causally related to cognitive flexibility as measured by task switching and reversal learning. MethodsUsing a crossover, double-blind, sham controlled, counterbalanced, randomized trial, we tested the effects of combining cathodal tDCS with tyrosine, a catecholaminergic precursor, with appropriate drug and tDCS placebo controls, on two measures of cognitive flexibility: probabilistic reversal learning, and task switching. ResultsWhile none of the manipulations had an effect on task switching, there was a significant main effect of cathodal tDCS and tyrosine on reversal learning. Reversal learning performance was significantly worsened by cathodal tDCS compared with sham tDCS, whilst tyrosine significantly improved performance compared with placebo. However, there was no significant tDCS × drugs interaction. Interestingly, and as predicted by our model, the combined administration of tyrosine with cathodal tDCS resulted in performance that was equivalent to the control condition (i.e. tDCS sham + placebo). ConclusionsOur results suggest a causative role for dopamine signalling and dorsolateral prefrontal cortex activity in regulating indices of cognitive flexibility in humans.

Comparison of prefrontal hemodynamic responses and cognitive deficits between adult patients with autism spectrum disorder and schizophrenia

Autism spectrum disorder (ASD) and schizophrenia share many phenotypic characteristics, but their association with prefrontal function have not been directly compared. The aim of this study is to compare cognitive profiles and their association with the prefrontal function between the two groups. We explored prefrontal dysfunction among adult individuals with ASD (n = 32), schizophrenia (n = 87), and healthy controls (HCs; n = 50). We assessed cognitive function in all participants using the Brief Assessment of Cognition in Schizophrenia (BACS). The BACS data of patients with schizophrenia were entered into hierarchical cluster analyses to assign subjects to a specific subgroup based on individual profiles. Using near-infrared spectroscopy, we measured hemodynamic responses in the fronto-temporal regions during a working memory task. Among the patients with schizophrenia, we defined 4 neurocognitive subgroups, including a global impairment, a mild impairment, and 2 selective impairment groups. Compared to the HCs, the ASD and schizophrenia groups had much weaker hemodynamic responses in the left DLPFC, left frontopolar cortex (FPC), and left inferior frontal gyrus. The ASD group showed a similar level of cognitive impairment with the mild level subgroup of schizophrenia. Additionally, the two groups shared reduced activity in the left DLPFC and left FPC during the task compared to HCs. Moreover, the BACS composite scores correlated positively with hemodynamic responses in a broad area involving fronto-temporal regions in the total patient sample. This research indicates considerable similarity in the left PFC dysfunction and its association with cognitive deficits between the disorders. These findings may guide future studies that investigate pathophysiological similarities between ASD and schizophrenia.

Language switching decomposed through MEG and evidence from bimodal bilinguals

A defining feature of human cognition is the ability to quickly and accurately alternate between complex behaviors. One striking example of such an ability is bilinguals' capacity to rapidly switch between languages. This switching process minimally comprises disengagement from the previous language and engagement in a new language. Previous studies have associated language switching with increased prefrontal activity. However, it is unknown how the subcomputations of language switching individually contribute to these activities, because few natural situations enable full separation of disengagement and engagement processes during switching. We recorded magnetoencephalography (MEG) from American Sign Language-English bilinguals who often sign and speak simultaneously, which allows to dissociate engagement and disengagement. MEG data showed that turning a language "off" (switching from simultaneous to single language production) led to increased activity in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (dlPFC), while turning a language "on" (switching from one language to two simultaneously) did not. The distinct representational nature of these on and off processes was also supported by multivariate decoding analyses. Additionally, Granger causality analyses revealed that (i) compared with "turning on" a language, "turning off" required stronger connectivity between left and right dlPFC, and (ii) dlPFC activity predicted ACC activity, consistent with models in which the dlPFC is a top-down modulator of the ACC. These results suggest that the burden of language switching lies in disengagement from the previous language as opposed to engaging a new language and that, in the absence of motor constraints, producing two languages simultaneously is not necessarily more cognitively costly than producing one.

Intrinsic connectivity network dynamics in PTSD during amygdala downregulation using real-time fMRI neurofeedback: A preliminary analysis.

Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real-time fMRI neurofeedback (rt-fMRI-NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala-a key region-of-interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt-fMRI-NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task-negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt-fMRI-NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.

Acute and past subjective stress influence working memory and related neural substrates

Stress has been proposed to affect cognitive control capacities, including working memory (WM) maintenance. This effect may depend on variability in stress reactivity and past subjective stress. However, as most studies employed between-subjects designs, evidence for within-subject stress effects remains scarce. To understand the role of intra-individual stress effects on WM, we adopted a within-subject design to study how acute stress, variability in stress reactivity, and past subjective stress influence behavioral and neural WM mechanisms. Thirty-four healthy males performed a WM task during functional magnetic resonance imaging (fMRI) in a control versus acute stress condition following the Trier Social Stress Test, a validated psychosocial stressor method. We tested for stress effects on WM performance and related neural activation by associating them with individual acute stress responsivity and past subjective stress experience using retrospective self-report questionnaires. We found no evidence of an effect of acute stress or related stress-reactivity on intra-individual WM performance. However, past subjective stress negatively influenced acute stress-induced changes to WM. On the neural level, acute stress reduced WM-related activation in the dorsolateral prefrontal cortex (dlPFC). The observed negative influence of inter-individual variability in past subjective stress experience on changes in WM performance, suggests that past subjective stress might induce vulnerability for impairing effects of acute stress on cognitive functioning. Because acute stress reduced WM-related dlPFC activation while WM performance remained unaffected, acute stress might boost neural processing efficiency in this group of high performing healthy individuals. Our study suggests that measures of past subjective stress should be considered when studying and interpreting the effects of acute stress on cognition.

Optical mapping of prefrontal brain connectivity and activation during emotion anticipation

Accumulated neuroimaging evidence shows that the dorsal lateral prefrontal cortex (dlPFC) is activated during emotion anticipation. The aim of this work is to examine the brain connectivity and activation differences in dlPFC between the positive, neutral and negative emotion anticipation by using functional near-infrared spectroscopy (fNIRS). The hemodynamic responses were first assessed for all subjects during the performance of various emotion anticipation tasks. And then small-world analysis was performed, in which the small-world network indicators including the clustering coefficient, average path length, average node degree, and measure of small-world index were calculated for the functional brain networks associated with the positive, neutral and negative emotion anticipation, respectively. We discovered that compared to negative and neutral emotion anticipation, the positive one exhibited enhanced brain activation in the left dlPFC. Although the functional brain networks for the three emotion anticipation cases manifested the small-world properties regarding the clustering coefficient, average path length, average node degree, and measure of small-world index, the positive one showed significantly higher clustering coefficient and shorter average path length than those from the neutral and negative cases. Consequently, the small-world network indicators and brain activation in dlPPC were able to distinguish well between the positive, neutral and negative emotion anticipation.

The neurocognitive mechanisms underlying food cravings and snack food consumption. A combined continuous theta burst stimulation (cTBS) and EEG study

Regulation of food cravings is thought to be critical for modulating eating behavior, yet we do not fully understand the mechanisms by which cognitive control operates in the eating context. The current study combined rTMS and EEG paradigms to examine the causal role of the left dorsolateral prefrontal cortex (dlPFC) in modulating visceral and behavioral responses to high calorie foods, and the mediational mechanisms underlying this relation. 28 right-handed female participants received both active and sham continuous theta burst stimulation (cTBS; a rTMS variant used to decrease cortical activity) targeting the left dlPFC in a counterbalanced order. Prior to and following each stimulation session participants completed a flanker and food-cue presentation (high and low calorie food) task. Following cTBS participants had the opportunity to consume both high and low calorie foods during a taste test. Findings revealed a reliable effect of cTBS on food consumption, such that participants selectively ingested significantly more calories from appetitive calorie dense snack foods following active relative to sham cTBS; this effect did not translate to control (low calorie) food consumption. In addition, attenuation of dlPFC activity resulted in the significant increase in N2 amplitude and P3b latency to incongruent flanker trials, and the selective significant increase in the P3a amplitude to and P3a amplitude bias for high calorie food stimuli. Results from the parallel mediation analysis revealed that only the indirect effect of flanker task performance was significant; the indirect effects of stimulation induced changes in the P3 bias for high calorie foods, the urge to consume high calorie foods, and the general liking ratings for high calorie foods were not significant. These findings confirm the causal role of the left dlPFC in the modulation of calorie dense food consumption via inhibitory control capacity.

Aberrant working memory processing in major depression: evidence from multivoxel pattern classification.

Major depressive disorder (MDD) is often accompanied by severe impairments in working memory (WM). Neuroimaging studies investigating the mechanisms underlying these impairments have produced conflicting results. It remains unclear whether MDD patients show hyper- or hypoactivity in WM-related brain regions and how potential aberrations in WM processing may contribute to the characteristic dysregulation of cognition-emotion interactions implicated in the maintenance of the disorder. In order to shed light on these questions and to overcome limitations of previous studies, we applied a multivoxel pattern classification approach to investigate brain activity in large samples of MDD patients (N = 57) and matched healthy controls (N = 61) during a WM task that incorporated positive, negative, and neutral stimuli. Results showed that patients can be distinguished from healthy controls with good classification accuracy based on functional activation patterns. ROI analyses based on the classification weight maps showed that during WM, patients had higher activity in the left DLPFC and the dorsal ACC. Furthermore, regions of the default-mode network (DMN) were less deactivated in patients. As no performance differences were observed, we conclude that patients required more effort, indexed by more activity in WM-related regions, to successfully perform the task. This increased effort might be related to difficulties in suppressing task-irrelevant information reflected by reduced deactivation of regions within the DMN. Effects were most pronounced for negative and neutral stimuli, thus pointing toward important implications of aberrations in WM processes in cognition-emotion interactions in MDD.

Aberrant dynamics of spontaneous brain activity and its integration in patients with autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disease with unknown etiology but high incidence. The objective biomarkers of ASD are urgently awaited to be developed using neuroimaging method including resting-state fMRI (R-fMRI). However, the majority of current R-fMRI studies only examined the static features of brain activity in ASD patients, but neglected the dynamic aspects especially for regional metrics. Furthermore, the concordance of the dynamic regional indices was reported imbedded in human intrinsic brain activity, while its abnormality in ASD is largely unknown. In order to shed light on the abnormity of ASD from dynamic perspective, we analyzed R-fMRI data of 480 ASD male patients and 539 healthy male controls (HC) gathered from ASD public database (ABIDE I/ABIDE II). We used sliding window method to calculate the dynamics of mainstream regional indices of R-fMRI (amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), voxel-mirrored homotopic connectivity (VMHC), degree centrality (DC) and the correlation with global signal (GSCorr)) and generated the SD statistic maps of these six dynamic regional indices. We performed z-standardization and smoothing on the SD statistic maps. After that, two-sample t -test between the SD statistic maps of ASD group and HC group was performed. We also calculated the concordance of dynamic regional indices for each time point, which is the Kendall’s coefficient of the ALFF, ReHo, DC, GSCorr and VMHC maps across voxels. Two-sample t -test between the SD and mean of concordance time series of ASD group and HC group was performed. We found a significant increase in the dynamics of ALFF and DC in the lateral frontal cortices in ASD patients as compared to HCs. Dorsal lateral frontal cortex (dlPFC) is a critical brain area for cognitive control and execution network. The abnormal activities in dlPFC indicate the disruption of control execution system and the impairment of relevant cognitive function. In the visual related brain areas, the dynamics of ALFF, DC and ReHo showed a decrease in fusiform gyrus, calcarine and lingual gyrus in ASD patients. Recent studies have indicated that the abnormal face processing in children with autism may be related with the impairment in social cognition of them. The deficits in face information processing of ASD patients may stem from the inflexible intrinsic brain activity in visual processing brain area (especially in fusiform gyrus). After further examining the concordance among these dynamic indices, the mean and SD of concordance of patients with ASD was found to be significantly lower than that of the HCs, demonstrating that the ASD patients’ inferior integration ability for different aspects of brain functions. These findings suggest that there exists abnormality in dynamics of spontaneous brain activity and its integration in ASD patients. Dynamic R-fMRI regional indices and the concordance of them could be efficient neuroimaging biomarkers for ASD.

Abnormal reward prediction-error signalling in antipsychotic naive individuals with first-episode psychosis or clinical risk for psychosis

Ongoing research suggests preliminary, though not entirely consistent, evidence of neural abnormalities in signalling prediction errors in schizophrenia. Supporting theories suggest mechanistic links between the disruption of these processes and the generation of psychotic symptoms. However, it is unknown at what stage in the pathogenesis of psychosis these impairments in prediction-error signalling develop. One major confound in prior studies is the use of medicated patients with strongly varying disease durations. Our study aims to investigate the involvement of the meso-cortico-striatal circuitry during reward prediction-error signalling in earliest stages of psychosis. We studied patients with first-episode psychosis (FEP) and help-seeking individuals at-risk for psychosis due to sub-threshold prodromal psychotic symptoms. Patients with either FEP (n = 14), or at-risk for developing psychosis (n = 30), and healthy volunteers (n = 39) performed a reinforcement learning task during fMRI scanning. ANOVA revealed significant (p < 0.05 family-wise error corrected) prediction-error signalling differences between groups in the dopaminergic midbrain and right middle frontal gyrus (dorsolateral prefrontal cortex, DLPFC). FEP patients showed disrupted reward prediction-error signalling compared to controls in both regions. At-risk patients showed intermediate activation in the midbrain that significantly differed from controls and from FEP patients, but DLPFC activation that did not differ from controls. Our study confirms that FEP patients have abnormal meso-cortical signalling of reward-prediction errors, whereas reward-prediction-error dysfunction in the at-risk patients appears to show a more nuanced pattern of activation with a degree of midbrain impairment but preserved cortical function.

Inequality signals in dorsolateral prefrontal cortex inform social preference models.

Humans typically display inequality aversion in social situations, which manifests itself as a preference for fairer distributions of resources. However, people differ in the degree to which they dislike being worse off [disadvantageous inequality (DI) aversion] or better off [advantageous inequality (AI) aversion] than others. Competing models explain such behavior by focusing on aversion to payoff differences, maximization of total payoff or reciprocity. Using functional near-infrared spectroscopy, we asked which of these theories could better explain dorsolateral prefrontal cortex (dlPFC) activity while participants accepted or punished fair vs unfair monetary transfers in an anonymous norm compliance task. We found that while all participants exhibited DI aversion, there were substantial differences in preferences for AI, which were strongly predicted by dlPFC activation. Model comparisons revealed that both punishment behavior and prefrontal activity were best explained by a model that allowed for AI seeking rather than imposing aversion. Moreover, enhancing this model by taking into account behavioral response times, as a proxy for choice difficulty, further improved model fits. Our data provide evidence that the dlPFC encodes subjective values of payoff inequality and that this representation is richer than envisaged by standard models of social preferences.

F162. MORE EFFORT, BUT LESS EFFICIENCY - WORKING MEMORY IN SCHIZOPHRENIA: AN INVESTIGATION INTO CAUSE FOR DIVERGENT RESULTS

BackgroundFunctional brain imaging studies of working memory in people with schizophrenia have reported divergent reports with some studies reporting hypofrontal activation while report hypofrontal activation. The inconsistencies in the literature have been postulated to be related to task requirements or poor task performance in schizophrenia. An alternative hypothesis proposed is that different regions within the PFC show either hypo or hyperactivity, depending on their location. In view of the inconsistencies in previous research, the aim of the current research is to examine abnormalities in a cohort of partially remitted people with schizophrenia and matched controlsMethodsTwenty people with schizophrenia and 20 matched healthy controls (matched on age, gender and parental social and economic status) were selected from the Nottingham area to undergo a functional magnetic resonance imaging (fMRI) scan while undergoing two levels of the visual n-back task (zeroback and two back). The behavioural results (latency and accuracy) on the nback task was compared using repeated measures analysis. The MR images were reoriented, realigned, co-registered to the T1-weighted anatomical image, and normalised to the MNI space. Normalised images were resliced to a voxel size of 3 mm3, smoothed with an 8 mm full-width half-maximum Gaussian kernel using SPM 5. The GLM approach implemented in SPM 5 was utilized for fMRI data modeling and analyses. Each epoch type (zero-back, two-back and rest) was modeled in a boxcar design, using a canonical hemodynamic response function and its temporal derivative. The single group second level analysis consisted of voxelwise one-sample t-tests with significance threshold set at voxel level p < .05, false discovery rate (FDR) corrected for multiple comparisons across the entire brain.The between-group comparison employed voxelwise two sample t-tests with the significance criterion based on the spatial extent of suprathreshold voxel clusters, a method proposed by (Friston et al., 1994). The criterion for inclusion of a voxel in a cluster was set at p < .05 (uncorrected) and a cluster was considered as significant at level of p < .05 (corrected).ResultsPatients exhibited relatively high general function and mild symptoms, but had significantly longer reaction time and decline in performance. Both controls and patients activated similar set of brain regions similar to Central executive network and deactivated brain areas comprising the default mode network. Most noteworthy, we did not find evidence for hypofrontality (reduced activity in DLPFC in patients compared to controls) in this study. Compared to controls, patients showed areas of greater activation in left postcentral gyrus, anterior and posterior medial frontal gyrus and left superior temporal gyrus.DiscussionBoth controls and patients showed activation in widespread brain areas consistent with the CEN, and deactivation in areas consistent with DMN regions. There was no evidence of hypofrontality in this sample of remitted people with schizophrenia. Patients showed activation patterns on the zeroback task similar to the activation patterns for controls on the two back task, suggesting that patients showed increased brain activation on a task with lesser requirements, though behavioural results suggest inefficiency despite the increased effort.

F150. OVERESTIMATING ENVIRONMENTAL VOLATILITY INCREASES SWITCHING BEHAVIOR AND IS LINKED TO ACTIVATION OF DORSOLATERAL PREFRONTAL CORTEX IN SCHIZOPHRENIA

BackgroundReward-based decision-making is impaired in schizophrenia, as reflected by increased switching between choices. The underlying cognitive mechanisms and associated neural signatures remain unknown. Reinforcement learning (RL) and hierarchical Bayesian learning account for this behavior in different ways. We hypothesized that enhanced switching during flexible reward-based decision-making in schizophrenia relates to higher-order beliefs about environmental volatility and examined the associated neural signatures.Methods46 medicated schizophrenia patients and 43 controls underwent a reward-based decision-making task requiring flexible behavior to changing action-outcome contingencies during functional Magnetic Resonance Imaging (fMRI). Computational modeling of behavior was performed, including RL and the Hierarchical Gaussian Filter (HGF). The estimated learning trajectories informed the analysis of fMRI data.ResultsA three-level HGF accounted best for the observed choice data and revealed a heightened prior belief about environmental volatility and a stronger influence of volatility on lower-level learning of action-outcome contingencies in schizophrenia. This finding was replicated in an independent sample of unmedicated patients. Beliefs about environmental volatility were reflected by higher activity in dorsolateral prefrontal cortex (dlPFC) of patients compared to controls.DiscussionThis study suggests a mechanistic explanation for instable behavior in schizophrenia: patients inferred the environment as being too volatile and thus overestimated environmental changes, leading to maladaptive choice switching. Our data suggest enhanced dlPFC activity related to beliefs about environmental volatility as a neural learning signature of instable behavior. Such detailed ‘computational phenotyping’ may provide useful information to dissect clinical heterogeneity and could improve prediction of outcome.

Neurocognitive mechanisms behind emotional attention: Inverse effects of anodal tDCS over the left and right DLPFC on gaze disengagement from emotional faces.

Attention to relevant emotional information in the environment is an important process related to vulnerability and resilience for mood and anxiety disorders. In the present study, the effects of left and right dorsolateral prefrontal cortex (i.e., DLPFC) stimulation on attentional mechanisms of emotional processing were tested and contrasted. A sample of 54 healthy participants received 20 min of active and sham anodal transcranial direct current stimulation (i.e., tDCS) either of the left (n = 27) or of the right DLPFC (n = 27) on two separate days. The anode electrode was placed over the left or the right DLPFC, the cathode over the corresponding contra lateral supraorbital area. After each neurostimulation session, participants completed an eye-tracking task assessing direct processes of attentional engagement towards and attentional disengagement away from emotional faces (happy, disgusted, and sad expressions). Compared to sham, active tDCS over the left DLPFC led to faster gaze disengagement, whereas active tDCS over the right DLPFC led to slower gaze disengagement from emotional faces. Between-group comparisons showed that such inverse change patterns were significantly different and generalized for all types of emotion. Our findings support a lateralized role of left and right DLPFC activity in enhancing/worsening the top-down regulation of emotional attention processing. These results support the rationale of new therapies for affective disorders aimed to increase the activation of the left over the right DLPFC in combination with attentional control training, and identify specific target attention mechanisms to be trained.

Working Memory Modulates Glutamate Levels in the Dorsolateral Prefrontal Cortex during 1H fMRS.

Glutamate is involved in excitatory neurotransmission and metabolic processes related to brain function. Previous studies using proton functional magnetic resonance spectroscopy (1H fMRS) have demonstrated elevated cortical glutamate levels by 2–4% during visual and motor stimulation, relative to periods of no stimulation. Here, we extended this approach to working memory cognitive task performance, which has been consistently associated with dorsolateral prefrontal cortex (dlPFC) activation. Sixteen healthy adult volunteers completed a continuous visual fixation “rest” task followed by a letter 2-back working memory task during 1H fMRS acquisition of the left dlPFC, which encompassed Brodmann areas 45 and 46 over a 4.5-cm3 volume. Using a 100% automated fitting procedure integrated with LCModel, raw spectra were eddy current-, phase-, and shift-corrected prior to quantification resulting in a 32s temporal resolution or 8 averages per spectra. Task compliance was high (95 ± 11% correct) and the mean Cramer-Rao Lower Bound of glutamate was 6.9 ± 0.9%. Relative to continuous passive visual fixation, left dlPFC glutamate levels were significantly higher by 2.7% (0.32 mmol/kg wet weight) during letter 2-back performance. Elevated dlPFC glutamate levels reflect increased metabolic activity and excitatory neurotransmission driven by working memory-related cognitive demands. These results provide the first in vivo demonstration of elevated dlPFC glutamate levels during working memory.

Aversive aftertaste changes visual food cue reactivity: An fMRI study on cross-modal perception

In western cultures, we are surrounded by appealing visual food cues that stimulate our desire to eat, overeating and subsequent weight gain. Cognitive control of appetite (reappraisal) requires substantial attentional resources and effort in order to work. Therefore, we tested an alternative approach for appetite regulation via functional magnetic resonance imaging. Healthy, normal-weight women were presented with images depicting food (high-/low-caloric), once in combination with a bitter aftertaste (a gustatory stop signal) and once with a neutral taste (water), in a retest design. The aversive aftertaste elicited increased activation in the orbitofrontal/dorsolateral prefrontal cortex (OFC, DLPFC), striatum and frontal operculum during the viewing of high-caloric food (vs. low-caloric food). In addition, the increase in DLPFC activity to high-caloric food in the bitter condition was correlated with reported appetite reduction. The findings indicate that this aftertaste procedure was able to reduce the appetitive value of visual food cues.

Are ventrolateral and dorsolateral prefrontal cortices involved in the computerized Corsi block-tapping test execution? An fNIRS study.

The Corsi block-tapping test (CBT) is an old neuropsychological test that, requiring the storage and the reproduction of spatial locations, assesses spatial working memory (WM). Despite its wide use in clinical practice, the specific contribution of prefrontal cortex (PFC) subregions during CBT execution has not been clarified yet. Considering the importance of spatial WM in daily life and the well-known role of ventrolateral-PFC/dorsolateral-PFC (VLPFC/DLPFC) in WM processes, the present study was aimed at investigating, by a 20-channel functional near-infrared spectroscopy (fNIRS) system (including four short-separation channels), the hemodynamic response of the VLPFC/DLPFC during a computerized version of the CBT. Thirty-nine university students were asked to perform CBT standard version (CBTs), block-suppression CBT (CBTb), and control task (CBTc). A VLPFC activation during CBTs and a DLPFC activation during CBTb were hypothesized. The results of the Bayesian analysis have not shown a delineated specific activation of VLPFC/DLPFC during either CBTs or CBTb. These results together with the related ones obtained by others using fMRI are not sufficient to definitively state the role of the PFC subregions during CBT execution. The adoption of high-density diffuse optical tomography would be helpful in further exploration of the PFC involvement in spatial WM tasks.

Extinction of Conditioned Fear in Adolescents and Adults: A Human fMRI Study.

Little is known about the neural correlates of fear learning in adolescents, a population at increased risk for anxiety disorders. Healthy adolescents (mean age 16.26) and adults (mean age 29.85) completed a fear learning paradigm across two stages during functional magnetic resonance imaging (fMRI). Stage 1 involved conditioning and extinction, and stage 2 involved extinction recall, re-conditioning, followed by re-extinction. During extinction recall, we observed a higher skin conductance response to the CS+ relative to CS− in adolescents compared to adults, which was accompanied by a reduction in dorsolateral prefrontal cortex (dlPFC) activity. Relative to adults, adolescents also had significantly reduced activation in the ventromedial PFC, dlPFC, posterior cingulate cortex (PCC), and temporoparietal junction (TPJ) during extinction recall compared to late extinction. Age differences in PCC activation between late extinction and late conditioning were also observed. These results show for the first time that healthy adolescent humans show different behavioral responses, and dampened PFC activity during short-term extinction recall compared to healthy adults. We also identify the PCC and TPJ as novel regions that may be associated with impaired extinction in adolescents. Also, while adults showed significant correlations between differential SCR and BOLD activity in some brain regions during late extinction and recall, adolescents did not show any significant correlations. This study highlights adolescent-specific neural correlates of extinction, which may explain the peak in prevalence of anxiety disorders during adolescence.

Processing and regulation of negative emotions in anorexia nervosa: An fMRI study.

Theoretical models and recent advances in the treatment of anorexia nervosa (AN) have increasingly focused on the role of alterations in the processing and regulation of emotions. To date, however, our understanding of these changes is still limited and reports of emotional dysregulation in AN have been based largely on self-report data, and there is a relative lack of objective experimental evidence or neurobiological data.The current functional magnetic resonance imaging (fMRI) study investigated the hemodynamic correlates of passive viewing and voluntary downregulation of negative emotions by means of the reappraisal strategy detachment in AN patients. Detachment is regarded as adaptive regulation strategy associated with a reduction in emotion-related amygdala activity and increased recruitment of prefrontal brain regions associated with cognitive control processes. Emotion regulation efficacy was assessed via behavioral arousal ratings and fMRI activation elicited by an established experimental paradigm including negative images. Participants were instructed to either simply view emotional pictures or detach themselves from feelings triggered by the stimuli.The sample consisted of 36 predominantly adolescent female AN patients and a pairwise age-matched healthy control group. Behavioral and neuroimaging data analyses indicated a reduction of arousal and amygdala activity during the regulation condition for both patients and controls. However, compared with controls, individuals with AN showed increased activation in the amygdala as well as in the right dorsolateral prefrontal cortex (dlPFC) during the passive viewing of aversive compared with neutral pictures.These results extend previous findings indicative of altered processing of salient emotional stimuli in AN, but do not point to a general deficit in the voluntary regulation of negative emotions. Increased dlPFC activation in AN during passive viewing of negative stimuli is in line with the hypothesis that the disorder may be characterized by excessive self-control. Taken together, the data seem to suggest that reappraisal via detachment may be an effective strategy to reduce negative arousal for individuals with AN.