Simultaneous fMRI and EEG during the Multi-Source Interference Task

Background

fMRI and EEG are two non-invasive functional imaging techniques within cognitive neuroscience that have complementary advantages to obtain both temporal and spatial information. The multi-source interference task (MSIT) has been shown to generate robust activations of the dorsal anterior cingulate cortex (dACC) on both a single-subject level and in group averages, in fMRI studies. We have now simultaneously acquired fMRI and EEG during a cognitive interference task.

Materials and Methods

Healthy volunteers were tested in an MRI scanner with simultaneous EEG and fMRI recordings during the MSIT.

Results

The interference condition significantly increased the reaction time in the task. The fMRI analyses revealed activation of dACC as expected, in all subjects at the individual level and in group analyses. The posterior cingulate cortex was de-activated. Simultaneous EEG showed the expected anterior distribution of the interference effect, as it was restricted to frontal sites within a time frame of 80–120 ms post response.

Conclusion

The MSIT task is a reliable task for interference evaluation. fMRI shows robust activation of dACC and by adding EEG, an interference effect can be noticed within a temporal interval of 80–120 ms after the response, as a CRN (correct response negativity). This means that EEG could add a more detailed temporal aspect to the fMRI data from an interference task, and that despite the hostile environment within an MRI scanner, EEG data could be used.     

Activation of Anterior Insula during Self-Reflection

Background

Functional neuroimaging studies have suggested activation of midline frontoparietal brain regions to be at the core of self-related processes. However, although some studies reported involvement of the insula, little attention has been paid to this region as forming part of the “self”-network.

Methodology/Principal Findings

Using functional magnetic resonance imaging (fMRI), we aimed at replicating and extending previous studies by scanning subjects whilst reflecting upon their own personal qualities as compared to those of an acquaintance. A third condition with statements about general knowledge was used to control for attention, semantic processing and decision making processes. The results showed a significant effect of task in brain activity, consistent with previous findings, by which both person conditions recruited a common set of medial prefrontal and posterior regions, yet significant differences between self and other were found in the medial prefrontal cortex (MPFC) and the anterior cingulate cortex (ACC). Notably, significant neural activation in the left anterior insula was observed as uniquely associated with self-reflection.

Conclusions/Significance

The results provide further evidence for the specific recruitment of anterior MPFC and ACC regions for self-related processing, and highlight a role for the insula in self-reflection. As the insula is closely connected with ascending internal body signals, this may indicate that the accumulation of changes in affective states that might be implied in self-processing may contribute to our sense of self.     

Opposite Modulation of Brain Functional Networks Implicated at Low vs. High Demand of Attention and Working Memory

Background

Functional magnetic resonance imaging (fMRI) studies indicate that the brain organizes its activity into multiple functional networks (FNs) during either resting condition or task-performance. However, the functions of these FNs are not fully understood yet.

Methodology/Principal Findings

To investigate the operation of these FNs, spatial independent component analysis (sICA) was used to extract FNs from fMRI data acquired from healthy participants performing a visual task with two levels of attention and working memory load. The task-related modulations of extracted FNs were assessed. A group of FNs showed increased activity at low-load conditions and reduced activity at high-load conditions. These FNs together involve the left lateral frontoparietal cortex, insula, and ventromedial prefrontal cortex. A second group of FNs showed increased activity at high-load conditions and reduced activity at low-load conditions. These FNs together involve the intraparietal sulcus, frontal eye field, lateral frontoparietal cortex, insula, and dorsal anterior cingulate, bilaterally. Though the two groups of FNs showed opposite task-related modulations, they overlapped extensively at both the lateral and medial frontoparietal cortex and insula. Such an overlap of FNs would not likely be revealed using standard general-linear-model-based analyses.

Conclusions

By assessing task-related modulations, this study differentiated the functional roles of overlapping FNs. Several FNs including the left frontoparietal network are implicated in task conditions of low attentional load, while another set of FNs including the dorsal attentional network is implicated in task conditions involving high attentional demands.     

Functional neuronal network activity differs with cognitive dysfunction in childhood-onset systemic lupus erythematosus

Introduction

Neuropsychiatric manifestations are common in childhood-onset systemic lupus erythematosus (cSLE) and often include neurocognitive dysfunction (NCD). Functional magnetic resonance imaging (fMRI) can measure brain activation during tasks that invoke domains of cognitive function impaired by cSLE. This study investigates specific changes in brain function attributable to NCD in cSLE that have potential to serve as imaging biomarkers.

Methods

Formal neuropsychological testing was done to measure cognitive ability and to identify NCD. Participants performed fMRI tasks probing three cognitive domains impacted by cSLE: visuoconstructional ability (VCA), working memory, and attention. Imaging data, collected on 3-Tesla scanners, included a high-resolution T1-weighted anatomic reference image followed by a T2*-weighted whole-brain echo planar image series for each fMRI task. Brain activation using blood oxygenation level-dependent contrast was compared between cSLE patients with NCD (NCD-group, n = 7) vs. without NCD (noNCD-group, n = 14) using voxel-wise and region of interest-based analyses. The relationship of brain activation during fMRI tasks and performance in formal neuropsychological testing was assessed.

Results

Greater brain activation was observed in the noNCD-group vs. NCD-group during VCA and working memory fMRI tasks. Conversely, compared to the noNCD-group, the NCD-group showed more brain activation during the attention fMRI task. In region of interest analysis, brain activity during VCA and working memory fMRI tasks was positively associated with the participants'' neuropsychological test performance. In contrast, brain activation during the attention fMRI task was negatively correlated with neuropsychological test performance. While the NCD group performed worse than the noNCD group during VCA and working memory tasks, the attention task was performed equally well by both groups.

Conclusions

NCD in patients with cSLE is characterized by differential activation of functional neuronal networks during fMRI tasks probing working memory, VCA, and attention. Results suggest a compensatory mechanism allows maintenance of attentional performance under NCD. This mechanism appears to break down for the VCA and working memory challenges presented in this study. The observation that neuronal network activation is related to the formal neuropsychological testing performance makes fMRI a candidate imaging biomarker for cSLE-associated NCD.     

Can the Neural Basis of Repression Be Studied in the MRI Scanner? New Insights from Two Free Association Paradigms

Background

The psychodynamic theory of repression suggests that experiences which are related to internal conflicts become unconscious. Previous attempts to investigate repression experimentally were based on voluntary, intentional suppression of stimulus material. Unconscious repression of conflict-related material is arguably due to different processes, but has never been studied with neuroimaging methods.

Methods

We used functional magnetic resonance imaging (fMRI) in addition with skin conductance recordings during two free association paradigms to identify the neural mechanisms underlying forgetting of freely associated words according to repression theory.

Results

In the first experiment, free association to subsequently forgotten words was accompanied by increases in skin conductance responses (SCRs) and reaction times (RTs), indicating autonomic arousal, and by activation of the anterior cingulate cortex. These findings are consistent with the hypothesis that these associations were repressed because they elicited internal conflicts. To test this idea more directly, we conducted a second experiment in which participants freely associated to conflict-related sentences. Indeed, these associations were more likely to be forgotten than associations to not conflict-related sentences and were accompanied by increases in SCRs and RTs. Furthermore, we observed enhanced activation of the anterior cingulate cortex and deactivation of hippocampus and parahippocampal cortex during association to conflict-related sentences.

Conclusions

These two experiments demonstrate that high autonomic arousal during free association predicts subsequent memory failure, accompanied by increased activation of conflict-related and deactivation of memory-related brain regions. These results are consistent with the hypothesis that during repression, explicit memory systems are down-regulated by the anterior cingulate cortex.     

An Event-Related fMRI Study of Phonological Verbal Working Memory in Schizophrenia

Background

While much is known about the role of prefrontal cortex (PFC) in working memory (WM) deficits of schizophrenia, the nature of the relationship between cognitive components of WM and brain activation patterns remains unclear. We aimed to elucidate the neural correlates of the maintenance component of verbal WM by examining correct and error trials with event-related fMRI.

Methodology/Findings

Twelve schizophrenia patients (SZ) and thirteen healthy control participants (CO) performed a phonological delayed-matching-to-sample-task in which a memory set of three nonsense words was presented, followed by a 6-seconds delay after which a probe nonsense word appeared. Participants decided whether the probe matched one of the targets, and rated the confidence of their decision. Blood-oxygen-level-dependent (BOLD) activity during WM maintenance was analyzed in relation to performance (correct/error) and confidence ratings. Frontal and parietal regions exhibited increased activation on correct trials for both groups. Correct and error trials were further segregated into true memory, false memory, guess, and true error trials. True memory trials were associated with increased bilateral activation of frontal and parietal regions in both groups but only CO showed deactivation in PFC. There was very little maintenance-related cortical activity during guess trials. False memory was associated with increased left frontal and parietal activation in both groups.

Conclusion

These findings suggest that a wider network of frontal and parietal regions support WM maintenance in correct trials compared with error trials in both groups. Furthermore, a more extensive and dynamic pattern of recruitment of the frontal and parietal networks for true memory was observed in healthy controls compared with schizophrenia patients. These results underscore the value of parsing the sources of memory errors in fMRI studies because of the non-linear nature of the brain-behavior relationship, and suggest that group comparisons need to be interpreted in more specific behavioral contexts.     

Simultaneous EEG-fMRI during a Working Memory Task: Modulations in Low and High Frequency Bands

Background

EEG studies of working memory (WM) have demonstrated load dependent frequency band modulations. FMRI studies have localized load modulated activity to the dorsolateral prefrontal cortex (DLPFC), medial prefrontal cortex (MPFC), and posterior parietal cortex (PPC). Recently, an EEG-fMRI study found that low frequency band (theta and alpha) activity negatively correlated with the BOLD signal during the retention phase of a WM task. However, the coupling of higher (beta and gamma) frequencies with the BOLD signal during WM is unknown.

Methodology

In 16 healthy adult subjects, we first investigated EEG-BOLD signal correlations for theta (5–7 Hz), alpha1 (8–10), alpha2 (10–12 Hz), beta1 (13–20), beta2 (20–30 Hz), and gamma (30–40 Hz) during the retention period of a WM task with set size 2 and 5. Secondly, we investigated whether load sensitive brain regions are characterised by effects that relate frequency bands to BOLD signals effects.

Principal Findings

We found negative theta-BOLD signal correlations in the MPFC, PPC, and cingulate cortex (ACC and PCC). For alpha1 positive correlations with the BOLD signal were found in ACC, MPFC, and PCC; negative correlations were observed in DLPFC, PPC, and inferior frontal gyrus (IFG). Negative alpha2-BOLD signal correlations were observed in parieto-occipital regions. Beta1-BOLD signal correlations were positive in ACC and negative in precentral and superior temporal gyrus. Beta2 and gamma showed only positive correlations with BOLD, e.g., in DLPFC, MPFC (gamma) and IFG (beta2/gamma). The load analysis revealed that theta and—with one exception—beta and gamma demonstrated exclusively positive load effects, while alpha1 showed only negative effects.

Conclusions

We conclude that the directions of EEG-BOLD signal correlations vary across brain regions and EEG frequency bands. In addition, some brain regions show both load sensitive BOLD and frequency band effects. Our data indicate that lower as well as higher frequency brain oscillations are linked to neurovascular processes during WM.     

Primary and Secondary Rewards Differentially Modulate Neural Activity Dynamics during Working Memory

Background

Cognitive control and working memory processes have been found to be influenced by changes in motivational state. Nevertheless, the impact of different motivational variables on behavior and brain activity remains unclear.

Methodology/Principal Findings

The current study examined the impact of incentive category by varying on a within-subjects basis whether performance during a working memory task was reinforced with either secondary (monetary) or primary (liquid) rewards. The temporal dynamics of motivation-cognition interactions were investigated by employing an experimental design that enabled isolation of sustained and transient effects. Performance was dramatically and equivalently enhanced in each incentive condition, whereas neural activity dynamics differed between incentive categories. The monetary reward condition was associated with a tonic activation increase in primarily right-lateralized cognitive control regions including anterior prefrontal cortex (PFC), dorsolateral PFC, and parietal cortex. In the liquid condition, the identical regions instead showed a shift in transient activation from a reactive control pattern (primary probe-based activation) during no-incentive trials to proactive control (primary cue-based activation) during rewarded trials. Additionally, liquid-specific tonic activation increases were found in subcortical regions (amygdala, dorsal striatum, nucleus accumbens), indicating an anatomical double dissociation in the locus of sustained activation.

Conclusions/Significance

These different activation patterns suggest that primary and secondary rewards may produce similar behavioral changes through distinct neural mechanisms of reinforcement. Further, our results provide new evidence for the flexibility of cognitive control, in terms of the temporal dynamics of activation.     

Dopamine Transporters in Striatum Correlate with Deactivation in the Default Mode Network during Visuospatial Attention

Background

Dopamine and dopamine transporters (DAT, which regulate extracellular dopamine in the brain) are implicated in the modulation of attention but their specific roles are not well understood. Here we hypothesized that dopamine modulates attention by facilitation of brain deactivation in the default mode network (DMN). Thus, higher striatal DAT levels, which would result in an enhanced clearance of dopamine and hence weaker dopamine signals, would be associated to lower deactivation in the DMN during an attention task.

Methodology/Principal Findings

For this purpose we assessed the relationship between DAT in striatum (measured with positron emission tomography and [¹¹C]cocaine used as DAT radiotracer) and brain activation and deactivation during a parametric visual attention task (measured with blood oxygenation level dependent functional magnetic resonance imaging) in healthy controls. We show that DAT availability in caudate and putamen had a negative correlation with deactivation in ventral parietal regions of the DMN (precuneus, BA 7) and a positive correlation with deactivation in a small region in the ventral anterior cingulate gyrus (BA 24/32). With increasing attentional load, DAT in caudate showed a negative correlation with load-related deactivation increases in precuneus.

Conclusions/Significance

These findings provide evidence that dopamine transporters modulate neural activity in the DMN and anterior cingulate gyrus during visuospatial attention. Our findings suggest that dopamine modulates attention in part by regulating neuronal activity in posterior parietal cortex including precuneus (region involved in alertness) and cingulate gyrus (region deactivated in proportion to emotional interference). These findings suggest that the beneficial effects of stimulant medications (increase dopamine by blocking DAT) in inattention reflect in part their ability to facilitate the deactivation of the DMN.     

Autistic traits and brain activation during face-to-face conversations in typically developed adults

Background

Autism spectrum disorders (ASD) are characterized by impaired social interaction and communication, restricted interests, and repetitive behaviours. The severity of these characteristics is posited to lie on a continuum that extends into the general population. Brain substrates underlying ASD have been investigated through functional neuroimaging studies using functional magnetic resonance imaging (fMRI). However, fMRI has methodological constraints for studying brain mechanisms during social interactions (for example, noise, lying on a gantry during the procedure, etc.). In this study, we investigated whether variations in autism spectrum traits are associated with changes in patterns of brain activation in typically developed adults. We used near-infrared spectroscopy (NIRS), a recently developed functional neuroimaging technique that uses near-infrared light, to monitor brain activation in a natural setting that is suitable for studying brain functions during social interactions.

Methodology

We monitored regional cerebral blood volume changes using a 52-channel NIRS apparatus over the prefrontal cortex (PFC) and superior temporal sulcus (STS), 2 areas implicated in social cognition and the pathology of ASD, in 28 typically developed participants (14 male and 14 female) during face-to-face conversations. This task was designed to resemble a realistic social situation. We examined the correlations of these changes with autistic traits assessed using the Autism-Spectrum Quotient (AQ).

Principal Findings

Both the PFC and STS were significantly activated during face-to-face conversations. AQ scores were negatively correlated with regional cerebral blood volume increases in the left STS during face-to-face conversations, especially in males.

Conclusions

Our results demonstrate successful monitoring of brain function during realistic social interactions by NIRS as well as lesser brain activation in the left STS during face-to-face conversations in typically developed participants with higher levels of autistic traits.     

Brain activation during processing of angry facial expressions in patients with alcohol dependency

Background

Alcoholism is associated with abnormal anger processing. The purpose of this study was to investigate brain regions involved in the evaluation of angry facial expressions in patients with alcohol dependency.

Methods

Brain blood-oxygenation-level-dependent (BOLD) responses to angry faces were measured and compared between patients with alcohol dependency and controls.

Results

During intensity ratings of angry faces, significant differences in BOLD were observed between patients with alcohol dependency and controls. That is, patients who were alcohol-dependent showed significantly greater activation in several brain regions, including the dorsal anterior cingulate cortex (dACC) and medial prefrontal cortex (MPFC).

Conclusions

Following exposure to angry faces, abnormalities in dACC and MPFC activation in patients with alcohol dependency indicated possible inefficiencies or hypersensitivities in social cognitive processing.     

Influence of Repressive Coping Style on Cortical Activation during Encoding of Angry Faces

Background

Coping plays an important role for emotion regulation in threatening situations. The model of coping modes designates repression and sensitization as two independent coping styles. Repression consists of strategies that shield the individual from arousal. Sensitization indicates increased analysis of the environment in order to reduce uncertainty. According to the discontinuity hypothesis, repressors are sensitive to threat in the early stages of information processing. While repressors do not exhibit memory disturbances early on, they manifest weak memory for these stimuli later. This study investigates the discontinuity hypothesis using functional magnetic resonance imaging (fMRI).

Methods

Healthy volunteers (20 repressors and 20 sensitizers) were selected from a sample of 150 students on the basis of the Mainz Coping Inventory. During the fMRI experiment, subjects evaluated and memorized emotional and neutral faces. Subjects performed two sessions of face recognition: immediately after the fMRI session and three days later.

Results

Repressors exhibited greater activation of frontal, parietal and temporal areas during encoding of angry faces compared to sensitizers. There were no differences in recognition of facial emotions between groups neither immediately after exposure nor after three days.

Conclusions

The fMRI findings suggest that repressors manifest an enhanced neural processing of directly threatening facial expression which confirms the assumption of hyper-responsivity to threatening information in repression in an early processing stage. A discrepancy was observed between high neural activation in encoding-relevant brain areas in response to angry faces in repressors and no advantage in subsequent memory for these faces compared to sensitizers.     

Complex Prospective Memory in Adults with Attention Deficit Hyperactivity Disorder

Objectives

Attention deficit hyperactivity disorder (ADHD) in adults has been associated with disturbances of attention and executive functions. Furthermore, impairments of verbal and figural retrospective memory were reported. However, little is known about the effects of ADHD on prospective memory, the execution of delayed intentions in the future.

Methods

The present study compared the performance of 45 adult patients with ADHD not treated with stimulant medication with the performance of 45 matched healthy individuals on a paradigm of complex prospective memory which measured task planning, plan recall, self-initiation and execution. Furthermore, the contribution of other cognitive functions to prospective memory functioning was assessed, including measures of attention, executive functions and memory.

Results

A large-scale impairment could be observed in task planning abilities in patients with ADHD. Only negligible to small effects were found for plan recall, self-initiation and execution. Inhibition was identified to contribute significantly to performance on task planning.

Conclusions

The present findings suggest that four cognitive components contribute to the performance of prospective memory. Impairments of prospective memory mainly emerged from deficient planning abilities in adults with ADHD. Implications on behavioral based intervention strategies are discussed.     

Evidence for Anomalous Network Connectivity during Working Memory Encoding in Schizophrenia: An ICA Based Analysis

Background

Numerous neuroimaging studies report abnormal regional brain activity during working memory performance in schizophrenia, but few have examined brain network integration as determined by “functional connectivity” analyses.

Methodology/Principal Findings

We used independent component analysis (ICA) to identify and characterize dysfunctional spatiotemporal networks in schizophrenia engaged during the different stages (encoding and recognition) of a Sternberg working memory fMRI paradigm. 37 chronic schizophrenia and 54 healthy age/gender-matched participants performed a modified Sternberg Item Recognition fMRI task. Time series images preprocessed with SPM2 were analyzed using ICA. Schizophrenia patients showed relatively less engagement of several distinct “normal” encoding-related working memory networks compared to controls. These encoding networks comprised 1) left posterior parietal-left dorsal/ventrolateral prefrontal cortex, cingulate, basal ganglia, 2) right posterior parietal, right dorsolateral prefrontal cortex and 3) default mode network. In addition, the left fronto-parietal network demonstrated a load-dependent functional response during encoding. Network engagement that differed between groups during recognition comprised the posterior cingulate, cuneus and hippocampus/parahippocampus. As expected, working memory task accuracy differed between groups (p<0.0001) and was associated with degree of network engagement. Functional connectivity within all three encoding-associated functional networks correlated significantly with task accuracy, which further underscores the relevance of abnormal network integration to well-described schizophrenia working memory impairment. No network was significantly associated with task accuracy during the recognition phase.

Conclusions/Significance

This study extends the results of numerous previous schizophrenia studies that identified isolated dysfunctional brain regions by providing evidence of disrupted schizophrenia functional connectivity using ICA within widely-distributed neural networks engaged for working memory cognition.     

Evidence of Impaired Brain Activity Balance after Passive Sensorimotor Stimulation in Multiple Sclerosis

Objectives

Examination of sensorimotor activation alone in multiple sclerosis (MS) patients may not yield a comprehensive view of cerebral response to task stimulation. Additional information may be obtained by examining the negative BOLD response (deactivation). Aim of this work was to characterize activation and deactivation patterns during passive hand movements in MS patients.

Methods

13 relapsing remitting-MS patients (RRMS), 18 secondary progressive-MS patients (SPMS) and 15 healthy controls (HC) underwent an fMRI study during passive right-hand movements. Activation and deactivation contrasts in the three groups were entered into ANOVA, age and gender corrected. Post-hoc analysis was performed with one-sample and two-sample t-tests. For each patient we obtained lesion volume (LV) from both T1- and T2-weighted images.

Results

Activations showed a progressive extension to the ipsilateral brain hemisphere according to the group and the clinical form (HC<RRMS<SPMS). Significant deactivation of the ipsilateral cortical sensorimotor areas was reduced in both patient groups with respect to HC. Deactivation of posterior cortical areas belonging to the default mode network (DMN), was increased in RRMS, but not in SPMS, with respect to HC. The amount of activation in the contralateral sensorimotor cortex was significantly correlated with that of deactivation in the DMN in HC and RRMS, but not in SPMS. Both increased activation and decreased deactivation patterns correlated with LV.

Conclusion

In RRMS patients, increased cortical activation was associated with increased deactivation of the posterior cortex suggesting a greater resting-state activity in the DMN, probably aimed at facilitating sensorimotor circuit engagement during task performance. In SPMS the coupling between increased sensorimotor activation/increased DMN deactivation was not observed suggesting disorganization between anticorrelated functional networks as a consequence of a higher level of disconnection.     

Dissociation of Regional Activity in Default Mode Network in Medication-Naive,First-Episode Somatization Disorder

Background

Patients with somatization disorder (SD) have altered neural activity in the brain regions of the default mode network (DMN). However, the regional alteration of the DMN in SD remains unknown. The present study was designed to investigate the regional alterations of the DMN in patients with SD at rest.

Methods

Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex-, education- matched healthy controls underwent a resting-state functional magnetic resonance imaging (fMRI) scan. The fractional amplitude of low-frequency fluctuations (fALFF) was applied to analyze the data.

Results

Patients with SD showed a dissociation pattern of resting-state fALFF in the DMN, with increased fALFF in the bilateral superior medial prefrontal cortex (MPFC, BA8, 9) and decreased fALFF in the left precuneus (PCu, BA7). Furthermore, significantly positive correlation was observed between the z values of the voxels within the bilateral superior MPFC and somatization subscale scores of the Symptom Check List (SCL-90) in patients with SD.

Conclusions

Our findings indicate that there is a dissociation pattern of the anterior and posterior DMN in first-episode, treatment-naive patients with SD. The results provide new insight for the importance of the DMN in the pathophysiology of SD.     

Personality Functioning and the Cortical Midline Structures – An Exploratory fMRI Study

Objective

Recent neuroscience studies explored the neuronal mechanisms underlying our sense of self. Thereby the cortical midline structures and their anterior and posterior regions have been shown to be central. What remains unclear though is how both, self and cortical midline structures, are related to the identity of the self which is of central importance in especially personality disorders.

Methods

Conducting an exploratory study with a dimensional approach, we here compared subjects with high and low level of personality functioning and identity integration as measured in a standardized way in fMRI during both, emotion- and reward-related tasks.

Results

Low levels of personality functioning and identity integration were predicted by significantly decreased degrees of deactivation in the anterior and posterior cortical midline structures.

Conclusions

Though exploratory our results show for the first time direct relationship between cortical midline structures and personality functioning in terms of identity integration. This does not only contribute to our understanding of the neuronal mechanism underlying self and identity but carries also major implications for the treatment of patients with personality disorders.     

Increased Cortical Activity in Binge Drinkers during Working Memory Task: A Preliminary Assessment through a Functional Magnetic Resonance Imaging Study

Background

Cerebral dysfunction is a common feature of both chronic alcohol abusers and binge drinkers. Here, we aimed to study whether, at equated behavioral performance levels, binge drinkers exhibited increased neural activity while performing simple cognitive tasks.

Methods

Thirty-two participants (16 binge drinkers and 16 matched controls) were scanned using functional magnetic resonance imaging (fMRI) while performing an n-back working memory task. In the control zero-back (N0) condition, subjects were required to press a button with the right hand when the number “2″ was displayed. In the two-back (N2) condition, subjects had to press a button when the displayed number was identical to the number shown two trials before.

Results

fMRI analyses revealed higher bilateral activity in the pre-supplementary motor area in binge drinkers than matched controls, even though behavioral performances were similar. Moreover, binge drinkers showed specific positive correlations between the number of alcohol doses consumed per occasion and higher activity in the dorsomedial prefrontal cortex, as well as between the number of drinking occasions per week and higher activity in cerebellum, thalamus and insula while performing the N2 memory task.

Conclusions

Binge alcohol consumption leads to possible compensatory cerebral changes in binge drinkers that facilitate normal behavioral performance. These changes in cerebral responses may be considered as vulnerability factors for developing adult substance use disorders.     

Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance

Background

Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known.

Methods

Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [¹²³I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [¹²³I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory.

Results

Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [¹²³I]IBZM and of [¹²³I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT.

Conclusions

Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.     

Effects of Attention to Auditory Motion on Cortical Activations during Smooth Pursuit Eye Tracking

Background

In contrast to traditional views that consider smooth pursuit as a relatively automatic process, evidence has been reported for the importance of attention for accurate pursuit performance. However, the exact role that attention might play in the maintenance of pursuit remains unclear.

Methodology/Principal Findings

We analysed the neuronal activity associated with healthy subjects executing smooth pursuit eye movements (SPEM) during concurrent attentive tracking of a moving sound source, which was either in-phase or in antiphase to the executed eye movements. Assuming that attentional resources must be allocated to the moving sound source, the simultaneous execution of SPEM and auditory tracking in diverging directions should result in increased load on common attentional resources. By using an auditory stimulus as a distractor rather then a visual stimulus we guaranteed that cortical activity cannot be caused by conflicts between two simultaneous visual motion stimuli. Our results revealed that the smooth pursuit task with divided attention led to significantly higher activations bilaterally in the posterior parietal cortex and lateral and medial frontal cortex, presumably containing the parietal, frontal and supplementary eye fields respectively.

Conclusions

The additional cortical activation in these areas is apparently due to the process of dividing attention between the execution of SPEM and the covert tracking of the auditory target. On the other hand, even though attention had to be divided the attentional resources did not seem to be exhausted, since the identification of the direction of the auditory target and the quality of SPEM were unaffected by the congruence between visual and auditory motion stimuli. Finally, we found that this form of task-related attention modulated not only the cortical pursuit network in general but also affected modality specific and supramodal attention regions.