Behavioral and Neural Correlates of Cognitive-Motor Interference during Multitasking in Young and Old Adults.

The concurrent performance of cognitive and postural tasks is particularly impaired in old adults and associated with an increased risk of falls. Biological aging of the cognitive and postural control system appears to be responsible for increased cognitive-motor interference effects. We examined neural and behavioral markers of motor-cognitive dual-task performance in young and old adults performing spatial one-back working memory single and dual tasks during semitandem stance. On the neural level, we used EEG to test for age-related modulations in the frequency domain related to cognitive-postural task load. Twenty-eight healthy young and 30 old adults participated in this study. The tasks included a postural single task, a cognitive-postural dual task, and a cognitive-postural triple task (cognitive dual-task with postural demands). Postural sway (i.e., total center of pressure displacements) was recorded in semistance position on an unstable surface that was placed on top of a force plate while performing cognitive tasks. Neural activation was recorded using a 64-channel mobile EEG system. EEG frequencies were attenuated by the baseline postural single-task condition and demarcated in nine Regions-of-Interest (ROIs), i.e., anterior, central, posterior, over the cortical midline, and both hemispheres. Our findings revealed impaired cognitive dual-task performance in old compared to young participants in the form of significantly lower cognitive performance in the triple-task condition. Furthermore, old adults compared with young adults showed significantly larger postural sway, especially in cognitive-postural task conditions. With respect to EEG frequencies, young compared to old participants showed significantly lower alpha-band activity in cognitive-cognitive-postural triple-task conditions compared with cognitive-postural dual tasks. In addition, with increasing task difficulty, we observed synchronized theta and delta frequencies, irrespective of age. Task-dependent alterations of the alpha frequency band were most pronounced over frontal and central ROIs, while alterations of the theta and delta frequency bands were found in frontal, central, and posterior ROIs. Theta and delta synchronization exhibited a decrease from anterior to posterior regions. For old adults, task difficulty was reflected by theta synchronization in the posterior ROI. For young adults, it was reflected by alpha desynchronization in bilateral anterior ROIs. In addition, we could not identify any effects of task difficulty and age on the beta frequency band. Our results shed light on age-related cognitive and postural declines and how they interact. Modulated alpha frequencies during high cognitive-postural task demands in young but not old adults might be reflective of a constrained neural adaptive potential in old adults. Future studies are needed to elucidate associations between the identified age-related performance decrements with task difficulty and changes in brain activity.

Motivational effects on the processing of delayed intentions in the anterior prefrontal cortex.

Delaying intentions bears the risk of interference from distracting activities during the delay interval. Motivation can increase intention retrieval success but little is known about the underlying brain mechanisms. Here, we investigated whether motivational incentives (monetary reward) modulate the processing of delayed intentions in the anterior prefrontal cortex (aPFC), known to be crucial for intention processing. Using a mixed blocked and event-related functional Magnetic Resonance Imaging design, we specifically tested whether reward affects intention processing in the aPFC in a transient or in a sustained manner and whether this is related to individual differences in retrieval success. We found a generalized effect of reward on both correct intention retrieval and ongoing task performance. Fronto-parietal regions including bilateral lateral aPFC showed sustained activity increases in rewarded compared to non-rewarded blocks as well as transient reward-related activity during the storage phase. Additionally, individual differences in reward-related performance benefits were related to the degree of transient signal increases in right lateral aPFC, specifically during intention encoding. This suggests that the ability to integrate motivational relevance into the encoding of future intentions is crucial for successful intention retrieval in addition to general increases in processing effort. Bilateral aPFC is central to these motivation-cognition interactions.

Striatal activation as a neural link between cognitive and perceptual flexibility.

Our brain continuously evaluates different perceptual interpretations of the available sensory data in order to enable flexible updates of conscious experience. Individuals' perceptual flexibility can be assessed using ambiguous stimuli that cause our perception to continuously switch between two mutually exclusive interpretations. Neural processes underlying perceptual switching are thought to involve the visual cortex, but also non-sensory brain circuits that have been implicated in cognitive processes, such as frontal and parietal regions. Perceptual flexibility varies strongly between individuals and has been related to dopaminergic neurotransmission. Likewise, there is also considerable individual variability in tasks that require flexibility in cognition, and dopamine-dependent striato-frontal signals have been associated with processes promoting cognitive flexibility. Given the anatomical and neurochemical similarities with regard to perceptual and cognitive flexibility, we here probed whether individual differences in perceptual flexibility during bistable perception are related to individual cognitive flexibility associated neural correlates. 126 healthy individuals performed rule-based task switching during functional magnetic resonance imaging (fMRI) and reported perceptual switching during the viewing of a modified version of the Necker cube. Mean phase duration as measure of perceptual flexibility correlated with task-switching associated activity in the right putamen as part of the basal ganglia. In addition, we found a tentative correlation between perceptual and cognitive flexibility. These results indicate that individual differences in cognitive flexibility and associated fronto-striatal processing contribute to differences in perceptual flexibility. Our findings thus provide empirical support for the general notion of shared mechanisms between perception and cognition.

Neural correlates of training and transfer effects in working memory in older adults.

As indicated by previous research, aging is associated with a decline in working memory (WM) functioning, related to alterations in fronto-parietal neural activations. At the same time, previous studies showed that WM training in older adults may improve the performance in the trained task (training effect), and more importantly, also in untrained WM tasks (transfer effects). However, neural correlates of these transfer effects that would improve understanding of its underlying mechanisms, have not been shown in older participants as yet. In this study, we investigated blood-oxygen-level-dependent (BOLD) signal changes during n-back performance and an untrained delayed recognition (Sternberg) task following 12sessions (45min each) of adaptive n-back training in older adults. The Sternberg task used in this study allowed to test for neural training effects independent of specific task affordances of the trained task and to separate maintenance from updating processes. Thirty-two healthy older participants (60-75years) were assigned either to an n-back training or a no-contact control group. Before (t1) and after (t2) training/waiting period, both the n-back task and the Sternberg task were conducted while BOLD signal was measured using functional Magnetic Resonance Imaging (fMRI) in all participants. In addition, neuropsychological tests were performed outside the scanner. WM performance improved with training and behavioral transfer to tests measuring executive functions, processing speed, and fluid intelligence was found. In the training group, BOLD signal in the right lateral middle frontal gyrus/caudal superior frontal sulcus (Brodmann area, BA 6/8) decreased in both the trained n-back and the updating condition of the untrained Sternberg task at t2, compared to the control group. fMRI findings indicate a training-related increase in processing efficiency of WM networks, potentially related to the process of WM updating. Performance gains in untrained tasks suggest that transfer to other cognitive tasks remains possible in aging.

Dissociable effects of motivation and expectancy on conflict processing: an fMRI study.

Previous studies suggest that both motivation and task difficulty expectations activate brain regions associated with cognitive control. However, it remains an open question whether motivational and cognitive determinants of control have similar or dissociable impacts on conflict processing on a neural level. The current study tested the effects of motivation and conflict expectancy on activity in regions related to processing of the target and the distractor information. Participants performed a picture-word interference task in which we manipulated the size of performance-dependent monetary rewards (level of motivation) and the ratio of congruent to incongruent trials within a block (level of conflict expectancy). Our results suggest that motivation improves conflict processing by facilitating task-relevant stimulus processing and task difficulty expectations mainly modulate the processing of distractor information. We conclude that motivation and conflict expectancy engage dissociable control strategies during conflict resolution.

Motivation by potential gains and losses affects control processes via different mechanisms in the attentional network.

Attentional control in demanding cognitive tasks can be improved by manipulating the motivational state. Motivation to obtain gains and motivation to avoid losses both usually result in faster reaction times and stronger activation in relevant brain areas such as the prefrontal cortex, but little is known about differences in the underlying neurocognitive mechanisms of these types of motivation in an attentional control context. In the present functional magnetic resonance imaging (fMRI) study, we tested whether potential gain and loss as motivating incentives lead to overlapping or distinct neural effects in the attentional network, and whether one of these conditions is more effective than the other. A Flanker task with word stimuli as targets and distracters was performed by 115 healthy participants. Using a mixed blocked and event-related design allowed us to investigate transient and sustained motivation-related effects. Participants could either gain money (potential gain) or avoid losing money (potential loss) in different task blocks. Participants showed a congruency effect with increased reaction times for incongruent compared to congruent trials. Potential gain led to generally faster responses compared to the neutral condition and to stronger improvements than potential loss. Potential loss also led to shorter response times compared to the neutral condition, but participants improved mainly during incongruent and not during congruent trials. The event-related fMRI data revealed a main effect of congruency with increased activity in the left inferior frontal gyrus (IFG) and inferior frontal junction area (IFJ), the pre-supplementary motor area (pre-SMA), bilateral insula, intraparietal sulcus (IPS) and visual word form area (VWFA). While potential gain led to increased activity in a cluster of the IFJ and the VWFA only during incongruent trials, potential loss was linked to activity increases in these regions during incongruent and congruent trials. The block analysis revealed greater activity in gain and loss blocks compared to the neutral condition in most of these regions but no differences in the direct comparison of gain and loss blocks. These findings show that potential monetary gain and loss rely on different mechanisms: Gain was more effective in reducing the reaction time compared to potential loss. Brain data indicate that in the gain context attentional control is executed specifically in incongruent trials, whereas the loss context induces an unspecific increase of attentional control. These findings extend previous studies by providing evidence for diverging neural mechanisms for the effects of different types of motivation on attentional control, specifying the underlying activity patterns in task- and stimulus-related regions.

Trait anxiety and the neural efficiency of manipulation in working memory.

The present study investigates the effects of trait anxiety on the neural efficiency of working memory component functions (manipulation vs. maintenance) in the absence of threat-related stimuli. For the manipulation of affectively neutral verbal information held in working memory, high- and low-anxious individuals (N = 46) did not differ in their behavioral performance, yet trait anxiety was positively related to the neural effort expended on task processing, as measured by BOLD signal changes in fMRI. Higher levels of anxiety were associated with stronger activation in two regions implicated in the goal-directed control of attention--that is, right dorsolateral prefrontal cortex (DLPFC) and left inferior frontal sulcus--and with stronger deactivation in a region assigned to the brain's default-mode network--that is, rostral-ventral anterior cingulate cortex. Furthermore, anxiety was associated with a stronger functional coupling of right DLPFC with ventrolateral prefrontal cortex. We interpret our findings as reflecting reduced processing efficiency in high-anxious individuals and point out the need to consider measures of functional integration in addition to measures of regional activation strength when investigating individual differences in neural efficiency. With respect to the functions of working memory, we conclude that anxiety specifically impairs the processing efficiency of (control-demanding) manipulation processes (as opposed to mere maintenance). Notably, this study contributes to an accumulating body of evidence showing that anxiety also affects cognitive processing in the absence of threat-related stimuli.

The future of the Affective Neuroscience Personality Scales: A reflection on seven pressing matters.

The Affective Neuroscience Personality Scales (ANPS) were designed to provide researchers in the mental sciences with an inventory to assess primary emotional systems according to Pankseppian Affective Neuroscience Theory (ANT). The original ANPS, providing researchers with such a tool, was published in 2003. In the present brief communication, about 20 years later, we reflect upon some pressing matters regarding the further development of the ANPS. We touch upon problems related to disentangling traits and states of the primary emotional systems with the currently available versions of the ANPS and upon its psychometric properties and its length. We reflect also on problems such as the large overlap between the SADNESS and FEAR dimensions, the disentangling of PANIC and GRIEF in the context of SADNESS, and the absence of a LUST scale. Lastly, we want to encourage scientists with the present brief communication to engage in further biological validation of the ANPS.

Effects of Physical and Mental Fatigue on Postural Sway and Cortical Activity in Healthy Young Adults.

Physical fatigue (PF) negatively affects postural control, resulting in impaired balance performance in young and older adults. Similar effects on postural control can be observed for mental fatigue (MF) mainly in older adults. Controversial results exist for young adults. There is a void in the literature on the effects of fatigue on balance and cortical activity. Therefore, this study aimed to examine the acute effects of PF and MF on postural sway and cortical activity. Fifteen healthy young adults aged 28 ± 3 years participated in this study. MF and PF protocols comprising of an all-out repeated sit-to-stand task and a computer-based attention network test, respectively, were applied in random order. Pre and post fatigue, cortical activity and postural sway (i.e., center of pressure displacements [CoPd], velocity [CoPv], and CoP variability [CV CoPd, CV CoPv]) were tested during a challenging bipedal balance board task. Absolute spectral power was calculated for theta (4-7.5 Hz), alpha-2 (10.5-12.5 Hz), beta-1 (13-18 Hz), and beta-2 (18.5-25 Hz) in frontal, central, and parietal regions of interest (ROI) and baseline-normalized. Inference statistics revealed a significant time-by-fatigue interaction for CoPd (p = 0.009, d = 0.39, Δ 9.2%) and CoPv (p = 0.009, d = 0.36, Δ 9.2%), and a significant main effect of time for CoP variability (CV CoPd: p = 0.001, d = 0.84; CV CoPv: p = 0.05, d = 0.62). Post hoc analyses showed a significant increase in CoPd (p = 0.002, d = 1.03) and CoPv (p = 0.003, d = 1.03) following PF but not MF. For cortical activity, a significant time-by-fatigue interaction was found for relative alpha-2 power in parietal (p < 0.001, d = 0.06) areas. Post hoc tests indicated larger alpha-2 power increases after PF (p < 0.001, d = 1.69, Δ 3.9%) compared to MF (p = 0.001, d = 1.03, Δ 2.5%). In addition, changes in parietal alpha-2 power and measures of postural sway did not correlate significantly, irrespective of the applied fatigue protocol. No significant changes were found for the other frequency bands, irrespective of the fatigue protocol and ROI under investigation. Thus, the applied PF protocol resulted in increased postural sway (CoPd and CoPv) and CoP variability accompanied by enhanced alpha-2 power in the parietal ROI while MF led to increased CoP variability and alpha-2 power in our sample of young adults. Potential underlying cortical mechanisms responsible for the greater increase in parietal alpha-2 power after PF were discussed but could not be clearly identified as cause. Therefore, further future research is needed to decipher alternative interpretations.

The acute effects of mental fatigue on balance performance in healthy young and older adults - A systematic review and meta-analysis.

Cognitive resources contribute to balance control. There is evidence that mental fatigue reduces cognitive resources and impairs balance performance, particularly in older adults and when balance tasks are complex, for example when trying to walk or stand while concurrently performing a secondary cognitive task. We conducted a systematic literature search in PubMed (MEDLINE), Web of Science and Google Scholar to identify eligible studies and performed a random effects meta-analysis to quantify the effects of experimentally induced mental fatigue on balance performance in healthy adults. Subgroup analyses were computed for age (healthy young vs. healthy older adults) and balance task complexity (balance tasks with high complexity vs. balance tasks with low complexity) to examine the moderating effects of these factors on fatigue-mediated balance performance. We identified 7 eligible studies with 9 study groups and 206 participants. Analysis revealed that performing a prolonged cognitive task had a small but significant effect (SMDwm = -0.38) on subsequent balance performance in healthy young and older adults. However, age- and task-related differences in balance responses to fatigue could not be confirmed statistically. Overall, aggregation of the available literature indicates that mental fatigue generally reduces balance in healthy adults. However, interactions between cognitive resource reduction, aging and balance task complexity remain elusive.

Modality-specific effects of mental fatigue in multitasking.

The mechanisms underlying increased dual-task costs in the comparison of modality compatible stimulus-response mappings (e.g., visual-manual, auditory-vocal) and modality incompatible mappings (e.g., visual-vocal, auditory-manual) remain elusive. To investigate whether additional control mechanisms are at work in simultaneously processing two modality incompatible mappings, we applied a transfer logic between both types of dual-task mappings in the context of a mental fatigue induction. We expected an increase in dual-task costs for both modality mappings after a fatigue induction with modality compatible tasks. In contrast, we expected an additional, selective increase in modality incompatible dual-task costs after a fatigue induction with modality incompatible tasks. We tested a group of 45young individuals (19-30 years) in an online pre-post design, in which participants were assigned to one of three groups. The two fatigue groups completed a 90-min time-on-task intervention with a dual task comprising either compatible or incompatible modality mappings. The third group paused for 90 min as a passive control group. Pre and post-session contained single and dual tasks in both modality mappings for all participants. In addition to behavioral performance measurements, seven subjective items (effort, focus, subjective fatigue, motivation, frustration, mental and physical capacity) were analyzed. Mean dual-task performance during and after the intervention indicated a practice effect instead of the presumed fatigue effect for all three groups. The modality incompatible intervention group showed a selective performance improvement for the modality incompatible mapping but no transfer to the modality compatible dual task. In contrast, the compatible intervention group showed moderately improved performance in both modality mappings. Still, participants reported increased subjective fatigue and reduced motivation after the fatigue intervention. This dynamic interplay of training and fatigue effects suggests that high control demands were involved in the prolonged performance of a modality incompatible dual task, which are separable from modality compatible dual-task demands.

Frontostriatal involvement in task switching depends on genetic differences in d2 receptor density.

Recent studies suggest an association of dopamine D2 receptor (DRD2) availability with flexibility in reward-based learning. We extend these results by demonstrating an association of genetically based differences in DRD2 density with the ability to intentionally switch between nonrewarded tasks: noncarriers of the A1 allele of the DRD2/ANKK1-TaqIa polymorphism, associated with higher DRD2 density, show increased task-switching costs, increased prefrontal switching activity in the inferior frontal junction area, and increased functional connectivity in dorsal frontostriatal circuits, relative to A1 allele carriers. A DRD2 haplotype analysis in the same sample confirmed these results, indicating an association between high D2 density and increased task-switching effort. Our results provide evidence that converges with that from association studies relating increased D2 density to deficits in cognitive flexibility in schizophrenia. We suggest that individual differences in striatal D2 signaling in healthy humans modulate goal-directed gating to prefrontal cortex, thus leading to individual differences in switching intentionally to newly relevant behaviors.

Trait anxiety modulates the neural efficiency of inhibitory control.

An impairment of attentional control in the face of threat-related distracters is well established for high-anxious individuals. Beyond that, it has been hypothesized that high trait anxiety more generally impairs the neural efficiency of cognitive processes requiring attentional control-even in the absence of threat-related stimuli. Here, we use fMRI to show that trait anxiety indeed modulates brain activation and functional connectivities between task-relevant brain regions in an affectively neutral Stroop task. In high-anxious individuals, dorsolateral pFC showed stronger task-related activation and reduced coupling with posterior lateral frontal regions, dorsal ACC, and a word-sensitive area in the left fusiform gyrus. These results support the assumption that a general (i.e., not threat-specific) impairment of attentional control leads to reduced neural processing efficiency in anxious individuals. The increased dorsolateral pFC activation is interpreted as an attempt to compensate for suboptimal connectivity within the cortical network subserving task performance.

Functional connectivity separates switching operations in the posterior lateral frontal cortex.

Task representations consist of different aspects such as the representations of the relevant stimuli, the abstract rules to be applied, and the actions to be performed. To be flexible in our daily lives, we frequently need to switch between some or all aspects of a task. In the present study, we examined whether switching between abstract task rules and switching between response hands is associated with overlapping regions in the posterior lateral frontal cortex and whether switching between these two aspects of a task representation is neurally implemented by distinct functional brain networks. Subjects performed a cue-based task-switching paradigm where the location of the task cue additionally specified the response hand to be used. Overlapping activity for switching between abstract rules versus response hands was present in the inferior frontal junction area of the posterolateral frontal cortex. This region, however, showed very distinct patterns of functional connectivity depending on the content of the switch: Increased functional connectivity with anterior prefrontal, superior frontal, and hippocampal regions was present for abstract rule switching, whereas response hand switching led to increased coupling with motor regions surrounding the central sulcus. These results reveal that a rather general involvement of the posterior lateral frontal cortex in different switching contexts can be further characterized by highly specific functional interactions with other task-relevant regions, depending on the content of the switch.

Interference effects of stimulus-response modality pairings in dual tasks and their robustness.

Recent evidence suggests that the degree of interference in dual-task situations depends crucially on the pairings of input- and output modalities of the two component tasks with increased dual-task costs for modality incompatible (i.e., visual-vocal and auditory-manual) compared to modality compatible (i.e., visual-manual and auditory-vocal) dual tasks. These effects of modality pairings in dual tasks have been related to the overlap of non-preferred processing pathways in modality incompatible tasks. Until now, modality compatibility has not yet been related to other sources of interference in a dual-task context, such as stimulus-response (S-R) compatibility or crosstalk. In the present study, we conducted two experiments using the paradigm of the psychological refractory period (PRP) to test the effects of S-R compatibility and crosstalk on the effects of modality compatibility in temporally overlapping task situations. Experiment 1 revealed an overadditive interaction between stimulus onset asynchrony and modality compatibility for tasks with S-R compatible mappings, indicating that modality compatibility effects are present in different task situations, even when S-R mappings are otherwise compatible. In Experiment 2, we aimed at pinpointing the boundaries of the effects of modality compatibility in dual-task situations. We showed that additional sources of dual-task interference in a modality compatible dual task could overwrite the pronounced PRP effect previously shown for modality incompatible tasks. Taken together, these data provide new evidence that the specific types of stimulus-response modality pairings are an additional factor that might interact with other sources of interference in dual-task situations.

Neurocognitive Effects of Self-Determined Choice and Emotional Arousal on Time Estimation.

Even though effects of emotion and motivation on cognition are well documented, the interaction of all three factors is rarely investigated. Here, we used electroencephalography (EEG) to examine the effects of self-determined choice-as an experimental manipulation of intrinsic motivation - and emotional stimulus content on task preparation and engagement in a temporal production task. Behavioral results indicated a modulation of time processing depending on choice and emotional content. Underlying EEG signals revealed differential modulations by choice on the contingent negative variation (CNV) during task and response preparation and by emotional content on the late positive potential (LPP) in response to the onset of an emotional picture during temporal production. Also, we obtained preliminary evidence for interaction effects of choice and emotional content on the LPP. The feedback-related negativity (FRN) in response to information regarding temporal production success was also affected by interactions of choice and emotional content. These findings indicate that besides separate effects of motivation and emotion, there may be time windows during task engagement in which both factors jointly affect cognitive processing. These results are interpreted as dynamic modulations of attentional resource allocation.

Cognitive-Postural Multitasking Training in Older Adults - Effects of Input-Output Modality Mappings on Cognitive Performance and Postural Control.

Older adults exhibit impaired cognitive and balance performance, particularly under multi-task conditions, which can be improved through training. Compatibility of modality mappings in cognitive tasks (i.e., match between stimulus modality and anticipated sensory effects of motor responses), modulates physical and cognitive dual-task costs. However, the effects of modality specific training programs have not been evaluated yet. Here, we tested the effects of cognitive-postural multi-tasking training on the ability to coordinate task mappings under high postural demands in healthy older adults. Twenty-one adults aged 65-85 years were assigned to one of two groups. While group 1 performed cognitive-postural triple-task training with compatible modality mappings (i.e., visual-manual and auditory-vocal dual n-back tasks), group 2 performed the same tasks with incompatible modality mappings (i.e., visual-vocal and auditory-manual n-back tasks). Throughout the 6-weeks balance training intervention, working-memory load was gradually increased while base-of-support was reduced. Before training (T0), after a 6-week passive control period (T1), and immediately after the intervention (T2), participants performed spatial dual one-back tasks in semi-tandem stance position. Our results indicate improved working-memory performance and reduced dual-task costs for both groups after the passive control period, but no training-specific performance gains. Furthermore, balance performance did not improve in response to training. Notably, the cohort demonstrated meaningful interindividual variability in training responses. Our findings raise questions about practice effects and age-related heterogeneity of training responses following cognitive-motor training. Following multi-modal balance training, neither compatible nor incompatible modality mappings had an impact on the observed outcomes.

The BDNF Val66Met polymorphism and anxiety: support for animal knock-in studies from a genetic association study in humans.

Mounting evidence shows that the brain derived neurotrophic factor (BDNF) plays a crucial role in depression and anxiety. The discovery of a functional variant of the BDNF gene--the BDNF Val66Met polymorphism--led to new insights into the molecular genetic mechanisms underlying these emotional disorders. Although there is evidence from animal research that the homozygous BDNF 66Met variant is associated with anxiety-like behaviour, findings from personality research using self-report-measures as indicators of trait anxiety are heterogenous. Recent seminal findings from a study using a knock-in mouse design suggest that this Met66Met group is of particular interest for the investigation of the molecular genetic mechanisms of anxiety and anxiety-related personality traits in humans. In a sample of 610 Caucasian participants, subjects homozygous for the 66Met allele scored significantly higher than Val66 allele carriers on anxiety-related facets of the construct 'harm avoidance' (i.e., 'anticipatory worry' and 'fear of uncertainty') of the Temperament and Character Inventory. This finding adds to a small plurality of studies that associates the 66Met allele, rather than the Val66 allele, with higher anxiety scores. Importantly, the present results furthermore suggest that it is the occurrence of not one but two 66Met alleles that is associated with high trait anxiety.

Neural mechanisms of concurrent stimulus processing in dual tasks.

Little is known about how the human brain processes multiple relevant information streams competing for behavior. The present study aimed at specifying the interaction of the lateral prefrontal cortex (lPFC) with task-relevant sensory brain regions during concurrent stimulus processing of two relevant stimuli (S1, S2) in a classical dual-task situation. In detail, we tested whether S1 processing is independent of the task relevance of S2 as has been hypothesised in cognitive theories on dual-task processing. Using functional Magnetic Resonance Imaging, we tested two neural mechanisms that might reflect effects of S2 relevance on S1 processing at different temporal overlaps. The results indicate that: (1) activity amplitudes in S1-relevant regions in the inferior temporal cortex were similarly affected by the temporal overlap between the two stimuli when S2 was relevant or irrelevant and (2) only when S2 was relevant in the dual task, significant increases in the functional coupling between S1-relevant regions and dual-task-related regions in the posterior lPFC were present at high temporal overlap. No similar effects were found for S2-relevant regions. These findings suggest that concurrent stimulus processing in dual tasks is realised by transient changes in functional coupling for stimuli with relatively higher priority (S1).

Effects of dopamine-related gene-gene interactions on working memory component processes.

Dopamine modulates complex cognitive functions like working memory and cognitive control. It is widely accepted that an optimal level of prefrontal dopamine supports working memory performance. In the present study we used a molecular genetic approach to test whether the optimal activity of the dopamine system for different component processes of working memory is additionally related to the availability of dopamine D2 receptors. We sought evidence for this assumption by investigating the interaction effect (epistasis) of variations in two dopaminergic candidate genes: the catechol-O-methyltransferase (COMT) Val(158)Met polymorphism, which has been shown to influence prefrontal dopamine concentration, and the DRD2/ANKK1-Taq-Ia polymorphism, which has been related to the density of D2 receptors. Our results show that COMT effects on working memory performance are modulated by the DRD2/ANKK1-TAQ-Ia polymorphism and the specific working memory component process under investigation. Val-participants--supposedly characterized by increased prefrontal dopamine concentrations--outperformed Val+ participants in the manipulation of working memory contents, but only when D2 receptor density could be considered to be high. No such effect was present for passive maintenance of working memory contents or for maintenance in the face of distracting information. This beneficial effect of a balance between prefrontal dopamine availability and D2 receptor density reveals the importance of considering epistasis effects and different working memory subprocesses in genetic association studies.