Stephan Getzmann

BDNF Val66Met polymorphism and goal-directed behavior in healthy elderly — evidence from auditory distraction

Aging affects the ability to focus attention on a given task and to ignore distractors. These functions subserve response control processes for which fronto-striatal networks have been shown to play an important role. Within these networks, the brain-derived-neurotrophic-factor (BDNF), which is known to underlie aging effects, plays a pivotal role. We investigated how cognitive subprocesses constituting a cycle of distraction, orientation and refocusing of attention are affected by the functional BDNF Val66Met polymorphism using event-related potentials (ERPs) in 122 healthy elderly. Using an auditory distraction paradigm we found that the Val/Val genotype confers a disadvantage to its carriers. This disadvantage was partly compensated by intensified attentional shifting mechanisms. It could be based on response selection processes being more vulnerable against interference from distractors in this genotype group. Processes reflecting transient sensory memory processes, or the re-orientation of attention were not affected by the BDNF Val66Met polymorphism, suggesting a higher importance of BDNF for mechanisms related to response control, than stimulus processing. The results add on recent literature showing that the Met allele confers some benefit to its carriers. We suggest an account for unifying different results of BDNF Val66Met association studies in executive functions, based on the role of BDNF in fronto-striatal circuits.

Does age increase auditory distraction? Electrophysiological correlates of high and low performance in seniors.

Aging usually affects the ability to focus attention on a given task and to ignore distractors. However, aging is also associated with increased between-subject variability, and it is unclear in which features of processing older high-performing and low-performing human beings may differ in goal-directed behavior. To study involuntary shifts in attention to task-irrelevant deviant stimuli and subsequent reorientation, we used an auditory distraction task and analyzed event-related potential measures (mismatch negativity), P3a and reorienting negativity) of 35 younger, 32 older high-performing, and 32 older low-performing participants. Although both high and low performing elderly individuals showed a delayed reorienting to the primary stimulus feature, relative to young participants, poor performance of the elderly participants in processing of deviant stimuli was associated with strong involuntary attention capture by task-irrelevant features. In contrast, high performance of the elderly group was associated with intensified attentional shifting toward the target features. Thus, it appears that performance deficits in aging are due to higher distractibility in combination with deficits in the orienting-reorienting mechanisms.

Long-Term Cardiovascular Fitness Is Associated with Auditory Attentional Control in Old Adults: Neuro- Behavioral Evidence

It has been shown that healthy aging affects the ability to focus attention on a given task and to ignore distractors. Here, we asked whether long-term physical activity is associated with lower susceptibility to distraction of auditory attention, and how physically active and inactive seniors may differ regarding subcomponents of auditory attention. An auditory duration discrimination task was employed, and involuntary attentional shifts to task-irrelevant rare frequency deviations and subsequent reorientation were studied by analysis of behavioral data and event-related potential measures. The frequency deviations impaired performance more in physically inactive than active seniors. This was accompanied by a stronger frontal positivity (P3a) and increased activation of anterior cingulate cortex, suggesting a stronger involuntary shift of attention towards task-irrelevant stimulus features in inactive compared to active seniors. These results indicate a positive relationship between physical fitness and attentional control in elderly, presumably due to more focused attentional resources and enhanced inhibition of irrelevant stimulus features.

N-Acetyltransferase 2: ultra-slow acetylators enter the stage.

of NAT2 in humans by the ratio of two caffeine metabolites in urine (Selinski et al. 2011). Recent in vivo studies indicate remarkable differences in the subgroup of slow acetylators leading to a differentiation between “ultra-slow” and “all other slow” acetylators (Selinski et al. 2013b; Ruiz et al. 2012). Ultra-slow acetylators are persons with two copies of the frequent NAT*6A haplotype and/or perhaps other infrequent haplotypes from the NAT2*6 (sharing rs1799930, G590A with *6A) cluster or NAT2*7B (sharing rs1041983, C282A with *6A). Two independent studies in Europeans found a 35 (Ruiz et al. 2012) and 46 % (Selinski et al. 2013b), respectively, decreased NAT2 capacity in NAT2*6/*6 genotypes compared to slow *5/*5. From the functional perspective, the missense SNP rs1799930 (G590A) is more likely than the synonymous rs1041983 (C282A) to result in an even more reduced metabolic capacity than the “all other slow” NAT2*5 and further less frequent slow haplotypes (*11 and *14). However, NAT2*7B shows in vivo also a reduced metabolic capacity though data are sparse (frequency: 2–3 % in Europeans). New studies and re-evaluation of older studies indicate that this further reduced metabolic capacity of the ultra-slow acetylators may have a particular impact on a number of biological outcomes ranging from drug efficacy and side effects, bladder cancer risk to agerelated impairments. Interestingly, in vitro studies show contrary results suggesting the NAT2*5 haplotype cluster (rs1801280, T341C) to result in clearly lower acetylation capacity than NAT2*6 and *7 haplotypes (Hein 2002). NAT2 shows a remarkable interethnic variability (Garcia-Martin 2008; Selinski et al. 2013a) regarding the haplotype distribution and the proportion of slow acetylators. So, interpretation of NAT2 effects should consider these differences, e.g. absence of particular haplotypes in certain populations. These interethnic differences give rise to the The polymorphic N-Acetyltransferase 2 (NAT2) is a wellcharacterised key enzyme in the phase II metabolism of aromatic amines and heterocyclic aromatic amines present in a wide range of xenobiotics such as pharmaceutical drugs and carcinogens from tobacco smoke, workplace, environment and food (Selinski et al. 2014). Patterns of polymorphisms—so-called haplotypes or NAT2 alleles— result in a reduced N-, Oand N,O-acetylation of aromatic and heterocyclic amines—in general rather due to a reduction in protein as due to structural changes in the enzyme (McDonagh et al. 2014; Hein et al. 2008). Persons with an impaired NAT2 capacity—so-called slow acetylators— have two slow copies of the gene, whereas the presence of one or two rapid or wild-type copies of the gene leads to an intermediate or rapid genotype—so-called rapid acetylators. The relationship between genotype and NAT2 activity has been investigated extensively in vitro using bacterial, yeast and eukaryotic cell systems (Selinski et al. 2014; Walraven et al. 2008; Garcia-Closas et al. 2011). Furthermore, the caffeine test (using a further NAT2 substrate) allows the determination of the metabolic capacity

On the neural mechanisms underlying the protective function of retroactive cuing against perceptual interference: Evidence by event-related potentials of the EEG

This EEG study investigated the protective effect of retroactive attentional focusing on working memory. To this effect, we used a visuo-spatial working memory task and presented block-wise distractor displays after working memory contents had been updated by means of a retroactive cue (retro-cue). Retroactive attention attenuated the interfering effect of distractors on memory precision. The reduction of working memory load by means of a selective retro-cue was reflected by a decline of a negative slow wave over parietal sites. Posterior N1 to the distractor was reduced following a selective retro-cue compared to a neutral retro-cue condition, most notably at left hemispheric sites. P3b referred to the distractor was suppressed completely only following a selective retro-cue. This suggests that focusing on only a subset of visuo-spatial information represented in working memory releases cognitive resources for preventing the in-depth processing of subsequently irrelevant visual events, thereby inhibiting their transfer into working memory.

Executive control, ERP and pro-inflammatory activity in emotionally exhausted middle-aged employees. Comparison between subclinical burnout and mild to moderate depression

Burnout is a syndrome occurring mainly in individuals with long-term stressful work. The main complaints are emotional exhaustion and reduced performance. Burnout also largely overlaps with depression. Both are characterized by increased incidence of infections due to dysregulation of the immune system, overexpression of pro-inflammatory cytokines and cognitive deficits, particularly related to executive functions. To distinguish between burnout and depression already at the pre-clinical stage, the present double-blinded study compared immunological and cognitive parameters in seventy-six employees from emotionally demanding occupations who were post-hoc subdivided into two groups scoring low (EE-) and high (EE+) in emotional exhaustion and low (DE-) and high (DE+) in depression. Immunological parameters were measured from blood samples. Executive functions were studied by analyzing event-related brain potentials (ERPs) and performance during a task switching paradigm. Psychosocial job parameters were measured with standardized questionnaires. Burnout and mild to moderate depression largely overlapped. However, several subjects showed burnout without depressive symptoms. Higher levels of the pro-inflammatory cytokines IL-6 and IL-12 were correlated with burnout severity and depressive symptoms in male individuals. In the switch task a trend for lower performance in the EE+ vs. EE- group and no difference between DE+ and DE- groups were found. In the ERPs, however, differences were observed which distinguished between subclinical burnout and depression: the terminal contingent negative variation (CNV), indicating preparatory activity and the P3b, related to allocation of cognitive resources were generally reduced in EE+ vs. EE-, whereas no differences were found in the DE+ vs. DE- groups. The frontal P3a was selectively reduced in switch trials in the EE+ vs. EE- group and showed only a trend in DE+ vs. DE-, indicating impairment of executive control in subclinical burnout. Taken together, the results unveil specific immunological changes and declines in brain functions in employees with subclinical burnout that are not apparent in persons with moderate depression. Hence, the combination of immunological, behavioral and ERP methods renders a promising method for distinguishing both syndromes and for improving an early diagnosis of burnout before a clinical stage is reached.

The mismatch negativity as a measure of auditory stream segregation in a simulated “cocktail-party” scenario: effect of age

With age the ability to understand speech in multitalker environments usually deteriorates. The central auditory system has to perceptually segregate and group the acoustic input into sequences of distinct auditory objects. The present study used electrophysiological measures to study effects of age on auditory stream segregation in a multitalker scenario. Younger and older adults were presented with streams of short speech stimuli. When a single target stream was presented, the occurrence of a rare (deviant) syllable among a frequent (standard) syllable elicited the mismatch negativity (MMN), an electrophysiological correlate of automatic deviance detection. The presence of a second, concurrent stream consisting of the deviant syllable of the target stream reduced the MMN amplitude, especially when located nearby the target stream. The decrease in MMN amplitude indicates that the rare syllable of the target stream was less perceived as deviant, suggesting reduced stream segregation with decreasing stream distance. Moreover, the presence of a concurrent stream increased the MMN peak latency of the older group but not that of the younger group. The results provide neurophysiological evidence for the effects of concurrent speech on auditory processing in older adults, suggesting that older adults need more time for stream segregation in the presence of concurrent speech.

The contribution of selective spatial attention to sound detection and sound localization: evidence from event-related potentials and lateralized alpha oscillations

Auditory selective attention can be directed toward spatial and non-spatial stimulus features. Here, we studied electrophysiological correlates of spatial attention under spatially-specific and purely feature-based demands. Using an auditory search paradigm, in which participants performed a target localization (left versus right) and a target detection task (present versus absent), we investigated whether attentional selection of a relevant sound from a two- or four-sound array necessarily involves the processing of spatial sound information. While the early N2 anterior contralateral component occurred irrespective of task, the subsequent lateralization of alpha power oscillations (8-12 Hz) over parieto-occipital scalp was modulated by the task-relevance of spatial information. Thus, the two correlates appear to reflect differential aspects of attentional orienting: We propose that the N2ac reflects an initial, modality-specific focusing of attention onto a lateralized target, while the subsequent alpha lateralization appears associated with the spatiotopic access to presumably supramodal representations of the sound array.

Searching for auditory targets in external space and in working memory: Electrophysiological mechanisms underlying perceptual and retroactive spatial attention

ABSTRACT Attention can be shifted within internal representations maintained in working memory. These retroactive processes are particularly inherent to the processing of auditory information that is especially transient over time and thus, requires us to continuously maintain, attend to, and integrate information in working memory. Using EEG recordings, the present study investigated the neurophysiological mechanisms underlying selective spatial attention in a retroactive as opposed to a perceptual auditory search task. Two kinds of sound stimuli were employed: a horizontal sound array consisting of two natural sounds presented simultaneously in the left and right hemispace and a central single target sound. The target sound was provided either after (retroactive search) or before the presentation of the sound array (perceptual search). In both search conditions, participants completed a sound localization and a sound detection task, indicating the position (left or right) or the presence versus absence (yes or no) of a particular target sound. Analyses revealed a lateralization of alpha power oscillations (8–12Hz) over parieto‐occipital scalp in both perceptual and retroactive sound localization tasks, but not in respective sound detection tasks, suggesting auditory alpha lateralization to be restricted to spatially‐specific task demands. The observed asymmetric modulations of alpha power in sound localization are consistent with analogous findings from the visual domain, supporting the supramodal role of alpha oscillations in the deployment of spatial attention. Hence, we conclude that auditory alpha lateralization is a higher‐order attention mechanism that operates in perceptual and mnemonic space reflecting the access to a spatially‐specific, supramodal response template.