COMT and DRD2/ANKK-1 gene-gene interaction account for resetting of gamma neural oscillations to auditory stimulus-driven attention.

Attention capture by potentially relevant environmental stimuli is critical for human survival, yet it varies considerably among individuals. A large series of studies has suggested that attention capture may depend on the cognitive balance between maintenance and manipulation of mental representations and the flexible switch between goal-directed representations and potentially relevant stimuli outside the focus of attention; a balance that seems modulated by a prefrontostriatal dopamine pathway. Here, we examined inter-individual differences in the cognitive control of attention through studying the effects of two single nucleotide polymorphisms regulating dopamine at the prefrontal cortex and the striatum (i.e., COMTMet108/158Val and ANKK1/DRD2TaqIA) on stimulus-driven attention capture. Healthy adult participants (N = 40) were assigned to different groups according to the combination of the polymorphisms COMTMet108/158Val and ANKK1/DRD2TaqIA, and were instructed to perform on a well-established distraction protocol. Performance in individuals with a balance between prefrontal dopamine display and striatal receptor density was slowed down by the occurrence of unexpected distracting events, while those with a rather unbalanced dopamine activity were able maintain task performance with no time delay, yet at the expense of a slightly lower accuracy. This advantage, associated to their distinct genetic profiles, was paralleled by an electrophysiological mechanism of phase-resetting of gamma neural oscillation to the novel, distracting events. Taken together, the current results suggest that the epistatic interaction between COMTVal108/158Met and ANKK1/DRD2 TaqIa genetic polymorphisms lies at the basis of stimulus-driven attention capture.

Involvement of the Serotonin Transporter Gene in Accurate Subcortical Speech Encoding.

A flourishing line of evidence has highlighted the encoding of speech sounds in the subcortical auditory system as being shaped by acoustic, linguistic, and musical experience and training. And while the heritability of auditory speech as well as nonspeech processing has been suggested, the genetic determinants of subcortical speech processing have not yet been uncovered. Here, we postulated that the serotonin transporter-linked polymorphic region (5-HTTLPR), a common functional polymorphism located in the promoter region of the serotonin transporter gene (SLC6A4), is implicated in speech encoding in the human subcortical auditory pathway. Serotonin has been shown as essential for modulating the brain response to sound both cortically and subcortically, yet the genetic factors regulating this modulation regarding speech sounds have not been disclosed. We recorded the frequency following response, a biomarker of the neural tracking of speech sounds in the subcortical auditory pathway, and cortical evoked potentials in 58 participants elicited to the syllable /ba/, which was presented >2000 times. Participants with low serotonin transporter expression had higher signal-to-noise ratios as well as a higher pitch strength representation of the periodic part of the syllable than participants with medium to high expression, possibly by tuning synaptic activity to the stimulus features and hence a more efficient suppression of noise. These results imply the 5-HTTLPR in subcortical auditory speech encoding and add an important, genetically determined layer to the factors shaping the human subcortical response to speech sounds. SIGNIFICANCE STATEMENT: The accurate encoding of speech sounds in the subcortical auditory nervous system is of paramount relevance for human communication, and it has been shown to be altered in different disorders of speech and auditory processing. Importantly, this encoding is plastic and can therefore be enhanced by language and music experience. Whether genetic factors play a role in speech encoding at the subcortical level remains unresolved. Here we show that a common polymorphism in the serotonin transporter gene relates to an accurate and robust neural tracking of speech stimuli in the subcortical auditory pathway. This indicates that serotonin transporter expression, eventually in combination with other polymorphisms, delimits the extent to which lifetime experience shapes the subcortical encoding of speech.

Modulation of large-scale brain networks by transcranial direct current stimulation evidenced by resting-state functional MRI.

BACKGROUND: Brain areas interact mutually to perform particular complex brain functions such as memory or language. Furthermore, under resting-state conditions several spatial patterns have been identified that resemble functional systems involved in cognitive functions. Among these, the default-mode network (DMN), which is consistently deactivated during task periods and is related to a variety of cognitive functions, has attracted most attention. In addition, in resting-state conditions some brain areas engaged in focused attention (such as the anticorrelated network, AN) show a strong negative correlation with DMN; as task demand increases, AN activity rises, and DMN activity falls. OBJECTIVE: We combined transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) to investigate these brain network dynamics. METHODS: Ten healthy young volunteers underwent four blocks of resting-state fMRI (10-minutes), each of them immediately after 20 minutes of sham or active tDCS (2 mA), on two different days. On the first day the anodal electrode was placed over the left dorsolateral prefrontal cortex (DLPFC) (part of the AN) with the cathode over the contralateral supraorbital area, and on the second day, the electrode arrangement was reversed (anode right-DLPFC, cathode left-supraorbital). RESULTS: After active stimulation, functional network connectivity revealed increased synchrony within the AN components and reduced synchrony in the DMN components. CONCLUSIONS: Our study reveals a reconfiguration of intrinsic brain activity networks after active tDCS. These effects may help to explain earlier reports of improvements in cognitive functions after anodal-tDCS, where increasing cortical excitability may have facilitated reconfiguration of functional brain networks to address upcoming cognitive demands.

Down-regulation of negative emotional processing by transcranial direct current stimulation: effects of personality characteristics.

Evidence from neuroimaging and electrophysiological studies indicates that the left dorsolateral prefrontal cortex (DLPFC) is a core region in emotional processing, particularly during down-regulation of negative emotional conditions. However, emotional regulation is a process subject to major inter-individual differences, some of which may be explained by personality traits. In the present study we used transcranial direct current stimulation (tDCS) over the left DLPFC to investigate whether transiently increasing the activity of this region resulted in changes in the ratings of positive, neutral and negative emotional pictures. Results revealed that anodal, but not cathodal, tDCS reduced the perceived degree of emotional valence for negative stimuli, possibly due to an enhancement of cognitive control of emotional expression. We also aimed to determine whether personality traits (extraversion and neuroticism) might condition the impact of tDCS. We found that individuals with higher scores on the introversion personality dimension were more permeable than extraverts to the modulatory effects of the stimulation. The present study underlines the role of the left DLPFC in emotional regulation, and stresses the importance of considering individual personality characteristics as a relevant variable, although replication is needed given the limited sample size of our study.

Poorer cognitive performance in humans with mild cognitive impairment carrying the T variant of the Glu/Asp NOS3 polymorphism.

Mild cognitive impairment (MCI) is a transitional state between normal aging and Alzheimer's disease (AD) and is a high-risk condition for dementia. The endothelial nitric oxide synthase (NOS3) gene encodes endothelial NOS, an enzyme that regulates the production of the vasodilatory nitric oxide associated with the cerebral small vessel pathology observed in early AD. We studied the distribution of genotype and allele frequencies of the NOS3 Glu/Asp polymorphism in a sample of 62 MCI subjects and 136 controls. Though no association between NOS3 gene variation and MCI status was observed, MCI cases carrying the Asp variant (T+) performed worse in the Mini-Mental State Examination, Wechsler Memory Scale (Revised) long-term visual memory and the phonetic verbal fluency tests. These results suggest that the T allele is a genetic risk factor for cognitive impairment in the elderly.