Highlights • Conventional go/no-go time-domain N2 and P3 measures each contain mixtures of independent and temporally overlapping medial-frontal theta and centro-parietal delta activity. • Theta and ...delta activity increase independently during no-go response inhibition. • The phase of theta and delta activity detail a principled mapping between time–frequency and conventional time-domain component measures.
While the P3 component during target detection and novelty processing has been widely studied, less is known about its underlying network dynamics. A recent cognitive model suggests that ...frontal‐parietal and frontal‐temporal interregional connectivity are related to attention/action selection and target‐related memory updating during the P3, respectively, but empirical work testing this model is lacking. Other work suggests the importance of theta‐ and delta‐band connectivity between the medial frontal cortex and distributed cortical regions during attention, stimulus detection, and response selection processes, and similar dynamics may underlie P3‐related network connectivity. The present study evaluated the functional connectivity elicited during a visual task, which combined oddball target and novelty stimuli, in a sample of 231 same‐sex twins. It was hypothesized that both target and novel conditions would involve theta frontoparietal connectivity and medial frontal theta power, but that target stimuli would elicit the strongest frontotemporal connectivity. EEG time‐frequency analysis revealed greater theta‐band frontoparietal connectivity and medial frontal power during both target and novel conditions compared to standards, which may index conflict/uncertainty resolution processes. Theta‐band frontotemporal connectivity was maximal during the target condition, potentially reflecting context updating or stimulus‐response activation. Delta‐band frontocentral‐parietal connectivity was also strongest following targets, which may be sensitive to response‐related demands. These results suggest the existence of functional networks related to P3 that are differentially engaged by target oddballs and novel distractors. Compared to simple P3 amplitude, network measures may provide a more nuanced view of the neural dynamics during target detection/novelty processing in normative and pathological populations.
Many researchers have used the standard Iowa Gambling Task (IGT) to assess decision-making in adolescence given increased risk-taking during this developmental period. Most studies are ...cross-sectional and do not observe behavioral trajectories over time, limiting interpretation. This longitudinal study investigated healthy adolescents' and young adults' IGT performance across a 10-year span. A total of 189 individuals (aged 9-23 at baseline) completed a baseline session and were followed at 2-year intervals yielding 5 time-points. IGT deck contingencies were shuffled over time to reduce practice effects. IGT performance (good minus bad decisions) was measured at each assessment point and separated into 3 metrics: overall performance (all blocks), decision-making under ambiguity (blocks 1 and 2), and decision-making under risk (blocks 3, 4, and 5). Covariates included estimated intelligence and affective dispositions as measured by the Behavioral Inhibition and Activation System (BIS/BAS) Scales. A linear effect of age yielded the best fit when comparing linear and quadratic effects of age on overall IGT performance. Age and intelligence positively predicted overall performance, whereas affective approach tendencies (BAS) negatively predicted overall performance. Practice effects were observed and controlled for. Models of ambiguity and risk metrics yielded different patterns of significant predictors. Age predicted better performance and affective approach tendencies predicted worse performance for both metrics. Intelligence was a significant predictor for risk, but not ambiguity. This longitudinal study extends prior work by showing age-related improvements in reward-based decision-making and associating those improvements with cognitive and affective variables. Implications of the results for adolescent development are discussed.
Subclinical adolescent alcohol use is highly prevalent and may have deleterious effects on important psychosocial and brain outcomes. Prior research has focused on identifying endophenotypes of ...pathological drinking, and the predictors of normative drinking remain understudied. This study investigated the incremental predictive value of two potential psychophysiological endophenotypes, P3 amplitude (an index of decision making) and midfrontal theta power (a correlate of attentional control), for prospectively predicting the expression and initiation of alcohol use emerging in adolescence.
A large (N = 594) epidemiological sample was prospectively assessed at ages 11/14/17. Alcohol/substance use was assessed at all ages via a computerized self-report inventory. EEG was recorded at age-14 during a visual oddball task to elicit P3 and theta.
Reduced target-related P3 and theta at age-14 prospectively predicted drinking at age-17 independent of one another. Among alcohol-naive individuals at age-14, attenuated P3 and theta increased the odds of new-onset alcohol behaviors 3 years later. Importantly, the endophenotypes provided significant incremental predictive power of future non-clinical alcohol use beyond relevant risk factors (prior alcohol use; tobacco/illicit drug initiation; parental alcohol use disorder).
The current report is the first of our knowledge to demonstrate that deviations in parietal P3 and midfrontal theta prospectively predict the emergence of normative/non-pathological drinking. P3 and theta provide modest yet significant explanatory variance beyond prominent self-report and familial risk measures. Findings offer strong evidence supporting the predictive utility of P3 and theta as candidate endophenotypes for adolescent drinking.
Research on substance use disorders is often compartmentalized, focused on understanding addiction to one substance or substance class at a time. Although this approach has contributed significantly ...to knowledge about addictions, early-onset substance use disorders appear to share common etiology with each other and with other disorders, traits, behaviors, and endophenotypes associated with behavioral disinhibition. We propose that a common genetic liability to behavioral disinhibition underlies the co-occurrence of these externalizing attributes. This liability is expressed in part through brain mechanisms related to cognitive control, impulsivity, and sensitivity to reward, all of which are maturing during adolescence. During this important transitional period, problem behaviors emerge, including the initiation of substance use. Exposure to various environmental risks further amplifies the risk associated with the common liability, increasing the likelihood of addiction generally. Specific environmental and genetic factors ultimately contribute to the differentiation among externalizing disorders.
Time–frequency representations of electroencephalographic signals lend themselves to a granular analysis of cognitive and psychological processes. Characterizing developmental trajectories of ...time–frequency measures can thus inform us about the development of the processes involved as well as correlated traits and behaviors. We decomposed electroencephalographic (EEG) activity in a large sample of individuals (N = 1692; 917 females), assessed at approximately 3‐year intervals from the age of 11 to their mid‐20s. Participants completed an oddball task that elicits a robust P3 response. Principal component analysis served to identify the primary dimensions of time–frequency energy. Component loadings were virtually identical across assessment waves. A common and stable set of time–frequency dynamics thus characterized EEG activity throughout this age range. Trajectories of changes in component scores suggest that aspects of brain development reflected in these components comprise two distinct phases, with marked decreases in component amplitude throughout much of adolescence followed by smaller yet significant rates of decreases into early adulthood. Although the structure of time–frequency activity was stable throughout adolescence and early adulthood, we observed subtle change in component loadings as well. Our findings suggest that striking developmental change in event‐related potentials emerges through a gradual change in the magnitude and timing of a stable set of dimensions of time–frequency activity, illustrating the usefulness of time–frequency representations of EEG signals and longitudinal designs for understanding brain development. In addition, we provide proof of concept that trajectories of time‐frequency activity can serve as potential endophenotypes for childhood externalizing psychopathology and alcohol use in adolescence and early adulthood.
Our findings suggest that a striking change in event‐related potentials in adolescence and early adulthood emerges through a gradual change in the magnitude and timing of a stable set of dimensions of time–frequency activity. These results illustrate the usefulness of time–frequency representations of EEG signals as well as longitudinal designs for understanding brain development. In addition, we provide proof of concept that developmental trajectories can serve as candidate endophenotypes for disinhibited behavior.
Impairments in inhibitory control and its underlying brain networks (control/salience areas) are associated with substance misuse. Research often assumes a causal substance exposure effect on brain ...structure. This assumption remains largely untested, and other factors (e.g., familial risk) may confound exposure effects. We leveraged a genetically informative sample of twins aged 24 years and a quasi-experimental co-twin control design to separate alcohol or cannabis exposure effects during emerging adulthood from familial risk on control/salience network cortical thickness.
In a population-based sample of 436 twins aged 24 years, dimensional measures of alcohol and cannabis use (e.g., frequency, density, quantity, intoxications) across emerging adulthood were assessed. Cortical thickness of control/salience network areas were assessed using magnetic resonance imaging and defined by a fine-grained cortical atlas.
Greater alcohol, but not cannabis, misuse was associated with reduced thickness of prefrontal (e.g., dorso/ventrolateral, right frontal operculum) and frontal medial cortices, as well as temporal lobe, intraparietal sulcus, insula, parietal operculum, precuneus, and parietal medial areas. Effects were predominately (pre)frontal and right lateralized. Co-twin control analyses suggested that the effects likely reflect both the familial predisposition to misuse alcohol and, specifically for lateral prefrontal, frontal/parietal medial, and right frontal operculum, an alcohol exposure effect.
This study provides novel evidence that alcohol-related reductions in cortical thickness of control/salience brain networks likely represent the effects of alcohol exposure and premorbid characteristics of the genetic predisposition to misuse alcohol. The dual effects of these two alcohol-related causal influences have important and complementary implications regarding public health and prevention efforts to curb youth drinking.
Endophenotype best practices Iacono, William G.; Malone, Stephen M.; Vrieze, Scott I.
International journal of psychophysiology,
01/2017, Letnik:
111
Journal Article
Recenzirano
Odprti dostop
This review examines the current state of electrophysiological endophenotype research and recommends best practices that are based on knowledge gleaned from the last decade of molecular genetic ...research with complex traits. Endophenotype research is being oversold for its potential to help discover psychopathology relevant genes using the types of small samples feasible for electrophysiological research. This is largely because the genetic architecture of endophenotypes appears to be very much like that of behavioral traits and disorders: they are complex, influenced by many variants (e.g., tens of thousands) within many genes, each contributing a very small effect. Out of over 40 electrophysiological endophenotypes covered by our review, only resting heart, a measure that has received scant advocacy as an endophenotype, emerges as an electrophysiological variable with verified associations with molecular genetic variants. To move the field forward, investigations designed to discover novel variants associated with endophenotypes will need extremely large samples best obtained by forming consortia and sharing data obtained from genome wide arrays. In addition, endophenotype research can benefit from successful molecular genetic studies of psychopathology by examining the degree to which these verified psychopathology-relevant variants are also associated with an endophenotype, and by using knowledge about the functional significance of these variants to generate new endophenotypes. Even without molecular genetic associations, endophenotypes still have value in studying the development of disorders in unaffected individuals at high genetic risk, constructing animal models, and gaining insight into neural mechanisms that are relevant to clinical disorder.
•The potential of endophenotypes for identifying psychopathology-related genes has been oversold.•Endophenotypes have largely failed to produce verified molecular genetic associations.•Endophenotypes are complex and influenced by many genes each with very small effect.•Extremely large samples are necessary to discover variants associated with endophenotypes.•Endophenotype research should be informed by molecular genetic findings.•Endophenotypes are valuable even without producing molecular genetic hits.
Oscillatory activity is crucial for information processing in the brain, and has a long history as a biomarker for psychopathology. Variation in oscillatory activity is highly heritable, but current ...understanding of specific genetic influences remains limited. We performed the largest genome‐wide association study to date of oscillatory power during eyes‐closed resting electroencephalogram (EEG) across a range of frequencies (delta 1–3.75 Hz, theta 4–7.75 Hz, alpha 8–12.75 Hz, and beta 13–30 Hz) in 8,425 subjects. Additionally, we performed KGG positional gene‐based analysis and brain‐expression analyses. GABRA2—a known genetic marker for alcohol use disorder and epilepsy—significantly affected beta power, consistent with the known relation between GABAA interneuron activity and beta oscillations. Tissue‐specific SNP‐based imputation of gene‐expression levels based on the GTEx database revealed that hippocampal GABRA2 expression may mediate this effect. Twenty‐four genes at 3p21.1 were significant for alpha power (FDR q < .05). SNPs in this region were linked to expression of GLYCTK in hippocampal tissue, and GNL3 and ITIH4 in the frontal cortex–genes that were previously implicated in schizophrenia and bipolar disorder. In sum, we identified several novel genetic variants associated with oscillatory brain activity; furthermore, we replicated and advanced understanding of previously known genes associated with psychopathology (i.e., schizophrenia and alcohol use disorders). Importantly, these psychopathological liability genes affect brain functioning, linking the genes' expression to specific cortical/subcortical brain regions.
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