28 research outputs found
Reconsidering electrophysiological markers of response inhibition in light of trigger failures in the stop-signal task
Human Resource Flexibility as a Mediating Variable Between High Performance Work Systems and Performance
Much of the human resource management literature has demonstrated the impact of high performance
work systems (HPWS) on organizational performance. A new generation of studies is
emerging in this literature that recommends the inclusion of mediating variables between HPWS
and organizational performance. The increasing rate of dynamism in competitive environments
suggests that measures of employee adaptability should be included as a mechanism that may
explain the relevance of HPWS to firm competitiveness. On a sample of 226 Spanish firms, the
studyâs results confirm that HPWS influences performance through its impact on the firmâs
human resource (HR) flexibility
Virtual Ontogeny of Cortical Growth Preceding Mental Illness
Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy
The genetic architecture of the human cerebral cortex
INTRODUCTION
The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure.
RATIONALE
To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations.
RESULTS
We identified 306 nominally genome-wide significant loci (P < 5 Ă 10â8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 Ă 10â10; 187 influencing surface area and 12 influencing thickness).
Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = â0.32, SE = 0.05, P = 6.5 Ă 10â12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness.
To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity.
We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinsonâs disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism.
CONCLUSION
This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function
Age at first birth in women is genetically associated with increased risk of schizophrenia
Prof. Paunio on PGC:n jÀsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe
An fMRI study of manipulation and maintenance processes in verbal working memory
Background: The purpose of this event-related fMIU study was to explore the sensitivity of prefrontal cortex (PFC) to maintenance and manipulation processes in verbal working memory. While previous studies have manipulated these two factors in isolation (Esposito et al., 1999), we used a 2x2 factorial design to investigate the differential effect within subjects.
Method: Imaging was carried out using a 3 Tesla Bruker Medspec scanner. A modified factorial version of DâEsposito et al.âs (1999) task was used on 12 healthy volunteers. The two factors were Maintenance (high vs low letter load) and Manipulation (letter strings were either maintained in the order that they were presented or were rearranged into alphabetical order). There were thus four conditions, namely, low load maintenance, low load manipulation, high load maintenance, and high load manipulation. Data were analysed using SPM99, treating inter-subject variability as a random effect. For each of the 4 conditions, the delay period between task instructions (to manipulate or maintain) and a subsequent test probe was modelled as the event of interest. Parameter estimates for these condition-specific models were compared across conditions. We present two contrasts below: Figure 1 shows the effect of load (high vs low) and Figure 2 shows the effect of task type (manipulation vs maintenance). In view of our restricted area of interest, a threshold of p < 0.001 (uncorrected for multiple comparisons) was set.
Results: With respect to main effects, both contrasts (manipulation vs maintenance, and high load vs low load) were associated with activation of ventrolateral and dorsolateral PFC. However, activation of these areas was clearly more pronounced for task type, ie, when manipulation processes were compared to maintenance processes, ventrolateral and dorsolateral PFC activation appeared greater than the load effect. This dissociation was confirmed by the results of the interaction between load and task type.
Conclusion: Both ventrolateral and dorsolateral PFC regions are important in maintenance and manipulation processes in verbal working memory. Manipulation processes seem to involve increased activation in these regions, independent of load
Reconsidering electrophysiological markers of response inhibition in light of trigger failures in the stop-signal task
This study investigates the neural correlates underpinning response inhibition using a parametric exâGaussian model of stopâsignal task performance, fit with hierarchical Bayesian methods, in a large healthy sample (N = 156). The parametric model accounted for both stopâsignal reaction time (SSRT) and trigger failure (i.e., failures to initiate the inhibition process). The returned SSRT estimate (SSRTEXG3) was attenuated by â65 ms compared to traditional nonparametric SSRT estimates (SSRTint). The amplitude and latency of the N1 and P3 eventârelated potential components were derived for both stopâsuccess and stopâfailure trials and compared to behavioral estimates derived from traditional (SSRTint) and parametric (SSRTEXG3, trigger failure) models. Both the frontoâcentral N1 and P3 peaked earlier and were larger for stopâsuccess than stopâfailure trials. For stopâfailure trials only, N1 peak latency correlated with both SSRT estimates as well as trigger failure and temporally coincided with SSRTEXG3, but not SSRTint. In contrast, P3 peak and onset latency were not associated with any behavioral estimates of inhibition for either trial type. While the N1 peaked earlier for stopâsuccess than stopâfailure trials, this effect was not found in poor task performers (i.e., high trigger failure/slow SSRT). These findings are consistent with attentional modulation of both the speed and reliability of the inhibition process, but not for poor performers. Together with the absence of any P3 onset latency effect, our findings suggest that attentional mechanisms are important in supporting speeded and reliable inhibition processes required in the stopâsignal task
Electrophysiological, cognitive and clinical profiles of at-risk mental state: The longitudinal Minds in Transition (MinT) study
The onset of schizophrenia is typically preceded by a prodromal period lasting several years during which sub-threshold symptoms may be identified retrospectively. Clinical interviews are currently used to identify individuals who have an ultra-high risk (UHR) of developing a psychotic illness with a view to provision of interventions that prevent, delay or reduce severity of future mental health issues. The utility of bio-markers as an adjunct in the identification of UHR individuals is not yet established. Several event-related potential measures, especially mismatch-negativity (MMN), have been identified as potential biomarkers for schizophrenia. In this 12-month longitudinal study, demographic, clinical and neuropsychological data were acquired from 102 anti-psychotic naive UHR and 61 healthy controls, of whom 80 UHR and 58 controls provided valid EEG data during a passive auditory task at baseline. Despite widespread differences between UHR and controls on demographic, clinical and neuropsychological measures, MMN and P3a did not differ between these groups. Of 67 UHR at the 12-month follow-up, 7 (10%) had transitioned to a psychotic illness. The statistical power to detect differences between those who did or did not transition was limited by the lower than expected transition rate. ERPs did not predict transition, with trends in the opposite direction to that predicted. In exploratory analysis, the strongest predictors of transition were measures of verbal memory and subjective emotional disturbance
Acute effects of Î9-tetrahydrocannabinol and cannabidiol on auditory mismatch negativity
Rationale: Mismatch negativity (MMN) is a candidate endophenotype for schizophrenia subserved by N-methyl-D-aspartate receptor (NMDAR) function and there is increasing evidence that prolonged cannabis use adversely affects MMN generation. Few human studies have investigated the acute effects of cannabinoids on brain-based biomarkers of NMDAR function and synaptic plasticity. Objectives: The current study investigated the acute effects of Îâč-tetrahydrocannabinol (THC) and cannabidiol (CBD) alone and in combination on the mismatch negativity (MMN). Methods: In a randomised, double-blind, crossover placebo-controlled study, 18 frequent and 18 less-frequent cannabis users underwent 5 randomised drug sessions administered via vaporiser: (1) placebo; (2) THC 8Â mg; (3) CBD 400Â mg; (4) THC 8Â mg + CBD 4Â mg [THC + CBD low]; (5) THC 12Â mg + CBD 400Â mg [THC + CBDhigh]. Participants completed a multifeature MMN auditory oddball paradigm with duration, frequency and intensity deviants (6% each). Results: Relative to placebo, both THC and CBD were observed to increase duration and intensity MMN amplitude in less-frequent users, and THC also increased frequency MMN in this group. The addition of low-dose CBD added to THC attenuated the effect of THC on duration and intensity MMN amplitude in less-frequent users. The same pattern of effects was observed following high-dose CBD added to THC on duration and frequency MMN in frequent users.ConclusionsThe pattern of effects following CBD combined with THC on MMN may be subserved by different underlying neurobiological interactions within the endocannabinoid system that vary as a function of prior cannabis exposure. These results highlight the complex interplay between the acute effects of exogenous cannabinoids and NMDAR function. Further research is needed to determine how this process normalises after the acute effects dissipate and following repeated acute exposure.Lisa-Marie Greenwood, Samantha J. Broyd, Hendrika H. van Hell, Juanita Todd, Alison Jones, Robin M. Murray, Rodney J. Croft, Patricia T. Michie, Nadia Solowi