Modulation of orbitofrontal-striatal reward activity by dopaminergic functional polymorphisms contributes to a predisposition to alcohol misuse in early adolescence.

BACKGROUND: Abnormalities in reward circuit function are considered a core feature of addiction. Yet, it is still largely unknown whether these abnormalities stem from chronic drug use, a genetic predisposition, or both. METHODS: In the present study, we investigated this issue using a large sample of adolescent children by applying structural equation modeling to examine the effects of several dopaminergic polymorphisms of the D1 and D2 receptor type on the reward function of the ventral striatum (VS) and orbital frontal cortex (OFC), and whether this relationship predicted the propensity to engage in early alcohol misuse behaviors at 14 years of age and again at 16 years of age. RESULTS: The results demonstrated a regional specificity with which the functional polymorphism rs686 of the D1 dopamine receptor (DRD1) gene and Taq1A of the ANKK1 gene influenced medial and lateral OFC activation during reward anticipation, respectively. Importantly, our path model revealed a significant indirect relationship between the rs686 of the DRD1 gene and early onset of alcohol misuse through a medial OFC × VS interaction. CONCLUSIONS: These findings highlight the role of D1 and D2 in adjusting reward-related activations within the mesocorticolimbic circuitry, as well as in the susceptibility to early onset of alcohol misuse.

Separate neural systems for behavioral change and for emotional responses to failure during behavioral inhibition.

To analyze the involvement of different brain regions in behavioral inhibition and impulsiveness, differences in activation were investigated in fMRI data from a response inhibition task, the stop-signal task, in 1709 participants. First, areas activated more in stop-success (SS) than stop-failure (SF) included the lateral orbitofrontal cortex (OFC) extending into the inferior frontal gyrus (ventrolateral prefrontal cortex, BA 47/12), and the dorsolateral prefrontal cortex (DLPFC). Second, the anterior cingulate and anterior insula (AI) were activated more on failure trials, specifically in SF versus SS. The interaction between brain region and SS versus SF activations was significant (P = 5.6 * 10-8 ). The results provide new evidence from this "big data" investigation consistent with the hypotheses that the lateral OFC is involved in the stop-related processing that inhibits the action; that the DLPFC is involved in attentional processes that influence task performance; and that the AI and anterior cingulate are involved in emotional processes when failure occurs. The investigation thus emphasizes the role of the human lateral OFC BA 47/12 in changing behavior, and inhibiting behavior when necessary. A very similar area in BA47/12 is involved in changing behavior when an expected reward is not obtained, and has been shown to have high functional connectivity in depression. Hum Brain Mapp 38:3527-3537, 2017. © 2017 Wiley Periodicals, Inc.

New evidence of factor structure and measurement invariance of the SDQ across five European nations.

The main purpose of the present study was to analyse the internal structure and to test the measurement invariance of the Strengths and Difficulties Questionnaire (SDQ), self-reported version, in five European countries. The sample consisted of 3012 adolescents aged between 12 and 17 years (M = 14.20; SD = 0.83). The five-factor model (with correlated errors added), and the five-factor model (with correlated errors added) with the reverse-worded items allowed to cross-load on the Prosocial subscale, displayed adequate goodness of-fit indices. Multi-group confirmatory factor analysis showed that the five-factor model (with correlated errors added) had partial strong measurement invariance by countries. A total of 11 of the 25 items were non-invariant across samples. The level of internal consistency of the Total difficulties score was 0.84, ranging between 0.69 and 0.78 for the SDQ subscales. The findings indicate that the SDQ's subscales need to be modified in various ways for screening emotional and behavioural problems in the five European countries that were analysed.

Acquisition-related morphological variability in structural MRI.

RATIONALE AND OBJECTIVES: Significant effort has been spent during the past decades to develop innovative image-processing algorithms and improve existing methods in terms of precision, reproducibility, and computational efficiency, but relatively little research was undertaken to find out the extent to which the validity of results obtained with these methods is limited by inherent imperfections of the input images. This observation is especially true for magnetic resonance imaging (MRI)-based morphometry, which aims at precise and highly reproducible determination of geometric properties of anatomic structures, although MRI images are geometrically distorted. MATERIALS AND METHODS: A method for characterization of site-specific geometric distortions and results of a long-term study designed to find the extent to which imperfections in the data-acquisition process limit the reliable detection of subtle morphological changes in MRI data acquired with state-of-the-art scanners are presented. Because of the long-term character of the study, results include effects resulting from limited hardware stability, as well as from imperfections in patient repositioning. RESULTS: Maximal relative morphological changes detected in our phantom data series were 1.0 mm positional and 2.0% volumetric difference (relative to a 7600-mm3 cuboid) in a subvolume relevant for whole-brain morphometry. Morphological variability was even greater for human volunteer data (up to 5% in local gray matter volume) because of movements during scan, natural morphological variability, and a presumably less precise segmentation procedure. CONCLUSION: Imperfections in the MRI data-acquisition process in combination with practical limitations in patient repositioning can substantially confound studies of subtle morphological changes.

Incomplete Hippocampal Inversion: A Comprehensive MRI Study of Over 2000 Subjects.

The incomplete-hippocampal-inversion (IHI), also known as malrotation, is an atypical anatomical pattern of the hippocampus, which has been reported in healthy subjects in different studies. However, extensive characterization of IHI in a large sample has not yet been performed. Furthermore, it is unclear whether IHI are restricted to the medial-temporal lobe or are associated with more extensive anatomical changes. Here, we studied the characteristics of IHI in a community-based sample of 2008 subjects of the IMAGEN database and their association with extra-hippocampal anatomical variations. The presence of IHI was assessed on T1-weighted anatomical magnetic resonance imaging (MRI) using visual criteria. We assessed the association of IHI with other anatomical changes throughout the brain using automatic morphometry of cortical sulci. We found that IHI were much more frequent in the left hippocampus (left: 17%, right: 6%, χ(2)-test, p < 10(-28)). Compared to subjects without IHI, subjects with IHI displayed morphological changes in several sulci located mainly in the limbic lobe. Our results demonstrate that IHI are a common left-sided phenomenon in normal subjects and that they are associated with morphological changes outside the medial temporal lobe.

Reduced frontotemporal functional connectivity in schizophrenia associated with auditory hallucinations.

BACKGROUND: We used functional magnetic resonance imaging (fMRI) to investigate the frontotemporal disconnection hypothesis of schizophrenia. METHODS: Eight DSM-IV schizophrenia patients and 10 control subjects were studied with fMRI while they thought of the missing last word in 128 visually presented sentences. The fMRI data were analyzed comparing the effect of sentence completion (vs. rest) using a random effects analysis. RESULTS: There were no significant group differences in regional brain responses. Correlation coefficients between left temporal cortex (x = -54, y = -42, z = 3) and left dorsolateral prefrontal cortex (x = -39, y = 12, z = 24) were significantly lower in the schizophrenic group and were negatively correlated with the severity of auditory hallucinations. CONCLUSIONS: Previous demonstrations of hypofrontality in schizophrenia may reflect particular task requirements. Frontotemporal functional connectivity is reduced in schizophrenia and may be associated with auditory hallucinations.

The effect of opioid receptor blockade on the neural processing of thermal stimuli.

The endogenous opioid system represents one of the principal systems in the modulation of pain. This has been demonstrated in studies of placebo analgesia and stress-induced analgesia, where anti-nociceptive activity triggered by pain itself or by cognitive states is blocked by opioid antagonists. The aim of this study was to characterize the effect of opioid receptor blockade on the physiological processing of painful thermal stimulation in the absence of cognitive manipulation. We therefore measured BOLD (blood oxygen level dependent) signal responses and intensity ratings to non-painful and painful thermal stimuli in a double-blind, cross-over design using the opioid receptor antagonist naloxone. On the behavioral level, we observed an increase in intensity ratings under naloxone due mainly to a difference in the non-painful stimuli. On the neural level, painful thermal stimulation was associated with a negative BOLD signal within the pregenual anterior cingulate cortex, and this deactivation was abolished by naloxone.

The neural basis for understanding non-intended actions.

We can often understand when actions done by others do or do not reflect their intentions. To investigate the neural basis of this capacity we carried out an fMRI study in which volunteers were presented with video-clips showing actions that did reflect the intention of the agent (intended actions) and actions that did not (non-intended actions). Observation of both types of actions activated a common set of areas including the inferior parietal lobule, the lateral premotor cortex and mesial premotor areas. The contrast non-intended vs. intended actions showed activation in the right temporo-parietal junction, left supramarginal gyrus, and mesial prefrontal cortex. The converse contrast did not show any activation. We conclude that our capacity to understand non intended actions is based on the activation of areas signaling unexpected events in spatial and temporal domains, in addition to the activity of the mirror neuron system. The concomitant activation of mesial prefrontal areas, known to be involved in self-referential processing, might reflect how deeply participants are involved in the observed scenes.