Brain Structural Correlates of Reward Sensitivity and Impulsivity in Adolescents with Normal and Excess Weight

Introduction

Neuroscience evidence suggests that adolescent obesity is linked to brain dysfunctions associated with enhanced reward and somatosensory processing and reduced impulse control during food processing. Comparatively less is known about the role of more stable brain structural measures and their link to personality traits and neuropsychological factors on the presentation of adolescent obesity. Here we aimed to investigate regional brain anatomy in adolescents with excess weight vs. lean controls. We also aimed to contrast the associations between brain structure and personality and cognitive measures in both groups.

Methods

Fifty-two adolescents (16 with normal weight and 36 with excess weight) were scanned using magnetic resonance imaging and completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the UPPS-P scale, and the Stroop task. Voxel-based morphometry (VBM) was used to assess possible between-group differences in regional gray matter (GM) and to measure the putative differences in the way reward and punishment sensitivity, impulsivity and inhibitory control relate to regional GM volumes, which were analyzed using both region of interest (ROI) and whole brain analyses. The ROIs included areas involved in reward/somatosensory processing (striatum, somatosensory cortices) and motivation/impulse control (hippocampus, prefrontal cortex).

Results

Excess weight adolescents showed increased GM volume in the right hippocampus. Voxel-wise volumes of the second somatosensory cortex (SII) were correlated with reward sensitivity and positive urgency in lean controls, but this association was missed in excess weight adolescents. Moreover, Stroop performance correlated with dorsolateral prefrontal cortex volumes in controls but not in excess weight adolescents.

Conclusion

Adolescents with excess weight have structural abnormalities in brain regions associated with somatosensory processing and motivation.     

Brain Structural Correlates of Risk-Taking Behavior and Effects of Peer Influence in Adolescents

Adolescents are characterized by impulsive risky behavior, particularly in the presence of peers. We discriminated high and low risk-taking male adolescents aged 18–19 years by assessing their propensity for risky behavior and vulnerability to peer influence with personality tests, and compared structural differences in gray and white matter of the brain with voxel-based morphometry (VBM) and diffusion tensor imaging (DTI), respectively. We also compared the brain structures according to the participants'' actual risk-taking behavior in a simulated driving task with two different social conditions making up a peer competition situation. There was a discrepancy between the self-reported personality test results and risky driving behavior (running through an intersection with traffic lights turning yellow, chancing a collision with another vehicle). Comparison between high and low risk-taking adolescents according to personality test results revealed no significant difference in gray matter volume and white matter integrity. However, comparison according to actual risk-taking behavior during task performance revealed significantly higher white matter integrity in the high risk-taking group, suggesting that increased risky behavior during adolescence is not necessarily attributed to the immature brain as conventional wisdom says.     

Length of Acupuncture Training and Structural Plastic Brain Changes in Professional Acupuncturists

Background

The research on brain plasticity has fascinated researchers for decades. Use/training serves as an instrumental factor to influence brain neuroplasticity. Parallel to acquisition of behavioral expertise, extensive use/training is concomitant with substantial changes of cortical structure. Acupuncturists, serving as a model par excellence to study tactile-motor and emotional regulation plasticity, receive intensive training in national medical schools following standardized training protocol. Moreover, their behavioral expertise is corroborated during long-term clinical practice. Although our previous study reported functional plastic brain changes in the acupuncturists, whether or not structural plastic changes occurred in acupuncturists is yet elusive.

Methodology/Principal Findings

Cohorts of acupuncturists (N = 22) and non-acupuncturists (N = 22) were recruited. Behavioral tests were delivered to assess the acupuncturists’ behavioral expertise. The results confirmed acupuncturists’ tactile-motor skills and emotion regulation proficiency compared to non-acupuncturists. Using the voxel-based morphometry technique, we revealed larger grey matter volumes in acupuncturists in the hand representation of the contralateral primary somatosensory cortex (SI), the right lobule V/VI and the bilateral ventral anterior cingulate cortex/ventral medial prefrontal cortex. Grey matter volumes of the SI and Lobule V/VI positively correlated with the duration of acupuncture practice.

Conclusions

To our best knowledge, this study provides first evidence for the anatomical alterations in acupuncturists, which would possibly be the neural correlates underlying acupuncturists’ exceptional skills. On one hand, we suggest our findings may have ramifications for tactile-motor rehabilitation. On the other hand, our results in emotion regulation domain may serve as a target for our future studies, from which we can understand how modulations of aversive emotions elicited by empathic pain develop in the context of expertise. Future longitudinal study is necessary to establish the presence and direction of a causal link between practice/use and brain anatomy.     

Brain Correlates of Self-Evaluation Deficits in Schizophrenia: A Combined Functional and Structural MRI Study

Self-evaluation plays an important role in adaptive functioning and is a process that is typically impaired in patients with schizophrenia. Underlying neural mechanisms for this dysfunction may be associated with manifested psychosis. However, the brain substrates underlying this deficit are not well known. The present study used brain blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and gray matter voxel-based morphometry to explore the functional and structural brain correlates of self-evaluation deficits in schizophrenia. Eighteen patients with schizophrenia and 17 healthy controls were recruited and asked to judge whether a set of personality-trait adjectives were appropriate for describing themselves, a familiar other, or whether the adjectives were of positive or negative valence. Patients had slower response times for negative trait attributions than controls did; responses to positive trait attributions were faster than those for negative traits among the patient group, while no differences were observed in the control group. Control subjects showed greater activation within the dorsal medial prefrontal cortex (dMPFC) and the anterior cingulate cortex (ACC) than the patient group during the self-evaluation > semantic positivity-evaluation contrast. Patients showed greater activation mainly within the posterior cingulate gyrus (PCC) as compared to controls for the other-evaluation > semantic positivity-evaluation contrast. Furthermore, gray matter volume was reduced in the MPFC, temporal lobe, cuneus, and the dorsal lateral prefrontal cortex (DLPFC) among the patient group when compared to controls. The present study adds to previous findings regarding self- and other-referential processing in schizophrenia, providing support for neurobiological models of self-reflection impairment.     

Frontal White Matter Volume Is Associated with Brain Enlargement and Higher Structural Connectivity in Anthropoid Primates

Previous research has indicated the importance of the frontal lobe and its ‘executive’ connections to other brain structures as crucial in explaining primate neocortical adaptations. However, a representative sample of volumetric measurements of frontal connective tissue (white matter) has not been available. In this study, we present new volumetric measurements of white and grey matter in the frontal and non-frontal neocortical lobes from 18 anthropoid species. We analyze this data in the context of existing theories of neocortex, frontal lobe and white versus grey matter hyperscaling. Results indicate that the ‘universal scaling law’ of neocortical white to grey matter applies separately for frontal and non-frontal lobes; that hyperscaling of both neocortex and frontal lobe to rest of brain is mainly due to frontal white matter; and that changes in frontal (but not non-frontal) white matter volume are associated with changes in rest of brain and basal ganglia, a group of subcortical nuclei functionally linked to ‘executive control’. Results suggest a central role for frontal white matter in explaining neocortex and frontal lobe hyperscaling, brain size variation and higher neural structural connectivity in anthropoids.     

Neuropsychological Correlates of Brain Perfusion SPECT in Patients with Macrophagic Myofasciitis

Background

Patients with aluminum hydroxide adjuvant-induced macrophagic myofasciitis (MMF) complain of arthromyalgias, chronic fatigue and cognitive deficits. This study aimed to characterize brain perfusion in these patients.

Methods

Brain perfusion SPECT was performed in 76 consecutive patients (aged 49±10 y) followed in the Garches-Necker-Mondor-Hendaye reference center for rare neuromuscular diseases. Images were acquired 30 min after intravenous injection of 925 MBq ^99mTc-ethylcysteinate dimer (ECD) at rest. All patients also underwent a comprehensive battery of neuropsychological tests, within 1.3±5.5 mo from SPECT. Statistical parametric maps (SPM12) were obtained for each test using linear regressions between each performance score and brain perfusion, with adjustment for age, sex, socio-cultural level and time delay between brain SPECT and neuropsychological testing.

Results

SPM analysis revealed positive correlation between neuropsychological scores (mostly exploring executive functions) and brain perfusion in the posterior associative cortex, including cuneus/precuneus/occipital lingual areas, the periventricular white matter/corpus callosum, and the cerebellum, while negative correlation was found with amygdalo-hippocampal/entorhinal complexes. A positive correlation was also observed between brain perfusion and the posterior associative cortex when the time elapsed since last vaccine injection was investigated.

Conclusions

Brain perfusion SPECT showed a pattern of cortical and subcortical changes in accordance with the MMF-associated cognitive disorder previously described. These results provide a neurobiological substrate for brain dysfunction in aluminum hydroxide adjuvant-induced MMF patients.     

Structural Correlates of Rotavirus Cell Entry

Cell entry by non-enveloped viruses requires translocation into the cytosol of a macromolecular complex—for double-strand RNA viruses, a complete subviral particle. We have used live-cell fluorescence imaging to follow rotavirus entry and penetration into the cytosol of its ∼700 Å inner capsid particle (“double-layered particle”, DLP). We label with distinct fluorescent tags the DLP and each of the two outer-layer proteins and track the fates of each species as the particles bind and enter BSC-1 cells. Virions attach to their glycolipid receptors in the host cell membrane and rapidly become inaccessible to externally added agents; most particles that release their DLP into the cytosol have done so by ∼10 minutes, as detected by rapid diffusional motion of the DLP away from residual outer-layer proteins. Electron microscopy shows images of particles at various stages of engulfment into tightly fitting membrane invaginations, consistent with the interpretation that rotavirus particles drive their own uptake. Electron cryotomography of membrane-bound virions also shows closely wrapped membrane. Combined with high resolution structural information about the viral components, these observations suggest a molecular model for membrane disruption and DLP penetration.     

Placebo Analgesia Affects Brain Correlates of Error Processing

Placebo analgesia (PA) is accompanied by decreased activity in pain-related brain regions, but also by greater prefrontal cortex (PFC) activation, which has been suggested to reflect increases in top-down cognitive control and regulation of pain. Here we test whether PA is associated with altered prefrontal monitoring functions that could adjust nociceptive processing to a mismatch between expected and experienced pain. We recorded event-related potentials to response errors in a go/nogo task during placebo vs. a matched control condition. Error commission was associated with two well-described components, the error-related negativity (ERN) and the error positivity (Pe). Results show that the Pe, but not the ERN, was amplified during placebo analgesia compared to the control condition, with neural sources in the lateral and medial PFC. This Pe increase was driven by participants showing a placebo-induced change in pain tolerance, but was absent in the group of non-responders. Our results shed new light on the possible functional mechanisms underlying PA, suggesting a placebo-induced transient change in prefrontal error monitoring and control functions.     

Preoperative Diffusion-Weighted Imaging of Single Brain Metastases Correlates with Patient Survival Times

Background

MRI-based diffusion-weighted imaging (DWI) visualizes the local differences in water diffusion in vivo. The prognostic value of DWI signal intensities on the source images and apparent diffusion coefficient (ADC) maps respectively has not yet been studied in brain metastases (BM).

Methods

We included into this retrospective analysis all patients operated for single BM at our institution between 2002 and 2010, in whom presurgical DWI and BM tissue samples were available. We recorded relevant clinical data, assessed DWI signal intensity and apparent diffusion coefficient (ADC) values and performed histopathological analysis of BM tissues. Statistical analyses including uni- and multivariate survival analyses were performed.

Results

65 patients (34 female, 31 male) with a median overall survival time (OS) of 15 months (range 0–99 months) were available for this study. 19 (29.2%) patients presented with hyper-, 3 (4.6%) with iso-, and 43 (66.2%) with hypointense DWI. ADCmean values could be determined in 32 (49.2%) patients, ranged from 456.4 to 1691.8*10⁻⁶ mm²/s (median 969.5) and showed a highly significant correlation with DWI signal intensity. DWI hyperintensity correlated significantly with high amount of interstitial reticulin deposition. In univariate analysis, patients with hyperintense DWI (5 months) and low ADCmean values (7 months) had significantly worse OS than patients with iso/hypointense DWI (16 months) and high ADCmean values (30 months), respectively. In multivariate survival analysis, high ADCmean values retained independent statistical significance.

Conclusions

Preoperative DWI findings strongly and independently correlate with OS in patients operated for single BM and are related to interstitial fibrosis. Inclusion of DWI parameters into established risk stratification scores for BM patients should be considered.     

Decreased Serum Hepcidin Concentration Correlates with Brain Iron Deposition in Patients with HBV-Related Cirrhosis

Purpose

Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV)-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level.

Methods

Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters.

Results

Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients.

Conclusions

Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional brain iron repletion. Serum hepcidin may be a clinical biomarker for brain iron deposition in cirrhotic patients, which may have therapeutic potential.     

Characterizing Behavioral and Brain Changes Associated with Practicing Reasoning Skills

We have reported previously that intensive preparation for a standardized test that taxes reasoning leads to changes in structural and functional connectivity within the frontoparietal network. Here, we investigated whether reasoning instruction transfers to improvement on unpracticed tests of reasoning, and whether these improvements are associated with changes in neural recruitment during reasoning task performance. We found behavioral evidence for transfer to a transitive inference task, but no evidence for transfer to a rule generation task. Across both tasks, we observed reduced lateral prefrontal activation in the trained group relative to the control group, consistent with other studies of practice-related changes in brain activation. In the transitive inference task, we observed enhanced suppression of task-negative, or default-mode, regions, consistent with work suggesting that better cognitive skills are associated with more efficient switching between networks. In the rule generation task, we found a pattern consistent with a training-related shift in the balance between phonological and visuospatial processing. Broadly, we discuss general methodological considerations related to the analysis and interpretation of training-related changes in brain activation. In summary, we present preliminary evidence for changes in brain activation associated with practice of high-level cognitive skills.     

Two Acidic Proteins Associated with Brain Development in Chick Embryo

The developmental changes in protein composition of the chick optic tectum were analyzed by two-dimensional gel electrophoresis. Staining with Coomassie Brilliant Blue R revealed 54 major proteins, eight of which remarkably changed their abundance during development: Four of these proteins (S8, S14, S30, and S54) increased and two of them (S7 and S37) decreased in the course of the brain development. The other two proteins (S5 and S6) appeared at specific embryonic stages and were not detected in the adult. The abundance of S5 protein was highest at day 7, and that of S6 protein at days 9-18. The two proteins were present in other regions of the embryonic brain but were not detected in the embryonic liver. The proteins were purified from the soluble fraction of embryonic chick brains by pH 5.5 precipitation, DEAE-Sepharose column chromatography, ammonium sulfate precipitation, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular weights of S5 and S6 proteins were 95,000 and 100,000, respectively, and their isoelectric points were about 4.5. They were compared by peptide mapping using V8 protease and found to share 11 common peptides out of 17 distinct ones. This indicates a strong degree of structural homology between these two proteins.     

药物滥用与神经元结构可塑性改变的关系

药物成瘾所导致的行为和生理方面的长时程改变可能与相关脑区突触连接的重构有关。安非他命、可卡因、吗啡和尼古丁滥用时,精神依赖和奖赏效应相关脑区神经元的树突和树突棘的结构发生改变,这反映药物滥用致相关神经回路突触连接方式的改变。这种改变足长时程的、脑区特异性的,是多种因素调节的结果。     

Cognitive Inflexibility in Obsessive-Compulsive Disorder and Major Depression Is Associated with Distinct Neural Correlates

Obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) are frequently co-morbid, and dysfunctional frontal-striatal circuits have been implicated in both disorders. Neurobiological distinctions between OCD and MDD are insufficiently clear, and comparative neuroimaging studies are extremely scarce. OCD and MDD may be characterized by cognitive rigidity at the phenotype level, and frontal-striatal brain circuits constitute the neural substrate of intact cognitive flexibility. In the present study, 18 non-medicated MDD-free patients with OCD, 19 non-medicated OCD-free patients with MDD, and 29 matched healthy controls underwent functional magnetic resonance imaging during performance of a self-paced letter/digit task switching paradigm. Results showed that both patient groups responded slower relative to controls during repeat events, but only in OCD patients slowing was associated with decreased error rates. During switching, patients with OCD showed increased activation of the putamen, anterior cingulate and insula, whereas MDD patients recruited inferior parietal cortex and precuneus to a lesser extent. Patients with OCD and MDD commonly failed to reveal anterior prefrontal cortex activation during switching. This study shows subtle behavioral abnormalities on a measure of cognitive flexibility in MDD and OCD, associated with differential frontal-striatal brain dysfunction in both disorders. These findings may add to the development of biological markers that more precisely characterize frequently co-morbid neuropsychiatric disorders such as OCD and MDD.