RÉSUMÉ
BACKGROUND/OBJECTIVES: Obesity has been ascribed to corticostriatal regions taking control over homeostatic areas. To test this assumption, we applied an effective connectivity approach to reveal the direction of information flow between brain regions and the valence of connections (excitatory versus inhibitory) as a function of increased BMI and homeostatic state. SUBJECTS/METHODS: Forty-one participants (21 overweight/obese) underwent two resting-state fMRI scans: after overnight fasting (hunger) and following a standardised meal (satiety). We used spectral dynamic causal modelling to unravel hunger and increased BMI-related changes in directed connectivity between cortical, insular, striatal and hypothalamic regions. RESULTS: During hunger, as compared to satiety, we found increased excitation of the ventromedial prefrontal cortex over the ventral striatum and hypothalamus, suggesting enhanced top-down modulation compensating energy depletion. Increased BMI was associated with increased excitation of the anterior insula over the hypothalamus across the hunger and satiety conditions. The interaction of hunger and increased BMI yielded decreased intra-cortical excitation from the dorso-lateral to the ventromedial prefrontal cortex. CONCLUSIONS: Our findings suggest that excess weight and obesity is associated with persistent top-down excitation of the hypothalamus, regardless of homeostatic state, and hunger-related reductions of dorso-lateral to ventromedial prefrontal inputs. These findings are compatible with eating without hunger and reduced self-regulation views of obesity.
Sujet(s)
Indice de masse corporelle , Hypothalamus/physiopathologie , Réseau nerveux/malformations , Cortex préfrontal/physiopathologie , Adulte , Femelle , Humains , Hypothalamus/malformations , Imagerie par résonance magnétique/méthodes , Imagerie par résonance magnétique/statistiques et données numériques , Mâle , Réseau nerveux/physiopathologie , Cortex préfrontal/malformationsRÉSUMÉ
In this review, we examine the role of microRNAs in the development of the prefrontal cortex (PFC) in adolescence and in individual differences in vulnerability to mental illness. We describe results from clinical and preclinical research indicating that adolescence coincides with drastic changes in local microRNA expression, including microRNAs that control gene networks involved in PFC and cognitive refinement. We highlight that altered levels of microRNAs in the PFC are associated with psychopathologies of adolescent onset, notably depression and schizophrenia. We show that microRNAs can be measured non-invasively in peripheral samples and could serve as longitudinal physiological readouts of brain expression and psychiatric risk in youth.
Sujet(s)
microARN/génétique , Cortex préfrontal/malformations , Cortex préfrontal/physiopathologie , Schizophrénie/génétique , Stress psychologique/génétique , Adolescent , Enfant , Femelle , Humains , MâleRÉSUMÉ
Spatial working memory (SWM) is a central cognitive process during which the hippocampus and prefrontal cortex (PFC) encode and maintain spatial information for subsequent decision-making. This occurs in the context of ongoing computations relating to spatial position, recall of long-term memory, attention, among many others. To establish how intermittently presented information is integrated with ongoing computations we recorded single units, simultaneously in hippocampus and PFC, in control rats and those with a brain malformation during performance of an SWM task. Neurons that encode intermittent task parameters are also well modulated in time and incorporated into a functional network across regions. Neurons from animals with cortical malformation are poorly modulated in time, less likely to encode task parameters, and less likely to be integrated into a functional network. Our results implicate a model in which ongoing oscillatory coordination among neurons in the hippocampal-PFC network describes a functional network that is poised to receive sensory inputs that are then integrated and multiplexed as working memory. The background temporal modulation is systematically altered in disease, but the relationship between these dynamics and behaviorally relevant firing is maintained, thereby providing potential targets for stimulation-based therapies.
Sujet(s)
Encéphale/malformations , Hippocampe/malformations , Hippocampe/physiologie , Cortex préfrontal/malformations , Cortex préfrontal/physiologie , Performance psychomotrice/physiologie , Animaux , Encéphale/physiopathologie , Région CA1 de l'hippocampe/malformations , Région CA1 de l'hippocampe/physiologie , Conditionnement opérant , Phénomènes électrophysiologiques , Fonction exécutive/physiologie , Femelle , Mâle , Mémoire à long terme/physiologie , Mémoire à court terme , Rappel mnésique/physiologie , Réseau nerveux/malformations , Réseau nerveux/physiopathologie , Neurones/physiologie , Grossesse , Rats , Rat Sprague-Dawley , Mémoire spatialeRÉSUMÉ
To characterize the fractional amplitude of low-frequency fluctuation (fALFF) in drug-naïve first-episode female patients with anorexia nervosa (AN) using resting-state functional magnetic resonance imaging (rs-fMRI).Whole brain rs-fMRI data were collected from 7 drug-naïve first-episode female patients with DSM-5 AN and 14 age-matched healthy female controls. fALFF values were calculated and compared between the two groups using a two-sample t test. Correlation analysis between the fALFF values in the entire brain and body mass index (BMI) was performed.Compared with the healthy controls, increased fALFF values were observed in the AN patients in their right hippocampus and left superior frontal gyrus, while decreased fALFF values were observed in their left rectus and left middle occipital gyrus. Moreover, low BMI was significantly associated with decreased fALFF in the left inferior frontal gyrus but increased fALFF in the left calcarine. In particular, the z-standardized fALFF (zfALFF) value of the left rectus was positive associated with BMI.Our findings suggest that spontaneous brain activity in the frontal region, hippocampus and rectus, characterized by fALFF values, was altered in drug-naïve, first-episode female patients with AN.
Sujet(s)
Anorexie mentale/traitement médicamenteux , Imagerie par résonance magnétique/normes , Adolescent , Adulte , Anorexie mentale/physiopathologie , Anorexie mentale/psychologie , Chine , Femelle , Humains , Imagerie par résonance magnétique/méthodes , Imagerie par résonance magnétique/statistiques et données numériques , Lobe occipital/malformations , Lobe occipital/anatomie et histologie , Cortex préfrontal/malformations , Cortex préfrontal/anatomie et histologieRÉSUMÉ
AIM: To evaluate the microstructural abnormalities of the white matter tracts (WMT) using diffusion tensor imaging (DTI) in children with global developmental delay (GDD). MATERIALS AND METHODS: Sixteen children with GDD underwent magnetic resonance imaging (MRI) and cross-sectional DTI. Formal developmental assessment of all GDD patients was performed using the Mullen Scales of Early Learning. An automated processing pipeline for the WMT assessment was implemented. The DTI-derived metrics of the children with GDD were compared to healthy children with normal development (ND). RESULTS: Only two out of the 17 WMT demonstrated significant differences (p<0.05) in DTI parameters between the GDD and ND group. In the uncinate fasciculus (UF), the GDD group had lower mean values for fractional anisotropy (FA; 0.40 versus 0.44), higher values for mean diffusivity (0.96 versus 0.91×10-3 mm2/s) and radial diffusivity (0.75 versus 0.68×10-3 mm2/s) compared to the ND group. In the superior cerebellar peduncle (SCP), mean FA values were lower for the GDD group (0.38 versus 0.40). Normal myelination pattern of DTI parameters was deviated against age for GDD group for UF and SCP. CONCLUSION: The UF and SCP WMT showed microstructural changes suggestive of compromised white matter maturation in children with GDD. The DTI metrics have potential as imaging markers for inadequate white matter maturation in GDD children.
Sujet(s)
Cervelet/malformations , Cervelet/imagerie diagnostique , Incapacités de développement/physiopathologie , Imagerie par résonance magnétique/méthodes , Cortex préfrontal/malformations , Cortex préfrontal/imagerie diagnostique , Substance blanche/malformations , Substance blanche/imagerie diagnostique , Anisotropie , Enfant d'âge préscolaire , Études transversales , Imagerie par résonance magnétique de diffusion , Études de faisabilité , Femelle , Humains , Nourrisson , MâleRÉSUMÉ
AIM: To determine neuroanatomical peculiarities of grey matter in some regions of the prefrontal cortex and several subcortical structures in patients with juvenile shift like schizophrenia (F20 ICD-10). MATERIAL AND METHODS: Forty-three young male patients and 54 mentally healthy men without family history of mental diseases underwent structural MRI with T1 high resolution images. RESULTS: As compared to mentally healthy subjects, there was a decrease of grey matter thickness in all tested regions of the prefrontal cortex in patients. No between-group differences in subcortical structures volumes were found. No correlations between structural changes and psychopathological symptoms were observed. CONCLUSION: Structural abnormalities of the frontal lobes in juvenile shift like schizophrenia are not associated with severity of psychopathological symptoms.
Sujet(s)
Substance grise , Cortex préfrontal , Schizophrénie , Adolescent , Substance grise/malformations , Substance grise/imagerie diagnostique , Humains , Traitement d'image par ordinateur , Imagerie par résonance magnétique , Mâle , Cortex préfrontal/malformations , Cortex préfrontal/imagerie diagnostique , Schizophrénie/imagerie diagnostiqueRÉSUMÉ
OBJECTIVE: Evidence suggests relationships between abnormalities in various cortical and subcortical brain structures and language dysfunction in individuals with schizophrenia, and to some extent in those with increased genetic risk for this diagnosis. The topological features of the structural brain network at the systems-level and their impact on language function in schizophrenia and in those at high genetic risk has been less well studied. METHOD: Single-subject morphological brain network was constructed in a total of 71 subjects (20 patients with schizophrenia, 19 individuals at high genetic risk for schizophrenia, and 32 controls). Among these 71 subjects, 56 were involved in our previous neuroimaging studies. Graphic Theoretical Techniques was applied to calculate the global and nodal topological characteristics of the morphological brain network of each participant. Index scores for five language-related cognitive tests were also attained from each participant. RESULTS: Significantly smaller nodal degree in bilateral superior occipital gyri (SOG) were observed in individuals with schizophrenia, as compared to the controls and those at high risk; while significantly reduced nodal betweenness centrality (quantifying the level of a node in connecting other nodes in the network) in right middle frontal gyrus (MFG) was found in the high-risk group, relative to controls. The right MFG nodal efficiency and hub capacity (represented by both nodal degree and betweenness centrality) of the morphological brain network were negatively associated with the wide range achievement test (WRAT) standard performance score; while the right SOG nodal degree was positively associated with the WRAT standard performance score, in the entire study sample. CONCLUSIONS: These findings enhance the understanding of structural brain abnormalities at the systems-level in individuals with schizophrenia and those at high genetic risk, which may serve as critical neural substrates for the origin of the language-related impairments and symptom manifestations of schizophrenia.
Sujet(s)
Encéphale/malformations , Encéphale/anatomopathologie , Prédisposition génétique à une maladie/génétique , Troubles du développement du langage/génétique , Troubles du développement du langage/anatomopathologie , Réseau nerveux/anatomopathologie , Schizophrénie/génétique , Schizophrénie/anatomopathologie , Langage schizophrène , Adolescent , Adulte , Encéphale/physiopathologie , Cartographie cérébrale , Dominance cérébrale/génétique , Dominance cérébrale/physiologie , Femelle , Humains , Troubles du développement du langage/physiopathologie , Imagerie par résonance magnétique , Mâle , Tests neuropsychologiques , Lobe occipital/malformations , Lobe occipital/anatomopathologie , Lobe occipital/physiopathologie , Cortex préfrontal/malformations , Cortex préfrontal/anatomopathologie , Cortex préfrontal/physiopathologie , Techniques psychologiques , Risque , Jeune adulteRÉSUMÉ
PURPOSE: Septo-optic dysplasia is a congenital disorder consisting of optic nerve hypoplasia and absent septum pellucidum. While associated anomalies have been described, olfactory sulcus and bulb-tract hypoplasia have been scantily reported and was the focus of this study. METHODS: The picture archival and communications system and radiology information system (PACS-RIS) was searched over 15 years for patients with suspected septo-optic dysplasia (nâ¯= 41) and cerebral magnetic resonance imaging (MRI). Included patients had coronal (≤3â¯mm), axial (≤4â¯mm), and sagittal (≤4â¯mm) imaging reviewed by two staff neuroradiologists by consensus. Both olfactory sulcus and bulb-tract hypoplasia were ascribed a grade of 0 (normal) to 3 (complete hypoplasia). Other associated congenital anomalies were recorded, if present. Incidence of anomalies were compared to age-matched and gender-matched control patients. RESULTS: Out of 41 septo-optic dysplasia patients 33 were included (mean ageâ¯= 120.7 months), with 8 excluded due to isolated septum pellucidum absence (nâ¯= 5), isolated bilateral optic hypoplasia (nâ¯= 2), or inadequate imaging (nâ¯= 1). An olfactory sulcus was hypoplastic on one or both sides in 14/33 (42.4%). Olfactory bulb hypoplasia was noted in one or both tracts in 15/33 (45.4%). A significant correlation was found between degree of olfactory sulcal and bulb-tract hypoplasia (ρâ¯= 0.528, pâ¯= 0.0009). Other anomalies were: anterior falx dysplasia (nâ¯= 16, 48.5%), incomplete hippocampal inversion (nâ¯= 14, 42.4%), polymicrogyria (nâ¯= 11, 33.3%), callosal complete or partial agenesis (nâ¯= 10, 30.3%), schizencephaly (nâ¯= 8, 24.2%), ectopic posterior pituitary (nâ¯= 6, 18.2%), and nodular heterotopia (nâ¯= 4, 12.1%). Of the age-matched control patients 10/33 (30.3%) had at least mild anterior falx hypoplasia, and 1 control patient was noted to have unilateral incomplete hippocampal inversion (IHI); none of the age-matched control patients had olfactory sulcus or bulb-tract hypoplasia. CONCLUSION: Olfactory sulcus and bulb-tract hypoplasia are fairly common in septo-optic dysplasia and can be discordant between sides. Of the other associated anomalies, anterior falx dysplasia seems to be the most common.
Sujet(s)
Imagerie par résonance magnétique , Bulbe olfactif/imagerie diagnostique , Cortex préfrontal/imagerie diagnostique , Dysplasie septo-optique/imagerie diagnostique , Adolescent , Adulte , Agénésie du corps calleux/imagerie diagnostique , Études cas-témoins , Enfant , Enfant d'âge préscolaire , Femelle , Hippocampe/malformations , Hippocampe/imagerie diagnostique , Humains , Nourrisson , Mâle , Adulte d'âge moyen , Bulbe olfactif/malformations , Cortex préfrontal/malformations , Études rétrospectives , Schizencéphalie/imagerie diagnostique , Dysplasie septo-optique/anatomopathologieRÉSUMÉ
Abnormalities of eye movements have been reported in patients with Parkinson's disease (PD). However, it is unclear if they occur in the prodromal stage of synucleinopathy represented by idiopathic rapid eye movement sleep behaviour disorder (iRBD). We thus aimed to study eye movements in subjects with iRBD and in de novo PD, to assess if their abnormalities may serve as a clinical biomarker of neurodegeneration. Fifty subjects with polysomnography-confirmed iRBD (46 male, age 40-79 years), 18 newly diagnosed, untreated PD patients (13 male, age 43-75 years) and 25 healthy controls (20 male, age 42-79 years) were prospectively enrolled. Horizontal and vertical ocular prosaccades and antisaccades were investigated with video-oculography. All patients completed the MDS-UPDRS and the Montreal Cognitive Assessment. In addition, a neuropsychological battery was performed on iRBD subjects. When compared with healthy controls, both de novo PD patients and iRBD subjects showed increased error rates in the horizontal antisaccade task (p < 0.01, p < 0.05 respectively). In the iRBD group, the error rates in horizontal and vertical antisaccades correlated with performances in the Prague Stroop Test and the Grooved Pegboard Test, as well as with motor scores of the MDS-UPDRS. De novo PD patients showed a lower gain (p < 0.01) compared with controls. In conclusion, the increased error rate in the antisaccade task of iRBD and PD patients reflects a dysfunction of the dorsolateral prefrontal cortex and is related to the impairment of executive functions and attention.
Sujet(s)
Mouvements oculaires/physiologie , Maladie de Parkinson/physiopathologie , Polysomnographie/méthodes , Cortex préfrontal/malformations , Trouble du comportement en sommeil paradoxal/complications , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Trouble du comportement en sommeil paradoxal/physiopathologieRÉSUMÉ
BACKGROUND AND OBJECTIVE: While noninvasive brain stimulation techniques show promise for language recovery after stroke, the underlying mechanisms remain unclear. We applied inhibitory repetitive transcranial magnetic stimulation (rTMS) to regions of interest in the right inferior frontal gyrus of patients with chronic poststroke aphasia and examined changes in picture naming performance and cortical activation. METHODS: Nine patients received 10 days of 1-Hz rTMS (Monday through Friday for 2 weeks). We assessed naming performance before and immediately after stimulation on the first and last days of rTMS therapy, and then again at 2 and 6 months post-rTMS. A subset of six of these patients underwent functional magnetic resonance imaging pre-rTMS (baseline) and at 2 and 6 months post-rTMS. RESULTS: Naming accuracy increased from pre- to post-rTMS on both the first and last days of treatment. We also found naming improvements long after rTMS, with the greatest improvements at 6 months post-rTMS. Long-lasting effects were associated with a posterior shift in the recruitment of the right inferior frontal gyrus: from the more anterior Brodmann area 45 to the more posterior Brodmann areas 6, 44, and 46. The number of left hemispheric regions recruited for naming also increased. CONCLUSIONS: This study found that rTMS to the right hemisphere Broca area homologue confers long-lasting improvements in picture naming performance. The mechanism involves dynamic bilateral neural network changes in language processing, which take place within the right prefrontal cortex and the left hemisphere more generally. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier NCT00608582).
Sujet(s)
Aphasie/thérapie , Imagerie par résonance magnétique/méthodes , Cortex préfrontal/malformations , Stimulation magnétique transcrânienne/méthodes , Sujet âgé , Cortex cérébral/physiopathologie , Maladie chronique , Femelle , Humains , Mâle , Adulte d'âge moyenSujet(s)
Épilepsies partielles/étiologie , Malformations corticales/complications , Cortex préfrontal/malformations , Crises épileptiques/étiologie , Adulte , Enfant , Enfant d'âge préscolaire , Épilepsies partielles/imagerie diagnostique , Épilepsies partielles/physiopathologie , Épilepsies partielles/thérapie , Femelle , Humains , Mâle , Malformations corticales/imagerie diagnostique , Malformations corticales/physiopathologie , Malformations corticales/thérapie , Cortex préfrontal/imagerie diagnostique , Cortex préfrontal/physiopathologie , Cortex préfrontal/chirurgie , Crises épileptiques/imagerie diagnostique , Crises épileptiques/physiopathologie , Crises épileptiques/thérapieRÉSUMÉ
Major depressive disorder (MDD) and bipolar disorder (BD) are severe psychiatric diseases with overlapping symptomatology. Although previous studies reported abnormal brain structures in MDD or BD patients, the disorder-specific underlying neural mechanisms remain poorly understood. The purpose of this study was to investigate the whole-brain gray matter morphological patterns in unmedicated patients with MDD or BD and to identify the shared and disease-specific brain morphological alterations in these two disorders. We acquired high-resolution brain structural MRI data from a sample of 36 MDD patients, 32 BD patients, and 30 healthy controls. Using FreeSurfer, we estimated their brain cortical thickness (CT) and compared between-group difference in multiple locations across the continuous cortical surface. Compared to the healthy controls, both the MDD and BD patient groups showed significantly reduced CT in the left inferior temporal cortex (ITC). However, compared to the MDD patients, the BD patients showed a significantly thinner CT in the left rostral middle frontal region. In addition, compared to the healthy controls, the BD patients displayed thinner CT in the left ITC, left frontal pole (FPO), left superior frontal, right lateral occipital, right pars triangularis (PTRI) and right lateral orbitofrontal regions. Further analysis revealed a significantly positive correlation between the mean CT in the left FPO and the onset age, but a negative correlation between the mean CT in the right PTRI and the number of episodes, in the BD patients. Our findings revealed that the BD and MDD patients had variations in CT that were in common, but many more that were distinct, suggesting potential differences in their neural mechanisms.
Sujet(s)
Trouble bipolaire/imagerie diagnostique , Encéphale/imagerie diagnostique , Cortex cérébral/imagerie diagnostique , Trouble dépressif majeur/imagerie diagnostique , Imagerie par résonance magnétique/méthodes , Adulte , Analyse de variance , Encéphale/malformations , Cortex cérébral/malformations , Femelle , Substance grise/malformations , Substance grise/imagerie diagnostique , Humains , Mâle , Cortex préfrontal/malformations , Cortex préfrontal/imagerie diagnostique , Reproductibilité des résultats , Sensibilité et spécificité , Lobe temporal/malformations , Lobe temporal/imagerie diagnostique , Jeune adulteRÉSUMÉ
IMPORTANCE: Patients with attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD) share impaired inhibitory control. However, it is unknown whether impairments are mediated by shared or disorder-specific neurostructural and neurofunctional abnormalities. OBJECTIVE: To establish shared and disorder-specific structural, functional, and overlapping multimodal abnormalities in these 2 disorders through a voxel-based meta-analytic comparison of whole-brain gray matter volume (GMV) and functional magnetic resonance imaging (fMRI) studies of inhibition in patients with ADHD and OCD. DATA SOURCES: Literature search using PubMed, ScienceDirect, Web of Knowledge, and Scopus up to September 30, 2015. STUDY SELECTION: Whole-brain voxel-based morphometry (VBM) or fMRI studies during inhibitory control comparing children and adults with ADHD or OCD with controls. DATA EXTRACTION AND SYNTHESIS: Voxel-wise meta-analyses of GMV or fMRI differences were performed using Seed-based d-Mapping. Regional structure and function abnormalities were assessed within each patient group and then a quantitative comparison was performed of abnormalities (relative to controls) between ADHD and OCD. MAIN OUTCOMES AND MEASURES: Meta-analytic disorder-specific and shared abnormalities in GMV, in inhibitory fMRI, and in multimodal functional and structural measures. RESULTS: The search revealed 27 ADHD VBM data sets (including 931 patients with ADHD and 822 controls), 30 OCD VBM data sets (928 patients with OCD and 942 controls), 33 ADHD fMRI data sets (489 patients with ADHD and 591 controls), and 18 OCD fMRI data sets (287 patients with OCD and 284 controls). Patients with ADHD showed disorder-contrasting multimodal structural (left z = 1.904, P < .001; right z = 1.738, P < .001) and functional (left z = 1.447, P < .001; right z = 1.229, P < .001) abnormalities in bilateral basal ganglia/insula, which were decreased in GMV and function in patients with ADHD relative to those with OCD (and controls). In OCD patients, they were enhanced relative to controls. Patients with OCD showed disorder-specific reduced function and structure in rostral and dorsal anterior cingulate/medial prefrontal cortex (fMRI z = 2.113, P < .001; VBM z = 1.622, P < .001), whereas patients with ADHD showed disorder-specific underactivation predominantly in the right ventrolateral prefrontal cortex (z = 1.229, P < .001). Ventromedial prefrontal GMV reduction was shared in both disorders relative to controls. CONCLUSIONS AND RELEVANCE: Shared impairments in inhibitory control, rather than representing a transdiagnostic endophenotype in ADHD and OCD, were associated with disorder-differential functional and structural abnormalities. Patients with ADHD showed smaller and underfunctioning ventrolateral prefrontal/insular-striatal regions whereas patients with OCD showed larger and hyperfunctioning insular-striatal regions that may be poorly controlled by smaller and underfunctioning rostro/dorsal medial prefrontal regions.
Sujet(s)
Trouble déficitaire de l'attention avec hyperactivité/diagnostic , Trouble déficitaire de l'attention avec hyperactivité/physiopathologie , Encéphale/malformations , Encéphale/physiopathologie , Imagerie par résonance magnétique , Trouble obsessionnel compulsif/diagnostic , Trouble obsessionnel compulsif/physiopathologie , Adulte , Amygdale (système limbique)/malformations , Amygdale (système limbique)/physiopathologie , Trouble déficitaire de l'attention avec hyperactivité/psychologie , Noyaux gris centraux/malformations , Noyaux gris centraux/physiopathologie , Études cas-témoins , Cortex cérébral/malformations , Cortex cérébral/physiopathologie , Enfant , Dominance cérébrale/physiologie , Femelle , Gyrus du cingulum/malformations , Gyrus du cingulum/physiopathologie , Humains , Mâle , Inhibition nerveuse/physiologie , Cortex préfrontal/malformations , Cortex préfrontal/physiopathologie , Valeurs de référenceRÉSUMÉ
Ketamine is commonly used for anesthesia and as a recreational drug. In pregnant users, a potential neurotoxicity in offspring has been noted. Our previous work demonstrated that ketamine exposure of pregnant rats induces affective disorders and cognitive impairments in offspring. As the prefrontal cortex (PFC) is critically involved in emotional and cognitive processes, here we studied whether maternal ketamine exposure influences the development of the PFC in offspring. Pregnant rats on gestational day 14 were treated with ketamine at a sedative dose for 2 hrs, and pups were studied at postnatal day 0 (P0) or P30. We found that maternal ketamine exposure resulted in cell apoptosis and neuronal loss in fetal brain. Upon ketamine exposure in utero, PFC neurons at P30 showed more dendritic branching, while cultured neurons from P0 PFC extended shorter neurites than controls. In addition, maternal ketamine exposure postponed the switch of NR2B/2A expression, and perturbed pre- and postsynaptic protein expression in the PFC. These data suggest that prenatal ketamine exposure impairs neuronal development of the PFC, which may be associated with abnormal behavior in offsprings.
Sujet(s)
Malformations dues aux médicaments et aux drogues/étiologie , Anesthésiques dissociatifs/toxicité , Antagonistes des acides aminés excitateurs/toxicité , Kétamine/toxicité , Cortex préfrontal/malformations , Effets différés de l'exposition prénatale à des facteurs de risque , Animaux , Apoptose/effets des médicaments et des substances chimiques , Encéphale/effets des médicaments et des substances chimiques , Encéphale/embryologie , Encéphale/anatomopathologie , Cellules cultivées , Homologue-4 de la protéine Disks Large/biosynthèse , Homologue-4 de la protéine Disks Large/génétique , Femelle , Âge gestationnel , Hypnotiques et sédatifs/toxicité , Substances illicites/toxicité , Neurites/effets des médicaments et des substances chimiques , Neurones/effets des médicaments et des substances chimiques , Neurones/anatomopathologie , Cortex préfrontal/effets des médicaments et des substances chimiques , Cortex préfrontal/embryologie , Cortex préfrontal/anatomopathologie , Grossesse , Répartition aléatoire , Rats , Rat Sprague-Dawley , Récepteurs du N-méthyl-D-aspartate/biosynthèse , Récepteurs du N-méthyl-D-aspartate/génétique , Synaptophysine/biosynthèse , Synaptophysine/génétiqueRÉSUMÉ
Identification of therapeutic targets following neurodegeneration is of major biomedical importance. Kolaviron (Kv) is a biflavonoid complex isolated from seeds of Garcina kola - a common oral masticatory agent in Nigeria known to hold medicinal value. Therefore this study evaluated the therapeutic potential of Kv on cells of the dorsolateral prefrontal cortex (DLPFC), before or after sodium azide (NaN3)-induced neurodegeneration. Rats were randomly assigned into 5 groups (6 each) and treated daily (orally) as follows: 1 ml of corn-oil (vehicle of Kv, 21 days); Kv only (200 mg/kg) for 21 days; NaN3 only (20 mg/kg for 5 days); NaN3 (20 mg/kg for 5 days) followed by Kv (200 mg/kg for 21 days); Kv (200 mg/kg for 21 days) followed by NaN3 (20 mg/kg for 5 days). After treatments, rats were sacrificed and perfused transcardially (with 4% PFA) with brains fixed in accordance with the technique to be used. The DLPFC was examined using histology (H&E), immunoperoxidase (GFAP), immunofluorescence (iNOS & nNOS) and Western blotting (MAPT, MAP2, Bax, BCL-2 and CAD). Quantitative analysis was done using ImageJ software and statistical analysis with Graphpad prism (ANOVA) at p<0.05. NaN3 treatment induced neuronal damage, characterized by reduced relative brain weight, pyknosis, karyorrhesis, astrogliosis, axonal/dendritic damage and cytoskeletal dysregualtion that subsequently resulted in increased expressions of apoptotic regulatory proteins. These degenerative changes were relatable to the observed iNOS and nNOS upregulations. However, Kv administration attenuated the NaN3- initiated destructive molecular cascades in the DLPFC of rats through mechanisms that involved inhibition of stressor molecules and toxic proteins, prevention of stress related biochemical redox, preservation of neuronal integrity, cytoskeletal framework and subsequently, reduced the level of apoptotic regulatory proteins. We conclude that Kv conferred therapeutic benefits on NaN3- induced neurodegeneration, particularly when administered before more than after the insult
No disponible
Sujet(s)
Humains , Cortex préfrontal/malformations , Biflavonoïdes/pharmacocinétique , Maladies neurodégénératives/induit chimiquement , Agents protecteurs/pharmacocinétique , Azoture de sodium/effets indésirables , CytosqueletteRÉSUMÉ
This review covers the literature of the last 25 years on the impact of childhood maltreatment on the mental health throughout the individual's life. Child abuse increases the risk of many mental disorders including depression, suicidal ideation and suicidal behavior, anxiety-related disorders, psychoses as well as alcohol and other drug abuse. The impact of child trauma on the mental health is largely due to structural and functional changes in the hippocampus, amygdala and prefrontal cortex. Early preventive interventions play a great role in the prevention of mental disorders associated with childhood adversities.
Sujet(s)
Maltraitance des enfants , Troubles mentaux/étiologie , Santé mentale , Adulte , Amygdale (système limbique)/malformations , Troubles anxieux , Enfant , Trouble dépressif , Femelle , Hippocampe/malformations , Humains , Mâle , Cortex préfrontal/malformations , Risque , Troubles liés à une substance , Idéation suicidaireRÉSUMÉ
Introducción. Las alteraciones cognitivas, emocionales y comportamentales secundarias al daño cerebral adquirido y las demencias degenerativas pueden valorarse cuantitativa y cualitativamente mediante la administración de autoinformes que interroguen a pacientes e informadores fiables sobre las dificultades de los pacientes en la vida cotidiana. Sujetos y métodos. Se administró el inventario de síntomas prefrontales (ISP) y el cuestionario de fallos de memoria en la vida cotidiana modificado (MFE-30) a 174 participantes emparejados: 87 pacientes con daño cerebral o demencias degenerativas y sus 87 informadores fiables. Se exploró, junto con la bondad psicométrica de las pruebas, la utilidad clínica de la aplicación de estos cuestionarios a pacientes e informadores para obtener un índice de discrepancia de las puntuaciones como medida de la anosognosia. Resultados. Los resultados muestran cómo aplicar el ISP-20 (20 ítems) o el ISP (46 ítems), sean o no administrados conjuntamente con el MFE-30 (30 ítems), resulta un procedimiento muy útil para la valoración de la sintomatología en los individuos con daño cerebral adquirido o demencias degenerativas, al proporcionar una gran cantidad de información sobre las dificultades de los pacientes en la vida cotidiana. Conclusiones. Se recomienda, junto con la obligada evaluación neuropsicológica, la cumplimentación de cuestionarios o inventarios de síntomas como los propuestos, dado que presentan ventajas desde el punto de vista clínico, además de resultar eficaces, efectivos y eficientes en términos económicos (AU)
Introduction. The cognitive, emotional and behavioural alterations secondary to acquired brain injury and degenerative dementias can be quantitatively and quantitatively appraised by administering self-reports that ask both patients and reliable informants about the difficulties patients have in their everyday life. Subjects and methods. The Prefrontal Symptoms Inventory (PSI) and the Modified Memory Failures in Everyday Life Questionnaire (MFE-30) were administered to 174 paired participants: 87 patients with brain damage or degenerative dementias and their 87 reliable informants. In addition to the psychometric goodness of the tests, the study also explored the clinical usefulness of applying these questionnaires to patients and their informants in order to obtain a rate of discrepancy in the scores as a measure of anosognosia. Results. The results show how applying the PSI-20 (20 items) or the PSI (46 items), whether administered together with the MFE-30 (30 items) or not, is a very useful procedure for assessing the symptoms in individuals with acquired brain injury or degenerative dementias, since it yields a great deal of information about patients difficulties in their daily life. Conclusions. We recommend that, in addition to the compulsory neuropsychological assessment, questionnaires or inventories of symptoms like those proposed here should be carried out, due to the fact that they offer a number of advantages from the clinical point of view, as well as being efficacious and effective in economic terms (AU)
Sujet(s)
Femelle , Humains , Mâle , Neuropsychologie/enseignement et éducation , Neuropsychologie/éthique , Souffrance cérébrale chronique/métabolisme , Souffrance cérébrale chronique/anatomopathologie , Démence/psychologie , Erreurs innées du métabolisme/génétique , Cortex préfrontal/malformations , Enquêtes et questionnaires/classification , Stage de formation clinique/méthodes , Dépistage de masse/analyse , Neuropsychologie/méthodes , Neuropsychologie/normes , Souffrance cérébrale chronique/complications , Souffrance cérébrale chronique/diagnostic , Démence/anatomopathologie , Erreurs innées du métabolisme/métabolisme , Cortex préfrontal/traumatismes , Enquêtes et questionnaires , Stage de formation clinique , Dépistage de masse/méthodesRÉSUMÉ
Neuronal heterotopia refers to brain malformations resulting from deficits of neuronal migration. Individuals with heterotopias show a high incidence of neurological deficits, such as epilepsy. More recently, it has come to be recognized that focal heterotopias may also show a range of psychiatric problems, including cognitive and behavioral impairments. However, because focal heterotopias are not always located in the brain areas responsible for the symptoms, the causal relationship between the symptoms and heterotopias remains elusive. In this study, we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited spatial working memory deficit and low competitive dominance behavior, which have been shown to be closely associated with the activity of the medial prefrontal cortex (mPFC) in rodents. Analysis of the mPFC activity revealed that the immediate-early gene expression was decreased and the local field potentials of the mPFC were altered in the mice with heterotopias compared with the control mice. Moreover, activation of these ectopic and overlying sister neurons using the DREADD (designer receptor exclusively activated by designer drug) system improved the working memory deficits. These findings suggest that cortical regions containing focal heterotopias can affect distant brain regions and give rise to behavioral abnormalities. Significance statement: Recent studies reported that patients with heterotopias have a variety of clinical symptoms, such as cognitive disturbance, psychiatric symptoms, and autistic behavior. However, the causal relationship between the symptoms and heterotopias remains elusive. Here we showed that mice with focal heterotopias in the somatosensory cortex generated by in utero electroporation exhibited behavioral deficits that have been shown to be associated with the mPFC activity in rodents. The existence of heterotopias indeed altered the neural activities of the mPFC, and direct manipulation of the neural activity of the ectopic neurons and their sister neurons in the overlying cortex improved the behavioral deficit. Thus, our results indicate that focal heterotopias could affect the activities of distant brain areas and cause behavioral abnormalities.
Sujet(s)
Malformations corticales/physiopathologie , Troubles mentaux/physiopathologie , Cortex préfrontal/physiopathologie , Cortex somatosensoriel/physiopathologie , Animaux , Gènes précoces , Apprentissage du labyrinthe , Mémoire , Souris , Cortex préfrontal/malformations , Cortex préfrontal/métabolisme , Comportement social , Cortex somatosensoriel/malformations , Cortex somatosensoriel/métabolismeRÉSUMÉ
IMPORTANCE: The continuum view of the psychosis spectrum (PS) implies that, in population-based samples, PS symptoms should be associated with neural abnormalities similar to those found in help-seeking clinical risk individuals and in schizophrenia. To our knowledge, functional neuroimaging has not previously been applied in large population-based PS samples and can help us understand the neural architecture of psychosis more broadly and identify brain phenotypes beyond symptoms that are associated with the extended psychosis phenotype. OBJECTIVE: To examine the categorical and dimensional relationships of PS symptoms to prefrontal hypoactivation during working memory and to amygdala hyperactivation during threat emotion processing. DESIGN, SETTING, AND PARTICIPANTS: The Philadelphia Neurodevelopmental Cohort is a genotyped, prospectively accrued, population-based sample of almost 10,000 youths who received a structured psychiatric evaluation and a computerized neurocognitive battery. The study was conducted at an academic and children's hospital health care network, between November 1, 2009 to November 30, 2011. A subsample of 1445 youths underwent neuroimaging, including functional magnetic resonance imaging tasks examined herein. Participants were youth aged 11 to 22 years old identified through structured interview as having PS features (PS group) (n = 260) and typically developing (TD) comparison youth without significant psychopathology (TD group) (n = 220). MAIN OUTCOMES AND MEASURES: Two functional magnetic resonance imaging paradigms were used: a fractal n-back working memory task probing executive system function and an emotion identification task probing amygdala responses to threatening faces. RESULTS: In the n-back task, working memory evoked lower activation in the PS group than the TD group throughout the executive control circuitry, including dorsolateral prefrontal cortex (cluster-corrected P < .05). Within the PS group, dorsolateral prefrontal cortex activation correlated with cognitive deficits (r = .32, P < .001), but no correlation was found with positive symptom severity. During emotion identification, PS demonstrated elevated responses to threatening facial expressions in amygdala, as well as left fusiform cortex and right middle frontal gyrus (cluster-corrected P < .05). The response in the amygdala correlated with positive symptom severity (r = .16, P = .01) but not with cognitive deficits. CONCLUSIONS AND RELEVANCE: The pattern of functional abnormalities observed in the PS group is similar to that previously found in schizophrenia and help-seeking risk samples. Specific circuit dysfunction during cognitive and emotion-processing tasks is present early in the development of psychopathology and herein could not be attributed to chronic illness or medication confounds. Hypoactivation in executive circuitry and limbic hyperactivation to threat could reflect partly independent risk factors for PS symptoms, with the former relating to cognitive deficits that increase the risk for developing psychotic symptoms and the latter contributing directly to positive psychotic symptoms.
Sujet(s)
Amygdale (système limbique)/malformations , Amygdale (système limbique)/physiopathologie , Cortex cérébral/malformations , Cortex cérébral/physiopathologie , Fonction exécutive , Expression faciale , Neuroimagerie fonctionnelle/méthodes , Mémoire à court terme , Reconnaissance visuelle des formes , Troubles psychotiques/physiopathologie , Troubles psychotiques/psychologie , Adolescent , Enfant , Cognition , Émotions , Femelle , Humains , Entretien psychologique , Imagerie par résonance magnétique , Mâle , Tests neuropsychologiques , Phénotype , Cortex préfrontal/malformations , Cortex préfrontal/physiopathologie , Études prospectives , Échelles d'évaluation en psychiatrie , Troubles psychotiques/anatomopathologie , Schizophrénie/physiopathologie , Psychologie des schizophrènes , Indice de gravité de la maladie , Analyse et exécution des tâches , Jeune adulteRÉSUMÉ
Introducción. En las personas con trastornos del espectro autista (TEA), las percepciones sensoriales aberrantes podrían ser tan características y disruptivas como la presencia de anomalías en la comunicación e interacción social, así como de intereses restringidos y repetitivos. La mayoría presenta trastornos de la modulación sensorial (hiper o hiporresponsividad) en varios canales sensoriales. Además, muestra un déficit en la integración de la información procedente de varios sistemas sensoriales (por ejemplo, auditivo y visual). Todo ello agravaría los síntomas nucleares relacionados con la comunicación y aumentaría la aparición de problemas conductuales. Objetivo. Revisar la evidencia experimental que aborda el papel de la corteza prefrontal en las experiencias sensoriales inusuales en los TEA y su implicación en los aspectos sociales. Hay evidencia de hipoactivación y disfunción en redes neurales, que incluyen la corteza prefrontal y participan en la cognición social, como la red por defecto y el sistema de neuronas espejo en niños con TEA. Conclusiones. Los problemas sensoriomotores a edad temprana suponen una disrupción de la organización y regulación no sólo de la percepción y la acción, sino también del lenguaje, el pensamiento, la emoción e incluso la memoria (AU)
Introduction. In persons with autism spectrum disorders (ASD), aberrant sensory perceptions could be as characteristic and disruptive as the presence of anomalies in social communication and interaction or restricted and repetitive interests. Most of them present sensory modulation disorders (hyper- or hypo-responsiveness) in several sensory channels. Furthermore, there is a deficit in the integration of the information from a number of sensory systems (for example, auditory and visual). All this would worsen the core symptoms related with communication and increase the appearance of behavioural problems. Aims. This study aims to review the experimental evidence that addresses the role played by the prefrontal cortex in unusual sensory experiences in ASD and its involvement in social aspects. There is evidence of hypoactivation and dysfunction of the neural networks, which include the prefrontal cortex and participate in social cognition, such as the default mode and the mirror neuron system in children with ASD. Conclusions. Sensory-motor problems at an early age correspond to a disruption in the organisation and regulation not only of perception and action but also language, thought, emotion and even memory (AU)