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The striatum receives projections from multiple regions of the cerebral cortex consistent with the role of the basal ganglia in diverse motor, affective, and cognitive functions. Within the striatum, the caudate receives projections from association cortex, including multiple distinct regions of prefrontal cortex. Building on recent insights about the details of how juxtaposed cortical networks are specialized for distinct aspects of higher-order cognition, we revisited caudate organization using within-individual precision neuroimaging initially in two intensively scanned individuals (each scanned 31 times). Results revealed that the caudate has side-by-side regions that are coupled to at least five distinct distributed association networks, paralleling the organization observed in the cerebral cortex. We refer to these spatial groupings of regions as striatal association megaclusters. Correlation maps from closely juxtaposed seed regions placed within the megaclusters recapitulated the five distinct cortical networks, including their multiple spatially distributed regions. Striatal association megaclusters were explored in 15 additional participants (each scanned at least 8 times), finding that their presence generalizes to new participants. Analysis of the laterality of the regions within the megaclusters further revealed that they possess asymmetries paralleling their cortical counterparts. For example, caudate regions linked to the language network were left lateralized. These results extend the general notion of parallel specialized basal ganglia circuits with the additional discovery that, even within the caudate, there is fine-grained separation of multiple distinct higher-order networks that reflects the organization and lateralization found in the cerebral cortex.NEW & NOTEWORTHY An individualized precision neuroimaging approach reveals juxtaposed zones of the caudate that are coupled with five distinct networks in association cortex. The organization of these caudate zones recapitulates organization observed in the cerebral cortex and extends the notion of specialized basal ganglia circuits.
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Núcleo Caudado , Humanos , Masculino , Adulto , Femenino , Núcleo Caudado/fisiología , Núcleo Caudado/diagnóstico por imagen , Cuerpo Estriado/fisiología , Cuerpo Estriado/diagnóstico por imagen , Corteza Cerebral/fisiología , Corteza Cerebral/diagnóstico por imagen , Imagen por Resonancia Magnética , Vías Nerviosas/fisiología , Vías Nerviosas/diagnóstico por imagen , Adulto Joven , Red Nerviosa/fisiología , Red Nerviosa/diagnóstico por imagen , Persona de Mediana EdadRESUMEN
The cerebral cortex is populated by specialized regions that are organized into networks. Here we estimated networks from functional MRI (fMRI) data in intensively sampled participants. The procedure was developed in two participants (scanned 31 times) and then prospectively applied to 15 participants (scanned 8-11 times). Analysis of the networks revealed a global organization. Locally organized first-order sensory and motor networks were surrounded by spatially adjacent second-order networks that linked to distant regions. Third-order networks possessed regions distributed widely throughout association cortex. Regions of distinct third-order networks displayed side-by-side juxtapositions with a pattern that repeated across multiple cortical zones. We refer to these as supra-areal association megaclusters (SAAMs). Within each SAAM, two candidate control regions were adjacent to three separate domain-specialized regions. Response properties were explored with task data. The somatomotor and visual networks responded to body movements and visual stimulation, respectively. Second-order networks responded to transients in an oddball detection task, consistent with a role in orienting to salient events. The third-order networks, including distinct regions within each SAAM, showed two levels of functional specialization. Regions linked to candidate control networks responded to working memory load across multiple stimulus domains. The remaining regions dissociated across language, social, and spatial/episodic processing domains. These results suggest that progressively higher-order networks nest outward from primary sensory and motor cortices. Within the apex zones of association cortex, there is specialization that repeatedly divides domain-flexible from domain-specialized regions. We discuss implications of these findings, including how repeating organizational motifs may emerge during development.NEW & NOTEWORTHY The organization of cerebral networks was estimated within individuals with intensive, repeat sampling of fMRI data. A hierarchical organization emerged in each individual that delineated first-, second-, and third-order cortical networks. Regions of distinct third-order association networks consistently exhibited side-by-side juxtapositions that repeated across multiple cortical zones, with clear and robust functional specialization among the embedded regions.
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Corteza Cerebral , Imagen por Resonancia Magnética , Red Nerviosa , Humanos , Corteza Cerebral/fisiología , Corteza Cerebral/diagnóstico por imagen , Masculino , Femenino , Adulto , Red Nerviosa/fisiología , Red Nerviosa/diagnóstico por imagen , Mapeo Encefálico , Adulto Joven , Persona de Mediana EdadRESUMEN
OBJECTIVE: To investigate the relation between parental age, and behavioral, cognitive and brain differences in the children. METHOD: Data with children aged 9-11 of 8709 mothers with parental age 15-45 years were analyzed from the Adolescent Brain Cognitive Development (ABCD) study. A general linear model was used to test the associations of the parental age with brain structure, and behavioral and cognitive problems scores. RESULTS: Behavioral and cognitive problems were greater in the children of the younger mothers, and were associated with lower volumes of cortical regions in the children. There was a linear correlation between the behavioral and cognitive problems scores, and the lower brain volumes (r > 0.6), which was evident when parental age was included as a stratification factor. The regions with lower volume included the anterior cingulate cortex, medial and lateral orbitofrontal cortex and amygdala, parahippocampal gyrus and hippocampus, and temporal lobe (FDR corrected p < 0.01). The lower cortical volumes and areas in the children significantly mediated the association between the parental age and the behavioral and cognitive problems in the children (all p < 10-4). The effects were large, such as the 71.4% higher depressive problems score, and 27.5% higher rule-breaking score, in the children of mothers aged 15-19 than the mothers aged 34-35. CONCLUSIONS: Lower parental age is associated with behavioral problems and reduced cognitive performance in the children, and these differences are related to lower volumes and areas of some cortical regions which mediate the effects in the children. The findings are relevant to psychiatric understanding and assessment.
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Encéfalo , Imagen por Resonancia Magnética , Adolescente , Niño , Cognición , Femenino , Humanos , Madres , Corteza PrefrontalRESUMEN
Parkinson's disease (PD) is primarily characterized by the loss of dopaminergic cells and atrophy in subcortical regions. However, the impact of these pathological changes on large-scale dynamic integration and segregation of the cortex are not well understood. In this study, we investigated the effect of subcortical dysfunction on cortical dynamics and cognition in PD. Spatiotemporal dynamics of the phase interactions of resting-state blood-oxygen-level-dependent signals in 159 PD patients and 152 normal control (NC) individuals were estimated. The relationships between subcortical atrophy, subcortical-cortical fiber connectivity impairment, cortical synchronization/metastability, and cognitive performance were then assessed. We found that cortical synchronization and metastability in PD patients were significantly decreased. To examine whether this is an effect of dopamine depletion, we investigated 45 PD patients both ON and OFF dopamine replacement therapy, and found that cortical synchronization and metastability are significantly increased in the ON state. The extent of cortical synchronization and metastability in the OFF state reflected cognitive performance and mediates the difference in cognitive performance between the PD and NC groups. Furthermore, both the thalamic volume and thalamocortical fiber connectivity had positive relationships with cortical synchronization and metastability in the dopaminergic OFF state, and mediate the difference in cortical synchronization between the PD and NC groups. In addition, thalamic volume also reflected cognitive performance, and cortical synchronization/metastability mediated the relationship between thalamic volume and cognitive performance in PD patients. Together, these results highlight that subcortical dysfunction and reduced dopamine levels are responsible for decreased cortical synchronization and metastability, further affecting cognitive performance in PD. This might lead to biomarkers being identified that can predict if a patient is at risk of developing dementia.
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Enfermedad de Parkinson , Atrofia , Cognición , Sincronización Cortical , Dopamina , Humanos , Pruebas Neuropsicológicas , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patologíaRESUMEN
Low sleep duration in adults is correlated with psychiatric and cognitive problems. We performed for the first time a large-scale analysis of sleep duration in children, and how this relates to psychiatric problems including depression, to cognition, and to brain structure. Structural MRI was analyzed in relation to sleep duration, and psychiatric and cognitive measures in 11,067 9-11-year-old children from the Adolescent Brain Cognitive Development (ABCD) Study, using a linear mixed model, mediation analysis, and structural equation methods in a longitudinal analysis. Dimensional psychopathology (including depression, anxiety, impulsive behavior) in the children was negatively correlated with sleep duration. Dimensional psychopathology in the parents was also correlated with short sleep duration in their children. The brain areas in which higher volume was correlated with longer sleep duration included the orbitofrontal cortex, prefrontal and temporal cortex, precuneus, and supramarginal gyrus. Longitudinal data analysis showed that the psychiatric problems, especially the depressive problems, were significantly associated with short sleep duration 1 year later. Further, mediation analysis showed that depressive problems significantly mediate the effect of these brain regions on sleep. Higher cognitive scores were associated with higher volume of the prefrontal cortex, temporal cortex, and medial orbitofrontal cortex. Public health implications are that psychopathology in the parents should be considered in relation to sleep problems in children. Moreover, we show that brain structure is associated with sleep problems in children, and that this is related to whether or not the child has depressive problems.
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Encéfalo , Trastornos del Sueño-Vigilia , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Niño , Cognición , Humanos , Imagen por Resonancia Magnética , Corteza Prefrontal , SueñoRESUMEN
BACKGROUND: Two studies have suggested that severe prolonged nausea and vomiting during pregnancy is associated with emotional and behavioral problems in offspring, with smaller sample size and short-term follow-up. Moreover, little information is available on the role of the brain structure in the associations. METHODS: In a US-based cohort, the association was investigated between severe prolonged nausea and vomiting in pregnancy (extending after the second trimester and termed SNVP), psychiatric and cognitive problems, and brain morphology, from the Adolescent Brain Cognitive Development (ABCD) study, from 10,710 children aged 9-11 years. We validated the emotional including psychiatric findings using the Danish National Cohort Study with 2,092,897 participants. RESULTS: SNVP was significantly associated with emotional and psychiatric problems (t = 8.89, Cohen's d = 0.172, p = 6.9 × 10-19) and reduced global cognitive performance (t = - 4.34, d = - 0.085, p = 1.4 × 10-5) in children. SNVP was associated with low cortical area and volume, especially in the cingulate cortex, precuneus, and superior medial prefrontal cortex. These lower cortical areas and volumes significantly mediated the relation between SNVP and the psychiatric and cognitive problems in children. In the Danish National Cohort, severe nausea and vomiting in pregnancy were significantly associated with increased risks of behavioral and emotional disorders in children (hazard ratio, 1.24; 95% confidence interval, 1.16-1.33). CONCLUSIONS: SNVP is strongly associated with psychiatric and cognitive problems in children, with mediation by brain structure. These associations highlight the clinical importance and potential benefits of the treatment of SNVP, which could reduce the risk of psychiatric disorder in the next generation.
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Encéfalo/fisiopatología , Disfunción Cognitiva/etiología , Trastornos Mentales/etiología , Náusea/etiología , Complicaciones del Embarazo/etiología , Vómitos/etiología , Niño , Disfunción Cognitiva/genética , Estudios de Cohortes , Femenino , Humanos , Masculino , Trastornos Mentales/genética , EmbarazoRESUMEN
MOTIVATION: Advances in neuroimaging and sequencing techniques provide an unprecedented opportunity to map the function of brain regions and identify the roots of psychiatric diseases. However, the results from most neuroimaging studies, i.e. activated clusters/regions or functional connectivities between brain regions, frequently cannot be conveniently and systematically interpreted, rendering the biological meaning unclear. RESULTS: We describe a brain annotation toolbox that generates functional and genetic annotations for neuroimaging results. The voxel-level functional description from the Neurosynth database and gene expression profile from the Allen Human Brain Atlas are used to generate functional/genetic information for region-level neuroimaging results. The validity of the approach is demonstrated by showing that the functional and genetic annotations for specific brain regions are consistent with each other; and further the region by region functional similarity network and genetic similarity network are highly correlated for major brain atlases. One application of brain annotation toolbox is to help provide functional/genetic annotations for newly discovered regions with unknown functions, e.g. the 97 new regions identified in the Human Connectome Project. Importantly, this toolbox can help understand differences between psychiatric patients and controls, and this is demonstrated using schizophrenia and autism data, for which the functional and genetic annotations for the neuroimaging changes in patients are consistent with each other and help interpret the results. AVAILABILITY AND IMPLEMENTATION: BAT is implemented as a free and open-source MATLAB toolbox and is publicly available at http://123.56.224.61:1313/post/bat. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Neuroimagen , Programas Informáticos , Encéfalo , Redes Reguladoras de Genes , Humanos , Anotación de Secuencia MolecularRESUMEN
The "Kraak Porcelain" was a kind of Blue and White Porcelain which exported from China to Europe in Ming and Qing period. The study of Kraak Porcelain is a focus issue in international field of porcelain research. In 2007, the discovery of "Nan'ao I" Shipwreck of Ming Dynasty and the porcelains loaded in it, provided precious materials for the research on Kraak Porcelain. In this paper, we explored the provenance of 10 Kraak Porcelain samples from Nan'ao I, using both traditional visual method and WDXRF.
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A previous study showed that antitumor-analgesic peptide (AGAP), a novel recombinant polypeptide, which had been expressed in Escherichia coli, exhibits analgesic and antitumor effects in mice. In the present study, we investigated the underlying analgesic mechanism of AGAP. The effect of AGAP on voltage-gated calcium channels (VGCCs) was assessed in acutely isolated rat dorsal root ganglia (DRG) neurons using the whole-cell patch clamp technique. The results showed that AGAP potently inhibited VGCCs, especially high-voltage activated (HVA) calcium channels. AGAP inhibited HVA and T-type calcium currents in a dose-dependent manner, but had no significant effect on their dynamic functions in rat small-diameter DRG neurons. AGAP inhibited N- and L-type calcium currents at 78.2% and 57.3%, respectively. Thus, the present study demonstrates that AGAP affects calcium currents through the inhibition of N-, L- and T-type channels in DRG neurons, explaining the potential mechanisms of antinociception.
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Canales de Calcio Tipo T/efectos de los fármacos , Ganglios Espinales/efectos de los fármacos , Activación del Canal Iónico/efectos de los fármacos , Venenos de Escorpión/toxicidad , Animales , Canales de Calcio Tipo T/fisiología , Ganglios Espinales/fisiología , RatasRESUMEN
Iron plays a fundamental role in multiple brain disorders. However, the genetic underpinnings of brain iron and its implications for these disorders are still lacking. Here, we conduct an exome-wide association analysis of brain iron, measured by quantitative susceptibility mapping technique, across 26 brain regions among 26,789 UK Biobank participants. We find 36 genes linked to brain iron, with 29 not being previously reported, and 16 of them can be replicated in an independent dataset with 3,039 subjects. Many of these genes are involved in iron transport and homeostasis, such as FTH1 and MLX. Several genes, while not previously connected to brain iron, are associated with iron-related brain disorders like Parkinson's (STAB1, KCNA10), Alzheimer's (SHANK1), and depression (GFAP). Mendelian randomization analysis reveals six causal relationships from regional brain iron to brain disorders, such as from the hippocampus to depression and from the substantia nigra to Parkinson's. These insights advance our understanding of the genetic architecture of brain iron and offer potential therapeutic targets for brain disorders.
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Encéfalo , Secuenciación del Exoma , Hierro , Humanos , Hierro/metabolismo , Encéfalo/metabolismo , Masculino , Femenino , Análisis de la Aleatorización Mendeliana , Estudio de Asociación del Genoma Completo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Persona de Mediana Edad , Predisposición Genética a la Enfermedad/genética , Anciano , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Adulto , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismoRESUMEN
The striatum receives projections from multiple regions of the cerebral cortex consistent with its role in diverse motor, affective, and cognitive functions. Supporting cognitive functions, the caudate receives projections from cortical association regions. Building on recent insights about the details of how multiple cortical networks are specialized for distinct aspects of higher-order cognition, we revisited caudate organization using within-individual precision neuroimaging (n=2, each participant scanned 31 times). Detailed analysis revealed that the caudate has side-by-side zones that are coupled to at least Give distinct distributed association networks, paralleling the specialization observed in the cerebral cortex. Examining correlation maps from closely juxtaposed seed regions in the caudate recapitulated the Give distinct cerebral networks including their multiple spatially distributed regions. These results extend the general notion of parallel specialized basal ganglia circuits, with the additional discovery that even within the caudate, there is Gine-grained separation of multiple distinct higher-order networks.
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The human cerebellum possesses multiple regions linked to cerebral association cortex. Here we mapped the cerebellum using precision functional MRI within individual participants (N=15), first estimating regions using connectivity and then prospectively testing functional properties using independent task data. Network estimates in all participants revealed a Crus I / II cerebellar megacluster of five higher-order association networks often with multiple, discontinuous regions for the same network. Seed regions placed within the megaclusters, including the disjointed regions, yielded spatially selective networks in the cerebral cortex. Compelling evidence for functional specialization within the cerebellar megaclusters emerged from the task responses. Reflecting functional distinctions found in the cerebrum, domain-flexible cerebellar regions involved in cognitive control dissociated from distinct domain-specialized regions with differential responses to language, social, and spatial / episodic task demands. These findings provide a clear demonstration that the cerebellum encompasses multiple zones dedicated to cognition, featuring juxtaposed regions specialized for distinct processing domains.
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The human cerebral cortex is populated by specialized regions that are organized into networks. Here we estimated networks using a Multi-Session Hierarchical Bayesian Model (MS-HBM) applied to intensively sampled within-individual functional MRI (fMRI) data. The network estimation procedure was initially developed and tested in two participants (each scanned 31 times) and then prospectively applied to 15 new participants (each scanned 8 to 11 times). Detailed analysis of the networks revealed a global organization. Locally organized first-order sensory and motor networks were surrounded by spatially adjacent second-order networks that also linked to distant regions. Third-order networks each possessed regions distributed widely throughout association cortex. Moreover, regions of distinct third-order networks displayed side-by-side juxtapositions with a pattern that repeated similarly across multiple cortical zones. We refer to these as Supra-Areal Association Megaclusters (SAAMs). Within each SAAM, two candidate control regions were typically adjacent to three separate domain-specialized regions. Independent task data were analyzed to explore functional response properties. The somatomotor and visual first-order networks responded to body movements and visual stimulation, respectively. A subset of the second-order networks responded to transients in an oddball detection task, consistent with a role in orienting to salient or novel events. The third-order networks, including distinct regions within each SAAM, showed two levels of functional specialization. Regions linked to candidate control networks responded to working memory load across multiple stimulus domains. The remaining regions within each SAAM did not track working memory load but rather dissociated across language, social, and spatial / episodic processing domains. These results support a model of the cerebral cortex in which progressively higher-order networks nest outwards from primary sensory and motor cortices. Within the apex zones of association cortex there is specialization of large-scale networks that divides domain-flexible from domain-specialized regions repeatedly across parietal, temporal, and prefrontal cortices. We discuss implications of these findings including how repeating organizational motifs may emerge during development.
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BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with longer screen time utilization (STU) at the behavioral level. However, whether there are shared neural links between ADHD symptoms and prolonged STU is not clear and has not been explored in a single large-scale dataset. METHODS: Leveraging the genetics, neuroimaging and behavioral data of 11,000+ children aged 9-11 from the Adolescent Brain Cognitive Development cohort, this study investigates the associations between the polygenic risk and trait for ADHD, STU, and white matter microstructure through cross-sectionally and longitudinal analyses. FINDINGS: Children with higher polygenic risk scores for ADHD tend to have longer STU and more severe ADHD symptoms. Fractional anisotropy (FA) values in several white matter tracts are negatively correlated with both the ADHD polygenic risk score and STU, including the inferior frontal-striatal tract, inferior frontal-occipital fasciculus, superior longitudinal fasciculus and corpus callosum. Most of these tracts are linked to visual-related functions. Longitudinal analyses indicate a directional effect of white matter microstructure on the ADHD scale, and a bi-directional effect between the ADHD scale and STU. Furthermore, reduction of FA in several white matter tracts mediates the association between the ADHD polygenic risk score and STU. INTERPRETATION: These findings shed new light on the shared neural overlaps between ADHD symptoms and prolonged STU, and provide evidence that the polygenic risk for ADHD is related, via white matter microstructure and the ADHD trait, to STU. FUNDING: This study was mainly supported by NSFC and National Key R&D Program of China.
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Trastorno por Déficit de Atención con Hiperactividad , Sustancia Blanca , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Trastorno por Déficit de Atención con Hiperactividad/genética , Encéfalo/diagnóstico por imagen , Niño , Cuerpo Calloso , Humanos , Tiempo de Pantalla , Sustancia Blanca/diagnóstico por imagenRESUMEN
Precision estimates of network organization from functional connectivity MRI in the human and tract-tracing data in the marmoset monkey converge to reveal an orderly macroscale gradient of sequential networks across the cerebral cortex. Parallel networks begin with a sequence of multiple nested sensory-motor networks in both species progressing to more distributed association networks in rostral prefrontal and temporal association zones, which are expanded and differentiated in the human. From this perspective, the spatially-distributed motif encountered in association networks appears to be on a continuum with primary sensory-motor networks. Network motifs supporting sophisticated forms of human cognition may arise from specializations of distributed anatomical networks formed in an ancestor at least 45 million years ago.
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Children's behavioral problems have been associated with their family environments. Here, we investigate whether specific features of brain structures could relate to this link. Using structural magnetic resonance imaging of 8756 children aged 9-11 from the Adolescent Brain Cognitive Developmental study, we show that high family conflict and low parental monitoring scores are associated with children's behavioral problems, as well as with smaller cortical areas of the orbitofrontal cortex, anterior cingulate cortex, and middle temporal gyrus. A longitudinal analysis indicates that psychiatric problems scores are associated with increased family conflict and decreased parental monitoring 1 year later, and mediate associations between the reduced cortical areas and family conflict, and parental monitoring scores. These results emphasize the relationships between the brain structure of children, their family environments, and their behavioral problems.
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Conflicto Familiar/psicología , Giro del Cíngulo/fisiología , Relaciones Padres-Hijo , Corteza Prefrontal/fisiología , Problema de Conducta/psicología , Lóbulo Temporal/fisiología , Niño , Cognición/fisiología , Ambiente , Salud de la Familia , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , MasculinoRESUMEN
Schizophrenia is a neurocognitive illness of synaptic and brain network-level dysconnectivity that often reaches a persistent chronic stage in many patients. Subtle language deficits are a core feature even in the early stages of schizophrenia. However, the primacy of language network dysconnectivity and language-related genetic variants in the observed phenotype in early stages of illness remains unclear. This study used two independent schizophrenia dataset consisting of 138 and 53 drug-naïve first-episode schizophrenia (FES) patients, and 112 and 56 healthy controls, respectively. A brain-wide voxel-level functional connectivity analysis was conducted to investigate functional dysconnectivity and its relationship with illness duration. We also explored the association between critical language-related genetic (such as FOXP2) mutations and the altered functional connectivity in patients. We found elevated functional connectivity involving Broca's area, thalamus and temporal cortex that were replicated in two FES datasets. In particular, Broca's area - anterior cingulate cortex dysconnectivity was more pronounced for patients with shorter illness duration, while thalamic dysconnectivity was predominant in those with longer illness duration. Polygenic risk scores obtained from FOXP2-related genes were strongly associated with functional dysconnectivity identified in patients with shorter illness duration. Our results highlight the criticality of language network dysconnectivity, involving the Broca's area in early stages of schizophrenia, and the role of language-related genes in this aberration, providing both imaging and genetic evidence for the association between schizophrenia and the determinants of language.
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Parcellation of the orbitofrontal cortex, anterior cingulate cortex, and inferior frontal gyrus based on their functional connectivity with the whole brain in resting state fMRI with 654 participants was performed to investigate how these regions with different functions in reward, emotion and their disorders are functionally connected to each other and to the whole brain. The human medial and lateral orbitofrontal cortex, the ventromedial prefrontal cortex, the anterior cingulate cortex, and the right and left inferior frontal gyrus have different functional connectivity with other brain areas and with each other; and each of these regions has several parcels with different functional connectivity with other brain areas. In terms of functional connectivity, the lateral orbitofrontal cortex extends especially on the right into the orbital part of the inferior frontal gyrus and provides connectivity with premotor cortical areas. The orbitofrontal cortex, especially the lateral orbitofrontal cortex, has connectivity not only with language-related areas in the inferior frontal gyrus (Broca's area), but also with the angular and supramarginal gyri. In this context, whereas the connectivity of the orbitofrontal cortex, ventromedial prefrontal cortex, and anterior cingulate cortex is symmetrical, the connectivity of the inferior frontal gyrus triangular and opercular parts is asymmetrical for the right and the left hemispheres. These findings have implications for understanding the neural bases of human emotion and decision-making, and for their disorders including depression.
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Corteza Cerebral/fisiopatología , Vías Nerviosas/fisiopatología , Lóbulo Parietal/fisiopatología , Corteza Prefrontal/fisiopatología , Adulto , Trastorno Depresivo Mayor/fisiopatología , Femenino , Giro del Cíngulo/fisiopatología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The orbitofrontal cortex extends into the laterally adjacent inferior frontal gyrus. We analyzed how voxel-level functional connectivity of the inferior frontal gyrus and orbitofrontal cortex is related to depression in 282 people with major depressive disorder (125 were unmedicated) and 254 controls, using FDR correction P < 0.05 for pairs of voxels. In the unmedicated group, higher functional connectivity was found of the right inferior frontal gyrus with voxels in the lateral and medial orbitofrontal cortex, cingulate cortex, temporal lobe, angular gyrus, precuneus, hippocampus and frontal gyri. In medicated patients, these functional connectivities were lower and toward those in controls. Functional connectivities between the lateral orbitofrontal cortex and the precuneus, posterior cingulate cortex, inferior frontal gyrus, ventromedial prefrontal cortex and the angular and middle frontal gyri were higher in unmedicated patients, and closer to controls in medicated patients. Medial orbitofrontal cortex voxels had lower functional connectivity with temporal cortex areas, the parahippocampal gyrus and fusiform gyrus, and medication did not result in these being closer to controls. These findings are consistent with the hypothesis that the orbitofrontal cortex is involved in depression, and can influence mood and behavior via the right inferior frontal gyrus, which projects to premotor cortical areas.
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Trastorno Depresivo Mayor/fisiopatología , Corteza Prefrontal/fisiopatología , Adulto , Depresión , Femenino , Lóbulo Frontal/fisiopatología , Giro del Cíngulo/fisiopatología , Hipocampo/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Giro Parahipocampal/fisiopatología , Lóbulo Parietal/fisiopatología , Lóbulo Temporal/fisiopatologíaRESUMEN
OBJECTIVE: To identify biotypes in patients with newly diagnosed Parkinson disease (PD) and to test whether these biotypes could explain interindividual differences in longitudinal progression. METHODS: In this longitudinal analysis, we use a data-driven approach clustering PD patients from the Parkinson's Progression Markers Initiative (n = 314, age 61.0 ± 9.5, years 34.1% female, 5 years of follow-up). Voxel-level neuroanatomic features were estimated with deformation-based morphometry (DBM) of T1-weighted MRI. Voxels with deformation values that were significantly correlated (p < 0.01) with clinical scores (Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale Parts I-III and total score, tremor score, and postural instability and gait difficulty score) at baseline were selected. Then, these neuroanatomic features were subjected to hierarchical cluster analysis. Changes in the longitudinal progression and neuroanatomic pattern were compared between different biotypes. RESULTS: Two neuroanatomic biotypes were identified: biotype 1 (n = 114) with subcortical brain volumes smaller than heathy controls and biotype 2 (n = 200) with subcortical brain volumes larger than heathy controls. Biotype 1 had more severe motor impairment, autonomic dysfunction, and much worse REM sleep behavior disorder than biotype 2 at baseline. Although disease durations at the initial visit and follow-up were similar between biotypes, patients with PD with smaller subcortical brain volume had poorer prognosis, with more rapid decline in several clinical domains and in dopamine functional neuroimaging over an average of 5 years. CONCLUSION: Robust neuroanatomic biotypes exist in PD with distinct clinical and neuroanatomic patterns. These biotypes can be detected at diagnosis and predict the course of longitudinal progression, which should benefit trial design and evaluation.