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1.
Behav Brain Res ; : 112301, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31644928

RESUMO

Self-initiated action is critical to social interaction and individuals with social anxiety find it particularly difficult to initiate social interactions. We showed earlier that social exclusion encumbered self-initiated actions in the Cyberball task in young adults. Here, we examined whether behavioral performance and regional responses during self-initiated actions vary with age in 53 participants (21-74 years; 27 men). Behaviorally, participants were slower in tossing the ball during exclusion (EX) than during fair game (FG) sessions in both men and women. In women but not in men the reaction time (RT) burden (RT_EX - RT_FG; RT prolonged during social exclusion) of ball toss was positively correlated with age despite no observed sex difference in Social Interaction Anxiety Scale scores. The pregenual anterior cingulate cortex (pgACC), thalamus, left occipital cortex (OC) and left insula/orbitofrontal cortex (OFC) responded to ball toss in EX vs. FG in negative correlation with age in women but not in men. Further, the activation of left OC fully mediated the relationship between age and RT burden in women. Thus, older women are more encumbered in self-initiated action during social exclusion, although this behavioral burden is not reflected in subjective reports of social anxiety. Age-related diminution in OC activities may reflect the neural processes underlying the difficulty in initiating social interactions in women. Together, the findings identified age-sensitive behavioral and neural processes of self-initiated action in the Cyberball task and suggest the importance of considering age and sex differences in studies of social interaction.

2.
J Investig Med High Impact Case Rep ; 7: 2324709619850216, 2019 Jan-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31132886

RESUMO

BACKGROUND: Cutaneous squamous cell carcinoma is a common type of skin cancer, with aggressive metastatic or locally advanced disease representing an uncommon minority of presentations. Emerging data have supported the Food and Drug Administration approval of the anti-PD1 human monoclonal antibody cemiplimab in select patients with advanced disease. However, there is limited data regarding durability of effect and generalizability of anti-PD1 effectiveness across therapies. Additionally, information regarding applicability of these regimens to the rare spindle cell variant and to central nervous system metastases for cutaneous squamous cell carcinoma is unfortunately limited. CASE PRESENTATION: A 72-year-old gentleman presented with facial neurological deficits and a dermal nodule and was diagnosed with spindle cell squamous cell carcinoma with perineural invasion. His course was notable for early intracranial metastasis with progressive neurological deficits despite recurrent radiation therapy with intermittent response. When progressive left-sided weakness prompted imaging evaluation that was concerning for disease recurrence after exhaustion of radiation therapy options, the patient was started on systemic therapy with the anti-PD-1 monoclonal antibody treatment prior to the approval of cemiplimab. Pembrolizumab was chosen due to the fact that the patient was ineligible for clinical trials and for its every 21-day dosing. With this treatment, he has achieved a durable clinical response, resulting in near resolution of neurological deficits and more than a year of progression-free survival to date, despite aggressive intracranial disease. CONCLUSIONS: This case suggests that anti-PD-1 therapy with pembrolizumab may represent an effective and well-tolerated treatment for patients with metastatic spindle cell squamous cell carcinoma including patients with metastatic disease to the central nervous system.

3.
Brain Imaging Behav ; 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-31011949

RESUMO

Previous research has reported reduced efficiency in reactive inhibition, along with reduced brain activations, in older adults. The current study investigated age-related behavioral and neural changes in proactive inhibition, and whether age may influence the relationship between proactive and reactive inhibition. One-hundred-and-forty-nine adults (18 to 72 years) underwent fMRI while performing a stop signal task (SST). Proactive inhibition was defined by the sequential effect, the correlation between the estimated probability of stop signal - p(Stop) - and go trial reaction time (goRT). P(Stop) was estimated trial by trial with a Bayesian belief model; reactive inhibition was defined by the stop signal reaction time (SSRT). Behaviorally the magnitude of sequential effect was not correlated with age, replicating earlier reports of spared proactive control in older adults. Age was associated with greater activations to p(Stop) in the lateral prefrontal cortex (PFC), paracentral lobule, superior parietal lobule, and cerebellum, and activations to goRT in the inferior occipital gyrus (IOG). Granger Causality analysis demonstrated that the PFC Granger caused IOG, with the PFC-IOG connectivity significantly correlated with p(Stop) in older but not younger adults. These findings suggest that the PFC and IOG activations and PFC-IOG connectivity may compensate for proactive control during aging. In contrast, while the activations of the ventromedial prefrontal cortex and caudate head to p(Stop) were negatively correlated with SSRT, relating proactive to reactive control, these activities did not vary with age. These findings highlighted distinct neural processes underlying proactive inhibition and limited neural plasticity to support cognitive control in the aging brain.

4.
Medicine (Baltimore) ; 98(16): e15301, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31008981

RESUMO

To investigate the relationship between depression and the self-reported prospective memory (SPM) problems in breast cancer survivors who have received chemotherapy.Sixty-three breast cancer patients were administered with self-rating depression scale (SDS) and the prospective memory questionnaire as part of extensive neuropsychological assessments before and after chemotherapy. The performance of SDS and SPM were compared, with the level of significance set at P < .05.Compared with the group before chemotherapy, there is a significant difference on the SPM score (t = 6.069, P = .000) in breast cancer patients after chemotherapy. Further, there is also a significant difference on the SPM score (t = -4.348, P = .000) between the patients with and without depression group after chemotherapy.The present result indicated that the depression in breast cancer survivors after chemotherapy may be involved in their chemotherapy-induced SPM impairment.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Depressão/etiologia , Transtornos da Memória/etiologia , Memória Episódica , Antineoplásicos/uso terapêutico , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Estudos de Casos e Controles , Feminino , Humanos , Transtornos da Memória/induzido quimicamente , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Autorrelato
5.
Oncol Rep ; 41(5): 3089-3099, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896887

RESUMO

Piwi­interacting RNAs (piRNAs) comprise the largest class of non­coding RNAs. They represent a molecular feature shared by all non­aging biological systems, including germline and somatic cancer stem cells, which display an indefinite capacity of renewal and proliferation and are potentially immortal. They have been identified in animal stomachs, but their relationship with human gastric cancers remains largely unclear. The present study aimed to identify the piRNAs associated with human gastric cancers across the whole transcriptome. Fresh tumor tissues and adjacent non­tumorous tissues from stomachs were examined using a piRNA microarray (23,677 piRNAs) that was then validated by qPCR. The differential expression of piRNAs between cases and controls was analyzed. The transposable elements (TEs) that are potentially targeted by the risk piRNAs were searched. The expression of the nearest genes that are complementary to the sequences of the piRNAs was examined in the stomach tissue. The regulatory effects of genome­wide significant and replicated cancer­risk DNA variants on the piRNA expression in stomach were tested. Based on the findings, we identified a total of 8,759 piRNAs in human stomachs. Of all, 50 were significantly (P<0.05) and differentially (>2­fold change) expressed between the cases and controls, and 64.7% of the protein­coding genes potentially regulated by the gastric cancer­associated piRNAs were expressed in the human stomach. The expression of many cancer­associated piRNAs was correlated with the genome­wide and replicated cancer­risk SNPs. In conclusion, we conclude that piRNAs are abundant in human stomachs and may play important roles in the etiological processes of gastric cancers.


Assuntos
Regulação Neoplásica da Expressão Gênica , RNA Interferente Pequeno/genética , Neoplasias Gástricas/genética , Transcriptoma/genética , Adulto , Idoso , Animais , Estudos de Coortes , Elementos de DNA Transponíveis/genética , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Polimorfismo de Nucleotídeo Único/genética , RNA Interferente Pequeno/metabolismo , Estômago/patologia , Neoplasias Gástricas/patologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-30711509

RESUMO

BACKGROUND: Positive alcohol expectancy (AE) contributes to excessive drinking. Many imaging studies have examined cerebral responses to alcohol cues and how these regional processes related to problem drinking. However, it remains unclear how AE relates to cue response and whether AE mediates the relationship between cue response and problem drinking. METHODS: A total of 61 nondependent drinkers were assessed with the Alcohol Expectancy Questionnaire and Alcohol Use Disorder Identification Test and underwent functional magnetic resonance imaging while exposed to alcohol and neutral cues. Imaging data were processed and analyzed with published routines, and mediation analyses were conducted to examine the interrelationships among global positive score of the Alcohol Expectancy Questionnaire, Alcohol Use Disorder Identification Test score, and regional responses to alcohol versus neutral cues. RESULTS: Alcohol as compared with neutral cues engaged the occipital, retrosplenial, and medial orbitofrontal cortex as well as the left caudate head and red nucleus. The bilateral thalamus showed a significant correlation in cue response and in left superior frontal cortical connectivity with global positive score in a linear regression. Mediation analyses showed that global positive score completely mediated the relationship between thalamic cue activity as well as superior frontal cortical connectivity and Alcohol Use Disorder Identification Test score. The alternative models that AE contributed to problem drinking and, in turn, thalamic cue activity and connectivity were not supported. CONCLUSIONS: The findings suggest an important role of the thalamic responses to alcohol cues in contributing to AE and at-risk drinking in nondependent drinkers. AEs may reflect a top-down modulation of the thalamic processing of alcohol cues, influencing the pattern of alcohol use.

7.
Sci Rep ; 8(1): 13801, 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30218006

RESUMO

To investigate chemotherapy dosage-related cognitive impairment and its neural mechanisms in breast cancer (BC) patients. Twenty-eight breast cancer patients after each chemotherapy cycle and matched 29 healthy control subjects underwent structural magnetic resonance imaging. Voxel-based morphometry analysis was performed to compare group differences in the gray matter for the whole brain. Furthermore, mediation analysis was conducted to explore the role of brain structures in chemotherapy dosage-related cognitive impairment. Voxel-based morphometry analysis was performed in gray matter for the whole brain of BC patients after chemotherapy. The results revealed that the gray matter density in the left inferior frontal gyrus, right middle frontal gyrus, right fusiform area, and bilateral cerebellum was decreased in the BC patients compared to controls. The number of chemotherapy cycles was negatively associated with general cognitive capacity, verbal fluency and digit span performance in the BC patients. In addition, decreased gray matter density in the right middle frontal gyrus could mediate the chemotherapy dosage effects on verbal fluency performance. These findings indicate that the dose-response relationship between chemotherapy and cognitive impairment may depend on the decreases in gray matter density of the frontal cortical structures.

8.
Brain Connect ; 8(8): 487-502, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30198312

RESUMO

Alcohol misuse is associated with thalamic dysfunction. The thalamus comprises subnuclei that relay and integrate information between cortical and subcortical structures. However, it is unclear how the subnuclei contribute to thalamic dysfunctions in problem drinking. We investigated resting-state functional connectivity (rsFC) of thalamic subregions in 107 nondependent drinkers (57 women), using masks delineated by white matter tractography. Thalamus was parceled into motor, somatosensory, visual, premotor, frontal association, parietal association, and temporal association subregions. Whole-brain linear regression, each against Alcohol Use Disorders Identification Test (AUDIT) and positive alcohol expectancy (AE) score with age as a covariate, was performed for each seed, for men and women combined, and separately. Overall, problem drinking was associated with increased thalamic connectivities, whereas AE was associated with a mixed pattern of increased and decreased connectivities. Motor, premotor, somatosensory, and frontal association thalamic connectivity with bilateral caudate head was positively correlated with AUDIT score in men and women combined. Connectivity of the right caudate head with frontal association and premotor thalamus was also positively correlated with AE score in men and women combined. In contrast, motor and premotor thalamic connectivity with a number of cortical and subcortical structures showed sex differences in the correlation each with AUDIT and AE score. In mediation analyses, AE score completely mediated the correlation between thalamic caudate connectivity and AUDIT score, whereas the model where AE contributed to problem drinking and, in turn, altered thalamic caudate connectivity was not supported. To conclude, thalamic subregional rsFCs showed both shared and distinct changes and sex differences in association with problem drinking and AE. Increased thalamic caudate connectivity may contribute to problem drinking via enhanced AE. The findings suggest the importance of examining thalamic subdivisions and sex in investigating the functional roles of thalamus in problem drinking.

9.
J Oncol ; 2018: 3625302, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30174692

RESUMO

The aim of this study was to investigate the relationship between psychosocial distress and quality of life (QOL) in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Fifty-three patients with an initial diagnosis of NPC were enrolled in this study. The psychological Distress Thermometer (DT) and Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N) were conducted before and after radiotherapy in NPC patients. We compared the differences in psychological distress and QOL before and after radiotherapy and analyzed the correlation between psychological distress and QOL after radiotherapy. The performance on the DT was 6.60 ± 1.42 and 2.81 ± 1.43 before and after chemotherapy, respectively, with a significant difference between the time points (t = -13.73, P < 0.01). The performance on the FACT-H&N was 68.30 ± 6.14 and 39.84 ± 6.14 before and after chemotherapy, respectively, with a significant difference between the time points (t = -19.9, P< 0.01). There was a significant negative correlation between the DT score and the FACT-H&N score (r = -3.64, P< 0.01). Patients with NPC experience different degrees of psychological distress, an important factor that affects quality of life, after radiotherapy.

10.
Hum Brain Mapp ; 39(12): 5085-5096, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30113124

RESUMO

Inhibitory control or the ability to refrain from incorrect responses is a critical executive function known to diminish during aging. Imaging studies have elucidated cerebral changes that may underlie the age-related deficits. However, it remains unclear whether the structural and functional changes occur in the same brain regions and whether reduced gray matter volumes (GMV) mediate decreased activation during inhibition. Here, in a sample of 149 participants, we addressed the issues using structural and functional magnetic resonance imaging. Individual's response inhibition was evaluated by the stop signal reaction time (SSRT) in a stop signal task. The results showed that age was associated with prolonged SSRT across participants. Many cortical and subcortical regions demonstrated age-related reduction in GMV and activation to response inhibition. Additionally, age-related diminution in inhibitory control, as indexed by the SSRT, was associated with both shared and distinct morphometric and functional changes. Voxel-based morphometry demonstrated age-related reduction in GMV in the right dorsolateral prefrontal cortex and caudate head as well as bilateral insula, in association with prolonged SSRT. In a contrast of stop success versus go success trials, age was associated with lower activation in the medial and inferior frontal cortex and inferior parietal cortex. Further, reduction in GMV mediated age-related differences in activations only of the medial prefrontal cortex, providing limited evidence for structure function association. Thus, the decline in inhibitory control, as evidenced in the stop signal task, manifest with both shared and distinct structural and functional processes during aging.

11.
Front Aging Neurosci ; 10: 209, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30061823

RESUMO

Functional connectivities of the amygdala support emotional and cognitive processing. Life-span development of resting-state functional connectivities (rsFC) of the amygdala may underlie age-related differences in emotion regulatory mechanisms. To date, age-related changes in amygdala rsFC have been reported through adolescence but not as thoroughly for adulthood. This study investigated age-related differences in amygdala rsFC in 132 young and middle-aged adults (19-55 years). Data processing followed published routines. Overall, amygdala showed positive rsFC with the temporal, sensorimotor and ventromedial prefrontal cortex (vmPFC), insula and lentiform nucleus, and negative rsFC with visual, frontoparietal, and posterior cingulate cortex and caudate head. Amygdala rsFC with the cerebellum was positively correlated with age, and rsFCs with the dorsal medial prefrontal cortex (dmPFC) and somatomotor cortex were negatively correlated with age, at voxel p < 0.001 in combination with cluster p < 0.05 FWE. These age-dependent changes in connectivity appeared to manifest to a greater extent in men than in women, although the sex difference was only evident for the cerebellum in a slope test of age regressions (p = 0.0053). Previous studies showed amygdala interaction with the anterior cingulate cortex (ACC) and vmPFC during emotion regulation. In region of interest analysis, amygdala rsFC with the ACC and vmPFC did not show age-related changes. These findings suggest that intrinsic connectivity of the amygdala evolved from young to middle adulthood in selective brain regions, and may inform future studies of age-related emotion regulation and maladaptive development of the amygdala circuits as an etiological marker of emotional disorders.

12.
Exp Hematol Oncol ; 7: 15, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29989046

RESUMO

Bullous hemorrhagic dermatosis (BHD) is a systemic side-effect of low molecular weight heparin, characterized by multiple intra-epidermal hemorrhages distant from the site of injection. There have been several small case series and literature reviews on BHD, but none have captured a complete set of reported patients. We sought to describe a case of BHD with late diagnosis and completely summarize the existing English and Spanish literature with searches of Pubmed, Scopus, Ovid Embase and Ovid Medline. After narrowing to 33 relevant reports, we describe 90 reported cases worldwide from 2004 to 2017, in addition to a new case from our institution as a means of comparison. We found that BHD was common in elderly men (mean age 72 ± 12; male:female, 1.9:1) and typically occurred within 7 days of administration of anticoagulation (median 7 days ± 6.4) usually with enoxaparin use (66% of cases). Lesions occurred primarily on the extremities only (67.9% of cases). Coagulation testing was most often normal before administration, and the majority of patients had coagulation testing in therapeutic range during treatment. Most practitioners stopped anticoagulation if continued therapeutic intervention was no longer required (57% of cases), or changed therapy to another anticoagulation if continued treatment was required (14.3% of cases). Therapy was continued outright in 23% of patients. The lesions usually resolved within 2 weeks (mean days, 13.0 ± 7.4). There was no difference in time to resolution between patients who continued the culprit anticoagulant or changed to a different anticoagulant, and those who discontinued anticoagulation altogether (13.9 days vs. 12.1, p = 0.49). Four deaths have been reported in this clinical context, two specified as intracranial hemorrhage. These deaths were unrelated to the occurrence of BHD. Continuation of low-molecular weight heparins appeared to be safe in patients with BHD.

13.
Artigo em Inglês | MEDLINE | ID: mdl-29859929

RESUMO

BACKGROUND: Error-related brain activities are altered in individuals with substance use disorders. Here we examined error-related activities in relation to problem drinking in nondependent alcohol drinkers. In particular, we investigated sex differences and whether altered error responses are related to post-error behavioral control. METHODS: A sample of 145 nondependent drinkers (77 women) performed the stop-signal task during functional magnetic resonance imaging. Imaging data were processed and modeled using statistical parametric mapping. Independent sample t test and linear regression were employed to examine sex differences in error response and relationship between error response and problem drinking. RESULTS: Compared with men, women showed greater error-related (stop error > go success) activations in the bilateral thalamus, right middle/superior temporal cortex, and bilateral dorsal anterior cingulate cortex. In whole-brain linear regression of error responses against the Alcohol Use Disorders Identification Test score, a wide swath of cortical and subcortical regions, including the thalamus, showed decreased activation in association with problem drinking in women but not in men. However, men and women were not different in the extent of post-error slowing and decreased thalamic error response in association with problem drinking was not related to the extent of post-error slowing in women. CONCLUSIONS: The results suggest sex differences in error-related activations with heavier drinking associated with reduced error activations in women but not in men. These differences in cerebral activations may reflect higher physiological arousal in response to errors and greater vulnerability of saliency-related arousal response to problem drinking in female as compared with male social drinkers.

14.
Drug Alcohol Depend ; 185: 173-180, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29454928

RESUMO

Alcohol misuse is associated with dysfunction of the amygdala-prefrontal cortical circuit. The amygdala and its cortical targets show decreased activity during a variety of task challenges in individuals engaged in problem drinking. On the other hand, it is less clear how amygdala resting state functional connectivity (rsFC) may be altered in association with alcohol misuse and whether such changes are restricted to prefrontal cortical structures. Further, the influences of comorbid substance use and depression and potential sex differences have not been assessed in earlier work. Here, with fMRI data from a Nathan Kline Institute/Rockland sample of 83 non-dependent alcohol drinkers (26 men), we addressed changes in whole brain rsFC of the amygdala in association with problem drinking as indexed by an alcohol involvement score. Imaging data were processed with Statistical Parametric Mapping following standard routines and all results were examined at voxel p < 0.001 uncorrected in combination with cluster p < 0.05 corrected for false discovery rate. Alcohol misuse was correlated with decreased amygdala connectivity with the dorsal anterior cingulate cortex (dACC) irrespective of depression and other substance use. Changes in amygdala-dACC connectivity manifested in the latero-basal subdivision of the amygdala. Further, men as compared to women showed a significantly stronger relationship in decreased amygdala-dACC connectivity and problem drinking, although it should be noted that men also showed a trend toward higher alcohol involvement score than women. The findings add to a growing literature documenting disrupted amygdala-prefrontal cortical functions in relation to alcohol misuse.


Assuntos
Alcoolismo/fisiopatologia , Tonsila do Cerebelo/fisiopatologia , Rede Nervosa/fisiopatologia , Caracteres Sexuais , Adulto , Idoso , Alcoolismo/diagnóstico por imagem , Tonsila do Cerebelo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia
15.
Oncotarget ; 9(7): 7322-7331, 2018 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-29484113

RESUMO

Peripheral neuropathy is a major adverse effect in the use of chemotherapeutic drugs. In nearly 50% of patients, chemotherapy induced peripheral neuropathy (CIPN) has been reported as irreversible. With increasing numbers of patients surviving treatment as well as increasing duration of survival after treatment, reducing the side effects of chemotherapy and improving the quality of life has become a major focus of cancer survivorship. Multiple classes of chemotherapeutic drugs including taxanes, platinum agents and vinka alkaloids list peripheral neuropathy as the main dose-limiting side effect of treatment. We previously found that drugs that interfere with the microtubule function, including taxanes and vinca alkaloids, bind to neuronal calcium sensor 1 (NCS1), leading to aberrant calcium signaling. The altered calcium signaling can be mitigated by application of drugs used to treat bipolar disease (e.g., lithium and valproic acid) prior to initiation of chemotherapy. Because pre-treatment with these drugs prevented CIPN in mice treated with taxanes, we sought clinical evidence by performing a retrospective chart review study of the VA electronic health record to see whether or not there would be evidence to support our scientific belief that patients treated with lithium or valproic acid while receiving chemotherapy have a lower risk for development of CIPN than patients who received chemotherapy alone. Our data did provide evidence supporting the belief that treatment with lithium or valproic acid concurrently with chemotherapy was associated with a decreased incidence of developing CIPN.

16.
Front Hum Neurosci ; 11: 52, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28223929

RESUMO

Dysfunction of the dopaminergic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) is implicated in psychiatric disorders including attention-deficit/ hyperactivity disorder (ADHD), addiction, schizophrenia and movement disorders such as Parkinson's disease (PD). Although the prevalence of these disorders varies by age and sex, the underlying neural mechanism is not well understood. The objective of this study was to delineate the distinct resting state functional connectivity (rsFC) of the VTA and SNc and examine the effects of age, from young to middle-adulthood, and sex on the rsFC of these two dopaminergic structures in a data set of 250 healthy adults (18-49 years of age, 104 men). Using blood oxygenation level dependent (BOLD) signals, we correlated the time course of the VTA and SNc to the time courses of all other brain voxels. At a corrected threshold, paired t-test showed stronger VTA connectivity to bilateral angular gyrus and superior/middle and orbital frontal regions and stronger SNc connectivity to the insula, thalamus, parahippocampal gyrus (PHG) and amygdala. Compared to women, men showed a stronger VTA/SNc connectivity to the left posterior orbital gyrus. In linear regressions, men but not women showed age-related changes in VTA/SNc connectivity to a number of cortical and cerebellar regions. Supporting shared but also distinct cerebral rsFC of the VTA and SNc and gender differences in age-related changes from young and middle adulthood in VTA/SNc connectivity, these new findings help advance our understanding of the neural bases of many neuropsychiatric illnesses that implicate the dopaminergic systems.

17.
Brain Struct Funct ; 222(6): 2573-2583, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28110447

RESUMO

Resting-state functional connectivity (rsFC) is widely used to examine cerebral functional organization. The ventral striatum (VS) is critical to motivated behavior, with extant studies suggesting functional hemispheric asymmetry. The current work investigated differences in rsFC between the left (L) and right (R) VS and explored gender differences in the extent of functional lateralization. In 106 adults, we computed a laterality index (fcLI) to query whether a target region shows greater or less connectivity to the L vs R VS. A total of 45 target regions with hemispheric masks were examined from the Automated Anatomic Labeling atlas. One-sample t test was performed to explore significant laterality in the whole sample and in men and women separately. Two-sample t test was performed to examine gender differences in fcLI. At a corrected threshold (p < 0.05/45 = 0.0011), the dorsomedial prefrontal cortex (dmPFC) and posterior cingulate cortex (pCC) showed L lateralization and the intraparietal sulcus (IPS) and supramarginal gyrus (SMG) showed R lateralization in VS connectivity. Except for the pCC, these findings were replicated in a different data set (n = 97) from the Human Connectome Project. Furthermore, the fcLI of VS-pCC was negatively correlated with a novelty seeking trait in women but not in men. Together, the findings may suggest a more important role of the L VS in linking saliency response to self control and other internally directed processes. Right lateralization of VS connectivity to the SMG and IPS may support attention and action directed to external behavioral contingencies.


Assuntos
Cérebro/fisiologia , Lateralidade Funcional , Vias Neurais/fisiologia , Estriado Ventral/fisiologia , Adulto , Fatores Etários , Mapeamento Encefálico/métodos , Cérebro/diagnóstico por imagem , Comportamento Exploratório , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/efeitos dos fármacos , Personalidade , Fatores Sexuais , Estriado Ventral/diagnóstico por imagem , Adulto Jovem
18.
Front Hum Neurosci ; 10: 546, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27857686

RESUMO

Proactive control allows us to maneuver a changing environment and individuals are distinct in how they anticipate and approach such changes. Here, we examined how individual differences in personality traits influence cerebral responses to conflict anticipation, a critical process of proactive control. We explored this issue in an fMRI study of the stop signal task, in which the probability of stop signal - p(Stop) - was computed trial by trial with a Bayesian model. Higher p(Stop) is associated with prolonged go trial reaction time, indicating conflict anticipation and proactive control of motor response. Regional brain activations to conflict anticipation were correlated to novelty seeking (NS), harm avoidance (HA), reward dependence, as assessed by the Tridimensional Personality Questionnaire, with age and gender as covariates, in a whole-brain linear regression. Results showed that increased anticipation of the stop signal is associated with activations in the bilateral inferior parietal lobules (IPL), right lateral orbitofrontal cortex (lOFC), middle frontal gyrus (MFG), anterior pre-supplementary motor area (pre-SMA), and bilateral thalamus, with men showing greater activation in the IPL than women. NS correlated negatively to activity in the anterior pre-SMA, right IPL, and MFG/lOFC, and HA correlated negatively to activity in the thalamus during conflict anticipation. In addition, the negative association between NS and MFG/lOFC activity was significant in men but not in women. Thus, NS and HA traits are associated with reduced mobilization of cognitive control circuits when enhanced behavioral control is necessary. The findings from this exploratory study characterize the influence of NS and HA on proactive control and provide preliminary evidence for gender differences in these associations.

19.
Neuroimage ; 134: 466-474, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27126003

RESUMO

Response inhibition and salience detection are among the most studied psychological constructs of cognitive control. Despite a growing body of work, how inhibition and salience processing interact and engage regional brain activations remains unclear. Here, we examined this issue in a stop signal task (SST), where a prepotent response needs to be inhibited to allow an alternative, less dominant response. Sixteen adult individuals performed two versions of the SST each with 25% (SST25) and 75% (SST75) of stop trials. We posited that greater regional activations to the infrequent trial type in each condition (i.e., to stop as compared to go trials in SST25 and to go as compared to stop trials in SST75) support salience detection. Further, successful inhibition in stop trials requires attention to the stop signal to trigger motor inhibition, and the stop signal reaction time (SSRT) has been used to index the efficiency of motor response inhibition. Therefore, greater regional activations to stop as compared to go success trials in association with the stop signal reaction time (SSRT) serve to expedite response inhibition. In support of an interactive role, the dorsal anterior cingulate cortex (dACC) increases activation to salience detection in both SST25 and SST75, but only mediates response inhibition in SST75. Thus, infrequency response in the dACC supports motor inhibition only when stopping has become a routine. In contrast, although the evidence is less robust, the pre-supplementary motor area (pre-SMA) increases activity to the infrequent stimulus and supports inhibition in both SST25 and SST75. These findings clarify a unique role of the dACC and add to the literature that distinguishes dACC and pre-SMA functions in cognitive control.


Assuntos
Função Executiva/fisiologia , Giro do Cíngulo/fisiologia , Inibição (Psicologia) , Desempenho Psicomotor , Adulto , Atenção , Mapeamento Encefálico , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Glicoproteínas de Membrana , Tempo de Reação , Receptores de Interleucina-1 , Adulto Jovem
20.
Alcohol Clin Exp Res ; 40(2): 319-28, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26833431

RESUMO

BACKGROUND: Deficits in inhibitory control have been widely implicated in alcohol misuse. However, the literature does not readily distinguish the effects of drinking problems and chronic alcohol use. Here, we examined how years of drinking and the Alcohol Use Disorders Identification Test (AUDIT) score each influences the cerebral responses to inhibitory control in nondependent drinkers. METHODS: Fifty-seven adult drinkers and 57 age- and gender-matched nondrinkers participated in one 40-minute functional magnetic resonance imaging scan of the stop signal task. Data were preprocessed and modeled using SPM8. In a regression model, we contrasted stop and go success trials for individuals and examined activities of response inhibition each in link with the AUDIT score and years of alcohol use in group analyses. We specified the effects of duration of use by contrasting regional activations of drinkers and age-related changes in nondrinkers. In mediation analyses, we investigated how regional activities mediate the relationship between drinking problems and response inhibition. RESULTS: Higher AUDIT score but not years of drinking was positively correlated with prolonged stop signal reaction time (SSRT) and diminished responses in the cerebellum, thalamus, frontal and parietal regions, independent of years of alcohol use. Further, activity of the thalamus, anterior cingulate cortex, and presupplementary motor area significantly mediates the association, bidirectionally, between the AUDIT score and SSRT. The duration of alcohol use was associated with decreased activation in the right inferior frontal gyrus extending to superior temporal gyrus, which was not observed for age-related changes in nondrinkers. CONCLUSIONS: The results distinguished the association of drinking problems and years of alcohol use to inhibitory control in young adult nondependent drinkers. These new findings extend the imaging literature of alcohol misuse and may have implications for treatment to prevent the escalation from social to dependent drinking. More research is needed to confirm age-independent neural correlates of years of alcohol use.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/psicologia , Encéfalo/fisiologia , Inibição (Psicologia) , Autocontrole/psicologia , Adulto , Estudos de Casos e Controles , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Masculino
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