RESUMO
Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) can provide long-term symptom relief for treatment-resistant depression (TRD)1. However, achieving stable recovery is unpredictable2, typically requiring trial-and-error stimulation adjustments due to individual recovery trajectories and subjective symptom reporting3. We currently lack objective brain-based biomarkers to guide clinical decisions by distinguishing natural transient mood fluctuations from situations requiring intervention. To address this gap, we used a new device enabling electrophysiology recording to deliver SCC DBS to ten TRD participants (ClinicalTrials.gov identifier NCT01984710). At the study endpoint of 24 weeks, 90% of participants demonstrated robust clinical response, and 70% achieved remission. Using SCC local field potentials available from six participants, we deployed an explainable artificial intelligence approach to identify SCC local field potential changes indicating the patient's current clinical state. This biomarker is distinct from transient stimulation effects, sensitive to therapeutic adjustments and accurate at capturing individual recovery states. Variable recovery trajectories are predicted by the degree of preoperative damage to the structural integrity and functional connectivity within the targeted white matter treatment network, and are matched by objective facial expression changes detected using data-driven video analysis. Our results demonstrate the utility of objective biomarkers in the management of personalized SCC DBS and provide new insight into the relationship between multifaceted (functional, anatomical and behavioural) features of TRD pathology, motivating further research into causes of variability in depression treatment.
Assuntos
Estimulação Encefálica Profunda , Depressão , Transtorno Depressivo Maior , Humanos , Inteligência Artificial , Biomarcadores , Estimulação Encefálica Profunda/métodos , Depressão/fisiopatologia , Depressão/terapia , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/terapia , Eletrofisiologia , Resultado do Tratamento , Medida de Potenciais de Campo Local , Substância Branca , Lobo Límbico/fisiologia , Lobo Límbico/fisiopatologia , Expressão FacialRESUMO
BACKGROUND AND AIMS: The working memory (WM) ability of internet addicts and the topology underlying the WM processing in internet addiction (IA) are poorly understood. In this study, we employed a graph theoretical framework to characterize the topological properties of the IA brain network in the source cortical space during WM task. METHODS: A sample of 24 subjects with IA and 23 matched healthy controls (HCs) performed visual 2-back task. Exact Low Resolution Electromagnetic Tomography was adopted to project the pre-processed EEG signals into source space. Subsequently, Lagged phase synchronization was calculated between all pairs of Brodmann areas, the graph theoretical approaches were then employed to estimate the brain topological properties of all participants during the WM task. RESULTS: We found better WM behavioral performance in IA subjects compared with the HCs. Moreover, compared to the HC group, more integrated and hierarchical brain network was revealed in the IA subjects in alpha band. And altered regional centrality was mainly resided in frontal and limbic lobes. In addition, significant relationships between the IA severity and the significant altered graph indices were found. CONCLUSIONS: In conclusion, these findings provide evidence to support the notion that altered topological configuration may underline changed WM function observed in IA.
Assuntos
Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Eletroencefalografia/métodos , Transtorno de Adição à Internet/fisiopatologia , Memória de Curto Prazo/fisiologia , Rede Nervosa/fisiopatologia , Adolescente , Adulto , Sincronização Cortical/fisiologia , Feminino , Lobo Frontal/fisiopatologia , Humanos , Lobo Límbico/fisiopatologia , Masculino , Adulto JovemRESUMO
Migraine is a chronic neurological disorder characterized by attacks of moderate or severe headache accompanying functionally and structurally maladaptive changes in brain. As the headache days/month is often measured by patient self-report and tends to be overestimated than actually experienced, the possibility of using neuroimaging data to predict migraine attack frequency is of great interest. To identify neuroimaging features that could objectively evaluate patients' headache days, a total of 179 migraineurs were recruited from two data center with one dataset used as the training/test cohort and the other used as the validating cohort. The guidelines for controlled trials of prophylactic treatment of chronic migraine in adults were used to identify the frequency of attacks and migraineurs were divided into low (MOl) and high (MOh) subgroups. Whole-brain functional connectivity was used to build multivariate logistic regression models with model iteration optimization to identify MOl and MOh. The best model accurately discriminated MOh from MOl with AUC of 0.91 (95%CI [0.86, 0.95]) in the training/test cohort and 0.79 in the validating cohort. The discriminative features were mainly located within the limbic lobe, frontal lobe, and temporal lobe. Permutation tests analysis demonstrated that the classification performance of these features was significantly better than chance. Furthermore, the indicator of functional connectivity had a higher odds ratio than behavioral variables with implementing a holistic regression analysis. The current findings suggested that the migraine attack frequency could be distinguished by using machine-learning algorithms, and highlighted the role of brain functional connectivity in revealing underlying migraine-related neurobiology.
Assuntos
Conectoma/métodos , Lobo Frontal/fisiopatologia , Lobo Límbico/fisiopatologia , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/fisiopatologia , Rede Nervosa/fisiopatologia , Lobo Temporal/fisiopatologia , Adulto , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Lobo Límbico/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Prognóstico , Lobo Temporal/diagnóstico por imagemRESUMO
BACKGROUND: The pathogenesis of major depressive disorder (MDD) is complicated and equivocal. Previous studies have found an incidence of abnormal changes of neural networks, with plentiful evidence pointing the finger of suspicion firmly at the default mode network (DMN) and cortico-limbic networks. The aim of the present study was to use the approach of functional connectivity strength (FCS) to directly investigate the features of spontaneous brain activity in the case of first-episode, drug-naïve adult patients with MDD at rest. METHODS: Resting-state functional magnetic resonance imaging (MRI) scans were performed on 23 first-episode drug-naïve major depressive disorder (MDD) patients and 20 healthy controls (HCs). In this study, using graph-theory approaches(FCS), we computed the characteristics of brain connectivity. Simultaneously, we used a series of validated test procedures to evaluate the patients' cognitive function. Subsequently, the results were compared with the peak of FCS value and a correlation analysis was conducted. RESULTS: Compared with the HCs group, MDD patients showed significantly decreased FCS in bilateral posterior cingulate cortex (PCC)/precuneus and bilateral prefrontal cortex(PFC) and increased FCS in right posterior central gyrus, left thalamus and left temporal lobe. These brain regions belongs to the default-mode network and cortico-limbic networks. Finally, the correlation analyses showed the negative correlation of the FCS values in the left posterior cingulate cortex (PCC)/precuneus and Hamilton Anxiety Rating Scale (HAMA, râ¯=â¯-0.472, pâ¯=â¯.023), Stroop Color Word Test-A(SCWT-A, râ¯=â¯-0.451, pâ¯=â¯.031), Stroop Color Word Test-B(SCWT-B, râ¯=â¯-0.588, pâ¯=â¯.003).Meanwhile, there was negative correlation between the FCS values in the left thalamus and SCWT-A(râ¯=â¯-0.473, pâ¯=â¯.023), SCWT-B(râ¯=â¯-0.465, pâ¯=â¯.025), SCWTC(râ¯=â¯-0.524, pâ¯=â¯.010).In addition, the FCS values in the right PCC has negative correlation with Montgomery Asberg Depression Rating Scale (MADRS) (râ¯=â¯-0.433, pâ¯=â¯.039). CONCLUSIONS: DMN is an important node of MDD. FCS within the default mode network and cortico-limbic networks in patients with major depressive disorder has been changed in the early stage of MDD. FCS can provide favourable and additional evidence in the investigation of brain pathophysiology and therapy in depression.
Assuntos
Encéfalo/fisiopatologia , Cognição/fisiologia , Rede de Modo Padrão/fisiopatologia , Transtorno Depressivo Maior/fisiopatologia , Adolescente , Adulto , Estudos de Casos e Controles , Córtex Cerebral/fisiopatologia , Feminino , Neuroimagem Funcional , Humanos , Lobo Límbico/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Teste de Stroop/estatística & dados numéricos , Adulto JovemRESUMO
BACKGROUND: Clinical levels of a social anxiety disorder (SAD) often appear during childhood and rise to a peak during late adolescence. The temperament trait behavioral inhibition (BI), evident early in childhood, has been linked to increased risk for SAD. Functional and structural variations in brain regions associated with the identification of, and response to, fear may support the BI-SAD relation. Whereas relevant functional studies are emerging, the few extant structural studies have focused on adult samples with mixed findings. METHODS: A moderated-mediation model was used to examine the relations between BI, SAD symptoms, and brain-volume individual differences in a sample of children at risk for anxiety (ages 9-12; N = 130, 52 BI). RESULTS: Our findings indicate that at higher levels of BI, children with smaller anterior insula volumes showed stronger correlations between BI and SAD. In addition, larger ventrolateral prefrontal cortex (vlPFC) volumes were associated with fewer SAD symptoms. CONCLUSIONS: These findings support previous reports linking SAD levels with variations in volume and reactivity in both limbic (insula) and prefrontal (vlPFC) regions. These findings set the foundation for further examination of networks of neural structures that influence the transition from BI to SAD across development, helping further clarify mechanisms of risk and resilience.
Assuntos
Medo/psicologia , Lobo Límbico/fisiopatologia , Fobia Social/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Temperamento/fisiologia , Adolescente , Criança , Feminino , Humanos , Inibição Psicológica , Lobo Límbico/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , RiscoRESUMO
BACKGROUND: Late-life generalized anxiety disorder (GAD) is one of the most common anxiety disorders in older adults. However, its neural markers have received relatively little attention. In this study, we explored the association between worry severity and limbic-prefrontal connectivity during emotional reactivity in late-life GAD. METHODS: We recruited 16 anxious (GAD) and 20 non-anxious (HC) older adults to perform the faces/shapes emotional reactivity task during functional magnetic resonance imaging (fMRI). We investigated the functional connectivity of both the amygdala and the bed nucleus of stria terminalis (BNST) with the prefrontal cortex (PFC) using generalized psychophysiological interaction (gPPI) analysis. We tested for (1) group differences in connectivity, (2) association between worry severity and connectivity, and (3) interaction between group and worry severity and its association with connectivity. RESULTS: Amygdala-PFC and BNST-PFC functional connectivity were associated with worry severity in an inverse U-shape, and was independent of depression severity, global anxiety, neuroticism, and general cognitive function. LIMITATIONS: Our limitations include slightly skewed PSWQ distributions, lack of non-anxious individuals with high worry, small sample size, and low depression comorbidity in a sample of late-life GAD that may not generalize to GAD in younger populations. CONCLUSIONS: This suggests that moderate worry is associated with maximum engagement of the limbic-PFC connectivity, while severe worry is associated with failure of the limbic-PFC emotional regulation circuit. This may explain the aberrant and exaggerated responses to negative stimuli observed in participants with pathological worry.
Assuntos
Transtornos de Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/fisiopatologia , Emoções/fisiologia , Imageamento por Ressonância Magnética , Índice de Gravidade de Doença , Idoso , Tonsila do Cerebelo/fisiopatologia , Feminino , Humanos , Lobo Límbico/diagnóstico por imagem , Lobo Límbico/fisiopatologia , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologiaRESUMO
Mechanisms and predictors for the successful treatment of anxiety and depression have been elusive, limiting the effectiveness of existing treatments and curtailing the development of new interventions. In this study, we evaluated the utility of three widely used neural probes of emotion (experience, regulation, and perception) in their ability to predict symptom improvement and correlate with symptom change following two first-line treatments-selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT). Fifty-five treatment-seeking adults with anxiety and/or depression were randomized to 12 weeks of SSRI or CBT treatment (ClinicalTrials.gov identifier: NCT01903447). Functional magnetic resonance imaging (fMRI) was used to examine frontolimbic brain function during emotion experience, regulation, and perception, as probed by the Emotion Regulation Task (ERT; emotion experience and regulation) and emotional face assessment task (EFAT; emotion perception). Brain function was then related to anxiety and depression symptom change. Results showed that both SSRI and CBT treatments similarly attenuated insula and amygdala activity during emotion perception, and greater treatment-related decrease in insula and amygdala activity was correlated with greater reduction in anxiety symptoms. Both treatments also reduced amygdala activity during emotion experience but brain change did not correlate with symptom change. Lastly, greater pre-treatment insula and amygdala activity during emotion perception predicted greater anxiety and depression symptom improvement. Thus, limbic activity during emotion perception is reduced by both SSRI and CBT treatments, and predicts anxiety and depression symptom improvement. Critically, neural reactivity during emotion perception may be a non-treatment-specific mechanism for symptom improvement.
Assuntos
Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/métodos , Transtorno Depressivo/terapia , Lobo Frontal/diagnóstico por imagem , Lobo Límbico/diagnóstico por imagem , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Adulto , Transtornos de Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Transtorno Depressivo/diagnóstico por imagem , Transtorno Depressivo/fisiopatologia , Regulação Emocional/fisiologia , Emoções , Reconhecimento Facial/fisiologia , Feminino , Lobo Frontal/fisiopatologia , Neuroimagem Funcional , Humanos , Lobo Límbico/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Prognóstico , Adulto JovemRESUMO
An important reasons for drug relapse is the retrieval of drug withdrawal memory induced by conditioned context. Previous studies have suggested that the basolateral amygdala (BLA) plays an important role in conditioned context-induced retrieval of morphine withdrawal memory. However, the downstream neuronal circuits of the activation of the BLA in conditioned context-induced retrieval of morphine withdrawal memory remain unknown. Using retrograde labeling, immunohistochemical, and optogenetic approaches, we found that, although BLA neurons projecting to the prelimbic cortex (PrL) played an important role in conditioned context-induced retrieval of morphine withdrawal memory, they do not exhibit increased expression of the neuronal plasticity marker Arc. However, when PrL neurons activated by the BLA send feedback signals to the BLA, a neuronal-related process is induced in other BLA neurons that do not project to the PrL, a finding that is relevant to conditioned context-induced retrieval of morphine withdrawal memory.
Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiopatologia , Lobo Límbico/fisiopatologia , Memória , Morfina , Transdução de Sinais , Síndrome de Abstinência a Substâncias/fisiopatologia , Animais , Masculino , CamundongosRESUMO
Social anxiety disorder (SAD) is a common and disabling condition characterized by excessive fear and avoidance of public scrutiny. Psychoradiology studies have suggested that the emotional and behavior deficits in SAD are associated with abnormalities in regional brain function and functional connectivity. However, little is known about whether intrinsic functional brain networks in patients with SAD are topologically disrupted. Here, we collected resting-state fMRI data from 33 drug-naive patients with SAD and 32 healthy controls (HC), constructed functional networks with 34 predefined regions based on previous meta-analytic research with task-based fMRI in SAD, and performed network-based statistic and graph-theory analyses. The network-based statistic analysis revealed a single connected abnormal circuitry including the frontolimbic circuit (termed the "fear circuit", including the dorsolateral prefrontal cortex, ventral medial prefrontal cortex and insula) and posterior cingulate/occipital areas supporting perceptual processing. In this single altered network, patients with SAD had higher functional connectivity than HC. At the global level, graph-theory analysis revealed that the patients exhibited a lower normalized characteristic path length than HC, which suggests a disorder-related shift of network topology toward randomized configurations. SAD-related deficits in nodal degree, efficiency and participation coefficient were detected in the parahippocampal gyrus, posterior cingulate cortex, dorsolateral prefrontal cortex, insula and the calcarine sulcus. Aspects of abnormal connectivity were associated with anxiety symptoms. These findings highlight the aberrant topological organization of functional brain network organization in SAD, which provides insights into the neural mechanisms underlying excessive fear and avoidance of social interactions in patients with debilitating social anxiety.
Assuntos
Córtex Cerebral/fisiopatologia , Conectoma/métodos , Lobo Límbico/fisiopatologia , Rede Nervosa/fisiopatologia , Lobo Occipital/fisiopatologia , Fobia Social/fisiopatologia , Adolescente , Adulto , Córtex Cerebral/diagnóstico por imagem , Feminino , Humanos , Lobo Límbico/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Lobo Occipital/diagnóstico por imagem , Fobia Social/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Adulto JovemRESUMO
Psychotic experiences may be understood as altered information processing due to aberrant neural computations. A prominent example of such neural computations is the computation of prediction errors (PEs), which signal the difference between expected and experienced events. Among other areas showing PE coding, hippocampal-prefrontal-striatal neurocircuits play a prominent role in information processing. Dysregulation of dopaminergic signaling, often secondary to psychosocial stress, is thought to interfere with the processing of biologically important events (such as reward prediction errors) and result in the aberrant attribution of salience to irrelevant sensory stimuli and internal representations. Bayesian hierarchical predictive coding offers a promising framework for the identification of dysfunctional neurocomputational processes and the development of a mechanistic understanding of psychotic experience. According to this framework, mismatches between prior beliefs encoded at higher levels of the cortical hierarchy and lower-level (sensory) information can also be thought of as PEs, with important consequences for belief updating. Low levels of precision in the representation of prior beliefs relative to sensory data, as well as dysfunctional interactions between prior beliefs and sensory data in an ever-changing environment, have been suggested as a general mechanism underlying psychotic experiences. Translating the promise of the Bayesian hierarchical predictive coding into patient benefit will come from integrating this framework with existing knowledge of the etiology and pathophysiology of psychosis, especially regarding hippocampal-prefrontal-striatal network function and neural mechanisms of information processing and belief updating.
Assuntos
Encéfalo/fisiopatologia , Cognição/fisiologia , Aprendizagem/fisiologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Teorema de Bayes , Encéfalo/metabolismo , Neurociência Cognitiva , Corpo Estriado/metabolismo , Corpo Estriado/fisiopatologia , Delusões/metabolismo , Delusões/fisiopatologia , Delusões/psicologia , Dopamina/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Humanos , Lobo Límbico/metabolismo , Lobo Límbico/fisiopatologia , Modelos Neurológicos , Modelos Psicológicos , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Neurofisiologia , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Transtornos Psicóticos/metabolismo , Transtornos Psicóticos/psicologia , Reforço Psicológico , Recompensa , Esquizofrenia/metabolismo , Transmissão Sináptica , Lobo Temporal/metabolismo , Lobo Temporal/fisiopatologiaRESUMO
Few studies have compared performance on neurocognitive measures between violent and nonviolent schizophrenia samples. A better understanding of neurocognitive dysfunction in violent individuals with schizophrenia could increase the efficacy of violence reduction strategies and aid in risk assessment and adjudication processes. This study aimed to compare neuropsychological performance between 25 homicide offenders with schizophrenia and 25 nonviolent schizophrenia controls. The groups were matched for age, race, sex, and handedness. Independent t-tests and Mann-Whitney U-tests were used to compare the schizophrenia groups' performance on measures of cognition, including composite scores assessing domain level functioning and individual neuropsychological tests. Results indicated the violent schizophrenia group performed worse on measures of memory and executive functioning, and the Intellectual Functioning composite score, when compared to the nonviolent schizophrenia sample. These findings replicate previous research documenting neuropsychological deficits specific to violent individuals with schizophrenia and support research implicating fronto-limbic dysfunction among violent offenders with schizophrenia.
Assuntos
Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Violência/psicologia , Adulto , Estudos de Casos e Controles , Função Executiva/fisiologia , Feminino , Lobo Frontal/fisiopatologia , Humanos , Inteligência/fisiologia , Lobo Límbico/fisiopatologia , Masculino , Memória/fisiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
Aberrant cortical-striatal-thalamic-cortical circuits have been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). However, the neurobiological basis of OCD remains unclear. We compared patterns of functional connectivity in patients with OCD and in healthy controls using resting-state magnetoencephalography (MEG). Participants comprised 24 patients with OCD (21 men, 3 women) and 22 age- and sex-matched healthy controls (19 men, 3 women). Resting-state measurements were obtained over a 6-min period using a 152-channel whole-head MEG system. We examined group differences in oscillatory activity and distribution of functional cortical hubs based on the nodal centrality of phase-locking value (PLV) maps. Differences in resting-state functional connectivity were examined through PLV analysis in selected regions of interest based on these two findings. Patients with OCD demonstrated significantly lower delta band activity in the cortical regions of the limbic lobe, insula, orbitofrontal, and temporal regions, and theta band activity in the parietal lobe regions than healthy controls. Patients with OCD exhibited fewer functional hubs in the insula and orbitofrontal cortex and additional hubs in the cingulate and temporo-parietal regions. The OCD group exhibited significantly lower phase synchronization among the insula, orbitofrontal cortex, and cortical regions of the limbic lobe in all band frequencies, except in the delta band. Altered functional networks in the resting state may be associated with the pathophysiology of OCD. These MEG findings indicate that OCD is associated with decreased functional connectivity in terms of phase synchrony, particularly in the insula, orbitofrontal cortex, and cortical regions of the limbic lobe.
Assuntos
Ondas Encefálicas/fisiologia , Córtex Cerebral/fisiopatologia , Conectoma/métodos , Função Executiva/fisiologia , Lobo Límbico/fisiopatologia , Magnetoencefalografia/métodos , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
The majority of MRI studies in temporal lobe epilepsy (TLE) have utilized morphometry to map widespread cortical alterations. Morphological markers, such as cortical thickness or grey matter density, reflect combinations of biological events largely driven by overall cortical geometry rather than intracortical tissue properties. Because of its sensitivity to intracortical myelin, quantitative measurement of longitudinal relaxation time (qT1) provides and an in vivo proxy for cortical microstructure. Here, we mapped the regional distribution of qT1 in a consecutive cohort of 24 TLE patients and 20 healthy controls. Compared to controls, patients presented with a strictly ipsilateral distribution of qT1 increases in temporopolar, parahippocampal and orbitofrontal cortices. Supervised statistical learning applied to qT1 maps could lateralize the seizure focus in 92% of patients. Intracortical profiling of qT1 along streamlines perpendicular to the cortical mantle revealed marked effects in upper levels that tapered off at the white matter interface. Findings remained robust after correction for cortical thickness and interface blurring, suggesting independence from previously reported morphological anomalies in this disorder. Mapping of qT1 along hippocampal subfield surfaces revealed marked increases in anterior portions of the ipsilateral CA1-3 and DG that were also robust against correction for atrophy. Notably, in operated patients, qualitative histopathological analysis of myelin stains in resected hippocampal specimens confirmed disrupted internal architecture and fiber organization. Both hippocampal and neocortical qT1 anomalies were more severe in patients with early disease onset. Finally, analysis of resting-state connectivity from regions of qT1 increases revealed altered intrinsic functional network embedding in patients, particularly to prefrontal networks. Analysis of qT1 suggests a preferential susceptibility of ipsilateral limbic cortices to microstructural damage, possibly related to disrupted myeloarchitecture. These alterations may reflect atypical neurodevelopment and affect the integrity of fronto-limbic functional networks.
Assuntos
Mapeamento Encefálico/métodos , Córtex Cerebral , Epilepsia do Lobo Temporal , Imageamento por Ressonância Magnética/métodos , Adulto , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Córtex Cerebral/fisiopatologia , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Hipocampo/fisiopatologia , Humanos , Lobo Límbico/diagnóstico por imagem , Lobo Límbico/patologia , Lobo Límbico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Blast-induced tinitus is the number one service-connected disability that currently affects military personnel and veterans. To elucidate its underlying mechanisms, we subjected 13 Sprague Dawley adult rats to unilateral 14 psi blast exposure to induce tinnitus and measured auditory and limbic brain activity using manganese-enhanced MRI (MEMRI). Tinnitus was evaluated with a gap detection acoustic startle reflex paradigm, while hearing status was assessed with prepulse inhibition (PPI) and auditory brainstem responses (ABRs). Both anxiety and cognitive functioning were assessed using elevated plus maze and Morris water maze, respectively. Five weeks after blast exposure, 8 of the 13 blasted rats exhibited chronic tinnitus. While acoustic PPI remained intact and ABR thresholds recovered, the ABR wave P1-N1 amplitude reduction persisted in all blast-exposed rats. No differences in spatial cognition were observed, but blasted rats as a whole exhibited increased anxiety. MEMRI data revealed a bilateral increase in activity along the auditory pathway and in certain limbic regions of rats with tinnitus compared to age-matched controls. Taken together, our data suggest that while blast-induced tinnitus may play a role in auditory and limbic hyperactivity, the non-auditory effects of blast and potential traumatic brain injury may also exert an effect.
Assuntos
Córtex Auditivo/fisiopatologia , Lobo Límbico/fisiopatologia , Zumbido/fisiopatologia , Animais , Comportamento Animal , Modelos Animais de Doenças , Imageamento por Ressonância Magnética , Ratos Sprague-DawleyRESUMO
BACKGROUND: People with fragile X syndrome (FXS) often have deficits in social behavior, and a substantial portion meet criteria for autism spectrum disorder. Though the genetic cause of FXS is known to be due to the silencing of FMR1, and the Fmr1 null mouse model representing this lesion has been extensively studied, the contributions of this gene and its protein product, FMRP, to social behavior are not well understood. METHODS: Fmr1 null mice and wildtype littermates were exposed to a social or non-social stimulus. In one experiment, subjects were assessed for expression of the inducible transcription factor c-Fos in response to the stimulus, to detect brain regions with social-specific activity. In a separate experiment, tissue was taken from those brain regions showing differential activity, and RNA sequencing was performed. RESULTS: Immunohistochemistry revealed a significantly greater number of c-Fos-positive cells in the lateral amygdala and medial amygdala in the brains of mice exposed to a social stimulus, compared to a non-social stimulus. In the prelimbic cortex, there was no significant effect of social stimulus; although the number of c-Fos-positive cells was lower in the social condition compared to the non-social condition, and negatively correlated with c-Fos in the amygdala. RNA sequencing revealed differentially expressed genes enriched for molecules known to interact with FMRP and also for autism-related genes identified in the Simons Foundation Autism Research Initiative gene database. Ingenuity Pathway Analysis detected enrichment of differentially expressed genes in networks and pathways related to neuronal development, intracellular signaling, and inflammatory response. CONCLUSIONS: Using the Fmr1 null mouse model of fragile X syndrome, we have identified brain regions, gene networks, and molecular pathways responsive to a social stimulus. These findings, and future experiments following up on the role of specific gene networks, may shed light on the neural mechanisms underlying dysregulated social behaviors in fragile X syndrome and more broadly.
Assuntos
Tonsila do Cerebelo/metabolismo , Modelos Animais de Doenças , Proteína do X Frágil da Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/genética , Lobo Límbico/metabolismo , Tonsila do Cerebelo/fisiopatologia , Animais , Comportamento Animal , Biomarcadores/análise , Mapeamento Encefálico , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Síndrome do Cromossomo X Frágil/diagnóstico , Síndrome do Cromossomo X Frágil/fisiopatologia , Deleção de Genes , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Relações Interpessoais , Lobo Límbico/fisiopatologia , Masculino , Camundongos , Camundongos Knockout , Anotação de Sequência Molecular , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Análise de Sequência de RNA , Transdução de SinaisRESUMO
OBJECTIVES: Although generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders in older adults, very little is known about the neurobiology of worry, the hallmark symptom of GAD in adults over the age of 60. This study investigated the neurobiology and neural circuitry of worry in older GAD patients and controls. METHOD: Twenty older GAD patients and 16 age-matched controls (mean age = 67.88) were compared on clinical measures and neural activity during worry using functional magnetic resonance imaging. RESULTS: As expected, worry elicited activation in frontal regions, amygdala, and insula within the GAD group, with a similar but less prominent frontal pattern was observed in controls. Effective connectivity analyses revealed a positive directional circuit in the GAD group extending from ventromedial through dorsolateral prefrontal cortices, converging on the amygdala. A less complex circuit was observed in controls with only dorsolateral prefrontal regions converging on the amygdala; however, a separate circuit passing through the orbitofrontal cortex converged on the insula. CONCLUSION: Results elucidate a different neurobiology of pathological versus normal worry in later life. A limited resource model is implicated wherein worry in GAD competes for the same neural resources (e.g. prefrontal cortical areas) that are involved in the adaptive regulation of emotion through cognitive and behavioral strategies.
Assuntos
Transtornos de Ansiedade/fisiopatologia , Ansiedade/fisiopatologia , Lobo Límbico/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Idoso , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Mapeamento Encefálico/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , MasculinoRESUMO
Cognitive biases may play a significant role in disorders of decision making such as pathological gambling and addiction. Understanding the neurobiology of these biases could lead to more effective pharmacological and therapeutic treatments for disorders in which aberrant decision making is prominent. The rodent Betting Task (rBT) was designed to measure one commonly observed decision-making heuristic in rodents, namely "escalation of commitment" in which subjects become more risk averse as the stakes increase, even if the odds of success remain constant. In the rodent task, the animal is presented with a choice between two options of equivalent expected value, such that reward on one option is guaranteed while the other has a 50% chance of double the prize or nothing. Past work has shown that a subset of animals (termed wager sensitive) adopt an irrationally risk-averse choice preference in which they shift their choice away from the uncertain option as the bet size grows larger. In the current study, the orbitofrontal (OFC), prelimbic (PrL), and infralimbic cortex (IL) were inactivated to evaluate the contributions made by these regions to choice behavior on the rBT. Inactivation of the OFC (but not the IL or the PrL) selectively ameliorated the risk-averse choice pattern characteristic of wager-sensitive animals. This finding suggests that the OFC may have a relatively unique role in promoting this type of non-normative decision-making under uncertainty, an effect that is potentially related to its role in representing the subjective value of reinforcing outcomes.
Assuntos
Comportamento de Escolha/fisiologia , Jogo de Azar/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Animais , Baclofeno/farmacologia , Agonistas de Receptores de GABA-A/farmacologia , Agonistas dos Receptores de GABA-B/farmacologia , Julgamento/fisiologia , Lobo Límbico/efeitos dos fármacos , Lobo Límbico/fisiopatologia , Masculino , Muscimol/farmacologia , Testes Neuropsicológicos , Córtex Pré-Frontal/efeitos dos fármacos , Ratos Long-EvansRESUMO
Cigarette smoking is a chronic relapsing brain disorder, and remains a premier cause of morbidity and mortality. Functional neuroimaging has been used to assess differences in the mean strength of brain activity in smokers' brains, however less is known about the temporal dynamics within smokers' brains. Temporal dynamics is a key feature of a dynamic system such as the brain, and may carry information critical to understanding the brain mechanisms underlying cigarette smoking. We measured the temporal dynamics of brain activity using brain entropy (BEN) mapping and compared BEN between chronic non-deprived smokers and non-smoking controls. Because of the known sex differences in neural and behavioral smoking characteristics, comparisons were also made between males and females. Associations between BEN and smoking related clinical measures were assessed in smokers. Our data showed globally higher BEN in chronic smokers compared to controls. The escalated BEN was associated with more years of smoking in the right limbic area and frontal region. Female nonsmokers showed higher BEN than male nonsmokers in prefrontal cortex, insula, and precuneus, but the BEN sex difference in smokers was less pronounced. These findings suggest that BEN mapping may provide a useful tool for probing brain mechanisms related to smoking.
Assuntos
Mapeamento Encefálico/métodos , Encéfalo/fisiopatologia , Tabagismo/diagnóstico por imagem , Adulto , Estudos de Casos e Controles , Estudos Transversais , Entropia , Feminino , Lobo Frontal/fisiologia , Lobo Frontal/fisiopatologia , Humanos , Lobo Límbico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Fumantes , Tabagismo/fisiopatologia , Adulto JovemRESUMO
Focal temporal lobe seizures often cause impaired cortical function and loss of consciousness. Recent work suggests that the mechanism for depressed cortical function during focal seizures may depend on decreased subcortical cholinergic arousal, which leads to a sleep-like state of cortical slow-wave activity. To test this hypothesis, we sought to directly activate subcortical cholinergic neurons during focal limbic seizures to determine the effects on cortical function. Here we used an optogenetic approach to selectively stimulate cholinergic brainstem neurons in the pedunculopontine tegmental nucleus during focal limbic seizures induced in a lightly anesthetized rat model. We found an increase in cortical gamma activity and a decrease in delta activity in response to cholinergic stimulation. These findings support the mechanistic role of reduced subcortical cholinergic arousal in causing cortical dysfunction during seizures. Through further work, electrical or optogenetic stimulation of subcortical arousal networks may ultimately lead to new treatments aimed at preventing cortical dysfunction during seizures.
Assuntos
Tronco Encefálico/fisiopatologia , Córtex Cerebral/fisiopatologia , Neurônios Colinérgicos/fisiologia , Lobo Límbico/fisiopatologia , Optogenética/métodos , Convulsões/fisiopatologia , Animais , Channelrhodopsins , Modelos Animais de Doenças , Feminino , Masculino , Núcleo Tegmental Pedunculopontino/fisiopatologia , Estimulação Luminosa , Ratos , Ratos Long-EvansRESUMO
Borderline personality disorder is characterized by three domains of dysfunction: affect dysregulation, behavioral dyscontrol, and interpersonal hypersensitivity. Interpersonal hypersensitivity is associated with a (pre)attentive bias toward negative social information and, on the level of the brain, enhanced bottom-up emotion generation, while affect dysregulation results from abnormal top-down processes. Additionally, the problems of patients with borderline personality disorder in interpersonal functioning appear to be related to alterations in the (social) reward and empathy networks. There is increasing evidence that the oxytocinergic system may be involved in these domains of dysfunction and may thus contribute to borderline psychopathology and even open new avenues for targeted pharmacotherapeutic approaches. From studies in healthy and clinical subjects (including first studies with borderline personality disorder patients), the authors provide a conceptual framework for future research in borderline personality disorder that is based on oxytocinergic modulation of the following biobehavioral mechanisms: 1) the brain salience network favoring adaptive social approach behavior, 2) the affect regulation circuit normalizing top-down processes, 3) the mesolimbic circuit improving social reward experiences, and 4) modulating brain regions involved in cognitive and emotional empathy. In addition, preliminary data point to interactions between the oxytocin and cannabinoid system, with implications for pain processing. These mechanisms, which the authors believe to be modulated by oxytocin, may not be specific for borderline personality disorder but rather may be common to a host of psychiatric disorders in which disturbed parent-infant attachment is a major etiological factor.