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Background: Posttraumatic stress disorder and medically unexplained pain frequently co-occur. While pain is common during traumatic events, the processing of pain during trauma and its relation to audiovisual and pain intrusions is poorly understood.Objective: Here we investigate neural activations during painful analogue trauma, focusing on areas that have been related to threat and pain processing, and how they predict intrusion formation. We also examine the moderating role of cumulative lifetime adversity.Methods: Sixty-five healthy women were assessed using functional magnetic resonance imaging. An analogue trauma was induced by an adaptation of the trauma-film paradigm extended by painful electrical stimulation in a 2 (film: aversive, neutral) x 2 (pain: pain, no-pain) design, followed by 7-day audiovisual and pain intrusion assessment using event-based ecological momentary assessment. Intrusions were fitted with Bayesian multilevel regression and a hurdle lognormal distribution.Results: Conjunction analysis confirmed a wide network including anterior insula (AI) and dorsal anterior cingulate cortex (dACC) being active both, during aversive films and pain. Pain resulted in activation in areas amongst posterior insula and deactivation in a network around ventromedial prefrontal cortex (VMPFC). Higher AI and dACC activity during aversive>neutral film predicted greater audiovisual intrusion probability over time and predicted greater audiovisual intrusion frequency particularly for participants with high lifetime adversity. Lower AI, dACC, hippocampus, and VMPFC activity during pain>no-pain predicted greater pain intrusion probability particularly for participants with high lifetime adversity. Weak regulatory VMPFC activation was associated with both increased audiovisual and pain intrusion frequency.Conclusions: Enhanced AI and dACC processing during aversive films, poor pain vs. no-pain discrimination in AI and dACC, as well as weak regulatory VMPFC processing may be driving factors for intrusion formation, particularly in combination with high lifetime adversity. Results shed light on a potential path for the etiology of PTSD and medically unexplained pain.
AI and dACC play a common role for both trauma- and pain-processing.In combination with high lifetime adversity, higher AI and dACC aversive film processing was associated with higher audiovisual intrusion frequency, whereas weaker AI and dACC pain discrimination enhanced the chance for pain intrusions.Weak regulatory VMPFC activity in aversive situations increased both audiovisual and pain intrusion formation.
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Imagen por Resonancia Magnética , Dolor , Trastornos por Estrés Postraumático , Humanos , Femenino , Adulto , Dolor/psicología , Dolor/fisiopatología , Trastornos por Estrés Postraumático/fisiopatología , Trastornos por Estrés Postraumático/psicología , Giro del Cíngulo/fisiopatología , Giro del Cíngulo/diagnóstico por imagen , Adulto Joven , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Teorema de BayesRESUMEN
The absence of a comprehensive understanding of the neural basis of spontaneous pain limits the development of therapeutic strategies targeting this primary complaint of patients with chronic pain. Here we report a distinct neuronal ensemble within the prelimbic cortex which processes signals related to spontaneous pain in rats with chronic inflammatory pain. This neuronal ensemble specifically encodes spontaneous pain-related behaviors, independently of other locomotive and evoked behaviors. Activation of this neuronal ensemble elicits marked spontaneous pain-like behaviors and enhances nociceptive responses, whereas prolonged silencing of its activities alleviates spontaneous pain and promotes overall recovery from inflammatory pain. Notably, afferents from the primary somatosensory cortex and infralimbic cortex bidirectionally modulate the activities of the spontaneous pain-responsive prelimbic cortex neuronal ensemble and pain behaviors. These findings reveal the cortical basis of spontaneous pain at the neuronal level, highlighting a distinct neuronal ensemble within the prelimbic cortex and its associated pain-regulatory brain networks.
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Inflamación , Neuronas , Ratas Sprague-Dawley , Corteza Somatosensorial , Animales , Neuronas/metabolismo , Neuronas/fisiología , Masculino , Ratas , Corteza Somatosensorial/fisiopatología , Dolor/fisiopatología , Conducta Animal , Modelos Animales de Enfermedad , Dolor Crónico/fisiopatología , Corteza Prefrontal/fisiopatologíaRESUMEN
Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with lifelong impairments. ADHD-related behaviors have been observed as early as toddlerhood for children who later develop ADHD. Children with ADHD have disrupted connectivity in neural circuitry involved in executive control of attention, including the prefrontal cortex (PFC) and dorsal attention network (DAN). It is not known if these alterations in connectivity can be identified before the onset of ADHD. Children (N = 51) 1.5-3 years old were assessed using functional near-infrared spectroscopy while engaging with a book. The relation between mother-reported ADHD-related behaviors and neural connectivity, computed using robust innovation-based correlation, was examined. Task engagement was high across the sample and unrelated to ADHD-related behaviors. Observed attention was associated with greater connectivity between the right lateral PFC and the right temporal parietal junction (TPJ). Children with greater ADHD-related behaviors had greater frontoparietal connectivity, particularly between the PFC bilaterally and the right TPJ. Toddlers at risk for developing ADHD may require increased frontoparietal connectivity to sustain attention. Future work is needed to examine early interventions that enhance developing attention and their effect on neural connectivity between the PFC and attention networks.
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Trastorno por Déficit de Atención con Hiperactividad , Atención , Lóbulo Parietal , Corteza Prefrontal , Espectroscopía Infrarroja Corta , Humanos , Femenino , Masculino , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Lóbulo Parietal/fisiopatología , Lóbulo Parietal/diagnóstico por imagen , Preescolar , Lactante , Atención/fisiología , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Función Ejecutiva/fisiología , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagen , Conducta Infantil/fisiologíaRESUMEN
Mindfulness has garnered attention for its potential in alleviating cigarette cravings; however, the neural mechanisms underlying its efficacy remain inadequately understood. This study (N=46, all men) aims to examine the impact of a mindfulness strategy on regulating cue-induced craving and associated brain activity. Twenty-three smokers, consuming over 10 cigarettes daily for at least 2 yearsï¼ were compared to twenty-three non-smokers. During a regulation of craving task, participants were asked to practice mindfulness during smoking cue-exposure or passively view smoking cues while fMRI scans were completed. A 2 (condition: mindfulness-cigarette and look-cigarette) × 2 (phase: early, late of whole smoking cue-exposure period) repeated measures ANOVA showed a significant interaction of the craving scores between condition and phase, indicating that the mindfulness strategy dampened late-phase craving. Additionally, within the smoker group, the fMRI analyses revealed a significant main effect of mindfulness condition and its interaction with time in several brain networks involving reward, emotion, and interoception. Specifically, the bilateral insula, ventral striatum, and amygdala showed lower activation in the mindfulness condition, whereas the activation of right orbitofrontal cortex mirrored the strategy-time interaction effect of the craving change. This study illuminates the dynamic interplay between mindfulness, smoking cue-induced craving, and neural activity, offering insights into how mindfulness may effectively regulate cigarette cravings.
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Ansia , Señales (Psicología) , Imagen por Resonancia Magnética , Atención Plena , Fumadores , Humanos , Ansia/fisiología , Masculino , Atención Plena/métodos , Adulto , Fumadores/psicología , Adulto Joven , Amígdala del Cerebelo/fisiopatología , Estriado Ventral/fisiopatología , Estriado Ventral/diagnóstico por imagen , Recompensa , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Interocepción/fisiología , Emociones/fisiología , Corteza Insular/fisiopatología , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Fumar Cigarrillos/psicología , Fumar Cigarrillos/terapiaRESUMEN
Autism spectrum disorder (ASD) has proven to be highly enigmatic due to the diversity of its underlying genetic causes and the huge variability in symptom presentation. Uncovering common phenotypes across people with ASD and pre-clinical models allows us to better understand the influence on brain function of the many different genetic and cellular processes thought to contribute to ASD aetiology. One such feature of ASD is the convergent evidence implicating abnormal functioning of the medial prefrontal cortex (mPFC) across studies. The mPFC is a key part of the 'social brain' and may contribute to many of the changes in social behaviour observed in people with ASD. Here we review recent evidence for mPFC involvement in both ASD and social behaviours. We also highlight how pre-clinical mouse models can be used to uncover important cellular and circuit-level mechanisms that may underly atypical social behaviours in ASD. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".
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Trastorno del Espectro Autista , Corteza Prefrontal , Conducta Social , Corteza Prefrontal/fisiopatología , Humanos , Animales , Trastorno del Espectro Autista/fisiopatología , Trastorno del Espectro Autista/psicología , Vías Nerviosas/fisiopatología , Modelos Animales de Enfermedad , Ratones , Red Nerviosa/fisiopatología , Trastorno Autístico/fisiopatología , Trastorno Autístico/psicologíaRESUMEN
Cognitive flexibility enables individuals to alter their behavior in response to changing environmental demands, facilitating optimal behavior in a dynamic world. The inability to do this, called behavioral inflexibility, is a pervasive behavioral phenotype in alcohol use disorder (AUD), driven by disruptions in cognitive flexibility. Research has repeatedly shown that behavioral inflexibility not only results from alcohol exposure across species but can itself be predictive of future drinking. Like many high-level executive functions, flexible behavior requires healthy functioning of the prefrontal cortex (PFC). The scope of this review addresses two primary themes: first, we outline tasks that have been used to investigate flexibility in the context of AUD or AUD models. We characterize these based on the task features and underlying cognitive processes that differentiate them from one another. We highlight the neural basis of flexibility measures, focusing on the PFC, and how acute or chronic alcohol in humans and non-human animal models impacts flexibility. Second, we consolidate findings on the molecular, physiological and functional changes in the PFC elicited by alcohol, that may contribute to cognitive flexibility deficits seen in AUD. Collectively, this approach identifies several key avenues for future research that will facilitate effective treatments to promote flexible behavior in the context of AUD, to reduce the risk of alcohol related harm, and to improve outcomes following AUD. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".
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Alcoholismo , Corteza Prefrontal , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiología , Corteza Prefrontal/fisiopatología , Humanos , Animales , Alcoholismo/fisiopatología , Alcoholismo/psicología , Etanol/farmacología , Etanol/administración & dosificación , Cognición/fisiología , Cognición/efectos de los fármacos , Función Ejecutiva/fisiología , Función Ejecutiva/efectos de los fármacosRESUMEN
BACKGROUND: Borderline personality disorder (BPD) is a severe mental illness, with high rates of co-morbid depression and suicidality. Despite the importance of optimizing treatment in BPD, little is known about how neural processes relate to individual treatment response. This study examines how baseline regional brain blood oxygen level dependent (BOLD) activation during a functional magnetic resonance imaging (fMRI) task of emotion regulation is related to treatment response following a six-month randomized clinical trial of Dialectical Behavior Therapy (DBT) or Selective Serotonin Reuptake Inhibitor (SSRI) treatment. METHODS: Unmedicated females with BPD (N = 37), with recent suicidal behavior or self-injury, underwent an fMRI task in which negative personal memories were presented and they were asked to distance (i.e., downregulate their emotional response) or immerse (i.e., experience emotions freely). Patients were then randomized to DBT (N = 16) or SSRI (N = 21) treatment, with baseline and post-treatment depression and BPD severity assessed. RESULTS: BOLD activity in prefrontal cortex, anterior cingulate, and insula was associated with distancing. Baseline BOLD during distancing in dorsolateral, ventrolateral, and orbital prefrontal cortex (dlPFC, vlPFC, OFC) differentially predicted depression response across treatment groups, with higher activity predicting better response in the SSRI group, and lower activity predicting better response in the DBT group. LIMITATIONS: All female samples. DISCUSSION: Findings indicate that greater prefrontal engagement during emotion regulation may predict more antidepressant benefit from SSRIs, whereas lower engagement may predict better response to DBT. These results suggest different mechanisms of action for SSRI and DBT treatment, and this may allow fMRI to guide individualized treatment selection.
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Trastorno de Personalidad Limítrofe , Regulación Emocional , Imagen por Resonancia Magnética , Corteza Prefrontal , Inhibidores Selectivos de la Recaptación de Serotonina , Humanos , Trastorno de Personalidad Limítrofe/fisiopatología , Trastorno de Personalidad Limítrofe/terapia , Trastorno de Personalidad Limítrofe/tratamiento farmacológico , Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Femenino , Regulación Emocional/fisiología , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Adulto , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Terapia Conductual Dialéctica , Adulto Joven , Resultado del Tratamiento , Giro del Cíngulo/fisiopatología , Giro del Cíngulo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatología , Emociones/fisiología , Conducta Autodestructiva/fisiopatología , Conducta Autodestructiva/terapiaRESUMEN
Individuals with low social status are at heightened risk of major depressive disorder (MDD), and MDD also influences social status. While the interrelationship between MDD and social status is well-defined, the behavioral causality between these two phenotypes remains unexplored. Here, we investigated the behavioral relationships between depressive and dominance behaviors in male mice exposed to chronic restraint stress and the role of medial prefrontal cortex (mPFC) astrocytes in these behaviors. Chronic restraint stress induced both depressive and submissive behaviors. Chemogenetic mPFC astrocyte activation significantly enhanced dominance in chronic stress-induced submissive mice by increasing the persistence of defensive behavior, although it did not affect depressive behaviors. Notably, repetitive winning experiences following mPFC astrocyte stimulation exerted anti-depressive effects in chronic restraint stress-induced depressive mice. These data indicate that mPFC astrocyte-derived winning experience renders anti-depressive effects, and may offer a new strategy for treating depression caused by low status in social hierarchies by targeting mPFC astrocytes.
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Astrocitos , Conducta Animal , Depresión , Ratones Endogámicos C57BL , Corteza Prefrontal , Estrés Psicológico , Animales , Astrocitos/metabolismo , Masculino , Estrés Psicológico/complicaciones , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/patología , Depresión/fisiopatología , Predominio Social , Enfermedad Crónica , Restricción Física , RatonesRESUMEN
BACKGROUND: Our previous study synthesized the analgesic effects of repetitive Transcranial Magnetic Stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) trials up to 2019. There has been a significant increase in pain trials in the past few years, along with methodological variabilities such as sample size, stimulation intensity, and rTMS paradigms. OBJECTIVES/METHODS: This study therefore updated the effects of DLPFC-rTMS on chronic pain and quantified the impact of methodological differences across studies. RESULTS: A total of 36 studies were included. Among them, 26 studies were clinical trials (update = 9, 307/711 patients), and 10 (update = 1, 34/249 participants) were provoked pain studies. The updated meta-analysis does not support an effect on neuropathic pain after including the additional trials (pshort-term = 0.20, pmid-term = 0.50). However, there is medium-to-large analgesic effect in migraine trials extending up to six weeks follow-up (SMDmid-term = -0.80, SMDlong-term = -0.51), that was not previously reported. Methodological differences wthine the studies were considered. DLPFC-rTMS also induces potential improvement in the emotional aspects of pain (SMDshort-term = -0.28). CONCLUSIONS: The updated systematic meta-analysis continues to support analgesic effects for chronic pain overall. However, the updated results no longer support DLPFC-rTMS for pain relief in neuropathic pain, and do supports DLPFC-rTMS in the management of migraine. There is also evidence for DLPFC-rTMS to improve emotional aspects of pain.
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Corteza Prefontal Dorsolateral , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Corteza Prefontal Dorsolateral/fisiología , Manejo del Dolor/métodos , Dolor Crónico/terapia , Neuralgia/terapia , Corteza Prefrontal/fisiología , Corteza Prefrontal/fisiopatologíaRESUMEN
Approximately 50 million Americans suffer from chronic pain, and nearly a quarter of chronic pain patients have reported misusing opioid prescriptions. Repeated drug seeking is associated with reactivation of an ensemble of neurons sparsely scattered throughout the dorsomedial prefrontal cortex (dmPFC). Prior research has demonstrated that chronic pain increases intrinsic excitability of dmPFC neurons, which may increase the likelihood of reactivation during drug seeking. We tested the hypothesis that chronic pain would increase oxycodone-seeking behaviour and that the pain state would differentially increase intrinsic excitability in dmPFC drug-seeking ensemble neurons. TetTag mice self-administered intravenous oxycodone. After 7 days of forced abstinence, a drug-seeking session was performed, and the ensemble was tagged. Mice received spared nerve injury (SNI) to induce chronic pain during the period between the first and second seeking session. Following the second seeking session, we performed electrophysiology on individual neurons within the dmPFC to assess intrinsic excitability of the drug-seeking ensemble and non-ensemble neurons. SNI had no impact on sucrose seeking or intrinsic excitability of dmPFC neurons from these mice. In females, SNI increased oxycodone seeking and intrinsic excitability of non-ensemble neurons. In males, SNI had no impact on oxycodone seeking or neuron excitability. Data from females are consistent with clinical reports that chronic pain can promote drug craving and relapse and support the hypothesis that chronic pain itself may lead to neuroadaptations which promote opioid seeking.
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Analgésicos Opioides , Comportamiento de Búsqueda de Drogas , Neuralgia , Neuronas , Oxicodona , Corteza Prefrontal , Animales , Oxicodona/farmacología , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/fisiopatología , Comportamiento de Búsqueda de Drogas/efectos de los fármacos , Ratones , Neuralgia/fisiopatología , Neuronas/efectos de los fármacos , Masculino , Femenino , Analgésicos Opioides/farmacología , Autoadministración , Dolor Crónico/fisiopatología , Factores SexualesRESUMEN
AIMS: Previous neuroimaging research in alcohol use disorder (AUD) has found altered functional connectivity in the brain's salience, default mode, and central executive (CEN) networks (i.e. the triple network model), though their specific associations with AUD severity and heavy drinking remains unclear. This study utilized resting-state fMRI to examine functional connectivity in these networks and measures of alcohol misuse. METHODS: Seventy-six adult heavy drinkers completed a 7-min resting-state functional MRI scan during visual fixation. Linear regression models tested if connectivity in the three target networks was associated with past 12-month AUD symptoms and number of heavy drinking days in the past 30 days. Exploratory analyses examined correlations between connectivity clusters and impulsivity and psychopathology measures. RESULTS: Functional connectivity within the CEN network (right and left lateral prefrontal cortex [LPFC] seeds co-activating with 13 and 15 clusters, respectively) was significantly associated with AUD symptoms (right LPFC: ß = .337, p-FDR = .016; left LPFC: ß = .291, p-FDR = .028) but not heavy drinking (p-FDR > .749). Post-hoc tests revealed six clusters co-activating with the CEN network were associated with AUD symptoms-right middle frontal gyrus, right inferior parietal gyrus, left middle temporal gyrus, and left and right cerebellum. Neither the default mode nor the salience network was significantly associated with alcohol variables. Connectivity in the left LPFC was correlated with monetary delay discounting (r = .25, p = .03). CONCLUSIONS: These findings support previous associations between connectivity within the CEN network and AUD severity, providing additional specificity to the relevance of the triple network model to AUD.
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Alcoholismo , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Adulto , Alcoholismo/fisiopatología , Alcoholismo/diagnóstico por imagen , Alcoholismo/psicología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Persona de Mediana Edad , Descanso/fisiología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Adulto Joven , Consumo de Bebidas Alcohólicas/fisiopatología , Consumo de Bebidas Alcohólicas/psicología , Conducta Impulsiva/fisiología , Red en Modo Predeterminado/diagnóstico por imagen , Red en Modo Predeterminado/fisiopatologíaRESUMEN
BACKGROUND: Depression is closely related to suicidal ideation (SI); however, it is unclear who is most vulnerable to SI within the context of depression. Research suggests that individual differences in emotion reactivity and regulation may be potential moderators of the link between depression and SI. Therefore, the current study tested this hypothesis using objective markers of emotion reactivity and volitional cognitive regulation capacity during functional magnetic resonance imaging (fMRI). METHODS: Adults (n = 91) with active SI completed validated self-report measures of current depressive symptoms and SI severity. Participants completed an fMRI task designed to probe neural response to aversive stimuli and during cognitive reappraisal - a form of volitional emotion regulation. Activation of the amygdala during aversive emotion reactivity was measured. Activation of ventrolateral, dorsolateral, and dorsomedial prefrontal cortex (vlPFC, dlPFC, and dmPFC) during cognitive reappraisal were also measured. A series of hierarchical linear regressions testing the unique and interactive effects of depression symptoms and neural activation on severity of SI were conducted. RESULTS: Analyses revealed a depression x amygdala activation interaction. The positive association between depression and SI severity was more robust in the context of high amygdala reactivity than low amygdala reactivity. Analyses also indicated there was no PFC activity (neural cognitive reappraisal) by depression interaction. LIMITATIONS: Psychoactive medications were allowed and all participants endorsed suicidal intent. CONCLUSION: Strategies aimed at targeting exaggerated emotion reactivity within the context of depression may be beneficial.
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Amígdala del Cerebelo , Depresión , Regulación Emocional , Emociones , Imagen por Resonancia Magnética , Corteza Prefrontal , Ideación Suicida , Humanos , Masculino , Femenino , Adulto , Amígdala del Cerebelo/fisiopatología , Amígdala del Cerebelo/diagnóstico por imagen , Regulación Emocional/fisiología , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Depresión/fisiopatología , Depresión/psicología , Emociones/fisiología , Adulto Joven , Persona de Mediana EdadRESUMEN
OBJECTIVE: To explore cognitive load in people with transfemoral amputations fitted with socket or bone-anchored prostheses by describing activity in the left and right dorsolateral prefrontal cortices during single- and dual-task walking. DESIGN: Cross-sectional pilot study. PATIENTS: 8 socket prosthesis users and 8 bone-anchored prosthesis users. All were fitted with microprocessor-controlled prosthetic knees. METHODS: Participants answered self-report questionnaires and performed gait tests during 1 single-task walking condition and 2 dual-task walking conditions. While walking, activity in the dorsolateral prefrontal cortex was measured using functional near-infrared spectroscopy. Cognitive load was investigated for each participant by exploring the relative concentration of oxygenated haemoglobin in the left and right dorsolateral prefrontal cortex. Symmetry of brain activity was investigated by calculating a laterality index. RESULTS: Self-report measures and basic gait variables did not show differences between the groups. No obvious between-group differences were observed in the relative concentration of oxygenated haemoglobin for any walking condition. There was a tendency towards more right-side brain activity for participants using a socket prosthesis during dual-task conditions. CONCLUSIONS: This pilot study did not identify substantial differences in cognitive load or lateralization between socket prosthesis users and bone-anchored prosthesis users.
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Miembros Artificiales , Cognición , Caminata , Humanos , Proyectos Piloto , Masculino , Persona de Mediana Edad , Estudios Transversales , Femenino , Caminata/fisiología , Cognición/fisiología , Adulto , Anciano , Fémur/cirugía , Amputación Quirúrgica/rehabilitación , Diseño de Prótesis , Prótesis Anclada al Hueso , Corteza Prefrontal/fisiopatología , Amputados/rehabilitación , Amputados/psicología , Espectroscopía Infrarroja Corta , Marcha/fisiologíaRESUMEN
Understanding the neuropathogenesis of impaired social cognition in autism spectrum disorders (ASD) is challenging. Altered cortical parvalbumin-positive (PV+) interneurons have been consistently observed in ASD, but their roles and the underlying mechanisms remain poorly understood. In our study, we observed a downward-shifted spectrum of PV expression in the developing medial prefrontal cortex (mPFC) of ASD mouse models due to decreased activity of PV+ neurons. Surprisingly, chemogenetically suppressing PV+ neuron activity during postnatal development failed to induce ASD-like behaviors. In contrast, lowering excitatory activity in the developing mPFC not only dampened the activity state and PV expression of individual PV+ neurons, but also replicated ASD-like social deficits. Furthermore, enhancing excitation, but not PV+ interneuron-mediated inhibition, rescued social deficits in ASD mouse models. Collectively, our findings propose that reduced excitatory activity in the developing mPFC may serve as a shared local circuitry mechanism triggering alterations in PV+ interneurons and mediating impaired social functions in ASD.
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Trastorno del Espectro Autista , Modelos Animales de Enfermedad , Interneuronas , Parvalbúminas , Corteza Prefrontal , Cognición Social , Trastorno del Espectro Autista/fisiopatología , Animales , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/metabolismo , Ratones , Interneuronas/metabolismo , Interneuronas/fisiología , Parvalbúminas/metabolismo , Masculino , Conducta Animal/fisiología , Conducta Social , Ratones Endogámicos C57BL , FemeninoRESUMEN
BACKGROUND: Fatigue is one of the most common neurological symptoms reported post coronavirus disease 2019 (COVID-19) infection. In order to establish effective early intervention strategies, more emphasis should be placed on the correlation between fatigue and cortical neurophysiological changes, especially in healthcare workers, who are at a heightened risk of COVID-19 infection. METHODS: A prospective cohort study was conducted involving 29 COVID-19 medical workers and 24 healthy controls. The assessment included fatigue, sleep and health quality, psychological status, and physical capacity. Functional near-infrared spectroscopy (fNIRS) was employed to detect activation of brain regions. Bilateral primary motor cortex (M1) excitabilities were measured using single- and paired-pulse transcranial magnetic stimulation. Outcomes were assessed at 1, 3, and 6 months into the disease course. RESULTS: At 1-month post-COVID-19 infection, 37.9% of patients experienced severe fatigue symptoms, dropping to 10.3% at 3 months. Interestingly, the remarkable decreased activation/excitability of bilateral prefrontal lobe (PFC) and M1 were closely linked to fatigue symptoms after COVID-19. Notably, greater increase in M1 region excitability correlated with more significant fatigue improvement. Re-infected patients exhibited lower levels of brain activation and excitability compared to single-infection patients. CONCLUSIONS: Both single infection and reinfection of COVID-19 lead to decreased activation and excitability of the PFC and M1. The degree of excitability improvement in the M1 region correlates with a greater recovery in fatigue. Based on these findings, targeted interventions to enhance and regulate the excitability of M1 may represent a novel strategy for COVID-19 early rehabilitation. TRIAL REGISTRATION: The Ethics Review Committee of Xijing Hospital, No. KY20232051-F-1; www.chictr.org.cn , ChiCTR2300068444.
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COVID-19 , Fatiga , Personal de Salud , Corteza Motora , Corteza Prefrontal , Estimulación Magnética Transcraneal , Humanos , COVID-19/fisiopatología , Fatiga/fisiopatología , Masculino , Femenino , Estudios Longitudinales , Adulto , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Corteza Motora/fisiopatología , Persona de Mediana Edad , SARS-CoV-2/aislamiento & purificación , Estudios Prospectivos , Espectroscopía Infrarroja Corta , Estudios de CohortesRESUMEN
BACKGROUND: Depression is a significant public health concern. Identifying biopsychosocial risk factors for depression is important for developing targeted prevention. Studies have demonstrated that blunted striatal activation during reward processing is a risk factor for depression; however, few have prospectively examined whether adolescent reward-related resting-state functional connectivity (rsFC) predicts depression symptoms in adulthood and how this relates to known risk factors (e.g., childhood trauma). METHODS: At baseline, 66 adolescents (mean age = 14.7, SD = 1.4, 68 % female) underwent rsFC magnetic resonance imaging and completed the Children's Depression Inventory (CDI). At follow-up (mean time between adolescent scan and adult follow-up = 10.1 years, SD = 1.6, mean adult age = 24.8 years, SD = 1.7), participants completed the Childhood Trauma Questionnaire (CTQ) and Beck Depression Inventory- Second Edition (BDI-2). Average rsFC was calculated between nodes in mesocorticolimbic reward circuitry: ventral striatum (VS), rostral anterior cingulate cortex (rACC), medial orbitofrontal cortex, and ventral tegmental area. Linear regressions assessed associations between rsFC, BDI-2, and CTQ, controlling for adolescent CDI, sex assigned at birth, and scan age (Bonferroni corrected). RESULTS: Greater childhood trauma was associated with higher adulthood depression symptoms. Stronger VS-rACC rsFC during adolescence was associated with greater depression symptoms in adulthood and greater childhood trauma. LIMITATIONS: The small sample size, limited depression severity, and seed-based approach are limitations. CONCLUSIONS: The associations between adolescent striatal-cingulate rsFC and childhood trauma and adult depression symptoms suggest this connectivity may be an early neurobiological risk factor for depression and that early life experience plays an important role. Increased VS-rACC connectivity may represent an over-regulatory response on the striatum, commonly reported in depression, and warrants further investigation.
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Depresión , Giro del Cíngulo , Imagen por Resonancia Magnética , Recompensa , Estriado Ventral , Humanos , Femenino , Adolescente , Masculino , Estriado Ventral/fisiopatología , Estriado Ventral/diagnóstico por imagen , Depresión/fisiopatología , Adulto Joven , Giro del Cíngulo/fisiopatología , Giro del Cíngulo/diagnóstico por imagen , Adulto , Factores de Riesgo , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Escalas de Valoración PsiquiátricaRESUMEN
One of the most prevalent psychiatric disorders is major depressive disorder (MDD), which increases the probability of suicidal ideation or untimely demise. Abnormal frontal hemodynamic changes detected by functional near-infrared spectroscopy (fNIRS) during verbal fluency task (VFT) have the potential to be used as an objective indicator for assessing clinical symptoms. However, comprehensive quantitative and objective assessment instruments for individuals who exhibit symptoms suggestive of depression remain undeveloped. Drawing from a total of 467 samples in a large-scale dataset comprising 289 MDD patients and 178 healthy controls, fNIRS measurements were obtained throughout the VFT. To identify unique MDD biomarkers, this research introduced a data representation approach for extracting spatiotemporal features from fNIRS signals, which were subsequently utilized as potential predictors. Machine learning classifiers (e.g., Gradient Boosted Decision Trees (GBDT) and Multilayer Perceptron) were implemented to assess the ability to predict selected features. The mean and standard deviation of the cross-validation indicated that the GBDT model, when combined with the 180-feature pattern, distinguishes patients with MDD from healthy controls in the most effective manner. The accuracy of correct classification for the test set was 0.829 ± 0.053, with an AUC of 0.895 (95 % CI: 0.864-0.925) and a sensitivity of 0.914 ± 0.051. Channels that made the most important contribution to the identification of MDD were identified using Shapley Additive Explanations method, located in the frontopolar area and the dorsolateral prefrontal cortex, as well as pars triangularis Broca's area. Assessment of abnormal prefrontal activity during the VFT in MDD serves as an objectively measurable biomarker that could be utilized to evaluate cognitive deficits and facilitate early screening for MDD. The model suggested in this research could be applied to large-scale case-control fNIRS datasets to detect unique characteristics of MDD and offer clinicians an objective biomarker-based analytical instrument to assist in the evaluation of suspicious cases.
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Biomarcadores , Trastorno Depresivo Mayor , Aprendizaje Automático , Espectroscopía Infrarroja Corta , Humanos , Trastorno Depresivo Mayor/fisiopatología , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/diagnóstico , Espectroscopía Infrarroja Corta/métodos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Algoritmos , Estudios de Casos y Controles , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Pruebas Neuropsicológicas , Adulto Joven , Neuroimagen/métodosRESUMEN
Social controllability, or the ability to exert control during social interactions, is crucial for optimal decision-making. Inability to do so might contribute to maladaptive behaviors such as smoking, which often takes place in social settings. Here, we examined social controllability in nicotine-dependent humans as they performed an fMRI task where they could influence the offers made by simulated partners. Computational modeling revealed that smokers under-estimated the influence of their actions and self-reported a reduced sense of control, compared to non-smokers. These findings were replicated in a large independent sample of participants recruited online. Neurally, smokers showed reduced tracking of forward projected choice values in the ventromedial prefrontal cortex, and impaired computation of social prediction errors in the midbrain. These results demonstrate that smokers were less accurate in estimating their personal influence when the social environment calls for control, providing a neurocomputational account for the social cognitive deficits in this population. Pre-registrations: OSF Registries|How interoceptive state interacts with value-based decision-making in addiction (fMRI study). OSF Registries|COVID-19: social cognition, mental health, and social distancing (online study).
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Imagen por Resonancia Magnética , Tabaquismo , Humanos , Masculino , Femenino , Adulto , Tabaquismo/fisiopatología , Tabaquismo/psicología , Toma de Decisiones , COVID-19/psicología , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Persona de Mediana Edad , Adulto Joven , Interacción Social , Cognición Social , Nicotina/efectos adversos , Nicotina/farmacologíaRESUMEN
Post-traumatic stress disorder (PTSD) has been linked to altered communication within the limbic system, including reduced structural connectivity in the uncinate fasciculus (UNC; i.e., decreased fractional anisotropy; FA) and reduced resting-state functional connectivity (RSFC) between the hippocampus and ventromedial prefrontal cortex (vmPFC). Previous research has demonstrated attenuation of PTSD symptoms and alterations in RSFC following exposure-based psychotherapy. However, the relationship between changes in structural and functional connectivity patterns and PTSD symptoms following treatment remains unclear. To investigate this, we conducted a secondary analysis of data from a randomized clinical trial of intensive exposure therapy, evaluating alterations in UNC FA, hippocampus-vmPFC RSFC, and PTSD symptoms before (pre-treatment), 7 days after (post-treatment), and 30 days after (follow-up) the completion of therapy. Our results showed that post-treatment changes in RSFC were positively correlated with post-treatment and follow-up changes in UNC FA and that post-treatment changes in UNC FA were positively correlated with post-treatment and follow-up changes in PTSD symptoms. These findings suggest that early changes in functional connectivity are associated with sustained changes in anatomical connectivity, which in turn are linked to reduced PTSD symptom severity.
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Corteza Prefrontal , Trastornos por Estrés Postraumático , Sustancia Blanca , Humanos , Trastornos por Estrés Postraumático/diagnóstico por imagen , Trastornos por Estrés Postraumático/fisiopatología , Trastornos por Estrés Postraumático/terapia , Trastornos por Estrés Postraumático/patología , Trastornos por Estrés Postraumático/psicología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Sustancia Blanca/fisiopatología , Masculino , Adulto , Femenino , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiopatología , Corteza Prefrontal/patología , Terapia Implosiva/métodos , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Hipocampo/fisiopatología , Imagen de Difusión Tensora/métodos , Persona de Mediana Edad , Imagen por Resonancia Magnética , Vías Nerviosas/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Resultado del TratamientoRESUMEN
BACKGROUND: Youth with attention-deficit/hyperactivity disorder (ADHD) exhibit increased effort aversion, likely due to deficits in anticipatory dopamine firing. Previous research has shown that transcranial direct current stimulation (tDCS) targeting the right prefrontal cortex can enhance activity in dopaminergic meso-striatal regions. However, the extent to which this specific tDCS configuration effectively modulates effort behavior in anticipation of rewards in ADHD remains uncertain. HYPOTHESIS: We expected an increase of effort maintenance and invigoration during and following our tDCS set-up compared to sham in subjects with ADHD. METHODS: Twenty-four children and adolescents with ADHD (mean age: 11.6 years; 95 % CI [10.7, 12.4]) received 2 mA and sham tDCS for 20 min each. The anode was positioned over the ventromedial prefrontal cortex (PFC), while the cathode was placed over the right dorsolateral PFC, generating an electrical field with maximal strength in the right PFC. During and after the tDCS sessions, participants performed a button-pressing task aimed at earning delayed monetary rewards. Primary outcomes were effort maintenance (frequency of button presses) and invigoration (slopes of button presses), measuring motor task performance. RESULTS: We observed a significant increase in effort maintenance both during (b = 2.66; p < 0.001) and after tDCS (b = 2.04; p= .007) compared to sham. No significant difference was found for invigoration during stimulation, while after bonferroni correction (p = 0.025) a non-significant decrease was found after tDCS compared to sham (b = -5.18; p = 0.041). CONCLUSION: tDCS targeting the ventromedial PFC (anodal) and right dorsolateral PFC (cathodal) increases effort maintenance in children and adolescents with ADHD.