RESUMO
BACKGROUND: Exposure-based psychotherapy is a first-line treatment for posttraumatic stress disorder (PTSD), but its mechanisms are poorly understood. Functional brain connectivity is a promising metric for identifying treatment mechanisms and biosignatures of therapeutic response. To this end, we assessed amygdala and insula treatment-related connectivity changes and their relationship to PTSD symptom improvements. METHODS: Individuals with a primary PTSD diagnosis (N = 66) participated in a randomized clinical trial of prolonged exposure therapy (n = 36) versus treatment waiting list (n = 30). Task-free functional magnetic resonance imaging was completed prior to randomization and 1 month following cessation of treatment/waiting list. Whole-brain blood oxygenation level-dependent responses were acquired. Intrinsic connectivity was assessed by subregion in the amygdala and insula, limbic structures key to the disorder pathophysiology. Dynamic causal modeling assessed evidence for effective connectivity changes in select nodes informed by intrinsic connectivity findings. RESULTS: The amygdala and insula displayed widespread patterns of primarily subregion-uniform intrinsic connectivity change, including increased connectivity between the amygdala and insula; increased connectivity of both regions with the ventral prefrontal cortex and frontopolar and sensory cortices; and decreased connectivity of both regions with the left frontoparietal nodes of the executive control network. Larger decreases in amygdala-frontal connectivity and insula-parietal connectivity were associated with larger PTSD symptom reductions. Dynamic causal modeling evidence suggested that treatment decreased left frontal inhibition of the left amygdala, and larger decreases were associated with larger symptom reductions. CONCLUSIONS: PTSD psychotherapy adaptively attenuates functional interactions between frontoparietal and limbic brain circuitry at rest, which may reflect a potential mechanism or biosignature of recovery.
Assuntos
Terapia Implosiva , Transtornos de Estresse Pós-Traumáticos , Tonsila do Cerebelo , Encéfalo , Humanos , Imageamento por Ressonância Magnética , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Transtornos de Estresse Pós-Traumáticos/terapiaRESUMO
OBJECTIVE: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms. METHOD: Individuals with PTSD underwent functional MRI (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30) and underwent a second scan approximately 4 weeks after the last treatment session or a comparable waiting period, respectively. RESULTS: Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayed a greater variety of temporal resting-state signal pattern changes after treatment. Concurrent transcranial magnetic stimulation and fMRI in healthy participants demonstrated that the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum. CONCLUSIONS: Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy and that the frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works, and they identify a promising target for stimulation-based therapeutics.
Assuntos
Corpo Estriado/fisiopatologia , Emoções/fisiologia , Lobo Frontal/fisiopatologia , Terapia Implosiva , Córtex Pré-Frontal/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/terapia , Adolescente , Adulto , Feminino , Lobo Frontal/fisiologia , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Estimulação Magnética Transcraniana , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients do not respond. Brain functions governing treatment outcome are not well characterized. The authors examined brain systems relevant to emotional reactivity and regulation, constructs that are thought to be central to PTSD and exposure therapy effects, to identify the functional traits of individuals most likely to benefit from treatment. METHOD: Individuals with PTSD underwent functional MRI (fMRI) while completing three tasks assessing emotional reactivity and regulation. Participants were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30). A random subset of the prolonged exposure group (N=17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with fMRI to examine whether predictive activation patterns reflect causal influence within circuits. Linear mixed-effects modeling in line with the intent-to-treat principle was used to examine how baseline brain function moderated the effect of treatment on PTSD symptoms. RESULTS: At baseline, individuals with larger treatment-related symptom reductions (compared with the waiting list condition) demonstrated 1) greater dorsal prefrontal activation and 2) less left amygdala activation, both during emotion reactivity; 3) better inhibition of the left amygdala induced by single TMS pulses to the right dorsolateral prefrontal cortex; and 4) greater ventromedial prefrontal/ventral striatal activation during emotional conflict regulation. Reappraisal-related activation was not a significant moderator of the treatment effect. CONCLUSIONS: Capacity to benefit from prolonged exposure in PTSD is gated by the degree to which prefrontal resources are spontaneously engaged when superficially processing threat and adaptively mitigating emotional interference, but not when deliberately reducing negative emotionality.
Assuntos
Tonsila do Cerebelo/fisiopatologia , Corpo Estriado/fisiopatologia , Emoções/fisiologia , Terapia Implosiva , Córtex Pré-Frontal/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/terapia , Adolescente , Adulto , Feminino , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Inibição Neural , Córtex Pré-Frontal/fisiologia , Estimulação Magnética Transcraniana , Resultado do Tratamento , Adulto JovemRESUMO
Emotion context sensitivity is the ability to respond emotionally in a manner that is functionally appropriate for the context in which the emotion arises. This study examined the relationship between emotion context sensitivity and treatment adherence in adults with the chronic illness Thalassemia. Emotional responses were measured by examining the frequency of positive and negative emotional words used to answer two interview questions that created two different emotional contexts. Consistent with previous research on adaptive and contextually appropriate emotions, negative emotion words were related to adherence in the context of the disease itself, while positive emotion words were related to adherence in the context of coping.