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The study evaluated if rumination of patients during therapy (i.e., in-session rumination) relates to whether or not they do less well in CBT treatment. We developed a reliably assessed in-session rumination observational measure and evaluated its relationship to depression over the course of CBT. Rated sessions came from 63 treatment-naïve patients with major depressive disorder who participated in CBT in the PReDICT study (Dunlop et al., 2017). In-session rumination was operationalized as repetitive, negative, and passive talking about depressive topics. Trained undergraduates rated the intensity and duration of in-session rumination occurring during 57 initial therapy sessions (i.e., session one) and 45 sessions in the middle of treatment (i.e., session eight). The observational ratings were sufficiently reliable (all ICCs > 0.69). Mixed model results indicated that greater intensity of in-session rumination during the initial treatment session predicted higher levels of subsequent clinician-rated depressive symptoms (p < .023). Regression results indicated that greater intensity and duration of in-session rumination at session 8 significantly predicted higher clinician-rated symptoms at end of treatment (p's < 0.02). In-session rumination intensity and duration were not, however, related to subsequent self-reported depressive symptoms. The results support efforts to identify which patients might benefit from rumination-specific interventions.
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Trastorno Depresivo Mayor , Humanos , Trastorno Depresivo Mayor/terapia , Depresión/terapia , Depresión/diagnóstico , AutoinformeRESUMEN
Target identification and contact selection are known contributors to variability in efficacy across different clinical indications of deep brain stimulation surgery. A retrospective analysis of responders to subcallosal cingulate deep brain stimulation (SCC DBS) for depression demonstrated the common impact of the electrical stimulation on a stereotypic connectome of converging white matter bundles (forceps minor, uncinate fasciculus, cingulum and fronto-striatal fibers). To test the utility of a prospective connectomic approach for SCC DBS surgery, this pilot study used the four-bundle tractography 'connectome blueprint' to plan surgical targeting in 11 participants with treatment-resistant depression. Before surgery, targets were selected individually using deterministic tractography. Selection of contacts for chronic stimulation was made by matching the post-operative probabilistic tractography map to the pre-surgical deterministic tractography map for each subject. Intraoperative behavioral responses were used as a secondary verification of location. A probabilistic tract map of all participants demonstrated inclusion of the four bundles as intended, matching the connectome blueprint previously defined. Eight of 11 patients (72.7%) were responders and 5 were remitters after 6 months of open-label stimulation. At one year, 9 of 11 patients (81.8%) were responders, with 6 of them in remission. These results support the utility of a group probabilistic tractography map as a connectome blueprint for individualized, patient-specific, deterministic tractography targeting, confirming retrospective findings previously published. This new method represents a connectomic approach to guide future SCC DBS studies.
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Estimulación Encefálica Profunda/métodos , Trastorno Depresivo Resistente al Tratamiento/terapia , Corteza Prefrontal/fisiología , Adulto , Conectoma/métodos , Depresión/terapia , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Resistente al Tratamiento/fisiopatología , Imagen de Difusión Tensora , Femenino , Giro del Cíngulo/fisiología , Humanos , Masculino , Persona de Mediana Edad , Red Nerviosa , Proyectos Piloto , Corteza Prefrontal/metabolismo , Corteza Prefrontal/cirugía , Estudios Prospectivos , Estudios Retrospectivos , Sustancia Blanca/fisiologíaRESUMEN
BACKGROUND: Early life stress (ELS) is a significant risk factor for depression. The effects of ELS exposure on neural network organization have not been differentiated from the effect of depression. Furthermore, many individuals exposed to ELS do not develop depression, yet the network organization patterns differentiating resiliency versus susceptibility to the depressogenic effects of ELS are not clear. METHOD: Women aged 18-44 years with either a history of ELS and no history of depression (n = 7), a history of ELS and current or past depression (n = 19), or a history of neither ELS nor depression (n = 12) underwent a resting-state 3-T functional magnetic resonance imaging (fMRI) scan. An emotion regulation brain network consisting of 21 nodes was described using graph analyses and compared between groups. RESULTS: Group differences in network topology involved decreased global connectivity and hub-like properties for the right ventrolateral prefrontal cortex (vlPFC) and decreased local network connectivity for the dorsal anterior cingulate cortex (dACC) among resilient individuals. Decreased local connectivity and increased hub-like properties of the left amygdala, decreased hub-like properties of the dACC and decreased local connectivity of the left vlPFC were observed among susceptible individuals. Regression analyses suggested that the severity of ELS (measured by self-report) correlated negatively with global connectivity and hub-like qualities for the left dorsolateral PFC (dlPFC). CONCLUSIONS: These preliminary results suggest functional neural connectivity patterns specific to ELS exposure and resiliency versus susceptibility to the depressogenic effects of ELS exposure.
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Trastorno Depresivo Mayor/fisiopatología , Inteligencia Emocional/fisiología , Acontecimientos que Cambian la Vida , Modelos Biológicos , Red Nerviosa/fisiopatología , Estrés Psicológico/fisiopatología , Adolescente , Adulto , Maltrato a los Niños/psicología , Conectoma , Susceptibilidad a Enfermedades , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Sistema Límbico/fisiopatología , Imagen por Resonancia Magnética/métodos , Corteza Prefrontal/fisiopatología , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Resiliencia Psicológica , Descanso , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Chronic deep brain stimulation (DBS) of subgenual cingulate white matter results in dramatic remission of symptoms in some previously treatment-resistant depression patients. The effects of stimulation may be mediated locally or via corticocortical or corticosubcortical connections. We use tractography to define the likely connectivity of cingulate regions stimulated in DBS-responsive patients using diffusion imaging data acquired in healthy control subjects. We defined 2 distinct regions within anterior cingulate cortex based on anatomical connectivity: a pregenual region strongly connected to medial prefrontal and anterior midcingulate cortex and a subgenual region with strongest connections to nucleus accumbens, amygdala, hypothalamus, and orbitofrontal cortex. The location of electrode contact points from 9 patients successfully treated with DBS lies within this subgenual region. The anatomical connectivity of the subgenual cingulate region targeted with DBS for depression supports the hypothesis that treatment efficacy is mediated via effects on a distributed network of frontal, limbic, and visceromotor brain regions. At present, targeting of DBS for depression is based on landmarks visible in conventional magnetic resonance imaging. Preoperatively acquired diffusion imaging for connectivity-based cortical mapping could improve neurosurgical targeting. We hypothesize that the subgenual region with greatest connectivity across the distributed network described here may prove most effective.
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Estimulación Encefálica Profunda/métodos , Trastorno Depresivo/fisiopatología , Trastorno Depresivo/terapia , Giro del Cíngulo/fisiología , Adulto , Trastorno Depresivo/psicología , Femenino , Humanos , MasculinoRESUMEN
This paper reports the results of an across lab metanalysis of effective connectivity in major depression (MDD). Using FDG PET data and Structural Equation Modeling, a formal depression model was created to explicitly test current theories of limbic-cortical dysfunction in MDD and to characterize at the path level potential sources of baseline variability reported in this patient population. A 7-region model consisting of lateral prefrontal cortex (latF9), anterior thalamus (aTh), anterior cingulate (Cg24), subgenual cingulate (Cg25), orbital frontal cortex (OF11), hippocampus (Hc), and medial frontal cortex (mF10) was tested in scans of 119 depressed patients and 42 healthy control subjects acquired during three separate studies at two different institutions. A single model, based on previous theory and supported by anatomical connectivity literature, was stable for the three groups of depressed patients. Within the context of this model, path differences among groups as a function of treatment response characteristics were also identified. First, limbic-cortical connections (latF9-Cg25-OF11-Hc) differentiated drug treatment responders from nonresponders. Second, nonresponders showed additional abnormalities in limbic-subcortical pathways (aTh-Cg24-Cg25-OF11-Hc). Lastly, more limited limbic-cortical (Hc-latF9) and cortical-cortical (OF11-mF10) path differences differentiated responders to cognitive behavioral therapy (CBT) from responders to pharmacotherapy. We conclude that the creation of such models is a first step toward full characterization of the depression phenotype at the neural systems level, with implications for the future development of brain-based algorithms to determine optimal treatment selection for individual patients.
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Trastorno Depresivo Mayor/patología , Lóbulo Frontal/patología , Sistema Límbico/patología , Red Nerviosa/patología , Algoritmos , Antidepresivos de Segunda Generación/uso terapéutico , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Resistencia a Medicamentos , Terapia Electroconvulsiva , Fluorodesoxiglucosa F18 , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Neurológicos , Paroxetina/uso terapéutico , Radiofármacos , Tomografía Computarizada de EmisiónRESUMEN
BACKGROUND: As interventions for severe, treatment-refractory obsessive compulsive disorder (OCD), neurosurgical procedures are associated with only modest efficacy. The purpose of this study was to identify cerebral metabolic correlates as potential predictors of treatment response to anterior cingulotomy for OCD. METHODS: Clinical data were analyzed in the context of a retrospective design. Subjects were 11 patients who underwent stereotactic anterior cingulotomy for OCD. Symptom severity was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before and at approximately 6 months postoperative. Preoperative F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) data were available. Statistical parametric mapping methods were used to identify loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in Y-BOCS scores. RESULTS: One locus within right posterior cingulate cortex was identified, where preoperative metabolism was significantly correlated with improvement in OCD symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at that locus were associated with better postoperative outcome. CONCLUSIONS: A possible predictor of treatment response was identified for patients with OCD undergoing anterior cingulotomy. Further research, utilizing a prospective design, is indicated to determine the validity and reliability of this finding. If confirmed, an index for noninvasively predicting response to cingulotomy for OCD would be of great value.
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Giro del Cíngulo/metabolismo , Giro del Cíngulo/cirugía , Procedimientos Neuroquirúrgicos/métodos , Trastorno Obsesivo Compulsivo/diagnóstico , Trastorno Obsesivo Compulsivo/cirugía , Adulto , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Giro del Cíngulo/anatomía & histología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Cuidados Preoperatorios , Radiofármacos/farmacocinética , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Técnicas Estereotáxicas , Encuestas y Cuestionarios , Tomografía Computarizada de Emisión , Resultado del TratamientoRESUMEN
OBJECTIVE: Depression is commonly associated with frontal hypometabolic activity accompanied by hypermetabolism in certain limbic regions. It is unclear whether successful antidepressant treatments reverse these abnormalities or create new resting levels of metabolism. The aim of the present study was to assess the effects of successful paroxetine treatment on regional glucose metabolism in patients with major depression. METHOD: Positron emission tomography with [(18)F]fluorodeoxyglucose was performed on 13 male patients before and after 6 weeks of paroxetine therapy. Resting state scans were also acquired under similar conditions in 24 healthy male subjects for comparison. RESULTS: After successful paroxetine therapy, increased glucose metabolism occurred in dorsolateral, ventrolateral, and medial aspects of the prefrontal cortex (left greater than right), parietal cortex, and dorsal anterior cingulate. Areas of decreased metabolism were noted in both anterior and posterior insular regions (left) as well as right hippocampal and parahippocampal regions. In comparison to metabolism levels in a group of healthy volunteers, the increase in prefrontal metabolic activity represented a normalization of previously reduced metabolic activity, whereas the reduction in pregenual anterior cingulate activity represented a decrease from previously elevated metabolic levels. CONCLUSIONS: These results provide further support for a dysfunction in cortical-limbic circuitry in depression, which is at least partly reversed after successful paroxetine treatment.
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Encéfalo/metabolismo , Trastorno Depresivo/tratamiento farmacológico , Glucosa/metabolismo , Paroxetina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tomografía Computarizada de Emisión/estadística & datos numéricos , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Trastorno Depresivo/diagnóstico por imagen , Trastorno Depresivo/metabolismo , Fluorodesoxiglucosa F18 , Lateralidad Funcional , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/efectos de los fármacos , Giro del Cíngulo/metabolismo , Hipocampo/diagnóstico por imagen , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Humanos , Sistema Límbico/diagnóstico por imagen , Sistema Límbico/efectos de los fármacos , Sistema Límbico/metabolismo , Masculino , Persona de Mediana Edad , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/efectos de los fármacos , Lóbulo Parietal/metabolismo , Paroxetina/sangre , Paroxetina/farmacocinética , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/sangre , Inhibidores Selectivos de la Recaptación de Serotonina/farmacocinética , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the relationship between regional cerebral blood flow (rCBF) and chronic fatigue syndrome (CFS) in monozygotic twins discordant for CFS. MATERIALS AND METHODS: The authors conducted a co-twin control study of 22 monozygotic twins in which one twin met criteria for CFS and the other was healthy. Twins underwent a structured psychiatric interview and resting technetium 99m-hexamethyl-propyleneamine oxime single photon emission computed tomography of the brain. They also rated their mental status before the procedure. Scans were interpreted independently by two physicians blinded to illness status and then at a blinded consensus reading. Imaging fusion software with automated three-dimensional matching of rCBF images was used to coregister and quantify results. Outcomes were the number and distribution of abnormalities at both reader consensus and automated quantification. Mean rCBF levels were compared by using random effects regression models to account for the effects of twin matching and potential confounding factors. RESULTS: The twins with and those without CFS were similar in mean number of visually detected abnormalities and in mean differences quantified by using image registration software. These results were unaltered with adjustments for fitness level, depression, and mood before imaging. CONCLUSION: The study results did not provide evidence of a distinctive pattern of resting rCBF abnormalities associated with CFS. The described method highlights the importance of selecting well-matched control subjects.
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Encéfalo/diagnóstico por imagen , Circulación Cerebrovascular , Enfermedades en Gemelos/genética , Síndrome de Fatiga Crónica/diagnóstico por imagen , Síndrome de Fatiga Crónica/genética , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Entrevista Psicológica , Masculino , Radiofármacos , Exametazima de Tecnecio Tc 99m , Gemelos MonocigóticosRESUMEN
Depressed individuals show impaired performance in tests of attention and concentration. They also exhibit PET resting state abnormalities in dorsal prefrontal cortex and anterior cingulate, regions known to be substrates of attentional processing in healthy individuals. This chapter outlines a strategy to study neuropsychological mechanisms in emotional disorders using functional imaging methods. It reviews evidence strongly implicating the dorsolateral prefrontal cortex, particularly in the right hemisphere, as a key brain structure in emotion/cognition interactions in negative mood states. It will be argued that this neocortical region is a crucial convergence zone, being the substrate of sustained attention to the external environment, and the main target of limbic-cortical influences during changes in mood state across health and disease.
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Atención , Depresión/fisiopatología , Depresión/psicología , Corteza Prefrontal/fisiopatología , Tomografía Computarizada de Emisión , Afecto , Estudios de Casos y Controles , Depresión/diagnóstico por imagen , Dominancia Cerebral , Electroencefalografía , Humanos , Sistema Límbico/fisiopatología , Corteza Prefrontal/diagnóstico por imagenRESUMEN
OBJECTIVE: In the cortex of animals, serotonin (5-HT) levels increase after several weeks of treatment with selective serotonin reuptake inhibitors (SSRIs). Studies using an intrasubject design to examine the effects of SSRI treatment on 5-HT(2A) receptors in the cortex of drug-free depressed patients are needed. In theory, agonist stimulation of 5-HT(2A) receptors could be relevant to SSRI treatment by promoting neuronal growth and survival as well as direct elevation of mood. The objective of this study was to evaluate the effect of 6 weeks of paroxetine treatment on 5-HT(2A) receptors in depressed patients. METHOD: After a medication-free period of at least 3 months, 19 depressed patients were treated for 6 weeks with paroxetine, 20 mg/day. The authors used [(18)F]setoperone and positron emission tomography to assess 5-HT(2A) receptor binding potential in the patients before and after treatment and in 19 age-matched healthy subjects. RESULTS: 5-HT(2A) binding potential declined with age in all cortical regions in the depressed and healthy subjects. There was a significant interaction between age and treatment effect on 5-HT(2A) binding potential in all cortical regions. Subjects aged 20 to 30 years had a 10% decrease in 5-HT(2A) binding potential after treatment, whereas subjects aged 30 to 40 had no change. No regional differences in 5-HT(2A) binding potential between depressed and healthy subjects were found. CONCLUSIONS: 5-HT(2A) receptors down-regulate in young depressed subjects after treatment with paroxetine, but this down-regulation attenuates with age. This suggests that over 6 weeks paroxetine treatment increases 5-HT agonism on 5-HT(2A) receptors in the cortex of young patients with depression.
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Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/diagnóstico por imagen , Trastorno Depresivo/tratamiento farmacológico , Paroxetina/uso terapéutico , Receptores de Serotonina/efectos de los fármacos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Tomografía Computarizada de Emisión , Adolescente , Adulto , Factores de Edad , Corteza Cerebral/metabolismo , Trastorno Depresivo/diagnóstico por imagen , Regulación hacia Abajo/efectos de los fármacos , Femenino , Radioisótopos de Flúor , Humanos , Masculino , Paroxetina/farmacología , Pirimidinonas , Receptor de Serotonina 5-HT2A , Receptores de Serotonina/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Tomografía Computarizada de Emisión/estadística & datos numéricos , Resultado del TratamientoRESUMEN
BACKGROUND: Treatment of major depression with antidepressants is generally associated with a delay in onset of clinical response. Functional brain correlates of this phenomenon have not been previously characterized. METHODS: Time course of changes in brain glucose metabolism were measured using positron emission tomography in hospitalized unipolar depressed patients treated with fluoxetine. Time-specific and response-specific effects were examined at 1 and 6 weeks of treatment. RESULTS: Changes were seen over time, and characterized by three distinct patterns: 1) common changes at 1 and 6 weeks, 2) reversal of the 1-week pattern at 6 weeks, and 3) unique changes seen only after chronic treatment. Fluoxetine responders and nonresponders, similar at 1 week, were differentiated by their 6-week pattern. Clinical improvement was uniquely associated with limbic and striatal decreases (subgenual cingulate, hippocampus, insula, and pallidum) and brain stem and dorsal cortical increases (prefrontal, parietal, anterior, and posterior cingulate). Failed response was associated with a persistent 1-week pattern and absence of either subgenual cingulate or prefrontal changes. CONCLUSIONS: Chronic treatment and clinical response to fluoxetine was associated with a reciprocal pattern of subcortical and limbic decreases and cortical increases. Reversal in the week-1 pattern at 6 weeks suggests a process of adaptation in specific brain regions over time in response to sustained serotonin reuptake inhibition. The inverse patterns in responders and nonresponders also suggests that failure to induce these adaptive changes may underlie treatment nonresponse.
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Trastorno Depresivo Mayor/tratamiento farmacológico , Fluoxetina/farmacocinética , Fluoxetina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/farmacocinética , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Encéfalo/metabolismo , Esquema de Medicación , Fluoxetina/administración & dosificación , Glucosa/metabolismo , Humanos , Sistema Límbico/metabolismo , Masculino , Persona de Mediana Edad , Corteza Prefrontal/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Factores de Tiempo , Tomografía Computarizada de Emisión , Resultado del TratamientoRESUMEN
BACKGROUND: Affective disorders are associated with comorbidity of depression and anxiety symptoms. Positron emission tomography resting-state studies in affective disorders have generally failed to isolate specific symptom effects. Emotion provocation studies in healthy volunteers have produced variable results, due to differences in experimental paradigm and instructions. METHODS: To better delineate the neural correlates of sad mood and anxiety, this study used autobiographical memory scripts in eight healthy women to generate sadness, anxiety, or a neutral relaxed state in a within-subject design. RESULTS: Sadness and anxiety, when contrasted to a neutral emotional state, engaged a set of distinct paralimbic-cortical regions, with a limited number of common effects. Sadness was accompanied by specific activations of the subgenual cingulate area (BA) 25 and dorsal insula, specific deactivation of the right prefrontal cortex BA 9, and more prominent deactivation of the posterior parietal cortex BAs 40/7. Anxiety was associated with specific activations of the ventral insula, the orbitofrontal and anterior temporal cortices, specific deactivation of parahippocampal gyri, and more prominent deactivation of the inferior temporal cortex BAs 20/37. CONCLUSIONS: These findings are interpreted within a model in which sadness and anxiety are represented by segregated corticolimbic pathways, where a major role is played by selective dorsal cortical deactivations during sadness, and ventral cortical deactivations in anxiety.
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Ansiedad , Corteza Cerebral/fisiología , Circulación Cerebrovascular , Depresión , Sistema Límbico/fisiología , Tomografía Computarizada de Emisión , Adulto , Ansiedad/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Depresión/diagnóstico por imagen , Femenino , Humanos , Imaginación , Sistema Límbico/diagnóstico por imagen , Imagen por Resonancia Magnética , Trastornos del Humor/fisiopatología , Red Nerviosa , Valores de ReferenciaRESUMEN
The electrophysiological correlates of the Stroop color-word interference effect were studied in eight healthy subjects using high-density Event-Related Potentials (ERPs). Three response modalities were compared: Overt Verbal, Covert Verbal, and Manual. Both Overt Verbal and Manual versions of the Stroop yielded robust Stroop color-word interference as indexed by longer RT for incongruent than congruent color words. The Incongruent vs Congruent ERP difference wave presented two effects. A first effect was a medial dorsal negativity between 350-500 ms post-stimulus (peak at 410 ms). This effect had a significantly different scalp distribution in the Verbal and Manual Stroop versions, with an anterior-medial focus for overt or covert speech, and a broader medial-dorsal distribution for the manual task. Dipole source analysis suggested two independent generators in anterior cingulate cortex. Later on in time, a prolonged positivity developed between 500-800 ms post-stimulus over left superior temporo-parietal scalp. This effect was present for all the three response modalities. A possible interpretation of these results is that Stroop color-word interference first activates anterior cingulate cortex (350-500 ms post-stimulus), followed by activation of the left temporo-parietal cortex, possibly related to the need of additional processing of word meaning.
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Percepción de Color/fisiología , Potenciales Evocados/fisiología , Pruebas Neuropsicológicas , Adulto , Análisis de Varianza , Electroencefalografía , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Estimulación Luminosa , Desempeño Psicomotor/fisiologíaRESUMEN
OBJECTIVE: Theories of human behavior from Plato to Freud have repeatedly emphasized links between emotion and reason, a relationship now commonly attributed to pathways connecting phylogenetically "old" and "new" brain regions. Expanding on this theory, this study examined functional interactions between specific limbic and neocortical regions accompanying normal and disease-associated shifts in negative mood state. METHOD: Regions of concordant functional change accompanying provocation of transient sadness in healthy volunteers and resolution of chronic dysphoric symptoms in depressed patients were examined with two positron emission tomography techniques: [15O]water and [18F]fluorodeoxyglucose, respectively. RESULTS: With sadness, increases in limbic-paralimbic blood flow (subgenual cingulate, anterior insula) and decreases in neocortical regions (right dorsolateral prefrontal, inferior parietal) were identified. With recovery from depression, the reverse pattern, involving the same regions, was seen--limbic metabolic decreases and neocortical increases. A significant inverse correlation between subgenual cingulate and right dorsolateral prefrontal activity was also demonstrated in both conditions. CONCLUSIONS: Reciprocal changes involving subgenual cingulate and right prefrontal cortex occur with both transient and chronic changes in negative mood. The presence and maintenance of functional reciprocity between these regions with shifts in mood in either direction suggests that these regional interactions are obligatory and probably mediate the well-recognized relationships between mood and attention seen in both normal and pathological conditions. The bidirectional nature of this limbic-cortical reciprocity provides additional evidence of potential mechanisms mediating cognitive ("top-down"), pharmacological (mixed), and surgical ("bottom-up") treatments of mood disorders such as depression.
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Afecto/fisiología , Depresión/diagnóstico , Trastorno Depresivo/diagnóstico , Sistema Límbico/irrigación sanguínea , Neocórtex/irrigación sanguínea , Atención/fisiología , Depresión/diagnóstico por imagen , Depresión/metabolismo , Trastorno Depresivo/diagnóstico por imagen , Trastorno Depresivo/metabolismo , Femenino , Fluorodesoxiglucosa F18 , Glucosa/metabolismo , Humanos , Sistema Límbico/diagnóstico por imagen , Sistema Límbico/metabolismo , Persona de Mediana Edad , Neocórtex/diagnóstico por imagen , Neocórtex/metabolismo , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Radioisótopos de Oxígeno , Corteza Prefrontal/diagnóstico por imagen , Corteza Prefrontal/fisiología , Flujo Sanguíneo Regional , Tomografía Computarizada de EmisiónRESUMEN
Subjective and physiologic effects of 33% inhaled Xe were measured with 15O-water positron emission tomography (PET) in 3 subjects at rest and during visual stimulation. The procedure was well tolerated. Robust functional activations of the visual cortex were obtained after xenon (Xe) inhalation as well as air breathing. However, Xe inhalation was followed by smaller size, but significant decreases of regional cerebral blood flow (rCBF) in visual cortex relative to the air-breathing baseline, both during visual stimulation and at rest. No such decreases were found in other sensory or motor regions.
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Encéfalo/diagnóstico por imagen , Circulación Cerebrovascular/efectos de los fármacos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada de Emisión , Xenón/farmacología , Adulto , Depresión Química , Humanos , Masculino , Radioisótopos de Oxígeno , Estimulación Luminosa , Corteza Visual/irrigación sanguínea , Corteza Visual/efectos de los fármacos , Corteza Visual/fisiología , Agua , Xenón/administración & dosificaciónRESUMEN
A working model of depression implicating failure of the coordinated interactions of a distributed network of limbic-cortical pathways is proposed. Resting state patterns of regional glucose metabolism in idiopathic depressed patients, changes in metabolism with antidepressant treatment, and blood flow changes with induced sadness in healthy subjects were used to test and refine this hypothesis. Dorsal neocortical decreases and ventral paralimbic increases characterize both healthy sadness and depressive illness; concurrent inhibition of overactive paralimbic regions and normalization of hypofunctioning dorsal cortical sites characterize disease remission. Normal functioning of the rostral anterior cingulate, with its direct connections to these dorsal and ventral areas, is postulated to be additionally required for the observed reciprocal compensatory changes, since pretreatment metabolism in this region uniquely predicts antidepressant treatment response. This model is offered as an adaptable framework to facilitate continued integration of clinical imaging findings with complementary neuroanatomical, neurochemical, and electrophysiological studies in the investigation of the pathogenesis of affective disorders.
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Corteza Cerebral/fisiopatología , Trastorno Depresivo/fisiopatología , Sistema Límbico/fisiopatología , Biomarcadores , Trastorno Depresivo/psicología , Humanos , Modelos BiológicosRESUMEN
The relationship between pretreatment regional cerebral glucose metabolism and eventual antidepressant drug response was measured using positron emission tomography (PET) in hospitalized patients with unipolar depression. Rostral anterior cingulate metabolism uniquely differentiated eventual treatment responders from non-responders. Hypometabolism characterized non-responders when compared with controls, in contrast to responders who were hypermetabolic. Metabolism in no other region discriminated the two groups, nor did associated demographic, clinical or behavioral measures, including motor speed, cognitive performance, depression severity or illness chronicity. Cingulate hypermetabolism may represent an important adaptive response to depression and failure of this response may underlie poor outcome. A critical role for rostral cingulate area 24a/b in the limbic-cortical network involved in abnormal mood states is proposed.
Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Desoxiglucosa/análogos & derivados , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/metabolismo , Glucosa/metabolismo , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/metabolismo , Adulto , Análisis de Varianza , Ansiedad , Desoxiglucosa/farmacocinética , Trastorno Depresivo/diagnóstico por imagen , Femenino , Fluorodesoxiglucosa F18 , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Pronóstico , Valores de Referencia , Tomografía Computarizada de EmisiónRESUMEN
Measurements of cerebral metabolism in patients with Alzheimer's disease (AD) using PET are artifactually depressed due to partial volume averaging of brain tissue activity with enlarged CSF spaces. To investigate the effects of correction for the expansion of CSF spaces on regional metabolic measures, as well as the correlations between neuropsychological test results and resting cerebral metabolism before and after partial volume correction, we applied an MRI-based method of partial volume correction to 18F-fluorodeoxyglucose (FDG)-PET data from eight patients diagnosed with probable AD and ten healthy elderly individuals. Before correction, the AD group had significantly lower cortex-to-cerebellum ratios in the posterior temporal, parietal, and frontal lobes in comparison to the control subjects. Partial volume correction of PET data resulted in 19 to 49% increases in regional activity in the AD group and 16 to 38% increases in the control group. The patients' persistence of significant hypometabolism in the frontal, posterior temporal, and parietal regions after partial volume correction suggests that a true reduction in regional cerebral glucose metabolism occurs in AD, even though its magnitude is a result of both metabolic reductions and the effects of atrophy. Partial volume correction of PET data in the AD group had a significant impact on the correlations between regional glucose metabolism and neuropsychological performance. These findings suggest that accounting for differential extent and distribution of cerebral atrophy in patients with AD and in healthy individuals may potentially improve our ability to interpret specific cognitive dysfunction in the context of the functional imaging data.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/psicología , Análisis de Varianza , Mapeo Encefálico , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Tomografía Computarizada de EmisiónAsunto(s)
Depresión/etiología , Enfermedad de Parkinson/complicaciones , Encéfalo/diagnóstico por imagen , Depresión/diagnóstico , Depresión/diagnóstico por imagen , Depresión/fisiopatología , Dopamina/metabolismo , Humanos , Norepinefrina/metabolismo , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Serotonina/metabolismo , Tomografía Computarizada de EmisiónRESUMEN
Functional imaging studies in patients with dementia have focused primarily on the reliability of scan patterns to correctly diagnose specific diseases, particularly Alzheimer's disease. Results from these studies have important implications as disease-specific treatments become available. A complementary approach is to examine the relationships between patterns of altered brain function and specific behaviors. This tactic has potential impact on understanding normal brain organization as well as targeting symptom-specific treatments. Regional abnormalities have been identified in dementia patients that correlate with specific behavioral deficits: disturbances of language and visuospatial function, impaired verbal fluency and selective attention, and the presence of delusions and depression. These patterns are seen in patients with Alzheimer's disease as well as with dementias of other etiologies. The specificity of these patterns for disease-specific and disease-independent symptoms is unknown.