RESUMEN
Face memory deficits may be a bipolar disorder (BD) endophenotype. BD (n=27) and unaffected youth at risk (n=13) exhibited middle frontal gyrus hypoactivation during successful vs. unsuccessful encoding. Parahippocampal gyrus dysfunction was found in BD and at-risk youth (vs. low-risk, n=37). Middle occipital gyrus hypoactivation was only present in BD.
Asunto(s)
Trastorno Bipolar/fisiopatología , Trastorno Bipolar/psicología , Encéfalo/fisiopatología , Emociones , Expresión Facial , Imagen por Resonancia Magnética , Adolescente , Endofenotipos , Femenino , Lóbulo Frontal/fisiopatología , Humanos , Masculino , Memoria , Lóbulo Occipital/fisiopatología , Giro Parahipocampal/fisiopatología , RiesgoRESUMEN
BACKGROUND: Research in bipolar disorder (BD) implicates fronto-limbic-striatal dysfunction during face emotion processing but it is unknown how such dysfunction varies by task demands, face emotion and patient age. METHOD: During functional magnetic resonance imaging (fMRI), 181 participants, including 62 BD (36 children and 26 adults) and 119 healthy comparison (HC) subjects (57 children and 62 adults), engaged in constrained and unconstrained processing of emotional (angry, fearful, happy) and non-emotional (neutral) faces. During constrained processing, subjects answered questions focusing their attention on the face; this was processed either implicitly (nose width rating) or explicitly (hostility; subjective fear ratings). Unconstrained processing consisted of passive viewing. RESULTS: Pediatric BD rated neutral faces as more hostile than did other groups. In BD patients, family-wise error (FWE)-corrected region of interest (ROI) analyses revealed dysfunction in the amygdala, inferior frontal gyrus (IFG), anterior cingulate cortex (ACC) and putamen. Patients with BD showed amygdala hyperactivation during explicit processing (hostility ratings) of fearful faces and passive viewing of angry and neutral faces but IFG hypoactivation during implicit processing of neutral and happy faces. In the ACC and striatum, the direction of dysfunction varied by task demand: BD demonstrated hyperactivation during unconstrained processing of angry or neutral faces but hypoactivation during constrained processing (implicit or explicit) of angry, neutral or happy faces. CONCLUSIONS: Findings suggest amygdala hyperactivation in BD while processing negatively valenced and neutral faces, regardless of attentional condition, and BD IFG hypoactivation during implicit processing. In the cognitive control circuit involving the ACC and putamen, BD neural dysfunction was sensitive to task demands.
Asunto(s)
Amígdala del Cerebelo/fisiopatología , Atención/fisiología , Trastorno Bipolar/fisiopatología , Expresión Facial , Giro del Cíngulo/fisiopatología , Corteza Prefrontal/fisiopatología , Putamen/fisiopatología , Adolescente , Adulto , Niño , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Major depressive disorder (MDD) is associated with deficits in recalling specific autobiographical memories (AMs). Extensive research has examined the functional anatomical correlates of AM in healthy humans, but no studies have examined the neurophysiological underpinnings of AM deficits in MDD. The goal of the present study was to examine the differences in the hemodynamic response between patients with MDD and controls while they engage in AM recall. METHOD: Participants (12 unmedicated MDD patients; 14 controls) underwent functional magnetic resonance imaging (fMRI) scanning while recalling AMs in response to positive, negative and neutral cue words. The hemodynamic response during memory recall versus performing subtraction problems was compared between MDD patients and controls. Additionally, a parametric linear analysis examined which regions correlated with increasing arousal ratings. RESULTS: Behavioral results showed that relative to controls, the patients with MDD had fewer specific (p=0.013), positive (p=0.030), highly arousing (p=0.036) and recent (p=0.020) AMs, and more categorical (p<0.001) AMs. The blood oxygen level-dependent (BOLD) response in the parahippocampus and hippocampus was higher for memory recall versus subtraction in controls and lower in those with MDD. Activity in the anterior insula was lower for specific AM recall versus subtraction, with the magnitude of the decrement greater in MDD patients. Activity in the anterior cingulate cortex was positively correlated with arousal ratings in controls but not in patients with MDD. CONCLUSIONS: We replicated previous findings of fewer specific and more categorical AMs in patients with MDD versus controls. We found differential activity in medial temporal and prefrontal lobe structures involved in AM retrieval between MDD patients and controls as they engaged in AM recall. These neurophysiological deficits may underlie AM recall impairments seen in MDD.
Asunto(s)
Corteza Cerebral/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Neuroimagen Funcional/métodos , Memoria Episódica , Recuerdo Mental/fisiología , Adulto , Femenino , Neuroimagen Funcional/instrumentación , Hipocampo/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Giro Parahipocampal/fisiopatologíaRESUMEN
We investigated the neural basis of auditory object processing in the cerebral cortex by combining neural modeling and functional neuroimaging. We developed a large-scale, neurobiologically realistic network model of auditory pattern recognition that relates the neuronal dynamics of cortical auditory processing of frequency modulated (FM) sweeps to functional neuroimaging data of the type obtained using PET and fMRI. Areas included in the model extend from primary auditory to prefrontal cortex. The electrical activities of the neuronal units of the model were constrained to agree with data from the neurophysiological literature regarding the perception of FM sweeps. We also conducted an fMRI experiment using stimuli and tasks similar to those used in our simulations. The integrated synaptic activity of the neuronal units in each region of the model, convolved with a hemodynamic response function, was used as a correlate of the simulated fMRI activity, and generally agreed with the experimentally observed fMRI data in the brain areas corresponding to the regions of the model. Our results demonstrate that the model is capable of exhibiting the salient features of both electrophysiological neuronal activities and fMRI values that are in agreement with empirically observed data. These findings provide support for our hypotheses concerning how auditory objects are processed by primate neocortex.
Asunto(s)
Percepción Auditiva/fisiología , Corteza Cerebral/fisiología , Aumento de la Imagen , Procesamiento de Imagen Asistido por Computador , Imagenología Tridimensional , Imagen por Resonancia Magnética , Redes Neurales de la Computación , Oxígeno/sangre , Adulto , Corteza Auditiva/fisiología , Vías Auditivas/fisiología , Mapeo Encefálico , Dominancia Cerebral/fisiología , Femenino , Humanos , Masculino , Memoria a Corto Plazo/fisiología , Neuronas/fisiología , Percepción de la Altura Tonal/fisiología , Corteza Prefrontal/fisiología , Psicoacústica , Valores de Referencia , Retención en Psicología/fisiología , Localización de Sonidos/fisiología , Espectrografía del Sonido , Percepción del Habla/fisiología , Tomografía Computarizada de EmisiónRESUMEN
A number of computer-assisted methods have been described for the derivation of enzyme-catalyzed steady-state rate equations [K. R. Runyan and R. B. Gunn (1989) Methods Enzymol. 171, 164-190; R. Varon, F. Garcia-Seville, M. Garvia-Moreno, F. Garcia-Canovas, R. Peyro, and R. G. Duggleby (1997) Comput. Appl. Biosci. 13, 159-167]; however, the required programs are either not readily available or require special software. We present here a two-step computer-assisted procedure for deriving steady-state rate equations using the widely available program Mathematica. In the first step, the differential equations for a particular kinetic mechanism that describe changes in enzyme concentration as a function of time are set equal to zero and entered into Mathematica in matrix form. In the second step, a single command allows for the computation of the distribution equations for the free enzyme and each enzyme-ligand complex.
Asunto(s)
Simulación por Computador , Enzimas/metabolismo , Interpretación Estadística de Datos , Cinética , Programas InformáticosRESUMEN
Heparin is a polydisperse, highly sulfated polysaccharide consisting of repeating 1-->4 linked uronic acid and glucosamine sugar residues that binds to coagulation proteins, complement proteins, and growth factors to regulate a variety of biological activities. Heparin is best known as an anticoagulant, an activity that results largely from a specific pentasaccharide sequence in heparin that interacts with a unique site in antithrombin III. Little is known about additional structures within heparin that might interact with antithrombin III or the heparin structures that interact with the myriad of other heparin-binding proteins and peptides. Unfractionated glycosaminoglycan heparin that had been prepared from porcine intestinal mucosa was examined for its capacity to bind antithrombin III using a new technique developed to quantitate that interaction. Two-dimensional affinity resolution electrophoresis is a powerful method that allows assessment of unique species of heparin molecules that bind to protein, allowing determination of heparin molecular weight for each protein-binding heparin species as well as the dissociation constant of each interaction. This study provides the first definitive evidence that glycosaminoglycan heparin contains at least three populations of molecules with affinity for antithrombin III. Furthermore, the affinity of each heparin species for antithrombin III appears to vary inversely with the size of the heparin chain, with some smaller oligosaccharides having greater affinity for antithrombin III than larger oligosaccharides.