Trauma, dream, and psychic change in psychoanalyses: a dialog between psychoanalysis and the neurosciences.

To many psychoanalysts dreams are a central source of knowledge of the unconscious-the specific research object of psychoanalysis. The dialog with the neurosciences, devoted to the testing of hypotheses on human behavior and neurophysiology with objective methods, has added to psychoanalytic conceptualizations on emotion, memory, sleep and dreams, conflict and trauma. To psychoanalysts as well as neuroscientists, the neurological basis of psychic functioning, particularly concerning trauma, is of special interest. In this article, an attempt is made to bridge the gap between psychoanalytic findings and neuroscientific findings on trauma. We then attempt to merge both approaches in one experimental study devoted to the investigation of the neurophysiological changes (fMRI) associated with psychoanalytic treatment in chronically depressed patients. We also report on an attempt to quantify psychoanalysis-induced transformation in the manifest content of dreams. To do so, we used two independent methods. First, dreams reported during the cure of chronic depressed analysands were assessed by the treating psychoanalyst. Second, dreams reported in an experimental context were analyzed by an independent evaluator using a standardized method to quantify changes in dream content (Moser method). Single cases are presented. Preliminary results suggest that psychoanalysis-induced transformation can be assessed in an objective way.

Endowing self-binding feature restores the activities of a loss-of-function chimerized anti-GM2 antibody.

Our previous studies have described a rare type of antibody that spontaneously binds to itself, or homodimerizes. This self-binding, or autophilic antibody provides stronger protection against bacterial infection than a non-self-binding antibody with identical specificity and affinity, due to an increase of polymeric avidity. Furthermore, we have shown that a peptide derived from the self-binding domain of the autophilic T15 antibody can be crosslinked to the Fc carbohydrate of monoclonal antibodies specific for the B-cell receptor of B-cell tumors. These peptide-crosslinked antibodies can exert self-binding properties, leading to an increase in binding efficiency to the target cells as well as an increase in potential to induce apoptosis. Herein, we report a novel finding that crosslinking of the autophilic T15 peptide rescues a loss-of-function chimerized (ch) anti-GM2 antibody. The parental antibody demonstrates in vivo anti-tumor activity against melanoma xenografts. The T15 peptide-conjugated antibody shows the ability to bind to itself, as well as an increased binding to its antigen, ganglioside GM2. Moreover, the peptide-conjugated antibody also demonstrates an increased ability to bind to two GM2-positive tumor cell lines and notably important, restores its ability to induce apoptosis in two types of tumor cells. These results provide strong support for the clinical potential of the autophilic technology.

Therapeutic applications of superantibodies.

Superantibody technology represents a method to enhance the potency and utility of monoclonal antibodies. The blueprint for superantibody technology is taken from rare naturally occurring superantibodies with unique sequence regions, conferring specific biological functions not detected on most antibodies. In superantibody technology, peptides with specific amino acid sequences are crosslinked to antibodies using affinity-site-specific chemistry. Three types of superantibodies have been engineered: dimerizing superantibodies with enhanced effector potency, superantibodies with the ability to penetrate living cells and superantibodies as vaccines with built-in molecular adjuvant. Collectively, superantibody technology generates a new class of antibodies with higher levels of therapeutic potency.

[Convergence of psychotherapeutic and neurobiological outcome measure in a patient with OCD]. / Konvergenzen psychotherapeutischer und neurobiologischer Ergebniskontrolle bei einer schweren Zwangsstörung.

We used psychotherapeutic measures and functional magnetic resonance imaging (fMRI) to assess the effect of a combined psychodynamic and cognitive behavioral treatment of a patient suffering from a severe obsessive compulsive disorder (OCD). The clinical outcome was controlled by a detailed case description and psychometric test instruments. Intensive exploration of the patient made possible the creation of an idiosyncratic imagination paradigm suitable for fMRI. The patient shows at the end of treatment a decrease in symptoms as assessed by clinical as well as psychometric instruments. Especially recapitulation and cleaning obsessions decreased, but the cognitive avoidance strategies remained almost unchanged. fMRI showed no orbito-fronto-striatothalamic activation corresponding to obsessive compulsive symptoms, but an increased activation of the medial prefrontal (MFC) and anterior cingulate cortex (ACC). The lack of activation of the orbito-fronto-striatothalamic circuits and at the same time the occurrence of the increased activation of the MFC and ACC reflects the cognitive avoidance strategies still triggered by the symptom provoking stimulus.

Engagement of lateral and medial prefrontal areas in the ecphory of sad and happy autobiographical memories.

Autobiographic memory is usually affect-laden, either positively or negatively. A central question is whether the retrieval of both emotive forms of memory engages the same or a different neural net. To test this we studied 13 normal subjects with functional magnetic resonance imaging while they retrieved a number of distinct episodes, all of which were either rated as strongly positive (happy) or strongly negative (sad) in affect. Comparing the retrieval of sad with that of happy episodes revealed activation in both lateral orbital cortices symmetrically (extending into the ventrolateral prefrontal cortex as well), together with a small region in the right lateral temporal cortex and the left cerebellum. Vice versa, comparing the retrieval of happy with that of sad episodes revealed a major activation in the left hippocampal region, bilateral (though more right-sided) activation in the medial orbitofrontal/subgenual cingulate and a left sided activation in the dorsolateral prefrontal activation. These findings point to the importance of the orbitofrontal cortex for affect-laden information processing and to the existence of distinct neural nets for the re-activation of positively and negatively viewed autobiographic episodes.

Enactment effect in memory: evidence concerning the function of the supramarginal gyrus.

Experimental behavioral data show that written action descriptions are remembered better when encoded by enacting them compared with merely verbal encoding. To explore this facilitating effect of encoding by performing actions ('enactment effect'), a functional magnetic resonance imaging (fMRI) study was conducted with n=18 normal subjects. During a learning condition, subjects encoded action phrases like 'cut the bread' either by reading aloud or by enacting them. The same phrases plus additional distractors were presented during fMRI scanning, and the task was to decide (yes/no key press) whether a displayed phrase was previously learned or whether it was a new one. Retrieval--independent of encoding type--activated anterior cingulate, SMA, and visual cortex bilaterally. Activations of the inferior frontal and sensorimotor cortex, and the precentral sulcus, were only left sided. The right cerebellum was also activated. The subtraction of the brain activations in the verbal condition from the enactment condition resulted in significant clusters located in middle temporal and inferior parietal left cortical areas, and, on the right side, in superior temporal, postcentral and inferior parietal cortical areas. Most striking were the bilateral inferior parietal activations, covering the supramarginal gyrus (SMG). Therefore it is concluded that SMG may be a central structure in a neurofunctional explanation of the enactment effect.

A supramodal number representation in human intraparietal cortex.

The triple-code theory of numerical processing postulates an abstract-semantic "number sense." Neuropsychology points to intraparietal cortex as a potential substrate, but previous functional neuroimaging studies did not dissociate the representation of numerical magnitude from task-driven effects on intraparietal activation. In an event-related fMRI study, we presented numbers, letters, and colors in the visual and auditory modality, asking subjects to respond to target items within each category. In the absence of explicit magnitude processing, numbers compared with letters and colors across modalities activated a bilateral region in the horizontal intraparietal sulcus. This stimulus-driven number-specific intraparietal response supports the idea of a supramodal number representation that is automatically accessed by presentation of numbers and may code magnitude information.

Functional magnetic resonance imaging in acute unilateral optic neuritis.

Despite good clinical criteria for diagnosing optic neuritis (ON), only a few techniques can precisely assess its impact on visual brain function. The authors studied whether functional magnetic resonance imaging (fMRI) of visual activation reliably reflects the cerebral consequences of acute unilateral ON, and how fMRI correlates with clinical function and visual evoked potentials (VEPs). Twenty ON patients, before and after steroid treatment, were compared to 20 controls. Each eye was stimulated separately with a checkerboard pattern reversing at 1, 2, 4, and 8 Hz. VEPs were recorded the same day. Initially, affected eye responses differed significantly from those of unaffected counterparts and controls in 12 patients. Post hoc classification by fMRI criteria was correct in approximately 85%. fMRI and VEP response parameters (as well as visual acuity) correlated significantly. The higher stimulation frequencies yielded greater fMRI responses from unaffected eyes, but not from affected eyes, in controls. The fMRI responses were quantifiable in every subject, whereas in 11 ON eyes, no VEPs were obtained during the acute stage. The authors conclude that fMRI is sensitive to the cerebral response alteration during ON and might therefore contribute to evaluating the temporal evolution of the visual functional deficit during recovery or therapy.

Neural correlates of spontaneous direction reversals in ambiguous apparent visual motion.

Looking at bistable visual stimuli, the observer experiences striking transitions between two competing percepts while the physical stimulus remains the same. Using functional imaging techniques, it is therefore possible to isolate neural correlates of perceptual changes that are independent of the low-level aspects of the stimulus. Previous experiments have demonstrated distributed activations in human extrastriate visual cortex related to switches between competing percepts. Here we asked where extrastriate responses still occur with a bistable stimulus that minimizes the cognitive difference between the two percepts. We used the "spinning wheel illusion," a bistable apparent motion stimulus of which both possible percepts correspond to the same object, share the same center, and are perceived as identically patterned stimuli moving at the same speed and changing only in direction. Using functional magnetic resonance imaging, we analyzed the spatial distribution of event-related activations occurring during spontaneous reversals of perceived direction of motion. In accordance with earlier neuroimaging findings for bistable percepts, we observed event-related activations in several frontal and parietal areas, including the superior parietal cortex bilaterally, the right inferior parietal cortex, and the premotor and inferior frontal cortex of both hemispheres. Furthermore, we found bilateral activations in the occipitotemporal junction (hMT+/V5) and in the lateral occipital sulcus ("KO") posterior to hMT+/V5, but not in areas of the "ventral stream" of cortical visual processing. Our data suggest that, while a frontoparietal network subserves more general aspects in bistable visual perception, the activations in functionally specialized extrastriate visual cortex are highly category- or attribute-specific.