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PubMed2004

Adaptive and maladaptive self-focus in depression.

BACKGROUND: Studies of rumination suggest that self-focused attention is maladaptive and perpetuates depression. Conversely, self-focused attention can be adaptive, facilitating self-knowledge and the development of the alternative functional interpretations of negative thoughts and feelings on which cognitive therapy of depression depends. Increasing evidence suggests there are distinct varieties of self-focus, each with distinct functional properties. This study tested the prediction that in depressed patients brief inductions of analytical versus experiential self-focus would differentially affect overgeneral autobiographical memory, a phenomenon associated with poor clinical course. It was predicted that, relative to analytical self-focus, experiential self-focus would reduce overgeneral memory. METHODS: 28 depressed patients either thought analytically about, or focused on their momentary experience of, identical symptom-focused induction items from [Cogn. Emotion 7 (1993) 561] rumination task. Participants completed the Autobiographical Memory Test [J. Abnorm. Psychol. 95 (1986) 144] before and after self-focus manipulations. RESULTS: Experiential self-focus reduced overgeneral memory compared to analytical self-focus. Analytical and experiential self-focus did not differ in their effects on mood. LIMITATIONS: In the absence of a reference condition, only conclusions concerning the relative effects of analytical and experiential self-focus can be made. CONCLUSIONS: Results (1) support the differentiation of self-focus into distinct modes of self-attention with distinct functional effects in depression; (2) provide further evidence for the modifiability of overgeneral memory; and (3) provide further evidence for the dissociation of overgeneral memory and depressed mood. Clinically, results support the usefulness of training recovered depressed patients in adaptive experiential forms of self-awareness, as in mindfulness-based cognitive therapy.

Adaptation, Psychological↗
PubMed2000

The Nazi's daughter: the therapist as Jewish mother.

The article gives an inside look at a case where posttraumatic stress is intertwined with disturbances in object relations and ego-identity. The patient was a victim of a brutal authoritarian father who had abused her sexually. The trauma left her powerless and isolated. The treatment was aimed at enabling the patient to achieve connection and empowerment. Hypnotherapy, psychoanalytic psychotherapy and hypnosis allowed the patient to understand and overcome symptoms and underlying conflicts in the context of the therapeutic relationship. In spite of regressions and resistances during the course of treatment, therapy yielded the following results: 1. Symptoms were in remission at the end of treatment, and at one- and two-year follow-ups. 2. During the course of psychotherapy the patient was able to process traumatic events cognitively and affectively. 3. There were corrective changes in relatedness modes. 4. Modifications in object internalization and representation were made.

Adult↗
PubMed2005

Functional focal retrograde amnesia: lost access to abstract autobiographical knowledge?

We describe three patients exhibiting an acute reversible amnesia characterised by an impaired recollection of past events with preserved anterograde memory, thus consistent with a focal retrograde amnesia (FRA). This occurred after variable events: state of fugue, road accident, post-traumatic headache. Retrograde amnesia affected autobiographical memory so severely as to cover all of the patients' lives and to erase knowledge of their own identity. The retrieval of public events was variably affected, ranging from normality to severe impairment. No lesions were found on neuroimaging, and neurophysiological findings were unimpressive. FRA subsided in a few days, leaving a gap for the onset. The hypothesis of a psychogenic amnesia is considered, but overcoming the organic/psychogenic dichotomy the episodes appear as examples of "functional" memory inhibition, potentially triggered by different conditions, including events classifiable as psychic trauma. The clinical and neuropsychological traits of functional FRA are discussed. According to a current theory of autobiographical memory, the memory profile may be explained by a lost access to abstract autobiographical knowledge. Given some analogies with the more common transient global amnesia, a mechanism of spreading depression may also be hypothesised for functional FRA.

Adult↗
PubMed2002

Ribosome-associated factor Y adopts a fold resembling a double-stranded RNA binding domain scaffold.

Escherichia coli protein Y (pY) binds to the small ribosomal subunit and stabilizes ribosomes against dissociation when bacteria experience environmental stress. pY inhibits translation in vitro, most probably by interfering with the binding of the aminoacyl-tRNA to the ribosomal A site. Such a translational arrest may mediate overall adaptation of cells to environmental conditions. We have determined the 3D solution structure of a 112-residue pY and have studied its backbone dynamic by NMR spectroscopy. The structure has a betaalphabetabetabetaalpha topology and represents a compact two-layered sandwich of two nearly parallel alpha helices packed against the same side of a four-stranded beta sheet. The 23 C-terminal residues of the protein are disordered. Long-range angular constraints provided by residual dipolar coupling data proved critical for precisely defining the position of helix 1. Our data establish that the C-terminal region of helix 1 and the loop linking this helix with strand beta2 show significant conformational exchange in the ms- micro s time scale, which may have relevance to the interaction of pY with ribosomal subunits. Distribution of the conserved residues on the protein surface highlights a positively charged region towards the C-terminal segments of both alpha helices, which most probably constitutes an RNA binding site. The observed betaalphabetabetabetaalpha topology of pY resembles the alphabetabetabetaalpha topology of double-stranded RNA-binding domains, despite limited sequence similarity. It appears probable that functional properties of pY are not identical to those of dsRBDs, as the postulated RNA-binding site in pY does not coincide with the RNA-binding surface of the dsRBDs.

Amino Acid Sequence↗
PubMedDate not supplied

An individual patient comparison of response to a memory training program--psychogenic V organic amnesia: brief report.

Psychogenic amnesia ("dissociative amnesia" in DSM-IV) has received relatively little attention in the literature. We compared neuropsychological and behavioral findings between a patient with psychogenic amnesia and one with organic amnesia from their early stages in a rehabilitation program. A 52-yr-old man developed anterograde and retrograde amnesia and short-term memory disturbance 1 mo after an operation for esophageal carcinoma, with no loss of personal identity and information. No apparent organic causes were identified, but because the patient and his wife rejected psychiatric treatment and memory deficit characteristics were compatible with that of an organic origin, the patient was referred to a physiatrist. A 46-yr-old man with anterograde amnesia was diagnosed with limbic encephalitis based on findings of magnetic resonance imaging and single-photon emission computed tomography, which showed lesions in both medial temporal lobes. Both patients underwent "memory book" training because they showed preserved performance in motor learning tasks. The first patient's responses to training contrasted with the other's and were indicative of psychogenic amnesia, with cancer representing a precipitating stress. Counseled by the physiatrist, the patient and his wife accepted suggestions to undergo psychiatric treatment. We propose that it is important to consider behavioral responses to memory rehabilitation as well as neuropsychological findings in differentiating psychogenic amnesia from an organic one and that physiatrists may be pivotal in diagnosing and initiating treatment in such psychiatric disorders.

Amnesia↗
PubMed2001

The development of dissociation in maltreated preschool-aged children.

Dissociation reflects disruptions in the integration of memories, perception, and identity into a coherent sense of self, and may develop following childhood maltreatment. The preschool years were identified as an important period for the development of dissociation. However, prior research has not examined the development of dissociation during this time. In order to address this gap, evidence of dissociation in 45 maltreated children, assessed for sexual abuse, physical abuse, and neglect, was compared with dissociation in 33 nonmaltreated children. Rather than depend on adult observer reports of behavior, the study sought to gain an understanding of dissociation from the child's own point of view. Because self-reports have limitations with such young children, a measure of dissociation evidenced in children's narrative story-stem completions was utilized. Maltreated children, especially physically abused children and sexually abused children, demonstrated more dissociation than did nonmaltreated children. Moreover, during the preschool period maltreated and nonmaltreated children followed different trajectories such that dissociation increased for maltreated children but did not do so for nonmaltreated children. Findings suggest that although the self is normatively integrated during the preschool period, it becomes increasingly fragmented for some maltreated children. Results are discussed in terms of cascading effects of maltreatment throughout development, and the importance of developmentally sensitive interventions.

Child Abuse↗
PubMed2004

Epileptic-like convulsions associated with LIS-1 in the cytoskeletal control of neurotransmitter signaling in Caenorhabditis elegans.

Cortical malformations are a collection of disorders affecting brain development. Mutations in the LIS1 gene lead to a disorganized and smooth cerebral cortex caused by failure in neuronal migration. Among the clinical consequences of lissencephaly are mental retardation and intractable epilepsy. It remains unclear whether the seizures result from aberrant neuronal placement, disruption of intrinsic properties of neurons, or both. The nematode Caenorhabditis elegans offers an opportunity to study such convulsions in a simple animal with a defined nervous system. Here we show that convulsions mimicking epilepsy can be induced by a mutation in a C. elegans lis-1 allele (pnm-1), in combination with a chemical antagonist of gamma-aminobutyric acid (GABA) neurotransmitter signaling. Identical convulsions were obtained using C. elegans mutants defective in GABA transmission, whereas none of these mutants or the antagonist alone caused convulsions, indicating a threshold was exceeded in response to this combination. Crosses between pnm-1 and fluorescent marker strains designed to exclusively illuminate either the processes of GABAergic neurons or synaptic vesicles surprisingly showed no deviations in neuronal architecture. Instead, presynaptic defects in GABAergic vesicle distribution were clearly evident and could be phenocopied by RNAi directed against cytoplasmic dynein, a known LIS1 interactor. Furthermore, mutations in UNC-104, a neuronal-specific kinesin, and SNB-1, a synaptic vesicle-associated protein termed synaptobrevin, exhibit similar convulsion phenotypes following chemical induction. Taken together, these studies establish C. elegans as a system to investigate subtle cytoskeletal mechanisms regulating intrinsic neuronal activity and suggest that it may be possible to dissociate the epileptic consequences of lissencephaly from the more phenotypically overt cortical defects associated with neuronal migration.

Alleles↗
PubMed1997

Glucocorticoid receptors, fibromyalgia and low back pain.

Recently, fibromyalgia (FMS) was shown to be a disorder associated with an altered functioning of the stress response system. FMS patients display a hyperreactive pituitary adrenocorticotropic hormone (ACTH) release in response to corticotropin-releasing hormone (CRH) and to insulin-induced hypoglycemia. We suggested that negative feedback of cortisol could be deranged. Therefore we investigated the properties and function of the glucocorticoid receptors (GR) in FMS patients and compared the results with those of healthy persons and patients with chronic low back pain (LBP a localized pain condition). Forty primary FMS patients (F:M = 36:4), 28 LBP patients (25:3) and 14 (12:2) healthy, sedentary control persons were recruited for the study. Urinary free cortisol excretion in FMS and LBP patients was lower compared to controls. Only FMS patients displayed lower CBG and basal serum cortisol concentrations when compared to controls. However, plasma free cortisol concentrations were similar in the three groups. There was no difference in the number of GR per cell among the three groups (FMS: 6498 +/- 252, LBP: 6625 +/- 284, controls: 6576 +/- 304), but the dissociation constant (Kd) of the FMS (14.5 +/- 0.9 nmol/l) and LBP (14.7 +/- 1.3 nmol/l) subjects was significantly higher than that of the controls (10.9 +/- 0.8 nmol/l) (p < .05). The maximal stimulation of the lymphocytes, as measured by the maximal thymidine incorporation (in the absence of cortisol) in the FMS group was approximately 1.5 times higher (p < .05) than in the control or LBP group. The ED50 (the cortisol concentration giving 50% inhibition of the thymidine incorporation), however, was identical in all three groups. We conclude that FMS patients have a mild hypocortisolemia, increased cortisol feedback resistance in combination probably with a reduced CRH synthesis or release in the hypothalamus. The role of the GR and mineralocorticoid receptor (MR) in the CRH regulation in the FMS patients remains to be solved.

Adult↗
PubMed1992

Face processing in psychiatric conditions.

Functional models of face processing have indicated that dissociations exist between the various processes involved, e.g. between familiar face recognition and matching of unfamiliar faces, and between familiar face recognition and facial expression analysis. These models have been successfully applied to the understanding of the different types of impairment that can exist in neuropsychological patients. In the present study, aspects of face processing in psychiatric patients were investigated in relation to Bruce & Young's (1986) model. Based on this functional model different predictions can be made. We contrast here the impaired expression analysis hypothesis, which is that psychiatric patients would show a deficit in facial expression recognition, but not in facial identity recognition or unfamiliar face matching, with the generalized deficit hypothesis, that patients would be impaired on all tasks. These hypotheses were examined using three forced-choice tasks (facial recognition, facial expression recognition, and unfamiliar face matching) which were presented to schizophrenic and depressed patients, and to non-patient controls. Results showed that schizophrenic patients performed at a significantly lower level than non-patient controls on all three tasks, supporting the generalized deficit hypothesis.

Adult↗
PubMedDate not supplied

Dissociating mental transformations and visuo-spatial storage in working memory: evidence from representational neglect.

A study is reported of visuo-spatial working memory in two individuals suffering from a cognitive deficit known as unilateral spatial neglect, and seven healthy control participants. Both patients have difficulties reporting details on the left side of imaged representations, and one has an additional difficulty with perceptual input to the left of his body midline. All participants were asked to report the location and identity of objects presented in novel 2 x 2 arrays that were either present throughout or were described orally by the experimenter, with no visual input. On half of the trials, the report was to be made from the opposite perspective, requiring 180 degree mental rotation of the mentally represented array. The patients show an impaired ability to report details from the presented or the imagined left, but had no difficulty with mental rotation. Results point to a clear separation between the processes of perception and those of visuo-spatial working memory. Results also suggest that the patients might be suffering from damage to the system used for holding visuo-spatial representations rather than a difficulty with attending to elements of that representation.

Aged↗
PubMed1997

[Contribution of animal models in the understanding of AIDS encephalopathy].

The neuropathology associated with HIV (Human Immunodeficiency Virus) infection is one of the major complications of this disease. The virological and cellular mechanisms by which HIV infection induces motor and cognitive disorders remain unknown. This lack of understanding of the pathophysiology is partly due to the difficulty of experimental analysis in man because only post-mortem samples from terminal phases of the disease and cerebrospinal fluid samples are available. Two animal models, very closely resembling human HIV infection, are available: the cat model infected by FIV (Feline Immunodeficiency Virus) and the macaque model infected by the SIVmac (Simian Immunodeficiency Virus) which have enabled us to conduct a longitudinal study of encephalopathy during primo-infection and the asymptomatic and pre-AIDS (Acquired Immune Deficiency Syndrome) phases. In the cat-FIV model, which presents the advantage of being non-infectious to man, and therefore easier to manipulate, it was shown that infected cats develop behavioural abnormalities and a neuropathology which resemble HIV dementia. Central nervous system lesions induced by FIV are similar to those of HIV infection apart from the absence of multinucleated giant cells. This model was used to analyse the relationship between CNS lesions and the viral load of the brain and showed that the severity of the lesions contrasted with a low viral load. The pathophysiology of SIVmac infection in the rhesus macaque is almost identical to human infection with a more rapid course, since the duration of the asymptomatic phase is 6 months to 5 years, depending on the animal. We studied the relationship between lesions, viral load and cytokine production (IL-1 beta, IL-2, IL-6, TNF alpha, INF gamma, TGF-beta 1) within the CNS. Our results show early, low-grade and constant infection of the brain. The dissociation between the viral load and the lesions observed is our favour of an indirect mechanism for the pathogenesis of these lesions. The relationship between lesions and the cytokine profile studied shows the importance of glial cells in the pathogenesis of the lesions.

AIDS Dementia Complex↗
PubMed1993

Face perception after brain injury. Selective impairments affecting identity and expression.

Current theoretical models of face perception postulate separate routes for processing information needed in the recognition of a familiar face, for matching photographs of unfamiliar faces and for the analysis of facial expressions. The present study investigated this claim in a group of ex-servicemen who had sustained unilateral brain injuries affecting posterior areas of the left or right cerebral hemisphere. Care was taken to confirm the nature of impairment by using two different tasks to assess each of the three theoretically defined abilities (leading to a total of six tasks). We adopted a stringent application of the double dissociation methodology to investigate the pattern of performance across tasks of individual ex-servicemen. A selective impairment was defined as a significantly impoverished performance on both tests of a specific ability, while all other tasks were performed within normal limits. In addition, we used both accuracy and response latency measures to substantiate evidence for spared or defective abilities. The results showed selective impairments of all three abilities on accuracy scores. Response latency data confirmed the finding of a selective deficit in the processing of facial expressions, but produced evidence suggesting that impairments affecting familiar face recognition and unfamiliar face matching were not completely independent from each other in this group of ex-servicemen.

Brain Injuries↗
PubMed1990

[Akinesia and associated motor involvement in Parkinson's disease and basal ganglia lesions].

The paralysis due to lesions of the cortico-spinal tract disturb movements in their different modes while dissociated paralysis result from cortical and particular biopercular lesions. Movements cannot be executed on command whereas they are accomplished in their total complexity when they accompanied certain emotional states or when they are part of an automatic activity. Such a dissociation suggest that the motor program which does not respond to voluntary command will eventually be applied thanks to emotional or affective stimuli. Basal ganglia lesions induce other symptoms. The first to be observed concern the movements and postures implied in automatic series after learning. Akinesias which results from these lesions can be partially controlled by a voluntary command, particularly when helped by sensori stimuli. Such symptoms are observed sometimes from its beginning in the Parkinson's disease. Emotion and sleep are also able to improve these akinesias: therefore they appear either on a deficitary form implying a sensitive reinforcement or on a hyperactive form, which is alleviated by hypotonia and sleep. The localized lesions of striatum or of pallidum provoke identical symptoms but at the interruption of akinesia, a distortion of movement appears, contrary to what is observed in Parkinson's disease. Mechanisms of anticipation and adjustment of postural reaction are disturbed concerning not only the body axis but also the different segments of the limbs. This disturbance provokes unsteadiness and sometimes falls. At the level of the limbs the anomaly of postural reactions slows down the movement and disturbs specially the repetitive gestures.(ABSTRACT TRUNCATED AT 250 WORDS)

Basal Ganglia Diseases↗
PubMed2000

Impaired distractor inhibition on a selective attention task in unmedicated, depressed subjects.

BACKGROUND: Impaired distractor inhibition may contribute to the selective attention deficits observed in depressed patients, but studies to date have not tested the distractor inhibition theory against the possibility that processes such as transient memory review processes may account for the observed deficits. A negative priming paradigm can dissociate inhibition from such a potentially confounding process called object review. The negative priming task also isolates features of the distractor such as colour and location for independent examination. METHOD: A computerized negative priming task was used in which colour, identification and location features of a stimulus and distractor were systematically manipulated across successive prime and probe trials. Thirty-two unmedicated subjects with DSM-IV diagnoses of non-psychotic unipolar depression were compared with 32 age, sex and IQ matched controls. RESULTS: Depressed subjects had reduced levels of negative priming for conditions where the colour feature of the stimulus was repeated across prime and probe trials but not when identity or location was the repeated feature. When both the colour and location feature were the repeated feature across trials, facilitation in response was apparent. CONCLUSIONS: The pattern of results supports studies that found reduced distractor inhibition in depressed subjects, and suggests that object review is intact in these subjects. Greater impairment in negative priming for colour versus location suggests that subjects may have greater impairment in the visual stream associated with processing colour features.

Adolescent↗
PubMed1992

Functional dissociation of acute and persistent cognitive deficits accompanying amygdala-kindled seizures.

The effects of amygdala-kindled seizures on cognitive function were examined using long-delay flavor-aversion and passive-avoidance conditioning paradigms in rats. Experiments were conducted to compare the functional consequences of unilateral and bilateral kindled seizures (transient deficits) with those due to a kindling history only (persistent deficits). Animals with a history of unilateral or bilateral kindling demonstrated flavor-aversion conditioning that varied inversely with the delay separating saccharin (CS) and lithium (US). Unilateral stimulation during the CS-US interval produced an attenuation of flavor-aversion conditioning that was independent of delay value; bilateral stimulation eliminated conditioning all together. The effects of kindling and kindled seizures on passive-avoidance conditioning were functionally identical. Animals with a history of unilateral kindling demonstrated strong evidence of conditioning with no effect of posttraining seizures. In contrast, animals with a history of bilateral kindling were impaired in a passive-avoidance task. The impairment was evident in the presence or absence of seizure induction during training. Electrographic and behavioral indices of epileptiform activity produced by unilateral and bilateral stimulation failed to reveal any differences in seizure duration or severity. The results support the conclusion that cognitive disruption by amygdala-kindled seizures is task-dependent, does not show a temporal dependence, and cannot be explained on the basis of electrographic or behavioral measures of seizure severity alone.

Amygdala↗
PubMed2004

Covert processing of visual form in the absence of area LO.

The patient D.F., who suffers from severe visual form agnosia, has been found to have a bilateral lesion of area LO, an area known to be intimately involved in the perception of object shape. Despite her perceptual impairment, however, D.F. retains residual form processing abilities that can provide distal visuomotor control, for example in the configuration of her grasp when reaching to pick up objects of different shapes and sizes. This dissociation has been interpreted as reflecting the sparing of a dedicated system for processing the physical properties of objects solely for purposes of guiding action. Here we test this hypothesis in two studies designed to examine whether or not spared shape processing capacities might be revealed under other kinds of indirect test conditions. First, we exploited the fact that a redundant shape cue will speed search for a coloured stimulus within an array, and vice versa. Unlike our control subjects, D.F. showed no facilitation effect of either kind. Second, we used two Stroop tasks in which single coloured uppercase letters were presented. Our intention was to determine (a) whether naming the colour would be influenced by whether the letter was the initial letter of the correct or incorrect colour name (e.g. 'R' or 'G'); and (b) whether the reverse might be true, that is that D.F.'s guesses at letter identity might be influenced by their colour. We found no evidence for a Stroop effect of the former (standard) kind in D.F., but we did find evidence for reverse-Stroop effects. This result may reflect a partial sparing of ventral stream areas specialised for letter-form processing.

Agnosia↗
PubMed2006

Construction and psychometric properties of a novel test for body representational neglect (Vest Test).

PURPOSE: Multimodal spatial neglect manifests itself also in nonvisual modalities such as audition, touch and body representation. Yet, quantitative tests for the diagnosis of nonvisual neglect are still quite rare. The purpose of the present paper was to develop and evaluate a novel, simple and sensitive test for the assessment of body representational neglect (BRN) in patients with left or right cerebral hemispheric lesions. METHODS: The vest test covers the front part of the trunk. The blindfolded subject wears the vest and is instructed to pick up all objects from the 24 pockets of the vest (12 on each side) as quickly as possible using the ipsilesional, nonparetic hand. Two samples of healthy control subjects (each N=25) using either their left or their right hand performed the test in identical way to obtain normative data for patients searching with their left hand (i.e. left hemisphere stroke patients) versus their right hand (i.e. right hemisphere stroke patients). The test can be performed within 5~minutes, even with aphasic or apractic stroke patients. RESULTS: Psychometric evaluations in a sample of 50 patients with unilateral stroke (25 leftsided, 25 rightsided) show high objectivity, high internal consistency (Cronbach's alpha=0.96), good retest-reliability (0.79 after 1 week in neglect patients) and good validity as compared with two other measures of BRN or multimodal neglect. Patient examples show that BRN as assessed with the vest test allows the detection of qualitatively and quantitatively different patterns of BRN, and shows double dissociations from visual neglect and from apraxia in left hemisphere stroke patients. Details of the test including instructions and cut-off values are given for users in the appendix of this article. CONCLUSIONS: In conclusion, the vest test is a sensitive, quick and reliable test for BRN which complements the assessment of visuo- and audiospatial neglect and allows to measure recovery (spontaneous or treatment-induced) in patients with BRN. Furthermore, it can help to improve our knowledge about the multisensory coding of our body and the surrounding space in the human brain.

Activities of Daily Living↗
PubMed2004

Improving left hemispatial neglect using virtual reality.

BACKGROUND: In hemispatial neglect, space can be dissociated on the basis of "near" peripersonal vs "far" extrapersonal space. The clinical manifestations of neglect can be modified by having patients use a tool to explore "far" extrapersonal space. An explanation for this is that the use of a stick produced an extension of body space resulting in a remapping of "far" space as "near" space. OBJECTIVE: S: To determine whether the remapping of space can be generalized to the amelioration of the "affected" vs the "nonaffected" space, rather than being confined to the selective amelioration of "far" vs "near" neglect; and to determine whether tool use is a necessary condition for the remapping of space. METHODS: Using virtual reality, the authors asked six hemispatial neglect patients to reach and grasp a real object while simultaneously observing the grasping of a virtual object located within a virtual environment by a virtual hand. The virtual hand was commanded in real time by their real hand. RESULTS: After a period of adaptation, hemispatial neglect patients coded the visual stimuli within the neglected space in an identical fashion as those presented within the preserved portions of space. CONCLUSIONS: It is possible to re-create links between the affected and the nonaffected space. Wielding a tool is not a necessary condition in reopening neglected space.

Aged↗