A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system.

Glucocorticoids (GC) released during stress response exert feedforward effects in the whole brain, but particularly in the limbic circuits that modulates cognition, emotion and behavior. GC are the most commonly prescribed anti-inflammatory and immunosuppressant medication worldwide and pharmacological GC treatment has been paralleled by the high incidence of acute and chronic neuropsychiatric side effects, which reinforces the brain sensitivity for GC. Synapses can be bi-directionally modifiable via potentiation (long-term potentiation, LTP) or depotentiation (long-term depression, LTD) of synaptic transmission efficacy, and the phosphorylation state of Ser831 and Ser845 sites, in the GluA1 subunit of the glutamate AMPA receptors, are a critical event for these synaptic neuroplasticity events. Through a quasi-randomized controlled study, we show that a single high dexamethasone dose significantly reduces in a dose-dependent manner the levels of GluA1-Ser831 phosphorylation in the amygdala resected during surgery for temporal lobe epilepsy. This is the first report demonstrating GC effects on key markers of synaptic neuroplasticity in the human limbic system. The results contribute to understanding how GC affects the human brain under physiologic and pharmacologic conditions.

Functional (dissociative) retrograde amnesia.

Retrograde amnesia is described as condition which can occur after direct brain damage, but which occurs more frequently as a result of a psychiatric illness. In order to understand the amnesic condition, content-based divisions of memory are defined. The measurement of retrograde memory is discussed and the dichotomy between "organic" and "psychogenic" retrograde amnesia is questioned. Briefly, brain damage-related etiologies of retrograde amnesia are mentioned. The major portion of the review is devoted to dissociative amnesia (also named psychogenic or functional amnesia) and to the discussion of an overlap between psychogenic and "brain organic" forms of amnesia. The "inability of access hypothesis" is proposed to account for most of both the organic and psychogenic (dissociative) patients with primarily retrograde amnesia. Questions such as why recovery from retrograde amnesia can occur in retrograde (dissociative) amnesia, and why long-term new learning of episodic-autobiographic episodes is possible, are addressed. It is concluded that research on retrograde amnesia research is still in its infancy, as the neural correlates of memory storage are still unknown. It is argued that the recollection of episodic-autobiographic episodes most likely involves frontotemporal regions of the right hemisphere, a region which appears to be hypometabolic in patients with dissociative amnesia.

Real-life memory and spatial navigation in patients with focal epilepsy: ecological validity of a virtual reality supermarket task.

Ecological assessment and training of real-life cognitive functions such as visual-spatial abilities in patients with epilepsy remain challenging. Some studies have applied virtual reality (VR) paradigms, but external validity of VR programs has not sufficiently been proven. Patients with focal epilepsy (EG, n=14) accomplished an 8-day program in a VR supermarket, which consisted of learning and buying items on a shopping list. Performance of the EG was compared with that of healthy controls (HCG, n=19). A comprehensive neuropsychological examination was administered. Real-life performance was investigated in a real supermarket. Learning in the VR supermarket was significantly impaired in the EG on different VR measures. Delayed free recall of products did not differ between the EG and the HCG. Virtual reality scores were correlated with neuropsychological measures of visual-spatial cognition, subjective estimates of memory, and performance in the real supermarket. The data indicate that our VR approach allows for the assessment of real-life visual-spatial memory and cognition in patients with focal epilepsy. The multimodal, active, and complex VR paradigm may particularly enhance visual-spatial cognitive resources.

Processing of subliminal facial expressions of emotion: a behavioral and fMRI study.

The recognition of emotional facial expressions is an important means to adjust behavior in social interactions. As facial expressions widely differ in their duration and degree of expressiveness, they often manifest with short and transient expressions below the level of awareness. In this combined behavioral and fMRI study, we aimed at examining whether or not consciously accessible (subliminal) emotional facial expressions influence empathic judgments and which brain activations are related to it. We hypothesized that subliminal facial expressions of emotions masked with neutral expressions of the same faces induce an empathic processing similar to consciously accessible (supraliminal) facial expressions. Our behavioral data in 23 healthy subjects showed that subliminal emotional facial expressions of 40 ms duration affect the judgments of the subsequent neutral facial expressions. In the fMRI study in 12 healthy subjects it was found that both, supra- and subliminal emotional facial expressions shared a widespread network of brain areas including the fusiform gyrus, the temporo-parietal junction, and the inferior, dorsolateral, and medial frontal cortex. Compared with subliminal facial expressions, supraliminal facial expressions led to a greater activation of left occipital and fusiform face areas. We conclude that masked subliminal emotional information is suited to trigger processing in brain areas which have been implicated in empathy and, thereby in social encounters.

[Memory and brain imaging]. / Gedächtnis und Brain Imaging.

Presented are current views about memory and memory disturbances. Subsequently, cases of patients are given in whom environmentally-induced stress and trauma situations provoked enduring amnesic conditions in the autobiographic area. It is shown that for many of the patients activity changes can be demonstrated on the brain level, which are evoked by stress and trauma events. Consequently, after the field of neurologically caused, also psychiatrically caused disturbances become available for functional brain imaging.

Neuropsychological and neural correlates of autobiographical deficits in a mother who killed her children.

We report a case of a delusional patient who had killed two of her children in an attempted 'extended suicide'. She was convinced of a genetic defect that caused autobiographical memory and emotional deficits and made life 'senseless'. Neuropsychological tests revealed dysfunctions in remembering emotional details of personal episodes and theory of mind. Water positron emission tomography (15O) with a paradigm used in a former study by Fink et al. (1996) with healthy controls elicited abnormal activations during autobiographical memory retrieval characterised by a lack of prefrontal and limbic activity. We conclude that these imaging findings reflect neural correlates of the self-reported and objectified autobiographical dysfunctions. Furthermore, they indicate that beliefs or prejudices may have a major impact on the brain's processing of the personal past.

Elevated emotional reactivity in affective but not cognitive components of theory of mind: a psychophysiological study.

Recent research proposes that theory of mind (ToM), that is the ability to infer other people's mental state, is a multidimensional construct and that a distinction may be made between affective and cognitive ToM. We examined whether these two subcomponents of ToM correspond to different levels in skin conductance responses (SCRs). Seventeen healthy adults listened to ten affective (faux pas) ToM stories, ten cognitive ToM stories and ten non-ToM stories. Results demonstrated significantly elevated SCR for affective ToM as compared with cognitive ToM and control stories, with no differences in SCR levels in the latter two story types. We discuss the possible underlying mechanisms for these differential psychophysiological correlates of affective and cognitive ToM processing, and suggest further investigations especially in clinical populations.

Cognitive performance of patients with mesial temporal lobe epilepsy and incidental calcified neurocysticercosis.

OBJECTIVES: Although chronic calcified neurocysticercosis (NCC) has been considered a major cause of symptomatic epilepsy in developing countries, it can also be an incidental pathological finding in epileptic patients from endemic regions. The mechanisms of brain plasticity occurring in patients with NCC during and after the inflammatory process related to the parasite infection, death, degeneration, and calcification within the host brain might be an independent factor for cognitive impairment in patients with NCC and epilepsy. In order to assess this possibility cognitive performance of patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) with and without NCC was investigated through structured neuropsychological testing. METHODS: Cognitive performance of long term MTLE-HS patients with (HS-NCC group, n = 32) and without NCC (HS only, n = 48) was compared. Imbalances between the two groups with respect to clinical, demographic, neuroimaging, and electrophysiological variables were adjusted by linear multiple regression analysis and Bonferroni correction for multiple tests. RESULTS AND CONCLUSIONS: There were no cognitive performance differences between HS-NCC and HS only patients, leading to the conclusion that chronic calcified NCC per se does not aggravate the cognitive performance of patients with long term MTLE-HS.

No morning cortisol response in patients with severe global amnesia.

Activity of the hypothalamus pituitary adrenal (HPA) axis is characterized by a pronounced circadian rhythm. An acute increase in cortisol levels occurs after awakening in the morning with continuously declining levels over the course of the remaining day. The morning cortisol increase probably reflects an activational response of the HPA axis aimed at preparing the body for the day. Some studies found patterns of enhanced or blunted waking cortisol responses observed under chronic stress, burnout, or post traumatic stress disorder. The present study wanted to characterize the morning cortisol response and the circadian cortisol day profile in a sample of six male patients with severe amnesia due to hypoxia, herpes simplex encephalitis or closed head injury. Age and gender matched relatives or friends served as controls. Cortisol was measured from saliva samples collected at home on two consecutive days. The patients were woken up in the morning by their partners or caregivers. The morning cortisol increase typically observed in healthy subjects and also observed in the control group was absent in the amnesic patients. In contrast, a normal circadian day profile was found in the amnesic patients, with a pronounced circadian cortisol decrease. Further studies are needed to understand the neurological or psychological mechanisms leading to a missing morning cortisol response in amnesic patients.

[Memory and brain--neurobiological correlates of memory disturbances]. / Gedächtnis und Gehirn--Neurobiologische Korrelate von Gedächtnisstörungen.

A differentiation of memory is possible on the basis of chronological and contents-related aspects. Furthermore, it is possible to make process-specific subdivisions (encoding, transfer, consolidation, retrieval). The time-related division on the one hand refers to the general differentiation into short-term and long-term memory, and, on the other, to that between anterograde and retrograde memory ("new" and "old memory"; measured from a given time point, usually that when brain damage occurred). Anterograde memory means the successful encoding and storing of new information; retrograde the ability to retrieve successfully acquired and/or stored information. On the contents-based level, memory can be divided into five basic long-term systems--episodic memory, the knowledge system, perceptual, procedural and the priming form of memory. Neural correlates for these divisions are discussed with special emphasis of the episodic and the knowledge systems, based both on normal individuals and brain-damaged subjects. It is argued that structures of the limbic system are important for encoding of information and for its transfer into long-term memory. For this, two independent, but interacting memory circuits are proposed--one of them controlling and integrating primarily the emotional, and the other primarily the cognitive components of newly incoming information. For information storage principally neocortical structures are regarded as important and for the recall of information from the episodic and semantic memory systems the combined action of portions of prefrontal and anterior temporal regions is regarded as essential. Within this fronto-temporal agglomerate, a moderate hemispheric-specificity is assumed to exist with the right-hemispheric combination being mainly engaged in episodic memory retrieval and the left-hemispheric in that of semantic information. Evidence for this specialization comes from the results from focally brain-damaged patients as well as from that functional brain imaging in normal human subjects. Comparing results from imaging studies in memory disturbed patients with brain damage and from patients with a psychiatric diagnosis (e. g., psychogenic amnesia) revealed that both patient groups demonstrate comparable metabolic changes on the brain level. It can therefore be concluded that in neurological patients distinct, identifiable tissue damage is existent, while in psychiatric patients changes in the brain's biochemistry (release of stress hormones, and transmitters) constitute the physiological bases for the memory disturbances.

Pioneers of affective neuroscience and early concepts of the emotional brain.

Views on the representation of emotion in the brain, as formulated about a century ago, are described, with a focus on the Vienna physiologist and psychologist Sigmund Exner, the psychoanalyst Sigmund Freud, and the French physician Israel Waynbaum. All three can be characterized as forerunners in the field of "affective neuroscience". By the turn of the century, they had developed a neural network theory of emotion which included a stage of pre-cortical processing. In spite of their otherwise very diverse theoretical backgrounds, their concepts of parallel processing routes were highly similar. It is interesting to note that their ideas were on line with present-day views on the neural substrates and physiological characteristics of emotional processing, although none of the three scientists could rely on the refined anatomical knowledge available nowadays.

The neural correlates of person familiarity. A functional magnetic resonance imaging study with clinical implications.

Neural activity was measured in 10 healthy volunteers by functional MRI while they viewed familiar and unfamiliar faces and listened to familiar and unfamiliar voices. The familiar faces and voices were those of people personally known to the subjects; they were not people who are more widely famous in the media. Changes in neural activity associated with stimulus modality irrespective of familiarity were observed in modules previously demonstrated to be activated by faces (fusiform gyrus bilaterally) and voices (superior temporal gyrus bilaterally). Irrespective of stimulus modality, familiarity of faces and voices (relative to unfamiliar faces and voices) was associated with increased neural activity in the posterior cingulate cortex, including the retrosplenial cortex. Our results suggest that recognizing a person involves information flow from modality-specific modules in the temporal cortex to the retrosplenial cortex. The latter area has recently been implicated in episodic memory and emotional salience, and now seems to be a key area involved in assessing the familiarity of a person. We propose that disturbances in the information flow described may underlie neurological and psychiatric disorders of the recognition of familiar faces, voices and persons (prosopagnosia, phonagnosia and Capgras delusion, respectively).

[Word generation in bilinguals--fMRI study with implications for language and memory processes]. / Wortgenerierung bei Bilingualen--eine fMRT-Studie mit Implikationen für Sprach- und Gedächtnisprozesse.

For over a century the cerebral representation of language functions is a matter of debate. In Neuroscience language is regarded as one of the most lateralized cognitive functions. Thus, while the language which is acquired first in most cases is processed by the left hemisphere some studies in brain damaged but also experimental investigations propose a pivotal role of the right hemisphere in second language processing. By the advent of modern neuroimaging it is now possible to study language lateralization and bilinguality also in healthy subjects. We studied first and second language abilities in a group of bilingual, healthy individuals by means of functional magnetic resonance imaging (fMRI) with a word-fluency paradigm. While we found a predominantly left prefrontal activity during both first and also second language processing an additional right prefrontal activation was registered during the use of second language. Our findings are discussed on the basis of an interaction between language and memory processes.

Continuing cognitive impairment after isolated transient global amnesia.

Fourteen patients were investigated 3-4 days after end of their transient global amnesia (TGA) with a number of neuropsychological tests. Their performance was compared with that of a control group, matched for age, education, and profession. It was found that in spite of the common definition of TGA, impairments in both verbal and non-verbal long term memory and verbal fluency persisted and were in fact impaired to such a degree that it seemed unlikely that full recovery would have occurred within the next few days. We propose a major role of stress in the etiology and the recovery process of TGA and consider it likely that stress hormones are of major influence both in the triggering of TGA and the subsequent continuation of cognitive impairments.

Learning face-name associations and the effect of age and performance: a PET activation study.

Learning face-name associations is a complex task to be mastered in every day life that approaches the limits of cognitive capacity in most normal humans. We studied brain activation during face-name learning using positron emission tomography (PET) in 11 normal volunteers. The most intense activation was seen in occipital association cortex (BA 18) bilaterally, also involving lingual and fusiform gyrus (BA 37). In the left hemisphere additional activation were located in inferior temporal gyrus, the inferior part of pre- and postcentral gyrus, and orbitofrontal cortex (BA 11), whereas in the right hemisphere only a region in the precuneus (BA 19) was activated additionally. There was considerable interindividual variation of encoding success, which was significantly related to activation of BA 18 bilaterally. Subject ages covered a range of 26-72 years, but - in contrast to the effect of encoding success - there was no significant age effect on activations. Task-independent habituation effects were seen in cerebellum and left middle temporal gyrus. These results indicate that the intensity of information processing in ventral occipital association cortex is most important for success of face-name encoding. Learning is further mediated by a predominantly left-hemispheric network including inferior temporal and orbitofrontal cortex.

Massive impairment in executive functions with partial preservation of other cognitive functions: the case of a young patient with severe degeneration of the prefrontal cortex.

Historical bases for the special role of the prefrontal cortex are outlined and the case of a 27-year-old woman with massive bilateral prefrontal damage of unknown etiology is then described. Frontal lobe degeneration was repeatedly examined with magnetic resonance imaging and fluoro-deoxy-D-glucose-positron emission tomography and was found to include both orbital and dorsolateral aspects of the frontal lobes. While the degeneration initially measured was limited to portions of the orbital, medial and dorsolateral parts of both frontal lobes, with right-sided predominance, a second brain scan 15 months later revealed massive shrinkage of both frontal lobes, together with additional involvement of the posterior association cortices. The patient had completed her high-school education and had superior verbal long-term memory, normal short-term memory, and normal priming, but manifested grossly deficient scores in various frontal lobe-sensitive tests. Though a number of neurological examinations were performed, no plausible cause for the damage was established.

Neuroimaging and behavioral correlates of recovery from mnestic block syndrome and other cognitive deteriorations.

OBJECTIVE: We conducted a follow-up study on a patient with enduring psychic shock-induced cognitive impairment to study by neuropsychological and functional imaging methods the degree of his recovery process on the brain and cognitive levels. BACKGROUND: Based on the assumption that trauma and stress conditions can alter the functions of the nervous systems, we report on a patient whom we studied 2 and 12 months after he suffered "mnestic block syndrome" and additional cognitive deterioration symptoms. METHODS: We report on a patient studied 2 and 12 months after he suffered "mnestic block syndrome" and additional cognitive deterioration symptoms. Magnetic resonance imaging and fluorodeoxyglucose positron emission tomography were used for neural and detailed neuropsychological testing for cognitive deficits. RESULTS: The patient initially manifested severe intellectual decline, including severe anterograde and retrograde amnesia. His symptoms were correlated with major, although selective, reductions in his brain metabolism (2-3 SD below those of controls). Presently, he shows a normal brain metabolism and has regained parts of his memory and many of his other intellectual capabilities. Nevertheless, he still has long-term memory impairments. CONCLUSIONS: This case demonstrates a close relation between brain metabolism and cognitive performance, with major deficits of both at 2 months and major recovery of both at 12 months after a shocking event. It can serve as an example for possible stress-related deteriorations in certain brain regions, which can be partly corrected by psychotherapeutic interventions, passing time, and favorable environmental conditions.