Changes in electrical brain activity in patients with panic disorders

Brain electrical activity was recorded in 38 patients with typical and in 42 patients with atypical panic disorders, also in 30 normal controls. Compared to controls, patients both with typical and with atypical panic disorders differed significantly in reduced spectral power of the EEG alpha band in the right hemisphere. Moreover, in patients with typical panic disorders, the spectral power of the EEG beta1 band was increased in the frontal, temporal, central, and parietal areas of the right hemisphere. In patients with atypical panic disorders, the spectral power of the theta band was increased in the temporal areas of the right hemisphere. The changes in the EEG activity in patients with typical panic disorders are supposed to reflect an increase in activity of non-specific systems of the mesencephalic reticular formation, and the EEG changes in patients with atypical panic attacks may be associated with increased activity of the temporolimbic brain structures.     

Neural coding for the retrieval of multiple memory patterns

We investigate the retrieval dynamics in a feature-based semantic memory model, in which the features are coded by neurons of the Hindmarsh-Rose type in the chaotic regime. We consider the retrieval process as consisting of the synchronized firing activity of the neurons coding for the same memory pattern. The retrieval dynamics is investigated for multiple patterns, with particular attention to the case of overlapping memories. In this case, we hypothesize a dynamical nontransitive mechanism based on synchronization, that allows for a shared feature to participate in multiple memory representations. The problem of the choice of a cognitive plausible time-scale for the retrieval analysis is investigated by analyzing the information that can be inferred from finite-time analyses. Different types of indicators are proposed in order to evaluate the temporal dynamics of the neurons engaged in the retrieval process. We interpret the simulation results as suggestive of a role for chaotic dynamics in allowing for flexible composition of elementary meaningful units in memory representations.     

Investigation of changes in EEG complexity during memory retrieval: the effect of midazolam

The aim of this study is applying nonlinear methods to assess changes in brain dynamics in a placebo-controlled study of midazolam-induced amnesia. Subjects injected with saline and midazolam during study, performed old/new recognition memory tests with EEG recording. Based on previous studies, as midazolam causes anterograde amnesia, we expected that midazolam would affect the EEG’s degree of complexity. Recurrence quantification analysis, and approximate entropy were used in this assessment. These methods compare with other nonlinear techniques such as computation of the correlation dimension, are suitable for non-stationary EEG signals. Our findings suggest that EEG’s complexity decreases during memory retrieval. Although this trend is observed in nonlinear curves related to the midazolam condition, the overall complexity were greater than in the saline condition. This result implies that impaired memory function caused by midazolam is associated with greater EEG’s complexity compared to normal memory retrieval in saline injection.     

Neural coding for the retrieval of multiple memory patterns

We investigate the retrieval dynamics in a feature-based semantic memory model, in which the features are coded by neurons of the Hindmarsh–Rose type in the chaotic regime. We consider the retrieval process as consisting of the synchronized firing activity of the neurons coding for the same memory pattern. The retrieval dynamics is investigated for multiple patterns, with particular attention to the case of overlapping memories. In this case, we hypothesize a dynamical nontransitive mechanism based on synchronization, that allows for a shared feature to participate in multiple memory representations. The problem of the choice of a cognitive plausible time-scale for the retrieval analysis is investigated by analyzing the information that can be inferred from finite-time analyses. Different types of indicators are proposed in order to evaluate the temporal dynamics of the neurons engaged in the retrieval process. We interpret the simulation results as suggestive of a role for chaotic dynamics in allowing for flexible composition of elementary meaningful units in memory representations.     

A Computational Predictor of Human Episodic Memory Based on a Theta Phase Precession Network

In the rodent hippocampus, a phase precession phenomena of place cell firing with the local field potential (LFP) theta is called “theta phase precession” and is considered to contribute to memory formation with spike time dependent plasticity (STDP). On the other hand, in the primate hippocampus, the existence of theta phase precession is unclear. Our computational studies have demonstrated that theta phase precession dynamics could contribute to primate–hippocampal dependent memory formation, such as object–place association memory. In this paper, we evaluate human theta phase precession by using a theory–experiment combined analysis. Human memory recall of object–place associations was analyzed by an individual hippocampal network simulated by theta phase precession dynamics of human eye movement and EEG data during memory encoding. It was found that the computational recall of the resultant network is significantly correlated with human memory recall performance, while other computational predictors without theta phase precession are not significantly correlated with subsequent memory recall. Moreover the correlation is larger than the correlation between human recall and traditional experimental predictors. These results indicate that theta phase precession dynamics are necessary for the better prediction of human recall performance with eye movement and EEG data. In this analysis, theta phase precession dynamics appear useful for the extraction of memory-dependent components from the spatio–temporal pattern of eye movement and EEG data as an associative network. Theta phase precession may be a common neural dynamic between rodents and humans for the formation of environmental memories.     

Altered glyoxalase 1 expression in psychiatric disorders: cause or consequence?

Glyoxalase 1 is an enzyme, shown to protect against dicarbonyl glycation and the formation of advanced glycation end products. Recent findings suggest glyoxalase 1 as a molecular marker of psychiatric disorders. In clinical studies aberrant expression of glyoxalase 1 was shown to be involved in major depression, panic disorders and schizophrenia. In mouse models glyoxalase 1 was identified as a molecular marker of trait anxiety. However, anxiety-related behaviour in mice was inconsistently reported to correlate with elevated or reduced expression of glyoxalase 1. As yet, those findings were considered contradicting and the contribution of glyoxalase 1 to the aetiology of psychiatric disorders remained elusive. This review summarizes recent clinical and animal studies. In order to unravel the role of glyoxalase 1 in mental disease, findings are discussed with a particular focus on dicarbonyl substrate concentration. Prevailing the impact of dicarbonyl substrates on anxiety-related behaviour over the influence of glyoxalase 1 expression may consolidate findings that have been considered inconsistent. Taken together, this report suggests that physiological concentration of dicarbonyl compounds may differentiate a remedy from a poison.     

Mechanisms of long-term memory

Long-term potentiation (LTP) of the hippocampus provides an excellent model on which to build hypotheses for the laying down of memories in the cerebral cortex. After repetitive activation, the primary happening seems to be the increase in transmitter sensitivity brought about by the increased Ca2+ in the recipient neurons. There may be secondary presynaptic changes. The extreme duration of the LTP may require structural changes of the synaptic spines. The hippocampus plays an essential role in the laying down of cognitive memories, the pathway to the frontal lobe being via the MD thalamus. The thalamo-cortical fibres activate stellate cells whose axons make climbing fibre-like ramifications up the apical dendrites of the pyramidal cells. On the Marr hypothesis repetitive conjunction of synaptic activation by these climbing fibres with synaptic activation by horizontal fibres on the apical dendrites produces prolonged potentiation of the horizontal fibre synapses, which is the neural basis of memory. Presumably this is a consequence of the raised Ca2+ of the apical dendrites, acting as it does on the hippocampal LTP. It will be considered how this elemental unit for cerebral memory can be developed into the varieties of cerebral memories that have been located by study of the regional cerebral blood flow during their retrieval. These sites for memory are in the frontal lobe, usually in the superior prefrontal area.     

Rapid memory reactivation revealed by oscillatory entrainment

Episodic memory refers to humans' unique ability to mentally reconstruct past events. Neurocomputational models predict that remembering entails the reinstatement of brain activity that was present when an event was initially experienced [1-5], a claim that has recently gained support from functional imaging work in humans [6-14]. The nature of this reactivation, however, is still unclear. Cognitive models claim that retrieval is set off by an early reactivation of stored memory representations ("ecphory") [15-17]. However, reinstatement as found in imaging studies might also reflect postretrieval processes that operate on the products of retrieval and are thus a consequence rather than a precondition of remembering. Here, we used frequency entrainment as a novel method of tagging memories in the human electroencephalogram (EEG). Participants studied words presented on flickering backgrounds, entraining a steady-state brain response at either 6 or 10?Hz. We found that these frequency signatures rapidly reemerged during a later memory test when participants successfully recognized?a word. An additional behavioral experiment suggested that this reactivation occurs in the absence of conscious memory for the frequencies entrained during study. The findings provide empirical evidence for the role of rapid, likely unconscious memory reactivation during retrieval.     

Electroencephalographic Correlates of Brain States during Verbal Learning: II. Characteristics of EEG Spatial Synchronization

Spatial EEG synchronization was studied using mean EEG coherences in 57 subjects in a resting state with the eyes open, during memorization of verbal bilingual semantic pairs (Latin and Russian), and during retrieval (monitoring) of the learned information. Statistical comparison of the EEG spectral power in the frequency bands θ, α ₁, α₂, β₁, β₂, and γ showed that induction of the states of memorization and retrieval of the verbal information resulted in multiple significant increases in the mean coherence (spatial synchronization) as compared to the state of rest. These increases were significantly higher in the state of retrieval than in the state of memorization. Such changes simultaneously occurred in different frequency bands and over the entire cortex. The highest relative augmentations of coherence with the highest significance estimates were observed in long-distance derivation pairs involving the temporal areas or combining the anterofrontal and frontal derivations with the parietal and occipital ones. The results are discussed in combination with data obtained in the same study for changes in EEG local synchronization and reported earlier. The intense rearrangements of the bioelectrical activity of the cortex may be determined both by the effect of cognitively specific mechanisms of encoding-decoding of information in the memory system and by a cognitively nonspecific modulating system of the brain.     

Electroencephalogram abnormalities in panic disorder patients: a study of symptom characteristics and pathology

Background  

Since the 1980s, a high EEG abnormality rate has been reported for patients with panic disorder. However, how the EEG abnormalities of panic disorder patients are related to the clinical features and pathology of these patients has yet to be clarified. In this study we investigated whether or not EEG abnormalities are related to the 13 symptoms in the DSM-IV criteria for a diagnosis of panic attacks.     

Comparative study of the gamma-rhythm in the norm, pre-examination stress and patients with the first depressive episode

The work gives the results of comparative analysis of gamma-rhythm (30-40 Hz) spectral power and synchronization indices in the healthy subjects both in normal situation and before the examination with that of depressive patients with the first episode, in the rest condition and during cognitive tests performance. It is demonstrated that gamma-rhythm spectral power in frontal and temporal areas of depressive patients was significantly higher than that in the norm. In stressful situation the number of differences of healthy subjects from depressive patients decreased in the rest condition and in Kraepelin test. Spatial imagination revealed more significant differences between depressive patients and healthy subjects both in normal and in stressful situations. Gamma-rhythm synchronization level was the same in healthy subjects both in the rest condition and during the tests performance, but in stressful situation it increased in the latter situation as well as in depressive patients. Thus, in the most cases stressful situation decreases the differences of EEG indices between healthy subjects and depressive patients both in the rest condition (by spectral power) and during the tests performance (by both indices). This may point out stress as the "trigger" of depression.     

Sequential use of mushroom body neuron subsets during drosophila odor memory processing

Drosophila mushroom bodies (MB) are bilaterally symmetric multilobed brain structures required for olfactory memory. Previous studies suggested that neurotransmission from MB neurons is only required for memory retrieval. Our unexpected observation that Dorsal Paired Medial (DPM) neurons, which project only to MB neurons, are required during memory storage but not during acquisition or retrieval, led us to revisit the role of MB neurons in memory processing. We show that neurotransmission from the alpha'beta' subset of MB neurons is required to acquire and stabilize aversive and appetitive odor memory, but is dispensable during memory retrieval. In contrast, neurotransmission from MB alphabeta neurons is only required for memory retrieval. These data suggest a dynamic requirement for the different subsets of MB neurons in memory and are consistent with the notion that recurrent activity in an MB alpha'beta' neuron-DPM neuron loop is required to stabilize memories formed in the MB alphabeta neurons.     

Sleep loss produces false memories

People sometimes claim with high confidence to remember events that in fact never happened, typically due to strong semantic associations with actually encoded events. Sleep is known to provide optimal neurobiological conditions for consolidation of memories for long-term storage, whereas sleep deprivation acutely impairs retrieval of stored memories. Here, focusing on the role of sleep-related memory processes, we tested whether false memories can be created (a) as enduring memory representations due to a consolidation-associated reorganization of new memory representations during post-learning sleep and/or (b) as an acute retrieval-related phenomenon induced by sleep deprivation at memory testing. According to the Deese, Roediger, McDermott (DRM) false memory paradigm, subjects learned lists of semantically associated words (e.g., "night", "dark", "coal",...), lacking the strongest common associate or theme word (here: "black"). Subjects either slept or stayed awake immediately after learning, and they were either sleep deprived or not at recognition testing 9, 33, or 44 hours after learning. Sleep deprivation at retrieval, but not sleep following learning, critically enhanced false memories of theme words. This effect was abolished by caffeine administration prior to retrieval, indicating that adenosinergic mechanisms can contribute to the generation of false memories associated with sleep loss.     

The Hippocampus Remains Activated over the Long Term for the Retrieval of Truly Episodic Memories

The role of the hippocampus in declarative memory consolidation is a matter of intense debate. We investigated the neural substrates of memory retrieval for recent and remote information using functional magnetic resonance imaging (fMRI). 18 young, healthy participants learned a series of pictures. Then, during two fMRI recognition sessions, 3 days and 3 months later, they had to determine whether they recognized or not each picture using the "Remember/Know" procedure. Presentation of the same learned images at both delays allowed us to track the evolution of memories and distinguish consistently episodic memories from those that were initially episodic and then became familiar or semantic over time and were retrieved without any contextual detail. Hippocampal activation decreased over time for initially episodic, later semantic memories, but remained stable for consistently episodic ones, at least in its posterior part. For both types of memories, neocortical activations were observed at both delays, notably in the ventromedial prefrontal and anterior cingulate cortices. These activations may reflect a gradual reorganization of memory traces within neural networks. Our data indicate maintenance and strengthening of hippocampal and cortico-cortical connections in the consolidation and retrieval of episodic memories over time, in line with the Multiple Trace theory (Nadel and Moscovitch, 1997). At variance, memories becoming semantic over time consolidate through strengthening of cortico-cortical connections and progressive disengagement of the hippocampus.     

Hippocampus-dependent retrieval and hippocampus-independent extinction of place avoidance navigation,and stress-induced out-of-context activation of a memory revealed by reversible lesion experiments in rats

The use of reversible lesion techniques in memory research was pioneered in the laboratory of Jan Bures and Olga Buresova. We use the occasion of Jan's 75th birthday to briefly review the experimental utility of this approach. Two experiments from our current research are reported in which reversible lesioning methods are used to ask otherwise experimentally untenable questions about memory retrieval. The first experiment used intra-hippocampal injections of tetrodotoxin to temporarily inactivate the hippocampus during retrieval of a well-learned place avoidance navigation memory. This revealed that the hippocampus is necessary for place avoidance retrieval but that the extinction of place avoidance can occur independently of retrieving the memory and intact hippocampal function. The second experiment used KCl-induced cortical spreading depression in an interhippocampal transfer paradigm to demonstrate that a Y-maze memory that is learned by only one cortical hemisphere can be made to transfer to the other hemisphere by forcing the rat to swim, a unique stressful experience that occurred in a different apparatus, different behavioral context, and involved different behaviors than the Y-maze training. This demonstrates, we believe for the first time behaviorally, that memories can be activated outside of the behavioral context of their acquisition and expression in rats.     

Symptoms of somatization as a rapid screening tool for mitochondrial dysfunction in depression

Recent progress in neuroscience revealed diverse regions of the CNS which moderate autonomic and affective responses. The ventro-medial prefrontal cortex (vmPFC) plays a key role in these regulations. There is evidence that vmPFC activity is associated with cardiovascular changes during a motor task that are mediated by parasympathetic activity. Moreover, vmPFC activity makes important contributions to regulations of affective and stressful situations. This review selectively summarizes literature in which vmPFC activation was studied in healthy subjects as well as in patients with affective disorders. The reviewed literature suggests that vmPFC activity plays a pivotal role in biopsychosocial processes of disease. Activity in the vmPFC might link affective disorders, stressful environmental conditions, and immune function.     

A distinct role for norepinephrine in memory retrieval

A role for norepinephrine in learning and memory has been elusive and controversial. A longstanding hypothesis states that the adrenergic nervous system mediates enhanced memory consolidation of emotional events. We tested this hypothesis in several learning tasks using mutant mice conditionally lacking norepinephrine and epinephrine, as well as control mice and rats treated with adrenergic receptor agonists and antagonists. We find that adrenergic signaling is critical for the retrieval of intermediate-term contextual and spatial memories, but is not necessary for the retrieval or consolidation of emotional memories in general. The role of norepinephrine in retrieval requires signaling through the beta(1)-adrenergic receptor in the hippocampus. The results demonstrate that mechanisms of memory retrieval can vary over time and can be different from those required for acquisition or consolidation. These findings may be relevant to symptoms in several neuropsychiatric disorders as well as the treatment of cardiac failure with beta blockers.     

Glucocorticoids are necessary for enhancing the acquisition of associative memories after acute stressful experience

Exposure to acute stressful experience can enhance the later ability to acquire new memories about associations between stimuli. This enhanced learning is observed during classical eyeblink conditioning of both hippocampal-dependent and -independent learning. It can be induced within minutes of the stressful event and persists for days. Here we examined the role of the major stress hormones glucocorticoids in the enhancement of learning after stress. In the first two experiments, it was determined that adrenalectomy (ADX), with and without replacement of basal levels of corticosterone, prevented the stress-induced enhancement of trace conditioning, a task that is dependent on the hippocampus for acquisition. In a third experiment, demedullation, which removes the adrenal medulla but leaves the adrenal cortex and corticosterone levels intact, did not affect the enhancement of learning after stress. In a fourth experiment, ADX prevented the stress-induced enhancement of delay conditioning, a hippocampal-independent task. In a final experiment, it was determined that one injection of stress levels of corticosterone enhanced new learning within minutes but not new learning 24 h later. Together these results suggest that endogenous glucocorticoids are necessary and sufficient for transiently enhancing acquisition of new associative memories and necessary but insufficient for persistently enhancing their acquisition after exposure to an acute stressful experience.     

Stress-induced hormonal and mood responses in scuba divers: a field study

The majority of injuries in scuba-divers are attributable to inappropriate behavior under stressful diving conditions, predominantly involving panic reactions emerging from elevated levels of anxiety. Divers with an elevated level of anxiety and poor coping are at higher risk of developing panic reactions than those possessing more adequate stress-coping-mechanisms. In the comparison of two extreme groups of seven divers each with opposite stress coping strategies, prolactin was found to be a hormonal marker with a significant increase in the sub-group of the stress-controllers. This hormonal response was observed in a recreational and a stressful dive, and in the latter with a more distinct elevation. Along with the self-reported emotional conditions under immersion, these data suggest that an increased prolactin level reflects a state of elevated physical and mental activation and vigilance. Facing a stressful situation subjects with more emotional concern and the tendency to surrender react by "blunted responses" and show significantly lower elevations of the prolactin levels in contrast to subjects with the very opposite psychological features. The other observed somatic parameters (epinephrine, norepinephrine) showed significant increases during and after dives (with the exception of saliva cortisol), however without any significant group difference.     

Differential responses to anxiogenic drugs in a mouse model of panic disorder as revealed by Fos immunocytochemistry in specific areas of the fear circuitry

Summary. Sensitivity to pharmacological challenges has been reported in patients with panic disorder. We have previously validated transgenic mice overexpressing the neurotrophin-3 (NT-3) receptor, TrkC (TgNTRK3), as an engineered murine model of panic disorder. We could determine that TgNTRK3 mice presented increased cellularity in brain regions, such as the locus ceruleus, that are important neural substrates for the expression of anxiety in severe anxiety states. Here, we investigated the sensitivity to induce anxiety and panic-related symptoms by sodium lactate and the effects of various drugs (the α2-adrenoceptor antagonist, yohimbine and the adenosine antagonist, caffeine), in TgNTRK3 mice. We found enhanced panicogenic sensitivity to sodium lactate and an increased intensity and a differential pattern of Fos expression after the administration of yohimbine or caffeine in TgNTRK3. Our findings validate the relevance of the NT-3/TrkC system to pathological anxiety and raise the possibility that a specific set of fear-related pathways involved in the processing of anxiety-related information may be differentially activated in panic disorder.