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PubMed2005

Processing efficiency of a verbal working memory system is modulated by amphetamine: an fMRI investigation.

RATIONALE: Working memory performance may be improved or decreased by amphetamine, depending on baseline working memory capacity and amphetamine dosage. This variable effect suggests an optimal range of monaminergic activity for working memory, either below or above which it is compromised. We directly tested this possibility with human participants by varying amphetamine dosage and measuring the efficiency of cortical processing in brain regions associated with working memory. OBJECTIVES: The modulation of cortical processing in a verbal working memory network by dextroamphetamine (D-amph) was examined using BOLD functional magnetic resonance imaging (fMRI) with healthy participants. The goal of the study was to test the hypothesis of an inverted U-shaped relationship between D-amph dose and processing efficiency of a verbal working memory system. METHODS: D-amph dosage was increased cumulatively every 2 h across four scanning sessions collected in a single day. The primary measure used for analyses in this study was the extent of activation in brain regions empirically defined as a working memory network. RESULTS: An inverted U-shaped relationship was observed between the amount of D-amph administered and working memory processing efficiency. This relationship was specific to brain areas functionally defined as working memory regions and to the encoding/maintenance phase (as opposed to the response phase) of the task. CONCLUSION: The results are consistent with the hypothesis that the neurochemical effects of amphetamine modulate the efficiency of a verbal working memory system. The effect of amphetamine on working memory in healthy individuals may provide insight regarding the working memory deficits seen in schizophrenia, given the overlap between neurochemical systems affected by amphetamine, and those disordered in schizophrenia.

Adult↗

PubMed2006

Group therapy for memory impaired patients: a partial remediation is possible.

BACKGROUND AND PURPOSE: To analyse the prospect of memory training for patients with organic brain damage. METHODS: Sixty-two patients with memory disorder were assigned to three different groups: a control group (n=16) with low dose memory training, a process oriented memory training group (POT) (n=24) and a group (ST) who was taught to compensate for memory problems with different strategies (n=22). Most of the patients had suffered a stroke. Inclusion criteria were medium to weak memory impairment defined by the patients' performance in the California Verbal Learning Test. Patients with complete amnesia were excluded. Specific care was taken that the groups did not differ in age, time since illness, duration of rehabilitation effort, verbal and performance IQ, memory and attention performance. The two treatment groups received 20 hours memory training, the low dose memory training control group 7 sessions. RESULTS: The treatment groups improved in verbal and prospective memory, but only the group with POT experienced a significant improvement compared with the control group. Training effects were specific, i. e. they affected verbal memory, but were not encapsulated, i. e. generalized to the recall of prose passages and of appointments. The POT group also showed a statistically weak outperformance compared with the ST group and some attentional improvement as well. CONCLUSION: Memory training is effective in patients with organic brain lesion, but only if applied frequently. Comparing the two training high intensity treatments, a POT focus seems to be superior to teaching a set of compensation strategies.

Aged↗

PubMed1994

Effect of AIT-082, a purine analog, on working memory in normal and aged mice.

Because working memory is the primary type of memory which is disrupted by Alzheimer's disease and stroke and during aging, any therapeutic drug for these conditions should improve and/or restore working memory. The win-shift memory paradigm has been shown to be an excellent model of working memory. In the present study, we examined the effects of a novel purine derivative, 4-[[3-(1,6-dihydro-6-oxo-9-purin-9-yl)-1- oxopropyl]amino]benzoic acid (AIT-082) and physostigmine (PHY) on working memory. Both AIT-082 and PHY improved memory in young mice and restored memory in mice with mild age-induced memory deficits; however only AID-082 was also effective in subjects with moderate deficits. Neither drug improved memory in mice with severe memory deficits. AIT-082 exhibited effectiveness over a broad dose range (0.5-60 mg/kg), and the effects lasted for seven days after a single high-dose drug administration. AIT-082 was devoid of any effects on performance variables and has not shown any toxic side effects, thus making it an interesting potential treatment for working memory deficits associated with aging, strokes, and Alzheimer's disease.

Aging↗

PubMed1995

The importance of calmodulin in the accessory olfactory bulb in the formation of an olfactory memory in mice.

Female mice form an olfactory memory to the pheromones of the mating male, during a critical period after mating. Failure to form this memory results in the male being treated as strange, and hence, his pheromones block pregnancy. Previous studies have shown that formation of this memory is dependent on synaptic mechanisms in the accessory olfactory bulb. A number of studies have pointed to calmodulin as a critical mediator of synaptic plasticity. In this study we have examined the effects of local infusions of drugs which block calmodulin-regulated processes, into the accessory olfactory bulb on the formation of this memory. Infusions of the calmodulin antagonist calmidazolium during the critical period prevented memory formation. However, the specific inhibitor of calcium/calmodulin-dependent protein kinase II, KN-62, or the selective inhibitor of calcium/calmodulin-dependent protein phosphatase 2B (calcineurin), FK506, was without effect on memory formation at any of the doses used. Instead of preventing memory formation, FK506 permitted the formation of a non-selective memory to strange male pheromones in the presence of mating, although FK506 alone could not induce a memory without the occurrence of mating. These results suggest that calmodulin in the accessory olfactory bulb is important in the formation of the olfactory memory to male pheromones. However, memory formation may be independent of calmodulin-kinase II. Calcineurin may play a role in processes antagonizing memory formation.

Animals↗

PubMed2006

Posttraumatic stress disorder: memory and learning performance in children and adolescents.

BACKGROUND: Despite the wealth of information in adult posttraumatic stress disorder (PTSD) literature, few studies have explored the memory and learning performance of trauma-exposed youth. This study examined if memory deficits are associated with PTSD or with trauma exposure in the absence of PTSD. METHODS: Youth exposed to traumatic incidents underwent clinical interviews to diagnose PTSD and exclude major comorbid disorders. Youth with conditions that could impede performance on a memory scale (e.g., limited intellectual functioning, current substance abuse, psychopharmacological treatment) were excluded. Three groups of participants were identified (PTSD positives [n = 29], traumatized PTSD negatives [n = 62], and nontraumatized control subjects [n = 40]). Participants completed the Wide Range Assessment of Memory and Learning (WRAML). RESULTS: Youth with PTSD evidenced significantly lower scores on the WRAML General Memory, Verbal Memory, and Learning indices compared with nontraumatized control subjects. With the exception of Verbal Memory, youth with and without PTSD performed comparably on all other indices. Nonsignificant differences were noted on the Visual Memory Index. CONCLUSIONS: General memory and verbal memory impairments as evidenced in adult populations were observed among this sample of youth. Given the developmental trajectory of memory capabilities, the implications of such early trauma exposure and memory deficits are considered.

Adolescent↗

PubMed2004

Sparing of perceptual implicit memory despite suppression of the electrophysiological word repetition effect: a study with general anesthetic isoflurane.

OBJECTIVE: Much effort has been devoted to the search for the neurophysiological correlates of implicit memory. A commonly held view is that the early portion (250-500 ms) of the event-related potential (ERP) word repetition effect reflects processes important for perceptual implicit memory whereas the latter portion reflects processes implicated in explicit memory. It is, however, difficult to disentangle with certainty the relative contributions of each form of memory on ERPs since both forms co-exist in normal subjects. To dissociate ERP effect related to implicit and explicit memory, we used isoflurane sedation in normal subjects to suppress explicit remembering while sparing implicit memory. These ERPs were compared with those of non-medicated control subjects. METHODS: Thirteen subjects performed an incidental encoding task for words presented auditorily during the inhalation of a subanesthetic dose of isoflurane. After termination of isoflurane administration, we assessed free recall and recorded ERPs during a syllable completion task (implicit memory) and during a passive listening task (ERP repetition effect). Eleven non-medicated control subjects were tested in a similar manner. RESULTS: The controls showed robust early and late ERP repetition effect. The isoflurane group had implicit memory without free recall and showed no ERP repetition effect. CONCLUSIONS: These findings failed to show an association between any part of the repetition effect and perceptual implicit memory. The results are consistent with the view that processes linked to explicit memory contribute to the ERP repetition effect since there was a marked difference in free recall between the control and isoflurane groups. SIGNIFICANCE: The present study shows that the reversible alterations of memory by general anesthetics can be used to study the neurophysiological correlates of memory processes.

Adult↗

PubMed2004

Episodic memory in nonhumans: what, and where, is when?

Episodic memory is defined as the recollection of specific events in one's past, accompanied by the experience of having been there personally. This definition presents high hurdles to the investigation of episodic memory in nonhumans. Recent studies operationalize episodic memory as memory for when and where an event occurred, for the order in which events occurred, or for an animal's own behavior. None of these approaches has yet generalized across species, and each fails to capture features of human episodic memory. Nonetheless, the study of episodic memory in nonhumans seems less daunting than it did five years ago. To demonstrate a correspondence between human episodic memory and nonhuman memory, progress is needed in three areas. Putative episodic memories in nonhumans should be shown to be; first, represented in long-term memory, rather than short-term or working memory; second, explicit, or accessible to introspection; and third, distinct from semantic memory, or general knowledge about the world.

Animals↗

PubMed2006

Drosophila dorsal paired medial neurons provide a general mechanism for memory consolidation.

Memories are formed, stabilized in a time-dependent manner, and stored in neural networks. In Drosophila, retrieval of punitive and rewarded odor memories depends on output from mushroom body (MB) neurons, consistent with the idea that both types of memory are represented there. Dorsal Paired Medial (DPM) neurons innervate the mushroom bodies, and DPM neuron output is required for the stability of punished odor memory. Here we show that stable reward-odor memory is also DPM neuron dependent. DPM neuron expression of amnesiac (amn) in amn mutant flies restores wild-type memory. In addition, disrupting DPM neurotransmission between training and testing abolishes reward-odor memory, just as it does with punished memory. We further examined DPM-MB connectivity by overexpressing a DScam variant that reduces DPM neuron projections to the MB alpha, beta, and gamma lobes. DPM neurons that primarily project to MB alpha' and beta' lobes are capable of stabilizing punitive- and reward-odor memory, implying that both forms of memory have similar circuit requirements. Therefore, our results suggest that the fly employs the local DPM-MB circuit to stabilize punitive- and reward-odor memories and that stable aspects of both forms of memory may reside in mushroom body alpha' and beta' lobe neurons.

Animals↗

PubMed2006

Delusional memories from the intensive care unit--experienced by patients with physical trauma.

During and after intensive care unit (ICU) stays some patients report unreal experiences or so called delusional memories, which can be a source of distress. The aims of this study were: to describe trauma patients' memories of their stay in the ICU, factors that may influence delusional memories, problems experienced after discharge from the ICU and the patients' return to work. In this multi-centre study, 239 trauma patients filled in a self-administered questionnaire (ICUM tool) 6-18 months after their ICU stay. Clinical data were obtained from patient records. Fifteen percent of the respondents had no memory whatsoever of the ICU. Factual memories such as visits by family members were recalled by 83%. Delusional memories were reported by 26%, nightmares being the most common. These patients' also had more memories of pain, fear and panic. Significant factors associated with delusional memories were age <50 year, ICU stay >or=3 days, temperature >or=38 degrees C, S-Haemaglobin <or=100g/l, renal failure, surgery, ventilator support, sedative drugs, and opioids. A logistic regression analysis of all significant factors revealed that age was the best predictor of delusional memories. Significantly more patients with delusional memories reported unexplained feelings of panic after discharge from the ICU and had still not returned to work 1 year after the trauma. In conclusion, patients with delusional memories are younger and these memories affect them even after discharge from the ICU.

Adult↗

PubMed2005

Neuropharmacology of cognition and memory: a unifying theory of neuromodulator imbalance in psychiatry and amnesia.

The case of HM, a man with intractable epilepsy who became amnesic following bilateral medial temporal lobe surgery nearly half a century ago has instigated ongoing research and theoretical speculation on the nature of memory and the role of the hippocampus. Neuropsychological testing showed that although HM had extensive anterograde memory loss he could still acquire motor and cognitive skills implicitly, but could not remember the context of this learning. This has lead to declarative and procedural descriptions of the memory process. Cholinergic and monoaminergic neurotransmitter systems have also been implicated in the memory process and anticholinergic drugs traditionally have been associated with impairment of declarative memory. The cholinergic hypothesis of Alzheimer's disease is a classic example of an application of these neuropharmacological findings. In schizophrenia, preattentive deficits have been amply demonstrated by unconscious priming studies. Memory processes are also impaired in these patients. Dopamine, glutamate and even cholinergic dysfunction has been implicated in the clinical picture of schizophrenia. The present paper will attempt to bring together both the anatomical and pharmacological data from these disparate fields of research under a cohesive theory of cognition and memory. A hypothesis is presented for an inverse relationship between monoaminergic and cholinergic systems in the modulation of implicit (unconscious) and explicit (conscious) cognitive processes. It is postulated that muscarinic cholinergic receptors and monoaminergic systems facilitate unconscious and conscious processes, respectively, and they disfacilitate conscious and unconscious processes, respectively (the purported inverse relationship). In fact, the muscarinic and monoaminergic modulations of a neural network are proposed to be finely balanced such that, if, the activity of one receptor system is modified then this by necessity has effects on the other system. It takes into account receptor subtypes and their effects mediated through excitatory and inhibitory G-protein complexes. For example, m1/D2 and D1/m4 paired receptor subtypes, colocalized on separate neurons would have opposing functional effects. A theory is then presented that the critical underlying pathophysiology of schizophrenia involves a hypofunctional muscarinic cholinergic system, which induces abnormal facilitation of monoaminergic subsystems such as dopamine (e.g., a decrease in m1R function would potentiate D2R function). This extends the idea of an inverted U function for optimal monoaminergic concentrations. Not only would this impair unconscious preattentive processes, but according to the hypothesis, explicit cognition as well including memory deficits and would underlie the mechanism of psychosis. Contrary to current thinking a different view is also presented for the role of the hippocampus in the memory process. It is postulated that long-term explicit memory traces in the neocortex are laid down by phasic coactivation of forebrain projecting monoaminergic systems above some basal firing rate, such as the rostral serotonergic raphe, which projects diffusely to the cortex and according to a modified Hebbian principle. This is the proposed principal function of the hippocampal theta rhythm. The phasic activation of the cholinergic basal forebrain is mediated by projections from a separate cortical structure, possibly the lateral prefrontal cortex. Phasic muscarinic receptor activation is proposed to strengthen implicit memory traces (at a synaptic level) in the neocortex. Thus, the latter are spared by medial temporal surgery explaining the dissociation of explicit from implicit memory.

Amnesia↗

PubMed2004

Autobiographical and episodic memory--one and the same? Evidence from prefrontal activation in neuroimaging studies.

Laboratory investigations of episodic memory often require participants to encode and later retrieve lists of items (words, pictures, or faces). The underlying assumption is that recollection of items from the list is analogous to recollection of events from one's past, i.e. autobiographical re-experiencing. Functional neuroimaging studies of episodic memory have provided extensive evidence suggesting that regions of the prefrontal cortex (PFC) play a role in episodic memory retrieval. A review of PFC activations reported in imaging studies of autobiographical memory and matched sub-sets of list-learning episodic memory studies reveals patterns of similarity but also substantial differences. Episodic memory studies often report activations in the right mid-dorsolateral PFC, but such activations are absent in autobiographical memory studies. Additionally, activations in the ventromedial PFC, primarily on the left, are almost invariably found in autobiographical memory studies, but rarely occur in studies of episodic memory. It is suggested that these two regions mediate different modes of post-retrieval monitoring and verification. Autobiographical memory relies on quick intuitive 'feeling of rightness' to monitor the veracity and cohesiveness of retrieved memories in relation to an activated self-schema. Episodic memory for lists requires more conscious elaborate monitoring to avoid omissions, commissions and repetitions. The present analysis suggests that care and caution should be exercised in extrapolating from the way we recollect 'events' from a list learned in the laboratory to the way we recollect events from our lives.

Brain Mapping↗

PubMed2006

Recall and recognition memory in amnesia: patients with hippocampal, medial temporal, temporal lobe or frontal pathology.

The relationship between recall and recognition memory impairments was examined in memory-disordered patients with either hippocampal, medial temporal, more widespread temporal lobe or frontal pathology. The Hirst [Hirst, W., Johnson, M. K., Phelps, E. A., & Volpe, B. T. (1988). More on recognition and recall in amnesics. Journal of Experimental Psychology: Learning, Memory, & Cognition, 14, 758-762] technique for titrating exposure times was used to match recognition memory performance as closely as possible before comparing recall memory scores. Data were available from two different control groups given differing exposure times. Each of the patient groups showed poorer recall memory performance than recognition scores, proportionate to the difference seen in healthy participants. When patients' scores were converted to Z-scores, there was no significant difference between mean Z-recall and Z-recognition scores. When plotted on a scatterplot, the majority of the data-points indicating disproportionately low recall memory scores came from healthy controls or patients with pathology extending into the lateral temporal lobes, rather than from patients with pathology confined to the medial temporal lobes. Patients with atrophy extending into the parahippocampal gyrus (H+) performed worse than patients with atrophy confined to the hippocampi (H-); but, when H- patients were given a shorter exposure time (5s) and compared with H+ at a longer exposure (10s), their performance was virtually identical and did not indicate any disproportionate recall memory impairment in the H- group. Parahippocampal volumes on MRI correlated significantly with both recall and recognition memory. The possibility that findings were confounded by inter-stimulus artefacts was examined and rejected. These findings argue against the view that hippocampal amnesia or memory disorders in general are typically characterised by a disproportionate impairment in recall memory. Disproportionate recall memory impairment has been observed in a number of published cases, and the reason for the varying pattern obtained across hippocampal patients requires further examination.

Adult↗

PubMed2003

Male mice exhibit better spatial working and reference memory than females in a water-escape radial arm maze task.

The present study examined sex differences in spatial working and reference memory in C57BL/6 mice. Males and females were tested in a version of the spatial 8-arm radial arm maze in which the motivating stimulus was escape from water. To test spatial working memory, four arms were baited with submerged escape platforms, each of which was removed after it was found. Four arms that never contained platforms assessed spatial reference memory. In addition to determining the number of working memory and reference memory errors made in each session, working memory errors made in each trial were analyzed to examine performance as the number of arms to be remembered (i.e. the working memory load) increased. Males committed significantly fewer working memory and reference memory errors than females throughout testing. Within a session, males committed fewer working memory errors than females as the working memory load increased. These sex differences were particularly evident during task acquisition. The data indicate that male C57BL/6 mice learn both the working and reference memory components of a water-escape motivated radial arm maze task better than female mice.

Animals↗

PubMed2001

Social memory in the rat: circadian variation and effect of circadian rhythm disruption.

Disruption of circadian rhythm can impair long-term passive avoidance memory of rats and mice. The present study investigated whether disruption of circadian rhythm can also impair social memory of male rats. Social memory was assessed using the social discrimination test, in which a short-term olfactory memory is formed by social interaction with a juvenile rat during a learning trial. After an intertrial interval, a retrieval trial is performed, in which social memory is expressed as a decreased attention paid to the same juvenile as compared to a new juvenile. First, the social memory at four different time points across the light-dark cycle was measured with an intertrial interval of 10 or 25 min. There was no significant circadian variation of social memory across the light-dark cycle. Subsequently, the effect of a -6 or 12-h phase shift on social memory was studied. These phase shifts were previously found to impair long-term passive avoidance memory. However, no effect of either phase shift was observed in the social discrimination test. It is concluded that the disruption of circadian rhythm had no effect on the social memory of rats. Differences between short-term social memory and long-term passive avoidance memory are discussed in relation to their apparent differential susceptibility to the effects of circadian rhythm disruption.

Animals↗

PubMed1998

On memories of childhood abuse: a phenomenological study.

OBJECTIVE: To explore the phenomenon of memories and reported recovered memories of childhood abuse, and to examine ways in which clients and therapists assess the veridicality of such memories. METHOD: Qualitative methodology utilizing phenomenological inquiry. Within the context of a wider study exploring perceptions of helpful and unhelpful factors in the therapeutic process, a sub-sample of 36 in-depth interviews with clients, therapists, and therapists who considered themselves to have been abused as children included a focus on abuse-memory experiences. Data were analyzed according to Grounded Theory principles. RESULTS: Participants described six types of abuse-memory experiences. The most frequently reported type was where abuse was known about but kept "out of mind." The six types can be collapsed into three main categories: (1) continual knowledge of abuse (69.5%); (2) unexpected abuse-memories recovered from a prior state of partial knowledge of abuse (16.5%); and (3) abuse-memories recovered from a prior state of no knowledge of abuse (30%). Independent corroboration of recovered memories was rare; and criteria which were reportedly used to assess the veridicality of such memories were problematic when viewed in the light of cognitive psychology research on memory processes. CONCLUSION: It seems that most people who were abused as children have always had continual knowledge of this, although it is often only much later than many connect problems in adult life with the consequences of such abuse. People also experience the recovery of memories of abuse about which they were previously unaware. There is a danger that the specific controversy surrounding "false memories" may become over-generalized contributing to increased public scepticism about the prevalence and negative impact of child abuse, and the potential effectiveness of appropriate therapeutic services.

Adult↗

PubMed2007

Remembering to age successfully: evaluation of a successful aging approach to memory enhancement.

BACKGROUND: Memory enhancement programs that can significantly improve actual memory performance and subjective perceptions of everyday memory in elderly people are rare. This study was designed to evaluate a new memory enhancement program incorporating principles of successful aging, designed to enhance subjective and objective everyday memory in community-dwelling old people. METHODS: Two matched groups of 20 healthy community-dwelling elderly adults were assessed on measures of objective and subjective memory performance before and after participating in a memory enhancement or active control condition. RESULTS: Planned multivariate analysis of variance (MANOVA) on change scores showed that participants in the memory enhancement program improved significantly on both objective and subjective measures. Specifically, greater improvement was demonstrated on a verbal paired associates task, story recall, face recognition, contentment with memory, and use of memory strategies. CONCLUSIONS: Although a fully randomized design was not used, the results are promising, suggesting that memory training incorporating principles of successful aging can enhance memory performance in healthy old people, objectively and subjectively.

Achievement↗

PubMed2003

Adult age differences in temporal and item memory.

Three experiments tested whether the relationship between age differences in temporal and item memory depends on the degree to which the item memory measure relies on memory for context. The authors predicted a stronger relationship of temporal memory to free recall than to recognition memory. Results showed that age differences in temporal memory could be eliminated after controlling for free recall but not recognition memory performance. Under some conditions recognition memory accounted for a significant portion of age-related variance in temporal memory. These results challenge past research that has interpreted age differences in temporal and item memory as independent and suggest that a generalized decline in context memory may underlie reduced performance in older adults on all types of memory tests.

Adolescent↗

PubMed2006

The effect of anticipation and the specificity of sex differences for amygdala and hippocampus function in emotional memory.

Prior research has shown memory is enhanced for emotional events. Key brain areas involved in emotional memory are the amygdala and hippocampus, which are also recruited during aversion and its anticipation. This study investigated whether anticipatory processes signaling an upcoming aversive event contribute to emotional memory. In an event-related functional MRI paradigm, 40 healthy participants viewed aversive and neutral pictures preceded by predictive warning cues. Participants completed a surprise recognition task directly after functional MRI scanning or 2 weeks later. In anticipation of aversive pictures, bilateral dorsal amygdala and anterior hippocampus activations were associated with better immediate recognition memory. Similar associations with memory were observed for activation of those areas in response to aversive pictures. Anticipatory activation predicted immediate memory over and above these associations for picture viewing. Bilateral ventral amygdala activations in response to aversive pictures predicted delayed memory only. We found that previously reported sex differences of memory associations with left amygdala for women and with right amygdala for men were confined to the ventral amygdala during picture viewing and delayed memory. Results support an established animal model elucidating the functional neuroanatomy of the amygdala and hippocampus in emotional memory, highlight the importance of anticipatory processes in such memory for aversive events, and extend neuroanatomical evidence of sex differences for emotional memory.

Adult↗