Electrophysiological markers of memory consolidation in the human brain when memories are reactivated during sleep.

Human accomplishments depend on learning, and effective learning depends on consolidation. Consolidation is the process whereby new memories are gradually stored in an enduring way in the brain so that they can be available when needed. For factual or event knowledge, consolidation is thought to progress during sleep as well as during waking states and to be mediated by interactions between hippocampal and neocortical networks. However, consolidation is difficult to observe directly but rather is inferred through behavioral observations. Here, we investigated overnight memory change by measuring electrical activity in and near the hippocampus. Electroencephalographic (EEG) recordings were made in five patients from electrodes implanted to determine whether a surgical treatment could relieve their seizure disorders. One night, while each patient slept in a hospital monitoring room, we recorded electrophysiological responses to 10 to 20 specific sounds that were presented very quietly, to avoid arousal. Half of the sounds had been associated with objects and their precise spatial locations that patients learned before sleep. After sleep, we found systematic improvements in spatial recall, replicating prior results. We assume that when the sounds were presented during sleep, they reactivated and strengthened corresponding spatial memories. Notably, the sounds also elicited oscillatory intracranial EEG activity, including increases in theta, sigma, and gamma EEG bands. Gamma responses, in particular, were consistently associated with the degree of improvement in spatial memory exhibited after sleep. We thus conclude that this electrophysiological activity in the hippocampus and adjacent medial temporal cortex reflects sleep-based enhancement of memory storage.

The effect of language proficiency and associative strength on false memory.

In two experiments we examined the role of language proficiency and associative strength in the production of false memory. We constructed Deese-Roediger-McDermott lists using both Spanish and English free association norms. Lists were constructed to vary in backward associative strength (BAS). Experiment 1 participants were native Spanish speakers with some proficiency in English while Experiment 2 participants were native Spanish participants that had either high, intermediate, or low English proficiency. Results showed that, in both Experiment 1 and Experiment 2, false recognition was greater in participants' dominant language (L1 or Spanish) than in their non-dominant language (L2 or English), and false recognition in L2 increased with L2 proficiency when low-BAS lists were studied (Experiment 2). Further, false recognition was higher in high-BAS lists than in low-BAS lists in both L1 and L2. Finally, we collected a measure of participants' knowledge of our stimulus words in L2. These data showed that participants had far from perfect knowledge of all L2 stimuli. Analyses that factored out the effects of L2 word knowledge failed to alter the effects of L1 vs. L2, L2 proficiency and BAS on false recognition.

The influence of forward and backward associative strength on false memories for encoding context.

Two experiments examined the effects of forward associative strength (FAS) and backward associative strength (BAS) on false recollection of unstudied lure items. Themes were constructed such that four associates were strongly related to a lure item in terms of FAS or BAS and four associates were weakly related to a lure item in terms of FAS or BAS. Further, when FAS was manipulated, BAS was controlled across strong and weak associates, while FAS was controlled across strong and weak associates when BAS was manipulated. Strong associates were presented in one font while weak associates were presented in a second font. At test, lure items were disproportionately attributed to the source used to present lures' strong associates compared to lures' weak associates, both when BAS was manipulated and when FAS was manipulated. This outcome demonstrates that both BAS and FAS influence lure item false recollection, which favours global-matching models' explanation of false recollection over the explanation offered by spreading activation theories.

Hemispheric asymmetries in the activation and monitoring of memory errors.

Previous research on the lateralization of memory errors suggests that the right hemisphere's tendency to produce more memory errors than the left hemisphere reflects hemispheric differences in semantic activation. However, all prior research that has examined the lateralization of memory errors has used self-paced recognition judgments. Because activation occurs early in memory retrieval, with more time to make a decision, other memory processes, like strategic monitoring processes, may affect memory errors. By manipulating the time subjects were given to make memory decisions, this study separated the influence of automatic memory processes (activation) from strategic memory processes (monitoring) on the production of false memories. The results indicated that when retrieval was fast, the right hemisphere produced more memory errors than the left hemisphere. However, when retrieval was slow, the left hemisphere's error-proneness increased compared to the fast retrieval condition, while the right hemisphere's error-proneness remained the same. These results suggest that the right hemisphere's errors are largely due to activation, while the left hemisphere's errors are influenced by both activation and monitoring.

Primary infundibular stenosis and pedigree analysis in three Golden Retriever littermates.

Three eight-week-old Golden Retriever puppy littermates were evaluated because of left basilar systolic murmurs and were diagnosed with primary infundibular stenosis. Pedigree analysis in this line was also performed to identify a mode of inheritance. All dogs were asymptomatic at the time of diagnosis; two of the three had congenital lesions in addition to primary infundibular stenosis. Two additional affected dogs were identified in the line, and pedigree analysis suggested an autosomal recessive mode of inheritance. Another, unrelated golden retriever was also identified with isolated infundibular stenosis in the record database. Primary infundibular stenosis should be considered in the differential diagnoses for golden retriever dogs with a left basilar systolic murmur, and is often associated with complex congenital cardiac disease. Primary infundibular stenosis may worsen in severity with time, and in this line of dogs an autosomal recessive pattern of inheritance is likely.

Questioning the Role of Forward Associative Strength in False Memories: Evidence From Deese-Roediger-McDermott Lists With Three Critical Lures.

We report an experiment examining the factors that produce false recognition in the Deese-Roediger-McDermott (DRM) paradigm. We selectively manipulated the probability that critical lures produce study items in free association, known as forward associative strength (FAS), while controlling the probability that study items produce critical lures in free association, known as backward associative strength (BAS). Results showed that false recognition of critical lures failed to differ between strong and weak FAS conditions. Follow-up correlational analyses further supported this outcome, showing that FAS was not correlated with false recognition, despite substantial variability in both variables across our stimulus sets. However, these correlational analyses did produce a significant and strong relationship between BAS and false recognition. These results support views that propose false memory is produced by activation spreading from study items to critical lures during encoding, which leads critical lures to be confused with episodically-experienced events.

Percutaneous transendocardial delivery of self-complementary adeno-associated virus 6 achieves global cardiac gene transfer in canines.

Achieving efficient cardiac gene transfer in a large animal model has proven to be technically challenging. Previous strategies have used cardiopulmonary bypass or dual catheterization with the aid of vasodilators to deliver vectors, such as adenovirus, adeno-associated virus (AAV), or plasmid DNA. Although single-stranded AAV (ssAAV) vectors have shown the greatest promise, they suffer from delayed expression, which might be circumvented using self-complementary vectors. We sought to optimize cardiac gene transfer using a percutaneous transendocardial injection catheter to deliver adeno-associated viral vectors to the canine myocardium. Four vectors were evaluated--ssAAV9, self-complementary AAV9 (scAAV9), scAAV8, scAAV6--so that comparison could be made between single-stranded and self-complementary vectors as well as among serotypes 9, 8, and 6. We demonstrate that scAAV is superior to ssAAV and that AAV 6 is superior to the other serotypes evaluated. Biodistribution studies revealed that vector genome copies were 15-4,000 times more abundant in the heart than in any other organ for scAAV6. Percutaneous transendocardial injection of scAAV6 is a safe, effective method to achieve efficient cardiac gene transfer.

Percutaneous Transendocardial Delivery of Self-complementary Adeno-associated Virus 6 Achieves Global Cardiac Gene Transfer in Canines.

Achieving efficient cardiac gene transfer in a large animal model has proven to be technically challenging. Previous strategies have used cardiopulmonary bypass or dual catheterization with the aid of vasodilators to deliver vectors, such as adenovirus, adeno-associated virus (AAV), or plasmid DNA. Although single-stranded AAV (ssAAV) vectors have shown the greatest promise, they suffer from delayed expression, which might be circumvented using self-complementary vectors. We sought to optimize cardiac gene transfer using a percutaneous transendocardial injection catheter to deliver adeno-associated viral vectors to the canine myocardium. Four vectors were evaluated-ssAAV9, self-complementary AAV9 (scAAV9), scAAV8, scAAV6-so that comparison could be made between single-stranded and self-complementary vectors as well as among serotypes 9, 8, and 6. We demonstrate that scAAV is superior to ssAAV and that AAV 6 is superior to the other serotypes evaluated. Biodistribution studies revealed that vector genome copies were 15-4,000 times more abundant in the heart than in any other organ for scAAV6. Percutaneous transendocardial injection of scAAV6 is a safe, effective method to achieve efficient cardiac gene transfer.

Sample Size Determination for Evaluation of Time Domain Heart Rate Variability Indices in Canine Lameness.

Heart rate variability (HRV) is a physiologic phenomenon that occurs due to changing autonomic tone resulting in variable RR intervals. A reduction in HRV is used as an index of pain in neonatal human patients. Objective measures of pain would be valuable in the evaluation of canine patients and assessment of response to pain management strategies. We hypothesized that dogs with diseases associated with discomfort (osteoarthritis and bone neoplasia) would have reduced HRV compared with normal, healthy dogs. The aim of the study was to calculate the sample size necessary to investigate this hypothesis. Seventeen dogs from the Ryan Veterinary Hospital of the University of Pennsylvania patient population or owned by Ryan Veterinary Hospital of the University of Pennsylvania staff were enrolled in this single-blind, prospective pilot study. A 30 min electrocardiogram (ECG) was obtained from each dog using an ambulatory electrocardiographic monitor. All ECGs were obtained between 10 a.m. and 2 p.m. ECGs were analyzed and time-domain HRV indices computed. Sample size calculations suggest that 207 dogs would be necessary to ascertain if HRV is reduced in dogs experiencing discomfort or pain (50 in the arthritis group, 79 in the bone cancer group, and 78 in the control group).

The role of backward associative strength in false recognition of DRM lists with multiple critical words.

BACKGROUND: Memory is a reconstruction of the past and is prone to errors. One of the most widely-used paradigms to examine false memory is the Deese/Roediger-McDermott (DRM) paradigm. In this paradigm, participants studied words associatively related to a non-presented critical word. In a subsequent memory test critical words are often falsely recalled and/or recognized. METHOD: In the present study, we examined the influence of backward associative strength (BAS) on false recognition using DRM lists with multiple critical words. In forty-eight English DRM lists, we manipulated BAS while controlling forward associative strength (FAS). Lists included four words (e.g., prison, convict, suspect, fugitive) simultaneously associated with two critical words (e.g., CRIMINAL, JAIL). RESULTS: The results indicated that true recognition was similar in high-BAS and low-BAS lists, while false recognition was greater in high-BAS lists than in low-BAS lists. Furthermore, there was a positive correlation between false recognition and the probability of a resonant connection between the studied words and their associates. CONCLUSIONS: These findings suggest that BAS and resonant connections influence false recognition, and extend prior research using DRM lists associated with a single critical word to studies of DRM lists associated with multiple critical words.