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remote memory [keywords]
- Development of abstract thinking during childhood and adolescence: The role of rostrolateral prefrontal cortex. [REVIEW]
- Dev Cogn Neurosci 2014 Aug 12.:57-76.
Rostral prefrontal cortex (RPFC) has increased in size and changed in terms of its cellular organisation during primate evolution. In parallel emerged the ability to detach oneself from the immediate environment to process abstract thoughts and solve problems and to understand other individuals' thoughts and intentions. Rostrolateral prefrontal cortex (RLPFC) is thought to play an important role in supporting the integration of abstract, often self-generated, thoughts. Thoughts can be temporally abstract and relate to long term goals, or past or future events, or relationally abstract and focus on the relationships between representations rather than simple stimulus features. Behavioural studies have provided evidence of a prolonged development of the cognitive functions associated with RLPFC, in particular logical and relational reasoning, but also episodic memory retrieval and prospective memory. Functional and structural neuroimaging studies provide further support for a prolonged development of RLPFC during adolescence, with some evidence of increased specialisation of RLPFC activation for relational integration and aspects of episodic memory retrieval. Topics for future research will be discussed, such as the role of medial RPFC in processing abstract thoughts in the social domain, the possibility of training abstract thinking in the domain of reasoning, and links to education.
- Cerebellar Mechanisms of Learning and Plasticity Revealed by Delay Eyelid Conditioning. [JOURNAL ARTICLE]
- Int Rev Neurobiol 2014.:21-37.
The analysis of well-defined behaviors that require the cerebellum has helped reveal many key mechanisms operating in the cerebellum to mediate learning and feed-forward prediction. These systems include eyelid conditioning, adaptation of the vestibuloocular reflex, smooth pursuit eye movements, and arm-reaching tasks. This review focuses specifically on the variety of findings that have come from the use of eyelid conditioning to study the cerebellum. Phenomena discussed include sites and rules for plasticity, temporal coding and mechanisms of timing, cerebellar control of climbing fibers and its role in bidirectional learning, extinction of conditioned responses, and the phenomenon of savings.
- Learning-Induced Structural Plasticity in the Cerebellum. [JOURNAL ARTICLE]
- Int Rev Neurobiol 2014.:1-19.
Activity-dependent changes in synaptic properties are considered key neural mechanisms of learning and memory. Most studies focus on changes in synaptic function such as long-term potentiation (LTP) and long-term depression (LTD), while changes in synaptic structure have been largely ignored. However, structural synaptic changes are also important. In fact, LTP and LTD are often associated with structural alterations of dendritic spines. Furthermore, experimental evidence indicates that behavioral learning often induces structural rewiring of synaptic circuitry through the formation of new synapses and elimination of existing ones. To discuss the role of structural plasticity in cerebellar learning, this chapter mainly focuses on parallel fiber-Purkinje cell synapses in the cerebellar cortex and reviews their structural changes under several different forms of motor learning.
- Chronic behavioral and cognitive deficits in a rat survival model of paraoxon toxicity. [JOURNAL ARTICLE]
- Neurotoxicology 2014 Aug 26.
Organophosphate (OP) compounds, including paraoxon (POX), are similar to nerve agents such as sarin. There is a growing concern that OP agents could be weaponized to cause mass civilian causalities. We have developed a rodent survival model of POX toxicity that is being used to evaluate chronic morbidity and to screen for medical countermeasures against severe OP exposure. It is well known that the survivors of nerve gas and chronic OP exposure exhibit neurobehavioral deficits such as mood changes, depression, and memory impairments. In this study we investigated whether animals surviving severe POX exposure exhibited long-term neurological impairments. POX exposure produced overt signs of cholinergic toxicity. Rats were rescued using an optimized atropine, 2-PAM and diazepam therapy. Surviving rats were studied using established behavioral assays for identifying symptoms of depression and memory impairment 3-months after POX exposure. In the forced swim test, POX rats exhibited increased immobility time indicative of a despair-like state. In the sucrose preference test, POX rats consumed significantly less sucrose water indicating anhedonia-like condition. POX rats also displayed increased anxiety as characterized by significantly lower performance in the open arm of the elevated plus maze. Further, when tested with a novel object recognition paradigm, POX rats exhibited a negative discrimination ratio indicative of impaired recognition memory. The results indicate that this model of survival from severe POX exposure can be employed to study some of the molecular bases for OP-induced chronic behavioral and cognitive comorbidities and develop therapies for their treatment.
- Cardiac memory during rather than after termination of left bundle branch block. [JOURNAL ARTICLE]
- J Electrocardiol 2014 Aug 2.
An 83-year-old woman with chronic left bundle branch block and remote history of pacemaker implantation for intermittent AV block was hospitalized for fatigue and leg swelling. She had no cardiac complaints. Routine 12-lead electrocardiogram showed sinus rhythm with left bundle branch block. There were diffuse negative T waves in the inferior and anterolateral leads that were concordant with the QRS complexes. Echocardiogram was normal and nuclear perfusion heart scan showed no abnormality. It was noted that the negative T waves during left bundle branch block were in the exact same leads as were the deep negative QRS complexes during ventricular pacing. The electrocardiographic changes were consistent with cardiac memory. This case is unique because cardiac memory in patients with intermittent left bundle branch block typically occurs when the QRS complexes normalize and not during left bundle branch block itself. Our findings indicate that memory Ts can develop not only after normalization of wide complex rhythms but also with alternating wide complex rhythms as in the presented case where a ventricular paced rhythm was replaced by left bundle branch block.
- Anisomycin injection in area CA3 of the hippocampus impairs both short-term and long-term memories of contextual fear. [JOURNAL ARTICLE]
- Learn Mem 2014; 21(6):311-315.
Protein synthesis is involved in the consolidation of short-term memory into long-term memory. Previous electrophysiological data concerning LTP in CA3 suggest that protein synthesis in that region might also be necessary for short-term memory. We tested this hypothesis by locally injecting the protein synthesis inhibitor anisomycin in hippocampal area CA1 or CA3 immediately after contextual fear conditioning. As previously shown, injections in CA1 impaired long-term memory but spared short-term memory. Conversely, injections in CA3 impaired both long-term and short-term memories. We conclude that early steps of experience-induced plasticity occurring in CA3 and underlying short-term memory require protein synthesis.
- Validation assessment of risk tools to predict outcome after thrombolytic therapy for acute ischemic stroke. [JOURNAL ARTICLE]
- Clin Neurol Neurosurg 2014 Aug 15.:189-193.
We evaluated the reliability of eight clinical prediction models for symptomatic intracerebral hemorrhage (sICH) and long-term functional outcome in stroke patients treated with thrombolytics according to clinical practice.In a cohort of 169 patients, 60 patients (35.5%) received IV rtPA according to the European license criteria. The remaining patients received off-label IV rtPA and/or were treated with intra-arterial thrombolysis. We used receiver operator characteristic curves to analyze the discriminative capacity of the MSS score, the HAT score, the SITS SICH score, the SEDAN score and the GRASPS score for sICH according to the NINDS and the ECASSII criteria. Similarly, the discriminative capacity of the s-TPI, the iScore and the DRAGON score were assessed for the modified Rankin Scale (mRS) score at 3 months poststroke. An area under the curve (c-statistic) >0.8 was considered to reflect good discriminative capacity. The reliability of the best performing prediction model was further examined with calibration curves. Separate analyses were performed for patients meeting the European license criteria for IV rtPA and patients outside these criteria.For prediction of sICH c-statistics were 0.66-0.86 and the MMS yielded the best results. For functional outcome c-statistics ranged from 0.72 to 0.86 with s-TPI as best performer. The s-TPI had the lowest absolute error on the calibration curve for predicting excellent outcome (mRS 0-1) and catastrophic outcome (mRS 5-6).All eight clinical models for outcome prediction after thrombolysis for acute ischemic stroke showed fair predictive value in patients treated according daily practice. The s-TPI had the best discriminatory ability and was well calibrated in our study population.
- Neuropsychiatric and seizure outcomes in nonparaneoplastic autoimmune limbic encephalitis. [JOURNAL ARTICLE]
- Epilepsy Behav 2014 Aug 23.:21-25.
Autoimmune limbic encephalitis is an inflammatory condition often associated with an underlying neoplasm. However, a subset of patients does not have an underlying tumor and have a nonparaneoplastic form of this condition. The focus in the literature has been on the acute phase of this illness, but long-term follow-up is lacking.A retrospective chart review, over a period of 15years, of patients carrying a diagnosis of encephalitis was performed. Inclusion criteria included a clinical presentation consistent with limbic encephalitis (subacute behavioral change, seizures, or anterograde memory decline) and an identifiable autoantibody, inflammatory CSF (>5white blood cells/mm(3)), or limbic hyperintensities on MRI. Readmission rates and long-term psychiatric, psychosocial, and seizure outcomes were evaluated.A total of 16 patients were identified. Clinical presentation included new-onset seizures in 14 (88%), behavioral changes in 7 (44%), and memory decline in 5 (31%). Four (25%) patients presented with status epilepticus. Five patients had antibodies against NMDAR (N-methyl-d-aspartate receptor) and four against VGKC (voltage gated potassium channel) complex. An inflammatory CSF was noted in 7 (44%) and MRI changes in 9 (56%). Four were readmitted during the follow-up period. Around half the patients continued to have medically drug/treatment-refractory seizures, while 7 (44%) had a new psychiatric diagnosis (mood disorder, anxiety disorder, or impulse control disorder). The majority of the patients continued to reside at home, while 43% of previously employed patients lost employment.Nonparaneoplastic autoimmune limbic encephalitis is a neuropsychiatric condition presenting with a combination of seizures (sometimes status epilepticus), behavioral changes, and memory decline. After the acute phase, patients are at risk of readmissions, medically refractory seizures, chronic mood and anxiety disorders, and loss of employment.
- Vagal tone as a biomarker of long-term memory for a stressful social event at 4 months. [JOURNAL ARTICLE]
- Dev Psychobiol 2014 Aug 29.
This study investigates infants' memory for social stress after a 15-day retention interval using behavior and respiratory sinus arrhythmia (RSA). Experimental group infants were exposed to face-to-face still-face paradigm (FFSF) two times; the first time at 4 months and after a 2-week interval. Control group infants were exposed to FFSF only once at 4 months plus 2 weeks. Infants were categorized as suppressors or non-suppressors based on the direction of RSA change at first FFSF exposure. No behavioral differences were found among groups and exposure conditions. In the experimental group suppressors changed and showed no suppression when re-exposed 2 weeks later to FFSF. Non-suppressors showed no change in RSA from the first to the second exposure to FFSF. Control infants showed similar RSA changes to experimental infants at their first exposure. Findings indicate that 4-month-old infants have memory for social stress related to individual differences in autonomic reactivity. © 2014 Wiley Periodicals, Inc. Dev Psychobiol.
- Caffeic acid protects mice from memory deficits induced by focal cerebral ischemia. [JOURNAL ARTICLE]
- Behav Pharmacol 2014 Oct; 25(7):637-647.
Brain ischemia pathophysiology involves a complex cascade of events such as inflammation and oxidative stress that lead to neuronal loss and cognitive deficits. Caffeic acid (CA) is a natural phenolic compound with antioxidant and anti-inflammatory properties. To evaluate the neuroprotective efficacy of this compound in mice subjected to a permanent middle cerebral artery occlusion, animals were pretreated and post-treated with CA, 2, 20, and 60 mg/kg/day, intraperitoneally, at 24, 48, 72, 96, or 120 h after ischemia. Animals were evaluated at 24 h after the permanent middle cerebral artery occlusion for brain infarction and neurological deficit score. At 72 h after the occlusion, animals were evaluated for locomotor activity, working memory, and short-term aversive memory; long-term aversive memory was evaluated 24 h after the evaluation of short-term aversive memory. Finally, at 120 h after the event, spatial memory and the expression levels of synaptophysin (SYP), SNAP-25, and caspase 3 were evaluated. The treatment with CA reduced the infarcted area and improved neurological deficit scores. There was no difference in locomotor activity between groups. The working, spatial, and long-term aversive memory deficits improved with CA. Furthermore, western blotting data showed that the expression of SYP, which correlates with synaptic formation and function, decreased after ischemic insult, and CA inhibited the reduction of SYP expression. Ischemia also increased, and CA treatment decreased, caspase 3 expression. These results suggest that CA exerts neuroprotective and antidementia effects, at least in part, by preventing the loss of neural cells and synapses in ischemic brain injury.