Recognition Memory Task Research Articles

Single neuron recordings of bilinguals performing in a continuous recognition memory task.

We report the results of a bilingual continuous recognition memory task during which single- and multi-neuron activity was recorded in human subjects with intracranial microwire implants. Subjects (n = 5) were right-handed Spanish-English bilinguals who were undergoing evaluation prior to surgery for severe epilepsy. Subjects were presented with Spanish and English words and the task was to determine whether any given word had been seen earlier in the testing session, irrespective of the language in which it had appeared. Recordings in the left and right hippocampus revealed notable laterality, whereby both Spanish and English items that had been seen previously in the other language (switch trials) triggered increased neural firing in the left hippocampus. Items that had been seen previously in the same language (repeat trials) triggered increased neural firings in the right hippocampus. These results are consistent with theories that propose roles of both the left- and right-hemisphere in real-time linguistic processing. Importantly, this experiment presents the first instance of intracranial recordings in bilinguals performing a task with switching demands.

Visual cortical networks align with behavioral measures of context-sensitivity in early childhood

This study investigates how visual cortical networks align with context-sensitivity, namely the relative focus on the object versus the background of a visual scene, in early childhood. Context-sensitivity was assessed by a picture description and a recognition memory task. To segregate object and background processing in the visual cortex in 5- and 7-year-old children, object and background were presented at different frequencies (12 Hz or 15 Hz), evoking disparate neuronal responses (steady state visually evoked potentials, SSVEPs) in the electroencephalogram. In younger compared to older children the background elicited higher SSVEPs. Visual cortical processing of object versus background was associated with behavioral measures for older but not for younger children. This relation was strongest for verbal descriptions and generalized to the cortical processing of abstract stimuli and object and background presented alone. Thus, visual cortical networks restructure and align with behavioral measures of context-sensitivity in early childhood.

Experiences in Virtual Reality: a Window to Autobiographical Memory

VR-based paradigms could substantially increase the ecological validity of various psychological research topics as VR allows for submerging into real-life experiences under controlled laboratory conditions. In particular, in the field of mnemonic research, concerns have been raised that “laboratory memory” differs significantly from “real-life” autobiographical memory. Our study aimed to assess the immersive qualities of VR not only upon application but -more importantly- during the retrieval of the virtual experiences subsequent to a VR session. We presented participants with either a 360° VR or a 2D video of a motorcycle ride followed by an unannounced recognition memory task 48 h later. Increased retrieval success and delayed reaction times in the VR group indicate that immersive VR experiences become part of an extensive autobiographical associative network, whereas the conventional video experience remains an isolated episodic event.

Early life stress explains reduced positive memory biases in remitted depression

BackgroundThere is contradictory evidence regarding negative memory biases in major depressive disorder (MDD) and whether these persist into remission, which would suggest their role as vulnerability traits rather than correlates of mood state. Early life stress (ELS), common in patients with psychiatric disorders, has independently been associated with memory biases, and confounds MDD versus control group comparisons. Furthermore, in most studies negative biases could have resulted from executive impairments rather than memory difficulties per se. MethodsTo investigate whether memory biases are relevant to MDD vulnerability and how they are influenced by ELS, we developed an associative recognition memory task for temporo-spatial contexts of social actions with low executive demands, which were matched across conditions (self-blame, other-blame, self-praise, other-praise). We included fifty-three medication-free remitted MDD (25 with ELS, 28 without) and 24 healthy control (HC) participants without ELS. ResultsOnly MDD patients with ELS showed a reduced bias (accuracy/speed ratio) towards memory for positive vs. negative materials when compared with MDD without ELS and with HC participants; attenuated positive biases correlated with number of past major depressive episodes, but not current symptoms. There were no biases towards self-blaming or self-praising memories. ConclusionsThis demonstrates that reduced positive biases in associative memory were specific to MDD patients with ELS rather than a general feature of MDD, and were associated with lifetime recurrence risk which may reflect a scarring effect. If replicated, our results would call for stratifying MDD patients by history of ELS when assessing and treating emotional memories.

OBJECT AND SCENE MEMORY ARE DIFFERENTIALLY ASSOCIATED WITH CSF MARKERS OF ALZHEIMER’S DISEASE AND MRI VOLUMETRY

Alzheimer's Disease (AD) is characterized by progressive tau-pathology in perirhinal and entorhinal cortices (ErC), hippocampus, parahippocampal cortex and the retrosplenial/posterior cingulate region (RsC/PCC). The latter also shows early amyloid plaque accumulation. While these regions form a network for complex objects-in-scene memories, there is a segregation of object memory into a perirhinal-entorhinal and scene-layout memory into a RsC/PCC-parahippocampal-entorhinal pathway. Here we investigated whether complex objects-in-scene memory, as opposed to isolated object or scene-layout memory is correlated with CSF levels of Aß42 and phospho-tau and MR volume and thickness measures. 204 participants (cognitively healthy, subjective memory complaints, mild cognitive impairment or early AD) of the DELCODE study of the DZNE performed a complex scene recognition memory task. CSF samples were available from 80 participants. 78 participants also performed a second task on mnemonic discrimination of objects (in the absence of scenes) and scenes (in the absence of objects). Of these 28 CSF samples were available. MR thickness measures were obtained from T1 and T2-weighted images using Freesurfer 6. Objects-in-scene recognition memory correlated with right and left PCC volume (p=0.005; p=0.047), right and left hippocampal volume (p=0.002; p=0.001), Aß42, phospho-tau and their ratio (p=0.002; p=0.002; p=0.000). Isolated object and scene discrimination correlated with left and right hippocampal volume (Scene: p=0.039; p=0.006; Object: p=0.011; p=0.001); scene memory correlated with right and object memory with both left and right ErC thickness (Scene: p=0.027; Object: p=0.024; p=0.031). A scene-minus-object difference score correlated with Aß42 levels indicating that decreasing levels of Aß42 were associated with selective decline of scene discrimination (p=0.034). When considering only healthy older adults, object discrimination relatively selectively correlated with right and left hippocampal volume (n=57; rp=0.022; p=0.005), left entorhinal thickness (p=0.042) and with phospho-tau levels (n=19; p=0.052). These data suggest that complex object-in-scene recognition captures variance caused by both tau and amyloid pathology. A domain-specific breakdown, however, indicates that tau-related variance tends to be captured by object discrimination whereas amyloid pathology is captured by scene discrimination performance. The findings are compatible with the possibility that object and scene discrimination track different stages of disease progression in AD.

CROSSCULTURAL NEUROPSYCHOLOGICAL ASSESSMENT OF DEMENTIA: DIRECTIONS FOR TEST DEVELOPMENT

Neuropsychological assessment plays an important role in the diagnostic work-up for dementia. Increasing evidence suggests that Western neuropsychological measures are inappropriate for culturally and linguistically diverse populations, due to multiple obstacles: language barriers, cultural differences such as inexperience with timed tests, insufficient normative data and the use of culture-specific stimuli. Considering the rising numbers of non-Western elderly immigrants with dementia in the Netherlands, there is an urgent need for appropriate cross-cultural neuropsychological measures. The aim of the current study was to assess which test characteristics were suitable for a population of non-Western immigrants. 49 Moroccan, Turkish and Cape Verdean patients with diverse cognitive complaints visited the multicultural memory clinic of the Alzheimer Center Rotterdam, The Netherlands. 35% of the patients were illiterate; 71% did not complete primary education. An adapted test protocol including the Cross Cultural Dementia screening test (CCD‡) was used, as well as Dutch neuropsychological tests that are considered cross-culturally applicable. A medical interpreter translated the test instructions. Nearly all patients could complete the recognition memory task of the CCD, a test that is not timed and contains culture-sensitive photographs. 24% of patients were unable to finish the CCD's timed task involving dot counting (similar to TMT A); 60% of all patients were unable to complete the combined counting/switching task. Most of the other cognitive tests required too many scholastic skills and abstract reasoning (e.g. figure copy, digit span, BADS key search test) and were therefore not even attempted with many patients. Qualitative analysis of the results revealed difficulties in recognizing line drawings (e.g. visual-associative memory), drawing linear designs and processing depth cues. Similarly, tests relying heavily on verbal responses and vocabulary (such as naming tasks, verbal memory, orientation questions) often were not administered. In the memory clinic, neuropsychological assessments requiring basic scholastic skills, involving line drawings and relying heavily on language/vocabulary are unfit for use in linguistically and culturally diverse populations. Adapting stimuli to include life-like material (e.g. photographs) might be promising. Our future research will focus on the development of cross-cultural tests measuring all cognitive domains. ‡ Goudsmit et al. 2016 J Clin Exp Neuropsychol.

Guanfacine Attenuates Adverse Effects of Dronabinol (THC) on Working Memory in Adolescent-Onset Heavy Cannabis Users: A Pilot Study.

The cannabinoid-1 receptor (CB1R) agonist Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, adversely effects working memory performance in humans. The α2A-adrenoceptor (AR) agonist guanfacine improves working memory performance in humans. The authors aimed to determine the effects of short-term (6 days) treatment with guanfacine on adverse cognitive effects produced by THC. Employing a double-blind, placebo-controlled crossover design, the cognitive, subjective, and cardiovascular effects produced by oral THC (20 mg) administration were determined twice in the same cannabis users: once after treatment with placebo and once after treatment with guanfacine (3 mg/day). Compared with performance at baseline, THC negatively affected accuracy on spatial working memory trials while participants were maintained on placebo (p=0.012) but not guanfacine (p=0.497); compared with placebo, accuracy was significantly (p=0.003, Cohen's d=-0.640) improved while individuals were treated with guanfacine. Similarly, compared with baseline, THC increased omission errors on an attentional task while participants were maintained on placebo (p=0.017) but not on guanfacine (p=0.709); compared with placebo, there were significantly (p=0.034, Cohen's d=0.838) fewer omissions while individuals were maintained on guanfacine. Although THC increased visual analog scores of subjective effects and heart rate, these increases were similar during treatment with placebo and guanfacine. THC did not significantly affect performance of a recognition memory task or blood pressure while individuals were maintained on either treatment. Although preliminary, these results suggest that guanfacine warrants further testing as a potential treatment for cannabis-induced cognitive deficits.

Functional brain networks during picture encoding and recognition in different odor contexts

Contextual odors can serve as retrieval cues when applied during encoding and recall/recognition of information. To investigate the neuronal basis of these observations, we collected functional MRI data while participants (n=51) performed an encoding and recognition memory task during which odors (congruent: CO or incongruent: IO) were presented as contextual cues. Recognition performance was not influenced by odor, but there was increased activation in the piriform cortex during successful encoding in the CO group, possibly indicating enhanced retrieval of information previously integrated with an olfactory percept. Moreover, group-independent component analysis revealed a stronger task-modulation of subcortical networks for IO versus CO during the recognition task, pointing to differences in olfactory processing. These observations provide a deeper understanding of the involvement of functional neuronal networks in memory tasks and a basis for further evaluation of the impact of odor contexts.

Cingulo-opercular activity affects incidental memory encoding for speech in noise

Correctly understood speech in difficult listening conditions is often difficult to remember. A long-standing hypothesis for this observation is that the engagement of cognitive resources to aid speech understanding can limit resources available for memory encoding. This hypothesis is consistent with evidence that speech presented in difficult conditions typically elicits greater activity throughout cingulo-opercular regions of frontal cortex that are proposed to optimize task performance through adaptive control of behavior and tonic attention. However, successful memory encoding of items for delayed recognition memory tasks is consistently associated with increased cingulo-opercular activity when perceptual difficulty is minimized. The current study used a delayed recognition memory task to test competing predictions that memory encoding for words is enhanced or limited by the engagement of cingulo-opercular activity during challenging listening conditions. An fMRI experiment was conducted with twenty healthy adult participants who performed a word identification in noise task that was immediately followed by a delayed recognition memory task. Consistent with previous findings, word identification trials in the poorer signal-to-noise ratio condition were associated with increased cingulo-opercular activity and poorer recognition memory scores on average. However, cingulo-opercular activity decreased for correctly identified words in noise that were not recognized in the delayed memory test. These results suggest that memory encoding in difficult listening conditions is poorer when elevated cingulo-opercular activity is not sustained. Although increased attention to speech when presented in difficult conditions may detract from more active forms of memory maintenance (e.g., sub-vocal rehearsal), we conclude that task performance monitoring and/or elevated tonic attention supports incidental memory encoding in challenging listening conditions.

Real‐time activation of central cholinergic circuits during recognition memory

Short latency afferent inhibition (SAI) is a paired-pulse transcranial magnetic stimulation (TMS) protocol that consists in the inhibition of the motor evoked potentials (MEPs) by afferent sensory impulses. SAI is thought to be mediated by cholinergic projections over M1 and can be considered a putative marker of central cholinergic activity. It is known that memory processes are regulated by acetylcholine. Nonetheless, the influence of memory tasks on SAI has not been investigated. Here we tested changes in SAI circuits in healthy subjects performing a computerized non-verbal recognition memory task (RMT) requiring to recognize previously encoded faces. SAI protocol was recorded during five phases of the RMT: baseline, encoding, consolidation, retrieval, and post-task. In the control task, subjects were asked to judge a visual feature of not previously presented faces. SAI protocol was applied over the same conditions as in the RMT. We found that SAI remarkably increases during the retrieval phase of the RMT as compared to baseline. On the other hand no change was observed during the control task. These findings show that SAI can be modulated by ongoing memory processes and support the hypothesis that SAI can be considered as a neurophysiological marker of central cholinergic activity.

The onset and time course of semantic priming during rapid recognition of visual words.

In 2 experiments, we assessed the effects of response latency and task-induced goals on the onset and time course of semantic priming during rapid processing of visual words as revealed by ocular response tasks. In Experiment 1 (ocular lexical decision task), participants performed a lexical decision task using eye movement responses on a sequence of 4 words. In Experiment 2, the same words were encoded for an episodic recognition memory task that did not require a metalinguistic judgment. For both tasks, survival analyses showed that the earliest observable effect (divergence point [DP]) of semantic priming on target-word reading times occurred at approximately 260 ms, and ex-Gaussian distribution fits revealed that the magnitude of the priming effect increased as a function of response time. Together, these distributional effects of semantic priming suggest that the influence of the prime increases when target processing is more effortful. This effect does not require that the task include a metalinguistic judgment; manipulation of the task goals across experiments affected the overall response speed but not the location of the DP or the overall distributional pattern of the priming effect. These results are more readily explained as the result of a retrospective, rather than a prospective, priming mechanism and are consistent with compound-cue models of semantic priming. (PsycINFO Database Record

Behavioral and Neural Manifestations of Reward Memory in Carriers of Low-Expressing versus High-Expressing Genetic Variants of the Dopamine D2 Receptor.

Dopamine is critically important in the neural manifestation of motivated behavior, and alterations in the human dopaminergic system have been implicated in the etiology of motivation-related psychiatric disorders, most prominently addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor (DRD2) availability in the striatum, and the DRD2 TaqIA (rs1800497) and C957T (rs6277) genetic polymorphisms have previously been linked to individual differences in striatal dopamine metabolism and clinical risk for alcohol and nicotine dependence. Here, we investigated the hypothesis that the variants of these polymorphisms would show increased reward-related memory formation, which has previously been shown to jointly engage the mesolimbic dopaminergic system and the hippocampus, as a potential intermediate phenotype for addiction memory. To this end, we performed functional magnetic resonance imaging (fMRI) in 62 young, healthy individuals genotyped for DRD2 TaqIA and C957T variants. Participants performed an incentive delay task, followed by a recognition memory task 24 h later. We observed effects of both genotypes on the overall recognition performance with carriers of low-expressing variants, namely TaqIA A1 carriers and C957T C homozygotes, showing better performance than the other genotype groups. In addition to the better memory performance, C957T C homozygotes also exhibited a response bias for cues predicting monetary reward. At the neural level, the C957T polymorphism was associated with a genotype-related modulation of right hippocampal and striatal fMRI responses predictive of subsequent recognition confidence for reward-predicting items. Our results indicate that genetic variations associated with DRD2 expression affect explicit memory, specifically for rewarded stimuli. We suggest that the relatively better memory for rewarded stimuli in carriers of low-expressing DRD2 variants may reflect an intermediate phenotype of addiction memory.

Aging Impairs Hippocampal- Dependent Recognition Memory and LTP and Prevents the Associated RyR Up-regulation.

Recognition memory comprises recollection judgment and familiarity, two different processes that engage the hippocampus and the perirhinal cortex, respectively. Previous studies have shown that aged rodents display defective recognition memory and alterations in hippocampal synaptic plasticity. We report here that young rats efficiently performed at short-term (5 min) and long-term (24 h) hippocampus-associated object-location tasks and perirhinal cortex-related novel-object recognition tasks. In contrast, aged rats successfully performed the object-location and the novel-object recognition tasks only at short-term. In addition, aged rats displayed defective long-term potentiation (LTP) and enhanced long-term depression (LTD). Successful long-term performance of object-location but not of novel-object recognition tasks increased the protein levels of ryanodine receptor types-2/3 (RyR2/RyR3) and of IP3R1 in young rat hippocampus. Likewise, sustained LTP induction (1 h) significantly increased RyR2, RyR3 and IP3R1 protein levels in hippocampal slices from young rats. In contrast, LTD induction (1 h) did not modify the levels of these three proteins. Naïve (untrained) aged rats displayed higher RyR2/RyR3 hippocampal protein levels but similar IP3R1 protein content relative to young rats; these levels did not change following exposure to either memory recognition task or after LTP or LTD induction. The perirhinal cortex from young or aged rats did not display changes in the protein contents of RyR2, RyR3, and IP3R1 after exposure at long-term (24 h) to the object-location or the novel-object recognition tasks. Naïve aged rats displayed higher RyR2 channel oxidation levels in the hippocampus compared to naïve young rats. The RyR2/RyR3 up-regulation and the increased RyR2 oxidation levels exhibited by aged rat hippocampus are likely to generate anomalous calcium signals, which may contribute to the well-known impairments in hippocampal LTP and spatial memory that take place during aging.

Behavioural and neural evidence for the impact of fluency context on conscious memory

It has been recently suggested that fluency may impact recognition memory performance when the fluency context varies from trial-to-trial. Surprisingly, such an effect has proved difficult to detect in the masked priming paradigm, one of the most popular means to increase fluency-based memory judgements. We conducted a functional magnetic resonance imaging (fMRI) experiment in which participants encoded words at study and, at test, performed a recognition memory task within a masked priming procedure. In order to optimise the chances of finding priming effects on recognition memory performance, we used low-frequency words, which have been shown to increase hits relative to false alarms and enhance masked priming effects. Fluency context was manipulated by either mixing primed and unprimed trials [Random context (RC) experiment] or blocking primed and unprimed trials [Blocked context (BC) experiment]. Behaviourally, priming affected high-confidence memory performance only in the RC experiment. This behavioural effect correlated positively with neural priming in several recognition memory regions. Moreover, we observed a functional coupling between the left middle temporal gyrus and the left parietal and posterior cingulate cortices that was greater for primed relative to unprimed words. In contrast, in the BC experiment, despite similar activity in recognition-memory-related regions, we did not find any significant correlations between neural and behavioural priming. Finally, we observed striking differences in the neural correlates of masked priming between the RC and BC experiments not only in location but also in direction of the neural response. Possible implications of these findings are discussed.

Chronic sleep restriction promotes brain inflammation and synapse loss, and potentiates memory impairment induced by amyloid-β oligomers in mice

It is increasingly recognized that sleep disturbances and Alzheimer’s disease (AD) share a bidirectional relationship. AD patients exhibit sleep problems and alterations in the regulation of circadian rhythms; conversely, poor quality of sleep increases the risk of development of AD. The aim of the current study was to determine whether chronic sleep restriction potentiates the brain impact of amyloid-β oligomers (AβOs), toxins that build up in AD brains and are thought to underlie synapse damage and memory impairment. We further investigated whether alterations in levels of pro-inflammatory mediators could play a role in memory impairment in sleep-restricted mice. We found that a single intracerebroventricular (i.c.v.) infusion of AβOs disturbed sleep pattern in mice. Conversely, chronically sleep-restricted mice exhibited higher brain expression of pro-inflammatory mediators, reductions in levels of pre- and post-synaptic marker proteins, and exhibited increased susceptibility to the impact of i.c.v. infusion of a sub-toxic dose of AβOs (1pmol) on performance in the novel object recognition memory task. Sleep-restricted mice further exhibited an increase in brain TNF-α levels in response to AβOs. Interestingly, memory impairment in sleep-restricted AβO-infused mice was prevented by treatment with the TNF-α neutralizing monoclonal antibody, infliximab. Results substantiate the notion of a dual relationship between sleep and AD, whereby AβOs disrupt sleep/wake patterns and chronic sleep restriction increases brain vulnerability to AβOs, and point to a key role of brain inflammation in increased susceptibility to AβOs in sleep-restricted mice.

Brain signatures of early lexical and morphological learning of a new language

Morphology is an important part of language processing but little is known about how adult second language learners acquire morphological rules. Using a word-picture associative learning task, we have previously shown that a brief exposure to novel words with embedded morphological structure (suffix for natural gender) is enough for language learners to acquire the hidden morphological rule. Here we used this paradigm to study the brain signatures of early morphological learning in a novel language in adults. Behavioural measures indicated successful lexical (word stem) and morphological (gender suffix) learning. A day after the learning phase, event-related brain potentials registered during a recognition memory task revealed enhanced N400 and P600 components for stem and suffix violations, respectively. An additional effect observed with combined suffix and stem violations was an enhancement of an early N2 component, most probably related to conflict-detection processes. Successful morphological learning was also evident in the ERP responses to the subsequent rule-generalization task with new stems, where violation of the morphological rule was associated with an early (250–400ms) and late positivity (750–900ms). Overall, these findings tend to converge with lexical and morphosyntactic violation effects observed in L1 processing, suggesting that even after a short exposure, adult language learners can acquire both novel words and novel morphological rules.

Specialized Information Processing Deficits and Distinct Metabolomic Profiles Following TM-Domain Disruption of Nrg1.

Although there is considerable genetic and pathologic evidence for an association between neuregulin 1 (NRG1) dysregulation and schizophrenia, the underlying molecular and cellular mechanisms remain unclear. Mutant mice containing disruption of the transmembrane (TM) domain of the NRG1 gene constitute a heuristic model for dysregulation of NRG1-ErbB4 signaling in schizophrenia. The present study focused on hitherto uncharacterized information processing phenotypes in this mutant line. Using a mass spectrometry-based metabolomics approach, we also quantified levels of unique metabolites in brain. Across 2 different sites and protocols, Nrg1 mutants demonstrated deficits in prepulse inhibition, a measure of sensorimotor gating, that is, disrupted in schizophrenia; these deficits were partially reversed by acute treatment with second, but not first-, generation antipsychotic drugs. However, Nrg1 mutants did not show a specific deficit in latent inhibition, a measure of selective attention that is also disrupted in schizophrenia. In contrast, in a “what–where–when” object recognition memory task, Nrg1 mutants displayed sex-specific (males only) disruption of “what–when” performance, indicative of impaired temporal aspects of episodic memory. Differential metabolomic profiling revealed that these behavioral phenotypes were accompanied, most prominently, by alterations in lipid metabolism pathways. This study is the first to associate these novel physiological mechanisms, previously independently identified as being abnormal in schizophrenia, with disruption of NRG1 function. These data suggest novel mechanisms by which compromised neuregulin function from birth might lead to schizophrenia-relevant behavioral changes in adulthood.

Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative.

Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up.Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD.Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ2 = 38.23, df = 14, p < 0.001).Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI.

Carbonic anhydrase activation enhances object recognition memory in mice through phosphorylation of the extracellular signal-regulated kinase in the cortex and the hippocampus

Rats injected with by d-phenylalanine, a carbonic anhydrase (CA) activator, enhanced spatial learning, whereas rats given acetazolamide, a CA inhibitor, exhibited impairments of fear memory consolidation. However, the related mechanisms are unclear. We investigated if CAs are involved in a non-spatial recognition memory task assessed using the object recognition test (ORT). Systemic administration of acetazolamide to male CD1 mice caused amnesia in the ORT and reduced CA activity in brain homogenates, while treatment with d-phenylalanine enhanced memory and increased CA activity. We provided also the first evidence that d-phenylalanine administration rapidly activated extracellular signal-regulated kinase (ERK) pathways, a critical step for memory formation, in the cortex and the hippocampus, two brain areas involved in memory processing. Effects elicited by d-phenylalanine were completely blunted by co-administration of acetazolamide, but not of 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate (C18), a CA inhibitor that, differently from acetazolamide, does not cross the blood brain barrier. Our results strongly suggest that brain but not peripheral CAs activation potentiates memory as a result of ERK pathway enhanced activation.

Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice

Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5μg/μl of insulin twice daily for 30 and 60days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice did not perform differently than controls, regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3 fold increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors – as reported to elicit a modulatory effect with acute administration. This leads to two alternative interpretations regarding long-term insulin IND in mice: 1) It causes an initial stage of insulin resistance to dampen the behaviors that would normally be modulated under acute insulin IND, but ability to clear a glucose challenge is still retained, or 2) There is a lack of behavioral modulation at high concentration of insulin attributed to the twice daily intervals of hyperinsulinemia caused by insulin IND administration without any insulin resistance, per se.