Memory In Subjects Research Articles

Functional activity changes in memory and emotional systems of healthy subjects with déjà vu

Déjà vu (DV) is a fascinating and mysterious human experience that has attracted interest from psychologists and neuroscientists for over a century. In recent years, several studies have been conducted to unravel the psychological and neurological correlates of this phenomenon. However, the neural mechanisms underlying the DV experience in benign manifestations are still poorly understood.Thirty-three healthy volunteers completed an extensive neuropsychiatric and neuropsychological battery including personality evaluation. The presence of DV was assessed with the Inventory for Deja vu Experiences Assessment. Participants underwent episodic memory learning test, and 2 days later during event-related functional magnetic resonance imaging (fMRI), they are asked to rate old and new pictures as a novel, moderately/very familiar, or recollected.We identified 18 subjects with DV (DV+) and 15 without DV (DV−) matched for demographical, neuropsychological, and personality characteristics. At a behavioral level, no significant difference was detected in the episodic memory tasks between DV+ and DV−. Functional magnetic resonance imaging analysis revealed that DV+, independently from task conditions, were characterized by increased activity of the bilateral insula coupled with reduced activation in the right parahippocampal, both hippocampi, superior/middle temporal gyri, thalami, caudate nuclei, and superior frontal gyri with respect to DV−. Our study demonstrates that individuals who experienced DV are not characterized by different performance underlying familiarity/recollection memory processes. However, fMRI results provide evidence that the physiological DV experience is associated with the employment of different neural responses of brain regions involved in memory and emotional processes.

Blueberry Extracts Supplementation Improves Cognitive Function in Elderly Patients with Mild Cognitive Impairment (P14-013-19)

ObjectivesAn intervention study was performed to determine if supplement containing blueberry extracts could improve cognitive function in the elderly patients with mild cognitive impairment (MCI). MethodsForty six MCI patients participated in the intervention study were paired based on their age, education level and initial the basic cognitive aptitude test (BCAT) scores and then randomly assigned to the intervention group (n = 23, which received 1.0 g/day of blueberry extracts) or blank control group (n = 23). The endpoint was the improvement in cognitive function as evaluated by BCATs. All parameters were measured before and after the treatment period of 12 weeks. ResultsAfter 12 weeks of intervention, we observed significant improvement in their total BCAT score, space imagery efficiency, working memory and recognition memory of subjects in patients with blueberry extracts supplementation comparing to those in the control group (P = 0.006, 0.023, 0.000, 0.005, respectively). However the levels of inflammatory factors (IL-6 and TNF-α in serum) showed no significant changes after intervention. ConclusionsThe data indicated that blueberry has a beneficial effect on cognitive function of the elderly MCI patients, which might provide therapeutic potential for Alzheimer’s disease. Funding SourcesThis work was supported by the State Key Program of National Natural Science Foundation of China and the State Key Program of National Natural Science Foundation of Tianjin. Supporting Tables, Images and/or Graphs▪▪▪▪▪

Role of Multivalency and Antigenic Threshold in Generating Protective Antibody Responses.

Vaccines play a vital role in protecting our communities against infectious disease. Unfortunately, some vaccines provide only partial protection or in some cases vaccine-mediated immunity may wane rapidly, resulting in either increased susceptibility to that disease or a requirement for more booster vaccinations in order to maintain immunity above a protective level. The durability of antibody responses after infection or vaccination appears to be intrinsically determined by the structural biology of the antigen, with multivalent protein antigens often providing more long-lived immunity than monovalent antigens. This forms the basis for the Imprinted Lifespan model describing the differential survival of long-lived plasma cell populations. There are, however, exceptions to this rule with examples of highly attenuated live virus vaccines that are rapidly cleared and elicit only short-lived immunity despite the expression of multivalent surface epitopes. These exceptions have led to the concept that multivalency alone may not reliably determine the duration of protective humoral immune responses unless a minimum number of long-lived plasma cells are generated by reaching an appropriate antigenic threshold of B cell stimulation. Examples of long-term and in some cases, potentially lifelong antibody responses following immunization against human papilloma virus (HPV), Japanese encephalitis virus (JEV), Hepatitis B virus (HBV), and Hepatitis A virus (HAV) provide several lessons in understanding durable serological memory in human subjects. Moreover, studies involving influenza vaccination provide the unique opportunity to compare the durability of hemagglutinin (HA)-specific antibody titers mounted in response to antigenically repetitive whole virus (i.e., multivalent HA), or detergent-disrupted “split” virus, in comparison to the long-term immune responses induced by natural influenza infection. Here, we discuss the underlying mechanisms that may be associated with the induction of protective immunity by long-lived plasma cells and their importance in future vaccine design.

Influence of two functional polymorphisms in NOS1 on baseline cortisol and working memory in healthy subjects

IntroductionThe neuronal isoform of the nitric oxide synthase (NOS-I) encoded by NOS1 is the main source of nitric oxide (NO) in the brain. Reduced NO signaling in the prefrontal cortex has been linked to schizophrenia and cognitive processes while reduced striatal NOS1 expression has been associated with impulsive behavior. MethodsTo evaluate the effect of two functional polymorphisms in alternative first exons of NOS1, ex1f-VNTR and ex1c-SNP rs41279104, on the HPA stress axis and neurocognitive abilities, 280 healthy subjects were genotyped, had their salivary cortisol levels measured and were assessed in verbal memory, verbal fluency, working memory and verbal IQ by using the California Verbal Learning Test (CVLT), the Regensburger test of verbal fluency (RWT), a n-back task and subscales of the Wechsler Adult Intelligence Scale III (WAIS-III). ResultsSchizophrenia risk (A)-allele carriers of NOS1 ex1c-SNP rs41279104 displayed significantly lower baseline cortisol levels (p = 0.004). NOS1 ex1f-VNTR genotype carriers showed differences in working memory performance (p = 0.05) in a gene-dose effect manner, with homozygous carriers of the short impulsivity-risk allele committing most commission errors. Finally, A-allele carriers of the NOS1 ex1c-SNP rs41279104 tended to react faster during the working memory task (p = 0.065). ConclusionFor the first time, we demonstrated an influence of the NOS1 ex1c-SNP rs41279104 on salivary cortisol levels and additionally implicate the A-allele in an enhanced reaction time during a working memory task. Regarding the NOS1 ex1f-VNTR our study supports the previously reported influence on impulsivity, lending further support to the hypothesis that this genetic variant underlies impulsive behavior.

Glycated Hemoglobin, but not Insulin Sensitivity, is Associated with Memory in Subjects with Obesity.

Obesity has been related to later-life dementia. Serum glucose levels and insulin resistance are known to influence cognition in individuals with diabetes. This study aimed to evaluate memory function in middle-aged individuals with obesity in association with glucose metabolism and brain iron content. This was a cross-sectional case-control study including 121 participants aged 27.2 to 66.6years (56 without obesity, 65 with obesity) stratified according to sex and menopausal status. Insulin sensitivity, body composition, brain iron content, and memory function were evaluated by euglycemic hyperinsulinemic clamp, dual-energy x-ray absorptiometry, magnetic resonance relaxometry (R2*), and California Verbal Learning Test, respectively. Women with obesity, but not men, had lower scores in some California Verbal Learning Tests in association with metabolic parameters and increased brain iron content compared with controls. Fasting plasma glucose, glycated hemoglobin (HbA1c; within normal range), and R2* were negatively associated with memory scores, whereas insulin sensitivity showed positive associations. Remarkably, only HbA1c levels and R2* in the right inferior fronto-orbital region remained significant after controlling for age, sex, education, and BMI. Impairments in memory function in middle-aged women with obesity are associated with HbA1c levels and brain iron content independently of insulin sensitivity. These results may have implications in the design of therapeutic strategies in women with obesity.

Slow oscillatory transcranial direct current stimulation (so-tDCS) during slow wave sleep has no effects on declarative memory in healthy young subjects

BackgroundThe manipulation of specific brain oscillations by applying transcranial electrical stimulation techniques in order to enhance memory processes during sleep has become an intriguing field of research. A seminal study found a positive effect of slow-oscillatory transcranial direct current stimulation (so-tDCS) on sleep-dependent consolidation of declarative memories. Since then several studies have tried to replicate this result with inconsistent findings. Objective/HypothesisThis study aimed to reexamine effects of so-tDCS on declarative memory observed in young participants based on a previously described stimulation protocol used in elderly subjects. Methods23 healthy participants (mean ± SD: 23.2 ± 1.9 years; 13 women) completed a word-pair test and a sequential finger tapping test before and after sleep. Participants received anodal so-tDCS bifrontaly at a frequency of 0.75 Hz or sham stimulation during NREM sleep N2, following a double-blind, placebo controlled, counterbalanced, randomized crossover design. Data were analyzed with respect to possible effects of stimulation on memory performances, sleep staging, spindle densities and EEG power in eight frequency bands. ResultsStimulation had no significant effect on sleep dependent memory consolidation or on sleep macro- and microstructure. Independent of stimulation, procedural memory performances increased and declarative memory performances decreased overnight. This decline was less pronounced when participants had more than one learning opportunity. Fast parietal but not slow frontal spindle densities diminished from baseline to stimulation-free intervals under both stimulation conditions. ConclusionThe present study could not reproduce the results of the seminal study in young subjects, but it is consistent with results observed in elderly subjects using the same protocol. Irrespective of stimulation, re-encoding opportunities in the word-pair test had an impact on memory strength and retrieval performance.

Abstract # 2050 The effect of Intranasal Insulin in the CNS in Alzheimer’s disease

Research on intranasal delivery of drugs, peptides, and proteins has grown over the past decade as an alternate way to deliver substrates to the brain. Recent work has shown intranasal delivery of insulin in humans improves memory and cognition in healthy subjects as well as patients with Alzheimer’s disease. However, the molecular mechanism for the beneficial effect of insulin on memory has yet to be elucidated. To determine how intranasal insulin may be improving cognition, we utilized the SAMP8 mouse model of Alzheimer’s disease. These mice are known to develop cognitive impairments by 9 months of age and intranasal insulin can improve memory in 12-month old mice. We performed RNA sequencing analysis on the hippocampus in young SAMP8 mice and aged SAMP8 mice treated with and without insulin. While many genes and pathways were changed in our comparisons, we found genes were predominantly upregulated in 3 key pathways with age and downregulated with insulin administration. These pathways include the T cell receptor signaling pathway, cytokine-cytokine receptor interaction, and cell adhesion molecule pathway. Based on these inflammatory pathways driven by gene changes, we further investigated the impact of intranasal insulin on brain inflammation. This work further shows the important role of insulin in improving memory.

Characteristics of the rhythmic memory of healthy subjects and Parkinson’s patients:

Characteristics of the rhythmic memory of healthy subjects and Parkinson’s patients:

Relationship between Alzheimer's disease-associated SNPs within the CLU gene, local DNA methylation and episodic verbal memory in healthy and schizophrenia subjects

Genetic variation may impact on local DNA methylation patterns. Therefore, information about allele-specific DNA methylation (ASM) within disease-related loci has been proposed to be useful for the interpretation of GWAS results. To explore mechanisms that may underlie associations between Alzheimer's disease (AD) and schizophrenia risk CLU gene and verbal memory, one of the most affected cognitive domains in both conditions, we studied DNA methylation in a region between AD-associated SNPs rs9331888 and rs9331896 in 72 healthy individuals and 73 schizophrenia patients. Using single-molecule real-time bisulfite sequencing we assessed the haplotype-dependent ASM in this region. We then investigated whether its methylation could influence episodic verbal memory measured with the Rey Auditory Verbal Learning Test in these two cohorts. The region showed a complex methylation pattern, which was similar in healthy and schizophrenia individuals and unrelated to haplotypes. The pattern predicted memory scores in controls. The results suggest that epigenetic modifications within the CLU locus may play a role in memory variation, independent of ASM.

Disrupted Functional Connectivity of Cornu Ammonis Subregions in Amnestic Mild Cognitive Impairment: A Longitudinal Resting-State fMRI Study.

Background: The cornu ammonis (CA), as part of the hippocampal formation, represents a primary target region of neural degeneration in amnestic mild cognitive impairment (aMCI). Previous studies have revealed subtle structural deficits of the CA subregions (CA1-CA3, bilateral) in aMCI; however, it is not clear how the network function is impacted by aMCI. The present study examined longitudinal changes in resting state functional connectivity (FC) of each CA subregion and how these changes relate to neuropsychological profiles in aMCI.Methods: Twenty aMCI and 20 healthy control (HC) participants underwent longitudinal cognitive assessment and resting state functional MRI scans at baseline and 15 months afterward. Imaging data were processed with published routines in SPM8 and CONN software. Two-way analysis of covariance was performed with covariates of age, gender, education level, follow up interval, gray matter volume, mean FD, as well as global correlation (GCOR). Pearson’s correlation was conducted to evaluate the relationship between the longitudinal changes in CA subregional FC and neuropsychological performance in aMCI subjects.Results: Resting state FC between the right CA1 and right middle temporal gyrus (MTG) as well as between the left CA2 and bilateral cuneal cortex (CC) were decreased in aMCI subjects as compared to HC. Longitudinal decrease in FC between the right CA1 and right MTG was correlated with reduced capacity of episodic memory in aMCI subjects.Conclusion: The current findings suggest functional alterations in the CA subregions. CA1 connectivity with the middle temporal cortex may represent an important neural marker of memory dysfunction in aMCI.

Does memantine improve memory in subjects with focal-onset epilepsy and memory dysfunction? A randomized, double-blind, placebo-controlled trial

ObjectiveExcitotoxic injury involving N-methyl-d-aspartate (NMDA) receptor hyperactivity contributes to epilepsy-related memory dysfunction (ERMD). Current treatment strategies for ERMD have limited efficacy and fail to target the underlying pathophysiology. The present pilot study evaluated the efficacy of memantine, an NMDA receptor antagonist, for the treatment of ERMD in adults with focal-onset seizures. MethodsSubjects underwent cognitive testing at baseline, after a 13-week randomized, parallel-group, double-blinded phase (of memantine titrated to 10 mg bid or placebo), and following a 13-week open-label extension phase (of memantine titrated to 10 mg bid). The selective reminding test (SRT) continuous long-term retrieval (CLTR) score and 7/24 Spatial Recall Test learning score served as the primary outcome measures. Secondary measures included tests of attention span, fluency, visual construction, and response inhibition, as well as assessments of quality of life, depression, sleepiness, and side effects. ResultsSeventeen subjects contributed data to the blinded phase (n = 8 memantine, n = 9 placebo). No significant differences were seen between groups on the primary or secondary outcome measures. Pooled data at the end of the open-label phase from 10 subjects (initially randomized to memantine n = 3 or placebo n = 7) demonstrated statistically significant improvement from baseline in CLTR score, memory-related quality of life, spatial span, and response inhibition. No significant changes were evident in depression, sleepiness, side effects, or seizure frequency throughout the trial. SignificanceResults demonstrated no significant effect of memantine on cognition when assessed at the end of the blinded period. Pooled data at the end of the open-label phase showed significant improvement over baseline performance in measures of verbal memory, frontal-executive function, and memory-related quality of life. These improvements, however, may be due to practice effects and should be interpreted cautiously. Findings suggest a favorable safety profile of memantine in the setting of epilepsy.

Memory of Subjects of Communication: The Structural and Functional Components

The essence of psychological theories of memory is highlighted in the article. It is proved that the memory of subjects of communication has a three-component structure: the sensory register, short-term and long-term memory. The specifics of the work of psychological mechanisms of each of its structural and functional components are revealed. Physical signs of new information items that are valuable to communication subjects, are transmitted to processing and preservation, and invaluable and unrecognized – are sent to the sensory register buffer. Two directions of movement of the signs of information units in the short-term memory – incoming and outgoing – are considered. Through the incoming direction, psychological mechanisms supply valuable signs of information units for parallel or sequential processing, integration into a holistic image and encoding, and through the outgoing – direct them to reproduction or to long-term memory for storage. In long-term memory, they activate the appropriate and inappropriate codes and represent their semantic concepts for both recognizing the signs of new information units and for reproducing memorized information in order to enrich, modify, consolidate or implement it.

Early disruption of parvalbumin expression and perineuronal nets in the hippocampus of the Tg2576 mouse model of Alzheimer's disease can be rescued by enriched environment.

Recent findings show that parvalbumin (PV) interneuron function is impaired in Alzheimer's disease (AD), and that this impairment in PV function can be linked to network dysfunction and memory deficits. PV cells are often associated with a specific extracellular matrix, the perineuronal net (PNN). PNNs are believed to protect PV cell integrity, and whether the amyloidopathy affects PNNs remains unclear. Here, we evaluated the number of PV cells with and without PNNs in the hippocampus of the Tg2576 mouse model of AD at different stages of the disease. We show a deficit of PV+ and/or PV+/PNN+ cells in the areas CA1, CA2, and CA3 in Tg2576 as young as 3months of age. Importantly, transient exposure to an enriched environment, which has proven long-lasting beneficial effects on memory in AD subjects, rescues the PV/PNN cell number deficits. We conclude that cognitive improvements induced by enriched environment in AD mouse models could be supported by a remodeling of hippocampal PV cell network and their PNNs.

Polyphenols From Grape and Blueberry Improve Episodic Memory in Healthy Elderly with Lower Level of Memory Performance: A Bicentric Double-Blind, Randomized, Placebo-Controlled Clinical Study.

Polyphenols are promising nutritional bioactives exhibiting beneficial effect on age-related cognitive decline. This study evaluated the effect of a polyphenol-rich extract from grape and blueberry (PEGB) on memory of healthy elderly subjects (60-70 years-old). A bicentric, randomized, double-blind, placebo-controlled trial was conducted with 215 volunteers receiving 600 mg/day of PEGB (containing 258 mg flavonoids) or a placebo for 6 months. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test. Secondary outcomes included verbal episodic and recognition memory (VRM) and working memory (SSP). There was no significant effect of PEGB on the PAL on the whole cohort. Yet, PEGB supplementation improved VRM-free recall. Stratifying the cohort in quartiles based on PAL at baseline revealed a subgroup with advanced cognitive decline (decliners) who responded positively to the PEGB. In this group, PEGB consumption was also associated with a better VRM-delayed recognition. In addition to a lower polyphenol consumption, the urine metabolomic profile of decliners revealed that they excreted more metabolites. Urinary concentrations of specific flavan-3-ols metabolites were associated, at the end of the intervention, with the memory improvements. Our study demonstrates that PEGB improves age-related episodic memory decline in individuals with the highest cognitive impairments.

A Comparison Study of Working Memory Deficits between Patients with Methamphetamine-Associated Psychosis and Patients with Schizophrenia.

BackgroundBoth patients with methamphetamine-associated psychosis (MAP) and patients with schizophrenia suffer from obvious cognitive deficits in working memory, and this affects the functional prognosis of patients.AimThis study is to investigate the difference of working memory deficits between patients with MAP and patients with schizophrenia, especially the difference of central executive system function, and the relevance of working memory deficits and clinical characteristics.MethodsTwenty-eight male patients with MAP and twenty-eight patients with schizophrenia were recruited. The working memory of subjects was evaluated with the n-back task edited and adapted from English language materials. The positive syndrome scale of PANSS and CGI were employed to assess psychotic symptoms and the severity of patients.ResultsAccording to the results of repeated measure variance analysis, it was found that both the between-group variable (group) and within-group variable (n) had significant main effects, and the interaction between the between-group variable and the within-group variable was also significant. After Z-transformation, mean (sd) working memory scores of patients with MAP and schizophrenia were 0.91 (0.77) and -0.91 (2.11) respectively, and the difference between these two groups were statistically significant (F=19.253, p<0.001). The relevance between working memory deficits and clinical characteristics was low in both the patients with MAP and patients with schizophrenia.ConclusionPatients with MAP were better at regulating, updating, executing and controlling active information than patients with schizophrenia.

Neural Correlates for Intrinsic Motivational Deficits of Schizophrenia; Implications for Therapeutics of Cognitive Impairment.

The ultimate goal of the treatment of schizophrenia is recovery, a notion related to improvement of cognitive and social functioning. Cognitive remediation therapies (CRT), one of the most effective cognition enhancing methods, have been shown to moderately improve social functioning. For this purpose, intrinsic motivation, related to internal values such as interest and enjoyment, has been shown to play a key role. Although the impairment of intrinsic motivation is one of the characteristics of schizophrenia, its neural mechanisms remain unclear. This is related to the lack of feasible measures of intrinsic motivation, and its response to treatment. According to the self-determination theory (SDT), not only intrinsic motivation, but extrinsic motivation has been reported to enhance learning and memory in healthy subjects to some extent. This finding suggests the contribution of different types of motivation to potentiate the ability of the CRT to treat cognitive impairment of schizophrenia. In this paper, we provide a review of psychological characteristics, assessment methods, and neural correlates of intrinsic motivation in healthy subjects and patients with schizophrenia. Particularly, we focus on neuroimaging studies of intrinsic motivation, including our own. These considerations are relevant to enhancement of functional outcomes of schizophrenia.

Altered hippocampal replay is associated with memory impairment in mice heterozygous for the Scn2a gene.

An accumulating body of experimental evidence has implicated hippocampal replay occurring within sharp wave ripples (SPW-Rs) as crucial for learning and memory in healthy subjects. This raises speculation that neurological disorders impairing memory disrupt either SPW-Rs or their underlying neuronal activity. We report that mice heterozygous for the gene Scn2a, a site of frequent de novo mutations in humans with intellectual disability, displayed impaired spatial memory. While we observed no changes during encoding, to either single place cells or cell assemblies, we identified abnormalities restricted to SPW-R episodes that manifest as decreased cell assembly reactivation strengths and truncated hippocampal replay sequences. Our results suggest that alterations to hippocampal replay content may underlie disease-associated memory deficits.

Hippocampal Network Modularity Is Associated With Relational Memory Dysfunction in Schizophrenia

BackgroundFunctional dysconnectivity has been proposed as a major pathophysiological mechanism for cognitive dysfunction in schizophrenia. The hippocampus is a focal point of dysconnectivity in schizophrenia, with decreased hippocampal functional connectivity contributing to the marked memory deficits observed in patients. Normal memory function relies on the interaction of complex corticohippocampal networks. However, only recent technological advances have enabled the large-scale exploration of functional networks with accuracy and precision. MethodsWe investigated the modularity of hippocampal resting-state functional networks in a sample of 45 patients with schizophrenia spectrum disorders and 38 healthy control subjects. Modularity was calculated for two distinct functional networks: a core hippocampal-medial temporal lobe cortex network and an extended hippocampal-cortical network. As hippocampal function differs along its longitudinal axis, follow-up analyses examined anterior and posterior networks separately. To explore effects of resting network function on behavior, we tested associations between modularity and relational memory ability. Age, sex, handedness, and parental education were similar between groups. ResultsNetwork modularity was lower in schizophrenia patients, especially in the posterior hippocampal network. Schizophrenia patients also showed markedly lower relational memory ability compared with control subjects. We found a distinct brain-behavior relationship in schizophrenia that differed from control subjects by network and anterior/posterior division—while relational memory in control subjects was associated with anterior hippocampal-cortical modularity, schizophrenia patients showed an association with posterior hippocampal-medial temporal lobe cortex network modularity. ConclusionsOur findings support a model of abnormal resting-state corticohippocampal network coherence in schizophrenia, which may contribute to relational memory deficits.

Short-term memory and verbal fluency in Type 2 diabetes

Background: Neuropathy is common in people with Type 2 (non-insulin-dependent) diabetes for a long duration. Hence, it is possible that deficits in cognitive function might also be found in those who have had diabetes for a long duration. Our objective was to assess the short-term memory and verbal fluency in subjects above 40 years with Type 2 diabetes. Aims and Objectives: The aims and objectives of this study were to determine the effect of duration of uncomplicated Type 2 diabetes on short-term memory and verbal fluency. Materials and Methods: A cross-sectional comparative study was done. One hundred male participants, between 50 and 60 years of age with uncomplicated Type 2 diabetes for at least 2 years duration, were selected. They did not have any other chronic medical disorders. An informed consent was obtained. The duration of diabetes was noted from the date of the first diagnosis. The addenbrooke’s cognitive examination-revised (ACE-R) was used to evaluate short-term memory and verbal fluency. A cross-sectional comparative study was done, and the performances were based on the scores obtained. Statistical analysis was performed using the coefficient of correlation. We considered P < 0.05 to be significant. Results: For short-term memory, the mean score obtained by the subjects was 6.35 ± 0.66, and for verbal fluency, the mean scores obtained were 7.07 ± 2.05. Duration of diabetes correlated significantly with poorer performance on short-term memory (r = −0.371) and verbal fluency (r = −0.837). Conclusion: Within the study group, an association between duration of diabetes and short-term memory and verbal fluency was found. Early diabetics performed well, whereas those who were diabetics for a longer duration performed less well. Such changes may give us insight to the process of accelerated aging in diabetes.

Serotonergic and cholinergic modulation of functional brain connectivity: A comparison between young and older adults

Aging is accompanied by changes in neurotransmission. To advance our understanding of how aging modifies specific neural circuitries, we examined serotonergic and cholinergic stimulation with resting state functional magnetic resonance imaging (RS-fMRI) in young and older adults. The instant response to the selective serotonin reuptake inhibitor citalopram (30 mg) and the acetylcholinesterase inhibitor galantamine (8 mg) was measured in 12 young and 17 older volunteers during a randomized, double blind, placebo-controlled, crossover study. A powerful dataset consisting of 522 RS-fMRI scans was obtained by acquiring multiple scans per subject before and after drug administration. Group × treatment interaction effects on voxelwise connectivity with ten functional networks were investigated (p < .05, FWE-corrected) using a non-parametric multivariate analysis technique with cerebrospinal fluid, white matter, heart rate and baseline measurements as covariates. Both groups showed a decrease in sensorimotor network connectivity after citalopram administration. The comparable findings after citalopram intake are possibly due to relatively similar serotonergic systems in the young and older subjects. Galantamine altered connectivity between the occipital visual network and regions that are implicated in learning and memory in the young subjects. The lack of a cholinergic response in the elderly might relate to the well-known association between cognitive and cholinergic deterioration at older age.