To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Life experiences have been associated with significant changes in brain structure and functioning. This experience-dependent plasticity is thought to reflect the capacity of our nervous systems to adapt to environmental demands, and ultimately shape cognition. This chapter focuses on how such experiences and environment can specifically impact the hippocampus, a structure important for learning, memory, and healthy cognition. The hippocampal memory system maintains a competitive relationship with other memory systems, in particular the caudate nucleus of the striatum, part of the basal ganglia. Specific types of behavior, such as spatial-based vs. response-based navigational strategies, can influence these memory systems both positively and negatively and lead to long-term neuroplastic changes. Overreliance on non-hippocampus dependent navigational strategies is associated with a reduction in hippocampus volume and activity across the lifespan. Emerging research is now pointing to the wide use of electronic devices – GPS, smartphones, and video games – as a contributing factor to greater reliance on non-hippocampus dependent memory. Given the limited, but concerning, evidence that reliance on electronic devices can interact with already established factors related to underuse of the hippocampal memory system, further study is needed to better understand how these imbalances occur and how they can be mitigated.
Patients with post-traumatic stress disorder (PTSD) show a different stress-related cognitive style compared with healthy controls (HC). The FK506 binding protein 5 gene (FKBP5), one of the PTSD known risk factors, is involved in the stress response through the hypothalamic-pituitary-adrenal axis and brain volumetric alterations. The present study aimed to uncover the neural correlates of stress-related cognitive styles through the analysis of the regional brain volumes and FKBP5 genotype in patients with PTSD compared with HC.
In this study, 51 patients with PTSD and 94 HC were assessed for stress-related cognitive styles, PTSD symptoms severity, and genotype of FKBP5 single nucleotide polymorphisms, and underwent T1-weighted structural magnetic resonance imaging. Diagnosis-by-genotype interaction for regional brain volumes was examined in 16 brain regions of interest.
Patients with PTSD showed significantly higher levels of catastrophizing, ruminative response, and repression, and reduced distress aversion and positive reappraisal compared with HC (p < 0.001). Significant diagnosis-by-genotype interactions for regional brain volumes were observed for bilateral hippocampi and left frontal operculum. A significant positive correlation between the severity of the repression and left hippocampal volume was found in a subgroup of patients with PTSD with FKBP5 rs3800373 (AA genotype) or rs1360780 (CC genotype).
The present study showed the influences of FKBP5 genotype on the distorted cognitive styles in PTSD by measuring the volumetric alteration of hippocampal regions, providing a possible role of the hippocampus and left frontal operculum as significant neurobiological correlates of PTSD.
Decreasing high fat and high carbohydrate intake, together with the administration of natural bioactive drugs, is assumed to have a protective effect in the prevention and amelioration of the metabolic syndrome (MetS). The aim of the study was to evaluate effects of diet improvement and/or a phenolic compound (rosmarinic acid; RA) administration (100 mg/kg per d) on metabolic as well as functional changes of vessels and hippocampus caused by the MetS-like conditions. The MetS-like conditions were induced by a high-fat-fructose diet (HFFD) in Prague hereditary hypertriacylglycerolaemic (HTG) rats. The effect of diet improvement and RA administration was studied using biochemical and functional measurements. Consumption of HFFD by HTG rats resulted in the development of conditions like the MetS. The fat and fructose restriction from the diet led to amelioration of basic indicators of metabolic state in rats fed HFFD and to amendment parameters of glucose tolerance test and reduction of the IL-1β serum levels. Moreover, aortic endothelial function was improved with an impact on blood pressure. The functional measurement of electrophysiology of the hippocampus showed that long-term potentiation of neuronal transmission course deteriorated after HFFD was improved by energy restriction. Oral administration of RA had a supporting effect not only on lipid and glucose metabolism but also on the vascular endothelium. Combination of both types of therapy induced beneficial effect on glucose tolerance and lipid peroxidation. Thus, combined improvement of diet habits and treatment with natural bioactive drugs is assumed to have protective effect in prevention and amelioration of the MetS.
To date, there is a controversy on effects of cognitive intervention to maintain or improve hippocampal function for older adults with mild cognitive impairment (MCI).
The main objective of this study was to exam effects of virtual reality-based spatial cognitive training (VR-SCT) using VR on hippocampal function of older adults with MCI.
Fifty-six older adults with MCI were randomly allocated to the experimental group (EG) that received the VR-SCT or the waitlist control group (CG) for a total of 24 sessions. To investigate effects of the VR-SCT on spatial cognition and episodic memory, the Weschsler Adult Intelligence Scale-Revised Block Design Test (WAIS-BDT) and the Seoul Verbal Learning Test (SVLT) were used.
During the sessions, the training performances gradually increased (p < .001). After the intervention, the EG showed significant greater improvements in the WAIS-BDT (p < .001, η2 = .667) and recall of the SVLT (p < .05, η2 =.094) compared to the CG but in recognition of the SVLT (p > .05, η2 =.001).
These results suggest that the VR-SCT might be clinically beneficial to enhance spatial cognition and episodic memory of older adults with MCI.
Few topics in cognitive neuroscience can be said to have spurred intense research interest and vigorous debate as much as the neurocognitive architecture of imagination. Despite the tendency to view imagination as a unitary mental faculty, its multifaceted nature implicates a diverse range of underlying processes. Episodic memory has been ascribed a foundational role in furnishing the contents of mental constructions. By contrast, semantic memory has long been overlooked in the discourse, despite converging evidence of its centrality for all forms of inner mentation. Here, I expand upon the idea that the undifferentiated and flexible nature of semantic memory renders it particularly well suited to support imagination in its many guises. The imagined scenario thus reflects the output of a dynamic process that shifts back and forth along an episodic-semantic continuum, the weighting of which hinges largely upon task demands and integrity of the underlying memory system. Accordingly, the aim of this chapter is to move the focus away from the traditional episodic/semantic dichotomy in favour of a unified account in which episodic and semantic processes coalesce in the service of constructive endeavors.
Electroconvulsive therapy (ECT) is the most effective antidepressant treatment for severe depression. Although recent structural magnetic resonance imaging (MRI) studies have consistently reported ECT-induced hippocampal volume increases, most studies did not find the association of the hippocampal volume changes with clinical improvement. To understand the underlying mechanisms of ECT action, we aimed to identify the longitudinal effects of ECT on hippocampal functional connectivity (FC) and their associations with clinical improvement.
Resting-state functional MRI was acquired before and after bilateral ECT in 27 depressed individuals. A priori hippocampal seed-based FC analysis and a data-driven multivoxel pattern analysis (MVPA) were conducted to investigate FC changes associated with clinical improvement. The statistical threshold was set at cluster-level false discovery rate-corrected p < 0.05.
Depressive symptom improvement after ECT was positively associated with the change in the right hippocampus-ventromedial prefrontal cortex FC, and negatively associated with the right hippocampus-superior frontal gyrus FC. MVPA confirmed the results of hippocampal seed-based analyses and identified the following additional clusters associated with clinical improvement following ECT: the thalamus, the sensorimotor cortex, and the precuneus.
ECT-induced change in the right frontotemporal connectivity and thalamocortical connectivity, and changes in the nodes of the default mode network were associated with clinical improvement. Modulation of these networks may explain the underlying mechanisms by which ECT exert its potent and rapid antidepressant effect.
Aging is marked by cognitive decline, which in the case of Alzheimer’s disease is associated with tremendous global economic burden. Identifying modifiable risk factors for cognitive decline is therefore of paramount importance. In this chapter, we describe how aging compromises sleep quality and sleep architecture at a rate that parallels normal age-related cognitive decline. We argue that understanding the neurocognitive functions of sleep – frontal lobe restoration, memory consolidation, and metabolite clearance – and how such functions change in later life will be key to informing why some older individuals maintain healthy cognitive functioning and other older individuals do not. Critically, by investigating how sleep, cognition, and aging interact, researchers and clinicians can develop sleep-related treatments that target preventing, or at least ameliorating, pathologies such as Alzheimer’s disease.
Decline and deterioration are prominent features of cognitive aging. Against this background, successful cognitive aging is usually conceptualized as buffering, protecting against, or compensating for disrupted neural integrity in the aged brain. Here we review evidence for a parallel dynamic, comprising a life course trajectory of neuroadaptive plasticity, extending from gene expression to cognitive organization. The encouraging implication is that, alongside the search for treatments that target mechanisms of decline, designing interventions to promote neuroadaptive aging may be a feasible alternative.
Much of the extant work in the cognitive neurosciences of aging has focused on identifying the neural correlates of age-related declines in episodic memory and working memory. This chapter reviews evidence from human studies that speaks to the hypothesis that age-related dysfunctions in specific neurotransmitter systems play a critical role in cognitive decline. Based in large part on results from functional neuroimaging studies including positron emission tomography (PET) and pharmacological functional magnetic resonance imaging (fMRI), we conclude that there is emerging evidence that dysfunctions in the dopamine, noradrenaline, and cholinergic systems play a critical role in age-related cognitive decline of working memory and episodic memory. These conclusions are important and encourage further study in order to tailor interventions that preserve cognitive functions in older age via augmentation of neurotransmitter functions.
Decreased hippocampal volume reported in neuropsychiatric and endocrine disorders is considered a result of putative neuronal damage mediated by corticosteroids. This is the first prospective study of hippocampal volume and function in patients treated with corticosteroids.
14 subjects treated systemically with prednisone or betamethasone for dermatological or rheumatic disorders underwent prospective neurocognitive testing (Auditory Verbal Learning Test—AVLT, Trail Making Test—TMT, Digit Span—DS) and nine of them also repeated magnetic resonance volumetry.
The mean duration of treatment between the first and the second assessment was 73 ± 38 days with mean daily dose of 37 ± 17 mg prednisone and 193 ± 29 days, with mean daily dose of 24 ± 15 mg prednisone between the first and the third assessment. There was a trend towards decreases in total AVLT scores and an improvement in the TMT and DS, but no significant changes in the volumes of the right or the left hippocampi between the assessments. Prednisone dose did not correlate with the hippocampal volume change.
We observed a trend for decline in verbal memory despite improvement in psychomotor speed, attention/working memory and no macroscopic hippocampal volume changes during 36–238 days of treatment with therapeutic doses of corticosteroids.
Neuronal plasticity or remodeling is most often discussed with regard to cellular and behavioral models of learning and memory. However, neuronal plasticity is a fundamental process by which the brain acquires information and makes the appropriate adaptive responses in future-related settings. Dysfunction of these fundamental processes could thereby contribute to the pathophysiology of mood disorders, and recovery could occur by induction of the appropriate plasticity or remodeling. These possibilities are supported by preclinical and clinical studies demonstrating that there are structural alterations that occur in response to stress and in patients with mood disorders. Moreover, antidepressant treatment may oppose these effects by regulation of signal transduction and gene expression pathways linked to neuronal plasticity. These findings comprise a novel conceptual framework for future studies of the etiology of mood disorders and for the development of novel therapeutic interventions.
Several studies have found a reduction in hippocampal volume in borderline personality disorder (BPD) patients.
In order to investigate the degree to which comorbid posttraumatic stress disorder (PTSD) could account for reduction in hippocampal volume in these patients, we conducted a systematic review and meta-analysis of studies that compared hippocampal volume in BPD patients with and without PTSD relative to healthy controls.
Seven articles, involving 124 patients and 147 controls, were included. We found a statistically significant reduction for the left and right hippocampus. Data from the four studies that discriminated BPD patients with and without PTSD indicate that hippocampal volumes were reduced bilaterally in BPD patients with PTSD, relative to healthy controls, but that results were mixed for BPD patients without PTSD, relative to healthy controls.
Results from this meta-analysis suggest that hippocampal volumes are reduced in patients with BPD, relative to healthy controls, but particularly in cases in which patients are diagnosed with comorbid PTSD.
The hippocampal formation, a structure involved in declarative, spatial and contextual memory, undergoes atrophy in depressive illness along with impairment in cognitive function. Animal model studies have shown that the hippocampus is a particularly sensitive and vulnerable brain region that responds to stress and stress hormones. Studies on models of stress and glucocorticoid actions reveal that the hippocampus shows a considerable degree of structural plasticity in the adult brain. Stress suppresses neurogenesis of dentate gyrus granule neurons, and repeated stress causes remodeling of dendrites in the CA3 region, a region that is particularly important in memory processing. Both forms of structural remodeling of the hippocampus are mediated by adrenal steroids working in concert with excitatory amino acids (EAA) and N-methyl-D-aspartate (NMDA) receptors. EAA and NMDA receptors are also involved in neuronal death that is caused in pyramidal neurons by seizures, head trauma, and ischemia, and alterations of calcium homeostasis that accompany age-related cognitive impairment. Tianeptine (tianeptine) is an effective antidepressant that prevents and even reverses the actions of stress and glucocorticoids on dendritic remodeling in an animal model of chronic stress. Multiple neurotransmitter systems contribute to dendritic remodeling, including EAA, serotonin, and gamma-aminobutyric acid (GABA), working synergistically with glucocorticoids. This review summarizes findings on neurochemical targets of adrenal steroid actions that may explain their role in the remodeling process. In studying these actions, we hope to better understand the molecular and cellular targets of action of tianeptine in relation to its role in influencing structural plasticity of the hippocampus.
Stress elicits adaptive responses from the brain, but it can also lead to maladaptive consequences. For example, stress can precipitate mental illness, including depression. Prolonged stress also causes damage to neurons in the hippocampus. Antidepressant drugs must be evaluated, not only for their ability to potentiate adaptive responses, but also to inhibit maladaptive consequences of stress. Ongoing research in our laboratory has compared the atypical tricyclic antidepressant, tianeptine, with the typical tricyclics, desipramine and imipramine, with respect to the effects of isolation and repeated restraint stress. Tianeptine and desipramine similarly attenuated isolation stress-induced increases in locus coeruleus and midbrain tyrosine hydroxylase mRNA levels and isolation-stress induced decreases in preproenkephalin mRNA levels in striatum and nucleus accumbens. However, tianeptine and imipramine differed in their effects in the cerebral cortex and hippocampus on 5HT2, and 5HT1A receptor levels but, surprisingly, produced similar effects on levels of the serotonin transporter labelled with [3H] paroxetine. Tianeptine also prevented stress-induced reductions in the length and number of branchpoints of dendrites of CA3 pyramidal neurons in hippocampus; comparison with effects of typical tricyclics are ongoing. Tianeptine also blocked effects of corticosterone treatment to reduce branching and length of CA3 dendrites. These actions of tianeptine may be due to interactions between 5HT and excitatory amino acids in the mossy fiber terminals on CA3 pyramidal neurons. Taken together, these results indicate that tianeptine has unique properties compared to some other antidepressant drugs, but shares in common with those drugs the ability to attenuate stress effects on tyrosine hydroxylase gene expression and on the serotonin transporter. It remains to be seen whether these actions are the basis of a common antidepressant action.
The effect of depression on the hippocampus has become the focus of a number of structural and functional neuroimaging studies. In the past two decades, advances in neuroimaging techniques now allow the examination of subtle changes in both regional structure and function that are associated with the pathophysiology of depression. Many studies using 3-dimensional magnetic resonance imaging (MRI) volumetric measurement have reported decreases in hippocampal volume among depressed subjects compared with controls, whereas other studies have not found any volume loss. Differences among studies have been discussed. In some studies, the volume loss appears to have functional significance including an association with memory loss. Furthermore, we have found a trend towards loss of 5-HT2A receptors in the hippocampus using positron emission tomography (PET) to detect regional changes in [18F]altanserin binding. Functional imaging extends the sensitivity and specificity of structural imaging and will lead to a better understanding of affective disorders.
Previous experiments have shown that tianeptine, a new psychotropic agent with antidepressant properties, improves performance in several learning and memory tasks in mice. In more recent investigations, tianeptine was found to completely alleviate working memory deficits produced by long-term alcohol intoxication and to prevent abnormal memory loss in aged animals (Jaffard et al, 1991b, 1991c). The aim of this paper was to examine how this last finding may be integrated in our understanding of brain mechanisms involved in memory loss. For this purpose, we present a brief review of experimental data and theories which, at different levels of analysis, seems to be relevant to this issue. Together with the subsequent examination of the conditions in which tianeptine was found to improve long-term retention, we suggest that: i) long-term memory loss would be largely determined by the initial encoding of information, so that ii) tianeptine would help aged animals to use spatial mapping or configural associations more efficiently at the time of initial acquisition. This, in turn, suggests that one of the main brain target sites for tianeptine in enhancing memory is the hippocampal formation.
Several preclinical studies have demonstrated neuronal effects of glucocorticoids on the hippocampus (HC), a limbic structure with anterior–posterior anatomical and functional segmentation. We propose a volumetric magnetic resonance imaging analysis of hippocampus head (HH), body (HB) and tail (HT) using Cushing's disease (CD) as model, to investigate whether there is a differential sensitivity to glucocorticoid neuronal damage in these segments. We found a significant difference in the HH bilaterally after 12 months from trans-sphenoidal surgical selective resection of the adrenocorticotropic hormone (ACTH)-secreting pituitary micro-adenomas. This pre–post surgery difference could contribute to better understand the pathopysiology of CD as an in vivo model for stress-related hypercortisolemic neuropsychiatric disorders.
Stress-induced structural and cellular alterations in the hippocampus can contribute to the pathophysiology of depression. The reversal of these alterations may be a mechanism by which antidepressants achieve their therapeutic effect. The aim of the present study was therefore to investigate the effect of tianeptine on stress-induced structural changes and alterations in cerebral metabolites. To this end, psychosocially stressed male tree shrews were treated with tianeptine. A combination of in vivo and postmortem methods was used to evaluate the antidepressant treatment on the preservation of neuronal plasticity. It was found that all stress-induced effects were prevented by the administration of tianeptine. It is concluded that these findings provide experimental evidence for recent theories that impairment of neuronal viability and neuroplasticity might be important causal factors in mood disorders, suggesting tianeptine as a potential stimulator of neural resilience.
People use marijuana for nonmedical reasons because they like how it affects the brain, and therefore their mind and subjective experience. However, regular use of marijuana alters brain structure and function in ways that persist well beyond the period of acute intoxication. Progressively more powerful research tools are documenting effects in high risk populations with considerably less than daily use. These impacts are generally reversible but may be permanent if they occur during stages of rapid neurodevelopment typical of early adolescence. The volume of gray matter and the number of synaptic connections can be reduced by marijuana use, most importantly in the hippocampus, amygdala, and frontal lobes. Gender differences exist in the impact of marijuana on cortical thickness during adolescence. The functional integrity of white matter interconnecting areas of the brain can also be reduced by chronic marijuana use, which interferes with the endogenous cannabinoid system’s formation of the microtubule skeleton within axons.
Science explains how marijuana produces the experience of being high after Herkenham mapped location of the densest concentrations of CB1 receptors. The hippocampus, amygdala, and basal ganglia/cerebellum have especially dense cannabinoid receptors and THC impacts the functions produced by these areas in conspicuously noticeable ways. The hippocampus produces short term memory, an important element in learning. Reduced working memory is the most documented cognitive impairment caused by acute marijuana use. The endocannabinoid system is also uniquely responsible for forgetting negative experiences. The amygdala modulates anxiety, appetites, the sense of novelty and the hypothalamus. When THC stimulates the amygdala, most people experience relaxation, hunger (“munchies”) and altered sensory experience due to dishabituation to stimuli. Hypothalamic modulation by the amygdala results in reduction of the stress response, leading to the “chill” of being high. And genetic differences in CB1 density determines aspects of temperament. Supranormal stimulation of CB1 receptors in the basal ganglia reduces spontaneous motor activity and THC stimulation of the cerebellum reduces fine motor control and alters the sense of time and driving skills. The experience of being high is the culmination of altered brain function in the above areas with the highest CB1 density.