Abnormal hippocampal activation in patients with extensive history of major depression: an fMRI study

Background

Impairment of recollection memory is consistently reported in patients with major depressive disorder (MDD) and may reflect underlying functional hippocampal changes, particularly in those with extensive histories of illness. We hypothesized that relative to controls, patients with a protracted course of illness would show diminished hippocampal activation on functional magnetic resonance imaging (fMRI) during a recollection memory task.

Methods

Patients who experienced 3 or more previously treated depressive episodes were compared with age- and sex-matched controls. We acquired fMRI data while participants performed a recollection memory process dissociation task.

Results

Using bilateral regions of interest (ROIs) prescribed for the right and left hippocampal/ parahippocampal complex, we observed increased activation of the right hippocampal and left parahippocampal gyrus in controls compared with patients with MDD during recollection memory trials. Within-group comparisons revealed heightened engagement of the hippocampal head (R/L) for controls during recollection trials, and greater activation of the hippocampal body/tail (R/L) during the learn-list encoding period in both the MDD and control groups. Recollection memory performance was significantly correlated with changes in blood oxygen level–dependent signal during recollection trials in the ROIs of the right hippocampus and right hippocampal head.

Limitations

This study was limited by the inclusion of patients taking antidepressant medication, raising the possibility that the reported findings were treatment effects.

Conclusion

The findings of decreased recruitment of the right hippocampal and left parahippocampal gyrus in patients with MDD suggest that these regions may be sensitive to the impact of disease burden and repeated episodes of MDD. This attenuated activation may represent stable changes in hippocampal function that occur over the course of illness in patients with MDD. The findings from within-group comparisons show that the group differences in the activation of the right hippocampal head were driven by greater engagement of this region among controls during recollection memory performance. These results also associate recollection performance impairments in patients with MDD with diminished hippocampal engagement.     

Effects of emotionally valenced working memory taxation on negative memories

Background and objectives

Memories enter a labile state during recollection. Thus, memory changes that occur during recollection can affect future instances of its activation. Having subjects perform a secondary task that taxes working memory while they recall a negative emotional memory often reduces its vividness and emotional intensity during subsequent recollections. However, researchers have not manipulated the emotional valence of the secondary task itself.

Methods

Subjects viewed a video depicting the aftermath of three fatal road traffic accidents, establishing the same negative emotional memory for all subjects. We then tested their memory for the video after randomly assigning them to no secondary task or a delayed match-to-sample secondary task involving photographs of positive, negative, or neutral emotional valence.

Results

The positive secondary task reduced memory for details about the video, whereas negative and neutral tasks did not.

Limitations

We did not assess the vividness and emotionality of the subjects' memory of the video.

Conclusions

Having subjects recall a stressful experience while performing a positively valent secondary task can decrement details of the memory and perhaps its emotionality.     

An exploratory model for G × E interaction on hippocampal volume in schizophrenia; obstetric complications and hypoxia-related genes

Background

Smaller hippocampal volume has repeatedly been reported in schizophrenia patients. Obstetric complications (OCs) and single nucleotide polymorphism (SNP) variation in schizophrenia susceptibility genes have independently been related to hippocampal volume. We investigated putative independent and interaction effects of severe hypoxia-related OCs and variation in four hypoxia-regulated schizophrenia susceptibility genes (BDNF, DTNBP1, GRM3 and NRG1) on hippocampal volume in schizophrenia patients and healthy controls.

Methods

Clinical assessment, structural MRI scans, and blood samples for genotyping of 32 SNPs were obtained from 54 schizophrenia patients and 53 control subjects. Information on obstetric complications was collected from original birth records.

Results

Severe OCs were related to hippocampal volume in both patients with schizophrenia and healthy control subjects. Of the 32 SNPs studied, effects of severe OCs on hippocampal volume were associated with allele variation in GRM3 rs13242038, but the interaction effect was not specific for schizophrenia. SNP variation in any of the four investigated genes alone did not significantly affect hippocampal volume.

Conclusions

The findings suggest a gene–environment (G × E) interaction between GRM3 gene variants and severe obstetric complications on hippocampus volume, independent of a diagnosis of schizophrenia. Due to the modest sample size, the results must be considered preliminary and require replication in independent samples.     

Semantic strategy training increases memory performance and brain activity in patients with prefrontal cortex lesions

Objective

Memory deficit is a frequent cognitive disorder following acquired prefrontal cortex lesions. In the present study, we investigated the brain correlates of a short semantic strategy training and memory performance of patients with distinct prefrontal cortex lesions using fMRI and cognitive tests.

Methods

Twenty-one adult patients with post-acute prefrontal cortex (PFC) lesions, twelve with left dorsolateral PFC (LPFC) and nine with bilateral orbitofrontal cortex (BOFC) were assessed before and after a short cognitive semantic training using a verbal memory encoding paradigm during scanning and neuropsychological tests outside the scanner.

Results

After the semantic strategy training both groups of patients showed significant behavioral improvement in verbal memory recall and use of semantic strategies. In the LPFC group, greater activity in left inferior and medial frontal gyrus, precentral gyrus and insula was found after training. For the BOFC group, a greater activation was found in the left parietal cortex, right cingulated and precuneus after training.

Conclusion

The activation of these specific areas in the memory and executive networks following cognitive training was associated to compensatory brain mechanisms and application of the semantic strategy.     

Reorganization of anterior and posterior hippocampal networks associated with memory performance in mesial temporal lobe epilepsy

Objective

To investigate the pattern of functional demarcation of hippocampal network and its relationship with memory performance in mesial temporal lobe epilepsy (mTLE) with unilateral hippocampal sclerosis.

Un nuevo test para la valoración de la memoria episódica. Test episódico y test episódico del cuidador

Introduction and objectives

The purpose of the episodic memory test and the caregiver's episodic memory test is to evaluate episodic memory according to its definition in a way that is feasible for families and achieves high degrees of sensitivity and specificity.

Methods and results

We administered a test consisting of 10 questions about episodic events to 332 subjects, of whom 65 had Alzheimer's disease (AD), 115 had amnestic MCI (aMCI) and 152 showed no cognitive impairment according to Reisberg's global deterioration scale (GDS). We calculated the test's sensitivity and specificity to distinguish AD from episodic aMCI and from normal ageing. The area under the ROC curve for the diagnosis of aMCI was 0.94 and the best cut-off value was 20; for that value, sensitivity was 89% and specificity was 82%. For a diagnosis of AD, the area under the ROC curve was 0.99 and the best cut-off point was 17, with a sensitivity of 98% and a specificity of 91%. A subsequent study using similar methodology yielded similar results when the test was administered directly by the caregiver.

Conclusions

The episodic memory test and the caregiver's episodic memory test are useful as brief screening tools for identifying patients with early-stage AD. It is suitable for use by primary care medical staff and in the home, since it can be administered by a caregiver. The test's limitations are that it must be administered by a reliable caregiver and the fact that it measures episodic memory only.     

Neuropsychological testing and event-related potentials in the assessment of cognitive performance in the patients with multiple sclerosis—A pilot study

Aims

The aim of the study was to evaluate cognitive impairment in multiple sclerosis (MS) patients using neuropsychological testing (NT) and auditory event-related potentials (ERPs) with reference to clinical variables, with an attempt to re-assess NT and ERP results after a year.

Methods

The study comprised 21 patients with MS. ERPs results were compared to age-matched controls. Correlations were searched among ERPs and NT results, duration of MS and disability. NT and ERPs were repeated after a year and their results were compared with the initial ones.

Results

In NT, 90–100% of patients showed impaired memory and attention. Latencies of ERPs were prolonged in patients compared with controls. NT results correlated with clinical variables and N2 parameters. Results of NT, but not ERPs, improved after a year.

Conclusions

MS patients present with moderate cognitive impairment and ERP abnormalities, with dysfunction of subcortical–prefrontal circuit as their possible background. NT are more useful than ERP in monitoring cognitive performance in MS patients.     

Relationship between hippocampal structure and memory function in elderly humans

With progressing age, the ability to recollect personal events declines, whereas familiarity-based memory remains relatively intact. It has been hypothesized that age-related hippocampal atrophy may contribute to this pattern because of its critical role for recollection in younger humans and after acute injury. Here, we show that hippocampal volume loss in healthy older persons correlates with gray matter loss (estimated with voxel-based morphometry) of the entire limbic system and shows no correlation with an electrophysiological (event-related potential [ERP]) index of recollection. Instead, it covaries with more substantial and less specific electrophysiological changes of stimulus processing. Age-related changes in another complementary structural measure, hippocampal diffusion, on the other hand, seemed to be more regionally selective and showed the expected correlation with the ERP index of recollection. Thus, hippocampal atrophy in older persons accompanies limbic atrophy, and its functional impact on memory is more fundamental than merely affecting recollection.     

Beneficios de la codificación profunda en la enfermedad de Alzheimer. Análisis del rendimiento en una tarea de memoria mediante el Item Specific Deficit Approach

Introduction

the aim of this study is to test the encoding deficit hypothesis in Alzheimer disease (AD) using a recent method for correcting memory tests. To this end, a Spanish-language adaptation of the Free and Cued Selective Reminding Test was interpreted using the Item Specific Deficit Approach (ISDA), which provides three indices: Encoding Deficit Index, Consolidation Deficit Index, and Retrieval Deficit Index.

Methods

We compared the performances of 15 patients with AD and 20 healthy control subjects and analysed results using either the task instructions or the ISDA approach.

Results

patients with AD displayed deficient encoding of more than half the information, but items that were encoded properly could be retrieved later with the help of the same semantic clues provided individually during encoding. Virtually all the information retained over the long-term was retrieved by using semantic clues. Encoding was shown to be the most impaired process, followed by retrieval and consolidation. Discriminant function analyses showed that ISDA indices are more sensitive and specific for detecting memory impairments in AD than are raw scores.

Conclusions

These results indicate that patients with AD present impaired information encoding, but they benefit from semantic hints that help them recover previously learned information. This should be taken into account for intervention techniques focusing on memory impairments in AD.     

Does attachment anxiety increase vulnerability to headache?

Background

Attachment-related anxiety and avoidance are potentially important aspects of pain experience and management, but have not been investigated in episodic headache sufferers or in relation to experimentally-evoked headache.

Objective

To determine whether adult insecure attachment styles were associated with sensitivity to pain or headache before, during or after stressful mental arithmetic in an episodic migraine or tension-type headache (T-TH) sample.

Methods

Thirty-eight participants with episodic migraine, 28 with episodic T-TH and 20 headache-free participants intermittently received a mild electric shock to the forehead before, during and after stressful mental arithmetic.

Results

A preoccupied attachment style and attachment anxiety, but not attachment avoidance, were associated with forehead pain and the intensity of headache before and after, but not during stressful mental arithmetic. These relationships were independent of Five Factor Model personality traits. Neither attachment anxiety nor avoidance was associated with episodic migraine or T-TH.

Conclusions

Anxiously attached individuals may express greater pain or show a stronger attentional bias toward painful sensations than securely attached individuals. However, distraction during psychological stress may override this attentional bias.     

Análisis morfológico de la región del hipocampo asociado a una tarea conductual innata en el modelo de ratón transgénico (3xTg-AD) para la enfermedad de Alzheimer

Introduction

Different animal models for Alzheimer disease (AD) have been designed to support the hypothesis that the neurodegeneration (loss of neurons and synapses with reactive gliosis) associated with Aβ and tau deposition in these models is similar to that in the human brain. These alterations produce functional changes beginning with decreased ability to carry out daily and social life activities, memory loss, and neuropsychiatric disorders in general. Neuronal alteration plays an important role in early stages of the disease, especially in the CA1 area of hippocampus in both human and animal models.

Methods

Two groups (WT and 3xTg-AD) of 11-month-old female mice were used in a behavioural analysis (nest building) and a morphometric analysis of the CA1 region of the dorsal hippocampus.

Results

The 3xTg-AD mice showed a 50% reduction in nest quality associated with a significant increase in damaged neurons in the CA1 hippocampal area (26% ± 6%, P < .05) compared to the WT group.

Conclusions

The decreased ability to carry out activities of daily living (humans) or nest building (3xTg-AD mice) is related to the neuronal alterations observed in AD. These alterations are controlled by the hippocampus. Post-mortem analyses of the human hippocampus, and the CA1 region in 3xTg-AD mice, show that these areas are associated with alterations in the deposition of Aβ and tau proteins, which start accumulating in the early stages of AD.     

Episodic memory,semantic memory,and amnesia

Episodic memory and semantic memory are two types of declarative memory. There have been two principal views about how this distinction might be reflected in the organization of memory functions in the brain. One view, that episodic memory and semantic memory are both dependent on the integrity of medial temporal lobe and midline diencephalic structures, predicts that amnesic patients with medial temporal lobe/diencephalic damage should be proportionately impaired in both episodic and semantic memory. An alternative view is that the capacity for semantic memory is spared, or partially spared, in amnesia relative to episodic memory ability. This article reviews two kinds of relevant data: 1) case studies where amnesia has occurred early in childhood, before much of an individual's semantic knowledge has been acquired, and 2) experimental studies with amnesic patients of fact and event learning, remembering and knowing, and remote memory. The data provide no compelling support for the view that episodic and semantic memory are affected differently in medial temporal lobe/diencephalic amnesia. However, episodic and semantic memory may be dissociable in those amnesic patients who additionally have severe frontal lobe damage. Hippocampus 1998;8:205–211. Published 1998 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Hippocampal contributions to recollection in retrograde and anterograde amnesia

Lesions restricted to the hippocampal formation and/or extended hippocampal system (hippocampal formation, fornix, mammillary bodies, and anterior thalamic nuclei) can disrupt conscious recollection in anterograde amnesia, while leaving familiarity-based memory relatively intact. Familiarity may be supported by extra-hippocampal medial temporal lobe (MTL) structures. Within-task dissociations in recognition memory best exemplify this distinction in anterograde amnesia. The authors report for the first time comparable dissociations within recognition memory in retrograde amnesia. An amnesic patient (A.D.) with bilateral fornix and septal nuclei lesions failed to recognize details pertaining to personal past events only when recollection was required, during recognition of episodic details. His intact recognition of generic and semantic details pertaining to the same events was ascribed to intact familiarity processes. Recollective processes in the controls were reflected by asymmetrical Receiver's Operating Characteristic curves, whereas the patient's Receiver's Operating Characteristic was symmetrical, suggesting that his inferior recognition performance on episodic details was reliant on familiarity processes. Anterograde and retrograde memories were equally affected, with no temporal gradient for retrograde memories. By comparison, another amnesic person (K.C.) with extensive MTL damage (involving extra-hippocampal MTL structures in addition to hippocampal and fornix lesions) had very poor recognition and no recollection of either episodic or generic/semantic details. These data suggest that the extended hippocampal system is required to support recollection for both anterograde and retrograde memories, regardless of their age.     

Métamémoire, remémoration et familiarité dans la maladie d’Alzheimer

Introduction

The main objective of this review is to present a new approach to the memory deficit in Alzheimer's disease. Recent memory models suggest that information is recovered either on the basis of recollection or on the basis on familiarity. Recollection, unlike familiarity, requires the retrieval of contextual details related to the encoded information.

State of the art

This review suggests that recollection is particularly affected in Alzheimer's disease. In contrast, familiarity seems to be relatively preserved. A related deficit in metamemory is observed when recollection is required; a decrease in recollection in Alzheimer's disease could explain the pattern of metamemory problems. The deficit in recollection could be explained by a disconnection between medial temporal areas and frontal areas.

Perspectives

This novel approach to memory gives research perspectives concerning both early diagnosis and rehabilitation strategies of Alzheimer disease.

Conclusion

This overview showed deficits in conscious memory processes conceived of as recollection. These novel insights should provide new explanations for the deficits observed in Alzheimer's disease, particularly metamemory.     

La mémoire autobiographique et le self dans les troubles du spectre autistique sans déficience intellectuelle (TSASDI) à l’âge adulte

Introduction

Autism spectrum disorder combines deficits in socio-communication, restricted, repetitive patterns but also disorders of self and cognitive impairments. Among them, people with ASD have autobiographical memory deficits as shown by several recent studies. Autobiographical memory is a critical function supporting socialization but it represents also an important support for the self as illustrated by the model of Self Memory System put forward by Conway. This cognitive model describes the reciprocal relationships between autobiographical memory and self and then provides a relevant theoretical framework to explore disorders of self by examining autobiographical memory deficits.

Structural changes in the hippocampus in major depressive disorder: contributions of disease and treatment

Background

Previous magnetic resonance imaging (MRI) studies of patients with major depressive disorder (MDD) have consistently shown bilateral and unilateral reductions in hippocampal volume relative to healthy controls. Recent structural MRI studies have addressed the question of whether changes in the volume of hippocampal subregions may be associated with MDD.

Methods

We used a comprehensive and reliable 3-dimensional tracing protocol that enables delineation of hippocampal subregions (head, body, tail) to study changes in the hippocampus of patients with MDD. We recruited 39 MDD patients (16 medicated, 23 unmedicated) and 34 healthy age- and sex-matched controls. We acquired images using a magnetization-prepared rapid acquisition gradient echo sequence on a 1.5-T scanner with a spatial resolution of 1.5 mm × 0.5 mm × 0.5 mm. We performed volumetric analyses, blinded to diagnosis, using the interactive software package Display. All volumes were adjusted for intracranial volume.

Results

We found a significant reduction in the volume of the hippocampal tail bilaterally, right hippocampal head and right total hippocampus in MDD patients. Medicated MDD patients showed increased hippocampal body volume compared with both healthy controls and unmedicated patients.

Limitations

This study was cross-sectional. Further prospective studies are needed to determine the direct effect of antidepressant treatment.

Conclusion

Our results suggest that decreased hippocampal tail and hippocampal head volumes could be trait changes, whereas hippocampal body changes may be dependent on treatment. We showed that long-term antidepressant treatment may affect hippocampal volume in patients with MDD.     

Alteraciones del metabolismo oxidativo y de la memoria y el aprendizaje en un modelo de hipoperfusión cerebral en ratas

Introduction

Chronic hypoperfusion in rats produces memory and learning impairments due to permanent occlusion of commun carotid arteries (POCCA). Molecular mechanisms leading to behavioural disorders have been poorly studied. For this reason, the aim of the present study was to characterise oxidative metabolism disorders and their implications in memory and learning impairments.

Methods

Superoxide dismutase (SOD) and catalase (CAT) activities were determined in cortex, hippocampus and striatum homogenates at 24 hours and at 22 days after the lesion. Haematoxylin-eosin staining and glial fibrillary acidic protein (GFAP) immunoreactivity were performed on coronal sections. Behavioural impairments were explored using the Morris water maze (MWM). Escape latencies were determined in all behavioural studies.

Results

The lesion induced a significant increase (P<.01) in CAT activity in the cortex at 24 hours, while SOD activity was significantly higher (P<.01) in the cortex and hippocampus at 22 days. An intense vacuolization was observed in the cortex and striatum as a result of the lesion. A neuronal loss in the striatum and hippocampus was observed. The glial reaction increased in the cortex and striatum. Visual alterations were observed in the lesion group with the lowest evolution time (P<.001). Escape latencies, corresponding to MWM schemes for long-term and short-term memory evaluation increased significantly (P<.05) in both groups of lesioned animals.

Conclusion

It was concluded that changes in SOD and CAT activities indicate a possible implication of oxidative imbalance in the pathology associated with chronic cerebral hypoperfusion. In addition, the POCCA model in rats is useful for understanding mechanisms by which cerebral hypoperfusion produces memory and learning impairments.     

Hypothyroxinemia during pregnancy: the effect on neurodevelopment in the child

Context

Experimental studies have shown that maternal hypothyroxinemia during early pregnancy is associated with poor neurodevelopment in affected offspring.

Objective

The aim of this study was to assess the impact of maternal serum free T4 on psychomotor development of offspring.

Materials and methods

The study involved 147 women in the third trimester (week 37) of pregnancy. TSH and free T4 serum levels were measured at 37 week gestation. The children were evaluated between 38 and 60 months of age by the McCarthy Scales of Children's Abilities.

Results

54.4% of the women had a free T4 below the threshold of hypothyroxinemia. We find a significant effect of maternal hypothyroxinemia on the general cognitive index, and on perceptual-manipulative and memory coefficients.     

Hippocampal volume in borderline personality disorder with and without comorbid posttraumatic stress disorder: A meta-analysis

Background

Several studies have found a reduction in hippocampal volume in borderline personality disorder (BPD) patients.

Methods

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.

Results

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.

Conclusions

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.     

Sugary beverage intake and preclinical Alzheimer's disease in the community

Introduction

Excess sugar consumption has been linked with Alzheimer's disease (AD) pathology in animal models.