Hippocampal Theta-Phase Modulation of Replay Correlates with Configural-Relational Short-Term Memory Performance

Thereis now growing evidencethatthe hippocampus generatestheta rhythmsthat can phase biasfast neural oscillationsinthe neocortex, allowing coordination of widespread fast oscillatory populations outside limbic areas. A recent magnetoencephalographic study showed that maintenance of configural-relational scene information in a delayed match-to-sample (DMS) task was associated with replay of that information during the delay period. The periodicity of the replay was coordinated by the phase of the ongoing theta rhythm, and the degree of theta coordination during the delay period was positively correlated with DMS performance. Here, we reanalyzed these data to investigate which brain regions were involved in generating the theta oscillations that coordinated the periodic replay of configural- relational information. We used a beamformer algorithm to produce estimates of regional theta rhythms and constructed volumetric images of the phase-locking between the local theta cycle and the instances of replay (in the 13- 80 Hz band). We found that individual differences in DMS performancefor configural-relational associations were relatedtothe degree of phase coupling of instances of cortical reactivations to theta oscillations generated in the right posterior hippocampus and the right inferior frontal gyrus. This demonstrates that the timing of memory reactivations in humans is biased toward hippocampal theta phase

Executive dysfunction and memory impairment in schizoaffective disorder: a comparison with bipolar disorder, schizophrenia and healthy controls.

BACKGROUND: Deficits in memory and executive performance are well-established features of bipolar disorder and schizophrenia. By contrast, data on cognitive impairment in schizoaffective disorder are scarce and the findings are conflicting. METHOD: We used the Wechsler Memory Scale (WMS-III) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to test memory and executive function in 45 schizophrenic patients, 26 schizomanic patients and 51 manic bipolar patients in comparison to 65 healthy controls. The patients were tested when acutely ill. RESULTS: All three patient groups performed significantly more poorly than the controls on global measures of memory and executive functioning, but there were no differences among the patient groups. There were few differences in memory and executive function subtest scores within the patient groups. There were no differences in any test scores between manic patients with and without psychotic symptoms. CONCLUSIONS: Schizophrenic, schizomanic and manic patients show a broadly similar degree of executive and memory deficits in the acute phase of illness. Our results do not support a categorical differentiation across different psychotic categories with regard to neuropsychological deficits.

Dendritic Spine Abnormalities in Hippocampal CA1 Pyramidal Neurons Underlying Memory Deficits in the SAMP8 Mouse Model of Alzheimer's Disease

SAMP8 is a strain of mice with accelerated senescence. These mice have recently been the focus of attention as they show several alterations that have also been described in Alzheimer"s disease (AD) patients. The number of dendritic spines, spine plasticity, and morphology are basic to memory formation. In AD, the density of dendritic spines is severely decreased. We studied memory alterations using the object recognition test. We measured levels of synaptophysin as a marker of neurotransmission and used Golgi staining to quantify and characterize the number and morphology of dendritic spines in SAMP8 mice and in SAMR1 as control animals. While there were no memory differences at 3 months of age, the memory of both 6- and 9-month-old SAMP8 mice was impaired in comparison with age-matched SAMR1 mice or young SAMP8 mice. In addition, synaptophysin levels were not altered in young SAMP8 animals, but SAMP8 aged 6 and 9 months had less synaptophysin than SAMR1 controls and also less than 3-month-old SAMP8 mice. Moreover, while spine density remained stable with age in SAMR1 mice, the number of spines started to decrease in SAMP8 animals at 6 months, only to get worse at 9 months. Our results show that from 6 months onwards SAMP8 mice show impaired memory. This age coincides with that at which the levels of synaptophysin and spine density decrease. Thus, we conclude that together with other studies that describe several alterations at similar ages, SAMP8 mice are a very suitable model for studying AD.

Birth Weight, Working Memory and Epigenetic Signatures in IGF2 and Related Genes: A MZ Twin Study.

Neurodevelopmental disruptions caused by obstetric complications play a role in the etiology of several phenotypes associated with neuropsychiatric diseases and cognitive dysfunctions. Importantly, it has been noticed that epigenetic processes occurring early in life may mediate these associations. Here, DNA methylation signatures at IGF2 (insulin-like growth factor 2) and IGF2BP1-3 (IGF2-binding proteins 1-3) were examined in a sample consisting of 34 adult monozygotic (MZ) twins informative for obstetric complications and cognitive performance. Multivariate linear regression analysis of twin data was implemented to test for associations between methylation levels and both birth weight (BW) and adult working memory (WM) performance. Familial and unique environmental factors underlying these potential relationships were evaluated. A link was detected between DNA methylation levels of two CpG sites in the IGF2BP1 gene and both BW and adult WM performance. The BW-IGF2BP1 methylation association seemed due to non-shared environmental factors influencing BW, whereas the WM-IGF2BP1 methylation relationship seemed mediated by both genes and environment. Our data is in agreement with previous evidence indicating that DNA methylation status may be related to prenatal stress and later neurocognitive phenotypes. While former reports independently detected associations between DNA methylation and either BW or WM, current results suggest that these relationships are not confounded by each other.

Accessing forgotten memory traces from long-term memory via visual movements

Because memory retrieval often requires overt responses, it is difficult to determine to what extend forgetting occurs as a problem in explicit accessing of long-term memory traces. In this study, we used eye-tracking measures in combination with a behavioural task that favoured high forgetting rates to investigate the existence of memory traces from long-term memory in spite of failure in accessing them consciously. In 2 experiments, participants were encouraged to encode a large set of sound-picture56 location associations. In a later test, sounds were presented and participants were instructed to visually scan, before a verbal memory report, for the correct location of the associated pictures in an empty screen. We found the reactivation of associated memories by sound cues at test biased oculomotor behaviour towards locations congruent with memory representations, even when participants failed to consciously provide a memory report of it. These findings reveal the emergence of a memory-guided behaviour that can be used to map internal representations of forgotten memories from long-term memory.

Individual Differences in True and False Memory Retrieval Are Related to White Matter Brain Microstructure

We sometimes vividly remember things that did not happen, a phenomenon with general relevance, not only in the courtroom. It is unclear to what extent individual differences in false memories are driven by anatomical differences in memory-relevant brain regions. Here we show in humans that microstructural properties of different white matter tracts as quantified using diffusion tensor imaging are strongly correlated with true and false memory retrieval. To investigate these hypotheses, we tested a large group of participants in a version of the Deese-Roediger-McDermott paradigm (recall and recognition) and subsequently obtained diffusion tensor images. A voxel-based whole-brain level linear regression analysis was performedto relatefractional anisotropyto indices oftrue andfalse memory recall and recognition. True memory was correlated to diffusion anisotropy in the inferior longitudinal fascicle, the major connective pathway of the medial temporal lobe, whereas a greater proneness to retrieve false items was related to the superior longitudinal fascicle connecting frontoparietal structures. Our results show that individual differences in white matter microstructure underlie true and false memory performance.

El papel de la memoria de trabajo en el cálculo mental un cuarto de siglo después de Hitch = The role of working memory in mental arithmetic a quarter of century after Hitch

Desde que Hitch (1978) publicó el primer estudio sobre el rol de la memoria de trabajo en el cálculo han idoaumentando las investigaciones en este campo. Muchos trabajos han estudiado un único subsistema, pero nuestroobjetivo es identificar qué subsistema de la memoria de trabajo (bucle fonológico, agenda viso-espacial o ejecutivocentral) está más implicado en el cálculo mental. Para ello hemos realizado un estudio correlacional en el quehemos administrado dos pruebas aritméticas y nueve pruebas de la “Bateria de Test de Memòria de Treball” dePickering, Baqués y Gathercole (1999) a una muestra de 94 niños españoles de 7-8 años. Nuestros resultadosindican que el bucle fonológico y sobretodo el ejecutivo central inciden de forma estadísticamente significativa enel rendimiento aritmético

Studying Memory Encoding to Promote Reliable Engagement of the Medial Temporal Lobe at the Single-subject Level

The medial temporal lobe (MTL)-comprising hippocampus and the surrounding neocortical regions-is a targeted brain area sensitive to several neurological diseases. Although functional magnetic resonance imaging (fMRI) has been widely used to assess brain functional abnormalities, detecting MTL activation has been technically challenging. The aim of our study was to provide an fMRI paradigm that reliably activates MTL regions at the individual level, thus providing a useful tool for future research in clinical memory-related studies. Twenty young healthy adults underwent an event-related fMRI study consisting of three encoding conditions: word-pairs, face-name associations and complex visual scenes. A region-of-interest analysis at the individual level comparing novel and repeated stimuli independently for each task was performed. The results of this analysis yielded activations in the hippocampal and parahippocampal regions in most of the participants. Specifically, 95% and 100% of participants showed significant activations in the left hippocampus during the face-name encoding and in the right parahippocampus, respectively, during scene encoding. Additionally, a whole brain analysis, also comparing novel versus repeated stimuli at the group level, showed mainly left frontal activation during the word task. In this group analysis, the face-name association engaged the HP and fusiform gyri bilaterally, along with the left inferior frontal gyrus, and the complex visual scenes activated mainly the parahippocampus and hippocampus bilaterally. In sum, our task design represents a rapid and reliable manner to study and explore MTL activity at the individual level, thus providing a useful tool for future research in clinical memory-related fMRI studies.