Childhood adversity modulates structural brain changes in borderline personality but not in major depression disorder.

Adverse childhood experiences (ACEs) negatively affect the function and structure of emotion brain circuits, increasing the risk of various psychiatric disorders. It is unclear if ACEs show disorder specificity with respect to their effects on brain structure. We aimed to investigate whether the structural brain effects of ACEs differ between patients with major depression (MDD) and borderline personality disorder (BPD). These disorders share many symptoms but likely have different etiologies. To achieve our goal, we obtained structural 3T-MRI images from 20 healthy controls (HC), 19 MDD patients, and 18 BPD patients, and measured cortical thickness and subcortical gray matter volumes. We utilized the Adverse Childhood Experiences (ACE) questionnaire to quantify self-reported exposure to childhood trauma. Our findings suggest that individuals with MDD exhibit a smaller cortical thickness when compared to those with BPD. However, ACEs showed a significantly affected relationship with cortical thickness in BPD but not in MDD. ACEs were found to be associated with thinning in cortical regions involved in emotional behavior in BPD, whereas HC showed an opposite association. Our results suggest a potential mechanism of ACE effects on psychopathology involving changes in brain structure. These findings highlight the importance of early detection and intervention strategies.

Abnormal brain network community structure related to psychological stress in schizophrenia.

Recent functional imaging studies in schizophrenia consistently report a disruption of brain connectivity. However, most of these studies analyze the brain connectivity during resting state. Since psychological stress is a major factor for the emergence of psychotic symptoms, we sought to characterize the brain connectivity reconfiguration induced by stress in schizophrenia. We tested the hypothesis that an alteration of the brain's integration-segregation dynamic could be the result of patients with schizophrenia facing psychological stress. To this end, we studied the modular organization and the reconfiguration of networks induced by a stress paradigm in forty subjects (twenty patients and twenty controls), thus analyzing the dynamics of the brain in terms of integration and segregation processes by using 3T-fMRI. Patients with schizophrenia did not show statistically significant differences during the control task compared with controls, but they showed an abnormal community structure during stress condition and an under-connected reconfiguration network with a reduction of hub nodes, suggesting a deficit of integration dynamic with a greater compromise of the right hemisphere. These results provide evidence that schizophrenia has a normal response to undemanding stimuli but shows a disruption of brain functional connectivity between key regions involved in stress response, potentially leading to altered functional brain dynamics by reducing integration capacity and showing deficits recruiting right hemisphere regions. This could in turn underlie the hyper-sensitivity to stress characteristic of schizophrenia.

Are Brain Responses to Emotion a Reliable Endophenotype of Schizophrenia? An Image-Based Functional Magnetic Resonance Imaging Meta-analysis.

BACKGROUND: Impaired emotion processing constitutes a key dimension of schizophrenia and a possible endophenotype of this illness. Empirical studies consistently report poorer emotion recognition performance in patients with schizophrenia as well as in individuals at enhanced risk of schizophrenia. Functional magnetic resonance imaging studies also report consistent patterns of abnormal brain activation in response to emotional stimuli in patients, in particular, decreased amygdala activation. In contrast, brain-level abnormalities in at-risk individuals are more elusive. We address this gap using an image-based meta-analysis of the functional magnetic resonance imaging literature. METHODS: Functional magnetic resonance imaging studies investigating brain responses to negative emotional stimuli and reporting a comparison between at-risk individuals and healthy control subjects were identified. Frequentist and Bayesian voxelwise meta-analyses were performed separately, by implementing a random-effect model with unthresholded group-level T-maps from individual studies as input. RESULTS: In total, 17 studies with a cumulative total of 677 at-risk individuals and 805 healthy control subjects were included. Frequentist analyses did not reveal significant differences between at-risk individuals and healthy control subjects. Similar results were observed with Bayesian analyses, which provided strong evidence for the absence of meaningful brain activation differences across the entire brain. Region of interest analyses specifically focusing on the amygdala confirmed the lack of group differences in this region. CONCLUSIONS: These results suggest that brain activation patterns in response to emotional stimuli are unlikely to constitute a reliable endophenotype of schizophrenia. We suggest that future studies instead focus on impaired functional connectivity as an alternative and promising endophenotype.

Childhood adversity modulation of central autonomic network components during cognitive regulation of emotion in major depressive disorder and borderline personality disorder.

Adverse childhood experiences (ACEs) have lifelong effects on emotional behavior and are frequent in Borderline Personality Disorder (BPD) and Major Depressive Disorder (MDD). The Central Autonomic Network (CAN), which modulates heart rate variability (HRV), comprises brain regions that mediate emotion regulation processes. However, it remains unclear the effect of ACEs on CAN dynamics and its relationship with HRV in these disorders. We studied the effects of ACEs on the brain and HRV simultaneously, during regulation of psychological stress in 19 BPD, 20 MDD and 20 healthy controls (HC). Participants underwent a cognitive reappraisal task during fMRI with simultaneous ECG acquisition. ACEs exposure was associated with increased activity of CAN and salience network components in patients with MDD compared to BPD during cognitive reappraisal. A brain-autonomic coupling was found in BPD relative to HC during emotion regulation, whereby greater activity of left anterior cingulate and medial superior frontal gyrus areas was coupled with increased HRV. Results suggest that ACEs exposure is associated with a distinct activation of the CAN and salience network regions governing responses to psychological stress in MDD compared to BPD. These alterations may constitute a distinctive neurobiological mechanism for abnormal emotion processing and regulation related to ACEs in MDD.

An fMRI study of cognitive reappraisal in major depressive disorder and borderline personality disorder.

BACKGROUND: One common denominator to the clinical phenotypes of borderline personality disorder (BPD) and major depressive disorder (MDD) is emotion regulation impairment. Although these two conditions have been extensively studied separately, it remains unclear whether their emotion regulation impairments are underpinned by shared or distinct neurobiological alterations. METHODS: We contrasted the neural correlates of negative emotion regulation across an adult sample of BPD patients (n = 19), MDD patients (n = 20), and healthy controls (HCs; n = 19). Emotion regulation was assessed using an established functional magnetic resonance imaging cognitive reappraisal paradigm. We assessed both task-related activations and modulations of interregional connectivity. RESULTS: When compared to HCs, patients with BPD and MDD displayed homologous decreased activation in the right ventrolateral prefrontal cortex (vlPFC) during cognitive reappraisal. In addition, the MDD group presented decreased activations in other prefrontal areas (i.e., left dorsolateral and bilateral orbitofrontal cortices), while the BPD group was characterized by a more extended pattern of alteration in the connectivity between the vlPFC and cortices of the visual ventral stream during reappraisal. CONCLUSIONS: This study identified, for the first time, a shared neurobiological contributor to emotion regulation deficits in MDD and BPD characterized by decreased vlPFC activity, although we also observed disorder-specific alterations. In MDD, results suggest a primary deficit in the strength of prefrontal activations, while BPD is better defined by connectivity disruptions between the vlPFC and temporal emotion processing regions. These findings substantiate, in neurobiological terms, the different profiles of emotion regulation alterations observed in these disorders.

Amyloid and anatomical correlates of executive functioning in middle-aged offspring of patients with late-onset Alzheimer's disease.

A traditional hallmark of cognitive impairment associated with late-onset Alzheimer´s disease (LOAD) is episodic memory impairment. However, early alterations have been identified in brain regions associated with executive function in asymptomatic, middle-age offspring of patients with LOAD (O-LOAD) compared to those with no family history. We hypothesized that executive function among O-LOAD would correlate with structural and amyloid brain imaging differently from those without a family history of LOAD (control subjects, CS). Executive function, cortical thickness, and in-vivo Aß deposits were quantified in 30 O-LOAD and 25 CS. Associations were observed among O-LOAD only. Cortical thickness in the left lateral orbitofrontal cortex was positively associated with Design Fluency. The Stroop Color and Word Test, correlated positively with right rostral mid-frontal cortex thickness. Trails Making Test-B was inversely related to left medial orbitofrontal thickness. Tower of London total time was positively associated with ß-amyloid deposition in the right precuneus. These results support previous evidence that early executive dysfunction might reflect subtle, early changes in persons at risk of LOAD and suggests that executive function alterations deserve further exploration in the LOAD literature.

Distinct Neural Processing of Acute Stress in Major Depression and Borderline Personality Disorder.

BACKGROUND: Major depressive disorder (MDD) and borderline personality disorder (BPD) are highly prevalent and often comorbid psychiatric conditions, with abnormal processing of negative affect resulting from psychological stress. Characteristics of central processing of autonomic response to stress in each disorder are not clearly settled. METHODS: We obtained whole brain 3T fMRI with concurrent skin conductance, respiration rate, and heart rate variability measures in a cohort of MDD (N=19), BPD (N=19) patients, and healthy (N=20) individuals. Experiments were conducted in resting conditions, during a control mental arithmetic task, during highly stressful mental arithmetic, and in the period immediately following psychological stress. RESULTS: Widespread activation of central autonomic network (CAN) structures was observed during stress compared to a control task in the group of healthy participants, whereas CAN activation during stress was less intense in both BPD and MDD. Both patient groups displayed increased sympathetic and decreased parasympathetic activation compared to healthy subjects, as previously reported. The relationship between peripheral sympathetic or parasympathetic activity and simultaneous regional brain BOLD activity was similar in BPD patients and healthy subjects, and markedly different from that seen in MDD patients. LIMITATIONS: The sample size, the fact it belonged to a single study site, and low grade affective symptomatology in both patient groups limit the generalizability of the present findings. CONCLUSIONS: The diverging neurobiological signature in the homeostatic response to stress in MDD and BPD possibly represents a heuristically valuable candidate biomarker to help discern MDD and BPD patients.

Insular functional alterations in emotional processing of schizophrenia patients revealed by Multivariate Pattern Analysis fMRI.

Emotion perception is impaired in schizophrenia patients (SP) and related to reduced social skills performance. There is a remarkable variability across subjects for functional neuroimaging alterations related to this phenomenon. In contrast to the univariate approaches of fMRI, Multivariate Pattern Analysis (MVPA) maintains the within-subject voxel-level variability. The purpose of this study was to assess emotion processing in SP, in previously identified ROIs -i.e. amygdala, hippocampus, insula, and thalamus-, while retaining the functional heterogeneity that may exist between subjects. We evaluated 23 SP and 23 healthy controls (HC). Happy, sad, and neutral faces were presented. A single trial fMRI model was applied. Patterns of activation within each ROI were classified at the subject level. Within each group, stimuli classification scores were tested against random label classification scores. In ROIs with significant results, a whole ROI classification was performed, to test whether en bloc stimuli discrimination was present. A between-group analysis was conducted also. For the classification of stimuli above chance, in the HC results were significant in the left insula in all of the stimuli dichotomies, but were non-significant in SP for happy vs. sad. In whole ROI classification, SP had significant results in bilateral insular cortex for happy vs. neutral. The left amygdala showed diminished stimuli classification scores in SP for sad vs. neutral. In conclusion, MVPA seems useful to study emotional processing in schizophrenia. In SP, either en bloc or no stimuli discrimination was seen in the insula, and reduced stimuli discrimination was seen in the left amygdala.

Disrupted functional connectivity of the locus coeruleus in healthy adults with parental history of Alzheimer's disease.

Prevention and early treatment strategies for Alzheimer's disease (AD) are hampered by the lack of research biomarkers. Neuropathological changes in the Locus Coeruleus (LC) are detected early in AD, and noradrenaline plays a neuroprotective role in LC projecting areas. We assessed functional connectivity (FC) of the brainstem in asymptomatic individuals at familial risk for AD hypothesizing that FC of the LC will be decreased in relation to not-at-risk individuals. Thirty-one offspring of patients with late-onset AD (O-LOAD) (22 females; mean age ± SD = 50.36 ± 8.32) and 28 healthy controls (HC) (20 females; mean age ± SD = 53.90 ± 8.44) underwent a neurocognitive evaluation and a resting-state functional magnetic resonance imaging acquisition. In FC analyses we evaluated whole-brain global connectivity of the brainstem area, and subsequently assessed seed-to-voxel FC patterns from regions showing between-group differences. O-LOAD individuals scored worse in neurocognitive measures of memory and overall functioning (pFDR<0.05). In imaging analyses, we observed that O-LOAD individuals showed decreased global connectivity in a cluster encompassing the left LC (peak = -4, -34, -32, pTFCE<0.05). Seed-to-voxel analyses revealed that this finding was largely explained by decreased connectivity between the LC and the cerebellar cortex. Moreover, FC between the LC and the left cerebellum correlated positively with delayed recall scores. FC between the LC and the cerebellar cortex is decreased in the healthy offspring of patients with LOAD, such connectivity measurements being associated with delayed memory scores. The assessment of FC between the LC and the cerebellum may serve as a biomarker of AD vulnerability.

White matter fiber density abnormalities in cognitively normal adults at risk for late-onset Alzheimer's disease.

Tau accumulation affecting white matter tracts is an early neuropathological feature of late-onset Alzheimer's disease (LOAD). There is a need to ascertain methods for the detection of early LOAD features to help with disease prevention efforts. The microstructure of these tracts and anatomical brain connectivity can be assessed by analyzing diffusion MRI (dMRI) data. Considering that family history increases the risk of developing LOAD, we explored the microstructure of white matter through dMRI in 23 cognitively normal adults who are offspring of patients with Late-Onset Alzheimer's Disease (O-LOAD) and 22 control subjects (CS) without family history of AD. We also evaluated the relation of white matter microstructure metrics with cortical thickness, volumetry, in vivo amyloid deposition (with the help of PiB positron emission tomography -PiB-PET) and regional brain metabolism (as FDG-PET) measures. Finally we studied the association between cognitive performance and white matter microstructure metrics. O-LOAD exhibited lower fiber density and fractional anisotropy in the posterior portion of the corpus callosum and right fornix when compared to CS. Among O-LOAD, reduced fiber density was associated with lower amyloid deposition in the right hippocampus, and greater cortical thickness in the left precuneus, while higher mean diffusivity was related with greater cortical thickness of the right superior temporal gyrus. Additionally, compromised white matter microstructure was associated with poorer semantic fluency. In conclusion, white matter microstructure metrics may reveal early differences in O-LOAD by virtue of parental history of the disorder, when compared to CS without a family history of LOAD. We demonstrate that these differences are associated with lower fiber density in the posterior portion of the corpus callosum and the right fornix.

Spectral signatures of serotonergic psychedelics and glutamatergic dissociatives.

Classic serotonergic psychedelics are remarkable for their capacity to induce reversible alterations in consciousness of the self and the surroundings, mediated by agonism at serotonin 5-HT2A receptors. The subjective effects elicited by dissociative drugs acting as N-methyl-D-aspartate (NMDA) antagonists (e.g. ketamine and phencyclidine) overlap in certain domains with those of serotonergic psychedelics, suggesting some potential similarities in the brain activity patterns induced by both classes of drugs, despite different pharmacological mechanisms of action. We investigated source-localized magnetoencephalography recordings to determine the frequency-specific changes in oscillatory activity and long-range functional coupling that are common to two serotonergic compounds (lysergic acid diethylamide [LSD] and psilocybin) and the NMDA-antagonist ketamine. Administration of the three drugs resulted in widespread and broadband spectral power reductions. We established their similarity by using different pairs of compounds to train and subsequently evaluate multivariate machine learning classifiers. After applying the same methodology to functional connectivity values, we observed a pattern of occipital, parietal and frontal decreases in the low alpha and theta bands that were specific to LSD and psilocybin, as well as decreases in the low beta band common to the three drugs. Our results represent a first effort in the direction of quantifying the similarity of large-scale brain activity patterns induced by drugs of different mechanism of action, confirming the link between changes in theta and alpha oscillations and 5-HT2A agonism, while also revealing the decoupling of activity in the beta band as an effect shared between NMDA antagonists and 5-HT2A agonists. We discuss how these frequency-specific convergences and divergences in the power and functional connectivity of brain oscillations might relate to the overlapping subjective effects of serotonergic psychedelics and glutamatergic dissociative compounds.

Author Correction: Retrieval of retrained and reconsolidated memories are associated with a distinct neural network.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Executive functioning in cognitively normal middle-aged offspring of late-onset Alzheimer's disease patients.

Episodic memory deficits are traditionally seen as the hallmark cognitive impairment during the prodromal continuum of late-onset Alzheimer's disease (LOAD). Previous studies identified early brain alterations in regions subserving executive functions in asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD), suggesting that premature episodic memory deficits could be associated to executive dysfunction in this model. We hypothesized that O-LOAD would exhibit reduced executive performance evidenced by increased errors and decreased strategy use on an episodic memory task. We assessed 32 asymptomatic middle-aged O-LOAD and 28 age-equivalent control subjects (CS) with several tests that measure executive functions and the Rey Auditory Verbal Learning Test (RAVLT) to measure memory performance. All tests were scored using both traditional and process scores (quantification of errors and strategies underlying overall performance). T-tests were used to compare performance between both groups and Spearman correlations were implemented to measure associations between variables. O-LOAD participants exhibited decreased executive performance compared to CS as it relates to initiation time (Tower of London), mental switching (Trail Making Test B), and interference effects (Stroop Word-Color condition). Traditional RAVLT measures showed a poorer performance by O-LOAD and RAVLT process scores revealed increased interference effects on this group. Positive correlations (rs) were found between the executive measures and several RAVLT measures for O-LOAD but not for CS. In conclusion, O-LOAD participants exhibited early subtle cognitive changes in executive processing. Observed memory difficulties may be associated in part to executive deficits suggesting an interplay between memory and executive functions. Process score impairments were observed earlier than clinical decline on neuropsychological scores in this at-risk cohort and might be useful cognitive markers of preclinical LOAD.

Retrieval of retrained and reconsolidated memories are associated with a distinct neural network.

Consolidated memories can persist from a single day to years, and persistence is improved by retraining or retrieval-mediated plasticity. One retrieval-based way to strengthen memory is the reconsolidation process. Strengthening occurs simply by the presentation of specific cues associated with the original learning. This enhancement function has a fundamental role in the maintenance of memory relevance in animals everyday life. In the present study, we made a step forward in the identification of brain correlates imprinted by the reconsolidation process studying the long-term neural consequences when the strengthened memory is stable again. To reach such a goal, we compared the retention of paired-associate memories that went through retraining process or were labilizated-reconsolidated. Using functional magnetic resonance imaging (fMRI), we studied the specific areas activated during retrieval and analyzed the functional connectivity of the whole brain associated with the event-related design. We used Graph Theory tools to analyze the global features of the network. We show that reconsolidated memories imprint a more locally efficient network that is better at exchanging information, compared with memories that were retrained or untreated. For the first time, we report a method to elucidate the neural footprints associated with a relevant function of memory reconsolidation.

Brain Structural and Amyloid Correlates of Recovery From Semantic Interference in Cognitively Normal Individuals With or Without Family History of Late-Onset Alzheimer's Disease.

Failure to recover from proactive semantic interference (frPSI) has been shown to be more sensitive than traditional cognitive measures in different populations with preclinical Alzheimer's disease. The authors sought to characterize the structural and amyloid in vivo correlates of frPSI in cognitively normal offspring of patients with late-onset Alzheimer's disease (O-LOAD), compared with individuals without a family history of neurodegenerative disorders (CS). The authors evaluated the LASSI-L, a test tapping frPSI and other types of semantic interference and delayed recall on the RAVLT, along with 3-T MRI volumetry and positron emission tomography Pittsburgh compound B, in 27 O-LOAD and 18 CS with equivalent age, sex, years of education, ethnicity, premorbid intelligence, and mood symptoms. Recovery from proactive semantic interference (frPSI) and RAVLT delayed recall were lower in O-LOAD cases. Structural correlates of both cognitive dimensions were different in CS and O-LOAD, involving brain regions concerned with autonomic, motor, and motivational control in the former, and regions traditionally implicated in Alzheimer's disease in the latter. Better recovery from retroactive semantic interference was associated with less amyloid load in the left temporal lobe in O-LOAD but not CS. In middle-aged cognitively normal individuals with one parent affected with LOAD, frPSI was impaired compared with persons without a family history of LOAD. The neuroimaging correlates of such cognitive measure in those with one parent with LOAD involve Alzheimer's-relevant brain regions even at a relatively young age.

Cortical thickness, brain metabolic activity, and in vivo amyloid deposition in asymptomatic, middle-aged offspring of patients with late-onset Alzheimer's disease.

The natural history of preclinical late-onset Alzheimer's disease (LOAD) remains obscure and has received less attention than that of early-onset AD (EOAD), in spite of accounting for more than 99% of cases of AD. With the purpose of detecting early structural and functional traits associated with the disorder, we sought to characterize cortical thickness and subcortical grey matter volume, cerebral metabolism, and amyloid deposition in persons at risk for LOAD in comparison with a similar group without family history of AD. We obtained 3T T1 images for gray matter volume, FDG-PET to evaluate regional cerebral metabolism, and PET-PiB to detect fibrillar amyloid deposition in 30 middle-aged, asymptomatic, cognitively normal individuals with one parent diagnosed with LOAD (O-LOAD), and 25 comparable controls (CS) without family history of neurodegenerative disorders (CS). We observed isocortical thinning in AD-relevant areas including posterior cingulate, precuneus, and areas of the prefrontal and temporoparietal cortex in O-LOAD. Unexpectedly, this group displayed increased cerebral metabolism, in some cases overlapping with the areas of cortical thinning, and no differences in bilateral hippocampal volume and hippocampal metabolism. Given the importance of age in this sample of individuals potentially developing early AD-related changes, we controlled results for age and observed that most differences in cortical thickness and metabolism became nonsignificant; however, greater deposition of ß-amyloid was observed in the right hemisphere including temporoparietal cortex, postcentral gyrus, fusiform inferior and middle temporal and lingual gyri. If replicated, the present observations of morphological, metabolic, and amyloid changes in cognitively normal persons with family history of LOAD may bear important implications for the definition of very early phenotypes of this disorder.

Failure to Recover from Proactive Semantic Interference and Abnormal Limbic Connectivity in Asymptomatic, Middle-Aged Offspring of Patients with Late-Onset Alzheimer's Disease.

BACKGROUND: We have obtained previous evidence of limbic dysfunction in middle-aged, asymptomatic offspring of late-onset Alzheimer's disease (LOAD) patients, and failure to recover from proactive semantic interference has been shown to be a sensitive cognitive test in other groups at risk for LOAD. OBJECTIVE: To assess the effects of specific proactive semantic interference deficits as they relate to functional magnetic resonance imaging (fMRI) neocortical and limbic functional connectivity in middle aged offspring of individuals with LOAD (O-LOAD) and age-equivalent controls. METHODS: We examined 21 O-LOAD and 20 controls without family history of neurodegenerative disorders (CS) on traditional measures of cognitive functioning and the LASSI-L, a novel semantic interference test uniquely sensitive to the failure to recover from proactive interference (frPSI). Cognitive tests then were correlated to fMRI connectivity of seeds located in entorhinal cortex and anterodorsal thalamic nuclei among O-LOAD and CS participants. RESULTS: Relative to CS, O-LOAD participants evidenced lower connectivity between entorhinal cortex and orbitofrontal, anterior cingulate, and anterior temporal cortex. In the offspring of LOAD patients, LASSI-L measures of frPSI were inversely associated with connectivity between anterodorsal thalamus and contralateral posterior cingulate. Intrusions on the task related to frPSI were inversely correlated with a widespread connectivity network involving hippocampal, insular, posterior cingulate, and dorsolateral prefrontal cortices, along with precunei and anterior thalamus in this group. Different patterns of connectivity associated with frPSI were observed among controls. CONCLUSION: The present results suggest that both semantic interference deficits and connectivity abnormalities might reflect limbic circuit dysfunction as a very early clinical signature of LOAD pathology, as previously demonstrated for other limbic phenotypes, such as sleep and circadian alterations.

Relationship between Cognitive and Sleep-wake Variables in Asymptomatic Offspring of Patients with Late-onset Alzheimer's Disease.

Early neuropathological changes characteristic of late-onset Alzheimer's disease (LOAD) involve brain stem and limbic structures that regulate neurovegetative functions, including sleep-wake rhythm. Indeed, sleep pattern is an emerging biomarker and a potential pathophysiological mechanism in LOAD. We hypothesized that cognitively asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD) would display a series of circadian rhythm abnormalities prior to the onset of objective cognitive alterations. We tested 31 children of patients with LOAD (O-LOAD) and 19 healthy individuals without family history of Alzheimer's disease (control subjects, CS) with basic tests of cognitive function, as well as actigraphy measures of sleep-wake rhythm, cardiac autonomic function, and bodily temperature. Unexpectedly, O-LOAD displayed subtle but significant deficits in verbal episodic memory (Rey Auditory Verbal Learning Test delayed recall 10.6 ± 0.4 vs. 8.6 ± 0.6, t = 4.97, df = 49, p < 0.01) and language (Weschler's vocabulary 51.4 ± 1.3 vs. 44.3 ± 1.5, t = 2.49, df = 49, p < 0.001) compared to CS, even though all participants had results within the clinically normal range. O-LOAD showed a phase-delayed rhythm of body temperature (2.56 ± 0.47 h vs. 3.8 ± 0.26 h, t = 2.48, df = 40, p = 0.031). Cognitive performance in O-LOAD was associated with a series of cardiac autonomic sleep-wake variables; specifically indicators of greater sympathetic activity at night were related to poorer cognition. The present results suggest sleep pattern deserves further study as a potential neurobiological signature in LOAD, even in middle-aged, at risk individuals.

Differential Left Hippocampal Activation during Retrieval with Different Types of Reminders: An fMRI Study of the Reconsolidation Process.

Consolidated memories return to a labile state after the presentation of cues (reminders) associated with acquisition, followed by a period of stabilization (reconsolidation). However not all cues are equally effective in initiating the process, unpredictable cues triggered it, predictable cues do not. We hypothesize that the different effects observed by the different reminder types on memory labilization-reconsolidation depend on a differential neural involvement during reminder presentation. To test it, we developed a declarative task and compared the efficacy of three reminder types in triggering the process in humans (Experiment 1). Finally, we compared the brain activation patterns between the different conditions using functional magnetic resonance imaging (fMRI) (Experiment 2). We confirmed that the unpredictable reminder is the most effective in initiating the labilization-reconsolidation process. Furthermore, only under this condition there was differential left hippocampal activation during its presentation. We suggest that the left hippocampus is detecting the incongruence between actual and past events and allows the memory to be updated.