Anterior Hippocampus Research Articles

Aberrant intra- and internetwork functional connectivity patterns of the anterior and posterior hippocampal networks in schizophrenia.

Schizophrenia is associated with abnormal hippocampal structure and function. Available evidence suggests that the anterior and posterior hippocampus are differentially affected by schizophrenia pathology. This study was designed to provide new insight into the anterior and posterior hippocampus in schizophrenia from the perspective of functional connectivity. Based on resting-state functional magnetic resonance imaging data of 71 schizophrenia patients and 74 normal controls, we utilized a data-driven approach to functionally segment the hippocampus into anterior and posterior segments and then investigated the functional connectivity patterns within and between the two hippocampal networks at the network, edge, and nodal levels. We found that schizophrenia patients showed hyperconnectivity of both the anterior and posterior hippocampal networks. We also observed that the network alterations appear somewhat greater in the anterior hippocampal network than the posterior network, the left side than the right, and the intranetwork connectivity than the internetwork connectivity. The results reveal convergent and divergent intranetwork and internetwork connectivity patterns of the anterior and posterior hippocampus in schizophrenia, providing novel and important insights into the mechanisms of hippocampal pathology in schizophrenia.

Exogenous L-lactate administration in rat hippocampus increases expression of key regulators of mitochondrial biogenesis and antioxidant defense.

L-lactate plays a critical role in learning and memory. Studies in rats showed that administration of exogenous L-lactate into the anterior cingulate cortex and hippocampus (HPC) improved decision-making and enhanced long-term memory formation, respectively. Although the molecular mechanisms by which L-lactate confers its beneficial effect are an active area of investigations, one recent study found that L-lactate supplementation results in a mild reactive oxygen species burst and induction of pro-survival pathways. To further investigate the molecular changes induced by L-lactate, we injected rats with either L-lactate or artificial CSF bilaterally into the dorsal HPC and collected the HPC after 60 minutes for mass spectrometry. We identified increased levels of several proteins that include SIRT3, KIF5B, OXR1, PYGM, and ATG7 in the HPC of the L-lactate treated rats. SIRT3 (Sirtuin 3) is a key regulator of mitochondrial functions and homeostasis and protects cells against oxidative stress. Further experiments identified increased expression of the key regulator of mitochondrial biogenesis (PGC-1α) and mitochondrial proteins (ATPB, Cyt-c) as well as increased mitochondrial DNA (mtDNA) copy number in the HPC of L-lactate treated rats. OXR1 (Oxidation resistance protein 1) is known to maintain mitochondrial stability. It mitigates the deleterious effects of oxidative damage in neurons by inducing a resistance response against oxidative stress. Together, our study suggests that L-lactate can induce expression of key regulators of mitochondrial biogenesis and antioxidant defense. These findings create new research avenues to explore their contribution to the L-lactate's beneficial effect in cognitive functions as these cellular responses might enable neurons to generate more ATP to meet energy demand of neuronal activity and synaptic plasticity as well as attenuate the associated oxidative stress.

Nonlinear Theta-Gamma Coupling between the Anterior Thalamus and Hippocampus Increases as a Function of Running Speed.

The hippocampal theta rhythm strongly correlates to awake behavior leading to theories that it represents a cognitive state of the brain. As theta has been observed in other regions of the Papez circuit, it has been theorized that activity propagates in a reentrant manner. These observations complement the energy cascade hypothesis in which large-amplitude, slow-frequency oscillations reflect activity propagating across a large population of neurons. Higher frequency oscillations, such as gamma, are related to the speed with which inhibitory and excitatory neurons interact and distribute activity on the local level. The energy cascade hypothesis suggests that the larger anatomic loops, maintaining theta, drive the smaller loops. As hippocampal theta increases in power with running speed, so does the power and frequency of the gamma rhythm. If theta is propagated through the circuit, it stands to reason that the local field potential (LFP) recorded in other regions would be coupled to the hippocampal theta, with the coupling increasing with running speed. We explored this hypothesis using open-source simultaneous recorded data from the CA1 region of the hippocampus and the anterior dorsal and anterior ventral thalamus. Cross-regional theta coupling increased with running speed. Although the power of the gamma rhythm was lower in the anterior thalamus, there was an increase in the coupling of hippocampal theta to anterior thalamic gamma. Broadly, the data support models of how activity moves across the nervous system, suggesting that the brain uses large-scale volleys of activity to support higher cognitive processes.

Functional re-organization of hippocampal-cortical gradients during naturalistic memory processes

The functional organization of the hippocampus mirrors that of the cortex, changing smoothly along connectivity gradients and abruptly at inter-areal boundaries. Hippocampal-dependent cognitive processes require flexible integration of these hippocampal gradients into functionally related cortical networks. To understand the cognitive relevance of this functional embedding, we acquired fMRI data while participants viewed brief news clips, either containing or lacking recently familiarized cues. Participants were 188 healthy mid-life adults and 31 adults with mild cognitive impairment (MCI) or Alzheimer's disease (AD). We employed a recently developed technique - connectivity gradientography - to study gradually changing patterns of voxel to whole brain functional connectivity and their sudden transitions. We observed that functional connectivity gradients of the anterior hippocampus map onto connectivity gradients across the default mode network during these naturalistic stimuli. The presence of familiar cues in the news clips accentuates a stepwise transition across the boundary from the anterior to the posterior hippocampus. This functional transition is shifted in the posterior direction in the left hippocampus of individuals with MCI or AD. These findings shed new light on the functional integration of hippocampal connectivity gradients into large-scale cortical networks, how these adapt with memory context and how these change in the presence of neurodegenerative disease.

Social navigation modulates the anterior and posterior hippocampal circuits in the resting brain.

Social navigation is a dynamic and complex process that requires the collaboration of multiple brain regions. However, the neural networks for navigation in a social space remain largely unknown. This study aimed to investigate the role of hippocampal circuit in social navigation from a resting-state fMRI data. Here, resting-state fMRI data were acquired before and after participants performed a social navigation task. By taking the anterior and posterior hippocampus (HPC) as the seeds, we calculated their connectivity with the whole brain using the seed-based static functional connectivity (sFC) and dynamic FC (dFC) approaches. We found that the sFC and dFC between the anterior HPC and supramarginal gyrus, sFC or dFC between posterior HPC and middle cingulate cortex, inferior parietal gyrus, angular gyrus, posterior cerebellum, medial superior frontal gyrus were increased after the social navigation task. These alterations were related to social cognition of tracking location in the social navigation. Moreover, participants who had more social support or less neuroticism showed a greater increase in hippocampal connectivity. These findings may highlight a more important role of the posterior hippocampal circuit in the social navigation, which is crucial for social cognition.

The impact of iron deposition on the fear circuit of the brain in patients with Parkinson's disease and anxiety.

Anxiety is one of the most common psychiatric symptoms of Parkinson's disease (PD), and brain iron deposition is considered to be one of the pathological mechanisms of PD. The objective of this study was to explore alterations in brain iron deposition in PD patients with anxiety compared to PD patients without anxiety, especially in the fear circuit. Sixteen PD patients with anxiety, 23 PD patients without anxiety, and 26 healthy elderly controls were enrolled prospectively. All subjects underwent neuropsychological assessments and brain magnetic resonance imaging (MRI) examinations. Voxel-based morphometry (VBM) was used to study morphological brain differences between the groups. Quantitative susceptibility mapping (QSM), an MRI technique capable of quantifying susceptibility changes in brain tissue, was used to compare susceptibility changes in the whole brain among the three groups. The correlations between brain susceptibility changes and anxiety scores quantified using the Hamilton Anxiety Rating Scale (HAMA) were compared and analyzed. PD patients with anxiety had a longer duration of PD and higher HAMA scores than PD patients without anxiety. No morphological brain differences were observed between the groups. In contrast, voxel-based and ROI-based QSM analyses showed that PD patients with anxiety had significantly increased QSM values in the medial prefrontal cortex, anterior cingulate cortex, hippocampus, precuneus, and angular cortex. Furthermore, the QSM values of some of these brain regions were positively correlated with the HAMA scores (medial prefrontal cortex: r = 0.255, p = 0.04; anterior cingulate cortex: r = 0.381, p < 0.01; hippocampus: r = 0.496, p < 0.01). Our findings support the idea that anxiety in PD is associated with iron burden in the brain fear circuit, providing a possible new approach to explaining the potential neural mechanism of anxiety in PD.

Effective Connectivity Between the Orbitofrontal Cortex and the Precuneus Differentiates Major Psychiatric Disorders: Results from a Transdiagnostic Spectral DCM Study.

We have previously identified aberrant connectivity of the left precuneus, ventrolateral prefrontal cortex, anterior cingulate cortex, and anterior insula in patients with either a paranoid (schizophrenia), or a depressive syndrome (both unipolar and bipolar). In the current study, we attempted to replicate and expand these findings by including a healthy control sample and separating the patients in a depressive episode into two groups: unipolar and bipolar depression. We hypothesized that the connections between those major nodes of the resting state networks would demonstrate different patterns in the three patient groups compared to the healthy subjects. Resting-state functional MRI was performed on a sample of 101 participants, of which 26 patients with schizophrenia (current psychotic episodes), 24 subjects with Bipolar Disorder (BD), 33 with Major Depressive Disorder (MDD) (both BD and MDD patients were in a current depressive episode), and 21 healthy controls. Spectral Dynamic Causal Modeling was used to calculate the coupling values between eight regions of interest, including the anterior precuneus (PRC), anterior hippocampus, anterior insula, angular gyrus, lateral Orbitofrontal Cortex (OFC), middle frontal gyrus, planum temporale, and anterior thalamus. We identified disturbed effective connectivity from the left lateral orbitofrontal cortex to the left anterior precuneus that differed significantly between unipolar depression, where the influence was inhibitory, and bipolar depression, where the effect was excitatory. A logistic regression analysis correctly classified 75% of patients with unipolar and bipolar depression based solely on the coupling values of this connection. In addition, patients with schizophrenia demonstrated negative effective connectivity from the anterior PRC to the lateral OFC, which distinguished them from healthy controls and patients with major depression. Future studies with unmedicated patients will be needed to establish the replicability of our findings.

The high frequency oscillation in orbitofrontal cortex is susceptible to phenethylamine psychedelic 25C–NBOMe in male rats

Serotoninergic psychedelics induced extensive alterations in perception and cognition, which has been attributable to its disruptive effect on oscillatory rhythms of prefrontal cortex. However, there is a lack of information how serotoninergic psychedelics affect the intra-prefrontal network, which intrinsically interact to accomplish perceptual processing. Uncovering the altered neural network caused by psychedelics helps to understand the mechanisms of their psychoactive effects and contribute to develop biological markers of psychedelic effects. In present study, we investigated the effects of substituted phenethylamine psychedelic 25C–NBOMe on neural oscillations in the intra-prefrontal and hippocampal-prefrontal network. The effective dose of 25C–NBOMe (0.1 mg/kg) disrupting sensorimotor gating in male Sprague–Dawley rats was used to observe its effects on neural oscillations in the prelimbic cortex, anterior cingulate cortex, orbitofrontal cortex (OFC) and hippocampus CA1. The power of high frequency oscillation (HFO, 120–150 Hz) was potentiated by 25C–NBOMe selectively in the OFC, with peaking at 20–30 min after treatment. 25C–NBOMe strengthened HFO coherence within the intra-prefrontal, rather than hippocampal-prefrontal network. Potentiated HFO in the OFC had a strong positive correlation with the strengthened inter-prefrontal HFO coherence by 25C–NBOMe. The 25C–NBOMe-induced alterations of rhythmic patterns were prevented by pre-treatment with selective serotonin 2A receptor antagonist MDL100,907. These results demonstrate that OFC rhythmic activity in HFO is relatively susceptible to substituted phenethylamine and potentially drives drug-induced rhythmic coherence within intra-prefrontal regions. Our findings provide additional insight into the neuropathophysiology of the psychoactive effects of psychedelics and indicate that the altered HFO might be applied as a potential biological marker of psychedelic effect.

The effect of d-cycloserine on brain processing of breathlessness over pulmonary rehabilitation: an experimental medicine study.

Pulmonary rehabilitation is the best treatment for chronic breathlessness in COPD but there remains an unmet need to improve efficacy. Pulmonary rehabilitation has strong parallels with exposure-based cognitive behavioural therapies (CBT), both clinically and in terms of brain activity patterns. The partial N-methyl-d-aspartate (NMDA)-receptor agonist d-cycloserine has shown promising results in enhancing efficacy of CBT, thus we hypothesised that it would similarly augment the effects of pulmonary rehabilitation in the brain. Positive findings would support further development in phase 3 clinical trials. 72 participants with mild-to-moderate COPD were recruited to a double-blind pre-registered (ClinicalTrials.gov identifier: NCT01985750) experimental medicine study running parallel to a pulmonary rehabilitation course. Participants were randomised to 250 mg d-cycloserine or placebo, administered immediately prior to the first four sessions of pulmonary rehabilitation. Primary outcome measures were differences between d-cycloserine and placebo in brain activity in the anterior insula, posterior insula, anterior cingulate cortices, amygdala and hippocampus following completion of pulmonary rehabilitation. Secondary outcomes included the same measures at an intermediate time point and voxel-wise difference across wider brain regions. An exploratory analysis determined the interaction with breathlessness anxiety. No difference between d-cycloserine and placebo groups was observed across the primary or secondary outcome measures. d-cycloserine was shown instead to interact with changes in breathlessness anxiety to dampen reactivity to breathlessness cues. Questionnaire and measures of respiratory function showed no group difference. This is the first study testing brain-active drugs in pulmonary rehabilitation. Rigorous trial methodology and validated surrogate end-points maximised statistical power. Although increasing evidence supports therapeutic modulation of NMDA pathways to treat symptoms, we conclude that a phase 3 clinical trial of d-cycloserine would not be worthwhile.

Spatial coding in the hippocampus and hyperpallium of flying owls

The elucidation of spatial coding in the hippocampus requires exploring diverse animal species. While robust place-cells are found in the mammalian hippocampus, much less is known about spatial coding in the hippocampus of birds. Here we used a wireless-electrophysiology system to record single neurons in the hippocampus and other two dorsal pallial structures from freely flying barn owls (Tyto alba), a central-place nocturnal predator species with excellent navigational abilities. The owl's 3D position was monitored while it flew between perches. We found place cells-neurons that fired when the owl flew through a spatially restricted region in at least one direction-as well as neurons that encoded the direction of flight, and neurons that represented the owl's perching position between flights. Many neurons encoded combinations of position, direction, and perching. Spatial coding was maintained stable and invariant to lighting conditions. Place cells were observed in owls performing two different types of flying tasks, highlighting the generality of the result. Place coding was found in the anterior hippocampus and in the posterior part of the hyperpallium apicale, and to a lesser extent in the visual Wulst. The finding of place-cells in flying owls suggests commonalities in spatial coding across mammals and birds.

The Role of the Left Inferior Frontal Gyrus in Introspection during Verbal Communication.

Conversation enables the sharing of our subjective experiences through verbalizing introspected thoughts and feelings. The mentalizing network represents introspection, and successful conversation is characterized by alignment through imitation mediated by the mirror neuron system (MNS). Therefore, we hypothesized that the interaction between the mentalizing network and MNS mediates the conversational exchange of introspection. To test this, we performed hyperscanning functional magnetic resonance imaging during structured real-time conversations between 19 pairs of healthy participants. The participants first evaluated their preference for and familiarity with a presented object and then disclosed it. The control was the object feature identification task. When contrasted with the control, the preference/familiarity evaluation phase activated the dorso-medial prefrontal cortex, anterior cingulate cortex, precuneus, left hippocampus, right cerebellum, and orbital portion of the left inferior frontal gyrus (IFG), which represents introspection. The left IFG was activated when the two participants' statements of introspection were mismatched during the disclosure. Disclosing introspection enhanced the functional connectivity of the left IFG with the bilateral superior temporal gyrus and primary motor cortex, representing the auditory MNS. Thus, the mentalizing system and MNS are hierarchically linked in the left IFG during a conversation, allowing for the sharing of introspection of the self and others.

Altered Resting-State functional connectivity in the anterior and posterior hippocampus in Post-traumatic stress disorder: The central role of the anterior hippocampus

BackgroundPost-traumatic stress disorder can be viewed as a memory disorder, with trauma-related flashbacks being a core symptom. Given the central role of the hippocampus in autobiographical memory, surprisingly, there is mixed evidence concerning altered hippocampal functional connectivity in PTSD. We shed light on this discrepancy by considering the distinct roles of the anterior versus posterior hippocampus and examine how this distinction may map onto whole-brain resting-state functional connectivity patterns among those with and without PTSD. MethodsWe first assessed whole-brain between-group differences in the functional connectivity profiles of the anterior and posterior hippocampus within a publicly available data set of resting-state fMRI data from 31 male Vietnam war veterans diagnosed with PTSD (mean age = 67.6 years, sd = 2.3) and 29 age-matched combat-exposed male controls (age = 69.1 years, sd = 3.5). Next, the connectivity patterns of each subject within the PTSD group were correlated with their PTSD symptom scores. Finally, the between-group differences in whole-brain functional connectivity profiles discovered for the anterior and posterior hippocampal seeds were used to prescribe post-hoc ROIs, which were then used to perform ROI-to-ROI functional connectivity and graph-theoretic analyses. ResultsThe PTSD group showed increased functional connectivity of the anterior hippocampus with affective brain regions (anterior/posterior insula, orbitofrontal cortex, temporal pole) and decreased functional connectivity of the anterior/posterior hippocampus with regions involved in processing bodily self-consciousness (supramarginal gyrus). Notably, decreased anterior hippocampus connectivity with the posterior cingulate cortex/precuneus was associated with increased PTSD symptom severity. The left anterior hippocampus also emerged as a central locus of abnormal functional connectivity, with graph-theoretic measures suggestive of a more central hub-like role for this region in those with PTSD compared to trauma-exposed controls. ConclusionsOur results highlight that the anterior hippocampus plays a critical role in the neurocircuitry underlying PTSD and underscore the importance of the differential roles of hippocampal sub-regions in serving as biomarkers of PTSD. Future studies should investigate whether the differential patterns of functional connectivity stemming from hippocampal sub-regions is observed in PTSD populations other than older war veterans.

Effects of Physical Exercise Training on Cerebral Blood Flow Measurements: A Systematic Review of Human Intervention Studies.

The aim of this systematic review was to examine the effects of physical exercise training on cerebral blood flow (CBF), which is a physiological marker of cerebrovascular function. Relationships between training-induced effects on CBF with changes in cognitive performance were also discussed. A systematic search was performed up to July 2022. Forty-five intervention studies with experimental, quasi-experimental, or pre-post designs were included. Sixteen studies (median duration: 14weeks) investigated effects of physical exercise training on CBF markers using magnetic resonance imaging, 20 studies (median duration: 14weeks) used transcranial Doppler ultrasound, and eight studies (median duration: 8weeks) used near-infrared spectroscopy. Studies using magnetic resonance imaging observed consistent increases in CBF in the anterior cingulate cortex and hippocampus, but not in whole-brain CBF. Effects on resting CBF-measured with transcranial Doppler ultrasound and near-infrared spectroscopy-were variable, while middle cerebral artery blood flow velocity increased in some studies following exercise or hypercapnic stimuli. Interestingly, concomitant changes in physical fitness and regional CBF were observed, while a relation between training-induced effects on CBF and cognitive performance was evident. In conclusion, exercise training improved cerebrovascular function because regional CBF was changed. Studies are however still needed to establish whether exercise-induced improvements in CBF are sustained over longer periods of time and underlie the observed beneficial effects on cognitive performance.

Contemporary Approaches Toward Neuromodulationof Fear Extinction and Its Underlying Neural Circuits.

Neuroscience and neuroimaging research have now identified brain nodes that are involved in the acquisition, storage, and expression of conditioned fear and its extinction. These brain regions include the ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), amygdala, insular cortex, and hippocampus. Psychiatric neuroimaging research shows that functional dysregulation of these brain regions might contribute to the etiology and symptomatology of various psychopathologies, including anxiety disorders and post traumatic stress disorder (PTSD) (Barad et al. Biol Psychiatry 60:322-328, 2006; Greco and Liberzon Neuropsychopharmacology 41:320-334, 2015; Milad et al. Biol Psychiatry 62:1191-1194, 2007a, Biol Psychiatry 62:446-454, b; Maren and Quirk Nat Rev Neurosci 5:844-852, 2004; Milad and Quirk Annu Rev Psychol 63:129, 2012; Phelps et al. Neuron 43:897-905, 2004; Shin and Liberzon Neuropsychopharmacology 35:169-191, 2009). Combined, these findings indicate that targeting the activation of these nodes and modulating their functional interactions might offer an opportunity to further our understanding of how fear and threat responses are formed and regulated in the human brain, which could lead to enhancing the efficacy of current treatments or creating novel treatments for PTSD and other psychiatric disorders (Marin et al. Depress Anxiety 31:269-278, 2014; Milad et al. Behav Res Ther 62:17-23, 2014). Device-based neuromodulation techniques provide a promising means for directly changing or regulating activity in the fear extinction network by targeting functionally connected brain regions via stimulation patterns (Raij et al. Biol Psychiatry 84:129-137, 2018; Marković et al. Front Hum Neurosci 15:138, 2021). In the past ten years, notable advancements in the precision, safety, comfort, accessibility, and control of administration have been made to the established device-based neuromodulation techniques to improve their efficacy. In this chapter we discuss ten years of progress surrounding device-based neuromodulation techniques-Electroconvulsive Therapy (ECT), Transcranial Magnetic Stimulation (TMS), Magnetic Seizure Therapy (MST), Transcranial Focused Ultrasound (TUS), Deep Brain Stimulation (DBS), Vagus Nerve Stimulation (VNS), and Transcranial Electrical Stimulation (tES)-as research and clinical tools for enhancing fear extinction and treating PTSD symptoms. Additionally, we consider the emerging research, current limitations, and possible future directions for these techniques.

Association between lesion location and depressive symptoms in acute ischemic stroke patients using voxel-based lesion-symptom mapping

Objective: The study aimed to investigate the association between lesion location and post-stroke depression (PSD) in acute ischemic stroke patients. Methods: In this case-control study, acute ischemic stroke patients were recruited from the Department of Neurology, First Affiliated Hospital of the University of Science and Technology of China (USTC), between September 2020 and June 2021. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, the patients were divided into the PSD and non-PSD groups. The 24-item Hamilton Rating Scale (HAMD) was used to evaluate the severity of depression. The Student's t-test, Mann-Whitney test, and Chi-square test were used to compare the clinical baseline characteristics of PSD and non-PSD groups. Voxel-based lesion-symptom mapping (VLSM) was applied to investigate the association between lesion location and depression occurrence and severity. Results: A total of 70 and 173 patients were admitted to the PSD and non-PSD groups, respectively. The mean age of patients was 59 years (23-86). There were 153 males and 90 females. Univariate analysis showed a significant difference only in Hamilton Anxiety (P=0.025) and Depression (P<0.001) scores between the PSD and non-PSD groups. VLSM analysis identified clusters within the anterior cingulate gyrus (Z=-3.05, P<0.001), left hippocampus (Z=-3.15, P<0.001), and left lingual lobe (Z=-3.08, P<0.001) where lesions were significantly associated with PSD. Additionally, the severity of PSD was associated with damage in the anterior cingulate gyrus (Z=-3.64, P<0.001), left hippocampus (Z=-3.51, P<0.001), left lingual lobe (Z=-4.18, P<0.001), and pericalcarine cortex (Z=-3.65, P<0.001). Conclusion: VLSM demonstrated that lesion location could be used to predict the occurrence of PSD in patients with acute ischemic stroke.

Clinical Practice Guidelines for the Use of Transcranial Direct Current Stimulation in Psychiatry.

Clinical Practice Guidelines for the Use of Transcranial Direct Current Stimulation in Psychiatry.

Sleep spindles and slow waves are physiological markers for age-related changes in gray matter in brain regions supporting problem-solving skills.

As we age, the added benefit of sleep for memory consolidation is lost. One of the hallmark age-related changes in sleep is the reduction of sleep spindles and slow waves. Gray matter neurodegeneration is related to both age-related changes in sleep and age-related changes in memory, including memory for problem-solving skills. Here, we investigated whether spindles and slow waves might serve as biological markers for neurodegeneration of gray matter and for the related memory consolidation deficits in older adults. Forty healthy young adults (20-35 yr) and 30 healthy older adults (60-85 yr) were assigned to either nap or wake conditions. Participants were trained on the Tower of Hanoi in the morning, followed by either a 90-min nap opportunity or period of wakefulness, and were retested afterward. We found that age-related changes in sleep spindles and slow waves were differentially related to gray matter intensity in young and older adults in brain regions that support sleep-dependent memory consolidation for problem-solving skills. Specifically, we found that spindles were related to gray matter in neocortical areas (e.g., somatosensory and parietal cortex), and slow waves were related to gray matter in the anterior cingulate, hippocampus, and caudate, all areas known to support problem-solving skills. These results suggest that both sleep spindles and slow waves may serve as biological markers of age-related neurodegeneration of gray matter and the associated reduced benefit of sleep for memory consolidation in older adults.

Age-related effects on the anterior and posterior hippocampal volumes in 6-21 year olds: A model selection approach.

Although recent studies support significant differences in intrinsic structure, function, and connectivity along the longitudinal axis of the hippocampus, few studies have investigated the normative development of this dimension. In addition, factors known to influence hippocampal structure, such as sex or puberty, have yet to be characterized when assessing age-related effects on its subregions. This study addresses this gap by investigating the relationship of the anterior (antHC) and posterior (postHC) hippocampus volumes with age, and how these are moderated by sex or puberty, in structural magnetic resonance imaging scans from 183 typically developing participants aged 6-21 years. Based on previous literature, we first anticipated that non-linear models would best represent the relationship between age and the antHC and postHC volumes. We found that age-related effects are region-specific, such that the antHC volume remains stable with increasing age, while the postHC shows a cubic function characterized by overall volume increase with age but a slower rate during adolescence. Second, we hypothesized that models, which include biological sex or pubertal status would best describe these relationships. Contrary to expectation, models comprising either biological sex or pubertal status did not significantly improve model performance. Further longitudinal research is needed to evaluate their effects on the antHC and postHC development.

Progressive Transcriptional Changes in the Amygdala Implicate Neuroinflammation in the Effects of Repetitive Low-Level Blast Exposure in Male Rats.

Chronic mental health problems are common among military veterans who sustained blast-related traumatic brain injuries. The reasons for this association remain unexplained. Male rats exposed to repetitive low-level blast overpressure (BOP) exposures exhibit chronic cognitive and post-traumatic stress disorder (PTSD)-related traits that develop in a delayed fashion. We examined blast-induced alterations on the transcriptome in four brain areas (anterior cortex, hippocampus, amygdala, and cerebellum) across the time frame over which the PTSD-related behavioral phenotype develops. When analyzed at 6 weeks or 12 months after blast exposure, relatively few differentially expressed genes (DEGs) were found. However, longitudinal analysis of amygdala, hippocampus, and anterior cortex between 6 weeks and 12 months revealed blast-specific DEG patterns. Six DEGs (hyaluronan and proteoglycan link protein 1 [Hapln1], glutamate metabotropic receptor 2 [Grm2], purinergic receptor P2y12 [P2ry12], C-C chemokine receptor type 5 [Ccr5], phenazine biosynthesis-like protein domain containing 1 [Pbld1], and cadherin related 23 [Cdh23]) were found altered in all three brain regions in blast-exposed animals. Pathway enrichment analysis using all DEGs or those uniquely changed revealed different transcription patterns in blast versus sham. In particular, the amygdala in blast-exposed animals had a unique set of enriched pathways related to stress responses, oxidative phosphorylation, and mitochondrial dysfunction. Upstream analysis implicated tumor necrosis factor (TNF)α signaling in blast-related effects in amygdala and anterior cortex. Eukaryotic initiating factor eIF4E (EIF4e), an upstream regulator of P2ry12 and Ccr5, was predicted to be activated in the amygdala. Quantitative polymerase chain reaction (qPCR) validated longitudinal changes in two TNFα regulated genes (cathepsin B [Ctsb], Hapln1), P2ry12, and Grm2. These studies have implications for understanding how blast injury damages the brain and implicates inflammation as a potential therapeutic target.

Sex differences implications in hippocampal volumetry during midlife

AbstractBackgroundSex differences in adult brain morphology are frequently reported. Hippocampal and medio‐temporal (MTL) cortices in women and men are frequently implicated in Alzheimer’s Disease (AD) pathology, and women are disproportionally more affected by AD than men. Modifications in these regions’ volumetry are described during aging and in pathology, but their specificities during midlife regarding sex are still debated. Also, the multifaceted interactions between sex and dementia risk factors in these brain areas are not fully established. The aim of this study is to precisely identify the differences between women and men in the volumetry of hippocampal and MTL subregions, as well as the moderation effects of risk factors for dementia such as hypertension (diastolic blood pressure), hypercholesterolemia, obesity (body mass index), physical inactivity, and inflammation (C‐Reactive Protein), on sex.MethodData from 210 cognitively healthy participants were analyzed (106 women; 104 men; age 40‐65). Automatic segmentation was performed to determine the volume of the bilateral anterior and posterior hippocampus, and of entorhinal, perirhinal (BA35 and BA36), and parahippocampal cortices (ASHS‐PMC‐T1 atlas). The total intracranial volume was obtained to calculate adjusted‐volumes for every participant. An analysis of covariance (ANCOVA) was performed to compare women and men subregions’ volumes, corrected for age. Linear regressions were performed to analyze the interactions between sex and dementia risk factors on the volumetry of these regions.ResultWomen and men were significantly different in the volume of the left (p &lt; .001) and right (p &lt; .001) hippocampus, on the right BA35 (p = .008), and on the left (p &lt; .001) and right (p &lt; .001) parahippocampal cortices. No significant interaction was highlighted between sex and risk factor variables.ConclusionBeyond basic demography, sex is essential to consider in research, as women and men appear to be inherently different in their brain morphometry, even from midlife. Volumetric differences in AD‐linked brain regions, regardless of potential dementia risk factors, may be an innocuous sex‐specific feature at the preclinical phase. In this regard, women’s vulnerability to AD may not occur until later in aging, potentially linked to hormonal decline.