Changes In Several Brain Regions Research Articles

Changes in Structural Covariance among Olfactory-related Brain Regions in Anosmia Patients.

Anosmia, characterized by the loss of smell, is associated not only with dysfunction in the peripheral olfactory system but also with changes in several brain regions involved in olfactory processing. Specifically, the orbitofrontal cortex is recognized for its pivotal role in integrating olfactory information, engaging in bidirectional communication with the primary olfactory regions, including the olfactory cortex, amygdala, and entorhinal cortex. However, little is known about alterations in structural connections among these brain regions in patients with anosmia. In this study, high-resolution T1-weighted images were obtained from participants. Utilizing the volumes of key brain regions implicated in olfactory function, we employed a structural covariance approach to investigate brain reorganization patterns in patients with anosmia (n=22) compared to healthy individuals (n=30). Our structural covariance analysis demonstrated diminished connectivity between the amygdala and entorhinal cortex, components of the primary olfactory network, in patients with anosmia compared to healthy individuals (z=-2.22, FDR-corrected p=0.039). Conversely, connectivity between the orbitofrontal cortex-a major region in the extended olfactory network-and amygdala was found to be enhanced in the anosmia group compared to healthy individuals (z=2.32, FDR-corrected p=0.039). However, the structural connections between the orbitofrontal cortex and entorhinal cortex did not differ significantly between the groups (z=0.04, FDR-corrected p=0.968). These findings suggest a potential structural reorganization, particularly of higher-order cortical regions, possibly as a compensatory effort to interpret the limited olfactory information available in individuals with olfactory loss.

Multimodal and multiregional atlas of Alzheimer’s disease changes

AbstractBackgroundAlzheimer’s disease (AD) is the most common form of dementia. The progression of AD throughout the brain follows a stereotypical pattern that can be described by the quantification of histopathological changes in several brain regions. As part of The Seattle Alzheimer’s Disease Cell Atlas (SEA‐AD, https://sea-ad.org), we previously quantified pathological proteins in the middle temporal gyrus (MTG) and used them to describe disease progression, vulnerable cell types, and the MTG molecular changes related to diseaseMethodIn this work, we expanded our results and undertook a comparative approach. We measured a battery of neuropathological proteins (staining NeuN, AT8, IBA1, GFAP, 6e10, pTDP43, and a‐Syn immunoreactivity, and analyzing them with machine learning) in the middle temporal gyrus, the middle frontal gyrus, and medial entorhinal cortex in 84 donors. In addition, we undertook a multimodal single‐cell analysis of such regions, profiling cells using single‐cell RNA‐seq, ATAC‐seq, Multiome, and spatial transcriptomic.Borrowing from our hierarchically resolved cell types in MTG, based on the BRAIN initiative cell type reference, we used machine learning algorithms to create multimodal cell type maps across regions. We used Bayesian statistics to identify differentially accessible regulatory elements, link them to the affected genes and the regulatory transcriptional machinery binding in such elements.ResultWe identified regional vulnerable neuronal populations and a core set of transcriptionally similar cell types susceptible to disease across the cortex. We created a cortex‐wide disease progression map combining neuropathological data from our three profiled regions with latent Bayesian statistical algorithms. In each area, we developed an AD pseudo‐progression timescale that describes the burden of disease in the area and, next, combined all areas to create a cortex‐wide holistic pseudo‐progression. We used the mapped cell types and our developed scale to synchronize changes occurring in each patient, describing abundances, gene expression, and chromatin accessibility modifications.ConclusionThe progression scale developed in this study serves as a reference to align changes across brain regions and, in the future, to reconcile differences across cohorts.

Mild hypoxia-induced structural and functional changes of the hippocampal network.

Hypoxia causes structural and functional changes in several brain regions, including the oxygen-concentration-sensitive hippocampus. We investigated the consequences of mild short-term hypoxia on rat hippocampus in vivo. The hypoxic group was treated with 16% O2 for 1 h, and the control group with 21% O2. Using a combination of Gallyas silver impregnation histochemistry revealing damaged neurons and interneuron-specific immunohistochemistry, we found that somatostatin-expressing inhibitory neurons in the hilus were injured. We used 32-channel silicon probe arrays to record network oscillations and unit activity from the hippocampal layers under anaesthesia. There were no changes in the frequency power of slow, theta, beta, or gamma bands, but we found a significant increase in the frequency of slow oscillation (2.1-2.2 Hz) at 16% O2 compared to 21% O2. In the hilus region, the firing frequency of unidentified interneurons decreased. In the CA3 region, the firing frequency of some unidentified interneurons decreased while the activity of other interneurons increased. The activity of pyramidal cells increased both in the CA1 and CA3 regions. In addition, the regularity of CA1, CA3 pyramidal cells' and CA3 type II and hilar interneuron activity has significantly changed in hypoxic conditions. In summary, a low O2 environment caused profound changes in the state of hippocampal excitatory and inhibitory neurons and network activity, indicating potential changes in information processing caused by mild short-term hypoxia.

Pain-motor integration in chronic pain: A neurophysiological study

ObjectiveChronic pain may lead to functional changes in several brain regions, including the primary motor cortex (M1). Our neurophysiological study aimed to probe M1 plasticity, through a non-invasive transcranial magnetic stimulation protocol, in a cohort of patients with chronic pain. MethodsTwenty patients with chronic pain (age ± SD: 62.9 ± 9.9) and 20 age- and sex-matched healthy controls (age ± SD: 59.6 ± 15.8) were recruited. Standardized scales were used for the evaluation of pain severity. Neurophysiological measures included laser-evoked potentials (LEPs) and motor-evoked potentials (MEPs) collected at baseline and over 60 minutes following a standardized Laser-paired associative stimulation (Laser-PAS) protocol. ResultsLEPs and MEPs were comparable in patients with chronic pain and controls. The pain threshold was lower in patients than in controls. Laser-PAS elicited decreased responses in patients with chronic pain. The response to Laser-PAS was similar in subgroups of patients with different chronic pain phenotypes. ConclusionsM1 plasticity, as tested by Laser-PAS, is altered in patients with chronic pain, possibly reflecting abnormal pain-motor integration processes. SignificanceChronic pain is associated with a disorder of M1 plasticity raising from abnormal pain-motor integration.

Anti-amphiphysin encephalitis: Expanding the clinical spectrum.

An analysis of the clinical features of autoimmune encephalitis accompanied by anti-amphiphysin antibodies. The data of encephalitis patients with anti-amphiphysin antibodies were retrospectively evaluated, including demographics, neurological and laboratory findings, imaging, treatment, and prognostic predictions. Ten patients aged between 29 and 78 years (median age 52 years) were included. The male: female ratio was 4:6. Limbic encephalitis was found in nine patients while epileptic seizures were present in seven patients. All patients showed anti-amphiphysin antibody positivity in sera while one ninth was positive for CSF antibody. The EEG findings were abnormal, including reductions in background activity, and the presence of diffuse slow waves, sharp waves, and spikes and waves. Five patients showed signs of increased T2 signals in the medial temporal lobe on MRI while PET showed either hyper- or hypo-metabolic changes in several brain regions, including the temporal lobe, hippocampus, basal ganglia, frontal and parietal cortices. Nine of ten patients were treated with immunotherapy, with improvements of varying degrees. There was a significant reduction in seizure frequency, and all patients were seizure-free at last follow-up. Autoimmune encephalitis with anti-amphiphysin antibodies has a variety of clinical manifestations. The most common symptom is limbic encephalitis. Although relief from seizures can be achieved relatively easily, many patients suffer psychiatric, cognitive, and sleep sequelae. The disease was found to be associated with a lower incidence of cancer than has been previously reported for paraneoplastic neurologic syndromes.

Structural and Functional Brain Changes Associated with Vitamin B12 Deficiency using Magnetic Resonance Imaging: A Systematic Review and Meta-analysis.

This review was conducted to assess the structural and functional brain changes associated with vitamin B12 deficiency in different age groups using MRI. PubMed, Embase, Medline, CINAHL, Scopus, Web of Science, and Google Scholar were searched for magnetic resonance imaging (MRI) studies that explored structural and functional brain changes associated with vitamin B12 deficiency in different age groups. The inclusion criteria were as follows: (1) the population consisted of people and not animals; (2) patients with known B12 deficiency; (3) English publications; (3) at least one of the following brain MRI techniques had been employed: VBM, DWI, DTI, fMRI, or rs-fMRI. However, case reports, systematic reviews and meta-analyses were excluded. Twelve articles met the inclusion criteria. The results of my review show a connection between vitamin B12 deficiency and abnormal structural and functional brain changes in several brain regions. These changes were observed in different age groups ranging from a mean age of seven years to a mean age in the 70s. The results also highlight the association between brain changes and cognitive decline among affected subjects. Improvements in damaged brain regions post-vitamin B12 treatment were also studied. Structural and functional brain damage was found to be associated with vitamin B12 deficiency in all age groups. Vitamin B12 treatment may lead to partial or complete structural and/or functional recovery, as well as a cognitive recovery.

Can biomarkers be used to diagnose attention deficit hyperactivity disorder?

Currently, the diagnosis of attention deficit hyperactivity disorder (ADHD) is solely based on behavioral tests prescribed by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). However, biomarkers can be more objective and accurate for diagnosis and evaluating treatment efficacy. Thus, this review aimed to identify potential biomarkers for ADHD. Search terms "ADHD," and "biomarker" combined with one of "protein," "blood/serum," "gene," and "neuro" were used to identify human and animal studies in PubMed, Ovid Medline, and Web of Science. Only papers in English were included. Potential biomarkers were categorized into radiographic, molecular, physiologic, or histologic markers. The radiographic analysis can identify specific activity changes in several brain regions in individuals with ADHD. Several molecular biomarkers in peripheral blood cells and some physiologic biomarkers were found in a small number of participants. There were no published histologic biomarkers for ADHD. Overall, most associations between ADHD and potential biomarkers were properly controlled. In conclusion, a series of biomarkers in the literature are promising as objective parameters to more accurately diagnose ADHD, especially in those with comorbidities that prevent the use of DSM-5. However, more research is needed to confirm the reliability of the biomarkers in larger cohort studies.

Association of Intensive vs Standard Blood Pressure Control With Regional Changes in Cerebral Small Vessel Disease Biomarkers

Little is known about the associations of strict blood pressure (BP) control with microstructural changes in small vessel disease markers. To investigate the regional associations of intensive vs standard BP control with small vessel disease biomarkers, such as white matter lesions (WMLs), fractional anisotropy (FA), mean diffusivity (MD), and cerebral blood flow (CBF). The Systolic Blood Pressure Intervention Trial (SPRINT) is a multicenter randomized clinical trial that compared intensive systolic BP (SBP) control (SBP target <120 mm Hg) vs standard control (SBP target <140 mm Hg) among participants aged 50 years or older with hypertension and without diabetes or a history of stroke. The study began randomization on November 8, 2010, and stopped July 1, 2016, with a follow-up duration of approximately 4 years. A total of 670 and 458 participants completed brain magnetic resonance imaging at baseline and follow-up, respectively, and comprise the cohort for this post hoc analysis. Statistical analyses for this post hoc analysis were performed between August 2020 and October 2022. At baseline, 355 participants received intensive SBP treatment and 315 participants received standard SBP treatment. The main outcomes were regional changes in WMLs, FA, MD (in white matter regions of interest), and CBF (in gray matter regions of interest). At baseline, 355 participants (mean [SD] age, 67.7 [8.0] years; 200 men [56.3%]) received intensive BP treatment and 315 participants (mean [SD] age, 67.0 [8.4] years; 199 men [63.2%]) received standard BP treatment. Intensive treatment was associated with smaller mean increases in WML volume compared with standard treatment (644.5 mm3 vs 1258.1 mm3). The smaller mean increases were observed specifically in the deep white matter regions of the left anterior corona radiata (intensive treatment, 30.3 mm3 [95% CI, 16.0-44.5 mm3]; standard treatment, 80.5 mm3 [95% CI, 53.8-107.2 mm3]), left tapetum (intensive treatment, 11.8 mm3 [95% CI, 4.4-19.2 mm3]; standard treatment, 27.2 mm3 [95% CI, 19.4-35.0 mm3]), left superior fronto-occipital fasciculus (intensive treatment, 3.2 mm3 [95% CI, 0.7-5.8 mm3]; standard treatment, 9.4 mm3 [95% CI, 5.5-13.4 mm3]), left posterior corona radiata (intensive treatment, 26.0 mm3 [95% CI, 12.9-39.1 mm3]; standard treatment, 52.3 mm3 [95% CI, 34.8-69.8 mm3]), left splenium of the corpus callosum (intensive treatment, 45.4 mm3 [95% CI, 25.1-65.7 mm3]; standard treatment, 83.0 mm3 [95% CI, 58.7-107.2 mm3]), left posterior thalamic radiation (intensive treatment, 53.0 mm3 [95% CI, 29.8-76.2 mm3]; standard treatment, 106.9 mm3 [95% CI, 73.4-140.3 mm3]), and right posterior thalamic radiation (intensive treatment, 49.5 mm3 [95% CI, 24.3-74.7 mm3]; standard treatment, 102.6 mm3 [95% CI, 71.0-134.2 mm3]). This study suggests that intensive BP treatment, compared with standard treatment, was associated with a slower increase of WMLs, improved diffusion tensor imaging, and FA and CBF changes in several brain regions that represent vulnerable areas that may benefit from more strict BP control. ClinicalTrials.gov Identifier: NCT01206062.

Changes in brain structure and related functional connectivity during menstruation in women with primary dysmenorrhea.

Neuroimaging studies have identified altered brain structures and functions in women with primary dysmenorrhea (PDM). However, previous studies focused on either structural or functional changes in specific brain regions rather than combining structural and functional analysis. Therefore, this prospective cross-sectional study aimed to investigate the changes in whole brain structure, and functional variation along with structural abnormalities in women with PDM during menstruation. In all, 31 patients with PDM (PTs) and 31 healthy controls (HCs) were recruited. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) analyses were applied to investigate structural changes based on high-resolution T1-weighted magnetic resonance images. Functional connectivity (FC) analysis was performed to evaluate functional variations related to the brain regions that showed structural group differences. Pearson correlation analysis was performed to assess the relationship between neuroimaging changes and clinical measures. Compared to HCs, PTs had reduced gray matter volume (GMV) in the right superior temporal gyrus (STG) and reduced thickness in the bilateral orbitofrontal cortex (OFC), left postcentral gyrus (PoCG), and left superior occipital gyrus (SOG). Among these areas, the STG and PoCG are responsible for altered resting-state FC patterns in PTs. Results showed decreased FC between the STG and the left cerebellar posterior lobe (poCb), the right dorsolateral prefrontal cortex (DLPFC), and the left precentral gyrus (PrCG). Results also showed decreased FC between the PoCG and the right precuneus and the right DLPFC. We also found greater FCs between the PoCG and the bilateral poCb, the left middle temporal gyrus (MTG), and the left angular gyrus. In addition, the FCs between the STG and poCb, and DLPFC in PTs were positively correlated with history and Cox menstrual symptom scale (CMSS) scores, respectively, while the FCs between STG and PrCG were negatively correlated with the onset age of PDM. Our research found structural abnormalities and related FC changes in several brain regions that were mainly involved in the emotional and sensory aspects of menstrual pain in PDM. These findings could help us understand the occurrence of PDM from a neuroimaging perspective.

An ecological animal model of subthreshold depression in adolescence: behavioral and resting state 18F-FDG PET imaging characterization

The different depressive disorders that exist can take root at adolescence. For instance, some functional and structural changes in several brain regions have been observed from adolescence in subjects that display either high vulnerability to depressive symptoms or subthreshold depression. For instance, adolescents with depressive disorder have been shown to exhibit hyperactivity in hippocampus, amygdala and prefrontal cortex as well as volume reductions in hippocampus and amygdala (prefrontal cortex showing more variable results). However, no animal model of adolescent subthreshold depression has been developed so far. Our objective was to design an animal model of adolescent subthreshold depression and to characterize the neural changes associated to this phenotype. For this purpose, we used adolescent Swiss mice that were evaluated on 4 tests assessing cognitive abilities (Morris water maze), anhedonia (sucrose preference), anxiety (open-field) and stress-coping strategies (forced swim test) at postnatal day (PND) 28–35. In order to identify neural alterations associated to behavioral profiles, we assessed brain resting state metabolic activity in vivo using 18F-FDG PET imaging at PND 37. We selected three profiles of mice distinguished in a composite Z-score computed from performances in the behavioral tests: High, Intermediate and Low Depressive Risk (HDR, IDR and LDR). Compared to both IDR and LDR, HDR mice were characterized by passive stress-coping behaviors, low cognition and high anhedonia and anxiety and were associated with significant changes of 18F-FDG uptakes in several cortical and subcortical areas including prelimbic cortex, infralimbic cortex, nucleus accumbens, amygdala, periaqueductal gray and superior colliculus, all displaying higher metabolic activity, while only the thalamus was associated with lower metabolic activity (compared to IDR). LDR displayed an opposing behavioral phenotype and were associated with significant changes of 18F-FDG uptakes in the dorsal striatum and thalamus that both exhibited markedly lower metabolic activity in LDR. In conclusion, our study revealed changes in metabolic activities that can represent neural signatures for behavioral profiles predicting subthreshold depression at adolescence in a mouse model.

The effect of polycyclic aromatic hydrocarbons on changes in the brain structure of firefighters: An analysis using data from the Firefighters Research on Enhancement of Safety & Health study

Polycyclic aromatic hydrocarbons (PAHs) are formed during incomplete combustion of organic matter, and firefighters are highly exposed to these toxic compounds at fire sites. Exposure to PAHs can cause cognitive decline and neurodegeneration; however, to date, few studies have examined the potential effects of PAH exposure on structural changes in the brain. We aimed to investigate the association between the four types of PAH metabolites and the corresponding changes in neuroimaging markers based on smoking status and hypertension in male firefighters. For this, we utilized the 2-year follow-up data of 301 Korean male firefighters aged over 40 years. The concentrations of four PAH metabolites in urine were measured. Subcortical volume and cortical thickness were estimated using 3 T magnetic resonance imaging of the brain. A generalized linear model was used to investigate the effects of PAHs on changes in the subcortical volume and cortical thickness. We found an association between 1-hydroxyphenathrene (1-OHPHE) and 2-hydroxyfluorene (2-OHF) and changes in several brain regions in all the study participants. Individuals who had never smoked showed significantly thinner frontal (p < 0.001), parietal (p < 0.001), temporal (p < 0.001), and cingulate lobes (p < 0.001) with 1% increase each in the urinary concentration of 1-OHPHE. Hypertension interacted with the concentration of 1-OHPHE to reduce the volume of gray matter and cause cortical thinning in the frontal, parietal, and temporal lobes. Exposure to PAHs may reduce cortical thickness and subcortical volume, which are definitive markers of neurodegeneration. Notably, hypertension can accelerate the degenerative effects of PAHs.

The hallmarks of environmental issues and the brain

BACKGROUND AND AIM: The aim of this presentation is to discuss the knowledge regarding the impact of the hallmark environmental insults on the brain. Air pollution, noise, heat, light at night, industrial chemicals, and lack of green space have been associated with the impairment of brain development and function and higher risk of neurological diseases and neurodegeneration. METHODS: Several hallmarks (oxidative stress, methylation, endocrine disruption, mitochondrial disfunction, telomers, intravesicular cells, miRNA, microbiome, autonomous nervous system irritation) have been suggested to underline these relationships via direct and indirect pathways. The nervous system itself controls the body's physiological processes and as such could impair the cardiovascular, metabolic/endocrine, and respiratory systems, among others. RESULTS:The efforts in understanding the intermediate role of the cellular hallmarks between the exposure and the brain effects is a path to establish causal relationships. For instance, a key development is to discover the windows of greatest sensitivity of structural and functional brain changes to air pollution. The brain has the widest vulnerable window among all systems. Prenatal exposures may have more severe consequences for the brain because brain structures are forming during this period and may cause permanent brain injury and predict cognitive impairment later in life. Supporting the importance of the prenatal period, mice experiments consistently reported that prenatal exposure to fine PM and diesel exhaust could induce inflammatory reactions and structural changes in several brain regions related with the myelination process which has been replicated in humans, in part, through impairing placental function via PM deposition in the placenta or indirectly via several of the hallmarks in peripheral blood and in the placenta itself. CONCLUSIONS:Hallmarks could be relevant for informing about the persistence or tracking of the effects until later life. It is important to simultaneously study the effect of these hallmarks together on the brain in relation to the exposome. KEYWORDS: omics technologies,Neurologic and mental health outcomes, air pollution, chemical exposues, climate

Diffusion kurtosis imaging detects the time-dependent progress of pathological changes in the oral rotenone mouse model of Parkinson's disease.

Clinical diagnosis of Parkinson's disease (PD) occurs typically when a substantial proportion of dopaminergic neurons in the substantia nigra (SN) already died, and the first motor symptoms appear. Therefore, tools enabling the early diagnosis of PD are essential to identify early-stage PD patients in which neuroprotective treatments could have a significant impact. Here, we test the utility and sensitivity of the diffusion kurtosis imaging (DKI) in detecting progressive microstructural changes in several brain regions of mice exposed to chronic intragastric administration of rotenone, a mouse model that mimics the spatiotemporal progression of PD-like pathology from the ENS to the SN as described by Braak's staging. Our results show that DKI, especially kurtosis, can detect the progression of pathology-associated changes throughout the CNS. Increases in mean kurtosis were first observed in the dorsal motor nucleus of the vagus (DMV) after 2months of exposure to rotenone and before the loss of dopaminergic neurons in the SN occurred. Remarkably, we also show that limited exposure to rotenone for 2months is enough to trigger the progression of the disease in the absence of the environmental toxin, thus suggesting that once the first pathological changes in one region appear, they can self-perpetuate and progress within the CNS. Overall, our results show that DKI can be a useful radiological marker for the early detection and monitoring of PD pathology progression in patients with the potential to improve the clinical diagnosis and the development of neuroprotective treatments.

Gray matter abnormalities in Tourette Syndrome: a meta-analysis of voxel-based morphometry studies

Tourette syndrome (TS) is a neurobehavioral disorder for which the neurological mechanism has not been elucidated. Voxel-based morphometry (VBM) studies have revealed abnormalities in gray matter volume (GMV) in patients with TS; however, consistent results have not been obtained. The current study attempted to provide a voxel wise meta-analysis of gray matter changes using seed-based d mapping (SDM). We identified ten relevant studies that investigated gray matter alterations in TS patients and performed a meta-analysis using the SDM method to quantitatively estimate regional gray matter abnormalities. Next, we examined the relationships between GMV abnormalities and demographic and clinical characteristics. Our results demonstrated that TS patients had smaller GMV in the bilateral inferior frontal gyri and greater GMV in the cerebellum, right striatum (putamen), and bilateral thalami (pulvinar nucleus) than healthy controls. A meta-regression analysis did not identify correlations between GMV changes and demographic or clinical variables. This meta-analysis confirmed significant and consistent GMV changes in several brain regions of TS patients, primarily in the cortico-striato-thalamo-cortical network.

Footshock‐induced abstinence from compulsive methamphetamine self‐administration is associated with increased expression of cannabinoid receptors (CB1 and CB2) in the rat hippocampus

Methamphetamine (METH) use disorder is characterized by compulsive and repeated drug intake despite negative life consequences. Large intake of METH in humans and animals is accompanied by dysfunctions in learning and memory and learning and by neurodegenerative changes in several brain regions. Because the endocannabinoid system (eCB) has been implicated in the manifestations of substance use disorders (SUDs), we sought to identify potential changes in various enzymes and the receptors (CB1 and CB2) that are involved in mediating the effects of endocannabinoids. To reach that end, we used a model of METH self-administration (SA) paradigm that includes a punishment phase (footshocks) that has helped to separate rats into a compulsive METH phenotype (shock-resistant, compulsive) that continues to take METH and a non-compulsive METH (shock-sensitive, abstinent) that suppressed or became abstinent in the presence of punishment. We then measured mRNA expression of cannabinoid receptors (CB/Cnr), synthetic (Dagl-a, Dagl-b, Nape-pld), as well as metabolizing enzymes (Mgll, Faah, Cox2) of the eCB signaling cascade in the dorsal striatum (DStr), nucleus accumbens (NAc), midbrain (MBr), and hippocampus (Hip) of rats euthanized two hours after the last METH SA plus footshock session. The abstinent rats exhibited significant increases in the expression of CB1 and CB2 in the hippocampus. The mRNA levels for the synthetic enzyme, Dagl-a, and the metabolic enzymes, Mgll, and Faah, were also increased in the hippocampus. In contrast, compulsive rats exhibited significant decreases in the expression of Faah in both the DStr and MBr but showed increased mRNA expression of Cox2 in the DStr. There were no significant changes in any of these in the nucleus accumbens. Taken together, these observations implicate, in part, the hippocampal endocannabinoid system in the suppression of METH intake in the presence of adverse consequences. Pharmacological agents that augment the activity of this system may be beneficial against METH use disorder in humans.

In vivo reduction of hippocampal Caveolin-1 by RNA interference alters morphine addiction and neuroplasticity changes in male mice

Prescription opioids are powerful pain-controlling medications that have both benefits and potentially serious risks. Morphine is one of the preferred analgesics that are widely used to treat chronic pain. However, chronic morphine exposure has been found to cause both functional and structural changes in several brain regions, including the medial prefrontal cortex (mPFC), ventral tegmental area (VTA), and hippocampus (HPC), which lead to addictive behavior. Caveolin-1 (Cav-1), a scaffolding protein of membrane lipid rafts (MLRs), has been shown to organize GPCRs and multiple synaptic signaling proteins within the MLRs to regulate synaptic signaling and neuroplasticity. Previously, we showed that in vitro morphine treatment significantly elevates Cav-1 expression and causes neuroplasticity changes. In this study, we confirmed that chronic morphine exposure can significantly increase Cav-1 expression (P < 0.05) and microtubule-associated protein (MAP-2)-positive neuronal dendritic growth in the hippocampus. Moreover, the rewarding effect and dendritic growth in the HPC induced by chronic morphine exposure were significantly inhibited by hippocampal Cav-1 knockdown. Together, these data suggest that Cav-1 in the hippocampus plays an essential role in the neuroplasticity changes that underlie morphine addiction behaviors.

Brain functional networks associated with social bonding in monogamous voles.

Previous studies have related pair-bonding in Microtus ochrogaster, the prairie vole, with plastic changes in several brain regions. However, the interactions between these socially relevant regions have yet to be described. In this study, we used resting-state magnetic resonance imaging to explore bonding behaviors and functional connectivity of brain regions previously associated with pair-bonding. Thirty-two male and female prairie voles were scanned at baseline, 24 hr, and 2 weeks after the onset of cohabitation. By using network-based statistics, we identified that the functional connectivity of a corticostriatal network predicted the onset of affiliative behavior, while another predicted the amount of social interaction during a partner preference test. Furthermore, a network with significant changes in time was revealed, also showing associations with the level of partner preference. Overall, our findings revealed the association between network-level functional connectivity changes and social bonding.

Genetic and Neuroimaging Approaches to Understanding Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a highly disabling condition, increasingly recognized as both a disorder of mental health and social burden, but also as an anxiety disorder characterized by fear, stress, and negative alterations in mood. PTSD is associated with structural, metabolic, and molecular changes in several brain regions and the neural circuitry. Brain areas implicated in the traumatic stress response include the amygdala, hippocampus, and prefrontal cortex, which play an essential role in memory function. Abnormalities in these brain areas are hypothesized to underlie symptoms of PTSD and other stress-related psychiatric disorders. Conventional methods of studying PTSD have proven to be insufficient for diagnosis, measurement of treatment efficacy, and monitoring disease progression, and currently, there is no diagnostic biomarker available for PTSD. A deep understanding of cutting-edge neuroimaging genetic approaches is necessary for the development of novel therapeutics and biomarkers to better diagnose and treat the disorder. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review article explains the rationale and practical utility of neuroimaging genetics in PTSD and how the resulting information can aid the diagnosis and clinical management of patients with PTSD.

Neuromodulatory and possible anxiolytic-like effects of a spice functional food ingredient in a pig model of psychosocial chronic stress

Abstract Psychological chronic stress is associated with the development of mood disorders, and spices have shown protective properties in this context. This research investigated the effects of a supplementation with a functional food ingredient containing spice extracts in a pig model of psychosocial chronic stress. Its impact on behavior, neurophysiology, immune system and gastrointestinal tract were evaluated. Almost no significant results were found at the gut and immune levels. An increased expression of 5-HT1AR and BDNF in the hippocampus and prefrontal cortex, respectively, and blood perfusion changes in several brain regions including the olfactory bulb, hippocampus, dorsolateral prefrontal cortex and dorsal anterior cingulate cortex were observed. Also, slight anxiolytic-like effects were observed in the Open-field and Novelty-Suppressed Feeding tests. These modulations of brain regions associated with the regulation of emotions and cognition as well as the potential effects on anxiety might come from the repeated stimulation of the olfactory system.

Cortical thickness reductions in the middle frontal cortex in patients with panic disorder

BackgroundPanic disorder (PD), an anxiety disorder characterized by the recurrence of panic attacks, has been reported to be associated with volumetric changes in several brain regions. There are, however, very few studies investigating abnormalities in cortical thickness, and little is known about the relationship between cortical thickness and social dysfunction in PD. MethodsThirty-eight patients with PD and 38 healthy control participants (HC) were recruited for this study. A whole-brain analysis was performed to evaluate groupwise differences in cortical thickness using the FreeSurfer software. Symptom severity and social functioning were evaluated with the Panic Disorder Severity Scale (PDSS) and the Global Assessment of Functioning (GAF) scale. ResultsThe patients with PD demonstrated a significant reduction in cortical thickness in the left rostral middle frontal cortex (MFC), compared with the HC. Correlational analyses revealed that cortical thickness in the left rostral MFC showed a significant negative relationship with PDSS score and a significant positive relationship with GAF scores in the PD patients. LimitationsAll the patients received medication. ConclusionPD patients showed reduced cortical thickness in the left rostral MFC compared with HC. Furthermore, cortical thickness in this region was associated with patients’ symptom severity and degree of social dysfunction.