Neuroanatomical Changes Research Articles

The impact of music making on neural efficiency & dual-task walking performance in healthy older adults

ABSTRACT Music making is linked to improved cognition and related neuroanatomical changes in children and adults; however, this has been relatively under-studied in aging. The purpose of this study was to assess neural, cognitive, and physical correlates of music making in aging using a dual-task walking (DTW) paradigm. Study participants (N = 415) were healthy adults aged 65 years or older, including musicians (n = 70) who were identified by current weekly engagement in musical activity. A DTW paradigm consisting of single- and dual-task conditions, as well as portable neuroimaging (functional near-infrared spectroscopy), was administered. Outcome measures included neural activation in the prefrontal cortex assessed across task conditions by recording changes in oxygenated hemoglobin, cognitive performance, and gait velocity. Linear mixed effects models examined the impact of music making on outcome measures in addition to moderating their change between task conditions. Across participants (53.3% women; 76 ± 6.55 years), neural activation increased from single- to dual-task conditions (p < 0.001); however, musicians demonstrated attenuated activation between a single cognitive interference task and dual-task walking (p = 0.014). Musicians also displayed significantly smaller decline in behavioral performance (p < 0.001) from single- to dual-task conditions and faster gait overall (p = 0.014). Given evidence of lower prefrontal cortex activation in the context of similar or improved behavioral performance, results indicate the presence of enhanced neural efficiency in older adult musicians. Furthermore, improved dual-task performance in older adult musicians was observed. Results have important clinical implications for healthy aging, as executive functioning plays an essential role in maintaining functional ability in older adulthood.

Colonic motility adjustments in acute and chronic DSS-induced colitis

AimsInflammatory bowel disease is recurrent inflammation that affects the gastrointestinal tract causing changes in intestinal motility. The evolution of these changes is not completely understood. The aim of this study was to evaluate anatomical and functional changes in the colon during the development of acute and chronic DSS-induced ulcerative colitis (UC) in C57Bl/6 mice. Materials and methodsMice were relocated into 5 groups: control (GC) and groups exposed to DSS 3 % for 2 (DSS2d), 5 (DSS5d) and 7 DSS7d) days (acute UC) or 3 cycles (DSS3C; Chronic UC). Mice were monitored daily. After euthanasia, colonic tissue was assessed with histological, immunofluorescence and colon manometry methods. Key findingsUlcerative Colitis is a chronic disease characterized by overt inflammation of the colon. Here we investigate whether the morphological changes caused by UC in the colonic wall, in tuft cells and in enteric neurons also promote any alteration in colonic motility patterns. UC Promotes thickening in the colonic wall, fibrosis, reduction in the number of tuft cells and consequently goblet cells also, without promoting neuronal death however there is a change in the chemical code of myenteric neurons. All of these morphological changes were responsible for causing a change in colonic contractions, colonic migration motor complex, total time of gastrointestinal transit and therefore promoting dysmotility. Further studies stimulating a hyperplasia of tuft cells may be the way to try to keep the colonic epithelium healthy, reducing the damage caused by UC. SignificanceIncreasing disease pathology of DSS-induced UC induces structural and neuroanatomical changes and driven damage to cholinergic neurons causes colonic dysmotility, including increase of cholinergic myenteric neurons, followed by variations in the motility pattern of different regions of the colon that taking together characterize colonic dysmotility.

Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure

Maternal immune dysregulation is a prenatal risk factor for autism spectrum disorder (ASD). Importantly, a clinically relevant connection exists between inflammation and metabolic stress that can result in aberrant cytokine signaling and autoimmunity. In this study we examined the potential for maternal autoantibodies (aAbs) to disrupt metabolic signaling and induce neuroanatomical changes in the brains of exposed offspring. To accomplish this, we developed a model of maternal aAb exposure in rats based on the clinical phenomenon of maternal autoantibody-related ASD (MAR-ASD). Following confirmation of aAb production in rat dams and antigen-specific immunoglobulin G (IgG) transfer to offspring, we assessed offspring behavior and brain structure longitudinally. MAR-ASD rat offspring displayed a reduction in pup ultrasonic vocalizations and a pronounced deficit in social play behavior when allowed to freely interact with a novel partner. Additionally, longitudinal in vivo structural magnetic resonance imaging (sMRI) at postnatal day 30 (PND30) and PND70, conducted in a separate cohort of animals, revealed sex-specific differences in total and regional brain volume. Treatment-specific effects by region appeared to converge on midbrain and cerebellar structures in MAR-ASD offspring. Simultaneously, in vivo 1H magnetic resonance spectroscopy (1H-MRS) data were collected to examine brain metabolite levels in the medial prefrontal cortex. Results showed that MAR-ASD offspring displayed decreased levels of choline-containing compounds and glutathione, accompanied by increased taurine compared to control animals. Overall, we found that rats exposed to MAR-ASD aAbs present with alterations in behavior, brain structure, and neurometabolites; reminiscent of findings observed in clinical ASD.

Sex differences of brain cortical structure in major depressive disorder.

Major depressive disorder (MDD) has different clinical presentations in males and females. However, the neuroanatomical mechanisms underlying these sex differences are not fully understood. The purpose of present study was to explore the sex differences in brain cortical thickness (CT) and surface area (SA) of MDD and the relationship between these differences and clinical manifestations in different gender. High-resolution T1-weighted images were acquired from 61 patients with MDD and 61 healthy controls (36 females and 25 males, both). The sex differences in CT and SA were obtained using the FreeSurfer software and compared between every two groups by post hoc test. Spearman correlation analysis was also performed to explore the relationships between these regions and clinical characteristics. In male patients with MDD, the CT of the right precentral was thinner compared to female patients, although this did not survive Bonferroni correction. The SA of several regions, including right superior frontal, medial orbitofrontal gyrus, inferior frontal gyrus triangle, superior temporal, middle temporal, lateral occipital gyrus, and inferior parietal lobule in female patients with MDD was smaller than that in male patients (P<0.01 after Bonferroni correction). In female patients, the SA of the right superior temporal (r=0.438, P=0.008), middle temporal (r=0.340, P=0.043), and lateral occipital gyrus (r=0.372, P=0.025) were positively correlated with illness duration. The current study provides evidence of sex differences in CT and SA in patients with MDD, which may improve our understanding of the sex-specific neuroanatomical changes in the development of MDD.

Cyst of Septum Pellucidum in mental disorders: Schizophrenia and Mental Retardation: Two case reports

IntroductionA septum pellucidum cyst is defined as a fluid collection between the lateral ventricles whose walls have a lateral curvature and are separated by 10 mm or more . Most of these cysts are benign and their clinical significance should be considered as a neurodevelopmental anomaly that may contribute to neuropsychiatric abnormalities . It is often of incidental finding, of little clinical significance. However, an association between this developmental anomaly and a mental disorder, such as schizophrenia and/or intellectual disability, has been reportedObjectivesThe objective of this study is to discuss the relationship between the septum pellucidum cyst and mental disorders, especially schizophrenia and intellectual disability.MethodsWe report in this study two clinical cases, diagnosed with schizophrenia comorbid with intellectual disability and in whom brain imaging has objectified a cyst of the septum pellucidumResultsmultiple cases reports of patients with Schizophrenia and/or mental retardation revealed, on brain imaging, significant abnormalities in midline brain regions such as Septum Pellucidum. It is suggested that CSP, particularly if large, should be considered a developmental anomaly that may contribute to neuropsychiatric abnormalities.ConclusionsWhether the CSP may serve as a risk factor for psychosis or is only a reflection of neuroanatomical changes in individuals with chronic psychotic disorders remains ambiguous. More studies and case reports will be needed to establish the veritable association of CSP and neuropsychiatric disorders in the future, and perhaps to acknowledge the CSP as an early marker and predictor of psychosis.Disclosure of InterestNone Declared

Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.

Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.

Neuroanatomical and neurocognitive changes associated with subjective cognitive decline.

Subjective Cognitive Decline (SCD) can progress to mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia and thus may represent a preclinical stage of the AD continuum. However, evidence about structural changes observed in the brain during SCD remains inconsistent. This cross-sectional study aimed to evaluate, in subjects recruited from the CompAS project, neurocognitive and neurostructural differences between a group of forty-nine control subjects and forty-nine individuals who met the diagnostic criteria for SCD and exhibited high levels of subjective cognitive complaints (SCCs). Structural magnetic resonance imaging was used to compare neuroanatomical differences in brain volume and cortical thickness between both groups. Relative to the control group, the SCD group displayed structural changes involving frontal, parietal, and medial temporal lobe regions of critical importance in AD etiology and functionally related to several cognitive domains, including executive control, attention, memory, and language. Despite the absence of clinical deficits, SCD may constitute a preclinical entity with a similar (although subtle) pattern of neuroanatomical changes to that observed in individuals with amnestic MCI or AD dementia.

Avocado peel extract: The effect of radiation-induced on neuroanatomical and behavioral changes in rats

Avocado (Persea americana) contains a variety of physiological active substances such as polyphenol, which has excellent antioxidant properties. This study investigated the radioprotective effect of avocado peel extract on congenital malformations and on the behavior of Sprague-Dawley (SD) rats. Experimental animals were randomly classified into four groups: NC Group, normal control; PA Group, oral administration with avocado peel extract (200 mg/kg/day); IR Group, irradiation; and PA+IR Group, irradiation after orally administered with avocado peel extract. For irradiation, 2 Gy of 6 MV X-ray was used once for the whole body. After that, congenital malformations, histopathological evaluation of the brain, and behavioral evaluation were performed in the obtained offspring. Although the body weight of the offspring was decreased by radiation exposure, it was confirmed that the decrease in weight was smaller when treated with PA. As the congenital malformations, hydrocephalus, loss of eyes, and abnormal rat tail occurred, and the result for the PA+IR Group was significantly lower than that of IR Group. Histopathologically, the length of the cerebral cortex of the PA+IR Group was similar to that of the non-radiation group. It was confirmed that emotional and behavioral disorders such as anxiety and depression were improved in the open field test (OFT) and elevated plus maze (EPM) test. And proved that working memory and cognitive ability were enhanced in the novel object recognition (NOR) test and spontaneous alternation Y-maze (SAY) test. Therefore, it was concluded that avocado peel extract can reduce the incidence of congenital malformations and improve growth disorders, memory and cognitive abilities. In the future, based on these results, we will conduct research on the hippocampus and amygdala, which are major regions of the brain, and additional research on cell biology.

Anatomically interpretable deep learning of brain age captures domain-specific cognitive impairment

The gap between chronological age (CA) and biological brain age, as estimated from magnetic resonance images (MRIs), reflects how individual patterns of neuroanatomic aging deviate from their typical trajectories. MRI-derived brain age (BA) estimates are often obtained using deep learning models that may perform relatively poorly on new data or that lack neuroanatomic interpretability. This study introduces a convolutional neural network (CNN) to estimate BA after training on the MRIs of 4,681 cognitively normal (CN) participants and testing on 1,170 CN participants from an independent sample. BA estimation errors are notably lower than those of previous studies. At both individual and cohort levels, the CNN provides detailed anatomic maps of brain aging patterns that reveal sex dimorphisms and neurocognitive trajectories in adults with mild cognitive impairment (MCI, N = 351) and Alzheimer's disease (AD, N = 359). In individuals with MCI (54% of whom were diagnosed with dementia within 10.9 y from MRI acquisition), BA is significantly better than CA in capturing dementia symptom severity, functional disability, and executive function. Profiles of sex dimorphism and lateralization in brain aging also map onto patterns of neuroanatomic change that reflect cognitive decline. Significant associations between BA and neurocognitive measures suggest that the proposed framework can map, systematically, the relationship between aging-related neuroanatomy changes in CN individuals and in participants with MCI or AD. Early identification of such neuroanatomy changes can help to screen individuals according to their AD risk.

Identifying Shared Neuroanatomic Architecture between Cognitive Traits through Multiscale Morphometric Correlation Analysis.

We introduce an informative metric, called morphometric correlation, as a measure of shared neuroanatomic similarity between two cognitive traits. Traditional estimates of trait correlations can be confounded by factors beyond brain morphology. To exclude these confounding factors, we adopt a Gaussian kernel to measure the morphological similarity between individuals and compare pure neuroanatomic correlations among cognitive traits. In our empirical study, we employ a multiscale strategy. Given a set of cognitive traits, we first perform morphometric correlation analysis for each pair of traits to reveal their shared neuroanatomic correlation at the whole brain (or global) level. After that, we extend our whole brain concept to regional morphometric correlation and estimate shared neuroanatomic similarity between two cognitive traits at the regional (or local) level. Our results demonstrate that morphometric correlation can provide insights into shared neuroanatomic architecture between cognitive traits. Furthermore, we also estimate the morphometricity of each cognitive trait at both global and local levels, which can be used to better understand how neuroanatomic changes influence individuals' cognitive status.

Neuroanatomical changes of ionotropic glutamatergic and GABAergic receptor densities in male mice modeling idiopathic and syndromic autism spectrum disorder.

Autism spectrum disorder (ASD) comprises a wide range of neurodevelopment conditions primarily characterized by impaired social interaction and repetitive behavior, accompanied by a variable degree of neuropsychiatric characteristics. Synaptic dysfunction is undertaken as one of the key underlying mechanisms in understanding the pathophysiology of ASD. The excitatory/inhibitory (E/I) hypothesis is one of the most widely held theories for its pathogenesis. Shifts in E/I balance have been proven in several ASD models. In this study, we investigated three mouse lines recapitulating both idiopathic (the BTBR strain) and genetic (Fmr1 and Shank3 mutants) forms of ASD at late infancy and early adulthood. Using receptor autoradiography for ionotropic excitatory (AMPA and NMDA) and inhibitory (GABAA) receptors, we mapped the receptor binding densities in brain regions known to be associated with ASD such as prefrontal cortex, dorsal and ventral striatum, dorsal hippocampus, and cerebellum. The individual mouse lines investigated show specific alterations in excitatory ionotropic receptor density, which might be accounted as specific hallmark of each individual line. Across all the models investigated, we found an increased binding density to GABAA receptors at adulthood in the dorsal hippocampus. Interestingly, reduction in the GABAA receptor binding density was observed in the cerebellum. Altogether, our findings suggest that E/I disbalance individually affects several brain regions in ASD mouse models and that alterations in GABAergic transmission might be accounted as unifying factor.

Hyperorality in Frontotemporal dementia: Cognitive, Behavioral, and Neuroanatomic Profiles in Early‐Stage Disease

AbstractBackgroundHyperorality represents a key feature observed in the behavioral variant of frontotemporal dementia (bvFTD). While hyperorality is common in advanced cases of bvFTD, less is known about its frequency in early‐stage disease. The cognitive, behavioral, and neuroanatomic patterns of patients with early stage bvFTD and hyperorality have also not been well established. The primary aim of this study is to describe the frequency of hyperorality in a sample of patients with early stage bvFTD while also exploring patterns of cognitive, behavioral, and neuroanatomic change.MethodData are from subjects enrolled in the ALLFTD study, an established US consortium with an ongoing cohort study of FTD. Cognitive profiles were assessed using validated neuropsychological batteries, and social behavior was measured using validated scales. Psychiatric states were coded as binary variables. Differences in baseline characteristics and clinical outcomes were compared using t‐tests for continuous variables and Pearson χ2 tests for categorical variables. Statistical significance was based on p values &lt;0.05.ResultWe enrolled 1,694 subjects, comprising 145 with a CDR® plus NACC FTLD global score less than or equal to 1 at the first visit who were used in our analysis. 50% of subjects exhibited hyperorality. There were no demographic differences between groups other than CDR global scores which were higher in the hyperorality group (0.8 versus 0.7, p = 0.003). Cognitive profiles encompassing domains of processing speed, language, executive functioning, memory, and attention did not differ between groups. Subjects with hyperorality had lower scores on scales of self‐monitoring, empathetic concern, and perspective taking. Subjects with hyperorality had higher rates of motor disturbance, and ritualistic/compulsive behaviors. There were no volumetric differences in neuroanatomic regions of interest.ConclusionOur findings indicate that hyperorality is common in early stage bvFTD, arising prior to cognitive and neuroanatomic changes. Hyperorality travels with motor disturbances and ritualistic/compulsive behaviors alongside eroding social behavioral functioning. Hyperorality may serve as an early signal of disease, providing an opportunity for intervention prior to significant neurodegeneration using novel therapeutics and non‐invasive brain stimulation.

Structural brain abnormalities in endothelial nitric oxide synthase-deficient mice revealed by high-resolution magnetic resonance imaging.

Endothelial nitric oxide synthase (eNOS) produces nitric oxide, which is essential for a variety of physiological functions in the brain. Previous work has demonstrated the detrimental effects of eNOS deficiency on brain function in male eNOS knockout (eNOS KO) mice. However, the effect of eNOS deficiency on brain structure and any association between these effects and sex is unknown. This study used three-dimensional high-resolution ex vivo magnetic resonance imaging and behavioral tests of anxiety and cognitive performance to investigate structure-function relationships in the brain of female and male eNOS KO mice in young adulthood. While there were no differences in anxiety-like behavior or locomotion, there was a sex-specific deficit in contextual fear memory retention in male, but not in female, eNOS mice compared to wild-type controls. Moreover, we found that eNOS deficiency induced changes in multiple brain regions that are involved in learning and fear memory including the hippocampus, amygdala, hypothalamus, and areas of the cortex. Several of these MRI-detectable neuroanatomical changes were dependent on sex. The observation that eNOS deficiency impacts brain structure at an early age demonstrates the importance of eNOS for healthy brain development.

Prodromes and biological markers in schizophrenia: Importance for the dopamine, glutamate, and neurodevelopmental hypothesis

Background. Since schizophrenia is a multifactorial mental illness, a basic understanding of its etiological components improves its understanding, diagnosis, and the selection of therapeutic targets. Objective. To identify the prodromes and biological markers in schizophrenic or ultra-high risk (UHR) patients and elucidate their specificity. Method. Narrative review of relevant sources in English and Spanish in the Medline-PubMed database on minor physical abnormalities, cognitive abnormalities, neuroanatomical, and synaptic and cell changes present in schizophrenic patients and/or subjects with a high risk of developing schizophrenia Results. Patients with SZ and, to a lesser extent, UHR subjects present phenotypic and behavioral manifestations that correlate with underlying cell processes. The study of the latter makes it possible to characterize diagnostic biomarkers. At present, its clinical application is limited by factors such as poorly understood pathophysiology, lack of study models, homology with other psychiatric disorders, and the dearth of clinical trials conducted. Discussion and conclusion. Schizophrenia is the final manifestation of damage to prenatal and post-natal neurodevelopment and is reflected during the prodromal stage in early biological markers with clinical relevance. It is necessary to establish new study models that will increase knowledge to offer specific biomarkers for use in early clinical diagnosis.

Investigating the “two-hit hypothesis”: Effects of prenatal maternal immune activation and adolescent cannabis use on neurodevelopment in mice

Prenatal exposure to maternal immune activation (MIA) and chronic adolescent cannabis use are both risk factors for neuropsychiatric disorders. However, exposure to a single risk factor may not result in major mental illness, indicating that multiple exposures may be required for illness onset. Here, we examine whether combined exposure to prenatal MIA and adolescent delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, lead to enduring neuroanatomical and behavioural changes in adulthood.Mice were prenatally exposed to viral mimetic, poly I:C (5 mg/kg), or vehicle at gestational day (GD) 9, and postnatally exposed to chronic THC (5 mg/kg, intraperitoneal) or vehicle during adolescence (postnatal day [PND]28–45). Longitudinal magnetic resonance imaging (MRI) was performed pre-treatment, PND 25, post-treatment, PND 50, and in adulthood, PND85, followed by behavioural tests for anxiety-like, social, and sensorimotor gating. Post-mortem assessment of cannabinoid (CB)1 and 2 receptor expressing cells was performed in altered regions identified by MRI (anterior cingulate and somatosensory cortices, striatum, and hippocampus).Subtle deviations in neurodevelopmental trajectory and subthreshold anxiety-like behaviours were observed in mice exposed to both risk factors. Sex-dependent effects were observed in patterns of shared brain-behaviour covariation, indicative of potential sex differences in response to MIA and THC. Density of CB1 and CB2 receptor positive cells was significantly decreased in all mice exposed to MIA, THC, or both.These findings suggest that there may be a cumulative effect of risk factor exposure on gross neuroanatomical development, and that the endocannabinoid system may be sensitive to both prenatal MIA, adolescent THC, or the combination.

Changes in Stereotypies: Effects over Time and over Generations.

Simple SummaryHerein, we propose that there should be discussion about the function and effects of stereotypies in relation to the time during which they are shown. In the first stages, stereotypies may help animals deal with challenges. However, behavior can potentially alter the brain, impairing its function due the absence of a diverse repertory, and change brain connections, neurophysiology and later neuroanatomy. The neuroanatomical changes in individuals showing stereotypies could be an effect rather than a cause of the stereotypy. As a consequence, studies showing different outcomes for animal welfare from stereotypy expression could be due to variation in a timeline of expression. Stereotypies are widely used as an animal welfare indicator, and their expression can tell us about psychological states. However, there are questions about the longer-term consequences if animals express stereotypies: do the stereotypies help in coping? During the prenatal period, stereotypic behavior expressed by the mother can change the phenotype of the offspring, especially regarding emotionality, one mechanism acting via methylation in the limbic system in the brain. Are individuals that show stereotypies for shorter or longer periods all better adjusted, and hence have better welfare, or is the later welfare of some worse than that of individuals that do not show the behavior?Stereotypies comprise a wide range of repeated and apparently functionless behaviors that develop in individuals whose neural condition or environment results in poor welfare. While stereotypies are an indicator of poor welfare at the time of occurrence, they may have various consequences. Environmental enrichment modifies causal factors and reduces the occurrence of stereotypies, providing evidence that stereotypies are an indicator of poor welfare. However, stereotypy occurrence and consequences change over time. Furthermore, there are complex direct and epigenetic effects when mother mammals that are kept in negative conditions do or do not show stereotypies. It is proposed that, when trying to deal with challenging situations, stereotypies might initially help animals to cope. After further time in the conditions, the performance of the stereotypy may impair brain function and change brain connections, neurophysiology and eventually neuroanatomy. It is possible that reported neuroanatomical changes are an effect of the stereotypy rather than a cause.

Respiratory deficits in a female rat model of Parkinson's disease.

What is the central question of this study? How does the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease model affect the respiratory response in female rats? What effect does ovariectomy have on that response? What is the main finding and its importance? The results suggest a protective effect of ovarian hormones in maintaining normal neuroanatomical integrity of the medullary respiratory nucleus in females. It was observed that ovariectomy alone reduced neurokinin-1 density in the pre-Bötzinger complex and Bötzinger complex, and there was an incremental effect of 6-OHDA and ovariectomy on retrotrapezoid nucleus neurons. Emerging evidence indicates that the course of Parkinson's disease (PD) includes autonomic and respiratory deficiencies in addition to the classical motor symptoms. The prevalence of PD is lower in women, and it has been hypothesized that neuroprotection by ovarian hormones can explain this difference. While male PD animal models present changes in the central respiratory control areas, as well as ventilatory parameters under normoxia and hypercapnia, little is known about sex differences regarding respiratory deficits in this disease background. This study aimed to explore the neuroanatomical and functional respiratory changes in intact and ovariectomized (OVX) female rats subjected to chemically induced PD via a bilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). The respiratory parameters were evaluated by whole-body plethysmography, and the neuroanatomy was monitored using immunohistochemistry. It was found that dopaminergic neurons in the substantia nigra and neurokinin-1 receptor density in the rostral ventrolateral respiratory group, Bötzinger and pre-Bötzinger complex were reduced in the chemically induced PD animals. Additionally, reduced numbers of Phox2b neurons were only observed in the retrotrapezoid nucleus of PD-OVX rats. Concerning respiratory parameters, in OVX rats, the resting and hypercapnia-induced tidal volume (VT ) is reduced, and ventilation ( ) changes independently of 6-OHDA administration. Notably, there is a reduction in the number of retrotrapezoid nucleus Phox2b neurons and hypercapnia-induced respiratory changes in PD-OVX animals due to a 6-OHDA and OVX interaction. These results suggest a protective effect induced by ovarian hormones in neuroanatomical changes observed in a female experimental PD model.

Electrophysiological characterization of medial preoptic neurons in lactating rats and its modulation by hypocretin-1

The medial preoptic area (mPOA) undergoes through neuroanatomical changes across the postpartum period, during which its neurons play a critical role in the regulation of maternal behavior. In addition, this area is also crucial for sleep-wake regulation. We have previously shown that hypocretins (HCRT) within the mPOA facilitate active maternal behaviors in postpartum rats, while the blockade of endogenous HCRT in this area promotes nursing and sleep. To explore the mechanisms behind these HCRT actions, we aimed to evaluate the effects of juxta-cellular HCRT-1 administration on mPOA neurons in urethane-anesthetized postpartum and virgin female rats. We recorded mPOA single units and the electroencephalogram (EEG) and applied HCRT-1 juxta-cellular by pressure pulses. Our main results show that the electrophysiological characteristics of the mPOA neurons and their relationship with the EEG of postpartum rats did not differ from virgin rats. Additionally, neurons that respond to HCRT-1 had a slower firing rate than those that did not. In addition, administration of HCRT increased the activity in one group of neurons while decreasing it in another, both in postpartum and virgin rats. This study suggests that the mechanisms by which HCRT modulate functions controlled by the mPOA involve different cell populations.

Cortical neuroanatomical changes related to specific language impairments in primary progressive aphasia.

ObjectiveLanguage function test-specific neural substrates in Korean patients with primary progressive aphasia (PPA) might differ from those in other causes of dementia and English-speaking PPA patients. We investigated the correlation between language performance tests and cortical thickness to determine neural substrates in Korean patients with PPA.Materials and methodsNinety-six patients with PPA were recruited from the memory clinic. To acquire neural substrates, we performed linear regression using the scores of each language test as a predictor, cortical thickness as an outcome and age, sex, years of education, and intracranial volume as confounders.ResultsPoor performance in each language function test was associated with lower cortical thickness in specific cortical regions: (1) object naming and the bilateral anterior to mid-portion of the lateral temporal and basal temporal regions; (2) semantic generative naming and the bilateral anterior to mid-portion of the lateral temporal and basal temporal regions; (3) phonemic generative naming and the left prefrontal and inferior parietal regions; and (4) comprehension and the left posterior portion of the superior and middle temporal regions. In particular, the neural substrates of the semantic generative naming test in PPA patients, left anterior to mid-portion of the lateral and basal temporal regions, quite differed from those in patients with other causes of dementia.ConclusionOur findings provide a better understanding of the different pathomechanisms for language impairments among PPA patients from those with other causes of dementia.

Longitudinal trajectories of cortical development in 22q11.2 copy number variants and typically developing controls

Probing naturally-occurring, reciprocal genomic copy number variations (CNVs) may help us understand mechanisms that underlie deviations from typical brain development. Cross-sectional studies have identified prominent reductions in cortical surface area (SA) and increased cortical thickness (CT) in 22q11.2 deletion carriers (22qDel), with the opposite pattern in duplication carriers (22qDup), but the longitudinal trajectories of these anomalies—and their relationship to clinical symptomatology—are unknown. Here, we examined neuroanatomic changes within a longitudinal cohort of 261 22q11.2 CNV carriers and demographically-matched typically developing (TD) controls (84 22qDel, 34 22qDup, and 143 TD; mean age 18.35, ±10.67 years; 50.47% female). A total of 431 magnetic resonance imaging scans (164 22qDel, 59 22qDup, and 208 TD control scans; mean interscan interval = 20.27 months) were examined. Longitudinal FreeSurfer analysis pipelines were used to parcellate the cortex and calculate average CT and SA for each region. First, general additive mixed models (GAMMs) were used to identify regions with between-group differences in developmental trajectories. Secondly, we investigated whether these trajectories were associated with clinical outcomes. Developmental trajectories of CT were more protracted in 22qDel relative to TD and 22qDup. 22qDup failed to show normative age-related SA decreases. 22qDel individuals with psychosis spectrum symptoms showed two distinct periods of altered CT trajectories relative to 22qDel without psychotic symptoms. In contrast, 22q11.2 CNV carriers with autism spectrum diagnoses showed early alterations in SA trajectories. Collectively, these results provide new insights into altered neurodevelopment in 22q11.2 CNV carriers, which may shed light on neural mechanisms underlying distinct clinical outcomes.