Gray Matter Volume Reduction Research Articles

COMT-Val158Met polymorphism modulates antipsychotic effects on auditory verbal hallucinations and temporal lobe gray matter volumes in healthy individuals\u2014symptom relief accompanied by worrisome volume reductions

Investigation of auditory verbal hallucinations (AVHs) in schizophrenics is complicated by psychiatric symptoms. Investigating healthy individuals with AVHs (H-AVHs) can obviate such confounding factors. The objective of this study was to explore the effects of antipsychotic treatment on AVHs and gray matter volumes (GMVs) in H-AVH subjects and whether such are effects are influenced by COMT-Val158Met genotype. Magnetic resonance imaging (MRI) and genotyping studies were completed for 42 H-AVH subjects and 42 well-matched healthy controls (HCs). COMT-Met/Met homozygotes (158th codon) were identified as COMT-Met genotype; COMT-Met/Val heterozygotes and COMT-Val/Val homozygotes were identified as COMT-Val genotype. Data were compared across groups (H-AVH vs. HC, and between genotypes) with two-sample t-tests. The H-AVH COMT-Met group showed a stronger response to antipsychotic treatment than the H-AVH COMT-Val group (p < 0.001). Both H-AVH genotype groups exhibited temporal lobe GMV reductions after treatment, and relative to their respective genotype-matched HC groups. Antipsychotic treatment effects in H-AVH subjects were influenced by COMT-Val158Met genotype and associated with widespread GMV reductions. These findings provide clues for further exploration of treatment targets for AVHs. Treatment associated GMV reductions, however, raise concerns about use of antipsychotics in H-AVH subjects.

Emergent Prophylactic, Reparative and Restorative Brain Interventions for Infants Born Preterm With Cerebral Palsy.

Worldwide, an estimated 15 million babies are born preterm (<37 weeks' gestation) every year. Despite significant improvements in survival rates, preterm infants often face a lifetime of neurodevelopmental disability including cognitive, behavioral, and motor impairments. Indeed, prematurity remains the largest risk factor for the development of cerebral palsy. The developing brain of the preterm infant is particularly fragile; preterm babies exhibit varying severities of cerebral palsy arising from reductions in both cerebral white and gray matter volumes, as well as altered brain microstructure and connectivity. Current intensive care therapies aim to optimize cardiovascular and respiratory function to protect the brain from injury by preserving oxygenation and blood flow. If a brain injury does occur, definitive diagnosis of cerebral palsy in the first few hours and weeks of life is difficult, especially when the lesions are subtle and not apparent on cranial ultrasound. However, early diagnosis of mildly affected infants is critical, because these are the patients most likely to respond to emergent treatments inducing neuroplasticity via high-intensity motor training programs and regenerative therapies involving stem cells. A current controversy is whether to test universal treatment in all infants at risk of brain injury, accepting that some patients never required treatment, because the perceived potential benefits outweigh the risk of harm. Versus, waiting for a diagnosis before commencing targeted treatment for infants with a brain injury, and potentially missing the therapeutic window. In this review, we discuss the emerging prophylactic, reparative, and restorative brain interventions for infants born preterm, who are at high risk of developing cerebral palsy. We examine the current evidence, considering the timing of the intervention with relation to the proposed mechanism/s of action. Finally, we consider the development of novel markers of preterm brain injury, which will undoubtedly lead to improved diagnostic and prognostic capability, and more accurate instruments to assess the efficacy of emerging interventions for this most vulnerable group of infants.

Pregnancy and adolescence entail similar neuroanatomical adaptations: A comparative analysis of cerebral morphometric changes

Mapping the impact of pregnancy on the human brain is essential for understanding the neurobiology of maternal caregiving. Recently, we found that pregnancy leads to a long-lasting reduction in cerebral gray matter volume. However, the morphometric features behind the volumetric reductions remain unexplored. Furthermore, the similarity between these reductions and those occurring during adolescence, another hormonally similar transitional period of life, still needs to be investigated. Here, we used surface-based methods to analyze the longitudinal magnetic resonance imaging data of a group of 25 first-time mothers (before and after pregnancy) and compare them to those of a group of 25 female adolescents (during 2 years of pubertal development). For both first-time mothers and adolescent girls, a monthly rate of volumetric reductions of 0.09 mm3 was observed. In both cases, these reductions were accompanied by decreases in cortical thickness, surface area, local gyrification index, sulcal depth, and sulcal length, as well as increases in sulcal width. In fact, the changes associated with pregnancy did not differ from those that characterize the transition during adolescence in any of these measures. Our findings are consistent with the notion that the brain morphometric changes associated with pregnancy and adolescence reflect similar hormonally primed biological processes.

A novel neurocognitive approach for placebo analgesia in neurocognitive disorders.

Neural correlates of placebo analgesia (PA) in patients with neurocognitive disorders have not yet been elucidated. The present study aimed to evaluate how and to what extent executive (dys)functions of the medial prefrontal cortex (MPFC) may be related to PA. To this end, twenty-three subjects complaining of different cognitive deficits (from mild cognitive impairment likely due to Alzheimer's disease to mild AD) were recruited. PA was investigated by a well-known experimental venipuncture pain paradigm (open versus hidden [O-H] application of lidocaine). Patients also underwent a comprehensive neuropsychological evaluation and a functional magnetic resonance imaging (fMRI) GO/No-GO task for eliciting selective activation of the MPFC. Selected neuropsychological variables were correlated to the OH-PA paradigm. The association between the fMRI response on the "No-GO" versus "GO" contrast and PA was investigated over the whole-brain by regression analysis. We showed the existence of a relationship between a lower PA and MPFC dysfunctions through the neuropsychological and fMRI assessment. A separate voxel-based morphometry (VBM) analysis controlled for possible influence of grey matter (GM) volume reduction on both fMRI results and PA. fMRI results were not directly affected by, and therefore independent of, disease-specific GM atrophy, which was indeed located more anteriorly within the rostral anterior cingulate and inversely correlated with PA. Our findings shed new light on the underestimated contribution of executive (dys)functions mediated by the MPFC (response-inhibition, self-monitoring and set-shifting abilities) in PA pathogenesis, with a special purely (i.e. independently from brain structural alterations) functional role played by the MCC. Results are discussed in terms of possible clinical relevance in the management of patients with neurocognitive disorders.

Reduced gray matter volume in cognitively preserved COMT 158Val/Val Parkinson's disease patients and its association with cognitive decline.

The COMT Val158Met polymorphism has recently been identified as a predictor for cognitive decline in Parkinson's disease (PD). However, it remains unknown whether an early brain structural compromise could be involved in this clinical association. Here, in a cohort of 120 cognitively preserved de novo PD patients from the Parkinson's Progression Markers Initiative (PPMI) database, we found a widespread reduction in cerebral gray matter volume (GMV) in patients harboring the Val/Val genotype. The atrophic pattern included fronto-subcortical and parieto-temporal territories. Importantly, the GMV at some of the identified regions was associated with cognitive decline in a 4-year follow-up period. These findings suggest that GMV compromise in the early stages of PD may be a predisposing factor for cognitive decline of COMT Val/Val homozygotes.

The Neural Correlates of Impaired Self-Monitoring Among Individuals With Neurodegenerative Dementias.

Self-monitoring is a crucial component of human empathy and necessary for the formation and repair of social relations. Several studies have brought to light possible neuronal substrates associated with self-monitoring, but the information that they have provided is inconclusive. The authors, therefore, studied a large group of patients with dementia to assess what brain structures are necessary for the self-monitoring function.Methods: Seventy-seven patients with dementia of various types were screened using voxel-based morphometry to assess possible volume reduction in the brain structures of patients with self-monitoring problems, and the decrease of socioemotional expressiveness and modification of self-presentation was estimated using the Revised Self-Monitoring Scale. Regression analysis was employed to investigate the correlation between gray matter loss and deficient self-monitoring.Results: The socioemotional expressiveness scores were associated with decreased gray matter volume in the right olfactory cortex, inferior frontal gyrus, superior temporal pole, parahippocampal gyrus, insula, and medial temporal gyrus bilaterally. Self-presentation scores were associated with bilateral gray matter volume reduction in the olfactory cortex, insula, rectus gyrus and inferior frontal gyrus, right superior temporal pole, and parahippocampal gyrus, as well as the left medial temporal gyrus and anterior superior frontal gyrus.Conclusions: These results suggest that patients with dementia present decreased ability of self-monitoring, probably due to impaired insula and orbitofrontal cortex and their disconnection from structures of the salience network.

Gray Matter Volume Changes in Patients With Acute Eye Pain: A Voxel-Based Morphometry Study.

PurposeThe present study was attempted to compare the differences in gray matter volume (GMV) between the acute eye pain (EP) patients and the healthy controls (HCs) using voxel-based morphometry (VBM), and to explore the relationship with clinical features and behavioral performance.MethodsA total of 24 patients (17 males, 7 females) with acute EP and 24 (17 males, 7 females) age-, sex-, and education-matched HCs were recruited from the Ophthalmology Department of the First Affiliated Hospital of Nanchang University. Functional magnetic resonance imaging (fMRI) scans were conducted in all subjects. We analyzed the original three-dimensional (3D) T1 brain images by VBM and compared the GMV values with the HCs. The acute EP patients can be distinguished from the HCs by receiver operating characteristic (ROC) curve.ResultsCompared with HCs, the acute EP patients had significantly lower GMV values in the brain regions of the left cerebellum posterior lobe, the left limbic lobe, the right insula, the left insula, the left thalamus, the left caudate, and the right cuneus. In addition, the WMV values of the whole brain in acute EP patients decreased slightly.ConclusionsThese results demonstrated that the acute EP patients showed an abnormal reduction in GMV in some brain regions, which might provide valuable information for further exploration of underlying neural mechanisms. These abnormal brain regions may reflect the functional disorders of acute EP patients in somatosensory, motor, cognitive functions, and so on.Translational RelevanceThe VBM study provides a diagnostic method for identifying the cause of acute EP, additionally, a novel direction was presented for further exploration of underlying neural mechanisms of acute EP.

Associations between neuroanatomical abnormality and motor symptoms in paroxysmal kinesigenic dyskinesia

IntroductionThe pathophysiologic mechanism of paroxysmal kinesigenic dyskinesia (PKD) is largely unclear. Basal ganglia-thalamo-cortical circuit involvement is thought to underlie PKD pathophysiology. However, microstructural alternations in the motor circuit of PKD require further elucidation. MethodsDiffusion tensor imaging and high-resolution T1-weighted imaging were performed on 30 PKD patients (15 PRRT2 carriers, 15 PRRT2 non-carriers) and 15 matched healthy controls. Tract-based spatial statistics were conducted on diffusion indices to examine microstructural integrity of white matter. Voxel-based morphometry analysis was used to examine volumetric changes of gray matter. Multiple regression was employed to test the contribution of demography, disease duration, and PRRT2 status to pathological changes in brain structure. ResultsSix (including two novel) PRRT2 mutations were identified in PKD patients who exhibited significantly reduced mean diffusivity mainly along the left corticospinal tract, and reduced gray matter volume in pre-supplementary motor area (preSMA) and right opercular part of inferior frontal gyrus (IFGoperc), compared to healthy controls. Both gray matter volume reductions in preSMA and diffusion indices of abnormal white matter negatively correlated with disease duration. Genotype-phenotype analysis revealed that PRRT2 mutation carriers had earlier onset age, longer attacks, and a larger proportion of bilateral symptoms than non-carriers. ConclusionsWe observed that PRRT2 mutations were associated with disease severity, while neuroanatomical abnormality was associated with disease duration in patients with PKD. Aberrant microstructural changes in preSMA and IFG areas, independent of mutation status, point to dysregulated motor inhibition in patients and provide new insights into neurobiological mechanisms underlying motor symptoms of PKD.

Similarities and differences in cerebellar grey matter volume and disrupted functional connectivity in idiopathic Parkinson's disease and multiple system atrophy

ObjectiveThis study investigated the potential differences in changes to cerebellar grey matter volume (GMV) and functional connectivity (FC) and the association between them, which might elucidate cerebellar function in multiple system atrophy (MSA) and idiopathic Parkinson's disease (IPD). MethodsResting-state functional magnetic resonance imaging and three-dimensional T1 scans were obtained from 38 IPD, 62 MSA, and 59 healthy controls (HC). Seed-based connectivity analysis and voxel-based morphometry analysis were performed to assess the changes of cerebellar FC and GMV between the patient groups. ResultDecreased cerebellar GMV was found in the motor cerebellum in both patient groups relative to HC, and broader reduction of GMV was observed in both cognitive and motor cerebellum in MSA compared with IPD and HC. Compared with IPD, the MSA group exhibited decreased FC between bilateral dentate nucleus (DN) and default mode network (DMN). Decreased intracerebellar FC was observed in both patient groups relative to HC. Cerebellar GMV was positively correlated with FC of intracerebellum and DN-DMN in MSA. Motor/cognitive scores were associated with DN-DMN FC, with considerable cerebellar GMV loss in MSA patients. ConclusionCerebellar GMV loss and cerebellar FC alterations showed similarities in IPD and MSA, along with more widespread changes to GMV in motor and cognitive cerebellum and altered DN-DMN FC in MSA. Further research is needed to better describe the alterations of cerebellar GMV in the cognitive cerebellum and association between cerebellar GMV and intracerebellar FC during the early stages of MSA and IPD.

Gray Matter Volume Reductions Were Associated with TPH1 Polymorphisms in Depressive Disorder Patients with Suicidal Attempts.

ObjectiveStructural changes of brain areas have been reported in depressive disorder and suicidal behavior (SB), in which TPH1 also has been known as a promising candidate gene. We investigated gray matter volume (GMV) differences, TPH1 rs1800532 and rs1799913 polymorphisms previously found to be associated with depressive disorder and SB, and the relationship between the two markers. MethodsThirteen depressive disorder patients with suicidal attempts (SA) and twenty healthy controls were included. We examined GMV differences using a voxel-based morphometry and regions of interest analysis. Direct sequencing was used for genotyping. ResultsThe patients showed significant GMV reduction in left cerebral region including middle frontal gyrus, inferior frontal gyrus, and anterior cingulate cortex; in right middle temporal gyrus; in left cerebellar tonsil; and in right cerebral region including precentral gyrus and postcentral gyrus (corrected p<0.005). The right precentral and postcentral gyri GMV values of AA and CA genotypes patients were significantly decreased compared to those of CC genotype subjects (corrected p=0.040). ConclusionThese findings show the possibility that both GMV reductions and TPH1 rs1800532/rs1799913 A allele may be involved in the pathogenesis of depressive disorder patients with SA.

Thalamic shape and volume abnormalities in female patients with panic disorder.

The thalamus is believed to play crucial role in processing viscero-sensory information, and regulating the activity of amygdala in patients with panic disorder (PD). Previous functional neuroimaging studies have detected abnormal activation in the thalamus in patients with PD compared with healthy control subjects (HC). Very few studies, however, have investigated for volumetric abnormalities in the thalamus in patients with PD. Furthermore, to the best of our knowledge, no previous study has investigated for shape abnormalities in the thalamus in patients with PD. Twenty-five patients with PD and 25 HC participants (all female) were recruited for the study. A voxel-wise volume comparison analysis and a vertex-wise shape analysis were conducted to evaluate structural abnormalities in the PD patients compared to HC. The patients with PD demonstrated significant gray matter volume reductions in the thalamus bilaterally, relative to the HC. The shape analysis detected significant inward deformation in some thalamic regions in the PD patients, including the anterior nucleus, mediodorsal nucleus, and pulvinar nucleus. PD patients showed shape deformations in key thalamic regions that are believed to play a role in regulating emotional and cognitive functions.

Gray matter substrates of depressive and anxiety symptoms in idiopathic REM sleep behavior disorder

IntroductionIdiopathic rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Depressive and anxiety symptoms are frequent features of PD, DLB and iRBD, and some studies suggest that depressive symptoms are a marker for neurodegeneration in iRBD. However, the pathophysiology of depressive and anxiety symptoms in iRBD is still unclear. This study aimed to investigate cortical and subcortical gray matter (GM) volume substrates of depressive and anxiety symptoms in iRBD patients. MethodsForty-six polysomnography-confirmed iRBD patients and 31 healthy controls (HC) without cognitive or mood impairment were recruited. All participants underwent 3-T magnetic resonance imaging and completed the Beck Depression Inventory Second Edition (BDI-II) and Beck Anxiety Inventory (BAI) questionnaires. Voxel-based morphometry analysis was performed to assess GM volume in cortical and subcortical structures. Between-group comparisons and regressions were performed. ResultsiRBD patients with depressive symptoms (BDI-II score > 13 or the use of antidepressants to treat depression) showed reduced GM volume in the caudate nucleus compared to HC and iRBD patients without depressive symptoms. Moreover, iRBD patients with anxiety symptoms (BAI score > 9 or the use of anxiolytics to treat anxiety) showed reduced GM volume in the left amygdala extending to the hippocampus compared to HC and iRBD patients without anxiety symptoms. In iRBD patients, higher BDI-II and BAI total scores were associated with lower GM volumes in these regions respectively. ConclusionDepressive and anxiety symptoms in iRBD patients are related to patterns of cortical and subcortical GM volume loss.

Specific Substantial Dysconnectivity in Schizophrenia: A Transdiagnostic Multimodal Meta-analysis of Resting-State Functional and Structural Magnetic Resonance Imaging Studies

BackgroundThis study investigated characteristic large-scale brain changes in schizophrenia. Numerous imaging studies have demonstrated brain changes in schizophrenia, particularly aberrant intrinsic functional connectivity (iFC) of ongoing brain activity, measured by resting-state functional magnetic resonance imaging, and aberrant gray matter volume (GMV) of distributed brain regions, measured by structural magnetic resonance imaging. It is unclear, however, which iFC changes are specific to schizophrenia compared with those of other disorders and whether such specific iFC changes converge with GMV changes. To address this question of specific substantial dysconnectivity in schizophrenia, we performed a transdiagnostic multimodal meta-analysis of resting-state functional and structural magnetic resonance imaging studies in schizophrenia and other psychiatric disorders. MethodsMultiple databases were searched up to June 2017 for whole-brain seed-based iFC studies and voxel-based morphometry studies in schizophrenia, major depressive disorder, bipolar disorder, addiction, and anxiety. Coordinate-based meta-analyses were performed to detect 1) schizophrenia-specific hyperconnectivity or hypoconnectivity of intrinsic brain networks (compared with hyperconnectivity or hypoconnectivity of each other disorder both separately and combined across comparisons) and 2) the overlap between dysconnectivity and GMV changes (via multimodal conjunction analysis). ResultsFor iFC meta-analysis, 173 publications comprising 4962 patients and 4575 control subjects were included, and for GMV meta-analysis, 127 publications comprising 6311 patients and 6745 control subjects were included. Disorder-specific iFC dysconnectivity in schizophrenia (consistent across comparisons with other disorders) was found for limbic, frontoparietal executive, default mode, and salience networks. Disorder-specific dysconnectivity and GMV reductions converged in insula, lateral postcentral cortex, striatum, and thalamus. ConclusionsResults demonstrated specific substantial dysconnectivity in schizophrenia in insula, lateral postcentral cortex, striatum, and thalamus. Data suggest that these regions are characteristic targets of schizophrenia.

Multimodal Data and Machine Learning for Detecting Specific Biomarkers in Pediatric Epilepsy Patients With Generalized Tonic-Clonic Seizures.

Previous neuroimaging studies of epilepsy with generalized tonic-clonic seizures (GTCS) focus mainly on adults. However, the neural mechanisms that underline this type of epilepsy remain unclear, especially for children. The aim of the present study was to detect the effect of epilepsy on brains of children with GTCS and to investigate whether the changes in the brain can be used to discriminate between epileptic children and healthy children at the level of the individual. To achieve this purpose, we measured gray matter (GM) volume and fractional amplitude of low-frequency fluctuation (fALFF) differences on multimodel magnetic resonance imaging in 14 children with GTCS and 30 age- and gender-matched healthy controls. The patients showed GM volume reduction and a fALFF increase in the thalamus, hippocampus, temporal and other deep nuclei. A significant decrease of fALFF was mainly found in the default mode network (DMN). In addition, epileptic duration was significantly negatively related to the GM volumes and significantly positively related to the fALFF value of right thalamus. A support vector machine (SVM) applied to the GM volume of the right thalamus correctly identified epileptic children with a statistically significant accuracy of 74.42% (P < 0.002). A SVM applied to the fALFF of the right thalamus correctly identified epileptic children with a statistically significant accuracy of 83.72% (P < 0.002). The consistent neuroimaging results indicated that the right thalamus plays an important role in reflecting the chronic damaging effect of GTCS epilepsy in children. The length of time of a child's epileptic history was correlated with greater GM volume reduction and a fALFF increase in the right thalamus. GM volumes and fALFF values in the right thalamus can identify children with GTCS from the healthy controls with high accuracy and at an individual subject level. These results are likely to be valuable in explaining the clinical problems and understanding the brain abnormalities underlying this disorder.

Reduced lateral occipital gray matter volume is associated with physical frailty and cognitive impairment in Parkinson's disease.

To investigate the structural changes of the brain that correlate with physical frailty and cognitive impairments in Parkinson's disease (PD) patients. Sixty-one PD patients and 59 age- and sex-matched healthy controls were enrolled. For each participant, a frailty assessment using Fried's criteria and comprehensive neuropsychological testing using the Wechsler Adult Intelligence Scale-III and Cognitive Ability Screening Instrument were conducted, and structural brain MR images were acquired for voxel-based morphometric analysis. The neuropsychological testing includes various tests in these five domains: attention, executive, memory, speech and language, and visuospatial functions. Exploratory group-wise comparisons of gray matter volume (GMV) in the PD patients and controls were conducted. Voxel-wise multiple linear regression analyses were conducted for physical frailty-related and cognitive impairment-related GMV changes in the PD patients. Voxel-wise multiple linear regressions were also performed with the five cognitive domains separated using the same model. The PD patients exhibited diffuse GMV reductions in comparison to the controls. In the PD patients, physical frailty-related decreases in GMV were observed in the bilateral frontal and occipital cortices, while cognitive impairment-related decreases in GMV were observed in the bilateral frontal, occipital, and temporal cortices. These regions overlap in the lateral occipital cortex. After the five domains of cognitive functions were analyzed separately, physical frailty-related decreases in GMV still overlap in lateral occipital cortices with every domain of cognitive impairment-related decreases in GMV. Reduced GMV in the lateral occipital cortex is associated with cognitive impairment and physical frailty in PD patients. • Physical frailty in PD was associated with decreased GMV in the frontal and occipital cortices, while cognitive impairment was associated with decreased GMV in the frontal, temporal, and occipital cortices. • Physical frailty and cognitive impairment were both associated with decreased GMV in the lateral occipital cortex, which is part of the ventral object-based visual pathway. • Decreased GMV in the lateral occipital cortex may serve as a potential imaging biomarker for physical frailty and cognitive impairment in PD.

Depression, auditory-verbal hallucinations, and delusions in patients with schizophrenia: Different patterns of association with prefrontal gray and white matter volume

Structural brain abnormalities, including decreased gray matter (GM) and white matter (WM) volume, have been observed in patients with schizophrenia. These decrements were found to be associated with positive and negative symptoms, but affective symptoms (depression and anxiety) were poorly explored. We hypothesized that abnormalities in GM and WM volume might also be related to affective symptoms. GM and WM volumes were calculated from high-resolution T1 structural images acquired from 24 patients with schizophrenia and 26 healthy controls, and the associations of positive, negative, and affective symptoms with the brain volumes that showed significant reduction in patients were investigated. Patients demonstrated GM volume reductions in the bilateral prefrontal cortex, and WM volume reductions in the right frontal and left corpus callosum. Prefrontal cortex volume was significantly and inversely associated with both auditory-verbal hallucinations and depression severity. WM volume alterations, in contrast, were related to alogia, anhedonia, and delusions. The combined impact of auditory-verbal hallucinations and depression on similar sub-regions of the prefrontal cortex suggests that depression is involved in hearing voices. Further, this adverse impact of depression on prefrontal GM volume may underlie the impairment demonstrated by these patients in cognitive tasks that rely on executive processes.

White matter volume is decreased in bipolar disorder at early and late stages.

Bipolar disorder (BD) is a debilitating mood condition that affects approximately 1.3% of people worldwide, although some studies report up to 3.9% lifetime prevalence and 4-6% in adults when broad diagnostic criteria are applied. To compare differences in total white matter (WM), corpus callosum (CC) and total gray matter (GM) volumes in patients with type I BD at early and late stages compared with controls. Fifty-five subjects were enrolled in this study protocol. The double case-control design included 14 patients with BD at early stage; 15 patients at late stage; and their respective matched controls (14 and 12 subjects). CC and total WM volumes were significantly smaller in patients with BD at early and late stages vs. controls. There was no difference for total GM volume in the early stage group, but in patients at late stage total GM volume was significantly smaller than in controls. The total GM volume reduction in patients at late stage is in agreement with the neuroprogression theory of BD. The reduction of WM volumes in total WM and in the CC at early and late stages supports the possibility that an early demyelination process could occur underlying the clinical manifestation of BD. Our findings may direct to the investigation of WM abnormalities in populations at high risk to develop BD, perhaps as early biomarkers before the overt syndrome.

Brain grey matter volume reduction and anxiety-like behavior in lipopolysaccharide-induced chronic pulmonary inflammation rats: A structural MRI study with histological validation

While there have been multiple fMRI studies into the brain functional changes after acutely stimulated peripheral infection, knowledge for the effect of chronic peripheral infection on whole brain morphology is still quite limited. The present study was designed to investigate the brain structural and emotional changes after peripheral local infection initiated chronic systemic inflammation and the relationship between circulating inflammatory markers and brain grey matter. Specifically, in-vivo T2-weighted MRI was performed on rats with lipopolysaccharide (LPS)-induced chronic pulmonary inflammation (CPI) and those without. Grey matter volume was quantified using diffeomorphic anatomical registration through exponentiated lie (DARTEL) enhanced voxel-based morphometry followed by between-group comparison. Open field experiment was conducted to test the potential anxiety-like behaviors after CPI, along with the ELISA estimated inflammatory markers were correlated to grey matter volume. Guided by image findings, we undertook a focused histological investigation with immunefluorescence and Nissl staining. A widespread decrease of grey matter volume in CPI-model rats was revealed. 8 of the 12 measured inflammatory markers presented differential neuroanatomical correlation patterns with three of the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and CRP being the most notable. Lower grey matter volumes in some of the inflammatory markers related regions (amygdala, CA2 and cingulate cortex) were associated with more-severe anxiety-like behaviors. Furthermore, grey matter volumes in amygdala and CA3 were correlated negatively with the expressions of glial proteins (S100β and Nogo-A), while the grey matter volume in hypo-thalamus was changing positively with neural cell area. Overall, the neuroanatomical association patterns and the histopathology underpinning the MRI observations we demonstrated here would probably serve as one explanation for the cerebral and emotional deficits presented in the patients with CPI, which would furthermore yield new insights into the adverse effects the many other systemic inflammation and inflammatory autoimmune diseases would pose on brain morphology.

Grey matter differences associated with age and sex hormone levels between premenopausal and perimenopausal women: A voxel-based morphometry study.

The present study aimed to explore brain morphological alterations associated with age and sex hormone levels between premenopausal and perimenopausal women using magnetic resonance imaging (MRI) T1 -weighted structural images. Thirty-two premenopausal women aged (mean±SD) 47.75±1.55years and twenty-five recently perimenopausal women aged 51.60±1.63years were evaluated for sex hormone levels, including prolactin, follicle-stimulating hormone, luteinising hormone, oestradiol, free testosterone and progesterone. A 3.0-Tesla MRI scanner was utilised to acquire T1 images. Voxel-based morphometry (VBM) was used to evaluate changes in grey matter volume between the two groups. The general linear model was applied with false discovery rate correction for between group voxel-wise statistics. Spearman partial correlation analyses were conducted between age, sex hormone levels and regions of grey matter volume showing significant differences between the two groups. The VBM analysis revealed that age and menopause per se lead to grey matter volume reduction in certain brain structures. These structural changes might be potential causes of sexual dysfunction, nervous system degeneration and depression, which need to be examined in future studies. Our findings might provide evidence and guide future research in understanding the menopausal transition.

Neocerebellar Crus I Abnormalities Associated with a Speech and Language Disorder Due to a Mutation in FOXP2

Bilateral volume reduction in the caudate nucleus has been established as a prominent brain abnormality associated with a FOXP2 mutation in affected members of the ‘KE family’, who present with developmental orofacial and verbal dyspraxia in conjunction with pervasive language deficits. Despite the gene’s early and prominent expression in the cerebellum and the evidence for reciprocal cerebellum-basal ganglia connectivity, very little is known about cerebellar abnormalities in affected KE members. Using cerebellum-specific voxel-based morphometry (VBM) and volumetry, we provide converging evidence from subsets of affected KE members scanned at three time points for grey matter (GM) volume reduction bilaterally in neocerebellar lobule VIIa Crus I compared with unaffected members and unrelated controls. We also show that right Crus I volume correlates with left and total caudate nucleus volumes in affected KE members, and that right and total Crus I volumes predict the performance of affected members in non-word repetition and non-verbal orofacial praxis. Crus I also shows bilateral hypo-activation in functional MRI in the affected KE members relative to controls during non-word repetition. The association of Crus I with key aspects of the behavioural phenotype of this FOXP2 point mutation is consistent with recent evidence of cerebellar involvement in complex motor sequencing. For the first time, specific cerebello-basal ganglia loops are implicated in the execution of complex oromotor sequences needed for human speech.