Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Subcortical microstructural diffusion changes correlate with gait impairment in Parkinson's disease.

BACKGROUND: Gait impairments are common in Parkinson's Disease (PD) and are likely caused by degeneration in multiple brain circuits, including the basal ganglia, thalamus and mesencephalic locomotion centers (MLC). Diffusion tensor imaging (DTI) assesses fractional anisotropy (FA) and mean diffusivity (MD) that reflect the integrity of neuronal microstructure. We hypothesized that DTI changes in motor circuits correlate with gait changes in PD. OBJECTIVE: We aimed to identify microstructural changes of brain locomotion control centers in PD via DTI and their correlations with clinical and quantitative measures of gait. METHODS: Twenty-one PD patients reporting gait impairment and 15 controls were recruited. Quantitative gait and clinical tests were recorded in PD subjects' medication ON and OFF states. Region of Interest (ROI) analysis of the thalamus, basal ganglia and MLC was performed using ExploreDTI. Correlations between FA/MD with clinical gait parameters were examined. RESULTS: Microstructural changes were seen in the thalamus, caudate and MLC in the PD compared to the control group. Thalamic microstructural changes significantly correlated with gait parameters in the pace domain including the Timed Up and Go in the ON state. Caudate changes correlated with cadence and stride time in the OFF state. CONCLUSIONS: Our pilot study suggests that PD is associated with a characteristic regional pattern of microstructural degradation in the thalamus, caudate and MLC. The DTI changes may represent subcortical locomotion network failure. Overall, DTI ROI analyses might provide a useful tool for assessing PD for functional status and specific motor domains, such as gait, and potentially could serve as an imaging marker.

Neural changes following equine-assisted therapy for posttraumatic stress disorder: A longitudinal multimodal imaging study.

BACKGROUND: While effective treatments for posttraumatic stress disorder (PTSD) exist, many individuals, including military personnel and veterans fail to respond to them. Equine-assisted therapy (EAT), a novel PTSD treatment, may complement existing PTSD interventions. This study employs longitudinal neuro-imaging, including structural magnetic resonance imaging (sMRI), resting state-fMRI (rs-fMRI), and diffusion tensor imaging (DTI), to determine mechanisms and predictors of EAT outcomes for PTSD. METHOD: Nineteen veterans with PTSD completed eight weekly group sessions of EAT undergoing multimodal MRI assessments before and after treatment. Clinical assessments were conducted at baseline, post-treatment and at 3-month follow-up. RESULTS: At post-treatment patients showed a significant increase in caudate functional connectivity (FC) and reduction in the gray matter density of the thalamus and the caudate. The increase of caudate FC was positively associated with clinical improvement seen immediately at post-treatment and at 3-month follow-up. In addition, higher baseline caudate FC was associated with greater PTSD symptom reduction post-treatment. CONCLUSIONS: This exploratory study is the first to demonstrate that EAT can affect functional and structural changes in the brains of patients with PTSD. The findings suggest that EAT may target reward circuitry responsiveness and produce a caudate pruning effect from pre- to post-treatment.

Brain volume changes after long-term injectable opioid treatment: A longitudinal voxel-based morphometry study.

Clinical research has demonstrated the efficacy of injectable opioid treatment for long-term, treatment-refractory opioid-dependent patients. It has been hypothesized that compulsive drug use is particularly associated with neuroplasticity changes in the networks corresponding to withdrawal/negative affect and preoccupation/anticipation rather than binge/intoxication. However, as yet, no study has investigated the effect of long-term opioid treatment on key regions within these networks. Magnetic resonance imaging (MRI) was used to assess brain volumes changes during long-term (approximately 9 years) injectable opioid agonist treatment with diacetylmorphine (DAM) in 22 patients with opioid use disorder. Voxel-based morphometry was applied to detect volumetric changes within the networks of binge/intoxication (ventral/dorsal striatum, globus pallidus and thalamus), withdrawal/negative affect (amygdala and ventral striatum) and preoccupation/anticipation (hippocampus, orbitofrontal and anterior cingulate cortex). The relationships between significant volume changes and features of opioid use disorder were tested using Pearson correlation. Long-term opioid agonist treatment was associated with the enlargement of the right caudate nucleus, which was related to the duration of opioid use disorder. In contrast, reduced volume in the right amygdala, anterior cingulate cortex and orbitofrontal cortex were found that were related to opioid dose, onset of opioid consumption and state anxiety. These findings suggest that long-term opioid agonist treatment is related to structural changes in key brain regions underlying binge/intoxication, withdrawal/negative affect and preoccupation/anticipation, suggesting sustained interaction between these systems.

Inhaled H2 or CO2 Do Not Augment the Neuroprotective Effect of Therapeutic Hypothermia in a Severe Neonatal Hypoxic-Ischemic Encephalopathy Piglet Model.

Hypoxic-ischemic encephalopathy (HIE) is still a major cause of neonatal death and disability as therapeutic hypothermia (TH) alone cannot afford sufficient neuroprotection. The present study investigated whether ventilation with molecular hydrogen (2.1% H2) or graded restoration of normocapnia with CO2 for 4 h after asphyxia would augment the neuroprotective effect of TH in a subacute (48 h) HIE piglet model. Piglets were randomized to untreated naïve, control-normothermia, asphyxia-normothermia (20-min 4%O2-20%CO2 ventilation; Tcore = 38.5 °C), asphyxia-hypothermia (A-HT, Tcore = 33.5 °C, 2-36 h post-asphyxia), A-HT + H2, or A-HT + CO2 treatment groups. Asphyxia elicited severe hypoxia (pO2 = 19 ± 5 mmHg) and mixed acidosis (pH = 6.79 ± 0.10). HIE development was confirmed by altered cerebral electrical activity and neuropathology. TH was significantly neuroprotective in the caudate nucleus but demonstrated virtually no such effect in the hippocampus. The mRNA levels of apoptosis-inducing factor and caspase-3 showed a ~10-fold increase in the A-HT group compared to naïve animals in the hippocampus but not in the caudate nucleus coinciding with the region-specific neuroprotective effect of TH. H2 or CO2 did not augment TH-induced neuroprotection in any brain areas; rather, CO2 even abolished the neuroprotective effect of TH in the caudate nucleus. In conclusion, the present findings do not support the use of these medical gases to supplement TH in HIE management.

Discrete changes in brain volume after deep brain stimulation in patients with Parkinson's disease.

OBJECTIVES: Deep brain stimulation (DBS), targeting the subthalamic nucleus (STN) and globus pallidus interna, is a surgical therapy with class 1 evidence for Parkinson's disease (PD). Bilateral DBS electrodes may be implanted within a single operation or in separate staged surgeries with an interval of time that varies patient by patient. In this study, we used the variation in the timing of implantation from the first to the second implantation allowing for examination of potential volumetric changes of the basal ganglia in patients with PD who underwent staged STN DBS. METHODS: Thirty-two patients with a mean time interval between implantations of 141.8 (±209.1; range: 7-700) days and mean duration of unilateral stimulation of 244.7 (±227.7; range: 20-672) days were included in this study. Using volumetric analysis of whole hemisphere and subcortical structures, we observed whether implantation or stimulation affected structural volume. RESULTS: We observed that DBS implantation, but not the duration of stimulation, induced a significant reduction of volume in the caudate, pallidum, putamen and thalamus ipsilateral to the implanted hemisphere. These findings were not dependent on the trajectory of the implanted electrode nor on first surgery pneumocephalus (0.07%: %Δ for intracranial volume between first and second surgery). In addition, unique regional atrophy differences were evident in each of the structures. CONCLUSION: Our results demonstrate that DBS implantation surgery may affect hemisphere volume at the level of subcortical structures connected to the surgical target.

Sleep Onset Problems and Subcortical Development in Infants Later Diagnosed With Autism Spectrum Disorder.

OBJECTIVE: Sleep patterns in children with autism spectrum disorder (ASD) appear to diverge from typical development in the second or third year of life. Little is known, however, about the occurrence of sleep problems in infants who later develop ASD and possible effects on early brain development. In a longitudinal neuroimaging study of infants at familial high or low risk for ASD, parent-reported sleep onset problems were examined in relation to subcortical brain volumes in the first 2 years of life. METHODS: A total of 432 infants were included across three study groups: infants at high risk who developed ASD (N=71), infants at high risk who did not develop ASD (N=234), and infants at low risk (N=127). Sleep onset problem scores (derived from an infant temperament measure) were evaluated in relation to longitudinal high-resolution T1 and T2 structural imaging data acquired at 6, 12, and 24 months of age. RESULTS: Sleep onset problems were more common at 6-12 months among infants who later developed ASD. Infant sleep onset problems were related to hippocampal volume trajectories from 6 to 24 months only for infants at high risk who developed ASD. Brain-sleep relationships were specific to the hippocampus; no significant relationships were found with volume trajectories of other subcortical structures examined (the amygdala, caudate, globus pallidus, putamen, and thalamus). CONCLUSIONS: These findings provide initial evidence that sleep onset problems in the first year of life precede ASD diagnosis and are associated with altered neurodevelopmental trajectories in infants at high familial risk who go on to develop ASD. If replicated, these findings could provide new insights into a potential role of sleep difficulties in the development of ASD.

Brain Volume Changes in Patients with Acute Brain Dysfunction Due to Sepsis.

BACKGROUND: Sepsis-induced brain dysfunction (SIBD) is often encountered in sepsis patients and is related to increased morbidity. No specific tests are available for SIBD, and neuroimaging findings are often normal. In this study, our aim was to analyze the diagnostic value of volumetric analysis of the brain structures and to find out its significance as a prognostic measure. METHODS: In this prospective observational study, brain magnetic resonance imaging (MRI) sections of 25 consecutively enrolled SIBD patients (17 with encephalopathy and 8 with coma) and 22 healthy controls underwent volumetric evaluation by an automated segmentation method. RESULTS: Ten SIBD patients had normal MRI, and 15 patients showed brain lesions or atrophy. The most prominent volume reduction was found in cerebral and cerebellar white matter, cerebral cortex, hippocampus, and amygdala, whereas deep gray matter regions and cerebellar cortex were relatively less affected. SIBD patients with normal MRI showed significantly reduced volumes in hippocampus and cerebral white matter. Caudate nuclei, putamen, and thalamus showed lower volume values in non-survivor SIBD patients, and left putamen and right thalamus showed a more pronounced volume reduction in coma patients. CONCLUSIONS: Volumetric analysis of the brain appears to be a sensitive measure of volumetric changes in SIBD. Volume reduction in specific deep gray matter regions might be an indicator of unfavorable outcome.

Widespread subcortical grey matter degeneration in primary lateral sclerosis: a multimodal imaging study with genetic profiling.

BACKGROUND: Primary lateral sclerosis (PLS) is a low incidence motor neuron disease which carries a markedly better prognosis than amyotrophic lateral sclerosis (ALS). Despite sporadic reports of extra-motor symptoms, PLS is widely regarded as a pure upper motor neuron disorder. The post mortem literature of PLS is strikingly sparse and very little is known of subcortical grey matter pathology in this condition. METHODS: A prospective imaging study was undertaken with 33 PLS patients, 117 healthy controls and 100 ALS patients to specifically assess the integrity of subcortical grey matter structures and determine whether PLS and ALS have divergent thalamic, hippocampal and basal ganglia signatures. Volumetric, morphometric, segmentation and vertex-wise analyses were carried out in the three study groups to evaluate the integrity of thalamus, hippocampus, caudate, amygdala, pallidum, putamen and accumbens nucleus in each hemisphere. The hippocampus was further parcellated to characterise the involvement of specific subfields. RESULTS: Considerable thalamic, caudate, and hippocampal atrophy was detected in PLS based on both volumetric and vertex analyses. Significant volume reductions were also detected in the accumbens nuclei. Hippocampal atrophy in PLS was dominated by dentate gyrus, hippocampal tail and CA4 subfield volume reductions. The morphometric comparison of ALS and PLS cohorts revealed preferential medial bi-thalamic pathology in PLS compared to the predominant putaminal degeneration detected in ALS. Another distinguishing feature between ALS and PLS was the preferential atrophy of the amygdala in ALS. CONCLUSIONS: PLS is associated with considerable subcortical grey matter degeneration and due to the extensive extra-motor involvement, it should no longer be regarded a pure upper motor neuron disorder. Given its unique pathological features and a clinical course which differs considerably from ALS, dedicated research studies and disease-specific therapeutic strategies are urgently required in PLS.

Regional subcortical shape analysis in premanifest Huntington's disease.

Huntington's disease (HD) involves preferential and progressive degeneration of striatum and other subcortical regions as well as regional cortical atrophy. It is caused by a CAG repeat expansion in the Huntingtin gene, and the longer the expansion the earlier the age of onset. Atrophy begins prior to manifest clinical signs and symptoms, and brain atrophy in premanifest expansion carriers can be studied. We employed a diffeomorphometric pipeline to contrast subcortical structures' morphological properties in a control group with three disease groups representing different phases of premanifest HD (far, intermediate, and near to onset) as defined by the length of the CAG expansion and the participant's age (CAG-Age-Product). A total of 1,428 magnetic resonance image scans from 694 participants from the PREDICT-HD cohort were used. We found significant region-specific atrophies in all subcortical structures studied, with the estimated abnormality onset time varying from structure to structure. Heterogeneous shape abnormalities of caudate nuclei were present in premanifest HD participants estimated furthest from onset and putaminal shape abnormalities were present in participants intermediate to onset. Thalamic, hippocampal, and amygdalar shape abnormalities were present in participants nearest to onset. We assessed whether the estimated progression of subcortical pathology in premanifest HD tracked specific pathways. This is plausible for changes in basal ganglia circuits but probably not for changes in hippocampus and amygdala. The regional shape analyses conducted in this study provide useful insights into the effects of HD pathology in subcortical structures.

Contribution of normal aging to brain atrophy in MS.

OBJECTIVE: To identify the top brain regions affected by MS-specific atrophy (i.e., atrophy in excess of normal aging) and to test whether normal aging and MS-specific atrophy increase or decrease in these regions with age. METHODS: Six hundred fifty subjects (2,790 MRI time points) were analyzed: 520 subjects with relapse-onset MS from a 5-year prospective cohort with annual standardized 1-mm 3D T1-weighted images (3DT1s; 2,483 MRIs) and 130 healthy controls with longitudinal 3DT1s (307 MRIs). Rates of change in all FreeSurfer regions (v5.3) and Structural Image Evaluation Using Normalization of Atrophy (SIENA) were estimated with mixed-effects models. All FreeSurfer regions were ranked by the MS-specific atrophy slope/standard error ratio (ßMS × time/SEßMS × time). In the top regions, age was added as an effect modifier to test whether MS-specific atrophy varied by age. RESULTS: The top-ranked regions were all gray matter structures. For SIENA, normal aging increased from 0.01%/y at age 30 years to -0.31%/y at age 60 years (-0.11% ± 0.032%/decade, p < 0.01), whereas MS-specific atrophy decreased from -0.38%/y at age 30 years to -0.12%/y at age 60 years (0.09% ± 0.035%/decade, p = 0.01). Similarly, in the thalamus, normal aging increased from -0.15%/y at age 30 years to -0.62%/y at age 60 years (-0.16% ± 0.079%/decade, p < 0.05), and MS-specific atrophy decreased from -0.59%/y at age 30 years to -0.05%/y at age 60 years (0.18% ± 0.08%/decade, p < 0.05). In the putamen and caudate, normal aging and MS-specific atrophy did not vary by age. CONCLUSIONS: For SIENA and thalamic atrophy, the contribution of normal aging increases with age, but does not change in the putamen and caudate. This may have substantial implications to understand the biology of brain atrophy in MS.

The asymmetry of neural symptoms in Wilson's disease patients detecting by diffusion tensor imaging, resting-state functional MRI, and susceptibility-weighted imaging.

Objective: To investigate the cause of the motor asymmetry in Wilson's disease (WD) patients using functional MRI. Methods: Fifty patients with WD and 20 age-matched healthy controls were enrolled. Neurological symptoms were scored using the modified Young Scale. All study subjects underwent diffusion tensor imaging (DTI), susceptibility-weighted imaging (SWI), and resting-state functional MRI (rs-fMRI) of the brain. Six regions of interest (ROI) were chosen. Fiber volumes between ROIs on DTI, corrected phase (CP) values on SWI, amplitude of low-frequency fluctuation (ALFF), and regional homogeneity (REHO) values on rs-fMRI were determined. Asymmetry index (right or left value/left or right value) was evaluated. Results: Asymmetry of rigidity, tremor, choreic movement, and gait abnormality (asymmetry index = 1.33, 1.39, 1.36, 1.40), fiber tracts between the GP and substantia nigra (SN), GP and PU, SN and thalamus (TH), SN and cerebellum, head of the caudate nucleus (CA) and SN, PU and CA, CA and TH, TH and cerebellum (asymmetry index = 1.233, 1.260, 1.269, 1.437, 1.503, 1.138, 1.145, 1.279), CP values in the TH, SN (asymmetry index = 1.327, 1.166), ALFF values, and REHO values of the TH (asymmetry index = 1.192, 1.233) were found. Positive correlation between asymmetry index of rigidity and fiber volumes between the GP and SN, SN and TH (r = .221, .133, p = .043, .036), and tremor and fiber volumes between the CA and TH (r = .045, p = .040) was found. Conclusions: The neurological symptoms of patients with WD were asymmetry. The asymmetry of fiber projections may be the main cause of motor asymmetry in patients with WD.

Cerebral Imaging Markers of GBA and LRRK2 Related Parkinson's Disease and Their First-Degree Unaffected Relatives.

Cerebral atrophy has been detected in patients with Parkinson's disease (PD) both with and without dementia, however differentiation based on genetic status has thus far not yielded robust findings. We assessed cortical thickness and subcortical volumes in a cohort of PD patients and healthy controls carriers of the G2019S mutation in the LRRK2 gene and the common GBA mutations, in an attempt to determine whether genetic status influences structural indexes. Cortical thickness and subcortical volumes were computed and compared between six groups of participants; idiopathic PD, GBA-PD, LRRK2-PD, non-manifesting non-carriers (NMNC), GBA-non-manifesting carriers (NMC) and LRRK2-NMC utilizing the FreeSurfer software program. All participants were cognitively intact based on a computerized cognitive assessment battery. Fifty-seven idiopathic PD patients, 9 LRRK2-PD, 12 GBA-PD, 49 NMNC, 41 LRRK2-NMC and 14 GBA-NMC participated in this study. Lower volumes among patients with PD compared to unaffected participants were detected in bilateral hippocampus, nucleus accumbens, caudate, thalamus, putamen and amygdala and the right pallidum (p = 0.016). PD patients demonstrated lower cortical thickness indexes in a majority of regions assessed compared with non-manifesting participants. No differences in cortical thickness and subcortical volumes were detected within each of the groups of participants based on genetic status. Mutations in the GBA and LRRK2 genes are not important determinants of cortical thickness and subcortical volumes in both patients with PD and non-manifesting participants. PD is associated with a general reduction in cortical thickness and sub-cortical atrophy even in cognitively intact patients.

Preventive effects of an intergenerational program on age-related hippocampal atrophy in older adults: The REPRINTS study.

OBJECTIVES: A growing body of literature indicates that social engagements, such as intergenerational programs, are effective strategies to improve a range of cognitive abilities. The present study examined whether the intergenerational program-REPRINTS-prevents age-related hippocampal atrophy. METHODS: After comprehensive baseline assessment, participants were allowed to decide whether to participate in the REPRINTS intervention or in the control group, which required only completion of assessments. REPRINTS participants engaged in group activities that involved reading picture books to children at kindergarten and elementary schools, once every 1 to 2 weeks. A follow-up assessment was conducted after 6 years. Two MRI scans were performed, one immediately after baseline assessment and the other after 6 years. Volumes of the hippocampus, thalamus, and caudate nucleus were derived from automated segmentation. The analysis included 17 REPRINTS and 42 control-group participants. RESULTS: There was no significant difference in any variable of participants' characteristics at baseline between the REPRINTS and control groups. Hippocampal volume significantly declined in the control group but was maintained in the REPRINTS group. No significant differences between groups in thalamus or caudate nucleus volume were observed. Although cognitive function was unaffected by the program, greater decreases in hippocampal volume were significantly correlated with greater decreases in cognitive performance scores. CONCLUSIONS: Our results suggest that the REPRINTS intergenerational program has protective effects on age-related hippocampal atrophy in older adults. These changes precede improvements in cognitive performance, suggesting the validity of the concept of brain plasticity in later life following social engagement.

Prenatal methamphetamine exposure is associated with reduced subcortical volumes in neonates.

OBJECTIVES: Prenatal exposure to methamphetamine is associated with a range of neuropsychological, behavioural and cognitive deficits. A small number of imaging studies suggests that these may be mediated by neurostructural changes, including reduced volumes of specific brain regions. This study investigated potential volumetric changes in the brains of neonates with prenatal methamphetamine exposure. To our knowledge no previous studies have examined methamphetamine effects on regional brain volumes at this age. STUDY DESIGN: Mothers were recruited antenatally and interviewed regarding methamphetamine use during pregnancy. Mothers in the exposure group reported using methamphetamine≥twice/month during pregnancy; control infants had no exposure to methamphetamine or other drugs and minimal exposure to alcohol. MRI scans were performed in the first postnatal month, following which anatomical images were processed using FreeSurfer. Subcortical and cerebellar regions were manually segmented and their volumes determined using FreeView. Pearson correlations were used to analyse potential associations between methamphetamine exposure and regional volumes. The associations between methamphetamine exposure and regional volumes were then examined adjusting for potential confounding variables. RESULTS: Methamphetamine exposure was associated with reduced left and right caudate and thalamus volumes. The association in the right caudate remained significant following adjustment for potential confounding variables. CONCLUSIONS: Our findings showing reduced caudate and thalamus volumes in neonates with prenatal methamphetamine exposure are consistent with previous findings in older exposed children, and demonstrate that these changes are already detectable in neonates. Continuing research is warranted to examine whether reduced subcortical volumes are predictive of cognitive, behavioural and affective impairment in older children.

T2 relaxation time measurements in the brains of scalded rats.

This study aimed to evaluate the T2 relaxation time of the brain in severely scalded rats using a magnetic resonance (MR) T2 mapping sequence, and to investigate the correlation between T2 relaxation time and plasma glucose level. Twenty-eight Wistar rats were randomly divided into the scalded group (n=21) and control group (n=7). Magnetic resonance scans were performed with T1WI, T2WI, and T2-mapping sequences in the scalded group; the scans were performed 1 day prior to scalding and 1, 3, 5, and 7 days post-scalding; in addition, identical MR scans were performed in the control group at the same time points. T2-maps were generated and T2 relaxation times were acquired from the following brain regions: the hippocampus, thalamus, caudate-putamen, and cerebrum. Pathological changes of the hippocampus were observed. The plasma glucose level of each rat was measured before each MR scan, and a correlation analysis was performed between T2 relaxation time and plasma glucose level. We found that conventional T1WI and T2WI did not reveal any abnormal signals or morphological changes in the hippocampus, thalamus, caudate-putamen, or cerebrum post-scalding. Both the T2 relaxation times of the selected brain regions and plasma glucose levels increased 1, 3, and 5 days post-scalding, and returned to normal levels 7 days post-scalding. The most marked increase of T2 relaxation time was found in the hippocampus; similar changes were also revealed in the thalamus, caudate-putamen, and cerebrum. No correlation was found between T2 relaxation time and plasma glucose level in scalded rats. Pathological observation of the hippocampus showed edema 1, 3, and 5 days post-scalding, with recovery to normal findings at 7 days post-scalding. Thus, we concluded that T2 mapping is a sensitive method for detecting and monitoring scald injury in the rat brain. As the hippocampus is the main region for modulating a stress reaction, it showed significantly increased water content along with an increased plasma glucose level post-scalding.

Decreased subcortical volumes in alcohol dependent individuals: effect of polysubstance use disorder.

Chronic alcohol use has widespread effects on brain morphometry. Alcohol dependent individuals are often diagnosed with comorbid substance use disorders. Alterations in brain morphometry may be different in individuals that are dependent on alcohol alone and individuals dependent on alcohol and other substances. We examined subcortical brain volumes in 37 individuals with alcohol dependence only (ADO), 37 individuals with polysubstance use disorder (PS) and 37 healthy control participants (HC). Participants underwent a structural MR scan and a model-based segmentation tool was used to measure the volume of 14 subcortical regions (bilateral thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala and nucleus accumbens). Compared to HC, ADO had smaller volume in the bilateral hippocampus, right nucleus accumbens and right thalamus. PS only had volume reductions in the bilateral thalamus compared to HC. PS had a larger right caudate compared to ADO. Subcortical volume was negatively associated with drinking measures only in the ADO group. This study confirms the association between alcohol dependence and reductions in subcortical brain volume. It also suggests that polysubstance use interacts with alcohol use to produce limited subcortical volume reduction and at least one region of subcortical volume increase. These findings indicate that additional substance use may mask damage through inflammation or may function in a protective manner, shielding subcortical regions from alcohol-induced damage.

Age-related differences in the structural complexity of subcortical and ventricular structures.

It has been well established that the volume of several subcortical structures decreases in relation to age. Different metrics of cortical structure (e.g., volume, thickness, surface area, and gyrification) have been shown to index distinct characteristics of interindividual differences; thus, it is important to consider the relation of age to multiple structural measures. Here, we compare age-related differences in subcortical and ventricular volume to those differences revealed with a measure of structural complexity, quantified as fractal dimensionality. Across 3 large data sets, totaling nearly 900 individuals across the adult lifespan (aged 18-94 years), we found greater age-related differences in complexity than volume for the subcortical structures, particularly in the caudate and thalamus. The structural complexity of ventricular structures was not more strongly related to age than volume. These results demonstrate that considering shape-related characteristics improves sensitivity to detect age-related differences in subcortical structures.

Neuroimaging abnormalities in clade C HIV are independent of Tat genetic diversity.

Controversy remains regarding the neurotoxicity of clade C human immunodeficiency virus (HIV-C). When examined in preclinical studies, a cysteine to serine substitution in the C31 dicysteine motif of the HIV-C Tat protein (C31S) results in less severe brain injury compared to other viral clades. By contrast, patient cohort studies identify significant neuropsychological impairment among HIV-C individuals independent of Tat variability. The present study clarified this discrepancy by examining neuroimaging markers of brain integrity among HIV-C individuals with and without the Tat substitution. Thirty-seven HIV-C individuals with the Tat C31S substitution, 109 HIV-C individuals without the Tat substitution (C31C), and 34 HIV- controls underwent 3T structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Volumes were determined for the caudate, putamen, thalamus, corpus callosum, total gray matter, and total white matter. DTI metrics included fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). Tracts of interest included the anterior thalamic radiation (ATR), cingulum bundle (CING), uncinate fasciculus (UNC), and corpus callosum (CC). HIV+ individuals exhibited smaller volumes in subcortical gray matter, total gray matter and total white matter compared to HIV- controls. HIV+ individuals also exhibited DTI abnormalities across multiple tracts compared to HIV- controls. By contrast, neither volumetric nor diffusion indices differed significantly between the Tat C31S and C31C groups. Tat C31S status is not a sufficient biomarker of HIV-related brain integrity in patient populations. Clinical attention directed at brain health is warranted for all HIV+ individuals, independent of Tat C31S or clade C status.

Nigella sativa Oil Reduces Extrapyramidal Symptoms (EPS)-Like Behavior in Haloperidol-Treated Rats.

The symptoms of Parkinsonism and oral dyskinesia have been showing to be induced by neuroleptics that significantly affect its clinical use. In this study, we investigate whether Nigella sativa-oil (NS) (black cumin seeds)-a traditional medicine used for the seizure treatment in eastern country-may reduce the haloperidol (HAL)-induced extrapyramidal symptoms (EPS)-like behavior in rats. After combine treatment with HAL (1 mg/kg) on NS (0.2 ml/rat), rats displayed a significant decreased EPS-like behavior including movement disorders and oral dyskinesia as compared to controls. Immunohistochemical analysis indicates that NS reduced astrogliosis in caudate and accumbens nuclei. These results suggest that NS may consider as an adjunct to antipsychotics to reduce the EPS-like side effect.