Total Brain Gray Matter Volume Research Articles

Increased plasma lipocalin‐2 levels are associated with nonmotor symptoms and neuroimaging features in patients with Parkinson's disease

AbstractLipocalin‐2 (LCN2) is essential for the regulation of neuroinflammation and cellular uptake of iron. This study aimed to evaluate plasma LCN2 levels and explore their correlation with clinical and neuroimaging features in Parkinson's disease (PD) patients. Enzyme‐linked immunosorbent assay (ELISA) was used to measure plasma LCN2 levels in 120 subjects. Evaluation of motor symptoms and nonmotor symptoms in PD patients was assessed by the associated scales. Voxel‐based morphometry (VBM) was used to evaluate brain volume alterations, and quantitative susceptibility mapping (QSM) was used to quantitatively analyze brain iron deposition in 46 PD patients. Plasma LCN2 levels were significantly higher in PD patients than those in healthy controls. LCN2 levels were negatively correlated with Montreal Cognitive Assessment (MoCA) scores, total brain gray matter volume (GMV), and GMV/total intracranial volume (TIV) ratio, but positively correlated with Hamilton Anxiety Rating Scale (HAMD) scores and mean QSM values of the bilateral substantial nigra (SN). Receiver operating characteristic (ROC) curves confirmed that plasma LCN2 levels had good predictive accuracy for PD. The results suggest that plasma LCN2 levels have potential as a biomarker for the diagnosis of PD. LCN2 may be a therapeutic target for neuroinflammation and brain iron deposition.

Hyposmia and Neuroimaging Signature in Community-Dwelling Older Adults

Olfaction declines with aging, and hyposmia, or impaired sense of smell, is associated with neurodegenerative disorders including Alzheimer’s Disease (AD) and Parkinson’s Disease (PD). Neuroimaging studies of hyposmia in AD/PD patients have often examined pathology-specific brain regions. Our knowledge of neural correlates in regions that mediate olfaction in community-dwelling older adults, is limited. We quantified mean diffusivity (MD) of the gray matter (GM) using diffusion tensor imaging in a community-dwelling sample of 308 older adults (mean age: 82.9 years, 58% women, 40% black). We focused on total brain and these regions involved in olfaction- olfactory bulb, amygdala, entorhinal cortex, orbitofrontal cortex, and hippocampus. Smell was tested with a scratch-and-sniff validated odor identification test, the Brief Smell Identification Test (BSIT). Hyposmia was defined as BSIT score of ≤8, assessed about 7 years prior to neuroimaging. In our sample, 23% had hyposmia, more in in men (30%) than in women (19%). Hyposmia was not significantly associated with cardiovascular risk factors such as hypertension; diseases such as stroke; age; race; cognitive or mobility functions (all p>0.1). In linear regression models adjusted for demographics and brain atrophy (total brain gray matter volume divided by intracranial volume), hyposmia was significantly associated with higher GM MD (lower microstructural integrity) of the left orbitofrontal cortex (standardized beta: 0.142, t=2.56, p=0.011). Understanding the neural substrates involved in hyposmia in aging is an important step towards advancing research on hyposmia in non-clinic-based, community-dwelling populations.

Visual hallucinations and illusions in Parkinson's disease: the role of ocular pathology.

Whether different mechanisms, particularly ocular pathology, could lead to the emergence of visual hallucinations (VH) (defined as false perceptions with no external stimulus) versus visual illusions (VI) (defined as a misperception of a real stimulus) in Parkinson's disease (PD) remains debated. We assessed retinal, clinical and structural brain characteristics depending on the presence of VH or VI in PD. In this case-control study, we compared retinal thickness using optical coherence tomography (OCT), between PD patients with: VI (PD-I; n = 26), VH (PD-H; n = 28), and without VI or VH (PD-C; n = 28), and assessed demographic data, disease severity, treatment, anatomical and functional visual complaints, cognitive and visuo-perceptive functions and MRI brain volumetry for each group of PD patients. Parafoveal retina was thinner in PD-H compared to PD-C (p = 0.005) and PD-I (p = 0.009) but did not differ between PD-I and PD-C (p = 0.85). Multivariate analysis showed that 1/retinal parafoveal thinning and total brain gray matter atrophy were independently associated with the presence of VH compared to PD-I; 2/retinal parafoveal thickness, PD duration, sleep quality impairment and total brain gray matter volume were independent factors associated with the presence of VH compared to PD-C; 3/anterior ocular abnormalities were the only factor independently associated with the presence of illusions compared to PD-C. These findings reinforce the hypothesis that there may be different mechanisms contributing to VH and VI in PD, suggesting that these two entities may also have a different prognosis rather than simply lying along a continuous spectrum. Clinicaltrials.gov number NCT01114321.

The upper cervical spinal cord in ALS assessed by cross-sectional and longitudinal 3T MRI

The upper cervical spinal cord is measured in a large longitudinal amyotrophic lateral sclerosis (ALS) cohort to evaluate its role as a biomarker. Specifically, the cervical spinal cord´s cross-sectional area (CSA) in plane of the segments C1–C3 was measured semi-automatically with T1-weighted 3T MRI sequences in 158 ALS patients and 86 controls. Six-month longitudinal follow-up MRI scans were analyzed in 103 patients. Compared to controls, in ALS there was a significant mean spinal cord atrophy (63.8 mm² vs. 60.8 mm², p = 0.001) which showed a trend towards worsening over time (mean spinal cord CSA decrease from 61.4 mm² to 60.6 mm² after 6 months, p = 0.06). Findings were most pronounced in the caudal segments of the upper cervical spinal cord and in limb-onset ALS. Baseline CSA was related to the revised ALS functional rating scale, disease duration, precentral gyrus thickness and total brain gray matter volume. In conclusion, spinal cord atrophy as assessed in brain MRIs in ALS patients mirrors the extent of overall neurodegeneration and parallels disease severity.

Physical activity and hippocampal volume in middle-aged patients with type 1 diabetes.

To examine the cross-sectional association between physical activity (PA) and hippocampal volume in middle-aged adults with childhood-onset type 1 diabetes (T1D), and whether hyperglycemia and insulin sensitivity contribute to this relationship. We analyzed neuroimaging and self-reported PA data from 79 adults with T1D from the Pittsburgh Epidemiology of Diabetes Complications Study (mean age 50 years, mean duration 41 years) and 122 similarly aged adults without T1D (mean age 48 years). Linear regression models, controlling for intracranial volume, sex, education, and age, tested associations between PA and gray matter volumes of hippocampi and total brain in the 2 groups. For the T1D group, models further controlled for hyperglycemia and glucose disposal rate, a measure of insulin sensitivity. PA was significantly lower in the T1D than in the non-T1D group (median [interquartile range] 952 kcal [420-2,044] vs 1,614 kcal [588-3,091], respectively). Higher PA was significantly associated with larger hippocampi for T1D, but not for non-T1D (standardized β [p values] from regression models adjusted for intracranial volume, sex, age, and education: 0.270 [p < 0.001] and 0.098 [p = 0.12], respectively). Neither hyperglycemia nor glucose disposal rate substantially modified this association. Relationships between PA and total brain gray matter volume were similar. A cross-sectional association between higher PA and larger hippocampi is already detectable by middle age for these patients with T1D, and it appears robust to chronic hyperglycemia and insulin sensitivity. Proof-of-concept studies should investigate whether increasing PA preserves hippocampal volume and the mechanisms underlying the effects of PA on hippocampal volume.

Voxel-Based Morphometry and fMRI Revealed Differences in Brain Gray Matter in Breastfed and Milk Formula-Fed Children.

Infant diets may have significant impact on brain development in children. The aim of this study was to evaluate brain gray matter structure and function in 8-year-old children who were predominantly breastfed or fed cow's milk formula as infants. Forty-two healthy children (breastfed: n = 22, 10 boys and 12 girls; cow's milk formula: n = 20, 10 boys and 10 girls) were studied by using structural MR imaging (3D T1-weighted imaging) and blood oxygen level-dependent fMRI (while performing tasks involving visual perception and language functions). They were also administered standardized tests evaluating intelligence (Reynolds Intellectual Assessment Scales) and language skills (Clinical Evaluation of Language Fundamentals). Total brain gray matter volume did not differ between the breastfed and cow's milk formula groups. However, breastfed children had significantly higher (P < .05, corrected) regional gray matter volume measured by voxel-based morphometry in the left inferior temporal lobe and left superior parietal lobe compared with cow's milk formula-fed children. Breastfed children showed significantly more brain activation in the right frontal and left/right temporal lobes on fMRI when processing the perception task and in the left temporal/occipital lobe when processing the visual language task than cow's milk formula-fed children. The imaging findings were associated with significantly better performance for breastfed than cow's milk formula-fed children on both tasks. Our findings indicated greater regional gray matter development and better regional gray matter function in breastfed than cow's milk formula-fed children at 8 years of age and suggested that infant diets may have long-term influences on brain development in children.

Regional gray matter volume is associated with rejection sensitivity: A voxel-based morphometry study

Rejection sensitivity (RS) can be defined as the disposition that one tends to anxiously expect, readily perceive, and intensely react to rejection. High-RS individuals are more likely to suffer mental disorders. Previous studies have investigated brain activity during social rejection using different kinds of rejection paradigms and have provided neural evidence of individual differences in response to rejection cues, but the association between individual differences in RS and brain structure has never been investigated. In this study, voxel-based morphometry (VBM) was used to investigate the relationship between gray matter volume (GMV) and RS in a large healthy sample of 150 men and 188 women. The participants completed the RS Questionnaire and underwent an anatomical magnetic resonance imaging scan. Multiple regression was used to analyze the correlation between regional GMV and RS scores, adjusting for age, sex, and total brain GMV. These results showed that GMV in the region of the posterior cingulate cortex/precuneus was negatively associated with RS, and GMV in the region of the inferior temporal gyrus was positively correlated with RS. These findings suggest a relationship between individual differences in RS and GMV in brain regions that are primarily related to social cognition.

A Longitudinal Study of the Effects of Lithium Treatment on Prefrontal and Subgenual Prefrontal Gray Matter Volume in Treatment-Responsive Bipolar Disorder Patients

Article AbstractObjective: Recent molecular, preclinical, and preliminary clinical studies suggest that the therapeutic effects of mood stabilizers may be mediated by modulating expression of potent neurotrophic and neuroprotective factors having the potential to reverse impairments of cellular resilience, reductions in brain volume, and cell death or atrophy. Our main goal was to investigate the potential clinical significance of these findings in relation to bipolar disorder. Method: The longitudinal effect of lithium on brain gray matter volume was investigated in well-characterized (DSM-IV criteria) bipolar depressed subjects (N = 28) at baseline (medication-free) and after lithium administration (4 weeks). Total brain gray matter, prefrontal gray matter, and left subgenual prefrontal gray matter volumes were determined using validated semiautomated segmentation and region of interest methodology. The study was conducted from November 1997 until April 2004 at Wayne State University School of Medicine, Detroit, Mich.Results: Significant increases in total brain gray matter volume in bipolar subjects were observed after 4 weeks of lithium administration (p = .0043). Moreover, regional analyses in the bipolar subjects revealed significant differences between responders (>50% decrease in Hamilton Depression Rating Scale total score) and nonresponders; only responders showed a significant increase in gray matter volume in the prefrontal cortex (p = .003) and an increase at trend level in the left subgenual prefrontal cortex volume (p = .0786). Conclusion: The increase in gray matter volume in these areas, which various neuroimaging and postmortem neuropathology studies have implicated in the neuropathophysiology of bipolar disorder, suggests that the observed effects may be linked to clinical response. The findings also support the notion that future treatments that more directly target molecules in critical central nervous system pathways that regulate cellular plasticity hold promise as novel, improved, long-term treatments for mood disorders as well as some neurodegenerative conditions, such as Alzheimer's disease.

A Longitudinal Study of the Effects of Lithium Treatment on Prefrontal and Subgenual Prefrontal Gray Matter Volume in Treatment-Responsive Bipolar Disorder Patients

Recent molecular, preclinical, and preliminary clinical studies suggest that the therapeutic effects of mood stabilizers may be mediated by modulating expression of potent neurotrophic and neuroprotective factors having the potential to reverse impairments of cellular resilience, reductions in brain volume, and cell death or atrophy. Our main goal was to investigate the potential clinical significance of these findings in relation to bipolar disorder. The longitudinal effect of lithium on brain gray matter volume was investigated in well-characterized (DSM-IV criteria) bipolar depressed subjects (N = 28) at baseline (medication-free) and after lithium administration (4 weeks). Total brain gray matter, prefrontal gray matter, and left subgenual prefrontal gray matter volumes were determined using validated semiautomated segmentation and region of interest methodology. The study was conducted from November 1997 until April 2004 at Wayne State University School of Medicine, Detroit, Mich. Significant increases in total brain gray matter volume in bipolar subjects were observed after 4 weeks of lithium administration (p = .0043). Moreover, regional analyses in the bipolar subjects revealed significant differences between responders (>50% decrease in Hamilton Depression Rating Scale total score) and nonresponders; only responders showed a significant increase in gray matter volume in the prefrontal cortex (p = .003) and an increase at trend level in the left subgenual prefrontal cortex volume (p = .0786). The increase in gray matter volume in these areas, which various neuroimaging and postmortem neuropathology studies have implicated in the neuropathophysiology of bipolar disorder, suggests that the observed effects may be linked to clinical response. The findings also support the notion that future treatments that more directly target molecules in critical central nervous system pathways that regulate cellular plasticity hold promise as novel, improved, long-term treatments for mood disorders as well as some neurodegenerative conditions, such as Alzheimer's disease. clinicaltrials.gov Identifier: NCT00870311.

Teaching Neuro Image : MRI of diabetic lumbar plexopathy treated with local steroid injection

<h3>Objective:</h3> To examine the cross-sectional association between physical activity (PA) and hippocampal volume in middle-aged adults with childhood-onset type 1 diabetes (T1D), and whether hyperglycemia and insulin sensitivity contribute to this relationship. <h3>Methods:</h3> We analyzed neuroimaging and self-reported PA data from 79 adults with T1D from the Pittsburgh Epidemiology of Diabetes Complications Study (mean age 50 years, mean duration 41 years) and 122 similarly aged adults without T1D (mean age 48 years). Linear regression models, controlling for intracranial volume, sex, education, and age, tested associations between PA and gray matter volumes of hippocampi and total brain in the 2 groups. For the T1D group, models further controlled for hyperglycemia and glucose disposal rate, a measure of insulin sensitivity. <h3>Results:</h3> PA was significantly lower in the T1D than in the non-T1D group (median [interquartile range] 952 kcal [420–2,044] vs 1,614 kcal [588–3,091], respectively). Higher PA was significantly associated with larger hippocampi for T1D, but not for non-T1D (standardized β [<i>p</i> values] from regression models adjusted for intracranial volume, sex, age, and education: 0.270 [<i>p</i> &lt; 0.001] and 0.098 [<i>p</i> = 0.12], respectively). Neither hyperglycemia nor glucose disposal rate substantially modified this association. Relationships between PA and total brain gray matter volume were similar. <h3>Conclusions:</h3> A cross-sectional association between higher PA and larger hippocampi is already detectable by middle age for these patients with T1D, and it appears robust to chronic hyperglycemia and insulin sensitivity. Proof-of-concept studies should investigate whether increasing PA preserves hippocampal volume and the mechanisms underlying the effects of PA on hippocampal volume.

Brain structure and symptom dimension relationships in obsessive–compulsive disorder: A voxel-based morphometry study

Background Obsessive–compulsive disorder (OCD) is a clinically heterogenous disorder characterized by temporally stable symptom dimensions. Past inconsistent results from structural neuroimaging studies of OCD may have resulted from the effects of these specific symptom dimensions as well as other socio-demographic and clinical variables upon gray matter (GM) volume. Methods GM volume was measured in 25 adult OCD patients and 20 adult healthy controls using voxel-based morphometry (VBM), controlling for age and total brain GM volume. Univariate and multivariate regression analyses were carried out between regions of GM difference and age, age of onset, medication load, OCD severity, depression severity, and separate symptom dimension scores. Results Significant GM volumetric differences in OCD patients relative to controls were found in dorsal cortical regions, including bilateral BA6, BA46, BA9 and right BA8 (controls > patients), and bilateral midbrain (patients > controls). Stepwise regression analyses revealed highly significant relationships between greater total OCD symptom severity and smaller GM volumes in dorsal cortical regions and larger GM volumes in bilateral midbrain. Greater age was independently associated with smaller GM volumes in right BA6, left BA9, left BA46 and larger GM volumes in right midbrain. Greater washing symptom severity was independently associated with smaller GM volume in right BA6, while there was a trend association between greater hoarding symptom severity and lower GM volume in left BA6. Limitations The sample was relatively small to examine the relationship between symptom scores and GM volumes. Multiple patients were taking medication and had comorbid disorders. Conclusions These analyses suggest dorsal prefrontal cortical and bilateral midbrain GM abnormalities in OCD that appear to be primarily driven by the effects of total OCD symptom severity. The results regarding the relationship between GM volumes and symptom dimension scores require examination in larger samples.

Gray matter prefrontal changes in type 2 diabetes detected using MRI

To examine the volumes of the gray and white matter both globally and regionally in patients diagnosed with type 2 diabetes and controls. Our samples were comprised of 26 patients with type 2 diabetes, 26 patients with diabetes and major depressive disorder, and 25 nondiabetic, nondepressed control subjects. All subjects were studied cross-sectionally on a 1.5 T scanner and were recruited from medicine/diabetes clinics. Both gray and white matter volumes were estimated using an automated method, and the prefrontal areas studied included the anterior cingulate, the gyrus rectus, and the orbitofrontal regions. Patients with diabetes, both with and without depression, had smaller total brain gray matter volumes when compared with the control subjects after controlling for age, intracranial volume, and years of education. This group also had smaller gray matter volumes in the anterior cingulate and orbitofrontal regions when compared with the controls after additionally controlling for total gray matter volume. The depressed and nondepressed diabetic groups did not differ on any neuroimaging measure. Cerebrovascular risk factors correlated negatively with gray matter volumes. The findings indicate that type 2 diabetes is associated with specific neuroanatomical abnormalities in the prefrontal gray matter. Vascular disease might contribute to the findings observed in our sample. These observations have implications for the behavioral sequelae of diabetes.