Temporal Lobe Volume Research Articles

IC‐P‐044: Automated and robust algorithm to measure changes in medial temporal lobe volume in early Alzheimer's disease

IC‐P‐044: Automated and robust algorithm to measure changes in medial temporal lobe volume in early Alzheimer's disease

P2‐242: An automated and robust algorithm to measure changes in medial temporal lobe volume in early Alzheimer's disease

P2‐242: An automated and robust algorithm to measure changes in medial temporal lobe volume in early Alzheimer's disease

Seizure outcome 1 year after temporal lobe epilepsy: an analysis of MR volumetric and clinical parameters

The aim of this work was to determine predictors that may contribute to surgical success or failure. Relevant pre- and postoperative baseline data were analyzed, and temporal structures underwent a volumetric analysis. A total of 207 patients (107 female) underwent complete evaluation for epilepsy surgery. Prospectively collected data used for this analysis included the clinical and demographic data. Classic prognostic factors (e.g., gender, age at operation, age at epilepsy manifestation, duration of epilepsy, education, side of pathology, intracranial EEG recordings, secondarily generalized tonic-clonic seizures, etiological factors, histology) and a volumetric analysis of 12 temporal lobe subregions were used in a regression analysis to identify possible prognostic factors in surgery for TLE. Primary outcome measure was seizure freedom at 1year and during the full first year expressed as class I in the ILAE outcome scale. In the univariate analysis, we identified one negative predictor for a less favorable seizure outcome: intracranial EEG recordings (p = 0.010), hippocampal sclerosis as histological finding trended toward statistical significance (p = 0.054). No statistical outcome significance was found for preoperative temporal lobe compartment volume loss or postoperative lateral atrophy after mesial resection. Necessity for intracranial EEG recording is an independent factor of not optimal seizure control in the 1-year follow-up. Preoperative temporal lobe volume differences including smaller mesial subcompartments did not correlate with poorer seizure outcome.

Medial Temporal Lobe Volumes in Amnestic Mild Cognitive Impairment and Late-life Depression: Research Synthesis

There are important similarities and differences between the clinical presentation and prognosis of amnestic mild cognitive impairment (aMCI) and late-life depression (LLD). However, very little is known about the shared and distinct pathophysiological mechanisms between both conditions, even thought their frequent co-occurrence suggests a close association. In this research synthesis, we examined the extent of hippocampus (HC) and entorhinal cortex (ERC) atrophy as reported in 17 aMCI and 9 LLD studies. Total HC volume reduction was significant in almost 100% of aMCI and 50% of LLD studies when populations were compared to normal controls. Volume deficit for total and lateralized HC in LLD studies seemed fairly similar in terms of percentage to aMCI studies. Total ERC volume reduction was significant and larger than HC in all aMCI studies compared to normal controls. No LLD studies measured ERC volume. In general, exclusion criteria and demographic characteristics were fairly similar for most studies. However, imaging characteristics and segmentation protocols varied largely, which could impact the comparison of volume reductions in different studies. Future work investigating simultaneously both aMCI and LLD and using standardized imaging and segmentation protocol would be required to allow a better understanding of the association between aMCI and LLD. Keywords: Mild cognitive impairment, Depression, Alzheimer’s disease, Hippocampus; Entorhinal cortex, Magnetic resonance imaging, Late-life Depression, Neurobiology, cognition, Impairment, psychiatric

Magnetic resonance imaging volumetry and clinical analysis of epilepsy patients with unilateral hippocampal abnormality

In order to clarify the correlation between morphological characteristics and clinical features in epilepsy patients with unilateral hippocampal abnormality, morphological and morphometric magnetic resonance imaging studies were performed. We selected a series of childhood-onset epilepsy patients with unilateral hippocampal abnormality. The volume of hippocampal formation and anterior temporal lobe were measured, and the hippocampal morphology was compared with their clinical features. The morphological characteristics of the hippocampal formation were classified into three groups: group I, diffuse and severe volume reduction of the hippocampal formation and anterior temporal lobe with abnormal signal; group II, focal atrophy or focal abnormal signal in the hippocampal formation; and group III, no significant volume reduction but an enlargement of the temporal horn. All of the patients in group I had a history of status epilepticus in infancy. Temporal lobe epilepsy (TLE) was found in three of four patients. Group II contained TLE in three and frontal lobe epilepsy in one. One patient with intractable TLE had a history of status epilepticus in infancy. Group III contained miscellaneous epilepsies, including benign partial epilepsy with centro-temporal spikes in three of seven patients. Five patients in group III showed some characteristic features of hippocampal malrotation, which refers to incomplete hippocampal infolding. Diffuse and severe volume reduction of the hippocampal formation and anterior temporal lobe with unilateral hippocampal sclerosis was strongly associated with status epilepticus in infancy. Both hippocampal sclerosis and hippocampal malrotation suggest significant roles in the pathogenesis of epilepsy.

Voxel‐based morphometry in patients with obsessive‐compulsive behaviors in behavioral variant frontotemporal dementia

Obsessions and compulsive (OC) behaviors are a frequent feature of behavioral variant frontotemporal dementia (bvFTD), but their structural correlates have not been definitively established. Patients with bvFTD presenting to the Mayo Clinic Alzheimer's Disease Research Center were recruited. Each patient's caregiver was given the Yale-Brown Obsessive-Compulsive scale (YBOCS) to document the type and presence of OC behaviors and to rate their severity. All subjects underwent standardized magnetic resonance imaging (MRI) that was evaluated using voxel-based morphometry (VBM). Seventeen patients with bvFTD were recruited, and 11 were included in the study and compared with 11 age- and gender-matched controls. Six were excluded for lack of MRI at the time of survey or a pre-existing neurodegenerative condition. Nine of the 11 reported OC behaviors, with the most frequent compulsions being checking, hoarding, ordering/arranging, repeating rituals, and cleaning. In the VBM analysis, total YBOCS score correlated with gray matter loss in the bilateral globus pallidus, left putamen, and in the lateral temporal lobe, particularly the left middle and inferior temporal gyri (P < 0.001 uncorrected for multiple comparisons). Obsessive-compulsive behaviors were frequent among these patients. The correlation with basal ganglia atrophy may point to involvement of frontal subcortical neuronal networks. Left lateral temporal lobe volume loss probably reflects the number of MAPT mutation patients included but also provides additional data implicating temporal lobe involvement in OC behaviors.

Anatomical and functional correlates of human hippocampal volume asymmetry

Hemispheric asymmetry of the human hippocampus is well established, but poorly understood. We studied 110 healthy subjects with 3-Tesla MRI to explore the anatomical and functional correlates of the R>L volume asymmetry. We found that the asymmetry is limited to the anterior hippocampus (hemisphere×region interaction: F(1,109)=42.6, p<.001). Anterior hippocampal volume was correlated strongly with the volumes of all four cortical lobes. In contrast, posterior hippocampal volume was correlated strongly only with occipital lobe volume, moderately with the parietal and temporal lobe volumes and not with the frontal lobe volume. The degree of R>L anterior hippocampal volume asymmetry predicted performance on a measure of basic cognitive abilities. This provides evidence for regional specificity and functional implications of the well-known hemispheric asymmetry of hippocampal volume. We suggest that the developmental profile, genetic mechanisms and functional implications of R>L anterior hippocampal volume asymmetry in the human brain deserve further study.

Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression.

We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2. We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8 ± 2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain.

Brain volumetric and microstructural correlates of executive and motor performance in aged rhesus monkeys

The aged rhesus macaque exhibits brain atrophy and behavioral deficits similar to normal aging in humans. Here we studied the association between cognitive and motor performance and anatomic and microstructural brain integrity measured with 3T magnetic resonance imaging in aged monkeys. About half of these animals were maintained on moderate calorie restriction (CR), the only intervention shown to delay the aging process in lower animals. T1-weighted anatomic and diffusion tensor images were used to obtain gray matter (GM) volume and fractional anisotropy (FA) and mean diffusivity (MD), respectively. We tested the extent to which brain health indexed by GM volume, FA, and MD were related to executive and motor function, and determined the effect of the dietary intervention on this relationship. We hypothesized that fewer errors on the executive function test and faster motor response times would be correlated with higher volume, higher FA, and lower MD in frontal areas that mediate executive function, and in motor, premotor, subcortical, and cerebellar areas underlying goal-directed motor behaviors. Higher error percentage on a cognitive conceptual shift task was significantly associated with lower GM volume in frontal and parietal cortices, and lower FA in major association fiber bundles. Similarly, slower performance time on the motor task was significantly correlated with lower volumetric measures in cortical, subcortical, and cerebellar areas and decreased FA in several major association fiber bundles. Notably, performance during the acquisition phase of the hardest level of the motor task was significantly associated with anterior mesial temporal lobe volume. Finally, these brain-behavior correlations for the motor task were attenuated in CR animals compared to controls, indicating a potential protective effect of the dietary intervention.

CSF Biomarker and PIB-PET-Derived Beta-Amyloid Signature Predicts Metabolic, Gray Matter, and Cognitive Changes in Nondemented Subjects

Beta-amyloid (Aβ) is a histopathological hallmark of Alzheimer's disease dementia, but high levels of Aβ in the brain can also be found in a substantial proportion of nondemented subjects. Here we investigated which 2-year rate of brain and cognitive changes are present in nondemented subjects with high and low Aβ levels, as assessed with cerebrospinal fluid and molecular positron emission tomography (PET)-based biomarkers of Aβ. In subjects with mild cognitive impairment, increased brain Aβ levels were associated with significantly faster cognitive decline, progression of gray matter atrophy within temporal and parietal brain regions, and a trend for a faster decline in parietal Fludeoxyglucose (FDG)-PET metabolism. Changes in gray matter and FDG-PET mediated the association between Aβ and cognitive decline. In contrast, elderly cognitively healthy controls (HC) with high Aβ levels showed only a faster medial temporal lobe and precuneus volume decline compared with HC with low Aβ. In conclusion, the current results suggest not only that both functional and volumetric brain changes are associated with high Aβ years before the onset of dementia but also that HC with substantial Aβ levels show higher Aβ pathology resistance, lack other pathologies that condition neurotoxic effects of Aβ, or accumulated Aβ for a shorter time period.

C-reactive protein is related to memory and medial temporal brain volume in older adults

Recent research suggests a central role for inflammatory mechanisms in cognitive decline that may occur prior to evidence of neurodegeneration. Limited information exists, however, regarding the relationship between low-grade inflammation and cognitive function in healthy older adults. This study examined the relation between inflammation, verbal memory consolidation, and medial temporal lobe volumes in a cohort of older community-dwelling subjects. Subjects included 141 functionally intact, community-dwelling older adults with detectable (n=76) and undetectable (n=65) levels of C-reactive protein. A verbal episodic memory measure was administered to all subjects, and measures of delayed recall and recognition memory were assessed. A semiautomated parcellation program was used to analyze structural MRI scans. On the episodic memory task, analysis of covariance revealed a significant CRP group by memory recall interaction, such that participants with detectable levels of CRP evidenced worse performance after a delay compared to those with undetectable levels of CRP. Individuals with detectable CRP also demonstrated lower performance on a measure of recognition memory. Imaging data demonstrated smaller left medial temporal lobe volumes in the detectable CRP group as compared with the undetectable CRP group. These findings underscore a potential role for inflammation in cognitive aging as a modifiable risk factor.

CSF biomarker and PIB-PET–derived beta-amyloid signature predicts metabolic, grey matter and cognitive changes in nondemented subjects

Beta-amyloid (Ab) is a histopathological hallmark of Alzheimer’s disease dementia, but high levels of Ab in the brain can also be found in a substantial proportion of nondemented subjects. Here we investigated which 2-year rate of brain and cognitive changes are present in nondemented subjects with high and low Ab levels, as assessed with cerebrospinal fluid and molecular positron emission tomography (PET)--based biomarkers of Ab. In subjects with mild cognitive impairment, increased brain Ab levels were associated with significantly faster cognitive decline, progression of gray matter atrophy within temporal and parietal brain regions, and a trend for a faster decline in parietal Fludeoxyglucose (FDG)PET metabolism. Changes in gray matter and FDG-PET mediated the association between Ab and cognitive decline. In contrast, elderly cognitively healthy controls (HC) with high Ab levels showed only a faster medial temporal lobe and precuneus volume decline compared with HC with low Ab. In conclusion, the current results suggest not only that both functional and volumetric brain changes are associated with high Ab years before the onset of dementia but also that HC with substantial Ab levels show higher Ab pathology resistance, lack other pathologies that condition neurotoxic effects of Ab, or accumulated Ab for a shorter time period.

Medial temporal lobe volumes on MRI and neuropathology in autopsy confirmed Lewy body dementia

Medial temporal lobe volumes on MRI and neuropathology in autopsy confirmed Lewy body dementia

Quantifying change in individual subjects affected by frontotemporal lobar degeneration using automated longitudinal MRI volumetry

A novel method of automated MRI volumetry was used to study regional atrophy and disease progression in repeated MRI measurements of patients with frontotemporal lobar degeneration (FTLD). Fifty-nine structural MRI data sets of 17 clinically diagnosed FTLD patients were acquired over up to 30 months in intervals of 6 months and compared with data of 30 age-matched healthy controls. Patients were further subgrouped into behavioral variant FTLD (bvFTLD), progressive nonfluent aphasia (PNFA), and semantic dementia (SemD). Gray matter (GM) volumes of frontal lobes (FL) and temporal lobes (TL) were determined by voxel-based volumetry based on SPM5 algorithms and a probabilistic brain atlas. MRI volumetry revealed frontal and temporal GM atrophy across FTLD patients, with further progression over time. Significant side asymmetry of TL volumes was found in SemD. The ratio of TL to FL volumes was significantly reduced in SemD and increased in bvFTLD. Using this ratio, 6/7 SemD patients and 5/6 bvFTLD patients could be correctly differentiated. TL/FL ratios in bvFTLD and SemD further diverged significantly over a time span of only 6 months. Rates of temporal GM loss per 6 months were 3-4% in SemD, and 2.5% for frontal GM loss in bvFTLD, and thereby clearly exceeded published cerebral volume loss in healthy elderly subjects. The study presents a fully automated, observer-independent volumetric assessment of regional atrophy which allows differentiation of FTLD subgroups. Its sensitivity for atrophy progression--even in such short intervals like 6 months--might benefit future clinical trials as treatment outcome measure.

Mapping the brain in type II diabetes: Voxel-based morphometry using DARTEL

To investigate the pattern of brain volume changes of the brain in patients with type II diabetes mellitus using voxel-based morphometry. Institutional ethics approval and informed consent were obtained. VBM based on the high resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MRI images was obtained from 16 type II diabetes patients (mean age 61.2 years) and 16 normal controls (mean age 59.6 years). All images were spatially preprocessed using Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL) algorithm, and the DARTEL templates were made from 100 normal subjects. Statistical parametric mapping was generated using analysis of covariance (ANCOVA). An atrophy pattern of gray matter was seen in type II diabetes patients compared with controls that involved the right superior, middle, and inferior temporal gyri, right precentral gyrus, and left rolandic operculum region. The loss of white matter volume in type II diabetes mellitus was observed in right temporal lobe and left inferior frontal triangle region. ROI analysis revealed that the gray and white matter volume of right temporal lobe were significant lower in type II diabetes mellitus than that in controls (P<0.05). This work demonstrated that type II diabetes mellitus patients mainly exhibited gray and white matter atrophy in right temporal lobe, and this finding supported that type II diabetes mellitus could lead to subtle diabetic brain structural changes in patients without dementia or macrovascular complications.

The Association of Elevated Body Mass Index with Reduced Brain Volumes in First-Episode Mania

Compared with normal-weight patients, obese patients with bipolar I disorder (BD) suffer more manic and depressive episodes and make more suicide attempts. In the general population, obesity is associated with reduced total brain volume (TBV) and gray matter volume (GMV), but the neurobiology of obesity in BD has not been investigated. We used magnetic resonance imaging to examine TBV, GMV, white matter volume (WMV), as well as frontal, parietal, occipital, and temporal lobe volumes, in 55 healthy subjects (17 overweight/obese and 38 normal weight) and 57 patients with BD following their first manic episode (20 overweight/obese and 37 normal weight). Linear regression analyses demonstrated that when other predictors of brain volume were accounted for, increased body mass index (BMI) in healthy subjects was significantly associated with decreased TBV and GMV. In contrast, increased BMI in patients with BD was significantly associated with decreased WMV and temporal lobe volume, areas of known vulnerability in early BD. This is the first published report to show a relationship between elevated BMI and reduced brain volumes in BD, or any psychiatric illness. Our results suggest that obesity is associated with unique neurobiological changes in BD. They further imply a possible biological mechanism underlying the association between obesity and a more severe illness course in BD.

Age-related changes in the mesial temporal lobe: the parahippocampal white matter region

The perforant pathway originates from cells in the entorhinal cortex and relays sensory information from the neocortex to the hippocampus, a region critical for memory function. Imaging studies have demonstrated structural alterations in the parahippocampal white matter in the region of the perforant pathway in people at risk for developing Alzheimer's disease. It is not clear, however, if changes noted in this region are indicative of pathological aging or are a function of the normal aging process. We compared magnetic resonance imaging (MRI)-derived mesial temporal lobe volumes in 51 healthy older individuals and 40 young participants, with an emphasis on the parahippocampal white matter. Yearly clinical evaluations showed that 9 of the older cohort declined in cognitive function. Parahippocampal white matter, hippocampal, and entorhinal cortex volumes were significantly reduced in healthy older people who remained stable over time compared with young participants. These findings suggest that volume differences in mesial temporal lobe gray and white matter structures may take place as a result of the normative aging process.

Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia

Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.Electronic supplementary materialThe online version of this article (doi:10.1007/s00406-011-0202-x) contains supplementary material, which is available to authorized users.

Neuropathological correlates of volumetric MRI in autopsy-confirmed Lewy body dementia

The objective of this study was to determine the neuropathological correlates of regional medial temporal lobe volume measures on magnetic resonance imaging (MRI) in subjects with Lewy body dementia (LBD). Twenty-three autopsy-confirmed LBD cases with an MRI scan close to death (mean 1.5 years) were studied. MRI-based volumetric measures were calculated for total intracranial volume, hippocampus, entorhinal cortex, and amygdala. Quantitative neuropathological analysis of plaques, tangles, and Lewy bodies were carried out in the same regions. Spearman's rho was used to examine correlations between MRI volumes and neuropathology measures and linear regression to assess the relationship between neuropathology and MRI volumes. A significant inverse correlation was observed between normalized amygdala volume and percent area of Lewy bodies in the amygdala (r = −0.461, p = 0.035). There were no other significant correlations between regional MRI volume and measures of neuropathology. Lewy body, but not Alzheimer's disease (AD) pathology was associated with reduced amygdala volume in pathologically-verified LBD cases but neither Lewy body nor Alzheimer's disease pathology was associated with volume loss in the hippocampus or entorhinal cortex, suggesting other neuropathological factors account for atrophy in these structures in LBD.

Exercise training increases size of hippocampus and improves memory

The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function.