Task switching performance reveals heterogeneity amongst patients with mild cognitive impairment.

OBJECTIVE: To assess executive function in patients with mild cognitive impairment (MCI) and to determine whether task switching ability is associated with transition to Alzheimer's disease. METHODS: Twenty-seven MCI patients and 19 older controls were tested using a cued letter-digit classification switching task. Sixteen patients could perform the task (MCI-able), 6 could not (MCI-unable), and 5 were able only with cognitive support (MCI-cue). Demographic, neuropsychological, event-related potential (ERP), MRI, and genetic data were also collected. RESULTS: The four groups did not differ on age, gender, and APO E4 frequency. Compared to the controls, the MCI-unable group had significantly poorer performance on the Trail Making task (η2 = .430), lower education (η2 = .234), and smaller cortical volume (η2 = .245). Most MCI patients exhibited task-switching deficits but to vastly different degrees and with varying outcomes. The combined pattern of neuropsychological and task switching performance indicates that the MCI-able patients displayed memory retrieval difficulties (F(2,39) = 3.6, p = .036, MSE = 1.44), generally preserved task switching abilities, and had a high probability of remaining dementia-free at follow-up. The MCI-cue patients had increased mixing costs, F(2,39) = 11.0, p < .001, MSE = .07; the MCI-unable patients showed episodic memory deficits, and both groups had a high probability of poor outcome (i.e., developing AD or dying within four years). CONCLUSION: This study demonstrates that variability in performance on measures of task-switching can highlight important heterogeneity in the MCI population.

Patterns of cortical thinning in Alzheimer's disease and frontotemporal dementia.

In vivo measurement of cortical thickness is a sensitive representation of pathology in neurodegenerative disorders which primarily target the gray mantle. In this study we used magnetic resonance images to describe the patterns of cortical thinning in 11 frontotemporal dementia (FTD), 38 Alzheimer's disease (AD) and 34 healthy elderly (H(E)) subjects. AD and FTD displayed significant thinning of the cortical mantle compared to the H(E) group, but with distinctive distributions. AD subjects had significantly thinner cortex in all lobes whereas FTD compared to H(E) showed significant differences only in specific regions of frontal and temporal lobes. When compared to AD, the FTD subjects had a trend of thinner cortex in the anterior cingulate region and in selective regions of anterior frontal and temporal regions. In conclusion, the cortical thinning in dementia when compared to H(E), is disease specific whereby FTD subjects display a pattern distinct than that seen in Alzheimer's disease.

Magnetic resonance imaging evidence of progression of subacute brain atrophy in moderate to severe traumatic brain injury.

OBJECTIVE: To demonstrate subacute progression of brain atrophy (from 4.5-29mo postinjury) in moderate to severe traumatic brain injury (TBI) using structural magnetic resonance imaging (MRI). DESIGN: Within-subjects, repeated-measures design. SETTING: Inpatient neurorehabilitation program and teaching hospital (MRI department). PARTICIPANTS: Adults (N=14) with moderate to severe TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Neuroradiologist readings and volumetric measurements (total brain cerebrospinal fluid and hippocampus) at 4.5 months and 2.5 years postinjury. RESULTS: Ten of 14 patients showed visible atrophy progression. Significant increase in cerebrospinal fluid (CSF) volume (t(13)=-4.073, P<.001) and decrease in right and left hippocampal volumes (t(13)=4.221, P<.001 and t(13)=3.078, P<.005, respectively) were observed from 4.5 months to 2.5 years. Compared with published normative data, patients with TBI showed significantly more pathologic percent annual volume change for the hippocampi (t(26)=-3.864, P<.001, right; and t(26)=-2.737, P<.01, left), and a trend for CSF (t(26)=1.655, P=.059). CONCLUSIONS: This study provides strong MRI evidence for subacute progression of atrophy, as distinct from early, acute neurologic changes observed.

Cognitive function and brain structure in females with a history of adolescent-onset anorexia nervosa.

OBJECTIVE: Abnormalities in cognitive function and brain structure have been reported in acutely ill adolescents with anorexia nervosa, but whether these abnormalities persist or are reversible in the context of weight restoration remains unclear. Brain structure and cognitive function in female subjects with adolescent-onset anorexia nervosa assessed at long-term follow-up were studied in comparison with healthy female subjects, and associations with clinical outcome were investigated. PATIENTS AND METHODS: Sixty-six female subjects (aged 21.3 +/- 2.3 years) who had a diagnosis of adolescent-onset anorexia nervosa and treated 6.5 +/- 1.7 years earlier in a tertiary care hospital and 42 healthy female control subjects (aged 20.7 +/- 2.5 years) were assessed. All participants underwent a clinical examination, magnetic resonance brain scan, and cognitive evaluation. Clinical data were analyzed first as a function of weight recovery (n = 14, <85% ideal body weight; n = 52, >or=85% ideal body weight) and as a function of menstrual status (n = 18, absent/irregular menses; n = 29, oral contraceptive pill; n = 19, regular menses). Group comparisons were made across structural brain volumes and cognitive scores. RESULTS: Compared with control subjects, participants with anorexia nervosa who remained at low weight had larger lateral ventricles. Twenty-four-hour urinary free-cortisol levels were positively correlated with volumes of the temporal horns of the lateral ventricles and negatively correlated with volumes of the hippocampi in clinical participants. Participants who were amenorrheic or had irregular menses showed significant cognitive deficits across a broad range of many domains. CONCLUSIONS: Female subjects with adolescent-onset anorexia nervosa showed abnormal cognitive function and brain structure compared with healthy individuals despite an extended period since diagnosis. To our knowledge, this is the first study to report a specific relationship between menstrual function and cognitive function in this patient population. Possible mechanisms underlying neural and cognitive deficits with anorexia nervosa are discussed. Additional examination of the effects of estrogen on cognitive function in female subjects with anorexia nervosa is necessary.

Neurodevelopmental trajectories of the human cerebral cortex.

Understanding the organization of the cerebral cortex remains a central focus of neuroscience. Cortical maps have relied almost exclusively on the examination of postmortem tissue to construct structural, architectonic maps. These maps have invariably distinguished between areas with fewer discernable layers, which have a less complex overall pattern of lamination and lack an internal granular layer, and those with more complex laminar architecture. The former includes several agranular limbic areas, and the latter includes the homotypical and granular areas of association and sensory cortex. Here, we relate these traditional maps to developmental data from noninvasive neuroimaging. Changes in cortical thickness were determined in vivo from 764 neuroanatomic magnetic resonance images acquired longitudinally from 375 typically developing children and young adults. We find differing levels of complexity of cortical growth across the cerebrum, which align closely with established architectonic maps. Cortical regions with simple laminar architecture, including most limbic areas, predominantly show simpler growth trajectories. These areas have clearly identified homologues in all mammalian brains and thus likely evolved in early mammals. In contrast, polysensory and high-order association areas of cortex, the most complex areas in terms of their laminar architecture, also have the most complex developmental trajectories. Some of these areas are unique to, or dramatically expanded in primates, lending an evolutionary significance to the findings. Furthermore, by mapping a key characteristic of these development trajectories (the age of attaining peak cortical thickness) we document the dynamic, heterochronous maturation of the cerebral cortex through time lapse sequences ("movies").

Cerebral white matter deficiencies in pedophilic men.

The present investigation sought to identify which brain regions distinguish pedophilic from nonpedophilic men, using unbiased, automated analyses of the whole brain. T1-weighted magnetic resonance images (MRIs) were acquired from men who demonstrated illegal or clinically significant sexual behaviors or interests (n = 65) and from men who had histories of nonsexual offenses but no sexual offenses (n = 62). Sexual interest in children was assessed by participants' admissions of pedophilic interest, histories of committing sexual offenses against children, and psychophysiological responses in the laboratory to erotic stimuli depicting children or adults. Automated parcellation of the MRIs revealed significant negative associations between pedophilia and white matter volumes of the temporal and parietal lobes bilaterally. Voxel-based morphometry corroborated the associations and indicated that the regions of lower white matter volumes followed, and were limited to, two major fiber bundles: the superior fronto-occipital fasciculus and the right arcuate fasciculus. No significant differences were found in grey matter or in cerebrospinal fluid (CSF). Because the superior fronto-occipital and arcuate fasciculi connect the cortical regions that respond to sexual cues, these results suggest (1) that those cortical regions operate as a network for recognizing sexually relevant stimuli and (2) that pedophilia results from a partial disconnection within that network.

Spatial patterns of cortical thinning in mild cognitive impairment and Alzheimer's disease.

Cortical thickness is a more reliable measure of atrophy than volume due to the low variability in the cytoarchitectural structure of the grey matter. However, this more desirable measure of disease-related alterations is not fully evaluated in early dementia. The study presented here is the first to report the spatial patterns of cortical thickness in the pre-clinical stages of Alzheimer's disease, namely mild cognitive impairment (MCI). Cortical thickness measurements for 34 healthy elderly, 62 MCI and 42 Alzheimer's disease subjects were made using fully automated magnetic resonance imaging-based analysis techniques in order to determine the pattern of cortical thinning as a function of disease progression. The thickness of the cortex decreased significantly when the healthy elderly brains were compared to those with MCI, mainly in the medial temporal lobe region and in some regions of the frontal and the parietal cortices. With the progression of disease from MCI to Alzheimer's disease, a general thinning of the entire cortex with significant extension into the lateral temporal lobe was found. In all cases, the results were more pronounced in the left hemisphere. In conclusion, we have shown that there is a specific pattern in the thinning of the cortical ribbon which is in agreement with the previous histological reports. These novel findings support the notion of increased isocortical involvement with the progression of disease.

Volumetry of temporopolar, perirhinal, entorhinal and parahippocampal cortex from high-resolution MR images: considering the variability of the collateral sulcus.

Researchers in clinical and basic neuroscience frequently target structures of the human medial temporal lobe (MTL) for volumetric analysis with magnetic resonance imaging (MRI). In neurodegenerative diseases, a precise volumetric analysis of MTL structures can assist in differential diagnosis and can be used in guiding early treatment. Also, in functional neuroimaging, exact localization is crucial for the correct interpretation of focal MTL activations with respect to specific memory functions. In presently available protocols, precise and consistent volumetric analysis of MTL structures is compromised in numerous ways. Most importantly, in order to cover all structures of the MTL, the researcher is presently forced to combine independently developed segmentation protocols for different structures from different laboratories. This approach limits anatomical precision because these protocols are based on different anatomical guidelines and descriptions that cannot easily be integrated. The segmentation approach presented in this paper was designed to address this issue by presenting segmentation guidelines for all major structures of the parahippocampal gyrus (PHG). It was developed directly to complement a volumetric protocol for hippocampus and amygdala (Pruessner et al., 2000, Cereb Cortex 10:433-442), thus allowing volumetric assessment of all major MTL structures in an integrated and consistent manner. Furthermore, it takes into consideration the neuroanatomical appearance of the collateral sulcus by presenting a method to correct the volumes of the surrounding cortices for the variability of this sulcus. The protocol was validated using MR images of 40 healthy normal control subjects (20 men and 20 women, age range 18-42 years). Intra- and interrater coefficients are presented, together with mean values for the volumes of all PHG structures, correlations with age and sex, and tests for hemispheric differences.

Magnetization transfer ratio in mild cognitive impairment and dementia of Alzheimer's type.

Almost half of the elderly subjects that are diagnosed with mild cognitive impairment (MCI) go on to develop dementia of Alzheimer's type (DAT) over a 5-year follow-up. MCI and DAT subjects show regional decreases in the volume of brain structures, which correlate with the cognitive decline among these groups. Volumetric changes are found more consistently in the DAT group than in the MCI group. Since not all MCI subjects demonstrate volumetric decline, we propose that the underlying changes in the structural integrity of the brain, measured using magnetization transfer ratio (MTR), may be used as an additional predictor for abnormal cognitive decline in the elderly. Magnetic resonance (MR) images were obtained in 15 DAT, MCI, and elderly control subjects. Using automatic tissue classification, the brain region of each MR volume was segmented into gray matter and white matter. Mean and standard error of the mean MTR measured within the gray matter was found to be significantly lower in the MCI (30.77 +/-0.29; P = 0.037) and the DAT (29.37 +/-0.41; P = 0.000) group compared to the control group (32.11 +/-0.20). The MTR of white matter was significantly lower only in the DAT group. The gray matter volume was significantly lower (P = 0.000) in the DAT (387.29 +/-26.04 cm(3)) group compared to controls (532.93 +/-20.53 cm(3)) and MCI (464.64 +/-16.93 cm(3)). No significant differences were found in the white matter volume between the three groups. We conclude that changes in MTR are measurable even in the absence of detectable volumetric changes in gray and white matter in the MCI group. Furthermore, MTR changes may present a novel MRI measure for the early diagnosis of dementia of Alzheimer's type.

Regional magnetization transfer ratio changes in mild cognitive impairment.

Reduction in temporal lobe volume is consistently found in dementia of Alzheimer's type (DAT). However, due to the lack of a consistent association between brain volume and cognitive decline in mild cognitive impairment (MCI), volumetric measures are not a reliable predictor for the progression of the disease. In our study, we hypothesized that changes in the magnetization transfer ratio (MTR) may reflect underlying brain pathology in the absence of quantifiable volumetric changes. Such a measure may be used as a predictor for abnormal cognitive decline in elderly subjects. The study was carried out on 15 normal elderly controls, 11 subjects with DAT, and 12 subjects with MCI. We used MTRs with magnetic resonance imaging (MRI) to detect tissue changes in the four lobes of each hemisphere, and compared that to the volumetric changes in the same regions. Our results indicate that the MTR of both temporal lobes is significantly reduced in subjects with MCI in the absence of significant volumetric changes. In comparison, DAT subjects have significantly reduced temporal lobe volumes and MTR. We conclude that changes in MTR have the potential to mark the progression of MCI to DAT, before volumetric changes are detected on conventional MRI scans.