High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: manual segmentation to automatic atlas.

The amygdala is composed of multiple nuclei with unique functions and connections in the limbic system and to the rest of the brain. However, standard in vivo neuroimaging tools to automatically delineate the amygdala into its multiple nuclei are still rare. By scanning postmortem specimens at high resolution (100-150µm) at 7T field strength (n = 10), we were able to visualize and label nine amygdala nuclei (anterior amygdaloid, cortico-amygdaloid transition area; basal, lateral, accessory basal, central, cortical medial, paralaminar nuclei). We created an atlas from these labels using a recently developed atlas building algorithm based on Bayesian inference. This atlas, which will be released as part of FreeSurfer, can be used to automatically segment nine amygdala nuclei from a standard resolution structural MR image. We applied this atlas to two publicly available datasets (ADNI and ABIDE) with standard resolution T1 data, used individual volumetric data of the amygdala nuclei as the measure and found that our atlas i) discriminates between Alzheimer's disease participants and age-matched control participants with 84% accuracy (AUC=0.915), and ii) discriminates between individuals with autism and age-, sex- and IQ-matched neurotypically developed control participants with 59.5% accuracy (AUC=0.59). For both datasets, the new ex vivo atlas significantly outperformed (all p < .05) estimations of the whole amygdala derived from the segmentation in FreeSurfer 5.1 (ADNI: 75%, ABIDE: 54% accuracy), as well as classification based on whole amygdala volume (using the sum of all amygdala nuclei volumes; ADNI: 81%, ABIDE: 55% accuracy). This new atlas and the segmentation tools that utilize it will provide neuroimaging researchers with the ability to explore the function and connectivity of the human amygdala nuclei with unprecedented detail in healthy adults as well as those with neurodevelopmental and neurodegenerative disorders.

The parahippocampal gyrus in Alzheimer's disease. Clinical and preclinical neuroanatomical correlates.

The human parahippocampal gyrus forms a large part of the limbic lobe along the ventromedial part of the temporal cortical mantle. It is a variable and complicated cortex in terms of structure, and the latter is aggravated further by interfaces with the anterior insula anteriorly and the cingulate gyrus and occipital lobe posteriorly. Additional complications relate to its lateral border with the temporal cortex and especially the sulcal configurations that define this junction. The rhinal sulcus, which separates parahippocampal and temporal cortices in other species, including the anthropoid apes, is either lacking or rudimentary in the human brain. Thus, defining this junction requires cytoarchitectural examination and precludes the use of mere inspection of sulcal existing patterns. The cortical areas that form the parahippocampal gyrus are vulnerable to pathological changes in Alzheimer's disease (AD), and its entorhinal and perirhinal subdivisions are both the most heavily damaged cortical areas and the focus for disease onset. The neurons that acquire neurofibrillary tangles (NFTs) occupy the junction of the isocortical mantle with the limbic cortical mantle, but share, or partially share, a vulnerability phenotype with large neurons in both domains. The differential expression of this phenotype across time creates the false impression of NFT spread in cross-sectional comparisons of AD brains. The questions of what this phenotype is and why it is expressed first in the perirhinal and entorhinal cortices of the parahippocampal gyrus are the central molecular biological/neuroanatomical questions in understanding the etiology of AD.

Cerebellar hypoactivity in frequent marijuana users.

It is uncertain whether frequent marijuana use adversely affects human brain function. Using PET, regional cerebral blood flow was compared in frequent marijuana users and comparable, non-using controls after at least 26 h of monitored abstention by all subjects. Marijuana users showed substantially lower brain blood flow than controls in a large region of posterior cerebellum, indicating altered brain function in frequent marijuana users. A cerebellar locus of some chronic and acute effects of marijuana is plausible, e.g. the cerebellum has been linked to an internal timing system, and alterations of time sense are common following marijuana smoking.

Effects of frequent marijuana use on brain tissue volume and composition.

To investigate CNS effects of frequent marijuana use, brain tissue volume and composition were measured using magnetic resonance imaging (MRI) in 18 current, frequent, young adult marijuana users and 13 comparable, non-using controls. Automated image analysis techniques were used to measure global and regional brain volumes, including, for most regions, separate measures of gray and white matter. The marijuana users showed no evidence of cerebral atrophy or global or regional changes in tissue volumes. Volumes of ventricular CSF were not higher in marijuana users than controls, but were, in fact, lower. There were no clinically significant abnormalities in any subject's MRI. Sex differences were detected in several global volume measures.

Ventromedial temporal lobe pathology in dementia, brain trauma, and schizophrenia.

The ventromedial temporal area contains numerous anatomical structures collectively or selectively involved in a wide range of neurological and psychiatric disorders. Collective involvement is exemplified best by Alzheimer's disease where a host of anatomical structures and a host of cognitive and behavioral changes are manifested. Selective disease of the amygdala can yield deficits in the ability to judge and evaluate emotional expressions. While memory functions are nearly synonymous with the concept of ventromedial temporal area, they overshadow other functions associated with the diverse anatomical structures in this part of the brain. For example, it could be argued that in addition to output directed toward the hippocampal formation, the output of the ventromedial temporal area is equally strong to the ventral striatopallidal system of the basal forebrain. Denervation of these structures could be associated with the behavioral changes that occur in tandem with the memory-related changes of ventromedial temporal lobe pathology. Here we explore the anatomical and pathological correlate associated with ventromedial temporal area pathology and consider how these may impact on ventral striatopallidal conceptualizations. We conclude that ventromedial temporal area pathology deprives the basal forebrain of multimodal association information from the endstages of corticocortical sensory processing. This endstage information carries with it an analysis of real-time sensory awareness, historical-time or past sensory experiences, and decisions from hippocampal output structures regarding relevancy and novelty. In this sense, basal forebrain structures are in a unique position to regulate behavioral responses to a wide range of stimuli and to organize appropriate emotional, motor, autonomic, and endocrine responses to them.