Histological studies suggest that hippocampal subfields are differently affected by aging and Alzheimer's disease (AD). The aims of this study were: (1) To test if hippocampal subfields can be identified and marked using anatomical landmarks on high resolution MR images obtained on a 4T magnet. (2) To test if age-specific volume changes of subfields can be detected. Forty-two healthy controls (21-85 years) and three AD subjects (76-86 years) were studied with a high resolution T2 weighted fast spin echo sequence. The entorhinal cortex (ERC), subiculum, CA1, CA2 and CA3/4 and dentate were marked. A significant correlation between age and CA1 (r=-0.51, p=0.0002) which was most pronounced in the seventh decade of life was found in healthy controls. In AD subjects, CA1 and subiculum were smaller than in age-matched controls. These preliminary findings suggest that measurement of hippocampal subfields may be helpful to distinguish between normal aging and AD.

Proton magnetic resonance spectroscopy was performed at 4 T to determine effects of age, region and gender on glutamate and glutamine in the normal human brain. Furthermore, glutamate and glutamine alterations with age were tested for correlations with other cerebral metabolites. Two 8 cm 3 volumes were selected in corona radiata and mesial motor cortex in normal subjects (N = 24) between 24 and 68 years old. Older subjects had lower glutamate concentration in the motor cortex compared to younger subjects (p < 0.001). In corona radiata, older subjects demonstrated a trend in higher glutamine compared to younger subjects (p = 0.05). Glutamate in the motor cortex was positively correlated with glutamine, N-acetyl aspartate and creatine. Reduced glutamate and Nacetyl aspartate in the motor cortex is consistent with neuronal loss/shrinkage with age. In conclusion, different patterns in association with normal aging in these brain regions were detected in this study.

SummaryWorking memory allows information from transient events to persist as active neural representations [1] that can be used for goal-directed behaviors such as decision making and learning [2, 3]. Computational modeling based on neuronal firing patterns in animals suggests that one putative mechanism enabling working memory is periodic reactivation (henceforth termed “replay”) of the maintained information coordinated by neural oscillations at theta (4–8 Hz) and gamma (30–80 Hz) frequency [4–6]. To investigate this possibility, we trained multivariate pattern classifier decoding algorithms on oscillatory brain responses to images depicting natural scenes, recorded with high temporal resolution via magnetoencephalography. These classifiers were applied to brain activity recorded during the subsequent five second maintenance of the scenes. This decoding revealed replay during the entire maintenance interval. Replay was specific to whether an indoor or an outdoor scene was maintained and whether maintenance centered on configural associations of scene elements or just single scene elements. Replay was coordinated by the phase of theta and the amount of theta coordination was correlated with working memory performance. By confirming the predictions of a mechanistic model and linking these to behavioral performance in humans, these findings identify theta-coupled replay as a mechanism of working memory maintenance.

Summary:Purpose: In temporal lobe epilepsy (TLE) with evidence of hippocampal sclerosis (TLE-MTS) volumetric gray (GM) and white (WM) matter abnormalities are not restricted to the hippocampus but also are found in extrahippocampal structures. Less is known about extrahippocampal volumetric abnormalities in TLE without hippocampal sclerosis (TLE-no). In this study, we used optimized voxel-based morphometry (VBM) with and without modulation with the following aims: (a) to identify WM and GM abnormalities beyond the hippocampus in TLE-MTS and TLE-no; and (b) to determine whether extratemporal WM and GM abnormalities differ between TLE-MTS and TLEno.Methods: Optimized VBM of GM and WM with and without modulation was performed in 26 TLE-MTS (mean age, 35.6 ± 9.7 years), 17 TLE-no (mean age, 35.6 ± 11.1 years), and 30 healthy controls (mean age, 30.3 ± 11.1 years).Results: In TLE-MTS, GM/WM volume and concentration reductions were found in the ipsilateral limbic system, ipsi-and contralateral neocortical regions, thalamus, cerebellum, internal capsule, and brainstem when compared with controls. In contrast, no differences of GM/WM volumes/concentrations were found between TLE-no and controls or between TLE-no and TLE-MTS.Conclusions: In TLE-MTS, optimized VBM showed extensive GM and WM volume reductions in the ipsilateral hippocampus and in ipsi-and contralateral extrahippocampal regions. In contrast, no GM/WM volume or concentration reductions were found in TLE-no. This further supports the hypothesis that TLE-no is a distinct clinicopathologic entity from TLE-MTS and probably heterogeneous in itself. Key Words: TLE-Extratemporal-Voxel-based morphometryMesiotemporal sclerosis-Normal MRI.Mesial temporal lobe epilepsy (mTLE) is one of most frequent forms of partial epilepsy in adults. Based on neuroimaging and histologic characteristics, two main subtypes of mTLE can be distinguished: (a) TLE with hippocampal sclerosis (TLE-MTS), found in ∼60-70% of mTLE patients, which is characterized by an increased hippocampal T 2 signal and/or atrophied hippocampal formation on the MRI and significant neuronal loss in one or more hippocampal subfields in the histologic examination (1); and (b) MTLE without structural abnormalities on MRI (TLE-no) and only very mild or no neuronal loss in the hippocampus, which is found in ∼20-30% of mTLE patients. In both types of mTLE, seizures are not restricted to the medial temporal lobe but involve