21 research outputs found

    Entorhinal cortex volume is associated with episodic memory related brain activation in normal aging and amnesic mild cognitive impairment

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    The present study examined the relationship between entorhinal cortex and hippocampal volume with fMRI activation during episodic memory function in elderly controls with no cognitive impairment and individuals with amnesic mild cognitive impairment (aMCI). Both groups displayed limited evidence for a relationship between hippocampal volume and fMRI activation. Smaller right entorhinal cortex volume was correlated with reduced activation in left and right medial frontal cortex (BA 8) during incidental encoding for both aMCI and elderly controls. However, during recognition, smaller left entorhinal cortex volume correlated with reduced activation in right BA 8 for the control group, but greater activation for the aMCI group. There was no significant relationship between entorhinal cortex volume and activation during intentional encoding in either group. The recognition-related dissociation in structure/function relationships in aMCI paralleled our behavioral findings, where individuals with aMCI displayed poorer performance relative to controls during recognition, but not encoding. Taken together, these results suggest that the relationship between entorhinal cortex volume and fMRI activation during episodic memory function is altered in individuals with aMCI.Illinois. Department of Public HealthNational Institute on Aging (Grant P01 AG09466)National Institute on Aging (Grant P30 AG10161)National Institute on Aging (Grant R01 AG017917)National Institute on Aging (Grant T32 AG000257

    Regulation of Axonal HCN1 Trafficking in Perforant Path Involves Expression of Specific TRIP8b Isoforms

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    The functions of HCN channels in neurons depend critically on their subcellular localization, requiring fine-tuned machinery that regulates subcellular channel trafficking. Here we provide evidence that regulatory mechanisms governing axonal HCN channel trafficking involve association of the channels with specific isoforms of the auxiliary subunit TRIP8b. In the medial perforant path, which normally contains HCN1 channels in axon terminals in immature but not in adult rodents, we found axonal HCN1 significantly increased in adult mice lacking TRIP8b (TRIP8b−/−). Interestingly, adult mice harboring a mutation that results in expression of only the two most abundant TRIP8b isoforms (TRIP8b[1b/2]−/−) exhibited an HCN1 expression pattern similar to wildtype mice, suggesting that presence of one or both of these isoforms (TRIP8b(1a), TRIP8b(1a-4)) prevents HCN1 from being transported to medial perforant path axons in adult mice. Concordantly, expression analyses demonstrated a strong increase of expression of both TRIP8b isoforms in rat entorhinal cortex with age. However, when overexpressed in cultured entorhinal neurons of rats, TRIP8b(1a), but not TRIP8b(1a-4), altered substantially the subcellular distribution of HCN1 by promoting somatodendritic and reducing axonal expression of the channels. Taken together, we conclude that TRIP8b isoforms are important regulators of HCN1 trafficking in entorhinal neurons and that the alternatively-spliced isoform TRIP8b(1a) could be responsible for the age-dependent redistribution of HCN channels out of perforant path axon terminals

    Magnetoencephalography and New Imaging Modalities in Epilepsy

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    The success of epilepsy surgery is highly dependent on correctly identifying the entire epileptogenic region. Current state-of-the-art for localizing the extent of surgically amenable areas involves combining high resolution three-dimensional magnetic resonance imaging (MRI) with electroencephalography (EEG) and magnetoencephalography (MEG) source modeling of interictal epileptiform activity. Coupling these techniques with newer quantitative structural MRI techniques, such as cortical thickness measurements, however, may improve the extent to which the abnormal epileptogenic region can be visualized. In this review we assess the utility of EEG, MEG and quantitative structural MRI methods for the evaluation of patients with epilepsy and introduce a novel method for the co-localization of a structural MRI measurement to MEG and EEG source modeling. When combined, these techniques may better identify the extent of abnormal structural and functional areas in patients with medically intractable epilepsy

    Medically intractable temporal lobe epilepsy in patients with normal MRI: Surgical outcome in twenty-one consecutive patients

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    Abnormal MRI findings localizing to the mesial temporal lobe predict a favorable outcome in temporal lobe epilepsy surgery. The purpose of this study is to summarize the surgical outcome of patients who underwent a tailored antero-temporal lobectomy (ATL) with normal 1.5 T MRI. Specifically, factors that may be associated with favorable post-surgical seizure outcome are evaluated. A retrospective analysis of the Rush University Medical Center surgical epilepsy database between 1992 and 2003 was performed. Patients who underwent an ATL and had a normal MRI study documented with normal volumetric measurements of hippocampal formations and the absence of any other MRI abnormality were selected for this study. Demographic information was collected on all patients. Seizure outcomes were evaluated using Engel's classification. A two-sided Fisher exact test with Bonferroni correction was performed in statistical analyses. Twenty-one (21) patients met the inclusion criteria of normal 1.5 T MRI and underwent a tailored temporal lobectomy. Mean age at time of surgery was 28 years (SD = 8.1, range 11–44) and mean duration of the seizure disorder was 13.4 years (range 2–36). Risk factors for epilepsy included head injury ( n = 4), encephalitis ( n = 3), febrile seizures ( n = 2), and 12 patients had no risk factors. Pathological evaluation of resected tissue revealed no abnormal pathology in 12/21 patients (57%). After a mean 4.8 years follow-up post-surgical period, 15/21 (71%) patients were free of disabling seizures (Engel I outcome). At 8.3 years follow-up, 13/21 (62%) patients had similar results. Absence of prior epilepsy risk factors was the only statistically significant predictor of an Engel class I outcome ( p < 0.0022). Patients with medically intractable epilepsy and normal MRI appear to benefit from epilepsy surgery. Absence of prior epilepsy risk factors may be a positive prognostic factor
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