Hippocampal subfield segmentation in temporal lobe epilepsy: Relation to outcomes.

OBJECTIVE: To investigate the clinical and surgical outcome correlates of preoperative hippocampal subfield volumes in patients with refractory temporal lobe epilepsy (TLE) using a new magnetic resonance imaging (MRI) multisequence segmentation technique. METHODS: We recruited 106 patients with TLE and hippocampal sclerosis (HS) who underwent conventional T1-weighted and T2 short TI inversion recovery MRI. An automated hippocampal segmentation algorithm was used to identify twelve subfields in each hippocampus. A total of 76 patients underwent amygdalohippocampectomy and postoperative seizure outcome assessment using the standardized ILAE classification. Semiquantitative hippocampal internal architecture (HIA) ratings were correlated with hippocampal subfield volumes. RESULTS: Patients with left TLE had smaller volumes of the contralateral presubiculum and hippocampus-amygdala transition area compared to those with right TLE. Patients with right TLE had reduced contralateral hippocampal tail volumes and improved outcomes. In all patients, there were no significant relationships between hippocampal subfield volumes and clinical variables such as duration and age at onset of epilepsy. There were no significant differences in any hippocampal subfield volumes between patients who were rendered seizure free and those with persistent postoperative seizure symptoms. Ipsilateral but not contralateral HIA ratings were significantly correlated with gross hippocampal and subfield volumes. CONCLUSIONS: Our results suggest that ipsilateral hippocampal subfield volumes are not related to the chronicity/severity of TLE. We did not find any hippocampal subfield volume or HIA rating differences in patients with optimal and unfavorable outcomes. In patients with TLE and HS, sophisticated analysis of hippocampal architecture on MRI may have limited value for prediction of postoperative outcome

Recognition Memory Dysfunction Relates to Hippocampal Subfield Volume: A Study of Cognitively Normal and Mildly Impaired Older Adults.

ObjectivesThe current study examined recognition memory dysfunction and its neuroanatomical substrates in cognitively normal older adults and those diagnosed with mild cognitive impairment (MCI).MethodsParticipants completed the Mnemonic Similarity Task, which provides simultaneous measures of recognition memory and mnemonic discrimination. They also underwent structural neuroimaging to assess volume of medial temporal cortex and hippocampal subfields.ResultsAs expected, individuals diagnosed with MCI had significantly worse recognition memory performance and reduced volume across medial temporal cortex and hippocampal subfields relative to cognitively normal older adults. After controlling for diagnostic group differences, however, recognition memory was significantly related to whole hippocampus volume, and to volume of the dentate gyrus/CA3 subfield in particular. Recognition memory was also related to mnemonic discrimination, a fundamental component of episodic memory that has previously been linked to dentate gyrus/CA3 structure and function.DiscussionResults reveal that hippocampal subfield volume is sensitive to individual differences in recognition memory in older adults independent of clinical diagnosis. This supports the notion that episodic memory declines along a continuum within this age group, not just between diagnostic groups

Hippocampal subfields predict positive symptoms in schizophrenia: First evidence from brain morphometry

Alterations of hippocampal anatomy have been reported consistently in schizophrenia. Within the present study, we used FreeSurfer to determine hippocampal subfield volumes in 21 schizophrenic patients. A negative correlation between PANSS-positive symptom score and bilateral hippocampal subfield CA2/3 as well as CA1 volume was found on high-resolution magnetic resonance images. Our observation opens the gate for advanced investigation of the commonly reported hippocampal abnormalities in schizophrenia in terms of specific subfields

Differential expression of synaptophysin and synaptoporin during pre- and postnatal development of the hippocampal network

The closely related synaptic vesicle membrane proteins synaptophysin and synaptoporin are abundant in the hippocampal formation of the adult rat. But the prenatal hippocampal formation contains only synaptophysin, which is first detected at embryonic day 17 (E17) in perikarya and axons of the pyramidal neurons. At E21 synaptophysin immunoreactivity extends into the apical dendrites of these cells and in newly formed terminals contacting these dendrites. The transient presence of synaptophysin in axons and dendrites suggests a functional involvement of synaptophysin in fibre outgrowth of developing pyramidal neurons. Synaptoporin expression parallels the formation of dentate granule cell synaptic contacts with pyramidal neurons: the amount of hippocampal synaptoporin, determined in immunoblots and by synaptoporin immunostaining of developing mossy fibre terminals, increases during the first postnatal week. Moreover, in the adult, synaptoporin is found exclusively in the mossy fibre terminals present in the hilar region of the dentate gyrus and the regio inferior of the cornu ammonis. In contrast, synaptophysin is present in all synaptic fields of the hippocampal formation, including the mossy fibre terminals, where it colocalizes with synaptoporin in the same boutons. Our data indicate that granule neuron terminals differ from all other terminals of the hippocampal formation by the presence of both synaptoporin and synaptophysin. This difference, observed in the earliest synaptic contacts in the postnatal hippocampus and persisting into adult life, suggests distinct functions of synaptoporin in these nerve terminals

Hippocampal subregion abnormalities in schizophrenia: A systematic review of structural and physiological imaging studies.

AimThe hippocampus is considered a key region in schizophrenia pathophysiology, but the nature of hippocampal subregion abnormalities and how they contribute to disease expression remain to be fully determined. This study reviews findings from schizophrenia hippocampal subregion volumetric and physiological imaging studies published within the last decade.MethodsThe PubMed database was searched for publications on hippocampal subregion volume and physiology abnormalities in schizophrenia and their findings were reviewed.ResultsThe main replicated findings include smaller CA1 volumes and CA1 hyperactivation in schizophrenia, which may be predictive of conversion in individuals at clinical high risk of psychosis, smaller CA1 and CA4/DG volumes in first-episode schizophrenia, and more widespread smaller hippocampal subregion volumes with longer duration of illness. Several studies have reported relationships between hippocampal subregion volumes and declarative memory or symptom severity.ConclusionsTogether these studies provide support for hippocampal formation circuitry models of schizophrenia. These initial findings must be taken with caution as the scientific community is actively working on hippocampal subregion method improvement and validation. Further improvements in our understanding of the nature of hippocampal formation subregion involvement in schizophrenia will require the collection of structural and physiological imaging data at submillimeter voxel resolution, standardization and agreement of atlases, adequate control for possible confounding factors, and multi-method validation of findings. Despite the need for cautionary interpretation of the initial findings, we believe that improved localization of hippocampal subregion abnormalities in schizophrenia holds promise for the identification of disease contributing mechanisms

Prenatal morphine exposure reduces pyramidal neurons in CA1, CA2 and CA3 subfields of mice hippocampus

Objective(s): This study was carried out to evaluate the effect of maternal morphine exposure during gestational and lactation period on pyramidal neurons of hippocampus in 18 and 32 day mice offspring. Materials and Methods: Thirty female mice were randomly allocated into cases and controls. In case group, animals received morphine sulfate 10 mg/kg.body weight intraperitoneally during 7 days before mating, gestational period (GD 0-21), 18 and 32 days after delivery in the experimental groups. The control animals received an equivalent volume of normal saline. Cerebrum of six offsprings in each group was removed and stained with cresyl violet and a monoclonal antibody NeuN for immunohistochemical detection of surviving pyramidal neurons. Quantitative computer-assisted morphometric study was done on hippocampus. Results: The number of pyramidal neurons in CA1, CA2 and CA3 in treated groups was significantly reduced in postnatal day 18 and 32 (P18, P32) compared to control groups (P<0.05). The mean thickness of the stratum pyramidal layer was decreased in the treated groups in comparison with controls (P<0.05), whereas the mean thickness of the stratum oriens, stratum radiatum and stratum lacunosum-moleculare in CA1 field and stratum oriens, stratum lucidum, stratum radiatum and stratum lacunosum-moleculare in CA3 were significantly increased in morphine treated group in comparison with controls (P<0.05). Conclusion: Morphine administration before and during pregnancy and during lactation period causes pyramidal neurons loss in 18 and 32 days old infant mice