Medial Temporal Lobe Abnormalities Research Articles

A study to assess the magnitude of various minor physical anomalies in bipolar disorders and to compare them between bipolar disorder patients and their first degree relatives

Background: Bipolar disorder appears to be related to anatomic abnormalities in medial temporal lobe, in particular amygdale, prefrontal cortex and cerebellum. Two recent MRI findings have supported a neuro developmental etiology of bipolar disorders.Methods: It was a cross-sectional comparative hospital based study. The subjects were recruited for the study by the purposive sampling technique. The study was conducted at the Institute of Mental Health and Hospital Mathura Road Agra. The study sample consisted of 20 bipolar disorder patients diagnosed as per ICD-10 DCR (WHO, 1992) criteria, 20 first degree relatives, one for each patient. Total sample size is 40.Results: It was observed that in bipolar patients’ maximum anomalies were seen in Mouth (0.35±0.48) head (0.30±0.57) followed by anomalies of eyes (0.25±0.55) hand (0.20±0.41) and ear (0.05±0.22). It was observed that in Bipolar FDRs maximum anomalies were seen in mouth (0.20±0.04) ear (0.15±0.45) head (0.1±0.3) and then anomalies of eye and hand in equal propensity (0.05±0.22) and least anomalies in feet (0.00±0.00).Conclusions: The rate of MPAs in bipolar patients was more than their FDRs but not statically significant. Both sibling groups had fewer MPAs than the patients. When viewed within a vulnerability-stress model, the results are consistent with the theory that MPAs may reflect early, largely extra-genetic, stressful events.

Neurosyphilis.

This article reviews the etiology, clinical manifestations, diagnosis, and treatment of neurosyphilis, with a focus on issues of particular relevance to neurologists. The number of cases of infectious syphilis in the United States has steadily increased since 2000. The highest rates are among men who have sex with men, and approximately half of these individuals are infected with human immunodeficiency virus (HIV). Neurosyphilis is a serious complication of syphilis that can develop at any time in the course of syphilis. Two neuroimaging patterns should alert the neurologist to a diagnosis of neurosyphilis: cerebral gummas, which are dural-based lesions that can mimic meningiomas, and medial temporal lobe abnormalities that can mimic herpes encephalitis. Penicillin G is the recommended treatment for neurosyphilis, but ceftriaxone may be an acceptable alternative. The diagnosis of neurosyphilis can be challenging. A sound understanding of the clinical manifestations and the strengths and limitations of diagnostic tests are essential tools for the neurologist.

CTP in Transient Global Amnesia: A Single-Center Experience of 30 Patients.

Medial temporal lobe abnormalities on DWI and functional imaging are occasionally observed in patients with transient global amnesia. We used CTP to study these patients during or briefly after resolution of their amnesic syndrome. From 2002 onward, patients satisfying clinical criteria for transient global amnesia who underwent CTP were included. Patients with additional clinical features suggesting transient ischemic attack or stroke and those with an ischemic lesion on subsequent DWI were excluded. If deemed necessary by the clinician, DWI was performed within 10 days. Thirty patients with transient global amnesia underwent CTP at a median latency of 5.9 hours (interquartile range, 4.3-9.7 hours) after symptom onset. All findings, except for those in 1 patient, were normal, including those in the 14 patients with well-imaged hippocampi. In the patient with abnormal findings, CTP and PWI showed hypoperfusion in both lentiform nuclei extending into the insulae, with normalization on the repeat CTP 6 days later. In 10 patients, DWI was performed at a median latency of 2 days (interquartile range, 0-9 days). Of these, 2 showed punctate hippocampal lesions, often seen in transient global amnesia. In 2 patients excluded because of mildly atypical transient global amnesia and ischemic lesions on subsequent DWI, acute CTP findings were also normal. Patients with transient global amnesia had normal CTP findings in the acute phase with the exception of 1 patient with transient hypoperfusion in both basal ganglia. If imaging is performed for typical and atypical transient global amnesia, DWI should be the preferred method.

EPA-1759 - Brain structural abnormalities in medial temporal lobe are associated with mood and anxiety in methadone maintenance treatment

Several brain circuits are relevant in the neurobiology of addiction. Here we want to highlight symptoms related to the domains of mood, anhedonia and anxiety that may precede drug abuse and represent a specific risk factor for addiction. The mood regulation circuit that contributes to regulation of stress reactivity and the interoception circuit that contributes to awareness of drug craving and mood also participate in addiction but their involvement in the human brain has been much less investigated. Here we aim to investigate mood and anxiety in opiate dependent, treatment-seeking patients receiving Methadone Maintenance Treatment, to test hypothesis of regional grey matter reduction correlating with mood and anxiety. Cambridge Gambling Task (CGT) data were acquired from 30 patients receiving MMT and 23 controls. T1 weighted Magnetic Resonance Images were acquired from a representative subset of these volunteers. MMT patients exhibited grey matter reductions in the orbito-medial prefrontal cortex and basal ganglia. Additionally, patients exhibited significant abnormalities in the clinical rating scales BDI, Anhedonia, HAD-Anxiety, IDS and Snaith Hamilton. Increased BDI, HAD-Anxiety and IDS correlated with grey matter reductions in the hippocampus, amygdala, bed nucleus of stria terminalis and insula. Increased Snaith Hamilton correlated with grey matter reductions in periaqueductal gray, ventral tegmental area and nucleus caudate. These findings support an interpretation of a neurobiological underpinning of mood and addiction. However, the anatomically restricted correlates with mood and anxiety suggest that a rationale for adopting a mood addiction model should be further investigated.

Cognitive and volumetric predictors of response to repetitive transcranial magnetic stimulation (rTMS) — A prospective follow-up study

As the prevalence of treatment resistant depression (TRD) continues to rise, it remains a clinically important issue to identify neurobiological-, patient- and treatment-related factors that could potentially predict response to treatment. Medial temporal lobe (MTL) structures, in particular the hippocampus and amygdala have been implicated in inferior treatment response. The role of related structures such as the entorhinal cortex and the impact of MTL abnormalities on neurocognitive function, however, have not been systematically examined. The current study investigated MTL abnormalities and neurocognitive characteristics of eventual treatment responders and non-responders to a course of repetitive transcranial magnetic stimulation (rTMS) in order to identify potential predictors of treatment outcome. Prior to rTMS treatment all patients underwent magnetic resonance imaging (MRI) and neuropsychological assessment. MRI analysis was conducted using FreeSurfer 5.0. There was a 50% response rate following up to a 6-week course of daily rTMS treatments. Treatment response was defined as 50% reduction in Hamilton Depression Rating Scale and BDI-II scores from baseline. There was no difference in pre-treatment neurocognitive profiles and MTL volumes between eventual treatment responders and non-responders. Smaller pre-treatment left hippocampus volume showed a trend towards predicting eventual subjective improvement in depressive symptomatology. Although preliminary, our findings suggest that structural abnormalities may have some potential for predicting outcome to rTMS.

Increased parahippocampal and lingual gyrification in first-episode schizophrenia

Objective Cerebral gyrification is attributed to a large extent to genetic and intrauterine/perinatal factors. Hence, investigating gyrification might offer important evidence for disturbed neurodevelopmental mechanisms in schizophrenia. As an extension of recent ROI analyses of gyrification in schizophrenia the present study is the first to compare on a node-by-node basis mean curvature as a sensitive parameter for the identification of local gyrification changes of the whole cortex in first-episode schizophrenia. Methods A group of 54 patients with first-episode schizophrenia according to DSM-IV and 54 age and gender matched healthy control subjects were included. All participants underwent high-resolution T1-weighted MRI scans on a 1.5 T scanner. Mean curvature was calculated dividing the sum of the principal curvatures by two at each point of the curved surface as implemented in the Freesurfer Software package. Statistical cortical maps were created to estimate gyrification differences between groups based on a clustering approach. Results A significantly increased gyrification was observed in first-episode schizophrenia patients relative to controls in a right parahippocampal–lingual cortex area. The cluster encompassed a surface area of 750 mm². A further analysis of cortical thickness of this cluster demonstrated concurrent significant reduced cortical thickness of this area. Conclusions This is the first study to reveal an aberrant gyrification of the medial surface in first-episode schizophrenia. This finding is in line with substantial evidence showing medial temporal lobe abnormalities in schizophrenia. The present morphometric data provide further support for an early disruption of cortical maturation in schizophrenia.

Medial temporal lobe abnormalities in pediatric unipolar depression

In vivo anatomical magnetic resonance imaging (MRI) studies in adults with major depressive disorder (MDD) have implicated neurocircuitries involved in mood regulation in the pathophysiology of mood disorders. Specifically, abnormalities in the medial temporal lobe structures have been reported. This study examined a sample of children and adolescents with major depressive disorder to investigate anatomical abnormalities in these key medial temporal brain regions. Nineteen children and adolescents with DSM-IV major depression (mean age +/- S.D.=13.0 +/- 2.4 years; 10 unmedicated) and 24 healthy comparison subjects (mean age +/- S.D.=13.9 +/- 2.9 years) were studied using a 1.5T Philips MRI scanner. We measured hippocampus and amygdala gray matter volumes. MRI structural volumes were compared using analysis of covariance with age and total brain volumes as covariates. Pediatric depressed patients had significantly smaller left hippocampal gray matter volumes compared to healthy controls (1.89 +/- 0.16 cm(3) versus 1.99 +/- 0.18 cm(3), respectively; F=5.0, d.f.=1/39, p=0.03; effect size: eta2(p) =0.11). Unmedicated depressed patients showed a trend towards smaller left hippocampal volumes compared to medicated patients and healthy subjects (F=2.8, d.f.=2/38, p=0.07; effect size: eta2(p) =0.13). There were no statistically significant differences in mean volumes for left or right amygdala. Smaller left hippocampal volumes in children and adolescents with MDD are in agreement with findings from adult studies and suggest that such abnormalities are present early in the course of the illness. Amygdala volumes are not abnormal in this age group. Smaller hippocampal volumes may be related to an abnormal developmental process or HPA axis dysfunction.

Differential diagnosis of mesiotemporal lesions: case report of neurosyphilis

Sir, The September issue of Neuroradiology contained an interesting article by Vieira Santos et al. entitled “Differential diagnosis of mesiotemporal lesions: case report of neurosyphilis” [1]. Coincidentally, a paper by us on the same subject (the differential diagnosis of neuroradiologically apparent medial temporal lobe abnormalities [2]) was published in the September issue of the Journal of Neurology. As an author of the latter paper, I would like to make some remarks on the case report by Vieira Santos et al. [1]. The authors state that medial temporal lobe involvement in neurosyphilis had previously been described in only four patients. However, this statement is incorrect. First, the cited article by Kanamalla et al. does not include such a finding in the context of neurosyphilis. Second, as we document [2], although medial temporal lobe involvement in neurosyphilis can still be regarded as rare, it is not as rare as the authors suggest. In addition to the case report of Vieira Santos et al., as well as a report that was recently published in Neurology [3], at least 16 patients with this neuroimaging pattern can be found in the literature. With respect to its pathogenesis, we have already pointed out that the assumption of a meningovascular origin is questionable [2]. We would like to pose the questions: how do the authors interpret the discordant results of the serologic and CSF tests in syphilis and, as a result, which stage of syphilis do they see in their patient? Finally, the differential diagnosis of the clinical signs and symptoms of the patient include Lyme neuroborreliosis. Borrelia burgdorferi is well known as a confounder of serologic tests in syphilis [4]. As penicillin G may be a satisfactory treatment alternative in neuroborreliosis [5], the response to this kind of treatment cannot be regarded as a sufficient criterion of differentiation. We therefore ask whether the authors ruled out Lyme neuroborreliosis in this patient.

Hippocampal and Amygdala Volumes According to Psychosis Stage and Diagnosis

Magnetic resonance imaging studies have identified hippocampal volume reductions in schizophrenia and amygdala volume enlargements in bipolar disorder, suggesting different medial temporal lobe abnormalities in these conditions. These studies have been limited by small samples and the absence of patients early in the course of illness. To investigate hippocampal and amygdala volumes in a large sample of patients with chronic schizophrenia, patients with first-episode psychosis, and patients at ultra-high risk for psychosis compared with control subjects. Cross-sectional comparison between patient groups and controls. Individuals with chronic schizophrenia were recruited from a mental health rehabilitation service, and individuals with first-episode psychosis and ultra-high risk were recruited from the ORYGEN Youth Health Service. Control subjects were recruited from the community. The study population of 473 individuals included 89 with chronic schizophrenia, 162 with first-episode psychosis, 135 at ultra-high risk for psychosis (of whom 39 subsequently developed a psychotic illness), and 87 controls. Hippocampal, amygdala, whole-brain, and intracranial volumes were estimated on high-resolution magnetic resonance images and compared across groups, including first-episode subgroups. We used 1- and 2-way analysis of variance designs to compare hippocampal and amygdala volumes across groups, correcting for intracranial volume and covarying for age and sex. We investigated the effects of medication and illness duration on structural volumes. Patients with chronic schizophrenia displayed bilateral hippocampal volume reduction. Patients with first-episode schizophrenia but not schizophreniform psychosis displayed left hippocampal volume reduction. The remaining first-episode subgroups had normal hippocampal volumes compared with controls. Amygdala volume enlargement was identified only in first-episode patients with nonschizophrenic psychoses. Patients at ultra-high risk for psychosis had normal baseline hippocampal and amygdala volumes whether or not they subsequently developed a psychotic illness. Structural volumes did not differ between patients taking atypical vs typical antipsychotic medications, and they remained unchanged when patients treated with lithium were excluded from the analysis. Medial temporal structural changes are not seen until after the onset of a psychotic illness, and the pattern of structural change differs according to the type of psychosis. These findings have important implications for future neurobiological studies of psychotic disorders and emphasize the importance of longitudinal studies examining patients before and after the onset of a psychotic illness.

Working memory and executive functions in transient global amnesia.

Transient global amnesia (TGA) is usually considered to produce a profound impairment of long-term episodic memory, while at the same time sparing working memory. However, this neuropsychological dissociation has rarely been examined in detail. While a few studies have assessed some components of working memory in TGA, the results that have been obtained are far from conclusive. To clarify this issue, we carried out a comprehensive investigation of working memory in 10 patients during a TGA attack. In the first study, we report the results from three patients examined with a battery of neuropsychological tests designed to assess each of the three subcomponents of Baddeley's model of working memory. In a second study, seven different patients underwent neuropsychological investigations that focused specifically on the central executive system, using a protocol derived from a study by Miyake and colleagues. Our findings showed that subcomponents of working memory, such as the phonological loop and visuo-spatial sketch pad, were spared in TGA patients. Specific executive functions that entailed inhibitory control, dual task performance, updating and shifting mechanisms were also found to be normal. However, we found significantly impaired performance for the Brown-Peterson test, and that TGA patients were significantly impaired in the recollection of their episodic memories. They also made reduced numbers of 'remember' compared with 'know' judgments in the episodic memory test several days after TGA. On the basis of our findings, it would appear that the episodic memory deficit during TGA is not related to elementary aspects of executive functioning. Our data also highlight the nature of the cognitive mechanisms involved in the Brown-Peterson task, which may well depend on long-term memory (such as the process of semantic encoding). Lastly, the selective deficit in recollective episodic memories observed in TGA may be principally related to medial temporal lobe abnormalities that have been reported in this syndrome.

A review and new report of medial temporal lobe dysfunction as a vulnerability indicator for schizophrenia: a magnetic resonance imaging morphometric family study of the parahippocampal gyrus.

A central question in schizophrenia research is which brain abnormalities are independent of psychosis and which evolve before and after psychosis begins. This question can be addressed by longitudinal neuroimaging studies beginning in the prodrome, but at present there is only one published study. We reviewed the literature on structural brain imaging in persons with chronic and first episode schizophrenia, nonpsychotic persons at genetic high risk, and persons thought to be at risk for imminent psychosis ("prodromal" persons). Medial temporal lobe (MTL), especially hippocampal, volume alterations are among the most robust brain vulnerabilities for schizophrenia. Because verbal declarative memory (VDM) deficits are prominent and the parahippocampal gyrus (PHG) is considered to be centrally involved with the hippocampus in VDM processing, we analyzed PHG data from a family study of schizophrenia. Patients with schizophrenia and nonpsychotic relatives from "multiplex" families (families with multiple persons with schizophrenia) had significantly smaller right parahippocampal anterior (PHa) volumes than controls. Marginally significant findings were observed for the left PHa. Unexpectedly, relatives from "simplex" families (families with only one person with schizophrenia) had significantly larger PH posterior volumes than controls and did not differ from controls on PHa. Results provide some support for the hypothesis that the vulnerability to schizophrenia includes abnormal volumes of the PHG. These data provide additional support for the hypothesis that some MTL abnormalities in schizophrenia are independent of psychosis, at least in families with presumably high genetic loading. Implications of genetic risk studies for prodromal research are discussed.

A computational approach to memory deficits in schizophrenia

Episodic memory impairment is one of the most reliable neuropsychological findings in schizophrenia. It has been suggested that medial temporal lobe abnormalities in schizophrenia underlie this impairment. We suggest that the specific memory deficits in schizophrenia may be caused by abnormal hippocampo-cortical communication via parahippocampal areas. We have used connectionist simulations to investigate this notion. The simulations involve list learning in a model that incorporates characteristics of the hippocampal and parahippocampal region. In this model context is used to store and recall episodic memories. Reduction of the nodes in the parahippocampal module of the model resulted in a schizophrenia-like memory deficit profile.

Schizotypal personality disorder and MRI abnormalities of temporal lobe gray matter

Background: Structural MRI data indicate schizophrenics have reduced left-sided temporal lobe gray matter volumes, especially in the superior temporal gyrus (STG) and medial temporal lobe. Our data further suggest a specificity to schizophrenia spectrum disorders of STG volume reduction. Interpretation of research studies involving schizophrenics may be complicated by the effects of exposure to neuroleptics and chronic illness. Sharing the same genetic diathesis of schizophrenics, subjects with schizotypal personality disorder (SPD) offer a unique opportunity to evaluate commonalities between schizophrenia and SPD, particularly as SPD subjects are characterized by cognitive and perceptual distortions, an inability to tolerate close friendships, and odd behavior, but they are not psychotic and so have generally not been prescribed neuroleptics nor hospitalized. Evaluation of brain structure in SPD may thus offer insight into the “endophenotype” common to both disorders. In addition, differences between groups may suggest which are the brain structures of schizophrenics that contribute to the development of psychosis. Methods: To test the hypothesis of whether SPD subjects might show similar STG abnormalities, STG and medial temporal lobe regions of interest (ROI) were manually drawn on high resolution coronal MRI 1.5 mm thick slices. Images were derived from 16 right-handed male SPD subjects, without regard to family history, and 14 healthy, right-handed, comparison males who did not differ from the SPD group on parental socio-economic status, age, or verbal IQ. Results: As predicted, SPD subjects showed a reduction in left STG gray matter volume compared with age and gender matched comparison subjects. SPD subjects also showed reduced parahippocampal left/right asymmetry and a high degree of disordered thinking. Comparisons with chronic schizophrenics previously studied by us showed the SPD group had a similarity of left STG gray matter volume reduction, but fewer medial temporal lobe abnormalities. Conclusions: These abnormalities strengthen the hypothesis of a temporal lobe abnormality in SPD, and the similarity of STG findings in schizophrenia and SPD suggest that STG abnormalities may be part of the spectrum “endophenotype.” It is also possible that presence of medial temporal lobe abnormalities may help to differentiate who will develop schizophrenia and who will develop the less severe schizophrenia spectrum disorder, SPD.

Memory, Simple and Complex Language, and the Temporal Lobe

Nineteen patients with intractable temporal lobe epilepsy who underwent anterior temporal lobectomy were given a highly specific memory battery (23 tests) pre- and post- (1 week; 1, 2, and 6 months; 1 and 2 years), resection. Sixteen of 23 tests revealed that memory performance of temporal lobe epilepsy patients was worse than normal controls prior to surgery (p< .001), while the most profound differences were seen in the remembering and generation of inferences from connected discourse. Almost no differences were observed in delayed nonmatching to sample tasks (recognition without language task). MRI results revealed that anterior, middle, and posterior hippocampal abnormality was extensive in 12 of 19 patients, and 12 also showed medial temporal lobe abnormalities and volume loss. Hippocampal damage was negatively correlated with extended delay memory performance for connected discourse: worse performance was associated with greater damage. Few differences in less complex memory performance were observed pre–postsurgery. While ordinary recognition functions were preserved, results demonstrated that dominant medial temporal lobe structures appeared heavily involved in language-generated memory, and hippocampus is heavily implicated in both simple and complex language.

The medial temporal lobe in schizophrenia.

Evidence from diverse avenues of research has highlighted abnormalities in the anatomy, physiology, and function of medial temporal lobe structures in schizophrenia. Clinical similarities between schizophrenia and psychotic disorders associated with temporal lobe lesions have been recognized for decades. Neuropsychological studies have found selective impairments in learning and memory in schizophrenia consistent with medial temporal lobe dysfunction. Neuroimaging studies have identified medial temporal lobe abnormalities that have been correlated with clinical features. Postmortem findings in the hippocampus and entorhinal cortex have included differences in neuron density, size, and arrangement; abnormalities in synapse-related proteins; alterations in monoaminergic and glutamatergic innervation and receptor distribution; and abnormalities in the expression of cytoskeletal proteins. These findings appear most consistent with models of aberrant development of medial temporal lobe structures in schizophrenia.

Normal eye tracking is associated with abnormal morphology of medial temporal lobe structures in schizophrenia

Eye tracking and brain morphology assessed by magnetic resonance imaging were examined in 48 patients in their first episode of schizophrenia and in 15 normal controls. Schizophrenic patients showed higher rates of eye tracking dysfunction and more abnormal brain morphology involving the lateral ventricles, medial temporal lobe (MTL) structures and the frontal-parietal cortex than controls. Enlargement of the lateral ventricles and global rating of abnormal brain morphology were significantly more prevalent in male schizophrenics than female schizophrenics. These findings indicate that abnormalities in a variety of brain regions are present in some schizophrenics during the period shortly after the first hospitalization and could not be a function of treatment or chronic illness. We found no relation between abnormal eye tracking and any single feature of abnormal brain morphology. However, normal eye tracking was significantly associated with MTL abnormalities in schizophrenics, reflecting an inverse association between quality of eye tracking and degree of abnormality in MTL structures. These results suggest that abnormal eye tracking is not mediated by the same processes that lead to structural brain anomalies in schizophrenia.