Limbic System Pathology Research Articles

The Management of LG1-Associated Encephalitis that Presents with Acute Impaired Consciousness

Anti-LGI1-associated autoimmune encephalitis is a limbic system pathology characterized by persistent seizures, cognitive and neuropsychiatric symptoms and is treated with immunomodulators depending on the autoimmune etiology.

Prevalence of Asymmetry of Mamillary Body and Fornix Size on MR Imaging

Mamillary body and fornix asymmetry are frequent findings on MR imaging of the brain. We sought to determine the prevalence of asymmetry of the fornix and mamillary body on MR imaging in patients with or without seizures. MR images were retrospectively evaluated for asymmetry of the mamillary body and fornix in 178 patients who had a history of seizures, of whom 35 had suspected mesial temporal sclerosis (MTS). Additionally, 353 patients who had no limbic system pathology were reviewed. All patients were examined with spin-echo MR imaging, consisting of contiguous axial and/or coronal fluid-attenuated inversion recovery (FLAIR), T2-weighted, and sagittal T1-weighted imaging. Additionally, the patients with seizures had oblique coronal 3-mm T2-weighted, FLAIR, and 1.5-mm magnetization-preparation rapid gradient echo scanning through their temporal lobes. In the patients who had no limbic system pathology or seizure history, 6.5% (23/353) had MR imaging evidence of asymmetric mamillary bodies and 7.9% (28/353) had asymmetric fornix size. Asymmetry of the mamillary body and fornix size was found in 37.1% (13/35) and 34.3% (12/35), respectively, of subjects with suggested hippocampal sclerosis. The prevalence of asymmetry of the mamillary body and fornix was statistically significantly higher in the patients with MTS (chi(2) test, P <.0001). Although asymmetry of the mamillary bodies and fornices is highly associated with MTS, this could also be seen as a normal variation or congenital abnormality.

Thalamic Changes in Mesial Temporal Sclerosis: A Limbic System Pathology

Hippocampal abnormalities correlated with mesial temporal sclerosis (MTS) are well documented. MTS may be associated with extrahippocampal anomalies involving limbic structures along a known neuroanatomic pathway (Papez circuit). We report a patient with MTS and thalamic changes. Seizure-related thalamic damage could have been caused by abnormal electric discharges from the mamillary body to the anterior thalamus through the mamillothalamic tract. This suggests that MTS is not limited to the temporal lobe but could represent a limbic system pathology.

Bilateral limbic diffusion abnormalities in unilateral temporal lobe epilepsy

Diffusion tensor magnetic resonance imaging can acquire quantitative information on the microstructural integrity of white matter structures and depict brain connectivity in vivo based on the behavior of water diffusion. Diffusion tensor imaging-derived tractography has been used for virtual dissection of the fornix and cingulum in healthy subjects, but not in patients with temporal lobe epilepsy (TLE). Eight patients with medically intractable TLE and unilateral mesial temporal sclerosis and nine healthy control subjects were imaged using diffusion tensor imaging. Fiber tracking was performed to delineate the fornix and cingulum, which were quantitatively analyzed. Bilateral symmetrical reduction in fractional anisotropy was observed in the fornix of patients with TLE, together with an increase in water mobility perpendicular to the axis of the fibers. The findings in the cingulum are similar to those of the fornix with the exception of significantly increased bulk diffusivity in the latter. We observed strikingly symmetrical bilateral abnormalities of axonal integrity in the fornix and cingulum in a series of patients with unilateral mesial temporal sclerosis. Our findings suggest that TLE with unilateral mesial temporal sclerosis is associated with bilateral limbic system pathology.

A new rat model of the human serial reaction time task: contrasting effects of caudate and hippocampal lesions.

There is often little correspondence between human and animal examples of nondeclarative memory. The serial reaction time task (SRT) is a sequence learning example of human nondeclarative memory that may be suitable for development as an animal model. The SRT is believed to be impaired by basal ganglia, not limbic system damage, but there is uncertainty whether limbic system pathology does in fact leave the SRT unimpaired. We therefore developed a new rat model that closely approximated the human SRT, using intracranial self-stimulation to promote rapid continuous responding to four adjacent nose pokes in a single test session. Intact rats that experienced repeated sequences demonstrated robust interference effects when switched to a random sequence of cued responses (at 4-, 8-, and 12-sequence lengths), unlike intact controls that experienced the random sequences only. The interference effect in the human task is a key measure for nondeclarative sequence learning. Rats with dorsal caudate lesions that experienced massed sequence repetitions showed an interference effect at the four-sequence length only. By contrast, rats with dorsal hippocampal lesions showed an interference effect at all sequence lengths. This new rat SRT model clarifies the basal ganglia-limbic system dichotomy suggested by human work.

Ontogeny of Phencyclidine and Apomorphine-Induced Startle Gating Deficits in Rats

NMDA antagonists and dopamine (DA) agonists produce neuropathological and/or behavioral changes in rats that may model specific abnormalities in schizophrenia patients. In adult rats, NMDA antagonists and DA agonists disrupt sensorimotor gating—measured by prepulse inhibition (PPI)—modeling PPI deficits in schizophrenia patients. In addition, high doses of NMDA antagonists produce limbic system pathology that may model neuropathology in schizophrenia patients. We examined these behavioral and neuropathological models across development in rats. Both the NMDA antagonist phencyclidine (PCP) and the DA agonist apomorphine disrupted PPI in 16 day pups, demonstrating early developmental functionality in substrates regulating these drug effects on PPI. In contrast, PCP neurotoxicity was evident only in adult rats. Brain mechanisms responsible for the PCP disruption of PPI, and PCP-induced neurotoxicity, are dissociable across development.

Cholecystokinin octapeptide rapidly improves schizophrenic symptoms

Evidence is growing that schizophrenic patients show significant structural damage in the temporal lobe limbic system. We review event-related potentials abnormalities (ERPs) in schizophrenia that may be related to dysfunction in this brain region or its inputs; ERPs discussed include the N100/P200, P300 and N400 components. Additional CT and clinical data have led our laboratory to a unifying working hypothesis of the presence of temporal lobe damage in schizophrenics that is evidenced electrophysiologically as ERP alterations, structurally as tissue loss/derangement, and clinicallyas positive symptoms. The final section of this paper presents a new model of at least one form of schizophrenic pathology that, while speculative, incorporates experimentally based data from both our ERP work and from basic cellular physiology and pharmacology. The model proposes that positive symptoms of schizophrenia are related to limbic system pathology and in particular to a dysregulation of the NMDA form of excitatory amino acid transmission, potentiated by stress, and leading to cell damage and death due to ‘excitotoxicity’.

The neuropathology of schizophrenia. Limbic system, brain development and cerebral dominance

Recent development in the neuropathology of schizophrenia focus on three topics: 1. limbic system pathology. 2. disturbed brain development and 3. structural cerebral asymmetry. These topics are reviewed and possible implications for the pathophysiology and etiology of schizophrenia are discussed.

Event-related potentials in schizophrenia: their biological and clinical correlates and new model of schizophrenic pathophysiology

Evidence is growing that schizophrenic patients show significant structural damage in the temporal lobe limbic system. We review event-related potentials abnormalities (ERPs) in schizophrenia that may be related to dysfunction in this brain region or its inputs; ERPs discussed include the N100/P200, P300 and N400 components. Additional CT and clinical data have led our laboratory to a unifying working hypothesis of the presence of temporal lobe damage in schizophrenics that is evidenced electrophysiologically as ERP alterations, structurally as tissue loss/derangement, and clinicallyas positive symptoms. The final section of this paper presents a new model of at least one form of schizophrenic pathology that, while speculative, incorporates experimentally based data from both our ERP work and from basic cellular physiology and pharmacology. The model proposes that positive symptoms of schizophrenia are related to limbic system pathology and in particular to a dysregulation of the NMDA form of excitatory amino acid transmission, potentiated by stress, and leading to cell damage and death due to ‘excitotoxicity’.

The brains of the Vogt collection.

<h3>To the Editor.—</h3> Three years ago, we published an article in theArchivesentitled "Basal Ganglia and Limbic System Pathology in Schizophrenia: A Morphometric Study of Brain Volume and Shrinkage,"¹in which we presented morphometric data for brains of 13 schizophrenics and nine control cases belonging to the Vogt collection, University of Düsseldorf, West Germany. The normal and schizophrenic brains were collected by the Vogts and their coworkers between the years 1928 and 1953, ie, before the application of neuroleptic drug treatment. Recently, I was alerted by Elliot Gershon, MD, of the possibility that the brains investigated in this study came from the Holocaust. In the very extensive clinical records we have from all control cases and schizophrenics, there is a clear documentation that all control cases and schizophrenics had natural causes of death and died before 1935 or after 1945, with the exception of two 39- year-old schizophrenic