Neuropsychiatric Disorders Due to Limbic Encephalitis: Immunologic Aspect

Limbic encephalitis (LE) is a rare cause of encephalitis presenting as an acute and subacute onset of neuropsychiatric manifestations, particularly with memory deficits and confusion as core features, along with seizure occurrence, movement disorders, or autonomic dysfunctions. LE is caused by neuronal antibodies targeting the cellular surface, synaptic, and intracellular antigens, which alter the synaptic transmission, especially in the limbic area. Immunologic mechanisms involve antibodies, complements, or T-cell-mediated immune responses in different degree according to different autoantibodies. Sensitive cerebrospinal fluid markers of LE are unavailable, and radiographic findings may not reveal a typical mesiotemporal involvement at neurologic presentations; therefore, a high clinical index of suspicions is pivotal, and a neuronal antibody testing is necessary to make early diagnosis. Some patients have concomitant tumors, causing paraneoplastic LE; therefore, tumor survey and treatment are required in addition to immunotherapy. In this study, a review on the molecular and immunologic aspects of LE was conducted to gain awareness of its peculiarity, which we found quite different from our knowledge on traditional psychiatric illness.

The subiculum and its role in focal epileptic disorders

The subicular complex (hereafter referred as subiculum), which is reciprocally connected with the hippocampus and rhinal cortices, exerts a major control on hippocampal outputs. Over the last three decades, several studies have revealed that the subiculum plays a pivotal role in learning and memory but also in pathological conditions such as mesial temporal lobe epilepsy (MTLE). Indeed, subicular networks actively contribute to seizure generation and this structure is relatively spared from the cell loss encountered in this focal epileptic disorder. In this review, we will address: (i) the functional properties of subicular principal cells under normal and pathological conditions; (ii) the subiculum role in sustaining seizures in in vivo models of MTLE and in in vitro models of epileptiform synchronization; (iii) its presumptive role in human MTLE; and (iv) evidence underscoring the relationship between subiculum and antiepileptic drug effects. The studies reviewed here reinforce the view that the subiculum represents a limbic area with relevant, as yet unexplored, roles in focal epilepsy.

A Simple Pattern of Movement Is Not Able to Inhibit Experimental Pain in FM Patients and Controls: An sLORETA Study

Motor cortex activation seems to induce an analgesic effect on pain that would be different between patients with fibromyalgia (FM) and control subjects. This study was conducted to analyze the changes of the laser-evoked potentials (LEPs) induced during a finger tapping task in the FM patients and the controls employing a multi-dipolar analysis according to Standardized low resolution brain electromagnetic tomography (sLORETA) method. The LEPs from 38 FM patients and 21 controls were analyzed. The LEPs were recorded while subjects performed a slow and a fast finger tapping task. We confirmed that the difference between N1, N2 and P2 wave amplitudes between conditions and groups was not significant. In control subjects, the fast finger tapping task induced a modification of cortical source activation in the main areas processing laser stimulation from the moving hand independently from the movement speed. In summary, a simple and repetitive movement is not able to induce consistent inhibition of experimental pain evoked by the moving and the not moving hand in each group. It could interfere with LEP sources within the limbic area at least in control subjects, without inhibit cortical responses or explain the different pattern of motor and pain interaction in FM patients.

Positive Emotions from Brain Injury: The Emergence of Mirth and Happiness

Brain injury can result in an increase in positive emotions. We describe a 63-year-old man who presented with a prominent personality change after a gunshot wound to the head. He became “content,” light-hearted, and prone to joking and punning. Prior to his brain injury, he suffered from frequent depression and suicidal ideation, which subsequently resolved. Examination showed a large right calvarial defect and right facial weakness, along with memory impairment and variable executive functions. Further testing was notable for excellent performance on joke comprehension, good facial emotional recognition, adequate Theory of Mind, and elevated happiness. Neuroimaging revealed loss of much of the right frontal and right anterior lobes and left orbitofrontal injury. This patient, and the literature, suggests that frontal predominant injury can facilitate the emergence of mirth along with a sense of increased happiness possibly from disinhibited activation of the subcortical reward/pleasure centers of the ventral striatal limbic area.

Higher neuronal discharge rate in the motor area of the subthalamic nucleus of Parkinsonian patients

In Parkinson's disease, pathological synchronous oscillations divide the subthalamic nucleus (STN) of patients into a dorsolateral oscillatory region and ventromedial nonoscillatory region. This bipartite division reflects the motor vs. the nonmotor (associative/limbic) subthalamic areas, respectively. However, significant topographic differences in the neuronal discharge rate between these two STN subregions in Parkinsonian patients is still controversial. In this study, 119 STN microelectrode trajectories (STN length > 2 mm, mean = 5.32 mm) with discernible oscillatory and nonoscillatory regions were carried on 60 patients undergoing deep brain stimulation surgery for Parkinson's disease. 2,137 and 2,152 multiunit stable signals were recorded (recording duration > 10 s, mean = 21.25 s) within the oscillatory and nonoscillatory STN regions, respectively. Spike detection and sorting were applied offline on every multiunit stable signal using an automatic method with systematic quantification of the isolation quality (range = 0–1) of the identified units. In all, 3,094 and 3,130 units were identified in the oscillatory and nonoscillatory regions, respectively. On average, the discharge rate of better-isolated neurons (isolation score > 0.70) was higher in the oscillatory region than the nonoscillatory region (44.55 ± 0.87 vs. 39.97 ± 0.77 spikes/s, N = 665 and 761, respectively). The discharge rate of the STN neurons was positively correlated to the strength of their own and their surrounding 13- to 30-Hz beta oscillatory activity. Therefore, in the Parkinsonian STN, beta oscillations and higher neuronal discharge rate are correlated and coexist in the motor area of the STN compared with its associative/limbic area.

Associations between brain morphology and outcome in schizophrenia in a general population sample

ObjectiveTo analyse associations between brain morphology and longitudinal and cross-sectional measures of outcomes in schizophrenia in a general population sample.MethodsThe sample was the Northern Finland 1966 Birth Cohort. In 1999–2001, structural brain MRI and measures of clinical and functional outcomes were analysed for 54 individuals with schizophrenia around the age of 34. Sex, total grey matter, duration of illness and the use of antipsychotic medication were used as covariates.ResultsAfter controlling for multiple covariates, increased density of the left limbic area was associated with less hospitalisations and increased total white matter volume with being in remission. Higher density of left frontal grey matter was associated with not being on a disability pension and higher density of the left frontal lobe and left limbic area were related to better functioning. Higher density of the left limbic area was associated with better longitudinal course of illness.ConclusionsThis study, based on unselected general population data, long follow-up and an extensive database, confirms findings of previous studies, that morphological abnormalities in several brain structures are associated with outcome. The difference in brain morphology in patients with good and poor outcomes may reflect separable aetiologies and developmental trajectories in schizophrenia.

Neurocognitive processing of esophageal central sensitization in the insula and cingulate gyrus

The cingulate and insular cortices are parts of the limbic system that process and modulate gastrointestinal sensory signals. We hypothesized that sensitization of these two limbic area may operate in esophageal sensitization. Thus the objective of the study was to elucidate the neurocognitive processing in the cingulate and insular cortices to mechanical stimulation of the proximal esophagus following infusion of acid or phosphate buffer solution (PBS) into the esophagus. Twenty-six studies (14 to acid and 12 to PBS infusion) were performed in 20 healthy subjects (18–35 yr) using high-resolution (2.5 × 2.5 × 2.5 mm3 voxel size) functional MRI (fMRI). Paradigm-driven, 2-min fMRI scans were performed during randomly timed 15-s intervals of proximal esophageal barostatically controlled distentions and rest, before and after 30-min of distal esophageal acid or PBS perfusion (0.1 N HCl or 0.1 M PBS at 1 ml/min). Following distal esophageal acid infusion, at subliminal and liminal levels of proximal esophageal distentions, the number of activated voxels in both cingulate and insular cortices showed a significant increase compared with before acid infusion ( P < 0.05). No statistically significant change in cortical activity was noted following PBS infusion. We conclude that 1) acid stimulation of the esophagus results in sensitization of the cingulate and insular cortices to subliminal and liminal nonpainful mechanical stimulations, and 2) these findings can have ramifications with regard to the mechanisms of some esophageal symptoms attributed to reflux disease.

Changes in the Regional Cerebral Perfusion After Eye Movement Desensitization and Reprocessing: A SPECT Study of Two Cases

Eye movement desensitization and reprocessing (EMDR) has emerged as a promising new treatment for trauma and other anxiety-based disorders. However, the neurobiological mechanism of EMDR has not been well understood. This study reports changes in the resting regional cerebral blood flow after successful EMDR treatment in two patients with posttraumatic stress disorder (PTSD). Brain 99mTc-ECD-SPECT (Technetium 99m–ethyl cysteinate dimmer–single photon emission computerized tomography) was performed before and after EMDR, and, in addition, a pre- and posttreatment comparison was made with 10 non-PTSD participants as a control group. After EMDR, cerebral perfusion increased in bilateral dorsolateral prefrontal cortex and decreased in the temporal association cortex. The differences between participants and normal controls also decreased. Changes appeared mainly in the limbic area and the prefrontal cortex. These results are in line with current understanding of neurobiology of PTSD. EMDR treatment appears to reverse the functional imbalance between the limbic area and the prefrontal cortex.