Immunolesion of the cholinergic basal forebrain :effects on functional properties of hippocampal and septalneurons

Deficits in cholinergic function have been documented in a variety of brain disordersincluding Alzheimers Disease and, to a lesser extent, in normal ageing. In the present article, wehave reviewed our recent findings on the effects of the loss of basal forebrain cholinergic neuronson the functional properties of the septohippocampal pathway. In vivo and ex vivo investigations were performed in rats following basal forebrain cholinergic lesion with thespecific immunotoxin 192 IgG-saporin. Our results suggest a significant contribution ofcholinergic neurons in the rhythmically bursting activity recorded within the medial septum. Inaddition, they give evidence that acetylcholine may tonically decrease the glutamatergic synapticresponses in the hippocampus whereas the GABAergic mediated inhibitory potentials are notaffected. The possible contribution of these cholinergic mechanisms in the age-related functionalalterations of the septohippocampal activity is discussed.     

MRI study of posterior fossa structures and brain ventricles in bipolar patients

Previous brain imaging studies have suggested anatomical abnormalities in posterior fossa structures and brain ventricles in bipolar patients. Such abnormalities could possibly be implicated in the pathophysiology of bipolar disorder. Twenty-two DSM-IV bipolar outpatients (mean age±S.D.=36±10 years) and 22 healthy controls (mean age±S.D.=38±10 years) underwent an 1.5T MRI (3D-gradient echo-imaging SPGR), performed in the coronal plane (TR=25 ms, TE=5 ms, slice THICKNESS=1.5 mm). The brain structures of interest were traced blindly with a semi-automated software. No significant differences were found between bipolar patients and healthy controls for any posterior fossa measures, or for measures of third or lateral ventricles (MANOVA, age covariate, P>0.05). Age was directly correlated with 3rd ventricle volumes in bipolar patients (Pearson correlation COEFFICIENT=0.458, P=0.032), but not in healthy controls (Pearson correlation COEFFICIENT=0.313, P=0.155). There was a significant direct correlation between the number of prior illness episodes and right lateral ventricle volumes (Partial correlation COEFFICIENT=0.658, P=0.011). Familial patients had smaller left and right cerebellar hemispheres and total vermis volumes, and larger left lateral ventricle volumes compared with non-familial ones (MANOVA, age covariate, P<0.05). In this preliminary study, we were not able to replicate previous findings of abnormalities in cerebellum or brain ventricles in bipolar individuals. However, there were suggestions that abnormalities in cerebellum, vermis, and lateral ventricle sizes may be present in familial cases of the disorder, which should be further examined in future studies with larger patient samples.     

Saccadic ping pong gaze in coma

In this report, we describe the peculiar eye movements of a young man who became comatose after a head injury. The eyes moved rhythmically from one side to another, without pausing in the lateral positions. This phenomenon has been described as "ping pong gaze" (PPG), referring to short-cycling periodic alternating gaze with smooth eye deviations. In the present patient, however, a saccadic type of PPG could be confirmed by oculography. Possible clinical and pathophysiological implications are discussed.     

Functional magnetic resonance imaging in schizophrenia: cortical response to motor stimulation

Previous functional magnetic resonance imaging (fMRI) studies suggest that motor system abnormalities are present in schizophrenia. However, these studies have often produced conflicting or ambiguous findings. The purpose of this study was to ascertain whether activation differences could be identified in stable schizophrenic patients on the basis of BOLD measures in two motor regions, the primary motor cortex, Brodmann area 4 (BA4) and the premotor and supplementary motor area, Brodmann area 6 (BA6). Twenty-one schizophrenic patients and 21 healthy control subjects were studied with BOLD fMRI methods during a sequential finger tapping task. Statistical parametric maps were generated for each subject, and anatomic regions were automatically defined using an anatomic atlas. Compared with controls, the schizophrenic patients showed a significant reduction in contralateral activation for both BA4 and BA6 (P<0.001), and in ipsilateral activation in BA4 (P=0.007) and BA6 (P=0.002). In healthy controls, the coactivation in the ipsilateral cortex is reduced in comparison with the contralateral cortex for right and left handed tasks. In BA4, this reduction is significant for right (P=0.007) and left (P=0.003) finger tapping. Similar results were obtained for BA6. Further analyses are necessary to evaluate the activation in other motor system regions.     

Perseverative structuring of responses by schizophrenic and affective disorder patients

Some theoretical implications from a CNS stimulation model of psychosis were tested by analysing the response patterns of schizophrenic (N=34), affective disorder patients (N=18), schizoid personality disorder patients (N=9), neurotic patients (N=9) and normal controls (N=34) on a visual two-choice task with reinforcement. The subjects were required to press a left and right button in order to cause a cross (+) to appear on the monitor screen above one of the buttons. Certain subsequences of right and left presses were required in order for the cross to appear, and a coin-reinforcement was delivered on a variable-ratio schedule with respect to the cross condition. An analysis of structured responding in categories: one-side >6, switching (RLRL), 2-1 switching (RRL) and double alternations (RRLL), revealed that the schizophrenic and affective disorder patients were significantly more perseverative in these response categories than normal controls, schizoid or neurotic patients. The last three subject groups were not significantly different from each other. The majority of the schizophrenics and all four manic patients showed the highest percentage of responding in one sided responses >6, switching and 2-1 switching. Normal control subjects showed more varied response patterns with responses in double, triple and quadruple alternations and other combinations. The results are seen to support a CNS stimulation, behavioral competition model of psychosis.     

Right prefrontal activation produced by arterial baroreceptor stimulation: a PET study.

This study was performed to test the hypothesis of greater right hemispheric involvement in the processing of baroreceptor stimuli. Carotid sinus baroreceptors were stimulated by rhythmically decreasing air pressure in a neck chamber, and under control conditions the thorax was stimulated in a similar manner. Changes in regional cerebral blood flow (rCBF) were measured by PET. Baroreceptor stimulation resulted in rCBF increase in the right anterior-inferior prefrontal cortex (Brodmann areas (BA) 10/44/47) and bilaterally in BA 6/8. We conclude that in at least some stages of baroreceptor information processing the right hemisphere plays a greater role than the left hemisphere.     

Vasculitis of peripheral nerve and skeletal muscle: Clinicopathological correlation and immunopathic mechanisms

In order to elucidate the pathogenesis of vasculitis in muscle and nerve a clinicopathological study was performed in 23 patients. The patients could be classified into three groups: I multisystem vasculitis (n = 4); II multisystem disease with vasculitis detectable in nerve, muscle, or both (n = 11); and III localised disease with vasculitis in nerve, muscle, or both (n = 8). Ten of 23 patients had vasculitis in both muscle and nerve biopsies; 6 from groups I and II, and 4 from group III indicating that vasculitis confined to muscle and nerve represents a distinct clinicopathological entity. The neuromuscular manifestations in the 23 patients were sensori-motor polyneuropathy (n = 9), mononeuritis multiplex (n = 6), mononeuropathy (n = 3), proximal myopathy (n = 4), and muscle tenderness without weakness (n = 1). Sensori-motor polyneuropathy was found in 8/11 patients from group II, and mononeuritis multiplex in5/8 patients from group III. Immunotypic analysis, and immunofluorescence patterns indicate that the pathogenesis of vasculitis in muscle and nerve is heterogeneous and suggest that cell mediated and immune complex mechanisms predominate and may be operative in all three patient groups, with an antibody-mediated humoral mechanism in some patients with paraproteinaemic states (group II).     

Phosphorus-31 magnetic resonance brain spectroscopy of children at risk for a substance use disorder: Preliminary results

The purpose of this exploratory investigation was to evaluate the heuristic potential of ³¹P magnetic resonance spectroscopy (MRS) in elucidating a neurobiologic component of the liability for a substance use disorder (SUD). We investigated ³¹P MRS spectra employing chemical shift imaging (CSI) derived from four distinct anatomic brain locations (i.e. frontal, occipital, right parietal, left parietal) in three groups of peripubertal children who are hypothesized to be at increasing levels of familial SUD risk. Specifically, we studied children with a positive paternal family history of SUD and a disruptive behavior disorder (DBD) diagnosis (SUD+/DBD+; n=10), in contrast to those with a positive paternal SUD history in the absence of other psychopathology (SUD+/DBD−; n=13) and matched control children from normal families (SUD−/DBD−; n=13). In addition, we examined neurocognitive tests of our subjects to determine any associations between cognitive capacities with regional ³¹P MRS spectra. The highest-risk sample (SUD+/DBD+) demonstrated a diminished proportion of phosphodiesters confined to the right parietal voxel. This right parietal phosphodiester proportion correlated only with the Information Scale score on a standard intelligence test for children. This suggested a relationship between general learning ability and motivation for academic achievement and right parietal physiology in the highest-risk sample. Variations in synaptic pruning could account for this observation.     

Visual acuity and hemispheric asymmetries in pigeons

Pigeons and domestic chicks tested under monocular conditions in pattern distinction tasks generally show higher discrimination performances with the right eye seeing. At least two different mechanisms could mediate this asymmetry: the dominance of the right eye could either be due to hemispheric differences in the cognitive operations performed during these tasks, or may reflect a lateralization in the spatial frequency discrimination capacity of the left and the right eye system. The aim of the present study was to decide between these two hypotheses. Therefore nine adult homing pigeons (Columba livia) were tested with the left or the right eye seeing in a visual acuity task using high-contrast square wave gratings. Visual acuity, defined as the spatial frequency at which the psychometric function crossed the 75% correct line was virtually identical for the two eyes with 6.6 for the left and 6.4 c/deg for the right eye. Thus, visual lateralization as demonstrated in various pattern discrimination tasks seems not to depend on asymmetries in acuity but probably reflects hemispheric differences in the visual processing mode.     

Episodic memory in patients with focal frontal lobe lesions

Episodic memory was evaluated in patients with unilateral, frontal lobe damage and matched controls using a list- method directed forgetting paradigm. Directed forgetting instructions (forget vs. remember the word), encoding instructions (learn vs. judge the word) and test format (recall vs. recognition) were manipulated in order to explore how variations in encoding and retrieval affect verbal memory. Controls demonstrated a normal directed forgetting effect in recall and less directed forgetting in recognition. Patients with left frontal (LF) damage did not show directed forgetting in either recall or recognition and patients with right frontal (RF) damage showed directed forgetting in recall, but not in recognition. Furthermore, the LF group recalled significantly more of the judge than learn words, suggesting that this group's performance improves by providing them with an encoding strategy. Conversely, the RF group's performance did not depend on encoding instructions and their recognition memory was impaired relative to the other two groups when they were instructed to judge the words. Our results suggest that (a) patients with LF damage show deficits in the rehearsal of to-be-remembered information, (b) whereas patients with RF damage show impairments in recognition memory. Furthermore, both patient groups show a lack of directed forgetting when familiarity-based processes guide performance.     

Interaction between local and global visual orientation signals in subjects with unilateral brain lesions

Two groups of right handed, male stroke patients with lesions confined to the left (LH, n=10) or right (RH, n=10) cerebral hemisphere were tested on visual vertical judgements with isolated line stimuli and lines presented in the context of a tilted frame. The psychometric functions indicate no reduction in the precision of orientation judgements among the brain injured subjects when compared with age-matched controls (n=6) with cardiovascular disease, but the systematic shift in perceived vertical induced by a tilted visual frame was significantly larger for RH-subjects than for LH-subjects or controls (mean illusion 6 and 3° respectively). The results are interpreted within the “two visual systems”-theory of the rod-and-frame effect and it is suggested that the right hemisphere is dominantly involved in the integration of visual and vestibular input.     

Lateralization of predator-evasion response in a teleost fish (Girardinus falcatus)

Evidence of lateral asymmetries in the direction of turning during escape behaviour in a species of poeciliid fish, Girardinus falcatus, is reported. When repeatedly faced with a simulated predator (in five successive sessions, spaced 7 days apart), immature Girardinus falcatus exhibited a significant population bias to turn right on the first session and a progressive bias to turn left in subsequent sessions. Mature Girardinus were then tested to check whether the shift in the direction of turn with repeated sessions depended on maturation or habituation. It was found that adult Girardinus showed a slight population bias to turn right in the first session and a strong subsequent bias to turn left after repeated sessions. The implications of these findings to our current understanding of the evolution of brain lateralization are discussed.     

Inter-hemispheric interaction facilitates face processing

Many recent studies have revealed that interaction between the left and right cerebral hemispheres can aid in task performance, but these studies have tended to examine perception of simple stimuli such as letters, digits or simple shapes, which may have limited naturalistic validity. The present study extends these prior findings to a more naturalistic face perception task. Matching tasks required subjects to indicate when a target face matched one of two probe faces. Matches could be either across-field, requiring inter-hemispheric interaction, or within-field, not requiring inter-hemispheric interaction. Subjects indicated when faces matched in emotional expression (Experiment 1; n=32) or in character identity (Experiment 2; n=32). In both experiments, across-field performance was significantly better than within-field performance, supporting the primary hypothesis. Further, this advantage was greater for the more difficult character identity task. Results offer qualified support for the hypothesis that inter-hemispheric interaction is especially advantageous as task demands increase.     

Positron emission tomography in male violent offenders with schizophrenia

The FDG PET brain scans from 31 offenders with schizophrenia and schizoaffecive disorder from a maximum security mental hospital were compared with those of normal controls (N = 6) in terms of relative FDG uptake in a range of regions covering frontal and temporal regions. The patient sample was divided into those who had a history of repetitive violent offending (RVO, N = 17) and those without a repetitive violent history (NRVO, N = 14) according to the violence rating of their pre-admission convictions. Reduced FDG uptake was noted at both the right and left anterior inferior temporal (R and L AIT) regions in NRVOs but only at LAIT in RVOs. NRVOs had significantly lower FDG uptake at RAIT than RVOs. The findings suggest that metabolic changes at AIT may be related to different patterns of violent offending in patients with schizophrenia.     

Septo-hippocampal neurons in the rat: Further study of their physiological and pharmacological properties

Medial septal-nucleus of the diagonal band of Broca area (MS-nDBB) neurons, identified by their antidromic response to the electrical stimulation of the fimbria and/or hippocampus, were studied in the rat under various conditions of anesthesia. These septo-hippocampal neurons (SHNs) were classified into 4 groups on the basis of: (i) their antidromic latency; and (ii) the presence or absence of a rhythmically bursting pattern of spontaneous discharge. The rhythmically bursting activity (43.5% of the SHNs) was highly dependent on the anesthetic conditions. The groups of SHNs differed in their mean conduction velocity and rate of spontaneous activity. In contrast, irrespective of their classification in a particular group, the large majority of the SHNs could be excited by the iontophoretic application of cholinergic agonists. Beside the SHNs, two other populations of MS-nDBB neurons could be identified by electrical antidromic stimulation: neurons projecting to the amygdala (Am) and neurons projecting through the medial forebrain bundle (MFB). Half of the MS-nDBB neurons projecting to Am were also antidromically driven from the fimbria. The axonal branch projecting to Am had a slower conduction velocity than that projecting to hippocampus. In contrast MS-nDBB neurons projecting through the MFB were never antidromically driven from the fimbria, although they received orthodromic inputs. They had a slower conduction velocity than the other groups of MS-nDBB neurons.     

帕金森病伴冻结步态患者的静息态磁共振研究

目的 探讨帕金森病患者冻结步态与静息态脑功能成像之间的关系。方法 2021年9月-2022年9月于襄阳市第一人民医院就诊的28例伴有冻结步态的帕金森病患者以及32例不伴有冻结步态的帕金森病患者接受了全脑结构像和静息状态下的功能磁共振扫描,计算并比较2组全脑百分率振幅(Percent amplitude of fluctuation,PerAF)的差异,同时探寻2组被试者间差异脑区与大脑其他区域功能连接性(Functional connectivity,FC)的不同。结果 在静息状态下与非冻结组比较,冻结组双侧额中回的PerAF信号显著减低,同时冻结组快速动眼期(Rapid eye movement,REM)睡眠行为异常筛查量表得分分别与左侧额中回(r=0.436,P=0.020)和右侧额中回(r=0.453,P=0.015)的显著区域的PerAF信号均呈正相关。此外,右侧脑干与双侧额中回之间的功能连接性增加,且右侧脑干区域与脚桥核部分重合;同时左侧额上回与额中回之间的功能连接性显著增加,且两者之间的FC信号与新冻结步态问卷得分呈显著的负相关(r=-0.510,P=0.006)。结论 冻...     

The human striatum in schizophrenia. I. Increase in overall relative striatal volume in schizophrenics

Postmortem volumetry of the human striatum and its subdvisions (putamen, n.caudatus, n.accumbens) was performed on serial coronal sections of complete hemispheres. Both hemispheres of 9 male schizophrenic patients younger than 65 years were closely matched in age with the hemispheres of 9 male control individuals. All obtained values were corrected with individual and region-specific shrinkage factors; the intrarater reliability was 1% difference in volume. The absolute striatal volume was significantly correlated with the volume of the hemisphere (r = 0.931; P = 0.0003^***). Reflecting differences in the hemispheric volumes of the schizophrenic and the control group, the absolute striatal volume consequently did not differ both groups (P > 0.55). However, we found a clear increase in the volume density (i.e. the relative striatal portion of the hemisphere; the relative striatal volume) in the schizophrenic group, highly significant on both sides (P = 0.003^** for the right striatum, P = 0.002^** for the left striatum). The increase in volume density concerned both the putamen (P = 0.003^** for the right side) and the n.caudatus/n.accumbens (P = 0.01^* for the right side). Discrepant volumetric results of previous authors who compared only absolute volume values in samples not matched for identical hemispheric volume could thus be explained by this high positive correlation with the hemispheric volume. Since exact matching for identical hemispheric volume is not feasible and examined groups will never be large enough to rule out the influence of the hemispheric volume, the determination of relative volumes (i.e. volume densities) seems to be advantageous for future volumetric studies.     

Neisseria sicca meningitis following intracranial hemorrhage and ventriculostomy tube placement

A normal component of the flora of the oropharynx, Neisseria sicca was first isolated in 1906 and has since been reported as a rare cause of various human infections including endocarditis, pneumonia, sinusitis, sepsis, and urethritis. We report the case of a 44-year-old African-American female with a history of hypertension who presented with complaints of right frontal headache, nausea, photophobia, and vomiting. A computed tomography scan of the patient's brain showed a large subarachnoid hemorrhage, and an arteriogram confirmed a large posterior communicating artery aneurysm. A ventriculostomy tube was placed, and the patient subsequently developed an elevated temperature and elevated white blood cell count. Cerebrospinal fluid studies showed elevated protein and glucose levels and cultures positive for N. sicca. This is only the seventh reported case of culture-proven meningitis related to N. sicca, and the first reported case associated with intracranial hemorrhage and ventriculostomy tube placement.     

Is testing for inherited coagulation inhibitor deficiencies in young stroke patients worthwhile?

Objective. To test the hypothesis that in patients under age 50, with a first, arterial, ischemic cerebral infarct, whose family history and medical history do not suggest an inherited coagulation inhibitor deficiency, the yield of a laboratory search for these disorders will be low. Materials and methods. In 55 such patients under age 50, we systematically searched for deficiencies of protein C, protein S, and antithrombin III. Results. No abnormalities of protein C or antithrombin III were found. One patient had a deficiency of protein S, which was most likely acquired rather than inherited. Conclusions. In patients who lack clinical features of a prothrombotic state, the yield of testing for protein C, S and AT III deficiency is likely to be low.