Parallel pain processing in freely moving rats revealed by distributed neuron recording

The present study was designed to examine the possible differential roles of the medial and lateral pain systems in pain perception. We used a microwire array recording technique to record the pain-evoked neural activity of multiple neurons in freely moving rats. Noxious radiant heat was delivered to either hind-paw in a randomized order. A total of 256 single units were recorded in primary somatosensory cortex (SI), anterior cingulate cortex (ACC), and medial dorsal (MD) and ventral posterior (VP) thalamus during the painful stimulation. The results showed that SI neurons displayed a strong pain-related excitatory response with short duration and significant contralateral bias; VP had very similar functional patterns to that of SI. This suggested that SI, together with VP, participate in the processing of the sensory-discriminative aspect of pain. In contrast, ACC and MD shared common characteristics of moderate and longer-lasting increase of neural activity, bilateral receptive fields without contralateral preference, as well as the anticipatory response at the start of a painful stimulus, corresponding to the specific role of ACC and MD in the affective-motivational aspects of pain. The results provide an initial demonstration of distributed activity patterns within different pain systems in awake and freely moving rats, hence, providing confirmation of the existence of the dual pain pathways.     

Age-related neurodegenerative changes in the central nervous system of estrogen-deficient follitropin receptor knockout mice

Age-related neurodegenerative conditions are characterized by neuronal death and degeneration that lead to a progressive functional decline. Among the factors influencing degenerative processes during aging are altered levels of neurotrophic ovarian steroid 17beta-estradiol (E2). The follitropin receptor knockout (FORKO) female mouse displays hormonal imbalance characterized by very low levels of circulating E2 and high levels of testosterone. FORKO mice (24 days and 20 months) were used to investigate structural and functional changes in the central nervous system. We now show that the lifelong depletion of the sex hormone E2 in female FORKO mice correlates with abnormal behavior associated with defined alterations in brain morphology early in life, especially in aged animals. Immunohistochemical studies showed significant increases in the size and number of immunoreactive glial fibrillary acidic protein glial cells found in several brain regions (cortex and hippocampus) and a dramatic decline in estrogen receptors alpha and beta in the amygdala of FORKO females. These changes were associated with increased signs of anxiety in these animals. In the present study, we provide evidence that the chronic depletion of sex hormone E2 from early development leads to neural impairments in adult and aged FORKO mice that are associated with hypertrophy of glial cells, cell loss in distinct brain regions, and abnormal behavior. We suggest that the hormonal imbalance found in the female FORKO mouse provides an experimental paradigm for the study of morphological correlates of the behavioral changes that often accompany menopause in women.     

The effect of cingulate lesions on social behaviour and emotion

Functional and structural neuroimaging of the human cingulate cortex has identified this region with emotion and social cognition and suggested that cingulate pathology may be associated with emotional and social behavioural disturbances. The importance of the cingulate cortex for emotion and social behaviour, however, has not been clear from lesion studies. Bilateral lesions in the cingulate cortex were made in three macaques and their social interactions were compared with those of controls. Subsequently, cingulate lesions were made in the three controls and their behaviour was compared before and after surgery. Cingulate lesions were associated with decreases in social interactions, time spent in proximity with other individuals, and vocalisations but an increase in manipulation of an inanimate object. The results are consistent with a cingulate role in social behaviour and emotion.     

Transcingulate approach to lateral ventricle tumors. Technical case report

Surgical experience with treatment of two lateral ventricle tumors using the anterior transcingulate approach demonstrate that this route provides an excellent approach to tumors attached to the lateral wall of the anterior ventricle, without causing gross neurologic deficits, This approach deserves attention as an alternative to the transcallosal approach in selected patients.     

Autoradiographic localization of muscimol and baclofen binding sites in rodent cingulate cortex

Summary The laminar distribution of ³H-muscimol and ³H-baclofen binding was analyzed autoradiographically in areas 29c and 24b of rat cingulate cortex. Muscimol binding was heterogeneous in area 29c with a single peak in layer Ia of 320±26 grains per 2500 m². Binding in deeper layers was between 46% and 71% of that in layer Ia. There was a marked diurnal variation in muscimol binding in area 29c such that binding was elevated by 320% in layer Ia of brains perfused at 2200–0100 versus those perfused at 1100–1400. Muscimol binding in area 24b was uniform across all layers and was higher than that in area 29c except for in layer Ia. Baclofen binding was homogeneous in both areas, but was 120% greater in area 24b than in area 29c, and showed no diurnal variations. To localize muscimol binding sites at the cellular level, two types of lesion experiments were conducted in area 29c. First, ablation of neurons intrinsic to this cortex with the neurotoxin ibotenic acid reduced muscimol binding to homogeneity with a 70% reduction in layer Ia and a 29–42% reduction in deeper layers. Second, knife cuts, which were placed to isolate cingulate cortex from fiber pathways originating extrinsically, increased muscimol binding in all layers except layer Ia. Conversely, knife cuts which isolated superficial from deep layers yielded a marked drop in muscimol binding in all layers. In conclusion, muscimol binding sites are heterogeneously distributed in area 29c with peak binding in layer Ia at night. Since experimental observations suggest that muscimol binding is located on pyramidal cell apical tuft dendrites, it is possible that excitatory thalamic and intrinsic inhibitory input via GABA_A receptors on apical dendrites interact before arriving at the soma.     

Dynamic event-related potentials and rapid source analysis reveals an intermittent short-lasting dysfrontality in schizophrenia

Neuroimaging studies have identified regional brain dysfunctions in schizophrenia, but their dynamic consequences remain unclear. This study reports electrophysiological evaluation of medicated schizophrenic patients during performance of the Wisconsin Card Sorting Test. Using event-related potentials (ERPs), averaged after passing through several band pass filters, and source analysis with variable-resolution brain electrical tomography, cerebral sources were visualized at every latency point of the evoked potential. ERPs which differed from the control group were elicited principally in frontal, central, and parietal regions, within the delta and theta frequency ranges. Significant differences emerged at three different latencies (S1, S2, S3) in frontal/midline areas and at the anterior temporal electrode site T3 for slow potentials. The left occipitoparietal region showed significant differences within the alpha and beta 2 ranges, respectively. Medial fronto-orbital area and anterior cingulate cortex contributed to the development of the frontal ERPs and the lateral inferior frontal area to the temporal (T(3)) evoked-potential, while the precuneus/medial region generated the posterior activity recorded on the scalp. The significant intervals S1 and S3 were synchronous between the medial frontal and lateral inferior frontal region, while in the S2 interval the medial frontal areas were parallel with the precuneus/medial occipitotemporal region. A simultaneous functional imbalance between frontal subregions and posterior areas was uncovered. Here, we show for the first time an intermittent functional deficiency of specific brain areas during task-directed mentation in schizophrenia, which by its brevity is not accessible by neuroimaging methods measuring hemodynamic activity.     

Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins

There are several reports of ultrastructural and protein changes affecting synapses in the anterior cingulate cortex in schizophrenia. Altered cytoarchitecture has also been described in this region in schizophrenia as well as in mood disorders. In this paper we review the literature and present a new study investigating synaptic abnormalities in the anterior cingulate cortex (area 24) in the Stanley Foundation brain series. We used Western blotting to assess four synaptic proteins: synaptophysin, growth-associated protein-43 (GAP-43), complexin I and complexin II, which inform about somewhat different aspects of the synaptic circuitry. Synaptophysin, complexin II and GAP-43 were reduced in bipolar disorder. The decreases correlated with the duration of illness and tended to be greater in subjects without a family history. Complexin II was also reduced in major depression. Complexin I and the housekeeping protein beta-actin did not differ between groups. None of the proteins changed significantly in schizophrenia. The results indicate the presence of a synaptic pathology in the anterior cingulate cortex in mood disorders, especially bipolar disorder. The abnormalities may contribute to the dysfunction of cingulate neural circuits. The loss of synaptophysin is suggestive of decreased synaptic density whilst the decrease in GAP-43 may denote impaired synaptic plasticity and the reduction of complexin II but not complexin I implies that the alterations particularly affect excitatory connections. The reductions may be progressive.     

Stroke lesion in cortical neural circuits and post-stroke incidence of major depressive episode: A 4-month prospective study

Abstract

Objective. Little is known about the relevance of lesion in neural circuits reported to be associated with major depressive disorder. We investigated the association between lesion stroke size in the limbic-cortical-striatal-pallidal-thalamic (LCSPT) circuit and incidence of major depressive episode (MDE). Methods. We enrolled 68 patients with first-ever ischemic stroke and no history of major depressive disorder. Neurological and psychiatric examinations were performed at three time-points. We diagnosed major depressive episode, following DSM-IV criteria. Lesion location and volume were determined with magnetic resonance imaging, using a semi-automated method based on the Brodmann Cytoarchitectonic Atlas. Results. Twenty-one patients (31%) experienced major depressive episode. Larger lesions in the left cortical regions of the LCSPT circuit (3,760 vs. 660 mm³; P = 0.004) were associated with higher incidence of MDE. Secondary analyses revealed that major depressive episode was associated with larger lesions in areas of the medial prefrontal cortex including the ventral (BA24) and dorsal anterior cingulate cortex (BA32) and subgenual cortex (BA25); and also the subiculum (BA28/36) and amygdala (BA34). Conclusions Our findings indicate that depression due to stroke is aetiologically related to the disruption of the left LCSPT circuit and support the relevance of the medial prefrontal cortex dysfunction in the pathophysiology of depression.     

Benzodiazepine binding sites: Localization and characterization in the limbic system of the rat brain

The distribution of benzodiazepine binding sites was analysed in limbic structures of rat brain by quantitative radioautography of brain sections incubated with 3H-flunitrazepam (3H-FLU). Quantitative estimation of the binding parameters was made in each range of postero-anterior sections taken. Distribution of 3H-FLU binding sites was found to be rather homogeneous in most of the structures examined but there were regional differences which resulted from variations in the densities of sites rather than in their affinities. A particular distribution pattern of 3H-FLU binding sites was observed in the cingulate cortex contrasting with the homogeneous postero-anterior distribution measured in other cortical areas in the same slices. A significantly greater density of sites was found in the anterior part of the structure as compared to the posterior part. This difference, which corresponds to a change in the density of sites without alteration of their apparent affinity and occurs at a precise anatomical level, is discussed with reference to the anatomical organization of this brain structure and to its possible functional implications.     

心理性勃起功能障碍的功能磁共振成像研究

目的研究正常成年男性和心理性勃起功能障碍(ED)患者中枢神经系统的激活情况,探讨两者中枢神经系统兴奋性的差异。方法心理性ED患者12例,均为右利手,无任何精神及其他器质性疾病史。对照组为12例年龄性别相匹配的健康志愿者,均为右利手,无任何性功能障碍史,无器质性病变和其他可能影响脑结构和功能的不良生活习惯和药物滥用史。用色情录像和非色情录像刺激,每个录像片段60s,每个色情和非色情录像片段之间间隔12s。用GE1.5TMR扫描系统进行BOLD-fMRI扫描,头线圈。用3DSPGRT1WI序列进行全脑轴位扫描作为全脑解剖图。结果在视觉和听觉相关色情录像的刺激下,正常男性与心理性ED患者双侧小脑半球、小脑蚓部、双侧额下回、双颞叶、双侧扣带回、角回、左侧杏仁核、丘脑、海马、中脑及桥脑背侧均被激活;与正常男性相比,心理性ED患者双侧前扣带回激活的范围更大,两者的激活体积存在显著性差异(t=4.026,P<0.001),心理性ED患者平均激活体积为(979.64±25.33)mm3,正常男性为(795.43±20.35)mm3。结论边缘系统、脑干、丘脑等在调节男性性行为中起着重要的作用,心理性勃起功能障碍患者可能存在潜在的病因。