Limbic pathology in schizophrenia: the entorhinal region--a morphometric study

The volume of the entorhinal region is significantly reduced in postmortem brains of schizophrenics compared with controls (p less than 0.017). In addition, a significant reduction of neurons (p less than 0.017), but no significant increase in absolute glial cell numbers, is found. These results are consistent with the hypothesis that structural changes in the medial temporal lobe of schizophrenics may be developmental in origin.     

Thalamic burst firing — a neuronal code for temperature information?

A total number of 840 neurons was extracellularly recorded from the rat's thalamus (ventro-basal complex, VB, and nucleus posterior, NPT) and from the midbrain (raphe nuclei, MB) while thermal stimuli were given to the hindlimbs, scrotal skin, and the tongue. Of all neurons found, 407 exhibited burst patterns; the highest percentage of burst cells was found in VB (50–85%) whereas only 10–15% of the NPT and MB neurons were burst cells. About one-half of all burst cells responded to peripheral temperature stimulation by changing their mean firing rate.The question dealt with in this paper is whether burst firing gives a more detailed information on thermal sensations than mean firing rate alone. Therefore, 40 burst cells (20 of which were thermoresponsive according to their mean firing rate) were further analyzed by evaluating several burst parameters such as burst frequency, number of spikes/burst and bursting index. However, when mean discharge rate did not respond to skin temperature, the burst parameters were not correlated with the stimulus, either. Hence it is concluded that the burst firing in the thalamic neurons investigated does not provide an additional detailed information on skin temperature.     

Gyrification in first-episode schizophrenia: a morphometric study.

BACKGROUND: A number of studies have found localized differences in the appearance and extent of cortical folding between the brains of schizophrenic patients and healthy control subjects. This study aimed to determine whether there are differences in gyral folding in schizophrenia by conducting a detailed analysis of magnetic resonance images. METHODS: Thirty-four young adults in their first episode of schizophrenia and 36 age-matched, healthy control subjects were studied. The gyrification index (GI), the ratio of the inner and outer cortical surface contours, was measured bilaterally on every second 1.88-mm image slice in four specifically defined lobar regions. Independent t tests were conducted for each region, followed by post hoc analysis of variance testing for the effects of laterality. RESULTS: Gyrification index values between groups corresponded closely in the occipital and parietal regions but were significantly increased in the right temporal lobe of the schizophrenic patients. Calculating the GI by two different methods (used in previous studies) notably affected results. Gyrification index values were significantly lateralized in the frontal and temporal regions, with no group x side interactions. CONCLUSIONS: Differences in the temporal lobe GI of first-episode schizophrenic patients might reflect disturbed or abnormal connectivity. Further examination of specific sources of sulco-gyral difference in schizophrenia is required to clarify this.     

Differentiation in the immunocytochemical features of intrinsic and cortically projecting neurons in the rat claustrum — combined immunocytochemical and axonal transport study

Retrograde axonal transport method of the fluorescent tracer FluoroGold (FG) was combined with immunocytochemistry to investigate the occurrence of nitric oxide synthase (NOS), somatostatin (SOM), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) in both intrinsic and cortically projecting neurons of the rat claustrum. Only NOS was detected in both the scattered projecting neurons and internal neurons of the claustrum. Approximately 20% of NOS-immunoreactive neurons in the claustrum were also retrogradely labeled with FG after tracer injections into the frontal cortex. The other substances were exclusively confined to the population of interneurons, which mainly displayed an oval, round or fusiform shape and a medium size. Apart from the neuronal somata, the proximal parts of the dendritic arborization were clearly visible. The immunoreactive neurons were randomly distributed in the claustrum and their neuronal size and shape did not differ in the various parts of the studied structure. Co-localization of NOS and SOM or NOS and NPY was reported. In conclusion, SOM, VIP and NPY do not appear to play a significant role in the claustro-cortical projection but are most probably involved in modulation and information transfer in the claustrum. The appearance of NOS in both cortically projecting and intrinsic neurons of the claustrum may be indicative of a fundamentally different role in the functioning of the claustro-cortical loop.     

Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage

The volume of several parts of the basal ganglia and of the limbic system was measured by planimetry of myelin-stained serial sections in postmortem brains of 13 schizophrenic patients and nine control cases. The medial limbic structures of the temporal lobe (amygdala, hippocampal formation, and parahippocampal gyrus) and the pallidum internum were significantly smaller in the schizophrenic group, whereas the pallidum externum showed only a modest trend toward volume reduction. The volumes of the putamen, nucleus caudatus, nucleus accumbens, and the bed nucleus of the stria terminalis did not differ between patients and controls. The volume reductions of the limbic temporal structures and of the pallidum internum of schizophrenics are interpreted as degenerative shrinkages of unknown etiology.     

Late paraphrenia — a follow-up study

We report a 3.7 year follow-up study carried out on 42 patients with an original diagnosis of late paraphrenia who had had a CT scan and simple tests of cognition in addition to an assessment by means of the Geriatric Mental State Schedule. Mortality was found to be no different than in a control group. Patients showed improvement in target symptoms but exhibited a good deal of residual morbidity, particularly of motor and cognitive function. Cognitive performance, which was previously mildly impaired, showed some futher deterioration, usually falling short of clear-cut dementia. Ventricular size on the CT scan was not a predictor of outcome. The article highlights the organic substrate of late paraphrenia but suggests that the cerebral changes are relatively subtle and slowly progressive.     

Thalamic and amygdala-hippocampal volume reductions in first-degree relatives of patients with schizophrenia: an MRI-based morphometric analysis.

BACKGROUND: Schizophrenia is characterized by subcortical and cortical brain abnormalities. Evidence indicates that some nonpsychotic relatives of schizophrenic patients manifest biobehavioral abnormalities, including brain abnormalities. The goal of this study was to determine whether amygdala-hippocampal and thalamic abnormalities are present in relatives of schizophrenic patients. METHODS: Subjects were 28 nonpsychotic, and nonschizotypal, first-degree adult relatives of schizophrenics and 26 normal control subjects. Sixty contiguous 3 mm coronal, T1-weighted 3D magnetic resonance images of the brain were acquired on a 1.5 Tesla magnet. Cortical and subcortical gray and white matter and cerebrospinal fluid (CSF) were segmented using a semi-automated intensity contour mapping algorithm. Analyses of covariance of the volumes of brain regions, controlling for expected intellectual (i.e., reading) ability and diagnosis, were used to compare groups. RESULTS: The main findings were that relatives had significant volume reductions bilaterally in the amygdala-hippocampal region and thalamus compared to control subjects. Marginal differences were noted in the pallidum, putamen, cerebellum, and third and fourth ventricles. CONCLUSIONS: Results support the hypothesis that core components of the vulnerability to schizophrenia include structural abnormalities in the thalamus and amygdala-hippocampus. These findings require further work to determine if the abnormalities are an expression of the genetic liability to schizophrenia.     

Cholecystokinin peptides, dopamine and schizophrenia — A review

1. CCK-IR is co-localized with DA in some DA neurons projecting to limbic structures. The extent of the co-localization is species dependent. The co-localization of CCK and DA is of interest in view of the DA hypothesis of schizophrenia and the putative role of limbic dysfunction in the pathophysiology of this disorder.

2. In animals biochemical, electrophysiological and behavioural studies point to an interaction between CCK and DA. Whereas some investigations point to an inhibitory effect on DA function, which would be compatible with a potential antischizophrenic action, others point to an enhancement or no effect. CCK peptides show a neuroleptlc-like profile in several screening tests for neuroleptics but not in all studies.

3. In man there is endocrinological evidence for an inhibitory effect of CCK-33 and CCK-8 on DA function. However, alternate explanations are possible. CSF CCK-IR is unchanged or decreased in schizophrenia. Autopsy investigations have shown significant decreases, increases or no change in brain CCK-IR concentrations and a decrease in CCK-33 binding in schizophrenia. Eight of 11 clinical trials with CER, CCK-8 or CCK-33 have shown a therapeutic effect in schizophrenia; only two of these eight trials have been double-blind studies. The three controlled investigations which have shown no effect have used only small patient populations. None of the trials have used an active placebo.

4. It is difficult to reconcile the apparent long duration of antipsychotic activity with the short half-life of the peptides and problems of the peptides in crossing the blood brain barrier. Despite these apparent anomalies information to date is sufficiently impressive to warrant further detailed investigation of CCK-DA-interactions and the evaluation of the clinical effects of a variety of CCK peptides and related compounds, natural and synthetic, which may more easily cross the blood brain barrier and which may show regional selectivity in site of action in brain.     

Voxel-based morphometric multisite collaborative study on schizophrenia

Regional gray matter (GM) abnormalities are well known to exist in patients with chronic schizophrenia. Voxel-based morphometry (VBM) has been previously used on structural magnetic resonance images (MRI) data to characterize these abnormalities. Two multisite schizophrenia studies, the Functional Biomedical Informatics Research Network and the Mind Clinical Imaging Consortium, which include 9 data collection sites, are evaluating the efficacy of pooling structural imaging data across imaging centers. Such a pooling of data could yield the increased statistical power needed to elucidate effects that may not be seen with smaller samples. VBM analyses were performed to evaluate the consistency of patient versus control gray matter concentration (GMC) differences across the study sites, as well as the effects of combining multisite data. Integration of data from both studies yielded a large sample of 503 subjects, including 266 controls and 237 patients diagnosed with schizophrenia, schizoaffective or schizophreniform disorder. The data were analyzed using the combined sample, as well as analyzing each of the 2 multisite studies separately. A consistent pattern of reduced relative GMC in schizophrenia patients compared with controls was found across all study sites. Imaging center-specific effects were evaluated using a region of interest analysis. Overall, the findings support the use of VBM in combined multisite studies. This analysis of schizophrenics and controls from around the United States provides continued supporting evidence for GM deficits in the temporal lobes, anterior cingulate, and frontal regions in patients with schizophrenia spectrum disorders.     

Thalamic morphology in schizophrenia and schizoaffective disorder

Background

Biomarkers are needed that can distinguish between schizophrenia and schizoaffective disorder to inform the ongoing debate over the diagnostic boundary between these two disorders. Neuromorphometric abnormalities of the thalamus have been reported in individuals with schizophrenia and linked to core features of the disorder, but have not been similarly investigated in individuals with schizoaffective disorder. In this study, we examine whether individuals with schizoaffective disorder have a pattern of thalamic deformation that is similar or different to the pattern found in individuals with schizophrenia.

Method

T1-weighted magnetic resonance images were collected from individuals with schizophrenia (n = 47), individuals with schizoaffective disorder (n = 15), and controls (n = 42). Large-deformation, high-dimensional brain mapping was used to obtain three-dimensional surfaces of the thalamus. Multiple analyses of variance were used to test for group differences in volume and measures of surface shape.

Results

Individuals with schizophrenia or schizoaffective disorder have similar thalamic volumes. Thalamic surface shape deformation associated with schizophrenia suggests selective involvement of the anterior and posterior thalamus, while deformations in mediodorsal and ventrolateral regions were observed in both groups. Schizoaffective disorder had distinct deformations in medial and lateral thalamic regions.

Conclusions

Abnormalities distinct to schizoaffective disorder suggest involvement of the central and ventroposterior medial thalamus which may be involved in mood circuitry, dorsolateral nucleus which is involved in recall processing, and the lateral geniculate nucleus which is involved in visual processing.     

Cerebral cladosporiosis — a neuropathological and microbiological study

Cerebral cladosporiosis is a rare mycotic infection of the brain. So far only 21 culture-proven cases of cerebral cladosporiosis have been listed in literature (Fetter et al. 1967, Fetter and Klintworth, 1978). In view of the rarity of this mycotic infection and its clinical importance we report two cases of cultureproven cerebral cladosporiosis. They presented as meningoencephalitis with extensive areas of haemorrhagic infarctions of frontoparietal lobes. Both patients were middle-aged farmers from Karnataka State, South India. The clinical, neuropathological and mycological features are presented.     

A three-dimensional morphometric study of craniofacial shape in schizophrenia

BACKGROUND: Subtle dysmorphogenesis of the craniofacial region constitutes important corroborating evidence of the neurodevelopmental origins of schizophrenia. Advances in facial visualization now allow for three-dimensional anthropometric evaluations of potentially greater discriminatory power in examining the complex geometric relationships of facial topography. METHOD: Sixty-five anthropometrically derived landmarks were identified from three-dimensional facial images collected from 14 patients with schizophrenia and 11 comparison subjects, imaged with a high-resolution, portable laser scanner. RESULTS: Using the Procrustes morphometric approach for shape analysis, the difference in mean shapes was highly significant, with patients exhibiting superoinferior elongation of the face. CONCLUSIONS: The topography of craniofacial anomalies in schizophrenia is not random and points to midline deformation.     

Hippocampal pathologic findings in schizophrenia. A morphometric study

We studied hippocampal sections from 13 schizophrenic patients, 9 nonschizophrenic patients, and 16 normal controls from the Yakovlev brain collection. The three groups were similar in age, gender distribution, and brain weight. Most patients had never received neuroleptics, and the two patient groups had had similar types of leukotomies. We used a semiautomated image analysis system to compute volume and pyramidal-cell density in each of the four sectors of the cornu ammonis, Ca1 through CA4, in the right and left hippocampi. Sections from schizophrenic patients had almost consistently the lowest volume and pyramidal-cell density in all sectors. The differences were greatest in left CA4, with schizophrenic patients having significantly lower pyramidal-cell density than normal controls and significantly lower volume than leukotomy controls. Our findings confirm the results of several recent studies showing hippocampal pathologic features in schizophrenia. Our study suggests, however, that the hippocampal neuropathologic findings in schizophrenia may be more subtle and more localized than those reported previously.     

Response of cortical and pial arteries to changes of arterial CO2 tension in rats — a morphometric study

Changes of the internal (d) and external diameter (D) of cerebral arteries in response to the various levels of arterial pCO₂ were studied in anesthetized rats, of which brains were frozen in situ with isopentane cooled in liquid nitrogen. The parietal cortex was fixed with osmium tetroxide and stained with toluidine blue for morphometry of the cerebral arteries.In comparison with control animals (pCO₂ = 41.2mm Hg), the d/D ratio in animals with hypercapnia (pCO₂ = 69.9mm Hg) was increased by 11.7% in the pial arteries and 7.9% in the cortical arteries, indicating vasodilatation. In contrast, the d/D ratio in those with hypocapnia (pCO₂ = 27.7mm Hg) was decreased by 6.2% and 13.0%, respectively, indicating vasoconstriction. There was a significant linear correlation existing between the d/D ratio of either pial or cortical arteries and pCO₂. It is concluded that the cortical arteries respond to changes of arterial pCO₂ in a similar manner to the pial arteries.     

Thalamic morphometric changes induced by first‐person action videogame training

Cross‐sectional data suggest videogaming as promoting modifications in perceptual and cognitive skills of players, as well as inducing structural brain changes. However, whether such changes are both possible after a systematic gaming exposure, and last beyond the training period, is not known. Here, we originally quantified immediate and long‐lasting cognitive and morphometric impact of a systematic gaming experience on a first‐person shooter (FPS) game. Thirty‐five healthy participants, assigned to a videogaming and a control group, underwent a cognitive assessment and structural magnetic resonance imaging at baseline (T0), immediately post‐gaming (T1) and after  3 months (T2). Enhancements of cognitive performance were found on perceptual and attentional measures at both T1 and T2. Morphometric analysis revealed immediate structural changes involving bilateral medial and posterior thalamic nuclei, as well as bilateral superior temporal gyrus, right precentral gyrus, and left middle occipital gyrus. Notably, significant changes in pulvinar volume were still present at T2, while a voxel‐wise regression analysis also linked baseline pulvinar volume and individual changes in gaming performance. Present findings extend over the notion that videogame playing might impact cognitive and brain functioning in a beneficial way, originally showing long‐term brain structural changes even months after gaming practice. The involvement of posterior thalamic structures highlights a potential link between FPS games and thalamo‐cortical networks related to attention mechanisms and multisensory integration processing.     

Prenatal ontogeny of substance P-like immunoreactivity in the parabrachial nucleus of the human fetus — an immunocytochemical study

Using an immunocytochemical method, the prenatal ontogeny of substance P-like immunoreactivity (SP-LI) was demonstrated in the parabrachial nucleus (PB) of human fetus, fetal age (menstruation age) 11.5 to 40 weeks. The time of initial appearance of SP-LI in the human brainstem PB was between fetal age 11.5 weeks and 16 weeks. While the fetus grew, the density of SP-LI fibers and terminals in the human fetus brainstem PB increased constantly from fetal age 16 weeks to 40 weeks. These findings indicate that substance P (SP) might play an important role in the human parabrachial nucleus development and in its functional establishment during the prenatal period.