Conditional associative learning in drug-free schizophrenic patients

The performance on spatial and nonspatial associative learning tasks was tested in a sample of male drug-free DSM III-diagnosed schizophrenic patients and in a closely matched normal control group. Schizophrenics showed a worse performance on both versions of the task, but especially on the nonspatial one. A significant correlation was observed between some indices of the nonspatial task and the scores on two subscales (affective flattening and anhedonia) of the scale for the assessment of negative symptoms by Andreasen. These results are consistent with the hypothesis of a dysfunction of dorsolateral prefrontal cortex in schizophrenia and with the postulated linkage between such dysfunction and negative schizophrenic symptomatology.     

An electron microscope observation of the right and the two left portions of the habenular nuclei of the frog.

The right dorsal habenula (RDH), the left dorsal habenula, lateral portion (LDH-LP) and the left dorsal habenula, medial portion (LDH-MP) of the adult frog Rana esculenta have been studied by the electron microscope with the use of three types of fixatives: osmium tetroxide, aldehydes and potassium permangarate. The study has demonstrated in the habenulae of both sides a variety of syraptic vesicles, special synaptic patterns (en passant, serial, axo-somatic) containing small spherical transparent vesicles, never mixed with other types of vesicles, and large pale processes containing big granules. However, a particular type of synaptic vesicles characterized by small clear spherical vesicles with a tiny dark granule revealed by potassium permanganate fixition has been demonstrated only in the neuropil of the LDH and not in the RDH. Further, a peculiar type of intracytoplasmic inclusion appears in the form of myelin-like and crystal-like formations only in the LDH-MP. On the basis of these consistent ultrastructural differences, the dorsal habenular nuclei of the frog can be considered as composed of three individual nuclei, each with its own morphological characterization, dislocated, for some unknown reason, one on the right and two on the left side of the epithalamus. The results suggest that the LDH-MP is a nucleus metabolically different from the others and that the projections to the dorsal habenular nuclei are different on the right and left sides of the brain.     

Lateralization patterns of verbal stimuli processing assessed by reaction time and event-related potentials in schizophrenic patients

Event-related potentials (ERPs), reaction time (RT), number of errors and number of omissions were recorded by using a visual target detection paradigm in which consonant pairs were presented in a central and in a lateral condition. Fourteen DSM III drug-free schizophrenics and 19 healthy subjects took part in the study. All of them were male and right-handed. Independent principal component analysis and varimax rotation were performed for each condition. Separate ANOVAs were performed on factor scores computed for each rotated principal component. In the central condition, schizophrenic patients showed a reduction of the late positive complex (LPC) peak with respect to normal controls, and this reduction was associated with a predominant negative symptomatology. No pattern of lateral asymmetry was found in either group for behavioural and ERP measures. For the lateral condition, a significant advantage of the right visual field (RVF) presentation (shorter RT and larger LPC peak for RVF stimuli) was observed in normal subjects, while no visual field effect on these two measures was detected in schizophrenics. Significant differences were found between the two groups on both behavioural and ERP measures for the RVF only. Furthermore, two ERP components showed a marked advantage of the left visual field in the patient group, associated with a predominance of positive symptoms in the clinical picture.     

Lateralization patterns of event-related potential and performance indices in schizophrenia: relationship to clinical state and neuroleptic treatment

In a previous study we assessed lateralization patterns of verbal stimuli processing, by means of behavioural and neurophysiological measures, in a sample of drug-free schizophrenics and one of normal controls. The main findings obtained were the following: (1) a right visual field (RVF) advantage on reaction time (RT) and late positive complex (LPC) peak of the ERPs in normal subjects but not in schizophrenics; (2) a left visual field (LVF) significant advantage on P360 and slow wave (SW) amplitude in schizophrenics but not in controls; (3) a significantly longer RT and smaller P360 and SW for RVF stimuli in schizophrenics as compared to normals; (4) a significant contralateral effect of visual field on N180 at both the left and the right parietal site in normal controls and only at the right parietal site in schizophrenics. As a further step of this investigation we re-tested 9 schizophrenics after 28 days of haloperidol treatment. The post-treatment lateralization pattern of verbal stimuli processing was characterized by a RVF advantage on LPC peak amplitude and no visual field effect on P360 and SW, resembling the normal group pattern. Moreover, the N180 amplitude was found to be reduced. Relationships between lateralization pattern and clinical picture changes induced by haloperidol treatment are discussed.     

Cobalt injected into the right and left fasciculi retroflexes clarifies the organization of this pathway

A cobaltic lysine complex was injected separately into the right and left fasciculi retroflexes of the frog. This tracing technique labeled, in a Golgi-like manner, the neurons which initiate the fasciculi retroflexes and revealed details of their morphological pattern. The fasciculi retroflexes originate from various neurons distributed in the diencephalon and mesencephalon, but their main source is the habenular nuclei. In the frog there are dorsal and ventral habenulae which are homologous to the medial and lateral habenulae, respectively, of mammals. In the frog the dorsal habenulae are strikingly asymmetric. Our study shows that the fasciculus retroflexus is composed of several compact separated bundles of fibers and that the fibers originating from the dorsal habenular nuclei project to the interpeduncular nucleus, while those originating from the ventral habenular nuclei project beyond the interpeduncular nucleus, but so far we have not been able to show the exact site of their termination. The labeling of cells within the interpeduncular nucleus raises the possibility that the habenulo-interpeduncular tract is reciprocal in function. The finds support our previously reported hypothesis on the theoretical interpretation of the functional circuitry of the frog habenulo-interpeduncular system.     

Lithium and melatonin: morphological modifications induced in frog retina pigment screening

Pigment screening (PS) is a phenomenon occurring in the retina of lower vertebrates, which consists in the dispersion, induced by the light, of melatonin granules into processes of the pigment epithelium which extend between photoreceptors, and in the aggregation, induced by the dark, of the same granules within the cell bodies of the pigment epithelium. It has been hypothesized that this phenomenon might be modulated by melatonin, which is present not only in the pineal but also in the retina, and whose retinal content is high in the dark and low in the light. In the present study we demonstrate that a single intraperitoneal injection of lithium chloride affects in a peculiar way PS of light-adapted frogs and of frogs subjected to natural day/night conditions, but not that of dark-adapted frogs. The implications of this findings are briefly discussed, also in view of the reported effect of lithium on the 24-hour rhythm of retinal melatonin, and of the possible relationship between this effect and the altering properties of lithium on other biological rhythms.