Language processing and memory in ill and well siblings from multiplex families affected with schizophrenia.

The present study was designed to extend the investigation of genetic factors for schizophrenia to cognitive and linguistic signs of central nervous system dysfunction. Of 51 siblings studied from 19 schizophrenia multiplex families, 37 had a DSM-III-R diagnosis of schizophrenia or related schzophrenia spectrum disorder and 14 were well. Controls were 17 unrelated healthy individuals within the same social class and age range. Subjects were tested on measures of memory, attention, reading and expressive language ability. Schizophrenic and spectrum disorder siblings were significantly more impaired in tests of auditory discrimination and memory than their well siblings or controls and displayed significantly reduced syntactic complexity to their speech. While well siblings did not differ from controls on most measures, some aspects of language complexity were reduced. A familial effect was observed for tests of reading ability, attention, some syntactic measures, and short-term memory, although these were not the measures that distinguished patients from controls in this cohort, the scores were not correlated among the ill sibling pairs, and poorer scores did not segregate with schizophrenia within these families. Thus, while some measures of language, memory and attention are deviant in patients with schizophrenia, they may not be heritable and directly related to the genetics of the disorder. Instead, they may be a manifestation of, rather than a vulnerability to, the illness.

A prospective follow-up study of brain morphology and cognition in first-episode schizophrenic patients: preliminary findings.

Brain morphological abnormalities have been reported in several independent investigations of chronic schizophrenic patients. The present study is a prospective 4-year follow-up of first-episode schizophrenic patients to determine whether some of these abnormalities may be a consequence of regional brain structural change over time after the onset of a first psychotic episode. Whole hemisphere, temporal lobes, superior temporal gyrus, hippocampus, caudate, corpus callosum, and lateral ventricles were measured in a series of MRI scans taken over a 4-year period in 20 patients and five controls. Total volume reduction was noted in both hemispheres to a greater degree in patients than controls. When adjusted for total brain size, left ventricular enlargement occurred in patients, but not controls, over time. These preliminary data suggest that subtle cortical atrophy may be occurring over time after the onset of illness.

Geniculocalcarine hyperintensities on brain magnetic resonance imaging associated with visual hallucinations in the elderly.

Magnetic resonance scans of five geriatric patients presenting with formed visual hallucinations in the absence of other psychopathology were compared with those of 12 healthy elderly subjects for the presence and extent of subcortical and periventricular signal hyperintensity. While the number of discrete brain lesions did not differ between groups, scans from the patient group contained a higher incidence (100% vs. 50%) and greater mean size (11.1 vs. 2.9 mm) of periventricular signal hyperintensity in the posterior region. Peripheral visual acuity was impaired in all of the patients, but cerebrovascular risk factors were not elevated in this group. The authors suggest that structural abnormalities in the area of the primary visual pathway may predispose some older individuals, particularly those with poor peripheral visual acuity, to develop the symptom of visual hallucination.

Ipsilateral subcortical atrophy associated with temporal lobectomy.

Stereologic methods for determining the volume of cerebral structures in vivo via magnetic resonance imaging have identified unilateral hippocampal atrophy among patients with complex partial epilepsy of temporal lobe origin. Metabolic imaging has also identified altered metabolism in temporal as well as extratemporal regions among these patients. As the temporal cortex and subcortical nuclei of the limbic system are reciprocally connected with striatal projection fields, we examined the putamen nuclei for evidence of associated extratemporal volume asymmetry in patients before and after temporal lobectomy. There was no evidence of preoperative putamen volume asymmetry, but a significant postoperative decrement in ipsilateral putamen volume was observed. The magnitude of postsurgical putamen volume asymmetry was correlated with the duration of time since resection. Progressive degeneration of extratemporal projections of the temporal lobe may occur in association with temporal lobectomy.

The pattern of cerebral activity underlying verbal fluency shown by split-dose single photon emission tomography (SPET or SPECT) in normal volunteers.

Uptake of 99mTc-Exametazime, a marker of relative regional cerebral blood flow has been determined with Single Photon Emission Tomography (SPET or SPECT) in 20 healthy, elderly female subjects during neuropsychological challenge. Each subject was studied under basal conditions after injection of 125 MBq 99mTc-Exametazime. Without moving the head of the subject, they were scanned again after injection of 375 MBq 99mTc-Exametazime. The second injection was made in 10 subjects during a test of verbal fluency, usually regarded as a test of the integrity of function of the left frontal cortex. In the other 10 subjects the second injection was made during simple verbalization (counting). This method of splitting the normal full dose of 99mTc-Exametazime allows a novel comparison between basal and active conditions for different brain regions. Verbal fluency was associated with reduced uptake bilaterally in the region of the basal ganglia and in left temporal (peri-sylvian) cortex when compared with calcarine cortex, an unstimulated reference sensory area. By contrast, counting produced relative activation, greatest in frontal and parietal areas. Thus, a clinically relevant neuropsychological test can be characterized metabolically by a pattern of regional brain activity, whose localization cannot readily be predicted from classical studies of brain lesions. Reduction of regional uptake may suggest an important role for deactivation or inhibition of function in human cognition. The involvement of basal ganglia and temporal areas is of particular interest in relation to the investigation of functional psychiatric illness.

Neuroleptic dosage regimens in psychotic inpatients: a retrospective comparison.

The authors examined the inpatient records of consecutively discharged psychotic patients treated with neuroleptics in 1976 and a similar group of patients treated in 1985, when drug regimens at our institution changed considerably. Although demographic parameters were quite similar in the 2 years, the group of patients treated in 1985 received significantly less neuroleptic medication during the course of treatment. Nonetheless, clinical outcome in 1985 was as good as that in 1976. The implications of this result, that low dosages may be as efficacious as high dosages while exposing patients to less neuroleptic medication, are discussed.

Diminished ability to interpret and report internal states after bilateral medial temporal resection: case H.M.

These experiments centered around H.M., a 54-year-old man who became amnesic 27 years ago after a bilateral resection in the medial temporal lobe region for epilepsy. In order to document the clinical reports that he rarely comments on such internal states as pain, hunger, and thirst, his thermal pain perception was examined in relation to his other somatosensory capacities, and his reports of hunger and thirst were assessed before and after meals. In order to investigate the effect of limited memory ability on the reporting of internal states, H.M.'s performance was compared with that of 5 other subjects with global amnesia. The results provided evidence that H.M.'s information about internal states is less available or less accessible than normal and that his impairment is not attributable to his well-documented memory deficit. Instead, it is believed that the bilateral resection of the amygdala accounts for H.M.'s poor appreciation of his internal states.

Thalamocortical mechanisms in odor-guided behavior. I. Effects of lesions of the mediodorsal thalamic nucleus and frontal cortex on olfactory discrimination in the rat.

The "core" subnucleus of the mediodorsal thalamic nucleus (MD) receives direct input from olfactory cortex in the rat. This part of MD projects to the frontal neocortex of the rhinal sulcus (RS), while other parts of the MD project to the anterior medial wall of the neocortex (MW). In this study, rats were tested on odor threshold, detection of specific odors, and three odor discriminations both before and after lesions of MD, MW, RS, or sham lesions. Olfactory threshold and detection ability remained unaffected by any of these lesions; however, subjects with MD and RS lesions were markedly impaired on odor discriminations. Furthermore, subjects were more profoundly impaired when the stimuli to be discriminated were novel or difficult to associate. Thus, MD and its "olfactory" projection target, RS, seem to mediate cognitive, rather than sensory aspects of odor-guided behavior in the rat.