Paracingulate sulcus asymmetry; sex difference, correlation with semantic fluency and change over time in adolescent onset psychosis.

The left paracingulate sulcus (PCS) is longer than the right and the adjacent cortex is activated by the generation of words. In adult patients with chronic schizophrenia the anatomical asymmetry is reduced. In 35 controls and 38 adolescents with schizophrenia or schizoaffective disorder (mean age = 16 years) we found that semantic verbal fluency correlated with leftward PCS asymmetry in controls but not in patients. At intake, PCS length did not differ between patients and controls, but at follow-up (13 controls, 10 patients, mean age = 18 years) PCS asymmetry (comprising both increasing left and decreasing right length) increased significantly, the increase was greater in males than in females, and there was a trend for a diagnosis * sex * side * time interaction such that in controls leftward PCS asymmetry increased, while in patients of both sexes there was convergence toward symmetry. Thus sulcal anatomy develops differentially in the two sexes during adolescence, and the pattern of asymmetric sex-dependent change over time may distinguish patients with psychosis from controls. Greater change in asymmetry during adolescence may explain earlier age of onset in males and greater deficits in verbal fluency.

Dopamine: 50 years in perspective.

The discovery of dopamine as a neurotransmitter in brain by Arvid Carlsson approximately 50 years ago, and the subsequent insight provided by Paul Greengard into the cellular signalling mechanisms triggered by dopamine, gained these researchers the Nobel Prize for Medicine in 2000. Dopamine research has had a greater impact on the development of biological psychiatry and psychopharmacology than work on any other neurotransmitter. Neuropsychological views of the role of dopamine in the CNS have evolved from that of a simple reward signal to a more complex situation in which dopamine encodes the importance or 'salience' of events in the external world. Hypofunctional dopamine states underlie Parkinson's disease and attention deficit hyperactivity disorder, and there is increasing evidence for dopamine hyperactivity in schizophrenia. Some of the medicines that are most widely used in psychiatry, such as L-DOPA, methylphenidate and neuroleptic drugs, act on dopaminergic mechanisms.

Peter H. Kelly, Paul W. Seviour and Susan D. Iversen (1975) "Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum" [Brain Res. 94 (3) 507-522].

UNLABELLED: Eight µg of 6-hydroxydopamine (6-OHDA) injected bilaterally into the nucleus accumbens septi (NAS) or the caudate nucleus of the rat resulted in 79% and 50% depletion of endogenous dopamine (DA) at these respective sites. Fourteen days after the injection a low dose of amphetamine failed to induce the characteristic locomotor response in the NAS-lesioned rats but did so in the caudate-lesioned animals. By contrast the caudate lesion, but not the NAS lesion, abolished intense forms of stereotyped behaviour induced by higher doses of amphetamine. Both lesioned groups exhibited supersensitivity to the dopamine agonist, apomorphine; the NAS group showed enhanced locomotor activity and the caudate group enhanced stereotyped behaviour. The block of amphetamine locomotion and the enhanced response to apomorphine were maximal around 14 days after the operation and gradually attenuated up to 90 days. There is evidence that remaining DA levels in the NAS are greater at 90 than at 14 days postoperatively. Thus recovery of behavioural effects correlated with an increase in the remaining levels of DA in the NAS. ARTICLE ABSTRACT: The author reviews the impact of a paper published 40 years ago which was among the first to localise the different behavioural actions of amphetamine in rats to specific brain regions, using local 6-hydroxydopamine-induced lesions of dopaminergic pathways This article is part of a Special Issue entitled SI:50th Anniversary Issue.

Borderline personality disorder, impulsivity, and the orbitofrontal cortex.

OBJECTIVE: Orbitofrontal cortex lesions produce disinhibited or socially inappropriate behavior and emotional irregularities. Characteristics of borderline personality disorder include impulsivity and affective instability. The authors investigated whether aspects of borderline personality disorder, in particular impulsivity, are associated with orbitofrontal cortex dysfunction. METHOD: Measures of personality, emotion, impulsivity, time perception, sensitivity to reinforcers, and spatial working memory were administered to patients with borderline personality disorder (N=19), patients with orbitofrontal cortex lesions (N=23), patients with lesions in the prefrontal cortex but not in the orbitofrontal cortex (N=20), and healthy comparison subjects (N=39). RESULTS: The patients with orbitofrontal cortex lesions and the patients with borderline personality disorder performed similarly on several measures. Both groups were more impulsive and reported more inappropriate behaviors, borderline personality disorder characteristics, and anger and less happiness than the two comparison groups, and both groups were less open to experience and had a faster perception of time (underproduced time) than the healthy comparison subjects. The patients with orbitofrontal cortex lesions and the borderline personality disorder patients performed differently on other measures. The borderline personality disorder patients were less extraverted and conscientious and more neurotic and emotional than all other groups. Patients with orbitofrontal cortex lesions had deficits in reversing stimulus-reinforcer associations and a faster perception of time (overestimated time) than the healthy comparison subjects. CONCLUSIONS: Orbitofrontal cortex dysfunction may contribute to some core characteristics of borderline personality disorder, in particular impulsivity. Other characteristics of borderline personality disorder, such as high levels of emotionality and personality irregularities, do not appear to be related to the type of dysfunction produced by orbitofrontal cortex damage. The similarities and differences found between the borderline personality disorder patients and the patients with orbitofrontal cortex lesions may lead to a better understanding of the etiology of borderline personality disorder and the functions of the orbitofrontal cortex.

Amphetamine promotes task-dependent recovery following focal cortical ischaemic lesions in the rat.

This study investigated the effect of amphetamine (AMP) on skilled forelimb use following focal cortical ischaemic lesions in the rat. Unilateral lesions were produced by a novel method of intracortical microinjection of endothelin-1 (ET-1), intended to principally target the forelimb representation zone in primary motor-primary somatosensory cortex. Lesions were placed in the hemisphere contralateral to the preferred limb and produced deficits in skilled forelimb use on two tasks: the paw reach (PR) test and the foot fault (FF) test. Beginning on post-lesion day (D) 2, animals received injections of 2 mg/kg AMP and were injected every third day until D26. Animals were tested both during, and 24 h after, AMP administration. AMP facilitated recovery of skilled forelimb use on the PR test when assessed during drug-free test sessions. No such effect was seen on the FF test. These results demonstrate that sub-acute administration of AMP following a unilateral focal ischaemic lesion of FL can facilitate task-dependent recovery of skilled forelimb use in the rat. They also demonstrate that different behavioural tasks measuring superficially similar behavioural outputs may show different sensitivities to such drug effects.

The effects of intracortical endothelin-1 injections on skilled forelimb use: implications for modelling recovery of function after stroke.

Different methods of inducing experimental brain lesions can result in distinct neuropathological sequelae. This could be of consequence in attempts to establish animal models of recovery of function following stroke, as differences in the progression of experimental lesion pathology may have an impact on the magnitude and rate of recovery of function observable with any particular lesioning method. In the present study, a novel method of producing a focal ischaemic lesion by intracortical microinjection of endothelin-1 (ET-1) was compared with excitotoxic (microinjection of quinolinic acid) and mechanical (aspiration) lesioning procedures. Lesions were unilateral and were targeted at the forelimb representation zone in sensorimotor cortex. It was found that all three types of lesion had an essentially identical effect with regard to reaching accuracy in a paw-reaching task. All lesioned animals displayed a similar, significant long-term deficit in reaching accuracy and limited degree of recovery relative to sham animals. Off-line analysis of the performance of animals during post-lesion week 9 indicated that animals in each lesion group also displayed a similar deficit. The current results suggest that the spontaneous behavioural consequences of a unilateral lesion of FL in the rat appear to be independent of the nature of lesion production. However, the increased face validity of an ET-1-induced lesion, coupled with the ease of control of lesion placement and extent offered by this technique make for a potentially important animal model for research into drug effects on recovery of function following stroke.

The Placing Test: preliminary investigations of a quick and simple memory test designed to be sensitive to pre-dementia Alzheimer's disease but not to normal ageing.

The medial temporal lobe (MTL) memory system is damaged early in Alzheimer's disease. Cognitive tests designed to help diagnose the disease must detect dysfunction in this system, but must also be insensitive to the cognitive slowing that characterizes normal ageing. On the assumption that the MTL system forms new memories by binding together the many informational aspects of events into units, The Placing Test was designed to index this function by measuring the ability to remember associations between faces and their locations. The influence of normal ageing was minimized by using procedures that compensate for the difficulties in learning and retrieval caused by the cognitive slowing of normal ageing. In two experiments The Placing Test was administered as part of a battery of neuropsychological tests to a group of healthy older people. In both studies, performance in The Placing Test correlated significantly with other measures of memory, but had weaker associations than standard memory measures with other types of cognitive function. The Placing Test appeared not to be biased by age, education or gender, although a larger sample is needed to verify this. A final study examined the performance of 16 patients with suspected Alzheimer's disease. These patients showed clear impairment in The Placing Test, with 81% scoring below the 5th percentile, despite the majority having normal MMSE scores. It is concluded that The Placing Test provides a quick, simple and sensitive measure of memory that has potential to be useful in routine diagnostic investigations for Alzheimer's disease.

Sustained attention deficit in bipolar disorder.

BACKGROUND: Recovery in bipolar disorder is central to its definition but is rarely complete. Previous work has suggested that neuropsychological impairment persists during the euthymic state but has been confounded partly by mild affective symptoms in remitted patients. AIMS: To characterise neuropsychological functioning in the euthymic phase of bipolar disorder with an emphasis on tasks of executive functioning. METHOD: Thirty euthymic patients with bipolar disorder were compared with thirty healthy controls on neuropsychological tasks differentially sensitive to damage within prefrontal cortex. RESULTS: Bipolar I patients were impaired on tasks of attentional set shifting, verbal memory and sustained attention. Only sustained attention deficit survived controlling for mild affective symptoms. This deficit was related to progression of illness, but was none the less present in a subgroup of patients near illness onset. CONCLUSIONS: Sustained attention deficit may represent a neuropsychological vulnerability marker for bipolar disorder, providing a focus for further understanding of the phenotype and analysis of the neuronal networks involved.

Testing for dual brain processing routes in reading: a direct contrast of chinese character and pinyin reading using FMRI.

Chinese offers a unique tool for testing the effects of word form on language processing during reading. The processes of letter-mediated grapheme-to-phoneme translation and phonemic assembly (assembled phonology) critical for reading and spelling in any alphabetic orthography are largely absent when reading nonalphabetic Chinese characters. In contrast, script-to-sound translation based on the script as a whole (addressed phonology) is absent when reading the Chinese alphabetic sound symbols known as pinyin, for which the script-to-sound translation is based exclusively on assembled phonology. The present study aims to contrast patterns of brain activity associated with the different cognitive mechanisms needed for reading the two scripts. fMRI was used with a block design involving a phonological and lexical task in which subjects were asked to decide whether visually presented, paired Chinese characters or pinyin "sounded like" a word. Results demonstrate that reading Chinese characters and pinyin activate a common brain network including the inferior frontal, middle, and inferior temporal gyri, the inferior and superior parietal lobules, and the extrastriate areas. However, some regions show relatively greater activation for either pinyin or Chinese reading. Reading pinyin led to a greater activation in the inferior parietal cortex bilaterally, the precuneus, and the anterior middle temporal gyrus. In contrast, activation in the left fusiform gyrus, the bilateral cuneus, the posterior middle temporal, the right inferior frontal gyrus, and the bilateral superior frontal gyrus were greater for nonalphabetic Chinese reading. We conclude that both alphabetic and nonalphabetic scripts activate a common brain network for reading. Overall, there are no differences in terms of hemispheric specialization between alphabetic and nonalphabetic scripts. However, differences in language surface form appear to determine relative activation in other regions. Some of these regions (e.g., the inferior parietal cortex for pinyin and fusiform gyrus for Chinese characters) are candidate regions for specialized processes associated with reading via predominantly assembled (pinyin) or addressed (Chinese character) procedures.