Taste laterality in the split brain.

Two patients with corpus callosum resection, one complete and the other sparing the genu and the rostrum, were tested for discrimination of three basic taste stimuli (sour, bitter, salty) applied to the right or left sides of the tongue. Responses were made by pointing with either hand to written words or images of visual objects corresponding to the stimuli, a language-based discrimination. In both patients, response accuracy was significantly above chance for both hemitongues but there was a significant advantage for the left side. Reaction time was shorter for left stimuli than for right stimuli but the difference was not significant. Eight normal controls matched for age with the patients performed equally well with right and left hemitongue stimuli and so did a third callosotomy patient with sparing of the posterior callosum, including the splenium. Tactile and visual tests showed that the left hemisphere was responsible for language-based responses in the first two patients. The results confirm and extend previous findings in another callosotomy patient, indicating that: (i) taste information from either side of the tongue can reach the left hemisphere in the absence of the corpus callosum; (ii) the ipsilateral input from the tongue to the left hemisphere is more potent functionally than the contralateral input and (iii) in the normal brain, the corpus callosum, specifically its posterior part including the splenium, appears to equalize the effects of the ipsilateral and contralateral gustatory inputs on the left hemisphere. Taken together with evidence about lateralized taste deficits following unilateral cortical lesions, the results also suggest that the gustatory pathways from tongue to cortex are bilaterally-distributed with an ipsilateral predominance that may be subject to individual variations.

Posterior corpus callosum and interhemispheric transfer of somatosensory information: an fMRI and neuropsychological study of a partially callosotomized patient.

Interhemispheric somatosensory transfer was studied by functional magnetic resonance imaging (fMRI) and neuropsychological tests in a patient who underwent resection of the corpus callosum (CC) for drug-resistant epilepsy in two stages. The first resection involved the anterior half of the body of CC and the second, its posterior half and the splenium. For the fMRI study, the hand was stimulated with a rough sponge. The neuropsychological tests included: Tactile Naming Test (TNT), Same-Different Recognition Test (SDRT), and Tactile Finger Localization Test (intra- and intermanual tasks, TFLT). The patient was studied 1 week before and then 6 months and 1 year after the second surgery. Before this operation, unilateral tactile stimulation of either hand activated contralaterally the first (SI) and second (SII) somatosensory areas and the posterior parietal (PP) cortex, and SII and PP cortex ipsilaterally. All three tests were performed without errors. In both postoperative sessions, somatosensory activation was observed in contralateral SI, SII, and PP cortex, but not in ipsilateral SII and PP cortex. Performance was 100% correct in the TNT for the right hand, but below chance for the left; in the other tests, it was below chance except for TFLT in the intramanual task. This case provides the direct demonstration that activation of SII and PP cortex to stimulation of the ipsilateral hand and normal interhemispheric transfer of tactile information require the integrity of the posterior body of the CC.

Divided visuo-spatial attention systems with total and anterior callosotomy.

The role of the corpus callosum in the inter-hemispheric integration of the visuo-spatial attention system, was investigated in patients with a total callosotomy or with an anterior callosal section. Subjects produced simple reaction times (RTs) to visual targets shown to the left or right visual hemifield. Preceding the target by an interval of 500 ms, arrow cues predicting the target location were shown left and right of the point of ocular fixation. For a majority of total and anterior callosotomy patients, results with valid focused cues (both arrows pointing to the target location) and with divided-attention cues (arrows pointing away from fixation) did not differ and both conditions produced shorter RTs than with neutral cues (equal signs). In contrast, neurologically intact subjects showed equal RTs with divided-attention and neutral cues, whereas valid focused cues produced reduced RTs relative to neutral cues. These results indicate that most split-brains, in contrast to normal observers, are capable of directing their attention to left and right visual field locations simultaneously, and therefore that each cerebral hemisphere controls its own visuo-spatial attention mechanism.

Role of the corpus callosum in the somatosensory activation of the ipsilateral cerebral cortex: an fMRI study of callosotomized patients.

To verify whether the activation of the posterior parietal and parietal opercular cortices to tactile stimulation of the ipsilateral hand is mediated by the corpus callosum, a functional magnetic resonance imaging (fMRI, 1.0 tesla) study was performed in 12 control and 12 callosotomized subjects (three with total and nine with partial resection). Eleven patients were also submitted to the tactile naming test. In all subjects, unilateral tactile stimulation provoked a signal increase temporally correlated with the stimulus in three cortical regions of the contralateral hemisphere. One corresponded to the first somatosensory area, the second was in the posterior parietal cortex, and the third in the parietal opercular cortex. In controls, activation was also observed in the ipsilateral posterior parietal and parietal opercular cortices, in regions anatomically corresponding to those activated contralaterally. In callosotomized subjects, activation in the ipsilateral hemisphere was observed only in two patients with splenium and posterior body intact. These two patients and another four with the entire splenium and variable portions of the posterior body unsectioned named objects explored with the right and left hand without errors. This ability was impaired in the other patients. The present physiological and anatomical data indicate that in humans activation of the posterior parietal and parietal opercular cortices in the hemisphere ipsilateral to the stimulated hand is mediated by the corpus callosum, and that the commissural fibres involved probably cross the midline in the posterior third of its body.

Callosal and cortical contribution to procedural learning.

Acallosal and callosotomized subjects usually show impairments on tasks requiring bilateral interdependent motor control. However, few studies have assessed the ability of these subjects to learn a skill that requires the simultaneous contribution of each hemisphere in its acquisition. The present study examined whether acallosal and callosotomized subjects could learn a visuomotor skill that involved a motor control from either both or a single hemisphere. Eleven adult patients, six acallosal and five callosotomized, participated in this study. Seven of these patients had epileptic foci located in the frontal and/or temporal areas and one of the acallosal patients showed bilateral prefrontal atrophy following surgical removal of an orbitofrontal cyst. The performance of the experimental subjects was compared with that of 11 matched control subjects, on a modified version of a serial reaction time task developed by Nissen and Bullemer (Cogn Psychol 1987; 19: 1-32). This skill acquisition task involved bimanual or unimanual key-pressing responses to a sequence of 10 visual stimuli that was repeated 160 times. A declarative memory task was then performed to assess explicit knowledge of the sequence. None of the experimental subjects learned the task in the bimanual condition. Patients with frontal epileptic foci or orbitofrontal damage also failed to learn the task in the unimanual condition when they were using the hand contralateral to the damaged hemisphere. All other subjects, including the acallosal and callosotomized patients with temporal foci, learned the visuomotor skill as well as their controls in the unimanual condition. In spite of the absence of transfer and interhemispheric integration of procedural learning, some of the acallosal and callosotomized patients were able to learn the sequence explicitly. These findings indicate that the corpus callosum and the frontal cortical areas are important for procedural learning of a visuomotor skill. They also confirm the dissociation described by Squire (Science 1986; 232: 1612-9 and J Cogn Neurosci 1992; 4: 232-43) between the declarative and procedural memory systems and extend this dissociation to processes involving simultaneous bihemispheric co-operation.

Predictive factors of callosotomy in drug-resistant epileptic patients with a long follow-up.

Some possible factors to predict outcome after callosotomy were investigated in a personal series composed of 36 patients. Twenty-seven of them were submitted to anterior callosotomy, 1 to posterior callosotomy and the remaining 8 patients to two stage complete division of corpus callosum. All factors, either positive or negative, do not appear completely reliable; they can be envisaged only in relative terms and do not seem to be relevant to make surgical decision or to discard surgery. In author's series, dealing specifically with drop-attacks, it clearly appeared that abrupt falls to the ground unpreceded by other epileptic features did definitely better. This was the only statistically significant datum.

Modifications in morphology of epileptic seizures after callosotomy.

The callosotomy on drug-resistant epileptic seizures may abolish or reduce their frequency and may modified the morphology of different kind of seizures. Our series is composed of 36 patients. Drop-attacks and complex partial seizures (CP) were present in all patients, generalized tonic-clonic seizures (GTC) in 16 (44.4%) and simple partial seizures (SP) and myoclonic attacks (MY) in 6 patients each. We found two kinds of modifications: a) lateralization of hypotonia which becomes hemisomatic, with lateral bending to the hypotonic side; b) different way of falling, due not only to the lateralization of hypotonia but also to the gradual impairment of muscle tone. Modifications in CP mainly concerned automatisms, which disappeared in 39.1% of patients, while 34.8% of them had a significant reduction in automatisms; this reduction consisted in simplification of automatic movements and in shorter duration of seizures.

EEG Patterns after callosotomy.

In 36 patients with drug-resistant epilepsy submitted to anterior callosotomy (27 cases), to two-stage total callosotomy (8 cases) and to posterior callosotomy (1 case) the EEG variations concerning background activity, focal activity and sharp-waves (SW) bisynchronous activity were evaluated. EEG modifications observed after callosotomy are the following: background rhythm tends to be better organised as spectral analysis demonstrated, this finding usually coincide with reduction of bisynchronous discharges. It appears that improvement in background activity cannot be correlated with outcome, but it seems to be to some extent since at the same time cognitive functions also seem to improve; however, this last aspect need to be checked in much larger series. The number and location of EEG foci do not change, but they appear to be more active; this is likely to depend only on the concomitant reduction of bisynchronous activity. No correlation seems to exist between the number and the location of foci, which are generally multiple. Lateralization of bisynchronous discharges as well as the reduction of their frequency and duration were observed. However, the clinical course is quite different: in some patients we have achieved good clinical responses in others postoperative results were poor. Lateralization of bisynchronous discharges is never absolute, on the grounds that in prolonged recordings bisynchronous discharges are nearly always present. Bisynchronous discharges in some cases are alternatively predominant in both hemispheres even within minutes or seconds. It was observed that after certain time, generally some months, lateralized discharges tend to generalize again, confirming that corpus callosum is replaced in discharge diffusion by other structures (brain-stem, diencephalon).

Mutism in 36 patients who underwent callosotomy for drug-resistant epilepsy.

Thirty-six drug-resistant epileptic patients submitted to callosotomy were studied. Anterior callosotomy was performed in 27 patients, total two-stage callosotomy was performed in 8 patients and 1 patient had only posterior callosotomy. We found mutism in 10 patients (2 after complete callosotomy and 8 after anterior section). The patients did not speak, but the comprehension was present: they were able to carry out orders and to write. Their attitude to the environment was characterized by complete indifference. The mutism was always transient, lasting from 4 to 25 days (mean 7 days). Regression of mutism was always complete. We think that this complication should be chiefly attributed mainly to surgical manipulation, even if it is impossible to completely exclude a multi-factorial etiology.

Trail making test: normative values from 287 normal adult controls.

The Trail Making Test (TMT), which explores visual-conceptual and visual-motor tracking, is a frequently used neuropsychological test because of its ease of administration and sensitivity to brain damage. In this paper, norms are provided for the time scores derived from parts A and B, and for the (B-A) difference. The data were collected from 287 adult Italian subjects stratified by gender, schooling and age (from 20 to 79 years). The test scores were affected by age, education and general intelligence (as expressed by Raven's Coloured Progressive Matrices). Only for part A did females have longer time scores than males. Test-retest reliability was high for each score.

Influence of vigabatrin on cognitive performances and behaviour in patients with drug-resistant epilepsy.

INTRODUCTION: The aim of this research was to evaluate changes in cognitive performances, mood and quality of life in drug-resistant epileptic patients, after the introduction of Vigabatrin (VGB) as additional treatment. MATERIAL AND METHODS: A four-step evaluation was carried out in two groups of 20 patients each, randomly assigned to VGB or placebo treatment. A battery of neuropsychological tests investigating attention, memory and adaptive abilities, associated with inventories concerning depression, quality of life and the concern of families upon patient behaviour, were utilised. For each subject, four evaluations were performed, two before and two after VGB/placebo administration. RESULTS: No relevant side-effects regarding cognition and behavior were detected in the VGB group. The intra-group comparison between pre- and post-treatment phases showed a slight improvement in cognitive performances of VGB patients and a positive change in their overall psychological status. The inter-group comparison confirmed the selective improvement occurring in the trend of a few neuropsychological test scores in the VGB group. CONCLUSION: Such results help to reject the hypothesis that the addition of VGB to the current antiepileptic treatment may affect cognitive performances and behaviour.

Brain involvement in myotonic dystrophy: MRI features and their relationship to clinical and cognitive conditions.

A prospective, case-control study was carried out on 25 patients with myotonic dystrophy (MyD) and 25 healthy subjects using brain magnetic resonance imaging (MRI). The frequency and severity of white matter hyperintense lesions (WMHL) and brain atrophy in MyD patients were compared with their clinical features and cognitive impairment using an extensive neuropsychological battery. Eighty-four per cent of MyD patients showed WMHL, compared with 16% of controls (p < 0.0001). These lesions involved all cerebral lobes, without hemispheric prevalence. Twenty-eight per cent of MyD patients also showed particular WMHL at their temporal poles. Myotonic patients had significantly more cortical atrophy than controls. No relationship between atrophy and WMHL was found on the MRI scans. The extent of brain abnormalities (WMHL or atrophy) was not correlated to age, disease duration, physical disability or severity of neuropsychological impairment. Central nervous system abnormalities revealed by MRI appear to be an almost constant feature of MyD, but they are not found to be related to clinical or cognitive parameters. Their nature is still unclear: some of them, located at the temporal poles, seem to be characteristic of the disease, while others small, diffuse WMHLs, similar to the age related alterations revealed by MRI occurring during young and adult age in MyD patients.

Cognitive behavior in asymptomatic (CDC stage II and III) HIV--seropositive intravenous drug users (IVDUs).

To evaluate cognitive impairment in the early stages of HIV infection in intravenous drug users (IVDUs) we have studied 39 consecutive HIV-infected subjects (CDC stage II-III) whose only known risk factor for the infection was intravenous heroin addiction. The control group was represented by 30 seronegative IVDUs. All subjects were tested with an extensive neuropsychological battery assessing general intellectual abilities and single cognitive functions. The patients differed from controls only for tests of attention and visual-motor abilities: 20% of asymptomatic seronegative and PGL patients showed alterations in two or more cognitive tests, as opposed to 3% of controls (p < 0.001). Our findings suggest that cognitive deficits seem to be present in a substantial percentage of IVDUs with asymptomatic HIV infection. Cognitive damage at this stage seems to selectively involve attention and visual-motor abilities, sparing general intellectual performances.

Peripheral neuropathy in myotonic dystrophy: electrophysiological and clinical features.

Peripheral neuropathy was investigated in thirty-one patients with myotonic dystrophy (MyD) and sixteen relatives. Using standard electrophysiological criteria, a sensorimotor axonal peripheral neuropathy was found in 14 MyD cases (45%) and not in unaffected first-degree relatives. The whole group of the MyD patients showed significant impairment of mean motor and sensory conduction values, compared with controls. The presence of polyneuropathy was correlated with the patients' age and the severity and duration of the clinical manifestations of MyD.

Recognition impairment correlated with short bisynchronous epileptic discharges.

The occurrence of transitory cognitive impairment during diffuse subclinical electroencephalographic (EEG) discharges has been widely documented but the role of the parameters influencing the cognitive performance and the involvement of motor or verbal response in the tasks used is still under debate. Fifteen patients suffering from primary generalized epilepsy with frequent bisynchronous EEG epileptic bursts underwent a shape recognition task during EEG monitoring. The test sequence was as follows: memorandum, pause, and multiple choice set. After pressing the response button, the patient was asked to confirm the choice verbally. The following parameters were considered: geometrical complexity of the shape, chronological position of the burst occurring during the single test, and the duration of discharge ranging from 1 to 3 s. Results showed a significant increase in incorrect responses during the test when discharges occurred, with more errors occurring for difficult than for easy shapes. Neither the discharge position nor the duration of the epileptic burst influenced the performance. Diffuse epileptic activity of short duration produced selective effects on the cognitive process regardless of the motor component of the response.

Neuropsychological profile in myotonic dystrophy.

Twenty patients with myotonic dystrophy underwent neuropsychological evaluation. Performances were analysed with respect to general cognitive profile, family patterns of cognitive impairment, relation with sex, age, extent of muscular involvement, and sex of affected parent. Results showed severe intellectual deficit in 50% of patients and selective impairment of visuospatial and constructional functions. Female patients showed significantly worse global intellectual status than males. No difference in intellectual level was observed in patients with respect to age, extent of muscular involvement and sex of affected parent. No family pattern of cognitive impairment could be identified. Our results show that an extensive neuropsychological battery can reveal the existence of selective mental impairment. It may provide further data on cognitive impairment onset, progression and relation to muscular involvement.

Evolution of neuropsychological changes after partial callosotomy in intractable epilepsy.

Early neuropsychological changes following partial anterior callosotomy were evaluated in 15 patients with epilepsy (10 secondary generalized and 5 Lennox-Gastaut syndromes) by comparing their performances 1 month before surgery and then 15-20 and 90-100 days postoperatively without modifying the anticonvulsant treatment. The following neuropsychological and motor functions were tested: memory, attention, visuo-motor ability, posture, motor dexterity, language, praxis and gnosis. Social behaviour was also investigated. The main results are as follows: (i) most cognitive functions showed no significant variation; (ii) motor organization was still slightly impaired at the second check-up after the surgery; (iii) improvements in social behaviour and posture were frequently observed at the final evaluation. The analysis of individual cases highlights the influence of the extent of commissurotomy, lesions related to the surgical procedure and preoperative brain damage in determining the post-surgical profile. On this basis, the short-term neuropsychological cost of partial callosotomy appears to be low and seems to depend mostly on surgical parameters and brain conditions before the operation.

Callosotomy for the treatment of drug resistant generalized seizures.

Fifteen patients have been followed for more than one year following callosotomy having presented with long standing epilepsy, no well defined focus amenable to radical excision, and severely incapacitating atonic seizures that were refractory to anticonvulsant therapy. Atonic fits have been reduced by more than 80% in thirteen patients, with two patients suffering long term sequelae (slight dysarthria in one, and dyslexia with mild visuo-spatial disturbances in another). Anticonvulsant therapy was still required post-operatively.

May preclinical markers of brain infection by HIV be detected? A cognitive, CSF and neuroradiological investigation.

A group of patients with HIV infection in various stages of the disease was studied with regard to CSF, neuroradiological and neuropsychological aspects. A considerable number of them showed signs of CNS involvement, as revealed by abnormalities in all the three fields investigated, despite a frequently unremarkable neurological examination. The findings of CSF alterations, neuroradiological abnormalities and selective cognitive impairment in the absence of opportunistic infections of the CNS support the hypothesis of an early and direct action of HIV on the nervous system.

Reversible multifocal encephalopathy following tuberculous infection.

Tuberculous encephalic infection is commonly reported as confined to Asians or Africans or people living in poor hygienic conditions; very often it follows meningitis in patients with lung TB infection. We describe three western patients coming from good social environment and suffering from multifocal tuberculous encephalopathy. Two of them showed neither meningitis or lung TB when CNS involvement appeared. Complete recovery after therapy is described, together with the evolution of brain CT and, in 1 case, MRI features. The instrumental findings accompanying the complete recovery suggest that the lesions described in these cases are a localized form of encephalitis responsive to medical treatment, unlike tuberculomas, which often need surgical treatment. The occurrence of tuberculous encephalic infection in western, middle-class patients with or without meningitis emphasizes that tuberculous encephalopathy must be considered in the differential diagnosis of multifocal brain lesions.