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Showing papers in "Brain in 1998"


Journal ArticleDOI
01 Apr 1998-Brain
TL;DR: A constellation of deficits is suggestive of disruption of the Cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum, called the 'cerebellar cognitive affective syndrome'.
Abstract: Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state tests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the 'cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal, superior temporal and limbic cortices with the cerebellum.

2,640 citations


Journal ArticleDOI
01 Jun 1998-Brain
TL;DR: The destruction of transmodal epicentres causes global impairments such as multimodal anomia, neglect and amnesia, whereas their selective disconnection from relevant unimodal areas elicits modality-specific impairmentssuch as prosopagnosia, pure word blindness and category-specific anomias.
Abstract: Sensory information undergoes extensive associative elaboration and attentional modulation as it becomes incorporated into the texture of cognition. This process occurs along a core synaptic hierarchy which includes the primary sensory, upstream unimodal, downstream unimodal, heteromodal, paralimbic and limbic zones of the cerebral cortex. Connections from one zone to another are reciprocal and allow higher synaptic levels to exert a feedback (top-down) influence upon earlier levels of processing. Each cortical area provides a nexus for the convergence of afferents and divergence of efferents. The resultant synaptic organization supports parallel as well as serial processing, and allows each sensory event to initiate multiple cognitive and behavioural outcomes. Upstream sectors of unimodal association areas encode basic features of sensation such as colour, motion, form and pitch. More complex contents of sensory experience such as objects, faces, word-forms, spatial locations and sound sequences become encoded within downstream sectors of unimodal areas by groups of coarsely tuned neurons. The highest synaptic levels of sensory-fugal processing are occupied by heteromodal, paralimbic and limbic cortices, collectively known as transmodal areas. The unique role of these areas is to bind multiple unimodal and other transmodal areas into distributed but integrated multimodal representations. Transmodal areas in the midtemporal cortex, Wernicke's area, the hippocampal-entorhinal complex and the posterior parietal cortex provide critical gateways for transforming perception into recognition, word-forms into meaning, scenes and events into experiences, and spatial locations into targets for exploration. All cognitive processes arise from analogous associative transformations of similar sets of sensory inputs. The differences in the resultant cognitive operation are determined by the anatomical and physiological properties of the transmodal node that acts as the critical gateway for the dominant transformation. Interconnected sets of transmodal nodes provide anatomical and computational epicentres for large-scale neurocognitive networks. In keeping with the principles of selectively distributed processing, each epicentre of a large-scale network displays a relative specialization for a specific behavioural component of its principal neurospychological domain. The destruction of transmodal epicentres causes global impairments such as multimodal anomia, neglect and amnesia, whereas their selective disconnection from relevant unimodal areas elicits modality-specific impairments such as prosopagnosia, pure word blindness and category-specific anomias. The human brain contains at least five anatomically distinct networks. The network for spatial awareness is based on transmodal epicentres in the posterior parietal cortex and the frontal eye fields; the language network on epicentres in Wernicke's and Broca's areas; the explicit memory/emotion network on epicentres in the hippocampal-entorhinal complex and the amygdala; the face-object recognition network on epicentres in the midtemporal and temporopolar cortices; and the working memory-executive function network on epicentres in the lateral prefrontal cortex and perhaps the posterior parietal cortex. Individual sensory modalities give rise to streams of processing directed to transmodal nodes belonging to each of these networks. The fidelity of sensory channels is actively protected through approximately four synaptic levels of sensory-fugal processing. The modality-specific cortices at these four synaptic levels encode the most veridical representations of experience. Attentional, motivational and emotional modulations, including those related to working memory, novelty-seeking and mental imagery, become increasingly more pronounced within downstream components of unimodal areas, where they help to create a highly edited subjective version of the world. (ABSTRACT TRUNCATED)

2,624 citations


Journal ArticleDOI
01 Jan 1998-Brain
TL;DR: Functional neuroimaging confirmed that the amygdala and some of its functionally connected structures mediate specific neural responses to fearful expressions and demonstrated that amygdalar responses predict expression-specific neural activity in extrastriate cortex.
Abstract: Localized amygdalar lesions in humans produce deficits in the recognition of fearful facial expressions. We used functional neuroimaging to test two hypotheses: (i) that the amygdala and some of its functionally connected structures mediate specific neural responses to fearful expressions; (ii) that the early visual processing of emotional faces can be influenced by amygdalar activity. Normal subjects were scanned using PET while they performed a gender discrimination task involving static grey-scale images of faces expressing varying degrees of fear or happiness. In support of the first hypothesis, enhanced activity in the left amygdala, left pulvinar, left anterior insula and bilateral anterior cingulate gyri was observed during the processing of fearful faces. Evidence consistent with the second hypothesis was obtained by a demonstration that amygdalar responses predict expression-specific neural activity in extrastriate cortex.

1,282 citations


Journal ArticleDOI
01 Dec 1998-Brain
TL;DR: Gamma ERS may provide complementary information about cortical neurophysiology that is useful for mapping brain function in humans, and maps of sensorimotor function inferred from gamma ERS were consistent with maps generated by cortical electrical stimulation for clinical purposes.
Abstract: It has been shown in animals that neuronal activity in the 'gamma band' (>30 Hz) is associated with cortical activation and may play a role in multi-regional and multi-modal integration of cortical processing. Studies of gamma activity in human scalp EEG have typically focused on event-related synchronization (ERS) in the 40 Hz band. To assess further the gamma band ERS further, as an index of cortical activation and as a tool for human functional brain mapping, we recorded subdural electrocorticographic (ECoG) signals in five clinical subjects while they performed visual-motor decision tasks designed to activate the representations of different body parts in sensorimotor cortex. ECoG spectral analysis utilized a mixed-effects analysis of variance model in which within-trial temporal dependencies were accounted for. Taking an exploratory approach, we studied gamma ERS in 10-Hz-wide bands (overlapping by 5 Hz) ranging from 30 to 100 Hz, and compared these findings with changes in the alpha (8-13 Hz) and beta (15-25 Hz) bands. Gamma ERS (observed in three out of subjects) occurred in two broad bands-'low gamma' included the 35-45 and 40-50 Hz bands, and 'high gamma' the 75-85, 80-90, 85-95 and 90-100 Hz bands. The temporal and spatial characteristics of low and high gamma ERS were distinct, suggesting relatively independent neurophysiological mechanisms. Low gamma ERS often began after onset of the motor response and was sustained through much of it, in parallel with event-related desynchronization (ERD) in the alpha band. High gamma ERS often began during, or slightly before, the motor response and was transient, ending well before completion of the motor response. These temporal differences in low and high gamma suggest different functional associations with motor performance. Compared with alpha and beta ERD, the topographical patterns of low and high gamma ERS were more discrete and somatotopically specific and only occurred over contralateral sensorimotor cortex during unilateral limb movements (alpha and beta ERD were also observed ipsilaterally). Maps of sensorimotor function inferred from gamma ERS were consistent with maps generated by cortical electrical stimulation for clinical purposes. In addition, different task conditions in one subject produced consistent differences in both motor response latencies and onset latency of gamma ERS, particularly high gamma ERS. Compared with alpha and beta ERD, the topography of gamma ERS is more consistent with traditional maps of sensorimotor functional anatomy. In addition, gamma ERS may provide complementary information about cortical neurophysiology that is useful for mapping brain function in humans.

1,059 citations


Journal ArticleDOI
01 May 1998-Brain
TL;DR: A neuropathological study of autism was established and brain tissue examined from six mentally handicapped subjects with autism, finding the likely involvement of the cerebral cortex in autism.
Abstract: A neuropathological study of autism was established and brain tissue examined from six mentally handicapped subjects with autism. Clinical and educational records were obtained and standardized diagnostic interviews conducted with the parents of cases not seen before death. Four of the six brains were megalencephalic, and areas of cortical abnormality were identified in four cases. There were also developmental abnormalities of the brainstem, particularly of the inferior olives. Purkinje cell number was reduced in all the adult cases, and this reduction was sometimes accompanied by gliosis. The findings do not support previous claims of localized neurodevelopmental abnormalities. They do point to the likely involvement of the cerebral cortex in autism.

1,010 citations


Journal ArticleDOI
01 Sep 1998-Brain
TL;DR: It is suggested that patients with phantom limbs provide a valuable opportunity not only for exploring neural plasticity in the adult human brain but also for understanding the relationship between the activity of sensory neurons and conscious experience.
Abstract: Almost everyone who has a limb amputated will experience a phantom limb--the vivid impression that the limb is not only still present, but in some cases, painful. There is now a wealth of empirical evidence demonstrating changes in cortical topography in primates following deafferentation or amputation, and this review will attempt to relate these in a systematic way to the clinical phenomenology of phantom limbs. With the advent of non-invasive imaging techniques such as MEG (magnetoencephalogram) and functional MRI, topographical reorganization can also be demonstrated in humans, so that it is now possible to track perceptual changes and changes in cortical topography in individual patients. We suggest, therefore, that these patients provide a valuable opportunity not only for exploring neural plasticity in the adult human brain but also for understanding the relationship between the activity of sensory neurons and conscious experience. We conclude with a theory of phantom limbs, some striking demonstrations of phantoms induced in normal subjects, and some remarks about the relevance of these phenomena to the question of how the brain constructs a 'body image.'

968 citations


Journal ArticleDOI
01 Dec 1998-Brain
TL;DR: The topographical spread ofalpha ERD beyond expected functional-anatomical boundaries during early (and sometimes late) phases of motor responses invites a re-examination of traditional assumptions about sensorimotor functional neuroanatomy, as well as the role of alpha ERD as an index of cortical activation.
Abstract: Human scalp EEG studies have shown that event-related desynchronization (ERD) in the alpha (8-13 Hz) and beta (15-25 Hz) bands may be used to detect functional activation of sensorimotor cortex. However, in most previous studies somatotopy has not been examined in detail and brief, self-paced movements, focusing on the planning of motor output, have been used. We recorded electrocorticographic (ECoG) signals in five clinical subjects during a visual-motor decision task that was designed to activate the representations of different body parts in sensorimotor cortex. To focus more on execution of motor output than on its planning, subjects were instructed to make sustained isometric muscle contractions in different body parts (tongue protrusion, fist-clenching or foot dorsiflexion) in response to randomized visual stimuli depicting each action. ECoG spectral analysis utilized a mixed-effects analysis of variance model in which within-trial temporal dependencies were taken into account, and the magnitude and statistical significance of alpha and beta ERDs were mapped onto a surface rendering of each subject's brain MRI. Cortical electrical stimulation was performed in all subjects for clinical purposes, and the resulting maps of sensorimotor function were compared with those generated by ECoG spectral analysis. During the early phases of the motor responses, alpha ERD commonly occurred in a diffuse spatial pattern that was not somatotopically specific. During the late phases, the spatial pattern of alpha ERD usually became more focused and somatotopically specific. Maps of alpha ERD were closer to cortical stimulation maps when alpha ERD was sustained throughout the late phases of the motor responses. Thus, the topography of alpha ERD more resembled traditional somatotopy when its temporal profile approximated that of the motor response. The topography of beta ERD was often more discrete and somatotopically specific than that of alpha ERD, but beta ERD was often transient and sometimes absent. Sometimes, unilateral limb movement produced sustained alpha and beta ERD over bilateral sensorimotor cortices, with overlapping patterns for different body parts. The topographical spread of alpha ERD beyond expected functional-anatomical boundaries during early (and sometimes late) phases of motor responses invites a re-examination of traditional assumptions about sensorimotor functional neuroanatomy, as well as the role of alpha ERD as an index of cortical activation. We agree with others that the somatotopic representations of different body parts overlap more than previously thought. Also, unilateral limb movements may be associated with both contralateral and ipsilateral activation of sensorimotor cortex. We conjecture that alpha ERD may reflect activity within a broad synaptic network with distributed cortical representations.

935 citations


Journal ArticleDOI
01 Jul 1998-Brain
TL;DR: Evidence suggests that primary dystonia results from a functional disturbance of the basal ganglia, particularly in the striatal control of the globus pallidus (and substantia nigra pars reticulata) and abnormal regulation of brainstem and spinal cord inhibitory interneuronal mechanisms.
Abstract: Co-contraction and overflow of EMG activity of inappropriate muscles are typical features of all dystonic movements whether voluntary or involuntary. Voluntary movements are slow and more variable than normal, and there is particular difficulty switching between component movements of a complex task. Reduced spinal cord and brainstem inhibition is common to many reflex studies (long-latency reflexes, cranial reflexes and reciprocal inhibition). These reflex abnormalities may contribute to the difficulties in voluntary movements but cannot be causal as they can occur outside the clinically involved territory. Clinical and neurophysiological studies have emphasized the possible role of sensory feedback in the generation of dystonic movements. Abnormalities of cortical and basal ganglia function have been described in functional imaging and neurophysiological studies of patients with dystonia and in animal models of primary dystonia. Studies of cortical function have shown reduced preparatory activity in the EEG before the onset of voluntary movements, whilst magnetic brain stimulation has revealed changes in motor cortical excitability. Functional imaging of the brain in primary dystonia has suggested reduced pallidal inhibition of the thalamus with consequent overactivity of medial and prefrontal cortical areas and underactivity of the primary motor cortex during movements. These findings are supported by preliminary neuronal recordings from the globus pallidus and the thalamus at the time of stereotaxic surgery in patients with dystonia. All this evidence suggests that primary dystonia results from a functional disturbance of the basal ganglia, particularly in the striatal control of the globus pallidus (and substantia nigra pars reticulata). This causes altered thalamic control of cortical motor planning and executive areas, and abnormal regulation of brainstem and spinal cord inhibitory interneuronal mechanisms.

789 citations


Journal ArticleDOI
01 Oct 1998-Brain
TL;DR: Findings suggest that, at least for pairs of L1 and L2 languages that are fairly close, attained proficiency is more important than age of acquisition as a determinant of the cortical representation of L2.
Abstract: Functional imaging methods show differences in the pattern of cerebral activation associated with the subject's native language (L1) compared with a second language (L2). In a recent PET investigation on bilingualism we showed that auditory processing of stories in L1 (Italian) engages the temporal lobes and temporoparietal cortex more extensively than L2 (English). However, in that study the Italian subjects learned L2 late and attained a fair, but not an excellent command of this language (low proficiency, late acquisition bilinguals). Thus, the different patterns of activation could be ascribed either to age of acquisition or to proficiency level. In the current study we use a similar paradigm to evaluate the effect of early and late acquisition of L2 in highly proficient bilinguals. We studied a group of Italian-English bilinguals who acquired L2 after the age of 10 years (high proficiency, late acquisition bilinguals) and a group of Spanish-Catalan bilinguals who acquired L2 before the age of 4 years (high proficiency, early acquisition bilinguals). The differing cortical responses we had observed when low proficiency volunteers listened to stories in L1 and L2 were not found in either of the high proficiency groups in this study. Several brain areas, similar to those observed for L1 in low proficiency bilinguals, were activated by L2. These findings suggest that, at least for pairs of L1 and L2 languages that are fairly close, attained proficiency is more important than age of acquisition as a determinant of the cortical representation of L2.

679 citations


Journal ArticleDOI
01 Mar 1998-Brain
TL;DR: The overall results favour the neurosurgical treatment of Parkinson's disease by stimulating the STn rather than the GPi, and the reduction of levodopa dosage in the STN group led to an indirect reduction of LID similar to that in theGPi group during activities of everyday life.
Abstract: The aim of this study was to compare, retrospectively, the value of chronic bilateral stimulation of the internal globus pallidus (GPi) and the subthalamic nucleus (STN) in patients with young onset Parkinson's disease. We selected 13 consecutive patients with similar characteristics at the time of surgery: age at onset < 40 years, disabling motor fluctuations (Hoehn and Yahr stage 4 or 5 in off-drug phases) and levodopa-induced dyskinesias (LID). Eight patients were operated on in the STN and five in the GPi. The Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests and a LID scale were compared in on- and off-drug conditions before surgery and 6 months after surgery on stimulation using the chronic electrical parameters found to improve best the motor state of the individual patient, without adverse effects. In off-drug phases, the motor score of the UPDRS was improved by 71% with STN stimulation and by 39% with GPi stimulation on average. This difference was statistically significant (P < 0.05). Whereas rigidity and tremor showed good improvement in both groups, the decrease in the akinesia score was more pronounced in the STN group. In the STN group, the improvement of all motor symptoms was very close, or equal, to the best levodopa response. Thus the levodopa test was predictive of outcome. The improvement in off-drug period motor handicap allowed a decrease in the levodopa-equivalent dose only in the STN group (-56%). The voltage, frequency and pulse width used for chronic stimulation were lower in the STN group. In the on-drug phases there was a marked improvement in LID in the GPi group, as measured by the dyskinesias score during an acute levodopa test, whereas there was only a small decrease in the STN group (P < 0.05). However, in the long term, the reduction of levodopa dosage in the STN group led to an indirect reduction of LID similar to that in the GPi group during activities of everyday life. In conclusion, the overall results favour the neurosurgical treatment of Parkinson's disease by stimulating the STN rather than the GPi.

583 citations


Journal ArticleDOI
01 Jan 1998-Brain
TL;DR: This review summarizes the current uses of MR in multiple sclerosis, based on the proceedings of a recent international workshop, under four headings: technical issues; role in diagnosis; natural history studies in understanding the disease; application in clinical trials; and theory and methodology of relevant technical issues.
Abstract: Magnetic resonance (MR) techniques have had a major impact in the last 10-15 years in understanding and managing multiple sclerosis. This review summarizes the current uses of MR in multiple sclerosis, based on the proceedings of a recent international workshop, under four headings: (i) technical issues; (ii) role in diagnosis; (iii) natural history studies in understanding the disease; (iv) application in clinical trials. The theory and methodology of relevant technical issues is outlined, in order to provide a framework with which to understand the potential and limitations of MR in addressing biological and clinical questions in multiple sclerosis. The principles underlying signal-to-noise and contrast-to-noise ratio are discussed, along with the techniques and clinical results for conventional and fast spin echo T2-weighted imaging, fluid-attenuated inversion recovery, detection of blood-brain barrier break down and hypointense lesions on T1-weighted images, magnetization transfer, T2 decay-curve analysis, MR spectroscopy, spinal cord imaging, diffusion imaging, and quantification of lesion load and atrophy. MRI has an extremely valuable role in confirming the clinical diagnosis of multiple sclerosis. T2-weighted brain imaging remains the standard diagnostic tool, but in some instances it is usefully complemented with gadolinium enhancement and spinal imaging. The caveat that the diagnosis of multiple sclerosis remains primarily a clinical one cannot be over-emphasized. Serial MRI studies have added much to our understanding of the natural history and pathophysiology of the disease. Blood-brain barrier breakdown is a consistent early feature of new lesion development in relapsing-remitting and secondary progressive multiple, sclerosis, and this usually correlates with active inflammation and myelin breakdown. A number of the acute MR changes are reversible, but chronic persistent abnormalities in a number of MR parameters, such as reduced N-acetyl aspartate, low magnetization transfer ratios, atrophy and T1-hypointensity, suggest the presence of demyelination and/or axonal degeneration in many chronic lesions. The presence and extent of T2-weighted MRI abnormalities at first presentation with a clinically isolated syndrome suggestive of demyelination strongly predicts the risk of developing clinically definite multiple sclerosis in the next few years. In established multiple sclerosis, however, the correlations between T2 abnormalities and disability are modest. This poor relationship partly relates to the discrepancy between lesion site and function in attempting to correlate locomotor disability with brain MRI findings. However, the correlations between brain lesion load and cognitive dysfunction in multiple sclerosis, whilst more evident, are still modest. A more important limitation is the low pathological specificity of abnormalities seen on T2-weighted images. Stronger correlations have been found between disability and new putative MR markers for demyelination and/or axonal degeneration. Serial studies using multiple MR techniques are now needed to further clarify pathophysiological mechanisms in multiple sclerosis. Serial MR has become an important tool in monitoring treatment efficacy. It provides data which can be readily analysed in a blinded fashion and which directly inspects the pathological evolution; it also enables a rapid and sensitive measure of treatment outcome in early relapsing-remitting and secondary progressive disease. Because of the modest clinical correlations it is, however, still appropriate that the definitive determinant of treatment efficacy remains a clinical one. Further work is needed to address issues of quality control in serial studies, statistical calculation of appropriate sample sizes, and optimization of the nature and frequency of MR outcomes measured.

Journal ArticleDOI
01 Dec 1998-Brain
TL;DR: Representation of these cholinergic pathways within a 3D MRI volume helped to identify white matter lesion sites that could interfere with the corticopetal flow of cholinergy pathways.
Abstract: All sectors of the human cerebral cortex receive dense cholinergic input. The origin of this projection is located in the Ch4 cell group of the nucleus basalis of Meynert. However, very little is known about the location of the pathways which link the cholinergic neurons of the nucleus basalis to the human cerebral cortex. This question was addressed in whole-hemisphere sections processed for the visualization of multiple cholinergic markers. Two highly organized and discrete bundles of cholinergic fibres extended from the nucleus basalis to the cerebral cortex and amygdala and were designated as the medial and lateral cholinergic pathways. These bundles contained acetylcholinesterase, choline acetyltransferase and nerve growth factor receptors, confirming their cholinergic nature and origin within the basal forebrain. The medial pathway joined the white matter of the gyrus rectus, curved around the rostrum of the corpus callosum to enter the cingulum and merged with fibres of the lateral pathway within the occipital lobe. It supplied the parolfactory, cingulate, pericingulate and retrosplenial cortices. The lateral pathway was subdivided into a capsular division travelling in the white matter of the external capsule and uncinate fasciculus and a perisylvian division travelling within the claustrum. Branches of the perisylvian division supplied the frontoparietal operculum, insula and superior temporal gyrus. Branches of the capsular division innervated the remaining parts of the frontal, parietal and temporal neocortex. Representation of these cholinergic pathways within a 3D MRI volume helped to identify white matter lesion sites that could interfere with the corticopetal flow of cholinergic pathways.

Journal ArticleDOI
01 Aug 1998-Brain
TL;DR: It is concluded that indices of axonal damage or loss such as brain N-acetylaspartate may provide a specific measure of pathological changes relevant to disability.
Abstract: It has been difficult to establish a strong correlation between total brain T2-weighted lesion volume on MRI and clinical disability in multiple sclerosis, in part because of the lack of pathological specificity of T2-weighted MRI signal changes. Proton magnetic resonance spectroscopy studies have shown that measurements of the resonance intensity of N-acetylaspartate (which is localized exclusively in neurons and neuronal processes in the mature brain) can provide a specific index of axonal damage or dysfunction. Here we report a 30-month longitudinal study of 29 patients with multiple sclerosis who had either a relapsing or a secondary progressive clinical course. Conventional brain MRI and single-voxel proton magnetic resonance spectroscopy examinations were obtained at intervals of 6-8 months with concurrent clinical evaluation. At the onset of the study, the brain N-acetylaspartate:creatine resonance intensity ratio was abnormally low for the whole group of patients (control mean = 2.93 +/- 0.2, patient mean = 2.56 +/- 0.4, P < 0.005). There were no significant differences between the relapsing and secondary progressive subgroups. Over the follow-up period, there was a trend towards a decrease (8%) in the brain N-acetylaspartate:creatine ratio for the 11 relapsing patients and a significant (P < 0.001) correlation between changes in the brain N-acetylaspartate:creatine ratio and expanded disability scale scores for the patients in this group. This correlation was even more evident for the patients who had clinically relevant relapses during the 30 months of follow-up (seven of 11 patients). Increases in T2-weighted lesion volumes (35% in 30 months for the group as a whole, P < 0.0001, without differences between the subgroups) did not correlate with disability either in the group of patients as a whole or in the different subgroups. We conclude that indices of axonal damage or loss such as brain N-acetylaspartate may provide a specific measure of pathological changes relevant to disability. Total T2-weighted lesion volumes, although more sensitive to changes with time than brain N-acetylaspartate, may be less relevant to understanding the progression of disability.

Journal ArticleDOI
01 Oct 1998-Brain
TL;DR: It is suggested that perturbation of a distributed matrix may explain the production of similar, complex mental phenomena by relatively blunt insults at disparate sites.
Abstract: Complex visual hallucinations may affect some normal individuals on going to sleep and are also seen in pathological states, often in association with a sleep disturbance. The content of these hallucinations is striking and relatively stereotyped, often involving animals and human figures in bright colours and dramatic settings. Conditions causing these hallucinations include narcolepsy-cataplexy syndrome, peduncular hallucinosis, treated idiopathic Parkinson's disease, Lewy body dementia without treatment, migraine coma, Charles Bonnet syndrome (visual hallucinations of the blind), schizophrenia, hallucinogen-induced states and epilepsy. We describe cases of hallucinosis due to several of these causes and expand on previous hypotheses to suggest three mechanisms underlying complex visual hallucinations. (i) Epileptic hallucinations are probably due to a direct irritative process acting on cortical centres integrating complex visual information. (ii) Visual pathway lesions cause defective visual input and may result in hallucinations from defective visual processing or an abnormal cortical release phenomenon. (iii) Brainstem lesions appear to affect ascending cholinergic and serotonergic pathways, and may also be implicated in Parkinson's disease. These brainstem abnormalities are often associated with disturbances of sleep. We discuss how these lesions, outside the primary visual system, may cause defective modulation of thalamocortical relationships leading to a release phenomenon. We suggest that perturbation of a distributed matrix may explain the production of similar, complex mental phenomena by relatively blunt insults at disparate sites.

Journal ArticleDOI
01 Jan 1998-Brain
TL;DR: Results add to data suggesting that axonal damage or loss may be responsible for functional impairments in multiple sclerosis, and may be of particular significance for understanding chronic disability in this disease.
Abstract: The current study was designed to determine the relative distribution of decreases of N-acetylasparate (NAA), a marker of axonal damage, between lesions and normal-appearing white matter of patients with established multiple sclerosis and to test for associations between changes in the ratio of NAA to creatine/phosphocreatine (NAA:Cr) in those compartments and changes in disability. Data were collected from a 30-month longitudinal study of 28 patients with either a relapsing course with partial remissons and no progression between attacks (relapsing/remitting) (11 patients) or a course of progressively increasing disability, following a period of relapsing/remitting disease (secondary progressive) (17 patients). Proton magnetic resonance spectroscopic imaging (MRSI) and conventional MRI examinations were performed at 6-8-month intervals with concurrent clinical assessments of disability. General linear models were used to test associations between MRSI, MRI, lesion volume and clinical data. Analysis confirmed that the NAA:Cr ratio is lower in lesions than in the normal-appearing white matter (-15.3% in relapsing/remitting multiple sclerosis and -8.8% in secondary progressive multiple sclerosis). The lower NAA:Cr ratio per unit lesion volume previously observed for secondary progressive relative to relapsing/remitting patients was found to result from a lower ratio (8.2%, P < 0.01) in the normal-appearing white matter rather than from any differences within lesions. The importance of changes in the normal-appearing white matter was emphasized further with the observation that the NAA:Cr ratio in the normal-appearing white matter accounted for most of the observed 15.6% (P < 0.001) decrease in the NAA:Cr ratio in the brains of relapsing/remitting patients over the period of study. The decrease in the NAA:Cr ratio in normal-appearing white matter correlated strongly (P < 0.001) with changes in disability in the relapsing/remitting subgroup. These results add to data suggesting that axonal damage or loss may be responsible for functional impairments in multiple sclerosis. The accumulation of secondary axonal damage in the normal-appearing white matter may be of particular significance for understanding chronic disability in this disease.

Journal ArticleDOI
01 Mar 1998-Brain
TL;DR: Brain MRI at presentation with a clinically isolated syndrome is predictive of the long-term risk of subsequent development of multiple sclerosis, the type of disease and extent of disability.
Abstract: A definitive diagnosis of multiple sclerosis cannot be made at presentation on patients with a clinically isolated syndrome of the optic nerve, spinal cord or brainstem suggestive of demyelination, as dissemination in time is not established. To determine the long-term risk of abnormalities on brain MRI for the development of multiple sclerosis and disability we performed a 10-year follow-up on 81 such patients who had T2-weighted brain MRI at presentation. Initial brain MRI was abnormal in 54 (67%). Follow up of those patients with an abnormal MRI revealed progression to clinically definite multiple sclerosis in 45 out of 54 (83%), of whom 11 (20%) had relapsing/remitting disease (EDSS > 3), 13 (24%) secondary progressive and 21 (39%) benign (relapsing/remitting with EDSS < or = 3) disease. For those with a normal MRI progression to clinically definite multiple sclerosis occurred in only three out of 27 (11%), all benign. There was a significant relationship between the number of lesions at presentation and both EDSS (r = 0.45, P < 0.001) and the type of disease at follow-up (P < 0.0001). Brain MRI at presentation with a clinically isolated syndrome is predictive of the long-term risk of subsequent development of multiple sclerosis, the type of disease and extent of disability.

Journal ArticleDOI
01 Nov 1998-Brain
TL;DR: The findings of this PET study support the hypothesis that faces and names involve differential pre-semantic processing prior to accessing a common neural system of stored knowledge of personal identity which overlaps with the one associated with object knowledge.
Abstract: This PET study has revealed the neural system involved in implicit face, proper-name and object name processing during an explicit visual 'same' versus 'different' matching task. Within the identified system, some areas were equally active irrespective of modality (faces or names) or type of stimuli (famous and non-famous) while other areas exhibited differential effects. Our findings support the hypothesis that faces and names involve differential pre-semantic processing prior to accessing a common neural system of stored knowledge of personal identity which overlaps with the one associated with object knowledge. The areas specialized for the perceptual analysis of faces (irrespective of whether they are famous or non-famous) are the right lingual and bilateral fusiform gyri, while the areas specialized for famous stimuli (irrespective of whether they are faces or names) spread from the left anterior temporal to the left temporoparietal regions. One specific area, the more lateral portion of the left anterior middle temporal gyrus, showed increased activation for famous faces relative to famous proper names and for famous proper names relative to common names. The differential responsiveness of this region when processing familiar people suggests functional segregation of either personal attributes or, more likely, the demands placed on processes that retrieve stored knowledge when stimuli have highly similar visual features but unique semantic associations.

Journal Article
29 Nov 1998-Brain
TL;DR: In this paper, the authors show that the main cause of the variability may be random chance, and that if trials are small their estimate of magnitude of effect may be incorrect, simply because of the random play of chance.
Abstract: Abstract Variability in patients' response to interventions in pain and other clinical settings is large. Many explanations such as trial methods, environment or culture have been proposed, but this paper sets out to show that the main cause of the variability may be random chance, and that if trials are small their estimate of magnitude of effect may be incorrect, simply because of the random play of chance. This is highly relevant to the questions of ‘How large do trials have to be for statistical accuracy?’ and ‘How large do trials have to be for their results to be clinically valid?’ The true underlying control event rate (CER) and experimental event rate (EER) were determined from single‐dose acute pain analgesic trials in over 5000 patients. Trial group size required to obtain statistically significant and clinically relevant (0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value) results were computed using these values. Ten thousand trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to random chance alone. Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19. With such efficacy, to have a 90% chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60. For clinical relevance nearly 500 patients are required in each group. Only with an extremely effective drug (EER>0.8) will we be reasonably sure of obtaining a clinically relevant NNT with commonly used group sizes of around 40 patients per treatment arm. The simulated trials showed substantial variation in CER and EER, with the probability of obtaining the correct values improving as group size increased. We contend that much of the variability in control and experimental event rates is due to random chance alone. Single small trials are unlikely to be correct. If we want to be sure of getting correct (clinically relevant) results in clinical trials we must study more patients. Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional (small) size.

Journal ArticleDOI
01 Aug 1998-Brain
TL;DR: The data suggest that the neocerebellum (not the basal ganglia) is involved in monitoring and optimizing movements using sensory (proprioceptive) feedback and error detection and correction occurs during line re-tracing but not line generation.
Abstract: The role of the basal ganglia and cerebellum in the control of movements is unclear. We summarize results from three groups of PET studies of regional CBF. The results show a double dissociation between (i) selection of movements, which induces differential effects in the basal ganglia but not the cerebellum, and (ii) sensory information processing, which involves the cerebellum but not the basal ganglia. The first set of studies concerned motor learning of a sequence of finger movements; there was a shift of activation in the anterior-posterior direction of the basal ganglia which paralleled changes in the motor areas of the frontal cortex. During new learning, the dorsolateral prefrontal cortex and striatum (caudate nucleus and anterior putamen) were activated. When subjects had to select movements, the premotor cortex and mid-putamen were activated. With automatic (overlearned) movements, the sensorimotor cortex and posterior putamen were activated. When subjects paid attention to overlearned actions, activation shifted back to the dorsolateral prefrontal cortex and striatum. The cerebellum was not activated when subjects made new decisions, attended to their actions or selected movements. These results demonstrate components of basal ganglia-(thalamo)-cortical loops in humans. According to earlier studies in animals we propose that the basal ganglia may be concerned with selecting movements or the selection of appropriate muscles to perform a movement selected by cortical areas (e.g. premotor cortex). Secondly, a visuomotor co-ordination task was examined. In the absence of visual control over arm movements, subjects were required to use a computer mouse to either generate new lines or to re-trace lines on a computer screen. The neocerebellum (hemispheres of the posterior lobe, cerebellar nuclei and cerebellar vermis), not the basal ganglia, was more engaged when lines were re-traced (compared with new line generation). Animal experiments have shown that error detection (deviation from given lines) and correction occurs during line re-tracing but not line generation. Our data suggest that the neocerebellum (not the basal ganglia) is involved in monitoring and optimizing movements using sensory (proprioceptive) feedback. Thirdly, the relative contribution of sensory information processing to the signal during active/passive execution of a motor task (flexion and extension of the elbow) was examined; it was found that 80-90% of the neocerebellar signal could be attributed to sensory information processing. The basal ganglia were not involved in sensory information processing. They may be concerned with movement/ muscle selection (efferent motor component); the neocerebellum may be concerned with monitoring the outcome (afferent sensory component) and optimizing movements using sensory (feedback) information.

Journal ArticleDOI
01 Sep 1998-Brain
TL;DR: A PET activation study on CV was conducted and it was shown for the first time that visual motion stimulation with CV not only activates a medial parieto-occipital visual area bilaterally, separate from middle temporal/medial superior temporal areas, it also simultaneously deactivates the pariete-insular vestibular cortex.
Abstract: Summary The vestibular system—a sensor of head accelerations— cannot detect self-motion at constant velocity and thus requires supplementary visual information. The perception of self-motion during constant velocity movement is completely dependent on visually induced vection. This can be linear vection or circular vection (CV). CV is induced by large-field visual motion stimulation during which the stationary subject perceives the moving surroundings as being stable and himself as being moved. To determine the unknown cortical visual‐vestibular interaction during CV, we conducted a PET activation study on CV in 10 human volunteers. The PET images of cortical areas activated during visual motion stimulation without CV were compared with those with CV. Hitherto, CV was explained neurophysiologically by visual‐ vestibular convergence with activation of the vestibular nuclei, thalamic subnuclei and vestibular cortex. If CV were mediated by the vestibular cortex, one would expect

Journal ArticleDOI
01 Aug 1998-Brain
TL;DR: It is suggested that important aspects of information processing in the human motor system could be based on network-like oscillatory cortical activity and might be modulated on at least two levels, which to some extent can operate independently from each other: regional activation (task-related power) and inter-regional functional coupling.
Abstract: We studied the activation and interaction of cortical motor regions during simple, internally paced and externally paced right-hand finger extensions in healthy volunteers. We recorded EEGs from 28 scalp electrodes and analysed task-related coherence, task-related power and movement-related cortical potentials. Task-related coherence reflects inter-regional functional coupling of oscillatory neuronal activity, task-related power reflects regional oscillatory activity of neuronal assemblies and movement-related cortical potentials reflect summated potentials of apical dendrites of pyramidal cells. A combination of these three analytical techniques allows comprehensive evaluation of different aspects of information processing in neuronal assemblies. For both externally and internally paced finger extensions, movement-related regional activation was predominant over the contralateral premotor and primary sensorimotor cortex, and functional coupling occurred between the primary sensorimotor cortex of both hemispheres and between the primary sensorimotor cortex and the mesial premotor areas, probably including the supplementary motor area. The main difference between the different types of movement pacing was enhanced functional coupling of central motor areas during internally paced finger extensions, particularly inter-hemispherically between the left and right primary sensorimotor cortexes and between the contralateral primary sensorimotor cortex and the mesial premotor areas. Internally paced finger extensions were also associated with additional regional (premovement) activation over the mesial premotor areas. The maximal task-related coherence differences between internally and externally paced finger extensions occurred in the frequency range of 20-22 Hz rather than in the range of maximal task-related power differences (9-11 Hz). This suggests that important aspects of information processing in the human motor system could be based on network-like oscillatory cortical activity and might be modulated on at least two levels, which to some extent can operate independently from each other: (i) regional activation (task-related power) and (ii) inter-regional functional coupling. We propose that internal pacing of movement poses higher demands on the motor system than external pacing, and that the motor system responds not only by increasing regional activation of the mesial premotor system, including the supplementary motor area, but also by enhancing information flow between lateral and mesial premotor and sensorimotor areas of both hemispheres, even if the movements are simple and unimanual.

Journal ArticleDOI
01 Oct 1998-Brain
TL;DR: This study highlights the relevance of dissociating musical abilities into their most significant cognitive components in order to identify their separate cerebral locations.
Abstract: Music processing ability was studied in 65 right-handed patients who had undergone unilateral temporal cortectomy for the relief of intractable epilepsy, and 24 matched normal controls. The ability to recognize changes in note intervals and to distinguish between different rhythms and metres was tested by presentation of sequences of simple musical phrases with variations in either pitch or temporal dimensions. The responses (right or wrong) enabled us to determine in which component of the music processing mechanism the patients had deficits and hence, knowing the positions of the surgical lesions, to identify their separate cerebral locations. The results showed that a right temporal cortectomy impaired the use of both contour and interval information in the discrimination of melodies and a left temporal cortectomy impaired only the use of interval information. Moreover, they underlined the importance of the superior temporal gyrus in melody processing. The excision of a part of the auditory areas (posterior part of the superior temporal gyrus) was found to be most detrimental for pitch and temporal variation processing. In the temporal dimension, we observed a dissociation between metre and rhythm and the critical involvement of the anterior part of the superior temporal gyrus in metric processing. This study highlights the relevance of dissociating musical abilities into their most significant cognitive components in order to identify their separate cerebral locations.

Journal ArticleDOI
01 May 1998-Brain
TL;DR: It is concluded that the premotor cortex is important for selecting movements after a visual cue and that the left hemisphere is dominant for the rapid selection of action.
Abstract: It is known that damage to the left hemisphere can lead to movement deficits, and that patients with apraxia have difficulty in selecting movements. Neurophysiological recording studies and lesion studies have shown that the premotor cortex is important for the selection of movements in monkeys. In this study we used transcranial magnetic stimulation (TMS) to disrupt the processing in human premotor cortex. We applied TMS to normal healthy volunteers over the premotor and primary motor areas while they carried out choice reaction time and simple reaction-time tasks. We measured response times of either hand as subjects were stimulated over the left and right hemisphere separately. We found that we were able to delay responses by stimulating at short cue-stimulus intervals (100-140 ms) over premotor cortex and at longer cue-stimulus intervals (300-340 ms) over primary motor cortex while subjects performed the choice reaction-time task with the contralateral hand. We were also able to delay responses with the ipsilateral hand while stimulating over the left premotor cortex, but not while stimulating over the right premotor cortex or either sensorimotor cortex. Premotor cortex stimulation alone disrupts an early stage of movement selection; motor cortex stimulation disrupts the movements at a later stage of execution. There was no distinguishing short cue-stimulus interval effect when premotor cortex was stimulated in the simple reaction time paradigm, where the movement selection demands of the task are kept to a minimum. We conclude that the premotor cortex is important for selecting movements after a visual cue and that the left hemisphere is dominant for the rapid selection of action.

Journal ArticleDOI
01 Mar 1998-Brain
TL;DR: It is demonstrated that congenitally blind subjects show task-specific activation of extrastriate visual areas and parietal association areas during Braille reading, compared with auditory word processing.
Abstract: A key issue in developmental neuroscience is the role of activity-dependent mechanisms in the epigenetic induction of functional organization in visual cortex. Ocular blindness and ensuing visual deprivation is one of the rare models available for the investigation of experience-dependent cortical reorganization in man. In a PET study we demonstrate that congenitally blind subjects show task-specific activation of extrastriate visual areas and parietal association areas during Braille reading, compared with auditory word processing. In contrast, blind subjects who lost their sight after puberty show additional activation in the primary visual cortex with the same tasks. Studies in blind-raised monkeys show that crossmodal responses in extrastriate areas can be elicited by somatosensory stimulation. This is consistent with the crossmodal extrastriate activations elicited by tactile processing in our congenitally blind subjects. Since primary visual cortex does not show crossmodal responses in primate studies, the differential activation in late and congenitally blind subjects highlights the possibility of reciprocal activation by visual imagery in subjects with early visual experience.

Journal ArticleDOI
01 Feb 1998-Brain
TL;DR: The results suggest that sequential finger movements recruit discrete sets of brain areas with different functions, consistent with the hypothesis that these areas function in the storage of motor sequences in spatial working memory.
Abstract: The brain regions activated by simple repetitive and sequential finger movements of different length were localized by measuring regional cerebral blood flow (rCBF) with PET. The experimental design consisted of finger movements cued by auditory pacing at 0.5 Hz. In all conditions of different sequence length the contralateral primary sensorimotor and premotor cortex, supplementary motor area and ipsilateral cerebellar cortex were activated. These areas showed a large increase in activation from rest to simple repetitive movement, and a further increase with the shortest sequence, suggesting an executive role in running sequences. The ipsilateral premotor area (Brodmann area 6), bilateral posterior parietal areas (Brodmann area 7) and precuneus showed an increase in rCBF related only to the length of the sequences, without any change from rest to simple repetitive movement. These areas are more selectively related to sequence performance. This finding is consistent with the hypothesis that these areas function in the storage of motor sequences in spatial working memory. Our results suggest that sequential finger movements recruit discrete sets of brain areas with different functions.

Journal ArticleDOI
01 Jul 1998-Brain
TL;DR: It is suggested that these cognitive impairments relate to a common deficit in inhibitory control mechanisms, under the control of striatofrontal mechanisms, and that such a deficit is present in Huntington's disease mutation carriers prior to the onset of definite motor symptomatology.
Abstract: The performance of 54 subjects genetically at risk for Huntington's disease was examined in double-blind fashion on a series of computerized tests from the Cambridge Neuropsychological Test Automated Battery. None of the subjects exhibited clinical movement disorder characteristic of Huntington's disease. Of the 54 subjects, 22 were Huntington's disease mutation carriers and 32 were non-carriers. On a comprehensive battery of neuropsychological tests previously shown to be sensitive to the early stages of clinical Huntington's disease, Huntington's disease mutation carriers exhibited highly specific cognitive deficits. In particular, Huntington's disease mutation carriers performed significantly less well than non-carriers, matched for age and IQ, on tests of attentional set shifting and semantic verbal fluency. Furthermore, performance on these two tests was significantly correlated, even after partialling out the effects of age and IQ. It is suggested that these cognitive impairments relate to a common deficit in inhibitory control mechanisms, under the control of striatofrontal mechanisms, and that such a deficit is present in Huntington's disease mutation carriers prior to the onset of definite motor symptomatology. The implications for the nature of the cognitive decline seen in Huntington's disease, and possible future treatment strategies, are discussed.

Journal ArticleDOI
01 May 1998-Brain
TL;DR: Unlike capsaicin-induced pain, allodynia was characterized by bilateral activation of inferior prefrontal cortex, suggesting that prefrontal responses to pain are context dependent.
Abstract: The PET H2 15O-bolus method was used to image regional brain activity in normal human subjects during intense pain induced by intradermal injection of capsaicin and during post-capsaicin mechanical allodynia (the perception of pain from a normally non-painful stimulus). Images of regional cerebral blood flow were acquired during six conditions: (i) rest; (ii) light brushing of the forearm; (iii) forearm intradermal injection of capsaicin, (iv) and (v) the waning phases of capsaicin pain; and (vi) allodynia. Allodynia was produced by light brushing adjacent to the capsaicin injection site after ongoing pain from the capsaicin injection had completely subsided. Capsaicin treatment produced activation in many discrete brain regions which we classified as subserving four main functions: sensation-perception (primary somatosensory cortex, thalamus and insula); attention (anterior cingulate cortex); descending pain control (periaqueductal grey); and an extensive network related to sensory-motor integration (supplementary motor cortex, bilateral putamen and insula, anterior lobe and vermis of the cerebellum and superior colliculus). Comparison of the noxious and non-noxious stimuli yielded several new insights into neural organization of pain and tactile sensations. Capsaicin pain, which had no concomitant tactile component, produced little or no activation in secondary somatosensory cortex (SII), whereas light brushing produced a prominent activation of SII, suggesting a differential sensitivity of SII to tactile versus painful stimuli. The cerebellar vermis was strongly activated by capsaicin, whereas light brush and experimental allodynia produced little or no activation, suggesting a selective association with C-fibre stimulation and nociceptive second-order spinal neurons. The experimental allodynia activated a network that partially overlapped those activated by both pain and light brush alone. Unlike capsaicin-induced pain, allodynia was characterized by bilateral activation of inferior prefrontal cortex, suggesting that prefrontal responses to pain are context dependent.

Journal ArticleDOI
01 Jul 1998-Brain
TL;DR: The findings indicate that a key function of left dorsolateral PFC at encoding relates specifically to the use of executive processes necessary for the creation of an organizational structure.
Abstract: Functional neuroimaging studies of episodic memory consistently report an association between memory encoding operations and left prefrontal cortex (PFC) activation. Encoding-related activation has been described in dorsolateral, ventrolateral and anterior prefrontal regions. We tested the hypothesis that a specific component of this left PFC activation reflects organizational processes necessary for optimal memory encoding. Subjects underwent PET scans while learning auditorily presented word lists under dual task conditions. The degree to which they were required to organize word lists semantically was systematically varied across three experimental conditions. A task in which words were already organized produced the least degree of left PFC activity whereas a task requiring subjects to generate an organizational structure was associated with maximal activity in this region. This activation was localized to a region just above the inferior frontal sulcus. The functional specificity of this increased activity for organizational processes was tested using a concurrent distracting task known to disrupt these processes. Distraction resulted in a significant attenuation of this activation during the task emphasizing organizational processes but not other encoding tasks. In contrast, the distraction task resulted in reduced activity in a more ventral/anterior PFC region expressed equally for all memory tasks. The findings indicate that a key function of left dorsolateral PFC at encoding relates specifically to the use of executive processes necessary for the creation of an organizational structure. Activity in more ventral and anterior left PFC regions would appear to reflect a less specific component of episodic memory encoding.

Journal ArticleDOI
01 Jun 1998-Brain
TL;DR: The results indicate that learning to read and write during childhood influences the functional organization of the adult human brain.
Abstract: Learning a specific skill during childhood may partly determine the functional organization of the adult brain. This hypothesis led us to study oral language processing in illiterate subjects who, for social reasons, had never entered school and had no knowledge of reading or writing. In a brain activation study using PET and statistical parametric mapping, we compared word and pseudoword repetition in literate and illiterate subjects. Our study confirms behavioural evidence of different phonological processing in illiterate subjects. During repetition of real words, the two groups performed similarly and activated similar areas of the brain. In contrast, illiterate subjects had more difficulty repeating pseudowords correctly and did not activate the same neural structures as literates. These results are consistent with the hypothesis that learning the written form of language (orthography) interacts with the function of oral language. Our results indicate that learning to read and write during childhood influences the functional organization of the adult human brain.

Journal ArticleDOI
01 Apr 1998-Brain
TL;DR: In relapsing-remitting and secondarygressive multiple sclerosis both brain and spinal cord MRI may provide a tool for monitoring patients, while in primary progressive multiple sclerosis the clinicoradiological correlation is weak for brain imaging.
Abstract: We investigated various magnetic resonance MRI parameters for both brain and spinal cord to see if any improved the clinicoradiological correlation in multiple sclerosis. Ninety-one multiple sclerosis patients (28 relapsing-remitting, 32 secondary progressive and 31 primary progressive) were imaged using conventional T1, proton density- and T2-weighted MRI of the brain and spinal cord. Focal brain and spinal cord lesion load was scored, as were diffuse signal abnormalities, brain ventricular volume and spinal cord cross-sectional area. Clinical measures included the expanded disability status scale (EDSS), the functional systems score and a dedicated urology complaint questionnaire. Secondary progressive patients differed from relapsing-remitting and primary progressive patients by a larger number of hypointense T1 lesions in the brain, ventricular enlargement and spinal cord atrophy. Primary progressive patients more often had diffuse abnormalities in the brain and/or spinal cord than did relapsing-remitting and secondary progressive patients. In the entire study population, EDSS correlated with both brain and spinal cord MRI parameters, which were independent. The urological complaint score correlated only with spinal cord MRI parameters. In relapsing-remitting and secondary progressive multiple sclerosis, the correlation between MRI and clinical parameters was better than in the entire population. In this subgroup EDSS variance could be explained best by T1 brain lesion load, ventricle volume and spinal cord cross-sectional area. In the primary progressive subgroup the clinicoradiological correlation was weak for brain parameters but was present between spinal cord symptoms and spinal cord MRI parameters. In conclusion, the different brain and spinal cord MRI parameters currently available revealed considerable heterogeneity between clinical subtypes of multiple sclerosis. In relapsing-remitting and secondary progressive multiple sclerosis both brain and spinal cord MRI may provide a tool for monitoring patients, while in primary progressive multiple sclerosis the clinicoradiological correlation is weak for brain imaging.