Search PubMed⌕ Search

Biomedical subjects

M A Ron

Publications and source records attributed to M A Ron.

At least 19 recordsLinked to original sources
PubMed2006

Structural brain correlates of IQ changes in bipolar disorder.

BACKGROUND: There is increasing evidence that cognitive deficits are present in bipolar disorder (BP), but their neural correlates have not been fully explored. The aim of this study is to correlate structural brain abnormalities with cognitive performance in BP and to explore differences between clinical subtypes. METHOD: Thirty-six BP patients (13 men, 23 women) with a mean age of 39 years (range 21-63 years) underwent neuropsychological testing and imaging. Twenty-five patients had bipolar disorder I (BP I) and 11 had bipolar disorder II (BP II). Patients with co-morbid psychiatric diagnosis, drug and alcohol abuse or systemic illness were excluded. Correlations between cognitive performance and structural brain changes were explored using high-resolution anatomical imaging and magnetization transfer imaging (MTI). RESULTS: In the whole BP group the difference between estimated pre-morbid IQ and current IQ was significantly correlated with left-sided reduction of the magnetization transfer ratio (MTR) in the superior temporal gyrus, uncus and para-hippocampal gyrus. In BP II patients the areas where these correlations were significant extended to the right superior and middle temporal gyri, cingulate gyrus, pre-cuneus and adjacent frontal and parietal white matter. The volume of superior temporal white matter was also correlated with IQ difference in this subgroup. CONCLUSIONS: The study highlights the association between fronto-temporal abnormalities and decline in IQ in BP. The more extensive abnormalities present in BP II patients suggest that persistent depression, rather than mania, may be a key pathophysiological factor or that BP II represents a clinical phenotype with a higher risk of developing cognitive abnormalities.

Adult↗
PubMed2005

The corpus callosum in first episode schizophrenia: a diffusion tensor imaging study.

BACKGROUND: Neuropathological and imaging studies suggest that corpus callosum abnormalities (CC) are present in schizophrenia, but it remains to be determined whether these abnormalities are present at illness onset. Diffusion tensor imaging (DTI), which is more sensitive than conventional magnetic resonance imaging (MRI) in detecting subtle structural changes in the organisation and integrity of white matter tracts, is an ideal tool to investigate this question. OBJECTIVE: To determine whether CC abnormalities are present at illness onset in schizophrenia. METHODS: Twenty patients (14 men, six women) with first episode schizophrenia and 29 controls (11 men, 18 women) were studied. Both high resolution volumetric T1-weighted images and DTI were acquired. Regions of interest (ROI) were placed in the splenium and genu of the CC and fractional anisotropy (FA) and diffusivity (D) measured. RESULTS: No differences in FA or D were detected in these regions between patients and controls. In women, irrespective of group membership, FA was significantly lower and there was a trend for D to be higher than in men, indicating less barriers to diffusion in females. CONCLUSION: The negative findings of this study suggest that in the early stages of schizophrenia there is no disruption to the integrity of the CC and raise the possibility that the neuropathological abnormalities may appear later and be progressive, at least in some patients.

Adolescent↗
PubMed2004

A study of bipolar disorder using magnetization transfer imaging and voxel-based morphometry.

Bipolar disorder (BP) traditionally has been considered as a recurrent illness with full recovery between episodes, and the absence of neuropathological abnormalities has usually been taken for granted. In recent times, the realization that, for many BP carries a poor prognosis, that cognitive deficits are often persistent and that structural brain abnormalities are detectable with modern imaging techniques has spurred the search for its neuropathological substrate. The shortcomings of post-mortem studies make the use of imaging techniques sensitive to neuropathological changes compelling. We report here the first study of BP patients using two such techniques in conjunction: magnetization transfer imaging (MTI) and voxel-based morphometry (VBM). Thirty-nine patients with BP (13 males and 26 females; 28 with BPI and 11 with BPII) and 35 healthy controls were investigated. Both high-resolution volumetric T1-weighted images and MT images were acquired from all subjects. Images were processed using a voxel-by-voxel analysis in statistical parametric mapping 2 (SPM2). The magnetization transfer ratio MTR, an index indicative of loss of macromolecular density, was reduced in the right subgenual anterior cingulate and adjacent white matter in bipolar patients compared with controls. VBM did not reveal significant volumetric differences between BP patients and controls in grey and white matter, but white matter density was significantly reduced bilaterally in prefrontal areas encompassing fronto-striatal connections. Our findings suggest that subtle abnormalities are present in the anterior cingulate and subgyral white matter in patients with BP in the absence of significant volumetric changes. These findings are in keeping with those of previously reported neuropathological studies and illustrate important similarities (involvement of the anterior cingulate) and differences (lack of widespread cortical abnormalities in BP) with our previous studies in schizophrenic patients using the same methodology.

Adult↗
PubMed2004

Functional magnetic resonance imaging of the cerebral response to visual stimulation in medically unexplained visual loss.

BACKGROUND: Medically unexplained visual loss occurs in 1 to 5% of patients attending ophthalmology clinics and for many it runs a chronic course. A psychogenic aetiology is presumed in such cases, but little is known about the underlying neural mechanisms. Recent studies have established the value of functional magnetic resonance imaging (fMRI) in understanding the mechanisms of unexplained motor and sensory symptoms. The purpose of this study was to use a similar strategy (fMRI) to evaluate the cerebral responses to visual stimulation in a group of patients with medically unexplained visual loss, in an attempt to determine the underlying neural mechanisms. METHOD: Brain activation induced by periodic (monocular) 8 Hz visual stimulation was detected by fMRI in five patients with unexplained visual loss who fulfilled DSM-IV criteria for conversion disorder, and seven normal volunteers. Between-group differences in mean power of activation were estimated by fitting a one-way analysis of variance (ANOVA) model at each intracerebral voxel in standard space. RESULTS: Compared with controls, patients showed reduced activation in visual cortices, but increased activation in left inferior frontal cortex, left insula-claustrum, bilateral striatum and thalami, left limbic structures, and left posterior cingulate cortex. CONCLUSIONS: This preliminary study has identified novel neural correlates in patients with unexplained visual loss. The abnormal pattern of activation may reflect inhibition of primary visual cortex or a shift towards non-conscious (implicit) processing.

Adolescent↗
PubMed2002

Investigating regional white matter in schizophrenia using diffusion tensor imaging.

Diffusion tensor imaging (DTI) was used to investigate regional white matter in vivo in patients with schizophrenia. DTI is capable of providing information about the organization of white matter tracts and has only recently been used to study schizophrenia. In this study, a voxel based analysis of DTI maps in 14 patients and 19 controls did not reveal any areas of significant differences in DTI measures in white matter. The findings suggest that the structural integrity of white matter in these patients was not disrupted. These results are discussed in relation to previous studies reporting positive findings. It is concluded that further studies using DTI in larger samples, improved and standardised methods of data acquisition and analysis are needed.

Adult↗
PubMed2001

Neuropathological abnormalities in schizophrenia: evidence from magnetization transfer imaging.

Post-mortem and structural brain imaging studies in schizophrenia have reported macroscopic changes such as global and regional cortical volume reductions, but it has been more difficult to characterize the histopathological changes that underlie these abnormalities. Magnetization transfer imaging (MTI), a novel MRI technique, more sensitive to subtle or early neuropathological changes than conventional MRI, provides a quantitative measure of macromolecular structural integrity represented by the magnetization transfer ratio (MTR). In this study, we used MTI to examine 25 patients with schizophrenia compared with 30 age-matched controls. A voxel-based analysis of the MTR maps revealed widespread MTR reductions in the cortex unrelated to volume reduction, predominantly in the frontal and temporal regions, in the schizophrenic patients when compared with controls. MTR reductions in bilateral parieto-occipital cortex and the genu of the corpus callosum were associated with the severity of negative symptoms in the schizophrenic patients. However, MTR changes were not related to other clinical variables of age, duration of illness and current dose of antipsychotic medication. This study demonstrates that MTR abnormalities in the cortex can be detected in chronic schizophrenia that may reflect subtle neuropathological changes involving neurones or neuronal processes. Longitudinal studies are needed to determine whether these abnormalities are related to disease progression or other disease manifestations such as cognitive changes.

Adult↗
PubMed2000

A comparison of neuropsychological deficits in primary and secondary progressive multiple sclerosis.

Neuropsychological deficits and the relationship to brain pathology were examined in 13 primary progressive (PP) and 12 secondary progressive (SP) multiple sclerosis patients with a similar duration of the progressive phase and comparable physical disability. A battery of neuropsychological tests to assess attention, short-term and working memory was administered to the patients, and their performance was compared to that of 20 healthy controls matched for age and premorbid IQ. Total cerebral lesion load on T2-weighted magnetic resonance imaging was measured in the patients. Both PP and SP patients performed significantly worse than controls in most of the neuropsychological tests. There were only subtle differences between SP and PP on the working memory task although magnetic resonance imaging lesion load was significantly higher in SP than in PP patients. In this exploratory study only subtle differences in cognitive impairment were detected between SP and PP patients matched for physical disability and relevant illness features. The results also suggest that the severity of cognitive impairment cannot be fully explained by the extent of abnormalities detected on conventional T2-weighted magnetic resonance images, and that other pathological abnormalities such as in normal-appearing white matter are likely to be involved.

Adult↗
PubMed2000

Patterns of referral in patients with medically unexplained motor symptoms.

OBJECTIVE: To investigate the pattern and reasons for referrals in 64 patients with a stable diagnosis of motor conversion symptoms who had been assessed at the National Hospital for Neurology and Neurosurgery (NHNN). METHOD: Patients were interviewed on average 6 years after their original admission to the NHNN. Hospital notes and GP records were consulted. RESULTS: Psychiatrists at the NHNN saw 75% of patients. Treatment was initiated in 60% of these. During the 6-year follow up, many patients continued to be referred to neurologists and other specialists, but subsequent psychiatric referral was rare. Many changed their GP after discharge from the NHNN and a disproportionate number of re-referrals was made by GPs who had known their patients for less than 6 months. Psychological attribution of symptoms was rare and did not appear to be related to the pattern of referrals. CONCLUSION: The pattern of care of these patients was inconsistent and many felt dissatisfied with the treatment they received. This led to further referrals, unnecessary use of valuable resources and unnecessary exposure to iatrogenic damage. Further studies should aim to assist GPs and other clinicians in deciding when referral is likely to be beneficial.

Adult↗
PubMed2000

Schizophrenia, temporal lobe epilepsy and psychosis: an in vivo magnetic resonance spectroscopy and imaging study of the hippocampus/amygdala complex.

BACKGROUND: We have used proton magnetic resonance imaging and spectroscopy to measure hippocampus/amygdala volumes and anterior hippocampal metabolite concentrations (N-acetyl aspartate (NAA), creatine/phosphocreatine and choline) in subjects with temporal lobe epilepsy (TLE), schizophrenia and in normal controls. METHOD: Four groups of right-handed patients were selected: 12 with TLE and psychosis (EP), 12 with TLE and no psychosis (ENP), 26 with schizophrenia, and 38 normal controls. Imaging and spectroscopy were performed with a 1.5T Signa GE scanner. RESULTS: The schizophrenia group showed a significant left-sided reduction in all metabolites. In the epilepsy groups NAA was reduced bilaterally. The NAA reduction in the EP group was greater than in the ENP group, especially on the left, although the result did not reach significance. Total hippocampus/amygdala volumes showed no significant differences in any of the groups when compared with normal controls. When compared with controls significant, specific regional volume reductions were present bilaterally in the EP group and in the left hippocampus/amygdala in schizophrenia. The regional volume reduction found in schizophrenia was also present in EP but not in ENP. CONCLUSION: Spectroscopic abnormalities were more pronounced in the epilepsy groups and were bilateral, and abnormalities in schizophrenia were left sided. Specific regional hippocampus/amygdala volume reductions were more marked in the EP group and were bilateral. Left-sided regional volume reduction identified in the dominant hemisphere of schizophrenics was also present in EP patients, but not in ENP, suggesting that this region in the left temporal lobe may be significant in the aetiology of psychosis. This is further supported by the predominantly left-sided NAA reduction in schizophrenia. High resolution morphometric studies may identify specific regions of the brain associated with the development of psychosis.

Adult↗
PubMed2000

In vivo investigation of white matter pathology in schizophrenia with magnetisation transfer imaging.

OBJECTIVES: This study is the first to use magnetisation transfer imaging (MTI), a technique sensitive to myelin and axonal abnormalities, to investigate the white matter in vivo in patients with schizophrenia. METHODS: MTI was performed in 25 schizophrenic patients and 30 healthy controls. A region of interest (ROI) approach was used to obtain magnetisation transfer ratios (MTRs) in several regions of cerebral white matter. RESULTS: MTR values were significantly reduced in the right and left temporal regions in schizophrenic patients compared with controls (p<0.001). Clinical variables such as age, duration of symptoms, schizophrenic symptomatology, and soft neurological signs did not predict this reduction in MTR. There were no MTR abnormalities in the other regions sampled. However, the correlation between the left and right frontal MTR values was marginally significantly different in schizophrenic patients compared with controls suggesting that subtle differences in interhemispheric connections may be present. CONCLUSIONS: Subtle white matter pathology, most likely related to myelin and axonal abnormalities, can be detected in the temporal lobes in schizophrenic patients. MTI may be a useful tool in investigating the white matter in schizophrenia.

Adult↗
PubMed2000

Neuropathological abnormalities of the corpus callosum in schizophrenia: a diffusion tensor imaging study.

OBJECTIVES: Diffusion tensor imaging (DTI), a technique capable of examining water diffusion in different tissues and the organisation of white matter tracts, was used to investigate the neuropathology of the corpus callosum in vivo in patients with schizophrenia. METHODS: Diffusion tensor imaging was performed in 20 schizophrenic patients and 25 healthy controls. Two complementary measures, mean diffusivity and fractional anisotropy, which are considered to be sensitive indices of axonal integrity, were obtained from regions of interest in the genu (anterior) and splenium (posterior) of the corpus callosum. RESULTS: Mean diffusivity was significantly increased and fractional anisotropy significantly reduced in the splenium but not the genu of the corpus callosum in the schizophrenic group compared with controls. There were no significant sex differences in the DTI measures for either the schizophrenic or control group. Clinical variables such as age, duration of illness, dose of antipsychotic medication, and schizophrenic symptoms did not predict the DTI changes in the schizophrenic patients. CONCLUSIONS: The presence of DTI changes in the splenium but not the genu of the corpus callosum suggests that there may be a focal disruption of commisural connectivity in schizophrenia. However, these findings do not exclude the possibility of abnormalities in other areas of the corpus callosum or other regions of white matter and further research using different methods of analysis may enable us to clarify this. Diffusion tensor imaging is a valuable tool in investigating the structure of white matter in schizophrenia.

Adult↗
PubMed2000

A volumetric study of hippocampus and amygdala in depressed patients with subjective memory problems.

MRI was used to measure amygdalar and hippocampal volumes in 14 nondemented depressed patients who persistently complained of "memory" difficulties and in 14 control subjects. Mild neuropsychological impairment had been detected in 5 patients before the study but had later improved. The volume of the left amygdala was smaller in depressed subjects, and there was a trend for smaller left hippocampus in the 5 patients who had exhibited mild cognitive impairment. The authors conclude that subjective memory complaints in depressed patients do not translate into a clinical picture of dementia, but that abnormalities in the amygdala and hippocampus may be relevant in explaining affective and cognitive symptoms.

Adult↗
PubMed1999

Multiple sclerosis: the disease and its manifestations.

Multiple sclerosis is an immune-mediated inflammatory demyelinating disease of the central nervous system clinically characterized by relapses and remissions of neurological disturbance. A typical relapse, exemplified by optic neuritis, increases in severity over a week or two and after approximately one month begins to remit. Resolution takes place over the course of two to three months. In the early stages, clinical recovery is virtually complete, though persistent abnormalities of conduction can usually be detected by evoked potential techniques and persistent structural abnormalities can be detected by magnetic resonance imaging (MRI). These techniques, together with cerebrospinal fluid examination for oligoclonal IgG, provide supporting evidence for the diagnosis which, in the absence of a specific test, nevertheless remains primarily clinical. The course of the disease is very variable, but after a number of years neurological deficit begins to accumulate after each relapse. In most patients, the relapsing and remitting phase of the disease is followed by a phase of continuous progression of disability. Cognitive disturbances can be detected in many patients even quite early in the course of the illness. Deficits in attention, memory and executive skills may be prominent and tend to become increasingly prominent as neurological deficit increases, although this is not always the case. There is some correlation between the extent of MRI abnormalities in the cerebral white matter and the severity of cognitive deficit. Depression and anxiety are commonly experienced but are poorly correlated to the lesion load seen on MRI. In contrast, the much rarer psychotic symptoms, euphoria and emotional lability are closely linked to the severity of white matter disease.

Cognition Disorders↗
PubMed1999

Correlates of executive function in multiple sclerosis: the use of magnetic resonance spectroscopy as an index of focal pathology.

Proton magnetic resonance spectroscopy (MRS) was performed in a group of patients with multiple sclerosis (MS) and matched control subjects to examine the relationship between frontal lobe pathology and performance on tests of executive function. The N-acetyl aspartate/creatine ratio (NAA/Cr) was significantly reduced in frontal lesions and/or normal-appearing white matter in the patient group compared with the control group, but choline/creatine ratios did not differ. Although MRS abnormalities and executive deficits were not correlated for MS patients as a group, a few patients with more severe abnormalities of NAA/Cr ratio performed worse than other patients on the spatial working memory test, suggesting that subtle frontal neuropathological abnormalities detected by MRS may contribute to executive deficits. Further investigation is warranted to determine the value of MRS as an index of the pathophysiological processes leading to cognitive deficit.

Adult↗
PubMed1998

Slater revisited: 6 year follow up study of patients with medically unexplained motor symptoms.

OBJECTIVE: To investigate psychiatric and neurological morbidity, diagnostic stability, and indicators of prognosis in patients previously identified as having medically unexplained motor symptoms. DESIGN: Follow up study. SETTING: National Hospital for Neurology and Neurosurgery, London--a secondary and tertiary referral hospital for neurological disorders. SUBJECTS: 73 patients with medically unexplained motor symptoms admitted consecutively in 1989-91. 35 (48%) patients had absence of motor function (for example, hemiplegia) and 38 (52%) had abnormal motor activity (for example, tremor, dystonia, or ataxia). MAIN OUTCOME MEASURES: Neurological clinical diagnosis at face to face reassessment by a neurologist and a psychiatric diagnosis after a standardised assessment interview--the schedule for affective disorders and schizophrenia--conducted by a psychiatrist. RESULTS: Good follow up data were available for 64 subjects (88%). Only three subjects had new organic neurological disorders at follow up that fully or partly explained their previous symptoms. 44/59 (75%) subjects had had psychiatric disorders; in 33 (75%) patients, the psychiatric diagnosis coincided with their unexplained motor symptoms. 31/59 (45%) patients had a personality disorder. Three subjects had developed new psychiatric illnesses at follow up, but in only one did the diagnosis account for the previous motor symptoms. Resolution of physical symptoms was associated with short length of symptoms, comorbid psychiatric disorder, and a change in marital status during follow up. CONCLUSIONS: Unlike Slater's study of 1965, a low incidence of physical or psychiatric diagnoses which explained these patients' symptoms or disability was found. However, a high level of psychiatric comorbidity existed.

Adolescent↗
PubMed1998

Neuropsychological deficits in multiple sclerosis after acute relapse.

OBJECTIVES: To examine cognitive and neurological changes and their relation to brain pathology in patients with multiple sclerosis during acute relapse. METHODS: Thirteen patients with multiple sclerosis were examined with a battery of neuropsychological tests during acute relapse and six weeks later. Their performance was compared with the performance of 10 controls matched for age and premorbid IQ. Gadolinium (Gd) enhanced MRI was also performed in patients on both occasions. RESULTS: The patients with multiple sclerosis performed significantly worse than controls on most tests of attention and memory during acute relapse and in remission. At follow up there was a significant or trend of improvement in performance on some tests of attention for patients in whom the Gd enhanced lesion load had decreased. In this subgroup of patients, their improvement also correlated significantly with the reduction in acute lesion load. CONCLUSIONS: The findings suggest that certain neuropsychological deficits detected during an acute relapse may be reversible, particularly in patients who initially have mild cognitive impairment.

Activities of Daily Living↗