Mercader Jm

Amygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging.

It has been suggested that the pathophysiology of panic disorder (PD) may involve abnormalities in several brain structures, including the amygdala. To date, however, no study has used quantitative structural neuroimaging techniques to examine amygdalar anatomy in this disorder. Volumetric magnetic resonance imaging (MRI) studies of the amygdalas, hippocampi, and temporal lobes were conducted in 12 drug-free, symptomatic PD patients (six females and six males), and 12 case-matched healthy comparison subjects. Volumetric MRI data were normalized for brain size. PD patients were found to have smaller left-sided and right-sided amygdalar volumes than controls. No differences were found in either hippocampi or temporal lobes. These findings provide new evidence of changes in amygdalar structure in PD and warrant further anatomical and MRI brain studies of patients with this disorder.

Volume changes in gray matter in first-episode neuroleptic-naive schizophrenic patients treated with risperidone.

Abstract: Structural neuroimaging techniques have consistently shown that treatment of schizophrenic patients with conventional antipsychotics causes an increase in basal ganglia volume. However, findings in schizophrenic patients treated with the newer atypical antipsychotic drugs are less consistently reported. To explore this issue, the authors used a whole-brain, unbiased, and automated technique for comparing brain structural features across scans in schizophrenic patients before and after a treatment with the atypical antipsychotic risperidone. T1-weighted images from 11 first-episode neuroleptic-naive schizophrenic patients were processed and analyzed for regions of interest (basal ganglia) by using optimized voxel-based morphometry. Scans were repeated after 3 months of continuous treatment with risperidone. Region of interest-based voxel-based morphometry analyses revealed increases in gray matter volume for the right and left caudate nuclei and for the left accumbens after the treatment with risperidone. Hence, in our sample of schizophrenic patients, treatment with risperidone was associated, in contrast to the findings for other atypical antipsychotics, with an increase in basal ganglia volume. Such discrepancy could be related to the pharmacodynamics of risperidone (the atypical antipsychotic showing the higher affinity for D2 receptors) and the rather high mean doses used in our study (ie, 6.05 mg/d).

Cerebral correlates of declarative memory dysfunctions in early traumatic brain injury

We investigated residual brain damage in subjects who suffered severe traumatic brain injury (TBI) in childhood, and its relationship with declarative memory impairment. Magnetic resonance imaging (MRI) volumetric data and memory performance were compared between 16 adolescents with antecedents of severe TBI and 16 matched normal controls. Volumes of grey matter, white matter, cerebrospinal fluid (CSF), hippocampus, and caudate nuclei were measured. Verbal memory was assessed by the Rey’s Auditory Verbal Learning test and visual memory by the Rey’s Complex Figure. TBI patients performed significantly worse than controls in both verbal and visual memory. Patients presented decreased white matter volume and increased CSF. The hippocampus was reduced, but not the caudate nuclei. Memory performance correlated with CSF. Plasticity is incomplete for structural and functional deficits in children with TBI. Hippocampal atrophy, white matter loss, and memory impairment remain until adolescence. Memory sequelae are related more to diffuse brain injury, as reflected by MRI findings of increased CSF, than to hippocampal injury.

Cerebral response to speech in vegetative and minimally conscious states after traumatic brain injury

Primary objective: To study cerebral response in a functional magnetic resonance imaging (fMRI) task of speech perception in a sample of patients in vegetative state (VS) and minimally conscious state (MCS) after traumatic brain injury. Methods: Three patients in VS, four patients in MCS and 19 healthy volunteers were enrolled for the study. All subjects underwent an fMRI task of passive listening of narratives played forward and backward, alternated with periods of silence. This study analysed cerebral response to language and to complex sound processing in the healthy subjects’ group and in each patient, using SPM5. Results: One patient in VS and one in MCS showed cerebral responses to language and to complex sound very similar to those shown by the healthy volunteers. Two more patients, one in VS and one in MCS, showed significant responses to complex sound only. Finally, one patient in VS and one patient in MCS failed to show significant activation in response to either stimulus. Conclusions: Some patients in VS and MCS can preserve cerebral responses to language and auditory stimuli. fMRI may be useful to identify these responses, which may pass unnoticed in a bedside examination.

Reductions of Thalamic Volume and Regional Shape Changes in the Vegetative and the Minimally Conscious States

The thalamus is known to play a key role in arousal regulation and support of human consciousness. Neuropathological studies have identified thalamic damage as one of the most common abnormalities present in the brains of patients who were in a vegetative state (VS) or a minimally-conscious state (MCS) state at the time of their deaths. Nonetheless, no in vivo studies of thalamic abnormalities in these patients have been conducted. Using high-resolution T1-weighted magnetic resonance images and a novel approach to shape analysis, we investigated thalamic global and regional changes in a sample of patients in a VS or an MCS. Group comparisons and correlations with clinical variables were performed for the total thalamic volume and for each surface vertex. Total thalamic volume was significantly lower in patients than in healthy volunteers. Shape analysis revealed significant bilateral regional atrophy in the dorso-medial body in patients compared to controls; this atrophy was more widespread in VS than in MCS patients. Lower thalamic volume was significantly correlated with worse Disability Rating Scale scores. Shape analysis suggested that the dorso-medial nucleus and the internal medullar lamina were the main regions responsible for this correlation. Our findings suggest that MCS and VS patients present different patterns of regional thalamic abnormalities, and that these differences partially explain their clinical profile.

Dopamine DRD2 Taq I polymorphism associates with caudate nucleus volume and cognitive performance in memory impaired subjects

We studied the relationship among dopamine receptor D2 (DRD2) Taq I genetic polymorphism, caudate nucleus volumetry as measured using MRI and neuropsychological functions in 49 memory impaired older people. Compared with DRD2 A1 carriers, subjects homozygous for the DRD2 A2 allele performed poorer in a measure of general cognitive functioning (MMSE) and in long term verbal memory, and presented reduced left caudate nucleus volumes. Caudate nucleus atrophy correlated with cognitive measures influenced by the genetic polymorphism and with visual memory performance. Our findings suggest that among the aged with cognitive impairments, the homozygous status for the A2 allele of the DRD2 Taq I polymorphism is associated with diminished cognitive performance and increased atrophy in the striatum.

Combination of diffusion tensor and functional magnetic resonance imaging during recovery from the vegetative state

BackgroundThe rate of recovery from the vegetative state (VS) is low. Currently, little is known of the mechanisms and cerebral changes that accompany those relatively rare cases of good recovery. Here, we combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to study the evolution of one VS patient at one month post-ictus and again twelve months later when he had recovered consciousness.MethodsfMRI was used to investigate cortical responses to passive language stimulation as well as task-induced deactivations related to the default-mode network. DTI was used to assess the integrity of the global white matter and the arcuate fasciculus. We also performed a neuropsychological assessment at the time of the second MRI examination in order to characterize the profile of cognitive deficits.ResultsfMRI analysis revealed anatomically appropriate activation to speech in both the first and the second scans but a reduced pattern of task-induced deactivations in the first scan. In the second scan, following the recovery of consciousness, this pattern became more similar to that classically described for the default-mode network. DTI analysis revealed relative preservation of the arcuate fasciculus and of the global normal-appearing white matter at both time points. The neuropsychological assessment revealed recovery of receptive linguistic functioning by 12-months post-ictus.ConclusionsThese results suggest that the combination of different structural and functional imaging modalities may provide a powerful means for assessing the mechanisms involved in the recovery from the VS.

Apolipoproteins E and C1 and brain morphology in memory impaired elders

Previous research has shown that polymorphisms of the apolipoproteins E (APOE) and APOC1 represent genetic risk factors for dementia and for cognitive impairment in the elderly. The brain mechanisms by which these genetic variations affect behavior or clinical severity are poorly understood. We studied the effect of APOE and APOC1 genes on magnetic resonance imaging measures in a sample of 50 subjects with age-associated memory impairment. The APOE E4 allele was associated with reduced left hippocampal volumes and APOE*E3 status was associated with greater frontal lobe white matter volumes. However, no APOE effects were observed when analyses accounted for other potential confounding variables. The effects of APOC1 on hippocampal volumes appeared to be more robust than those of the APOE polymorphism. However, no modulatory effects on brain morphology outside the medial temporal lobe region were observed when demographic variables, clinical status, and other anatomical brain measurements were taken into consideration. Our results suggest that the role of the APOC1 polymorphism in brain morphology of the cognitively impaired elderly should be examined in further studies.

1H-MR spectroscopy is sensitive to subtle effects of perinatal asphyxia

The authors performed neuropsychological and 1H-MRS studies in 18 subclinical patients with antecedents of perinatal asphyxia (PA) and in 18 matched control subjects. Patients with PA showed reduced values of N-acetylaspartate (NAA) in both the basal ganglia and the midtemporal region (MTR) and reduced NAA/choline values in the MTR. Neuropsychological testing showed group differences in tasks related to attention and memory. These results indicate persistent dysfunctions in cerebral structures vulnerable to hypoxia and demonstrate the utility of MRS for the long-term evaluation of cerebral sequelae of neonatal asphyxia.

Increased cerebral activity in Parkinson's disease patients carrying the DRD2 TaqIA A1 allele during a demanding motor task: a compensatory mechanism?

Previous studies suggest that neuroimaging techniques are useful for detecting the effects of functional genetic polymorphisms on brain function in healthy subjects or in patients presenting with psychiatric or neurodegenerative conditions. Former evidence showed that individuals carrying risk alleles displayed broader patterns of brain activity during behavioural and cognitive tasks, despite being clinically comparable to non‐carriers. This suggests the presence of compensatory brain mechanisms. In the present study, we investigated this effect in Parkinson’s disease (PD) patients carrying the DRD2 TaqIA A1 allelic variant. This variant may confer an increased risk of developing the disease and/or influence the clinical presentation. During a complex sequential motor task, we evidenced by functional magnetic resonance imaging that A1 allele carriers activated a larger network of bilateral cerebral areas than non‐carriers, including cerebellar and premotor regions. Both groups had similar clinical and demographic measures. In addition, their motor performance during the functional magnetic resonance experiment was comparable. Therefore, our conclusions, pending replication in a larger sample, seem to reflect the recruitment of compensatory cerebral resources during motor processing in PD patients carrying the A1 allele.