Characteristic neuroimaging findings in patients with diabetes and the 8296 mitochondrial tRNA(Lys)
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RATIONALE: Schizophrenia patients display an excessive rate of smoking compared to the general population. Nicotine increases acoustic prepulse inhibition (PPI) in animals as well as healthy humans, suggesting that smoking may provide a way of restoring deficient sensorimotor gating in schizophrenia. No previous study has examined the neural mechanisms of the effect of nicotine on PPI in humans. OBJECTIVES: To investigate whether nicotine enhances tactile PPI in healthy subjects and patients with schizophrenia employing a double-blind, placebo-controlled, cross-over design and, if so, what are the neural correlates of nicotine-induced modulation of PPI. MATERIALS AND METHODS: In experiment 1, 12 healthy smokers, 12 healthy non-smokers and nine smoking schizophrenia patients underwent testing for tactile PPI on two occasions, 14 days apart, once after receiving (subcutaneously) 12 microg/kg body weight of nicotine and once after receiving saline (placebo). In experiment 2, six healthy subjects and five schizophrenia patients of the original sample (all male smokers) underwent functional magnetic resonance imaging (fMRI) under the same drug conditions and the same tactile PPI paradigm as in experiment 1. RESULTS: Nicotine enhanced PPI in both groups. A comparison of patterns of brain activation on nicotine vs placebo conditions showed increased activation of limbic regions and striatum in both groups after nicotine administration. Subsequent correlational analyses demonstrated that the PPI-enhancing effect of nicotine was related to increased hippocampal activity in both groups. CONCLUSIONS: Nicotine enhances tactile PPI in both healthy and schizophrenia groups. Our preliminary fMRI findings reveal that this effect is modulated by increased limbic activity.
In this study cerebral reorganization was investigated in thalidomide-damaged subjects who use their feet to compensate for their malformed upper extremities. Tactile localization across toes was combined with fMRI to study use-dependent plasticity of the human somatosensory cortex. The manner of compensatory foot use was assessed by a questionnaire. In the behavioural experiment toes were stimulated with above threshold monofilaments and subjects had to report which toe was stimulated. When feet were employed for all everyday actions subjects made significantly fewer errors in the localization task. In subjects who use their feet only for specific actions such as grasping objects there were as many localization errors as in the control group of thalidomide-affected subjects with normal extremities. However, the patterns of mislocalizations were different with less errors occurring for the toe of the dominant foot involved in these actions. Functional MRI showed stronger haemodynamic responses to electrical stimulation of the toes in subjects using their feet for everyday actions as compared to controls. Our data show that long-term use of the feet for fine sensorimotor skills leads to better performance in tactile localization and changes in cerebral SI representation supporting the notion of use-dependent plasticity in the somatosensory cortex.
A growing number of brain imaging studies are being undertaken in order to better understand the contributions of multisensory processes to human behavior and perception. Many of these studies are designed on the basis of the physiological findings from single neurons in animal models, which have shown that multisensory neurons have the capacity for integrating their different sensory inputs and give rise to a product that differs significantly from either of the unisensory responses. At certain points these multisensory interactions can be superadditive, resulting in a neural response that exceeds the sum of the unisensory responses. Because of the difficulties inherent in interpreting the results of imaging large neuronal populations, superadditivity has been put forth as a stringent criterion for identifying potential sites of multisensory integration. In the present manuscript we discuss issues related to using the superadditive model in human brain imaging studies, focusing on population responses to multisensory stimuli and the relationship between single neuron measures and functional brain imaging measures. We suggest that the results of brain imaging studies be interpreted with caution in regards to multisensory integration. Future directions for imaging multisensory integration are discussed in light of the ideas presented.
This study details a method to statistically determine, on a millisecond scale and for individual subjects, those brain areas whose activity differs between experimental conditions, using single-trial scalp-recorded EEG data. To do this, we non-invasively estimated local field potentials (LFPs) using the ELECTRA distributed inverse solution and applied non-parametric statistical tests at each brain voxel and for each time point. This yields a spatio-temporal activation pattern of differential brain responses. The method is illustrated here in the analysis of auditory-somatosensory (AS) multisensory interactions in four subjects. Differential multisensory responses were temporally and spatially consistent across individuals, with onset at approximately 50 ms and superposition within areas of the posterior superior temporal cortex that have traditionally been considered auditory in their function. The close agreement of these results with previous investigations of AS multisensory interactions suggests that the present approach constitutes a reliable method for studying multisensory processing with the temporal and spatial resolution required to elucidate several existing questions in this field. In particular, the present analyses permit a more direct comparison between human and animal studies of multisensory interactions and can be extended to examine correlation between electrophysiological phenomena and behavior.
Evidence is now converging which suggests that, at the area level, working-memory processes within the dorsolateral and ventrolateral frontal cortices are organised according to the type of processing required, rather than according to the nature (i.e. domain) of the information being processed, as has been widely assumed. In a recent study using functional magnetic-resonance imaging (fMRI), performance of visual spatial and visual non-spatial working-memory tasks was shown to involve identical regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material were appropriately controlled. These results concur fully with recent reviews of the imaging literature, which demonstrate that spatial, visuospatial and verbal working-memory studies have produced distributed patterns of overlapping activation foci within these lateral frontal regions. Moreover, two recent positron-emission tomography studies have demonstrated that either, or both, the ventrolateral and dorsolateral frontal regions can be activated in spatial working-memory tasks, depending on the precise executive processes that are called upon by the task being performed. Similarly, when the executive requirements of a simple verbal working-memory task (e.g. forwards versus backwards digit span) are manipulated, differential activation within these two frontal cortical areas is observed. The results provide further evidence that the mid-dorsolateral and mid-ventrolateral frontal cortical areas make distinct "executive" contributions to memory and correspond with a fractionation of working-memory processes in psychological terms.
Functional magnetic resonance imaging (fMRI) was used to assess cerebral activation during manipulation of various complex meaningless objects as compared to manipulation of a single simple object (a sphere). Significant activation was found bilaterally in the ventral premotor cortex (Brodmann's area 44), in the cortex lining the anterior part of the intraparietal sulcus (most probably corresponding to monkey anterior intraparietal area, AIP), in the superior parietal lobule and in the opercular parietal cortex including the secondary somatosensory area (SII). We suggest that the cortex lining the anterior part of the intraparietal sulcus and area 44 are functionally connected and mediate object manipulation in humans.
We reviewed the cranial MRI and radionuclide cisternograms of four adults with postural headache indicating spontaneous intracranial hypotension (SIH). All four underwent clinical and radiological follow-up. MRI showed diffuse, thin meningeal enhancement; bilateral subdural fluid collections; and morphological abnormalities secondary to "sagging" of the brain. Radionuclide cisternography revealed direct or indirect signs of leakage of cerebrospinal fluid (CSF) along the spinal axis, and the symptoms resolved after the leak treated by epidural injection of blood at a level indicated by the cisternogram. The diffuse meningeal enhancement decreased but persisted on follow-up MRI, although the patients were asymptomatic. All morphologic abnormalities resolved during 3-5 months follow-up.
A number of imaging techniques have been used to investigate changes produced in the brain by boxing. Most morphological studies have failed to show significant correlations between putative abnormalities on imaging and clinical evidence of brain damage. Fenestration of the septum pellucidum, with formation of a cavum, one of the most frequent observations, does not appear to correlate with neurological or physiological evidence of brain damage. Serial studies on large groups may be more informative. Magnetic resonance spectroscopy and cerebral blood flow studies have been reported in only small numbers of boxers; serial studies are not available to date.
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Childhood autism is now widely viewed as being of developmental neurobiological origin. Yet, localised structural and functional brain correlates of autism have to be established. Structural brain-imaging studies performed in autistic patients have reported abnormalities such as increased total brain volume and cerebellar abnormalities. However, none of these abnormalities fully account for the full range of autistic symptoms. Functional brain imaging, such as positron emission tomography (PET), single photon emission computed tomography (SPECT) and functional MRI (fMRI) have added a new perspective to the study of normal and pathological brain functions. In autism, functional studies have been performed at rest or during activation. However, first-generation functional imaging devices were not sensitive enough to detect any consistent dysfunction. Recently, with improved technology, two independent groups have reported bilateral hypoperfusion of the temporal lobes in autistic children. In addition, activation studies, using perceptive and cognitive paradigms, have shown an abnormal pattern of cortical activation in autistic patients. These results suggest that different connections between particular cortical regions could exist in autism. The purpose of this review is to present the main results of rest and activation studies performed in autism.
OBJECTIVE: To review the imaging features of glutaric aciduria type 1 (GA-1) in a group of 20 patients, the largest published series to date. To document the findings not previously reported and compare our findings with the imaging characteristics of GA-1 previously reported in the literature. MATERIALS AND METHODS: For 14 patients the original scans were examined and in the remaining 6, where the imaging was unavailable, the radiology reports were consulted. Nine patients had serial cranial US examinations, 13 had 18 CT scans performed and 14 patients had 39 MRI scans. RESULTS: Widening of the sylvian fissures and of the fluid spaces anterior to the temporal lobes was seen in 93% of cases. The mesencephalic cistern was also widened in 86%. Abnormal high-signal intensity on T2-weighted (T2-W) images was seen in the basal ganglia and periventricular white matter in 64% of children. Subdural collections were found in 3 patients, all of which resolved spontaneously. Four neonates followed with serial cranial US showed bilateral multiple caudothalamic cysts. Abnormal high signal on T2-W images was seen in the dentate nucleus, substantia nigra and the pontine medial lemniscus in 79, 43 and 64%, respectively. CONCLUSIONS: Widening of the sylvian fissure, mesencephalic cistern and expansion of CSF spaces anterior to the temporal lobes are cardinal signs of GA-1. If combined with abnormalities of the basal ganglia and white matter, GA-1 should be strongly suspected.
BACKGROUND: The filamin-1 (FLN-1) gene is responsible for periventricular nodular heterotopia (PNH), which is an X-linked dominant neuronal migration disorder. OBJECTIVE: To review the clinical and imaging findings in a series of patients with documented filamin-1 mutations. MATERIALS AND METHODS: A retrospective review of the medical records and MR studies of a series of patients with PNH and confirmed FLN-1 mutations was done. There were 16 female patients (age range: .67-71 years; mean = 28.6) with filamin-1 gene mutations. RESULTS: In six of the patients the same mutation was inherited in four generations in one pedigree. In a second pedigree, a distinct mutation was found in two patients in two generations. In a third pedigree, a third mutation was found in four patients in two generations. The remaining four patients had sporadic de novo mutations that were not present in the parents. Ten patients had seizures, and all patients had normal intelligence. In all 16 patients MR demonstrated bilateral near-continuous PNH. There were no consistent radiographic or clinical differences between patients carrying different mutations. CONCLUSION: Patients with confirmed FLN-1 gene mutations are usually female and have a distinctive MR pattern of PNH. Other female patients with this same MR pattern probably harbor FLN-1 mutations and risk transmission to their progeny. This information is important for genetic counseling.
BACKGROUND: The classification of cerebral cortical dysplasia is difficult and there are histological similarities between focal cortical dysplasia (FCD) and hemimegalencephaly. Objectives. To correlate the MR features and histological data of cortical dysplasias. MATERIALS AND METHODS: The MR appearances of 17 brains were examined. According to the signal intensity within the pathological area on T2-weighted (T2-W) sequences we selected two groups. RESULTS: Group 1 comprised ten patients with high signal in the dysplastic area on T2-W images. This group included five hemimegalencephalies, three frontal quadramegalencephalies, and one gyral dysplasia. The pathological hemisphere was reduced in size in one case. The cortex was thickened in all cases on T1-weighted (T1-W) images. There was loss of delineation between white matter (WM) and grey matter (GM) in all cases on both T1-W and T2-W sequences. The differential diagnosis with tumour, neoplastic-like malformation or polymicrogyria was questionable. Group 2 comprised seven patients presenting without increased signal within the dysplastic area on T2-W images. WM and GM were of similar signal intensity in six cases, and delineation between white and grey matter was absent in all cases. There were mild abnormalities on T1-W sequences in all cases. The dysplasias were limited to a lobe in five cases and a gyrus in two cases. In all cases, depiction of the malformation was a greater diagnostic problem than the differential diagnosis. CONCLUSIONS: A constant MR sign in our series was the loss of delineation between WM and GM in the dysplastic area. This correlated well with the observed histological disorganisation. Markedly high signal within the dysplastic area seems to be related to myelin abnormalities rather than glial cell abnormalities.
PURPOSE: Muscarinic acetylcholine receptors (mAChRs) play an important role in the generation of seizures. Single-photon emission computed tomography (SPECT) with 12I-iododexetimide (IDEX) depicts tracer uptake by mAChRs. Our aims were to: (a) determine the optimum time for interictal IDEX SPECT imaging; (b) determine the accuracy of IDEX scans in the localisation of seizure foci when compared with video EEG and MR imaging in patients with temporal lobe epilepsy (TLE); (c) characterise the distribution of IDEX binding in the temporal lobes and (d) compare IDEX SPECT and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in identifying seizure foci. METHODS: We performed sequential scans using IDEX SPECT imaging at 0, 3, 6 and 24 h in 12 consecutive patients with refractory TLE undergoing assessment for epilepsy surgery. Visual and region of interest analyses of the mesial, lateral and polar regions of the temporal lobes were used to compare IDEX SPECT, FDG PET and MR imaging in seizure onset localisation. RESULTS: The 6-h IDEX scan (92%; kappa=0.83, p=0.003) was superior to the 0-h (36%; kappa=0.01, p>0.05), 3-h (55%; kappa=0.13, p>0.05) and 24-h IDEX scans in identifying the temporal lobe of seizure origin. The 6-h IDEX scan correctly predicted the temporal lobe of seizure origin in two patients who required intracranial EEG recordings to define the seizure onset. Reduced ligand binding was most marked at the temporal pole and mesial temporal structures. IDEX SPECT was superior to interictal FDG PET (75%; kappa=0.66, p=0.023) in seizure onset localisation. MR imaging was non-localising in two patients in whom it was normal and in another patient in whom there was bilateral symmetrical hippocampal atrophy. CONCLUSION: The 6-h IDEX SPECT scan is a viable alternative to FDG PET imaging in seizure onset localisation in TLE.
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We describe a rare case of adult pilocytic astrocytoma in which exophytic growth from the brain stem presented as a right cerebellopontine angle mass. An initial MRI examination using T2- and T1-weighted images without and with contrast suggested the diagnosis of schwannoma. Subsequent use of 3D CISS (three-dimensional constructive interference in steady state) and T1-weighted contrast-enhanced 3D MP-RAGE (three-dimensional magnetization prepared rapid acquisition gradient echo) sequences led to the diagnosis of an exophytic brain stem tumor, documented the precise relationships of the tumor to cranial nerve VIII, revealed encasement of cranial nerves IX-XII (later confirmed intraoperatively), and provided the proper basis for planning surgical management.