Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. (9/1612)

BACKGROUND AND PURPOSE: Patients with spontaneous intracerebral hemorrhage (ICH) frequently have small areas of signal loss on gradient-echo T2*-weighted MR images, which have been suggested to represent remnants of previous microbleeds. Our aim was to provide histopathologic support for this assumption and to clarify whether the presence and location of microbleeds were associated with microangiopathy. METHODS: We performed MR imaging and correlative histopathologic examination in 11 formalin-fixed brains of patients who had died of an ICH (age range, 45-90 years). RESULTS: Focal areas of signal loss on MR images were noted in seven brains. They were seen in a corticosubcortical location in six brains, in the basal ganglia/thalami in five, and infratentorially in three specimens. Histopathologic examination showed focal hemosiderin deposition in 21 of 34 areas of MR signal loss. No other corresponding abnormalities were found; however, hemosiderin deposits were noted without MR signal changes in two brains. All specimens with MR foci of signal loss showed moderate to severe fibrohyalinosis, and there was additional evidence of amyloid angiopathy in two of those brains. CONCLUSION: Small areas of signal loss on gradient echo T2*-weighted images indicate previous extravasation of blood and are related to bleeding-prone microangiopathy of different origins.  (+info)

Multisecond oscillations in firing rate in the basal ganglia: robust modulation by dopamine receptor activation and anesthesia. (10/1612)

Multisecond oscillations in firing rate in the basal ganglia: robust modulation by dopamine receptor activation and anesthesia. Studies of CNS electrophysiology have suggested an important role for oscillatory neuronal activity in sensory perception, sensorimotor integration, and movement timing. In extracellular single-unit recording studies in awake, immobilized rats, we have found that many tonically active neurons in the entopeduncular nucleus (n = 15), globus pallidus (n = 31), and substantia nigra pars reticulata (n = 31) have slow oscillations in firing rate in the seconds-to-minutes range. Basal oscillation amplitude ranged up to +/-50% of the mean firing rate. Spectral analysis was performed on spike trains to determine whether these multisecond oscillations were significantly periodic. Significant activity in power spectra (in the 2- to 60-s range of periods) from basal spike trains was found for 56% of neurons in these three nuclei. Spectral peaks corresponded to oscillations with mean periods of approximately 30 s in each nucleus. Multisecond baseline oscillations were also found in 21% of substantia nigra dopaminergic neurons. The dopamine agonist apomorphine (0.32 mg/kg iv, n = 10-15) profoundly affected multisecond oscillations, increasing oscillatory frequency (means of spectral peak periods were reduced to approximately 15 s) and increasing the regularity of the oscillations. Apomorphine effects on oscillations in firing rate were more consistent from unit to unit than were its effects on mean firing rates in the entopeduncular nucleus and substantia nigra. Apomorphine modulation of multisecond periodic oscillations was reversed by either D1 or D2 antagonists and was mimicked by the combination of selective D1 (SKF 81297) and D2 (quinpirole) agonists. Seventeen percent of neurons had additional baseline periodic activity in a faster range (0.4-2.0 s) related to ventilation. Multisecond periodicities were rarely found in neurons in anesthetized rats (n = 29), suggesting that this phenomenon is sensitive to overall reductions in central activity. The data demonstrate significant structure in basal ganglia neuron spiking activity at unexpectedly long time scales, as well as a novel effect of dopamine on firing pattern in this slow temporal domain. The modulation of multisecond periodicities in firing rate by dopaminergic agonists suggests the involvement of these patterns in behaviors and cognitive processes that are affected by dopamine. Periodic firing rate oscillations in basal ganglia output nuclei should strongly affect the firing patterns of target neurons and are likely involved in coordinating neural activity responsible for motor sequences. Modulation of slow, periodic oscillations in firing rate may be an important mechanism by which dopamine influences motor and cognitive processes in normal and dysfunctional states.  (+info)

Relationships between the prefrontal cortex and the basal ganglia in the rat: physiology of the cortico-nigral circuits. (11/1612)

The prelimbic/medial orbital areas (PL/MO) of the rat prefrontal cortex are connected to substantia nigra pars reticulata (SNR) through three main circuits: a direct nucleus accumbens (NAcc)-SNR pathway, an indirect NAcc-SNR pathway involving the ventral pallidum (VP) and the subthalamic nucleus (STN), and a disynaptic cortico-STN-SNR pathway. The present study was undertaken to characterize the effect of PL/MO stimulation on SNR cells and to determine the contribution of these different pathways. The major pattern of responses observed in the SNR was an inhibition preceded by an early excitation and followed or not by a late excitation. The inhibition resulted from the activation of the direct NAcc-SNR pathway because it disappeared after acute blockade of the glutamatergic cortico-striatal transmission by CNQX application into the NAcc. The late excitation resulted from the activation of the indirect NAcc-VP-STN-SNR pathway via a disinhibition of the STN because it disappeared after either CNQX application into the NAcc or blockade of the GABAergic striato-pallidal transmission by bicuculline application into the VP. The early excitation, which was markedly decreased after blockade of the cortico-STN transmission by CNQX application into the STN, resulted from the activation of the disynaptic cortico-STN-SNR pathway. Finally, the blockade of the cortico-STN-VP circuit by CNQX application into STN or VP modified the influence of the trans-striatal circuits on SNR cells. This study suggests that, in the prefrontal cortex-basal ganglia circuits, the trans-subthalamic pathways, by their excitatory effects, participate in the shaping of the inhibitory influence of the direct striato-nigral pathway on SNR neurons.  (+info)

Language related brain potentials in patients with cortical and subcortical left hemisphere lesions. (12/1612)

The role of the basal ganglia in language processing is currently a matter of discussion. Therefore, patients with left frontal cortical and subcortical lesions involving the basal ganglia as well as normal controls were tested in a language comprehension paradigm. Semantically incorrect, syntactically incorrect and correct sentences were presented auditorily. Subjects were required to listen to the sentences and to judge whether the sentence heard was correct or not. Event-related potentials and reaction times were recorded while subjects heard the sentences. Three different components correlated with different language processes were considered: the so-called N400 assumed to reflect processes of semantic integration; the early left anterior negativity hypothesized to reflect processes of initial syntactic structure building; and a late positivity (P600) taken to reflect second-pass processes including re-analysis and repair. Normal participants showed the expected N400 component for semantically incorrect sentences and an early anterior negativity followed by a P600 for syntactically incorrect sentences. Patients with left frontal cortical lesions displayed an attenuated N400 component in the semantic condition. In the syntactic condition only a late positivity was observed. Patients with lesions of the basal ganglia, in contrast, showed an N400 to semantic violations and an early anterior negativity as well as a P600 to syntactic violations, comparable to normal controls. Under the assumption that the early anterior negativity reflects automatic first-pass parsing processes and the P600 component more controlled second-pass parsing processes, the present results suggest that the left frontal cortex might support early parsing processes, and that specific regions of the basal ganglia, in contrast, may not be crucial for early parsing processes during sentence comprehension.  (+info)

Matrix metalloproteinases increase very early during experimental focal cerebral ischemia. (13/1612)

Microvascular integrity is lost during focal cerebral ischemia. The degradation of the basal lamina and extracellular matrix are, in part, responsible for the loss of vascular integrity. Matrix metalloproteinases (MMPs) may play a primary role in basal lamina degradation. By using a sensitive modification of gelatin zymography, the authors investigated the activity of MMP-2 and MMP-9 in frozen 10-microm sections of ischemic and nonischemic basal ganglia and plasma samples of 27 non-human primates after middle cerebral artery occlusion/reperfusion (MCAO/R) for various periods. The gelatinolytic activities were compared with parallel cell dUTP incorporation in the ischemic zones of adjacent sections. In the brain, the integrated density of MMP-2 increased significantly by 1 hour after MCAO and was persistently elevated thereafter. Matrix metalloproteinase-2 expression was highly correlated with the extent of neuron injury and the number of injured neurons (r = 0.9763, SE = 0.004, 2P < 0.0008). Matrix metalloproteinase-9 expression only was significantly increased in subjects with hemorrhagic transformation. In plasma, only MMP-9 increased transiently at 2 hours of MCAO. These findings highlight the early potential role of MMP-2 in the degradation of basal lamina leading to neuronal injury, and an association of MMP-9 with hemorrhagic transformation after focal cerebral ischemia.  (+info)

Modeling cerebral blood flow and flow heterogeneity from magnetic resonance residue data. (14/1612)

Existing model-free approaches to determine cerebral blood flow by external residue detection show a marked dependence of flow estimates on tracer arrival delays and dispersion. In theory, this dependence can be circumvented by applying a specific model of vascular transport and tissue flow heterogeneity. The authors present a method to determine flow heterogeneity by magnetic resonance residue detection of a plasma marker. Probability density functions of relative flows measured in six healthy volunteers were similar among tissue types and volunteers, and were in qualitative agreement with literature measurements of capillary red blood cell and plasma velocities. Combining the measured flow distribution with a model of vascular transport yielded excellent model fits to experimental residue data. Fitted gray-to-white flow-rate ratios were in good agreement with PET literature values, as well as a model-free singular value decomposition (SVD) method in the same subjects. The vascular model was found somewhat sensitive to data noise, but showed far less dependence on vascular delay and dispersion than the model-free SVD approach.  (+info)

Neuronal activity in the primate motor thalamus during visually triggered and internally generated limb movements. (15/1612)

Single-unit recordings were made from the basal-ganglia- and cerebellar-receiving areas of the thalamus in two monkeys trained to make arm movements that were either visually triggered (VT) or internally generated (IG). A total of 203 neurons displaying movement-related changes in activity were examined in detail. Most of these cells (69%) showed an increase in firing rate in relation to the onset of movement and could be categorized according to whether they fired in the VT task exclusively, in the IG task exclusively, or in both tasks. The proportion of cells in each category was found to vary between each of the cerebellar-receiving [oral portion of the ventral posterolateral nucleus (VPLo) and area X] and basal-ganglia-receiving [oral portion of the ventral lateral nucleus (VLo) and parvocellular portion of the ventral anterior nucleus (VApc)] nuclei that were examined. In particular, in area X the largest group of cells (52%) showed an increase in activity during the VT task only, whereas in VApc the largest group of cells (53%) fired in the IG task only. In contrast to this, relatively high degree of task specificity, in both VPLo and VLo the largest group of cells ( approximately 55%) burst in relation to both tasks. Of the cells that were active in both tasks, a higher proportion were preferentially active in the VT task in VPLo and area X, and the IG task in VLo and VApc. In addition, cells in all four nuclei became active earlier relative to movement onset in the IG task compared with the VT task. These results demonstrate that functional distinctions do exist in the cerebellar- and basal-ganglia-receiving portions of the primate motor thalamus in relation to the types of cues used to initiate and control movement. These distinctions are most clear in area X and VApc, and are much less apparent in VPLo and VLo.  (+info)

Diffusion-weighted MR imaging of global cerebral anoxia. (16/1612)

BACKGROUND AND PURPOSE: Diffuse cerebral anoxia is a devastating event, and its acute findings, as revealed by conventional MR imaging and CT scanning, may be subtle. We analyzed diffusion-weighted and conventional MR images of patients with diffuse cerebral anoxia to determine their usefulness in establishing the diagnosis during the acute period and in determining the age of insult. METHODS: We reviewed 11 MR imaging studies of 10 patients who had experienced prolonged cardiac arrest. All of the patients underwent echo-planar diffusion-weighted imaging with low- and high-strength B values and multiplanar unenhanced MR imaging. We considered bright areas on the high-strength diffusion-weighted images to be abnormal when compared with low-strength images. Special attention was given to the cortex, basal ganglia, thalami, hippocampi, cerebellum, and white matter. Conventional MR studies also were reviewed, and abnormalities noted. The medical records of all of the patients were reviewed. RESULTS: Four patients who underwent imaging during the acute period (<24 hours) had bright basal ganglia (n = 2), bright cerebellum (n = 3), and bright cortex (n = 1) shown on their diffusion-weighted images. For these patients, conventional MR images showed questionable increased T2-weighted signal intensity in the basal ganglia (n = 1), and the results of two studies were judged to be normal. During the early subacute period (24 hours-13 days), four patients were studied, and were determined to have an abnormal cortex (n = 3) and basal ganglia (n = 2). For two of these patients, conventional MR images showed similar abnormalities, and the results of one study were normal. For two patients who underwent imaging during the late subacute period (14-20 days), diffusion-weighted images showed abnormalities mostly confined to white matter. Two patients who underwent imaging during the chronic phase (>21 days) had normal results of their diffusion-weighted imaging and one had evidence of laminar necrosis revealed by conventional MR imaging. CONCLUSION: During the acute period, high-strength diffusion-weighted images showed the abnormal basal ganglia, cerebellum, and cortex to a better extent than did conventional MR images. During the early subacute period, gray matter abnormalities were seen on diffusion-weighted images. During the late subacute period, diffusion-weighted images showed mostly white matter abnormalities. During the chronic stage, the results of diffusion-weighted imaging were normal. Our findings suggest that diffusion-weighted images are helpful for evaluating and dating diffuse cerebral anoxia, and therefore aid in the determination of prognosis and management of these patients.  (+info)