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Biomedical subjects

S Vanni

Publications and source records attributed to S Vanni.

At least 19 recordsLinked to original sources

Training-induced cortical representation of a hemianopic hemifield.

BACKGROUND: Patients with homonymous hemianopia often have some residual sensitivity for visual stimuli in their blind hemifield. Previous imaging studies suggest an important role for extrastriate cortical areas in such residual vision, but results of training to improve vision in patients with hemianopia are conflicting. OBJECTIVE: To show that intensive training with flicker stimulation in the chronic stage of stroke can reorganise visual cortices of an adult patient. METHODS: A 61-year-old patient with homonymous hemianopia was trained with flicker stimulation, starting 22 months after stroke. Changes in functioning during training were documented with magnetoencephalography, and the cortical organisation after training was examined with functional magnetic resonance imaging (fMRI). RESULTS: Both imaging methods showed that, after training, visual information from both hemifields was processed mainly in the intact hemisphere. The fMRI mapping results showed the representations of both the blind and the normal hemifield in the same set of cortical areas in the intact hemisphere, more specifically in the visual motion-sensitive area V5, in a region around the superior temporal sulcus and in retinotopic visual areas V1 (primary visual cortex), V2, V3 and V3a. CONCLUSIONS: Intensive training of a blind hemifield can induce cortical reorganisation in an adult patient, and this case shows an ipsilateral representation of the trained visual hemifield in several cortical areas, including the primary visual cortex.

Flicker Fusion↗

Temporal sensitivity in a hemianopic visual field can be improved by long-term training using flicker stimulation.

BACKGROUND: Blindness of a visual half-field (hemianopia) is a common symptom after postchiasmatic cerebral lesions. Although hemianopia severely limits activities of daily life, current clinical practice comprises no training of visual functions in the blind hemifield. OBJECTIVE: To find out whether flicker sensitivity in the blind hemifield can be improved with intensive training, and whether training with flicker stimulation can evoke changes in cortical responsiveness. METHODS: Two men with homonymous hemianopia participated in the experiments. They trained with flicker stimuli at 30 degrees or with flickering letters at 10 degrees eccentricity twice a week for a year, and continued training with more peripheral stimuli thereafter. Neuromagnetic responses were registered at 1-2-month intervals, and the Goldmann perimetry was recorded before, during and after training. RESULTS: Flicker sensitivity in the blind hemifield improved to the level of the intact hemifield within 30 degrees eccentricity in one participant and 20 degrees eccentricity in the other. Flickering letters were recognised equally at 10 degrees eccentricity in the blind and intact hemifields. Improvement spread from the stimulated horizontal meridian to the whole hemianopic field within 30 degrees. Before training, neuromagnetic recordings showed no signal above the noise level in the hemianopic side. During training, evoked fields emerged in both participants. No changes were found in the Goldmann perimetry. DISCUSSION: Results show that sensitivity to flicker could be fully restored in the stimulated region, that improvement in sensitivity spreads to the surrounding neuronal networks, and that, during training, accompanying changes occurred in the neuromagnetic fields.

Cerebral Cortex↗

Retinotopic distribution of chromatic responses in human primary visual cortex.

In non-human primates at least three anatomically and functionally distinct channels convey signals from the retina to the primary visual cortex (V1). Two of these channels, the parvocellular and the koniocellular, are sensitive to chromatic contrasts and form the basis of color vision. In humans, common phylogenetic history with other primates and psychophysical experiments suggest identical retinocortical mechanisms but separate evaluation of the distinct anatomical channels has been difficult because signals are already combined in V1. We studied the spatial distribution of activation to chromatic stimuli along the two opponent chromatic axes in human V1 with multifocal functional magnetic resonance imaging. The signal strength was quantified from three experiments with stimuli up to 20 degrees eccentricity. The hypothesis was that, although the parvo- and koniocellular signals are mixed in V1, distinct distributions of signal strength would be evident. We found that whereas different conditions activated the same areas of cortex, indicating that they have identical magnification factors, the responses to red/green stimulation were stronger close to the fovea whereas the blue/yellow responses were much less diminished with increasing eccentricity. Both chromatic axes showed saturating contrast response functions. Our measure directly from human V1 is in line with earlier psychophysical studies suggesting relatively stronger parvocellular channel representation close to the fovea, and more uniform distribution of the koniocellular and achromatic channels. In addition, our study presents a way to rapidly quantify retinotopic signal transmission in distinct retinocortical pathways of individual subjects.

Adult↗

Multifocal fMRI mapping of visual cortical areas.

The multifocal mapping of electroretinograms and visual evoked potentials has established an important role in both basic research and in diagnostic procedures. We have developed a multifocal mapping method for fMRI, which allows detailed analysis of multiple local visual field representations in the cortex with excellent spatial resolution. Visual field was divided into 60 regions in a dartboard configuration, scaled according to the human magnification factor. Within blocks of 7 s, half of the regions were stimulated with checkerboard patterns contrast reversing at 8 reversals per second, while the other half remained inactive at uniform luminance. The subset of active regions changed with each 7-s block, according to an orthogonal design. Functional MRI was done with a 3-T GE Signa and analyzed with SPM2. A general linear model was fitted producing activation maps for each of the 60 regions, and local signal changes were quantified from V1. These activation maps were next assigned to 3D surface models of the cortical sheet, and then unfolded, using the Brain à la Carte software package. Phase-encoded retinotopic analysis of conventional design served as qualitative comparison data. With multifocal fMRI, all regions were mapped with good signal-to-noise ratio in V1, and subsets of regions showed activation in V2 and V3. This method allows rapid and direct exploration of multiple local visual responses, and is thus able to give complementary information to phase encoded mapping of retinotopic areas.

Adult↗

High-dose methylprednisolone may cause myopathy in acute spinal cord injury patients.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: Although Bracken et al have demonstrated a significant neuroprotective effect of high-dose intravenous (i.v.) methylprednisolone (MP) within 8 h post spinal cord injury (SCI), this practice has recently been challenged. We hypothesized it is possible that acute corticosteroid myopathy (ACM) may occur secondary to the MP. This pilot study was performed to test this hypothesis. SETTING: University of Miami School of Medicine/Jackson Memorial Hospital, Miami VA Medical Center, FL, USA. METHODS: Subjects included five nonpenetrating traumatic SCI patients, who received 24 h MP according to National Acute Spinal Cord Injury Studies (NASCIS) protocol, and three traumatic patients who suffered SCI and did not receive MP. Muscle biopsies and electromyography (EMG) were performed to determine if myopathic changes existed in these patients. RESULTS: Muscle biopsies from the SCI patients who received 24 h of MP showed muscle damage consistent with ACM in four out of five cases. EMG studies demonstrated myopathic changes in the MP-treated patients. In the three patients who had SCI but did not receive MP, muscle biopsies were normal and EMGs did not reveal evidence of myopathy. CONCLUSION: Our data suggest that MP in the dose recommended by the NASCIS may cause ACM. If this is true, part of the improvement of neurological recovery showed in NASCIS may be only a recording of the natural recovery of ACM, instead of any protection that MP offers to the injured spinal cord.

Adenosine Triphosphatases↗

Timing of interactions across the visual field in the human cortex.

While it is generally believed that interactions across long distances in the visual field occur only in the higher-order cortical areas, other results suggest that such interactions are processed very early. In the preceding paper, we identified the latencies within a subset of cortical areas in the human visual system. In the present study, we test in which areas and at which latencies the responses to two visual patterns start interacting. We used functional magnetic resonance imaging directly combined with visual-evoked potential source analysis. Interactions appeared first anterolaterally to the retinotopic areas, at 80 ms for two stimuli presented in the left lower visual quadrant and at 100 ms for symmetrical stimulation of both lower quadrants. In the lateral occipital-V5 region (LOV5), two patterns presented simultaneously in one quadrant elicited a response with shorter latency and infra-linear addition of the amplitudes compared with the patterns presented separately. For bilateral stimulation, the timing of the LOV5 response coincided with the response to contralateral stimulation alone. Other visual areas showed interactions appearing later than within LOV5: starting at 150 ms in V1, at 120 ms in V3-V3a for the left visual hemifield stimulation and at 160 ms for both visual hemifields stimulation. Our data show that distinct patterns in the visual field interact first in LOV5, suggesting that this region must be the first to pool spatial information across the whole visual field.

Adult↗

Sequence of pattern onset responses in the human visual areas: an fMRI constrained VEP source analysis.

We measured the timing of activity in distinct functional areas of the human visual cortex after onset of a visual pattern. This is not possible with visual evoked potentials (VEPs) or magnetic fields alone, and direct combination of functional magnetic resonance imaging (fMRI) with electromagnetic data has turned out to be difficult. We tested a relatively new approach, where both position and orientation of the active cortex was given to the VEP source model. Subjects saw the same visual patterns flashed ON and OFF, both when recording VEPs and fMRI responses. We identified the positions and orientations of the activated cortex in four retinotopic areas in each individual, and the corresponding dipoles were seeded to model the individual evoked potential data. Unexplained variance, comprising signals from other areas, was inversely modeled. Despite the partially a priori fixed model and optimized signal-to-noise ratio of VEP data, full separation of retinotopic areas was only seldom possible due to crosstalk between the adjacent sources, but separation was usually possible between areas V1 and V3/V3a. Whereas the latencies generally followed the hierarchical organization of cortical areas (V1-V2-V3), with around 25 ms between the strongest responses, an early activation emerged 10-20 ms after V1, close to the temporo-occipital junction (LO/V5) and with an additional 20-ms latency in the corresponding region of the opposite hemisphere. Our approach shows that it is feasible to directly seed information from fMRI to electromagnetic source models and to identify the components and dynamics of VEPs in different retinotopic areas of a human individual.

Adult↗

Impairment of cardiopulmonary receptor sensitivity in the early phase of heart failure.

OBJECTIVES: To characterise the efficiency of the cardiopulmonary baroreflex system in the early phase of heart failure and its relation to limitation of physical activity. DESIGN: Forearm blood flow (venous occlusion plethysmography), vascular resistance, and central venous pressure (CVP), estimated from an antecubital vein, were measured in the supine position at baseline and 15 minutes after application of lower body negative pressure at -7 and -14 mm Hg (receptor downloading) or leg raising (receptor loading). SUBJECTS: Heart failure patients without limitation (NYHA class I; n = 18) or with slight limitation of physical activity (NYHA class II; n = 13), and 11 healthy controls. RESULTS: The efficiency of the cardiopulmonary baroreflex function, expressed by the slope of the relation between CVP changes and the corresponding changes of calculated forearm vascular resistance (gain), was reduced both in NYHA class I patients (mean (SD) -1.99 (0.83) v -2.78 (0.66) in controls; p < 0.05) and NYHA class II patients (-1.29 (0.5); p<0.001 v controls). However, change in peripheral vascular resistance during preload increase was similar in controls (-3.3 (0.9) units) and in NYHA class I patients (-3.3 (2.1) units; NS v controls), and was significantly reduced only in NYHA class II patients (-1.6 (1.3) units, p < 0.03 v controls). The gain in the cardiopulmonary reflex was related to the distance walked during the six minute corridor test. CONCLUSIONS: A reduced tonic efficacy of the cardiopulmonary reflex system is already detectable in the early phase of heart failure, the impairment in acute response to preload increase being detectable only in symptomatic patients.

Baroreflex↗

Biochemical changes and their relationship with morphological and functional findings in pig heart subjected to lasting volume overload: a possible role of acylphosphatase in the regulation of sarcoplasmic reticulum calcium pump.

We evaluated the changes in sarcoplasmic reticulum (SR) function and the parallel hemodynamic and morphological modifications in a heart subjected to volume overload. We also determined the levels of acylphosphatase, a cytosolic enzyme, that could play a regulatory effect on SR Ca(2+) pump by hydrolyzing the phosphorylated intermediate of this transport system. For this, swine hearts were subjected to volume overload by aorta-cava shunt for 1, 2, or 3 months. Changes in heart contractility reflected modifications of SR function, whose reduction after 1 month of overload was followed by a gradual recovery. A decrease in SERCA2a protein and mRNA content was shown from 1 month and remained for the following 2 months. Phospholamban content and its phosphorylation status were not modified. Acylphosphatase was unchanged at 1 month, but at 2 months this enzyme exhibited an increased activity, protein and mRNA expression. Morphological alterations consisting of the cytoskeletal architectures, intermyofibrillar oedema, swollen mitochondria and abnormality of the membrane system (T-tubule and SR cisternae) were particularly evident after 1 month but almost disappeared after 3 months. These results suggest that our overloaded hearts underwent a substantial recovery of their structural and biochemical properties at 3 months after surgery. A possible involvement of acylphosphatase in the modification of SR function is discussed.

Acid Anhydride Hydrolases↗

Cardiac angiotensin II formation in the clinical course of heart failure and its relationship with left ventricular function.

In 76 patients with heart failure (HF) (New York Heart Association [NYHA] classes I through IV) and in 15 control subjects, cardiac angiotensin II (Ang II) generation and its relationship with left ventricular function were investigated by measuring aorta-coronary sinus concentration gradients of endogenous angiotensins and in a part of patients by studying (125)I-labeled Ang I kinetics. Gene expression and cellular localization of the cardiac renin-angiotensin system components, the density of AT(1) and AT(2) on membranes and isolated myocytes, and the capacity of isolated myocytes for synthesizing the hypertrophying growth factors insulin-like growth factor-I (IGF-I) and endothelin (ET)-1 were also investigated on 22 HF explanted hearts (NYHA classes III and IV) and 7 nonfailing (NF) donor hearts. Ang II generation increased with progression of HF, and end-systolic wall stress was the only independent predictor of Ang II formation. Angiotensinogen and angiotensin-converting enzyme mRNA levels were elevated in HF hearts, whereas chymase levels were not, and mRNAs were almost exclusively expressed on nonmyocyte cells. Ang II was immunohistochemically detectable both on myocytes and interstitial cells. Binding studies showed that AT(1) density on failing myocytes did not differ from that of NF myocytes, with preserved AT(1)/AT(2) ratio. Conversely, AT(1) density was lower in failing membranes than in NF ones. Ang II induced IGF-I and ET-1 synthesis by isolated NF myocytes, whereas failing myocytes were unable to respond to Ang II stimulation. This study demonstrates that (1) the clinical course of HF is associated with progressive increase in cardiac Ang II formation, (2) AT(1) density does not change on failing myocytes, and (3) failing myocytes are unable to synthesize IGF-I and ET-1 in response to Ang II stimulation.

Analysis of Variance↗

Dynamics of cortical activation in a hemianopic patient.

Although residual vision in patients with cortical blindness is common, its brain mechanisms are poorly known. To study these mechanisms we measured neuromagnetic responses to visual stimuli in a patient with right posterior cerebral lesion and left visual field hemianopia. His vision had partially recovered with intensive training before our measurements. Compared with the processing in the healthy side, early occipital responses were attenuated for both passive viewing of checkerboard reversal patterns and a letter identification task. In both conditions there were prominent longer-latency responses at the right superior temporal cortex. We suggest that the activation in the superior temporal cortex can partially compensate for the failure to produce synchronized population responses at the early stages of visual cortical processing.

Blindness, Cortical↗

Coinciding early activation of the human primary visual cortex and anteromedial cuneus.

Proper understanding of processes underlying visual perception requires information on the activation order of distinct brain areas. We measured dynamics of cortical signals with magnetoencephalography while human subjects viewed stimuli at four visual quadrants. The signals were analyzed with minimum current estimates at the individual and group level. Activation emerged 55-70 ms after stimulus onset both in the primary posterior visual areas and in the anteromedial part of the cuneus. Other cortical areas were active after this initial dual activation. Comparison of data between species suggests that the anteromedial cuneus either comprises a homologue of the monkey area V6 or is an area unique to humans. Our results show that visual stimuli activate two cortical areas right from the beginning of the cortical response. The anteromedial cuneus has the temporal position needed to interact with the primary visual cortex V1 and thereby to modify information transferred via V1 to extrastriate cortices.

Adult↗

Polymorphism of quinone-metabolizing enzymes and susceptibility to ozone-induced acute effects.

The role of the genetic polymorphism of NAD(P)H:quinone oxidoreductase (NQO1) and glutathione-S-transferase micro-1 (GSTM1) in the responsiveness to O(3)-induced acute effects was investigated in 24 healthy nonsmokers performing 2-h bike rides at ambient O(3) varying from 32 to 103 ppb. Before and after rides, each subject performed spirometric tests and provided a blood sample for the measurement of the Clara cell protein CC16. NQO1 and GSTM1 polymorphisms were characterized by polymerase chain reaction- based methods. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct was also measured in DNA of peripheral leukocytes. Rides at O(3) > 80 ppb resulted in significant decrements of pulmonary function tests and increased levels of serum CC16, consistent with mild impairment in respiratory function and increased lung epithelial permeability, respectively. Whereas NQO1wt and GSTM1null subjects showed both functional changes and increased serum CC16 after acute O(3) exposure, people with other haplotypes showed a rise in serum CC16 but no changes in lung function tests. In NQO1wt and GSTM1null subjects, partial correlation analysis showed that functional decrements and increased serum CC16 are closely associated with each other and with O(3) levels, whereas no such relationships were found among subjects bearing other haplotypes. An increased reaction rate between O(3) and hydroquinones would be consistent with the greater increase in 8-OHdG after O(3) exposure in this "susceptible" group.

8-Hydroxy-2'-Deoxyguanosine↗

Selective upregulation of cardiac endothelin system in patients with ischemic but not idiopathic dilated cardiomyopathy: endothelin-1 system in the human failing heart.

Only scarce information is available on the activity and modifications of the cardiac endothelin (ET)-1 system in heart failure due to ischemic (ICM) or idiopathic dilated (DCM) cardiomyopathy. The activity of the ET-1 system was investigated by measuring cardiac ET-1 and big ET-1 formation and quantifying cardiac mRNA for prepro-ET-1 (ppET-1), ET-converting enzyme-1, and ET(A) and ET(B) receptors both in myocardium and in isolated myocytes using Northern blot, reverse transcription-polymerase chain reaction, and in situ hybridization in 22 patients with DCM and 20 with ICM who underwent cardiac transplantation and in 7 potential heart transplant donors (nonfailing hearts). Notwithstanding a similar increase of plasma ET-1 in the 2 groups, cardiac ET formation, mRNA levels for ppET-1, and ET(A) and ET(B) receptors were higher on both the myocardium and isolated myocytes from ICM than on those from DCM hearts (P<0.001 for all). ppET-1 and ET-converting enzyme-1 mRNAs were expressed on myocytes and endothelial and interstitial cells in ICM, whereas in DCM and nonfailing hearts they were mainly expressed on nonmyocyte cells. In both ICM and DCM, the ET(A) mRNA signal was expressed on both myocytes and nonmyocyte cells, whereas ET(B) mRNA was almost exclusively localized on nonmyocyte cells. ET(A)- and ET(B)-specific receptor binding was increased on both myocytes and cardiac membranes, showing a positive correlation with left ventricular ejection fraction in ICM (r=0.78 and 0.70) but not in DCM patients. The present results show that human ventricular myocytes express all of the components of the ET-1 system, which is selectively upregulated in ICM patients and appears to be functionally important in the maintenance of cardiac function.

Adult↗

Early sequence of cardiac adaptations and growth factor formation in pressure- and volume-overload hypertrophy.

To investigate the time sequence of cardiac growth factor formation, echocardiographic and hemodynamic measurements were performed at scheduled times, and mRNAs for angiotensinogen, prepro-endothelin-1 (ppET-1), and insulin-like growth factor I (IGF-I) were quantified with RT-PCR and localized with in situ hybridization in pigs (fluothane anesthesia) by use of pressure or volume overload (aortic banding and aorta-cava fistula, respectively). Relative peptide formation was also measured by radioimmunoassay. In pressure overload, angiotensinogen and ppET-1 mRNA overexpression on myocytes (13 times vs. sham at 3 h and 112 times at 6 h, respectively) was followed by recovery (12 h) of initially decreased (0.5-6 h) myocardial contractility. In volume overload, contractility was not decreased, the angiotensinogen gene was slightly upregulated at 6 h (6.7 times), and ppET-1 was not overexpressed. IGF-I mRNA was overexpressed on myocytes (at 24 h) in both volume and pressure overload (14 times and 37 times, respectively). In the latter setting, a second ppET-1 overexpression was detectable on myocytes at 7 days. In conclusion, acute cardiac adaptation responses involve different growth factor activation over time in pressure versus volume overload; growth factors initially support myocardial contractility and thereafter induce myocardial hypertrophy.

Adaptation, Physiological↗

Foveal attention modulates responses to peripheral stimuli.

When attending to a visual object, peripheral stimuli must be monitored for appropriate redirection of attention and gaze. Earlier work has revealed precentral and posterior parietal activation when attention has been directed to peripheral vision. We wanted to find out whether similar cortical areas are active when stimuli are presented in nonattended regions of the visual field. The timing and distribution of neuromagnetic responses to a peripheral luminance stimulus were studied in human subjects with and without attention to fixation. Cortical current distribution was analyzed with a minimum L1-norm estimate. Attention enhanced responses 100-160 ms after the stimulus onset in the right precentral cortex, close to the known location of the right frontal eye field. In subjects whose right precentral region was not distinctly active before 160 ms, focused attention commonly enhanced right inferior parietal responses between 180 and 240 ms, whereas in the subjects with clear earlier precentral response no parietal enhancement was detected. In control studies both attended and nonattended stimuli in the peripheral visual field evoked the right precentral response, whereas during auditory attention the visual stimuli failed to evoke such response. These results show that during focused visual attention the right precentral cortex is sensitive to stimuli in all parts of the visual field. A rapid response suggests bypassing of elaborate analysis of stimulus features, possibly to encode target location for a saccade or redirection of attention. In addition, load for frontal and parietal nodi of the attentional network seem to vary between individuals.

Adult↗

Endothelin receptors in adult human and swine isolated ventricular cardiomyocytes.

The present study aimed to investigate endothelin-1 (ET-1) receptors in human and swine cardiomyocytes with binding studies using ET(A) and ET(B) selective receptor antagonists (BMS-182874 and BQ-788, respectively). Cell distribution of mRNA expression for ET(A) and ET(B) subtypes was investigated by in situ hybridization using specific cDNA probes. The 1251-ET-1 binding, which reached equilibrium in about 120 min (Kobs = 0.051+/-0.003 min(-1)), was only partially displaceable by the addition of a large excess of ET-1 (about 15% with a half-life of 20 min). In equilibrium binding studies, 125I-ET-1 had a Kd of 0.43+/-0.08 nM and a maximum binding (Bmax) of 42.8+/-6.6 fmol/mg protein. ET(A) and ET(B) receptors are represented in human and swine cardiomyocytes with an 85:15 ratio as indicated by the biphasic pattern of competition of both BMS-182874 and BQ-788. In situ hybridization studies confirmed that myocytes mainly expressed mRNA for ET(A), whereas expression of mRNA for the ET(B) subtype was documented in non-myocyte cells. These results showed that ET-1 binds with high affinity and poor reversibility to specific receptors, in both human and swine isolated ventricular cardiomyocytes, without significant species differences.

Adult↗