Biomedical subjects

Peter Lakatos

Publications and source records attributed to Peter Lakatos.

12 recordsLinked to original sources

PubMed2007

Neuronal oscillations and multisensory interaction in primary auditory cortex.

Recent anatomical, physiological, and neuroimaging findings indicate multisensory convergence at early, putatively unisensory stages of cortical processing. The objective of this study was to confirm somatosensory-auditory interaction in A1 and to define both its physiological mechanisms and its consequences for auditory information processing. Laminar current source density and multiunit activity sampled during multielectrode penetrations of primary auditory area A1 in awake macaques revealed clear somatosensory-auditory interactions, with a novel mechanism: somatosensory inputs appear to reset the phase of ongoing neuronal oscillations, so that accompanying auditory inputs arrive during an ideal, high-excitability phase, and produce amplified neuronal responses. In contrast, responses to auditory inputs arriving during the opposing low-excitability phase tend to be suppressed. Our findings underscore the instrumental role of neuronal oscillations in cortical operations. The timing and laminar profile of the multisensory interactions in A1 indicate that nonspecific thalamic systems may play a key role in the effect.

Afferent Pathways↗

PubMed2006

Multisensory processing and oscillatory activity: analyzing non-linear electrophysiological measures in humans and simians.

Stimulus-related oscillations are known to be closely linked to integrative processing in the brain. One research domain within which there has been tremendous interest in oscillatory mechanisms is in the integration of inputs across the widely separated sensory systems. Under the standard approach of assessing multisensory interactions in electrophysiological datasets, the event-related response to a multisensory stimulus is directly compared with the sum of the responses to its unisensory constituents when presented alone. When using methods like wavelet transformation or fast Fourier transformation to derive induced oscillatory signals, however, such linear operations are not appropriate. Here we introduce a simple bootstrapping procedure wherein the linear summation of single unisensory trials forms a distribution against which multisensory trials may be statistically compared, an approach that circumvents the issue of non-linearity when combining unisensory oscillatory responses. To test this approach we applied it to datasets from intracranial recordings in non-human primates and human scalp-recorded EEG, both derived from a simple audio-visual integration paradigm. Significant multisensory interactions were revealed in oscillatory activity centered at 15 and 20 Hz (the so-called beta band). Simulations of different levels of background noise further validated the results obtained by this method. By demonstrating super- and sub-additive effects, our analyses showed that this approach is a valuable metric for studying multisensory interactions reflected in induced oscillatory responses.

Adult↗

PubMed2006

Functional anatomy and interaction of fast and slow visual pathways in macaque monkeys.

We measured the timing, areal distribution, and laminar profile of fast, wavelength-insensitive and slower, wavelength-sensitive responses in V1 and extrastriate areas, using laminar current-source density analysis in awake macaque monkeys. There were 3 main findings. 1) We confirmed previously reported significant ventral-dorsal stream latency lags at the level of V4 (V4 mean = 38.7 ms vs. middle temporal mean = 26.9 ms) and inferotemporal cortex (IT mean = 43.4 ms vs. dorsal bank of the superior temporal sulcus mean = 33.9 ms). 2) We found that wavelength-sensitive inputs in areas V1, V4, and IT lagged the wavelength-insensitive responses by significant margins; this lag increased over successive levels of the system. 3) We found that laminar activation profiles in V4 and IT were inconsistent with "feedforward" input through the ascending ventral cortical pathway; the likely alternative input routes include both lateral inputs from the dorsal stream and direct inputs from nonspecific thalamic neurons. These findings support a "Framing" Model of ventral stream visual processing in which rapidly conducted inputs, mediated by one or more accessory pathways, modulate the processing of more slowly conducted feedforward inputs.

Animals↗

PubMed2005

Timing of pure tone and noise-evoked responses in macaque auditory cortex.

We compared onset latencies for characteristic frequency pure tone and broadband noise responses in AI and posterior belt regions of the auditory cortex in awake macaques. We found that (1) in AI, responses to characteristic frequency tones and broadband noise have similar latencies, (2) in belt regions, characteristic frequency tone and broadband noise latencies differ significantly; broadband noise latencies are shorter, while characteristic frequency tone latencies are longer than corresponding values in AI, (3) for both pure tone and broadband noise responses in AI, latency decreases with increasing characteristic frequency and (4) despite a similar inverse relationship of tone latency and local characteristic frequency in belt areas, broadband noise latencies are uniformly short, and appear unrelated to local characteristic frequency. Dissociation of broadband noise and pure tone latencies may reflect the use of parallel anatomical routes into belt regions.

Acoustic Stimulation↗

PubMed2005

An oscillatory hierarchy controlling neuronal excitability and stimulus processing in the auditory cortex.

EEG oscillations are hypothesized to reflect cyclical variations in the neuronal excitability, with particular frequency bands reflecting differing spatial scales of brain operation. However, despite decades of clinical and scientific investigation, there is no unifying theory of EEG organization, and the role of ongoing activity in sensory processing remains controversial. This study analyzed laminar profiles of synaptic activity [current source density CSD] and multiunit activity (MUA), both spontaneous and stimulus-driven, in primary auditory cortex of awake macaque monkeys. Our results reveal that the EEG is hierarchically organized; delta (1-4 Hz) phase modulates theta (4-10 Hz) amplitude, and theta phase modulates gamma (30-50 Hz) amplitude. This oscillatory hierarchy controls baseline excitability and thus stimulus-related responses in a neuronal ensemble. We propose that the hierarchical organization of ambient oscillatory activity allows auditory cortex to structure its temporal activity pattern so as to optimize the processing of rhythmic inputs.

Acoustic Stimulation↗

PubMed2005

Serum leptin, soluble leptin receptor, free leptin index and bone mineral density in patients with primary biliary cirrhosis.

BACKGROUND/AIM: The pathophysiology of osteoporosis in chronic liver diseases is unknown. Recent data suggest that serum leptin is associated with bone mineral density (BMD). In animal studies leptin was found to be a potent inhibitor of bone formation. We investigated the relationship between serum leptin levels, soluble leptin receptor (sOB-R), free leptin index (FLI) and BMD in patients with primary biliary cirrhosis (PBC). PATIENTS AND METHODS: Ninety-four female patients with PBC were included in this study; 122 healthy women served as controls. Serum leptin levels were measured by radioimmunoassay, sOB-R by enzyme-linked immunosorbent assay. BMD was measured by dual energy X-ray absorptiometry in the lumbar spine and femoral neck. RESULTS: Serum leptin was significantly lower in patients with PBC compared with healthy controls. No difference was found between the body mass index (BMI) of patients and controls. There was a strong positive correlation between leptin and BMI. In PBC no association was found between leptin, sOB-R and liver function tests, histological stages or the presence of osteoporosis. Osteoporosis was present in 38 patients. A positive correlation was found between serum leptin and femoral neck z-score even after adjustment for BMI, whereas serum sOB-R correlated inversely with the serum leptin level. There was no difference in FLI between the subgroups of PBC patients according to the stages of the disease. CONCLUSIONS: We found a lower serum leptin level and a higher sOB-R in patients with PBC, which could not be explained by the difference in BMI. As leptin was associated with BMD, it may be hypothesized that leptin is involved in the complex regulation of bone metabolism in PBC.

Absorptiometry, Photon↗

PubMed2004

Timing and laminar profile of eye-position effects on auditory responses in primate auditory cortex.

We examined effects of eye position on auditory cortical responses in macaques. Laminar current-source density (CSD) and multiunit activity (MUA) profiles were sampled with linear array multielectrodes. Eye position significantly modulated auditory-evoked CSD amplitude in 24/29 penetrations (83%), across A1 and belt regions; 4/24 cases also showed significant MUA AM. Eye-position effects occurred mainly in the supragranular laminae and lagged the co-located auditory response by, on average, 38 ms. Effects in A1 and belt regions were indistinguishable in amplitude, laminar profile, and latency. The timing and laminar profile of the eye-position effects suggest that they are not combined with auditory signals at a subcortical stage of the lemniscal auditory pathways and simply "fed-forward" into cortex. Rather, these effects may be conveyed to auditory cortex by feedback projections from parietal or frontal cortices, or alternatively, they may be conveyed by nonclassical feedforward projections through auditory koniocellular (calbindin positive) neurons.

Acoustic Stimulation↗

PubMed2004

Relationship between serum calcium and CA 19-9 levels in colorectal cancer.

AIM: To examine the calcium metabolism of colorectal cancer (CRC) in patients with colorectal cancer and control patients. METHODS: Seventy newly diagnosed CRC patients were included. The healthy control group was age and gender matched (n=32). Particular attention was devoted to the relationship between serum calcium of patients, and levels of AFP, CEA, carbohydrate antigen 19-9 (CA 19-9) (that could be considered as prognostic factors). Furthermore, the Ca-sensing receptor (CaSR) gene A986S polymorphism was investigated in these patients, as well as the relationship between different CaSR genotypes and the data stated above. RESULTS: A lower level of ionized calcium (also corrected for albumin) was found in the serum of CRC patients with normal 25(OH) vitamin D levels. The ionized calcium concentration was inversely correlated with the serum level of CA 19-9. There was no difference in the distribution of CaSR genotypes, between CRC patients and general population. The genotypes did not correlate with other data examined. CONCLUSION: Based on these results, lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer.

Biomarkers, Tumor↗

PubMed2004

Attention and arousal related modulation of spontaneous gamma-activity in the auditory cortex of the cat.

Sensory information processing in neocortex is associated with rhythmic synchronized gamma frequency firing of sensory cortical units and similar frequency oscillations of the field potentials. Different aspects of the gamma activity (20-80 Hz) have been suggested as correlates of attention, arousal and sensory binding. It is clear that attention has a modality selective influence, while arousal has a more general effect on the sensory systems. We used an experimental conditioning paradigm to separate these differential effects of attention and arousal on spontaneous neocortical gamma activity. We recorded field potentials with epidural electrodes placed above the auditory cortical areas of cats. The animals performed a simple instrumental alimentary conditioning task with different modality (visual and auditory) conditioned stimuli. When they attended to the auditory conditioned stimulus, both frequency and power increase of spontaneous gamma activity were detected. However when they attended visual, we found no power increase of gamma activity recorded above auditory areas, while the frequency increase was the same as in the "attend auditory" condition. We conclude that the power modulation of gamma activity is modality specific and thus can be attributed to selective attention, whereas the frequency modulation of gamma activity shows no modality specificity, it is influenced by the arousal level.

Acoustic Stimulation↗

PubMed2004

Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond.

Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.

Angioedema↗

PubMed2004

Insulin-like growth factor I gene microsatellite repeat, collagen type Ialpha1 gene Sp1 polymorphism, and bone disease in primary biliary cirrhosis.

BACKGROUND: Genetic factors have been implicated in the pathogenesis of osteoporosis, a common disorder in primary biliary cirrhosis. Insulin-like growth factor I (IGF-I) gene microsatellite repeat polymorphism was found to be associated with osteoporosis in some studies, and collagen-Ialpha1 (COLIA1) Sp1 s allele was associated with lower bone mineral density in primary biliary cirrhosis. IGF-I treatment restored osteopenia and reduced fibrogenesis in experimental cirrhosis. We investigated IGF-I and COLIA1 gene polymorphisms and bone mineral density in Hungarian primary biliary cirrhosis patients. PATIENTS AND METHODS: Seventy female patients with primary biliary cirrhosis were enrolled (mean age 57.6 years, range 37-76 years; all anti-mitochondrial antibody M2-positive; stage II-IV). One hundred and thirty-nine age-matched female subjects served as controls (mean age 55.9 years, range 43-72 years). COLIA1 and IGF-I polymorphisms were determined by polymerase chain reaction. Bone mineral density was measured by dual-energy X-ray absorptiometry in the lumbar spine and femoral neck. RESULTS: The IGF-I was not different between primary biliary cirrhosis patients and controls. The genotype frequency of COLIA1 polymorphism was also not different between primary biliary cirrhosis patients and controls. However, the s allele was significantly less frequent in patients with primary biliary cirrhosis. Osteoporosis was detected in 22 patients. The IGF-I 192/192 genotype was associated with higher femoral-neck z-scores compared with other genotypes. CONCLUSION: In contrast to previous studies, the s allele was less frequent in patients with primary biliary cirrhosis, and its presence was not associated with bone mineral density. Since IGF-I polymorphism was associated with bone mineral density, it may be hypothesised that not COLIA1 but IGF-I together with other genetic and environmental factors may be involved in the complex regulation of bone mineral density in primary biliary cirrhosis.

Adult↗

PubMed2003

High serum osteoprotegerin and low RANKL in primary biliary cirrhosis.

BACKGROUND/AIMS: Osteoprotegerin is decoy receptor for osteoclast activating factor, RANKL, and impairs osteoclast funtion. Since osteoporosis is common in primary biliary cirrhosis (PBC), we investigated osteoprotegerin, RANKL and markers of bone turnover in PBC. METHODS: Serum osteoprotegerin, RANKL, osteocalcin (OC) and C-terminal cross-linking telopeptide of type I collagen (CTX-I) were measured by ELISA in 41 patients with PBC, 16 women with chronic hepatitis C (CHC), and as controls in 44 age-matched healthy and 74 post-menopausal osteopenic otherwise healthy women. RESULTS: Serum osteoprotegerin levels were higher in PBC patients (7.8+/-3.0 pmol/l) than in healthy controls (4.4+/-2.3 pmol/l) and osteopenic women (4.0+/-1.0 pmol/l, P<0.0001 for both). RANKL levels were lower in PBC (0.9+/-1.8 pmol/l, P<0.0001) than in healthy controls (1.3+/-0.5 pmol/l). In CHC both osteoprotegerin (9.7+/-4.2 pmol/l) and RANKL (3.2+/-4.7 pmol/l) were elevated compared to the control groups (P<0.0001, for both). There was a positive correlation between serum osteoprotegerin and OC, CTX-I and AST but not with bone mineral density in PBC. CONCLUSIONS: The mechanisms and role of elevated osteoprotegerin and low RANKL in PBC are unclear, but it might partly represent a compensatory mechanism to negative balance of bone remodeling. High OPG and RANKL levels found in CHC might suggest that inflammatory process in the liver could also contribute to the elevation of osteoprotegerin.

Adult↗