A resonant sextuplet of sub-Neptunes transiting the bright star HD 110067.

Planets with radii between that of the Earth and Neptune (hereafter referred to as 'sub-Neptunes') are found in close-in orbits around more than half of all Sun-like stars1,2. However, their composition, formation and evolution remain poorly understood3. The study of multiplanetary systems offers an opportunity to investigate the outcomes of planet formation and evolution while controlling for initial conditions and environment. Those in resonance (with their orbital periods related by a ratio of small integers) are particularly valuable because they imply a system architecture practically unchanged since its birth. Here we present the observations of six transiting planets around the bright nearby star HD 110067. We find that the planets follow a chain of resonant orbits. A dynamical study of the innermost planet triplet allowed the prediction and later confirmation of the orbits of the rest of the planets in the system. The six planets are found to be sub-Neptunes with radii ranging from 1.94R⊕ to 2.85R⊕. Three of the planets have measured masses, yielding low bulk densities that suggest the presence of large hydrogen-dominated atmospheres.

Fractional viscoelastic models for power-law materials.

Soft materials often exhibit a distinctive power-law viscoelastic response arising from broad distribution of time-scales present in their complex internal structure. A promising tool to accurately describe the rheological behaviour of soft materials is fractional calculus. However, its use in the scientific community remains limited due to the unusual notation and non-trivial properties of fractional operators. This review aims to provide a clear and accessible description of fractional viscoelastic models for a broad audience and to demonstrate the ability of these models to deliver a unified approach for the characterisation of power-law materials. The use of a consistent framework for the analysis of rheological data would help classify the empirical behaviours of soft and biological materials, and better understand their response.

A unified rheological model for cells and cellularised materials.

The mechanical response of single cells and tissues exhibits a broad distribution of time-scales that often gives rise to a distinctive power-law rheology. Such complex behaviour cannot be easily captured by traditional rheological approaches, making material characterisation and predictive modelling very challenging. Here, we present a novel model combining conventional viscoelastic elements with fractional calculus that successfully captures the macroscopic relaxation response of epithelial monolayers. The parameters extracted from the fitting of the relaxation modulus allow prediction of the response of the same material to slow stretch and creep, indicating that the model captured intrinsic material properties. Two characteristic times, derived from the model parameters, delimit different regimes in the materials response. We compared the response of tissues with the behaviour of single cells as well as intra and extra-cellular components, and linked the power-law behaviour of the epithelium to the dynamics of the cell cortex. Such a unified model for the mechanical response of biological materials provides a novel and robust mathematical approach to consistently analyse experimental data and uncover similarities and differences in reported behaviour across experimental methods and research groups. It also sets the foundations for more accurate computational models of tissue mechanics.

A multi-channel low-power system-on-chip for single-unit recording and narrowband wireless transmission of neural signal.

This paper reports a multi-channel neural recording system-on-chip (SoC) with digital data compression and wireless telemetry. The circuit consists of a 16 amplifiers, an analog time division multiplexer, an 8-bit SAR AD converter, a digital signal processor (DSP) and a wireless narrowband 400-MHz binary FSK transmitter. Even though only 16 amplifiers are present in our current die version, the whole system is designed to work with 64 channels demonstrating the feasibility of a digital processing and narrowband wireless transmission of 64 neural recording channels. A digital data compression, based on the detection of action potentials and storage of correspondent waveforms, allows the use of a 1.25-Mbit/s binary FSK wireless transmission. This moderate bit-rate and a low frequency deviation, Manchester-coded modulation are crucial for exploiting a narrowband wireless link and an efficient embeddable antenna. The chip is realized in a 0.35- εm CMOS process with a power consumption of 105 εW per channel (269 εW per channel with an extended transmission range of 4 m) and an area of 3.1 × 2.7 mm(2). The transmitted signal is captured by a digital TV tuner and demodulated by a wideband phase-locked loop (PLL), and then sent to a PC via an FPGA module. The system has been tested for electrical specifications and its functionality verified in in-vivo neural recording experiments.

A power-efficient analog integrated circuit for amplification and detection of neural signals.

We present a neural amplifier that optimizes the trade-off between power consumption and noise performance down to the best so far reported. In the perspective of realizing a fully autonomous implantable system we also address the problem of spike detection by using a new simple algorithm and we discuss the implementation with analog integrated circuits. Implemented in 0.35-microm CMOS technology and with total current consumption of about 20 microA, the whole circuit occupies an area of 0.18 mm(2). Reduced power consumption and small area make it suited to be used in chronic multichannel recording systems for neural prosthetics and neuroscience experiments.

A compact multichannel system for acquisition and processing of neural signals.

An increasing popularity of multichannel recordings from freely behaving animals and the need to develop a practical brain-machine interface has fuelled the development of miniature multichannel recording systems. Here we describe our prototype miniature 64-channel acquisition system that could be used for multichannel recordings in freely behaving monkeys or other large animals. The system's features include an high impedance input for neurophysiology electrodes, an integrated battery fed circuitry with a 64 low-noise multiplexed amplifiers array that permits the parallel recording of all channels, a 10-bit resolution ADC, an FPGA digital core for online processing and data transmission, a USB 2.0 link and a custom software for data visualization and whole system control.

A switched-capacitor neural preamplifier with an adjustable pass-band for fast recovery following stimulation.

For extracellular recordings from neurons, it is desirable to use the same electrode for stimulation as well as for recording. Since neural preamplifiers usually exhibit high-pass filtering at frequencies as low as 0.1 Hz, the recovery from saturation is typically very slow. Consequently, following stimulation, no signal can be detected for up to several seconds. This is unacceptably slow response of the preamplifier because the majority of neurons fires action potentials within first milliseconds following stimulation. Here we propose to use a switched-capacitor preamplifier with adjustable pass-band for fast recovery from saturation caused by stimulation via the recording electrode. The idea was tested in a real preamplifier manufactured with a standard CMOS technology (0.35 microm). In control conditions, the high-pass filter was set to 100 Hz and, during stimulation, was shifted to 10 kHz. Such a shift allows the reduction of the recovery time from tens of milliseconds to sub-millisecond range.

Inhibitory presynaptic 5-hydroxytryptamine(2A) receptors regulate evoked glutamate release from rat cerebellar mossy fibers.

We studied the pharmacological characterization of the 5-hydroxytryptamine(2) (5-HT(2)) heteroreceptor located on glutamatergic cerebellar mossy fiber nerve terminals. Depolarization-evoked overflow of endogenous glutamate from rat cerebellar "giant" mossy fiber synaptosomes was inhibited by 5-HT or (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)-DOI], exhibiting pD(2) (= -log EC(50)) values of 7.37 and 7.29, respectively. Trazodone inhibited the depolarization-evoked glutamate overflow, exhibiting lower potency (pD(2) = 6.42) and lower efficacy with respect to 5-HT or (+/-)-DOI (maximal inhibition, 54%, compared with 70% for either 5-HT or (+/-)-DOI). Ketanserin, a 5-HT(2A)/5-HT(2C) receptor antagonist, counteracted the inhibitory effect of (+/-)-DOI or trazodone. Inhibition of glutamate overflow by 5-HT, (+/-)-DOI, or trazodone was prevented by the selective 5-HT(2A) receptor antagonist R-(+)-alpha-(2,3-dimethyoxyphenyl)-1-(2-(4-fluorophenyl)ethyl)-4-piperidine-methanol (MDL 100907), while the potent and selective 5-HT(2C) receptor antagonist 6-chloro-5-methyl-1-[6-(methylpyridin-3-yloxy)pyridin-3yl-carbamoyl] indoline (SB 242084) was ineffective. In cerebellar slices, MDL 100907 increased on its own the K(+)-evoked release of glutamate. It is concluded that the evoked release of glutamate from cerebellar mossy fibers can be controlled by inhibitory presynaptic 5-HT(2A) heteroreceptors, the receptors can be activated by endogenously released 5-HT, and trazodone behaves as a partial agonist at these receptors.

Abnormally enhanced blood concentrations of vascular endothelial growth factor (VEGF) in metastatic cancer patients and their relation to circulating dendritic cells, IL-12 and endothelin-1.

Elevated VEGF blood concentrations have been proven to be associated with poor prognosis in human neoplasms. This finding is generally explained as a consequence of the potential angiogenic properties of VEGF itself. However, preliminary experimental studies suggest that VEGF, in addition to its angiogenic activity, may also play an immunosuppressant role by inhibiting dendritic cell (DC) maturation. The present study was performed to analyze blood levels of VEGF in cancer patients in relation to those of another potentially angiogenic tumor growth factor, endothelin-1 (ET-1), and to the absolute number of circulating immature and mature DC, and serum levels of the best known antitumor cytokine, IL-12. The study was performed in 100 healthy controls and in 80 solid tumor patients (colorectal cancer: 24; gastric cancer: 17; cancer of pancreas: 4; lung cancer: 13; breast cancer: 11; renal cell cancer: 6; gynecologic tumors: 5), 48 of whom showed distant organ metastases. In each patient, we have evaluated serum concentrations of VEGF-165, total VEGF, ET-1, IL-12 and the circulating number of immature (CD123+) and mature (CD11c+) DC. Mean serum levels of VEGF-165 were significantly higher in metastatic patients than in controls or in non-metastatic patients, whereas the total amounts of VEGF were not significantly higher. Moreover, it has been observed that patients with abnormally elevated blood concentrations of VEGF-165 showed significantly lower mean values of immature DC, mature DC and IL-12 and significantly higher mean levels of ET-1 than those with normal concentrations. This study, by confirming that advanced neoplastic disease may be associated with increased endogenous secretion of VEGF, seems to suggest that the association between high blood levels of VEGF and poor prognosis in cancer does not depend only on VEGF-induced stimulation of the neovascularization, but also on VEGF-related immunosuppression.

Thrombopoietic properties of 5-methoxytryptamine plus melatonin versus melatonin alone in the treatment of cancer-related thrombocytopenia.

Recent studies have shown that the hematopoietic system is under neuroendocrine control. In particular, thrombopoiesis has been proven to be stimulated by melatonin, and the pineal indole has been shown to be effective in the treatment of thrombocytopenia resulting from different causes. At present, however, there are no data concerning the possible thrombopoietic activity of pineal indoles other than melatonin. The present study was carried out to evaluate the effect of a concomitant administration of the pineal indole 5-methoxytryptamine in patients with cancer-related thrombocytopenia who did not respond to melatonin alone. The present study included 30 patients, who were randomized to receive melatonin alone (20 mg/day orally in the evening) or melatonin plus 5-methoxytryptamine (1 mg/day orally in the early afternoon). A normalization of platelet count was achieved in 5/14 (36%) patients treated with melatonin plus 5-methoxytryptamine and in none of the patients treated with melatonin alone (P < 0.05). Moreover, mean platelet number significantly increased only in the patients treated with melatonin plus 5-methoxytryptamine. This preliminary clinical study would suggest that 5-methoxytryptamine, a pineal indole, may also exert thrombopoietic activity. Further studies, however, will be required to establish whether 5-methoxytryptamine may play a direct thrombopoietic activity, or whether it may act by improving melatonin's efficacy.

Effects of fluvoxamine treatment on the in vivo binding of [F-18]FESP in drug naive depressed patients: a PET study.

This study investigates the effect of chronic treatment with Fluvoxamine, a potent and specific serotonin reuptake sites inhibitor (SSRI), on 5HT(2) serotonin and D(2) dopamine receptors in the brain of drug naive unipolar depressed patients. Drug effect was evaluated in different cortical areas and in the basal ganglia by positron emission tomography (PET) and fluoro-ethyl-spiperone ([(18)F]FESP), an high affinity 5HT(2) serotonin and D(2) dopamine receptors antagonist. Patients underwent a PET study at recruitment and after clinical response to Fluvoxamine treatment. Nine of the 15 patients recruited completed the study. Fluvoxamine treatment significantly improved clinical symptoms and modified [(18)F]FESP binding in the frontal and occipital cortex of all of the nine patients who completed the study; in these regions a mean 31% increase in the in vivo [(18)F]FESP binding was found (P < 0.01). On the contrary, no significant changes in the in vivo [(18)F]FESP binding were found in the basal ganglia where [(18)F]FESP binds mainly to D(2) dopamine receptors. Chronic treatment with Fluvoxamine significantly increases the in vivo binding of [(18)F]FESP in the frontal and occipital cortex of drug naive unipolar depressed patients. The increase of the in vivo binding of [(18)F]FESP may reflect a modification in 5HT(2) binding capacity secondary to changes in cortical serotonin activity.

Changes in circulating dendritic cells and IL-12 in relation to the angiogenic factor VEGF during IL-2 immunotherapy of metastatic renal cell cancer.

Angiogenesis and immunosuppression are the main biological mechanisms responsible for cancer progression. Moreover, recent observations suggesting a negative influence of angiogenesis on anticancer immunity have shown that some angiogenic factors, such as VEGF, may induce immunosuppression. In addition, the evidence of abnormally high blood levels of VEGF has been proven to be associated with resistance to IL-2 immunotherapy. The present study was performed to establish a possible relation ship between the efficacy of IL-2 cancer immunotherapy and changes in circulating levels of VEGF, IL-12, mature and immature dendritic cells (DC). The study included 25 metastatic renal cell cancer patients who underwent subcutaneous low-dose IL-2 immunotherapy (6 MIU/day for 6 days/week for 4 weeks). Immature and mature DCs were identified as CD123+ and CD11c+ cells, respectively. The clinical response consisted of partial response (PR) in five, stable disease (SD) in 11 and progressive disease (PD) in the remaining nine patients. The mean IL-12 levels observed during IL-2 immunotherapy were significantly higher in patients with PR or SD than in those with PD, whereas the mean VEGF concentrations were significantly higher in patients who had PD than in those with PR or SD. Finally, a significant increase in the mean number of circulating mature DCs occurred only in patients with PR or SD, whereas no significant change was seen in patients with PD. By contrast, no significant change was observed in the mean number of immature DCs. This study shows that the efficacy of IL-2 immunotherapy is associated with a significant increase in circulating mature DCs and IL-12, without any concomitant increase in VEGF concentrations. Further studies will be required to better define the relationship between activation of anticancer immunity and control of angiogenesis-related mechanisms.

Disintegration propensity of tablets evaluated by means of disintegrating force kinetics.

The aim of this work was to measure the disintegrating force concomitantly with tablet disintegration, in order to evaluate the disintegration propensity of tablets. Disintegration and dissolution were measured on tablets containing two poorly soluble drugs (diclofenac sodium or ketoprofen), including different percentages of two disintegrants (Explotab or Ac-Di-Sol). Because of the experimental setup, the disintegrating force measured was the result of the force generated by disintegrant swelling and dissipated by tablet disintegration. The disintegrating force versus time curves had shapes ranging from a skewed distribution curve to a bell-shaped curve, depending on slow or rapid disintegration of tablets, respectively. Interestingly, the shape of the resulting curves was very sensitive to the composition of the tablet. When the disintegrant in the formula was increased, the force-time curve approached the bell-like shape. The disintegration propensity of the tablet can be evaluated by the disintegrating force development during disintegration. The disintegration improvement of the formula can be predicted. The disintegrating force curve allows for the clear identification of the optimal percentage of disintegrant to be used.

Somatostatin potentiates NMDA receptor function via activation of InsP(3) receptors and PKC leading to removal of the Mg(2+) block without depolarization.

N-methyl-D-aspartate (NMDA) receptors exist on noradrenergic axon terminals and mediate enhancement of noradrenaline (NA) release. We here investigated modulation by somatostatin (SRIF, somatotropin release inhibiting factor) of the NMDA-induced release of NA using superfused hippocampal synaptosomes. The NMDA response was increased by SRIF-28 and SRIF-14, but not SRIF-28((1 - 14)), whereas the release of [(3)H]-NA elicited by alpha-amino-3-hydroxy-5-methylisoxazide-4-propionic acid (AMPA) was unaffected. SRIF-14 did not mimic glycine at the NMDA receptor but activated SRIF receptors sited on noradrenergic terminals. The SRIF-14 effect was blocked by pertussis toxin but mimicked by mastoparan, a G-protein activator. BIM-23056, but not Cyanamid 154806, antagonized the SRIF-14 effect. This effect was mimicked by L362855, a partial agonist at the sst(5) subtype, but not by the new selective sst(1) - sst(4) receptor agonists L797591, L779976, L796778 and L803087. Protein kinase C (PKC) inhibitors (H7, staurosporine, GF 209103X, cheleritrine and sphingosine) prevented the SRIF-14 effect, while phorbol 12-myristate 13-acetate enhanced the NMDA response. SRIF-14 permitted NMDA receptor activation in the presence of 1.2 mM Mg(2+) ions, both in hippocampal synaptosomes and slices. Blockade of inositol-1,4,5-trisphosphate (InsP(3)) receptors with heparin abolished the effect of SRIF-14. It is concluded that SRIF receptors, possibly of the sst(5) subtype, can exert a permissive role on NMDA receptors colocalized on hippocampal noradrenergic terminals: activation of sst(5) receptors is coupled to pertussis toxin-sensitive G proteins enhancing phosphoinositide metabolism with activation of InsP(3) receptors and PKC; NMDA receptor subunits might be phosphorylated with consequent removal of the Mg(2+) block in absence of depolarization.

Aniracetam, 1-BCP and cyclothiazide differentially modulate the function of NMDA and AMPA receptors mediating enhancement of noradrenaline release in rat hippocampal slices.

Aniracetam, 1-(1,3-benzodioxol-5-yl-carbonyl)piperidine (1-BCP) and cyclothiazide, three compounds considered to enhance cognition through modulation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors, were evaluated in the 'kynurenate test', a biochemical assay in which some nootropics have been shown to prevent the antagonism by kynurenic acid of the N-methyl-D-aspartate (NMDA)-evoked [3H]noradrenaline ([3H]NA) release from rat hippocampal slices. Aniracetam attenuated the kynurenate (100 microM) antagonism of the [3H]NA release elicited by 100 microM NMDA with high potency (EC50< or =0.1 microM). Cyclothiazide and 1-BCP were about 10 and 100 times less potent than aniracetam, respectively. The effect of aniracetam persisted in the presence of the AMPA receptor antagonist 6-nitro-7-sulphamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) added at 5 microM, a concentration that did not affect NMDA receptors; in contrast, NBQX reduced the effect of 1-BCP and abolished that of cyclothiazide. The AMPA-evoked release of [3H]NA from hippocampal slices or synaptosomes was enhanced by cyclothiazide, less potently by 1-BCP and weakly by aniracetam. High concentrations of kynurenate (1 mM) antagonized the AMPA-evoked [3H]NA release in slices; this antagonism was attenuated by 1 microM cyclothiazide and reversed to an enhancement of AMPA-evoked [3H]NA release by 10 microM of the drug, but was insensitive to 1-BCP or aniracetam. It is concluded that aniracetam exerts a dual effect on glutamatergic transmission: modulation of NMDA receptor function at nanomolar concentrations, and modulation of AMPA receptors at high micromolar concentrations. As to cyclothiazide and 1-BCP, our data concur with the idea that both compounds largely act through AMPA receptors, although an NMDA component may be involved in the effect of 1-BCP.

Dehydroepiandrosterone sulfate (DHEAS) secretion in early and advanced solid neoplasms: selective deficiency in metastatic disease.

Several endogenous hormones have been proven to stimulate cancer growth, whereas at present very few hormones are known to display oncostatic activity. The most widely investigated antitumor hormone is the pineal indole melatonin (MLT), and cancer progression has been shown to be associated with a decline in MLT secretion. Recently, another hormone, the adrenal steroid dehydroepiandrosterone-sulfate (DHEAS), has appeared to exert antitumor effects similar to those previously described for MLT. In addition, experimental studies suggest a diminished DHEAS production with neoplastic progression. This preliminary study was performed to evaluate the daily secretion of DHEAS in a group of early and advanced cancer patients. The study included 70 patients with solid tumors (gastrointestinal tract tumors: 28; breast cancer: 24; non-small cell lung cancer: 18), 28 without and 42 with distant metastases. The serum levels of DHEAS were measured by RIA in blood samples collected in the morning. The control group consisted of 100 age- and sex-matched healthy subjects. No significant difference in mean serum levels of DHEAS was observed between controls and non-metastatic patients. In contrast, metastatic patients, irrespectively of tumor histotype, showed significantly lower mean levels of DHEAS with respect to either controls or non-metastatic patients. Moreover, metastatic patients with visceral locations showed significantly lower values of DHEAS than those with bone or soft-tissue metastases. This preliminary study would suggest there to be a deficiency in the daily DHEA secretion in patients with disseminated cancer. Further studies evaluating circadian DHEAS secretion in relation in that of the pineal hormone MLT will be required to better define the biological significance of the advanced cancer-related decline in endogenous DHEAS production.

Differential desensitization of ionotropic non-NMDA receptors having distinct neuronal location and function.

The release of tritium from rat hippocampal synaptosomes prelabeled with [3H]noradrenaline ([3H]NA) or [3H]5-hydroxytryptamine ([3H]5-HT) and from rat neocortex synaptosomes prelabeled with [3H]choline and the release of endogenous GABA and glutamate from rat neocortex synaptosomes were monitored during superfusion with media containing varying concentrations of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainic acid. Concentration-dependent release potentiations were elicited by both excitatory amino acids (EAAs) in all the transmitter systems investigated. The releases evoked by 100 microM AMPA were, in all cases, almost totally dependent on external Ca2+ and sensitive to 6.7-dinitroquinoxaline-2,3-dione (DNQX), indicating involvement of non-NMDA receptors. When cyclothiazide, a drug able to prevent desensitization of AMPA-preferring receptors, was added to the superfusion medium (at 1 or 10 microM) concomitantly with 100 microM AMPA or kainate, the EAA-evoked release of [3H]NA was significantly enhanced. Concanavalin A, a lectin thought to prevent desensitization of kainate-preferring receptors, had no effect (up to 10 microM) on the release of [3H]NA evoked by AMPA or kainate. The effect of cyclothiazide was lost if, after an 8-min pretreatment, the drug was removed just before the AMPA stimulus. When added concomitantly with the EAAs, cyclothiazide potentiated the release of [3H]5-HT elicited by AMPA and, less so, that evoked by kainate. Concanavalin A was ineffective. Neither cyclothiazide (1 or 10 microM) nor concanavalin A (3 or 10 microM) could affect the release of [3H]ACh or endogenous GABA provoked by 100 microM AMPA or kainate, suggesting that the receptors involved do not desensitize. Exposure of neocortex synaptosomes to AMPA or kainate concomitantly with cyclothiazide caused endogenous glutamate release that did not differ from that evoked by the EAAs alone. In contrast, the effects of AMPA and kainate were potentiated by concanavalin A. The activity of the lectin (3 microM) persisted when it was applied for 8 min and then removed before the AMPA or kainate (100 microM) pulse. When hippocampal synaptosomes prelabeled with [3H]NA were subjected to three subsequent AMPA (100 microM) stimuli (S1, S2 and S3), the release of [3H]NA decreased dramatically from S1 to S3 (S3/S1 = 0.14 +/- 0.04); a significant 'protection' of the AMPA effect was offered by 1 microM cyclothiazide (S3/S1 = 0.36 +/- 0.06). This value did not differ from the S3/S1 ratio (0.38 +/- 0.04) obtained in parallel experiments with 12 mM K+. The release evoked by high-K+ was insensitive to cyclothiazide. Finally, the effect of AMPA on the release of [3H]ACh did not respond to cyclothiazide also during three subsequent stimuli with 100 microM AMPA. To conclude: a) ionotropic non-NMDA receptors mediating enhancement of NA, 5-HT, ACh, GABA and glutamate release exist on the corresponding nerve terminals; b) the receptors present on noradrenergic and serotonergic neurons are AMPA-preferring receptors, whereas the glutamate autoreceptors resemble most the kainate-preferring subtype; the receptors mediating ACh and GABA release can not be subclassified at present; c) desensitization may not be a property of all non-NMDA ionotropic receptors. The receptors here characterized represent five models of native non-NMDA receptors suitable for pharmacological and molecular studies.

[18F]FDG PET study in obsessive-compulsive disorder. A clinical/metabolic correlation study after treatment.

BACKGROUND: We used [18F]FDG and PET in patients with obsessive-compulsive disorder (OCD) to evaluate cerebral metabolic involvement before and after treatment with serotonin-specific reuptake inhibitors. METHOD: In 11 untreated, drug-free adults, regional cerebral metabolic rate for glucose (rCMRglu) was compared with that of 15 age-matched normal controls. RESULTS: rCMRglu values were significantly increased in the cingulate cortex, thalamus and pallidum/putamen complex. After treatment a significant improvement in obsessive-compulsive symptoms on the Y-BOC scale (t = 3.59, P < 0.01) was associated with a significant bilateral decrease of metabolism in the whole cingulate cortex (P < 0.001). Clinical and metabolic data were significantly intercorrelated (Kendall's tau = 0.65; P < 0.01). CONCLUSIONS: These findings indicate that OCD is associated with functional hyperactivity of a selected neuronal network and that treatment to reduce symptoms may have a selective neuromodulatory effect on cingulate cortex.