Adding supraphysiologic doses of levothyroxine (L-T4) to standard treatment for bipolar depression shows promise, but the mechanisms underlying clinical improvement are unknown. In a previous pilot study, L-T4 treatment reduced depression scores and activity within the anterior limbic network. Here we extended this work in a randomized, double-blind, placebo-controlled study of patients with bipolar depression. Cerebral glucose metabolism was assessed with positron emission tomography and [F-18]fluorodeoxyglucose before and after 6 weeks of treatment with L-T4 ( n =15) or placebo ( n =10) in 12 volumes of interest (VOIs): the bilateral thalamus, amygdala, hippocampus, dorsal striatum and ventral striatum, and midline cerebellar vermis and subgenual cingulate cortex. Radioactivity in the VOIs, normalized to whole-brain radioactivity was taken as a surrogate index of glucose metabolism, and markers of thyroid function were assayed. Changes in brain activity and their association with clinical response were assessed using statistical parametric mapping. Adjunctive L-T4 treatment produced a significant decline in depression scores during the 6-week treatment. In patients treated with L-T4, we found a significant decrease in regional activity at P <0.05 after Bonferroni correction in the left thalamus, right amygdala, right hippocampus, left ventral striatum and the right dorsal striatum. Decreases in the left thalamus, left dorsal striatum and the subgenual cingulate were correlated with a reduction in depression scores ( P <0.05 after Bonferroni correction). Placebo treatment was associated with a significant decrease in activity only in the right amygdala, and no region had a change in activity that was correlated with change in depression scores. The groups differed significantly in the relationship between the changes in depression scores and in activity in the thalamus bilaterally and the left ventral striatum. The findings provide evidence that administration of supraphysiologic thyroid hormone improves depressive symptoms in patients with bipolar disorder by modulating function in components of the anterior limbic network.

See also: Stereotactic Biopsy of a Cerebral Capillary Telangiectasia after a Misleading F-18-FET-PETJ Neurol Surg A Cent Eur Neurosurg 2012; 73(06): 407-409DOI: 10.1055/s-0032-1313640

Introduction Fluid intelligence expresses the capacity for interpretation of novel stimuli and flexible behavioral adaptation to such cues. Phasic dopamine firing closely matches a temporal difference prediction error (PE) signal important for learning and rapid behavioral adaptation. Both fluid intelligence and dopaminergic neurotransmission decline with age. So far, no study investigated the relationship between fluid IQ, PE signal and direct measures of dopaminergic neurotransmission. Here we used a multimodal imaging approach that combines positron emission tomography and functional magnetic resonance imaging. Methods A group of healthy controls was investigated with both 6-[18F]FluoroDOPA PET and functional MRI with a probabilistic reversal task. The task required a constant behavioral adaptation to changes in reward contingencies, while choosing between two abstract stimuli. A reinforcement learning algorithm was used to compute a trial-by-trial prediction error, which was the used as a regressor in the fMRI data analysis with SPM8. Results The prediction error signal was associated with functional activation in the basal ganglia including the ventral striatum and putamen. Fluid intelligence was associated with the PE signal in the ventral striatum, which correlated with age-related changes in dopamine synthesis capacity in the prefrontal cortex. Conclusion These findings provide insight into the role of age-related changes in dopaminergic neurotransmission on behavioral adaptation. The multimodal imaging approach allows the characterization of interactions between dopamine metabolism and learning-related neuronal activation and may thus be a useful tool to clarify mechanisms underlying learning and plasticity in old age, which are crucial to our understanding of successful aging.

Blood platelets are thought to be a useful peripheral model for investigating the central serotoninergic mechanisms associated with the serotonin transporter (SERT). On the other hand, an in vivo investigation of SERT in the human brain has been made possible by the development of several promising SPECT radioligands, such as [123I]-ADAM. The aim of the present study was to investigate the possible correlation between the SERT measurements in the brain and those in platelets. Forty-four subjects (14 healthy subjects and 30 patients with the diagnosis of major depression or schizoaffective disorder) were examined. The [123I]-ADAM binding was assessed 4h after injection using MR-guided regions of interest (ROIs) in the midbrain and cerebellum. In a parallel investigation, serotonin (5HT) concentration and kinetic characteristics of 5HT uptake activity (Vmax and Km) were determined in platelet-rich plasma. Overall, there was no significant correlation between the Vmax of 5HT uptake in platelets and the specific to nonspecific partition coefficient of [123I]-ADAM (V″3) in the midbrain. However, low but significant Pearson correlation coefficients were found for Vmax and normalised activities measured in the midbrain (r=0.310, p=0.043). The correlation was stronger and significant in females (n=20, r=0.629, p=0.003) but low and non-significant in the 24 males (r=0.104). Although confirmation is necessary, it seems that the relationship between different indices of [123I]-ADAM binding in the brain and 5HT uptake characteristics in platelets is complex, nonuniform, and possibly gender-specific.

A number of aromatic dibromides have been treated with 2–3 equivalents of n-butyllithium in order to initiate two sequential chemical events, a Parham cyclization and an intermolecular reaction with DMF.

A high-level RF system, including a power amplifier and cavity, has been designed and built for the Alternating Gradient Synchrotron (AGS) Booster. It covers a frequency range of 2.4 to 4.2 MHz and will be used to accelerate high-intensity protons, low-intensity polarized protons and heavy ions to the 1.5-GeV level. A total accelerating voltage of up to 90 kV will be provided by two cavities, each having two gaps. The internally cross-coupled, pushpull cavities are driven by an adjacent power amplifier. In order to accommodate beam intensities of up to 0.75*10/sup 13/ protons per bunch, a low plate resistance power tetrode is used. The tube anode is magnetically coupled to one of the cavity's two parallel cells. The amplifier is a grounded cathode configuration driven by a remotely located solid-state amplifier. It has been tested in the laboratory at full gap voltage with satisfactory results.<>

In a storage ring, where beam lifetime is measured in hours, it is necessary to keep the longitudinal impedance, as seen by the beam, very low, even into the gigahertz region. This is necessary to prevent the excitation of longitudinal instabilities. These impedances are due to the resistive wall effect and any deviation from a smooth vacuum chamber such as at pick-up electrodes, vacuum pump stations, rf cavities, etc. At low frequencies, up to 10 to 20 MHz, the low impedance requirement for the cavities can be satisfied by designing the driving power amplifiers with a very low output impedance. For ISABELLE a method has been designed for building a network into the cavity accelerating gaps which will satisfy the impedance criteria to at least 1300 MHz. The maximum allowable impedance at any frequency, f, is given in the form Z/n where n = f/f/sub rotation/. For the ISABELLE accelerating cavity, operating at 235.5 KHz, Z/n must be less than 10 ohms. For the stacking cavity, operating at 4.45 MHz, Z/n < 1 ohm.

The AGS conversion requires twice the accelerating volts/turn and driving amplifiers removed from the ring to a central building. The accelerating cavities must be tuned over a frequency range of 2.5 MHz to 4.5 MHz. In addition the number of accelerating positions will be reduced from twelve to eight. These specifications combine to place severe restrictions on the accelerating cavity structure. T...

The 2-volt signal from the low-level swept oscillator in the Cosmotron frequency-control system is amplified to 2000 volts, for application at the accelerating gap, by two units. The first, the intermediate-level system, includes the functions of gating and a.v.c. The second, the high-level unit, is a push-pull broad-band amplifier capable of an output of 150 kw. The gap voltage is maintained constant by an a.v.c. system operated from a detector directly across the accelerating gap. Metering, protection, and control techniques are described.

Ferromagnetic ferrites are used in numerous applications in the Cosmotron. For example, in the accelerating unit over a ton of ferrite is included. During the design of the Cosmotron, much information was required about the various electrical and magnetic properties of ferrites. Since this information was not available, a detailed program of investigation of ferrite properties has been carried out. Results are presented of dielectric properties and of magnetic properties as functions of frequency, dc and ac field strengths, and temperature. A general discussion is included of the behavior of electromagnetic waves in ferrite structures.