Evaluation of dopamine transporter density in healthy Brazilians using Tc-99m TRODAT-1 SPECT

The presynaptic dopamine transporter (DAT) modulates the uptake of dopamine by regulating its concentration in the central nervous system. We aimed to evaluate the DAT binding potential (DAT-BP) in a sample of healthy Brazilians through technetium-99 metastable TRODAT-1 single-photon emission computed tomography imaging.We selected 126 healthy individuals comprising 72 men and 54 women, aged 18 to 80 years. We conducted semi-quantitative evaluation in transaxial slices, following which we identified the regions of interest in the striatal region using the occipital lobe as a region of non-specific DAT-BP.We found a decrease in DAT-BP in healthy individuals aged over 30 years, culminating in a 42% mean reduction after 80 years. There was no difference in the decrease by age group between the right (linear regression test [R²] linear = 0.466) and left striatum (R² linear = 0.510). Women presented a higher DAT-BP than men (women: R² linear = 0.431; men: R² linear = 0.457); nonetheless, their decrease by age group was equal to that in men.Our study sheds light on important DAT-BP findings in healthy Brazilian subjects. Our results will facilitate understanding of brain illnesses that involve the dopamine system, such as neuropsychiatric disorders.     

Brain alterations in low-frequency fluctuations across multiple bands in obsessive compulsive disorder

The extent of functional abnormalities in frontal-subcortical circuits in obsessive-compulsive disorder (OCD) is still unclear. Although neuroimaging studies, in general, and resting-state functional Magnetic Resonance Imaging (rs-fMRI), in particular, have provided relevant information regarding such alterations, rs-fMRI studies have been typically limited to the analysis of between-region functional connectivity alterations at low-frequency signal fluctuations (i.e., <0.08 Hz). Conversely, the local attributes of Blood Oxygen Level Dependent (BOLD) signal across different frequency bands have been seldom studied, although they may provide valuable information. Here, we evaluated local alterations in low-frequency fluctuations across different oscillation bands in OCD. Sixty-five OCD patients and 50 healthy controls underwent an rs-fMRI assessment. Alterations in the fractional amplitude of low-frequency fluctuations (fALFF) were evaluated, voxel-wise, across four different bands (from 0.01 Hz to 0.25 Hz). OCD patients showed decreased fALFF values in medial orbitofrontal regions and increased fALFF values in the dorsal-medial prefrontal cortex (DMPFC) at frequency bands <0.08 Hz. This pattern was reversed at higher frequencies, where increased fALFF values also appeared in medial temporal lobe structures and medial thalamus. Clinical variables (i.e., symptom-specific severities) were associated with fALFF values across the different frequency bands. Our findings provide novel evidence about the nature and regional distribution of functional alterations in OCD, which should contribute to refine neurobiological models of the disorder. We suggest that the evaluation of the local attributes of BOLD signal across different frequency bands may be a sensitive approach to further characterize brain functional alterations in psychiatric disorders.     

Melkerson Rosenthal syndrome

This case presentation of a facial swelling emphasizes the difficult and differential efforts of a team of doctors before we were able to reach a diagnosis of Melkerson Rosenthal Syndrome (MRS). This syndrome is an idiopathic, neurological disorder seen as a swelling of the face and lips, with folds and furrows of the tongue. Episodes are recurrent. This case is an example of positive networking by a dentist and physician to achieve the correct diagnosis of MRS.     

Dopamine Transporter Regulation during Four Nights of REM Sleep Deprivation Followed by Recovery – An in vivo Molecular Imaging Study in Humans

Objectives:

To assess the influence of total or selective REM sleep deprivation on the dopamine transporter (DAT) densities and sleep patterns of healthy volunteers.

Design:

Prospective study.

Setting:

Evaluation of polysomnography recordings and DAT density after 4 nights of selective REM sleep deprivation followed by 3 nights of sleep recovery compared to a control group and a group that was subjected to 2 nights of total sleep deprivation. Single positron emission computed tomography and [^99mTc]TRODAT-1 were used to assess the cerebral DAT density in the striatum at baseline, after REM sleep deprivation and total sleep deprivation as well as after sleep recovery. Blood was collected daily to examine prolactin and estradiol levels, which were correlated with dopaminergic activity.

Patients or Participants:

Thirty healthy male volunteers ranging from 19 to 29 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived).

Measurements and Results:

Four nights of REM sleep deprivation and 2 nights of total sleep deprivation induced distinct and heterogeneous patterns of sleep recovery. No significant modulation of DAT availability was observed within groups. In the recovery nights, changes in cortisol, prolactin and estradiol concentrations were significantly correlated with specific sleep stages in the total and REM sleep deprived groups. In addition, DAT density was positively correlated with estradiol concentration and inversely associated with SWS latency only after total sleep deprivation.

Conclusion:

Our study demonstrates that although sleep deprivation did not promote significant alterations in DAT density within the striatum, there were significant correlations among transporter availability, hormonal concentrations and sleep parameters.

Citation:

Martins, RCS; Andersen ML; Garbuio SA; Bittencourt LR: Guindalini C; Shih MC; Hoexter MQ; Bressan RA; Castiglioni MLV; Tufik S. Dopamine transporter regulation during four nights of REM sleep deprivation followed by recovery – an in vivo molecular imaging study in humans. SLEEP 2010;33(2):243-251.     

Global multi‐center and multi‐modal magnetic resonance imaging study of obsessive‐compulsive disorder: Harmonization and monitoring of protocols in healthy volunteers and phantoms

ObjectivesWe describe the harmonized MRI acquisition and quality assessment of an ongoing global OCD study, with the aim to translate representative, well‐powered neuroimaging findings in neuropsychiatric research to worldwide populations.MethodsWe report on T1‐weighted structural MRI, resting‐state functional MRI, and multi‐shell diffusion‐weighted imaging of 140 healthy participants (28 per site), two traveling controls, and regular phantom scans.ResultsHuman image quality measures (IQMs) and outcome measures showed smaller within‐site variation than between‐site variation. Outcome measures were less variable than IQMs, especially for the traveling controls. Phantom IQMs were stable regarding geometry, SNR, and mean diffusivity, while fMRI fluctuation was more variable between sites.ConclusionsVariation in IQMs persists, even for an a priori harmonized data acquisition protocol, but after pre‐processing they have less of an impact on the outcome measures. Continuous monitoring IQMs per site is valuable to detect potential artifacts and outliers. The inclusion of both cases and healthy participants at each site remains mandatory.     

Consequences of prolonged caffeine administration and its withdrawal on pilocarpine- and kainate-induced seizures in rats

PURPOSE: To investigate the consequences of caffeine consumption on epileptic seizures, we used the pilocarpine and the kainate models of epilepsy. We hypothesized that prolonged caffeine consumption or its withdrawal would alter adenosine levels and hence alter seizure susceptibility. METHODS: We administered a 0.1% caffeine solution in the drinking water of adult male Wistar rats over a 2-week period. We challenged another group of animals with the same doses of pilocarpine or kainate 12 h after the withdrawal of the same caffeine-administration protocol. RESULTS: This did not alter the threshold for the induction of seizures by a subconvulsant dose of pilocarpine (200 mg/kg, i.p.) or kainic acid (8 mg/kg, i.p.). Similarly, challenging another group of animals with the same doses of pilocarpine or kainate 12 h after the withdrawal of the same caffeine-administration protocol did not lead to any significant changes in seizures. CONCLUSIONS: With the pilocarpine model of epilepsy, we were not able to find any significant difference in seizure profile that could stem from either caffeine administration or its withdrawal. Despite the extensive laboratory evidence on the convulsant properties of xanthine derivatives in animal models of epilepsy, such strong evidence is lacking in clinical settings. Our current findings with the administration of caffeine at doses similar to those of daily life both support and confirm the clinical experience.