Leptospira spp. in Free-Ranging Capybaras (Hydrochoerus hydrochaeris) from Midwestern Brazil.

Background: Leptospirosis is a contagious disease that affects domestic and wild animals as well as humans. It is caused by infection with some pathogenic species of the genus Leptospira. In Brazil, studies on leptospirosis in capybaras are scarce or nonexistent in some regions, such as the Federal District. The objective of this study was to analyze the presence of DNA of the agent and/or anti-Leptospira spp. antibodies in capybaras. Materials and Methods: Blood samples were collected from 56 free-living capybaras captured in two different sites in the study region. The samples were submitted to hematology and clinical chemistry tests. To identify Leptospira positive samples, a conventional PCR (cPCR) and analysis of anti-Leptospira spp. antibodies by microscopic agglutination test (MAT) were used. Results: No animal showed cPCR amplification of the Lip32 gene, but 41.1% (23/56) of the animals had anti-Leptospira spp. antibodies on MAT. The serovars present were icterohaemorrhagiae (82.61%), copenhageni (65.22%), grippotyphosa (4.35%), and hardjo (4.35%). In the laboratorial tests, differences (p < 0.05) were observed in the biochemical assays of alkaline phosphatase, creatinine, albumin, and globulin. Although these values differed significantly between groups, they all remained within reference range (excluding albumin), and thus there is not enough to infer that this alteration could be caused by Leptospira infection. Conclusions: cPCR using whole blood samples to evaluate Leptospira spp. infection of free-living capybaras was not an efficient tool. The presence of Leptospira seroreactive capybaras shows that the bacteria are circulating in the urban environment of the Federal District.

Microdermabrasion facilitates direct current stimulation by lowering skin resistance.

Background: Transcranial direct current stimulation (tDCS) is reported to induce irritating skin sensations and occasional skin injuries, which limits the applied tDCS dose. Additionally, tDCS hardware safety profile prevents high current delivery when skin resistance is high. Objective: To test if decreasing skin resistance can enable high-dose tDCS delivery without increasing tDCS-related skin sensations or device hardware limits. Methods: We compared the effect of microdermabrasion and sonication on 2 mA direct current stimulation (DCS) through forearm skin for 2-3 min on 20 subjects. We also surveyed the subjects using a questionnaire throughout the procedure. We used a linear mixed-effects model for repeated-measures and multiple logistic regression, with adjustments for age, race, gender and visit. Results: Microdermabrasion, with/out sonication, led to significant decrease in skin resistance (1.6 ± 0.1 kΩ or ∼32% decrease, p < 0.0001). The decrease with sonication alone (0.4 ± 0.1 kΩ or ∼7% decrease, p = 0.0016) was comparable to that of sham (0.3 ± 0.1 kΩ or ∼5% decrease, p = 0.0414). There was no increase in the skin-electrode interface temperature. The perceived DCS-related sensations did not differ across skin preparation procedures (p > 0.16), but microdermabrasion (when not combined with sonication) led to increased perceived sensation (p < 0.01). Conclusions: Microdermabrasion (with/out sonication) resulted in reduced skin resistance without increase in perceived skin sensations with DCS. Higher current can be delivered with microdermabrasion-pre-treated skin without changing the device hardware while reducing, otherwise higher voltage required to deliver the same amount of current.

Anatomical and fMRI-network comparison of multiple DLPFC targeting strategies for repetitive transcranial magnetic stimulation treatment of depression.

BACKGROUND: The efficacy of repetitive transcranial magnetic stimulation (rTMS) for depression may vary depending on the subregion stimulated within the dorsolateral prefrontal cortex (DLPFC). Clinical TMS typically uses scalp-based landmarks for DLPFC targeting, rather than individualized MRI guidance. OBJECTIVE: In rTMS patients, determine the brain systems targeted by multiple DLPFC stimulation rules by computing several surrogate measures: underlying brain targets labeled with connectivity-based atlases, subgenual cingulate anticorrelation strength, and functionally connected networks. METHODS: Forty-nine patients in a randomized controlled trial of rTMS therapy for treatment resistant major depression underwent structural and functional MRI. DLPFC rules were applied virtually using MR-image guidance. Underlying cortical regions were labeled, and connectivity with the subgenual cingulate and whole-brain computed. RESULTS: Scalp-targeting rules applied post hoc to these MRIs that adjusted for head size, including Beam F3, were comparably precise, successful in directly targeting classical DLPFC and frontal networks, and anticorrelated with the subgenual cingulate. In contrast, all rules involving fixed distances introduced variability in regions and networks targeted. The 5 cm rule targeted a transitional DLPFC region with a different connectivity profile from the adjusted rules. Seed-based connectivity analyses identified multiple regions, such as posterior cingulate and inferior parietal lobe, that warrant further study in order to understand their potential contribution to clinical response. CONCLUSION: EEG-based rules consistently targeted DLPFC brain regions with resting-state fMRI features known to be associated with depression response. These results provide a bridge from lab to clinic by enabling clinicians to relate scalp-targeting rules to functionally connected brain systems.

Targeting location relates to treatment response in active but not sham rTMS stimulation.

BACKGROUND: Precise targeting of brain functional networks is believed critical for treatment efficacy of rTMS (repetitive pulse transcranial magnetic stimulation) in treatment resistant major depression. OBJECTIVE: To use imaging data from a "failed" clinical trial of rTMS in Veterans to test whether treatment response was associated with rTMS coil location in active but not sham stimulation, and compare fMRI functional connectivity between those stimulation locations. METHODS: An imaging substudy of 49 Veterans (mean age, 56 years; range, 27-78 years; 39 male) from a randomized, sham-controlled, double-blinded clinical trial of rTMS treatment, grouping participants by clinical response, followed by group comparisons of treatment locations identified by individualized fiducial markers on structural MRI and resting state fMRI derived networks. RESULTS: The average stimulation location for responders versus nonresponders differed in the active but not in the sham condition (P = .02). The average responder location derived from the active condition showed significant negative functional connectivity with the subgenual cingulate (P < .001) while the nonresponder location did not (P = .17), a finding replicated in independent cohorts of 84 depressed and 35 neurotypical participants. The responder and nonresponder stimulation locations evoked different seed based networks (FDR corrected clusters, all P < .03), revealing additional brain regions related to rTMS treatment outcome. CONCLUSION: These results provide evidence from a randomized controlled trial that clinical response to rTMS is related to accuracy in targeting the region within DLPFC that is negatively correlated with subgenual cingulate. These results support the validity of a neuro-functionally informed rTMS therapy target in Veterans.

Prolonged Microgravity Affects Human Brain Structure and Function.

BACKGROUND AND PURPOSE: Widespread brain structural changes are seen following extended spaceflight missions. The purpose of this study was to investigate whether these structural changes are associated with alterations in motor or cognitive function. MATERIALS AND METHODS: Brain MR imaging scans of National Aeronautics and Space Administration astronauts were retrospectively analyzed to quantify pre- to postflight changes in brain structure. Local structural changes were assessed using the Jacobian determinant. Structural changes were compared with clinical findings and cognitive and motor function. RESULTS: Long-duration spaceflights aboard the International Space Station, but not short-duration Space Shuttle flights, resulted in a significant increase in total ventricular volume (10.7% versus 0%, P < .001, n = 12 versus n = 7). Total ventricular volume change was significantly associated with mission duration (r = 0.72, P = .001, n = 19) but negatively associated with age (r = -0.48, P = .048, n = 19). Long-duration spaceflights resulted in significant crowding of brain parenchyma at the vertex. Pre- to postflight structural changes of the left caudate correlated significantly with poor postural control; and the right primary motor area/midcingulate correlated significantly with a complex motor task completion time. Change in volume of 3 white matter regions significantly correlated with altered reaction times on a cognitive performance task (bilateral optic radiations, splenium of the corpus callosum). In a post hoc finding, astronauts who developed spaceflight-associated neuro-ocular syndrome demonstrated smaller changes in total ventricular volume than those who did not (12.8% versus 6.5%, n = 8 versus n = 4). CONCLUSIONS: While cautious interpretation is appropriate given the small sample size and number of comparisons, these findings suggest that brain structural changes are associated with changes in cognitive and motor test scores and with the development of spaceflight-associated neuro-optic syndrome.

Cerebellar rTMS for motor control in progressive supranuclear palsy.

BACKGROUND: Stimulatory cerebellar TMS is a promising tool to improve motor control in neurodegenerative disorders. OBJECTIVE/HYPOTHESIS: Our goal was to use 10Hz cerebellar rTMS to augment cerebellar-brain inhibition (CBI) for improved postural stability and speech in patients with progressive supranuclear palsy (PSP). METHODS: We performed CBI assessments with neuronavigation before and after high frequency cerebellar rTMS or sham TMS in two patients with PSP, using a double cone coil for the conditioning pulse and a figure-of-eight coil for the test pulse and treatments. We collected posturography data and speech samples before and after treatment. RESULTS: After treatment, CBI increased by 50% in subject 1 and by 32% in subject 2, and postural stability and speech improved. The protocol was well tolerated, but the sham was not consistently believable. CONCLUSION: Cerebellar rTMS may improve postural stability and speech in PSP, but cooled coils with vibrotactile sham capability are needed for larger future studies.

Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines.

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak intensities above 2mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity 'conventional' TES defined as <4mA, up to 60min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13A/m2 that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence.

Unilateral ultra-brief pulse electroconvulsive therapy for depression in Parkinson's disease.

OBJECTIVES: Electroconvulsive therapy (ECT) has demonstrated efficacy in treating core symptoms of Parkinson's disease (PD); however, widespread use of ECT in PD has been limited due to concern over cognitive burden. We investigated the use of a newer ECT technology known to have fewer cognitive side effects (right unilateral [RUL] ultra-brief pulse [UBP]) for the treatment of medically refractory psychiatric dysfunction in PD. MATERIALS AND METHODS: This open-label pilot study included 6 patients who were assessed in the motoric, cognitive, and neuropsychiatric domains prior to and after RUL UBP ECT. Primary endpoints were changes in total score on the HAM-D-17 and GDS-30 rating scales. RESULTS: Patients were found to improve in motoric and psychiatric domains following RUL UBP ECT without cognitive side effects, both immediately following ECT and at 1-month follow-up. CONCLUSIONS: This study demonstrates that RUL UBP ECT is safe, feasible, and potentially efficacious in treating multiple domains of PD, including motor and mood, without clear cognitive side effects.

Inter-site and inter-scanner diffusion MRI data harmonization.

We propose a novel method to harmonize diffusion MRI data acquired from multiple sites and scanners, which is imperative for joint analysis of the data to significantly increase sample size and statistical power of neuroimaging studies. Our method incorporates the following main novelties: i) we take into account the scanner-dependent spatial variability of the diffusion signal in different parts of the brain; ii) our method is independent of compartmental modeling of diffusion (e.g., tensor, and intra/extra cellular compartments) and the acquired signal itself is corrected for scanner related differences; and iii) inter-subject variability as measured by the coefficient of variation is maintained at each site. We represent the signal in a basis of spherical harmonics and compute several rotation invariant spherical harmonic features to estimate a region and tissue specific linear mapping between the signal from different sites (and scanners). We validate our method on diffusion data acquired from seven different sites (including two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. Since the extracted rotation invariant spherical harmonic features depend on the accuracy of the brain parcellation provided by Freesurfer, we propose a feature based refinement of the original parcellation such that it better characterizes the anatomy and provides robust linear mappings to harmonize the dMRI data. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across multiple sites before and after data harmonization. We also show results using tract-based spatial statistics before and after harmonization for independent validation of the proposed methodology. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences can be accurately removed using the proposed method.

Daily left prefrontal repetitive transcranial magnetic stimulation for medication-resistant burning mouth syndrome.

Burning mouth syndrome (BMS) is a persistent and chronic burning sensation in the mouth in the absence of any abnormal organic findings. The pathophysiology of BMS is unclear and its treatment is not fully established. Although antidepressant medication is commonly used for treatment, there are some medication-resistant patients, and a new treatment for medication-resistant BMS is needed. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technology approved by the US Food and Drug Administration (FDA) for the treatment of depression. Recent studies have found beneficial effects of TMS for the treatment of pain. A case of BMS treated successfully with daily left prefrontal rTMS over a 2-week period is reported here. Based on this patient's clinical course and a recent pain study, the mechanism by which TMS may act to decrease the burning pain is discussed.

Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee.

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments.

Dorsolateral prefrontal cortex stimulation modulates electrocortical measures of visual attention: evidence from direct bilateral epidural cortical stimulation in treatment-resistant mood disorder.

Electrocortical activity is increasingly being used to study emotion regulation and the impact of cognitive control on neural response to visual stimuli. In the current study, we used direct epidural cortical stimulation (EpCS) to examine regional specificity of PFC stimulation on the parietally-maximal late positive potential (LPP), an event-related potential (ERP) biomarker of visual attention to salient stimuli. Five patients with treatment-resistant mood disorders were stereotactically implanted with stimulating paddles over frontopolar (FP) and dorsolateral (DL) prefrontal cortex bilaterally. On their first day of activation, patients underwent sham-controlled EpCS coupled with 64-channel electroencephalograph (EEG) recordings and passive viewing of aversive and neutral images. In addition to sham, patients had either FP or DL prefrontal cortex stimulated at 2 or 4 V while they viewed neutral and aversive pictures. As expected during the sham condition, LPP was larger for aversive compared to neutral stimuli (F(1,4)=232.07, P<.001). Stimulation of DL compared to FP prefrontal cortex resulted in a reduction of the LPP (F(1,4)=8.15, P=.048). These data provide additional and unique support to the role of the DL prefrontal cortex in regulating measures of neural activity that have been linked to emotional arousal and attention. Future studies with EpCS can help directly map out various prefrontal functions in treatment-resistant mood disorder.

The Sauve-Kapandji procedure and the Darrach procedure for distal radio-ulnar joint dysfunction after Colles' fracture.

This retrospective study evaluated the results of the Darrach procedure and the Sauve-Kapandji procedure for the treatment of distal radio-ulnar joint derangement following malunion of dorsally displaced, unstable, intraarticular fractures of the distal radius in patients under 50 years of age. Twelve of 18 possible patients in the Sauve-Kapandji group completed the disabilities of the arm, shoulder, and hand survey at a mean of 4 years postoperatively and nine of the 18 returned for a follow-up examination at a mean of 2 years. Twenty-one of 30 possible patients in the Darrach group completed the disabilities of the arm, shoulder, and hand survey at a mean of 6 years postoperatively and 13 of these 30 returned for follow-up examination at a mean of 4 years. The Darrach procedure and the Sauve-Kapandji procedure yielded comparable and unpredictable results with respect to both subjective and objective parameters.

A TMS coil positioning/holding system for MR image-guided TMS interleaved with fMRI.

OBJECTIVE: Transcranial magnetic stimulation (TMS) can be interleaved with fMRI to visualize regional brain activity in response to direct, non-invasive, cortical stimulation, making it a promising tool for studying brain function. A major practical difficulty is accurately positioning the TMS coil within the MRI scanner for stimulating a particular area of brain cortex. The objective of this work was to design and build a self-contained hardware/software system for MR-guided TMS coil positioning in interleaved TMS/fMRI studies. METHODS: A compact, manually operated, articulated TMS coil positioner/holder with 6 calibrated degrees of freedom was developed for use inside a cylindrical RF head coil, along with a software package for transforming between MR image coordinates, MR scanner space coordinates, and positioner/holder settings. RESULTS: Phantom calibration studies gave an accuracy for positioning within setups of dx=+/-1.9 mm, dy=+/-1.4 mm, dz=+/-0.8 mm and a precision for multiple setups of dx=+/-0.8 mm, dy=+/-0.1 mm, dz=+/-0.1 mm. CONCLUSIONS: This self-contained, integrated MR-guided TMS system for interleaved TMS/fMRI studies provides fast, accurate location of motor cortex stimulation sites traditionally located functionally, and a means of consistent, anatomy-based TMS coil positioning for stimulation of brain areas without overt response.

BOLD fMRI response to direct stimulation (transcranial magnetic stimulation) of the motor cortex shows no decline with age.

Previous studies using BOLD fMRI to examine age-related changes in cortical activation used tasks that relied on peripheral systems to activate the brain. They were unable to distinguish between alterations due to age-related changes in the periphery and actual changes in cortical physiology. Transcranial magnetic stimulation (TMS), which allows direct, noninvasive stimulation of cortical neurons, was interleaved with BOLD fMRI to study 6 young and 5 old subjects. Three different tasks were compared: direct stimulation by TMS, indirect active stimulation produced by a motor task, and indirect passive stimulation produced by hearing the TMS coil discharge. Direct neuronal stimulation by TMS produced similar fMRI signal increases in both groups, suggesting that cortical physiology itself may not necessarily decline with age.