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AbstractBOLD fMRI is widely applied in human neuroscience but is limited in its spatial specificity due to a cortical‐depth‐dependent venous bias. This reduces its localization specificity with respect to neuronal responses, a disadvantage for neuroscientific research. Here, we modified a submillimeter BOLD protocol to selectively reduce venous and tissue signal and increase cerebral blood volume weighting through a pulsed saturation scheme (dubbed Arterial Blood Contrast) at 7 T. Adding Arterial Blood Contrast on top of the existing BOLD contrast modulated the intracortical contrast. Isolating the Arterial Blood Contrast showed a response free of pial‐surface bias. The results suggest that Arterial Blood Contrast can modulate the typical fMRI spatial specificity, with important applications in in‐vivo neuroscience.

Recent evidence indicates subject-specific gyral folding patterns and white matter anisotropy uniquely shape electric fields generated by TMS. Current methods for predicting the brain regions influenced by TMS involve projecting the TMS coil position or center of gravity onto realistic head models derived from structural and functional imaging data. Similarly, spherical models have been used to estimate electric field distributions generated by TMS pulses delivered from a particular coil location and position. In the present paper we inspect differences between electric field computations estimated using the finite element method (FEM) and projection-based approaches described above. We then more specifically examined an approach for estimating cortical excitation volumes based on individualistic FEM simulations of electric fields. We evaluated this approach by performing neurophysiological recordings during MR-navigated motormapping experiments. We recorded motor evoked potentials (MEPs) in response to single pulse TMS using two different coil orientations (45° and 90° to midline) at 25 different locations (5×5 grid, 1cm spacing) centered on the hotspot of the right first dorsal interosseous (FDI) muscle in left motor cortex. We observed that motor excitability maps varied within and between subjects as a function of TMS coil position and orientation. For each coil position and orientation tested, simulations of the TMS-induced electric field were computed using individualistic FEM models and compared to MEP amplitudes obtained during our motormapping experiments. We found FEM simulations of electric field strength, which take into account subject-specific gyral geometry and tissue conductivity anisotropy, significantly correlated with physiologically observed MEP amplitudes (rmax=0.91, p=1.8×10(-5) rmean=0.81, p=0.01). These observations validate the implementation of individualistic FEM models to account for variations in gyral folding patterns and tissue conductivity anisotropy, which should help improve the targeting accuracy of TMS in the mapping or modulation of human brain circuits. peerReviewed

We investigated the differential effects of serotonergic and noradrenergic antidepressants on brain activation in patients with major depressive disorder during a Stroop task. We predicted that pretreatment hyperactivity in the rostral anterior cingulate cortex would predict better treatment outcomes.In total, 20 patients underwent naturalistic open-label clinical treatment with citalopram (n = 12) or reboxetine (n = 8). We performed functional magnetic resonance imaging at baseline and after 6 weeks of treatment.There were no significant group differences in clinical characteristics, treatment outcomes or baseline fMRI activations. The group by time interaction revealed significant voxels in the right amygdala-hippocampus complex (p0.05, family-wise error corrected by use of the bilateral amygdala and hippocampus mask image as a small volume), indicating a posttreatment blood oxygen level- dependent signal decrease in the citalopram group. Pretreatment hyperactivity in the rostral anterior cingulate cortex was not related to symptom improvement.Our study was a nonrandomized clinical trial.These results indicate that serotonergic and noradrenergic antidepressants have a differential effect on brain activity, especially in the amygdala and hippocampus.

ObjectiveTherapies targeting B cells have been used in the clinic for multiple sclerosis (MS). In patients with relapsing MS, anti-CD20 therapy often suppresses relapse activity; yet, their effect on disease progression has been disappointing. Most anti-CD20 therapeutic antibodies are type I, but within the unique microenvironment of the brain, type II antibodies may be more beneficial, as type II antibodies exhibit reduced complement-dependent cytotoxicity and they have an increased capacity to induce direct cell death that is independent of the host immune response.MethodsWe compared the effect of type I with type II anti-CD20 therapy in a new rodent model of secondary progressive MS (SPMS), which recapitulates the principal histopathologic features of MS including meningeal B-cell aggregates. Focal MS-like lesions were induced by injecting heat-killed Mycobacterium tuberculosis into the piriform cortex of MOG-immunized mice. Groups of mice were treated with anti-CD20 antibodies (type I [rituxumab, 10 mg/kg] or type II [GA101, 10 mg/kg]) 4 weeks after lesion initiation, and outcomes were evaluated by immunohistochemistry.ResultsAnti-CD20 therapy decreased the extent of glial activation, significantly decreased the number of B and T lymphocytes in the lesion, and resulted in disruption of the meningeal aggregates. Moreover, at the given dose, the type II anti-CD20 therapy was more efficacious than the type I and also protected against neuronal death.ConclusionsThese results indicate that anti-CD20 may be an effective therapy for SPMS with B-cell aggregates and that the elimination of CD20+ B cells alone is sufficient to cause disruption of aggregates in the brain.

Experiencing feelings of helplessness has repeatedly been reported to contribute to depressive symptoms and negative affect. In turn, depression and negative affective states are associated, among others, with impairments in performance monitoring. Thus, the question arises whether performance monitoring is also affected by feelings of helplessness. To this end, after the induction of feelings of helplessness via an unsolvable reasoning task, 37 participants (20 females) performed a modified version of a Flanker task. Based on a previously validated questionnaire, 17 participants were classified as helpless and 20 as not-helpless. Behavioral measures revealed no differences between helpless and not-helpless individuals. However, we observed enhanced Error-Related Negativity (ERN) amplitude differences between erroneous and correct responses in the helpless compared to the not-helpless group. Furthermore, correlational analysis revealed that higher scores of helplessness were associated with increased ERN difference scores. No influence of feelings of helplessness on later stages of performance monitoring was observed as indicated by Error-Positivity (Pe) amplitude. The present study is the first to demonstrate that feelings of helplessness modulate the neuronal correlates of performance monitoring. Thus, even a short-lasting subjective state manipulation can lead to ERN amplitude variation, probably via modulation of mesencephalic dopamine activity.

A technical description is presented of the low-energy ion and electron (LION) instrument on the SOHO spacecraft and its scientific goals are discussed. LION forms part of the comprehensive suprathermal and energetic particle analyzer (COSTEP), which is, in turn, a subset of the COSTEP/ERNE particle analyser collaboration (CEPAC).

Ischemic stroke initiates a robust inflammatory response that starts in the intravascular compartment and involves rapid activation of brain resident cells. A key mechanism of this inflammatory response is the migration of circulating immune cells to the ischemic brain facilitated by chemokine release and increased endothelial adhesion molecule expression. Brain-invading leukocytes are well-known contributing to early-stage secondary ischemic injury, but their significance for the termination of inflammation and later brain repair has only recently been noticed. Here, a simple protocol for the efficient isolation of immune cells from the ischemic mouse brain is provided. After transcardial perfusion, brain hemispheres are dissected and mechanically dissociated. Enzymatic digestion with Liberase is followed by density gradient (such as Percoll) centrifugation to remove myelin and cell debris. One major advantage of this protocol is the single-layer density gradient procedure which does not require time-consuming preparation of gradients and can be reliably performed. The approach yields highly reproducible cell counts per brain hemisphere and allows for measuring several flow cytometry panels in one biological replicate. Phenotypic characterization and quantification of brain-invading leukocytes after experimental stroke may contribute to a better understanding of their multifaceted roles in ischemic injury and repair.

Abstract This study addresses the question whether prosodic information can affect the choice for a syntactic analysis in auditory sentence processing. We manipulated the prosody (in the form of a prosodic break; PB) of locally ambiguous Dutch sentences to favor one of two interpretations. The experimental items contained two different types of so-called control verbs (subject and object control) in the matrix clause and were syntactically disambiguated by a transitive or by an intransitive verb. In Experiment 1, we established the default off-line preference of the items for a transitive or an intransitive disambiguating verb with a visual and an auditory fragment completion test. The results suggested that subject- and object-control verbs differently affect the syntactic structure that listeners expect. In Experiment 2, we investigated these two types of verbs separately in an on-line ERP study. Consistent with the literature, the PB elicited a closure positive shift. Furthermore, in subject-control items, an N400 effect for intransitive relative to transitive disambiguating verbs was found, both for sentences with and for sentences without a PB. This result suggests that the default preference for subject-control verbs goes in the same direction as the effect of the PB. In object-control items, an N400 effect for intransitive relative to transitive disambiguating verbs was found for sentences with a PB but no effect in the absence of a PB. This indicates that a PB can affect the syntactic analysis that listeners pursue.

Abstract Introduction Pre‐treatment blood oxygenation level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) has been used for the early identification of patients with major depressive disorder (MDD) who later respond or fail to respond to medication. However, BOLD responses early after treatment initiation may offer insight into early neural changes associated with later clinical response. The present study evaluated both pre‐treatment and early post‐treatment fMRI responses to an emotion processing task, to further our understanding of neural changes associated with a successful response to pharmacological intervention. Methods MDD patients who responded (n = 22) and failed to respond (n = 12) after 8 weeks of treatment with either citalopram or quetiapine extended release, and healthy controls (n = 18) underwent two fMRI scans, baseline (pre‐treatment), and early post‐treatment (one week after treatment commencement). Participants completed an emotional face matching task at both scans. Results Using threshold‐free cluster enhancement (TFCE) and non‐parametric permutation testing, fMRI activation maps showed that after one week of treatment, responders demonstrated increased activation in the left parietal lobule, precentral gyrus, and bilateral insula (all P < 0.05 threshold‐free cluster enhancement (TFCE) family‐wise error‐corrected) to negative facial expressions. Non‐responders showed some small increases in the precentral gyrus, while controls showed no differences between scans. Compared to non‐responders, responders showed some increased activation in the superior parietal lobule and middle temporal gyrus at the post‐treatment scan. There were no group differences between responders, non‐responders, and controls at baseline. Conclusions One week after treatment commencement, BOLD signal changes in the parietal lobules, insula, and middle temporal gyrus were related to clinical response to pharmacological treatment. Patients diagnosed MDD who later went on to respond to medication showed robust BOLD increases after one week of treatment to an emotion processing task. There were no differences between responders, non‐responders and healthy controls at baseline, indicating that BOLD fMRI can be used to identify mediating markers of treatment response.