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Schlaug, G.

Publications and source records attributed to Schlaug, G..

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Assessing the Dose-Dependent Effects of tDCS on Neurometabolites using Magnetic Resonance Spectroscopy

Concurrent transcranial direct current stimulation (tDCS) and proton Magnetic Resonance Spectroscopy (1H MRS) experiments have shown up- or downregulation of neurotransmitter concentration. However, effects have been modest applying mostly lower current doses and not all studies found significant effects. Dose of stimulation might be an important variable in eliciting a consistent response. To investigate dose effects of tDCS on neurometabolites, we placed an electrode over the left supraorbital region (with a return electrode over the right mastoid bone) and utilized an MRS voxel (3x3x3cm) that was centered over the anterior cingulate/inferior mesial prefrontal region which is in the path of the current distribution. We conducted 5 epochs of acquisition, each one with a 9:18min acquisition time, and applied tDCS in the third epoch. We observed significant dose and polarity dependent modulation of GABA and to a lesser degree of Glutamine/Glutamate (GLX) with the highest and reliable changes seen with the highest current dose, 5mA (current density 0.39 mA/cm2), during and after the stimulation epoch compared with pre-stimulation baselines. The strong effect on GABA concentration (achieving a mean change of 63% from baseline, more than twice as much as reported with lower doses of stimulation) establishes tDCS-dose as an important parameter in eliciting a regional brain engagement and response. Furthermore, our experimental design in examining tDCS parameters and effects using shorter epochs of acquisitions might constitute a framework to explore the tDCS parameter space further and establish measures of regional engagement by non-invasive brain-stimulation.

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Multielectrode Network Stimulation (ME-NETS) demonstrated by concurrent tDCS and fMRI

Non-invasive transcranial direct current stimulation (tDCS) can modulate activity of targeted brain regions. Whether tDCS can reliably and repeatedly modulate intrinsic connectivity of entire brain networks is unclear. We used concurrent tDCS-MRI to investigate the effect of high dose anodal tDCS on resting state connectivity within the Arcuate Fasciculus (AF) network, which spans the temporal, parietal, and frontal lobes and is connected via a structural backbone, the Arcuate Fasciculus (AF) white matter tract. Effects of high-dose tDCS (4mA) delivered via a single electrode placed over one of the AF nodes (single electrode stimulation, SE-S) was compared to the same dose split between multiple electrodes placed over AF-network nodes (multielectrode network stimulation, ME-NETS). While both SE-S and ME-NETS significantly modulated connectivity between AF network nodes (increasing connectivity during stimulation epochs), ME-NETS had a significantly larger and more reliable effect than SE-S. Moreover, comparison with a control network, the Inferior Longitudinal Fasciculus (ILF) network suggested that the effect of ME-NETS on connectivity was specific to the targeted AF-network. This finding was further supported by the results of a seed-to-voxel analysis wherein we found ME-NETS primarily modulated connectivity between AF-network nodes. Finally, an exploratory analysis looking at dynamic connectivity using sliding window correlation found strong and immediate modulation of connectivity during three stimulation epochs within the same imaging session.

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A machine learning approach to identify the engagement of a brain network targeted by non-invasive brain-stimulation

Transcranial direct current stimulation (tDCS) can noninvasively modulate behavior, cognition, and physiologic brain functions depending on polarity and dose of stimulation as well as montage of electrodes. Concurrent tDCS-fMRI presents a novel way to explore the parameter space of non-invasive brain stimulation and to inform the experimenter as well as the participant if a targeted brain region or a network of spatially separate brain regions has been engaged and modulated. We compared a multi-electrode (ME) with a single electrode (SE) montage and both active conditions with a no-stimulation (NS) control condition to assess the engagement of a brain network and the ability of different electrode montages to modulate network activity. The multi-electrode montage targeted nodal regions of the right Arcuate Fasciculus Network (AFN) with anodal electrodes placed over the skull position of the posterior superior temporal/middle temporal gyrus (STG/MTG), supramarginal gyrus (SMG), posterior inferior frontal gyrus (IFG) and a return cathodal electrode over the left supraorbital region. In comparison, the single electrode montage used only one anodal electrode over a nodal brain region of the AFN, but varied the location between STG/MTG, SMG, and posterior IFG for different participants. Whole-brain rs-fMRI was obtained every three seconds. The tDCS-stimulator was turned on at 3 minutes after the scanning started. A 4D rs-fMRI data set was converted to dynamic functional connectivity (DFC) matrices using a set of ROI pairs belonging to the AFN as well as other unrelated brain networks. In this study, we evaluated the performance of five algorithms to classify the DFC matrices from the three conditions (ME, SE, NS) into three different categories. The highest accuracy of 0.92 was obtained for the classification of the ME condition using the K Nearest Neighbor (KNN) algorithm. In other words, applying the classification algorithm allowed us to identify the engagement of the AFN and the ME condition was the best montage to achieve such an engagement. The top 5 ROI pairs that made a major contribution to the classification of participants rs-fMRI data were identified using model performance parameters; ROI pairs were mainly located within the right AFN. This proof-of-concept study using a classification algorithm approach can be expanded to create a real-time feedback system at a participant level to detect the engagement and modulation of a brain network that spans multiple brain lobes.

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Bayesian stroke modeling details sex biases in the white matter substrates of aphasia

Ischemic cerebrovascular events often lead to aphasia. Previous work provided hints that such strokes may affect women and men in distinct ways. Women tend to suffer strokes with more disabling language impairment, even if the lesion size is comparable to men. In 1,401 patients, we isolated data-led representations of anatomical lesion patterns and hand-tailored a Bayesian analytical solution to carefully model the degree of sex divergence in predicting language outcomes [~]3 months after stroke. We located lesion-outcome effects in the left-dominant language network that highlight the ventral pathway as a core lesion focus across different tests of language performance. We provide newly detailed evidence for sex-specific brain-behavior associations in the domain-general networks associated with cortico-subcortical pathways, with unique contributions of the fornix in women and cingular fiber bundles in men. Our collective findings suggest diverging white matter substrates in how stroke causes language deficits in women and men. Clinically acknowledging such sex disparities has the potential to improve personalized treatment for stroke patients worldwide.

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Effects of tDCS Dose and Electrode Montage on regional cerebral blood flow and motor behavior

We used three dose levels (Sham, 2mA, and 4mA) and two different electrode montages (unihemispheric or bihemispheric) to examine DOSE and MONTAGE effects on regional cerebral blood flow (rCBF) as a surrogate marker of neural activity, and on a finger sequence task, as a surrogate behavioral measure drawing on brain regions targeted by transcranial direct current stimulation (tDCS). We placed the anodal electrode over the right motor region (C4) while the cathodal or return electrode was placed either over a left supraorbital region (unihemispheric montage) or over the left motor region (C3 in the bihemispheric montage). Performance changes in the finger sequence task for both hands (left hand: p = 0.0026, and right hand: p = 0.0002) showed a linear tDCS dose response but no montage effect. rCBF in the right hemispheric perirolandic area increased with dose under the anodal electrode (p = 0.027). In contrast, in the perirolandic ROI in the left hemisphere, rCBF showed a trend to increase with dose (p = 0.053) and a significant effect of montage (p = 0.00004). The bihemispheric montage showed additional rCBF increases in frontomesial regions in the 4mA condition but not in the 2mA condition. Furthermore, we found correlations between rCBF changes in the right perirolandic region and improvements in the finger sequence task performance (FSP) for the left and right hand. Our data support not only a strong direct tDCS dose effect for rCBF and FSP as surrogate measures of targeted brain regions but also indirect effects on rCBF in functionally connected regions (e.g., frontomesial regions), particularly in the higher dose condition and on FSP of the ipsilateral hand (to the anodal electrode). At a higher dose and irrespective of polarity, a wider network of sensorimotor regions is positively affected by tDCS. HighlightsO_LItDCS-DOSE had a linear effect on finger sequence performance for both hands C_LIO_LIrCBF changes in both perirolandic ROIs demonstrated tDCS-DOSE effects, and left perirolandic ROI demonstrated tDCS-MONTAGE effects. C_LIO_LISimulated current intensity in the left and right perirolandic ROI strongly correlated with the contralateral hands finger sequence performance. C_LIO_LItDCS-Tolerability scores did not correlate with change in rCBF or finger sequence performance of the left hand. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=99 SRC="FIGDIR/small/429369v2_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@763dc5org.highwire.dtl.DTLVardef@d158f4org.highwire.dtl.DTLVardef@271d71org.highwire.dtl.DTLVardef@1fe0597_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Modulating short-term auditory memory with focal transcranial direct current stimulation applied to the Supramarginal Gyrus

Previous studies have shown that transcranial direct current stimulation (tDCS) can affect performance by decreasing regional excitability in a brain region that contributes to the task of interest. To our knowledge, no research to date has found both enhancing and diminishing effects on performance, depending upon which polarity of current is applied. The supramarginal gyrus (SMG) is an ideal brain region for testing tDCS effects because it is easy to identify using the 10-20 EEG coordinate system, and results of neuroimaging studies have implicated the left SMG in short-term memory for phonological and non-phonological sounds. In the present study, we found that applying tDCS to the left SMG affected pitch memory in a manner that depended upon the polarity of stimulation: cathodal tDCS had a negative impact on performance while anodal tDCS had a positive impact. These effects were significantly different from sham stimulation, which did not influence performance; they were also specific to the left hemisphere - no effect was found when applying cathodal stimulation to the right SMG - and were unique to pitch memory as opposed to memory for visual shapes. Our results provide further evidence that the left SMG is a nodal point for short-term auditory storage and demonstrate the potential of tDCS to influence cognitive performance, and to causally examine hypotheses derived from neuroimaging studies.

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Auditory aversion in absolute pitch possessors

Absolute pitch (AP) refers to the ability of identifying the pitch of a given tone without reliance on any reference pitch. The downside of possessing AP may be the experience of disturbance when exposed to out-of-tune tones. Here, we investigated this so-far unexplored phenomenon in AP, which we refer to as auditory aversion. Electroencephalography (EEG) was recorded in a sample of AP possessors and matched control musicians without AP while letting them perform a task underlying a so-called affective priming paradigm: Participants judged valenced pictures preceded by musical primes as quickly and accurately as possible. The primes were bimodal, presented as tones in combination with visual notations that either matched or mismatched the actually presented tone. Regardless of the prime condition, AP possessors performed more poorly in judging pleasant pictures and their EEG revealed later peaks at around 200 ms (P200) after prime onset. Their performance dropped when responding to pleasant pictures preceded by incongruent primes, especially when mistuned by one semitone. This interference was also reflected in an EEG deflection at around 400 ms (N400) after picture onset, preceding the behavior responses. These findings suggest that AP possessors process mistuned musical stimuli and pleasant pictures as affectively unrelated with each other, supporting an aversion towards out-of-tune tones in AP possessors. The longer prime-related P200 latencies exhibited by AP possessors suggest a delay in integrating musical stimuli, underlying an altered affinity towards pitch-label associations.

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Music perception in acquired prosopagnosia: An anterior temporal syndrome for faces, voices, and music

BackgroundAcquired prosopagnosia is often associated with other deficits, such as dyschromatopsia and topographagnosia, from damage to adjacent perceptual networks. A recent study showed that some subjects with developmental prosopagnosia also have congenital amusia, but problems with music perception have not been described in the acquired variant.\n\nObjectiveOur goal was to determine if music perception was also impaired in subjects with acquired prosopagnosia, and if so, its anatomic correlate.\n\nMethodsWe studied eight subjects with acquired prosopagnosia, all of whom had extensive neuropsychological and neuroimaging testing. They performed a battery of tests evaluating pitch and rhythm processing, including the Montreal Battery for the Evaluation of Amusia.\n\nResultsThree of eight subjects with acquired prosopagnosia had impaired musical pitch perception while rhythm perception was spared. Two of the three also showed reduced musical memory. These three reported alterations in their emotional experience of music: one reported music anhedonia and aversion, while the remaining two had changes consistent with musicophilia. The lesions of these three subjects affected the right or bilateral temporal poles as well as the right amygdala and insula. None of the three prosopagnosic subjects with lesions limited to the inferior occipitotemporal cortex had impaired pitch perception or musical memory, or reported changes in music appreciation.\n\nConclusionTogether with the results of our previous studies of voice recognition, these findings indicate an anterior temporal agnosia syndrome that can include the amnestic variant of prosopagnosia, phonagnosia, and various alterations in music perception, including acquired amusia, reduced musical memory, and altered emotional responses to music.

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