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1.  In-vivo Dynamics of the Human Hippocampus across the Menstrual Cycle 
Scientific Reports  2016;6:32833.
Sex hormones fluctuate during the menstrual cycle. Evidence from animal studies suggests similar subtle fluctuations in hippocampal structure, predominantly linked to estrogen. Hippocampal abnormalities have been observed in several neuropsychiatric pathologies with prominent sexual dimorphism. Yet, the potential impact of subtle sex-hormonal fluctuations on human hippocampal structure in health is unclear. We tested the feasibility of longitudinal neuroimaging in conjunction with rigorous menstrual cycle monitoring to evaluate potential changes in hippocampal microstructure associated with physiological sex-hormonal changes. Thirty longitudinal diffusion weighted imaging scans of a single healthy female subject were acquired across two full menstrual cycles. We calculated hippocampal fractional anisotropy (FA), a measure sensitive to changes in microstructural integrity, and investigated potential correlations with estrogen. We observed a significant positive correlation between FA values and estrogen in the hippocampus bilaterally, revealing a peak in FA closely paralleling ovulation. This exploratory, single-subject study demonstrates the feasibility of a longitudinal DWI scanning protocol across the menstrual cycle and is the first to link subtle endogenous hormonal fluctuations to changes in FA in vivo. In light of recent attempts to neurally phenotype single humans, our findings highlight menstrual cycle monitoring in parallel with highly sampled individual neuroimaging data to address fundamental questions about the dynamics of plasticity in the adult brain.
PMCID: PMC5054394  PMID: 27713470
2.  Instrument specific use-dependent plasticity shapes the anatomical properties of the corpus callosum: a comparison between musicians and non-musicians 
Long-term musical expertise has been shown to be associated with a number of functional and structural brain changes, making it an attractive model for investigating use-dependent plasticity in humans. Physiological interhemispheric inhibition (IHI) as examined by transcranial magnetic stimulation has been shown to be correlated with anatomical properties of the corpus callosum as indexed by fractional anisotropy (FA). However, whether or not IHI or the relationship between IHI and FA in the corpus callosum can be modified by different musical training regimes remains largely unknown. We investigated this question in musicians with different requirements for bimanual finger movements (piano and string players) and non-expert controls. IHI values were generally higher in musicians, but differed significantly from non-musicians only in string players. IHI was correlated with FA in the posterior midbody of the corpus callosum across all participants. Interestingly, subsequent analyses revealed that this relationship may indeed be modulated by different musical training regimes. Crucially, while string players had greater IHI than non-musicians and showed a positive structure-function relationship, the amount of IHI in pianists was comparable to that of non-musicians and there was no significant structure-function relationship. Our findings indicate instrument specific use-dependent plasticity in both functional (IHI) and structural (FA) connectivity of motor related brain regions in musicians.
PMCID: PMC4100438  PMID: 25076879
use-dependent plasticity; corpus callosum; musical training; pianists; string players; interhemispheric inhibition; fractional anisotropy; diffusion imaging
3.  Switching between hands in a serial reaction time task: a comparison between young and old adults 
Healthy aging is associated with a variety of functional and structural brain alterations. These age-related brain alterations have been assumed to negatively impact cognitive and motor performance. Especially important for the execution of everyday activities in older adults (OA) is the ability to perform movements that depend on both hands working together. However, bimanual coordination is typically deteriorated with increasing age. Hence, a deeper understanding of such age-related brain-behavior alterations might offer the opportunity to design future interventional studies in order to delay or even prevent the decline in cognitive and/or motor performance over the lifespan. Here, we examined to what extent the capability to acquire and maintain a novel bimanual motor skill is still preserved in healthy OA as compared to their younger peers (YA). For this purpose, we investigated performance of OA (n = 26) and YA (n = 26) in a bimanual serial reaction time task (B-SRTT), on two experimental sessions, separated by 1 week. We found that even though OA were generally slower in global response times, they showed preserved learning capabilities in the B-SRTT. However, sequence specific learning was more pronounced in YA as compared to OA. Furthermore, we found that switching between hands during B-SRTT learning trials resulted in increased response times (hand switch costs), a phenomenon that was more pronounced in OA. These hand switch costs were reduced in both groups over the time course of learning. More interestingly, there were no group differences in hand switch costs on the second training session. These results provide novel evidence that bimanual motor skill learning is capable of reducing age-related deficits in hand switch costs, a finding that might have important implications to prevent the age-related decline in sensorimotor function.
PMCID: PMC4569733  PMID: 26441638
motor skill learning; aging; hand switch costs; bimanual serial reaction time task
4.  Mirror Visual Feedback-Induced Performance Improvement and the Influence of Hand Dominance 
Mirror visual feedback (MVF) is a promising technique in clinical settings that can be used to augment performance of an untrained limb. Several studies with healthy volunteers and patients using transcranial magnetic stimulation (TMS) or functional magnetic resonance imaging (fMRI) indicate that functional alterations within primary motor cortex (M1) might be one candidate mechanism that could explain MVF-induced changes in behavior. Until now, most studies have used MVF to improve performance of the non-dominant hand (NDH). The question remains if the behavioral effect of MVF differs according to hand dominance. Here, we conducted a study with two groups of young, healthy right-handed volunteers who performed a complex ball-rotation task while receiving MVF of the dominant (n = 16, group 1, MVFDH) or NDH (n = 16, group 2, MVFNDH). We found no significant differences in baseline performance of the untrained hand between groups before MVF was applied. Furthermore, there was no significant difference in the amount of performance improvement between MVFDH and MVFNDH indicating that the outcome of MVF seems not to be influenced by hand dominance. Thus our findings might have important implications in neurorehabilitation suggesting that patients suffering from unilateral motor impairments might benefit from MVF regardless of the dominance of the affected limb.
PMCID: PMC4720001  PMID: 26834605
mirror visual feedback (MVF); hand dominance; motor learning; motor skill learning; handedness
5.  Structural correlates of skilled performance on a motor sequence task 
The brain regions functionally engaged in motor sequence performance are well-established, but the structural characteristics of these regions and the fiber pathways involved have been less well studied. In addition, relatively few studies have combined multiple magnetic resonance imaging (MRI) and behavioral performance measures in the same sample. Therefore, the current study used diffusion tensor imaging (DTI), probabilistic tractography, and voxel-based morphometry (VBM) to determine the structural correlates of skilled motor performance. Further, we compared these findings with fMRI results in the same sample. We correlated final performance and rate of improvement measures on a temporal motor sequence task (TMST) with skeletonized fractional anisotropy (FA) and whole brain gray matter (GM) volume. Final synchronization performance was negatively correlated with FA in white matter (WM) underlying bilateral sensorimotor cortex—an effect that was mediated by a positive correlation with radial diffusivity. Multi-fiber tractography indicated that this region contained crossing fibers from the corticospinal tract (CST) and superior longitudinal fasciculus (SLF). The identified SLF pathway linked parietal and auditory cortical regions that have been shown to be functionally engaged in this task. Thus, we hypothesize that enhanced synchronization performance on this task may be related to greater fiber integrity of the SLF. Rate of improvement on synchronization was positively correlated with GM volume in cerebellar lobules HVI and V—regions that showed training-related decreases in activity in the same sample. Taken together, our results link individual differences in brain structure and function to motor sequence performance on the same task. Further, our study illustrates the utility of using multiple MR measures and analysis techniques to specify the interpretation of structural findings.
PMCID: PMC3486688  PMID: 23125826
superior longitudinal fasciculus; individual differences; motor sequence performance; fractional anisotropy; diffusion tensor imaging; gray matter volume
6.  Quantification of Protoporphyrin IX Accumulation in Glioblastoma Cells: A New Technique 
ISRN Surgery  2014;2014:405360.
Introduction. 5-Aminolevulinic Acid (5-ALA) is a precursor of heme synthesis. A metabolite, protoporphyrin IX (PpIX), selectively accumulates in neoplastic tissue including glioblastoma. Presurgical administration of 5-ALA forms the basis of fluorescence-guided resection (FGR) of glioblastoma (GBM) tumors. However, not all gliomas accumulate sufficient quantities of PpIX to fluoresce, thus limiting the utility of FGR. We therefore developed an assay to determine cellular and pharmacological factors that impact PpIX fluorescence in GBM. This assay takes advantage of a GBM cell line engineered to express yellow fluorescent protein. Methods. The human GBM cell line U87MG was transfected with a YFP expression vector. After treatment with a series of 5-ALA doses, both PpIX and YFP fluorescence were measured. The ratio of PpIX to YFP fluorescence was calculated. Results. YFP fluorescence permitted the quantification of cell numbers and did not interfere with 5-ALA metabolism. The PpIX/YFP fluorescence ratio provided accurate relative PpIX levels, allowing for the assessment of PpIX accumulation in tissue. Conclusion. Constitutive YFP expression strongly correlates with cell number and permits PpIX quantification. Absolute PpIX fluorescence alone does not provide information regarding PpIX accumulation within the cells. Our research indicates that our PpIX/YFP ratio assay may be a promising model for in vitro 5-ALA testing and its interactions with other compounds during FGR surgery.
PMCID: PMC3960765  PMID: 24729904

Results 1-6 (6)