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Dive into the research topics where Jacob Lahr is active.

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Featured researches published by Jacob Lahr.


PLOS ONE | 2016

Effects of Different Analysis Strategies on Paired Associative Stimulation. A Pooled Data Analysis from Three Research Labs.

Jacob Lahr; Sven Paßmann; Jonathan List; Werner Vach; Agnes Flöel; Stefan Klöppel

Paired associative stimulation (PAS) is a widely used transcranial magnetic stimulation (TMS) paradigm to non-invasively induce synaptic plasticity in the human brain in vivo. Altered PAS-induced plasticity has been demonstrated for several diseases. However, researchers are faced with a high inter- and intra-subject variability of the PAS response. Here, we pooled original data from nine PAS studies from three centers and analyzed the combined dataset of 190 healthy subjects with regard to age dependency, the role of stimulation parameters and the effect of different statistical methods. We observed no main effect of the PAS intervention over all studies (F(2;362) = 0.44; p = 0.644). The rate of subjects showing the expected increase of motor evoked potential (MEP) amplitudes was 53%. The PAS effect differed significantly between studies as shown by a significant interaction effect (F(16;362) = 1.77; p = 0.034) but post-hoc testing did not reveal significant effects after correction for multiple tests. There was a trend toward increased variability of the PAS effect in older subjects. Acquisition parameters differed across studies but without systematically influencing changes in MEP-size. The use of post/baseline quotients systematically indicated stronger PAS effects than post/baseline difference or the logarithm of the post/baseline quotient. The non-significant PAS effects across studies and a wide range of responder rates between studies indicate a high variability of this method. We were thus not able to replicate findings from a previous meta-analysis showing robust effects of PAS. No pattern emerged regarding acquisition parameters that at this point could guide future studies to reduce variability and help increase response rate. For future studies, we propose to report the responder rate and recommend the use of the logarithmized post/baseline quotient for further analyses to better address the possibility that results are driven by few extreme cases.


Human Brain Mapping | 2016

Large-scale brain network abnormalities in Huntington's disease revealed by structural covariance.

Lora Minkova; Simon B. Eickhoff; Ahmed Abdulkadir; Christoph P. Kaller; Jessica Peter; Elisa Scheller; Jacob Lahr; Raymund A.C. Roos; Alexandra Durr; Blair R. Leavitt; Sarah J. Tabrizi; Stefan Klöppel

Huntingtons disease (HD) is a progressive neurodegenerative disorder that can be diagnosed with certainty decades before symptom onset. Studies using structural MRI have identified grey matter (GM) loss predominantly in the striatum, but also involving various cortical areas. So far, voxel‐based morphometric studies have examined each brain region in isolation and are thus unable to assess the changes in the interrelation of brain regions. Here, we examined the structural covariance in GM volumes in pre‐specified motor, working memory, cognitive flexibility, and social‐affective networks in 99 patients with manifest HD (mHD), 106 presymptomatic gene mutation carriers (pre‐HD), and 108 healthy controls (HC). After correction for global differences in brain volume, we found that increased GM volume in one region was associated with increased GM volume in another. When statistically comparing the groups, no differences between HC and pre‐HD were observed, but increased positive correlations were evident for mHD, relative to pre‐HD and HC. These findings could be explained by a HD‐related neuronal loss heterogeneously affecting the examined network at the pre‐HD stage, which starts to dominate structural covariance globally at the manifest stage. Follow‐up analyses identified structural connections between frontoparietal motor regions to be linearly modified by disease burden score (DBS). Moderator effects of disease load burden became significant at a DBS level typically associated with the onset of unequivocal HD motor signs. Together with existing findings from functional connectivity analyses, our data indicates a critical role of these frontoparietal regions for the onset of HD motor signs. Hum Brain Mapp 37:67–80, 2016.


Journal of Neural Engineering | 2015

Invasive brain-machine interfaces: a survey of paralyzed patients' attitudes, knowledge and methods of information retrieval.

Jacob Lahr; Christina Schwartz; Bernhard Heimbach; Ad Aertsen; Jörn Rickert; Tonio Ball

OBJECTIVEnBrain-machine interfaces (BMI) are an emerging therapeutic option that can allow paralyzed patients to gain control over assistive technology devices (ATDs). BMI approaches can be broadly classified into invasive (based on intracranially implanted electrodes) and noninvasive (based on skin electrodes or extracorporeal sensors). Invasive BMIs have a favorable signal-to-noise ratio, and thus allow for the extraction of more information than noninvasive BMIs, but they are also associated with the risks related to neurosurgical device implantation. Current noninvasive BMI approaches are typically concerned, among other issues, with long setup times and/or intensive training. Recent studies have investigated the attitudes of paralyzed patients eligible for BMIs, particularly patients affected by amyotrophic lateral sclerosis (ALS). These studies indicate that paralyzed patients are indeed interested in BMIs. Little is known, however, about the degree of knowledge among paralyzed patients concerning BMI approaches or about how patients retrieve information on ATDs. Furthermore, it is not yet clear if paralyzed patients would accept intracranial implantation of BMI electrodes with the premise of decoding improvements, and what the attitudes of a broader range of patients with diseases such as stroke or spinal cord injury are towards this new kind of treatment.nnnAPPROACHnUsing a questionnaire, we surveyed 131 paralyzed patients for their opinions on invasive BMIs and their attitude toward invasive BMI treatment options.nnnMAIN RESULTSnThe majority of the patients knew about and had a positive attitude toward invasive BMI approaches. The group of ALS patients was especially open to the concept of BMIs. The acceptance of invasive BMI technology depended on the improvements expected from the technology. Furthermore, the survey revealed that for paralyzed patients, the Internet is an important source of information on ATDs.nnnSIGNIFICANCEnWebsites tailored to prospective BMI users should be further developed to provide reliable information to patients, and also to help to link prospective BMI users with researchers involved in the development of BMI technology.


Journal of Alzheimer's Disease | 2016

Contribution of the Cholinergic System to Verbal Memory Performance in Mild Cognitive Impairment

Jessica Peter; Jacob Lahr; Lora Minkova; Eliza Lauer; Michel J. Grothe; Stefan J. Teipel; Lena Köstering; Christoph P. Kaller; Bernhard Heimbach; Michael Hüll; Claus Normann; Christoph Nissen; Janine Reis; Stefan Klöppel

Acetylcholine is critically involved in modulating learning and memory function, which both decline in neurodegeneration. It remains unclear to what extent structural and functional changes in the cholinergic system contribute to episodic memory dysfunction in mild cognitive impairment (MCI), in addition to hippocampal degeneration. A better understanding is critical, given that the cholinergic system is the main target of current symptomatic treatment in mild to moderate Alzheimer’s disease. We simultaneously assessed the structural and functional integrity of the cholinergic system in 20 patients with MCI and 20 matched healthy controls and examined their effect on verbal episodic memory via multivariate regression analyses. Mediating effects of either cholinergic function or hippocampal volume on the relationship between cholinergic structure and episodic memory were computed. In MCI, a less intact structure and function of the cholinergic system was found. A smaller cholinergic structure was significantly correlated with a functionally more active cholinergic system in patients, but not in controls. This association was not modulated by age or disease severity, arguing against compensational processes. Further analyses indicated that neither functional nor structural changes in the cholinergic system influence verbal episodic memory at the MCI stage. In fact, those associations were fully mediated by hippocampal volume. Although the cholinergic system is structurally and functionally altered in MCI, episodic memory dysfunction results primarily from hippocampal neurodegeneration, which may explain the inefficiency of cholinergic treatment at this disease stage.


Frontiers in Human Neuroscience | 2015

LTP-like plasticity in the visual system and in the motor system appear related in young and healthy subjects

Stefan Klöppel; Eliza Lauer; Jessica Peter; Lora Minkova; Christoph Nissen; Claus Normann; Janine Reis; F Mainberger; Michael Bach; Jacob Lahr

LTP-like plasticity measured by visual evoked potentials (VEP) can be induced in the intact human brain by presenting checkerboard reversals. Also associated with LTP-like plasticity, around two third of participants respond to transcranial magnetic stimulation (TMS) with a paired-associate stimulation (PAS) protocol with a potentiation of their motor evoked potentials. LTP-like processes are also required for verbal and motor learning tasks. We compared effect sizes, responder rates and intercorrelations as well as the potential influence of attention between these four assessments in a group of 37 young and healthy volunteers. We observed a potentiation effect of the N75 and P100 VEP component which positively correlated with plasticity induced by PAS. Subjects with a better subjective alertness were more likely to show PAS and VEP potentiation. No correlation was found between the other assessments. Effect sizes and responder rates of VEP potentiation were higher compared to PAS. Our results indicate a high variability of LTP-like effects and no evidence for a system-specific nature. As a consequence, studies wishing to assess individual levels of LTP-like plasticity should employ a combination of multiple assessments.


Clinical Neurophysiology | 2016

No difference in paired associative stimulation induced cortical neuroplasticity between patients with mild cognitive impairment and elderly controls.

Jacob Lahr; Jessica Peter; Lora Minkova; Eliza Lauer; Janine Reis; Bernhard Heimbach; Michael Hüll; Claus Normann; Christoph Nissen; Stefan Klöppel

OBJECTIVEnPaired associative stimulation (PAS) is a widely used transcranial magnetic stimulation (TMS) paradigm to induce synaptic long-term potentiation (LTP)-like plasticity in the intact human brain. The PAS effect is reduced in Alzheimers dementia (AD) but has not yet been assessed in patients with mild cognitive impairment (MCI).nnnMETHODSnPAS was assessed in a group of 24 MCI patients and 24 elderly controls. MCI patients were further stratified by their cognitive profile as well as hippocampal atrophy and Apolipoprotein E (ApoE) genotype.nnnRESULTSnThere was no difference in PAS effects between MCI patients and healthy controls. MCI patients tended to show a higher response rate and an average PAS effect. PAS effects were not correlated with markers of disease severity or ApoE genotype but were more pronounced in individuals with shorter sleep duration and in MCI subjects with higher ratings of subjective alertness.nnnCONCLUSIONSnContrary to our initial hypothesis, there was no clear difference in PAS between MCI patients and healthy controls.nnnSIGNIFICANCEnOur results argue against a continuous reduction of LTP-like plasticity along the spectrum of clinical MCI when stratified by MCI-subtype, APOE genotype or hippocampus atrophy.


Frontiers in Human Neuroscience | 2014

Heterogeneity of stimulus-specific response modification—an fMRI study on neuroplasticity

Jacob Lahr; Jessica Peter; Michael Bach; Irina Mader; Christoph Nissen; Claus Normann; Christoph P. Kaller; Stefan Klöppel

Long-term potentiation (LTP) is a key element of synaptic plasticity. At the macroscopic level, similar effects can be induced in the human brain using repetitive stimulation with identical stimuli. High-frequency stimulation (HFS) can increase neuronal responses whereas low-frequency stimulation may produce the opposite effect. Optimal stimulation frequencies and characteristics for inducing stimulus-specific response modification (SRM) differ substantially from those applied to brain tissue slices but have been explored in recent studies. In contrast, the individual manifestation of this effect in terms of its spatial location and extent are unclear. Using functional magnetic resonance imaging (fMRI) in 18 subjects (mean age 25.3 years), we attempted to induce LTP-like effects by HFS with checkerboard flashes at 9 Hz for 120 s. As expected, flashes induced strong activation in primary and secondary visual cortices. Contrary to our expectations, we found clusters of decreased activations induced by pattern flashes after HFS in the primary and secondary visual cortices. On the level of the individual subject, some showed significantly increased activations in the post-HFS session while the majority showed significant decreases. The locations of areas showing altered activations before and after HFS were only partly overlapping. No association between location, extent and direction of the HFS-effect was observed. The findings are unexpected in the light of existing HFS-studies, but mirror the high inter-subject variability, concerning even the directionality of the induced effects shown for other indices of LTP-like plasticity in the human brain. As this variability is not observed in LTP at the cellular level, a better understanding of LTP-like mechanisms on the macroscopic level is essential for establishing tools to quantify individual synaptic plasticity in-vivo.


IEEE Transactions on Biomedical Engineering | 2016

Electrical Stimulation of the Human Cerebral Cortex by Extracranial Muscle Activity: Effect Quantification With Intracranial EEG and FEM Simulations

Lukas Dominique Josef Fiederer; Jacob Lahr; Johannes Vorwerk; Felix Lucka; Ad Aertsen; Carsten H. Wolters; Andreas Schulze-Bonhage; Tonio Ball

Objective: Electric fields (EF) of approx. 0.2 V/m have been shown to be sufficiently strong to both modulate neuronal activity in the cerebral cortex and have measurable effects on cognitive performance. We hypothesized that the EF caused by the electrical activity of extracranial muscles during natural chewing may reach similar strength in the cerebral cortex and hence might act as an endogenous modality of brain stimulation. Here, we present first steps toward validating this hypothesis. Methods: Using a realistic volume conductor head model of an epilepsy patient having undergone intracranial electrode placement and utilizing simultaneous intracranial and extracranial electrical recordings during chewing, we derive predictions about the chewing-related cortical EF strength to be expected in healthy individuals. Results: We find that in the region of the temporal poles, the expected EF strength may reach amplitudes in the order of 0.1-1 V/m. Conclusion: The cortical EF caused by natural chewing could be large enough to modulate ongoing neural activity in the cerebral cortex and influence cognitive performance. Significance: The present study lends first support for the assumption that extracranial muscle activity might represent an endogenous source of electrical brain stimulation. This offers a new potential explanation for the puzzling effects of gum chewing on cognition, which have been repeatedly reported in the literature.


Neurobiology of Aging | 2017

APOE moderates compensatory recruitment of neuronal resources during working memory processing in healthy older adults

Elisa Scheller; Jessica Peter; Lena V. Schumacher; Jacob Lahr; Irina Mader; Christoph P. Kaller; Stefan Klöppel

The APOE ε4 allele increases the risk for sporadic Alzheimers disease and modifies brain activation patterns of numerous cognitive domains. We assessed cognitively intact older adults with a letter n-back task to determine if previously observed increases in ε4 carriers working-memory-related brain activation are compensatory such that they serve to maintain working memory function. Using multiple regression models, we identified interactions of APOE variant and age in bilateral hippocampus independently from task performance: ε4 carriers only showed a decrease in activation with increasing age, suggesting high sensitivity of fMRI data for detecting changes in Alzheimers disease-relevant brain areas before cognitive decline. Moreover, we identified ε4 carriers to show higher activations in task-negative medial and task-positive inferior frontal areas along with better performance under high working memory load relative to non-ε4 carriers. The increased frontal recruitment is compatible with models of neuronal compensation, extends on existing evidence, and suggests that ε4 carriers require additional neuronal resources to successfully perform a demanding working memory task.


NeuroImage: Clinical | 2018

Voxel-wise deviations from healthy aging for the detection of region-specific atrophy

Stefan Klöppel; Shan Yang; Elias Kellner; Marco Reisert; Bernhard Heimbach; Horst Urbach; Jennifer Linn; Stefan Weidauer; Tamara Andres; Maximilian Bröse; Jacob Lahr; Niklas Lützen; Philipp T. Meyer; Jessica Peter; Ahmed Abdulkadir; Sabine Hellwig; Karl Egger

The identification of pathological atrophy in MRI scans requires specialized training, which is scarce outside dedicated centers. We sought to investigate the clinical usefulness of computer-generated representations of local grey matter (GM) loss or increased volume of cerebral fluids (CSF) as normalized deviations (z-scores) from healthy aging to either aid human visual readings or directly detect pathological atrophy. Two experienced neuroradiologists rated atrophy in 30 patients with Alzheimers disease (AD), 30 patients with frontotemporal dementia (FTD), 30 with dementia due to Lewy-body disease (LBD) and 30 healthy controls (HC) on a three-point scale in 10 anatomical regions as reference gold standard. Seven raters, varying in their experience with MRI diagnostics rated all cases on the same scale once with and once without computer-generated volume deviation maps that were overlaid on anatomical slices. In addition, we investigated the predictive value of the computer generated deviation maps on their own for the detection of atrophy as identified by the gold standard raters. Inter and intra-rater agreements of the two gold standard raters were substantial (Cohens kappa κu202f>u202f0.62). The intra-rater agreement of the other raters ranged from fair (κu202f=u202f0.37) to substantial (κu202f=u202f0.72) and improved on average by 0.13 (0.57u202f<u202fκu202f<u202f0.87) when volume deviation maps were displayed. The seven other raters showed good agreement with the gold standard in regions including the hippocampus but agreement was substantially lower in e.g. the parietal cortex and did not improve with the display of atrophy scores. Rating speed increased over the course of the study and irrespective of the presentation of voxel-wise deviations. Automatically detected large deviations of local volume were consistently associated with gold standard atrophy reading as shown by an area under the receiver operator characteristic of up to 0.95 for the hippocampus region. When applying these test characteristics to prevalences typically found in a memory clinic, we observed a positive or negative predictive value close to or above 0.9 in the hippocampus for almost all of the expected cases. The volume deviation maps derived from CSF volume increase were generally better in detecting atrophy. Our study demonstrates an agreement of visual ratings among non-experts not further increased by displaying, region-specific deviations of volume. The high predictive value of computer generated local deviations independent from human interaction and the consistent advantages of CSF-over GM-based estimations should be considered in the development of diagnostic tools and indicate clinical utility well beyond aiding visual assessments.

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Eliza Lauer

University Medical Center Freiburg

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Janine Reis

University Medical Center Freiburg

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Bernhard Heimbach

University Medical Center Freiburg

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