Publications by authors named "Martin Lotze"

122 Publications

Using motor imagery practice for improving motor performance - A review.

Brain Cogn 2021 Feb 27;150:105705. Epub 2021 Feb 27.

Functional Imaging Unit, Center for Diagnostic Radiology, University Medicine of Greifswald, Germany. Electronic address:

Motor imagery practice is a current trend, but there is a need for a systematic integration of neuroscientific advances in the field. In this review, we describe the technique of motor imagery practice and its neural representation, considering different fields of application. The current practice of individualized motor imagery practice schemes often lacks systematization and is mostly based on experience. We review literature related to motor imagery practice in order to identify relevant modulators of practice effects like previous experience in motor training and motor imagery practice, the type of motor task to be trained, and strategies to increase sensory feedback during physical practice. Relevant discrepancies are identified between neuroscientific findings and practical consideration of these findings. To bridge these gaps, more effort should be directed at analyzing the brain network activities related to practically relevant motor imagery practice interventions.
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http://dx.doi.org/10.1016/j.bandc.2021.105705DOI Listing
February 2021

Gray Matter Brain Alterations in Temporomandibular Disorder Tested in a Population Cohort and Three Clinical Samples.

J Pain 2021 Jan 30. Epub 2021 Jan 30.

Functional Imaging Unit, Department of Diagnostic Radiology and Neuroradiology, University Medicine, Greifswald, Germany. Electronic address:

Temporomandibular pain (TMD) is a frequent symptom comprising pain around the mandibular jaw with a high dependence on stressors. Chronic pain has been associated with changes of the brains gray matter volume (GMV), but previous studies on GMV alterations associated with TMD have yielded contradictory results. This might be caused by divergent samples and study methods. We here tested GMV alterations using voxel based morphometry in three clinical samples (summing up to 47 TMD patients) and a population sample with 57 participants who indicated facial pain for the last 6 months. The GMV of pain patients was compared against age-matched and gender-matched participants without chronic pain (60 for the clinical sample comparison and 381 for the cohort sample comparison) who underwent the same assessments as the patient group (MRI measurements and data evaluation using CAT12). In a region of interest analysis, only the clinical samples showed an effect of decreased GMV in the anterior medial cingulate cortex reaching into the medial prefrontal cortex, known to be especially vulnerable for chronic pain gray matter volume reduction. The analysis of the population-based sample did not reveal relevant GMV differences. Overall, an important question remains as to whether most inconsistent results from voxel based morphometry-studies in chronic pain are related to chance results facilitated by small sample size and selection of patient samples. PERSPECTIVE: Using voxel based morphometry 2 samples with chronic temperomandibular pain were compared to controls investigating the brains GMV. Only the clinical sample showed a decrease in anterior cingulate GMV. Contradicting results on GMV loss in temperomandibular pain might be based on small samples in prior studies.
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http://dx.doi.org/10.1016/j.jpain.2021.01.003DOI Listing
January 2021

Fronto-parietal involvement in chronic stroke motor performance when corticospinal tract integrity is compromised.

Neuroimage Clin 2021 18;29:102558. Epub 2021 Jan 18.

University of South Australia, IIMPACT in Health, Adelaide, Australia.

Background: Preserved integrity of the corticospinal tract (CST) is a marker of good upper-limb behavior and recovery following stroke. However, there is less understanding of neural mechanisms that might help facilitate upper-limb motor recovery in stroke survivors with extensive CST damage.

Objective: The purpose of this study was to investigate resting state functional connectivity in chronic stroke survivors with different levels of CST damage and to explore neural correlates of greater upper-limb motor performance in stroke survivors with compromised ipsilesional CST integrity.

Methods: Thirty chronic stroke survivors (24 males, aged 64.7 ± 10.8 years) participated in this study. Three experimental sessions were conducted to: 1) obtain anatomical (T1, T2) structural (diffusion) and functional (resting state) MRI sequences, 2) determine CST integrity with transcranial magnetic stimulation (TMS) and conduct assessments of upper-limb behavior, and 3) reconfirm CST integrity status. Participants were divided into groups according to the extent of CST damage. Those in the extensive CST damage group did not show TMS evoked responses and had significantly lower ipsilesional fractional anisotropy.

Results: Of the 30 chronic stroke survivors, 12 were categorized as having extensive CST damage. Stroke survivors with extensive CST damage had weaker functional connectivity in the ipsilesional sensorimotor network and greater functional connectivity in the ipsilesional fronto-parietal network compared to those with preserved CST integrity. For participants with extensive CST damage, improved motor performance was associated with greater functional connectivity of the ipsilesional fronto-parietal network and higher fractional anisotropy of the ipsilesional rostral superior longitudinal fasciculus.

Conclusions: Stroke survivors with extensive CST damage have greater resting state functional connectivity of an ipsilesional fronto-parietal network that appears to be a behaviorally relevant neural mechanism that improves upper-limb motor performance.
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http://dx.doi.org/10.1016/j.nicl.2021.102558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841401PMC
January 2021

Modifications in fMRI Representation of Mental Rotation Following a 6 Week Graded Motor Imagery Training in Chronic CRPS Patients.

J Pain 2021 Jan 6. Epub 2021 Jan 6.

Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Germany. Electronic address:

Complex regional pain syndrome (CRPS) is a neuropathic pain condition that is difficult to treat. For behavioral interventions, graded motor imagery (GMI) showed relevant effects, but underlying neural substrates in patient groups have not been investigated yet. A previous study investigating differences in the representation of a left/right hand judgment task demonstrated less recruitment of subcortical structures, such as the putamen, in CRPS patients than in healthy controls. In healthy volunteers, the putamen activity increased after a hand judgment task training. In order to test for longitudinal effects of GMI training, we investigated 20 CRPS patients in a wait-list crossover design with 3 evaluation time points. Patients underwent a 6 week GMI treatment and a 6 week waiting period in a randomized group assignment and treatment groups were evaluated by a blinded rater. When compared to healthy matched controls at baseline, CRPS patients showed less functional activation in areas processing visual input, left sensorimotor cortex, and right putamen. Only GMI treatment, but not the waiting period showed an effect on movement pain and hand judgment task performance. Regression analyses revealed positive associations of movement pain with left anterior insula activation at baseline. Right intraparietal sulcus activation change during GMI was associated with a gain in performance of the hand judgment task. The design used here is reliable for investigating the functional representation of the hand judgment task in an intervention study. PERSPECTIVE: Twenty chronic CRPS patients underwent a 6 week GMI intervention in a randomized wait-list crossover design. functional MRI was tested pre and post for the hand lateralization task which improved over GMI but not over WAITING. Performance gain was positively related to right parietal functional MRI activation.
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http://dx.doi.org/10.1016/j.jpain.2020.12.003DOI Listing
January 2021

Multimodal Sensory-Spatial Integration and Retrieval of Trained Motor Patterns for Body Coordination in Musicians and Dancers.

Front Psychol 2020 17;11:576120. Epub 2020 Nov 17.

Functional Imaging Unit, Diagnostic Radiology and Neuroradiology, University of Greifswald, Greifswald, Germany.

Dancers and musicians are experts in spatial and temporal processing, which allows them to coordinate movement with music. This high-level processing has been associated with structural and functional adaptation of the brain for high performance sensorimotor integration. For these integration processes, adaptation does not only take place in primary and secondary sensory and motor areas but also in tertiary brain areas, such as the lateral prefrontal cortex (lPFC) and the intraparietal sulcus (IPS), providing vital resources for highly specialized performance. Here, we review evidence for the role of these brain areas in multimodal training protocols and integrate these findings into a new model of sensorimotor processing in complex motor learning.
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http://dx.doi.org/10.3389/fpsyg.2020.576120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704436PMC
November 2020

Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis.

Psychophysiology 2020 Oct 10. Epub 2020 Oct 10.

Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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http://dx.doi.org/10.1111/psyp.13688DOI Listing
October 2020

The Neural Correlates of Face-Voice-Integration in Social Anxiety Disorder.

Front Psychiatry 2020 15;11:657. Epub 2020 Jul 15.

Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany.

Faces and voices are very important sources of threat in social anxiety disorder (SAD), a common psychiatric disorder where core elements are fears of social exclusion and negative evaluation. Previous research in social anxiety evidenced increased cerebral responses to negative facial or vocal expressions and also generally increased hemodynamic responses to voices and faces. But it is unclear if also the cerebral process of face-voice-integration is altered in SAD. Applying functional magnetic resonance imaging, we investigated the correlates of the audiovisual integration of dynamic faces and voices in SAD as compared to healthy individuals. In the bilateral midsections of the superior temporal sulcus (STS) increased integration effects in SAD were observed driven by greater activation increases during audiovisual stimulation as compared to auditory stimulation. This effect was accompanied by increased functional connectivity with the visual association cortex and a more anterior position of the individual integration maxima along the STS in SAD. These findings demonstrate that the audiovisual integration of facial and vocal cues in SAD is not only systematically altered with regard to intensity and connectivity but also the individual location of the integration areas within the STS. These combined findings offer a novel perspective on the neuronal representation of social signal processing in individuals suffering from SAD.
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http://dx.doi.org/10.3389/fpsyt.2020.00657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381153PMC
July 2020

The modulating impact of cigarette smoking on brain structure in panic disorder: a voxel-based morphometry study.

Soc Cogn Affect Neurosci 2020 Oct;15(8):849-859

Department of Psychology, Humboldt-Universität zu Berlin, Berlin 10117, Germany.

Cigarette smoking increases the likelihood of developing anxiety disorders, among them panic disorder (PD). While brain structures altered by smoking partly overlap with morphological changes identified in PD, the modulating impact of smoking as a potential confounder on structural alterations in PD has not yet been addressed. In total, 143 PD patients (71 smokers) and 178 healthy controls (62 smokers) participated in a multicenter magnetic resonance imaging (MRI) study. T1-weighted images were used to examine brain structural alterations using voxel-based morphometry in a priori defined regions of the defensive system network. PD was associated with gray matter volume reductions in the amygdala and hippocampus. This difference was driven by non-smokers and absent in smoking subjects. Bilateral amygdala volumes were reduced with increasing health burden (neither PD nor smoking > either PD or smoking > both PD and smoking). As smoking can narrow or diminish commonly observed structural abnormalities in PD, the effect of smoking should be considered in MRI studies focusing on patients with pathological forms of fear and anxiety. Future studies are needed to determine if smoking may increase the risk for subsequent psychopathology via brain functional or structural alterations.
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http://dx.doi.org/10.1093/scan/nsaa103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543937PMC
October 2020

Functional representation of the symbol digit modalities test in relapsing remitting multiple sclerosis.

Mult Scler Relat Disord 2020 Aug 12;43:102159. Epub 2020 May 12.

Functional Imaging, Institute for Diagnostic Radiology and Neuroradiology, University Medicine of Greifswald, Germany. Electronic address:

Background: The Symbol Digit Modalities Test (SDMT) is essential in the screening of cognitive impairments in multiple sclerosis (MS). Methodological adaptions of the SDMT on functional MRI exist, but without specific investigation of more cognitive components of information processing speed (IPS). Additionally, there is only limited data on functional differences between MS-patients and healthy controls (HC).

Methods: 20 MS-patients and 20 HC were investigated executing the original version of the SDMT on fMRI. We analyzed (1) neural networks as indicated in the methodological adaptions (i.e. frontal (Brodman area BA6, BA9), parietal (BA7), occipital (BA17) and cerebellar), (2) functional activations of cognitive components of IPS and (3) functional differences between MS and HC during SDMT.

Results: MS patients performed worse during the SDMT. Both groups demonstrated activation on each region of interest. Cognitive component of IPS was driven by superior parietal and posterior cerebellar activation. MS-patients showed decreased cingulate activation during SDMT as compared to HC.

Conclusion: The original SDMT task revealed comparable fMRI-activation sites as reported for previous adaptions. Cognitive components of IPS depend on superior parietal and medial posterior cerebellar regions known to process visuo-spatial integration and anticipation. Attention related areas in the cingulate cortex were decreased in MS-patients.
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http://dx.doi.org/10.1016/j.msard.2020.102159DOI Listing
August 2020

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain-behavior relationships after stroke.

Hum Brain Mapp 2020 Apr 20. Epub 2020 Apr 20.

Department of Neurology, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta- and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large-scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided.
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http://dx.doi.org/10.1002/hbm.25015DOI Listing
April 2020

Sex-specific association of poor sleep quality with gray matter volume.

Sleep 2020 Sep;43(9)

Institute of Diagnostic Radiology and Neuroradiology, Functional Imaging Unit, University Medicine Greifswald, Greifswald, Germany.

Study Objectives: Previous studies were inconsistent with regard to the association of sleep dysfunction on the brain's gray matter volume (GMV). The current study set out to investigate if there is a moderating effect of sex on the relationship between sleep quality in healthy individuals and GMV.

Methods: We applied voxel-based morphometry in 1,074 young adults of the "Human Connectome Project." An analysis of variance with the factors "sleep quality" (good/poor according to the Pittsburgh Sleep Quality Index, cutoff >5) and "sex" (male, female) on GMV was conducted. Additionally, linear relationships between sleep quality and GMV were tested.

Results: The analysis of variance yielded no main effect for sleep quality, but an interaction between sex and sleep quality for the right superior frontal gyrus. Post hoc t-tests showed that female good sleepers in comparison to female poor sleepers had larger GMV in the right parahippocampal gyrus extending to the right hippocampus (whole-brain family-wise error [FWE]-corrected), as well as smaller GMV in the right inferior parietal lobule (whole-brain FWE-corrected) and the right inferior temporal gyrus (whole brain FWE-corrected). There were no significant effects when comparing male good sleepers to male poor sleepers. Linear regression analyses corroborated smaller GMV in the right parahippocampal gyrus in women with poor sleep quality.

Conclusions: Poor sleep quality was associated with altered GMV in females, but not in males. Future studies are needed to investigate the neurobiological mechanisms that underlie the sex differences in the association of sleep quality and brain differences found in this study.
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http://dx.doi.org/10.1093/sleep/zsaa035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487870PMC
September 2020

Empathic responses to unknown others are modulated by shared behavioural traits.

Sci Rep 2020 02 6;10(1):1938. Epub 2020 Feb 6.

Functional Imaging Unit, Center for Diagnostic Radiology, University Medicine Greifswald, Greifswald, Germany.

How empathically people respond to a stranger's pain or pleasure does not only depend on the situational context, individual traits and intentions, but also on interindividual factors. Here we ask whether empathic responses towards unknown others are modulated by behavioural similarity as a potential marker of genetic relatedness. Participants watched two supposed human players who were modelled as having a strong (player LP) or weak (player NLP) tendency to lead in social situations executing penalty shots in a virtual reality robot soccer game. As predicted, empathic response were modulated by shared behavioural traits: participants whose tendency to lead was more similar to player LP's tendency to lead experienced more reward, and showed stronger neural activity in reward-related brain regions, when they saw player LP score a goal, and participants whose tendency to lead was more similar to player NLP's tendency to lead showed stronger empathic responses when they saw player NLP score a goal. These findings highlight the potentially evolutionary grounded role of phenotypic similarity for neural processes underlying human social perception.
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http://dx.doi.org/10.1038/s41598-020-57711-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005154PMC
February 2020

Effect of CBT on Biased Semantic Network in Panic Disorder: A Multicenter fMRI Study Using Semantic Priming.

Am J Psychiatry 2020 03 16;177(3):254-264. Epub 2019 Dec 16.

Department of Psychiatry and Psychotherapy and Marburg Center for Mind, Brain, and Behavior, Philipps-University Marburg, Marburg, Germany (Yang, Konrad, Straube, Kircher); Department of Psychiatry, Psychosomatics, and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, University of Würzburg, Würzburg, Germany (Lueken, Herrmann, Deckert); Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany (Lueken); Department of Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany (Richter, Hamm); Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany (Wittmann, Ströhle); Department of Psychiatry, Agaplesion Diakonieklinikum Rotenburg (Wümme), Germany (Konrad); Department of Clinical Radiology, University of Münster, Münster, Germany (Pfleiderer); Christoph-Dornier-Foundation for Clinical Psychology, Bremen, Germany (Lang); Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg, Germany (Lang); Functional Imaging Unit, Institute for Diagnostic Radiology and Neuroradiology, University of Greifswald, Greifswald, Germany (Lotze); Department of Psychiatry, University of Münster, Münster, Germany (Arolt); and Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany (Wittchen).

Objective: Cognitive-behavioral therapy (CBT) has been hypothesized to act by reducing the pathologically enhanced semantic, anxiety-related associations of patients with panic disorder. This study investigated the effects of CBT on the behavioral and neural correlates of the panic-related semantic network in patients with panic disorder.

Methods: An automatic semantic priming paradigm specifically tailored for panic disorder, in which panic symptoms (e.g., "dizziness") were primed by panic triggers (e.g., "elevator") compared with neutral words (e.g., "bottle"), was performed during functional MRI scanning with 118 patients with panic disorder (compared with 150 healthy control subjects) before and 42 patients (compared with 52 healthy control subjects) after an exposure-based CBT. Neural correlates were investigated by comparing 103 pairs of matched patients and control subjects at the baseline (for patients) or T1 (for control subjects) assessment and 39 pairs at the posttreatment or T2 assessment.

Results: At baseline or T1, patients rated panic-trigger/panic-symptom word pairs with higher relatedness and higher negative valence compared with healthy control subjects. Patients made faster lexical decisions to the panic-symptom words when they were preceded by panic-trigger words. This panic-priming effect in patients (compared with control subjects) was reflected in suppressed neural activation in the left and right temporal cortices and insulae and enhanced activation in the posterior and anterior cingulate cortices. After CBT, significant clinical improvements in the patient group were observed along with a reduction in relatedness and negative valence rating and attenuation of neural activation in the anterior cingulate cortex for processing of panic-trigger/panic-symptom word pairs.

Conclusions: The findings support a biased semantic network in panic disorder, which is normalized after CBT. Attenuation of anterior cingulate cortex activation for processing of panic-related associations provides a potential mechanism for future therapeutic interventions.
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http://dx.doi.org/10.1176/appi.ajp.2019.19020202DOI Listing
March 2020

Effects of centric mandibular splint therapy on orofacial pain and cerebral activation patterns.

Clin Oral Investig 2020 Jun 13;24(6):2005-2013. Epub 2019 Sep 13.

Functional Imaging Unit, Center of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, 17489, Greifswald, Germany.

Objectives: To investigate the effects on pain, movement kinematics, and cerebral representation by a 3-month mandibular splint therapy.

Material And Methods: Thirteen patients with temporo-mandibular joint disease (TMD) and moderate pain intensity were investigated before (PRE), within (after 2 weeks, POST1) and after a period of 12 weeks (POST2) using functional magnetic resonance imaging (fMRI) of representation of occlusal movements on natural teeth and on an individually fitted mandibular splint. In addition, kinematic investigations of jaw movements, muscle electromyography and pain ratings using a pain diary (VAS-scale 0-100) were measured.

Results: Although the patient's pain ratings decreased about 60%, kinematic and electromyographic characteristics over therapy were not significantly altered. Over therapy, we observed a decrease of fMRI activation magnitude in the primary somatosensory cortex (S1) and secondary somatosensory cortex (S2) and insular cortex during occlusion. Left hemispheric anterior insula and the cerebellar fMRI activation decrease were associated with decrease in pain over time.

Conclusions: Within the limitations of this pilot study, a reduction in both discriminative (primary and secondary somatosensory cortex) and affective (anterior insula) areas for pain processing suggest that altered pain anticipation is critical for the therapeutic effects of mandibular splint therapy after TMD.

Clinical Relevance: A 3-month mandibular splint therapy moderately decreases pain and anticipatory anterior insular activation.
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http://dx.doi.org/10.1007/s00784-019-03064-yDOI Listing
June 2020

Editorial: Promoting Manual Dexterity Recovery After Stroke.

Front Neurol 2019 30;10:815. Epub 2019 Jul 30.

INSERM U1266 Institut de Psychiatrie et Neurosciences de Paris, Paris, France.

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http://dx.doi.org/10.3389/fneur.2019.00815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682586PMC
July 2019

Laughter is in the air: involvement of key nodes of the emotional motor system in the anticipation of tickling.

Soc Cogn Affect Neurosci 2019 08;14(8):837-847

Faculty of Science and Medicine, Department of Neuroscience, Anatomy, University of Fribourg, 1700 Fribourg, Switzerland.

In analogy to the appreciation of humor, that of tickling is based upon the re-interpretation of an anticipated emotional situation. Hence, the anticipation of tickling contributes to the final outburst of ticklish laughter. To localize the neuronal substrates of this process, functional magnetic resonance imaging (fMRI) was conducted on 31 healthy volunteers. The state of anticipation was simulated by generating an uncertainty respecting the onset of manual foot tickling. Anticipation was characterized by an augmented fMRI signal in the anterior insula, the hypothalamus, the nucleus accumbens and the ventral tegmental area, as well as by an attenuated one in the internal globus pallidus. Furthermore, anticipatory activity in the anterior insula correlated positively with the degree of laughter that was produced during tickling. These findings are consistent with an encoding of the expected emotional consequences of tickling and suggest that early regulatory mechanisms influence, automatically, the laughter circuitry at the level of affective and sensory processing. Tickling activated not only those regions of the brain that were involved during anticipation, but also the posterior insula, the anterior cingulate cortex and the periaqueductal gray matter. Sequential or combined anticipatory and tickling-related neuronal activities may adjust emotional and sensorimotor pathways in preparation for the impending laughter response.
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http://dx.doi.org/10.1093/scan/nsz056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6847157PMC
August 2019

Tuned to voices and faces: Cerebral responses linked to social anxiety.

Neuroimage 2019 08 7;197:450-456. Epub 2019 May 7.

Department of Psychiatry and Psychotherapy, University of Tübingen, Germany.

Voices and faces are the most common sources of threat in social anxiety (SA) where the fear of negative evaluation and social exclusion is the central element. SA itself is spectrally distributed among the general population and its clinical manifestation, termed social anxiety disorder, is one of the most common anxiety disorders. While heightened cerebral responses to angry or contemptuous facial or vocal expressions are well documented, it remains unclear if the brain of socially anxious individuals is generally more sensitive to voices and faces. Using functional magnetic resonance imaging, we investigated how SA affects the cerebral processing of voices and faces as compared to various other stimulus types in a study population with greatly varying SA (N = 50, 26 female). While cerebral voice-sensitivity correlated positively with SA in the left temporal voice area (TVA) and the left amygdala, an association of face-sensitivity and SA was observed in the right fusiform face area (FFA) and the face processing area of the right posterior superior temporal sulcus (pSTSFA). These results demonstrate that the increase of cerebral responses associated with social anxiety is not limited to facial or vocal expressions of social threat but that the respective sensory and emotion processing structures are also generally tuned to voices and faces.
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http://dx.doi.org/10.1016/j.neuroimage.2019.05.018DOI Listing
August 2019

Review on biomarkers in the resting-state networks of chronic pain patients.

Brain Cogn 2019 04 30;131:4-9. Epub 2018 Jun 30.

Functional Imaging Unit, Center for Diagnostic Radiology, University of Greifswald, Greifswald, Germany.

Biomarkers indicating characteristic alterations in the brains of pain patients would in comparison to behavioral examinations allow for earlier diagnoses of pain disease development, a more immediate monitoring of pain disease progression, and for the development of interventions to reverse or compensate for the alterations. To reveal causal relations between an observed alteration and the pain disease longitudinal examinations are essential. Resting-state fMRI examinations can readily be included in large longitudinal cohorts allowing to achieve sufficiently large patient samples even for rare diseases. Our literature review on longitudinal resting-state fMRI examinations of pain patients indicates that pain chronicity is predicted by alterations to the brain's reward system and default mode network. A brain wide reorganization of the resting-state networks is associated with the emergence of the chronic pain state. The functional connectivity of the left frontoparietal network predicts the evolution of pain intensity in the chronic state. Further investigations are necessary concerning the generalization of the biomarkers across the phases in pain development especially for the healthy state, across different pain etiologies, and their specificity to chronic pain. The currently acquired representative longitudinal cohorts will allow for clarification of those issues within the next decades.
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http://dx.doi.org/10.1016/j.bandc.2018.06.005DOI Listing
April 2019

Changes in Interhemispheric Motor Connectivity Across the Lifespan: A Combined TMS and DTI Study.

Front Aging Neurosci 2019 5;11:12. Epub 2019 Feb 5.

Department of Neurology, University Medicine of Greifswald, Greifswald, Germany.

Age-related decline in interhemispheric connectivity between motor areas has been reported with both transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) measurements. However, not all studies were able to confirm these findings, and previous studies did not apply structural (DTI) and functional (TMS) measurements within each individual appropriately. Here, we investigated age dependency of the ipsilateral silent period (ISP) and integrity of fibers in the corpus callosum as operationalized by fractional anisotrophy (FA), using TMS and DTI, respectively, in 20 participants between 19 and 72 years of age. We found age-dependent increase for ISP, and decrease of FA, both indicating a decrease in interhemispheric inhibition, with a negative association between FA and ISP for the dominant hemisphere ( = -0.39, = 0.043). Our findings suggest that aging leads to decline of interhemispheric motor connectivity, as evidenced in both structural and functional parameters, which should be taken into account when interpreting disease- or medication-related changes.
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http://dx.doi.org/10.3389/fnagi.2019.00012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371065PMC
February 2019

The association of health-related quality of life and cerebral gray matter volume in the context of aging: A voxel-based morphometry study with a general population sample.

Neuroimage 2019 05 19;191:470-480. Epub 2019 Feb 19.

Department Health and Prevention, Institute of Psychology, University of Greifswald, Germany.

Health-related quality of life is likely associated with the brain via processes relating to physiology, behavior, cognition, emotion and stress. Previous studies with small student or clinical samples have identified associations with gray matter volume in the anterior cingulate cortex, prefrontal cortex, insular cortex, (para)hippocampal area, amygdala, and precuneus. The present study investigated the association of gray matter volume of these brain areas with mental and physical components of health, as well as general health perception, measured with the 12-item Short Form Health Survey, in a large sample of 3027 participants from the Study of Health in Pomerania, using voxel-based morphometry for T1-weighted magnetic resonance imaging. Higher physical, but not mental, health-related quality of life and general health perception were associated with larger gray matter volume of the anterior cingulate cortex, medial prefrontal cortex, insular cortex, and the precuneus with a substantial decrease when controlling for lifestyle, comorbidity and symptoms. Age-stratified analyses revealed significantly higher partial correlations of physical health and left insular gray matter volume in the oldest age group. Our study emphasizes the importance of high medial prefrontal and anterior insula gray matter volume for health-related quality of life on the basis of a large sample size.
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http://dx.doi.org/10.1016/j.neuroimage.2019.02.035DOI Listing
May 2019

Parcellation of motor cortex-associated regions in the human corpus callosum on the basis of Human Connectome Project data.

Brain Struct Funct 2019 May 18;224(4):1447-1455. Epub 2019 Feb 18.

Functional Imaging Unit, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Walther- Rathenau-Str. 46, 17475, Greifswald, Germany.

The corpus callosum (CC) is the largest white matter structure of the brain and offers the structural basis for an intense interaction between both cerebral hemispheres. Especially with respect to the interaction of both motor cortices it shows a differentiated somatotopic organization. Neuropathological processes are often reflected in structural alterations of the CC and a spatially precise description of structures for the healthy brain is essential for further differentiation of structural damage in patients. We performed a fine-grained parcellation of the CC on 1065 diffusion-weighted data sets of the Human Connectome Project. Interhemispheric tractograms between interhemispherically corresponding functional subdivisions of the primary motor cortex (M1; Brainnetome Atlas) were calculated, transformed into a common space, averaged and thresholded, to be assessed for localization, fractional anisotropy (FA) and mean diffusivity (MD). Spatially distinct CC regions for each functional M1 subdivision (lower and upper limbs, head/face, tongue/larynx) were identified and will be available as anatomical masks. Non-parametrical statistics for the average FA and MD values showed significant differences between all callosal regions. The newly proposed callosal regions allow for a precise differentiation of M1-M1 motor connectivity and the structural integrity of these tracts. Availability of masked regions in a common space will help to better understand inter-hemispherical callosal connectivity in patients or healthy volunteers.
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http://dx.doi.org/10.1007/s00429-019-01849-1DOI Listing
May 2019

Novel findings from 2,838 Adult Brains on Sex Differences in Gray Matter Brain Volume.

Sci Rep 2019 02 8;9(1):1671. Epub 2019 Feb 8.

Functional Imaging Unit, Department of Radiology, University Medicine Greifswald, Greifswald, Germany.

There is still disagreement among studies with respect to the magnitude, location, and direction of sex differences of local gray matter volume (GMV) in the human brain. Here, we applied a state-of-the-art technique examining GMV in a well-powered sample (n = 2,838) validating effects in two independent general-population cohorts, age range 21-90 years, measured using the same MRI scanner. More GMV in women than in men was prominent in medial and lateral prefrontal areas, the superior temporal sulcus, the posterior insula, and orbitofrontal cortex. In contrast, more GMV in men than in women was detected in subcortical temporal structures, such as the amygdala, hippocampus, temporal pole, fusiform gyrus, visual primary cortex, and motor areas (premotor cortex, putamen, anterior cerebellum). The findings in this large-scale study may clarify previous inconsistencies and contribute to the understanding of sex-specific differences in cognition and behavior.
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http://dx.doi.org/10.1038/s41598-018-38239-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368548PMC
February 2019

Editorial for the special issue "Resting-state fMRI and cognition" in Brain and Cognition.

Brain Cogn 2019 04 31;131:1-3. Epub 2019 Jan 31.

Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Institute of Neuroscience and Medicine (INM-7), Research Centre Jülich, Jülich, Germany.

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http://dx.doi.org/10.1016/j.bandc.2019.01.003DOI Listing
April 2019

Differences in Neuronal Representation of Mental Rotation in Patients With Complex Regional Pain Syndrome and Healthy Controls.

J Pain 2019 08 31;20(8):898-907. Epub 2019 Jan 31.

Functional Imaging Unit, Center for Diagnostic Radiology, and. Electronic address:

Spatial integration of parts of the body is impaired in patients with complex regional pain syndrome (CRPS). Because the training of mental rotation (MR) has been shown to be among the effective therapy strategies for CRPS, impairment of MR is also important for the pathophysiological understanding of CRPS. The aim of this study was to evaluate whether differences in the neural representation of MR occur between patients with CRPS and healthy controls (HC). Therefore, we included 15 patients with chronic CRPS and 15 age- and gender-matched HC. We assessed behavioral (accuracy and reaction time for MR of both hands), clinical (Disabilities of Arm, Shoulder and Hand questionnaire) and magnetic resonance imaging (T1-weighted, function magnetic resonance imaging during MR) data. Reaction times in the patient group were delayed compared with HC without a lateralization effect for the affected hand side. Although both groups showed an activation pattern typical for MR, only HC showed a highly significant contrast for the rotated versus unrotated hands in the right intraparietal sulcus. Patients with CRPS showed a reduction of functional magnetic resonance imaging activation in areas including the subthalamic nucleus, nucleus accumbens, and putamen. Regression analysis for the CRPS group emphasized the importance of putamen and nucleus accumbens activation for MR performance. This study highlights the reduced access of patients with CRPS for mental resources modulating arousal, emotional response, and subcortical sensorimotor integration. PERSPECTIVE: This study localized the underlying neural responses for impaired mental rotation in patients with complex regional pain syndrome as a decrease in basal ganglia (putamen) and nucleus accumbens activation.
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http://dx.doi.org/10.1016/j.jpain.2019.01.330DOI Listing
August 2019

Cerebral plasticity as the basis for upper limb recovery following brain damage.

Neurosci Biobehav Rev 2019 04 30;99:49-58. Epub 2019 Jan 30.

Department for Neurology, SRH Health Center, Bad Wimpfen, Germany.

Neural plasticity is the basis for an adaptation process of functional and structural characteristics of the nervous system in response to a changing environment. However, changes during training in healthy volunteers are only partially comparable to that observed in patients with circumscribed lesions. Pathologies can even be associated with maladaptive plasticity. We first introduce basic processes underlying brain plasticity with respect to the sensorimotor system and outline their limitations. A number of methods showing potential in the evaluation of these processes are compared before literature on postlesional plasticity is reviewed. Approaches in monitoring plasticity processes of the healthy sensorimotor system are partially applicable after brain damage and for the documentation of recovery processes. Some of these techniques can further be used for outcome prediction or therapy selection and optimization. Extreme examples from athletes or professional musicians illustrate the amount of plastic changes the human brain can achieve. Profound understanding of neural plasticity in health and disease will help to modify and individually optimize therapy strategies in neurorehabilitation.
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http://dx.doi.org/10.1016/j.neubiorev.2019.01.027DOI Listing
April 2019

Intermittent theta burst stimulation over right somatosensory larynx cortex enhances vocal pitch-regulation in nonsingers.

Hum Brain Mapp 2019 05 21;40(7):2174-2187. Epub 2019 Jan 21.

Institute of Medical Psychology and Behavioral Neurobiology, Eberhard Karls University Tübingen, Tübingen, Germany.

While the significance of auditory cortical regions for the development and maintenance of speech motor coordination is well established, the contribution of somatosensory brain areas to learned vocalizations such as singing is less well understood. To address these mechanisms, we applied intermittent theta burst stimulation (iTBS), a facilitatory repetitive transcranial magnetic stimulation (rTMS) protocol, over right somatosensory larynx cortex (S1) and a nonvocal dorsal S1 control area in participants without singing experience. A pitch-matching singing task was performed before and after iTBS to assess corresponding effects on vocal pitch regulation. When participants could monitor auditory feedback from their own voice during singing (Experiment I), no difference in pitch-matching performance was found between iTBS sessions. However, when auditory feedback was masked with noise (Experiment II), only larynx-S1 iTBS enhanced pitch accuracy (50-250 ms after sound onset) and pitch stability (>250 ms after sound onset until the end). Results indicate that somatosensory feedback plays a dominant role in vocal pitch regulation when acoustic feedback is masked. The acoustic changes moreover suggest that right larynx-S1 stimulation affected the preparation and involuntary regulation of vocal pitch accuracy, and that kinesthetic-proprioceptive processes play a role in the voluntary control of pitch stability in nonsingers. Together, these data provide evidence for a causal involvement of right larynx-S1 in vocal pitch regulation during singing.
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http://dx.doi.org/10.1002/hbm.24515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865578PMC
May 2019

Arm Ability Training (AAT) Promotes Dexterity Recovery After a Stroke-a Review of Its Design, Clinical Effectiveness, and the Neurobiology of the Actions.

Front Neurol 2018 11;9:1082. Epub 2018 Dec 11.

Functional Imaging Unit, Center for Diagnostic Radiology, University of Greifswald, Greifswald, Germany.

Arm Ability Training (AAT) has been specifically designed to promote manual dexterity recovery for stroke patients who have mild to moderate arm paresis. The motor control problems that these patients suffer from relate to a lack of efficiency in terms of the sensorimotor integration needed for dexterity. Various sensorimotor arm and hand abilities such as speed of selective movements, the capacity to make precise goal-directed arm movements, coordinated visually guided movements, steadiness, and finger dexterity all contribute to our "dexterity" in daily life. All these abilities are deficient in stroke patients who have mild to moderate paresis causing focal disability. The AAT explicitly and repetitively trains all these sensorimotor abilities at the individual's performance limit with eight different tasks; it further implements various task difficulty levels and integrates augmented feedback in the form of intermittent knowledge of results. The evidence from two randomized controlled trials indicates the clinical effectiveness of the AAT with regard to the promotion of "dexterity" recovery and the reduction of focal disability in stroke patients with mild to moderate arm paresis. In addition, the effects have been shown to be superior to time-equivalent "best conventional therapy." Further, studies in healthy subjects showed that the AAT induced substantial sensorimotor learning. The observed learning dynamics indicate that different underlying sensorimotor arm and hand abilities are trained. Capacities strengthened by the training can, in part, be used by both arms. Non-invasive brain stimulation experiments and functional magnetic resonance imaging data documented that at an early stage in the training cortical sensorimotor network areas are involved in learning induced by the AAT, yet differentially for the tasks trained. With prolonged training over 2 to 3 weeks, subcortical structures seem to take over. While behavioral similarities in training responses have been observed in healthy volunteers and patients, training-induced functional re-organization in survivors of a subcortical stroke uniquely involved the ipsilesional premotor cortex as an adaptive recruitment of this secondary motor area. Thus, training-induced plasticity in healthy and brain-damaged subjects are not necessarily the same.
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http://dx.doi.org/10.3389/fneur.2018.01082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6298423PMC
December 2018

Predicting Training Gain for a 3 Week Period of Arm Ability Training in the Subacute Stage After Stroke.

Front Neurol 2018 11;9:854. Epub 2018 Oct 11.

Spinal Cord Injury Unit, Centre for Neurorehabilitation, Intensive and Ventilation Care, BDH-Klinik Greifswald, University of Greifswald, Greifswald, Germany.

Biomarkers for gains of evidence based interventions for upper limb motor training in the subacute stage following stroke have rarely been described. Information about these parameters might help to identify patients who benefit from specific interventions and to determine individually expected behavioral gains for a certain period of therapy. To evaluate predictors for hand motor outcome after arm ability training in the subacute stage after stroke selected from known potentially relevant parameters (initial motor strength, structural integrity of the pyramidal tract and functional motor cortex integrity). We applied the arm ability training (AAT) over 3 weeks to a subpopulation of stroke patients with mild arm paresis, i.e., in 14 patients on average 4 weeks after stroke. The following biomarkers were measured before therapy onset: grip strength on the affected hand, transcranial magnetic stimulation recruitment curve steepness over the primary motor hand area [slope ratio between the ipsilesional hemisphere (IH) and contralesional hemisphere (CH)], and diffusion weighted MRI fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC; determined as a lateralization index between IH and CH). Outcome was assessed as the AATgain (percentage improvement over training). The "Test d'Evaluation des Membres Supérieurs de Personnes Âgées" (TEMPA) was assessed before and after training to test for possible associations of AAT with activity of daily living. A stepwise linear regression identified the lateralization index of PLIC FA as the only significant predictor for AAT-gain ( = 0.519; = 0.029). AAT-gain was positively associated ( = 0.59; = 0.028) with improvement in arm function during daily activities (TEMPA). While all mildly affected patients achieved a clinically relevant therapeutic effect, pyramidal tract integrity nevertheless had a modifying role for clinical benefit.
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http://dx.doi.org/10.3389/fneur.2018.00854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193103PMC
October 2018

Voxel-based morphometry in creative writers: Grey matter increase in a prefronto-thalamic-cerebellar network.

Eur J Neurosci 2018 May 18. Epub 2018 May 18.

Institute of Diagnostic Radiology and Neuroradiology, Functional Imaging Unit, University Medicine Greifswald, Greifswald, Germany.

Continuous practice modulates those features of brain anatomy specifically associated with requirements of the respective training task. This study aimed to highlight brain structural changes going along with long-term experience in creative writing. To this end, we investigated the grey matter volume of 23 expert writers with voxel-based morphometry and compared it to 28 matched nonexpert controls. Expert writers had higher grey matter volume in the right superior frontal and middle frontal gyri (BA 9,10) as well as left middle frontal gyrus (BA 9, 10, 46), the bilateral medial dorsal nuclei of the thalamus and left posterior cerebellum. A regression analysis confirmed the association of enhanced grey matter volume in the right superior frontal gyrus (BA 10) with practice index of writing. In region-of-interest based regression analyses, we found associations of grey matter volume in the right Broca's analogue (BA 44) and right primary visual cortex (BA 17) with creativity ratings of the texts written during scanning, but not with a standardised verbal creativity test. Creative writing thus seems to be strongly connected to a prefronto-thalamic-cerebellar network that supports the continuous generation, organisation and revision of ideas that is necessary to write literary texts.
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http://dx.doi.org/10.1111/ejn.13952DOI Listing
May 2018

Enhancement of motor learning by focal intermittent theta burst stimulation (iTBS) of either the primary motor (M1) or somatosensory area (S1) in healthy human subjects.

Restor Neurol Neurosci 2018 ;36(1):117-130

Department of Functional Imaging, Center for Diagnostic Radiology and Neuroradiology, Ernst-Moritz-Arndt-Universität, Greifswald, Germany.

Background: Motor rehabilitation after brain damage relies on motor re-learning as induced by specific training. Non-invasive brain stimulation (NIBS) can alter cortical excitability and thereby has a potential to enhance subsequent training-induced learning. Knowledge about any priming effects of NIBS on motor learning in healthy subjects can help to design targeted therapeutic applications in brain-damaged subjects.

Objective: To examine whether complex motor learning in healthy subjects can be enhanced by intermittent theta burst stimulation (iTBS) to primary motor or sensory cortical areas.

Methods: Eighteen young healthy subjects trained eight different arm motor tasks (arm ability training, AAT) once a day for 5 days using their left non-dominant arm. Except for day 1 (baseline), training was performed after applying an excitatory form of repetitive transcranial magnetic stimulation (iTBS) to either (I) right M1 or (II) S1, or (III) sham stimulation to the right M1. Subjects were randomly assigned to conditions I, II, or III.

Results: A principal component analysis of the motor behaviour data suggested eight independent motor abilities corresponding to the 8 trained tasks. AAT induced substantial motor learning across abilities with generalisation to a non-trained test of finger dexterity (Nine-Hole-Peg-Test, NHPT). Participants receiving iTBS (to either M1 or S1) showed better performance with the AAT tasks over the period of training compared to sham stimulation as well as a bigger improvement with the generalisation task (NHPT) for the trained left hand after training completion.

Conclusion: Priming with an excitatory repetitive transcranial magnetic stimulation as iTBS of either M1 or S1 can enhance motor learning across different sensorimotor abilities.
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http://dx.doi.org/10.3233/RNN-170774DOI Listing
October 2018