Publications by authors named "Michaela Ruttorf"

22 Publications

  • Page 1 of 1

Brain-behaviour correlates of habitual motivation in chronic back pain.

Sci Rep 2020 07 6;10(1):11090. Epub 2020 Jul 6.

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany.

Chronic pain may sap the motivation for positive events and stimuli. This may lead to a negative behavioural cycle reducing the establishment of appetitive habitual engagement. One potential mechanism for this might be biased learning. In our experiment, chronic back pain patients and healthy controls completed an appetitive Pavlovian-instrumental transfer procedure. We examined participants` behaviour and brain activity and reported pain, depression and anxiety. Patients showed reduced habitual behaviour and increased responses in the hippocampus than controls. This behavioural bias was related to motivational value and reflected in the updating of brain activity in prefrontal-striatal-limbic circuits. Moreover, this was influenced by pain symptom duration, depression and anxiety (explained variance: up to 50.7%). Together, findings identify brain-behaviour pathways for maladaptive habitual learning and motivation in chronic back pain, which helps explaining why chronic pain can be resistant to change, and where clinical characteristics are significant modulators.
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http://dx.doi.org/10.1038/s41598-020-67386-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338353PMC
July 2020

Case report: a giant arachnoid cyst masking Alzheimer's disease.

BMC Psychiatry 2019 09 5;19(1):274. Epub 2019 Sep 5.

Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany.

Background: Intracranial arachnoid cysts are usually benign congenital findings of neuroimaging modalities, sometimes however, leading to focal neurological and psychiatric comorbidities. Whether primarily clinically silent cysts may become causally involved in cognitive decline in old age is neither well examined nor understood.

Case Presentation: A 66-year old caucasian man presenting with a giant left-hemispheric frontotemporal cyst without progression of size, presented with slowly progressive cognitive decline. Neuropsychological assessment revealed an amnestic mild cognitive impairment (MCI) without further neurological or psychiatric symptoms. The patient showed mild medio-temporal lobe atrophy on structural MRI. Diffusion tensor and functional magnetic resonance imaging depicted a rather sustained function of the strongly suppressed left hemisphere. Amyloid-PET imaging was positive for increased amyloid burden and he was homozygous for the APOEε3-gene. A diagnosis of MCI due to Alzheimer's disease was given and a co-morbidity with a silent arachnoid cyst was assumed. To investigate, if a potentially reduced CSF flow due to the giant arachnoid cyst contributed to the early manifestation of AD, we reviewed 15 case series of subjects with frontotemporal arachnoid cysts and cognitive decline. However, no increased manifestation of neurodegenerative disorders was reported.

Conclusions: With this case report, we illustrate the necessity of a systematic work-up for neurodegenerative disorders in patients with arachnoid cysts and emerging cognitive decline. We finally propose a modus operandi for the stratification and management of patients with arachnoid cysts potentially susceptive for cognitive dysfunction.
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http://dx.doi.org/10.1186/s12888-019-2247-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6728996PMC
September 2019

Resting-state connectivity alterations during transient global amnesia.

Neuroimage Clin 2019 23;23:101869. Epub 2019 May 23.

Department of Neurology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address:

While the pathophysiology of transient global amnesia (TGA) is not understood, due to the specific nature of the clinical deficits, transient dysfunction in the medial temporal lobe, especially in the hippocampus, is assumed; however, concomitant disturbances in other brain regions and in executive function have been postulated. In this study, a cohort of 16 patients was prospectively recruited from the emergency department for resting-state functional MRI (fMRI) during the acute stage of TGA, as confirmed by a standardized neuropsychological assessment. Twenty age- and sex-matched controls, as well as twenty patients with a history of TGA, were recruited for comparison. Functional data were processed using independent component analysis (ICA), allowing the complete automatic (data-driven) identification of spontaneous network dynamics. We documented a severe disturbance in anterograde episodic long-term memory in all patients. Group-based ICA of resting-state data in acute TGA patients versus that of controls and patients with a past TGA episode demonstrated reduced FC mainly of structures belonging to the executive network (EN), but also the hippocampus, confirming its pathophysiological involvement in the disorder, as well as areas belonging to the salience network and other subcortical regions. No significant differences were found when comparing connectivity in patients with a history of TGA and controls. Our findings strengthen previous empirical and theoretical accounts of hippocampal and executive dysfunction in TGA. The disruption of frontal, parietal and insular control regions, together with disruption in the hippocampus, provides a new interpretation for the pathophysiology and neuropsychological profile of this neurological disorder on a large-scale network level.
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http://dx.doi.org/10.1016/j.nicl.2019.101869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543172PMC
June 2020

Transcranial Direct Current Stimulation Alters Functional Network Structure in Humans: A Graph Theoretical Analysis.

IEEE Trans Med Imaging 2019 12 7;38(12):2829-2837. Epub 2019 May 7.

Transcranial direct current stimulation (tDCS) is routinely used in basic and clinical research, but its efficacy has been challenged on a methodological, statistical and technical basis recently. The arguments against tDCS derive from an insufficient understanding of how this technique interacts with brain processes physiologically. Because of its potential as a central tool in neuroscience, it is important to clarify whether tDCS affects neuronal activity. Here, we investigate influences of offline tDCS on network architecture measured by functional magnetic resonance imaging. Applied to one network node only, offline tDCS affects the architecture of the entire functional network. Furthermore, offline tDCS exerts polarity-specific effects on the topology of the functional network attached. Our results confirm in a functioning brain and in a bias free and independent fashion that offline tDCS influences neuronal activity. Moreover, our results suggest that network-specific connectivity has an important role in improving our understanding of the effects of tDCS.
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http://dx.doi.org/10.1109/TMI.2019.2915206DOI Listing
December 2019

Volumetric brain correlates of approach-avoidance behavior and their relation to chronic back pain.

Brain Imaging Behav 2020 Oct;14(5):1758-1768

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany.

Avoiding any harm, such as painful experiences, is an important ability for our physical and mental health. This avoidance behavior might be overactive under chronic pain, and the cortical and subcortical brain volumetry, which also often changes in chronic pain states, might be a significant correlate of this behavior. In the present study, we thus investigated the association between volumetric brain differences using 3 T structural magnetic resonance imaging and pain- versus pleasure-related approach-avoidance behavior using an Approach Avoidance Task in the laboratory in chronic back pain (N = 42; mean age: 51.34 years; 23 female) and healthy individuals (N = 43; mean age: 45.21 years; 15 female). We found significant differences in hippocampal, amygdala and accumbens volumes in patients compared to controls. The patients` hippocampal volume was significantly positively related to pain avoidance, the amygdala volume to positive approach, and the accumbens volume negatively to a bias to pain avoidance over positive approach. These associations were significantly moderated by pain symptom duration. Cortical structure may thus contribute to an overacting pain avoidance system in chronic back pain, and could, together with a reduction in approaching positive stimuli, be related to maladaptive choice and decision-making processes in chronic pain.
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http://dx.doi.org/10.1007/s11682-019-00110-xDOI Listing
October 2020

Default mode network connectivity of fear- and anxiety-related cue and context conditioning.

Neuroimage 2018 01 16;165:190-199. Epub 2017 Oct 16.

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany; Department of Psychology, Faculty for Social Sciences, University of Mannheim, Germany. Electronic address:

Classical fear conditioning is an important mechanism to adequately respond and adapt to environmental threats and has been related to the development of fear and anxiety. Both cue and context conditioning have been studied but little is known about their relation to relevant resting state networks. The default mode network (DMN) has been reported to be involved in affective learning and described as facilitating a state of readiness in responding to environmental changes. We examined resting state brain connectivity patterns of the default mode network (DMN) in 119 healthy volunteers. Specifically, we carried out correlation analyses between the DMN and skin conductance responses (SCRs) as well as arousal, valence and contingency ratings during learning. In addition, we examined the role of trait anxiety. Two different DMN patterns were identified in which stronger connectivity was linked to lower differential SCRs during fear and anxiety learning. One was related to cue conditioning and involved the amygdala and the medial prefrontal cortex, and one was associated with context conditioning and included the hippocampal formation and sensorimotor areas. These results were replicated in an independent sample. Functional connectivity of the DMN with these key regions at rest was also predictive of trait anxiety but this association could not be replicated in the second sample. We showed that DMN connectivity is differently associated with cued versus contextual learning mechanisms. Uncovering individual differences in baseline network connectivity of the DMN with these key regions might lead to a better understanding of fear and anxiety. Such findings could indeed help to identify vulnerability factors linked to network alterations at rest with dysregulation of learning processes involved in the pathophysiology of stress and anxiety disorders.
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http://dx.doi.org/10.1016/j.neuroimage.2017.10.024DOI Listing
January 2018

Polarity-specific transcranial direct current stimulation effects on object-selective neural responses in the inferior parietal lobe.

Cortex 2017 09 13;94:176-181. Epub 2017 Jul 13.

Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Germany.

Neuromodulation techniques such as transcranial direct current stimulation (tDCS) are routinely used for treating neurological and neuropsychiatric disorders, and for enhancement of cognitive abilities. Recently, their effectiveness in modulating behavioral and neural responses has been questioned. Here we use excitatory and inhibitory tDCS prior to a functional magnetic resonance imaging (fMRI) experiment to show that neural responses for an area's preferred stimuli depend on the polarity of stimulation. This is an important, yet overlooked, data point in demonstrating the effectiveness of these stimulation techniques. Our results show that response preferences in the target area are dependent on the polarity of the tDCS session preceding the fMRI experiment - these preferences are less distinct in the cathodal than in the anodal session. As such, we show unequivocally that tDCS modulates neural responses. This result is of the utmost importance in demonstrating the effectiveness of tDCS for clinical and experimental purposes.
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http://dx.doi.org/10.1016/j.cortex.2017.07.001DOI Listing
September 2017

Oxytocin differentially modulates pavlovian cue and context fear acquisition.

Soc Cogn Affect Neurosci 2017 06;12(6):976-983

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Fear acquisition and extinction have been demonstrated as core mechanisms for the development and maintenance of mental disorders, with different contributions of processing cues vs contexts. The hypothalamic peptide oxytocin (OXT) may have a prominent role in this context, as it has been shown to affect fear learning. However, investigations have focused on cue conditioning, and fear extinction. Its differential role for cue and context fear acquisition is still not known. In a randomized, double-blind, placebo (PLC)-controlled design, we administered an intranasal dose of OXT or PLC before the acquisition of cue and context fear conditioning in healthy individuals (n = 52), and assessed brain responses, skin conductance responses and self-reports (valence/arousal/contingency). OXT compared with PLC significantly induced decreased responses in the nucleus accumbens during early cue and context acquisition, and decreased responses of the anterior cingulate cortex and insula during early as well as increased hippocampal response during late context, but not cue acquisition. The OXT group additionally showed significantly higher arousal in late cue and context acquisition. OXT modulates various aspects of cue and context conditioning, which is relevant from a mechanism-based perspective and might have implications for the treatment of fear and anxiety.
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http://dx.doi.org/10.1093/scan/nsx028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5472122PMC
June 2017

Implicit Learning in Transient Global Amnesia and the Role of Stress.

Front Behav Neurosci 2016 17;10:222. Epub 2016 Nov 17.

Department of Neurology, Universitätsmedizin Mannheim, Heidelberg University Mannheim, Germany.

Transient global amnesia (TGA) is a disorder with reversible anterograde disturbance of explicit memory, frequently preceded by an emotionally or physically stressful event. By using magnetic resonance imaging (MRI) following an episode of TGA, small hippocampal lesions have been observed. Hence it has been postulated that the disorder is caused by the stress-related transient inhibition of memory formation in the hippocampus. In experimental studies, stress has been shown to affect both explicit and implicit learning-the latter defined as learning and memory processes that lack conscious awareness of the information acquired. To test the hypothesis that impairment of implicit learning in TGA is present and related to stress, we determined the effect of experimental exposure to stress on hippocampal activation patterns during an implicit learning paradigm in patients who suffered a recent TGA and healthy matched control subjects. We used a hippocampus-dependent aversive learning procedure (context conditioning with the phases habituation, acquisition, and extinction) during functional MRI following experimental stress exposure (socially evaluated cold pressor test). After a control procedure, controls showed successful learning during the acquisition phase, indicated by increased valence, arousal and contingency ratings to the paired (CON+) vs. the non-paired (CON-) conditioned stimulus, and successful extinction of the conditioned responses. Following stress, acquisition was still successful, however extinction was impaired with persistently increased contingency ratings. In contrast, TGA patients showed impairment of conditioned responses and insufficient extinction after the control procedure, indicated by a lack of significant differences between CON+ and CON- for valence and arousal ratings after the acquisition phase and by significantly increased contingency ratings after the extinction. After stress, aversive learning was not successful with non-significant ratings of all parameters. Concerning brain activation patterns after the control procedure, controls showed increased hippocampal response during acquisition after the control procedure. This was not seen after stress exposure. In TGA patients, we observed an increased response in the right ventral striatum in the acquisition phase following stress. These findings suggest that alterations in implicit learning processes, including impaired hippocampal and increased striatal responses, might play a role in TGA pathophysiology, partly related to acute stress.
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http://dx.doi.org/10.3389/fnbeh.2016.00222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112253PMC
November 2016

Deficient fear extinction memory in posttraumatic stress disorder.

Neurobiol Learn Mem 2016 Dec 26;136:116-126. Epub 2016 Sep 26.

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany. Electronic address:

Background: Posttraumatic stress disorder (PTSD) might be maintained by deficient extinction memory. We used a cued fear conditioning design with extinction and a post-extinction phase to provoke the return of fear and examined the role of the interplay of amygdala, hippocampus and prefrontal regions.

Methods: We compared 18 PTSD patients with two healthy control groups: 18 trauma-exposed subjects without PTSD (nonPTSD) and 18 healthy controls (HC) without trauma experience. They underwent a three-day ABC-conditioning procedure in a functional magnetic resonance imaging scanner. Two geometric shapes that served as conditioned stimuli (CS) were presented in the context of virtual reality scenes. Electric painful stimuli were delivered after one of the two shapes (CS+) during acquisition (in context A), while the other (CS-) was never paired with pain. Extinction was performed in context B and extinction memory was tested in a novel context C.

Results: The PTSD patients showed significantly higher differential skin conductance responses than the non-PTSD and HC and higher differential amygdala and hippocampus activity than the HC in context C. In addition, elevated arousal to the CS+ during extinction and to the CS- throughout the experiment was present in the PTSD patients but self-reported differential valence or contingency were not different. During extinction recall, differential amygdala activity correlated positively with the intensity of numbing and ventromedial prefrontal cortex activity correlated positively with behavioral avoidance.

Conclusions: PTSD patients show heightened return of fear in neural and peripheral measures. In addition, self-reported arousal was high to both danger (CS+) and safety (CS-) cues. These results suggest that a deficient maintenance of extinction and a failure to identify safety signals might contribute to PTSD symptoms, whereas non-PTSD subjects seem to show normal responses.
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http://dx.doi.org/10.1016/j.nlm.2016.09.016DOI Listing
December 2016

Reduced amygdala responsivity during conditioning to trauma-related stimuli in posttraumatic stress disorder.

Psychophysiology 2016 10 14;53(10):1460-71. Epub 2016 Jul 14.

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Exaggerated conditioned fear responses and impaired extinction along with amygdala overactivation have been observed in posttraumatic stress disorder (PTSD). These fear responses might be triggered by cues related to the trauma through higher-order conditioning, where reminders of the trauma may serve as unconditioned stimuli (US) and could maintain the fear response. We compared arousal, valence, and US expectancy ratings and BOLD brain responses using fMRI in 14 traumatized persons with PTSD and 14 without PTSD (NPTSD) and 13 matched healthy controls (HC) in a differential aversive conditioning paradigm. The US were trauma-specific pictures for the PTSD and NPTSD group and equally aversive and arousing for the HC; the conditioned stimuli (CS) were graphic displays. During conditioning, the PTSD patients compared to the NPTSD and HC indicated higher arousal to the conditioned stimulus that was paired with the trauma picture (CS+) compared to the unpaired (CS-), increased dissociation during acquisition and extinction, and failure to extinguish the CS/US-association compared to NPTSD. During early and late acquisition, the PTSD patients showed a significantly lower amygdala activation to CS+ versus CS- and a negative interaction between activation in the amygdala and dorsolateral prefrontal cortex (PFC), while NPTSD and HC displayed a negative interaction between amygdala and medial PFC. These findings suggest maladaptive anticipatory coping with trauma-related stimuli in patients with PTSD, indicated by enhanced conditioning, with related abnormal amygdala reactivity and connectivity, and delayed extinction.
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http://dx.doi.org/10.1111/psyp.12699DOI Listing
October 2016

Brain morphology correlates of interindividual differences in conditioned fear acquisition and extinction learning.

Brain Struct Funct 2016 05 26;221(4):1927-37. Epub 2015 Feb 26.

Department of Cognitive and Clinical Neuroscience, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, Square J 5, 68159, Mannheim, Germany.

The neural circuits underlying fear learning have been intensively investigated in pavlovian fear conditioning paradigms across species. These studies established a predominant role for the amygdala in fear acquisition, while the ventromedial prefrontal cortex (vmPFC) has been shown to be important in the extinction of conditioned fear. However, studies on morphological correlates of fear learning could not consistently confirm an association with these structures. The objective of the present study was to investigate if interindividual differences in morphology of the amygdala and the vmPFC are related to differences in fear acquisition and extinction learning in humans. We performed structural magnetic resonance imaging in 68 healthy participants who underwent a differential cued fear conditioning paradigm. Volumes of subcortical structures as well as cortical thickness were computed by the semi-automated segmentation software Freesurfer. Stronger acquisition of fear as indexed by skin conductance responses was associated with larger right amygdala volume, while the degree of extinction learning was positively correlated with cortical thickness of the right vmPFC. Both findings could be conceptually replicated in an independent sample of 53 subjects. The data complement our understanding of the role of human brain morphology in the mechanisms of the acquisition and extinction of conditioned fear.
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http://dx.doi.org/10.1007/s00429-015-1013-zDOI Listing
May 2016

Neural Mechanism of a Sex-Specific Risk Variant for Posttraumatic Stress Disorder in the Type I Receptor of the Pituitary Adenylate Cyclase Activating Polypeptide.

Biol Psychiatry 2015 Dec 9;78(12):840-7. Epub 2015 Jan 9.

Departments of Cognitive and Clinical Neuroscience, Medical Faculty Mannheim, Heidelberg University, Germany. Electronic address:

Background: Posttraumatic stress disorder (PTSD) is a frequent anxiety disorder with higher prevalence rates in female patients than in male patients (2.5:1). Association with a single nucleotide polymorphism (rs2267735) in the gene ADCYAP1R1 encoding the type I receptor (PAC1-R) of the pituitary adenylate cyclase activating polypeptide has been reported with PTSD in female patients. We sought to identify the neural correlates of the described PAC1-R effects on associative learning.

Methods: In a reverse genetic approach, we examined two independent healthy samples (N1 = 112, N2 = 73) using functional magnetic resonance imaging during cued and contextual fear conditioning. Skin conductance responses and verbal self-reports of arousal, valence, and contingency were recorded.

Results: We found that PAC1-R modulates the blood oxygenation level-dependent response of the hippocampus. Specifically, we observed decreased hippocampal activity during contextual, but not during cued, fear conditioning in female participants carrying the PAC1-R risk allele. We observed no significant differences in conditionability for skin conductance responses, verbal reports, or activation in other brain regions between the genotype groups in female participants.

Conclusions: Our results suggest that impaired contextual conditioning in the hippocampal formation may mediate the association between PAC1-R and PTSD symptoms. Our findings potentially identify a missing link between the involvement of PAC1-R in PTSD and the well-established structural and functional hippocampal deficits in these patients.
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http://dx.doi.org/10.1016/j.biopsych.2014.12.018DOI Listing
December 2015

Altered neural reward and loss processing and prediction error signalling in depression.

Soc Cogn Affect Neurosci 2015 Aug 6;10(8):1102-12. Epub 2015 Jan 6.

Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany,

Dysfunctional processing of reward and punishment may play an important role in depression. However, functional magnetic resonance imaging (fMRI) studies have shown heterogeneous results for reward processing in fronto-striatal regions. We examined neural responsivity associated with the processing of reward and loss during anticipation and receipt of incentives and related prediction error (PE) signalling in depressed individuals. Thirty medication-free depressed persons and 28 healthy controls performed an fMRI reward paradigm. Regions of interest analyses focused on neural responses during anticipation and receipt of gains and losses and related PE-signals. Additionally, we assessed the relationship between neural responsivity during gain/loss processing and hedonic capacity. When compared with healthy controls, depressed individuals showed reduced fronto-striatal activity during anticipation of gains and losses. The groups did not significantly differ in response to reward and loss outcomes. In depressed individuals, activity increases in the orbitofrontal cortex and nucleus accumbens during reward anticipation were associated with hedonic capacity. Depressed individuals showed an absence of reward-related PEs but encoded loss-related PEs in the ventral striatum. Depression seems to be linked to blunted responsivity in fronto-striatal regions associated with limited motivational responses for rewards and losses. Alterations in PE encoding might mirror blunted reward- and enhanced loss-related associative learning in depression.
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http://dx.doi.org/10.1093/scan/nsu158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526479PMC
August 2015

Neurofeedback of the difference in activation of the anterior cingulate cortex and posterior insular cortex: two functionally connected areas in the processing of pain.

Front Behav Neurosci 2014 15;8:357. Epub 2014 Oct 15.

Department of Cognitive and Clinical Neuroscience, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University Mannheim, Germany.

The aim of this study was the analysis of the effect of a learned increase in the dissociation between the rostral anterior cingulate cortex (rACC) and the left posterior insula (pInsL) on pain intensity and unpleasantness and the contribution of each region to the effect, exploring the possibility to influence the perception of pain with neurofeedback methods. We trained ten healthy subjects to increase the difference in the blood oxygenation level-dependent response between the rACC and pInsL to painful electric stimuli. Subjects learned to increase the dissociation with either the rACC (state 1) or the pInsL (state 2) being higher. For feedback we subtracted the signal of one region from the other and provided feedback in four conditions with six trials each yielding two different states: [rACC-pInsL increase (state 1), rACC-pInsL decrease (state 2), pInsL-rACC increase (state 2), pInsL-rACC decrease (state 1)]. Significant changes in the dissociation from trial one to six were seen in all conditions. There were significant changes from trial one to six in the pInsL in three of the four conditions, the rACC showed no significant change. Pain intensity or unpleasantness ratings were unrelated to the dissociation between the regions and the activation in each region. Learning success in the conditions did not significantly correlate and there was no significant correlation between the two respective conditions of one state, i.e., learning to achieve a specific state is not a stable ability. The pInsL seems to be the driving force behind changes in the learned dissociation between the regions. Despite successful differential modulation of activation in areas responsive to the painful stimulus, no corresponding changes in the perception of pain intensity or unpleasantness emerged. Learning to induce different states of dissociation between the areas is not a stable ability since success did not correlate overall or between two conditions of the the same state.
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http://dx.doi.org/10.3389/fnbeh.2014.00357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197653PMC
October 2014

Fast and robust design of time-optimal k-space trajectories in MRI.

IEEE Trans Med Imaging 2015 Feb 9;34(2):564-77. Epub 2014 Oct 9.

Many applications in MRI such as accelerated receive and transmit sequences require the synthesis of nonuniform 3-D gradient trajectories. Several methods have been proposed to design these gradient trajectories in a time-optimal manner, subject to hardware specific gradient magnitude and slew rate constraints. In this work a novel method is derived that designs time-optimal trajectories, solely based on a set of arbitrarily chosen control points in k-space. In particular, no path constraint is required for the k-space trajectory. It is shown that the above problem can be formulated as a constrained optimization problem. The fact that the objective function is derived in an analytic manner allows for designing time-optimal 3-D gradient trajectories within only few seconds without any significant numerical instabilities. The utilization of the shape of the trajectory--serving as a degree of freedom--results in significantly accelerated trajectories compared to current standard methods. This is proven in an extensive evaluation of the proposed method and in comparison with what can be considered the current Gold Standard method. The proposed Gradient Basis Function method provides significant benefits over current standard methods in terms of the duration of the trajectory (in average 9.2% acceleration), computation time (acceleration by at least 25% up to factors of 100), and robustness (no significant numerical instabilities).
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http://dx.doi.org/10.1109/TMI.2014.2362681DOI Listing
February 2015

Real time fMRI feedback of the anterior cingulate and posterior insular cortex in the processing of pain.

Hum Brain Mapp 2014 Dec 16;35(12):5784-98. Epub 2014 Jul 16.

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Self-regulation of brain activation using real-time functional magnetic resonance imaging has been used to train subjects to modulate activation in various brain areas and has been associated with behavioral changes such as altered pain perception. The aim of this study was to assess the comparability of upregulation versus downregulation of activation in the rostral anterior cingulate cortex (rACC) and left posterior insula (pInsL) and its effect on pain intensity and unpleasantness. In a first study, we trained 10 healthy subjects to separately upregulate and downregulate the blood oxygenation level-dependent response in the rACC or pInsL (six trials on 4 days) in response to painful electrical stimulation. The participants learned to significantly downregulate activation in pInsL and rACC and upregulate pInsL but not rACC. Success in the modulation of one region and direction of the modulation was not significantly correlated with success in another condition, indicating that the ability to control pain-related brain activation is site-specific. Less covariation between the areas in response to the nociceptive stimulus was positively correlated with learning success. Upregulation or downregulation of either region was unrelated to pain intensity or unpleasantness; however, our subjects did not learn rACC upregulation, which might be important for pain control. A significant increase in pain unpleasantness was found during upregulation of pInsL when covariation with the rACC was low. These initial results suggest that the state of the network involved in the processing of pain needs to be considered in the modulation of pain-evoked activation and its behavioral effects.
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http://dx.doi.org/10.1002/hbm.22585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6869183PMC
December 2014

Fully-automated quality assurance in multi-center studies using MRI phantom measurements.

Magn Reson Imaging 2014 Jul 3;32(6):771-80. Epub 2014 Feb 3.

Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University.

Phantom measurements allow for investigating the overall quality characteristics of an MRI scanner. Especially within multicenter studies, these characteristics ensure the comparability of the results across different sites, in addition to the performance stability of a single scanner over time. This comparability requires consistent phantoms, sequence protocols, and quality assurance criteria. Within the scope of this work, a software library was implemented for fully-automated determination of important quality characteristics (comprising signal-to-noise ratio, image uniformity, ghosting artifacts, chemical shift and spatial resolution and linearity) including methods for data preparation, automated pre- and postprocessing as well as visualization and interpretation. All methods were evaluated using both synthetic images with predefined distortions and a set of 44 real phantom measurements involving eight sites and three manufacturers. Using the synthetic phantom images, predefined levels of distortion that were incorporated artificially were correctly detected by the automated routines with no more than 2.6% of relative error. In addition, the methods were applied to real phantom measurements - all data sets could be evaluated automatically considering all quality parameters as long as the acquisition protocols are followed. Shortcomings of the processability only occurred in the ghosting artifacts (39/44 evaluable) and the spatial linearity (43/44 evaluable) analysis due to gross misalignments of the phantom during image acquisition. Based on evaluation results, the accuracy of the evaluation appears to be robust to misalignments, artifacts, and distortions affecting the images, allowing for objective fully-automated evaluation and interpretation of large data set numbers.
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http://dx.doi.org/10.1016/j.mri.2014.01.017DOI Listing
July 2014

Cortico-subcortical activation patterns for itch and pain imagery.

Pain 2013 Oct 12;154(10):1989-1998. Epub 2013 Jun 12.

Department of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Department of Integrative Physiology, National Institute for Physiological Sciences, Okazaki, Japan Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

The imagery of itch and pain evokes emotional responses and covert motor responses (scratching to itch and withdrawal to pain). This suggests some similarity in cerebral mechanisms. However, itch is more socially contagious than pain, as evidenced by the fact that scratching behaviors can be easily initiated by watching itch-inducing situations, whereas withdrawal is less easily initiated by watching painful situations. Thus, we assumed that the cerebral mechanisms of itch imagery partly differ from those of pain imagery in particular with respect to motor regions. We addressed this issue in 18 healthy subjects using functional magnetic resonance imaging. The subjects were instructed to imagine itch and pain sensations in their own bodies while viewing pictures depicting stimuli associated with these sensations. Itch and pain imagery activated the anterior insular cortex (aIC) and motor-related regions such as supplementary motor area, basal ganglia, thalamus, and cerebellum. Activity in these regions was not significantly different between itch and pain imagery. However, functional connectivity between motor-related regions and the aIC showed marked differences between itch and pain imagery. Connectivity with the aIC was stronger in the primary motor and premotor cortices during pain imagery and stronger in the globus pallidus during itch imagery. These findings indicate that brain regions associated with imagery of itch are the same as those involved in imagery of pain, but their functional networks differ. These differences in brain networks may explain why motor responses to itch are more socially contagious than those related to pain.
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http://dx.doi.org/10.1016/j.pain.2013.06.007DOI Listing
October 2013

A risk variant for alcoholism in the NMDA receptor affects amygdala activity during fear conditioning in humans.

Biol Psychol 2013 Sep 18;94(1):74-81. Epub 2013 May 18.

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

People at high risk for alcoholism show deficits in aversive learning, as indicated by impaired electrodermal responses during fear conditioning, a basic form of associative learning that depends on the amygdala. A positive family history of alcohol dependence has also been related to decreased amygdala responses during emotional processing. In the present study we report reduced amygdala activity during the acquisition of conditioned fear in healthy carriers of a risk variant for alcoholism (rs2072450) in the NR2A subunit-containing N-methyl-d-aspartate (NMDA)-receptor. These results indicate that rs2072450 might confer risk for alcohol dependence through deficient fear acquisition indexed by a diminished amygdala response during aversive learning, and provide a neural basis for a weak behavioral inhibition previously documented in individuals at high risk for alcohol dependence. Carriers of the risk variant additionally exhibit dampened insula activation, a finding that further strengthens our data, given the importance of this brain region in fear conditioning.
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http://dx.doi.org/10.1016/j.biopsycho.2013.05.006DOI Listing
September 2013

Activation of the ventral striatum during aversive contextual conditioning in humans.

Biol Psychol 2012 Sep 26;91(1):74-80. Epub 2012 Apr 26.

Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.

The goal of this study was to investigate the function of the ventral striatum and brain regions involved in anxiety and learning during aversive contextual conditioning. Functional magnetic resonance imaging was used to assess the hemodynamic brain response of 118 healthy volunteers during a differential fear conditioning paradigm. Concurrently obtained skin conductance responses and self-reports indicated successful context conditioning. Increased hemodynamic responses in the ventral striatum during presentation of the conditioned visual stimulus that predicted the aversive event (CS+) compared to a second stimulus never paired with the aversive event (CS-) were observed in the late acquisition phase. Additionally, we found significant brain responses in the amygdala, hippocampus, insula and medial prefrontal cortex. Our data suggest the involvement of the ventral striatum during contextual fear conditioning, and underline its role in the processing of salient stimuli in general, not only during reward processing.
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http://dx.doi.org/10.1016/j.biopsycho.2012.04.004DOI Listing
September 2012

Protein exchange dynamics at chemoreceptor clusters in Escherichia coli.

Proc Natl Acad Sci U S A 2008 Apr 21;105(17):6403-8. Epub 2008 Apr 21.

Zentrum für Molekulare Biologie and Interdisziplinäres Zentrum für Wissenschaftliches Rechnen, Universität Heidelberg, D-69120 Heidelberg, Germany.

Signal processing in bacterial chemotaxis relies on large sensory complexes consisting of thousands of protein molecules. These clusters create a scaffold that increases the efficiency of pathway reactions and amplifies and integrates chemotactic signals. The cluster core in Escherichia coli comprises a ternary complex composed of receptors, kinase CheA, and adaptor protein CheW. All other chemotaxis proteins localize to clusters by binding either directly to receptors or to CheA. Here, we used fluorescence recovery after photobleaching (FRAP) to investigate the turnover of chemotaxis proteins at the cluster and their mobility in the cytoplasm. We found that cluster exchange kinetics were protein-specific and took place on several characteristic time scales that correspond to excitation, adaptation, and cell division, respectively. We further applied analytical and numerical data fitting to analyze intracellular protein diffusion and to estimate the rate constants of cluster equilibration in vivo. Our results indicate that the rates of protein turnover at the cluster have evolved to ensure optimal performance of the chemotaxis pathway.
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http://dx.doi.org/10.1073/pnas.0710611105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359816PMC
April 2008