Publications by authors named "Anne Assmann"

16 Publications

  • Page 1 of 1

Detection of Cerebral Microbleeds With Venous Connection at 7 Tesla MRI.

Neurology 2021 Mar 2. Epub 2021 Mar 2.

Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany.

Objective: Cerebral microbleeds (MBs) are a common finding in cerebral small vessel disease (CSVD) and Alzheimer's disease patients as well as in healthy elderly people, but their pathophysiology remains unclear. To investigate a possible role of veins in the development of MBs, we performed an exploratory study, assessing in vivo presence of MBs with a direct connection to a vein.

Methods: 7 Tesla (7 T) MRI was conducted and MBs were counted on Quantitative Susceptibility Mapping (QSM). A submillimeter resolution QSM-based venogram allowed identification of MBs with a direct spatial connection to a vein.

Results: 51 subjects (mean age [SD] 70.5[8.6] years, 37% females) participated in the study: 20 were patients with CSVD (cerebral amyloid angiopathy (CAA) with strictly lobar MBs (n=8), hypertensive arteriopathy (HA) with strictly deep MBs (n=5), and mixed lobar and deep MBs (n=7), 72.4 [6.1] years, 30% females) and 31 were healthy controls (69.4 [9.9] years, 42% females). In our cohort, we counted a total of 96 MBs with a venous connection, representing 14% of all detected MBs on 7T QSM. Most venous MBs (86%, n = 83) were observed in lobar locations and all of these were cortical. CAA subjects showed the highest ratio of venous to total MBs (19%) (HA=9%, mixed=18%, controls=5%) CONCLUSIONS: Our findings establish a link between cerebral MBs and the venous vasculature, pointing towards a possible contribution of veins to CSVD in general and to CAA in particular. Pathological studies are needed to confirm our observations.
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http://dx.doi.org/10.1212/WNL.0000000000011790DOI Listing
March 2021

Bayesian model selection favors parametric over categorical fMRI subsequent memory models in young and older adults.

Neuroimage 2021 04 29;230:117820. Epub 2021 Jan 29.

German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany; Leibniz Institute for Neurobiology (LIN), Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Magdeburg, Germany; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany. Electronic address:

Subsequent memory paradigms allow to identify neural correlates of successful encoding by separating brain responses as a function of memory performance during later retrieval. In functional magnetic resonance imaging (fMRI), the paradigm typically elicits activations of medial temporal lobe, prefrontal and parietal cortical structures in young, healthy participants. This categorical approach is, however, limited by insufficient memory performance in older and particularly memory-impaired individuals. A parametric modulation of encoding-related activations with memory confidence could overcome this limitation. Here, we applied cross-validated Bayesian model selection (cvBMS) for first-level fMRI models to a visual subsequent memory paradigm in young (18-35 years) and older (51-80 years) adults. Nested cvBMS revealed that parametric models, especially with non-linear transformations of memory confidence ratings, outperformed categorical models in explaining the fMRI signal variance during encoding. We thereby provide a framework for improving the modeling of encoding-related activations and for applying subsequent memory paradigms to memory-impaired individuals.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117820DOI Listing
April 2021

MRI phenotyping of underlying cerebral small vessel disease in mixed hemorrhage patients.

J Neurol Sci 2020 Dec 9;419:117173. Epub 2020 Oct 9.

Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Leipziger Straße 44, 39120 Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Universitätsplatz 2, 39106 Magdeburg, Germany. Electronic address:

Objective: To investigate underlying cerebral small vessel disease (CSVD) in patients with mixed cerebral hemorrhages patterns and phenotype them according to the contribution of the two most common sporadic CSVD subtypes: cerebral amyloid angiopathy (CAA) vs. hypertensive arteriopathy (HA).

Methods: Brain MRIs of patients with intracerebral hemorrhages (ICHs) and/or cerebral microbleeds (CMBs) were assessed for the full spectrum of CSVD markers using validated scales: ICHs, CMBs, cortical superficial siderosis (cSS), white matter hyperintensities, MRI-visible perivascular spaces (PVS). PVS predominance pattern was grouped as centrum-semiovale (CSO)-PVS predominance, basal-ganglia (BG)-PVS predominance, CSO-PVS and BG-PVS equality. Patients with mixed cerebral hemorrhages were classified into mixed CAA-pattern or mixed HA-pattern according to the existence of cSS and/or a CSO-PVS predominance pattern and comparisons were performed.

Results: We included 110 patients with CAA (strictly lobar ICHs/CMBs), 33 with HA (strictly deep ICHs/CMBs) and 97 with mixed lobar/deep ICHs/CMBs. Mixed patients were more similar to HA with respect to their MRI-CSVD markers, vascular risk profile and cerebrospinal fluid (CSF) measures. In the mixed patients, 33 (34%) had cSS, a CSO-PVS predominance pattern, or both, and were defined as mixed CAA-pattern cases. The mixed CAA-pattern patients were more alike CAA patients regarding their MRI-CSVD markers, CSF and genetic profile.

Conclusion: Our findings suggest that the heterogeneous group of patients with mixed cerebral hemorrhages distribution can be further phenotyped according to the predominant underlying CSVD. cSS presence and a CSO-PVS predominance pattern could serve as strongly suggestive markers of a contribution from CAA among patients with mixed hemorrhages.
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http://dx.doi.org/10.1016/j.jns.2020.117173DOI Listing
December 2020

Modification of In-Hospital Recommendation and Prescription of Anticoagulants for Secondary Prevention of Stroke after Launch of Direct Oral Anticoagulants and Change of National Guidelines.

Cerebrovasc Dis 2020 5;49(4):412-418. Epub 2020 Aug 5.

Department of Neurology, Magdeburg University Vascular and Stroke Center, Magdeburg, Germany.

Introduction: Approximately 1 out of 4 stroke patients suffers ischemic stroke secondary to atrial fibrillation (AF). Although indicated, withholding of anticoagulants for secondary prevention is a widespread phenomenon.

Objective: We examined the longitudinal change of recommendation and prescription of secondary preventive anticoagulation in AF patients in an acute stroke center setting focusing on the impact of the introduction of direct oral anticoagulants (DOACs) and the change of national stroke prevention guidelines.

Methods: Consecutive patients admitted with an acute cerebrovascular ischemic event underwent regular diagnostic work-up. Pseudonymized clinical data were entered into the institution's stroke registry. In those patients with AF, discharge letters were collected and evaluated for temporal trends and affecting factors of recommended and prescribed antithrombotic secondary medication at the time of discharge from hospital.

Results: Of 7,175 patients admitted between January 2009 and December 2018, 1,812 (25.3%) suffered stroke caused by AF. Frequency of patients with recommended anticoagulation increased within the observation period from 66.7 to 95.8% (per year; adjusted odds ratio [OR], 1.309; confidence interval [CI], 1.153-1.486). Independently from this time trend, DOAC approval (adjusted OR, 4.026; CI 1.962-8.265) and guideline change (adjusted OR, 2.184; CI, 1.006-4.743) were associated with an increasing frequency of recommendation for anticoagulation. The rate of patients already receiving recommended anticoagulation for secondary prevention at discharge increased from 42.1 to 62.5%. Introduction of DOACs was not associated with this trend, and guideline change was even associated with decreasing frequency of anticoagulated patients at hospital discharge (adjusted OR, 0.641; CI, 0.414-0.991). Fear of early intracerebral bleeding was the most common reason for withholding anticoagulation (37%) at hospital discharge and stayed stable during the observation period.

Conclusions: Changing national guidelines with discard of contraindications for anticoagulation and the introduction of DOACs led to a broader recommendation of oral anticoagulation. However, both, new guidelines and DOACs, were not found to be associated with an increasing percentage of patients discharged from our hospital already on recommended anticoagulant prevention. This might be explained by the decreasing length of hospital stay during the study period and a missing evidence of early bleeding risk of DOACs in patients with acute brain infarction. Evidence-based data to close this therapeutic gap are needed.
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http://dx.doi.org/10.1159/000509416DOI Listing
November 2020

Neurocan genome-wide psychiatric risk variant affects explicit memory performance and hippocampal function in healthy humans.

Eur J Neurosci 2020 Jun 24. Epub 2020 Jun 24.

Leibniz Institute for Neurobiology, Magdeburg, Germany.

Alterations of the brain extracellular matrix (ECM) can perturb the structure and function of brain networks like the hippocampus, a key region in human memory that is commonly affected in psychiatric disorders. Here, we investigated the potential effects of a genome-wide psychiatric risk variant in the NCAN gene encoding the ECM proteoglycan neurocan (rs1064395) on memory performance, hippocampal function and cortical morphology in young, healthy volunteers. We assessed verbal memory performance in two cohorts (N = 572, 302) and found reduced recall performance in risk allele (A) carriers across both cohorts. In 117 participants, we performed functional magnetic resonance imaging using a novelty-encoding task with visual scenes. Risk allele carriers showed higher false alarm rates during recognition, accompanied by inefficiently increased left hippocampal activation. To assess effects of rs1064395 on brain morphology, we performed voxel-based morphometry in 420 participants from four independent cohorts and found lower grey matter density in the ventrolateral and rostral prefrontal cortex of risk allele carriers. In silico eQTL analysis revealed that rs1064395 SNP is linked not only to increased prefrontal expression of the NCAN gene itself, but also of the neighbouring HAPLN4 gene, suggesting a more complex effect of the SNP on ECM composition. Our results suggest that the NCAN rs1064395 A allele is associated with lower hippocampus-dependent memory function, variation of prefrontal cortex structure and ECM composition. Considering the well-documented hippocampal and prefrontal dysfunction in bipolar disorder and schizophrenia, our results may reflect an intermediate phenotype by which NCAN rs1064395 contributes to disease risk.
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http://dx.doi.org/10.1111/ejn.14872DOI Listing
June 2020

Hippocampal vascular reserve associated with cognitive performance and hippocampal volume.

Brain 2020 02;143(2):622-634

Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University, Magdeburg, Germany.

Medial temporal lobe dependent cognitive functions are highly vulnerable to hypoxia in the hippocampal region, yet little is known about the relationship between the richness of hippocampal vascular supply and cognition. Hippocampal vascularization patterns have been categorized into a mixed supply from both the posterior cerebral artery and the anterior choroidal artery or a single supply by the posterior cerebral artery only. Hippocampal arteries are small and affected by pathological changes when cerebral small vessel disease is present. We hypothesized, that hippocampal vascularization patterns may be important trait markers for vascular reserve and modulate (i) cognitive performance; (ii) structural hippocampal integrity; and (iii) the effect of cerebral small vessel disease on cognition. Using high-resolution 7 T time-of-flight angiography we manually classified hippocampal vascularization patterns in older adults with and without cerebral small vessel disease in vivo. The presence of a mixed supplied hippocampus was an advantage in several cognitive domains, including verbal list learning and global cognition. A mixed supplied hippocampus also was an advantage for verbal memory performance in cerebral small vessel disease. Voxel-based morphometry showed higher anterior hippocampal grey matter volume in mixed, compared to single supply. We discuss that a mixed hippocampal supply, as opposed to a single one, may increase the reliability of hippocampal blood supply and thereby provide a hippocampal vascular reserve that protects against cognitive impairment.
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http://dx.doi.org/10.1093/brain/awz383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009470PMC
February 2020

Toward in vivo determination of peripheral nervous system immune activity in amyotrophic lateral sclerosis.

Muscle Nerve 2019 05 8;59(5):567-576. Epub 2019 Mar 8.

Department of Neurology, Otto-von-Guericke University, Leipziger Straße 44, 39120 Magdeburg, Germany.

Introduction: We sought to identify patients with amyotrophic lateral sclerosis (ALS) who displayed suspected peripheral nervous system (PNS) inflammation to compare them to those with suspected PNS degeneration.

Methods: We measured sonographic median and ulnar nerve cross-sectional area (CSA) and cerebrospinal fluid albumin/serum albumin ratio (Q ) in patients with ALS to classify them as having suspected PNS degeneration (small CSA/low Q ) or inflammation (larger CSA/high Q ).

Results: Fifty-seven percent of patients had suspected PNS degeneration, 21% had suspected PNS inflammation, and 21% displayed suspected "normal PNS state." Suspected PNS degeneration was related to classic ALS, shorter disease duration, and a smaller hypoechoic nerve area. Suspected PNS inflammation was associated with men, longer disease duration, and a larger hypoechoic nerve area and was the dominant finding in superoxide dismutase 1 mutation carriers.

Discussion: Our simple approach might aid in the in vivo differentiation of supposed ALS subtypes, those with suspected PNS degeneration vs. inflammation, for stratification in clinical trials. Muscle Nerve 59:567-567, 2019.
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http://dx.doi.org/10.1002/mus.26444DOI Listing
May 2019

Behavioral and Neural Manifestations of Reward Memory in Carriers of Low-Expressing versus High-Expressing Genetic Variants of the Dopamine D2 Receptor.

Front Psychol 2017 1;8:654. Epub 2017 May 1.

Leibniz Institute for NeurobiologyMagdeburg, Germany.

Dopamine is critically important in the neural manifestation of motivated behavior, and alterations in the human dopaminergic system have been implicated in the etiology of motivation-related psychiatric disorders, most prominently addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor (DRD2) availability in the striatum, and the TaqIA (rs1800497) and C957T (rs6277) genetic polymorphisms have previously been linked to individual differences in striatal dopamine metabolism and clinical risk for alcohol and nicotine dependence. Here, we investigated the hypothesis that the variants of these polymorphisms would show increased reward-related memory formation, which has previously been shown to jointly engage the mesolimbic dopaminergic system and the hippocampus, as a potential intermediate phenotype for addiction memory. To this end, we performed functional magnetic resonance imaging (fMRI) in 62 young, healthy individuals genotyped for TaqIA and C957T variants. Participants performed an incentive delay task, followed by a recognition memory task 24 h later. We observed effects of both genotypes on the overall recognition performance with carriers of low-expressing variants, namely TaqIA A1 carriers and C957T C homozygotes, showing better performance than the other genotype groups. In addition to the better memory performance, C957T C homozygotes also exhibited a response bias for cues predicting monetary reward. At the neural level, the C957T polymorphism was associated with a genotype-related modulation of right hippocampal and striatal fMRI responses predictive of subsequent recognition confidence for reward-predicting items. Our results indicate that genetic variations associated with DRD2 expression affect explicit memory, specifically for rewarded stimuli. We suggest that the relatively better memory for rewarded stimuli in carriers of low-expressing variants may reflect an intermediate phenotype of addiction memory.
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http://dx.doi.org/10.3389/fpsyg.2017.00654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410587PMC
May 2017

Vascular basement membrane alterations and β-amyloid accumulations in an animal model of cerebral small vessel disease.

Clin Sci (Lond) 2017 May 27;131(10):1001-1013. Epub 2017 Mar 27.

Department of Neurology, Otto-von-Guericke University Magdeburg, Germany, German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany

Non-amyloid cerebral small vessel disease (CSVD) and cerebral amyloid angiopathy (CAA) may be interrelated through the damaged basement membranes (BMs) and extracellular matrix changes of small vessels, resulting in a failure of β-amyloid (Aβ) transport and degradation. We analyzed BM changes and the pattern of deposition of Aβ in the walls of blood vessels in spontaneously hypertensive stroke-prone rats (SHRSP), a non-transgenic CSVD model. In 45 SHRSP and 38 Wistar rats aged 18 to 32 weeks: (i) the percentage area immunostained for vascular collagen IV and laminin was quantified; (ii) the capillary BM thickness as well as endothelial and pericyte pathological changes were analysed using transmission electron microscopy (TEM); and (iii) the presence of vascular Aβ was assessed. Compared with controls, SHRSP exhibited a significantly higher percentage area immunostained with collagen IV in the striatum and thalamus. SHRSP also revealed an age-dependent increase of the capillary BM thickness and of endothelial vacuoles (caveolae) within subcortical regions. Endogenous Aβ deposits in the walls of small blood vessels were observed in the cortex (with the highest incidence found within fronto-parietal areas), striatum, thalamus and hippocampus. Vascular β-amyloid accumulations were frequently detected at sites of small vessel wall damage. Our data demonstrate changes in the expression of collagen IV and of the ultrastructure of BMs in the small vessels of SHRSP. Alterations are accompanied by vascular deposits of endogenous Aβ. Impaired β-amyloid clearance along perivascular and endothelial pathways and failure of extracellular Aβ degradation may be the key mechanisms connecting non-amyloid CSVD and CAA.
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http://dx.doi.org/10.1042/CS20170004DOI Listing
May 2017

Inhibition of Information Flow to the Default Mode Network During Self-Reference Versus Reference to Others.

Cereb Cortex 2017 08;27(8):3930-3942

Department of Behavioral Neurology, Leibniz Institute for Neurobiology, Magdeburg, Germany.

The default mode network (DMN), a network centered around the cortical midline, shows deactivation during most cognitive tasks and pronounced resting-state connectivity, but is actively engaged in self-reference and social cognition. It is, however, yet unclear how information reaches the DMN during social cognitive processing. Here, we addressed this question using dynamic causal modeling (DCM) of functional magnetic resonance imaging (fMRI) data acquired during self-reference (SR) and reference to others (OR). Both conditions engaged the left inferior frontal gyrus (LIFG), most likely reflecting semantic processing. Within the DMN, self-reference preferentially elicited rostral anterior cingulate and ventromedial prefrontal cortex (rACC/vmPFC) activity, whereas OR engaged posterior cingulate and precuneus (PCC/PreCun). DCM revealed that the regulation of information flow to the DMN was primarily inhibitory. Most prominently, SR elicited inhibited information flow from the LIFG to the PCC/PreCun, while OR was associated with suppression of the connectivity from the LIFG to the rACC/vmPFC. These results suggest that task-related DMN activation is enabled by inhibitory down-regulation of task-irrelevant information flow when switching from rest to stimulus-specific processing.
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http://dx.doi.org/10.1093/cercor/bhw206DOI Listing
August 2017

Gender-specific modulation of neural mechanisms underlying social reward processing by Autism Quotient.

Soc Cogn Affect Neurosci 2015 Nov 4;10(11):1537-47. Epub 2015 May 4.

Leibniz Institute for Neurobiology, Magdeburg, Germany, Otto-von-Guericke University, Magdeburg, Germany, Department of Psychiatry, Campus Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany, and Center for Behavioral Brain Sciences, Magdeburg, Germany

Autism spectrum disorder refers to a neurodevelopmental condition primarily characterized by deficits in social cognition and behavior. Subclinically, autistic features are supposed to be present in healthy humans and can be quantified using the Autism Quotient (AQ). Here, we investigated a potential relationship between AQ and neural correlates of social and monetary reward processing, using functional magnetic resonance imaging in young, healthy participants. In an incentive delay task with either monetary or social reward, reward anticipation elicited increased ventral striatal activation, which was more pronounced during monetary reward anticipation. Anticipation of social reward elicited activation in the default mode network (DMN), a network previously implicated in social processing. Social reward feedback was associated with bilateral amygdala and fusiform face area activation. The relationship between AQ and neural correlates of social reward processing varied in a gender-dependent manner. In women and, to a lesser extent in men, higher AQ was associated with increased posterior DMN activation during social reward anticipation. During feedback, we observed a negative correlation of AQ and right amygdala activation in men only. Our results suggest that social reward processing might constitute an endophenotype for autism-related traits in healthy humans that manifests in a gender-specific way.
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http://dx.doi.org/10.1093/scan/nsv044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4631150PMC
November 2015

Corrigendum: Valenced action/inhibition learning in humans is modulated by a genetic variant linked to dopamine D2 receptor expression.

Front Syst Neurosci 2015 11;9:36. Epub 2015 Mar 11.

Department of Neurochemistry and Molecular Biology and Department of Behavioral Neurology, Leibniz Institute for Neurobiology Magdeburg, Germany ; Center for Behavioral Brain Sciences, Otto von Guericke University of Magdeburg Magdeburg, Germany ; Department of Psychiatry, Charité University Hospital Berlin, Germany ; Department of Neurology, Otto von Guericke University Magdeburg, Germany.

[This corrects the article on p. 140 in vol. 8, PMID: 25147510.].
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http://dx.doi.org/10.3389/fnsys.2015.00036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356065PMC
March 2015

Valenced action/inhibition learning in humans is modulated by a genetic variant linked to dopamine D2 receptor expression.

Front Syst Neurosci 2014 6;8:140. Epub 2014 Aug 6.

Department of Neurochemistry and Molecular Biology, Department of Behavioral Neurology, Leibniz Institute for Neurobiology Magdeburg, Germany ; Center for Behavioral Brain Sciences, Otto von Guericke University of Magdeburg Magdeburg, Germany ; Department of Psychiatry, Charité University Hospital Berlin, Germany ; Department of Neurology, University of Magdeburg Magdeburg, Germany.

Motivational salience plays an important role in shaping human behavior, but recent studies demonstrate that human performance is not uniformly improved by motivation. Instead, action has been shown to dominate valence in motivated tasks, and it is particularly difficult for humans to learn the inhibition of an action to obtain a reward, but the neural mechanism behind this behavioral specificity is yet unclear. In all mammals, including humans, the monoamine neurotransmitter dopamine is particularly important in the neural manifestation of appetitively motivated behavior, and the human dopamine system is subject to considerable genetic variability. The well-studied TaqIA restriction fragment length polymorphism (rs1800497) has previously been shown to affect striatal dopamine metabolism. In this study we investigated a potential effect of this genetic variation on motivated action/inhibition learning. Two independent cohorts consisting of 87 and 95 healthy participants, respectively, were tested using the previously described valenced go/no-go learning paradigm in which participants learned the reward-associated no-go condition significantly worse than all other conditions. This effect was modulated by the TaqIA polymorphism, with carriers of the A1 allele showing a diminished learning-related performance enhancement in the rewarded no-go condition compared to the A2 homozygotes. This result highlights a modulatory role for genetic variability of the dopaminergic system in individual learning differences of action-valence interaction.
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http://dx.doi.org/10.3389/fnsys.2014.00140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4123722PMC
August 2014

Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory.

Front Hum Neurosci 2014 29;8:260. Epub 2014 Apr 29.

Department of Behavioral Neurology and Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology Magdeburg, Germany ; Department of Psychiatry, Charité Universitätsmedizin Berlin Berlin, Germany ; Center for Behavioral Brain Sciences Magdeburg, Germany ; Department of Neurology, Otto von Guericke University Magdeburg, Germany.

The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP) rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT) and the logical memory section of the Wechsler Memory Scale (WMS). Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI) studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e., the myopia risk allele) showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point toward pleitropic effects of RASGRF1 genetic variations on complex neural function in humans.
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http://dx.doi.org/10.3389/fnhum.2014.00260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010733PMC
May 2014

Motivational salience and genetic variability of dopamine D2 receptor expression interact in the modulation of interference processing.

Front Hum Neurosci 2013 5;7:250. Epub 2013 Jun 5.

Department of Behavioral Neurology and Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology Magdeburg, Germany.

Dopamine has been implicated in the fine-tuning of complex cognitive and motor function and also in the anticipation of future rewards. This dual function of dopamine suggests that dopamine might be involved in the generation of active motivated behavior. The DRD2 TaqIA polymorphism of the dopamine D2 receptor gene (rs1800497) has previously been suggested to affect striatal function with carriers of the less common A1 allele exhibiting reduced striatal D2 receptor density and increased risk for addiction. Here we aimed to investigate the influences of DRD2 TaqIA genotype on the modulation of interference processing by reward and punishment. Forty-six young, healthy volunteers participated in a behavioral experiment, and 32 underwent functional magnetic resonance imaging (fMRI). Participants performed a flanker task with a motivation manipulation (monetary reward, monetary loss, neither, or both). Reaction times (RTs) were shorter in motivated flanker trials, irrespective of congruency. In the fMRI experiment motivation was associated with reduced prefrontal activation during incongruent vs. congruent flanker trials, possibly reflecting increased processing efficiency. DRD2 TaqIA genotype did not affect overall RTs, but interacted with motivation on the congruency-related RT differences, with A1 carriers showing smaller interference effects to reward alone and A2 homozygotes exhibiting a specific interference reduction during combined reward (REW) and punishment trials (PUN). In fMRI, anterior cingulate activity showed a similar pattern of genotype-related modulation. Additionally, A1 carriers showed increased anterior insula activation relative to A2 homozygotes. Our results point to a role for genetic variations of the dopaminergic system in individual differences of cognition-motivation interaction.
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http://dx.doi.org/10.3389/fnhum.2013.00250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672681PMC
June 2013