Genetic Neuroimaging Research Articles

Similar imaging changes and their relations to genetic profiles in bipolar disorder across different clinical stages

Bipolar disorder (BD) across different clinical stages may present shared and distinct changes in brain activity. We aimed to reveal the neuroimaging homogeneity and heterogeneity of BD and its relationship with clinical variables and genetic variations. In present study, we conducted fractional amplitude of low-frequency fluctuations (fALFF), functional connectivity (FC) and genetic neuroimaging association analyses with 32 depressed, 26 manic, 35 euthymic BD patients and 87 healthy controls (HCs). Significant differences were found in the bilateral pre/subgenual anterior cingulate cortex (ACC) across the four groups, and all bipolar patients exhibited decreased fALFF values in the ACC when compared to HCs. Furthermore, positive associations were significantly observed between fALFF values in the pre/subgenual ACC and participants' cognitive functioning. No significant changes were found in ACC-based FC. We identified fALFF-alteration-related genes in BD, with enrichment in biological progress including synaptic and ion transmission. Taken together, abnormal activity in ACC is a characteristic change associated with BD, regardless of specific mood stages, serving as a potential neuroimaging feature in BD patients. Our genetic neuroimaging association analysis highlights possible heterogeneity in biological processes that could be responsible for different clinical stages in BD.

Genetic variations in DOCK4 contribute to schizophrenia susceptibility in a Chinese cohort: A genetic neuroimaging study

BackgroundEmerging evidence suggests that the DOCK4 gene increases susceptibility to schizophrenia. However, no study has hitherto repeated this association in Chinese, and further investigated the relationship between DOCK4 and clinical symptoms in schizophrenic patients using clinical scales and functional magnetic resonance imaging (fMRI). MethodsIn this study, we genotyped three single nucleotide polymorphisms (SNPs) (rs2074127, rs2217262, and rs2074130) within the DOCK4 gene using a case-control design (including 1289 healthy controls and 1351 patients with schizophrenia). 55 first-episode schizophrenia (FES) patients and 59 healthy participants were divided by the genotypes of rs2074130 into CC and CT+TT groups. We further investigated the association with clinical symptoms and neural characteristics (brain activation/connectivity and nodal network metrics). ResultsOur results showed significant associations between all selected SNPs and schizophrenia (all P < 0.05). In patients, letter fluency and motor speed scores of T allele carriers were significantly higher than the CC group (all P < 0.05). Interestingly, greater brain activity, functional connectivity, and betweenness centrality (BC) in language processing and motor coordination were also observed in the corresponding brain zones in patients with the T allele based on a two-way ANCOVA model. Moreover, a potential positive correlation was found between brain activity/connectivity of these brain regions and verbal fluency and motor speed. ConclusionOur findings suggest that the DOCK4 gene may contribute to the onset of schizophrenia and lead to language processing and motor coordination dysfunction in this patient population from China.

Clinical and sociodemographic characteristics of patients with Neurocognitive Disorder (NCD) (dementia) at the Ramón de la Fuente Muñiz National Institute of Psychiatry (INPRFM) Psychogeriatrics Clinic in Mexico City, between 2011 and 2020.

AbstractBackgroundThe demographic and epidemiological transition, increased life expectancy and decreased fertility rate have increased the prevalence of dementia that affects 55 million people worldwide; it is estimated to affect 75 million by 2030 and increase three times by 2050. The clinical and sociodemographic characteristics of the studied population are unknown. It is the first study of its kind in the region. It’s also an unaddressed issue where an exploratory type protocol was carried out and a hypothesis was not formulated.MethodsDescriptive, observational, cross‐sectional, retrospective study. A Mexican population database including subjects from a previous work was created and then a secondary analysis was made. Every patient diagnosed with NCD was included regardless of age and with a clinical, psychiatric and/or geriatric syndrome diagnosis. No instrument or scale was used. There was no funding. Statistical analysis was done in SPSS 20.0.Results2056 records were found, 675 met the inclusion criteria. Age 74.71 (±9.02) years, from the urban area 93.78% (n = 633), women 72.15% (n = 487), primary school 49.90% (n = 243), widows 37.99% (n = 185), household occupation 77.21% (n = 376), low socioeconomic status 57.08% (n = 278). 59.86% (n = 404) had a major NCD, MMSE of 18.88 points (±6.68), Alzheimer’s disease was present in 31.56% (n = 213) both in those under 60 years of age 25.64% (n = 10) and in those older than 60 years old 31.92% (n = 203). Mild NCD was present in 9.19% (n = 62), the diagnosis was ruled out in 3.11% (n = 21) and a diagnosis could not be concluded in 25.93% (175). The most common psychiatric pathologies were Depressive and anxious disorder with 80.00% (n = 540) and 9.19% (n = 62) respectively; Clinical diagnosis were Arterial Hypertension 50.07% (n = 338), diabetes mellitus 22.22% (n = 150) and geriatric syndromes in 14.57% (n = 218).ConclusionThe study analyzes the characteristics of the clinic’s patients. The first of its kind which differentiates it from population based studies. The results are not intended to be extrapolated to the general population. Due to limitations in the diagnostic process of dementias, there were no diagnostic methods such as biomarkers in cerebrospinal fluid, functional or genetic neuroimaging. The intention is to promote dementia research and highlight the extent of the problem to Latinamerican Governments.

The serotonin transporter gene variants modulate acute stress-induced hippocampus and dorsomedial prefrontal cortex activity during memory retrieval.

The short (s) allele of a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is related to reduced serotonin transporter efficiency and an increased vulnerability to stress and mental disorders. In the present study, we investigated how 5-HTTLPR impacts on memory retrieval under stress and related neural activity by reanalyzing a small genetic neuroimaging data set. Twenty-seven healthy male volunteers participated in both the Trier Social Stress Test (TSST) and a respective control procedure and then their brain activity was measured with functional MRI (fMRI) while they performed an emotional-face-recognition task. Sixteen participants were carriers of the short allele (ss/sl carriers) and 11 were homozygous for the long allele (ll carriers). Genotype groups were compared with respect to stress-related physiological changes, memory performance, and brain activity. No significant genotype-dependent effects on memory performance or cortisol levels were found. The ss/sl carriers showed significantly higher systolic and diastolic blood pressure than the ll carriers, independent of stress. The ss/sl carriers reported stronger stress-induced nervous mood than the ll carriers. Our fMRI data revealed that the ss/sl carriers showed significantly weaker left hippocampus activation and stronger dorsomedial prefrontal cortex (dmPFC) deactivation when retrieving memories under stress as compared with the ll carriers. Subsequent analyses revealed that the distinct hippocampal activation pattern in both genotypes was associated with stress-induced cortisol elevation, while the distinct dmPFC activation pattern in both genotypes was associated with stress-induced changes in reaction times. Our results thus add new evidence that serotonin signaling modulates neural activity in the hippocampus and dmPFC during memory retrieval under acute psychosocial stress.

Serotonin-1A receptor C-1019G polymorphism affects brain functional networks

The serotonin-1A (5-HT1A) receptor is strongly implicated in major depression and other affective disorders due to its negative regulation of serotonin neurone firing rates. Behavioural and clinical studies have repeatedly reported that the −1019G allele carries a high susceptibility for affective disorders. However, the underlying pathophysiology remains unknown. Here, we employed a genetic neuroimaging strategy in 99 healthy human subjects to explore the effect of serotonin-1A receptor polymorphism on brain resting-state functional connectivity (FC). We used functional magnetic resonance imaging, along with a seed-based approach, to identify three main brain networks: the default mode network (DMN), the salience network (SN) and the central executive network. We observed a significant decrease in the FC of the DMN within the dorsolateral and ventromedial prefrontal cortices in G-carriers. Furthermore, compared with the C-homozygote group, we observed decreased FC of the SN within the ventromedial prefrontal cortex and subgenual anterior cingulate cortex in the G-carrier group. Our results indicate that 5-HT1A receptor genetic polymorphism modulates the activity of resting-state FC within brain networks including the DMN and SN. These genotype-related alterations in brain networks and FC may provide novel insights into the neural mechanism underlying the predisposition for affective disorders in G allele carriers.

The oxytocinergic system modulates sadistic context-dependent empathy in humans

The oxytocinergic system is crucial for sociality and well-being and is associated with empathy. It is suggested that the oxytocinergic system exerts context- and person-dependent effects. We examined how sexual sadistic contexts influenced the effects of the oxytocinergic system on empathic-related behaviors and brain activity in healthy adults. Combining genetic neuroimaging, pharmacological techniques and a psychological paradigm of empathy, we recorded EEG neural responses in female OXTR rs53756 G/G and A/A carriers and measured subjective empathic ratings after intranasal administration of oxytocin/placebo in healthy male adults during the perception of painful facial expressions in sadistic/general social contexts. The results revealed that sadistic contexts modulate oxytocinergic effects on empathy at both behavioral and neural levels. The oxytocinergic system preferentially modulated empathic responses to sadistic contexts. These effects are moderated by individual’s trait empathy. Our combined genetic-pharmacological-imaging results provide a neurochemical mechanism for sadistic context-dependent effects of the oxytocinergic system on empathy.

Random Projection for Fast and Efficient Multivariate Correlation Analysis of High-Dimensional Data: A New Approach.

In recent years, the advent of great technological advances has produced a wealth of very high-dimensional data, and combining high-dimensional information from multiple sources is becoming increasingly important in an extending range of scientific disciplines. Partial Least Squares Correlation (PLSC) is a frequently used method for multivariate multimodal data integration. It is, however, computationally expensive in applications involving large numbers of variables, as required, for example, in genetic neuroimaging. To handle high-dimensional problems, dimension reduction might be implemented as pre-processing step. We propose a new approach that incorporates Random Projection (RP) for dimensionality reduction into PLSC to efficiently solve high-dimensional multimodal problems like genotype-phenotype associations. We name our new method PLSC-RP. Using simulated and experimental data sets containing whole genome SNP measures as genotypes and whole brain neuroimaging measures as phenotypes, we demonstrate that PLSC-RP is drastically faster than traditional PLSC while providing statistically equivalent results. We also provide evidence that dimensionality reduction using RP is data type independent. Therefore, PLSC-RP opens up a wide range of possible applications. It can be used for any integrative analysis that combines information from multiple sources.

Clinicopathological findings in mitochondrial disorders

Mitochondrial encephalomyopathies have shifted from being regarded just a few years ago as a category of rare metabolic diseases to a current recognition that they are much more common than previously thought, are a large and heterogeneous group of distinct diseases, and that they may occur not only as primary biochemical and genetic defects, but also as secondary defects in a wide spectrum of both genetic and acquired diseases of the nervous system ranging from Pompe disease (glycogenosis II, acid maltase deficiency), spinal muscular atrophy, septo-optic-pituitary dysplasia, some inflammatory myopathies, and secondary to a broad range of drugs that include immunosuppressive and chemotherapeutic agents, statins and valproic acid. Most of the research on mitochondrial diseases has been generated, not surprisingly, in the countries with the greatest funding and biochemical laboratory resources for investigating them, including detailed biochemical and genetic studies, neuroimaging and neuropathological studies, mainly from western Europe and North America. It is therefore encouraging to see studies of mitochondrial diseases eminating also from countries with fewer resources, such as the paper by Selim et al. [1] from Egypt, in this current issue of the JPN.

Genetic and Environmental Neuroimaging Markers for Major Depression

Environment early in life may have a long-lasting impact on mental health through epigenetic mechanisms. We studied the effect of early life adversity (ELA) on high risk subjects for Depression (MDD). 20 unaffected first degree relatives (FHP) and 20 controls (FHN) underwent high resolution MRI. We used CTQ questionnaire to assess ELA. Manual tracing of hippocampal subregions and voxel-based morphometry (VBM) analysis were used. We concluded that FHP individuals had reduced volume of those brain areas of emotional processing, in particular if they had a history of ELA. This suggests that ELA might influence brain structure via epigenetic mechanisms and structural changes may precede MDD. We determined how the brain-derived neurotrphic factor (BDNF) Val66Met polymorphism and ELA affect volumetric measures of hippocampus. 62 MDD patients and 71 healthy controls underwent high-resolution MRI. We manually teaced hippocampi, assessed childhood adversity with CTQ and genotyped Val66Met BDNF. Met-allele carriers showed significantly smaller hippocampal volumes when they had a history of ELA, both in patients and controls. Our results highlight how relevant stress-gene interactions are for hippocampal volume reductions. Another 37 patients with MDD and 42 healthy participants underwent Diffussion Tensor Imaging (DTI). Deterministic tractography was applied and Val66Met BDNF polymorphism genotyped. Patients carrying the BDNF met-allele had smaller FA in Uncinate Fasciculus (UF) compared to homozygous for val-allele and controls. The met allele of the BDNF polymorphism seems to render subjects more vulnerable for dysfunctions associated with the UF, a brain region which is very closely related to emotional and cognitive function.

Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity.

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain–behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the brain at the core of fundamental research, prevention and therapy in the context of obesity and eating disorders. First, we will discuss the possibility to identify new biological markers of brain functions. Second, we will highlight the potential of neuroimaging and neuromodulation in individualized medicine. Third, we will introduce the ethical questions that are concomitant to the emergence of new neuromodulation therapies.

ADRA2B genotype differentially modulates stress-induced neural activity in the amygdala and hippocampus during emotional memory retrieval.

Noradrenaline interacts with stress hormones in the amygdala and hippocampus to enhance emotional memory consolidation, but the noradrenergic-glucocorticoid interaction at retrieval, where stress impairs memory, is less understood. We used a genetic neuroimaging approach to investigate whether a genetic variation of the noradrenergic system impacts stress-induced neural activity in amygdala and hippocampus during recognition of emotional memory. This study is based on genotype-dependent reanalysis of data from our previous publication (Li et al. Brain Imaging Behav 2014). Twenty-two healthy male volunteers were genotyped for the ADRA2B gene encoding the α2B-adrenergic receptor. Ten deletion carriers and 12 noncarriers performed an emotional face recognition task, while their brain activity was measured with fMRI. During encoding, 50 fearful and 50 neutral faces were presented. One hour later, they underwent either an acute stress (Trier Social Stress Test) or a control procedure which was followed immediately by the retrieval session, where participants had to discriminate between 100 old and 50 new faces. A genotype-dependent modulation of neural activity at retrieval was found in the bilateral amygdala and right hippocampus. Deletion carriers showed decreased neural activity in the amygdala when recognizing emotional faces in control condition and increased amygdala activity under stress. Noncarriers showed no differences in emotional modulated amygdala activation under stress or control. Instead, stress-induced increases during recognition of emotional faces were present in the right hippocampus. The genotype-dependent effects of acute stress on neural activity in amygdala and hippocampus provide evidence for noradrenergic-glucocorticoid interaction in emotional memory retrieval.

Ethical evaluation of genetic testing and neuroimaging for children at risk for mental illness

Ethical evaluation of genetic testing and neuroimaging for children at risk for mental illness

Imaging Epigenetics in Alzheimer’s Disease

Sporadic Alzheimer's disease (AD) is a prevalent, complex and chronically progressive brain disease. Its course is non-linear, dynamic, adaptive to maladaptive, and compensatory to decompensatory, affecting large-scale neural networks through a plethora of mechanistic and signaling pathway alterations that converge into regional and cell type-specific neurodegeneration and, finally, into clinically overt cognitive and behavioral decline. This decline includes reductions in the activities of daily living, quality of life, independence, and life expectancy. Evolving lines of research suggest that epigenetic mechanisms may play a crucial role during AD development and progression. Epigenetics designates molecular mechanisms that alter gene expression without modifications of the genetic code. This topic includes modifications on DNA and histone proteins, the primary elements of chromatin structure. Accumulating evidence has revealed the relevant processes that mediate epigenetic modifications and has begun to elucidate how these processes are apparently dysregulated in AD. This evidence has led to the clarification of the roles of specific classes of therapeutic compounds that affect epigenetic pathways and characteristics of the epigenome. This insight is accompanied by the development of new methods for studying the global patterns of DNA methylation and chromatin alterations. In particular, high-throughput sequencing approaches, such as next-generation DNA sequencing techniques, are beginning to drive the field into the next stage of development. In parallel, genetic imaging is beginning to answer additional questions through its ability to uncover genetic variants, with or without genome-wide significance, that are related to brain structure, function and metabolism, which impact disease risk and fundamental network-based cognitive processes. Neuroimaging measures can further be used to define AD systems and endophenotypes. The integration of genetic neuroimaging methods with epigenetic markers in humans appears promising. This evolving development may lead to a new research discipline - imaging epigenetics - that will provide deeper insight into the causative pathogenetic and pathophysiological pathways through which genes and environment interrelate during life and impact human brain development, physiology, aging and disease. This knowledge may open doors for the development of novel biomarkers and preventive and disease-modifying treatments.

Effect of the Interleukin-1β Gene on Dorsolateral Prefrontal Cortex Function in Schizophrenia: A Genetic Neuroimaging Study

Genetic studies have found that the interleukin-1β gene (IL1B, 2q13) influences the risk for schizophrenia, but the underlying biological mechanisms of the association are still unclear. Investigation of the effects of genetic variability in this gene on brain function could provide more information about its role in the disorder. The present study examined the effects of a functional polymorphism at IL1B gene promoter (-511C/T; rs16944) on brain correlates of working memory performance in schizophrenia. Forty-eight schizophrenia patients and 46 control subjects underwent functional magnetic resonance imaging while performing the n-back task. In the pooled sample, genetic variability at this locus was associated with differential brain activation in a bilateral frontal region including the dorsolateral prefrontal cortex. There was also a significant diagnosis × genotype interaction effect in an overlapping frontal region: the IL1B polymorphism did not affect activation in the control subjects in this area, but the schizophrenia patients who were T carriers showed significantly higher activation than the CC homozygotes. The findings support a role for IL1B variability in the dorsolateral prefrontal cortex dysfunction classically associated with schizophrenia.

The IMAGEN study: reinforcement-related behaviour in normal brain function and psychopathology

A fundamental function of the brain is to evaluate the emotional and motivational significance of stimuli and to adapt behaviour accordingly. The IMAGEN study is the first multicentre genetic-neuroimaging study aimed at identifying the genetic and neurobiological basis of individual variability in impulsivity, reinforcer sensitivity and emotional reactivity, and determining their predictive value for the development of frequent psychiatric disorders. Comprehensive behavioural and neuropsychological characterization, functional and structural neuroimaging and genome-wide association analyses of 2000 14-year-old adolescents are combined with functional genetics in animal and human models. Results will be validated in 1000 adolescents from the Canadian Saguenay Youth Study. The sample will be followed up longitudinally at the age of 16 years to investigate the predictive value of genetics and intermediate phenotypes for the development of frequent psychiatric disorders. This review describes the strategies the IMAGEN consortium used to meet the challenges posed by large-scale multicentre imaging-genomics investigations. We provide detailed methods and Standard Operating Procedures that we hope will be helpful for the design of future studies. These include standardization of the clinical, psychometric and neuroimaging-acquisition protocols, development of a central database for efficient analyses of large multimodal data sets and new analytic approaches to large-scale genetic neuroimaging analyses.

The effect of G72 genotype on neural correlates of memory encoding and retrieval

Polymorphisms in the G72 (also named d-amino acid oxidase activator, DAOA) gene increase the vulnerability for schizophrenia and affective psychosis. Three recent genetic neuroimaging studies showed that variation in G72 influences the brain activity in the medial temporal lobe (MTL), supporting the hypothesis that G72 might play a modulatory role on brain activity in MTL structures. In the present study we therefore investigated the effect of G72 on the neural correlates of long-term memory encoding and retrieval in a large sample of healthy subjects (n=83) using functional magnetic resonance imaging. A face encoding and a face retrieval memory task were chosen because on the one hand they specifically activate MTL structures and on the other hand they tap into memory processes that are compromised in patients with schizophrenia and affective disorder. Despite a strong a-priori hypothesis of genotype group activation differences in the MTL along with a large sample size we did neither find an effect of G72 genotype status on brain activity in the MTL nor in any other brain regions. The present data therefore do not support the view of a general modulatory role of G72 on MTL brain activity, at least not in the domain of long-term memory encoding and retrieval. Our results highlight the importance of replication studies in genetic neuroimaging.

Microarrays

Microarrays are revolutionizing genetics by making it possible to genotype hundreds of thousands of DNA markers and to assess the expression (RNA transcripts) of all of the genes in the genome. Microarrays are slides the size of a postage stamp that contain millions of DNA sequences to which single-stranded DNA or RNA can hybridize. This miniaturization requires little DNA or RNA and makes the method fast and inexpensive; multiple assays of each target make the method highly accurate. DNA microarrays with hundreds of thousands of DNA markers have made it possible to conduct systematic scans of the entire genome to identify genetic associations with complex disorders or dimensions likely to be influenced by many genes of small effect size. RNA microarrays can provide snapshots of gene expression across all of the genes in the genome at any time in any tissue, which has far-reaching applications such as structural and functional ‘genetic neuroimaging’ and providing a biological basis for understanding environmental influence.

NeuroImaging bei schizophrenen Erkrankungen

This overview is focused on functional neuroimaging including functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT). Recent evidence for the "dopamine hypothesis of schizophrenia" is summarized including alterations of presynaptic dopamine metabolism and postsynaptic receptor binding potential. Emphasis is given to dopaminergic challenge studies using amphetamine and AMPT. Several PET and SPECT studies have shown a pronounced increase of amphetamine-induced dopamine release as well as decrease of AMPT-induced dopamine depletion in drug-naive schizophrenic patients, indicating a dysregulation of dopaminergic neurotransmission. Results of studies combining amphetamine challenge and the NMDA receptor antagonist ketamine are related to glutaminergic dysfunction and neurotransmitter interactions. FMRI and PET results demonstrating alterations in task-specific functional connectivity between brain areas are discussed with a focus on the prefrontal cortex and temporal structures. Increase of serotonin-1A receptor binding potential in prefrontal and mesotemporal cortex is related to the serotonin-dopamine interaction. Genetic neuroimaging techniques, including voxel-based morphometry (VBM) and fMRI, revealing significant effects of the dopamine metabolizing enzyme COMT on functional activation in prefrontal areas are also discussed. Functional neuroimaging based on challenge-paradigms in PET as well as task-specific state- or trait-dependent alterations of activation patterns in fMRI, seems to be a promising candidate for the development of biological marker tests for schizophrenia.

Neuroethics: Dialogue on a Continuum from Tradition to Innovation

In “Imaging or Imagining” (Illes and Racine 2005), we reviewed modern neuroimaging capabilities and explored how previous work in the ethics of genomics informs the ethics of neuroscience. We focused on functional neuroimaging with MRI as one area of neuroscience in which tremendous progress has been made, and we introduced ethical challenges that such progress carries with it. Our comparative and case-inspired method is reminiscent of casuistry, but is shared by most approaches in bioethics. It allowed us to analyze similarities and differences between genetic research and neuroimaging and led us to highlight data interpretation as a prime focus for neuroethics. We strongly believe that clarifying the broadly-construed scientific and social meaning of neuroscience, which includes anthropological and philosophical considerations as well as the interaction of all levels of interpretation, is one of the fundamental tasks of neuroethics. As clearly pointed out in Kennedy’s (2005) commentary on our target article, and by others who have actively participated in neuroethics debates, the scientific complexity underlying the creation of neuroimages in basic research is concealed by the visual simplicity with which they are presented (see also Illes and Racine 2005, Table 2). Overinterpretation and over-simplification are among the possible consequences of modern visualization techniques, inasmuch as visual simplicity is key to the power of an image. The commentary by Ford and Kubu (2005) highlights the challenges of interpretation of neuroimaging data in the clinical arena, in which sensitivity and specificity have a profound impact on the accuracy of pre-surgical mapping of motor and language areas. When we move to examine the implications of neuroimaging in the real-world setting, we find tantalizing yet still scientifically-unfounded claims. For example, while the research may increasingly seek to capture fundamental new knowledge about higher-order cognition and social behaviors (Illes et al. 2003), the media already uses the data to discuss topics as varied as retirement plans (Porter 2005) and U.S. intelligence training (Brooks 2005). In fact, in an analysis we did of fMRI in the press (Racine et al. 2005), we found a seemingly uncritical enthusiasm for the trans-