A miR-137-Related Biological Pathway of Risk for Schizophrenia Is Associated With Human Brain Emotion Processing.

BACKGROUND: miR-137 is a microRNA involved in brain development, regulating neurogenesis and neuronal maturation. Genome-wide association studies have implicated miR-137 in schizophrenia risk but do not explain its involvement in brain function and underlying biology. Polygenic risk for schizophrenia mediated by miR-137 targets is associated with working memory, although other evidence points to emotion processing. We characterized the functional brain correlates of miR-137 target genes associated with schizophrenia while disentangling previously reported associations of miR-137 targets with working memory and emotion processing. METHODS: Using RNA sequencing data from postmortem prefrontal cortex (N = 522), we identified a coexpression gene set enriched for miR-137 targets and schizophrenia risk genes. We validated the relationship of this set to miR-137 in vitro by manipulating miR-137 expression in neuroblastoma cells. We translated this gene set into polygenic scores of coexpression prediction and associated them with functional magnetic resonance imaging activation in healthy volunteers (n1 = 214; n2 = 136; n3 = 2075; n4 = 1800) and with short-term treatment response in patients with schizophrenia (N = 427). RESULTS: In 4652 human participants, we found that 1) schizophrenia risk genes were coexpressed in a biologically validated set enriched for miR-137 targets; 2) increased expression of miR-137 target risk genes was mediated by low prefrontal miR-137 expression; 3) alleles that predict greater gene set coexpression were associated with greater prefrontal activation during emotion processing in 3 independent healthy cohorts (n1, n2, n3) in interaction with age (n4); and 4) these alleles predicted less improvement in negative symptoms following antipsychotic treatment in patients with schizophrenia. CONCLUSIONS: The functional translation of miR-137 target gene expression linked with schizophrenia involves the neural substrates of emotion processing.

Phase I clinical trial of intracerebroventricular transplantation of allogeneic neural stem cells in people with progressive multiple sclerosis.

We report the analysis of 1 year of data from the first cohort of 15 patients enrolled in an open-label, first-in-human, dose-escalation phase I study (ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of secondary progressive multiple sclerosis. Participants were treated with hNSCs delivered via intracerebroventricular injection in combination with an immunosuppressive regimen. No treatment-related deaths nor serious adverse events (AEs) were observed. All participants displayed stability of clinical and laboratory outcomes, as well as lesion load and brain activity (MRI), compared with the study entry. Longitudinal metabolomics and lipidomics of biological fluids identified time- and dose-dependent responses with increased levels of acyl-carnitines and fatty acids in the cerebrospinal fluid (CSF). The absence of AEs and the stability of functional and structural outcomes are reassuring and represent a milestone for the safe translation of stem cells into regenerative medicines.

Dopamine and schizophrenia from bench to bedside: Discovery of a striatal co-expression risk gene set that predicts in vivo measures of striatal function.

Schizophrenia (SCZ) is characterized by a polygenic risk architecture implicating diverse molecular pathways important for synaptic function. However, how polygenic risk funnels through these pathways to translate into syndromic illness is unanswered. To evaluate biologically meaningful pathways of risk, we used tensor decomposition to characterize gene co-expression in post-mortem brain (of neurotypicals: N=154; patients with SCZ: N=84; and GTEX samples N=120) from caudate nucleus (CN), hippocampus (HP), and dorsolateral prefrontal cortex (DLPFC). We identified a CN-predominant gene set showing dopaminergic selectivity that was enriched for genes associated with clinical state and for genes associated with SCZ risk. Parsing polygenic risk score for SCZ based on this specific gene set (parsed-PRS), we found that greater pathway-specific SCZ risk predicted greater in vivo striatal dopamine synthesis capacity measured by [ 18 F]-FDOPA PET in three independent cohorts of neurotypicals and patients (total N=235) and greater fMRI striatal activation during reward anticipation in two additional independent neurotypical cohorts (total N=141). These results reveal a 'bench to bedside' translation of dopamine-linked genetic risk variation in driving in vivo striatal neurochemical and hemodynamic phenotypes that have long been implicated in the pathophysiology of SCZ.

Heritability of amygdala reactivity to angry faces and its replicable association with the schizophrenia risk locus of miR-137.

BACKGROUND: Among healthy participants, the interindividual variability of brain response to facial emotions is associated with genetic variation, including common risk variants for schizophrenia, a heritable brain disorder characterized by anomalies in emotion processing. We aimed to identify genetic variants associated with heritable brain activity during processing of facial emotions among healthy participants and to explore the impact of these identified variants among patients with schizophrenia. METHODS: We conducted a data-driven stepwise study including samples of healthy twins, unrelated healthy participants and patients with schizophrenia. Participants approached or avoided pictures of faces with negative emotional valence during functional magnetic resonance imaging (fMRI). RESULTS: We investigated 3 samples of healthy participants - including 28 healthy twin pairs, 289 unrelated healthy participants (genome-wide association study [GWAS] discovery sample) and 90 unrelated healthy participants (replication sample) - and 1 sample of 48 patients with schizophrenia. Among healthy twins, we identified the amygdala as the brain region with the highest heritability during processing of angry faces (heritability estimate 0.54, p < 0.001). Subsequent GWAS in both discovery and replication samples of healthy non-twins indicated that amygdala activity was associated with a polymorphism in the miR-137 locus (rs1198575), a micro-RNA strongly involved in risk for schizophrenia. A significant effect in the same direction was found among patients with schizophrenia (p = 0.03). LIMITATIONS: The limited sample size available for GWAS analyses may require further replication of results. CONCLUSION: Our data-driven approach shows preliminary evidence that amygdala activity, as evaluated with our task, is heritable. Our genetic associations preliminarily suggest a role for miR-137 in brain activity during explicit processing of facial emotions among healthy participants and patients with schizophrenia, pointing to the amygdala as a brain region whose activity is related to miR-137.

Changes in patterns of age-related network connectivity are associated with risk for schizophrenia.

Alterations in fMRI-based brain functional network connectivity (FNC) are associated with schizophrenia (SCZ) and the genetic risk or subthreshold clinical symptoms preceding the onset of SCZ, which often occurs in early adulthood. Thus, age-sensitive FNC changes may be relevant to SCZ risk-related FNC. We used independent component analysis to estimate FNC from childhood to adulthood in 9,236 individuals. To capture individual brain features more accurately than single-session fMRI, we studied an average of three fMRI scans per individual. To identify potential familial risk-related FNC changes, we compared age-related FNC in first-degree relatives of SCZ patients mostly including unaffected siblings (SIB) with neurotypical controls (NC) at the same age stage. Then, we examined how polygenic risk scores for SCZ influenced risk-related FNC patterns. Finally, we investigated the same risk-related FNC patterns in adult SCZ patients (oSCZ) and young individuals with subclinical psychotic symptoms (PSY). Age-sensitive risk-related FNC patterns emerge during adolescence and early adulthood, but not before. Young SIB always followed older NC patterns, with decreased FNC in a cerebellar-occipitoparietal circuit and increased FNC in two prefrontal-sensorimotor circuits when compared to young NC. Two of these FNC alterations were also found in oSCZ, with one exhibiting reversed pattern. All were linked to polygenic risk for SCZ in unrelated individuals (R2 varied from 0.02 to 0.05). Young PSY showed FNC alterations in the same direction as SIB when compared to NC. These results suggest that age-related neurotypical FNC correlates with genetic risk for SCZ and is detectable with MRI in young participants.

Castleman disease: a rare case in a young woman.

Castleman disease is a rare lymphoproliferative disorder characterized by benign enlargement of lymph nodes. It is divided into unicentric disease, which involves a single enlarged lymph node, and multicentric disease, which affects multiple lymph node stations. In this report, we describe a rare case of a 28-year-old female patient with an unicentric Castleman disease. Computed tomography and magnetic resonance imaging revealed a well-circumscribed large mass in the left neck, characterized by intense homogenous enhancement and suspected for a malignant disease. The patient underwent an excisional biopsy for definitive diagnosis of unicentric Castleman disease and ruled out malignant conditions.

Twig-like middle cerebral artery in a case of neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with multisystemic involvement, affecting central nervous system, skin, bone system and vessels, with a very heterogeneous clinical presentation. Vascular abnormalities are typically recognized in neurofibromatosis type 1 affecting cardiovascular and cerebrovascular systems. The incidence of circle of Willis anomalies in children with NF1 is twofold higher than in general population. In this paper, we report of 19-years-old female with NF1 and twig-like middle cerebral artery.

Imaging of thoracolumbar spine traumas.

Spine trauma is an ominous event with a high morbidity, frequent mortality, and significant psychological, social, and financial consequences for patients, their relatives and society. On average three out of four spinal fractures involve the thoracolumbar spine and up to one-third are complicated by spinal cord injury. Spinal cord injuries (SCI) are a significant cause of disability in US and in all western countries. Knowledge of the main principles of biomechanics is essential in understanding the patho-morphology of spinal injuries, and the evolution of the various classification systems. Classification systems should be able to create a common language between specialists in order to improve patients' prognosis, guide treatment and compare treatment outcomes. Imaging has always been crucial in the evaluation of the injury type and accompanied the development of different classification systems. Thoracolumbar spine (TLS) trauma has a wide spectrum ranging from minor isolated fractures to highly unstable fracture-dislocations. Early classification systems were based on the analysis of the pattern of bony injuries on radiographs and CT. Traditionally, conventional radiographs are performed to confirm the clinical suspicion and to depict the level and type of bone injury. However, because of their inherent limitations, radiographs are often more helpful in proving the existence of a suspected bony spinal injury rather than excluding it. Multidetector computed tomography (MDCT) is superior in evaluating bone anatomy and, especially in polytrauma patients, it is the first line imaging modality. Morphological bone damage may be accurately shown and classified on CT. the most recent classifications also incorporate the integrity of soft tissues structures, which is considered equally relevant to spinal stability. Injuries to ligaments and discs can only be suspected on radiographs and conventional CT, although dual-energy CT is offering new insights on collagen mapping of damaged discs. Magnetic resonance imaging (MRI) may directly assess disc and ligamentous injuries, but also subtle osseous injuries, playing a complementary role in defining the whole spinal damage and an eventual instability. MRI is the only valid modality to assess the spinal cord (SC) and is indicated whenever a neurologic injury is suspected. Advanced MRI techniques, such as diffusion weighted imaging (DWI) and tractography, may provide further information regarding the integrity of the white matter which may improve outcome prognostication. Despite challenges in terms of costs, availability, accessibility and specificity, MRI and advanced MRI techniques are increasingly being used in spinal injuries. We present a review on TLS traumas discussing on the development of different classification system used in their evaluation, the role of imaging for their detection and the correlation to the patients' outcomes and treatment options.

Endovascular repair of isolated post-traumatic subclavian artery false-aneurysm (FA) using gore viabahn vbx-balloon-expandable (BE) stent-graft: case report and literature review.

True and false aneurysms (FA) of the subclavian artery are at high risk of rupture due to their localization and proximity/closeness to the articular bone structures of the upper thoracic outlet and shoulders. Surgical and endovascular treatments are good options to avoid complications such as aneurysms rupture, thrombosis and distal embolism alone or in combination. Self-expandable (SE) covered stents are the most used devices for the treatment of subclavian artery aneurysms. We report on a case of post traumatic left intra-thoracic subclavian artery FA treated using endovascular technique, highlighting the usefulness of the new covered Gore Viabahn VBX-BE stent-graft that combines the advantages of a high radial strength of a BE stent with the deliverability and conformability of a SE stent.

The interaction between cannabis use and a CB1-related polygenic co-expression index modulates dorsolateral prefrontal activity during working memory processing.

Convergent findings indicate that cannabis use and variation in the cannabinoid CB1 receptor coding gene (CNR1) modulate prefrontal function during working memory (WM). Other results also suggest that cannabis modifies the physiological relationship between genetically induced expression of CNR1 and prefrontal WM processing. However, it is possible that cannabis exerts its modifying effect on prefrontal physiology by interacting with complex molecular ensembles co-regulated with CB1. Since co-regulated genes are likely co-expressed, we investigated how genetically predicted co-expression of a molecular network including CNR1 interacts with cannabis use in modulating WM processing in humans. Using post-mortem human prefrontal data, we first computed a polygenic score (CNR1-PCI), combining the effects of single nucleotide polymorphisms (SNPs) on co-expression of a cohesive gene set including CNR1, and positively correlated with such co-expression. Then, in an in vivo study, we computed CNR1-PCI in 88 cannabis users and 147 non-users and investigated its interaction with cannabis use on brain activity during WM. Results revealed an interaction between cannabis use and CNR1-PCI in the dorsolateral prefrontal cortex (DLPFC), with a positive relationship between CNR1-PCI and DLPFC activity in cannabis users and a negative relationship in non-users. Furthermore, DLPFC activity in cannabis users was positively correlated with the frequency of cannabis use. Taken together, our results suggest that co-expression of a CNR1-related network predicts WM-related prefrontal activation as a function of cannabis use. Furthermore, they offer novel insights into the biological mechanisms associated with the use of cannabis.

Balò's concentric sclerosis in a case of cocaine-levamisole abuse.

Baló's concentric sclerosis is a rare variant of multiple sclerosis. It belongs to the group of primary inflammatory central nervous system demyelinating diseases having no clear etiology. Peculiar radiological findings on magnetic resonance imaging are alternating rings of demyelinated and myelinated axons resembling an "onion bulb." We report on a case of a patient with cocaine abuse who presented with Balò's-like acute multifocal leukoencephalopathy supported by histological and radiological findings. The abuse of cocaine and its most frequent adulterant, levamisole, may induce ischemic or hemorrhagic stroke and metabolic or multifocal inflammatory leukoencephalopathy. Only a few studies described levamisole-induced leukoencephalopathy mimicking Balò round lesions. Nevertheless, it has not yet been established the correlation between them; it might also be possible that the cocaine/levamisole addiction represents just a coincidence in some of those patients affected by Balò sclerosis disease.

Imaging of cranio-cervical junction traumas.

The craniocervical junction (CCJ) or upper cervical spine (UCS) has anatomic features and a biomechanics completely different from the other spinal segment of the spine. Several ligaments and muscles control its motion and function and ensure the maximum mobility and the visual and auditory spatial exploration. UCS traumas represent approximately one-third of all cervical spine injuries. Most of UCS traumas results from blows to the head and sudden deceleration of the body. Thanks to the improvement of the Advanced Trauma Life Support protocols dissociative injuries of CCJ have become less lethal onsite. In other less severe but unstable injuries, patients are neurologically intact at presentation, but they may deteriorate during the stay in hospital, with important clinical and medico-legal consequences. Knowing the peculiarities of UCS is fundamental for the early detection of imaging findings that influences the patient management and outcome. The classification of UCS traumas is mechanistic. More than in any other spinal segment, fractures of CCJ bones can occur without generating instability; on the contrary highly unstable injuries may not be associated with bone fractures. An early and correct diagnosis of occipito-cervical instability may prevent secondary neurological injury. The goal of imaging is to identify which patients can benefit of surgical stabilization and prevent secondary neurologic damage. Actual helical multidetector-CT (MDCT) offers high sensitivity and specificity for bone lesions and displacements in cervical spine traumas, but magnetic resonance imaging (MRI) is increasingly being used to evaluate soft tissues and ligaments, and mainly to identify possible spinal cord injury.

Multivariate patterns of gray matter volume in thalamic nuclei are associated with positive schizotypy in healthy individuals.

BACKGROUND: Previous models suggest biological and behavioral continua among healthy individuals (HC), at-risk condition, and full-blown schizophrenia (SCZ). Part of these continua may be captured by schizotypy, which shares subclinical traits and biological phenotypes with SCZ, including thalamic structural abnormalities. In this regard, previous findings have suggested that multivariate volumetric patterns of individual thalamic nuclei discriminate HC from SCZ. These results were obtained using machine learning, which allows case-control classification at the single-subject level. However, machine learning accuracy is usually unsatisfactory possibly due to phenotype heterogeneity. Indeed, a source of misclassification may be related to thalamic structural characteristics of those HC with high schizotypy, which may resemble structural abnormalities of SCZ. We hypothesized that thalamic structural heterogeneity is related to schizotypy, such that high schizotypal burden would implicate misclassification of those HC whose thalamic patterns resemble SCZ abnormalities. METHODS: Following a previous report, we used Random Forests to predict diagnosis in a case-control sample (SCZ = 131, HC = 255) based on thalamic nuclei gray matter volumes estimates. Then, we investigated whether the likelihood to be classified as SCZ (π-SCZ) was associated with schizotypy in 174 HC, evaluated with the Schizotypal Personality Questionnaire. RESULTS: Prediction accuracy was 72.5%. Misclassified HC had higher positive schizotypy scores, which were correlated with π-SCZ. Results were specific to thalamic rather than whole-brain structural features. CONCLUSIONS: These findings strengthen the relevance of thalamic structural abnormalities to SCZ and suggest that multivariate thalamic patterns are correlates of the continuum between schizotypy in HC and the full-blown disease.

Assessment of lumbar disc herniaton using fractional anisotropy in diffusion tensor imaging along with conventional T2-weighted imaging.

OBJECTIVE: To assess the usefulness of diffusion tensor imaging and its fractional anisotropy map along with conventional T2-weighted imaging in evaluating the anisotropic water diffusion variations of annulus fibres involved in herniation disc pathology. MATERIALS AND METHODS: Seventy-five patients with previous medical ethics committee approval and informed consent experiencing low back pain were selected for this prospective randomised blinded trial. Lumbar disc fractional anisotropy maps were obtained acquiring diffusion tensor sequences on a 3T machine. The matrix of nucleus pulposus and structures of annulus fibres were analysed using fractional anisotropy textural features to highlight any presence of lumbar disc herniation. Observer variability and reliability between two neuroradiologists were evaluated. The χ2 test, two-tailed t test and linear regression analysis were used to focus differences in patients' demographic data and magnetic resonance imaging findings. RESULTS: Annular fissures with extrusions were identified using diffusion tensor imaging in 10 out of 17 discs (study group) previously assessed as bulging discs using conventional magnetic resonance imaging. Eighteen extrusions out of 39 (study group) disc levels were identified on diffusion tensor imaging compared to eight extrusions highlighted on T2-weighted imaging (P < 0.01). All eight (study group) disc extrusions evaluated on T2-weighted imaging showed annular fissures on diffusion tensor imaging. Seven out of 14 (study group) protrusions highlighted on T2-weighted imaging had no annular fissures on diffusion tensor imaging; thirty-six disc levels in the control group had no evidence of annular fissures on diffusion tensor imaging (P > 0.01). CONCLUSIONS: The addition of diffusion tensor imaging sequences and fractional anisotropy mapping to a conventional magnetic resonance imaging protocol could be useful in detecting annular fissures and lumbar disc herniation.

Cerebral Infarcts After Coronary Angiography and Percutaneous Coronary Intervention: A Prospective Propensity-Score-Adjusted Comparison of Right Radial, Left Radial, and Femoral Approaches.

BACKGROUND: New cerebral infarcts (CIs) detected at magnetic resonance imaging (MRI) are reported after cardiac procedures. Clinical and procedural aspects are implicated as potential causal factors. The aim of this study was to evaluate the incidence of new CIs after coronary angiography and percutaneous coronary intervention according to the arterial access site. METHODS: 180 patients undergoing elective coronary angiography were studied with cerebral MRI the day before and the day after the procedure. Unadjusted and propensity score (PS) analyses were performed comparing the occurrence of CIs in right radial (RR), left radial (LR) and transfemoral (TF) access groups. RESULTS: New CIs were observed in 14 patients (7.8% of the total sample, one with neurological sequelae). CIs were detected in 15.5% vs 4.9% vs 3.3% of RR, LR and TF groups, respectively (p = .026). In PS adjusted analyses, the RR approach was associated with more CIs compared with the TF approach (odds ratio [OR] estimate from logistic regression adjusted by PS quartiles: 0.158; 95% confidence interval: 0.031 to 0.814; p = .027) and the LR approach (OR: 0.266; 95% confidence interval: 0.066 to 1.080; p = .064). In a secondary analysis, a comparison of RR vs non-RR approach (TF + LR) was performed, showing that post-procedural CIs were more frequent in the RR group (OR: 0.170; 95% confidence interval: 0.050 to 0.574; p = .004). CONCLUSIONS: Our study suggests that the RR approach may be associated with a higher rate of new CIs after coronary angiography compared with LR and TF approaches.

Imaging of cervical spine traumas.

Spinal traumas represent a significant proportion of muscle-skeletal injuries worldwide. Spinal injuries involve a complex structure with components having different traumatic susceptibility and variable healing capabilities. The interaction of numerous variables at time of trauma creates a great variety of lesions which makes challenging the creation and comparison of homogeneous groups, with difficulties in classifying spinal lesions, in assessing their instability, and in defining the indication and outcome of different treatment strategies. The evolution of concepts on instability has accompanied that of traumas classification schemes and treatment strategies. The assessment of instability in a spinal injury is actually crucial in front of newer surgical techniques and hardwares. Despite a long history of attempts to classify spinal traumas, it remains some degree of controversy in describing imaging data and a wide variety of treatment strategies. Acute cervical spine injuries affect from 1.9% to 4.6% of subjects reporting a blunt trauma, and up to 5.9% of multiple-injured patients. Most of spinal cord injuries are a consequence of unstable fractures of the cervical spine. An accurate and early diagnosis is mandatory to prevent neurological damage in unstable fractures. Classic and newer classifications are primarily based on features identifiable by using conventional imaging and CT scan, which are the most available modalities at most trauma centers. Even though multidetector-CT remains superior in assessing with high accuracy bone injuries, MRI is the most sensitive modality for detecting soft tissues injuries and spinal cord damage.

Thalamic connectivity measured with fMRI is associated with a polygenic index predicting thalamo-prefrontal gene co-expression.

The functional connectivity between thalamic medio-dorsal nucleus (MD) and cortical regions, especially the dorsolateral prefrontal cortex (DLPFC), is implicated in attentional processing and is anomalous in schizophrenia, a brain disease associated with polygenic risk and attentional deficits. However, the molecular and genetic underpinnings of thalamic connectivity anomalies are unclear. Given that gene co-expression across brain areas promotes synchronous interregional activity, our aim was to investigate whether coordinated expression of genes relevant to schizophrenia in MD and DLPFC may reflect thalamic connectivity anomalies in an attention-related network including the DLPFC. With this aim, we identified in datasets of post-mortem prefrontal mRNA expression from healthy controls a gene module with robust overrepresentation of genes with coordinated MD-DLPFC expression and enriched for schizophrenia genes according to the largest genome-wide association study to date. To link this gene cluster with imaging phenotypes, we computed a Polygenic Co-Expression Index (PCI) combining single-nucleotide polymorphisms predicting module co-expression. Finally, we investigated the association between PCI and thalamic functional connectivity during attention through fMRI Independent Component Analysis in 265 healthy participants. We found that PCI was positively associated with connectivity strength of a thalamic region overlapping with the MD within an attention brain circuit. These findings identify a novel association between schizophrenia-related genes and thalamic functional connectivity. Furthermore, they highlight the association between gene expression co-regulation and brain connectivity, such that genes with coordinated MD-DLPFC expression are associated with coordinated activity between the same brain regions. We suggest that gene co-expression is a plausible mechanism underlying biological phenotypes of schizophrenia.

Isolated fungus ball in sphenoid sinus: tips and pitfalls of T 1 hyperintense lesions.

Isolated sphenoid sinus fungus ball is a very rare condition. CT is the most used imaging investigation for diagnosis. In some cases, MRI may provide further information to evaluate the extracompartmental invasion. We report the case of an elderly female patient who presented with headache and a soft tissue mass filling the right sphenoid sinus on CT, misdiagnosed as simple sinusitis. After 1 year, with recrudescence of symptoms, brain MRI showed a hyperintense soft tissue mass on T 1 weighted images within the right sphenoidal sinus; a new CT examination revealed calcifications within the mass. Surgical histological examination showed fungus ball. Fungal ball should be included in the differential diagnosis of T 1 hyperintense lesions in the sphenoid sinus.

Transcriptomic context of DRD1 is associated with prefrontal activity and behavior during working memory.

Dopamine D1 receptor (D1R) signaling shapes prefrontal cortex (PFC) activity during working memory (WM). Previous reports found higher WM performance associated with alleles linked to greater expression of the gene coding for D1Rs (DRD1). However, there is no evidence on the relationship between genetic modulation of DRD1 expression in PFC and patterns of prefrontal activity during WM. Furthermore, previous studies have not considered that D1Rs are part of a coregulated molecular environment, which may contribute to D1R-related prefrontal WM processing. Thus, we hypothesized a reciprocal link between a coregulated (i.e., coexpressed) molecular network including DRD1 and PFC activity. To explore this relationship, we used three independent postmortem prefrontal mRNA datasets (total n = 404) to characterize a coexpression network including DRD1 Then, we indexed network coexpression using a measure (polygenic coexpression index-DRD1-PCI) combining the effect of single nucleotide polymorphisms (SNPs) on coexpression. Finally, we associated the DRD1-PCI with WM performance and related brain activity in independent samples of healthy participants (total n = 371). We identified and replicated a coexpression network including DRD1, whose coexpression was correlated with DRD1-PCI. We also found that DRD1-PCI was associated with lower PFC activity and higher WM performance. Behavioral and imaging results were replicated in independent samples. These findings suggest that genetically predicted expression of DRD1 and of its coexpression partners stratifies healthy individuals in terms of WM performance and related prefrontal activity. They also highlight genes and SNPs potentially relevant to pharmacological trials aimed to test cognitive enhancers modulating DRD1 signaling.