Creative thinking represents one of our highest-order cognitive processes, involving multiple cortical structures and an intricate interplay between several cortical and subcortical networks. It results in novel ideas that translate to useful products or concepts. The evolutionary purpose of creativity is therefore apparent, as it advances our adaptation and survival. Elucidating the neurobiology and neuroanatomy of creative cognition is challenging because the construct of creativity is not clearly defined, and the many neuropsychological measures attempting to assess it are often biased, leading to imprecise findings. Using examples from the medical and music fields, creativity is demonstrably linked to the default mode network (DMN), which has the unique property of becoming activated at times of "quiet wakefulness," facilitating "defaulted" internally focused cognitive operations. Creative thoughts result from a process involving the activation and deactivation of the DMN as part of a dynamic interplay shared with the central executive network and affective salience network. The question is posed whether seizures originating from DMN-related cortical areas should be considered as having overlap with eloquent cortex, potentially exempting them from removal in epilepsy surgery. PLAIN LANGUAGE SUMMARY: Creative thinking is a higher-order cognitive process involving multiple brain structures and networks. It results in insightful and original thoughts that translate to useful products or concepts, which allow us to adapt to our surroundings. This Narrative Review presents conceptual, investigational, and neurobiological aspects of creativity, including information about a unique brain network termed "default mode network (DMN)," which activates at times of "quiet wakefulness," facilitating internally focused cognitive operations. The review ends with a discussion on whether regions of the DMN from which seizures originate should be regarded as "eloquent" and their removal should be deferred by epilepsy surgery.
Intracerebral hemorrhages (ICH) during implantation of stereo-EEG electrodes are rare. The impact of tobacco-free nicotine consumption on periprocedural bleeding is uncertain. We present a 20+ year-old man with drug-resistant epilepsy who underwent stereo-EEG with 17 depth electrodes. Within a few days after insertion, the patient developed multiple ICHs in the electrode trajectories and an intradural hemorrhage after a diagnostic spinal tap. We performed the investigation of the clotting system and whole-exome sequencing (WES). WES identified a heterozygous mutation c.4698G>T, p.(Trp1566Cys) in COL4A2 (NM_001846.4) encoding a collagen type-IV alpha-2 chain inherited from his seemingly healthy mother. As COL4A2 mutations had been identified in four adult patients with ICH we postulated that the identified variant presents a potential risk factor. Notably, mutations encoding other collagens have been linked to cerebral hemorrhages (COL4A1) and increased propensity to trigger ICH upon smoking (COL1A2). Our patient consumed at least 24 oral nicotine pouches (containing 11 mg nicotine each) per day. We consider the patient's COL4A2 mutation in combination with his substantial nicotine consumption as likely predisposition to multiple ICHs precipitated by stereo-EEG. Patients with nicotine consumption and any collagen mutation may have a substantially higher risk for hemorrhagic complications in SEEG and other neurosurgical procedures.
A young man with drug-resistant epilepsy experienced multiple intracerebral hemorrhages after implantation of SEEG electrodes for presurgical evaluation and concomitantly a intradural hemorrhage after a lumbar spinal tap. A collagen IV mutation of unclear significance and heavy use of oral nicotine pouches were the only potential risk factors identified. As collagen mutations were previously described risk factors and smoking in particular worsens the bleeding risk in collagen mutations, further research is warranted to prevent hemorrhages in neurosurgical procedures. Nicotine consumption in any form is a preventable risk factor.
Vigabatrin-associated brain abnormalities on MRI (VABAM) are observed in approximately 20% of children who receive vigabatrin for treatment of infantile epileptic spasms syndrome. Although usually reversible and asymptomatic, VABAM is occasionally symptomatic. Whereas asymptomatic VABAM appears to be dose-dependent, symptomatic VABAM is possibly associated with co-administration of vigabatrin and hormonal therapy (i.e., corticosteroids or adrenocorticotropic hormone). With retrospective study of a cohort of vigabatrin-treated children, we evaluated candidate risk factors for VABAM. Among 108 children with detailed vigabatrin exposure data, we identified VABAM in 17 children (11 symptomatic). Symptomatic VABAM was strongly associated with simultaneous exposure to hormonal therapy (p = 0.001). Neither symptomatic nor asymptomatic VABAM were associated with peak vigabatrin dose. Although these data support the hypothesis that symptomatic VABAM risk is higher with coadministration of vigabatrin and hormonal therapy, this study does not establish a causal link. Further study is warranted to better understand the pathogenesis of VABAM and devise strategies to mitigate risk. Clinicians should carefully weigh the potential risk of symptomatic vigabatrin toxicity against the known benefit of vigabatrin and hormonal therapy coadministration.
Several case reports suggest that the combination of vigabatrin and hormonal therapy for treatment of infantile spasms may provoke an adverse reaction known as symptomatic vigabatrin MRI toxicity (sVABAM, which includes characteristic changes on MRI images and associated symptoms). In response to these reports, we studied a large single-center cohort of children with infantile spasms and determined that combination therapy is indeed statistically associated with sVABAM. However, we have not proven that combination therapy actually causes sVABAM. Further study is needed to clarify the nature of sVABAM and risk factors thereof.
While metabolic imbalances have been observed in individuals with epilepsy, the direct involvement of specific metabolites in the development of the condition remains underexplored. A comprehensive analysis of the causality between cerebrospinal fluid metabolites (CSF) and epilepsy is pivotal in discovering innovative therapeutic interventions and prophylactic approaches.
Summary data from genome-wide association studies (GWAS) of CSF metabolites and epilepsy subtypes were obtained separately. A total of 338 CSF metabolites were investigated as exposures, and 11 epilepsy phenotypes were examined as the outcomes. A two sample Mendelian randomization (MR) approach was utilized to explore the causal influence of these metabolites on epilepsy. Causality was primarily estimated through inverse variance weighted (IVW) analysis, complemented by a range of sensitivity analyses to ensure result stability. Additionally, reverse MR analysis was performed to explore the possibility of bidirectional causality.
The IVW method, reinforced by sensitivity analyses, pinpointed 17 CSF metabolites with causal implications for six epilepsy phenotypes. After False Discovery Rate (FDR) multiple testing correction, two metabolites (Methylmalonate and Gamma-glutamyl-alpha-lysine) were found to have robust causal links to epilepsy (p < 0.05 and FDR<0.05). The other 15 metabolites exhibited suggestive evidence of a causal association (p < 0.05 and FDR>0.05).
This study highlights CSF metabolites that could serve as valuable biomarkers and may be critical in developing targeted treatments and preventing epilepsy.
This study explores how certain chemicals in the brain fluid might influence the development of epilepsy, aiming to find new ways to treat or prevent it. Researchers looked at the relationship between 338 cerebrospinal fluid metabolites and 11 types of epilepsy using genetic data. They found that 17 of these chemicals could potentially cause six types of epilepsy. Two of these chemicals were strongly linked to epilepsy, suggesting they could be important for creating specific treatments or prevention strategies.
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