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Neurosurgical Focus Aug 2018Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed... (Review)
Review
Traumatic brain injury (TBI) is a looming epidemic, growing most rapidly in the elderly population. Some of the most devastating sequelae of TBI are related to depressed levels of consciousness (e.g., coma, minimally conscious state) or deficits in executive function. To date, pharmacological and rehabilitative therapies to treat these sequelae are limited. Deep brain stimulation (DBS) has been used to treat a number of pathologies, including Parkinson disease, essential tremor, and epilepsy. Animal and clinical research shows that targets addressing depressed levels of consciousness include components of the ascending reticular activating system and areas of the thalamus. Targets for improving executive function are more varied and include areas that modulate attention and memory, such as the frontal and prefrontal cortex, fornix, nucleus accumbens, internal capsule, thalamus, and some brainstem nuclei. The authors review the literature addressing the use of DBS to treat higher-order cognitive dysfunction and disorders of consciousness in TBI patients, while also offering suggestions on directions for future research.
Topics: Animals; Brain Injuries, Traumatic; Cognition; Consciousness; Deep Brain Stimulation; Epilepsy; Humans; Thalamus
PubMed: 30064315
DOI: 10.3171/2018.5.FOCUS18168 -
Translational Psychiatry May 2023The fornix is a white matter bundle located in the center of the hippocampaldiencephalic limbic circuit that controls memory and executive functions, yet its genetic...
The fornix is a white matter bundle located in the center of the hippocampaldiencephalic limbic circuit that controls memory and executive functions, yet its genetic architectures and involvement in brain disorders remain largely unknown. We carried out a genome-wide association analysis of 30,832 UK Biobank individuals of the six fornix diffusion magnetic resonance imaging (dMRI) traits. The post-GWAS analysis allowed us to identify causal genetic variants in phenotypes at the single nucleotide polymorphisms (SNP), locus, and gene levels, as well as genetic overlap with brain health-related traits. We further generalized our GWAS in adolescent brain cognitive development (ABCD) cohort. The GWAS identified 63 independent significant variants within 20 genomic loci associated (P < 8.33 × 10) with the six fornix dMRI traits. Geminin coiled-coil domain containing (GMNC) and NUAK family SNF1-like kinase 1 (NUAK1) gene were highlighted, which were found in UKB and replicated in ABCD. The heritability of the six traits ranged from 10% to 27%. Gene mapping strategies identified 213 genes, where 11 were supported by all of four methods. Gene-based analyses revealed pathways relating to cell development and differentiation, with astrocytes found to be significantly enriched. Pleiotropy analyses with eight neurological and psychiatric disorders revealed shared variants, especially with schizophrenia under the conjFDR threshold of 0.05. These findings advance our understanding of the complex genetic architectures of fornix and their relevance in neurological and psychiatric disorders.
Topics: Humans; Genetic Predisposition to Disease; Genome-Wide Association Study; White Matter; Phenotype; Schizophrenia; Polymorphism, Single Nucleotide; Protein Kinases; Repressor Proteins
PubMed: 37236919
DOI: 10.1038/s41398-023-02475-6 -
Cellular and Molecular Life Sciences :... Sep 2020Deep brain stimulation is used to alleviate symptoms of neurological and psychiatric disorders including Parkinson's disease, epilepsy, and... (Review)
Review
Deep brain stimulation is used to alleviate symptoms of neurological and psychiatric disorders including Parkinson's disease, epilepsy, and obsessive-compulsive-disorder. Electrically stimulating limbic structures has been of great interest, and in particular, the region of the fornix. We conducted a systematic search for studies that reported clinical and preclinical outcomes of deep brain stimulation within the fornix up to July 2019. We identified 13 studies (7 clinical, 6 preclinical) that examined the effects of fornix stimulation in Alzheimer's disease (n = 9), traumatic brain injury (n = 2), Rett syndrome (n = 1), and temporal lobe epilepsy (n = 1). Overall, fornix stimulation can lead to decreased rates of cognitive decline (in humans), enhanced memory (in humans and animals), visuo-spatial memorization (in humans and animals), and improving verbal recollection (in humans). While the exact mechanisms of action are not completely understood, studies suggest fornix DBS to be involved with increased functional connectivity and neurotransmitter levels, as well as enhanced neuroplasticity.
Topics: Alzheimer Disease; Animals; Brain Injuries, Traumatic; Deep Brain Stimulation; Epilepsy; Fornix, Brain; Humans; Memory; Memory Disorders; Rett Syndrome
PubMed: 31974655
DOI: 10.1007/s00018-020-03456-4 -
Cureus Apr 2024Background The aim of this study is to evaluate the clinical and radiological findings of metastatic tumors and primary brain tumors affecting the fornix. Methods ...
Background The aim of this study is to evaluate the clinical and radiological findings of metastatic tumors and primary brain tumors affecting the fornix. Methods Between January 2015 and March 2023, we retrospectively evaluated 1087 patients of both sexes who underwent cranial magnetic resonance imaging (MRI) for a preliminary diagnosis of intracranial malignancy in the radiology department of our hospital. Two radiologists with six and 10 years of experience in MRI examination assessed the relationship between primary and metastatic tumors and the fornix. Results Involvement of the fornix was diagnosed in 29 of the 1087 patients (2.66%), of which fornix was affected by metastatic lesions in 14 patients (48.2%) and primary tumors in 15 patients (51.7%). The majority of metastatic lesions were from lung and breast cancers, with other tumor types including osteosarcoma, renal cell carcinoma, pancreatic adenocarcinoma, pleomorphic sarcoma, and diffuse large B-cell lymphoma. Among all primary tumors, glioblastoma was the most common primary brain tumor invading the fornix, with other diagnoses including diffuse astrocytoma, medulloblastoma, and anaplastic oligodendroglioma. Metastatic and primary brain tumors affecting the fornix were detected over a broad timeline, from the time of diagnosis up to 120 months after diagnosis. A retrospective evaluation of medical records revealed memory deficits in four patients. Conclusion The fornix can be affected by both metastatic and primary brain tumors. It is crucial to understand the relevant neuroanatomical relationships when evaluating lesions that affect the fornix.
PubMed: 38689678
DOI: 10.7759/cureus.57612 -
Neurobiology of Learning and Memory Oct 2020Many neurological patients suffer from memory loss. To date, pharmacological treatments for memory disorders have limited and short-lasting effects. Therefore,... (Review)
Review
Many neurological patients suffer from memory loss. To date, pharmacological treatments for memory disorders have limited and short-lasting effects. Therefore, researchers are investigating novel therapies such as deep brain stimulation (DBS) to alleviate memory impairments. Up to now stimulation of the fornix, nucleus basalis of Meynert and entorhinal cortex have been found to enhance memory performance. Here, we provide an overview of the different DBS targets and mechanisms within the memory circuit, which could be relevant for enhancing memory in patients. Future studies are warranted, accelerating the efforts to further unravel mechanisms of action of DBS in memory-related disorders and develop stimulation protocols based on these mechanisms.
Topics: Alzheimer Disease; Animals; Basal Nucleus of Meynert; Brain; Cognition; Deep Brain Stimulation; Entorhinal Cortex; Fornix, Brain; Humans; Memory; Translational Research, Biomedical
PubMed: 32739395
DOI: 10.1016/j.nlm.2020.107283