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Stem Cell Research & Therapy Apr 2023The first human brain organoid protocol was presented in the beginning of the previous decade, and since then, the field witnessed the development of many new brain...
BACKGROUND
The first human brain organoid protocol was presented in the beginning of the previous decade, and since then, the field witnessed the development of many new brain region-specific models, and subsequent protocol adaptations and modifications. The vast amount of data available on brain organoid technology may be overwhelming for scientists new to the field and consequently decrease its accessibility. Here, we aimed at providing a practical guide for new researchers in the field by systematically reviewing human brain organoid publications.
METHODS
Articles published between 2010 and 2020 were selected and categorised for brain organoid applications. Those describing neurodevelopmental studies or protocols for novel organoid models were further analysed for culture duration of the brain organoids, protocol comparisons of key aspects of organoid generation, and performed functional characterisation assays. We then summarised the approaches taken for different models and analysed the application of small molecules and growth factors used to achieve organoid regionalisation. Finally, we analysed articles for organoid cell type compositions, the reported time points per cell type, and for immunofluorescence markers used to characterise different cell types.
RESULTS
Calcium imaging and patch clamp analysis were the most frequently used neuronal activity assays in brain organoids. Neural activity was shown in all analysed models, yet network activity was age, model, and assay dependent. Induction of dorsal forebrain organoids was primarily achieved through combined (dual) SMAD and Wnt signalling inhibition. Ventral forebrain organoid induction was performed with dual SMAD and Wnt signalling inhibition, together with additional activation of the Shh pathway. Cerebral organoids and dorsal forebrain model presented the most cell types between days 35 and 60. At 84 days, dorsal forebrain organoids contain astrocytes and potentially oligodendrocytes. Immunofluorescence analysis showed cell type-specific application of non-exclusive markers for multiple cell types.
CONCLUSIONS
We provide an easily accessible overview of human brain organoid cultures, which may help those working with brain organoids to define their choice of model, culture time, functional assay, differentiation, and characterisation strategies.
Topics: Humans; Brain; Organoids; Prosencephalon; Induced Pluripotent Stem Cells; Neurons; Cell Differentiation
PubMed: 37061699
DOI: 10.1186/s13287-023-03302-x -
Neuroscience and Biobehavioral Reviews Jul 2023In recent decades, numerous structural brain imaging studies investigated purported morphometric changes in early (EB) and late onset blindness (LB). The results of... (Meta-Analysis)
Meta-Analysis Review
In recent decades, numerous structural brain imaging studies investigated purported morphometric changes in early (EB) and late onset blindness (LB). The results of these studies have not yielded very consistent results, neither with respect to the type, nor to the anatomical locations of the brain morphometric alterations. To better characterize the effects of blindness on brain morphometry, we performed a systematic review and an Anatomical-Likelihood-Estimation (ALE) coordinate-based-meta-analysis of 65 eligible studies on brain structural changes in EB and LB, including 890 EB, 466 LB and 1257 sighted controls. Results revealed atrophic changes throughout the whole extent of the retino-geniculo-striate system in both EB and LB, whereas changes in areas beyond the occipital lobe occurred in EB only. We discuss the nature of some of the contradictory findings with respect to the used brain imaging methodologies and characteristics of the blind populations such as the onset, duration and cause of blindness. Future studies should aim for much larger sample sizes, eventually by merging data from different brain imaging centers using the same imaging sequences, opt for multimodal structural brain imaging, and go beyond a purely structural approach by combining functional with structural connectivity network analyses.
Topics: Humans; Likelihood Functions; Brain; Occipital Lobe; Blindness; Brain Mapping; Magnetic Resonance Imaging
PubMed: 37054803
DOI: 10.1016/j.neubiorev.2023.105165 -
Neurosurgery Sep 2023Focused ultrasound (FUS-T) and stereotactic radiosurgery thalamotomy (SRS-T) targeting the ventral intermediate nucleus are effective incisionless surgeries for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Focused ultrasound (FUS-T) and stereotactic radiosurgery thalamotomy (SRS-T) targeting the ventral intermediate nucleus are effective incisionless surgeries for essential tremor (ET). However, their efficacy for tremor reduction and, importantly, adverse event incidence have not been directly compared.
OBJECTIVE
To present a comprehensive systematic review with network meta-analysis examining both efficacy and adverse events (AEs) of FUS-T vs SRS-T for treating medically refractory ET.
METHODS
We conducted a systematic review and network meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the PubMed and Embase databases. We included all primary FUS-T/SRS-T studies with approximately 1-year follow-up, with unilateral Fahn-Tolosa-Marin Tremor Rating Scale or Clinical Rating Scale for Tremor scores prethalamotomy/post-thalamotomy and/or AEs. The primary efficacy outcome was Fahn-Tolosa-Marin Tremor Rating Scale A+B score reduction. AEs were reported as an estimated incidence.
RESULTS
Fifteen studies of 464 patients and 3 studies of 62 patients met inclusion criteria for FUS-T/SRS-T efficacy comparison, respectively. Network meta-analysis demonstrated similar tremor reduction between modalities (absolute tremor reduction: FUS-T: -11.6 (95% CI: -13.3, -9.9); SRS-T: -10.3 (95% CI: -14.2, -6.0). FUS-T had a greater 1-year adverse event rate, particularly imbalance and gait disturbances (10.5%) and sensory disturbances (8.3%). Contralateral hemiparesis (2.7%) often accompanied by speech impairment (2.4%) were most common after SRS-T. There was no correlation between efficacy and lesion volume.
CONCLUSION
Our systematic review found similar efficacy between FUS-T and SRS-T for ET, with trend toward higher efficacy yet greater adverse event incidence with FUS-T. Smaller lesion volumes could mitigate FUS-T off-target effects for greater safety.
Topics: Humans; Essential Tremor; Magnetic Resonance Imaging; Radiosurgery; Thalamus; Treatment Outcome; Tremor; Ultrasonic Surgical Procedures; Network Meta-Analysis
PubMed: 37010324
DOI: 10.1227/neu.0000000000002462 -
JAMA Psychiatry May 2023Individuals with bipolar disorder (BD) experience cognitive and emotional dysfunctions. Various brain circuits are implicated in BD but have not been investigated in a... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Individuals with bipolar disorder (BD) experience cognitive and emotional dysfunctions. Various brain circuits are implicated in BD but have not been investigated in a meta-analysis of functional magnetic resonance imaging (fMRI) studies.
OBJECTIVE
To investigate the brain functioning of individuals with BD compared with healthy control individuals in the domains of emotion processing, reward processing, and working memory.
DATA SOURCES
All fMRI experiments on BD published before March 2020, as identified in a literature search of PubMed, Embase, Web of Science, Cochrane Library, PsycInfo, Emcare, Academic Search Premier, and ScienceDirect. The literature search was conducted on February 21, 2017, and March 2, 2020, and data were analyzed from January 2021 to January 2022.
STUDY SELECTION
fMRI experiments comparing adult individuals with BD and healthy control individuals were selected if they reported whole-brain results, including a task assessing at least 1 of the domains. In total, 2320 studies were screened, and 253 full-text articles were evaluated.
DATA EXTRACTION AND SYNTHESIS
A total of 49 studies were included after selection procedure. Coordinates reporting significant activation differences between individuals with BD and healthy control individuals were extracted. Differences in brain region activity were tested using the activation likelihood estimation method.
MAIN OUTCOMES AND MEASURES
A whole-brain meta-analysis evaluated whether reported differences in brain activation in response to stimuli in 3 cognitive domains between individuals with BD and healthy control individuals were different.
RESULTS
The study population included 999 individuals with BD (551 [55.2%] female) and 1027 healthy control individuals (532 [51.8%] female). Compared with healthy control individuals, individuals with BD showed amygdala and hippocampal hyperactivity and hypoactivation in the inferior frontal gyrus during emotion processing (20 studies; 324 individuals with BD and 369 healthy control individuals), hyperactivation in the orbitofrontal cortex during reward processing (9 studies; 195 individuals with BD and 213 healthy control individuals), and hyperactivation in the ventromedial prefrontal cortex and subgenual anterior cingulate cortex during working memory (20 studies; 530 individuals with BD and 417 healthy control individuals). Limbic hyperactivation was only found during euthymia in the emotion and reward processing domains; abnormalities in frontal cortex activity were also found in individuals with BD with mania and depression.
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis revealed evidence for activity disturbances in key brain areas involved in cognitive and emotion processing in individuals with BD. Most of the regions are part of the fronto-limbic network. The results suggest that aberrations in the fronto-limbic network, present in both euthymic and symptomatic individuals, may be underlying cognitive and emotional dysfunctions in BD.
Topics: Adult; Humans; Female; Male; Bipolar Disorder; Brain; Emotions; Prefrontal Cortex; Magnetic Resonance Imaging; Cognition
PubMed: 36988918
DOI: 10.1001/jamapsychiatry.2023.0131 -
European Archives of... Sep 2023We aimed to summarize the available data on the objective rhinologic outcome after endoscopic transnasal-transsphenoidal (ETT) surgery. (Meta-Analysis)
Meta-Analysis
PURPOSE
We aimed to summarize the available data on the objective rhinologic outcome after endoscopic transnasal-transsphenoidal (ETT) surgery.
METHODS
Retrospective study on a consecutive cohort of treatment-naïve patients undergoing ETT pituitary gland surgery. Additionally, a systematic review and meta-analysis with focus on the rhinologic outcome, including postoperative smell function was performed.
RESULTS
The institutional series incorporated 168 patients. A concomitant endoscopic septoplasty was performed in 29/168 patients (17.3%). A nasoseptal flap was used for reconstruction of large skull-base defects or high-flow CSF leaks in 4/168 (2.4%) patients. Early postoperative rhinologic complications (< 4 weeks) included epistaxis (3%), acute rhinosinusitis (1.2%) and late postoperative complications (≥ 8 weeks) comprised prolonged crusting (15.6%), symptomatic synechiae (11.9%) and septal perforation (0.6%). Postoperative smell function was not impaired (Fisher's exact test, p = 1.0). The systematic review included 19 studies on 1533 patients with a median postoperative epistaxis rate of 1.4% (IQR 1.0-2.2), a postoperative acute rhinosinusitis rate of 2.3% (IQR 2.1-3.0), a postoperative synechiae rate of 7.5% (IQR 1.8-19.1) and a postoperative septal perforation rate of 2.2% (IQR 0.5-5.4). Seven studies including a total of 206 patients reported adequate outcome measures for smell function before and after ETT surgery. Only 2/7 studies reported an impairment of smell function postoperatively, especially in patients with nasoseptal flap harvesting.
CONCLUSION
Early and late postoperative rhinologic complication rates after ETT surgery for pituitary lesions seem to be low. A thorough evaluation of smell function, in particular in patients at risk for nasoseptal flap harvesting, may be an important factor in optimal postoperative care.
Topics: Humans; Retrospective Studies; Epistaxis; Surgical Flaps; Endoscopy; Pituitary Gland; Skull Base; Pituitary Diseases; Pituitary Neoplasms; Postoperative Complications; Treatment Outcome
PubMed: 36988686
DOI: 10.1007/s00405-023-07934-w -
Experimental Brain Research Apr 2023Over the last three decades, transcranial magnetic stimulation (TMS) has gained popularity as a tool to modulate human somatosensation. However, the effects of different... (Review)
Review
Over the last three decades, transcranial magnetic stimulation (TMS) has gained popularity as a tool to modulate human somatosensation. However, the effects of different stimulation types on the multiple distinct subdomains of somatosensation (e.g., tactile perception, proprioception and pain) have not been systematically compared. This is especially notable in the case of newer theta-burst stimulation protocols now in widespread use. Here, we aimed to systematically and critically review the existing TMS literature and provide a complete picture of current knowledge regarding the role of TMS in modulating human somatosensation across stimulation protocols and somatosensory domains. Following the PRISMA guidelines, fifty-four studies were included in the current review and were compared based on their methodologies and results. Overall, findings from these studies provide evidence that different types of somatosensation can be both disrupted and enhanced by targeted stimulation of specific somatosensory areas. Some mixed results, however, were reported in the literature. We discussed possible reasons for these mixed results, methodological limitations of existing investigations, and potential avenues for future research.
Topics: Humans; Transcranial Magnetic Stimulation; Somatosensory Cortex; Touch Perception; Pain
PubMed: 36949150
DOI: 10.1007/s00221-023-06579-9 -
Brain and Behavior Apr 2023Corpus callosotomy (CC) is appropriate for patients with seizures of a bilateral or diffuse origin, or those with seizures of a unilateral origin with rapid spread to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Corpus callosotomy (CC) is appropriate for patients with seizures of a bilateral or diffuse origin, or those with seizures of a unilateral origin with rapid spread to the contralateral cerebral hemisphere. The efficiency of CC in patients with drug-resistant epilepsy is a long-term concern because most articles reporting the surgical results of CC arise from small case series, and the durations of follow-up vary.
METHODS
PubMed, Embase, Cochrane Library, and Web of Science were searched to identify papers published before November 8, 2021. The systematic review was completed following PRISMA guidelines. Outcomes were analyzed by meta-analysis of the proportions.
RESULTS
A total of 1644 patients with drug-resistant epilepsy (49 retrospective or prospective case series studies) underwent CC, and the follow-up time of all patients was at least 1 year. The rate of complete seizure freedom (SF) was 12.38% (95% confidence interval [CI], 8.17%-17.21%). Meanwhile, the rate of complete SF from drop attacks was 61.86% (95% CI, 51.87%-71.41%). The rates of complete SF after total corpus callosotomy (TCC) and anterior corpus callosotomy (ACC) were 11.41% (95% CI, 5.33%-18.91%) and 6.75% (95% CI, 2.76%-11.85%), respectively. Additionally, the rate of complete SF from drop attacks after TCC was significantly higher than that after ACC (71.52%, 95% CI, 54.22%-86.35% vs. 57.11%, 95% CI, 42.17%-71.49%). The quality of evidence for the three outcomes by GRADE assessment was low to moderate.
CONCLUSION
There was no significant difference in the rate of complete SF between TCC and ACC. TCC had a significantly higher rate of complete SF from drop attacks than did ACC. Furthermore, CC for the treatment of drug-resistant epilepsy remains an important problem for further investigation because there are no universally accepted standardized guidelines for the extent of CC and its benefit to patients. In future research, we will focus on this issue.
Topics: Humans; Follow-Up Studies; Treatment Outcome; Retrospective Studies; Corpus Callosum; Seizures; Drug Resistant Epilepsy; Syncope
PubMed: 36929636
DOI: 10.1002/brb3.2964 -
Systematic Reviews Mar 2023Pineal gland calcification is the formation of corpora arenacea predominantly composed of calcium and phosphorus. It plays an important role in regulating the light/dark... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pineal gland calcification is the formation of corpora arenacea predominantly composed of calcium and phosphorus. It plays an important role in regulating the light/dark circadian changes to synchronize their daily physiological activities like feeding, metabolism, reproduction, and sleep through the secretion of melatonin. Therefore, this study aimed to assess the pooled prevalence of pineal gland calcification.
METHODS
A systematic review was done using published research articles from different electronic databases. Cross-sectional studies were included for systematic review and only studies conducted on the human population were included for quantitative analysis. Published articles were selected by assessing the title and abstract for relevance to the review objectives. Finally, the full text was retrieved for further assessment.
RESULTS
The pooled prevalence of pineal gland calcification was 61.65% [95% CI: 52.81, 70.49], with a heterogeneity of I = 97.7%, P ≤ 0.001. According to the qualitative analysis, an increase in age, male sex, and white ethnicity are the major socio-demographic characteristics that increase the prevalence of pineal gland calcification.
CONCLUSION
The pooled prevalence of pineal gland calcification was higher compared with reports from previous studies. Different studies reported pineal gland calcification was most prevalent in the adult population compared with the pediatric age groups. According to the qualitative analysis, an increase in age, male sex, and white ethnicity are the major socio-demographic characteristics that increase the prevalence of pineal gland calcification.
Topics: Adult; Humans; Child; Male; Cross-Sectional Studies; Pineal Gland; Prevalence; Calcium; Databases, Factual
PubMed: 36879256
DOI: 10.1186/s13643-023-02205-5 -
Seizure Mar 2023Despite significant advances in epileptology, there are still many uncertainties about the role of the insula in epilepsy. Until recently, most insular onset seizures...
PURPOSE
Despite significant advances in epileptology, there are still many uncertainties about the role of the insula in epilepsy. Until recently, most insular onset seizures were wrongly attributed to the temporal lobe. Further, there are no standardised approaches to the diagnosis and treatment of insular onset seizures. This systematic review gathers the available information about insular epilepsy and synthesizes current knowledge as a basis for future research.
METHOD
Adhering to the PRISMA guidelines, studies were meticulously extracted from the PubMed database. The empirical data pertaining to the semiology of insular seizures, insular networks in epilepsy, techniques of mapping the insula, and the surgical intricacies of non-lesional insular epilepsy were reviewed from published studies. The corpus of information available was then subjected to a process of concise summarization and astute synthesis.
RESULTS
Out of 235 studies identified for full-text review, 86 studies were included in the systematic review. The insula emerges as a brain region with a number of functional subdivisions. The semiology of insular seizures is diverse and depends on the involvement of particular subdivisions. The semiological heterogeneity of insular seizures is explained by the extensive connectivity of the insula and its subdivisions with all four lobes of the brain, deep grey matter structures, and remote brainstem areas. The mainstay of the diagnosis of seizure onset in the insula is stereoelectroencephalography (SEEG). The surgical resection of the insular epileptogenic zone (when possible) is the most effective treatment. Open surgery on the insula is challenging but magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) also holds promise.
CONCLUSION
The physiological and functional roles of the insula in epilepsy have remained obfuscated. The dearth of precisely defined diagnostic and therapeutic protocols acts as an impediment to scientific advancement. This review could potentially facilitate forthcoming research endeavours by establishing a foundational framework for uniform data collection protocols, thereby enhancing the feasibility of comparing findings across future studies and promoting progress in this domain.
Topics: Humans; Cerebral Cortex; Electroencephalography; Epilepsy; Seizures; Stereotaxic Techniques; Magnetic Resonance Imaging
PubMed: 36878050
DOI: 10.1016/j.seizure.2023.02.019 -
World Journal of Surgical Oncology Mar 2023Currently, endoscopic transsphenoidal surgery is the main treatment for pituitary neuroendocrine tumors (PitNETs). Excision of the tumor may have positive or negative... (Meta-Analysis)
Meta-Analysis
PURPOSE
Currently, endoscopic transsphenoidal surgery is the main treatment for pituitary neuroendocrine tumors (PitNETs). Excision of the tumor may have positive or negative effects on pituitary endocrine function, and the pituitary function of somatotroph tumors is a point of particular concern after the operation. This study aimed to conduct a meta-analysis on the effect of endoscopic transsphenoidal somatotroph tumor resection on pituitary function.
METHODS
A systematic literature search was conducted for articles that included the evaluation of pituitary target gland before and after endoscopic transsphenoidal pituitary tumor resection and were published between 1992 and 2022 in PubMed, Cochrane, and Ovid MEDLINE.
RESULTS
Sixty-eight studies that included biochemical remission rates in 4524 somatotroph tumors were concluded. According to the 2000 consensus, the biochemical remission rate after transsphenoidal endoscopic surgery was 66.4% (95% CI, 0.622-0.703; P = 0.000), the biochemical remission rate was 56.2% according to the 2010 consensus (95% CI, 0.503-0.620; P = 0.041), and with the rate of biochemical remission ranging from 30.0 to 91.7% with investigator's definition. After endoscopic resection, adrenal axis dysfunction was slightly higher than that before surgery, but the difference was not statistically significant. Hypothyroidism was 0.712 times higher risk than that before surgery (OR = 0.712; 95% CI, 0.527-0.961; P = 0.027). Hypogonadism was 0.541 times higher risk than that before surgery (OR = 0.541; 95% CI, 0.393-0.746; P = 0.000). Hyperprolactinemia was 0.131 times higher risk than that before surgery (OR = 0.131; 95% CI, 0.022-0.783; P = 0.026). The incidence of pituitary insufficiency was 1.344 times the risk before surgery after endoscopic resection of somatotroph tumors, but the difference was not statistically significant.
CONCLUSIONS
In patients with somatotroph tumors after undergoing endoscopic surgery, the risk of dysfunction and pituitary insufficiency tend to increase, while preoperative thyroid insufficiency, gonadal insufficiency, and hyperprolactinemia will be partially relieved.
Topics: Humans; Hyperprolactinemia; Somatotrophs; Pituitary Hormones; Endoscopy; Hypopituitarism; Pituitary Neoplasms
PubMed: 36859291
DOI: 10.1186/s12957-023-02958-2