Pub Date : 2023-02-27eCollection Date: 2023-01-01DOI: 10.3389/fnint.2023.1059679
Emily J Doherty, Cara A Spencer, Jeremy Burnison, Marta Čeko, Jenna Chin, Lucca Eloy, Kerstin Haring, Pilyoung Kim, Daniel Pittman, Shannon Powers, Samuel L Pugh, Demetris Roumis, Jaclyn A Stephens, Tom Yeh, Leanne Hirshfield
Functional Near-Infrared Spectroscopy (fNIRS) is an innovative and promising neuroimaging modality for studying brain activity in real-world environments. While fNIRS has seen rapid advancements in hardware, software, and research applications since its emergence nearly 30 years ago, limitations still exist regarding all three areas, where existing practices contribute to greater bias within the neuroscience research community. We spotlight fNIRS through the lens of different end-application users, including the unique perspective of a fNIRS manufacturer, and report the challenges of using this technology across several research disciplines and populations. Through the review of different research domains where fNIRS is utilized, we identify and address the presence of bias, specifically due to the restraints of current fNIRS technology, limited diversity among sample populations, and the societal prejudice that infiltrates today's research. Finally, we provide resources for minimizing bias in neuroscience research and an application agenda for the future use of fNIRS that is equitable, diverse, and inclusive.
{"title":"Interdisciplinary views of fNIRS: Current advancements, equity challenges, and an agenda for future needs of a diverse fNIRS research community.","authors":"Emily J Doherty, Cara A Spencer, Jeremy Burnison, Marta Čeko, Jenna Chin, Lucca Eloy, Kerstin Haring, Pilyoung Kim, Daniel Pittman, Shannon Powers, Samuel L Pugh, Demetris Roumis, Jaclyn A Stephens, Tom Yeh, Leanne Hirshfield","doi":"10.3389/fnint.2023.1059679","DOIUrl":"10.3389/fnint.2023.1059679","url":null,"abstract":"<p><p>Functional Near-Infrared Spectroscopy (fNIRS) is an innovative and promising neuroimaging modality for studying brain activity in real-world environments. While fNIRS has seen rapid advancements in hardware, software, and research applications since its emergence nearly 30 years ago, limitations still exist regarding all three areas, where existing practices contribute to greater bias within the neuroscience research community. We spotlight fNIRS through the lens of different end-application users, including the unique perspective of a fNIRS manufacturer, and report the challenges of using this technology across several research disciplines and populations. Through the review of different research domains where fNIRS is utilized, we identify and address the presence of bias, specifically due to the restraints of current fNIRS technology, limited diversity among sample populations, and the societal prejudice that infiltrates today's research. Finally, we provide resources for minimizing bias in neuroscience research and an application agenda for the future use of fNIRS that is equitable, diverse, and inclusive.</p>","PeriodicalId":56016,"journal":{"name":"Frontiers in Integrative Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10010439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10281134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnint.2023.1118240
Jeroen B J Smeets, Eli Brenner
The laws of physics and mathematics describe the world we live in as internally consistent. As these rules provide a very effective description, and our interaction with the world is also very effective, it seems self-evident that our perception follows these laws. As a result, when trying to explain imperfections in perception, we tend to impose consistency and introduce concepts such as deformations of visual space. In this review, we provide numerous examples that show that in many situations we perceive related attributes to have inconsistent values. We discuss how our tendency to assume consistency leads to erroneous conclusions on how we process sensory information. We propose that perception is not about creating a consistent internal representation of the outside world, but about answering specific questions about the outside world. As the information used to answer a question is specific for that question, this naturally leads to inconsistencies in perception and to an apparent dissociation between some perceptual judgments and related actions.
{"title":"The cost of aiming for the best answers: Inconsistent perception.","authors":"Jeroen B J Smeets, Eli Brenner","doi":"10.3389/fnint.2023.1118240","DOIUrl":"https://doi.org/10.3389/fnint.2023.1118240","url":null,"abstract":"<p><p>The laws of physics and mathematics describe the world we live in as internally consistent. As these rules provide a very effective description, and our interaction with the world is also very effective, it seems self-evident that our perception follows these laws. As a result, when trying to explain imperfections in perception, we tend to impose consistency and introduce concepts such as deformations of visual space. In this review, we provide numerous examples that show that in many situations we perceive related attributes to have inconsistent values. We discuss how our tendency to assume consistency leads to erroneous conclusions on how we process sensory information. We propose that perception is not about creating a consistent internal representation of the outside world, but about answering specific questions about the outside world. As the information used to answer a question is specific for that question, this naturally leads to inconsistencies in perception and to an apparent dissociation between some perceptual judgments and related actions.</p>","PeriodicalId":56016,"journal":{"name":"Frontiers in Integrative Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10114592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9444858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnint.2023.1145924
Zoé Dary, Christophe Lopez
The last two decades have seen a surge of interest in the mechanisms underpinning bodily self-consciousness (BSC). Studies showed that BSC relies on several bodily experiences (i.e., self-location, body ownership, agency, first-person perspective) and multisensory integration. The aim of this literature review is to summarize new insights and novel developments into the understanding of the neural bases of BSC, such as the contribution of the interoceptive signals to the neural mechanisms of BSC, and the overlap with the neural bases of conscious experience in general and of higher-level forms of self (i.e., the cognitive self). We also identify the main challenges and propose future perspectives that need to be conducted to progress into the understanding of the neural mechanisms of BSC. In particular, we point the lack of crosstalk and cross-fertilization between subdisciplines of integrative neuroscience to better understand BSC, especially the lack of research in animal models to decipher the neural networks and systems of neurotransmitters underpinning BSC. We highlight the need for more causal evidence that specific brain areas are instrumental in generating BSC and the need for studies tapping into interindividual differences in the phenomenal experience of BSC and their underlying mechanisms.
{"title":"Understanding the neural bases of bodily self-consciousness: recent achievements and main challenges.","authors":"Zoé Dary, Christophe Lopez","doi":"10.3389/fnint.2023.1145924","DOIUrl":"https://doi.org/10.3389/fnint.2023.1145924","url":null,"abstract":"<p><p>The last two decades have seen a surge of interest in the mechanisms underpinning bodily self-consciousness (BSC). Studies showed that BSC relies on several bodily experiences (i.e., self-location, body ownership, agency, first-person perspective) and multisensory integration. The aim of this literature review is to summarize new insights and novel developments into the understanding of the neural bases of BSC, such as the contribution of the interoceptive signals to the neural mechanisms of BSC, and the overlap with the neural bases of conscious experience in general and of higher-level forms of self (i.e., the cognitive self). We also identify the main challenges and propose future perspectives that need to be conducted to progress into the understanding of the neural mechanisms of BSC. In particular, we point the lack of crosstalk and cross-fertilization between subdisciplines of integrative neuroscience to better understand BSC, especially the lack of research in animal models to decipher the neural networks and systems of neurotransmitters underpinning BSC. We highlight the need for more causal evidence that specific brain areas are instrumental in generating BSC and the need for studies tapping into interindividual differences in the phenomenal experience of BSC and their underlying mechanisms.</p>","PeriodicalId":56016,"journal":{"name":"Frontiers in Integrative Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10316713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10160039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnint.2023.1234613
Mónica Del Carmen Alvarado-Navarrete, Adriana C Pliego-Carrillo, Claudia Ivette Ledesma-Ramírez, Carlos A Cuellar
The comprehension of the neural elements interacting in the spinal cord affected by vestibular input will contribute to the understanding of movement execution in normal and pathological conditions. In this context, Hoffman's reflex (H-reflex) has been used to evaluate transient excitability changes on the spinal cord descending pathways. The post-activation depression (P-AD) of the H-reflex consists of evoking consecutive responses (>1 Hz) provoking an amplitude depression, which has been shown to diminish in pathological conditions (i.e., spasticity, diabetic neuropathy). Galvanic Vestibular Stimulation (GVS) is a non-invasive method that activates the vestibular afferents and has been used to study the excitability of the H-reflex applied as a conditioning pulse. To our knowledge, there are no reports evaluating the P-AD during and after GVS. Our primary aim was to determine if GVS alters the P-AD evoked by stimulating the tibial nerve at 0.1, 1, 5, and 10 Hz, recording in the gastrocnemius and soleus muscles. Direct current stimulation of 2.0 ± 0.6 mA with the cathode ipsilateral (Ipsi) or contralateral (Contra) to the H-reflex electrode montage was applied bilaterally over the mastoid process in 19 healthy subjects. The P-AD's immediate post-GVS response (P Ipsi, P Contra) was also analyzed. Secondarily, we analyzed the excitability of the H-reflex during GVS. Responses evoked at 0.1 Hz with GVS, post-GVS, and a Control (no GVS) condition were used for comparisons. Our results show that P-AD persisted in all subjects despite increased excitability induced by GVS: statistical significance was found when comparing P-AD at 1, 5, and 10 Hz with the corresponding condition (Control, Ipsi, P Ipsi, Contra, P Contra) at 0.1 Hz (p < 0.001). Additionally, the increase in excitability produced by GVS was quantified for the first H-reflex of each P-AD stimulation frequency. The percentage change for all GVS conditions surpassed the Control by at least 20%, being statistically significant for Contra compared to Control (p < 0.01). In summary, although GVS increases the excitability of the vestibulospinal pathway at a premotor level, the neural inhibitory mechanism present in P-AD remains unaltered in healthy subjects.
{"title":"Post-activation depression of the Hoffman reflex is not altered by galvanic vestibular stimulation in healthy subjects.","authors":"Mónica Del Carmen Alvarado-Navarrete, Adriana C Pliego-Carrillo, Claudia Ivette Ledesma-Ramírez, Carlos A Cuellar","doi":"10.3389/fnint.2023.1234613","DOIUrl":"https://doi.org/10.3389/fnint.2023.1234613","url":null,"abstract":"<p><p>The comprehension of the neural elements interacting in the spinal cord affected by vestibular input will contribute to the understanding of movement execution in normal and pathological conditions. In this context, Hoffman's reflex (H-reflex) has been used to evaluate transient excitability changes on the spinal cord descending pathways. The post-activation depression (P-AD) of the H-reflex consists of evoking consecutive responses (>1 Hz) provoking an amplitude depression, which has been shown to diminish in pathological conditions (i.e., spasticity, diabetic neuropathy). Galvanic Vestibular Stimulation (GVS) is a non-invasive method that activates the vestibular afferents and has been used to study the excitability of the H-reflex applied as a conditioning pulse. To our knowledge, there are no reports evaluating the P-AD during and after GVS. Our primary aim was to determine if GVS alters the P-AD evoked by stimulating the tibial nerve at 0.1, 1, 5, and 10 Hz, recording in the gastrocnemius and soleus muscles. Direct current stimulation of 2.0 ± 0.6 mA with the cathode ipsilateral (Ipsi) or contralateral (Contra) to the H-reflex electrode montage was applied bilaterally over the mastoid process in 19 healthy subjects. The P-AD's immediate post-GVS response (P Ipsi, P Contra) was also analyzed. Secondarily, we analyzed the excitability of the H-reflex during GVS. Responses evoked at 0.1 Hz with GVS, post-GVS, and a Control (no GVS) condition were used for comparisons. Our results show that P-AD persisted in all subjects despite increased excitability induced by GVS: statistical significance was found when comparing P-AD at 1, 5, and 10 Hz with the corresponding condition (Control, Ipsi, P Ipsi, Contra, P Contra) at 0.1 Hz (<i>p</i> < 0.001). Additionally, the increase in excitability produced by GVS was quantified for the first H-reflex of each P-AD stimulation frequency. The percentage change for all GVS conditions surpassed the Control by at least 20%, being statistically significant for Contra compared to Control (<i>p</i> < 0.01). In summary, although GVS increases the excitability of the vestibulospinal pathway at a premotor level, the neural inhibitory mechanism present in P-AD remains unaltered in healthy subjects.</p>","PeriodicalId":56016,"journal":{"name":"Frontiers in Integrative Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10499171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10268131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnint.2023.1254972
Paul F Smith
Many studies have documented cognitive deficits, especially spatial cognitive deficits, in patients with some form of vestibular loss. Almost 20 years ago, hippocampal (HPC) atrophy was reported to be correlated with spatial memory deficits in such patients and the idea has gradually emerged that HPC atrophy may be causally responsible for the cognitive deficits. However, the results of studies of HPC volume following vestibular loss have not always been consistent, and a number of studies have reported no evidence of HPC atrophy. This paper argues that HPC atrophy, if it does occur following vestibular loss, may not be directly, causally responsible for the cognitive deficits, and that it is more likely that rapid functional changes in the HPC are responsible, due to the interruption of the transmission of vestibular information to the HPC. The argument presented here rests on 3 tranches of evidence: (1) Cognitive deficits have been observed in humans even in the absence of HPC atrophy; (2) HPC atrophy has not been reported in animal studies following vestibular loss, despite cognitive deficits; and (3) Animal studies have shown that the interruption of the transmission of vestibular information to the HPC has immediate consequences for HPC place cells, far too quickly to be explained by HPC atrophy. It is possible that HPC atrophy, when it does occur, is related to the longer-term consquences of living with vestibular loss, which are likely to increase circulating cortisol.
{"title":"Interpreting the meaning of changes in hippocampal volume associated with vestibular loss.","authors":"Paul F Smith","doi":"10.3389/fnint.2023.1254972","DOIUrl":"https://doi.org/10.3389/fnint.2023.1254972","url":null,"abstract":"<p><p>Many studies have documented cognitive deficits, especially spatial cognitive deficits, in patients with some form of vestibular loss. Almost 20 years ago, hippocampal (HPC) atrophy was reported to be correlated with spatial memory deficits in such patients and the idea has gradually emerged that HPC atrophy may be causally responsible for the cognitive deficits. However, the results of studies of HPC volume following vestibular loss have not always been consistent, and a number of studies have reported no evidence of HPC atrophy. This paper argues that HPC atrophy, if it does occur following vestibular loss, may not be directly, causally responsible for the cognitive deficits, and that it is more likely that rapid functional changes in the HPC are responsible, due to the interruption of the transmission of vestibular information to the HPC. The argument presented here rests on 3 tranches of evidence: (1) Cognitive deficits have been observed in humans even in the absence of HPC atrophy; (2) HPC atrophy has not been reported in animal studies following vestibular loss, despite cognitive deficits; and (3) Animal studies have shown that the interruption of the transmission of vestibular information to the HPC has immediate consequences for HPC place cells, far too quickly to be explained by HPC atrophy. It is possible that HPC atrophy, when it does occur, is related to the longer-term consquences of living with vestibular loss, which are likely to increase circulating cortisol.</p>","PeriodicalId":56016,"journal":{"name":"Frontiers in Integrative Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10440551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10058014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: One factor which influences the speech intelligibility of cochlear implant (CI) users is the number and the extent of the functionality of spiral ganglion neurons (SGNs), referred to as "cochlear health." To explain the interindividual variability in speech perception of CI users, a clinically applicable estimate of cochlear health could be insightful. The change in the slope of the electrically evoked compound action potentials (eCAP), amplitude growth function (AGF) as a response to increased interphase gap (IPG) (IPGEslope) has been introduced as a potential measure of cochlear health. Although this measure has been widely used in research, its relationship to other parameters requires further investigation.
Methods: This study investigated the relationship between IPGEslope, demographics and speech intelligibility by (1) considering the relative importance of each frequency band to speech perception, and (2) investigating the effect of the stimulus polarity of the stimulating pulse. The eCAPs were measured in three different conditions: (1) Forward masking with anodic-leading (FMA) pulse, (2) Forward masking with cathodic-leading (FMC) pulse, and (3) with alternating polarity (AP). This allowed the investigation of the effect of polarity on the diagnosis of cochlear health. For an accurate investigation of the correlation between IPGEslope and speech intelligibility, a weighting function was applied to the measured IPGEslopes on each electrode in the array to consider the relative importance of each frequency band for speech perception. A weighted Pearson correlation analysis was also applied to compensate for the effect of missing data by giving higher weights to the ears with more successful IPGEslope measurements.
Results: A significant correlation was observed between IPGEslope and speech perception in both quiet and noise for between-subject data especially when the relative importance of frequency bands was considered. A strong and significant correlation was also observed between IPGEslope and age when stimulation was performed with cathodic-leading pulses but not for the anodic-leading pulse condition.
Conclusion: Based on the outcome of this study it can be concluded that IPGEslope has potential as a relevant clinical measure indicative of cochlear health and its relationship to speech intelligibility. The polarity of the stimulating pulse could influence the diagnostic potential of IPGEslope.
{"title":"Factors influencing the relationship between cochlear health measures and speech recognition in cochlear implant users.","authors":"Ladan Zamaninezhad, Berkutay Mert, Heval Benav, Jochen Tillein, Carolyn Garnham, Uwe Baumann","doi":"10.3389/fnint.2023.1125712","DOIUrl":"https://doi.org/10.3389/fnint.2023.1125712","url":null,"abstract":"<p><strong>Background: </strong>One factor which influences the speech intelligibility of cochlear implant (CI) users is the number and the extent of the functionality of spiral ganglion neurons (SGNs), referred to as \"cochlear health.\" To explain the interindividual variability in speech perception of CI users, a clinically applicable estimate of cochlear health could be insightful. The change in the slope of the electrically evoked compound action potentials (eCAP), amplitude growth function (AGF) as a response to increased interphase gap (IPG) (IPGE<sub><i>slope</i></sub>) has been introduced as a potential measure of cochlear health. Although this measure has been widely used in research, its relationship to other parameters requires further investigation.</p><p><strong>Methods: </strong>This study investigated the relationship between IPGE<sub><i>slope</i></sub>, demographics and speech intelligibility by (1) considering the relative importance of each frequency band to speech perception, and (2) investigating the effect of the stimulus polarity of the stimulating pulse. The eCAPs were measured in three different conditions: (1) Forward masking with anodic-leading (FMA) pulse, (2) Forward masking with cathodic-leading (FMC) pulse, and (3) with alternating polarity (AP). This allowed the investigation of the effect of polarity on the diagnosis of cochlear health. For an accurate investigation of the correlation between IPGE<sub><i>slope</i></sub> and speech intelligibility, a weighting function was applied to the measured IPGE<sub><i>slopes</i></sub> on each electrode in the array to consider the relative importance of each frequency band for speech perception. A weighted Pearson correlation analysis was also applied to compensate for the effect of missing data by giving higher weights to the ears with more successful IPGE<sub><i>slope</i></sub> measurements.</p><p><strong>Results: </strong>A significant correlation was observed between IPGE<sub><i>slope</i></sub> and speech perception in both quiet and noise for between-subject data especially when the relative importance of frequency bands was considered. A strong and significant correlation was also observed between IPGE<sub><i>slope</i></sub> and age when stimulation was performed with cathodic-leading pulses but not for the anodic-leading pulse condition.</p><p><strong>Conclusion: </strong>Based on the outcome of this study it can be concluded that IPGE<sub><i>slope</i></sub> has potential as a relevant clinical measure indicative of cochlear health and its relationship to speech intelligibility. The polarity of the stimulating pulse could influence the diagnostic potential of IPGE<sub><i>slope</i></sub>.</p>","PeriodicalId":56016,"journal":{"name":"Frontiers in Integrative Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10213548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10212975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnint.2023.1128529
Matthew N Svalina, Regina Sullivan, Diego Restrepo, Molly M Huntsman
Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a repeat expansion mutation in the promotor region of the FMR1 gene resulting in transcriptional silencing and loss of function of fragile X messenger ribonucleoprotein 1 protein (FMRP). FMRP has a well-defined role in the early development of the brain. Thus, loss of the FMRP has well-known consequences for normal cellular and synaptic development leading to a variety of neuropsychiatric disorders including an increased prevalence of amygdala-based disorders. Despite our detailed understanding of the pathophysiology of FXS, the precise cellular and circuit-level underpinnings of amygdala-based disorders is incompletely understood. In this review, we discuss the development of the amygdala, the role of neuromodulation in the critical period plasticity, and recent advances in our understanding of how synaptic and circuit-level changes in the basolateral amygdala contribute to the behavioral manifestations seen in FXS.
脆性X综合征(Fragile X syndrome, FXS)是一种由脆性X信使核糖核蛋白1 (FMRP)启动子区域重复扩增突变导致的神经发育障碍,导致脆性X信使核糖核蛋白1蛋白(FMRP)转录沉默和功能丧失。FMRP在大脑的早期发育中有着明确的作用。因此,FMRP的缺失对正常的细胞和突触发育造成了众所周知的后果,导致各种神经精神疾病,包括杏仁核基础疾病的患病率增加。尽管我们对FXS的病理生理学有了详细的了解,但对杏仁核基础疾病的精确细胞和电路水平的基础还不完全了解。在这篇综述中,我们讨论了杏仁核的发育,神经调节在关键期可塑性中的作用,以及我们对基底外侧杏仁核突触和回路水平变化如何影响FXS行为表现的理解的最新进展。
{"title":"From circuits to behavior: Amygdala dysfunction in fragile X syndrome.","authors":"Matthew N Svalina, Regina Sullivan, Diego Restrepo, Molly M Huntsman","doi":"10.3389/fnint.2023.1128529","DOIUrl":"https://doi.org/10.3389/fnint.2023.1128529","url":null,"abstract":"<p><p>Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a repeat expansion mutation in the promotor region of the <i>FMR1</i> gene resulting in transcriptional silencing and loss of function of fragile X messenger ribonucleoprotein 1 protein (FMRP). FMRP has a well-defined role in the early development of the brain. Thus, loss of the FMRP has well-known consequences for normal cellular and synaptic development leading to a variety of neuropsychiatric disorders including an increased prevalence of amygdala-based disorders. Despite our detailed understanding of the pathophysiology of FXS, the precise cellular and circuit-level underpinnings of amygdala-based disorders is incompletely understood. In this review, we discuss the development of the amygdala, the role of neuromodulation in the critical period plasticity, and recent advances in our understanding of how synaptic and circuit-level changes in the basolateral amygdala contribute to the behavioral manifestations seen in FXS.</p>","PeriodicalId":56016,"journal":{"name":"Frontiers in Integrative Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9546055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnint.2023.898215
Jordan E Norris, Lauren M Schmitt, Lisa A De Stefano, Ernest V Pedapati, Craig A Erickson, John A Sweeney, Lauren E Ethridge
Introduction: Fragile X Syndrome (FXS) is rare genetic condition characterized by a repeat expansion (CGG) in the Fragile X messenger ribonucleoprotein 1 (FMR1) gene where individuals with greater than 200 repeats are defined as full mutation. FXS clinical presentation often includes intellectual disability, and autism-like symptoms, including anxiety and sensory hypersensitivities. Individuals with 55 to <200 CGG repeats are said to have the FMR1 premutation, which is not associated with primary characteristics of the full mutation, but with an increased risk for anxiety, depression, and other affective conditions, as well as and impaired cognitive processing differences that vary in severity. Defining subgroups of premutation carriers based on distinct biological features may identify subgroups with varying levels of psychiatric, cognitive, and behavioral alterations.
Methods: The current pilot study utilized 3 cluster subgroupings defined by previous k means cluster analysis on neuropsychiatric, cognitive, and resting EEG variables in order to examine basic sensory auditory chirp task-based EEG parameters from 33 females with the FMR1 premutation (ages 17-78).
Results: Based on the predefined, neuropsychiatric three-cluster solution, premutation carriers with increased neuropsychiatric features and higher CGG repeat counts (cluster 1) showed decreased stimulus onset response, similar to previous ERP findings across a number of psychiatric disorders but opposite to findings in individuals with full mutation FXS. Premutation carriers with increased executive dysfunction and resting gamma power (cluster 2) exhibited decreased gamma phase locking to a chirp stimulus, similar to individuals with full mutation FXS. Cluster 3 members, who were relatively unaffected by psychiatric or cognitive symptoms, showed the most normative task-based EEG metrics.
Discussion: Our findings suggest a spectrum of sensory processing characteristics present in subgroups of premutation carriers that have been previously understudied due to lack of overall group differences. Our findings also further validate the pre-defined clinical subgroups by supporting links between disturbances in well-defined neural pathways and behavioral alterations that may be informative for identifying the mechanisms supporting specific risk factors and divergent therapeutic needs in individuals with the FMR1 premutation.
{"title":"Neuropsychiatric feature-based subgrouping reveals neural sensory processing spectrum in female FMR1 premutation carriers: A pilot study.","authors":"Jordan E Norris, Lauren M Schmitt, Lisa A De Stefano, Ernest V Pedapati, Craig A Erickson, John A Sweeney, Lauren E Ethridge","doi":"10.3389/fnint.2023.898215","DOIUrl":"https://doi.org/10.3389/fnint.2023.898215","url":null,"abstract":"<p><strong>Introduction: </strong>Fragile X Syndrome (FXS) is rare genetic condition characterized by a repeat expansion (CGG) in the Fragile X messenger ribonucleoprotein 1 (FMR1) gene where individuals with greater than 200 repeats are defined as full mutation. FXS clinical presentation often includes intellectual disability, and autism-like symptoms, including anxiety and sensory hypersensitivities. Individuals with 55 to <200 CGG repeats are said to have the FMR1 premutation, which is not associated with primary characteristics of the full mutation, but with an increased risk for anxiety, depression, and other affective conditions, as well as and impaired cognitive processing differences that vary in severity. Defining subgroups of premutation carriers based on distinct biological features may identify subgroups with varying levels of psychiatric, cognitive, and behavioral alterations.</p><p><strong>Methods: </strong>The current pilot study utilized 3 cluster subgroupings defined by previous k means cluster analysis on neuropsychiatric, cognitive, and resting EEG variables in order to examine basic sensory auditory chirp task-based EEG parameters from 33 females with the FMR1 premutation (ages 17-78).</p><p><strong>Results: </strong>Based on the predefined, neuropsychiatric three-cluster solution, premutation carriers with increased neuropsychiatric features and higher CGG repeat counts (cluster 1) showed decreased stimulus onset response, similar to previous ERP findings across a number of psychiatric disorders but opposite to findings in individuals with full mutation FXS. Premutation carriers with increased executive dysfunction and resting gamma power (cluster 2) exhibited decreased gamma phase locking to a chirp stimulus, similar to individuals with full mutation FXS. Cluster 3 members, who were relatively unaffected by psychiatric or cognitive symptoms, showed the most normative task-based EEG metrics.</p><p><strong>Discussion: </strong>Our findings suggest a spectrum of sensory processing characteristics present in subgroups of premutation carriers that have been previously understudied due to lack of overall group differences. Our findings also further validate the pre-defined clinical subgroups by supporting links between disturbances in well-defined neural pathways and behavioral alterations that may be informative for identifying the mechanisms supporting specific risk factors and divergent therapeutic needs in individuals with the FMR1 premutation.</p>","PeriodicalId":56016,"journal":{"name":"Frontiers in Integrative Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10766165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.3389/fnint.2023.1207610
Daniel L Cooke, Hui Shen, Madhavi Duvvuri, Daniel Thompson, Thomas Neylan, William Wolfe, Steven Hetts, Bruce Ovbiagele, Mary Whooley, Beth Cohen
Background: Brain aneurysms represent a significant cause of hemorrhagic stroke. Prior research has demonstrated links between stress and stroke, including brain aneurysms. We aimed to determine relationships between select psychiatric disorders and aneurysms and aneurysmal SAH.
Methods: We performed retrospective, case-control study of a National Veterans Affairs population with two experimental groups (aneurysm-only and aneurysmal SAH) and 10-fold controls per group matched by age, date, and clinical data source. The studied the presence of 4 psychiatric disorders: Posttraumatic stress disorder (PTSD), major depressive disorder (MDD), generalized anxiety disorder (GAD), and other mood disorders. Our main outcomes Unadjusted and multivariable adjusted ORs of PTSD, MDD, GAD, and mood disorders within aneurysm-only and aSAH groups.
Results: In 6,320,789 US Veterans who were enrolled for at least 5 years in Medicare and/or the Veterans Health Administration, we identified 35,094 cases of aneurysm without SAH and 5,749 cases of aneurysm with SAH between 1/2005 and 12/2019. In analyses adjusted for sex, hypertension, and tobacco use, patients with aneurysm were more likely than matched controls to have a history of PTSD (OR 1.48), MDD (OR 1.33), GAD (OR 1.26), and other mood disorders (OR 1.34) (all p-values < 0.0001). Similarly, patients with aSAH were more likely than controls to have a history of PTSD (OR 1.35), MDD (OR 1.38), GAD (OR 1.18), and other mood disorders (OR 1.30) (all p-values < 0.0001).
Conclusion: The study, the largest of its kind, further suggests links between psychiatric disorders and stroke. This is important as patients with aneurysms are not routinely screened for such psychiatric risk factors. Additional research on this topic could lead to novel strategies to improve stroke prevention.
{"title":"Association of select psychiatric disorders with incident brain aneurysm and subarachnoid hemorrhage among veterans.","authors":"Daniel L Cooke, Hui Shen, Madhavi Duvvuri, Daniel Thompson, Thomas Neylan, William Wolfe, Steven Hetts, Bruce Ovbiagele, Mary Whooley, Beth Cohen","doi":"10.3389/fnint.2023.1207610","DOIUrl":"https://doi.org/10.3389/fnint.2023.1207610","url":null,"abstract":"<p><strong>Background: </strong>Brain aneurysms represent a significant cause of hemorrhagic stroke. Prior research has demonstrated links between stress and stroke, including brain aneurysms. We aimed to determine relationships between select psychiatric disorders and aneurysms and aneurysmal SAH.</p><p><strong>Methods: </strong>We performed retrospective, case-control study of a National Veterans Affairs population with two experimental groups (aneurysm-only and aneurysmal SAH) and 10-fold controls per group matched by age, date, and clinical data source. The studied the presence of 4 psychiatric disorders: Posttraumatic stress disorder (PTSD), major depressive disorder (MDD), generalized anxiety disorder (GAD), and other mood disorders. Our main outcomes Unadjusted and multivariable adjusted ORs of PTSD, MDD, GAD, and mood disorders within aneurysm-only and aSAH groups.</p><p><strong>Results: </strong>In 6,320,789 US Veterans who were enrolled for at least 5 years in Medicare and/or the Veterans Health Administration, we identified 35,094 cases of aneurysm without SAH and 5,749 cases of aneurysm with SAH between 1/2005 and 12/2019. In analyses adjusted for sex, hypertension, and tobacco use, patients with aneurysm were more likely than matched controls to have a history of PTSD (OR 1.48), MDD (OR 1.33), GAD (OR 1.26), and other mood disorders (OR 1.34) (all <i>p</i>-values < 0.0001). Similarly, patients with aSAH were more likely than controls to have a history of PTSD (OR 1.35), MDD (OR 1.38), GAD (OR 1.18), and other mood disorders (OR 1.30) (all <i>p</i>-values < 0.0001).</p><p><strong>Conclusion: </strong>The study, the largest of its kind, further suggests links between psychiatric disorders and stroke. This is important as patients with aneurysms are not routinely screened for such psychiatric risk factors. Additional research on this topic could lead to novel strategies to improve stroke prevention.</p>","PeriodicalId":56016,"journal":{"name":"Frontiers in Integrative Neuroscience","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10433370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10105524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}