Pub Date : 2023-06-07DOI: 10.1101/2023.06.05.543812
Li-Ann Leow, Anjeli Marcos, Esteban Nielsen, David K. Sewell, Tim Ballard, P. Dux, H. Filmer
Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), show promise in treating a range of psychiatric and neurologic conditions. However, optimization of such applications requires a better understanding of how tDCS alters cognition and behavior. Existing evidence implicates dopamine in tDCS alterations of brain activity and plasticity; however, there is as yet no causal evidence for a role of dopamine in tDCS effects on cognition and behavior. Here, in a preregistered, double-blinded study, we examined how pharmacologically manipulating dopamine altered the effect of tDCS on the speed–accuracy trade-off, which taps ubiquitous strategic operations. Cathodal tDCS was delivered over the left prefrontal cortex and the superior medial frontal cortex before participants (N = 62, 24 males, 38 females) completed a dot-motion task, making judgments on the direction of a field of moving dots under instructions to emphasize speed, accuracy, or both. We leveraged computational modeling to uncover how our interventions altered latent decisional processes driving the speed–accuracy trade-off. We show that dopamine in combination with tDCS (but not tDCS alone nor dopamine alone) not only impaired decision accuracy but also impaired discriminability, which suggests that these manipulations altered the encoding or representation of discriminative evidence. This is, to the best of our knowledge, the first direct evidence implicating dopamine in the way tDCS affects cognition and behavior. SIGNIFICANCE STATEMENT tDCS can improve cognitive and behavioral impairments in clinical conditions; however, a better understanding of its mechanisms is required to optimize future clinical applications. Here, using a pharmacological approach to manipulate brain dopamine levels in healthy adults, we demonstrate a role for dopamine in the effects of tDCS in the speed–accuracy trade-off, a strategic cognitive process ubiquitous in many contexts. In doing so, we provide direct evidence implicating dopamine in the way tDCS affects cognition and behavior.
{"title":"Dopamine Alters the Effect of Brain Stimulation on Decision-Making","authors":"Li-Ann Leow, Anjeli Marcos, Esteban Nielsen, David K. Sewell, Tim Ballard, P. Dux, H. Filmer","doi":"10.1101/2023.06.05.543812","DOIUrl":"https://doi.org/10.1101/2023.06.05.543812","url":null,"abstract":"Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), show promise in treating a range of psychiatric and neurologic conditions. However, optimization of such applications requires a better understanding of how tDCS alters cognition and behavior. Existing evidence implicates dopamine in tDCS alterations of brain activity and plasticity; however, there is as yet no causal evidence for a role of dopamine in tDCS effects on cognition and behavior. Here, in a preregistered, double-blinded study, we examined how pharmacologically manipulating dopamine altered the effect of tDCS on the speed–accuracy trade-off, which taps ubiquitous strategic operations. Cathodal tDCS was delivered over the left prefrontal cortex and the superior medial frontal cortex before participants (N = 62, 24 males, 38 females) completed a dot-motion task, making judgments on the direction of a field of moving dots under instructions to emphasize speed, accuracy, or both. We leveraged computational modeling to uncover how our interventions altered latent decisional processes driving the speed–accuracy trade-off. We show that dopamine in combination with tDCS (but not tDCS alone nor dopamine alone) not only impaired decision accuracy but also impaired discriminability, which suggests that these manipulations altered the encoding or representation of discriminative evidence. This is, to the best of our knowledge, the first direct evidence implicating dopamine in the way tDCS affects cognition and behavior. SIGNIFICANCE STATEMENT tDCS can improve cognitive and behavioral impairments in clinical conditions; however, a better understanding of its mechanisms is required to optimize future clinical applications. Here, using a pharmacological approach to manipulate brain dopamine levels in healthy adults, we demonstrate a role for dopamine in the effects of tDCS in the speed–accuracy trade-off, a strategic cognitive process ubiquitous in many contexts. In doing so, we provide direct evidence implicating dopamine in the way tDCS affects cognition and behavior.","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"25 1","pages":"6909 - 6919"},"PeriodicalIF":0.0,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86376301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-07DOI: 10.1523/JNEUROSCI.twij.43.23.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/JNEUROSCI.twij.43.23.2023","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.twij.43.23.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"56 1","pages":"4190 - 4190"},"PeriodicalIF":0.0,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85968512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Lang, Kenyaria V. Noble, J. Barth, J. Rumschlag, Tyreek R. Jenkins, Shelby Storm, M. Eckert, J. Dubno, B. A. Schulte
Age-related hearing loss, or presbyacusis, is a common degenerative disorder affecting communication and quality of life for millions of older adults. Multiple pathophysiologic manifestations, along with many cellular and molecular alterations, have been linked to presbyacusis; however, the initial events and causal factors have not been clearly established. Comparisons of the transcriptome in the lateral wall (LW) with other cochlear regions in a mouse model (of both sexes) of “normal” age-related hearing loss revealed that early pathophysiological alterations in the stria vascularis (SV) are associated with increased macrophage activation and a molecular signature indicative of inflammaging, a common form of immune dysfunction. Structure-function correlation analyses in mice across the lifespan showed that the age-dependent increase in macrophage activation in the stria vascularis is associated with a decline in auditory sensitivity. High-resolution imaging analysis of macrophage activation in middle-aged and aged mouse and human cochleas, along with transcriptomic analysis of age-dependent changes in mouse cochlear macrophage gene expression, support the hypothesis that aberrant macrophage activity is an important contributor to age-dependent strial dysfunction, cochlear pathology, and hearing loss. Thus, this study highlights the SV as a primary site of age-related cochlear degeneration and aberrant macrophage activity and dysregulation of the immune system as early indicators of age-related cochlear pathology and hearing loss. Importantly, novel new imaging methods described here now provide a means to analyze human temporal bones in a way that had not previously been feasible and thereby represent a significant new tool for otopathological evaluation. SIGNIFICANCE STATEMENT Age-related hearing loss is a common neurodegenerative disorder affecting communication and quality of life. Current interventions (primarily hearing aids and cochlear implants) offer imperfect and often unsuccessful therapeutic outcomes. Identification of early pathology and causal factors is crucial for the development of new treatments and early diagnostic tests. Here, we find that the SV, a nonsensory component of the cochlea, is an early site of structural and functional pathology in mice and humans that is characterized by aberrant immune cell activity. We also establish a new technique for evaluating cochleas from human temporal bones, an important but understudied area of research because of a lack of well-preserved human specimens and difficult tissue preparation and processing approaches.
{"title":"The Stria Vascularis in Mice and Humans Is an Early Site of Age-Related Cochlear Degeneration, Macrophage Dysfunction, and Inflammation","authors":"H. Lang, Kenyaria V. Noble, J. Barth, J. Rumschlag, Tyreek R. Jenkins, Shelby Storm, M. Eckert, J. Dubno, B. A. Schulte","doi":"10.2139/ssrn.4226200","DOIUrl":"https://doi.org/10.2139/ssrn.4226200","url":null,"abstract":"Age-related hearing loss, or presbyacusis, is a common degenerative disorder affecting communication and quality of life for millions of older adults. Multiple pathophysiologic manifestations, along with many cellular and molecular alterations, have been linked to presbyacusis; however, the initial events and causal factors have not been clearly established. Comparisons of the transcriptome in the lateral wall (LW) with other cochlear regions in a mouse model (of both sexes) of “normal” age-related hearing loss revealed that early pathophysiological alterations in the stria vascularis (SV) are associated with increased macrophage activation and a molecular signature indicative of inflammaging, a common form of immune dysfunction. Structure-function correlation analyses in mice across the lifespan showed that the age-dependent increase in macrophage activation in the stria vascularis is associated with a decline in auditory sensitivity. High-resolution imaging analysis of macrophage activation in middle-aged and aged mouse and human cochleas, along with transcriptomic analysis of age-dependent changes in mouse cochlear macrophage gene expression, support the hypothesis that aberrant macrophage activity is an important contributor to age-dependent strial dysfunction, cochlear pathology, and hearing loss. Thus, this study highlights the SV as a primary site of age-related cochlear degeneration and aberrant macrophage activity and dysregulation of the immune system as early indicators of age-related cochlear pathology and hearing loss. Importantly, novel new imaging methods described here now provide a means to analyze human temporal bones in a way that had not previously been feasible and thereby represent a significant new tool for otopathological evaluation. SIGNIFICANCE STATEMENT Age-related hearing loss is a common neurodegenerative disorder affecting communication and quality of life. Current interventions (primarily hearing aids and cochlear implants) offer imperfect and often unsuccessful therapeutic outcomes. Identification of early pathology and causal factors is crucial for the development of new treatments and early diagnostic tests. Here, we find that the SV, a nonsensory component of the cochlea, is an early site of structural and functional pathology in mice and humans that is characterized by aberrant immune cell activity. We also establish a new technique for evaluating cochleas from human temporal bones, an important but understudied area of research because of a lack of well-preserved human specimens and difficult tissue preparation and processing approaches.","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"1 1","pages":"5057 - 5075"},"PeriodicalIF":0.0,"publicationDate":"2023-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75804592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-31DOI: 10.1523/JNEUROSCI.twij.43.22.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/JNEUROSCI.twij.43.22.2023","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.twij.43.22.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":" 5","pages":"3985 - 3985"},"PeriodicalIF":0.0,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91414973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-24DOI: 10.1523/JNEUROSCI.twij.43.21.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/JNEUROSCI.twij.43.21.2023","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.twij.43.21.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"51 1","pages":"3786 - 3786"},"PeriodicalIF":0.0,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80133597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-24DOI: 10.1101/2023.01.02.522486
Guy Rens, Teresa D. Figley, J. Gallivan, Yuqi Liu, J. Culham
In daily life, prehension is typically not the end goal of hand-object interactions but a precursor for manipulation. Nevertheless, functional MRI (fMRI) studies investigating manual manipulation have primarily relied on prehension as the end goal of an action. Here, we used slow event-related fMRI to investigate differences in neural activation patterns between prehension in isolation and prehension for object manipulation. Sixteen (seven males and nine females) participants were instructed either to simply grasp the handle of a rotatable dial (isolated prehension) or to grasp and turn it (prehension for object manipulation). We used representational similarity analysis (RSA) to investigate whether the experimental conditions could be discriminated from each other based on differences in task-related brain activation patterns. We also used temporal multivoxel pattern analysis (tMVPA) to examine the evolution of regional activation patterns over time. Importantly, we were able to differentiate isolated prehension and prehension for manipulation from activation patterns in the early visual cortex, the caudal intraparietal sulcus (cIPS), and the superior parietal lobule (SPL). Our findings indicate that object manipulation extends beyond the putative cortical grasping network (anterior intraparietal sulcus, premotor and motor cortices) to include the superior parietal lobule and early visual cortex. SIGNIFICANCE STATEMENT A simple act such as turning an oven dial requires not only that the CNS encode the initial state (starting dial orientation) of the object but also the appropriate posture to grasp it to achieve the desired end state (final dial orientation) and the motor commands to achieve that state. Using advanced temporal neuroimaging analysis techniques, we reveal how such actions unfold over time and how they differ between object manipulation (turning a dial) versus grasping alone. We find that a combination of brain areas implicated in visual processing and sensorimotor integration can distinguish between the complex and simple tasks during planning, with neural patterns that approximate those during the actual execution of the action.
{"title":"Grasping with a Twist: Dissociating Action Goals from Motor Actions in Human Frontoparietal Circuits","authors":"Guy Rens, Teresa D. Figley, J. Gallivan, Yuqi Liu, J. Culham","doi":"10.1101/2023.01.02.522486","DOIUrl":"https://doi.org/10.1101/2023.01.02.522486","url":null,"abstract":"In daily life, prehension is typically not the end goal of hand-object interactions but a precursor for manipulation. Nevertheless, functional MRI (fMRI) studies investigating manual manipulation have primarily relied on prehension as the end goal of an action. Here, we used slow event-related fMRI to investigate differences in neural activation patterns between prehension in isolation and prehension for object manipulation. Sixteen (seven males and nine females) participants were instructed either to simply grasp the handle of a rotatable dial (isolated prehension) or to grasp and turn it (prehension for object manipulation). We used representational similarity analysis (RSA) to investigate whether the experimental conditions could be discriminated from each other based on differences in task-related brain activation patterns. We also used temporal multivoxel pattern analysis (tMVPA) to examine the evolution of regional activation patterns over time. Importantly, we were able to differentiate isolated prehension and prehension for manipulation from activation patterns in the early visual cortex, the caudal intraparietal sulcus (cIPS), and the superior parietal lobule (SPL). Our findings indicate that object manipulation extends beyond the putative cortical grasping network (anterior intraparietal sulcus, premotor and motor cortices) to include the superior parietal lobule and early visual cortex. SIGNIFICANCE STATEMENT A simple act such as turning an oven dial requires not only that the CNS encode the initial state (starting dial orientation) of the object but also the appropriate posture to grasp it to achieve the desired end state (final dial orientation) and the motor commands to achieve that state. Using advanced temporal neuroimaging analysis techniques, we reveal how such actions unfold over time and how they differ between object manipulation (turning a dial) versus grasping alone. We find that a combination of brain areas implicated in visual processing and sensorimotor integration can distinguish between the complex and simple tasks during planning, with neural patterns that approximate those during the actual execution of the action.","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"129 1","pages":"5831 - 5847"},"PeriodicalIF":0.0,"publicationDate":"2023-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81715181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-17DOI: 10.1523/JNEUROSCI.twij.43.20.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/JNEUROSCI.twij.43.20.2023","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.twij.43.20.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"66 1","pages":"3598 - 3598"},"PeriodicalIF":0.0,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76383401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-10DOI: 10.1523/JNEUROSCI.twij.43.19.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/JNEUROSCI.twij.43.19.2023","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.twij.43.19.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"56 1","pages":"3391 - 3391"},"PeriodicalIF":0.0,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81162179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-03DOI: 10.1523/JNEUROSCI.twij.43.18.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/JNEUROSCI.twij.43.18.2023","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.twij.43.18.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"14 1","pages":"3198 - 3198"},"PeriodicalIF":0.0,"publicationDate":"2023-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88741526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-26DOI: 10.1523/JNEUROSCI.twij.43.17.2023
{"title":"This Week in The Journal","authors":"","doi":"10.1523/JNEUROSCI.twij.43.17.2023","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.twij.43.17.2023","url":null,"abstract":"","PeriodicalId":22786,"journal":{"name":"The Journal of Neuroscience","volume":"68 1","pages":"3008 - 3008"},"PeriodicalIF":0.0,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75605904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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