N. Padilla, Victor M. Saenger, T. V. van Hartevelt, H. Fernandes, F. Lennartsson, J. Andersson, M. Kringelbach, G. Deco, U. Ådén
Abstract The brain operates at a critical point that is balanced between order and disorder. Even during rest, unstable periods of random behavior are interspersed with stable periods of balanced activity patterns that support optimal information processing. Being born preterm may cause deviations from this normal pattern of development. We compared 33 extremely preterm (EPT) children born at < 27 weeks of gestation and 28 full-term controls. Two approaches were adopted in both groups, when they were 10 years of age, using structural and functional brain magnetic resonance imaging data. The first was using a novel intrinsic ignition analysis to study the ability of the areas of the brain to propagate neural activity. The second was a whole-brain Hopf model, to define the level of stability, desynchronization, or criticality of the brain. EPT-born children exhibited fewer intrinsic ignition events than controls; nodes were related to less sophisticated aspects of cognitive control, and there was a different hierarchy pattern in the propagation of information and suboptimal synchronicity and criticality. The largest differences were found in brain nodes belonging to the rich-club architecture. These results provide important insights into the neural substrates underlying brain reorganization and neurodevelopmental impairments related to prematurity.
{"title":"Breakdown of Whole-brain Dynamics in Preterm-born Children","authors":"N. Padilla, Victor M. Saenger, T. V. van Hartevelt, H. Fernandes, F. Lennartsson, J. Andersson, M. Kringelbach, G. Deco, U. Ådén","doi":"10.1093/CERCOR/BHZ156","DOIUrl":"https://doi.org/10.1093/CERCOR/BHZ156","url":null,"abstract":"Abstract The brain operates at a critical point that is balanced between order and disorder. Even during rest, unstable periods of random behavior are interspersed with stable periods of balanced activity patterns that support optimal information processing. Being born preterm may cause deviations from this normal pattern of development. We compared 33 extremely preterm (EPT) children born at < 27 weeks of gestation and 28 full-term controls. Two approaches were adopted in both groups, when they were 10 years of age, using structural and functional brain magnetic resonance imaging data. The first was using a novel intrinsic ignition analysis to study the ability of the areas of the brain to propagate neural activity. The second was a whole-brain Hopf model, to define the level of stability, desynchronization, or criticality of the brain. EPT-born children exhibited fewer intrinsic ignition events than controls; nodes were related to less sophisticated aspects of cognitive control, and there was a different hierarchy pattern in the propagation of information and suboptimal synchronicity and criticality. The largest differences were found in brain nodes belonging to the rich-club architecture. These results provide important insights into the neural substrates underlying brain reorganization and neurodevelopmental impairments related to prematurity.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"19 4 1","pages":"1159 - 1170"},"PeriodicalIF":0.0,"publicationDate":"2019-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81260638","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}
Abstract The pulvinar is the largest extrageniculate visual nucleus in mammals. Given its extensive reciprocal connectivity with the visual cortex, it allows the cortico-thalamocortical transfer of visual information. Nonetheless, knowledge of the nature of the pulvinar inputs to the cortex remains elusive. We investigated the impact of silencing the pulvinar on the contrast response function of neurons in 2 distinct hierarchical cortical areas in the cat (areas 17 and 21a). Pulvinar inactivation altered the response gain in both areas, but with larger changes observed in area 21a. A theoretical model was proposed, simulating the pulvinar contribution to cortical contrast responses by modifying the excitation-inhibition balanced state of neurons across the cortical hierarchy. Our experimental and theoretical data showed that the pulvinar exerts a greater modulatory influence on neuronal activity in area 21a than in the primary visual cortex, indicating that the pulvinar impact on cortical visual neurons varies along the cortical hierarchy.
{"title":"Pulvinar Modulates Contrast Responses in the Visual Cortex as a Function of Cortical Hierarchy","authors":"B. O. F. de Souza, Nelson Cortes, C. Casanova","doi":"10.1093/cercor/bhz149","DOIUrl":"https://doi.org/10.1093/cercor/bhz149","url":null,"abstract":"Abstract The pulvinar is the largest extrageniculate visual nucleus in mammals. Given its extensive reciprocal connectivity with the visual cortex, it allows the cortico-thalamocortical transfer of visual information. Nonetheless, knowledge of the nature of the pulvinar inputs to the cortex remains elusive. We investigated the impact of silencing the pulvinar on the contrast response function of neurons in 2 distinct hierarchical cortical areas in the cat (areas 17 and 21a). Pulvinar inactivation altered the response gain in both areas, but with larger changes observed in area 21a. A theoretical model was proposed, simulating the pulvinar contribution to cortical contrast responses by modifying the excitation-inhibition balanced state of neurons across the cortical hierarchy. Our experimental and theoretical data showed that the pulvinar exerts a greater modulatory influence on neuronal activity in area 21a than in the primary visual cortex, indicating that the pulvinar impact on cortical visual neurons varies along the cortical hierarchy.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"513 ","pages":"1068 - 1086"},"PeriodicalIF":0.0,"publicationDate":"2019-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91448872","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}
Kristoffer N. T. Månsson, Diana S Cortes, A. Manzouri, Tie-Qiang Li, S. Hau, H. Fischer
Abstract Measuring brain morphology with non-invasive structural magnetic resonance imaging is common practice, and can be used to investigate neuroplasticity. Brain morphology changes have been reported over the course of weeks, days, and hours in both animals and humans. If such short-term changes occur even faster, rapid morphological changes while being scanned could have important implications. In a randomized within-subject study on 47 healthy individuals, two high-resolution T1-weighted anatomical images were acquired (á 263 s) per individual. The images were acquired during passive viewing of pictures or a fixation cross. Two common pipelines for analyzing brain images were used: voxel-based morphometry on gray matter (GM) volume and surface-based cortical thickness. We found that the measures of both GM volume and cortical thickness showed increases in the visual cortex while viewing pictures relative to a fixation cross. The increase was distributed across the two hemispheres and significant at a corrected level. Thus, brain morphology enlargements were detected in less than 263 s. Neuroplasticity is a far more dynamic process than previously shown, suggesting that individuals’ current mental state affects indices of brain morphology. This needs to be taken into account in future morphology studies and in everyday clinical practice.
{"title":"Viewing Pictures Triggers Rapid Morphological Enlargement in the Human Visual Cortex","authors":"Kristoffer N. T. Månsson, Diana S Cortes, A. Manzouri, Tie-Qiang Li, S. Hau, H. Fischer","doi":"10.1093/cercor/bhz131","DOIUrl":"https://doi.org/10.1093/cercor/bhz131","url":null,"abstract":"Abstract Measuring brain morphology with non-invasive structural magnetic resonance imaging is common practice, and can be used to investigate neuroplasticity. Brain morphology changes have been reported over the course of weeks, days, and hours in both animals and humans. If such short-term changes occur even faster, rapid morphological changes while being scanned could have important implications. In a randomized within-subject study on 47 healthy individuals, two high-resolution T1-weighted anatomical images were acquired (á 263 s) per individual. The images were acquired during passive viewing of pictures or a fixation cross. Two common pipelines for analyzing brain images were used: voxel-based morphometry on gray matter (GM) volume and surface-based cortical thickness. We found that the measures of both GM volume and cortical thickness showed increases in the visual cortex while viewing pictures relative to a fixation cross. The increase was distributed across the two hemispheres and significant at a corrected level. Thus, brain morphology enlargements were detected in less than 263 s. Neuroplasticity is a far more dynamic process than previously shown, suggesting that individuals’ current mental state affects indices of brain morphology. This needs to be taken into account in future morphology studies and in everyday clinical practice.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"29 1","pages":"851 - 857"},"PeriodicalIF":0.0,"publicationDate":"2019-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90378811","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}
Abstract Behavioral change studies and interventions focus on self-control and external reinforcements to influence preferences. Cue-approach training (CAT) has been shown to induce preference changes lasting months by merely associating items with neutral cues and speeded responses. We utilized this paradigm to study neural representation of preferences and their modification without external reinforcements. We scanned 36 participants with fMRI during a novel passive viewing task before, after and 30 days following CAT. We preregistered the predictions that activity in memory, top-down attention, and value-processing regions will underlie preference modification. While most theories associate preferences with prefrontal regions, we found that “bottom-up” perceptual mechanisms were associated with immediate change, whereas reduced “top-down” parietal activity was related to long-term change. Activity in value-related prefrontal regions was enhanced immediately after CAT for trained items and 1 month after for all items. Our findings suggest a novel neural mechanism of preference representation and modification. We suggest that nonreinforced change of preferences occurs initially in perceptual representation of items, putatively leading to long-term changes in “top-down” processes. These findings offer implementation of bottom-up instead of top-down targeted interventions for long-lasting behavioral change.
{"title":"Enhanced Bottom-Up and Reduced Top-Down fMRI Activity Is Related to Long-Lasting Nonreinforced Behavioral Change","authors":"Rotem Botvinik-Nezer, Tom Salomon, T. Schonberg","doi":"10.1093/cercor/bhz132","DOIUrl":"https://doi.org/10.1093/cercor/bhz132","url":null,"abstract":"Abstract Behavioral change studies and interventions focus on self-control and external reinforcements to influence preferences. Cue-approach training (CAT) has been shown to induce preference changes lasting months by merely associating items with neutral cues and speeded responses. We utilized this paradigm to study neural representation of preferences and their modification without external reinforcements. We scanned 36 participants with fMRI during a novel passive viewing task before, after and 30 days following CAT. We preregistered the predictions that activity in memory, top-down attention, and value-processing regions will underlie preference modification. While most theories associate preferences with prefrontal regions, we found that “bottom-up” perceptual mechanisms were associated with immediate change, whereas reduced “top-down” parietal activity was related to long-term change. Activity in value-related prefrontal regions was enhanced immediately after CAT for trained items and 1 month after for all items. Our findings suggest a novel neural mechanism of preference representation and modification. We suggest that nonreinforced change of preferences occurs initially in perceptual representation of items, putatively leading to long-term changes in “top-down” processes. These findings offer implementation of bottom-up instead of top-down targeted interventions for long-lasting behavioral change.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"60 1","pages":"858 - 874"},"PeriodicalIF":0.0,"publicationDate":"2019-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89166858","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}
Balaji Sriram, Lillian Li, A. Cruz-Martín, Anirvan Ghosh
Abstract The cortical code that underlies perception must enable subjects to perceive the world at time scales relevant for behavior. We find that mice can integrate visual stimuli very quickly (<100 ms) to reach plateau performance in an orientation discrimination task. To define features of cortical activity that underlie performance at these time scales, we measured single-unit responses in the mouse visual cortex at time scales relevant to this task. In contrast to high-contrast stimuli of longer duration, which elicit reliable activity in individual neurons, stimuli at the threshold of perception elicit extremely sparse and unreliable responses in the primary visual cortex such that the activity of individual neurons does not reliably report orientation. Integrating information across neurons, however, quickly improves performance. Using a linear decoding model, we estimate that integrating information over 50–100 neurons is sufficient to account for behavioral performance. Thus, at the limits of visual perception, the visual system integrates information encoded in the probabilistic firing of unreliable single units to generate reliable behavior.
{"title":"A Sparse Probabilistic Code Underlies the Limits of Behavioral Discrimination","authors":"Balaji Sriram, Lillian Li, A. Cruz-Martín, Anirvan Ghosh","doi":"10.1093/cercor/bhz147","DOIUrl":"https://doi.org/10.1093/cercor/bhz147","url":null,"abstract":"Abstract The cortical code that underlies perception must enable subjects to perceive the world at time scales relevant for behavior. We find that mice can integrate visual stimuli very quickly (<100 ms) to reach plateau performance in an orientation discrimination task. To define features of cortical activity that underlie performance at these time scales, we measured single-unit responses in the mouse visual cortex at time scales relevant to this task. In contrast to high-contrast stimuli of longer duration, which elicit reliable activity in individual neurons, stimuli at the threshold of perception elicit extremely sparse and unreliable responses in the primary visual cortex such that the activity of individual neurons does not reliably report orientation. Integrating information across neurons, however, quickly improves performance. Using a linear decoding model, we estimate that integrating information over 50–100 neurons is sufficient to account for behavioral performance. Thus, at the limits of visual perception, the visual system integrates information encoded in the probabilistic firing of unreliable single units to generate reliable behavior.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"1 1","pages":"1040 - 1055"},"PeriodicalIF":0.0,"publicationDate":"2019-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87741740","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}
Jost-Julian Rumpf, L. May, C. Fricke, J. Classen, G. Hartwigsen
Abstract The acquisition of novel motor skills is a fundamental process of lifelong learning and crucial for everyday behavior. Performance gains acquired by training undergo a transition from an initially labile state to a state that is progressively robust towards interference, a phenomenon referred to as motor consolidation. Previous work has demonstrated that the primary motor cortex (M1) is a neural key region for motor consolidation. However, it remains unknown whether physiological processes underlying posttraining motor consolidation in M1 are active already during an ongoing training phase or only after completion of the training. We examined whether 10-Hz interleaved repetitive transcranial magnetic stimulation (i-rTMS) of M1 during rest periods between active motor training in an explicit motor learning task affects posttraining offline consolidation. Relative to i-rTMS to the vertex (control region), i-rTMS to the M1hand area of the nondominant hand facilitated posttraining consolidation assessed 6 h after training without affecting training performance. This facilitatory effect generalized to delayed performance of the mirror-symmetric sequence with the untrained (dominant) hand. These findings indicate that posttraining consolidation can be facilitated independently from training-induced performance increments and suggest that consolidation is initiated already during offline processing in short rest periods between active training phases.
{"title":"Interleaving Motor Sequence Training With High-Frequency Repetitive Transcranial Magnetic Stimulation Facilitates Consolidation","authors":"Jost-Julian Rumpf, L. May, C. Fricke, J. Classen, G. Hartwigsen","doi":"10.1093/cercor/bhz145","DOIUrl":"https://doi.org/10.1093/cercor/bhz145","url":null,"abstract":"Abstract The acquisition of novel motor skills is a fundamental process of lifelong learning and crucial for everyday behavior. Performance gains acquired by training undergo a transition from an initially labile state to a state that is progressively robust towards interference, a phenomenon referred to as motor consolidation. Previous work has demonstrated that the primary motor cortex (M1) is a neural key region for motor consolidation. However, it remains unknown whether physiological processes underlying posttraining motor consolidation in M1 are active already during an ongoing training phase or only after completion of the training. We examined whether 10-Hz interleaved repetitive transcranial magnetic stimulation (i-rTMS) of M1 during rest periods between active motor training in an explicit motor learning task affects posttraining offline consolidation. Relative to i-rTMS to the vertex (control region), i-rTMS to the M1hand area of the nondominant hand facilitated posttraining consolidation assessed 6 h after training without affecting training performance. This facilitatory effect generalized to delayed performance of the mirror-symmetric sequence with the untrained (dominant) hand. These findings indicate that posttraining consolidation can be facilitated independently from training-induced performance increments and suggest that consolidation is initiated already during offline processing in short rest periods between active training phases.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"29 1","pages":"1030 - 1039"},"PeriodicalIF":0.0,"publicationDate":"2019-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81411584","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}
P. Baldinger-Melich, Maria F Urquijo Castro, R. Seiger, A. Ruef, D. Dwyer, G. Kranz, M. Klöbl, J. Kambeitz, U. Kaufmann, C. Windischberger, S. Kasper, P. Falkai, R. Lanzenberger, N. Koutsouleris
Abstract Univariate analyses of structural neuroimaging data have produced heterogeneous results regarding anatomical sex- and gender-related differences. The current study aimed at delineating and cross-validating brain volumetric surrogates of sex and gender by comparing the structural magnetic resonance imaging data of cis- and transgender subjects using multivariate pattern analysis. Gray matter (GM) tissue maps of 29 transgender men, 23 transgender women, 35 cisgender women, and 34 cisgender men were created using voxel-based morphometry and analyzed using support vector classification. Generalizability of the models was estimated using repeated nested cross-validation. For external validation, significant models were applied to hormone-treated transgender subjects (n = 32) and individuals diagnosed with depression (n = 27). Sex was identified with a balanced accuracy (BAC) of 82.6% (false discovery rate [pFDR] < 0.001) in cisgender, but only with 67.5% (pFDR = 0.04) in transgender participants indicating differences in the neuroanatomical patterns associated with sex in transgender despite the major effect of sex on GM volume irrespective of the self-identification as a woman or man. Gender identity and gender incongruence could not be reliably identified (all pFDR > 0.05). The neuroanatomical signature of sex in cisgender did not interact with depressive features (BAC = 74.7%) but was affected by hormone therapy when applied in transgender women (P < 0.001).
{"title":"Sex Matters: A Multivariate Pattern Analysis of Sex- and Gender-Related Neuroanatomical Differences in Cis- and Transgender Individuals Using Structural Magnetic Resonance Imaging","authors":"P. Baldinger-Melich, Maria F Urquijo Castro, R. Seiger, A. Ruef, D. Dwyer, G. Kranz, M. Klöbl, J. Kambeitz, U. Kaufmann, C. Windischberger, S. Kasper, P. Falkai, R. Lanzenberger, N. Koutsouleris","doi":"10.1093/cercor/bhz170","DOIUrl":"https://doi.org/10.1093/cercor/bhz170","url":null,"abstract":"Abstract Univariate analyses of structural neuroimaging data have produced heterogeneous results regarding anatomical sex- and gender-related differences. The current study aimed at delineating and cross-validating brain volumetric surrogates of sex and gender by comparing the structural magnetic resonance imaging data of cis- and transgender subjects using multivariate pattern analysis. Gray matter (GM) tissue maps of 29 transgender men, 23 transgender women, 35 cisgender women, and 34 cisgender men were created using voxel-based morphometry and analyzed using support vector classification. Generalizability of the models was estimated using repeated nested cross-validation. For external validation, significant models were applied to hormone-treated transgender subjects (n = 32) and individuals diagnosed with depression (n = 27). Sex was identified with a balanced accuracy (BAC) of 82.6% (false discovery rate [pFDR] < 0.001) in cisgender, but only with 67.5% (pFDR = 0.04) in transgender participants indicating differences in the neuroanatomical patterns associated with sex in transgender despite the major effect of sex on GM volume irrespective of the self-identification as a woman or man. Gender identity and gender incongruence could not be reliably identified (all pFDR > 0.05). The neuroanatomical signature of sex in cisgender did not interact with depressive features (BAC = 74.7%) but was affected by hormone therapy when applied in transgender women (P < 0.001).","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"1 1","pages":"1345 - 1356"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75416174","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}
M. E. Hervig, Leanne Fiddian, L. Piilgaard, Tadej Božič, M. Blanco-Pozo, C. Knudsen, S. F. Olesen, J. Alsiö, T. W. Robbins
ABSTRACT Much evidence suggests that reversal learning is mediated by cortico-striatal circuitries with the orbitofrontal cortex (OFC) playing a prominent role. The OFC is a functionally heterogeneous region, but potential differential roles of lateral (lOFC) and medial (mOFC) portions in visual reversal learning have yet to be determined. We investigated the effects of pharmacological inactivation of mOFC and lOFC on a deterministic serial visual reversal learning task for rats. For reference, we also targeted other areas previously implicated in reversal learning: prelimbic (PrL) and infralimbic (IL) prefrontal cortex, and basolateral amygdala (BLA). Inactivating mOFC and lOFC produced opposite effects; lOFC impairing, and mOFC improving, performance in the early, perseverative phase specifically. Additionally, mOFC inactivation enhanced negative feedback sensitivity, while lOFC inactivation diminished feedback sensitivity in general. mOFC and lOFC inactivation also affected novel visual discrimination learning differently; lOFC inactivation paradoxically improved learning, and mOFC inactivation had no effect. We also observed dissociable roles of the OFC and the IL/PrL. Whereas the OFC inactivation affected only perseveration, IL/PrL inactivation improved learning overall. BLA inactivation did not affect perseveration, but improved the late phase of reversal learning. These results support opponent roles of the rodent mOFC and lOFC in deterministic visual reversal learning.
{"title":"Dissociable and Paradoxical Roles of Rat Medial and Lateral Orbitofrontal Cortex in Visual Serial Reversal Learning","authors":"M. E. Hervig, Leanne Fiddian, L. Piilgaard, Tadej Božič, M. Blanco-Pozo, C. Knudsen, S. F. Olesen, J. Alsiö, T. W. Robbins","doi":"10.1093/cercor/bhz144","DOIUrl":"https://doi.org/10.1093/cercor/bhz144","url":null,"abstract":"ABSTRACT Much evidence suggests that reversal learning is mediated by cortico-striatal circuitries with the orbitofrontal cortex (OFC) playing a prominent role. The OFC is a functionally heterogeneous region, but potential differential roles of lateral (lOFC) and medial (mOFC) portions in visual reversal learning have yet to be determined. We investigated the effects of pharmacological inactivation of mOFC and lOFC on a deterministic serial visual reversal learning task for rats. For reference, we also targeted other areas previously implicated in reversal learning: prelimbic (PrL) and infralimbic (IL) prefrontal cortex, and basolateral amygdala (BLA). Inactivating mOFC and lOFC produced opposite effects; lOFC impairing, and mOFC improving, performance in the early, perseverative phase specifically. Additionally, mOFC inactivation enhanced negative feedback sensitivity, while lOFC inactivation diminished feedback sensitivity in general. mOFC and lOFC inactivation also affected novel visual discrimination learning differently; lOFC inactivation paradoxically improved learning, and mOFC inactivation had no effect. We also observed dissociable roles of the OFC and the IL/PrL. Whereas the OFC inactivation affected only perseveration, IL/PrL inactivation improved learning overall. BLA inactivation did not affect perseveration, but improved the late phase of reversal learning. These results support opponent roles of the rodent mOFC and lOFC in deterministic visual reversal learning.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"58 1","pages":"1016 - 1029"},"PeriodicalIF":0.0,"publicationDate":"2019-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81436703","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}
Amanda K. Tilot, E. Khramtsova, Katrina L. Grasby, N. Jahanshad, J. Painter, L. Colodro-Conde, J. Bralten, D. Hibar, P. Lind, Siyao Liu, Sarah M. Brotman, P. Thompson, S. Medland, F. Macciardi, B. Stranger, L. Davis, S. Fisher, J. Stein
Structural brain changes along the lineage that led to modern Homo sapiens have contributed to our unique cognitive and social abilities. However, the evolutionarily relevant molecular variants impacting key aspects of neuroanatomy are largely unknown. Here, we integrate evolutionary annotations of the genome at diverse timescales with common variant associations from large-scale neuroimaging genetic screens in living humans, to reveal how selective pressures have shaped neocortical surface area. We show that variation within human gained enhancers active in the developing brain is associated with global surface area as well as that of specific regions. Moreover, we find evidence of recent polygenic selection over the past 2,000 years influencing surface area of multiple cortical regions, including those involved in spoken language and visual processing.
{"title":"The Evolutionary History of Common Genetic Variants Influencing Human Cortical Surface Area","authors":"Amanda K. Tilot, E. Khramtsova, Katrina L. Grasby, N. Jahanshad, J. Painter, L. Colodro-Conde, J. Bralten, D. Hibar, P. Lind, Siyao Liu, Sarah M. Brotman, P. Thompson, S. Medland, F. Macciardi, B. Stranger, L. Davis, S. Fisher, J. Stein","doi":"10.1101/703793","DOIUrl":"https://doi.org/10.1101/703793","url":null,"abstract":"Structural brain changes along the lineage that led to modern Homo sapiens have contributed to our unique cognitive and social abilities. However, the evolutionarily relevant molecular variants impacting key aspects of neuroanatomy are largely unknown. Here, we integrate evolutionary annotations of the genome at diverse timescales with common variant associations from large-scale neuroimaging genetic screens in living humans, to reveal how selective pressures have shaped neocortical surface area. We show that variation within human gained enhancers active in the developing brain is associated with global surface area as well as that of specific regions. Moreover, we find evidence of recent polygenic selection over the past 2,000 years influencing surface area of multiple cortical regions, including those involved in spoken language and visual processing.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"75 1","pages":"1873 - 1887"},"PeriodicalIF":0.0,"publicationDate":"2019-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86171534","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 : 2019-06-09DOI: 10.1101/2022.04.07.487457
L. Edwards, P. McColgan, Saskia Helbling, A. Zarkali, L. Vaculčiaková, K. Pine, F. Dick, N. Weiskopf
Quantitative MRI (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of the qMRI parameters longitudinal relaxation rate (R1), effective transverse relaxation rate (R2∗), and magnetization transfer saturation (MTsat) to gene expression from the Allen Human Brain Atlas, then combining this with lists of genes enriched in specific cell types found in the human brain. As qMRI parameters are magnetic field strength-dependent, the analysis was performed on MRI data at 3T and 7T. All qMRI parameters significantly covaried with genes enriched in GABA- and glutamatergic neurons, i.e. they were associated with cytoarchitecture. The qMRI parameters also significantly covaried with the distribution of genes enriched in astrocytes (R2∗ at 3T, R1 at 7T), endothelial cells (R1 and MTsat at 3T), microglia (R1 and MTsat at 3T, R1 at 7T), and oligodendrocytes (R1 at 7T). These results advance the potential use of qMRI parameters as biomarkers for specific cell types.
{"title":"Quantitative MRI maps of human neocortex explored using cell type-specific gene expression analysis","authors":"L. Edwards, P. McColgan, Saskia Helbling, A. Zarkali, L. Vaculčiaková, K. Pine, F. Dick, N. Weiskopf","doi":"10.1101/2022.04.07.487457","DOIUrl":"https://doi.org/10.1101/2022.04.07.487457","url":null,"abstract":"Quantitative MRI (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of the qMRI parameters longitudinal relaxation rate (R1), effective transverse relaxation rate (R2∗), and magnetization transfer saturation (MTsat) to gene expression from the Allen Human Brain Atlas, then combining this with lists of genes enriched in specific cell types found in the human brain. As qMRI parameters are magnetic field strength-dependent, the analysis was performed on MRI data at 3T and 7T. All qMRI parameters significantly covaried with genes enriched in GABA- and glutamatergic neurons, i.e. they were associated with cytoarchitecture. The qMRI parameters also significantly covaried with the distribution of genes enriched in astrocytes (R2∗ at 3T, R1 at 7T), endothelial cells (R1 and MTsat at 3T), microglia (R1 and MTsat at 3T, R1 at 7T), and oligodendrocytes (R1 at 7T). These results advance the potential use of qMRI parameters as biomarkers for specific cell types.","PeriodicalId":9825,"journal":{"name":"Cerebral Cortex (New York, NY)","volume":"10 1","pages":"5704 - 5716"},"PeriodicalIF":0.0,"publicationDate":"2019-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73250313","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}