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Instituto do Cérebro do Rio Grande do Sul

Centre Hospitalier Universitaire Vaudois (CHUV)

Frontiers in Neuroimaging

Neuroimaging for Cognitive Neuroscience

Global Excellence in Neuroimaging for Cognitive Neuroscience

Areas of the dorsolateral prefrontal cortex (DLPFC) are part of the frontoparietal control, default mode, salience, and ventral attention networks. The DLPFC is involved in executive functions, like working memory, value encoding, attention, decision-making, and behavioral control. This functional heterogeneity is not reflected in existing neuroanatomical maps. For example, previous cytoarchitectonic studies have divided the DLPFC into two or four areas. Macroanatomical parcellations of this region rely on gyri and sulci, which are not congruent with cytoarchitectonic parcellations. Therefore, this study aimed to provide a microstructural analysis of the human DLPFC and 3D maps of cytoarchitectonic areas to help address the observed functional variability in studies of the DLPFC. We analyzed ten human post-mortem brains in serial cell-body stained brain sections and mapped areal boundaries using a statistical image analysis approach. Five new areas (i.e., SFG2, SFG3, SFG4, MFG4, and MFG5) were identified on the superior and middle frontal gyrus, i.e., regions corresponding to parts of Brodmann areas 9 and 46. Gray level index profiles were used to determine interregional cytoarchitectural differences. The five new areas were reconstructed in 3D, and probability maps were generated in commonly used reference spaces, considering the variability of areas in stereotaxic space. Hierarchical cluster analysis revealed a high degree of similarity within the identified DLPFC areas while neighboring areas (frontal pole, Broca's region, area 8, and motoric areas) were separable. Comparisons with functional imaging studies revealed specific functional profiles of the DLPFC areas. Our results indicate that the new areas do not follow a simple organizational gradient assumption in the DLPFC. Instead, they are more similar to those of the ventrolateral prefrontal cortex (Broca's areas 44, 45) and frontopolar areas (Fp1, Fp2) than to the more posterior areas. Within the DLPFC, the cytoarchitectonic similarities between areas do not seem to follow a simple anterior-to-posterior gradient either, but cluster along other principles. The new maps are part of the publicly available Julich Brain Atlas and provide a microstructural reference for existing and future imaging studies. Thus, our study represents a further step toward deciphering the structural-functional organization of the human prefrontal cortex.

Areas of the dorsolateral prefrontal cortex (DLPFC) are part of the frontoparietal control, default mode, salience, and ventral attention networks. The DLPFC is involved in executive functions, like working memory, value encoding, attention, decision-making, and behavioral control. This functional heterogeneity is not reflected in existing neuroanatomical maps. For example, previous cytoarchitectonic studies have divided the DLPFC into two or four areas. Macroanatomical parcellations of this region rely on gyri and sulci, which are not congruent with cytoarchitectonic parcellations. Therefore, this study aimed to provide a microstructural analysis of the human DLPFC and 3D maps of cytoarchitectonic areas to help address the observed functional variability in studies of the DLPFC. We analyzed ten human post-mortem brains in serial cell-body stained brain sections and mapped areal boundaries using a statistical image analysis approach. Five new areas (i.e., SFG2, SFG3, SFG4, MFG4, and MFG5) were identified on the superior and middle frontal gyrus, i.e., regions corresponding to parts of Brodmann areas 9 and 46. Gray level index profiles were used to determine interregional cytoarchitectural differences. The five new areas were reconstructed in 3D, and probability maps were generated in commonly used reference spaces, considering the variability of areas in stereotaxic space. Hierarchical cluster analysis revealed a high degree of similarity within the identified DLPFC areas while neighboring areas (frontal pole, Broca&apos;s region, area 8, and motoric areas) were separable. Comparisons with functional imaging studies revealed specific functional profiles of the DLPFC areas. Our results indicate that the new areas do not follow a simple organizational gradient assumption in the DLPFC. Instead, they are more similar to those of the ventrolateral prefrontal cortex (Broca&apos;s areas 44, 45) and frontopolar areas (Fp1, Fp2) than to the more posterior areas. Within the DLPFC, the cytoarchitectonic similarities between areas do not seem to follow a simple anterior-to-posterior gradient either, but cluster along other principles. The new maps are part of the publicly available Julich Brain Atlas and provide a microstructural reference for existing and future imaging studies. Thus, our study represents a further step toward deciphering the structural-functional organization of the human prefrontal cortex.

New organizational principles and 3D cytoarchitectonic maps of the dorsolateral prefrontal cortex in the human brain

In recent years the common marmoset homolog of the human default mode network (DMN) has been a hot topic of discussion in the marmoset research field. Previously, the posterior cingulate cortex regions (PGM, A19M) and posterior parietal cortex regions (LIP, MIP) were defined as the DMN, but some studies claim that these form the frontoparietal network (FPN). We restarted from a neuroanatomical point of view and identified two DMN candidates: Comp-A (which has been called both the DMN and FPN) and Comp-B. We performed GLM analysis on auditory task-fMRI and found Comp-B to be more appropriate as the DMN, and Comp-A as the FPN. Additionally, through fingerprint analysis, a DMN and FPN in the tasking human was closer to the resting common marmoset. The human DMN appears to have an advanced function that may be underdeveloped in the common marmoset brain.

In recent years the common marmoset homolog of the human default mode network (DMN) has been a hot topic of discussion in the marmoset research field. Previously, the posterior cingulate cortex regions (PGM, A19M) and posterior parietal cortex regions (LIP, MIP) were defined as the DMN, but some studies claim that these form the frontoparietal network (FPN). We restarted from a neuroanatomical point of view and identified two DMN candidates: Comp-A (which has been called both the DMN and FPN) and Comp-B. We performed GLM analysis on auditory task-fMRI and found Comp-B to be more appropriate as the DMN, and Comp-A as the FPN. Additionally, through fingerprint analysis, a DMN and FPN in the tasking human was closer to the resting common marmoset. The human DMN appears to have an advanced function that may be underdeveloped in the common marmoset brain.

A reappraisal of the default mode and frontoparietal networks in the common marmoset brain

Age-related changes of asymmetries in the auditory system and decreasing efficiency of hemispheric interaction have been discussed for some time. This mini-review discusses recent neuroimaging studies on alterations in lateralization of cortical processing and structural changes concerning the division of labor and interaction between hemispheres during auditory processing in elderly people with the focus on people without severe hearing loss. Several changes of asymmetries in anatomy, function and neurotransmitter concentration were observed in auditory cortical areas of older compared to younger adults. It was shown that connections between left and right auditory cortex are reduced during aging. Functionally, aging seems to lead to a reduction in asymmetry of auditory processing. However, the results do not always point into the same direction. Furthermore, correlations between function, anatomy and behavior in the left and right hemisphere appear to differ between younger and older adults. The changes in auditory cortex asymmetries with aging might be due to compensation of declining processing capacities, but at the same time these mechanisms could impair the balanced division of labor between the two hemispheres that is required for the processing of complex auditory stimuli such as speech. Neuroimaging studies are essential to follow the slow changes with aging as in the beginning no behavioral effects might be visible due to compensation. Future studies should control well for peripheral hearing loss and cognitive decline. Furthermore, for the interpretability of results it is necessary to use specific tasks with well-controlled task difficulty.

Age-related changes of asymmetries in the auditory system and decreasing efficiency of hemispheric interaction have been discussed for some time. This mini-review discusses recent neuroimaging studies on alterations in lateralization of cortical processing and structural changes concerning the division of labor and interaction between hemispheres during auditory processing in elderly people with the focus on people without severe hearing loss. Several changes of asymmetries in anatomy, function and neurotransmitter concentration were observed in auditory cortical areas of older compared to younger adults. It was shown that connections between left and right auditory cortex are reduced during aging. Functionally, aging seems to lead to a reduction in asymmetry of auditory processing. However, the results do not always point into the same direction. Furthermore, correlations between function, anatomy and behavior in the left and right hemisphere appear to differ between younger and older adults. The changes in auditory cortex asymmetries with aging might be due to compensation of declining processing capacities, but at the same time these mechanisms could impair the balanced division of labor between the two hemispheres that is required for the processing of complex auditory stimuli such as speech. Neuroimaging studies are essential to follow the slow changes with aging as in the beginning no behavioral effects might be visible due to compensation. Future studies should control well for peripheral hearing loss and cognitive decline. Furthermore, for the interpretability of results it is necessary to use specific tasks with well-controlled task difficulty.

Asymmetries and hemispheric interaction in the auditory system of elderly people

IntroductionThe brainstem locus coeruleus (LC) influences a broad range of brain processes, including cognition. The so-called LC contrast is an accepted marker of the integrity of the LC that consists of a local hyperintensity on specific Magnetic Resonance Imaging (MRI) structural images. The small size of the LC has, however, rendered its functional characterization difficult in humans, including in aging. A full characterization of the structural and functional characteristics of the LC in healthy young and late middle-aged individuals is needed to determine the potential roles of the LC in different medical conditions. Here, we wanted to determine whether the activation of the LC in a mismatch negativity task changes in aging and whether the LC functional response was associated to the LC contrast.</sec>MethodsWe used Ultra-High Field (UHF) 7-Tesla functional MRI (fMRI) to record brain response during an auditory oddball task in 53 healthy volunteers, including 34 younger (age: 22.15y ± 3.27; 29 women) and 19 late middle-aged (age: 61.05y ± 5.3; 14 women) individuals.</sec>ResultsWhole-brain analyses confirmed brain responses in the typical cortical and subcortical regions previously associated with mismatch negativity. When focusing on the brainstem, we found a significant response in the rostral part of the LC probability mask generated based on individual LC images. Although bilateral, the activation was more extensive in the left LC. Individual LC activity was not significantly different between young and late middle-aged individuals. Importantly, while the LC contrast was higher in older individuals, the functional response of the LC was not significantly associated with its contrast.</sec>DiscussionThese findings may suggest that the age-related alterations of the LC structural integrity may not be related to changes in its functional response. The results further suggest that LC responses may remain stable in healthy individuals aged 20 to 70.</sec>

Introduction: The brainstem locus coeruleus (LC) influences a broad range of brain processes, including cognition. The so-called LC contrast is an accepted marker of the integrity of the LC that consists of a local hyperintensity on specific Magnetic Resonance Imaging (MRI) structural images. The small size of the LC has, however, rendered its functional characterization difficult in humans, including in aging. A full characterization of the structural and functional characteristics of the LC in healthy young and late middle-aged individuals is needed to determine the potential roles of the LC in different medical conditions. Here, we wanted to determine whether the activation of the LC in a mismatch negativity task changes in aging and whether the LC functional response was associated to the LC contrast.Methods: We used Ultra-High Field (UHF) 7-Tesla functional MRI (fMRI) to record brain response during an auditory oddball task in 53 healthy volunteers, including 34 younger (age: 22.15y ± 3.27; 29 women) and 19 late middle-aged (age: 61.05y ± 5.3; 14 women) individuals.Results: Whole-brain analyses confirmed brain responses in the typical cortical and subcortical regions previously associated with mismatch negativity. When focusing on the brainstem, we found a significant response in the rostral part of the LC probability mask generated based on individual LC images. Although bilateral, the activation was more extensive in the left LC. Individual LC activity was not significantly different between young and late middle-aged individuals. Importantly, while the LC contrast was higher in older individuals, the functional response of the LC was not significantly associated with its contrast.Discussion: These findings may suggest that the age-related alterations of the LC structural integrity may not be related to changes in its functional response. The results further suggest that LC responses may remain stable in healthy individuals aged 20 to 70.