Pub Date : 2025-08-28DOI: 10.1007/s00429-025-03002-7
Elibeth Monroy, Leonardo Aguilar-Hernandez, Fidel de la Cruz-López, Gonzalo Flores, Julio César Morales-Medina
Human populations are experiencing an increase in aging, which is associated with cognitive deficits. Animal models of aging have shown that these behavioral impairments are associated with neuroarchitecture modifications in the prefrontal cortex (PFC) and hippocampus; however, most studies have focused on rats or lack multiple key ages. In this study, we evaluated spatial and recognition memory in male mice at critical ages [3 months (M), 6, 12 and 18] using the Morris water maze (MWM) and novel object recognition test (NORT), respectively. Moreover, we quantified dendritic arborization, spine density and the type of spines in the PFC, CA1 hippocampus and nucleus Accumbens Core (NAcC). Locomotion, assessed in the first phase of NORT, revealed age-dependent reductions. Notably, the 18 M group revealed significant recognition memory deficits. Spatial memory impairments were especially evident at the 12 M group in the MWM. Spine density was increased at 6 M in the NAcC, whereas a reduction was noted at 12 M and 18 M in the PFC. Morphological assessment of spines indicated age-dependent changes, including a notable increase in the proportion of thin spines in the CA1 and PFC regions. However, dendritic arborization remained largely unchanged across the examined brain regions and age groups. Overall, our findings observed age-dependent alterations in memory and morphological alterations in spines in mice, emerging as possible contributors to cognitive decline. These results highlight the potential for anti-aging interventions targeting synaptic structures to enhance cognitive health and extend the healthspan of aging individuals.
{"title":"Dendritic spine degeneration is associated with age-related decline in recognition and spatial memory in male mice.","authors":"Elibeth Monroy, Leonardo Aguilar-Hernandez, Fidel de la Cruz-López, Gonzalo Flores, Julio César Morales-Medina","doi":"10.1007/s00429-025-03002-7","DOIUrl":"10.1007/s00429-025-03002-7","url":null,"abstract":"<p><p>Human populations are experiencing an increase in aging, which is associated with cognitive deficits. Animal models of aging have shown that these behavioral impairments are associated with neuroarchitecture modifications in the prefrontal cortex (PFC) and hippocampus; however, most studies have focused on rats or lack multiple key ages. In this study, we evaluated spatial and recognition memory in male mice at critical ages [3 months (M), 6, 12 and 18] using the Morris water maze (MWM) and novel object recognition test (NORT), respectively. Moreover, we quantified dendritic arborization, spine density and the type of spines in the PFC, CA1 hippocampus and nucleus Accumbens Core (NAcC). Locomotion, assessed in the first phase of NORT, revealed age-dependent reductions. Notably, the 18 M group revealed significant recognition memory deficits. Spatial memory impairments were especially evident at the 12 M group in the MWM. Spine density was increased at 6 M in the NAcC, whereas a reduction was noted at 12 M and 18 M in the PFC. Morphological assessment of spines indicated age-dependent changes, including a notable increase in the proportion of thin spines in the CA1 and PFC regions. However, dendritic arborization remained largely unchanged across the examined brain regions and age groups. Overall, our findings observed age-dependent alterations in memory and morphological alterations in spines in mice, emerging as possible contributors to cognitive decline. These results highlight the potential for anti-aging interventions targeting synaptic structures to enhance cognitive health and extend the healthspan of aging individuals.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"230 7","pages":"142"},"PeriodicalIF":2.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942932","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 : 2025-08-26DOI: 10.1007/s00429-025-02974-w
Kurt G Schilling, Fan Zhang, J-Donald Tournier, Francesco Vergani, Stamatios N Sotiropoulos, Ariel Rokem, Lauren J O'Donnell
The first annual International Society of Tractography (IST) debate in Corsica in 2024 explored key challenges and controversies in tractography. This article examines the debate sparked by the provocative statement, "Tractography cannot give us anything we can't get from an atlas template." This debate contrasted two approaches: (1) white matter atlas templates, which provide standardized, population-based brain representations useful for studying brain structure and performing group comparisons, and (2) subject-specific tractography, which reconstructs individual brain connections using diffusion MRI, enabling in vivo "virtual dissection" of white matter pathways. We introduce key concepts, present arguments for and against this statement, and, as advocates of tractography, highlight its value while acknowledging the strengths of both approaches.
{"title":"Atlas-based templates vs. subject-specific tractography: resolving the debate.","authors":"Kurt G Schilling, Fan Zhang, J-Donald Tournier, Francesco Vergani, Stamatios N Sotiropoulos, Ariel Rokem, Lauren J O'Donnell","doi":"10.1007/s00429-025-02974-w","DOIUrl":"10.1007/s00429-025-02974-w","url":null,"abstract":"<p><p>The first annual International Society of Tractography (IST) debate in Corsica in 2024 explored key challenges and controversies in tractography. This article examines the debate sparked by the provocative statement, \"Tractography cannot give us anything we can't get from an atlas template.\" This debate contrasted two approaches: (1) white matter atlas templates, which provide standardized, population-based brain representations useful for studying brain structure and performing group comparisons, and (2) subject-specific tractography, which reconstructs individual brain connections using diffusion MRI, enabling in vivo \"virtual dissection\" of white matter pathways. We introduce key concepts, present arguments for and against this statement, and, as advocates of tractography, highlight its value while acknowledging the strengths of both approaches.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"230 7","pages":"141"},"PeriodicalIF":2.9,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12380923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942866","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 : 2025-08-25DOI: 10.1007/s00429-025-03000-9
Lauren E Welbourne, Joel T Martin, Federico G Segala, Anisa Y Morsi, Daniel H Baker, Alex R Wade
Important parts of the visual pathway occur in relatively small subcortical structures that are often difficult to identify and segment using standard structural scans in MRI (e.g. T1 and T2 scans). Studies of the Lateral Geniculate Nucleus (LGN) often use proton density (PD) scan protocols, repeated up to 40 times, then manually segment the LGN structure from the average image. Efficiency is crucial when conducting MRI scans: minimising time spent on structural scanning can increase time available for complementary functional MRI scans and/or reduce scanning costs. In this study we asked how segmentation accuracy depended on the number of PD repeats. Four raters segmented the LGN of five participants, using different numbers of PD scans in the average image (1, 2, 4, 8, 16, 24, 32, 40), and an additional experienced expert rater segmented the LGN for just the 40PD average for all participants. We compared how the rater LGN masks at each scan average level overlapped with the expert masks. One rater performed the segmentation for the 40PD average on four separate days, to measure intra-rater variability across repeats. We also used a state-of-the-art automated segmentation process to compare the reliability to manual segmentation. We found that the average overlap between rater masks and the expert masks increased up to the 16PD scan average level, after which there was no additional benefit to including more PD scans. The automated segmentation masks were comparable to the overlap between the raters (40PD) and expert masks.
{"title":"Evaluating the effective segmentation of human lateral geniculate nucleus.","authors":"Lauren E Welbourne, Joel T Martin, Federico G Segala, Anisa Y Morsi, Daniel H Baker, Alex R Wade","doi":"10.1007/s00429-025-03000-9","DOIUrl":"10.1007/s00429-025-03000-9","url":null,"abstract":"<p><p>Important parts of the visual pathway occur in relatively small subcortical structures that are often difficult to identify and segment using standard structural scans in MRI (e.g. T1 and T2 scans). Studies of the Lateral Geniculate Nucleus (LGN) often use proton density (PD) scan protocols, repeated up to 40 times, then manually segment the LGN structure from the average image. Efficiency is crucial when conducting MRI scans: minimising time spent on structural scanning can increase time available for complementary functional MRI scans and/or reduce scanning costs. In this study we asked how segmentation accuracy depended on the number of PD repeats. Four raters segmented the LGN of five participants, using different numbers of PD scans in the average image (1, 2, 4, 8, 16, 24, 32, 40), and an additional experienced expert rater segmented the LGN for just the 40PD average for all participants. We compared how the rater LGN masks at each scan average level overlapped with the expert masks. One rater performed the segmentation for the 40PD average on four separate days, to measure intra-rater variability across repeats. We also used a state-of-the-art automated segmentation process to compare the reliability to manual segmentation. We found that the average overlap between rater masks and the expert masks increased up to the 16PD scan average level, after which there was no additional benefit to including more PD scans. The automated segmentation masks were comparable to the overlap between the raters (40PD) and expert masks.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"230 7","pages":"140"},"PeriodicalIF":2.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12638374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942966","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 : 2025-08-25DOI: 10.1007/s00429-025-03005-4
Yahya Farid, Bryan Lukyanenko, Sandra F Witelson, Joan S Baizer
The superior olivary complex (SOC) receives auditory information from the cochlear nuclei. In nonhuman mammals, the SOC contains three nuclei: the lateral and medial superior olives (LSO, MSO) and the medial nucleus of the trapezoid body (MNTB). There are also periolivary neurons that are assigned to different nuclei in different mammals. The configuration of the SOC in the human differs from that in other species. The LSO is less well-defined; some authors do, and others do not, find an MNTB, and different authors recognize different periolivary nuclei. We have studied the organization of the human SOC using Nissl and immunostained sections of 12 brains from the Witelson Normal Brain Collection. We found an MSO in all cases although it varied in rostro-caudal extent. We did not consistently see a grouping of neurons consistent with an LSO in Nissl sections. Calbindin (CB) is expressed in neurons of the MNTB in several species. We found CB-immunoreactive (ir) cells in all human cases, some in the expected location of the MNTB, however these CB-ir neurons varied in number and location among cases. The variability in SOC configuration suggests there may also be individual variability in sound localization, a major function mediated by the SOC.
{"title":"Individual variability in the nuclei of the human superior olivary complex.","authors":"Yahya Farid, Bryan Lukyanenko, Sandra F Witelson, Joan S Baizer","doi":"10.1007/s00429-025-03005-4","DOIUrl":"10.1007/s00429-025-03005-4","url":null,"abstract":"<p><p>The superior olivary complex (SOC) receives auditory information from the cochlear nuclei. In nonhuman mammals, the SOC contains three nuclei: the lateral and medial superior olives (LSO, MSO) and the medial nucleus of the trapezoid body (MNTB). There are also periolivary neurons that are assigned to different nuclei in different mammals. The configuration of the SOC in the human differs from that in other species. The LSO is less well-defined; some authors do, and others do not, find an MNTB, and different authors recognize different periolivary nuclei. We have studied the organization of the human SOC using Nissl and immunostained sections of 12 brains from the Witelson Normal Brain Collection. We found an MSO in all cases although it varied in rostro-caudal extent. We did not consistently see a grouping of neurons consistent with an LSO in Nissl sections. Calbindin (CB) is expressed in neurons of the MNTB in several species. We found CB-immunoreactive (ir) cells in all human cases, some in the expected location of the MNTB, however these CB-ir neurons varied in number and location among cases. The variability in SOC configuration suggests there may also be individual variability in sound localization, a major function mediated by the SOC.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"230 7","pages":"139"},"PeriodicalIF":2.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12378517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942886","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 : 2025-08-21DOI: 10.1007/s00429-025-02988-4
Heather Woodhouse, Gerard Hall, Callum Simpson, Csaba Kozma, Frances Turner, Gabrielle M Schroeder, Beate Diehl, John S Duncan, Jiajie Mo, Kai Zhang, Aswin Chari, Martin Tisdall, Friederike Moeller, Chris Petkov, Matthew A Howard, George M Ibrahim, Elizabeth Donner, Nebras M Warsi, Raheel Ahmed, Peter N Taylor, Yujiang Wang
Understanding healthy human brain function is crucial to identify and map pathological tissue within it. Whilst previous studies have mapped intracranial EEG (icEEG) from non-epileptogenic brain regions, they often neglect age and sex effects. Further, they are limited by small sample sizes due to the modality's invasive nature. This study substantially expands the subject pool compared to existing literature, to create a multi-centre, normative map of brain activity which considers the effects of age, sex and recording hospital. Using interictal icEEG recordings from [Formula: see text] subjects across 15 centres, we constructed a normative map of non-pathological brain activity by regressing age and sex on relative band power in five frequency bands. A linear mixed model was implemented to account for the hospital effect. Variable importance was assessed using standard statistical measures, and regression coefficients (and their standard errors) were analysed at both whole-brain and regional scales. Recording hospital significantly impacted normative icEEG maps in all frequency bands, and age was a more influential predictor of band power than sex. The age effect varied by frequency band, but no spatial patterns were observed at the region-specific level. Certainty about regression coefficients was also frequency band specific and moderately impacted by sample size. The concept of a normative map is well-established in neuroscience research and particularly relevant to the icEEG modality, which does not allow healthy control baselines. Our key results regarding the hospital site and age effect guide future work utilising normative maps in icEEG.
{"title":"Multi-centre normative brain mapping of intracranial EEG lifespan patterns in the human brain.","authors":"Heather Woodhouse, Gerard Hall, Callum Simpson, Csaba Kozma, Frances Turner, Gabrielle M Schroeder, Beate Diehl, John S Duncan, Jiajie Mo, Kai Zhang, Aswin Chari, Martin Tisdall, Friederike Moeller, Chris Petkov, Matthew A Howard, George M Ibrahim, Elizabeth Donner, Nebras M Warsi, Raheel Ahmed, Peter N Taylor, Yujiang Wang","doi":"10.1007/s00429-025-02988-4","DOIUrl":"10.1007/s00429-025-02988-4","url":null,"abstract":"<p><p>Understanding healthy human brain function is crucial to identify and map pathological tissue within it. Whilst previous studies have mapped intracranial EEG (icEEG) from non-epileptogenic brain regions, they often neglect age and sex effects. Further, they are limited by small sample sizes due to the modality's invasive nature. This study substantially expands the subject pool compared to existing literature, to create a multi-centre, normative map of brain activity which considers the effects of age, sex and recording hospital. Using interictal icEEG recordings from [Formula: see text] subjects across 15 centres, we constructed a normative map of non-pathological brain activity by regressing age and sex on relative band power in five frequency bands. A linear mixed model was implemented to account for the hospital effect. Variable importance was assessed using standard statistical measures, and regression coefficients (and their standard errors) were analysed at both whole-brain and regional scales. Recording hospital significantly impacted normative icEEG maps in all frequency bands, and age was a more influential predictor of band power than sex. The age effect varied by frequency band, but no spatial patterns were observed at the region-specific level. Certainty about regression coefficients was also frequency band specific and moderately impacted by sample size. The concept of a normative map is well-established in neuroscience research and particularly relevant to the icEEG modality, which does not allow healthy control baselines. Our key results regarding the hospital site and age effect guide future work utilising normative maps in icEEG.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"230 7","pages":"138"},"PeriodicalIF":2.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12370820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942905","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 : 2025-08-19DOI: 10.1007/s00429-025-02996-4
C Saiz-Masvidal, V De la Peña-Arteaga, S Bertolín, I Diez, A Juaneda-Seguí, I Martínez-Zalacaín, P Chavarría-Elizondo, M Subirà, J M Menchón, J Sepulcre, Miquel Àngel Fullana, Carles Soriano-Mas
Monoaminergic systems, including serotonin, dopamine, and norepinephrine, are essential for regulating brain activity and facilitating behavioral flexibility. These systems originate from brainstem nuclei and project widely to modulate functions such as mood, attention, memory, and adaptability. Using resting-state functional MRI (rs-fMRI), this study aimed to investigate the connectivity networks of key monoaminergic nuclei in 193 healthy adults and explore their correspondence with molecular imaging maps of neurotransmitter-specific biochemical markers. Functional connectivity (FC) was assessed using seed-based rs-fMRI analyses with seeds placed in the dorsal raphe nucleus (DRN), nucleus centralis superior (NCS), ventral tegmental area (VTA), substantia nigra pars compacta (SNc), and locus coeruleus (LC). Cross-modal analyses using molecular imaging data were performed to correlate these rs-FC maps with the distribution of neurotransmitter-related receptors, transporters, and synthesis enzymes, providing insights into the molecular architecture underlying the FC of monoaminergic systems. Whole-brain FC maps revealed distinct patterns for each nucleus. DRN projections were extensive, connecting to subcortical regions such as the hippocampus and amygdala and cortical areas including the precuneus, cingulate, and medial frontal cortex. NCS projections overlapped partially but uniquely targeted the orbitofrontal and insular cortices. Dopaminergic pathways exhibited connectivity with the striatum, thalamus, and prefrontal cortex, while noradrenergic LC projections displayed lateralized connectivity to occipital, temporal, and frontal regions. Cross-modal correlations with molecular imaging demonstrated significant spatial associations between rs-FC maps and neurotransmitter-specific markers, including 5HTT, DAT, and FDOPA. This study enhances our understanding of neurotransmitter networks, highlighting their relevance in brain function and potential as biomarkers for neuropsychiatric conditions.
{"title":"Mapping cross-modal functional connectivity of major neurotransmitter systems in the human brain.","authors":"C Saiz-Masvidal, V De la Peña-Arteaga, S Bertolín, I Diez, A Juaneda-Seguí, I Martínez-Zalacaín, P Chavarría-Elizondo, M Subirà, J M Menchón, J Sepulcre, Miquel Àngel Fullana, Carles Soriano-Mas","doi":"10.1007/s00429-025-02996-4","DOIUrl":"10.1007/s00429-025-02996-4","url":null,"abstract":"<p><p>Monoaminergic systems, including serotonin, dopamine, and norepinephrine, are essential for regulating brain activity and facilitating behavioral flexibility. These systems originate from brainstem nuclei and project widely to modulate functions such as mood, attention, memory, and adaptability. Using resting-state functional MRI (rs-fMRI), this study aimed to investigate the connectivity networks of key monoaminergic nuclei in 193 healthy adults and explore their correspondence with molecular imaging maps of neurotransmitter-specific biochemical markers. Functional connectivity (FC) was assessed using seed-based rs-fMRI analyses with seeds placed in the dorsal raphe nucleus (DRN), nucleus centralis superior (NCS), ventral tegmental area (VTA), substantia nigra pars compacta (SNc), and locus coeruleus (LC). Cross-modal analyses using molecular imaging data were performed to correlate these rs-FC maps with the distribution of neurotransmitter-related receptors, transporters, and synthesis enzymes, providing insights into the molecular architecture underlying the FC of monoaminergic systems. Whole-brain FC maps revealed distinct patterns for each nucleus. DRN projections were extensive, connecting to subcortical regions such as the hippocampus and amygdala and cortical areas including the precuneus, cingulate, and medial frontal cortex. NCS projections overlapped partially but uniquely targeted the orbitofrontal and insular cortices. Dopaminergic pathways exhibited connectivity with the striatum, thalamus, and prefrontal cortex, while noradrenergic LC projections displayed lateralized connectivity to occipital, temporal, and frontal regions. Cross-modal correlations with molecular imaging demonstrated significant spatial associations between rs-FC maps and neurotransmitter-specific markers, including 5HTT, DAT, and FDOPA. This study enhances our understanding of neurotransmitter networks, highlighting their relevance in brain function and potential as biomarkers for neuropsychiatric conditions.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"230 7","pages":"137"},"PeriodicalIF":2.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12364969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871487","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 : 2025-08-14DOI: 10.1007/s00429-025-02992-8
Christopher J Hammond, Liangsuo Ma, James M Bjork, F Gerard Moeller, Albert J Arias
Impairments in emotional regulation and mood symptoms are interrelated and associated with alcohol use disorder (AUD) risk, but the underlying aberrant neural circuitry involved is poorly understood. In the present study, we examined alterations in effective (directional) connectivity (EC) during emotional face processing in individuals with and without AUD. We utilized functional MRI data from the Human Connectome Project obtained during an emotional face processing task in 70 participants with AUD and 70 controls (CON). Focusing on ventromedial prefrontal cortex (VMPFC), bilateral ventrolateral prefrontal cortex (VLPFC), amygdala (AMY), and fusiform gyrus (FG), and right (R) hypothalamus (HTN) nodes, we performed dynamic causal modeling analysis to test group-level differences in EC. Linear regressions characterized EC relationships with measures of cumulative alcohol exposure and depression and anxiety. Compared to CON participants, AUD participants had lower ECs from VMPFC → bilateral VLPFC, left (L)-VLPFC → L-VLPFC and VMPFC, R-VLPFC → L-FG, R-FG → HTN, and R-AMY → L-VLPFC; and greater ECs from VMPFC → VMPFC, L-VLPFC → R-VLPFC and bilateral FG, L-FG → R-AMY and HTN, R-AMY → VMPFC and L-FG, and L-AMY → HTN connectivities. In regression analyses, these cortical-to-cortical and cortical-to-subcortical ECs were associated with cumulative alcohol exposure. EC from R-VLPFC to L-FG was negatively associated with depression. Individuals with AUD have disrupted EC in cortical-to-cortical and cortical-to-subcortical circuits during emotional face processing in brain regions purported to govern emotion control, which may explain linkages between cumulative alcohol exposure and depression.
{"title":"Altered effective connectivity of emotion perception and regulation networks during an emotional face perception task in adults with alcohol use disorder.","authors":"Christopher J Hammond, Liangsuo Ma, James M Bjork, F Gerard Moeller, Albert J Arias","doi":"10.1007/s00429-025-02992-8","DOIUrl":"10.1007/s00429-025-02992-8","url":null,"abstract":"<p><p>Impairments in emotional regulation and mood symptoms are interrelated and associated with alcohol use disorder (AUD) risk, but the underlying aberrant neural circuitry involved is poorly understood. In the present study, we examined alterations in effective (directional) connectivity (EC) during emotional face processing in individuals with and without AUD. We utilized functional MRI data from the Human Connectome Project obtained during an emotional face processing task in 70 participants with AUD and 70 controls (CON). Focusing on ventromedial prefrontal cortex (VMPFC), bilateral ventrolateral prefrontal cortex (VLPFC), amygdala (AMY), and fusiform gyrus (FG), and right (R) hypothalamus (HTN) nodes, we performed dynamic causal modeling analysis to test group-level differences in EC. Linear regressions characterized EC relationships with measures of cumulative alcohol exposure and depression and anxiety. Compared to CON participants, AUD participants had lower ECs from VMPFC → bilateral VLPFC, left (L)-VLPFC → L-VLPFC and VMPFC, R-VLPFC → L-FG, R-FG → HTN, and R-AMY → L-VLPFC; and greater ECs from VMPFC → VMPFC, L-VLPFC → R-VLPFC and bilateral FG, L-FG → R-AMY and HTN, R-AMY → VMPFC and L-FG, and L-AMY → HTN connectivities. In regression analyses, these cortical-to-cortical and cortical-to-subcortical ECs were associated with cumulative alcohol exposure. EC from R-VLPFC to L-FG was negatively associated with depression. Individuals with AUD have disrupted EC in cortical-to-cortical and cortical-to-subcortical circuits during emotional face processing in brain regions purported to govern emotion control, which may explain linkages between cumulative alcohol exposure and depression.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"230 7","pages":"136"},"PeriodicalIF":2.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854590","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 : 2025-08-14DOI: 10.1007/s00429-025-03003-6
Ardeshir Nabizadeh, Ali Rafati, Narges Karbalaei, Mohammad Reza Namavar, Saeid Hosseinzadeh, Hadi Moatamed Jahromi, Atefeh Rahimi, Maryam Naseh
Alzheimer's disease (AD) is a deteriorating neurodegenerative disorder defined by cognitive decline and neuronal damage, with oxidative stress and neuroinflammation as central pathological features. Emerging evidence suggests the gut-brain axis is a key modulator in neurodegeneration, highlighting probiotics' potential in mitigating AD progression. This study investigates the effects of Lactobacillus acidophilus ATCC4356, Lactobacillus reuteri DSM 17938, and their combination on cognitive performance, oxidative stress, and hippocampal structure in a streptozotocin (STZ)-induced AD-like rat model. Thirty-Five male Sprague-Dawley rats were randomly assigned to five groups: Sham, AD-like model (STZ), STZ + Ac, STZ + Re, and STZ + Comb. The AD-like model was induced via intracerebroventricular (icv) injection of STZ. Probiotics were administered by gavage for 35 days. Behavioral assessments, including the open field test and Morris water maze, were conducted to evaluate cognitive and anxiety-like behaviors. Hippocampal oxidative stress markers, including malondialdehyde (MDA), glutathione, superoxide dismutase, and catalase , were analyzed biochemically. Additionally, stereological techniques were used to assess hippocampal volume and cellular densities. Behavioral results demonstrated significant improvement in anxiety-like behavior and spatial memory in probiotic-treated groups compared to the STZ group. Biochemical analysis revealed reduced MDA levels and enhanced antioxidant markers following probiotic intervention. Histological and stereological analyses indicated increased neuronal density and reduced glial cell activation in hippocampal subregions (CA1, CA3, DG), though hippocampal volume loss remained unaltered. These findings underscore the neuroprotective potential of probiotics in alleviating AD-related neurodegeneration, possibly through antioxidative and anti-inflammatory mechanisms. Further pre-clinical studies are warranted to optimize probiotic regimens for AD prevention and treatment.
{"title":"Probiotic effects on cognitive performance, hippocampal oxidative stress, and structural damage induced by icv STZ in Alzheimer-like rat model.","authors":"Ardeshir Nabizadeh, Ali Rafati, Narges Karbalaei, Mohammad Reza Namavar, Saeid Hosseinzadeh, Hadi Moatamed Jahromi, Atefeh Rahimi, Maryam Naseh","doi":"10.1007/s00429-025-03003-6","DOIUrl":"10.1007/s00429-025-03003-6","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a deteriorating neurodegenerative disorder defined by cognitive decline and neuronal damage, with oxidative stress and neuroinflammation as central pathological features. Emerging evidence suggests the gut-brain axis is a key modulator in neurodegeneration, highlighting probiotics' potential in mitigating AD progression. This study investigates the effects of Lactobacillus acidophilus ATCC4356, Lactobacillus reuteri DSM 17938, and their combination on cognitive performance, oxidative stress, and hippocampal structure in a streptozotocin (STZ)-induced AD-like rat model. Thirty-Five male Sprague-Dawley rats were randomly assigned to five groups: Sham, AD-like model (STZ), STZ + Ac, STZ + Re, and STZ + Comb. The AD-like model was induced via intracerebroventricular (icv) injection of STZ. Probiotics were administered by gavage for 35 days. Behavioral assessments, including the open field test and Morris water maze, were conducted to evaluate cognitive and anxiety-like behaviors. Hippocampal oxidative stress markers, including malondialdehyde (MDA), glutathione, superoxide dismutase, and catalase , were analyzed biochemically. Additionally, stereological techniques were used to assess hippocampal volume and cellular densities. Behavioral results demonstrated significant improvement in anxiety-like behavior and spatial memory in probiotic-treated groups compared to the STZ group. Biochemical analysis revealed reduced MDA levels and enhanced antioxidant markers following probiotic intervention. Histological and stereological analyses indicated increased neuronal density and reduced glial cell activation in hippocampal subregions (CA1, CA3, DG), though hippocampal volume loss remained unaltered. These findings underscore the neuroprotective potential of probiotics in alleviating AD-related neurodegeneration, possibly through antioxidative and anti-inflammatory mechanisms. Further pre-clinical studies are warranted to optimize probiotic regimens for AD prevention and treatment.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"230 7","pages":"135"},"PeriodicalIF":2.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-13DOI: 10.1007/s00429-025-02993-7
Steven Seung-Suk Kang, Joseph Bodenheimer, Kayley Morris, Tracy Butler
The claustrum is a thin gray matter structure in each brain hemisphere, characterized by exceptionally high connectivity with nearly all brain regions. Despite extensive animal studies on its anatomy and function and growing evidence of claustral deficits in neuropsychiatric disorders, its specific roles in normal and abnormal human brain function remain largely unknown. This is primarily due to its thin and complex morphology, which limits accurate anatomical delineation and neural activity isolation in conventional in vivo neuroimaging. To facilitate future neuroimaging studies, we developed a comprehensive and reliable manual segmentation protocol based on a cellular-resolution brain atlas and high-resolution (0.7 mm isotropic) MRI data. The protocols involve detailed guidelines to delineate the entire claustrum, including the inferior parts that have not been clearly described in earlier MRI studies. Additionally, we propose a geometric method to parcellate the claustrum into three subregions (the dorsal, ventral, and temporal claustrum) along the superior-to-inferior axis. The mean bilateral claustrum volume in 10 young adults was 3307.5 mm3, approximately 0.21% of total intracranial volume. Our segmentation protocol demonstrated high inter- and intra-rater reliability (ICC > 0.89, DSC > 0.85), confirming its replicability. This comprehensive and reliable manual segmentation protocol offers a robust foundation for anatomically precise neuroimaging investigations of the human claustrum.
{"title":"A comprehensive and reliable protocol for manual segmentation of the human claustrum using high-resolution MRI.","authors":"Steven Seung-Suk Kang, Joseph Bodenheimer, Kayley Morris, Tracy Butler","doi":"10.1007/s00429-025-02993-7","DOIUrl":"10.1007/s00429-025-02993-7","url":null,"abstract":"<p><p>The claustrum is a thin gray matter structure in each brain hemisphere, characterized by exceptionally high connectivity with nearly all brain regions. Despite extensive animal studies on its anatomy and function and growing evidence of claustral deficits in neuropsychiatric disorders, its specific roles in normal and abnormal human brain function remain largely unknown. This is primarily due to its thin and complex morphology, which limits accurate anatomical delineation and neural activity isolation in conventional in vivo neuroimaging. To facilitate future neuroimaging studies, we developed a comprehensive and reliable manual segmentation protocol based on a cellular-resolution brain atlas and high-resolution (0.7 mm isotropic) MRI data. The protocols involve detailed guidelines to delineate the entire claustrum, including the inferior parts that have not been clearly described in earlier MRI studies. Additionally, we propose a geometric method to parcellate the claustrum into three subregions (the dorsal, ventral, and temporal claustrum) along the superior-to-inferior axis. The mean bilateral claustrum volume in 10 young adults was 3307.5 mm<sup>3</sup>, approximately 0.21% of total intracranial volume. Our segmentation protocol demonstrated high inter- and intra-rater reliability (ICC > 0.89, DSC > 0.85), confirming its replicability. This comprehensive and reliable manual segmentation protocol offers a robust foundation for anatomically precise neuroimaging investigations of the human claustrum.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"230 7","pages":"134"},"PeriodicalIF":2.9,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-12DOI: 10.1007/s00429-025-02994-6
Caterina A Pedersini, Alessio Fracasso, Amna Dogar, Bas Rokers, Pawan Sinha
Blindness provides a unique model for investigating brain plasticity in response to sensory deprivation. While structural changes in both gray and white matter have been widely documented, particularly in cases of early or congenital visual deprivation, gray matter studies have traditionally focused on cortical thickness, often finding cortical thickening in posterior regions. However, other aspects of gray matter integrity, such as cortical myelin content, remain underexplored. In this study, we examined the effects of visual deprivation on cortical structure in a cohort of early blind individuals who received eye surgery during adolescence, expanding beyond conventional measures to include cortical thickness, curvature, and T1-weighted signal intensity. This multi-faceted approach offers a more comprehensive view of cortical adaptations to early sensory deprivation. While blindness offers valuable insights into sensory-driven brain plasticity, an intriguing and unresolved question is whether structural plasticity reverses after sight restoration, enabling typical visual processing circuits to develop despite the initial period of deprivation. To address this, we assessed the effect of sight-recovering eye surgery on gray matter changes. Critically, individuals in this cohort received surgery after the closure of the sensitive period for visual development. We did not find evidence of gray matter changes after surgery. However, in a previous study conducted on the same cohort, we reported that notable plasticity in white matter emerged in this same population. These results suggest that white matter may potentially serve as a biomarker of structural plasticity following sight restoration, even beyond the sensitive developmental window.
{"title":"Gray matter abnormalities in sight deprivation and sight restoration.","authors":"Caterina A Pedersini, Alessio Fracasso, Amna Dogar, Bas Rokers, Pawan Sinha","doi":"10.1007/s00429-025-02994-6","DOIUrl":"10.1007/s00429-025-02994-6","url":null,"abstract":"<p><p>Blindness provides a unique model for investigating brain plasticity in response to sensory deprivation. While structural changes in both gray and white matter have been widely documented, particularly in cases of early or congenital visual deprivation, gray matter studies have traditionally focused on cortical thickness, often finding cortical thickening in posterior regions. However, other aspects of gray matter integrity, such as cortical myelin content, remain underexplored. In this study, we examined the effects of visual deprivation on cortical structure in a cohort of early blind individuals who received eye surgery during adolescence, expanding beyond conventional measures to include cortical thickness, curvature, and T1-weighted signal intensity. This multi-faceted approach offers a more comprehensive view of cortical adaptations to early sensory deprivation. While blindness offers valuable insights into sensory-driven brain plasticity, an intriguing and unresolved question is whether structural plasticity reverses after sight restoration, enabling typical visual processing circuits to develop despite the initial period of deprivation. To address this, we assessed the effect of sight-recovering eye surgery on gray matter changes. Critically, individuals in this cohort received surgery after the closure of the sensitive period for visual development. We did not find evidence of gray matter changes after surgery. However, in a previous study conducted on the same cohort, we reported that notable plasticity in white matter emerged in this same population. These results suggest that white matter may potentially serve as a biomarker of structural plasticity following sight restoration, even beyond the sensitive developmental window.</p>","PeriodicalId":9145,"journal":{"name":"Brain Structure & Function","volume":"230 7","pages":"133"},"PeriodicalIF":2.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12343673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820589","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}