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  • 1. Burhanoglu, Birce Begum
    et al.
    Dinçer, Gulsah
    Yilmaz, Alpaslan
    Özalay, Özgun
    SoCAT Lab, Department of Psychiatry, School of Medicine, Ege University, 35100 Bornova, Izmir, Turkey; Department of Neuroscience, Institute of Health Sciences, Ege University, Izmir, Turkey.
    Uslu, Ozgul
    Unaran, Esmin
    Kitis, Omer
    Gonul, Ali Saffet
    Brain areas associated with resilience to depression in high-risk young women2021Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 226, nr 3, s. 875-888Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous structural brain-imaging studies in first-degree relatives of depressed patients showed alterations that are generally accepted as vulnerability markers for depression. However, only half of the relatives had depression at follow-up, while the other half did not. The aim of this study was to identify the brain areas associated with resilience to depression in high-risk subjects with familial depression. We recruited 59 young women with a history of depressed mothers. Twenty-nine of them (high-risk group [HRG]) had no depression history, while 30 (depressive group) had at least 1 depressive episode in adolescence. The brain structures of the groups were compared through voxel-based morphometry and analysis of cortical thickness. Individual amygdala nuclei and hippocampal subfield volumes were measured. The analysis showed larger amygdala volume, thicker subcallosal cortex and bilateral insula in the women in the HRG compared with those in the depressive group. In addition, we detected more gray matter in the left temporal pole in the HRG. The larger gray matter volume and increased cortical thickness in the key hub regions of the salience network (amygdala and insula) and structurally connected regions in the limbic network (subcallosal area and temporal pole) might prevent women in the HRG from converting to depression.

  • 2. Garzón, Benjamín
    et al.
    Lövdén, Martin
    de Boer, Lieke
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Bäckman, Lars
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Guitart-Masip, Marc
    Role of dopamine and gray matter density in aging effects and individual differences of functional connectomes2021Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 226, nr 3, s. 743-758Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    With increasing age, functional connectomes become dissimilar across normal individuals, reflecting heterogenous aging effects on functional connectivity (FC). We investigated the distribution of these effects across the connectome and their relationship with age-related differences in dopamine (DA) D1 receptor availability and gray matter density (GMD). With this aim, we determined aging effects on mean and interindividual variance of FC using fMRI in 30 younger and 30 older healthy subjects and mapped the contribution of each connection to the patterns of age-related similarity loss. Aging effects on mean FC accounted mainly for the dissimilarity between connectomes of younger and older adults, and were related, across brain regions, to aging effects on DA D1 receptor availability. Aging effects on the variance of FC indicated a global increase in variance with advancing age, explained connectome dissimilarity among older subjects and were related to aging effects on variance of GMD. The relationship between aging and the similarity of connectomes can thus be partly explained by age differences in DA modulation and gray matter structure.

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  • 3. Giddaluru, Sudheer
    et al.
    Espeseth, Thomas
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet and Stockholm University, 11330 Stockholm, Sweden.
    Westlye, Lars T
    Lundquist, Anders
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Christoforou, Andrea
    Cichon, Sven
    Adolfsson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Psykiatri.
    Steen, Vidar M
    Reinvang, Ivar
    Nilsson, Lars Göran
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). ARC, Karolinska Institutet, Stockholm, Sweden.
    Le Hellard, Stéphanie
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Genetics of structural connectivity and information processing in the brain2016Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 221, nr 9, s. 4643-4661Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10(-08)). Suggestive associations (Meta P value <1 × 10(-06)) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 × 10(-08)). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 × 10(-07)). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 × 10(-08)), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 × 10(-07)) and the multimodal analysis (Fisher P value = 1 × 10(-07)). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain.

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  • 4. Hamodeh, Salah
    et al.
    Bozkurt, Ayse
    Mao, Haian
    Sultan, Fahad
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Department of Cognitive Neurology, HIH for Clinical Brain Research, Otfried-Müller-Str. 27, 72076 Tübingen, Germany.
    Uncovering specific changes in network wiring underlying the primate cerebrotype2017Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 222, nr 7, s. 3255-3266Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Regular scaling of brain networks during evolution has been proposed to be the major process leading to enlarged brains. Alternative views, however, suggest that deviations from regular scaling were crucial to the evolution of the primate brain and the emergence of different cerebrotypes. Here, we examined the scaling within the major link between the cerebellum and the cerebral cortex by studying the deep cerebellar nuclei (DCN). We compared the major axonal and dendritic wiring in the DCN of rodents and monkeys in search of regular scaling. We were able to confirm regular scaling within the density of neurons, the general dendritic length per neuron and the Purkinje cell axon length. However, we also observed specific modification of the scaling rules within the primates' largest and phylogenetically newest DCN, the dentate nucleus (LN/dentate). Our analysis shows a deviation from regular scaling in the predicted dendritic length per neuron in the LN/dentate. This reduction in the dendritic length is also associated with a smaller dendritic region-of-influence of these neurons. We also detected specific changes in the dendritic diameter distribution, supporting the theory that there is a shift in the neuronal population of the LN/dentate towards neurons that exhibit spatially restricted, clustered branching trees. The smaller dendritic fields would enable a larger number of network modules to be accommodated in the primate LN/dentate and would provide an explanation for the unique folded structure of the primate LN/dentate. Our results show that, in some brain regions, connectivity maximization (i.e., an increase of dendritic fields) is not the sole optimum and that increases in the number of network modules may be important for the emergence of a divergent primate cerebrotype.

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  • 5.
    Login, Hande
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Butowt, Rafal
    Bohm, Staffan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Activity-dependent and graded BACE1 expression in the olfactory epithelium is mediated by the retinoic acid metabolizing enzyme CYP26B12015Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 220, nr 4, s. 2143-2157Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is well established that environmental influences play a key role in sculpting neuronal connectivity in the brain. One example is the olfactory sensory map of topographic axonal connectivity. While intrinsic odorant receptor signaling in olfactory sensory neurons (OSN) determines anterior-posterior counter gradients of the axonal guidance receptors Neuropilin-1 and Plexin-A1, little is known about stimulus-dependent gradients of protein expression, which correlates with the functional organization of the olfactory sensory map along its dorsomedial (DM)-ventrolateral (VL) axis. Deficiency of the Alzheimer's β-secretase BACE1, which is expressed in a DM(low)-VL(high) gradient, results in OSN axon targeting errors in a DM > VL and gene dose-dependent manner. We show that expression of BACE1 and the all-trans retinoic acid (RA)-degrading enzyme Cyp26B1 form DM-VL counter gradients in the olfactory epithelium. Analyses of mRNA and protein levels in OSNs after naris occlusion, in mice deficient in the olfactory cyclic nucleotide-gated channel and in relation to onset of respiration, show that BACE1 and Cyp26B1 expression in OSNs inversely depend on neuronal activity. Overexpression of a Cyp26B1 or presence of a dominant negative RA receptor transgene selectively in OSNs, inhibit BACE1 expression while leaving the DM(low)-VL(high) gradient of the axonal guidance protein Neuropilin-2 intact. We conclude that stimulus-dependent neuronal activity can control the expression of the RA catabolic enzyme Cyp26B1 and downstream genes such as BACE1. This result is pertinent to an understanding of the mechanisms by which a topographic pattern of connectivity is achieved and modified as a consequence of graded gene expression and sensory experience.

  • 6. Mao, Haian
    et al.
    Hamodeh, Salah
    Skodras, Angelos
    Sultan, Fahad
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Quantitative organization of the excitatory synapses of the primate cerebellar nuclei: further evidence for a specialized architecture underlying the primate cerebellum2019Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 224, nr 6, s. 1987-1998Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The cerebellar intrinsic connectivity is of remarkable regularity with a similar build repeated many times over. However, several modifications of this basic circuitry occur that can provide important clues to evolutionary adaptations. We have observed differences in the wiring of the cerebellar output structures (the deep cerebellar nuclei, DCN) with higher dendritic length density in the phylogenetically newer DCN. In rats, we showed that an increase in wiring is associated with an increase in the presynaptic vesicular glutamate transporter 1 (vGluT1). In this study, we have extended our analysis to the rhesus monkey and can show similarities and differences between the two species. The similarities confirm a higher density in vGluT1+ boutons in the lateral (LN/dentate) and posterior interpositus nucleus compared to the phylogenetically older DCN. In general, we also observe a lower density of vGluT1 and 2+boutons in the monkey, which however, yields a similar number of excitatory boutons per neuron in both species. The only exception is the vGlut1+boutons in the macaque LN/dentate, which showed a significantly lower number of vGluT1+boutons per neuron. We also detected a higher percentage of co-labelled vGluT1 and 2 boutons in the macaque than we found in the rat. In summary, these results confirm that the hyposcalled dendrites of the monkey LN/dentate also show a lower number of vGluT1+boutons per neuron. These results provide further support of our model relating the dendritic morphology of the LN/dentate neurons to the morphology of the specially enlarged LN/dentate nucleus in primates.

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  • 7. Mongia, S.
    et al.
    Tripathi, Anushree
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Center for Applied Medical Research (CIMA), Division of Neurosciences, Universidad de Navarra, Pamplona, Spain.
    Mengual, E.
    Arborization patterns of amygdalopetal axons from the rat ventral pallidum2016Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 221, nr 9, s. 4549-4573Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We previously analyzed the arborization patterns of rat ventral pallidal (VP) axons that coursed caudally to innervate the thalamus and brainstem (Tripathi et al. in Brain Struct Funct 218:1133-1157, 2013). Here, we have reconstructed 16 previously undetected axons from the same tracer deposits that follow a more lateral trajectory. Virtually all 16 axons emanating from the different VP compartments collateralized in the extended amygdala system (EAS) and amygdaloid complex. The most frequent targets of axons from the lateral and medial (VPm) VP compartments were the rostral sublenticular extended amygdala, the extended amygdala (EA), the central nucleus of the amygdala and the posterior part of the basolateral amygdaloid nucleus. In contrast, axons from the rostral extension of the VP preferentially innervated the anterior amygdaloid area, the magnocellular preoptic nucleus, and the anterior part of the basomedial amygdaloid nucleus. We additionally found and reconstructed a single corticopetal axon arising from the VPm. The new results show that both direct and indirect projections from the basolateral complex and EAS to the ventral striatopallidal system are reciprocated by VP projections, and suggest that the systems can be activated simultaneously. The results additionally suggest that the amygdaloid complex and cortex are innervated separately from the VP. Finally, the combination of new and previous data indicate that approximately 84 % of VP axons (88/105) participate in basal ganglia circuits, 15 % (16/105) target the amygdaloid complex, and less than 1 % innervate the cortex.

  • 8. Papenberg, Goran
    et al.
    Jonasson, Lars S.
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Karalija, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Johansson, Jarkko
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Koehncke, Ylva
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Aging Research Center, Karolinska Institutet and Stockholm University, Tomtebodavägen 18A, 171 65 Solna, Sweden.
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Axelsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Wåhlin, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Riklund, Katrine
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Lindenberger, Ulman
    Lovden, Martin
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Diagnostisk radiologi. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI).
    Backman, Lars
    Mapping the landscape of human dopamine D2/3 receptors with [11C]raclopride2019Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 224, nr 8, s. 2871-2882Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The dopamine D2/3 system is fundamental for sensory, motor, emotional, and cognitive aspects of behavior. Small-scale human histopathological and animal studies show high density of D2/3 dopamine receptors (D2/3DR) in striatum, but also demonstrate the existence of such receptors across cortical and limbic regions. Assessment of D2/3DR BPND in the extrastriatal regions with [C-11]raclopride has long been considered unreliable due to the relatively low density of D2/3DR outside the striatum. We describe the distribution and interregional links of D2/3DR availability measured with PET and [C-11]raclopride across the human brain in a large sample (N = 176; age range 64-68 years). Structural equation modeling revealed that D2/3DR availability can be organized according to anatomical (nigrostriatal, mesolimbic, mesocortical) and functional (limbic, associative, sensorimotor) dopamine pathways. D2/3DR availability in corticolimbic functional subdivisions showed differential associations to corresponding striatal subdivisions, extending animal and pharmacological work. Our findings provide evidence on the dimensionality and organization of [C-11]raclopride D2/3DR availability in the living human brain that conforms to known dopaminergic pathways.

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  • 9.
    Pedale, Tiziana
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Department of Psychology, Sapienza University of Rome, Via dei Marsi, 78, 00158 Rome, Italy; Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Via Ardeatina, 306, 00179 Rome, Italy.
    Macaluso, Emiliano
    Santangelo, Valerio
    Enhanced insular/prefrontal connectivity when resisting from emotional distraction during visual search2019Ingår i: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 224, nr 6, s. 2009-2026Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous literature demonstrated that the processing of emotional stimuli can interfere with goal-directed behavior. This has been shown primarily in the context of working memory tasks, but emotional distraction may affect also other processes, such as the orienting of visuo-spatial attention. During fMRI, we presented human subjects with emotional stimuli embedded within complex everyday life visual scenes. Emotional stimuli could be either the current target to be searched for or task-irrelevant distractors. Behavioral and eye-movement data revealed faster detection of emotional than neutral targets. Emotional distractors were found to be fixated later and for a shorter duration than emotional targets, suggesting efficient top-down control in avoiding emotional distraction. The fMRI data demonstrated that negative (but not positive) stimuli were mandatorily processed by limbic/para-limbic regions (namely, the right amygdala and the left insula), irrespective of current task relevance: that is, these regions activated for both emotional targets and distractors. However, analyses of inter-regional connectivity revealed a functional coupling between the left insula and the right prefrontal cortex that increased specifically during search in the presence of emotional distractors. This indicates that increased functional coupling between affective limbic/para-limbic regions and control regions in the frontal cortex can attenuate emotional distraction, permitting the allocation of spatial attentional resources toward task-relevant neutral targets in the presence of distracting emotional signals.

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