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  • 1. Bannbers, Elin
    et al.
    Gingnell, Malin
    Engman, Jonas
    Morell, Arvid
    Sylven, Sara
    Skalkidou, Alkistis
    Kask, Kristiina
    Bäckström, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Wikstrom, Johan
    Poromaa, Inger Sundstrom
    Prefrontal activity during response inhibition decreases over time in the postpartum period2013Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 241, s. 132-138Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The postpartum period is characterized by complex hormonal changes, but human imaging studies in the postpartum period have thus far predominantly focused on the neural correlates of maternal behavior or postpartum depression, whereas longitudinal studies on neural correlates of cognitive function across the postpartum period in healthy women are lacking. The aim of this study was to longitudinally examine response inhibition, as a measure of executive function, during the postpartum period and its neural correlates in healthy postpartum women and non-postpartum controls. Thirteen healthy postpartum women underwent event-related functional magnetic resonance imaging while performing a Go/NoGo task. The first assessment was made within 48 h of delivery, and the second at 4-7 weeks postpartum. In addition, 13 healthy women examined twice during the menstrual cycle were included as non-postpartum controls. In postpartum women region of interest analyses revealed task-related decreased activations in the right inferior frontal gyrus, right anterior cingulate, and bilateral precentral gyri at the late postpartum assessment. Generally, postpartum women displayed lower activity during response inhibition in the bilateral inferior frontal gyri and precentral gyri compared to non-postpartum controls. No differences in performance on the Go/NoGo task were found between time-points or between groups. In conclusion, this study has discovered that brain activity in prefrontal areas during a response inhibition task decreases throughout the course of the first postpartum weeks and is lower than in non-postpartum controls. Further studies on the normal adaptive brain activity changes that occur during the postpartum period are warranted. (C) 2012 Elsevier B.V. All rights reserved.

  • 2. Gruden, Marina A.
    et al.
    Davidova, Tatiana V.
    Yanamandra, Kiran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Kucheryanu, Valery G.
    Morozova-Roche, Ludmilla A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Sherstnev, Vladimir V.
    Sewell, Robert D. E.
    Nasal inoculation with a-synuclein aggregates evokes rigidity, locomotor deficits and immunity to such misfolded species as well as dopamine2013Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 243, s. 205-212Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Animal models of Parkinson's disease (PD) have been widely used to investigate the pathogenesis of this neurodegenerative disorder which is typically associated with the specific and largely disordered protein alpha-synuclein (alpha-syn). In the current study, the nasal vector was used to deliver alpha-syn aggregates to the brain. Both alpha-syn oligomers and its fibrils were firstly characterized using atomic force microscopy and the thioflavin T binding assay. The toxic oligomers alone (0.48 mg/kg) or their 50:50 combination with fibrils (in a total dose of 0.48 mg/kg) were then given intranasally for ten days in mice and PD-mimetic symptoms as well as humoral immunity to these species and dopamine (DA) were evaluated simultaneously. Open-field behavioral deficits indicated by rigidity and reduced locomotor activity were induced by the dual administration of alpha-syn oligomers plus fibrils but not the oligomers by themselves under the 10-day dosing regimen. In contrast, using ELISA, high levels of serum autoantibodies to alpha-syn monomeric, oligomeric and fibrillar conformers as well as DA were observed in both treatment groups reflecting immune system activation and this substantiates previous clinical studies in Parkinson's disease patients. Thus, nasal administration of alpha-syn amyloidogenic species may be a potential experimental PD model which results not only in motor deficits but also incitement of humoral protection to mimic the disease. Such a paradigm may be exploitable in the quest for potential therapeutic strategies and further studies are warranted.

  • 3. Gruden, Marina A
    et al.
    Davydova, Tatiana V
    Narkevich, Victor B
    Fomina, Valentina G
    Wang, Chao
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Kudrin, Vladimir S
    Morozova-Roche, Ludmilla A
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Sewell, Robert D E
    Noradrenergic and serotonergic neurochemistry arising from intranasal inoculation with α-synuclein aggregates which incite parkinsonian-like symptoms2015Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 279, s. 191-201Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alpha-synuclein (α-syn) toxic aggregates delivered by the nasal vector have been shown to modify the neurochemistry of dopamine (DA) which is associated with parkinsonian-like motor symptoms. The aim was therefore to study the intranasal effects of α-syn oligomers, fibrils or their combination on the motor behavior of aged mice in relation to possible noradrenergic and serotonergic correlates. In vitro generated α-syn oligomers and fibrils were verified using atomic force microscopy and the thioflavin T binding assay. Levels of noradrenaline (NA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were detected using HPLC with electrochemical detection in the substantia nigra (SN) and striatum. The oligomers or fibrils administered alone or in a 50:50 combination (total dose of 0.48mg/kg) were given intranasally for 14 days and "open-field" behaviour was tested on days 0, 15 and 28 of the protocol, at which time brain structures were sampled. Behavioral deficits at the end of the 14-day dosing regime and on day 28 (i.e. 14 days after treatment completion) induced hypokinesia and immobility whilst the aggregate combination additionally produced rigidity. The α-Syn oligomer/fibril mixture also instigated PD-like motor symptoms which correlated heterochronically with elevated NA levels in the striatum but then later in the SN while intranasal fibrils alone augmented 5-HT and 5-HIAA nigral concentrations throughout the protocol. In contrast, α-syn oligomers displayed a delayed serotonin upsurge in the SN. Neurodegenerative and/or actions on neurotransmitter transporters (such as NET, SERT and VMAT2) are discussed as being implicated in these α-syn amyloid induced neurochemical and motoric disturbances.

  • 4. Gruden, Marina A
    et al.
    Davydova, Tatiana V
    Narkevich, Victor B
    Fomina, Valentina G
    Wang, Chao
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Kudrin, Vladimir S
    Morozova-Roche, Ludmilla A
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Sewell, Robert DE
    Intranasal administration of alpha-synuclein aggregates: a Parkinson's disease model with behavioral and neurochemical correlates2014Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 263, s. 158-168Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Parkinson's disease (PD) is a neurodegenerative disorder in which both alpha-synuclein (alpha-syn) and dopamine (DA) have a critical role. Our previous studies instigated a novel PD model based on nasal inoculation with alpha-syn aggregates which expressed parkinsonian-like behavioral and immunological features. The current study in mice substantiated the robustness of the amyloid nasal vector model by examining behavioral consequences with respect to DA-ergic neurochemical corollaries. In vitro generated alpha-syn oligomers and fibrils were characterized using atomic force microscopy and the thioflavin T binding assay. These toxic oligomers or fibrils administered alone (0.48 mg/kg) or their 50:50 combination (total dose of 0.48 mg/kg) were given intranasally for 14 days and "open-field" behavior was tested on days 0, 15 and 28 of the protocol. Behavioral deficits at the end of the 14-day dosing regime and on day 28 (i.e., 14 days after treatment completion) induced rigidity, hypokinesia and immobility. This was accompanied by elevated nigral but not striatal DA, DOPAC and HVA concentrations in response to dual administration of alpha-syn oligomers plus fibrils but not the oligomers by themselves. alpha-Syn fibrils intensified not only the hypokinesia and immobility 14 days post treatment, but also reduced vertical rearing and enhanced DA levels in the substantia nigra. Only nigral DA turnover (DOPAC/DA but not HVA/DA ratio) was augmented in response to fibril treatment but there were no changes in the striatum. Compilation of these novel behavioral and neurochemical findings substantiate the validity of the alpha-syn nasal vector model for investigating parkinsonian-like symptoms.

    (C) 2014 Elsevier B.V. All rights reserved.

  • 5. Gruden, Marina A.
    et al.
    Davydova, Tatiana V.
    Wang, Chao
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Narkevich, Victor B.
    Fomina, Valentina G.
    Kudrin, Vladimir S.
    Morozova-Roche, Ludmilla A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Sewell, Robert D. E.
    The misfolded pro-inflammatory protein S100A9 disrupts memory via neurochemical remodelling instigating an Alzheimer's disease-like cognitive deficit2016Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 306, s. 106-116Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Memory deficits may develop from a variety of neuropathologies including Alzheimer's disease dementia. During neurodegenerative conditions there are contributory factors such as neuroinflammation and amyloidogenesis involved in memory impairment. In the present study, dual properties of S100A9 protein as a pro-inflammatory and amyloidogenic agent were explored in the passive avoidance memory task along with neurochemical assays in the prefrontal cortex and hippocampus of aged mice. S100A9 oligomers and fibrils were generated in vitro and verified by AFM, Thioflavin T and All antibody binding. Native S100A9 as well as S100A9 oligomers and fibrils or their combination were administered intranasally over 14 days followed by behavioral and neurochemical analysis. Both oligomers and fibrils evoked amnestic activity which correlated with disrupted prefrontal cortical and hippocampal dopaminergic neurochemistry. The oligomer-fibril combination produced similar but weaker neurochemistry to the fibrils administered alone but without passive avoidance amnesia. Native S100A9 did not modify memory task performance even though it generated a general and consistent decrease in monoamine levels (DA, 5-HT and NA) and increased metabolic marker ratios of DA and 5-HT turnover (DOPAC/DA, HVA/DA and 5-HIAA) in the prefrontal cortex. These results provide insight into a novel pathogenetic mechanism underlying amnesia in a fear-aggravated memory task based on amyloidogenesis of a pro-inflammatory factor leading to disrupted brain neurochemistry in the aged brain. The data further suggests that amyloid species of S100A9 create deleterious effects principally on the dopaminergic system and this novel finding might be potentially exploited during dementia management through a neuroprotective strategy.

  • 6.
    McGlone, Francis
    et al.
    University of Wales, Bangor.
    Kelly, Edward F
    University of North Carolina.
    Trulsson, Mats
    Karolinska Institute.
    Francis, Susan T
    University of Nottingham.
    Westling, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Bowtell, Richard
    University of Nottingham.
    Functional neuroimaging studies of human somatosensory cortex2002Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 135, nr 1-2, s. 147-158, PII S0166-4328(02)00144-4Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Two studies were carried out to assess the applicability of echoplanar fMRI at 3.0 T to the analysis of somatosensory mechanisms in humans. Vibrotactile stimulation of the tips of digits two and five reliably generated significant clusters of activation in primary (SI) and secondary (SII) somatosensory cortex, area 43, the pre-central gyrus, posterior insula, posterior parietal cortex and posterior cingulate. Separation of these responses by digit in SI was possible in all subjects and the activation sites reflected the known lateral position of the representation of digit 2 relative to that of digit 5. A second study employed microneurographic techniques in which individual median-nerve mechanoreceptive afferents were isolated, physiologically characterized, and microstimulated in conjunction with fMRI. Hemodynamic responses, observed in every case, were robust, focal, and physiologically orderly. These techniques will enable more detailed studies of the representation of the body surface in human somatosensory cortex, the relationship of that organization to short-term plasticity in responses to natural tactile stimuli, and effects of stimulus patterning and unimodal/cross-modal attentional manipulations. They also present unique opportunities to investigate the basic physiology of the BOLD effect, and to optimize the operating characteristics of two important human functional neuroimaging modalities-high-field fMRI and high-resolution EEG-in an unusually specific and well-characterized neurophysiological setting.

  • 7. Månsson, Kristoffer
    et al.
    Salami, Alireza
    Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Carlbring, Per
    Boraxbekk, Carl-Johan
    Umeå universitet, Samhällsvetenskapliga fakulteten, Enheten för demografi och åldrandeforskning (CEDAR). Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark.
    Andersson, Gerhard
    Furmark, Tomas
    Structural but not functional neuroplasticity one year after effective cognitive behaviour therapy for social anxiety disorder2017Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 318, s. 45-51Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Effective psychiatric treatments ameliorate excessive anxiety and induce neuroplasticity immediately after the intervention, indicating that emotional components in the human brain are rapidly adaptable. Still, the interplay between structural and functional neuroplasticity is poorly understood, and studies of treatment-induced long-term neuroplasticity are rare. Functional and structural magnetic resonance imaging (using 3 T MRI) was performed in 13 subjects with social anxiety disorder on 3 occasions over 1 year. All subjects underwent 9 weeks of Internet-delivered cognitive behaviour therapy in a randomized cross-over design and independent assessors used the Clinically Global Impression-Improvement (CGI-I) scale to determine treatment response. Gray matter (GM) volume, assessed with voxel-based morphometry, and functional blood-oxygen level-dependent (BOLD) responsivity to self-referential criticism were compared between treatment responders and non-responders using 2 × 2 (group × time; pretreatment to follow-up) ANOVA. At 1-year follow-up, 7 (54%) subjects were classified as CGI-I responders. Left amygdala GM volume was more reduced in responders relative to non-responders from pretreatment to 1-year follow-up (Z = 3.67, Family-Wise Error corrected p = 0.02). In contrast to previous short-term effects, altered BOLD activations to self-referential criticism did not separate responder groups at follow-up. The structure and function of the amygdala changes immediately after effective psychological treatment of social anxiety disorder, but only reduced amygdala GM volume, and not functional activity, is associated with a clinical response 1 year after CBT.

  • 8. Persson, Jonas
    et al.
    Herlitz, Agneta
    Engman, Jonas
    Morell, Arvid
    Sjolie, Daniel
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Wikstrom, Johan
    Soderlund, Hedvig
    Remembering our origin: Gender differences in spatial memory are reflected in gender differences in hippocampal lateralization2013Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 256, s. 219-228Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Gender differences in spatial memory favoring men are frequently reported, and the involvement of the hippocampus in these functions is well-established. However, little is known of whether this behavioral gender difference is mirrored in a gender difference in hippocampal function. Here we assessed hippocampal activity, using functional MRI, while 24 men and women moved through three-dimensional virtual mazes (navigation phase) of varying length, and at the end-point estimated the direction of the starting-point (pointing phase). Men were indeed more accurate than women at estimating direction, and this was especially true in longer mazes. Both genders activated the posterior hippocampus throughout the whole task. During the navigation phase, men showed a larger activation in the right hippocampus than women, while in the pointing phase, women showed a larger activation in the left hippocampus than men. Right-lateralized activation during the navigation phase was associated with greater task performance, and may reflect a spatial strategy that is beneficial in this task. Left-sided activation during the pointing phase might reflect a less efficient post hoc verbal recapitulation of the route. This study is the first to identify neural correlates of the commonly observed male advantage in recalling one's original position, and points to hippocampal lateralization as a possible explanation for this behavioral gender difference. (C) 2013 Elsevier B.V. All rights reserved.

  • 9.
    Ruotsalainen, Ilona
    et al.
    Department of Psychology, Centre for Interdisciplinary Brain Research, University of Jyväskylä.
    Renvall, Ville
    Department of Neuroscience and Biomedical Engineering, Aalto University.
    Gorbach, Tetiana
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik. Department of Mathematics and Statistics, University of Jyväskylä, Jyväskylä, Finland.
    Syväoja, Heidi J.
    LIKES Research Centre for Physical Activity and Health, Jyväskylä, Finland.
    Tammelin, Tuija H.
    LIKES Research Centre for Physical Activity and Health, Jyväskylä, Finland.
    Karvanen, Juha
    Department of Mathematics and Statistics, University of Jyväskylä.
    Parviainen, Tiina
    Department of Psychology, Centre for Interdisciplinary Brain Research, University of Jyväskylä,.
    Aerobic fitness, but not physical activity, is associated with grey matter volume in adolescents2019Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 362, s. 122-130Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Higher levels of aerobic fitness and physical activity are linked to beneficial effects on brain health, especially in older adults. The generalizability of these earlier results to young individuals is not straightforward, because physiological responses (such as cardiovascular responses) to exercise may depend on age. Earlier studies have mostly focused on the effects of either physical activity or aerobic fitness on the brain. Yet, while physical activity indicates the amount of activity, aerobic fitness is an adaptive state or attribute that an individual has or achieves. Here, by measuring both physical activity and aerobic fitness in the same study, we aimed to differentiate the association between these two measures and grey matter volume specifically. Magnetic resonance imaging scans were used to study volumes of 30 regions of interest located in the frontal, motor and subcortical areas of 60 adolescents (12.7–16.2 years old). Moderate-to-vigorous intensity physical activity (MVPA) was measured with hip-worn accelerometers and aerobic fitness was assessed with a 20-m shuttle run. Multiple regression analyses revealed a negative association between aerobic fitness and left superior frontal cortex volume and a positive association between aerobic fitness and the left pallidum volume. No associations were found between MVPA and any brain region of interest. These results demonstrate unequal contribution of physical activity and aerobic fitness on grey matter volumes, with inherent or achieved capacity (aerobic fitness) showing clearer associations than physical activity.

  • 10.
    Trulsson, Mats
    et al.
    Karolinska Institutet.
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Orofacial mechanoreceptors in humans: encoding characteristics and responses during natural orofacial behaviors.2002Inngår i: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 135, nr 1-2, s. 27-33Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We used microneurography to characterize stimulus-encoding properties of low-threshold mechanoreceptive afferents in human orofacial tissues. Signals were recorded from single afferents in the infraorbital, lingual and inferior alveolar nerves while localized, controlled, mechanical stimuli were delivered to the facial skin, lips, oral mucosa and teeth. We likewise analyzed activity in these afferents during orofacial behaviors such as speech, chewing and biting. The afferents in the soft tissues functionally resemble four types described in the human hand: hair follicle afferents, slowly adapting (SA) type I and type II afferents and fast adapting (FA) type I afferents. Afferents in the facial skin, lips and buccal mucosa respond not only to contact with environmental objects, but also to contact between the lips, changes in air pressure generated for speech sounds, and to facial skin and mucosa deformations that accompany lip and jaw movements associated with chewing and swallowing. Hence, in addition to exteroceptive information, these afferents provide proprioceptive information. In contrast, afferents terminating superficially in the tongue do not signal proprioceptive information about tongue movements in this manner. They only respond when the receptive field is brought into contact with other intraoral structures or objects, e.g. the teeth or food. All human periodontal afferents adapt slowly to maintained tooth loads. Populations of periodontal afferents encode information about both which teeth are loaded and the direction of forces applied to individual teeth. Most afferents exhibit a markedly curved relationship between discharge rate and force amplitude, featuring the highest sensitivity to changes in tooth load at low forces (below 1 N). Accordingly, periodontal afferents efficiently encode tooth load when subjects first contact, hold, and gently manipulate food by the teeth. In contrast, only a minority of the afferents encodes the rapid and strong force increase generated when biting through food. We conclude, that humans use periodontal afferent signals to control jaw actions associated with intraoral manipulation of food rather than exertion of jaw power actions.

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