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Persson, Jonas
Publications (10 of 19) Show all publications
Persson, J., Szalisznyo, K., Antoni, G., Wall, A., Fällmar, D., Zora, H. & Bodén, R. (2019). Phosphodiesterase 10A levels are related to striatal function in schizophrenia: a combined positron emission tomography and functional magnetic resonance imaging study. European Archives of Psychiatry and Clinical Neuroscience
Open this publication in new window or tab >>Phosphodiesterase 10A levels are related to striatal function in schizophrenia: a combined positron emission tomography and functional magnetic resonance imaging study
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2019 (English)In: European Archives of Psychiatry and Clinical Neuroscience, ISSN 0940-1334, E-ISSN 1433-8491Article in journal (Refereed) Published
Abstract [en]

Pharmacological inhibition of phosphodiesterase 10A (PDE10A) is being investigated as a treatment option in schizophrenia. PDE10A acts postsynaptically on striatal dopamine signaling by regulating neuronal excitability through its inhibition of cyclic adenosine monophosphate (cAMP), and we recently found it to be reduced in schizophrenia compared to controls. Here, this finding of reduced PDE10A in schizophrenia was followed up in the same sample to investigate the effect of reduced striatal PDE10A on the neural and behavioral function of striatal and downstream basal ganglia regions. A positron emission tomography (PET) scan with the PDE10A ligand [11C]Lu AE92686 was performed, followed by a 6 min resting-state magnetic resonance imaging (MRI) scan in ten patients with schizophrenia. To assess the relationship between striatal function and neurophysiological and behavioral functioning, salience processing was assessed using a mismatch negativity paradigm, an auditory event-related electroencephalographic measure, episodic memory was assessed using the Rey auditory verbal learning test (RAVLT) and executive functioning using trail-making test B. Reduced striatal PDE10A was associated with increased amplitude of low-frequency fluctuations (ALFF) within the putamen and substantia nigra, respectively. Higher ALFF in the substantia nigra, in turn, was associated with lower episodic memory performance. The findings are in line with a role for PDE10A in striatal functioning, and suggest that reduced striatal PDE10A may contribute to cognitive symptoms in schizophrenia.

National Category
Psychiatry Neurosciences
Identifiers
urn:nbn:se:uu:diva-392015 (URN)10.1007/s00406-019-01021-0 (DOI)
Available from: 2019-08-28 Created: 2019-08-28 Last updated: 2019-08-28Bibliographically approved
Persson, J., Stening, E., Nordin, K. & Söderlund, H. (2018). Predicting episodic and spatial memory performance from hippocampal resting-state functional connectivity: Evidence for an anterior-posterior division of function. Hippocampus, 28(1), 53-66
Open this publication in new window or tab >>Predicting episodic and spatial memory performance from hippocampal resting-state functional connectivity: Evidence for an anterior-posterior division of function
2018 (English)In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 28, no 1, p. 53-66Article in journal (Refereed) Published
Abstract [en]

fMRI studies have identified distinct resting-state functional connectivity (RSFC) networks associated with the anterior and posterior hippocampus. However, the functional relevance of these two networks is still largely unknown. Hippocampal lesion studies and task-related fMRI point to a role for the anterior hippocampus in non-spatial episodic memory and the posterior hippocampus in spatial memory. We used Relevance Vector Regression (RVR), a machine-learning method that enables predictions of continuous outcome measures from multivariate patterns of brain imaging data, to test the hypothesis that patterns of whole-brain RSFC associated with the anterior hippocampus predict episodic memory performance, while patterns of whole-brain RSFC associated with the posterior hippocampus predict spatial memory performance. Magnetic resonance imaging (MRI) and memory assessment took place at two separate occasions. The anterior and posterior RSFC largely corresponded with previous findings, and showed no effect of laterality. Supporting the hypothesis, RVR produced accurate predictions of episodic performance from anterior, but not posterior, RSFC, and accurate predictions of spatial performance from posterior, but not anterior, RSFC. In contrast, a univariate approach could not predict performance from resting-state connectivity. This supports a functional dissociation between the anterior and posterior hippocampus, and indicates a multivariate relationship between intrinsic functional networks and cognitive performance within specific domains, that is relatively stable over time.

Keywords
episodic memory, hippocampus, machine learning, resting state, spatial memory
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-331607 (URN)10.1002/hipo.22807 (DOI)000418452700006 ()29028135 (Scopus ID)
Funder
Swedish Research Council, 2009-2035
Available from: 2017-10-16 Created: 2017-10-16 Last updated: 2018-01-18Bibliographically approved
Nordin, K., Persson, J., Stening, E., Herlitz, A., Larsson, E.-M. & Söderlund, H. (2018). Structural whole-brain covariance of the anterior and posterior hippocampus: Associations with age and memory. Hippocampus, 28(2), 151-163
Open this publication in new window or tab >>Structural whole-brain covariance of the anterior and posterior hippocampus: Associations with age and memory
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2018 (English)In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 28, no 2, p. 151-163Article in journal (Refereed) Published
Abstract [en]

The hippocampus (HC) interacts with distributed brain regions to support memory and shows significant volume reductions in aging, but little is known about age effects on hippocampal whole-brain structural covariance. It is also unclear whether the anterior and posterior HC show similar or distinct patterns of whole-brain covariance and to what extent these are related to memory functions organized along the hippocampal longitudinal axis. Using the multivariate approach partial least squares, we assessed structural whole-brain covariance of the HC in addition to regional volume, in young, middle-aged and older adults (n = 221), and assessed associations with episodic and spatial memory. Based on findings of sex differences in both memory and brain aging, we further considered sex as a potential modulating factor of age effects. There were two main covariance patterns: one capturing common anterior and posterior covariance, and one differentiating the two regions by capturing anterior-specific covariance only. These patterns were differentially related to associative memory while unrelated to measures of single-item memory and spatial memory. Although patterns were qualitatively comparable across age groups, participants' expression of both patterns decreased with age, independently of sex. The results suggest that the organization of hippocampal structural whole-brain covariance remains stable across age, but that the integrity of these networks decreases as the brain undergoes age-related alterations.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
aging, episodic memory, longitudinal axis, sex, spatial memory
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-335505 (URN)10.1002/hipo.22817 (DOI)000422974700008 ()29171897 (PubMedID)
Funder
Swedish Research Council, 2009-2035Swedish Research Council, 2011-1943
Available from: 2017-12-06 Created: 2017-12-06 Last updated: 2019-06-28Bibliographically approved
Stening, E., Persson, J., Eriksson, E., Wahlund, L.-O., Zetterberg, H. & Söderlund, H. (2017). Specific patterns of whole-brain structural covariance of the anterior and posterior hippocampus in young APOE ε4 carriers. Behavioural Brain Research, 326, 256-264
Open this publication in new window or tab >>Specific patterns of whole-brain structural covariance of the anterior and posterior hippocampus in young APOE ε4 carriers
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2017 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 326, p. 256-264Article in journal (Refereed) Published
Abstract [en]

Apolipoprotein E (APOE) ε4 has been associated with smaller hippocampal volumes in healthy aging, while findings in young adults are inconclusive. Previous studies have mostly used univariate methods, and without considering potential anterior/posterior differences. Here, we used a multivariate method, partial least squares, and assessed whole-brain structural covariance of the anterior (aHC) and posterior (pHC) hippocampus in young adults (n = 97) as a function of APOE ε4 status and sex. Two significant patterns emerged: 1) specific structural covariance of the aHC with frontal regions, temporal and occipital areas in APOE ε4 women, whereas the volume of both the aHC and pHC in all other groups co-varied with frontal, parietal and cerebellar areas; and 2) opposite structural covariance of the pHC in ε4 carriers compared to the aHC in non-carriers, with the pHC of ε4 carriers covarying with parietal and frontal areas, and the aHC of ε4 non-carriers covarying with motor areas and the middle frontal gyrus. APOE ε4 has in young adults been associated with better episodic and spatial memory, functions involving the aHC and pHC, respectively. We found no associations between structural covariance and performance, suggesting that other factors underlie the performance differences seen between carriers and non-carriers. Our findings indicate that APOE ε4 carriers and non-carriers differ in hippocampal organization and that there are differences as a function of sex and hippocampal segment. They stress the need to consider the hippocampus as a heterogeneous structure, and highlight the benefits of multivariate methods in assessing group differences in the brain.

Keywords
APOE ε4, hippocampus, structural covariance, young adults, partial least squares, memory
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-317322 (URN)10.1016/j.bbr.2017.03.013 (DOI)000401678300028 ()28284953 (PubMedID)
Funder
Swedish Research Council, 2009-2035
Available from: 2017-03-13 Created: 2017-03-13 Last updated: 2017-07-06Bibliographically approved
Bodén, R., Persson, J., Wall, A., Lubberink, M., Ekselius, L., Larsson, E.-M. & Antoni, G. (2017). Striatal Phosphodiesterase 10A and Medial Prefrontal Cortical Thickness in Patients with Schizophrenia: A PET and MRI Study. Paper presented at 72nd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 18-20, 2017, San Diego, CA. Biological Psychiatry, 81(10), S386-S387
Open this publication in new window or tab >>Striatal Phosphodiesterase 10A and Medial Prefrontal Cortical Thickness in Patients with Schizophrenia: A PET and MRI Study
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2017 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 81, no 10, p. S386-S387Article in journal, Meeting abstract (Other academic) Published
Keywords
Schizophrenia, Positron Emission Tomography, Magnetic resonance imaging, striatum, Cortical Thickness
National Category
Psychiatry Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-331804 (URN)10.1016/j.biopsych.2017.02.681 (DOI)000400348701048 ()
Conference
72nd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), MAY 18-20, 2017, San Diego, CA
Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2017-10-18Bibliographically approved
Bodén, R., Persson, J., Wall, A., Lubberink, M., Ekselius, L., Larsson, E.-M. & Antoni, G. (2017). Striatal phosphodiesterase 10A and medial prefrontal cortical thickness in patients with schizophrenia: a PET and MRI study. Translational Psychiatry, 7(3), Article ID e1050.
Open this publication in new window or tab >>Striatal phosphodiesterase 10A and medial prefrontal cortical thickness in patients with schizophrenia: a PET and MRI study
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2017 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 7, no 3, article id e1050Article in journal (Refereed) Published
Abstract [en]

The enzyme phosphodiesterase 10A (PDE10A) is abundant in striatal medium spiny neurons and has been implicated in the pathophysiology of schizophrenia in animal models and is investigated as a possible new pharmacological treatment target. A reduction of prefrontal cortical thickness is common in schizophrenia, but how this relates to PDE10A expression is unknown. Our study aim was to compare, we believe for the first time, the striatal non-displaceable binding potential (BPND) of the new validated PDE10A ligand [(11)C]Lu AE92686 between patients with schizophrenia and healthy controls. Furthermore, we aimed to assess the correlation of PDE10A BPND to cortical thickness. Sixteen healthy male controls and 10 male patients with schizophrenia treated with clozapine, olanzapine or quetiapine were investigated with positron emission tomography (PET) and magnetic resonance imaging (MRI). Striatal binding potential (BPND) of [(11)C]Lu AE92686 was acquired through dynamic PET scans and cortical thickness by structural MRI. Clinical assessments of symptoms and cognitive function were performed and the antipsychotic dosage was recorded. Patients with schizophrenia had a significantly lower BPND of [(11)C]Lu AE92686 in striatum (P=0.003) than healthy controls. The striatal BPND significantly correlated to cortical thickness in the medial prefrontal cortex and superior frontal gyrus across patients with schizophrenia and healthy controls. No significant correlation was observed between the BPND for [(11)C]Lu AE92686 in striatum and age, schizophrenia symptoms, antipsychotic dosage, coffee consumption, smoking, duration of illness or cognitive function in the patients. In conclusion, PDE10A may be important for functioning in the striato-cortical interaction and in the pathophysiology of schizophrenia.

National Category
Psychiatry Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-316901 (URN)10.1038/tp.2017.11 (DOI)000397228200002 ()28267149 (PubMedID)
Funder
Swedish Research Council, 2016-02362
Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2018-01-13Bibliographically approved
Stening, E., Persson, J., Eriksson, E., Wahlund, L.-O., Zetterberg, H. & Söderlund, H. (2016). Apolipoprotein E ϵ4 is positively related to spatial performance but unrelated to hippocampal volume in healthy young adults. Behavioural Brain Research, 299, 11-18
Open this publication in new window or tab >>Apolipoprotein E ϵ4 is positively related to spatial performance but unrelated to hippocampal volume in healthy young adults
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2016 (English)In: Behavioural Brain Research, ISSN 0166-4328, E-ISSN 1872-7549, Vol. 299, p. 11-18Article in journal (Refereed) Published
Abstract [en]

The apolipoprotein E (APOE) ϵ4 allele is known to be a major genetic risk factor for Alzheimer's disease (AD). It has been linked to especially episodic memory decline and hippocampal atrophy in both healthy and demented elderly populations. In young adults, ϵ4 carriers have shown better performance in episodic memory compared to non-carriers. Spatial memory, however, has not been thoroughly assessed in relation to APOE in spite of its dependence on the hippocampus. In this study, we assessed the effect of APOE genotype on a variety of spatial and episodic memory tasks as well as hippocampal volume assessed through manual tracing in a sample of young adults (N=123). We also assessed whether potential effects were modulated by sex. The presence of one or more ϵ4 alleles had positive effects on spatial function and memory and object location memory, but no effect on word recognition. Men were superior to women in spatial function and memory but there were no sex differences in the other tasks. In spite of APOE ϵ4 carriers having superior performance in several memory tasks, no difference was found as a function of APOE genotype in hippocampal volume. To our knowledge, this study is the first to show that APOE ϵ4 has a positive effect on spatial ability in young adults.

Keywords
APOE epsilon 4; Spatial memory; Episodic memory; Hippocampus; Manual tracing; Young adults
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-269688 (URN)10.1016/j.bbr.2015.11.006 (DOI)000368565000003 ()26581118 (PubMedID)
External cooperation:
Funder
Swedish Research Council, 2009-2035
Available from: 2015-12-17 Created: 2015-12-17 Last updated: 2017-12-01
Persson, J. & Söderlund, H. (2015). Hippocampal hemispheric and long-axis differentiation of stimulus content during episodic memory encoding and retrieval: An activation likelihood estimation meta-analysis. Hippocampus, 25(12), 1614-1631
Open this publication in new window or tab >>Hippocampal hemispheric and long-axis differentiation of stimulus content during episodic memory encoding and retrieval: An activation likelihood estimation meta-analysis
2015 (English)In: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 25, no 12, p. 1614-1631Article in journal (Refereed) Published
Abstract [en]

While there is ample evidence that the hippocampus is functionally heterogeneous along its longitudinal axis, there is still no consensus regarding its exact organization. Whereas spatial memory tasks frequently engage the posterior hippocampus, the regions engaged during episodic memory are more varying and may depend on the specific nature of the stimuli. Here, we investigate the effect of stimulus content on the location of hippocampal recruitment during episodic memory encoding and retrieval of pictorial and verbal material with a meta-analysis approach, using activation likelihood estimation and restricting the analysis to the hippocampus. Verbal material was associated with left-lateralized anterior activation, compared to pictorial material that recruited a more posterior aspect of the hippocampus, primarily within the right hemisphere. This effect held for encoding of both single items and item-item associations but was less clear during retrieval. The findings lend further support to a functional subdivision of the hippocampus along its longitudinal axis and indicate that the content of episodic memories is one factor that determines the location of hippocampal recruitment.

Keywords
meta-analysis; hippocampus; episodic memory; spatial memory; activation likelihood estimation; encoding; retrieval
National Category
Psychology
Identifiers
urn:nbn:se:uu:diva-259778 (URN)10.1002/hipo.22482 (DOI)000368281700012 ()26108671 (PubMedID)
Available from: 2015-08-11 Created: 2015-08-11 Last updated: 2017-12-04Bibliographically approved
Persson, J. (2015). Making Head or Tail of the Hippocampus: A Long-Axis Account of Episodic and Spatial Memory. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Making Head or Tail of the Hippocampus: A Long-Axis Account of Episodic and Spatial Memory
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

While episodic and spatial memory both depend on the hippocampus, opposite gender differences in these functions suggest they are partly separate, with different neural underpinnings. The anterior and posterior hippocampus differ  in structure and whole-brain connectivity, and studies point to the posterior hippocampus being more involved in spatial memory while the anterior hippocampus’ role in episodic memory is less clear. This thesis aims to explore the role of the anterior and posterior hippocampus, and associated brain regions, in episodic and spatial memory. Paper I studied gender differences in hippocampal activation underlying differences in spatial memory performance. Better performance in men was accompanied by greater right-lateralization of hippocampal activation compared to women. Paper II investigated regions of gray matter that covaried in volume with the anterior and posterior hippocampus, and whether these covariance patterns depended on gender and were related to behavior. The anterior and posterior hippocampus showed different patterns of covariance, with the anterior hippocampus covariance pattern observed in women and the posterior hippocampus covariance pattern primarily in men. Paper III considered whether the location of hippocampal recruitment in episodic memory depends on memory content. Verbal stimuli were associated with more anterior, and left-lateralized, encoding activations than pictorial stimuli, which in turn were associated with more posterior and bilateral encoding activations. This was not observed during retrieval. Paper IV investigated whether resting-state connectivity associated with the anterior and posterior hippocampus predicts episodic and spatial memory performance, respectively. Resting-state connectivity associated with the anterior, not posterior, hippocampus predicted episodic memory performance, while resting-state connectivity associated with the posterior, not anterior, hippocampus predicted spatial memory performance. This thesis lends further support to differences in function and structure between the anterior and posterior hippocampus suggesting that these two sub–segments play different roles in episodic and spatial memory. Further, it suggests that gender differences in anterior and posterior hippocampus function underlies gender differences in episodic and spatial memory, respectively. Considering the anterior and posterior hippocampus, as well as men and women, separately, is hence important when studying the effect of age and pathology on the hippocampus and associated memory functions.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. p. 81
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences, ISSN 1652-9030 ; 114
Keywords
hippocampus, fMRI, episodic memory, spatial memory, gender differences
National Category
Psychology (excluding Applied Psychology) Neurosciences
Research subject
Psychology
Identifiers
urn:nbn:se:uu:diva-261340 (URN)978-91-554-9328-8 (ISBN)
Public defence
2015-10-23, Auditorium Minus, Gustavianum, Akademigatan 3, Uppsala, 10:15 (English)
Opponent
Supervisors
Available from: 2015-09-28 Created: 2015-09-01 Last updated: 2018-01-11
Åhs, F., Engman, J., Persson, J., Larsson, E.-M., Wikström, J., Kumlien, E. & Fredrikson, M. (2014). Medial temporal lobe resection attenuates superior temporal sulcus response to faces. Neuropsychologia, 61, 291-298
Open this publication in new window or tab >>Medial temporal lobe resection attenuates superior temporal sulcus response to faces
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2014 (English)In: Neuropsychologia, ISSN 0028-3932, E-ISSN 1873-3514, Vol. 61, p. 291-298Article in journal (Refereed) Published
Abstract [en]

Face perception depends on activation of a core face processing network including the fusiform face area, the occipital face area and the superior temporal sulcus (STS). The medial temporal lobe (MTL) is also involved in decoding facial expression and damage to the anterior MTL, including the amygdala, generally interferes with emotion recognition. The impairment in emotion recognition following anterior MTL injury can be a direct result from injured MTL circuitry, as well as an indirect result from decreased MTL modulation of areas in the core face network. To test whether the MTL modulates activity in the core face network, we used functional magnetic resonance imaging to investigate activation in the core face processing network in patients with right or left anterior temporal lobe resections (ATR) due to intractable epilepsy. We found reductions of face-related activation in the right STS after both right and left ATR together with impaired recognition of facial expressions. Reduced activity in the fusiform and the occipital face areas was also observed in patients after right ATR suggesting widespread effects on activity in the core face network in this group. The reduction in face-related STS activity after both right and left ATR suggests that MTL modulation of the STS may facilitate recognition of facial expression.

National Category
Neurology Psychology
Identifiers
urn:nbn:se:uu:diva-230019 (URN)10.1016/j.neuropsychologia.2014.06.030 (DOI)000340980400028 ()25003207 (PubMedID)
Available from: 2014-08-19 Created: 2014-08-19 Last updated: 2017-12-05Bibliographically approved
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