Aaltodoc Repository :: Browsing by Author "Suvisaari, Jaana"

Browsing by Author "Suvisaari, Jaana"

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Activation of the motivation-related ventral striatum during delusional experience
(2018-12-01) Raij, Tuukka T.; Riekki, Tapani J.J.; Rikandi, Eva; Mäntylä, Teemu; Kieseppä, Tuula; Suvisaari, Jaana; Department of Neuroscience and Biomedical Engineering; University of Helsinki; Finnish Institute for Health and Welfare (THL)
Delusion is the most characteristic symptom of psychosis, occurring in almost all first-episode psychosis patients. The motivational salience hypothesis suggests delusion to originate from the experience of abnormal motivational salience. Whether the motivation-related brain circuitries are activated during the actual delusional experience remains, however, unknown. We used a forced-choice answering tree at random intervals during functional magnetic resonance imaging to capture delusional and non-delusional spontaneous experiences in patients with first-episode psychosis (n = 31) or clinical high-risk state (n = 7). The motivation-related brain regions were identified by an automated meta-analysis of 149 studies. Thirteen first-episode patients reported both delusional and non-delusional spontaneous experiences. In these patients, delusional experiences were related to stronger activation of the ventral striatum in both hemispheres. This activation overlapped with the most strongly motivation-related brain regions. These findings provide an empirical link between the actual delusional experience and the motivational salience hypothesis. Further use and development of the present methods in localizing the neurobiological basis of the most characteristic symptoms may be useful in the search for etiopathogenic pathways that result in psychotic disorders.
Altered Activation of Innate Immunity Associates with White Matter Volume and Diffusion in First-Episode Psychosis
(2015) Mäntylä, Teemu; Mantere, Outi; Raij, Tuukka T.; Kieseppä, Tuula; Laitinen, Hanna; Leiviskä, Jaana; Torniainen, Minna; Tuominen, Lauri; Vaarala, Outi; Suvisaari, Jaana; Department of Neuroscience and Biomedical Engineering
First-episode psychosis (FEP) is associated with inflammatory and brain structural changes, but few studies have investigated whether systemic inflammation associates with brain structural changes in FEP. Thirty-seven FEP patients (median 27 days on antipsychotic medication), and 19 matched controls were recruited. Serum levels of 38 chemokines and cytokines, and cardiovascular risk markers were measured at baseline and 2 months later. We collected T1- and diffusion-weighted MRIs with a 3 T scanner from the patients at baseline. We analyzed the association of psychosis-related inflammatory markers with gray and white matter (WM) volume using voxel-based morphometry and WM diffusion using tract-based spatial statistics with whole-brain and region-of-interest (ROI) analyses. FEP patients had higher CCL22 and lower TGFα, CXCL1, CCL7, IFN-α2 and ApoA-I than controls. CCL22 decreased significantly between baseline and 2 months in patients but was still higher than in controls. The association between inflammatory markers and FEP remained significant after adjusting for age, sex, smoking and BMI. We did not observe a correlation of inflammatory markers with any symptoms or duration of antipsychotic treatment. Baseline CCL22 levels correlated negatively with WM volume and positively with mean diffusivity and radial diffusivity bilaterally in the frontal lobes in ROI analyses. Decreased serum level of ApoA-I was associated with smaller volume of the medial temporal WM. In whole-brain analyses, CCL22 correlated positively with mean diffusivity and radial diffusivity, and CXCL1 associated negatively with fractional anisotropy and positively with mean diffusivity and radial diffusivity in several brain regions. This is the first report to demonstrate an association between circulating chemokine levels and WM in FEP patients. Interestingly, CCL22 has been previously implicated in autoimmune diseases associated with WM pathology. The results suggest that an altered activation of innate immunity may contribute to WM damage in psychotic disorders.
Associations between acceptance of the implausible bias, theory of mind and delusions in first-episode psychosis patients; A longitudinal study
(Elsevier, 2023-04) Panula, Jonatan M.; Lindgren, Maija; Kieseppä, Tuula; Suvisaari, Jaana; Raij, Tuukka T.; Department of Neuroscience and Biomedical Engineering; Finnish Institute for Health and Welfare (THL); University of Helsinki
Multiple different cognitive biases, among them the liberal acceptance (LA) bias, have been suggested to contribute to reality distortion in psychotic disorders. Earlier studies have been cross-sectional and considered a limited set of cognitive correlates of psychosis, thus the relationship between LA bias and psychosis remains poorly known. We studied a similar bias (acceptance of the implausible (AOI)) in 62 first-episode psychosis (FEP) patients and 62 control subjects, who watched movie scenes with varying degrees of realism and were asked to evaluate the probability of these events occurring in real life. We assessed theory of mind (ToM) performance using the Hinting task and delusion severity using Brief Psychiatric Rating Scale item 11. We correlated the magnitude of AOI with the severity of delusions and performance in the ToM task. Furthermore, we used 1-year follow-up data from 40 FEP patients and 40 control subjects to disentangle state vs trait-like characteristics of AOI. At baseline FEP patients expressed more AOI than control subjects, and the magnitude of AOI correlated positively with the severity of delusions and negatively with ToM performance. At the one-year follow-up, when most patients were in remission, patients still displayed increased AOI, which no longer correlated with delusions. These findings support the notion that the AOI bias could represent a trait rather than a state feature and support further studies to test the hypothesis that it could be one of the causal factors of psychotic disorders, possibly associated with ToM.
Connectivity alterations of mesostriatal pathways in first episode psychosis
(2023-12) Hayward, Nicholas Mark Edward Alexander; Triana, Ana María; Panula, Jonatan M.; Kieseppä, Tuula; Suvisaari, Jaana; Raij, Tuukka T.; Department of Neuroscience and Biomedical Engineering; Department of Computer Science; Ministry of Social Affairs and Health, Finland; Finnish Institute for Health and Welfare (THL)
Background and hypothesis: Pathogenic understanding of the psychotic disorders converges on regulation of dopaminergic signaling in mesostriatocortical pathways. Functional connectivity of the mesostriatal pathways may inform us of the neuronal networks involved. Study design: This longitudinal study of first episode psychosis (FEP) (49 patients, 43 controls) employed seed-based functional connectivity analyses of fMRI data collected during a naturalistic movie stimulus. Study results: We identified hypoconnectivity of the dorsal striatum with the midbrain, associated with antipsychotic medication dose in FEP, in comparison with the healthy control group. The midbrain regions that showed hypoconnectivity with the dorsal striatum also showed hypoconnectivity with cerebellar regions suggested to be involved in regulation of the mesostriatocortical dopaminergic pathways. None of the baseline hypoconnectivity detected was seen at follow-up. Conclusions: These findings extend earlier resting state findings on mesostriatal connectivity in psychotic disorders and highlight the potential for cerebellar regulation of the mesostriatocortical pathways as a target of treatment trials.
Delineating insight-processing-related functional activations in the precuneus in first-episode psychosis patients
(Elsevier Ireland Ltd, 2021-11-30) Mäntylä, Teemu; Kieseppä, Tuula; Suvisaari, Jaana; Raij, Tuukka T.; Department of Neuroscience and Biomedical Engineering; Finnish Institute for Health and Welfare
Poor insight is a central characteristic of psychotic disorders, and it has been suggested to result from a general dysfunction in self-reflection. However, brain processing of clinical insight and more general self-reflection has not been directly compared. We compared tasks on (1) self-reflection on psychosis-related mental functioning (clinical insight, in patients only), (2) self-reflection on mental functioning unrelated to psychosis (general metacognition), and (3) semantic control during blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging with 19 first-episode psychosis patients and 24 control participants. Arterial-spin-labeling (ASL) images were collected at rest. Clinical insight was evaluated with the Schedule for the Assessment of Insight. In patients, posterosuperior precuneus showed stronger activation during the insight task than during the semantic control task, while anteroinferior precuneus and posterior cingulate cortex (PCC) showed stronger activation during the insight task than during the general metacognition task. No significant group differences in brain activation emerged during the general metacognition task. Although the BOLD measures did not correlate with clinical insight measures, ASL-measured cerebral blood flow (CBF) values did correlate when extracted from the task-selective precuneus/PCC areas: higher CBF correlated with higher clinical insight scores. These results suggest that regions in the posteromedial cortex are selective for clinical insight.
FreeSurfer 7 quality control : Key problem areas and importance of manual corrections
(Academic Press, 2023-10) Vahermaa, Vesa; Aydogan, Dogu Baran; Raij, Tuukka; Armio, Reetta-Liina; Laurikainen, Heikki; Saramäki, Jari; Suvisaari, Jaana; Department of Computer Science; Department of Neuroscience and Biomedical Engineering; Computer Science Professors; Computer Science - Complex Systems (Cxsys); Helsinki Institute for Information Technology (HIIT); Professorship Saramäki J.; Department of Computer Science; University of Turku; Finnish Institute for Health and Welfare (THL)
We have studied the effects of manual quality control of brain Magnetic Resonance Imaging (MRI) images processed with Freesurfer. T1 images of first episode psychosis patients (N = 60) and healthy controls (N = 41) were inspected for gray matter boundary errors. The errors were fixed, and the effects of error correction on brain volume, thickness, and surface area were measured. It is commonplace to apply quality control to Freesurfer MRI recordings to ensure that the edges of gray and white matter are detected properly, as incorrect edge detection leads to changes in variables such as volume, cortical thickness, and cortical surface area. We find that while Freesurfer v7.1.1. does regularly make mistakes in identifying the edges of cortical gray matter, correcting these errors yields limited changes in the commonly measured variables listed above. We further find that the software makes fewer gray matter boundary errors when processing female brains. The results suggest that manually correcting gray matter boundary errors may not be worthwhile due to its small effect on the measurements, with potential exceptions for studies that focus on the areas that are more commonly affected by errors: the areas around the cerebellar tentorium, paracentral lobule, and the optic nerves, specifically the horizontal segment of the middle cerebral artery.
Functional network connectivity and topology during naturalistic stimulus is altered in first-episode psychosis
(Elsevier, 2022-03) Rikandi, Eva; Mäntylä, Teemu; Lindgren, Maija; Kieseppä, Tuula; Suvisaari, Jaana; Raij, Tuukka T.; Department of Neuroscience and Biomedical Engineering; Finnish Institute for Health and Welfare (THL); University of Helsinki
Background: Psychotic disorders have been suggested to derive from dysfunctional integration of signaling between brain regions. Earlier studies have found several changes in functional network synchronization as well as altered network topology in patients with psychotic disorders. However, studies have used mainly resting-state that makes it more difficult to link functional alterations to any specific stimulus or experience. We set out to examine functional connectivity as well as graph (topological) measures and their association to symptoms in first-episode psychosis patients during movie viewing. Our goal was to understand whole-brain functional dynamics of complex naturalistic information processing in psychosis and changes in brain functional organization related to symptoms. Methods: 71 first-episode psychosis patients and 57 control subjects watched scenes from the movie Alice in Wonderland during 3 T fMRI. We compared functional connectivity and graph measures indicating integration, segregation and centrality between groups, and examined the association between topology and symptom scores in the patient group. Results: We identified a subnetwork with predominantly decreased links of functional connectivity in first-episode psychosis patients. The subnetwork was mainly comprised of nodes of and links between the cingulo-opercular, sensorimotor and default-mode networks. In topological measures, we observed between-group differences in properties of centrality. Conclusions: Functional brain networks are affected during naturalistic information processing already in the early stages of psychosis, concentrated in salience- and cognitive control-related hubs and subnetworks. Understanding these aberrant dynamics could add to better targeted cognitive and behavioral interventions in the early stages of psychotic disorders.
Hippocampus-Centered Network Is Associated With Positive Symptom Alleviation in Patients With First-Episode Psychosis
(Elsevier, 2023-12) Alho, Jussi; Lahnakoski, Juha M.; Panula, Jonatan M.; Rikandi, Eva; Mäntylä, Teemu; Lindgren, Maija; Kieseppä, Tuula; Suvisaari, Jaana; Sams, Mikko; Raij, Tuukka T.; Department of Neuroscience and Biomedical Engineering; Finnish Institute for Health and Welfare; Forschungszentrum Jülich
Background: Previous functional magnetic resonance imaging studies have reported widespread brain functional connectivity alterations in patients with psychosis. These studies have mostly used either resting-state or simple-task paradigms, thereby compromising experimental control or ecological validity, respectively. Additionally, in a conventional functional magnetic resonance imaging intrasubject functional connectivity analysis, it is difficult to identify which connections relate to extrinsic (stimulus-induced) and which connections relate to intrinsic (non–stimulus-related) neural processes. Methods: To mitigate these limitations, we used intersubject functional connectivity (ISFC) to analyze longitudinal functional magnetic resonance imaging data collected while 36 individuals with first-episode psychosis (FEP) and 29 age- and sex-matched population control participants watched scenes from the fantasy movie Alice in Wonderland at baseline and again at 1-year follow-up. Furthermore, to allow unconfounded comparison and to overcome possible circularity of ISFC, we introduced a novel approach wherein ISFC in both the FEP and population control groups was calculated with respect to an independent group of participants (not included in the analyses). Results: Using this independent-reference ISFC approach, we found an interaction effect wherein the independent-reference ISFC in individuals with FEP, but not in the control group participants, was significantly stronger at baseline than at follow-up in a network centered in the hippocampus and involving thalamic, striatal, and cortical regions, such as the orbitofrontal cortex. Alleviation of positive symptoms, particularly delusions, from baseline to follow-up was correlated with decreased network connectivity in patients with FEP. Conclusions: These findings link deviation of naturalistic information processing in the hippocampus-centered network to positive symptoms.
The Impact of Forced Migration on Mortality: a Cohort Study of 242,075 Finns in 1939-2010
(Lippincott Williams and Wilkins, 2017-07) Haukka, Jari; Suvisaari, Jaana; Sarvimäki, Matti; Martikainen, Pekka; Department of Economics; University of Helsinki; Finnish Institute for Health and Welfare (THL)
Is It Possible to Predict the Future in First-Episode Psychosis?
(Frontiers Research Foundation, 2018-11-13) Suvisaari, Jaana; Mantere, Outi; Keinanen, Jaakko; Mantyla, Teemu; Rikandi, Eva; Lindgren, Maija; Kieseppa, Tuula; Raij, Tuukka T.; Department of Neuroscience and Biomedical Engineering; Finnish Institute for Health and Welfare (THL); University of Helsinki
The outcome of first-episode psychosis (FEP) is highly variable, ranging from early sustained recovery to antipsychotic treatment resistance from the onset of illness. For clinicians, a possibility to predict patient outcomes would be highly valuable for the selection of antipsychotic treatment and in tailoring psychosocial treatments and psychoeducation. This selective review summarizes current knowledge of prognostic markers in FEP. We sought potential outcome predictors from clinical and sociodemographic factors, cognition, brain imaging, genetics, and blood-based biomarkers, and we considered different outcomes, like remission, recovery, physical comorbidities, and suicide risk. Based on the review, it is currently possible to predict the future for FEP patients to some extent. Some clinical features-like the longer duration of untreated psychosis (DUP), poor premorbid adjustment, the insidious mode of onset, the greater severity of negative symptoms, comorbid substance use disorders (SUDs), a history of suicide attempts and suicidal ideation and having non-affective psychosis-are associated with a worse outcome. Of the social and demographic factors, male gender, social disadvantage, neighborhood deprivation, dysfunctional family environment, and ethnicity may be relevant. Treatment non-adherence is a substantial risk factor for relapse, but a small minority of patients with acute onset of FEP and early remission may benefit from antipsychotic discontinuation. Cognitive functioning is associated with functional outcomes. Brain imaging currently has limited utility as an outcome predictor, but this may change with methodological advancements. Polygenic risk scores (PRSs) might be useful as one component of a predictive tool, and pharmacogenetic testing is already available and valuable for patients who have problems in treatment response or with side effects. Most blood-based biomarkers need further validation. None of the currently available predictive markers has adequate sensitivity or specificity used alone. However, personalized treatment of FEP will need predictive tools. We discuss some methodologies, such as machine learning (ML), and tools that could lead to the improved prediction and clinical utility of different prognosticmarkers in FEP. Combination of differentmarkers inMLmodels with a user friendly interface, or novel findings from e.g., molecular genetics or neuroimaging, may result in computer-assisted clinical applications in the near future.
Multimodal prediction of the need of clozapine in treatment resistant schizophrenia; a pilot study in first-episode psychosis
(Elsevier, 2024-12) Panula, Jonatan M.; Gotsopoulos, Athanasios; Alho, Jussi; Suvisaari, Jaana; Lindgren, Maija; Kieseppä, Tuula; Raij, Tuukka T.; Department of Neuroscience and Biomedical Engineering; Finnish Institute for Health and Welfare (THL); University of Helsinki
As many as one third of the patients diagnosed with schizophrenia do not respond to first-line antipsychotic medication. This group may benefit from the atypical antipsychotic medication clozapine, but initiation of treatment is often delayed, which may worsen prognosis. Predicting which patients do not respond to traditional antipsychotic medication at the onset of symptoms would provide fast-tracked treatment for this group of patients. We collected data from patient records of 38 first-episode psychosis patients, of whom seven did not respond to traditional antipsychotic medications. We used clinical data including medical records, voxel-based morphometry MRI data and inter-subject correlation fMRI data, obtained during movie viewing, to predict future treatment resistance. Using a neural network model, we correctly predicted future treatment resistance in six of the seven treatment resistance patients and 25 of 31 patients who did not require clozapine treatment. Prediction improved significantly when using imaging data in tandem with clinical data. The accuracy of the neural network model was significantly higher than the accuracy of a support vector machine algorithm. These results support the notion that treatment resistant schizophrenia could represent a separate entity of psychotic disorders, characterized by morphological and functional changes in the brain which could represent biomarkers detectable at early onset of symptoms.
State-like changes in the salience network correlate with delusion severity in first-episode psychosis patients
(Elsevier BV, 2022) Panula, Jonatan M.; Alho, Jussi; Lindgren, Maija; Kieseppä, Tuula; Suvisaari, Jaana; Raij, Tuukka T.; Department of Neuroscience and Biomedical Engineering; Finnish Institute for Health and Welfare (THL); University of Helsinki
Background and hypothesis: Delusions are characteristic of psychotic disorders; however, the brain correlates of delusions remain poorly known. Imaging studies on delusions typically compare images across individuals. Related confounding of inter-individual differences beyond delusions may be avoided by comparing delusional and non-delusional states within individuals. Study design: We studied correlations of delusions using intra-subject correlation (intra-SC) and inter-subject correlation of functional magnetic resonance imaging (fMRI) signal time series, obtained during a movie stimulus at baseline and follow-up. We included 27 control subjects and 24 first-episode psychosis patients, who were free of delusions at follow-up, to calculate intra-SC between fMRI signals obtained during the two time points. In addition, we studied changes in functional connectivity at baseline and during the one-year follow-up using regions where delusion severity correlated with intra-SC as seeds. Results: The intra-SC correlated negatively with the baseline delusion severity in the bilateral anterior insula. In addition, we observed a subthreshold cluster in the anterior cingulate. These three regions constitute the cortical salience network (SN). Functional connectivity between the bilateral insula and the precuneus was weaker in the patients at baseline than in patients at follow-up or in control subjects at any time point. Conclusions: The results suggest that intra-SC is a powerful tool to study brain correlates of symptoms and highlight the role of the SN and internetwork dysconnectivity between the SN and the default mode network in delusions.

Browsing by Author "Suvisaari, Jaana"

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