scholarly journals Aberrant striatal dopamine links topographically with cortico-thalamic dysconnectivity in schizophrenia

Brain ◽  
2020 ◽  
Vol 143 (11) ◽  
pp. 3495-3505 ◽  
Author(s):  
Mihai Avram ◽  
Felix Brandl ◽  
Franziska Knolle ◽  
Jorge Cabello ◽  
Claudia Leucht ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Large Scale ◽  
Theoretical Models ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Salience Network ◽  
Thalamic Nuclei ◽  
Cortical Networks ◽  
Sensorimotor Network

Abstract Aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei are among the most consistent large-scale brain imaging findings in schizophrenia. A pathophysiological link between these two alterations is suggested by theoretical models based on striatal dopamine’s topographic modulation of cortico-thalamic connectivity within cortico-basal-ganglia-thalamic circuits. We hypothesized that aberrant striatal dopamine links topographically with aberrant cortico-thalamic iFC, i.e. aberrant associative striatum dopamine is associated with aberrant iFC between the salience network and thalamus, and aberrant sensorimotor striatum dopamine with aberrant iFC between the auditory-sensorimotor network and thalamus. Nineteen patients with schizophrenia during remission of psychotic symptoms and 19 age- and sex-comparable control subjects underwent simultaneous fluorodihydroxyphenyl-l-alanine PET (18F-DOPA-PET) and resting state functional MRI (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure striatal dopamine synthesis capacity; correlation coefficients between rs-fMRI time series of cortical networks and thalamic regions of interest were used to measure iFC. In the salience network-centred system, patients had reduced associative striatum dopamine synthesis capacity, which correlated positively with decreased salience network-mediodorsal-thalamus iFC. This correlation was present in both patients and healthy controls. In the auditory-sensorimotor network-centred system, patients had reduced sensorimotor striatum dopamine synthesis capacity, which correlated positively with increased auditory-sensorimotor network-ventrolateral-thalamus iFC. This correlation was present in patients only. Results demonstrate that reduced striatal dopamine synthesis capacity links topographically with cortico-thalamic intrinsic dysconnectivity in schizophrenia. Data suggest that aberrant striatal dopamine and cortico-thalamic dysconnectivity are pathophysiologically related within dopamine-modulated cortico-basal ganglia-thalamic circuits in schizophrenia.

scholarly journals S145. CORTICO-THALAMIC DYSCONNECTIVITY LINKS WITH ABERRANT STRIATAL DOPAMINE IN SCHIZOPHRENIA A SIMULTANEOUS 18F-DOPA-PET/RESTING-STATE FMRI STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S91-S91
Author(s):  
Mihai Avram ◽  
Felix Brandl ◽  
Franziska Knolle ◽  
Jorge Cabello ◽  
Claudia Leucht ◽  
...  
Keyword(s):  
Resting State ◽  
Dorsal Striatum ◽  
Correlation Coefficients ◽  
Striatal Dopamine ◽  
Dopamine Synthesis ◽  
Salience Network ◽  
Thalamic Nuclei ◽  
Cortical Networks ◽  
Sensorimotor Network ◽  
System Changes

Abstract Background In schizophrenia, among the most consistent brain changes are both aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei; however, it is unknown whether these changes are pathophysiologically related. Such a relationship is expected because cortico-thalamic-connectivity is modulated by striatal dopamine within topographically distinct, parallel but interacting cortico-basal-ganglia-thalamic circuits. We hypothesized: (1) Within-circuits, aberrant striatal dopamine contributes to aberrant cortico-thalamic-iFC, specifically, associative-striatum dopamine contributes to salience-network-thalamic-iFC, and sensorimotor-striatum dopamine to auditory-sensorimotor-network-thalamic-iFC. (2) Due to between-circuits interactions following an anterior-to-posterior gradient, salience-network-centered-system changes contribute to auditory-sensorimotor-network-centered-system changes. Methods To test these hypotheses, 19 patients with schizophrenia during symptomatic remission of positive symptoms and 19 age- and sex-comparable controls underwent simultaneous fluorodihydroxyphenyl-L-alanine positron emission tomography (18F-DOPA-PET) and resting-state functional magnetic resonance imaging (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure dopamine synthesis capacity (DSC), indicating striatal dopamine function; correlation coefficients between rs-fMRI time-series of cortical networks and thalamic regions-of-interest were used to measure iFC. Results In the salience-network(SAL)-centered-system, patients had reduced associative-striatum-DSC, which correlated positively with SAL-mediodorsal-thalamus-iFC and mediated the reduction of SAL-thalamic-iFC in patients. In the auditory-sensorimotor-network(ASM)-centered-system, patients had reduced sensorimotor-striatum-DSC, which correlated positively with ASM-ventrolateral-thalamus-iFC, but did not mediate increased ASM-thalamic-iFC in patients. Finally, aberrant DSC and iFC of the SAL-centered-system mediated corresponding changes in the ASM-centered-system. Discussion Results demonstrate that cortico-thalamic-dysconnectivity links with aberrant striatal dopamine in schizophrenia - in a topographically distinct way, with an anterior-to-posterior gradient, and primary changes in the SAL-centered system.

scholarly journals Cortico-thalamic dysconnectivity links with aberrant striatal dopamine in schizophrenia A simultaneous 18F-DOPA-PET/resting-state fMRI study

2019 ◽  
Author(s):  
Mihai Avram ◽  
Felix Brandl ◽  
Franziska Knolle ◽  
Jorge Cabello ◽  
Claudia Leucht ◽  
...  
Keyword(s):  
Resting State ◽  
Dorsal Striatum ◽  
Correlation Coefficients ◽  
Striatal Dopamine ◽  
Dopamine Synthesis ◽  
Salience Network ◽  
Thalamic Nuclei ◽  
Cortical Networks ◽  
Sensorimotor Network ◽  
System Changes

AbstractIn schizophrenia, among the most consistent brain changes are both aberrant dopamine function in the dorsal striatum and aberrant intrinsic functional connectivity (iFC) between distinct cortical networks and thalamic nuclei; however, it is unknown whether these changes are pathophysiologically related. Such a relationship is expected because cortico-thalamic-connectivity is modulated by striatal dopamine within topographically distinct, parallel but interacting cortico-basal-ganglia-thalamic circuits. We hypothesized: (1) Within-circuits, aberrant striatal dopamine contributes to aberrant cortico-thalamic-iFC, specifically, associative-striatum dopamine contributes to salience-network-thalamic-iFC, and sensorimotor-striatum dopamine to auditory-sensorimotor-network-thalamic-iFC. (2) Due to between-circuits interactions following an anterior-to-posterior gradient, salience-network-centered-system changes contribute to auditory-sensorimotor-network-centered-system changes. To test these hypotheses, 19 patients with schizophrenia during symptomatic remission of positive symptoms and 19 age- and sex-comparable controls underwent simultaneous fluorodihydroxyphenyl-L-alanine positron emission tomography (18F-DOPA-PET) and resting-state functional magnetic resonance imaging (rs-fMRI). The influx constant kicer based on 18F-DOPA-PET was used to measure dopamine synthesis capacity (DSC), indicating striatal dopamine function; correlation coefficients between rs-fMRI time-series of cortical networks and thalamic regions-of-interest were used to measure iFC. In the salience-network(SAL)-centered-system, patients had reduced associative-striatum-DSC, which correlated positively with SAL-mediodorsal-thalamus-iFC and mediated the reduction of SAL-thalamic-iFC in patients. In the auditory-sensorimotor-network(ASM)-centered-system, patients had reduced sensorimotor-striatum-DSC, which correlated positively with ASM-ventrolateral-thalamus-iFC, but did not mediate increased ASM-thalamic-iFC in patients. Finally, aberrant DSC and iFC of the SAL-centered-system mediated corresponding changes in the ASM-centered-system. Results demonstrate that cortico-thalamic-dysconnectivity links with aberrant striatal dopamine in schizophrenia - in a topographically distinct way, with an anterior-to-posterior gradient, and primary changes in the SAL-centered system.

scholarly journals Interactions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to adverse outcomes

2021 ◽  
Author(s):  
Gemma Modinos ◽  
Anja Richter ◽  
Alice Egerton ◽  
Ilaria Bonoldi ◽  
Matilda Azis ◽  
...  
Keyword(s):  
High Risk ◽  
Functional Outcomes ◽  
Mental States ◽  
Adverse Outcomes ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Clinical High Risk ◽  
Hippocampal Activity ◽  
The Relationship

AbstractPreclinical models propose that increased hippocampal activity drives subcortical dopaminergic dysfunction and leads to psychosis-like symptoms and behaviors. Here, we used multimodal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis and investigated its association with subsequent clinical and functional outcomes. Ninety-five participants (67 CHR and 28 healthy controls) underwent arterial spin labeling MRI and 18F-DOPA PET imaging at baseline. CHR participants were followed up for a median of 15 months to determine functional outcomes with the global assessment of function (GAF) scale and clinical outcomes using the comprehensive assessment of at-risk mental states (CAARMS). CHR participants with poor functional outcomes (follow-up GAF < 65, n = 25) showed higher rCBF in the right hippocampus compared to CHRs with good functional outcomes (GAF ≥ 65, n = 25) (pfwe = 0.026). The relationship between rCBF in this right hippocampal region and striatal dopamine synthesis capacity was also significantly different between groups (pfwe = 0.035); the association was negative in CHR with poor outcomes (pfwe = 0.012), but non-significant in CHR with good outcomes. Furthermore, the correlation between right hippocampal rCBF and striatal dopamine function predicted a longitudinal increase in the severity of positive psychotic symptoms within the total CHR group (p = 0.041). There were no differences in rCBF, dopamine, or their associations in the total CHR group relative to controls. These findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of adverse outcomes in the CHR state.

scholarly journals Brain Connectivity Dynamics in Untreated Transmen and Cisgender Individuals

2021 ◽  
Author(s):  
Carme Uribe ◽  
Carme Junque ◽  
Esther Gómez-Gil ◽  
María Díez-Cirarda ◽  
Antonio Guillamon
Keyword(s):  
Large Scale ◽  
Brain Connectivity ◽  
Positive Association ◽  
Brain Network ◽  
Functional Explanation ◽  
Salience Network ◽  
Temporal Perspective ◽  
Attention Regulation ◽  
Sensorimotor Network ◽  
Control Networks

Abstract Large-scale brain network interactions have been described between trans- and cis-gender identities. However, a temporal perspective of the brain spontaneous fluctuations is missing. We investigated the functional connectivity dynamics in transmen with gender incongruence and its relationship with interoceptive awareness. We describe four states in native and meta-state spaces: i) one state highly prevalent with sparse overall connections; ii) a second with strong couplings mainly involving components of the salience, default and executive control networks. Two states with global sparse connectivity but positive couplings iii) within the sensorimotor network, and iv) between salience network regions. Transmen had more dynamical fluidity than cismen, while cismen presented less meta-state fluidity and range dynamism than transmen and ciswomen. A positive association between attention regulation and fluidity, and meta-state range dynamism was found in transmen. There exist gender differences in the temporal brain dynamism, characterized by distinct interrelations of the salience network as catalyst interacting with other networks. We provide a functional explanation to the neurodevelopmental hypothesis proposing different brain phenotypes in the construction of the gendered-self.

scholarly journals Brain connectivity dynamics in cisgender and transmen people with gender incongruence before gender affirmative hormone treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Carme Uribe ◽  
Carme Junque ◽  
Esther Gómez-Gil ◽  
María Díez-Cirarda ◽  
Antonio Guillamon
Keyword(s):  
Large Scale ◽  
Brain Connectivity ◽  
Positive Association ◽  
Hormone Treatment ◽  
Brain Network ◽  
Functional Explanation ◽  
Salience Network ◽  
Temporal Perspective ◽  
Attention Regulation ◽  
Sensorimotor Network

AbstractLarge-scale brain network interactions have been described between trans- and cis-gender binary identities. However, a temporal perspective of the brain's spontaneous fluctuations is missing. We investigated the functional connectivity dynamics in transmen with gender incongruence and its relationship with interoceptive awareness. We describe four states in native and meta-state spaces: (i) one state highly prevalent with sparse overall connections; (ii) a second with strong couplings mainly involving components of the salience, default, and executive control networks. Two states with global sparse connectivity but positive couplings (iii) within the sensorimotor network, and (iv) between salience network regions. Transmen had more dynamical fluidity than cismen, while cismen presented less meta-state fluidity and range dynamism than transmen and ciswomen. A positive association between attention regulation and fluidity and meta-state range dynamism was found in transmen. There exist gender differences in the temporal brain dynamism, characterized by distinct interrelations of the salience network as catalyst interacting with other networks. We offer a functional explanation from the neurodevelopmental cortical hypothesis of a gendered-self.

scholarly journals Glutamatergic and dopaminergic function and the relationship to outcome in people at clinical high risk of psychosis: a multi-modal PET-magnetic resonance brain imaging study

2019 ◽  
Vol 45 (4) ◽  
pp. 641-648 ◽  
Author(s):  
Oliver D. Howes ◽  
Ilaria Bonoldi ◽  
Robert A. McCutcheon ◽  
Matilda Azis ◽  
Mathilde Antoniades ◽  
...  
Keyword(s):  
High Risk ◽  
Imaging Study ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Clinical High Risk ◽  
Magnetic Resonance Brain Imaging ◽  
The Relationship ◽  
Brain Imaging Study

Abstract Preclinical models of psychosis propose that hippocampal glutamatergic neuron hyperactivity drives increased striatal dopaminergic activity, which underlies the development of psychotic symptoms. The aim of this study was to examine the relationship between hippocampal glutamate and subcortical dopaminergic function in people at clinical high risk for psychosis, and to assess the association with the development of psychotic symptoms. 1H-MRS was used to measure hippocampal glutamate concentrations, and 18F-DOPA PET was used to measure dopamine synthesis capacity in 70 subjects (51 people at clinical high risk for psychosis and 19 healthy controls). Clinical assessments were undertaken at baseline and follow-up (median 15 months). Striatal dopamine synthesis capacity predicted the worsening of psychotic symptoms at follow-up (r = 0.35; p < 0.05), but not transition to a psychotic disorder (p = 0.22), and was not significantly related to hippocampal glutamate concentration (p = 0.13). There were no differences in either glutamate (p = 0.5) or dopamine (p = 0.5) measures in the total patient group relative to controls. Striatal dopamine synthesis capacity at presentation predicts the subsequent worsening of sub-clinical total and psychotic symptoms, consistent with a role for dopamine in the development of psychotic symptoms, but is not strongly linked to hippocampal glutamate concentrations.

Striatal dopamine synthesis capacity in twins discordant for schizophrenia

2011 ◽  
Vol 41 (11) ◽  
pp. 2331-2338 ◽  
Author(s):  
P. Shotbolt ◽  
P. R. Stokes ◽  
S. F. Owens ◽  
T. Toulopoulou ◽  
M. M. Picchioni ◽  
...  
Keyword(s):  
Control Sample ◽  
Chronic Schizophrenia ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Control Group ◽  
Positron Emission ◽  
Syndrome Scale ◽  
Increased Risk

BackgroundElevated striatal dopamine synthesis capacity is thought to be fundamental to the pathophysiology of schizophrenia and has also been reported in people at risk of psychosis. It is therefore unclear if striatal hyperdopaminergia is a vulnerability marker for schizophrenia, or a state feature related to the psychosis itself. Relatives of patients with schizophrenia are themselves at increased risk of developing the condition. In this study we examined striatal dopamine synthesis capacity in both members of twin pairs discordant for schizophrenia.MethodIn vivo striatal dopamine synthesis capacity was examined using fluorine-18-l-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET) scans in seven twin pairs discordant for schizophrenia and in a control sample of 10 healthy control twin pairs.ResultsStriatal 18F-DOPA uptake was not elevated in the unaffected co-twins of patients with schizophrenia (p=0.65) or indeed in the twins with schizophrenia (p=0.89) compared to the control group. Levels of psychotic symptoms were low in the patients with schizophrenia who were in general stable [mean (s.d.) Positive and Negative Syndrome Scale (PANSS) total=56.8 (25.5)] whereas the unaffected co-twins were largely asymptomatic.ConclusionsStriatal dopamine synthesis capacity is not elevated in symptom-free individuals at genetic risk of schizophrenia, or in well-treated stable patients with chronic schizophrenia. These findings suggest that striatal hyperdopaminergia is not a vulnerability marker for schizophrenia.

scholarly journals Interactions between hippocampal activity and striatal dopamine in people at clinical high risk for psychosis: relationship to clinical outcomes

2020 ◽  
Author(s):  
Gemma Modinos ◽  
Anja Richter ◽  
Alice Egerton ◽  
Ilaria Bonoldi ◽  
Matilda Azis ◽  
...  
Keyword(s):  
High Risk ◽  
Functional Outcome ◽  
Clinical Outcomes ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
Clinical High Risk ◽  
Hippocampal Activity ◽  
The Relationship

AbstractBackgroundPreclinical models propose that the onset of psychosis involves increased hippocampal activity which drives subcortical dopaminergic dysfunction. We used multi-modal neuroimaging to examine the relationship between hippocampal regional cerebral blood flow (rCBF) and striatal dopamine synthesis capacity in people at clinical high risk (CHR) for psychosis, and investigated its association with subsequent clinical outcomes.MethodsNinety-five participants (67 CHR and 28 healthy controls) underwent pseudo-continuous arterial spin labelling and 18F-DOPA PET imaging at baseline. Clinical outcomes in CHR participants were determined after a median of 15 months follow-up, using the Comprehensive Assessment of At Risk Mental States (CAARMS) and the Global Assessment of Function (GAF) scale.ResultsCHR participants with a poor functional outcome (follow-up GAF<65, n=25) showed higher rCBF in the right hippocampus compared to CHRs with a good functional outcome (GAF≥65, n=25) (familywise error [FWE] p=0·026). The relationship between right hippocampal rCBF and striatal dopamine synthesis capacity was also significantly different between groups (pFWE=0·035); the association was negative in CHR with poor outcomes (pFWE=0·012), but non-significant in CHR with good outcomes. The correlation between rCBF in this right hippocampal region and striatal dopamine function also predicted a longitudinal increase in the severity of positive psychotic symptoms (p=0·041). The relationship between hippocampal rCBF and striatal dopamine did not differ in the total CHR group relative to controls.InterpretationThese findings indicate that altered interactions between the hippocampus and the subcortical dopamine system are implicated in the pathophysiology of psychosis-related outcomes.

scholarly journals M149. THE TOPOGRAPHY OF STRIATAL DOPAMINE AND SYMPTOMS IN PSYCHOSIS: AN INTEGRATIVE PET AND MRI STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S192-S192
Author(s):  
Rob McCutcheon ◽  
Sameer Jauhar ◽  
Fiona Pepper ◽  
Matthew Nour ◽  
Maria Rogdaki ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Negative Symptoms ◽  
Striatal Dopamine ◽  
Psychotic Symptoms ◽  
Dopamine Synthesis ◽  
First Episode ◽  
Resting State Functional Connectivity ◽  
Positron Emission ◽  
Mri Study

Abstract Background Striatal dopamine dysfunction is proposed to underlie symptoms in psychosis, yet it is not known how changes in a single neurotransmitter could underlie the heterogenous presentations that are seen clinically. One hypothesis is that the symptomatic consequences of aberrant dopamine signalling may depend on where within the striatum dysfunction occurs. Positron emission tomography (PET) allows for the measurement of dopamine function across the striatum. However, when using typical atlas-based parcellation methods, the collinearity between measures of dopamine function within each striatal subdivision precludes investigation of this hypothesis. Methods We use a novel and data-driven parcellation method to address the above, and investigate relationships between spatial variability in dopamine synthesis capacity and psychotic symptoms. We employ a multimodal imaging approach combining 18F-DOPA PET and resting state MRI in 29 unmedicated and minimally-treated patients with first episode psychosis and 21 healthy controls. In each participant, we use resting state functional connectivity maps to quantify the functional connectivity of each striatal voxel to cortical networks. Network-specific striatal dopamine synthesis capacity (Kicer) was calculated for the resulting connectivity defined parcellations. Results Connectivity defined parcellations generated Kicer values with equivalent reliability, and significantly greater orthogonality to standard anatomical parcellation methods. Dopamine function within striatal areas connected to the default mode network is strongly associated with negative symptoms (p&lt;0.001). Discussion These findings suggest that individual differences in the topography of striatal dopamine dysfunction contribute to shaping psychotic symptomatology.

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