Functional disconnection and social cognition in schizophrenia

Introduction Social and emotional functions play a key role in schizophrenia. Both positive symptoms, such as hallucinations and persecutory delusions, as well as negative symptoms such as social withdrawal, and flattened affect impact socioemotional function. These functions involve distributed brain networks. The ‘Disconnection Hypothesis’, a plausible unifying theory of schizophrenia, proposes connectivity within such networks as a core pathological feature of schizophrenia. Connectivity is also related to specific genetic risk factors. Therefore the present project addresses the hypothesis that individuals with schizophrenia might show disconnection within socio-emotional brain networks, and examines the effects of a functional polymorphism of the BDNF gene on connectivity within these networks. Methods Here I examined the brain activation and connectivity for implicit emotional reaction and social judgment in schizophrenia, as well as with variation in the val66met polymorphism of BDNF. Brain activation was examined with functional magnetic resonance imaging, and effective connectivity was estimated using psycho-physiological interactions, from the bilateral amygdala to the whole brain (using a facial image paradigm for explicit approachability judgement and implicit fear response respectively). Results Individuals with schizophrenia showed reduced activation in the right lingual gyrus, right superior temporal gyrus and left amygdala during fear processing, as well as reduced connectivity from the left amygdala to the right temporo-parietal junction and precuneus. During approachability judgments, patients overactivated the right inferior frontal gyrus and right precuneus and showed reduced connectivity from the bilateral amygdala to the right inferior frontal gyrus. Met allele carriers of the BDNF val66met polymorphism showed overactivation in the medial anterior cingulate cortex, and bilateral insula, as well as reduced connectivity between the anterior cingulate cortex and hippocampus. For approachability judgment, met carriers overactivated the middle occipital gyrus, and showed reduced connectivity from the left amygdala to the right parahippocampal gyrus and medial frontal gyrus, as well as the left posterior cingulate gyrus, pre and post central gyrus, middle temporal gyrus and cerebellum. Conclusion In conclusion, connectivity between the amygdala and brain regions associated with a range of socially relevant functions were found to be reduced in both patients, and met allele carriers of the BDNF val66met SNP. Given the key role of the amygdala in affective processing this diffuse disconnection in networks for socio-emotional functions might mediate the aberrant emotional and social behavior seen in individuals with schizophrenia

Reprint of: Minimizing noise in pediatric task-based functional MRI; Adolescents with developmental disabilities and typical development

Functional Magnetic Resonance Imaging (fMRI) represents a powerful tool with which to examine brain functioning and development in typically developing pediatric groups as well as children and adolescents with clinical disorders. However, fMRI data can be highly susceptible to misinterpretation due to the effects of excessive levels of noise, often related to head motion. Imaging children, especially with developmental disorders, requires extra considerations related to hyperactivity, anxiety and the ability to perform and maintain attention to the fMRI paradigm. We discuss a number of methods that can be employed to minimize noise, in particular movement-related noise. To this end we focus on strategies prior to, during and following the data acquisition phase employed primarily within our own laboratory. We discuss the impact of factors such as experimental design, screening of potential participants and pre-scan training on head motion in our adolescents with developmental disorders and typical development. We make some suggestions that may minimize noise during data acquisition itself and finally we briefly discuss some current processing techniques that may help to identify and remove noise in the data. Many advances have been made in the field of pediatric imaging, particularly with regard to research involving children with developmental disorders. Mindfulness of issues such as those discussed here will ensure continued progress and greater consistency across studies

Functional disconnection and social cognition in schizophrenia

Introduction Social and emotional functions play a key role in schizophrenia. Both positive symptoms, such as hallucinations and persecutory delusions, as well as negative symptoms such as social withdrawal, and flattened affect impact socioemotional function. These functions involve distributed brain networks. The ‘Disconnection Hypothesis’, a plausible unifying theory of schizophrenia, proposes connectivity within such networks as a core pathological feature of schizophrenia. Connectivity is also related to specific genetic risk factors. Therefore the present project addresses the hypothesis that individuals with schizophrenia might show disconnection within socio-emotional brain networks, and examines the effects of a functional polymorphism of the BDNF gene on connectivity within these networks. Methods Here I examined the brain activation and connectivity for implicit emotional reaction and social judgment in schizophrenia, as well as with variation in the val66met polymorphism of BDNF. Brain activation was examined with functional magnetic resonance imaging, and effective connectivity was estimated using psycho-physiological interactions, from the bilateral amygdala to the whole brain (using a facial image paradigm for explicit approachability judgement and implicit fear response respectively). Results Individuals with schizophrenia showed reduced activation in the right lingual gyrus, right superior temporal gyrus and left amygdala during fear processing, as well as reduced connectivity from the left amygdala to the right temporo-parietal junction and precuneus. During approachability judgments, patients overactivated the right inferior frontal gyrus and right precuneus and showed reduced connectivity from the bilateral amygdala to the right inferior frontal gyrus. Met allele carriers of the BDNF val66met polymorphism showed overactivation in the medial anterior cingulate cortex, and bilateral insula, as well as reduced connectivity between the anterior cingulate cortex and hippocampus. For approachability judgment, met carriers overactivated the middle occipital gyrus, and showed reduced connectivity from the left amygdala to the right parahippocampal gyrus and medial frontal gyrus, as well as the left posterior cingulate gyrus, pre and post central gyrus, middle temporal gyrus and cerebellum. Conclusion In conclusion, connectivity between the amygdala and brain regions associated with a range of socially relevant functions were found to be reduced in both patients, and met allele carriers of the BDNF val66met SNP. Given the key role of the amygdala in affective processing this diffuse disconnection in networks for socio-emotional functions might mediate the aberrant emotional and social behavior seen in individuals with schizophrenia.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Reprint of: Minimizing noise in pediatric task-based functional MRI; Adolescents with developmental disabilities and typical development.

Functional Magnetic Resonance Imaging (fMRI) represents a powerful tool with which to examine brain functioning and development in typically developing pediatric groups as well as children and adolescents with clinical disorders. However, fMRI data can be highly susceptible to misinterpretation due to the effects of excessive levels of noise, often related to head motion. Imaging children, especially with developmental disorders, requires extra considerations related to hyperactivity, anxiety and the ability to perform and maintain attention to the fMRI paradigm. We discuss a number of methods that can be employed to minimize noise, in particular movement-related noise. To this end we focus on strategies prior to, during and following the data acquisition phase employed primarily within our own laboratory. We discuss the impact of factors such as experimental design, screening of potential participants and pre-scan training on head motion in our adolescents with developmental disorders and typical development. We make some suggestions that may minimize noise during data acquisition itself and finally we briefly discuss some current processing techniques that may help to identify and remove noise in the data. Many advances have been made in the field of pediatric imaging, particularly with regard to research involving children with developmental disorders. Mindfulness of issues such as those discussed here will ensure continued progress and greater consistency across studies

Reprint of: Minimizing noise in pediatric task-based functional MRI; Adolescents with developmental disabilities and typical development.

Functional Magnetic Resonance Imaging (fMRI) represents a powerful tool with which to examine brain functioning and development in typically developing pediatric groups as well as children and adolescents with clinical disorders. However, fMRI data can be highly susceptible to misinterpretation due to the effects of excessive levels of noise, often related to head motion. Imaging children, especially with developmental disorders, requires extra considerations related to hyperactivity, anxiety and the ability to perform and maintain attention to the fMRI paradigm. We discuss a number of methods that can be employed to minimize noise, in particular movement-related noise. To this end we focus on strategies prior to, during and following the data acquisition phase employed primarily within our own laboratory. We discuss the impact of factors such as experimental design, screening of potential participants and pre-scan training on head motion in our adolescents with developmental disorders and typical development. We make some suggestions that may minimize noise during data acquisition itself and finally we briefly discuss some current processing techniques that may help to identify and remove noise in the data. Many advances have been made in the field of pediatric imaging, particularly with regard to research involving children with developmental disorders. Mindfulness of issues such as those discussed here will ensure continued progress and greater consistency across studies

Minimizing noise in pediatric task-based functional MRI; Adolescents with developmental disabilities and typical development

Functional Magnetic Resonance Imaging (fMRI) represents a powerful tool with which to examine brain functioning and development in typically developing pediatric groups as well as children and adolescents with clinical disorders. However, fMRI data can be highly susceptible to misinterpretation due to the effects of excessive levels of noise, often related to head motion. Imaging children, especially with developmental disorders, requires extra considerations related to hyperactivity, anxiety and the ability to perform and maintain attention to the fMRI paradigm. We discuss a number of methods that can be employed to minimize noise, in particular movement-related noise. To this end we focus on strategies prior to, during and following the data acquisition phase employed primarily within our own laboratory. We discuss the impact of factors such as experimental design, screening of potential participants and pre-scan training on head motion in our adolescents with developmental disorders and typical development. We make some suggestions that may minimize noise during data acquisition itself and finally we briefly discuss some current processing techniques that may help to identify and remove noise in the data. Many advances have been made in the field of pediatric imaging, particularly with regard to research involving children with developmental disorders. Mindfulness of issues such as those discussed here will ensure continued progress and greater consistency across studies

Limbic and Executive Meso- and Nigrostriatal Tracts Predict Impulsivity Differences in Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Impulsivity is a defining characteristic of attention-deficit/hyperactivity disorder (ADHD), which has been associated with substance use disorders, higher accident rates, and lower educational and occupational outcomes. The meso- and nigrostriatal pathways of the dopamine system are hypothesized to be functionally heterogeneous, supporting diverse cognitive functions and impairments, including those associated with ADHD. We tested whether human midbrain pathways (where dopaminergic cell bodies originate) between the substantia nigra (SN) and ventral tegmental area (VTA) and the striatum differed between participants with ADHD and typically developing adolescent and young adult participants. We also assessed whether pathway connectivity predicted impulsivity regardless of diagnosis. METHODS: Diffusion tensor imaging data were used to predict impulsivity (parent and self-report ratings, task-based behavioral measures) from participants with ADHD and typically developing adolescent and young adult participants (n = 155; 86 male, 69 female). Using probabilistic tractography, we mapped these pathways and divided the tracts into limbic, executive, and sensorimotor based on frontostriatal connectivity. ADHD and typically developing participants differed on all behavioral measures of impulsivity. We used correlation and machine learning analyses to test for a relationship between tract probabilities and impulsivity regardless of diagnosis. RESULTS: Participants with ADHD had stronger structural connectivity between SN/VTA regions and the limbic striatum, weaker connectivity with the executive striatum, and no significant differences in sensorimotor tracts. Increased tract integrity between the limbic striatal and SN/VTA regions predicted greater impulsivity, while increased integrity between executive striatal and SN/VTA regions predicted reduced impulsivity. CONCLUSIONS: These findings support the theory that functional diversity in the dopamine system is an important consideration for understanding dysfunction in ADHD