Biology subjects

Suckling, J.

Publications and source records attributed to Suckling, J..

3 recordsLinked to original sources

bioRxiv2018

Meta-analytic evidence for the plurality of mechanisms in transdiagnostic structural MRI studies of hallucination status

BACKGROUNDHallucinations are transmodal and transdiagnostic phenomena, occurring across sensory modalities and presenting in psychiatric, neurodegenerative, neurological, and non-clinical populations. Despite their cross-category occurrence, little empirical work has directly compared between-group neural correlates of hallucinations.\n\nMETHODSWe performed whole-brain voxelwise meta-analyses of hallucination status across diagnoses using AES-SDM, and conducted a comprehensive systematic review in PubMed and Web of Science until May 2018 on other structural correlates of hallucinations, including cortical thickness and gyrification.\n\nFINDINGS3214 abstracts were identified. Patients with psychiatric disorders and hallucinations (eight studies) exhibited reduced gray matter (GM) in the left insula, right inferior frontal gyrus, left anterior cingulate/paracingulate gyrus, left middle temporal gyrus, and increased in the bilateral fusiform gyrus, while patients with neurodegenerative disorders with hallucinations (eight studies) showed GM decreases in the left lingual gyrus, right supramarginal gyrus/parietal operculum, left parahippocampal gyrus, left fusiform gyrus, right thalamus, and right lateral occipital gyrus. Group differences between meta-analyses were formally confirmed and a jackknife sensitivity analysis established the reproducibility of results across nearly all study combinations. For other measures (28 studies), the most consistent findings associated with hallucination status were reduced cortical thickness in temporal gyri in schizophrenia and altered hippocampal volume in Parkinsons disease and dementia.\n\nINTERPRETATIONDistinct patterns of neuroanatomical alteration characterize hallucination status in patients with psychiatric and neurodegenerative diseases, suggesting a plurality of anatomical signatures. This approach has implications for treatment, theoretical frameworks, and generates refutable predictions for hallucinations in other diseases and their occurrence within the general population.\n\nFUNDINGNone.\n\nResearch in contextO_ST_ABSEvidence before this studyC_ST_ABSThere is increasing recognition that hallucinations occur beyond the archetype of schizophrenia, presenting in other psychiatric disorders, neurological and neurodegenerative conditions, and among the general population. Not only are hallucinations a transdiagnostic phenomenon, but also the experience of hallucinating is phenomenologically diverse, varying in modality, content, frequency, and affect. It has been suggested that no one type of hallucination is pathognomic to any one disorder, but rather that hallucinations may exist on a continuum. However, limited research has been done to directly compare the underlying neuroanatomy of hallucinations between different disorders. With this aim, we conducted a meta-analysis and systematic review of structural MRI studies comparing individuals who experience hallucinations with those who do not, to investigate the brain morphology related to the transdiagnostic presentation of hallucinations. We searched PubMed and Web of Science with no start date limit, up to May 2018 using the keyword combination (hallucinat*) AND (MRI OR magnetic resonance imaging OR morphology OR voxel?based OR morphometr* OR neural correlate OR structur*). We included only studies with a within-group no-hallucination control to tease out structural changes specific to hallucinations from effects of the broader pathology. Neuroimaging meta-analyses were conducted on studies performing whole-brain voxelwise gray matter differences, while studies assessing other structural correlates were qualitatively synthesized.\n\nAdded value of this studyThis is the first meta-analysis to illustrate the brain structural correlates of hallucination occurrence derived from T1-weighted MRI, and to do so in a comparative manner across clinical groups. We identified two distinct gray matter substrates for hallucination presence in psychiatric compared to neurodegenerative diseases, which we hypothesise constitute at least two distinct mechanisms. In addition, we qualitatively assessed other structural neuroimaging studies over a variety of morphometric indices. We therefore provide a complete characterization of current knowledge of the brain morphology associated with hallucinations across clinical status and modality.\n\nImplications of all the available evidenceOur findings show at least two structural substrates that link to the hallucinatory experience. This informs theoretical work on hallucinations which have to date been limited in generating unifying direction-specific predictions of brain structure and function. Understanding the plurality of anatomical signatures of hallucinations may also inform treatment strategies. We predict that other disorders in which patients experience hallucinations can be categorised by our approach based on the broader phenotype; for example, hallucinations in personality disorder may be of the psychiatric type, and similarly for early onset hallucinations in the general population, whilst later onset will be neurodegenerative. Moreover, by differentiating the mechanisms of hallucinations we recommend the contextualising of research by the appropriate phenotype.

neuroscience↗

bioRxiv2017

Dopaminergic drug treatment remediates exaggerated cingulate prediction error responses in obsessive-compulsive disorder

RationalePatients with obsessive-compulsive disorder (OCD) have been found to show exaggerated error responses and prediction error learning signals in a variety of EEG and fMRI tasks, with data converging on the anterior cingulate cortex as a key locus of dysfunction. Considerable evidence has linked prediction error processing to dopaminergic function.\n\nObjectiveIn this study we investigate potential dopaminergic dysfunction during reward processing in the context of OCD.\n\nMethodsWe studied OCD patients (n=18) and controls (n=18) whilst they learned probabilistic associations between abstract stimuli and monetary rewards in the fMRI scanner involving administration (on separate visits) of: a dopamine receptor agonist, pramipexole 0.5mg; a dopamine receptor antagonist, amisulpride 400mg, and placebo. We fitted a Q-learning computational model to fMRI prediction error responses; group differences were examined in anterior cingulate and nucleus accumbens regions of interest.\n\nResultsThere were no significant group, drug or interaction effects in number of correct choices; computational modeling suggested a marginally significant difference in learning rates between groups (p=0.089, partial 2=0.1). In the imaging results, there was a significant interaction of group by drug (p=0.013, partial 2=0.13). OCD patients showed abnormally strong cingulate signaling of prediction errors during omission of an expected reward, with unexpected reduction by both pramipexole and amisulpride (p=0.014, partial 2=0.26, 1-{beta} error probability=0.94). Exaggerated cingulate prediction error signaling to omitted reward in placebo was related to trait subjective difficulty in self-regulating behavior in OCD.\n\nConclusionsOur data support cingulate dysfunction during reward processing in OCD, and bidirectional remediation by dopaminergic modulation, suggesting that exaggerated cingulate error signals in OCD may be of dopaminergic origin. The results help to illuminate the mechanisms through which dopamine receptor antagonists achieve therapeutic benefit in OCD. Further research is needed to disentangle the different functions of dopamine receptor agonists and antagonists during bidirectional modulation of cingulate activation.

neuroscience↗

bioRxiv2017

Global Effects Of Focal Brain Tumours On Functional Complexity And Network Robustness

BackgroundNeurosurgical management of brain tumours has entered a new paradigm of supra-marginal resections that demands thorough understanding of their peri-tumoural functional effects. Historically the effects of tumours have been considered as local, and long-range effects have not been considered. This work tests the hypothesis that focal tumours affect the brain at a global level producing long-range gradients in cortical function.\n\nMethodsResting state functional (f)MRI data were acquired from 11 participants with glioblastoma and split into discovery and validation datasets. Fractal complexity was computed with a wavelet-based estimator of the Hurst exponent. Distance related effects of the tumours were tested with a tumour mask dilation technique and parcellation of the underlying Hurst maps. Functional connectivity networks were constructed and validated with different parcellation and statistical dependency methods prior to graph theory analysis.\n\nResultsFractal complexity, measured through the Hurst exponent and tumour mask dilation technique, demonstrates a penumbra of suppression in the peri-tumoural region. At a global level, as distance from the tumour increases, this initial suppression is balanced by a subsequent over-activity before finally normalizing. These effects were best fit by a quadratic model, and were consistent across different network construction pipelines. The Hurst exponent was significantly correlated with multiple graph theory measures of centrality including network robustness, but graph theory measures did not demonstrate distance dependent effects.\n\nConclusionsThis work provides evidence to support the theory that focal brain tumours produce long-range and non-linear gradients in function. Consequently the effects of focal lesions, and the resultant clinical effects, need to be interpreted in terms of the global changes on whole brain functional complexity and network architecture rather than purely in terms of functional localisation. Determining whether the peri-tumoural changes represent adaption or potential plasticity, for example, may facilitate extended resection of the tumour without functional cost.

neuroscience↗