robotically-delivered-fmri-guided-personalized-transcranial-magnetic

Robotically Delivered fMRI-Guided Personalized Transcranial Magnetic Stimulation Therapy for Treatment-Resistant Depression

Improving the outcomes of transcranial magnetic stimulation (TMS) therapy for treatment-resistant depression may be achieved by personalizing the ...

QIMR Berghofer Medical Research Institute

Queensland Neurostimulation Centre

Building capacity in academic psychiatry: The Queensland Mental Health Research Alliance.

The first phase of molecular brain imaging of microglial activation in neuroinflammatory conditions began some 20 years ago with the introduction of [C]-( R)-PK11195, the prototype isoquinoline ligand for translocator protein (18 kDa) (TSPO). Investigations by positron emission tomography (PET) revealed microgliosis in numerous brain diseases, despite the rather low specific binding signal imparted by [C]-( R)-PK11195. There has since been enormous expansion of the repertoire of TSPO tracers, many with higher specific binding, albeit complicated by allelic dependence of the affinity. However, the specificity of TSPO PET for revealing microglial activation not been fully established, and it has been difficult to judge the relative merits of the competing tracers and analysis methods with respect to their sensitivity for detecting microglial activation. We therefore present a systematic comparison of 13 TSPO PET and single photon computed tomography (SPECT) tracers belonging to five structural classes, each of which has been investigated by compartmental analysis in healthy human brain relative to a metabolite-corrected arterial input. We emphasize the need to establish the non-displaceable binding component for each ligand and conclude with five recommendations for a standard approach to define the cellular distribution of TSPO signals, and to characterize the properties of candidate TSPO tracers.

Sifting through the surfeit of neuroinflammation tracers.

Welcome to the Breakfast Club: Building academic psychiatry capacity in Queensland.

Executive dysfunctions in early psychosis (EP) are subtle but persistent, hindering recovery. We asked whether changes in the cognitive control system (CCS) disrupt the response to increased cognitive load in persons with EP. In all, 30 EP and 30 control participants undertook multimodal MRI. Computational models of structural and effective connectivity amongst regions in the CCS were informed by cortical responses to the multi-source interference task, a paradigm that selectively introduces stimulus conflict. EP participants showed greater activation of CCS regions, including the superior parietal cortex, and were disproportionately slower at resolving stimulus conflict in the task. Computational models of the effective connectivity underlying this behavioral response suggest that the normative (control) group resolved stimulus conflict through an efficient and direct modulation of gain between the visual cortex and the anterior insula (AI). In contrast, the EP group utilized an indirect path, with parallel and multi-region hops to resolve stimulus conflict at the AI. Individual differences in task performance were dependent on initial linear gain modulations in the EP group versus a single nonlinear modulation in the control group. Effective connectivity in the EP group was associated with reduced structural integration amongst those connections critical for task execution. CCS engagement during stimulus conflict is hampered in EP owing to inefficient use of higher-order network interactions, with high tonic gain impeding task-relevant (phasic) signal amplification.

Sub-optimal modulation of gain by the cognitive control system in young adults with early psychosis.

To present a practical, easy-to-implement clinical framework designed to support evidence-based quality prescribing for people with early psychosis.

Quality prescribing in early psychosis: key pharmacotherapy principles.

The diagnosis of obsessive-compulsive disorder (OCD) has been linked with changes in frontostriatal resting-state connectivity. However, replication of prior findings is lacking, and the mechanistic understanding of these effects is incomplete. To confirm and advance knowledge on changes in frontostriatal functional connectivity in OCD, participants with OCD and matched healthy controls underwent resting-state functional, structural and diffusion neuroimaging. Functional connectivity changes in frontostriatal systems were here replicated in individuals with OCD (n = 52) compared with controls (n = 45). OCD participants showed greater functional connectivity (t = 4.3, PFWE = 0.01) between the nucleus accumbens (NAcc) and the orbitofrontal cortex (OFC) but lower functional connectivity between the dorsal putamen and lateral prefrontal cortex (t = 3.8, PFWE = 0.04) relative to controls. Computational modelling suggests that NAcc-OFC connectivity changes reflect an increased influence of NAcc over OFC activity and reduced OFC influence over NAcc activity (posterior probability, Pp > 0.66). Conversely, dorsal putamen showed reduced modulation over lateral prefrontal cortex activity (Pp > 0.90). These functional deregulations emerged on top of a generally intact anatomical substrate. We provide out-of-sample replication of opposite changes in ventro-anterior and dorso-posterior frontostriatal connectivity in OCD and advance the understanding of the neural underpinnings of these functional perturbations. These findings inform the development of targeted therapies normalizing frontostriatal dynamics in OCD.

Mechanisms of imbalanced frontostriatal functional connectivity in obsessive-compulsive disorder.

The mixed cognitive outcomes in early psychosis (EP) have important implications for recovery. In this longitudinal study, we asked whether baseline differences in the cognitive control system (CCS) in EP participants would revert toward a normative trajectory seen in healthy controls (HC). Thirty EP and 30 HC undertook functional MRI at baseline using the multi-source interference task-a paradigm that selectively introduces stimulus conflict-and 19 in each group repeated the task at 12 months. Activation of the left superior parietal cortex normalized over time for the EP group, relative to HC, coincident with improvements in reaction time and social-occupational functioning. To examine these group and timepoint differences, we used dynamic causal modeling to infer changes in effective connectivity between regions underlying the MSIT task execution, namely visual, anterior insula, anterior cingulate, and superior parietal cortical regions. To resolve stimulus conflict, EP participants transitioned from an indirect to a direct neuromodulation of sensory input to the anterior insula over timepoints, though not as strongly as HC participants. Stronger direct nonlinear modulation of the anterior insula by the superior parietal cortex at follow-up was associated with improved task performance. Overall, normalization of the CCS through adoption of more direct processing of complex sensory input to the anterior insula, was observed in EP after 12 months of treatment. Such processing of complex sensory input reflects a computational principle called gain control, which appears to track changes in cognitive trajectory within the EP group.

Longitudinal changes in neural gain and its relationship to cognitive control trajectory in young adults with early psychosis.

Impairments in the expression, experience, and recognition of emotion are common in early psychosis (EP). Computational accounts of psychosis suggest disrupted top-down modulation by the cognitive control system (CCS) on perceptual circuits underlies psychotic experiences, but their role in emotional deficits in EP is unknown.

Cognitive Control System Gates Insula Processing of Affective Stimuli in Early Psychosis.

Current behavioural treatment of obsessive-compulsive disorder (OCD) is informed by fear conditioning and involves iteratively re-evaluating previously threatening stimuli as safe. However, there is limited research investigating the neurobiological response to conditioning and reversal of threatening stimuli in individuals with OCD. A clinical sample of individuals with OCD (N = 45) and matched healthy controls (N = 45) underwent functional magnetic resonance imaging. While in the scanner, participants completed a well-validated fear reversal task and a resting-state scan. We found no evidence for group differences in task-evoked brain activation or functional connectivity in OCD. Multivariate analyses encompassing all participants in the clinical and control groups suggested that subjective appraisal of threatening and safe stimuli were associated with a larger difference in brain activity than the contribution of OCD symptoms. In particular, we observed a brain-behaviour continuum whereby heightened affective appraisal was related to increased bilateral insula activation during the task (r = 0.39, p  = .001). These findings suggest that changes in conditioned threat-related processes may not be a core neurobiological feature of OCD and encourage further research on the role of subjective experience in fear conditioning.

Revisiting deficits in threat and safety appraisal in obsessive-compulsive disorder.

Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an established treatment for refractory major depressive disorder (MDD), but treatment outcomes vary substantially from person to person. Recent evidence suggests that incorporating neuroimaging-based targeting may help improve clinical outcomes. Here, we report the initial clinical outcomes of our open-label fMRI-personalized treatment protocol from the Queensland Neurostimulation Centre.

Clinical and Neurophysiological Effects of Robotically Delivered fMRI-Guided Personalized Transcranial Magnetic Stimulation Therapy for Depression.

Obsessive-compulsive disorder (OCD) is associated with functional alterations in how the striatum interacts with the rest of the brain. However, the characterization of these changes in OCD is incomplete. Mapping functional striatal gradients provides a new opportunity to fill this knowledge gap. These gradients provide a spatial representation of continuous changes in whole-brain connectivity within striatal regions. Thus, OCD-related differences in striatal gradients imply changes in the functional organization of striatal connections.

Altered Striatal Functional Gradients in Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is associated with functional alterations in how the striatum interacts with the rest of the brain. However, the characterization of these changes in OCD is incomplete. Mapping functional striatal gradients provides a new opportunity to fill this knowledge gap. These gradients provide a spatial representation of continuous changes in whole-brain connectivity within striatal regions. Thus, OCD-related differences in striatal gradients imply changes in the functional organisation of striatal connections.

Article	Year
Building capacity in academic psychiatry: The Queensland Mental Health Research Alliance. The Australian and New Zealand journal of psychiatry\| PubMed ID: 25801661	2015
Sifting through the surfeit of neuroinflammation tracers. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism\| PubMed ID: 29256293
Welcome to the Breakfast Club: Building academic psychiatry capacity in Queensland. The Australian and New Zealand journal of psychiatry\| PubMed ID: 34219475	2021
Sub-optimal modulation of gain by the cognitive control system in young adults with early psychosis. Translational psychiatry\| PubMed ID: 34707092	2021
Quality prescribing in early psychosis: key pharmacotherapy principles. Australasian psychiatry : bulletin of Royal Australian and New Zealand College of Psychiatrists\| PubMed ID: 34748711	2022
Mechanisms of imbalanced frontostriatal functional connectivity in obsessive-compulsive disorder. Brain : a journal of neurology\| PubMed ID: 36380526	2023
Longitudinal changes in neural gain and its relationship to cognitive control trajectory in young adults with early psychosis. Translational psychiatry\| PubMed ID: 36864034	2023
Cognitive Control System Gates Insula Processing of Affective Stimuli in Early Psychosis. Schizophrenia bulletin\| PubMed ID: 36866458	2023
Revisiting deficits in threat and safety appraisal in obsessive-compulsive disorder. Human brain mapping\| PubMed ID: 37853935	2023
Clinical and Neurophysiological Effects of Robotically Delivered fMRI-Guided Personalized Transcranial Magnetic Stimulation Therapy for Depression. Psychotherapy and psychosomatics\| PubMed ID: 40203817	2025
Altered Striatal Functional Gradients in Obsessive-Compulsive Disorder. Biological psychiatry. Cognitive neuroscience and neuroimaging\| PubMed ID: 40716670	2025
Altered striatal functional gradients in obsessive-compulsive disorder. medRxiv : the preprint server for health sciences\| PubMed ID: 40791733	2025

Bjorn Burgher

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