Neuroimaging in Mental Health PDF

**[Core Principles ]** **[Neuroimaging in Mental Health]** [Why is imaging important:] - Brain pathology cannot be studied directly during life - Brain biopsy not routinely performed - Imaging can be used as a surrogate/biomarker of brain function [Neuroimaging Methods:] Structural: -...

**[Core Principles ]** **[Neuroimaging in Mental Health]** [Why is imaging important:] - Brain pathology cannot be studied directly during life - Brain biopsy not routinely performed - Imaging can be used as a surrogate/biomarker of brain function [Neuroimaging Methods:] Structural: - Computed Tomography (CT) - Magnetic Resonance Imaging (MRI) Functional: - Positron Emission Tomography (PET) - Single Photon Emission Computed Tomography (SPECT) - Diffusion Tensor Imaging (DTI) - Functional MRI (fMRI) - Electroencephalography (EEG) [Structural MRI Applications: ] Screen for reversible causes of altered mental state: - Meningioma - Subdural Haematoma - Normal Pressure Hydrocephalus Screen for severe/irreversible pathology: - Deep tumours - Infarcts - White matter hyper intensity Supporting Diagnosis: - Atrophy: present/absent/global/localised - Rule out organic pathology in new cases of psychosis Research: - Extensively used as research tool [Diffusion Tensor Imaging Scans:] - MRI imaging method - DTI looks at white-matter connectivity within the brain [BOLD Blood Oxygen Level Dependent effect in fMRI:] - fMRI relies on the BOLD effect as a proxy measure of brain activity - Blood releases oxygen to active neurons at greater rate than to inactive neurons - Known as the hemodynamic response - Causes a difference in magnetic properties of oxygenated and deoxygenated blood [SPECT Applications:] - Clinically used in neurology for epilepsy, stroke, brain, tumours, traumatic brain injury - In mental health for evaluating patient with suspected dementia including early detection, differential diagnosis, and in the pre-dementia phase [Comparison of different techniques:] +-------------+-------------+-------------+-------------+-------------+ | | **EEG** | **sMRI & | **SPECT** | **PET** | | | | fMRI** | | | +=============+=============+=============+=============+=============+ | **Is it | **Safest:** | **Not | **Invasive: | **Invasive: | | invasive?** | | Invasive:** | ** | ** | | | *Recorded | | | | | | naturally | *Magnet, | *Radioactiv | *Radioactiv | | | occurring | Noisy, | e | e | | | electrical | Enclosed | tracer + IV | tracer + IV | | | signal* | Space* | injection* | injection* | +-------------+-------------+-------------+-------------+-------------+ | **Temporal | **Superb:** | **Poor:** | **Good:** | **Good:** | | Resolution* | | | | | | * | *Millisecon | *BOLD | *Couple of | *Couple of | | | ds* | signal | seconds* | seconds* | | | | slow, | | | | | | 5-10secs* | | | +-------------+-------------+-------------+-------------+-------------+ | **Spatial | **Poor** | **High** | **Good** | **High** | | Resolution* | | | | | | * | | | | | +-------------+-------------+-------------+-------------+-------------+ | **Cost** | **Low** | **Medium** | **Medium** | **High** | +-------------+-------------+-------------+-------------+-------------+ | **Applicati | *Research* | *Research* | *Research* | *Research* | | ons** | | | | | | | *Clinical | *Clinical | *Clinical | *Dementia* | | | Use* | Use* | Use* | | +-------------+-------------+-------------+-------------+-------------+ **[Neuroimaging]** [The Brain:] - Neuroimaging allows us to see more of brain What can't we see: - Brain Activity Can only investigate neurotransmitters in different regions by cutting it up [Neuroimaging Methods:] - MRI - Structural - Functional - PET & SPECT - Functional - EEG & MEG - Functional [PET scan:] - Uses radioactive ligands that bind to molecular targets such as neurotransmitter receptors - Radiotracer is injected into the body - Coincidence detection of gamma ray being emitted in 2 opposite directions: shows that ligand is bound in this location - Overlay onto MRI scan, or just look at radioactivity map - SPECT is similar -- injects gamma ray (although usually more stable so lasts longer/cheaper than PET, BUT less spatial resolution) - PET is routinely used clinically in oncology: - tumour detection, studies of extension, monitoring response to treatment - PET has clinical use in mental health: - Licensed for amyloid imaging in dementia - Not frequently used due to high cost and limited access - PET is used for mental health research: - Research in neurodegeneration - Extensive research on neurotransmission in mental illness [Strengths:] - High Spatial Resolution - Good Temporal Resolution Limitations: - Expensive - Invasive (injection of radioactive substance) [Evidence for Dopamine Hypothesis:] 2 types of PET Imaging: 1. Radioligand binding to dopamine receptors 2. Measure synaptic uptake of radioactive dopamine - PET studies find increased dopamine uptake in striatum in Schizophrenia Vs. Controls [Electroencephalogram (EEG):] - Recording of electrical activity on scalp produced by neurons firing within brain - EEG can be studied directly or be processed to obtain event related potentials: - Mismatch Negativity - P50 Gating - P300 Wave Main Clinical Applications in Neurology/Neurosurgery: - Epilepsy where EEG is essential for its diagnosis/classification - Diagnosis of coma, encephalopathy & brain death - Neurophysiology guiding surgery In Mental Health it can support diagnosis: - Rule out epilepsy in unusual presentations [Event Related Potentials = ERP:] **Mismatch Negativity (MMN):** - Present oddball sequence of stimuli - E.g., number of beeps with the same tone, one "deviant" beep presented in a different tone or duration or loudness - MMN occurs whether or not you are paying attention = context-dependent sensory information processing - Reduced MMN amplitude in Schizophrenia, large effect size **P50 Gating:** - ERP occurs approximately 50ms after presentation of an auditory stimulus **Paired Click Test:** - Second auditory click will be presented 500ms after the first one - Second sound is considered redundant - A healthy control showing normal sensory gating will produce a reduced response to the second click *P50 gating deficit is found in 65% of SZ patients compared to 20% of healthy subjects without mental illness* *Cause deficits in sensory filtering and sensory overload* **P300:** - Use oddball task - Stimuli EEG change = P300 wave - P300 wave associated with decision making - Both amplitude & latency reduced in Schizophrenia [Magnetoencephalography (MEG):] - MEG measures small magnetic fields produced by electrical currents in the brain - Magnetic fields are detected by extremely sensitive devices called "super conducting detectors and amplifiers", also known as SQUIDs - Useful for measuring deeper subcortical structures like the hippocampus -- as scalp EEG can't measure there - Abnormal Hippocampal replay of task order in Schizophrenia could underlie disorganisation and cognitive deficits in Schizophrenia [MRI: How Does it Work?] - Uses strong magnetic fields and radio waves - Strength of magnetic field measured in Tesla - 0.00005 Tesla = magnetic field of earth - Hydrogen atoms (protons) have a property called spin, which is detectable by MRI - The human body is \~70% water - MRI scans measure spatial distribution of water in object being imaged [Strength:] - High Spatial Resolution - No Ionising Radiation - Moderate Cost [Weaknesses:] - Low Temporal Resolution - Uses Magnetic Field - Loud Enclosed Environment, Some People Cannot Tolerate [Magnetic Resonance Imaging (MRI) Methods:] +-----------------------+-----------------------+-----------------------+ | Structural | Functional | Neurochemical | +=======================+=======================+=======================+ | Grey Matter -- 2 | Functional MRI: | MRS -- Magnetic | | Computer Programs: | | Resonance | | | - Task-based fMRI | Spectroscopy | | - SPM (Voxel Based | (e.g., Stroop) | | | Morphometry) | | - Measure Glutamate | | | - Resting State | and GABA | | - Freesurfer | fMRI | | | (Measures | | | | geometry of | | | | surfaces rather | | | | than just | | | | measuring volume) | | | | | | | | White Matter: | | | | | | | | - Diffusion Tensor | | | | Imaging (DTI) | | | +-----------------------+-----------------------+-----------------------+ [Structural MRI:] - Voxel Based Morphometry - Compare grey matter mass between subjects [DTI: Diffusion Tensor Imaging: ] - Examine "motorways" of brain - Main motorway is corpus callosum, connects left and right hemispheres - Alien hand syndrome caused by damage to corpus callosum - A person experiences their limbs acting seemingly on their own, without conscious control over the actions - Language-linked left hemisphere, which controls dominant right hand, no longer has direct control over right hemisphere which controls left hand - DTI measured movement of water - Diffusion restricted by tissue boundaries, membranes, etc., - Diffusion anisotropic in white matter - Most common DTI measure of white matter integrity is fractional anisotropy [Enigma Study of White Matter in Schizophrenia:] - Significant reductions in fractional anisotropy in schizophrenia patients were observed in almost all regions analysed (20/25) - Greatest effects in anterior corona radiata (d = 0.40 -- carry messages to/from body) and corpus callosum (d = 0.39) - Altered excitation/inhibition altered oscillatory activity in EEG - Ketamine models = NMDAR antagonists - NMDAR autoimmune encephalitis - Risk polymorphisms - Top 10 rare coding variants: - NMDAR: GRIN2A - AMPAR: GRIA3 Can measure: Glutamate, Glutamine, Combination [MRS: Magnetic Resonance Spectroscopy: ] - Can only measure neurochemicals if at high concentration on the brain - Can measure glutamate, and its metabolite glutamine - Cannot measure dopamine, serotonin etc., use PET for this - Measure for large voxel: e.g., 2cm x 2cm x 2cm region of interest - Glutamate levels are elevated in treatment non-responders [Anatomy of Language Functions:] Broca's Area: - Deals with expressive language - Inferior frontal gyrus Wernicke's Area: - Deals with language reception, comprehension - Posterior part of superior temporal gyrus In patients experiencing auditory hallucinations greater activation in: - Left inferior parietal lobule - Left hippocampus/parahippocampal region - Left superior temporal gyrus - Globus pallidum - Broca's convolution - Right anterior insula - Frontal operculum -