Incorporating priors for EEG source imaging and connectivity analysis.

Neuroimaging is a standard part of a primary progressive aphasia (PPA) diagnostic work-up and an important component of research investigating changes in the speech-language network in patients with PPA. In this paper, structural neuroimaging, including computed tomography (CT), magnetic resonance imaging (MRI), and diffusion tensor imaging (DTI), as well as functional neuroimaging, including single photon emission computed tomography (SPECT), positron emission tomography (PET), and functional MRI (fMRI), are discussed. Neuroimaging, in conjunction with meticulous clinical and neuropsychological evaluation, can increase diagnostic certainty for PPA subtyping and identification of underlying pathology, which is important for justification of potential pharmacological treatments, such as cholinesterase inhibitors. MRI and, more recently, DTI, have expanded our knowledge of structural brain changes in PPA, including gray matter abnormalities as well as alterations in neuronal tracts. SPECT and PET provide information regarding brain regional blood perfusion (SPECT) or metabolism (PET). Recently, thanks to PET ligands that bind to amyloid protein, it has become possible to diagnose or rule out Alzheimer pathology as a cause for PPA and tau imaging may be forthcoming. Finally, fMRI provides a unique window into brain-behavior relations for language as well as reorganization of the language network in disease. fMRI has also been used to gauge the effects of therapeutic interventions, including language treatment, and can be used for implementation of neuromodulatory mediations, such as repetitive transcranial magnetic stimulation (TMS).

Chapter 11 - Cingulate role in Tourette syndrome

Background Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and vascular and frontotemporal dementia (FTD), are characterized by progressive cognitive and motor decline. So, timely detection, especially early in the disease process, is crucial. Positron Emission Tomography (PET), Functional Magnetic Resonance Imaging (fMRI), and Diffusion Tensor Imaging (DTI) are advanced neuroimaging techniques that have shown promise for early diagnosis. Objective This review evaluates the diagnostic accuracy and clinical utility of PET, fMRI, and DTI in the early detection of neurodegenerative diseases. Methods A systematic search was conducted using PubMed, Google Scholar, and Cochrane Library for studies published between 2014 and 2024. Inclusion criteria focused on phase 2 and 3 clinical trials involving adult patients with AD, PD, and FTD. Studies were assessed for diagnostic accuracy, sensitivity, specificity, and identification of early biomarkers using PET, fMRI, and DTI. Data were extracted and analyzed from 14 selected studies. Results PET imaging with tracers like 18F‐flortaucipir provided visualization of amyloid and tau aggregates in AD and dopaminergic changes in PD. PET showed a strong association with amyloid and tau pathology in AD, with up to 95% diagnostic performance. Another useful technique in identifying early changes in the brain networks was resting‐state fMRI (rs‐fMRI), with a diagnostic accuracy of 80%–95%. DTI offered essential data on white matter connectivity and showed microstructural alterations that pointed to early neurodegenerative processes. Integrating these neuroimaging modalities with machine learning models further enhanced diagnostic accuracy. Conclusion PET, fMRI, and DTI are valuable tools for the early diagnosis of neurodegenerative diseases. These techniques can identify structural and functional changes in the brain before the onset of clinical signs. Integrating these imaging techniques with machine learning improves diagnostic outcomes. Further large‐scale studies with standardized methodologies are needed to validate these findings and implement these techniques in clinical practice.

Chapter 37 TMS in stroke

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research.

SY1.3. Probing the pathophysiology of movement disorders with transcranial magnetic stimulation

Background MRI performed with echo-planar imaging (EPI) sequences is sensitive to susceptibility artifacts in the presence of metallic objects, which presents a substantial barrier for performing functional MRI and diffusion tensor imaging (DTI) in patients with metallic orthodontic material and other head implants. Purpose To evaluate the ability to reduce susceptibility artifacts in healthy human participants wearing metallic orthodontic braces for two alternative approaches: T2-prepared functional MRI and diffusion-prepared DTI with three-dimensional fast gradient-echo readout. Materials and Methods In this prospective study conducted from February to September 2018, T2-prepared functional MRI and diffusion-prepared DTI were performed in healthy human participants. Removable dental braces with bonding trays were used so that MRI could be performed with braces and without braces in the same participants. Results were evaluated in regions with strong (EPI dropout regions for functional MRI and the inferior fronto-occipital fasciculus for DTI) and minimal (motor cortex for functional MRI and the posterior limb of internal capsule for DTI) susceptibility artifacts. Signal-to-noise ratio (SNR), contrast-to-noise ratio for functional MRI, apparent diffusion coefficient and fractional anisotropy for DTI, and degree of distortion (quantified with the Jaccard index, which measures the similarity of geometric shapes) were compared in regions with strong or minimal susceptibility effects between the current standard EPI sequences and the proposed alternatives by using paired t test. Results Six participants were evaluated (mean age ± standard deviation, 40 years ± 6; three women). In brain regions with strong susceptibility effects from the metallic braces, T2-prepared functional MRI showed significantly higher SNR (37.8 ± 2.4 vs 15.5 ± 5.3; P < .001) and contrast-to-noise ratio (0.83 ± 0.16 vs 0.29 ± 0.10; P < .001), whereas diffusion-prepared DTI showed higher SNR (5.8 ± 1.5 vs 3.8 ± 0.7; P = .03) than did conventional EPI methods. Apparent diffusion coefficient and fractional anisotropy were consistent with the literature. Geometric distortion was substantially reduced throughout the brain with the proposed methods (significantly higher Jaccard index, 0.95 ± 0.12 vs 0.81 ± 0.61; P < .001). Conclusion T2-prepared functional MRI and diffusion-prepared diffusion tensor imaging can acquire functional and diffusion MRI, respectively, in healthy human participants wearing metallic dental braces with less susceptibility artifacts and geometric distortion than with conventional echo-planar imaging. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Dietrich in this issue.

Contribution of transcranial magnetic stimulation to assessment of brain connectivity and networks

Stroke characteristics vary widely between individuals making it difficult to assess the value of stroke rehabilitation interventions. To eliminate inter-subject variability, this study used an N-of-1 randomized, controlled design to explore the efficacy of repetitive transcranial magnetic stimulation (rTMS) in one unique individual with pontine stroke. We hypothesized that five days of active 6-Hz primed, low-frequency rTMS to the contralesional primary motor area (M1), combined with finger movement tracking training, would accomplish greater gains in hand function than sham rTMS combined with tracking training. We assessed hand function (Box and Block test and finger tracking test), cortical activation (laterality index during functional magnetic resonance imaging), and cortical excitability (interhemispheric inhibition testing (IHI) with transcranial magnetic stimulation (TMS)). Diffusion tensor imaging (DTI) assessed the integrity of his corticospinal tracts at baseline. Results showed no improvement in the Box and Block or finger tracking tests, unreliable IHI findings, and no change in laterality index following active rTMS. DTI suggested truncation of the left corticospinal tract (CST) at the pons. His non-dexterous hand movements combined with no elicitable motor evoked potentials with TMS to ipsilesional M1 and his DTI findings lead us to speculate a reticulospinal mechanism for preserving his rudimentary paretic hand control. We conclude that rTMS combined with tracking training was not effective in the absence of CST pathways and that research is needed to confirm markers of reticulospinal function in humans as an alternative to defective CST function.

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) are important tools in cognitive and clinical neuroscience. Combined EEG–fMRI has been shown to help to characterise brain networks involved in epileptic activity, as well as in different sensory, motor and cognitive functions. A good understanding of the electrophysiological correlates of the blood oxygen level‐dependent (BOLD) signal is necessary to interpret fMRI maps, particularly when obtained in combination with EEG. We review the current understanding of electrophysiological–haemodynamic correlates, during different types of brain activity. We start by describing the basic mechanisms underlying EEG and BOLD signals and proceed by reviewing EEG‐informed fMRI studies using fMRI to map specific EEG phenomena over the entire brain (EEG–fMRI mapping), or exploring a range of EEG‐derived quantities to determine which best explain colocalised BOLD fluctuations (local EEG–fMRI coupling). While reviewing studies of different forms of brain activity (epileptic and nonepileptic spontaneous activity; cognitive, sensory and motor functions), a significant attention is given to epilepsy because the investigation of its haemodynamic correlates is the most common application of EEG‐informed fMRI. Our review is focused on EEG‐informed fMRI, an asymmetric approach of data integration. We give special attention to the invasiveness of electrophysiological measurements and the simultaneity of multimodal acquisitions because these methodological aspects determine the nature of the conclusions that can be drawn from EEG‐informed fMRI studies. We emphasise the advantages of, and need for, simultaneous intracranial EEG–fMRI studies in humans, which recently became available and hold great potential to improve our understanding of the electrophysiological correlates of BOLD fluctuations. Hum Brain Mapp, 36:391–414, 2015. © 2014 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Psychiatry is a medical field without distinct biomarkers for diagnosis; thus, psychiatrists evaluate and diagnose based on interviews with patients and their relatives. On the other hand, during the past 30 years, there have been huge advancements in medical imaging technologies, which have made it possible to visualize the living human brain. Current neuroimaging methods provide living brain information from two aspects: structural and functional. The structural data can be measured by magnetic resonance imaging (MRI), which is widely distributed in hospitals and research organizations. Regional gray and white matter volumes have been measured in various types of mental illness and sulcogyral patterns are the unique index of brain structure. In this issue of Psychiatry and Clinical Neurosciences, the study by Yoshimi et al. (261–268) addresses the interesting association between the sulcogyral pattern of the orbitofrontal cortex in schizophrenia and NRG1 allele frequency, which is closely related to neurodevelopment. Diffusion tensor imaging provides white matter microstructure and tractography. Disruption of anatomical connectivity has been reported in schizophrenia, depression and autism. MRI also provides significant information about the functional aspects of the living brain. Event-related functional MRI (fMRI) is a method for detecting regional brain activity response to the cognitive task. The brain activity can be measured as regional blood flow change based on the blood oxygenation level dependent (BOLD) hemodynamic response to neural activity. Resting-state fMRI measures low-frequency BOLD fluctuations in different brain regions and synchronous activities between regions can be analyzed as functionally connected regions. Proton magnetic resonance spectroscopy measures various chemical components, such as N-acetylaspartate compounds, choline, and creatine in the brain. The study by Yang et al. (269–277) in the current issue addresses the increased left dorsolateral prefrontal cortex choline and creatine levels in depressed adolescents. Using a higher magnetic field (3-T or 7-T), multiple small signals can be quantified, such as glutamate, glutamine and GABA. Regarding the detection of the molecule in the living brain, positron emission tomography (PET) is the most sensitive system to measure nanomolar level concentration. The small molecule compound that binds to the molecular component of the brain like neurotransmitter receptors is labeled with positron-emitting radioisotope, such as carbon 11. Various molecular targets can be visualized by preparing the target-specific radiolabeled compound. Using PET, we can measure various neurotransmitter receptors and transporters, enzyme activity, such as acetylcholine esterase, and abnormal proteins, such as amyloid beta and tau. The amount of dopamine released at the striatum can be measured using C-11 raclopride. Although each modality has a specific in vivo signal to investigate brain activity, recent studies in neuroscience employ multimodal and model-based strategies. For example, to investigate the default state of the neural and molecular mechanism that generates positive self-evaluation, functional connectivity analyses of resting-state fMRI and dopamine neural transmission analyses of PET suggest that striatal dopaminergic activity attenuates functional connectivity between the anterior cingulate and striatum, leading to reduced control over positive self-evaluation.1 This combination of different kinds of neuroimaging methods demonstrates the molecular mechanism of the functional neuro-network of human behaviors and psychiatric symptoms. Furthermore, recent advancement of computational modeling provides new approaches to understanding the brain system using neuroimaging data. Based on the reinforcement learning or Bayesian model frameworks, the various symptoms of mental illness are mathematically modeled with neuroimaging data.2

Background. Repetitive transcranial magnetic stimulation (rTMS) modulates central neuropathic pain in some patients after stroke, but the mechanisms of action are uncertain. Objective. The authors used diffusion tensor imaging (DTI) and functional MRI (fMRI) to evaluate the integrity of the thalamocortical tract (TCT) and the activation pattern of the pain network in 22 patients with poststroke central pain. Methods. Each patient underwent daily 10-Hz rTMS sessions for 1000 pulses on 5 consecutive days over the hotspot for the first dorsal interosseus muscle. Pain severity was monitored using the Visual Analogue Scale (VAS). Mood was assessed by the Hamilton Depression Rating Scale. Results. Clinical data from all participants along with the DTI and fMRI findings from 10 patients were analyzed. VAS scores decreased significantly, if modestly, following administration of rTMS in 14 responders, which lasted for 2 weeks after the intervention. Regression analysis showed a significant correlation between less initial depression and higher antalgic effect of rTMS. Integrity of the superior TCT in the ipsilesional hemisphere showed significant correlation with change of VAS score after rTMS. fMRI showed significantly decreased activity in the secondary somatosensory cortex, insula, prefrontal cortex, and putamen in rTMS responders, whereas no change was noted in nonresponders. Conclusion. Mood may affect the modest antinociceptive effects of rTMS that we found, which may be mediated by the superior TCT through modulation of a distributed pain network.

Improvement of auditory hallucinations and reduction of primary auditory area's activation following TMS

Neuronal Dysfunction and Schizophrenia Symptoms

This study demonstrates normal white matter structures of the supratentorial system revealed by diffusion tensor imaging. Their anatomic connections and functional significance are discussed in the context of the lesion-induced deficits reported in the literature, which may not fully represent the lesion-induced effects on the white matter function and may not be entirely specific to the tract discussed. Nevertheless, understanding the most common effects of lesions on the functional connectivity provides a framework that we can use in advanced neuroimaging studies, like diffusion tensor imaging, functional magnetic resonance imaging, and positron emission tomography, and in our daily clinical practice.