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Tremor, which is defined as an oscillatory and rhythmic movement of a body part, is the most common movement disorder worldwide. The most frequent tremor syndromes are tremor in Parkinson’s disease, essential tremor, and dystonic tremor syndromes, whereas Holmes tremor, orthostatic tremor, and palatal tremor are less common in clinical practice. The pathophysiology of tremor consists of enhanced oscillatory activity in brain circuits, which are ofen modulated by tremor-related afferent signals from the periphery. The cerebello-thalamo-cortical circuit and the basal ganglia play a key role in most neurologic tremor disorders, but with different roles in each disorder. Here we review the pathophysiology of tremor, focusing both on neuronal mechanisms that promote oscillations (automaticity and synchrony) and circuit-level mechanisms that drive and maintain pathologic oscillations.
The complexity of movement disorders poses challenges for clinical management and research. Functional imaging with PET or SPECT allows in-vivo assessment of the molecular underpinnings of movement disorders, and biomarkers can aid clinical decision making and understanding of pathophysiology, or determine patient eligibility and endpoints in clinical trials. Imaging targets traditionally include functional processes at the molecular level, typically neurotransmitter systems or brain metabolism, and more recently abnormal protein accumulation, a pathologic hallmark of neurodegenerative diseases. Functional neuroimaging provides complementary information to structural neuroimaging (e.g. anatomic MRI), as molecular/functional changes can present in the absence of, prior to, or alongside structural brain changes. Movement disorder specialists should be aware of the indications, advantages and limitations of molecular functional imaging. An overview is given of functional molecular imaging in movement disorders, covering methodologic background information, typical molecular changes in common movement disorders, and emerging topics with potential for greater future importance.
The clinical and pathologic hallmarks of Parkinson’s disease (PD) are motor parkinsonism due to underlying progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta accompanied by an accumulation of intracytoplasmic protein inclusions known as Lewy bodies and Lewy neurites. The diagnostic criteria/guidelines based on the UK Parkinson’s Disease Society Brain Bank clinical diagnostic criteria have guided clinicians and researchers in the diagnosis of PD for many decades. This chapter discusses whether this description represents our current understanding of PD, and why it is time to integrate new research findings and accommodate our definition and diagnostic criteria of PD, such as Parkinson-associated non-motor symptoms, genetics, biomarkers, imaging findings, or heterogeneity of phenotypes and underlying molecular mechanisms. In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson’s disease, which were designed specifically for use in research but also as a general guide to clinical diagnosis of PD. These criteria and some of their limitations are also discussed.
Despite depression being a leading cause of global disability, neuroimaging studies have struggled to identify replicable neural correlates of depression or explain limited variance. This challenge may, in part, stem from the intertwined state (current symptoms; variable) and trait (general propensity; stable) experiences of depression.
Here, we sought to disentangle state from trait experiences of depression by leveraging a longitudinal cohort and stratifying individuals into four groups: those in remission (‘trait depression group’), those with large longitudinal severity changes in depression symptomatology (‘state depression group’), and their respective matched control groups (total analytic n = 1030). We hypothesized that spatial network organization would be linked to trait depression due to its temporal stability, whereas functional connectivity between networks would be more sensitive to state-dependent depression symptoms due to its capacity to fluctuate.
We identified 15 large-scale probabilistic functional networks from resting-state fMRI data and performed group comparisons on the amplitude, connectivity, and spatial overlap between these networks, using matched control participants as reference. Our findings revealed higher amplitude in visual networks for the trait depression group at the time of remission, in contrast to controls. This observation may suggest altered visual processing in individuals predisposed to developing depression over time. No significant group differences were observed in any other network measures for the trait-control comparison, nor in any measures for the state-control comparison. These results underscore the overlooked contribution of visual networks to the psychopathology of depression and provide evidence for distinct neural correlates between state and trait experiences of depression.
Methodological approaches in social neuroscience have been rapidly evolving in recent years. Fueling these changes is the adoption of a variety of multivariate approaches that allow researchers to ask a wider and richer set of questions than was previously possible with standard univariate methods. In this chapter, we introduce several of the most popular multivariate methods and discuss how they can be used to advance our understanding of how social cognition and personality processes are represented in the brain. These methods have the potential to allow neuroscience measures to inform and advance theories in social and personality psychology more directly and are likely to become the dominant approaches in social neuroscience in the near future.
Both childhood adversity (CA) and first-episode psychosis (FEP) have been linked to alterations in cortical thickness (CT). The interactive effects between different types of CAs and FEP on CT remain understudied.
Methods
One-hundred sixteen individuals with FEP (mean age = 23.8 ± 6.9 years, 34% females, 80.2% non-affective FEP) and 98 healthy controls (HCs) (mean age = 24.4 ± 6.2 years, 43% females) reported the presence/absence of CA <17 years using an adapted version of the Childhood Experience of Care and Abuse (CECA.Q) and the Retrospective Bullying Questionnaire (RBQ) and underwent magnetic resonance imaging (MRI) scans. Correlation analyses were used to assess associations between brain maps of CA and FEP effects. General linear models (GLMs) were performed to assess the interaction effects of CA and FEP on CT.
Results
Eighty-three individuals with FEP and 83 HCs reported exposure to at least one CA. CT alterations in FEP were similar to those found in participants exposed to separation from parents, bullying, parental discord, household poverty, and sexual abuse (r = 0.50 to 0.25). Exposure to neglect (β = −0.24, 95% CI [−0.37 to −0.12], p = 0.016) and overall maltreatment (β = −0.13, 95% CI [−0.20 to −0.06], p = 0.043) were associated with cortical thinning in the right medial orbitofrontal region.
Conclusions
Cortical alterations in individuals with FEP are similar to those observed in the context of socio-environmental adversity. Neglect and maltreatment may contribute to CT reductions in FEP. Our findings provide new insights into the specific neurobiological effects of CA in early psychosis.
Portable MRI for neuroimaging research in remote field settings can reach populations previously excluded from research, including communities underrepresented in current brain neuroscience databases and marginalized in health care. However, research conducted far from a medical institution and potentially in populations facing barriers to health care access raises the question of how to manage incidental findings (IFs) that may warrant clinical workup. Researchers should not withhold information about IFs from historically excluded and underserved population when members consent to receive it, and instead should facilitate access to information and a pathway to clinical care.
Portable MRI (pMRI) technology, which promises to transform brain imaging research by facilitating scanning in new geographic areas and the participation of new, diverse populations, raises many ethical, legal, and societal issues (ELSI). To understand this emerging pMRI ELSI landscape, we surveyed expert stakeholder views on ELSI challenges and solutions associated with pMRI research.
The paucity of existing baseline data for understanding neurologic health and the effects of injury on people from Indigenous populations is causally related to the limited representation of communities in neuroimaging research to date. In this paper, we explore ways to change this trend in the context of portable MRI, where portability has opened up imaging to communities that have been neglected or inaccessible in the past. We discuss pathways to engage local leadership, foster the participation of communities for this unprecedented opportunity, and empower field-based researchers to bring the holistic worldview embraced by Indigenous communities to neuroimaging research.
Highly portable and accessible MRI technology will allow researchers to conduct field-based MRI research in community settings. Previous guidance for researchers working with fixed MRI does not address the novel ethical, legal, and societal issues (ELSI) of portable MRI (pMRI). Our interdisciplinary Working Group (WG) previously identified 15 core ELSI challenges associated with pMRI research and recommended solutions. In this article, we distill those detailed recommendations into a Portable MRI Research ELSI Checklist that offers practical operational guidance for researchers contemplating using this technology.
Summary: The aging of the population poses significant challenges in healthcare, necessitating innovative approaches. Advancements in brain imaging and artificial intelligence now allow for characterizing an individual’s state through their brain age,’’ derived from observable brain features. Exploring an individual’s biological age’’ rather than chronological age is becoming crucial to identify relevant clinical indicators and refine risk models for age-related diseases. However, traditional brain age measurement has limitations, focusing solely on brain structure assessment while neglecting functional efficiency.
Our study focuses on developing neurocognitive ages’’ specific to cognitive systems to enhance the precision of decline estimation. Leveraging international (NKI2, ADNI) and Canadian (CIMA- Q, COMPASS-ND) databases with neuroimaging and neuropsychological data from older adults [control subjects with no cognitive impairment (CON): n = 1811; people living with mild cognitive impairment (MCI): n = 1341; with Alzheimer’s disease (AD): n= 513], we predicted individual brain ages within groups. These estimations were enriched with neuropsychological data to generate specific neurocognitive ages. We used longitudinal statistical models to map evolutionary trajectories. Comparing the accuracy of neurocognitive ages to traditional brain ages involved statistical learning techniques and precision measures.
The results demonstrated that neurocognitive age enhances the prediction of individual brain and cognition change trajectories related to aging and dementia. This promising approach could strengthen diagnostic reliability, facilitate early detection of at-risk profiles, and contribute to the emergence of precision gerontology/geriatrics.
Being married may protect late-life cognition. Less is known about living arrangement among unmarried adults and mechanisms such as brain health (BH) and cognitive reserve (CR) across race and ethnicity or sex/gender. The current study examines (1) associations between marital status, BH, and CR among diverse older adults and (2) whether one’s living arrangement is linked to BH and CR among unmarried adults.
Method:
Cross-sectional data come from the Washington Heights-Inwood Columbia Aging Project (N = 778, 41% Hispanic, 33% non-Hispanic Black, 25% non-Hispanic White; 64% women). Magnetic resonance imaging (MRI) markers of BH included cortical thickness in Alzheimer’s disease signature regions and hippocampal, gray matter, and white matter hyperintensity volumes. CR was residual variance in an episodic memory composite after partialing out MRI markers. Exploratory analyses stratified by race and ethnicity and sex/gender and included potential mediators.
Results:
Marital status was associated with CR, but not BH. Compared to married individuals, those who were previously married (i.e., divorced, widowed, and separated) had lower CR than their married counterparts in the full sample, among White and Hispanic subgroups, and among women. Never married women also had lower CR than married women. These findings were independent of age, education, physical health, and household income. Among never married individuals, living with others was negatively linked to BH.
Conclusions:
Marriage may protect late-life cognition via CR. Findings also highlight differential effects across race and ethnicity and sex/gender. Marital status could be considered when assessing the risk of cognitive impairment during routine screenings.
Radiologic imaging has become integral in not only the detection and diagnosis of subdural hematoma (SDH) but also in guiding potential treatment options. This is especially true for chronic SDH, which has conventionally been managed via surgical drainage, but can now be treated with embolization of the middle meningeal artery (MMA). We review the imaging manifestations of SDH as a function of chronicity and standardized methods of measurement and identify the MMA and its clinically significant variant anatomy as it pertains to embolization planning. Equipped with a more comprehensive approach to characterizing SDH, the radiologist will be able to curate findings of greater utility to the clinician.
This chapter provides a cross-sectional overview of current neuroimaging techniques and signals used to investigate the processing of linguistically relevant speech units in the bilingual brain. These techniques are reviewed in the light of important contributions to the understanding of perceptual and production processes in different bilingual populations. The chapter is structured as follows. First, we discuss several non-invasive technologies that provide unique insights in the study of bilingual phonetics and phonology. This introductory section is followed by a brief review of the key brain regions and pathways that support the perception and production of speech units. Next, we discuss the neuromodulatory effects of different bilingual experiences on these brain regions from shorter to longer neural latencies and timescales. As we will show, bilingualism can significantly alter the time course, strength, and nature of the neural responses to speech, when compared with monolinguals.
Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.
Design:
We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).
Results:
At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.
Conclusions:
Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.
Bipolar disorder (BD) is a recurrent chronic disorder characterised by fluctuations in mood and energy disposition. Diseases could lead to degenerative alterations in brain structures such as corpus callosum (CC). Studies demonstrated that abnormalities in CC are associated with BD symptoms. The present study aims to analyse the CC of the patients with statistical shape analysis (SSA) and compare the findings with healthy controls.
Methods:
Forty-one BD patients and 41 healthy individuals in similar age groups, which included 23 female and 18 male subjects, participated in the study. CC was marked with landmarks on the mid-sagittal images of each individual. The mean ‘Procrustes’ point was calculated, and shape deformations were analysed with thin-plate spline analysis.
Results:
Significant differences were observed in the shape of CC between the two groups, where maximum CC deformation was observed in posterior region marks in BD patients. There was no significant difference between the CC area of the BD patients and controls.
Conclusions:
CC analysis conducted with SSA revealed significant differences between patients and healthy controls. The study findings emphasised the abnormal distribution of white matter in CC and the variable subregional nature of CC in BD patients. This study may enable the development of more targeted and effective treatment strategies by taking into account biological factors and understanding the differences in the brain regions of individuals with BD.
Functional MRI (fMRI) has proven valuable in presurgical planning for people with brain tumors. However, it is underutilized for patients with epilepsy, likely due to less data on its added clinical value in this population. We reviewed clinical fMRI referrals at the QEII Health Sciences Center (Halifax, Nova Scotia) to determine the impact of fMRI on surgical planning for patients with epilepsy. We focused on reasons for fMRI referrals, findings and clinical decisions based on fMRI findings, as well as postoperative cognitive outcomes.
Methods:
We conducted a retrospective chart review of patients who underwent fMRI between June 2015 and March 2021.
Results:
Language lateralization represented the primary indication for fMRI (100%), with 7.7% of patients also referred for motor and sensory mapping. Language dominance on the side of resection was observed in 12.8% of patients; in 20.5%, activation was adjacent to the proposed resection site. In 18% of patients, fMRI provided an indication for further invasive testing due to the risk of significant cognitive morbidity (e.g., anterograde amnesia). Further invasive testing was avoided based on fMRI findings in 69.2% of patients. Cognitive outcomes based on combined neuropsychological findings and fMRI-determined language dominance were variable.
Conclusion:
fMRI in epilepsy was most often required to identify hemispheric language dominance. Although fMRI-determined language dominance was not directly predictive of cognitive outcomes, it helped identify patients at low risk of catastrophic cognitive morbidity and those at high risk who required additional invasive testing.
Disease-modifying therapies (DMTs) for Alzheimer’s disease (AD) are emerging following successful clinical trials of therapies targeting amyloid beta (Aβ) protofibrils or plaques. Determining patient eligibility and monitoring treatment efficacy and adverse events, such as Aβ-related imaging abnormalities, necessitates imaging with MRI and PET. The Canadian Consortium on Neurodegeneration in Aging (CCNA) Imaging Workgroup aimed to synthesize evidence and provide recommendations on implementing imaging protocols for AD DMTs in Canada.
Methods:
The workgroup employed a Delphi process to develop these recommendations. Experts from radiology, neurology, biomedical engineering, nuclear medicine, MRI and medical physics were recruited. Surveys and meetings were conducted to achieve consensus on key issues, including protocol standardization, scanner strength, monitoring protocols based on risk profiles and optimal protocol lengths. Draft recommendations were refined through multiple iterations and expert discussions.
Results:
The recommendations emphasize standardized acquisition imaging protocols across manufacturers and scanner strengths to ensure consistency and reliability of clinical treatment decisions, tailored monitoring protocols based on DMTs’ safety and efficacy profiles, consistent monitoring regardless of perceived treatment efficacy and MRI screening on 1.5T or 3T scanners with adapted protocols. An optimal protocol length of 20–30 minutes was deemed feasible; specific sequences are suggested.
Conclusion:
The guidelines aim to enhance imaging data quality and consistency, facilitating better clinical decision-making and improving patient outcomes. Further research is needed to refine these protocols and address evolving challenges with new DMTs. It is recognized that administrative, financial and logistical capacity to deliver additional MRI and positron emission tomography scans require careful planning.