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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.
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.
Anorexia nervosa is a psychiatric disorder characterised by undernutrition, significantly low body weight and large, although possibly transient, reductions in brain structure. Advanced brain ageing tracks accelerated age-related changes in brain morphology that have been linked to psychopathology and adverse clinical outcomes.
Aim
The aim of the current case–control study was to characterise cross-sectional and longitudinal patterns of advanced brain age in acute anorexia nervosa and during the recovery process.
Method
Measures of grey- and white-matter-based brain age were obtained from T1-weighted magnetic resonance imaging scans of 129 acutely underweight female anorexia nervosa patients (of which 95 were assessed both at baseline and after approximately 3 months of nutritional therapy), 39 recovered patients and 167 healthy female controls, aged 12–23 years. The difference between chronological age and grey- or white-matter-based brain age was calculated to indicate brain-predicted age difference (BrainAGEGM and BrainAGEWM).
Results
Acute anorexia nervosa patients at baseline, but not recovered patients, showed a higher BrainAGEGM of 1.79 years (95% CI [1.45, 2.13]) compared to healthy controls. However, the difference was largely reduced for BrainAGEWM. After partial weight restoration, BrainAGEGM decreased substantially (beta = −1.69; CI [−1.93, −1.46]). BrainAGEs were unrelated to symptom severity or depression, but larger weight gain predicted larger normalisation of BrainAGEGM in the longitudinal patient sample (beta = −0.65; CI [−0.75, −0.54]).
Conclusions
Our findings suggest that in patients with anorexia nervosa, undernutrition is an important predictor of advanced grey-matter-based brain age, which itself might be transient in nature and largely undetectable after weight recovery.
Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a ‘genome-wide association study (GWAS) by subtraction,’ subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal ‘cognitive’ and ‘non-cognitive’ factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear.
Methods
Using data from up to 5517 youth (ages 9–11) of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and cognition, risk tolerance, decision-making & personality, substance initiation, psychopathology, and brain structure (e.g. volume, fractional anisotropy [FA]). Within-sibling analyses estimated whether observed genetic associations may be consistent with direct genetic effects.
Results
Both PGSs were associated with greater cognition and lower impulsivity, drive, and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk tolerance, increased odds of choosing delayed reward, and decreased likelihood of ADHD and bipolar disorder; the non-cognitive PGS was associated with lack of perseverance and reward responsiveness. Cognitive PGS were more strongly associated with larger regional cortical volumes; non-cognitive PGS were more strongly associated with higher FA. All associations were characterized by small effects.
Conclusions
While the small sizes of these associations suggest that they are not effective for prediction within individuals, cognitive and non-cognitive PGS show unique associations with phenotypes in childhood at the population level.
What are the psychological mechanisms of racial “dog whistles” in American politics? Literature on race priming in American politics argues when race is primed implicitly, racial biases influence political evaluations, but when race is made salient, individuals can use controlled processing to inhibit automatic biases and abide by egalitarian norms. However, the neural mechanisms underlying these processes have yet to be examined directly. In a 2 × 2 within-groups experiment using functional magnetic resonance imaging, we examine these neural mechanisms. We find brain areas associated with conflict detection, evaluative processing, and controlled processing are more active when race is primed explicitly rather than implicitly, as expected, although we do not find substantial brain activation associated with automatic responses to be more active during implicit than explicit primes. Results are discussed in terms of understanding how racial cues influence political evaluations while considering America’s ever-changing racial norms.