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Positron emission tomography (PET) is the most sensitive technique for imaging of human physiology and molecular pathways in vivo. Here we provide an overview of PET instrumentation and modelling and illustrate how different PET techniques can be used for mapping the molecular basis of the human emotion circuit. We first cover the principles of PET imaging and the most common imaging targets, modelling methods, and experimental designs in brain PET. We then describe how metabolic studies and neuroreceptor mapping of the endogenous dopamine, opioid, serotonin, and cannabinoid systems have contributed to our understanding of the emotional brain. Finally, we review the recent state-of-the art developments in PET-fMRI and total-body PET, and discuss how these techniques can transform the landscape of systems-level biological imaging of the emotion circuits across the brain and periphery.
Social rewards (e.g. smiles) powerfully shape human behavior, starting from early childhood. Yet, the neural architecture that enables differential processing of social and nonsocial rewards remains largely unknown. Few previous studies that directly compared social vs nonsocial stimuli have used stimuli that have low ecological validity or are not matched on low-level stimulus parameters – limiting the scope of inference. To address this gap in knowledge, social and nonsocial reward images taken from the real world were matched on valence, arousal, and key low-level stimulus properties and presented to 37 adults in a functional magnetic resonance imaging (fMRI) study. Individual self-reported preference for social images was associated with the functional connectivity between the left anterior insula (LAI) and medial orbitofrontal cortex (mOFC), as well as that between the left Fusiform Gyrus (LFG) and the Anterior Cingulate Cortex (ACC). Autistic traits negatively modulated LAI – mOFC connectivity and LFG – ACC connectivity. Reduced functional connectivity between these regions may contribute to the lower social reward responsivity in individuals with high autistic traits, as also noted from their lower valence ratings to social rewards. This study provides evidence for a new experimental paradigm to test social reward processing at a behavioral and neural level, which can contribute to potential transdiagnostic biomarkers for social cognitive processes.
In addition to the international classification systems such as DSM-5 and ICD-11 discussed in earlier chapters of this book, we will now introduce three further diagnostic steps essential for diagnosing catatonia: (1) clinical rating scales, (2) the lorazepam challenge test, and (3) laboratory and neuroimaging work-up. This chapter will first present the widely used clinical rating scales for assessing catatonia, highlighting their advantages, limitations, and their role in scientific studies. While these scales are valuable tools, it is important to emphasize that clinical judgment remains crucial, as some catatonic symptoms may not be fully captured by these scales. Following this, we will explore the lorazepam challenge test, evaluating its diagnostic utility in light of current evidence. Lastly, the chapter will discuss the importance of laboratory and neuroimaging work-ups, including blood tests, lumbar puncture to examine cerebrospinal fluid, electroencephalogram, and magnetic resonance imaging, for both diagnosing catatonia and guiding therapeutic decisions.
Over the past three decades, catatonia research has experienced a remarkable renaissance, driven by the application of diverse methodologies and conceptual frameworks. This renewed interest has significantly reshaped our understanding of catatonia, a complex syndrome with multifactorial origins spanning epidemiology, historical context, phenomenology, genetics, immunology, and neurobiology. These advancements have offered a more comprehensive and nuanced perspective, culminating in the recognition of catatonia as a distinct diagnosis in the ICD-11 – a landmark development that underscores its clinical and scientific relevance. Despite these strides, several unresolved issues remain that require future research. Bridging these gaps is crucial not only to enhance our understanding of catatonia but also to identify the most effective treatments and uncover the mechanisms underlying their efficacy. Such advancements hold the promise of developing improved diagnostic markers and tailored therapeutic strategies, offering significant benefits to patients affected by this challenging condition. In this chapter, we explore the profound implications of catatonia research, spanning its impact on clinical psychiatry and neuroscience, as well as its broader contributions to our understanding of the intricate relationship between the brain and mind.
The macro-social and environmental conditions in which people live, such as the level of a country’s development or inequality, are associated with brain-related disorders. However, the relationship between these systemic environmental factors and the brain remains unclear. We aimed to determine the association between the level of development and inequality of a country and the brain structure of healthy adults.
Methods
We conducted a cross-sectional study pooling brain imaging (T1-based) data from 145 magnetic resonance imaging (MRI) studies in 7,962 healthy adults (4,110 women) in 29 different countries. We used a meta-regression approach to relate the brain structure to the country’s level of development and inequality.
Results
Higher human development was consistently associated with larger hippocampi and more expanded global cortical surface area, particularly in frontal areas. Increased inequality was most consistently associated with smaller hippocampal volume and thinner cortical thickness across the brain.
Conclusions
Our results suggest that the macro-economic conditions of a country are reflected in its inhabitants’ brains and may explain the different incidence of brain disorders across the world. The observed variability of brain structure in health across countries should be considered when developing tools in the field of personalized or precision medicine that are intended to be used across the world.
This chapter describes the many methods of Cognitive Neuroscience that are revealing the neural processes underlying complex cognitive processes in the brain. The benefits and limitations of each method are discussed, highlighting how there is no single “best” method and how the choice of method in any experiment should be motivated by the hypothesis being evaluated. Neuropsychology provides novel insights into the neural bases of cognitive processes but is limited because it relies on naturally occurring lesions. Neuroimaging methods (fMRI, PET, fNIRS) provide excellent spatial resolution but cannot assess the temporal order of neural activity across regions. Electroencephalography (EEG) and magnetoencephalography (MEG) can track neural activity in real time, but their spatial precision is limited because they are recorded from outside the head. Neurostimulation methods (TMS, tDCS, tACS) can uniquely assess causality by testing if, and when, a brain area is necessary for a particular function. Methods using non-human animals (e.g., single-unit recordings) can provide the highest levels of spatial and temporal precision, but they are limited to mental processes that the non-human animals can be trained to do. This chapter ends with a comparison of methods that includes portability, spatial precision, and temporal resolution.
We discuss the case of a postpartum patient that develops posterior reversible encephalopathy syndrome (PRES) as characterized by clinical and neuro-radiological findings. It is described as an acute or subacute syndrome that presents with elevated blood pressure and symptoms of headache, altered mental status, seizures, and vision changes. Diagnosis of PRES is made with neuroimaging, with magnetic resonance imaging being the preferred modality. Pathognomonic imaging includes findings of posterior encephalopathy. There is a strong correlation of PRES in patients with preeclampsia and eclampsia. The syndrome can be reversed with timely and aggressive control of symptoms and underlying causes, which in this case included blood pressure control as well as seizure prophylaxis.
The rising incidence of neurodegenerative diseases in an ageing global population has shifted research focus towards modifiable risk factors, such as diet. Despite potential links between dietary patterns and brain health, inconsistencies in neuroimaging outcomes underscore a gap in understanding how diet impacts brain ageing. This study explores the relationship between three dietary patterns – Mediterranean, Dietary Approaches to Stop Hypertension (DASH) and Mediterranean-DASH Intervention for Neurodegenerative Delay – and cognitive outcomes as well as brain connectivity. The study aimed to assess the association of these diets with brain structure and cognitive function, involving a middle-aged healthy group and an older cohort with subjective cognitive decline. The study included cognitive assessments and diffusion-weighted MRI data to analyse white matter microstructural integrity. Participants comprised fifty-five older individuals with subjective cognitive decline (54·5 % female, mean age = 64) and fifty-two healthy middle-aged individuals (48·1 % female, mean age = 53). Age inversely correlated with certain cognitive functions and global brain metrics, across both cohorts. Adherence to the Mediterranean, DASH and Mediterranean-DASH Intervention for Neurodegenerative Delay diets showed no significant cognitive or global brain metric improvements after adjusting for covariates (age, education, BMI). Network-based statistics analysis revealed differences in brain subnetworks based on DASH diet adherence levels in the subjective cognitive decline cohort. In the healthy cohort, lower white matter connectivity was associated with reduced adherence to Mediterranean-DASH Intervention for Neurodegenerative Delay and DASH diets. Ultimately, the study found no strong evidence connecting dietary patterns to cognitive or brain connectivity outcomes. Future research should focus on longitudinal studies and refine dietary assessments.
The choroid plexus produces cerebrospinal fluid, which is crucial for glymphatic system function. Evidence suggests that changes in the volume of the choroid plexus may be associated with glymphatic system function. Therefore, this study aimed to investigate alterations in choroid plexus volume in patients with migraines compared with healthy controls.
Methods:
We enrolled 59 patients with migraines (39 and 20 with episodic and chronic migraines, respectively) and 61 healthy controls. All participants underwent brain magnetic resonance imaging, including three-dimensional T1-weighted imaging. We analyzed and compared choroid plexus volumes between patients with episodic migraines, those with chronic migraines and healthy controls. Additionally, we evaluated the association between choroid plexus volume and the clinical characteristics of patients with migraine.
Results:
The choroid plexus volume in patients with chronic migraines was higher than that in healthy controls (2.018 vs. 1.698%, p = 0.002) and patients with episodic migraines (2.018 vs. 1.680%, p = 0.010). However, no differences were observed in choroid plexus volumes between patients with episodic migraine and healthy controls. Choroid plexus volume was positively correlated with age in patients with migraines (r = 0.301, p = 0.020) and in healthy controls (r = 0.382, p = 0.002).
Conclusion:
We demonstrated significant enlargement of the choroid plexus in patients with chronic migraine compared with healthy controls and those with episodic migraine. This finding suggests that chronic migraine may be associated with glymphatic system dysfunction.
Prior studies suggest that childhood maltreatment is associated with altered hippocampal volume. However, longitudinal studies are currently scarce, making it difficult to determine how alterations in hippocampal volume evolve over time. The current study examined the relationship between childhood maltreatment and hippocampal volumetric development across childhood and adolescence in a community sample.
Methods
In this longitudinal study, a community sample of 795 participants underwent brain magnetic resonance imaging (MRI) in three waves spanning ages 6–21 years. Childhood maltreatment was assessed using parent-report and children´s self-report at baseline (6–12 years old). Mixed models were used to examine the relationship between childhood maltreatment and hippocampal volume across time.
Results
The quadratic term of age was significantly associated with both right and left hippocampal volume development. High exposure to childhood maltreatment was associated with reduced offset of right hippocampal volume and persistent reduced volume throughout adolescence.
Critically, the relationship between childhood maltreatment and reduced right hippocampal volume remained significant after adjusting for the presence of any depressive disorder during late childhood and adolescence and hippocampal volume polygenic risk scores. Time-by-CM and Sex-by-CM interactions were not statistically significant.
Conclusions
The present study showed that childhood maltreatment is associated with persistent reduction of hippocampal volume in children and adolescents, even after adjusting for the presence of major depressive disorder and genetic determinants of hippocampal structure.
Reading difficulties (RD) frequently co-occur with attention-deficit/hyperactivity disorder (ADHD), and children with both RD + ADHD often demonstrate greater challenges in reading and executive functions (EF) than those with RD-only.
Methods:
This study examined the effect of a 4-week EF-based reading intervention on behavioral and neurobiological correlates of EF among 8–12 y.o. English-speaking children with RD + ADHD (n = 19), RD-only (n = 18), and typically developing children (n = 18). Behavioral and resting-state fMRI data were collected from all participants before and after 4 weeks of the EF-based reading computerized program. Group (RD + ADHD, RD-only, typical readers) x Test (pre- and post-intervention) repeated measures ANOVAs were conducted for reading, EF, and brain functional connectivity (FC) measures.
Results:
Across groups, reading (fluency, comprehension) and EF (inhibition, speed of processing) behavioral performance improved following the intervention. Exploratory subgroup comparisons revealed that children with RD + ADHD, but not RD-only, showed significant gains in reading comprehension, whereas inhibition improved in both RD groups, but not among typical readers. Furthermore, across groups, FC between the frontoparietal (FP) and cingulo-opercular (CO) networks decreased following the intervention. Exploratory subgroup comparisons revealed that children with RD + ADHD, but not RD-only, showed a significant decrease in FC of FP-CO and FP-dorsal attention network.
Conclusions:
These results support the differential response to an EF-based reading intervention of children with RD with and without comorbid ADHD at brain and behavioral levels.
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.
To compare structural alterations in the brains of Meige syndrome (MS) patients with those of healthy controls (HCs) by using surface-based morphometry (SBM) and compare structural differences between the brains of MS patients with sleep disorders and those of MS patients without sleep disorders.
Methods:
We investigated cortical surface parameters in 42 MS patients and 30 HCs. T1-weighted images were acquired and processed using CAT12 to perform vertexwise between-group comparisons of cortical thickness, gyrification, cortical complexity and sulcus depth with validated quality control protocols. We also performed SBM to analyze data from 19 patients with sleep disorders and 23 patients without sleep disorders.
Results:
Compared with HCs, MS patients had differences in large clusters of cortical regions, especially in postcentral, precentral, superior frontal and paracentral thickness. Differences were also observed in the parietal and occipital areas. Among MS patients with and without sleep disorders, altered cortical complexity and sulcal depth were observed.
Conclusions:
This study strongly suggested that MS patients have cortical structural abnormalities compared with HCs, thus elucidating the underlying pathophysiology of motor and nonmotor symptoms in MS patients.
The introduction of portable MRI (pMRI) has the potential to directly impact dementia research and ultimately clinical care. In this paper, we explore two ethical challenges facing the introduction of pMRI in dementia research. The first is the need to ensure that pMRI enhances rather than undermines efforts aimed at improving ethnoracial representation in dementia research. The second is the need to implement pMRI in dementia research in a dementia-friendly way that attends to the social context and lived experience of people with dementia.
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.
The primary objective of this study was to evaluate the feasibility and clinical impact of utilizing low-field portable MRI in a remote setting in Canada.
Methods:
This was a single-site prospective cohort study. An ultra-low-field (0.064 T) portable MRI was installed in Weeneebayko General Hospital, Moose Factory, Ontario. Adults presenting with any indication for neuroimaging between November 2021 and June 2023 were eligible for study inclusion. Clinical presentation, indication for imaging,and radiology report turnaround time were recorded. Images were evaluated for diagnostic quality, and radiology reports were analyzed to determine the diagnostic utility of ultra-low-field MRI.
Results:
An ultra-low-field portable MRI was successfully installed in a remote Canadian location. Fifty patients received a portable MRI scan. Comments on suboptimal image quality were made for 12 (24%) of the portable MRI examinations; however, only 2 (4%) of these were deemed nondiagnostic requiring conventional imaging for further evaluation. Clinically significant pathology was identified in 5 (10%) of the examinations.
Conclusion:
This first-of-its-kind study demonstrates the application of ultra-low-field portable MRI in a remote setting in Canada is feasible and offers clinical information that may help triage which patients require transfer to a center with conventional high-field MRI availability.