David Zald

Vanderbilt University | Vander Bilt · Department of Psychology and Psychiatry

Limbic and motor integration is enabled by a mesial temporal to motor cortex network. Parkinson's disease (PD) is characterized by a loss of dorsal striatal dopamine but relative preservation of mesolimbic dopamine early in disease, along with changes to motor action control. Here, we studied 47 patients with PD using the Simon conflict task and [1...

Objective: Antisocial behaviors are common and problematic among patients with behavioral variant frontotemporal dementia (bvFTD). In the present study, the investigators aimed to validate an informant-based questionnaire developed to measure the extent and severity of antisocial behaviors among patients with dementia. Methods: The Social Behavi...

Historically, researchers have proposed higher-order factors to explicate the structure of psychopathology, including Externalizing, Internalizing, Fear, Distress, Thought Disorder, and a general factor. Despite extensive research in this domain, the underlying structure of psychopathology remains unresolved. Here, we examine several issues in adju...

Language comprehension requires the rapid retrieval and integration of contextually-appropriate concepts ("semantic cognition"). Current neurobiological models of semantic cognition are limited by the spatial and temporal restrictions of single modality neuroimaging and lesion approaches. This is a major impediment given the rapid sequence of proce...

Historically, researchers have proposed higher-order factors to explicate the structure of psychopathology, including Externalizing, Internalizing, Fear, Distress, Thought Disorder, and a general factor. Despite extensive research in this domain, the underlying structure of psychopathology remains unresolved. Herein, we examine several issues in ad...

Objective: The causes of substance use disorders (SUDs) are largely unknown and the effectiveness of their treatments is limited. One crucial impediment to research and treatment progress surrounds how SUDs are classified and diagnosed. Given the substantial heterogeneity among individuals diagnosed with a given SUD (e.g., alcohol use disorder [AU...

Using a neurometric approach, we identify and validate a neural signature of reward encoded in a distributed pattern of brain activity using data collected from 21 different studies (N = 2,691). Our model can discriminate between receiving rewards from punishments in completely independent data with 99% accuracy and includes weights located in regi...

A robust medical image computing infrastructure must host massive multimodal archives, perform extensive analysis pipelines, and execute scalable job management. An emerging data format standard, the Brain Imaging Data Structure (BIDS), introduces complexities for interfacing with XNAT archives. Moreover, workflow integration is combinatorically pr...

Objective: The causes of substance use disorders (SUDs) are largely unknown and the effectiveness of their treatments is limited. One crucial impediment to research and treatment progress surrounds how SUDs are classified and diagnosed. Given the substantial heterogeneity among individuals diagnosed with a given SUD (e.g., alcohol use disorder), id...

Reports an error in "Emotional distractor images disrupt target processing in a graded manner" by Jonathan M. Keefe and David H. Zald (Emotion, Advanced Online Publication, Aug 27, 2020, np). In the article "Emotional Distractor Images Disrupt Target Processing in a Graded Manner" by Jonathan M. Keefe and David H. Zald (Emotion, advance online publ...

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a quantitative nosological system that addresses shortcomings of traditional mental disorder diagnoses, including arbitrary boundaries between psychopathology and normality, frequent disorder co-occurrence, substantial heterogeneity within disorders, and diagnostic unreliability over time and...

Although theoretical models suggest that an attentional bias for threat contributes to the development of post-traumatic stress disorder (PTSD) symptoms, this bias has not been consistently observed in the literature. In the present study, trauma exposed veterans (N = 114) performed an emotional attentional blink task in which task-irrelevant comba...

Impulsive-compulsive behaviors manifest in a substantial proportion of persons with Parkinson disease. Reduced ventral striatum dopamine receptor availability, and increased dopamine release is noted in patients with these symptoms. Prior studies of impulsivity suggest that midbrain D2 autoreceptors regulate striatal dopamine release in a feedback...

The stop-signal task is a well-established assessment of response inhibition, and in humans, proficiency is linked to dorsal striatum D2 receptor availability. Parkinson's disease (PD) is characterized by changes to efficiency of response inhibition. Here, we studied 17 PD patients (6 female and 11 male) using the stop-signal paradigm in a single-b...

People regularly give in to daily temptations in spite of conflict with personal goals. To test hypotheses about neuropharmacological influences on self-control, we used positron emission tomography to measure dopamine D2-like receptors (D2R) and experience sampling surveys to naturalistically track daily desires outside the laboratory in everyday...

Deficits in cognition, reward processing, and motor function are clinical features relevant to both aging and depression. Individuals with late-life depression often show impairment across these domains, all of which are moderated by the functioning of dopaminergic circuits. As dopaminergic function declines with normal aging and increased inflamma...

Brain atlases have proven to be valuable neuroscience tools for localizing regions of interest and performing statistical inferences on populations. Although many human brain atlases exist, most do not contain information about white matter structures, often neglecting them completely or labelling all white matter as a single homogenous substrate....

Humans possess a highly adaptive ability to draw inferences about the world by recognizing meaningful links between stimuli and events: making contingency judgements. We describe a systematic bias in contingency judgements that we label the negative contingency illusion in which individuals falsely judge a cue to be protective against an outcome. W...

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical effort to address limitations of traditional mental disorder diagnoses. These include arbitrary boundaries between disorder and normality, disorder co‐occurrence in the modal case, heterogeneity of presentation within dis­orders, and instability of diagnosis within patients. This...

Substantial evidence implicates the amygdala and related structures in the processing of negative emotions. Furthermore, neuroimaging evidence suggests that variations in amygdala volumes are related to trait-like individual differences in neuroticism/negative emotionality, although many questions remain about the nature of such associations. We co...

There is an ongoing revolution in psychology and psychiatry that will likely change how we conceptualize, study and treat psychological problems.­ Many theorists now support viewing psychopathology as consisting of continuous dimensions rather than discrete diagnostic categories. Indeed, recent papers have proposed comprehensive taxonomies of psych...

Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is ge...

Sluggish cognitive tempo (SCT) is characterized by behavioral symptoms reflecting slowness and lethargy (e.g., sluggishness, appearing sleepy) and inconsistent alertness/mental confusion (e.g., daydreaming, fogginess). SCT is substantially correlated with the inattentive symptoms of attention-deficit/hyperactivity disorder (ADHD) and may be part of...

The emotional attentional blink (EAB), also referred to as emotion-induced blindness, refers to a transient impairment in the ability to discriminate a single target when it is presented closely in time to an emotional distractor. Although the EAB has typically been characterized as representing a complete loss of target information due to attentio...

Diffusion magnetic resonance images may suffer from geometric distortions due to susceptibility induced off resonance fields, which cause geometric mismatch with anatomical images and ultimately affect subsequent quantification of microstructural or connectivity indices. State-of-the art diffusion distortion correction methods typically require dat...

Brain atlases have proven to be valuable neuroscience tools for localizing regions of interest and performing statistical inferences on populations. Although many human brain atlases exist, most do not contain information about white matter structures, often neglecting them completely or labelling all white matter as a single homogenous substrate....

The Hierarchical Taxonomy of Psychopathology (HiTOP) is a scientific effort to address shortcomings of traditional mental disorder diagnoses, which suffer from arbitrary boundaries between psychopathology and normality, frequent disorder co‐occurrence, heterogeneity within disorders, and diagnostic instability. This paper synthesizes evidence on th...

Predictive associations were estimated between socioemotional dispositions measured at 10–17 years using the Child and Adolescent Dispositions Scale (CADS) and future individual differences in white matter microstructure measured at 22–31 years of age. Participants were 410 twins (48.3% monozygotic) selected for later neuroimaging by oversampling o...

Objective Impulsive decision‐making is characterized by actions taken without considering consequences. Patients with Parkinson's disease (PD) who receive dopaminergic treatment, especially dopamine agonists, are at risk of developing impulsive–compulsive behaviors (ICBs). We assessed impulse‐related changes across a large heterogeneous PD populati...

Older adults report experiencing improved emotional health, such as more intense positive affect and less intense negative affect. However, there are mixed findings on whether older adults are better at regulating emotion-a hallmark feature of emotional health-and most research is based on laboratory studies that may not capture how people regulate...

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical structural model of psychological symptoms formulated to improve the reliability and validity of clinical assessment. Neurobiology can inform assessments of early risk and intervention strategies, and the HiTOP model has greater potential to interface with neurobiological measures...

Genetic discovery in psychiatry and clinical psychology is hindered by suboptimal phenotypic definitions. We argue that the hierarchical, dimensional, and data-driven classification system proposed by the Hierarchical Taxonomy of Psychopathology (HiTOP) consortium provides a more effective approach to identifying genes that underlie mental disorder...

Diffusion magnetic resonance images may suffer from geometric distortions due to susceptibility induced off resonance fields, which cause geometric mismatch with anatomical images and ultimately affect subsequent quantification of microstructural or connectivity indices. State-of-the art diffusion distortion correction methods typically require dat...

The process by which the value of delayed rewards is discounted varies from person to person. It has been suggested that these individual differences in subjective valuation of delayed rewards are supported by mesolimbic dopamine D2-like receptors (D2Rs) in the ventral striatum. However, no study to date has documented an association between direct...

The dentate nucleus (DN) is a gray matter structure deep in the cerebellum involved in motor coordination, sensory input integration, executive planning, language, and visuospatial function. The DN is an emerging biomarker of disease, informing studies that advance pathophysiologic understanding of neurodegenerative and related disorders. The main...

The evidence that dopamine function mediates the association between aging and cognition is one of the most cited findings in the cognitive neuroscience of aging. However, few and relatively small studies have directly examined these associations. Here we examined correlations among adult age, dopamine D2-like receptor (D2R) availability, and cogni...

We present cortical surface parcellation using spherical deep convolutional neural networks. Traditional multi-atlas cortical surface parcellation requires inter-subject surface registration using geometric features with slow processing speed on a single subject (2–3 h). Moreover, even optimal surface registration does not necessarily produce optim...

The process by which the value of delayed rewards is discounted varies from person to person. It has been suggested that these individual differences in subjective valuation of delayed rewards are supported by mesolimbic dopamine D2-like receptors (D2Rs) in the ventral striatum. However, no study to date has documented an association between direct...

Older adults report experiencing improved emotional health, such as higher levels of positive affect and lower levels of negative affect. However, there are mixed findings on whether older adults are better at regulating emotion—a hallmark feature of emotional health—and most research is based on laboratory studies that may not capture how people r...

We present cortical surface parcellation using spherical deep convolutional neural networks. Traditional multi-atlas cortical surface parcellation requires inter-subject surface registration using geometric features with high processing time on a single subject (2-3 hours). Moreover, even optimal surface registration does not necessarily produce op...

We previously hypothesized that the ubiquitous, but patterned correlations among all dimensions of psychopathology reflect a hierarchy of progressively more nonspecific causal influences, with a general factor of psychopathology-also dubbed the p factor-reflecting the most transdiagnostic causal influences. We further hypothesized that the general...

Parkinson's disease (PD) is characterized by dysfunction in frontal cortical and striatal networks that regulate action control. We investigated the pharmacological effect of dopamine agonist replacement therapy on frontal cortical activity and motor inhibition. Using Arterial Spin Labeling MRI, we examined 26 PD patients in the off- and on-dopamin...

Evidence suggests that Disgust Sensitivity (DS) is a personality trait that may confer risk for the development of some anxiety-related disorders. To examine the origins of this trait we administered the DS subscale of the Disgust Propensity and Sensitivity Scale-Revised to 90 monozygotic and 90 dizygotic twin pairs, of which 55% were women. The DS...

Theories of adult brain development, based on neuropsychological test results and structural neuroimaging, suggest differential rates of age‐related change in function across cortical and subcortical sub‐regions. However, it remains unclear if these trends also extend to the aging dopamine system. Here we examined cross‐sectional adult age differen...

For more than a century, research on psychopathology has focused on categorical diagnoses. Although this work has produced major discoveries, growing evidence points to the superiority of a dimensional approach to the science of mental illness. Here we outline one such dimensional system-the Hierarchical Taxonomy of Psychopathology (HiTOP)-that is...

Obsessive compulsive disorder (OCD) is associated with altered processing in brain regions involved in conflict resolution. However, limited research has examined the extent to which conflict from emotional distracters characterizes OCD such that responsiveness to task-irrelevant emotional stimuli is altered compared to controls. In the present stu...

Rationale Sex differences in the dopaminergic response to psychostimulants could have implications for drug abuse risk and other psychopathology involving the dopamine system, but human data are limited and mixed. Objectives Here, we sought to investigate sex differences in dopamine release after oral d-amphetamine administration. Methods We used...

Increasing data indicate that prevalent forms of psychopathology can be organized into second-order dimensions based on their correlations, including a general factor of psychopathology that explains the common variance among all disorders and specific second-order externalizing and internalizing factors. Nevertheless, most existing studies on the...

Understanding of the specific processes involved in development of brain microarchitecture and how these are altered by genetic, cognitive, or environmental factors is a key to more effective and efficient interventions. With the increasing number of publicly available neuroimaging databases, there is an opportunity to combine large-scale imaging s...

The evidence that dopamine function mediates the association between aging and cognition is one of the most widely cited findings in the cognitive neuroscience of aging. However, relatively few and relatively small studies have directly examined these associations. Here we examined correlations among adult age, dopamine D2-like receptor (D2R) avail...

Impulsivity is a transdiagnostic feature of a range of externalizing psychiatric disorders. Preclinical work links reduced ventral striatal dopamine transporter (DAT) availability with heightened impulsivity and novelty seeking. However, there is a lack of human data investigating the relationship between DAT availability, particularly in subregion...

Some people are more willing to make immediate, risky, or costly reward-focused choices than others, which has been hypothesized to be associated with individual differences in dopamine (DA) function. In two studies using PET imaging, one empirical (Study 1: N = 144 males and females across 3 samples) and one meta-analytic (Study 2: N = 307 across...

Increasing data indicate that prevalent forms of psychopathology can be organized into second-order dimensions based on their correlations, including a general factor of psychopathology that explains the common variance among all disorders and specific second-order externalizing and internalizing factors. Despite this organization, and high levels...

The emotional attentional blink (EAB) refers to a temporary impairment in the ability to identify a target when it is preceded by an emotional distractor. It is thought to occur because the emotional salience of the distractor exogenously captures attention for a brief duration, rendering the target unattended and preventing it from reaching awaren...

Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is ge...

Objectives The ventrolateral prefrontal cortex (vlPFC) has been speculated to play an important role in complex processes that allow emotional factors to influence human cognition. Accumulating evidence from human neuroimaging studies, in conjunction with studies of patients with lesions and animal models, shed light on the role of the vlPFC in emo...

Some people are more willing to make immediate, risky, or costly reward-focused choices than others, which has been hypothesized to be associated with individual differences in dopamine (DA) function. In two studies using PET imaging, one empirical (Study 1: N=144 males and females across 3 samples) and one meta-analytic (Study 2: N=307 across 12 s...

Theories of adult brain development, based on neuropsychological test results and structural neuroimaging, suggest differential rates of age-related change in function across cortical and subcortical sub-regions. However, it remains unclear if these trends also extend to the aging dopamine system. Here we examined cross-sectional adult age differen...

The latent structure of schizotypy and psychosis-spectrum symptoms remains poorly understood. Furthermore, molecular genetic substrates are poorly defined, largely due to the substantial resources required to collect rich phenotypic data across diverse populations. Sample sizes of phenotypic studies are often insufficient for advanced structural eq...

Reward valuation, which underlies all value-based decision-making, has been associated with dopamine function in many studies of nonhuman animals, but there is relatively less direct evidence for an association in humans. Here, we measured dopamine D2 receptor (DRD2) availability in vivo in humans to examine relations between individual differences...

Go/no-go tasks are widely used to index cognitive control. This construct has been linked to white matter microstructure in a circuit connecting the right inferior frontal gyrus (IFG), subthalamic nucleus (STN), and pre-supplementary motor area. However, the specificity of this association has not been tested. A general factor of white matter has b...

Every day, humans make countless decisions which require the integration of information about potential benefits (i.e., rewards) with other decision features (i.e., effort required, probability of an outcome, or time delays). Here we examine the overlap and dissociation of behavioral preferences and neural representations of subjective value in the...

The nigrostriatal and mesocorticolimbic dopamine networks regulate reward-driven behavior. Regional alterations to mesolimbic dopamine D2/3receptor expression are described in drug-seeking and addiction disorders. Parkinson’s disease (PD) patients are frequently prescribed D2-like dopamine agonist (DAgonist) therapy for motor symptoms, yet a propor...

The supplementary data section provides 1.) PET acquisition parameters; 2.) a full description of mean ROI volume and BPnd values; 3.) a measure of effect size for all ROI-based analyses; 4.) standard-space ROI visualization and standard-space ROI BPnd scatterplots; 5.) visualization of supplementary whole-brain voxel-wise analysis considering PD s...

Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D2/3 receptors c...

In addition to motor symptoms, Parkinson’s disease (PD) involves significant non-motor sequelae, including disruptions in cognitive and emotional processing. Fear recognition appears to be affected both by the course of the disease and by a common interventional therapy, deep brain stimulation of the subthalamic nucleus (STN-DBS). Here, we examined...