Susan Y Bookheimer

• Ph.D.
• Managing Director at University of California, Los Angeles

Background Low-intensity transcranial focused ultrasound (tFUS) is a brain stimulation approach that holds immense promise for the treatment of brain-based disorders. Several studies in humans have shown that tFUS can successfully modulate perfusion in focal sonication targets including the amygdala; however, limited research has explored how tFUS...

In youth broadly, EEG frontal alpha asymmetry (FAA) associates with affective style and vulnerability to psychopathology, with relatively stronger right activity predicting risk for internalizing and externalizing behaviors. In autistic youth, FAA has been related to ASD diagnostic features and to internalizing symptoms. Among our large, rigorously...

Background Low intensity, transcranial focused ultrasound (tFUS) is a re-emerging brain stimulation technique with the unique capability of reaching deep brain structures non-invasively. Objective/Hypothesis We sought to demonstrate that tFUS can selectively and accurately target and modulate deep brain structures in humans important for emotional...

Negative or stressful life events are robust risk factors for depression and anxiety. Less attention has been paid to the positive aspects of events and whether positivity buffers the impact of the negative aspects of events. In this study, we examined the positivity and negativity of interpersonal and noninterpersonal episodic life events in predi...

Depression and anxiety are associated with abnormalities in brain regions that process rewards including the medial orbitofrontal cortex (mOFC), the ventral striatum (VS), and the amygdala. However, there are inconsistencies in these findings. This may be due to past reliance on categorical diagnoses that, while valuable, provide less precision tha...

Overview of low-intensity focused ultrasound technology and mechanism. The pilot study on the potential treatment of anxiety disorders using low-intensity focused ultrasound technology is summarized.

Transcranial focused ultrasound sonication (tFUS) is an emerging neuromodulation technique with the potential to target deep brain regions non-invasively1,2. Precise targeting of subcortical regions is only currently accessible through invasive surgical interventions, posing high risks and costs3, ultimately restricting the applicatory potentials o...

Adolescence is characterized by the maturation of cortical microstructure and connectivity supporting complex cognition and behavior. Axonal myelination influences brain connectivity during development by enhancing neural signaling speed and inhibiting plasticity. However, the maturational timing of cortical myelination during human adolescence rem...

Letter to the editor + a response.

p>Experimental sleep deprivation has been shown to differentially affect behavioral indices of effort and temporal discounting, 2 domains of reward processing often observed to be impaired in depression. Experimental sleep deprivation is phenomenologically different from sleep deprivation in everyday life (e.g., poor quality sleep or habitual short...

Myelination influences brain connectivity during sensitive periods of development by enhancing neural signaling speed and regulating synapse formation to reduce plasticity. However, in vivo studies characterizing the maturational timing of cortical myelination during human development remain scant. Here, we take advantage of recent advances in high...

Background Identification of ASD biomarkers is a key priority for understanding etiology, facilitating early diagnosis, monitoring developmental trajectories, and targeting treatment efforts. Efforts have included exploration of resting state encephalography (EEG), which has a variety of relevant neurodevelopmental correlates and can be collected w...

Converging evidence implicates disrupted brain connectivity in autism spectrum disorder (ASD); however, the mechanisms linking altered connectivity early in development to the emergence of ASD symptomatology remain poorly understood. Here we examined whether atypicalities in the Salience Network (SN) -- an early-emerging neural network involved in...

Background The heterogeneous nature of mood and anxiety disorders highlights a need for dimensionally based descriptions of psychopathology that inform better classification and treatment approaches. Following the Research Domain Criteria approach, this investigation sought to derive constructs assessing positive and negative valence domains across...

Aggressive behaviors are common among youth with autism spectrum disorder (ASD) and correlate with pervasive social-emotional difficulties. Communication skill is an important correlate of disruptive behavior in typical development, and clarification of links between communication and aggression in ASD may inform intervention methods. We investigat...

Converging evidence from neuroimaging studies has revealed altered connectivity in cortical-subcortical networks in youth and adults with autism spectrum disorder (ASD). Comparatively little is known about the development of cortical-subcortical connectivity in infancy, before the emergence of overt ASD symptomatology. Here we examined early functi...

Low-intensity transcranial focused ultrasound sonication (tFUS) selectively increases regional cerebral perfusion in deeper brain structures METHODS DESIGN A randomized, double-blind, within-subject crossover study was conducted to investigate whether tFUS can selectively increase regional blood perfusion in the amygdala (AG) or the entorhinal cort...

Background Current diagnostic strategy for Bipolar Disorders relies on symptomological classification. Yet, response to both pharmacological and psychotherapeutic treatments vary widely, which suggests underlying neuropathological differences are not well-captured by current nosology. Classifying bipolar disorder patients based on Emotion Regulatio...

While research addressing late-life death anxiety (the fear of death or the dying process) has focused on end-of-life care decision-making, few have studied the effect of late-life death anxiety on financial decision-making. This is particularly relevant to financial decision-making as older adults are more vulnerable to fraud and deception. The ai...

Inhibitory control deficits represent one of many core cognitive deficits in Attention-Deficit/Hyperactivity Disorder (ADHD). Neuroimaging studies suggest that individuals with ADHD exhibit atypical engagement of neural systems during response inhibition, but the exact nature of this phenotype is obscured by mixed findings. We tested whether drug-f...

Background and Aims: Legalization of cannabis (CB) for both medicinal and, in some states, recreational use, has given rise to increasing usage rates across the country. Of particular concern are indications that frequent CB use may be selectively harmful to the developing adolescent brain compared with adult-onset usage. However, the long-term eff...

The cognitive and physiological processes underlying creativity remain unclear, and very few studies to date have attempted to identify the behavioral and brain characteristics that distinguish exceptional ("Big-C") from everyday ("little-c") creativity. The Big-C Project examined functional brain responses during tasks demanding divergent and conv...

Background Physical activity (PA) plays a major role in maintaining cognition in older adults. PA has been shown to be correlated with total hippocampal volume, a memory-critical region within the medial temporal lobe (MTL). However, research on associations between PA and MTL sub-region integrity is limited. Objective To examine the relationship...

In rare cases of severe and intractable epilepsy, cerebral hemispherectomy is performed to arrest seizure activity and improve quality of life. The remaining hemisphere is often capable of supporting many cognitive functions post-surgery, although the outcome depends on the underlying etiology, hemisphere removed, and age of resection. The mechanis...

Purpose A previous study showed that assessment of language laterality could be improved by adding grammar tests to the recovery phase of the intracarotid amobarbital procedure (IAP) (Połczyńska et al. 2014). The aim of this study was to further investigate the extent to which grammar tests lateralize language function during the recovery phase of...

Gender dysphoria (GD) is characterized by incongruence between one’s identity and gender assigned at birth. The biological mechanisms of GD are unclear. We investigated brain network connectivity patterns involved in own body perception in the context of self in GD. Twenty-seven female-to-male (FtM) individuals with GD, 27 male controls, and 27 fem...

Research on bilinguals with brain lesions is complicated by high patient variability, making it difficult to find well-matched controls. We benefitted from a database of over 700 patients and conducted an analysis of pre-operative functional magnetic resonance imaging data to assess language dominance in 25 early, highly proficient Spanish-English...

Activation in grammar and standard tests in epilepsy (E) and tumor (T) patients. Lesion images are included for all tumor patients. Images of three epilepsy patients (E3, E4, E13) show a prior resection cavity. Overall, the grammar tests generate more robust activations in language areas than the standard test.

Two-sample t-tests (uncorrected) run for patients with significant ANOVA tests (Table 4) to determine task type skew directionality (greater percent signal change in grammar or standard tests) within each ROI. Region stats with NaN denote regions which have been ablated by tumor masses or edema.

Introduction Brain surgery in the language dominant hemisphere remains challenging due to unintended post-surgical language deficits, despite using pre-surgical functional magnetic resonance (fMRI) and intraoperative cortical stimulation. Moreover, patients are often recommended not to undergo surgery if the accompanying risk to language appears to...

Sensory over-responsivity (SOR) is a common condition in autism spectrum disorders (ASD) that is associated with greater social impairment. However, the mechanisms through which sensory stimuli may affect social functioning are not well understood. This study used fMRI to examine brain activity while interpreting communicative intent in 15 high-fun...

Introduction: The translocase of outer mitochondrial membrane 40 (TOMM40), which lies in linkage disequilibrium with apolipoprotein E (APOE), has received attention more recently as a promising gene in Alzheimer's disease (AD) risk. TOMM40 influences AD pathology through mitochondrial neurotoxicity, and the medial temporal lobe (MTL) is the most l...

Across species structural and functional hemispheric asymmetry is a fundamental feature of the brain. Environmental and genetic factors determine this asymmetry during brain development and modulate its interaction with brain disorders. The e4 allele of the apolipoprotein E gene (APOE-4) is a risk factor for Alzheimer's disease, associated with reg...

Several common alleles in the oxytocin receptor gene (OXTR) are associated with altered brain function in reward circuitry in neurotypical adults and may increase risk for autism spectrum disorders (ASD). Yet, it is currently unknown how variation in the OXTR relates to brain functioning in individuals with ASD, and, critically, whether neural endo...

We found microstructural differences between adolescent COS siblings and age-matched control participants with greater mean diffusivity (MD) in the putamen in controls compared to COS siblings

Recent evidence for abnormal thalamic connectivity in autism spectrum disorders (ASD) and sensory processing disorders suggests the thalamus may play a role in sensory over-responsivity (SOR), an extreme negative response to sensory stimuli, which is common in ASD. However, there is yet little understanding of changes in thalamic connectivity durin...

Standard volumetric neuroimaging studies have demonstrated preferential atrophy of subcortical structures among individuals with HIV. However, to our knowledge, no study has investigated subcortical shape alterations secondary to HIV and whether advancing age impacts that relationship. This study employed 3D morphometry to examine the independent a...

Background: Performance during cognitive control functional magnetic resonance imaging (fMRI) tasks are associated with frontal lobe hypoactivation in patients with bipolar disorder, even while euthymic. Here, we study the structural underpinnings for this functional abnormality simultaneously with brain activation data. Methods: In a sample of...

Variants at 21 genetic loci have been associated with an increased risk for Alzheimer’s disease (AD). An important unresolved question is whether multiple genetic risk factors can be combined to increase the power to detect changes in neuroimaging biomarkers for AD. We acquired high-resolution structural images of the hippocampus in 66 healthy, old...

Objective: The salience network, an intrinsic brain network thought to modulate attention to internal versus external stimuli, has been consistently found to be atypical in autism spectrum disorders (ASD). However, little is known about how this altered resting-state connectivity relates to brain activity during information processing, which has i...

Objective: Exercise and diet impact body composition, but their age-related brain effects are unclear at the molecular imaging level. To address these issues, the authors determined whether body mass index (BMI), physical activity, and diet relate to brain positron emission tomography (PET) of amyloid plaques and tau tangles using 2-(1-(6-[(2-[F-1...

In pre-neurosurgery language mapping it is critical to identify language-specific regions in multilingual speakers. We conducted pre-operative functional magnetic resonance imaging, and intraoperative language mapping in the unique case of a highly proficient quadrilingual with a left frontal brain tumor who acquired her second language at age 5, a...

The hippocampal complex is affected early in Alzheimer's disease (AD). Increasingly, altered functional connectivity of the hippocampus is recognized as an important feature of preclinical AD. Carriers of the APOEɛ4 allele are at an increased risk for AD, which could lead to altered hippocampal connectivity even in healthy older adults. To test thi...

There is a great need for brain-based measures in the assessment of Attention Deficit/Hyperactivity Disorder (ADHD) for better diagnosis and treatment evaluation, and for development of brain-based models (in keeping with RDoC). Withinindividual variability in performance is commonly cited as reflecting inconsistent control of attention in ADHD, an...

Background: Deficits in lexical retrieval, present in approximately 40% of HIV+ patients, are thought to reflect disruptions to frontal-striatal functions and may worsen with immunosuppression. Coupling frontal-striatal tasks such as lexical retrieval with functional neuroimaging may help delineate the pathophysiologic mechanisms underlying HIV-as...

Background: Management of language difficulties is an important aspect of clinical care for glioma patients, and accurately identifying the possible language deficits in patients based on lesion location would be beneficial to clinicians. To that end, we examined the relationship between lesion presence and language performance on tests of receptiv...

Better characterization of the preclinical phase of Alzheimer’s disease (AD) is needed to develop effective interventions. Neuropathologic changes in AD, including neuronal loss and the formation of proteinaceous deposits, can begin 20 years before the onset of clinical symptoms. As such, the emergence of cognitive impairment should not be the sole...

Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased incidence of learning disabilities, attention deficits, and autism spectrum disorders. As a single-gene disorder, NF1 represents a valuable model for understanding gene-brain-behavior relation...

Transsexualism is characterized by feelings of incongruity between one's natal sex and one's gender identity. It is unclear whether transsexual individuals have a body image that is more congruent with their gender identity than their sex assigned at birth (natal sex) and, if so, whether there are contributions from perceptual dysfunctions. We comp...

Significance Neurons within the human hippocampus have been shown to respond to individual concepts such as varying photographs of a single famous person. However, the relationship between these invariant neuronal responses and hippocampal-dependent memory remains elusive. The current study explores whether the specificity of human hippocampal neur...

Body dysmorphic disorder (BDD) and anorexia nervosa (AN) are both characterized by distorted perception of appearance. Previous studies in BDD suggest abnormalities in visual processing of own and others' faces, but no study has examined visual processing of faces in AN, nor directly compared the two disorders in this respect. We collected function...

Altered network connectivity and own body perception in gender dysphoria.

More than half of youth with autism spectrum disorders (ASDs) have sensory overresponsivity (SOR), an extreme negative reaction to sensory stimuli. However, little is known about the neurobiological basis of SOR, and there are few effective treatments. Understanding whether SOR is due to an initial heightened sensory response or to deficits in regu...

Examining the function of individual human hippocampal subfields remains challenging because of their small sizes and convoluted structures. Previous human fMRI studies at 3 T have successfully detected differences in activation between hippocampal cornu ammonis (CA) field CA1, combined CA2, CA3, and dentate gyrus (DG) region (CA23DG), and the subi...

Over the past decade, in-vivo MRI studies have provided many invaluable insights into the neural substrates underlying autism spectrum disorder (ASD), which is now known to be associated with neurodevelopmental variations in brain anatomy, functioning, and connectivity. These systems-level features of ASD pathology seem to develop differentially ac...

Patterns of abnormal neural activation have been observed during working memory tasks in bipolar I depression, yet the neural changes associated with bipolar II depression have yet to be explored. Method. An n-back working memory task was administered during a 3T functional magnetic resonance imaging scan in age- and gender-matched groups of 19 un...

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) are characterized by distorted body image and are frequently co-morbid with each other, although their relationship remains little studied. While there is evidence of abnormalities in visual and visuospatial processing in both disorders, no study has directly compared the two. We used two com...

Patients with childhood onset schizophrenia (COS) display widespread gray matter (GM) structural brain abnormalities. Healthy siblings of COS patients share some of these structural abnormalities, suggesting that GM abnormalities are endophenotypes for schizophrenia. Another possible endophenotype for schizophrenia that has been relatively unexplor...

The Wada test is an invasive procedure used to determine cerebral memory and language dominance as well as risk of cognitive deficits following neurosurgery. However, the potential risks of Wada testing have led some to consider foregoing Wada testing in candidates for resective epilepsy surgery with right hemispheric seizure onset. We present two...

OBJECTIVE: We statistically examined the relationship between lesion presence and neurocognitive performance on tasks of attention and language on a voxel-by-voxel basis in adult brain tumor patients using voxel-based lesion-symptom mapping (VLSM). VLSM is an innovative technique that has primarily been used in studies of stroke patients. METHODS:...

Neuroimaging investigations of Autism Spectrum Disorders (ASDs) have advanced our understanding of atypical brain function and structure, and have recently converged on a model of altered network-level connectivity. Traditional task-based functional magnetic resonance imaging (MRI) and volume-based structural MRI studies have identified widespread...

Background: Children with ASD often exhibit sensory over-responsivity (SOR), which may cause them to react negatively to sensory stimuli such as noisy environments or scratchy clothing (Liss et al., 2006). Rates of SOR are over five times higher in children with ASD than in typically developing (TD) children (e.g., Baranek et al., 2006; Ben-Sasson...

Advances in functional imaging have provided noninvasive techniques to probe brain organization of multiple constructs including language and memory. Because of high overall rates of agreements with older techniques, including W ada testing and cortical stimulation mapping ( CSM ), some have proposed that those approaches should be largely abandone...

The spectrum of cognitive symptoms in Parkinson's disease (PD) can span various domains, including executive function, language, attention, memory, and visuospatial skills. These symptoms may be attributable to the degradation of projection fibers associated with the underlying neurodegenerative process. The primary purpose of this study is to find...

Hemispherectomy is a surgical procedure for severe cases of epilepsy where an entire brain hemisphere is resected. Many patients maintain relatively normal cognitive function. Understanding how the brain's connections are organized in such cases is of interest and has not yet been explored. Using diffusion tensor imaging, we analyzed structural bra...

We studied healthy, first-degree relatives of patients with schizophrenia to test the hypothesis that deficits in cognitive skill learning are associated with genetic liability to schizophrenia. Using the Weather Prediction Task (WPT), 23 healthy controls and 10 adult first-degree Relatives Of Schizophrenia (ROS) patients were examined to determine...

Rare autosomal dominant mutations result in familial Alzheimer's disease (FAD) with a relatively consistent age of onset within families. This provides an estimate of years until disease onset (relative age) in mutation carriers. Increased AD risk has been associated with differences in functional magnetic resonance imaging (fMRI) activity during m...

The purpose of the current study was to explore whether brain tumors disrupt the integrity of the default mode network (DMN), a well-characterized resting-state fMRI network. We evaluated whether tumor grade, volume, post-surgical/clinical status, or location decreased the functional connectivity within the DMN in patients with gliomas. Task-based...

Sensory over-responsivity (SOR), defined as a negative response to or avoidance of sensory stimuli, is both highly prevalent and extremely impairing in youth with autism spectrum disorders (ASD), yet little is known about the neurological bases of SOR. This study aimed to examine the functional neural correlates of SOR by comparing brain responses...

Patients with schizophrenia perform poorly on cognitive skill learning tasks. This study is the first to investigate the neural basis of impairment in cognitive skill learning in first-degree adolescent relatives of patients with schizophrenia. We used functional magnetic resonance imaging to compare activation in 16 adolescent siblings of patients...

This article reviews our current understanding of the cognitive changes that can accompany epilepsy and how these relate to cortical dysfunction. The authors explain the basics of the cognitive changes that accompany lesions frequently associated with epilepsy.

Significance Early adversity has profound and lasting effects on neurodevelopment and emotional behavior. Under typical environmental conditions, prefrontal cortex connections with the amygdala are immature during childhood and become adult-like during adolescence. Rodent models show that maternal deprivation accelerates this development as an onto...

Autism spectrum disorders (ASDs) represent a formidable challenge for psychiatry and neuroscience because of their high prevalence, lifelong nature, complexity and substantial heterogeneity. Facing these obstacles requires large-scale multidisciplinary efforts. Although the field of genetics has pioneered data sharing for these reasons, neuroimagin...

Mechanistic understandings of forms of incidental emotion regulation have implications for basic and translational research in the affective sciences. In this study we applied Dynamic Causal Modeling (DCM) for fMRI to a common paradigm of labeling facial affect to elucidate prefrontal to subcortical influences. Four brain regions were used to model...

Objectives: To determine whether psychological well-being in people with mild cognitive impairment (MCI), a risk state for Alzheimer disease (AD), is associated with in vivo measures of brain pathology. Methods: Cross-sectional clinical assessments and positron emission tomography (PET) scans after intravenous injections of 2-(1-{6-[(2-[F18]fluo...

Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. Although tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connectio...

The relationship of cerebrovascular risk and Alzheimer's disease (AD) pathology to cognition in pre-dementia has been extensively investigated and is well-established. Cerebrovascular risk can be measured using a Framingham Stroke Risk Profile (FSRP) score, while positron emission tomography (PET) scans with 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)am...

Mild traumatic brain injury due to contact sports may cause chronic behavioral, mood, and cognitive disturbances associated with pathological deposition of tau protein found at brain autopsy. To explore whether brain tau deposits can be detected in living retired players, we used positron emission tomography (PET) scans after intravenous injections...

Objective: We examined resting state functional connectivity in the brain between key emotion regulation regions in bipolar I disorder to delineate differences in coupling from healthy subjects. Methods: Euthymic subjects with bipolar I disorder (n = 20) and matched healthy subjects (n = 20) participated in a resting state functional magnetic re...

Structural and functional underconnectivity have been reported for multiple brain regions, functional systems, and white matter tracts in individuals with autism spectrum disorders (ASD). Although recent developments in complex network analysis have established that the brain is a modular network exhibiting small-world properties, network level org...