Conor Liston

Bio: Conor Liston is an academic researcher from Cornell University. The author has contributed to research in topics: Neuroscience & Prefrontal cortex. The author has an hindex of 33, co-authored 101 publications receiving 9919 citations. Previous affiliations of Conor Liston include Rockefeller University & Harvard University.

Resting-state connectivity biomarkers define neurophysiological subtypes of depression

Abstract: Biomarkers have transformed modern medicine but remain largely elusive in psychiatry, partly because there is a weak correspondence between diagnostic labels and their neurobiological substrates. Like other neuropsychiatric disorders, depression is not a unitary disease, but rather a heterogeneous syndrome that encompasses varied, co-occurring symptoms and divergent responses to treatment. By using functional magnetic resonance imaging (fMRI) in a large multisite sample (n = 1,188), we show here that patients with depression can be subdivided into four neurophysiological subtypes (‘biotypes’) defined by distinct patterns of dysfunctional connectivity in limbic and frontostriatal networks. Clustering patients on this basis enabled the development of diagnostic classifiers (biomarkers) with high (82–93%) sensitivity and specificity for depression subtypes in multisite validation (n = 711) and out-of-sample replication (n = 477) data sets. These biotypes cannot be differentiated solely on the basis of clinical features, but they are associated with differing clinical-symptom profiles. They also predict responsiveness to transcranial magnetic stimulation therapy (n = 154). Our results define novel subtypes of depression that transcend current diagnostic boundaries and may be useful for identifying the individuals who are most likely to benefit from targeted neurostimulation therapies.

Stress-Induced Alterations in Prefrontal Cortical Dendritic Morphology Predict Selective Impairments in Perceptual Attentional Set-Shifting

Abstract: Stressful life events have been implicated clinically in the pathogenesis of mental illness, but the neural substrates that may account for this observation remain poorly understood. Attentional impairments symptomatic of these psychiatric conditions are associated with structural and functional abnormalities in a network of prefrontal cortical structures. Here, we examine whether chronic stress-induced dendritic alterations in the medial prefrontal cortex (mPFC) and orbital frontal cortex (OFC) underlie impairments in the behaviors that they subserve. After 21 d of repeated restraint stress, rats were tested on a perceptual attentional set-shifting task, which yields dissociable measures of reversal learning and attentional set-shifting, functions that are mediated by the OFC and mPFC, respectively. Intracellular iontophoretic injections of Lucifer yellow were performed in a subset of these rats to examine dendritic morphology in layer II/III pyramidal cells of the mPFC and lateral OFC. Chronic stress induced a selective impairment in attentional set-shifting and a corresponding retraction (20%) of apical dendritic arbors in the mPFC. In stressed rats, but not in controls, decreased dendritic arborization in the mPFC predicted impaired attentional set-shifting performance. In contrast, stress was not found to adversely affect reversal learning or dendritic morphology in the lateral OFC. Instead, apical dendritic arborization in the OFC was increased by 43%. This study provides the first direct evidence that dendritic remodeling in the prefrontal cortex may underlie the functional deficits in attentional control that are symptomatic of stress-related mental illnesses.

Repeated Stress Induces Dendritic Spine Loss in the Rat Medial Prefrontal Cortex

Abstract: The prefrontal cortex (PFC) plays an important role in higher cognitive processes, and in the regulation of stress-induced hypothalamic--pituitary--adrenal (HPA) activity. Here we examined the effect of repeated restraint stress on dendritic spine number in the medial PFC. Rats were perfused after receiving 21 days of daily restraint stress, and intracellular iontophoretic injections of Lucifer Yellow were carried out in layer II/III pyramidal neurons in the anterior cingulate and prelimbic cortices. We found that stress results in a significant (16%) decrease in apical dendritic spine density in medial PFC pyramidal neurons, and confirmed a previous observation that total apical dendritic length is reduced by 20% in the same neurons. We estimate that nearly one-third of all axospinous synapses on apical dendrites of pyramidal neurons in medial PFC are lost following repeated stress. A decrease in medial PFC dendritic spines may not only be indicative of a decrease in the total population of axospinous synapses, but may impair these neurons’ capacity for biochemical compartmentalization and plasticity in which dendritic spines play a major role. Dendritic atrophy and spine loss may be important cellular features of stress-related psychiatric disorders where the PFC is functionally impaired.

Psychosocial stress reversibly disrupts prefrontal processing and attentional control

Abstract: Relatively little is known about the long-term neurobiological sequelae of chronic stress, which predisposes susceptible patients to neuropsychiatric conditions affecting the prefrontal cortex (PFC). Animal models and human neuroimaging experiments provide complementary insights, yet efforts to integrate the two are often complicated by limitations inherent in drawing comparisons between unrelated studies with disparate designs. Translating from a rodent model of chronic stress where we have shown reversible disruption of PFC function, we show that psychosocial stress induces long-lasting but reversible impairments in behavioral and functional magnetic resonance imaging (fMRI) measures of PFC function in humans. Twenty healthy adults, exposed to 1 month of psychosocial stress, confirmed by a validated rating scale, were scanned while performing a PFC-dependent attention-shifting task. One month later, they returned for a second scanning session after a period of reduced stress, and their performance was compared with a twice-scanned, matched group of low-stress controls. Psychosocial stress selectively impaired attentional control and disrupted functional connectivity within a frontoparietal network that mediates attention shifts. These effects were reversible: after one month of reduced stress, the same subjects showed no significant differences from controls. These results highlight the plasticity of PFC networks in healthy human subjects and suggest one mechanism by which disrupted plasticity may contribute to cognitive impairments characteristic of stress-related neuropsychiatric conditions in susceptible individuals.

Sources of Method Bias in Social Science Research and Recommendations on How to Control It

Abstract: Despite the concern that has been expressed about potential method biases, and the pervasiveness of research settings with the potential to produce them, there is disagreement about whether they really are a problem for researchers in the behavioral sciences. Therefore, the purpose of this review is to explore the current state of knowledge about method biases. First, we explore the meaning of the terms “method” and “method bias” and then we examine whether method biases influence all measures equally. Next, we review the evidence of the effects that method biases have on individual measures and on the covariation between different constructs. Following this, we evaluate the procedural and statistical remedies that have been used to control method biases and provide recommendations for minimizing method bias.

Physiology and Neurobiology of Stress and Adaptation: Central Role of the Brain

Abstract: The brain is the key organ of the response to stress because it determines what is threatening and, therefore, potentially stressful, as well as the physiological and behavioral responses which can be either adaptive or damaging. Stress involves two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms. Beyond the "flight-or-fight" response to acute stress, there are events in daily life that produce a type of chronic stress and lead over time to wear and tear on the body ("allostatic load"). Yet, hormones associated with stress protect the body in the short-run and promote adaptation ("allostasis"). The brain is a target of stress, and the hippocampus was the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. Stress and stress hormones produce both adaptive and maladaptive effects on this brain region throughout the life course. Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging. The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiological responses. As an adjunct to pharmaceutical therapy, social and behavioral interventions such as regular physical activity and social support reduce the chronic stress burden and benefit brain and body health and resilience.

Obesity and Overweight

Abstract: e w id r as e, se er t st al h r Overweight or obesity in adolescents has reache epidemic proportions in the USA and other industr alized countries. These conditions, although ofte lumped together in research and in commentarie reflect adolescents’ being toward the heavier point a continuum that would range from underweight morbidly obese. The terms may be used interchang ably, but there is no doubt that, in the US a considerable percentage of adolescents suffer fro too much body fat. The prevalence of obesity (bod mass index [BMI] >95th percentile) among adole cents aged 12–19 years is now one in six (17.6%); an one in three (34.9%) US adolescents are overweight obese (BMI>85th percentile) (Story et al. 2009). Oth industrialized countries, such as Canada, Japa Germany, and China also are beginning to experien increasing problems related to obesity (Cornette 2008 Being on the overweight side of the weight continuu means being afflicted with a serious, chronic disea that can cause substantial harm to adolescents’ curre and future health. Although terms may be used loosely, individua only are formally deemed obese by physicians. The are some rules of thumb and formulas that often a used, especially in social science studies, but physician diagnose whether adolescents are obese. Discussion measurements tends to focus on that diagnos A diagnosis of obesity typically involves using a bod mass index (BMI). BMI is a measure of weight propo tionate to height, which is deemed a useful measure the amount of body fat. Although there are other mo precise ways to measure excess fat, experts now recom mend using BMI because it is easily obtained, strong

The Adolescent Brain

Abstract: Adolescence is a developmental period characterized by suboptimal decisions and actions that are associated with an increased incidence of unintentional injuries, violence, substance abuse, unintended pregnancy, and sexually transmitted diseases. Traditional neurobiological and cognitive explanations for adolescent behavior have failed to account for the nonlinear changes in behavior observed during adolescence, relative to both childhood and adulthood. This review provides a biologically plausible model of the neural mechanisms underlying these nonlinear changes in behavior. We provide evidence from recent human brain imaging and animal studies that there is a heightened responsiveness to incentives and socioemotional contexts during this time, when impulse control is still relatively immature. These findings suggest differential development of bottom-up limbic systems, implicated in incentive and emotional processing, to top-down control systems during adolescence as compared to childhood and adulthood. This developmental pattern may be exacerbated in those adolescents prone to emotional reactivity, increasing the likelihood of poor outcomes.