NP_Publications

Preclinical evidence suggests that inter-individual variation in the structure of the hypothalamus at birth is associated with variation in the intrauterine environment, with downstream implications for future disease susceptibility. However, scientific advancement in humans is limited by a lack of validated methods for the automatic segmentation of the newborn hypothalamus. N = 215 healthy full-term infants with paired T1-/T2-weighted MR images across four sites were considered for primary...

Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying network layout. We tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2439 adults with...

Acceptance-enhanced behavior therapy for trichotillomania (AEBT-TTM) is effective in reducing trichotillomania (TTM) symptoms, but the durability of treatment effects remains in question. This study analyzed 6-month follow-up data from a large randomized clinical trial comparing AEBT-TTM to an active psychoeducation and supportive therapy control (PST). Adults with TTM (N=85; 92% women) received 10 sessions of AEBT-TTM or PST across 12 weeks. Independent evaluators assessed participants at...

The balance between excitation and inhibition is critical to brain functioning, and dysregulation of this balance is a hallmark of numerous psychiatric conditions. Measuring this excitation-inhibition (E:I) balance in vivo has remained difficult, but theoretical models have proposed that characteristics of local field potentials (LFP) may provide an accurate proxy. To establish a conclusive link between LFP and E:I balance, we recorded single units and LFP from the prefrontal cortex (mPFC) of...

CONCLUSION: PTSD in young women is associated with higher brachial and central pressures, increased arterial stiffness and blunted parasympathetic control of the heart. These findings illustrate potential mechanisms underlying high risk for CVD in young women with PTSD, suggesting possible treatment targets for this at-risk group.

Bayesian decision theory suggests that optimal decision-making should use and weigh prior beliefs with current information, according to their relative uncertainties. However, some characteristics of borderline personality disorder (BPD) patients, such as fast, drastic changes in the overall perception of themselves and others, suggest they may be underrelying on priors. Here, we investigated if BPD patients have a general deficit in relying on or combining prior with current information. We...

CONCLUSIONS AND RELEVANCE: Based on this systematic review and the proposed biomarker development framework, there is a pathway for the development and regulatory qualification of FDCR-based biomarkers of addiction and recovery. Further validation could support the use of FDCR-derived measures, potentially accelerating treatment development and improving diagnostic, prognostic, and predictive clinical judgments.

Schizophrenia results in part from a failure of prefrontal networks but we lack full understanding of how disruptions at a synaptic level cause failures at the network level. This is a crucial gap in our understanding because it prevents us from discovering how genetic mutations and environmental risks that alter synaptic function cause prefrontal network to fail in schizophrenia. To address that question, we developed a recurrent spiking network model of prefrontal local circuits that can...

Integrative experiment design is a needed improvement over ad hoc experiments, but the specific proposed method has limitations. We urge a further break with tradition through the use of an enormous untapped resource: Decades of causal discovery artificial intelligence (AI) literature on optimizing the design of systematic experimentation.

OBJECTIVE: Research on the natural course of symptoms of atypical anorexia nervosa (AN) relative to AN and bulimia nervosa (BN) is limited yet needed to inform nosology and improve understanding of atypical AN. This study aimed to 1) characterize trajectories of eating disorder and internalizing (anxiety, depression) symptoms in college students with and without a history of atypical AN, AN, and BN; and 2) compare sex and race/ethnicity distributions across groups.

CONCLUSIONS: Neural network connectivity supports ITRED as a novel neurobiologically based approach to classifying posttrauma psychopathology.

CONCLUSION: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.

Identification of replicable neuroimaging correlates of ADHD has been hindered by small sample sizes, small effects, and heterogeneity of methods. Given considerable evidence that ADHD is associated with alterations in widely distributed brain networks, and the small effects of individual brain features, a whole-brain perspective focusing on cumulative effects is warranted. Use of large, multi-site samples is crucial for improving reproducibility and clinical utility of brain-wide MRI...

Heritability of regional subcortical brain volumes (rSBVs) describes the role of genetics in middle and inner brain development. rSBVs are highly heritable in adults but are not characterized well in adolescents. The Adolescent Brain Cognitive Development study (ABCD), taken over 22 US sites, provides data to characterize the heritability of subcortical structures in adolescence. In ABCD, site-specific effects co-occur with genetic effects which can bias heritability estimates. Existing methods...

The red nucleus is a large brainstem structure that coordinates limb movement for locomotion in quadrupedal animals (Basile et al., 2021). The humans red nucleus has a different pattern of anatomical connectivity compared to quadrupeds, suggesting a unique purpose (Hatschek, 1907). Previously the function of the human red nucleus remained unclear at least partly due to methodological limitations with brainstem functional neuroimaging (Sclocco et al., 2018). Here, we used our most advanced...

Electrophysiological recording is a powerful technique to examine neuronal substrates underlying cognition and behavior. Neuropixels probes provide a unique capacity to capture neuronal activity across many brain areas with high spatiotemporal resolution. Neuropixels are also expensive and optimized for acute, head-fixed use, both of which limit the types of behaviors and manipulations that can be studied. Recent advances have addressed the cost issue by showing chronic implant, explant, and...

Measuring the function of decision-making systems is a central goal of computational psychiatry. Individual measures of decisional function could be used to describe neurocognitive profiles that underpin psychopathology and offer insights into deficits that are shared across traditional diagnostic classes. However, there are few demonstrably reliable and mechanistically relevant metrics of decision making that can accurately capture the complex overlapping domains of cognition whilst also...

Objective.Cortical function is under constant modulation by internally-driven, latent variables that regulate excitability, collectively known as 'cortical state'. Despite a vast literature in this area, the estimation of cortical state remains relatively ad hoc, and not amenable to real-time implementation. Here, we implement robust, data-driven, and fast algorithms that address several technical challenges for online cortical state estimation.Approach. We use unsupervised Gaussian mixture...

Efficient delivery of therapeutics to the central nervous system (CNS) remains a major challenge for the treatment of neurological diseases. Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide expansion mutation in the HTT gene which codes for a toxic mutant huntingtin (mHTT) protein. Pharmacological reduction of mHTT in the CNS using antisense oligonucleotides (ASO) ameliorates HD-like phenotypes in rodent models of HD, with such therapies...

Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder...