Month: September 2017

Jordan Hamm
Department of Biological Sciences
Columbia University

While prefrontal cortex and brain-wide, interregional networks are often studied in major neurological and psychiatric disorders, synaptic and cell-type specific pathophysiology has been identified in nearly all cortical areas in diseases like schizophrenia (SZ), suggesting that neuronal circuit function at the most basic level could play a critical role. Two-photon calcium imaging (2P-Ca++) studies in rodents have shown that local neuron populations in neocortical circuits (<1mm3) display distinct activity patterns made up of coactive “ensembles”, a level of detailed dynamics not captured by gross level (EEG, fMRI) or single neuron recordings. These activity patterns repeat during basic sensory and cognitive processing and also spontaneously at rest, suggesting that they make up the preferred, semi-stable “attractor” states of the cortex. Here I present findings from distinct mouse models of SZ-relevant disease processes (NMDA-receptor block, 22q11.2 microdeletion) that support the notion that a disorganization of local ensembles and the underlying “attractor” landscape could underlie basic perceptual and cognitive deficits in the disease. Interestingly, while acute manipulations of excitation, inhibition, or top-down inputs recreated cortical processing abnormalities at the single neuron level, key deficits in population-level synchrony patterns were only observed after chronic disease-relevant manipulations or in genetic models. Implications and future approaches for understanding and targeting altered synaptic plasticity processes across key neurodevelopmental periods will be discussed.

Travis Baker
Rutgers Center for Molecular and Behavioral Neuroscience
Rutgers University

Neurocognitive alterations to mesocorticolimbic reward function by drugs of abuse are thought to facilitate a progression towards excessive drug use. Despite efforts to identify methods to counteract such drug-induced neural alterations, brain-based treatments for this disorder remain underdeveloped and often ineffective. In this talk, I propose that the anterior cingulate cortex (ACC) putative function—selecting and motivating the execution of extended goal-directed behaviors—can be utilized as a biomarker for the abnormal reward processes underlying substance misuse. I will present support for this proposal utilizing the reward positivity as a quantifiable EEG metric of reward-related ACC function. First, people who abuse addictive substances produce a relatively small reward positivity to monetary incentives, and that this impairment is modulated by a genetic polymorphism that codes for the expression of dopamine D4 receptors. Second, drug rewards (puffs of a cigarette) elicit a relatively larger reward positivity than nondrug rewards (money) in abstinent smokers. Third, applying excitatory or inhibitory stimulation to a subject-specific frontal-cingulate reward pathway using robot-assisted fMRI-guided rTMS can alter the amplitude of the reward positivity elicited by drug and non-drug rewards. In sum, our efforts point to a decisive role of integrating multimodal neuroimaging methods as an early stage in treatment development for substance use disorders, with a highly sensitive EEG-based biomarker of addiction severity and treatment efficacy.

Emanuel Bubl
Department of Psychiatry and Psychotherapy
Albert-Ludwigs-University of Freiburg

The presentation evaluates the potential of visual contrast processing as a neurobiological correlate for depression and attention deficit hyperactivity disorder (ADHD) by targeting two questions:
1. the relevance of the findings in depression and ADHD compared to other disorders.
2. the distinct impact of treatment on these very early signals.