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Mihali, A.

Publications and source records attributed to Mihali, A..

2 recordsLinked to original sources

A low-level perceptual correlate of behavioral and clinical deficits in ADHD

In many studies of attention-deficit hyperactivity disorder (ADHD), stimulus encoding and processing (per-ceptual function) and response selection (executive function) have been intertwined. To dissociate deficits in these functions, we introduced a task that parametrically varied low-level stimulus features (orientation and color) for fine-grained analysis of perceptual function. It also required participants to switch their attention between feature dimensions on a trial-by-trial basis, thus taxing executive processes. Furthermore, we used a response paradigm that captured task-irrelevant motor output (TIMO), reflecting failures to use the correct stimulus-response rule. ADHD participants had substantially higher perceptual variability than Controls, especially for orientation, as well as higher TIMO. In both ADHD and Controls, TIMO was strongly affected by the switch manipulation. Across participants, the perceptual variability parameter was correlated with TIMO, suggesting that perceptual deficits are associated with executive function deficits. Based on perceptual variability alone, we were able to classify participants into ADHD and Controls with a mean accuracy of about 77%. Participants self-reported General Executive Composite score correlated not only with TIMO but also with the perceptual variability parameter. Our results highlight the role of perceptual deficits in ADHD and the usefulness of computational modeling of behavior in dissociating perceptual from executive processes.

neuroscience

Dopamine neuron dependent behaviors mediated by glutamate cotransmission

Dopamine neurons in the ventral tegmental area use glutamate as a cotransmitter. To elucidate the behavioral role of the cotransmission, we targeted the glutamate-recycling enzyme glutaminase (gene GLS1). In mice with a DAT-driven conditional heterozygous (cHET) reduction of GLS1 in their dopamine neurons, dopamine neuron survival and transmission were unaffected, while glutamate cotransmission at phasic firing frequencies was reduced, enabling focusing the cotransmission. DAT GLS1 cHET mice showed normal emotional and motor behaviors, and an unaffected response to acute amphetamine. Strikingly, amphetamine sensitization was reduced and latent inhibition potentiated. These behavioral effects, also seen in global GLS1 HETs with a schizophrenia resilience phenotype, were not seen in mice with an Emx1-driven forebrain reduction affecting most brain glutamatergic neurons. Thus, a reduction in dopamine neuron glutamate cotransmission appears to mediate significant components of the GLS1 HET schizophrenia resilience phenotype, and glutamate cotransmission appears to be important in attribution of motivational salience.

neuroscience