Neurogliaform (RELNϩ) and bipolar (VIPϩ) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been elucidated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP). Interestingly, Prox1 promotes the maturation of CGE-derived interneuron subtypes through intrinsic differentiation programs that operate in tandem with extrinsically driven neuronal activity-dependent pathways. Thus Prox1 represents the first identified transcription factor specifically required for the embryonic and postnatal acquisition of CGE-derived cortical interneuron properties.

In many studies of attention-deficit hyperactivity disorder (ADHD), stimulus encoding and processing (perceptual function) and response selection (executive function) have been intertwined. To dissociate these functions, we introduced a task that parametrically varied low-level stimulus features (orientation and color) for fine-grained analysis of perceptual function, and that also required participants to switch their attention between feature dimensions on a trial-by-trial basis, thus taxing executive processes. Our response paradigm captured task-irrelevant motor output (TIMO), reflecting failures to use the correct stimulus-response rule. ADHD patients had substantially worse perceptual function than Controls, especially for orientation. ADHD participants had also higher TIMO; this measure was strongly affected by the switch manipulation. Across participants, the perceptual variability parameter was correlated with TIMO, suggesting that perceptual deficits could underlie 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.In Attention Deficit Hyperactivity Disorder (ADHD), self-reported behavioral deficits have been attributed to differences in executive function, attention, and perceptual function. These brain functions can be objectively quantified with behavioral paradigms, but the individual components are often not well separated. ADHD patients tend to have worse executive function than Controls according to several metrics [1][2][3][4], predominantly in response execution and inhibition [5][6][7], but also in switching between stimulus-response rules [8][9][10][11]. It has been pointed out that non-executive processes, such as alertness, accumulation of evidence or drift rate, motivation, or reward processing, might interact with executive ones [12][13][14][15][16]. In the realm of visual attention, differences in accuracy or reaction time have been found in some visual search tasks but not in others [17,18], and no consistent deficits have been found in visuo-spatial orienting [19][20][21][22]. Despite evidence of impaired perceptual function in ADHD from psychiatric assessments [23,24], behavioral studies that examined the quality of perceptual encoding in ADHD in the absence of executive or attentional involvement found small and inconsistent differences (see [25] for a review). There have been attempts to dissociate executive from perceptual function in ADHD within a single task, but the results have been mixed [26][27][28][29]. One complicating factor could be that commonly used stimuli such as faces, letters, or numbers are high-dimensional and have content at many levels. Anot...

No abstract

In many studies of attention-deficit hyperactivity disorder (ADHD), stimulus encoding and processing (perceptual 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.

No abstract