Replication of a skills assessment for auditory-visual conditional discrimination training.

Auditory-visual conditional discrimination training (e.g., receptive identification training, listener responses; AVCD) is ubiquitous in early intervention and special education programs. Nevertheless, some learners with Autism Spectrum Disorder (ASD) do not appear to benefit from this training despite use of empirically validated treatments. To prevent exposure to extended training that does not lead to learning, a skills assessment that measures skills related to AVCD training will be useful for educators and practitioners. The current study replicated the skills assessment developed and evaluated by Kodak et al. (2015) with 8 participants with ASD who received behavior analytic intervention that included at least 1 goal related to AVCD training. Two of the 8 participants mastered all skills included in the assessment except scanning. In addition, 5 participants' responding failed to reach mastery during subsequent exposure to AVCD training, which further demonstrated the predictive utility of the skills assessment.

Enhancement of loudness discrimination acuity for self-generated sound is independent of musical experience.

Musicians tend to have better auditory and motor performance than non-musicians because of their extensive musical experience. In a previous study, we established that loudness discrimination acuity is enhanced when sound is produced by a precise force generation task. In this study, we compared the enhancement effect between experienced pianists and non-musicians. Without the force generation task, loudness discrimination acuity was better in pianists than non-musicians in the condition. However, the force generation task enhanced loudness discrimination acuity similarly in both pianists and non-musicians. The reaction time was also reduced with the force control task, but only in the non-musician group. The results suggest that the enhancement of loudness discrimination acuity with the precise force generation task is independent of musical experience and is, therefore, a fundamental function in auditory-motor interaction.

Preclinical and clinical research on the discriminative stimulus effects of nicotine.

Across species, nicotine can produce robust discriminative stimulus (DS) effects, as with other drugs of abuse, a feature that has been harnessed to advance our understanding on the neuropharmacological mechanisms of nicotine's actions. With the crucial role played by nicotine in supporting tobacco dependence, nicotine DS effects have presented an ideal platform to develop novel generation of smoking cessation compounds. Findings from preclinical strands of research have invigorated the field of human discrimination research to objectively assess nicotine's interoceptive stimulus effects. As such, translation studies provide proof of concept for nicotine DS research as a method to assess the subjective effects of nicotine per se, separate from non-nicotine stimuli involved in smoking. Recent clinical studies with low doses have demonstrated that perceiving nicotine's DS effects is necessary, yet not sufficient, for that dose to be reinforcing. These measures have been instrumental in developing novel strategies with regards to establishing threshold doses of nicotine contained in tobacco products, to then determine subthreshold doses that cannot be discriminated and, therefore, fail to maintain reinforcement. Findings from preclinical and clinical nicotine DS research could substantially inform public health policies aimed at regulating nicotine content of consumer products so that they minimize risks of dependency. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'.

Neural Patterns in Linguistic Cortices Discriminate the Content of Verbal Working Memory.

An influential theoretical account of working memory (WM) considers that WM is based on direct activation of long-term memory knowledge. While there is empirical support for this position in the visual WM domain, direct evidence is scarce in the verbal WM domain. This question is critical for models of verbal WM, as the question of whether short-term maintenance of verbal information relies on direct activation within the long-term linguistic knowledge base or not is still debated. In this study, we examined the extent to which short-term maintenance of lexico-semantic knowledge relies on neural activation patterns in linguistic cortices, and this by using a fast encoding running span task for word and nonword stimuli minimizing strategic encoding mechanisms. Multivariate analyses showed specific neural patterns for the encoding and maintenance of word versus nonword stimuli. These patterns were not detectable anymore when participants were instructed to stop maintaining the memoranda. The patterns involved specific regions within the dorsal and ventral pathways, which are considered to support phonological and semantic processing to various degrees. This study provides novel evidence for a role of linguistic cortices in the representation of long-term memory linguistic knowledge during WM processing.

Hypothalamic activation discriminates painful and non-painful initiation of the trigeminal autonomic reflex - an fMRI study.

BACKGROUND: The role of the trigeminal autonomic reflex in headache syndromes, such as cluster headache, is undisputed but sparsely investigated. The aim of the present study was therefore, to identify neural correlates that play a role in the initiation of the trigeminal autonomic reflex. We further aimed to discriminate between components of the reflex that are involved in nociceptive compared to non-nociceptive processing. METHODS: Kinetic Oscillation Stimulation (KOS) in the left nostril was applied in order to provoke autonomic symptoms (e.g. lacrimation) via the trigeminal autonomic reflex in 26 healthy participants using functional magnetic resonance imaging. Unpleasantness and painfulness were assessed on a visual analog scale (VAS), in order to assess the quality of the stimulus (e.g. pain or no pain). RESULTS: During non-painful activation, specific regions involved in the trigeminal autonomic reflex became activated, including several brainstem nuclei but also cerebellar and bilateral insular regions. However, when the input leading to activation of the trigeminal autonomic reflex was perceived as painful, activation of the anterior hypothalamus, the locus coeruleus (LC), the ventral posteriomedial nucleus of the thalamus (VPM), as well as an activation of ipsilateral insular regions, was observed. CONCLUSION: Our results suggest the anterior hypothalamus, besides the thalamus and specific brain stem regions, play a significant role in networks that mediate autonomic output (e.g. lacrimation) following trigeminal input, but only if the trigeminal system is activated by a stimulus comprising a painful component.

Prefrontal Cortex Regulates Sensory Filtering through a Basal Ganglia-to-Thalamus Pathway.

To make adaptive decisions, organisms must appropriately filter sensory inputs, augmenting relevant signals and suppressing noise. The prefrontal cortex (PFC) partly implements this process by regulating thalamic activity through modality-specific thalamic reticular nucleus (TRN) subnetworks. However, because the PFC does not directly project to sensory TRN subnetworks, the circuitry underlying this process had been unknown. Here, using anatomical tracing, functional manipulations, and optical identification of PFC projection neurons, we find that the PFC regulates sensory thalamic activity through a basal ganglia (BG) pathway. Engagement of this PFC-BG-thalamus pathway enables selection between vision and audition by primarily suppressing the distracting modality. This pathway also enhances sensory discrimination and is used for goal-directed background noise suppression. Overall, our results identify a new pathway for attentional filtering and reveal its multiple roles in sensory processing on the basis of internal goals.

A specific olfactory cortico-thalamic pathway contributing to sampling performance during odor reversal learning.

A growing body of evidence shows that olfactory information is processed within a thalamic nucleus in both rodents and humans. The mediodorsal thalamic nucleus (MDT) receives projections from olfactory cortical areas including the piriform cortex (PCX) and is interconnected with the orbitofrontal cortex (OFC). Using electrophysiology in freely moving rats, we recently demonstrated the representation of olfactory information in the MDT and the dynamics of functional connectivity between the PCX, MDT and OFC. Notably, PCX-MDT coupling is specifically increased during odor sampling of an odor discrimination task. However, whether this increase of coupling is functionally relevant is unknown. To decipher the importance of PCX-MDT coupling during the sampling period, we used optogenetics to specifically inactivate the PCX inputs to MDT during an odor discrimination task and its reversal in rats. We demonstrate that inactivating the PCX inputs to MDT does not affect the performance accuracy of an odor discrimination task and its reversal, however, it does impact the rats' sampling duration. Indeed, rats in which PCX inputs to MDT were inactivated during the sampling period display longer sampling duration during the odor reversal learning compared to controls-an effect not observed when inactivating OFC inputs to MDT. We demonstrate a causal link between the PCX inputs to MDT and the odor sampling performance, highlighting the importance of this specific cortico-thalamic pathway in olfaction.

Auditory perceptual learning and changes in the conceptualization of auditory cortex.

Perceptual learning, improvement in discriminative ability as a consequence of training, is one of the forms of sensory system plasticity that has driven profound changes in our conceptualization of sensory cortical function. Psychophysical and neurophysiological studies of auditory perceptual learning have indicated that the characteristics of the learning, and by implication the nature of the underlying neural changes, are highly task specific. Some studies in animals have indicated that recruitment of neurons to the population responding to the training stimuli, and hence an increase in the so-called cortical "area of representation" of those stimuli, is the substrate of improved performance, but such changes have not been observed in other studies. A possible reconciliation of these conflicting results is provided by evidence that changes in area of representation constitute a transient stage in the processes underlying perceptual learning. This expansion - renormalization hypothesis is supported by evidence from studies of the learning of motor skills, another form of procedural learning, but leaves open the nature of the permanent neural substrate of improved performance. Other studies have suggested that the substrate might be reduced response variability - a decrease in internal noise. Neuroimaging studies in humans have also provided compelling evidence that training results in long-term changes in auditory cortical function and in the auditory brainstem frequency-following response. Musical training provides a valuable model, but the evidence it provides is qualified by the fact that most such training is multimodal and sensorimotor, and that few of the studies are experimental and allow control over confounding variables. More generally, the overwhelming majority of experimental studies of the various forms of auditory perceptual learning have established the co-occurrence of neural and perceptual changes, but have not established that the former are causally related to the latter. Important forms of perceptual learning in humans are those involved in language acquisition and in the improvement in speech perception performance of post-lingually deaf cochlear implantees over the months following implantation. The development of a range of auditory training programs has focused interest on the factors determining the extent to which perceptual learning is specific or generalises to tasks other than those used in training. The context specificity demonstrated in a number of studies of perceptual learning suggests a multiplexing model, in which learning relating to a particular stimulus attribute depends on a subset of the diverse inputs to a given cortical neuron being strengthened, and different subsets being gated by top-down influences. This hypothesis avoids the difficulty of balancing system stability with plasticity, which is a problem for recruitment hypotheses. The characteristics of auditory perceptual learning reflect the fact that auditory cortex forms part of distributed networks that integrate the representation of auditory stimuli with attention, decision, and reward processes.

Blocking c-Fos Expression Reveals the Role of Auditory Cortex Plasticity in Sound Frequency Discrimination Learning.

The behavioral changes that comprise operant learning are associated with plasticity in early sensory cortices as well as with modulation of gene expression, but the connection between the behavioral, electrophysiological, and molecular changes is only partially understood. We specifically manipulated c-Fos expression, a hallmark of learning-induced synaptic plasticity, in auditory cortex of adult mice using a novel approach based on RNA interference. Locally blocking c-Fos expression caused a specific behavioral deficit in a sound discrimination task, in parallel with decreased cortical experience-dependent plasticity, without affecting baseline excitability or basic auditory processing. Thus, c-Fos-dependent experience-dependent cortical plasticity is necessary for frequency discrimination in an operant behavioral task. Our results connect behavioral, molecular and physiological changes and demonstrate a role of c-Fos in experience-dependent plasticity and learning.

Faster native vowel discrimination learning in musicians is mediated by an optimization of mnemonic functions.

The ability to discriminate phonemes varying in spectral and temporal attributes constitutes one of the most basic intrinsic elements underlying language learning mechanisms. Since previous work has consistently shown that professional musicians are characterized by perceptual and cognitive advantages in a variety of language-related tasks, and since vowels can be considered musical sounds within the domain of speech, here we investigated the behavioral and electrophysiological correlates of native vowel discrimination learning in a sample of professional musicians and non-musicians. We evaluated the contribution of both the neurophysiological underpinnings of perceptual (i.e., N1/P2 complex) and mnemonic functions (i.e., N400 and P600 responses) while the participants were instructed to judge whether pairs of native consonant-vowel (CV) syllables manipulated in the first formant transition of the vowel (i.e., from /tu/ to /to/) were identical or not. Results clearly demonstrated faster learning in musicians, compared to non-musicians, as reflected by shorter reaction times and higher accuracy. Most notably, in terms of morphology, time course, and voltage strength, this steeper learning curve was accompanied by distinctive N400 and P600 manifestations between the two groups. In contrast, we did not reveal any group differences during the early stages of auditory processing (i.e., N1/P2 complex), suggesting that faster learning was mediated by an optimization of mnemonic but not perceptual functions. Based on a clear taxonomy of the mnemonic functions involved in the task, results are interpreted as pointing to a relationship between faster learning mechanisms in musicians and an optimization of echoic (i.e., N400 component) and working memory (i.e., P600 component) functions.

Human Brainstem Exhibits higher Sensitivity and Specificity than Auditory-Related Cortex to Short-Term Phonetic Discrimination Learning.

Phonetic discrimination learning is an active perceptual process that operates under the influence of cognitive control mechanisms by increasing the sensitivity of the auditory system to the trained stimulus attributes. It is assumed that the auditory cortex and the brainstem interact in order to refine how sounds are transcribed into neural codes. Here, we evaluated whether these two computational entities are prone to short-term functional changes, whether there is a chronological difference in malleability, and whether short-term training suffices to alter reciprocal interactions. We performed repeated cortical (i.e., mismatch negativity responses, MMN) and subcortical (i.e., frequency-following response, FFR) EEG measurements in two groups of participants who underwent one hour of phonetic discrimination training or were passively exposed to the same stimulus material. The training group showed a distinctive brainstem energy reduction in the trained frequency-range (i.e., first formant), whereas the passive group did not show any response modulation. Notably, brainstem signal change correlated with the behavioral improvement during training, this result indicating a close relationship between behavior and underlying brainstem physiology. Since we did not reveal group differences in MMN responses, results point to specific short-term brainstem changes that precede functional alterations in the auditory cortex.

Benefits of fading in perceptual learning are driven by more than dimensional attention.

Individuals learn to classify percepts effectively when the task is initially easy and then gradually increases in difficulty. Some suggest that this is because easy-to-discriminate events help learners focus attention on discrimination-relevant dimensions. Here, we tested whether such attentional-spotlighting accounts are sufficient to explain easy-to-hard effects in auditory perceptual learning. In two experiments, participants were trained to discriminate periodic, frequency-modulated (FM) tones in two separate frequency ranges (300-600 Hz or 3000-6000 Hz). In one frequency range, sounds gradually increased in similarity as training progressed. In the other, stimulus similarity was constant throughout training. After training, participants showed better performance in their progressively trained frequency range, even though the discrimination-relevant dimension across ranges was the same. Learning theories that posit experience-dependent changes in stimulus representations and/or the strengthening of associations with differential responses, predict the observed specificity of easy-to-hard effects, whereas attentional-spotlighting theories do not. Calibrating the difficulty and temporal sequencing of training experiences to support more incremental representation-based learning can enhance the effectiveness of practice beyond any benefits gained from explicitly highlighting relevant dimensions.

Single-trial effective brain connectivity patterns enhance discriminability of mental imagery tasks.

OBJECTIVE: The majority of the current approaches of connectivity based brain-computer interface (BCI) systems focus on distinguishing between different motor imagery (MI) tasks. Brain regions associated with MI are anatomically close to each other, hence these BCI systems suffer from low performances. Our objective is to introduce single-trial connectivity feature based BCI system for cognition imagery (CI) based tasks wherein the associated brain regions are located relatively far away as compared to those for MI. APPROACH: We implemented time-domain partial Granger causality (PGC) for the estimation of the connectivity features in a BCI setting. The proposed hypothesis has been verified with two publically available datasets involving MI and CI tasks. MAIN RESULTS: The results support the conclusion that connectivity based features can provide a better performance than a classical signal processing framework based on bandpass features coupled with spatial filtering for CI tasks, including word generation, subtraction, and spatial navigation. These results show for the first time that connectivity features can provide a reliable performance for imagery-based BCI system. SIGNIFICANCE: We show that single-trial connectivity features for mixed imagery tasks (i.e. combination of CI and MI) can outperform the features obtained by current state-of-the-art method and hence can be successfully applied for BCI applications.

Predicting favorable and unfavorable consequences of perceptual learning: worsening and the peak shift.

Discrimination learning can cause improved and worsened ability to perceive differences. This subsequently affects how stimuli are associated with meanings and behaviors. Here, human listeners were trained with frequency-modulated (FM) tonal sweeps (500-1000 Hz) in a paradigm where one FM rate (8.29 octaves per second) required a 'Target' response, while a rate either slower (5.76 octaves per second) or faster (11.94 octaves per second) required a 'Non-Target' response. Training led to a shift in 'Target' responding along the FM rate dimension away from the 'Target' in a direction opposite the trained 'Non-Target'. This peak shift was paralleled by an asymmetry in acuity along the FM rate dimension in an untrained ABX task (a.k.a. match-to-sample). Performance improved relative to pre-training on trials where the 'Target' was contrasted with stimuli nearer the trained 'Non-Target'. Performance worsened on trials containing stimuli displaced along the FM dimension further from the trained 'Non-Target'. A connectionist model of perceptual learning containing non-associative representational modification and associative-based task-specific reweighting was able to simulate behavior. Simulations generated novel testable predictions regarding peak shift and worsening as a result of discrimination learning. Data have theoretical and practical consequences for predicting trends in the generalization of learned behaviors and modifiable perceptual acuities.

Acquisition and inhibition of conditioned fear is modulated by individual stimulus fear-relevance.

Inhibitory learning is an important factor for decreasing fear expression. We investigated conditioned inhibition of learned fear responses using conditioned excitors and inhibitors differing in fear-relevance in a sample of 48 healthy female students. To study the effect of stimulus fear-relevance, we used the fear potentiated startle paradigm in an AX+/BX- discrimination learning task with fear-relevant (spider) vs. fear-irrelevant (butterfly) pictures as CS+ (A) and CS- (B), respectively. We found that, during acquisition, participants with elevated fear of spiders showed stronger fear potentiated startle to AX+ compared to BX- when the inhibitor (B) was fear-irrelevant (butterfly) using both median split as well as correlational analyses. In contrast, when the excitor (A) was fear-irrelevant (butterfly), fear potentiated startle to AX+ compared to BX- was reduced for participants with higher fear of spiders. Effects of conditioned inhibition were studied in a summation test, where excitor and inhibitor were presented in compound (AB) and compared to the last four excitor trials during prior acquisition. Conditioned inhibition was stronger for participants with a higher fear of spiders, when the butterfly acted as conditioned inhibitor (B). On the other hand, when the spider served as conditioned inhibitor, effects of conditioned inhibition were weaker for participants with higher fear of spiders. Hence, rather than to a general preparedness our data point to a specific impairment in safety learning for individually fear-relevant stimuli.

Modulation of sensitivity to alcohol by cortical and thalamic brain regions.

The nucleus accumbens core (AcbC) is a key brain region known to regulate the discriminative stimulus/interoceptive effects of alcohol. As such, the goal of the present work was to identify AcbC projection regions that may also modulate sensitivity to alcohol. Accordingly, AcbC afferent projections were identified in behaviorally naïve rats using a retrograde tracer which led to the focus on the medial prefrontal cortex (mPFC), insular cortex (IC) and rhomboid thalamic nucleus (Rh). Next, to examine the possible role of these brain regions in modulating sensitivity to alcohol, neuronal response to alcohol in rats trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water was examined using a two-lever drug discrimination task. As such, rats were administered water or alcohol (1 g/kg, IG) and brain tissue was processed for c-Fos immunoreactivity (IR), a marker of neuronal activity. Alcohol decreased c-Fos IR in the mPFC, IC, Rh and AcbC. Lastly, site-specific pharmacological inactivation with muscimol + baclofen (GABAA agonist + GABAB agonist) was used to determine the functional role of the mPFC, IC and Rh in modulating the interoceptive effects of alcohol in rats trained to discriminate alcohol (1 g/kg, IG) vs. water. mPFC inactivation resulted in full substitution for the alcohol training dose, and IC and Rh inactivation produced partial alcohol-like effects, demonstrating the importance of these regions, with known projections to the AcbC, in modulating sensitivity to alcohol. Together, these data demonstrate a site of action of alcohol and the recruitment of cortical/thalamic regions in modulating sensitivity to the interoceptive effects of alcohol.

Auditory discrimination predicts linguistic outcome in Italian infants with and without familial risk for language learning impairment.

Infants' ability to discriminate between auditory stimuli presented in rapid succession and differing in fundamental frequency (Rapid Auditory Processing [RAP] abilities) has been shown to be anomalous in infants at familial risk for Language Learning Impairment (LLI) and to predict later language outcomes. This study represents the first attempt to investigate RAP in Italian infants at risk for LLI (FH+), examining two critical acoustic features: frequency and duration, both embedded in a rapidly-presented acoustic environment. RAP skills of 24 FH+ and 32 control (FH-) Italian 6-month-old infants were characterized via EEG/ERP using a multi-feature oddball paradigm. Outcome measures of expressive vocabulary were collected at 20 months. Group differences favoring FH- infants were identified: in FH+ infants, the latency of the N2* peak was delayed and the mean amplitude of the positive mismatch response was reduced, primarily for frequency discrimination and within the right hemisphere. Moreover, both EEG measures were correlated with language scores at 20 months. Results indicate that RAP abilities are atypical in Italian infants with a first-degree relative affected by LLI and that this impacts later linguistic skills. These findings provide a compelling cross-linguistic comparison with previous research on American infants, supporting the biological unity hypothesis of LLI.

Comprehensive auditory discrimination profiles recorded with a fast parametric musical multi-feature mismatch negativity paradigm.

OBJECTIVE: Mismatch negativity (MMN), a component of the auditory event-related potential (ERP) in response to auditory-expectancy violation, is sensitive to central auditory processing deficits associated with several clinical conditions and to auditory skills deriving from musical expertise. This sensitivity is more evident for stimuli integrated in complex sound contexts. This study tested whether increasing magnitudes of deviation (levels) entail increasing MMN amplitude (or decreasing latency), aiming to create a balanced version of the musical multi-feature paradigm towards measurement of extensive auditory discrimination profiles in auditory expertise or deficits. METHODS: Using electroencephalography, we measured MMNs in healthy young adults to six types of sound feature change (pitch, timbre, location, intensity, slide and rhythm) at three different magnitudes of deviation, embedded in a music-sounding context. We also behaviourally assessed the individual musical aptitude using the Musical Ear Test (MET). RESULTS: 16 of 18 sound feature changes elicited significant MMNs. For pitch, intensity, location, and slide, the MMN amplitude increased with increasing magnitude of feature change. We observed a ceiling effect for rhythm, and a floor effect for timbre. The slide MMN amplitude correlated positively with MET melody score and negatively with MET rhythm score. CONCLUSIONS: This novel paradigm provides an extensive, objective measure of auditory discrimination profile for different sound features embedded in a complex sound context. SIGNIFICANCE: The paradigm can be adopted to study the neurophysiology of individuals with music processing difficulties or with special musical skills, and may be a useful tool for investigating development, plasticity, and deficits of auditory processing.

Auditory Discrimination Learning: Role of Working Memory.

Perceptual training is generally assumed to improve perception by modifying the encoding or decoding of sensory information. However, this assumption is incompatible with recent demonstrations that transfer of learning can be enhanced by across-trial variation of training stimuli or task. Here we present three lines of evidence from healthy adults in support of the idea that the enhanced transfer of auditory discrimination learning is mediated by working memory (WM). First, the ability to discriminate small differences in tone frequency or duration was correlated with WM measured with a tone n-back task. Second, training frequency discrimination around a variable frequency transferred to and from WM learning, but training around a fixed frequency did not. The transfer of learning in both directions was correlated with a reduction of the influence of stimulus variation in the discrimination task, linking WM and its improvement to across-trial stimulus interaction in auditory discrimination. Third, while WM training transferred broadly to other WM and auditory discrimination tasks, variable-frequency training on duration discrimination did not improve WM, indicating that stimulus variation challenges and trains WM only if the task demands stimulus updating in the varied dimension. The results provide empirical evidence as well as a theoretic framework for interactions between cognitive and sensory plasticity during perceptual experience.

Evidence for Mediodorsal Thalamus and Prefrontal Cortex Interactions during Cognition in Macaques.

It is proposed that mediodorsal thalamus contributes to cognition via interactions with prefrontal cortex. However, there is relatively little evidence detailing the interactions between mediodorsal thalamus and prefrontal cortex linked to cognition in primates. This study investigated these interactions during learning, memory, and decision-making tasks in rhesus monkeys using a disconnection lesion approach. Preoperatively, monkeys learned object-in-place scene discriminations embedded within colorful visual backgrounds. Unilateral neurotoxic lesions to magnocellular mediodorsal thalamus (MDmc) impaired the ability to learn new object-in-place scene discriminations. In contrast, unilateral ablations to ventrolateral and orbital prefrontal cortex (PFv+o) left learning intact. A second unilateral MDmc or PFv+o lesion in the contralateral hemisphere to the first operation, causing functional MDmc-PFv+o disconnection across hemispheres, further impaired learning object-in-place scene discriminations, although object discrimination learning remained intact. Adaptive decision-making after reward satiety devaluation was also reduced. These data highlight the functional importance of interactions between MDmc and PFv+o during learning object-in-place scene discriminations and adaptive decision-making but not object discrimination learning. Moreover, learning deficits observed after unilateral removal of MDmc but not PFv+o provide direct behavioral evidence of the MDmc role influencing more widespread regions of the frontal lobes in cognition.