Dorsal anterior cingulate cortex (dACC) is a brain region that subserves cognition and motor control, but the mechanisms of these functions remain unknown. Human neuroimaging and monkey electrophysiology studies have provided valuable insights, but it has been difficult to link the two literatures. Based on monkey single-unit recordings, we hypothesized that human dACC is comprised of a mixture of functionally distinct cells that variously anticipate and detect targets, indicate novelty, influence motor responses, encode reward values, and signal errors. As an initial test of this conceptualization, the current event-related functional MRI study used a reward-based decision-making task to isolate responses from a subpopulation of dACC cells sensitive to reward reduction. As predicted, seven of eight subjects showed significant (P < 10 ؊4 ) dACC activation when contrasting reduced reward (REDrew) trials to fixation (FIX). Confirmatory group analyses then corroborated the predicted ordinal relationships of functional MRI activation expected during each trial type (REDrew > SWITCH > CONrew > FIX). The data support a role for dACC in reward-based decision making, and by linking the human and monkey literatures, provide initial support for the existence of heterogeneity within dACC. These findings should be of interest to those studying reward, cognition, emotion, motivation, and motor control. ʈ A nterior cingulate cortex (ACC) lies on the medial surfaces of the brain's frontal lobes and encompasses subdivisions that play key roles in cognitive, motor, and emotional processing (1). Dorsal ACC (dACC) in humans includes cortex on the dorsal and ventral banks of the cingulate sulcus, and overlaps the territory occupied by the rostral cingulate motor area (CMAr) in monkeys (2, 3), which has projections directly to the spinal cord (4) and motor and limbic cortices (5). Convergent data (6, 7) has established that dACC specifically subserves cognition (8) and motor control (9), but the mechanisms by which this region operates have not been elucidated. Based primarily on work in humans, different functions have been ascribed to this area, including attention-for-action͞target selection (10, 11), motivational valence assignment (12), motor response selection (13-15), error detection͞performance monitoring (16, 17), competition monitoring (18), anticipation (19), working memory (20), novelty detection (21), and reward assessment (22), but no single unifying model explains the diverse results from neuroimaging and electrophysiological studies (1). In addition to the intrinsic importance of providing new information about normal cognition and motor control, determining how dACC works is essential because abnormalities of different ACC subdivisions have been implicated in the pathophysiology of many neuropsychiatric disorders (23).Single-unit recording studies have confirmed heterogeneity in monkey CMAr. Niki and Watanabe (24) identified timing (stimulus anticipation) units, and others sensitive to targets, motor responses, rewa...

Dorsal anterior cingulate cortex (dACC) plays critical roles in cognitive processing, but groupaveraging techniques have generally been required to obtain significant dACC activation in functional neuroimaging studies. Development of a task that reliably and robustly activates dACC within individuals is needed to improve imaging studies of neuropsychiatric disorders and localization of dACC in normal volunteers. By combining sources of cognitive interference (Stroop, Eriksen and Simon) with factors known to increase dACC activity, the Multi-Source Interference Task (MSIT) maximally taxes dACC, making it possible to reliably activate dACC within individuals using functional magnetic resonance imaging (fMRI). In this study, eight normal adult volunteers performed the MSIT during fMRI. We compared fMRI responses and performance data between interference and control trials. Significant dACC activation (Po1.7 Â 10 À4) was observed in all eight individuals and in the group-averaged fMRI data. In addition to dACC activation, group data also showed activation of presumably networked regions including dorsolateral prefrontal, premotor, and parietal cortices. The MSIT's reaction time interference effect (overall mean 312761 ms) was up to 10 times greater than that of its component predecessors and temporally stable over hundreds of trials. The robustness, reliability and stability of the neuroimaging and performance data should make the MSIT a useful task with which to study normal human cognition and psychiatric pathophysiology.

To examine alterations in brain activation associated with pharmacologically induced memory impairment, we used functional MRI (fMRI) to study the effects of lorazepam and scopolamine on a face–name associative encoding paradigm. Ten healthy young subjects were scanned on four occasions, 2 weeks apart; they were administered i.v. saline during two placebo-scanning sessions and then alternately administered i.v. lorazepam (1 mg) or scopolamine (0.4 mg) in a double-blind, randomized, cross-over design. Both the extent and magnitude of activation within anatomic regions of interest (ROIs) were examined to determine the reproducibility of activation in the placebo sessions and the regional specificity of the pharmacologic effects. Activation within all ROIs was consistent across the two placebo scans during the encoding of novel face–name pairs (compared with visual fixation). With the administration of either lorazepam or scopolamine, significant decreases were observed in both the extent and magnitude of activation within the hippocampal, fusiform, and inferior prefrontal ROIs, but no significant alterations in activation in the striate cortex were found. Both medications impaired performance on postscan memory measures, and significant correlations between memory performance and extent of activation were found in hippocampal and fusiform ROIs. These findings suggest that pharmacologic effects can be detected with fMRI by using a reproducible experimental paradigm and that medications that impair memory also diminish activation in specific brain regions thought to subserve complex memory processes.

Methylphenidate OROS increased daMCC activation during the MSIT and may act, in part, by normalizing daMCC hypofunction in ADHD.

We hypothesized that atomoxetine (ATMX) would produce similar brain effects in attention-deficit/hyperactivity disorder (ADHD) as those of methylphenidate (MPH). Eleven ADHD adults performed the Multi-Source Interference Task (MSIT) during fMRI at baseline and after 6 weeks of ATMX treatment. ATMX was associated with increased fMRI activation of dorsolateral prefrontal cortex, parietal cortex and cerebellum; but not dorsal anterior midcingulate cortex (daMCC). These results suggest that ATMX and MPH have similar but non-identical brain effects.

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Autism Spectrum Condition (ASC) is a life-long diagnosis, which has a subset of individualized characteristics consisting of hyper-, seeking- and/or hypo-reactivity to sensory inputs or unusual interests (APA, 2013). These sensitivities are evident in both environmental (e.g. apparent response to specific sounds, visual fascination with lights or movements) and physiological domains (e.g. anxiety, respiration or euthermia). As part of a larger PhD Research Project (SensorAble), this pilot study proposes that autistic individuals who exhibit greater distractibility and reduced focus/attention resulting stimuli may benefit from interventions that alter, redirect and/or attenuate stimuli. In particular, Irrelevant-Sound Effect (ISE) consisting of un-targeted and/or modulated sonics cause greater disruption of performance of simultaneous and visual simple tasks compared to baseline ISE that are merely directed. Using gold-standard Stroop experiments, data collected among neurotypical (NT) and ASC individuals at baseline and at various ISE modes result in greater reaction time (RT) improvements among ASC than NT participants. In this study, which focuses on aural distractibility only, data supports that signal processing may provide a gateway to enhancing focus and attention while reduce distractibility and anxiety in other domains.