Matthew C. Davidson

Differential patterns of striatal activation in young children with and without ADHD

BACKGROUND Cognitive control, defined as the ability to suppress inappropriate thoughts and actions, is compromised in attention-deficit/hyperactivity disorder (ADHD). This study examines the neural basis of this deficit. METHODS We used a paradigm that incorporates a parametric manipulation within a go/nogo task, so that the number of go trials preceding a nogo trial is varied to tax the neural systems underlying cognitive control with increasing levels of interference. RESULTS Using this paradigm in combination with event-related functional magnetic resonance imaging (fMRI), we show that children without ADHD have increased susceptibility to interference with increasing numbers of go trials preceding a nogo trial, but children with ADHD have difficulty even with a single go trial preceding a nogo trial. In addition, children with ADHD do not activate frontostriatal regions in the same manner as normally developing children, but rather rely on a more diffuse network of regions, including more posterior and dorsolateral prefrontal regions. CONCLUSIONS Normal immature cognition may be characterized as being susceptible to interference and supported by the maturation of frontostriatal circuitry. ADHD children show a slightly different cognitive profile at 6 to 10 years of age that is paralleled by a relative lack of or delay in the maturation of ventral frontostriatal circuitry.

Prolonged institutional rearing is associated with atypically large amygdala volume and difficulties in emotion regulation.

Early adversity, for example poor caregiving, can have profound effects on emotional development. Orphanage rearing, even in the best circumstances, lies outside of the bounds of a species-typical caregiving environment. The long-term effects of this early adversity on the neurobiological development associated with socio-emotional behaviors are not well understood. Seventy-eight children, who include those who have experienced orphanage care and a comparison group, were assessed. Magnetic resonance imaging (MRI) was used to measure volumes of whole brain and limbic structures (e.g. amygdala, hippocampus). Emotion regulation was assessed with an emotional go-nogo paradigm, and anxiety and internalizing behaviors were assessed using the Screen for Child Anxiety Related Emotional Disorders, the Child Behavior Checklist, and a structured clinical interview. Late adoption was associated with larger corrected amygdala volumes, poorer emotion regulation, and increased anxiety. Although more than 50% of the children who experienced orphanage rearing met criteria for a psychiatric disorder, with a third having an anxiety disorder, the group differences observed in amygdala volume were not driven by the presence of an anxiety disorder. The findings are consistent with previous reports describing negative effects of prolonged orphanage care on emotional behavior and with animal models that show long-term changes in the amygdala and emotional behavior following early postnatal stress. These changes in limbic circuitry may underlie residual emotional and social problems experienced by children who have been internationally adopted.

Contributions of amygdala and striatal activity in emotion regulation

BACKGROUND Emotional information can facilitate or interfere with cognitive processes. In this study, we examined the influence of emotional information in biasing performance and the biological basis underlying this influence. METHODS Ten human subjects (five female) were scanned with functional magnetic resonance imaging while performing an emotional go/nogo task. RESULTS Subjects were slower to approach fearful target expressions and had more difficulty avoiding happy nontarget expressions. The amygdala was recruited most for negative emotional context, and activity in this region was positively correlated with response time when detecting negative expressions. Increased signal in the right caudate nucleus was observed when avoiding nontargets and was negatively correlated with the number of false alarms subjects made. CONCLUSIONS Emotional context can alter behavioral and biological responses when approaching or avoiding a stimulus. We showed that recruitment of the amygdala, a region implicated in evaluating emotional significance, was associated with longer response latencies when approaching negative information, whereas recruitment of the caudate nucleus, a structure previously implicated in reward and impulse control, was most active when avoiding positive information. Our findings have significant implications for exaggerated and inhibited emotional responses that are characteristic of a number of psychiatric disorders.

Anterior Cingulate and Posterior Parietal Cortices Are Sensitive to Dissociable Forms of Conflict in a Task-Switching Paradigm

The conflict-monitoring hypothesis posits that anterior cingulate cortex (ACC) monitors conflict in information processing and recruits dorsolateral prefrontal cortex (DLPFC) to resolve competition as needed. We used fMRI to test this prediction directly in the context of a task-switching paradigm, in which subjects responded to the color or the motion of a visual stimulus. Conflict was indexed in terms of the product of activities in areas specialized for color or motion processing on a trial-by-trial basis. Here, we report that ACC and posterior parietal cortex (PPC) were sensitive to distinct forms of conflict, at the level of the response and the stimulus representation, respectively. Activity in PPC preceded increased activity in DLPFC and predicted enhanced behavioral performance on subsequent trials. These findings suggest that ACC and PPC may act in concert to detect dissociable forms of conflict and signal to DLPFC the need for increased control.

Parametric manipulation of conflict and response competition using rapid mixed-trial event-related fMRI

In the current study we examined the influence of preceding context on attentional conflict and response competition using a flanker paradigm. Nine healthy right-handed adults participated in a rapid mixed trial event-related functional magnetic resonance imaging (fMRI) study, in which increasing numbers of either compatible or incompatible trials preceded an incompatible trial. Behaviorally, reaction times on incompatible trials increased as a function of the number of preceding compatible trials. Several brain regions showed monotonic changes to the preceding context manipulation. The most common pattern was observed in anterior cingulate, dorsolateral prefrontal, and superior parietal regions. These areas showed an increase in activity for incompatible trials as the number of preceding compatible trials increased and a decrease in activity for incompatible trials as the number of preceding incompatible trials increased. Post hoc analysis showed that while the MR signal in the anterior cingulate and dorsolateral prefrontal regions peaked before the superior parietal region, the dorsolateral prefrontal MR signal peaked early and remained at this level. These findings are consistent with the conflict monitoring theory that postulates that the anterior cingulate cortex detects or monitors conflict, while PFC is involved in control adjustments that may then lead to modulation of superior parietal cortex in top-down biasing of attention.

The role of ventral frontostriatal circuitry in reward-based learning in humans.

This study examined changes in behavior and neural activity with reward learning. Using an event-related functional magnetic resonance imaging paradigm, we show that the nucleus accumbens, thalamus, and orbital frontal cortex are each sensitive to reward magnitude, with the accumbens showing the greatest discrimination between reward values. Mean reaction times were significantly faster to cues predicting the greatest reward and slower to cues predicting the smallest reward. This behavioral change over the course of the experiment was paralleled by a shift in peak in accumbens activity from anticipation of the reward (immediately after the response), to the cue predicting the reward. The orbitofrontal and thalamic regions peaked in anticipation of the reward throughout the experiment. Our findings suggest discrete functions of regions within basal ganglia thalamocortical circuitry in adjusting behavior to maximize reward.

Memory Maintenance and Inhibitory Control Differentiate from Early Childhood to Adolescence

Existing evidence suggests that the organization of cognitive functions may differentiate during development. We investigated two key components of executive functions, memory maintenance and inhibitory control, by applying latent factor models appropriate for examining developmental differences in functional associations among aspects of cognition. Two-hundred and sixty-three children (aged 4 to 14 years) were administered tasks that required maintaining rules in mind or inhibiting a prepotent tendency to respond on the same side as the stimulus. Memory maintenance and inhibitory control were not separable in children of 4–7 or 7–9.5 years, but were differentiated in an older group (9.5–14.5 years).

Familial Vulnerability to ADHD Affects Activity in the Cerebellum in Addition to the Prefrontal Systems.

OBJECTIVE Familial vulnerability to attention-deficit/hyperactivity disorder (ADHD) has been shown to be related to atypical prefrontal activity during cognitive control tasks. However, ADHD is associated with deficits in the cerebellum as well as deficits in frontostriatal circuitry and associated cognitive control. In this study, we investigated whether cerebellar systems are sensitive to familial risk for ADHD in addition to frontostriatal circuitry. METHOD We used an event-related, rapid mixed-trial functional magnetic resonance imaging design. The paradigm was a variation on a go/no-go task, with expected (go) and unexpected (no-go) events at expected and unexpected times. A total of 36 male children and adolescents completed the study, including 12 sibling pairs discordant for ADHD and 12 matched controls. RESULTS Children and adolescents with ADHD were less accurate on unexpected events than control subjects. Performance by unaffected siblings was intermediate, between that of children and adolescents with ADHD and controls. Functional neuroimaging results showed dissociation between activation in the cerebellum and anterior cingulate cortex: Activity in the anterior cingulate cortex was decreased for subjects with ADHD and their unaffected siblings compared with controls for manipulations of stimulus type (no-go trials), but not timing. In contrast, cerebellar activity was decreased for subjects with ADHD and their unaffected siblings for manipulations of timing, but not stimulus type. CONCLUSIONS These findings suggest that activity in both the prefrontal cortex and cerebellum is sensitive to familial vulnerability to ADHD. Unaffected siblings of individuals with ADHD show deficits similar to affected probands in prefrontal areas for unexpected events and in cerebellum for events atunexpected times.

Differential cingulate and caudate activation following unexpected nonrewarding stimuli.

This study examined the effects of varying the predictability of nonrewarding events on behavior and neural activation using a rapid mixed-trial functional magnetic resonance imagery (fMRI) design. Twelve adult subjects were scanned with echo planar imaging during performance of a visual detection task where the probability of events (target and nontarget) varied. This task included expected and unexpected nonrewarding events (expected target, unexpected nontarget, and omission of target) in a design that closely parallels studies of dopamine function and reward processing in the alert monkey. We predicted that activation in dopamine-rich areas of the forebrain would behave like the animal literature shows that dopamine neurons in the midbrain behave. Specifically, we predicted increased activity in these regions when an unexpected event occurred and decreased activity when an expected event was omitted. Two main regions, the anterior cingulate and dorsal striatum, showed this pattern. The response in these regions was distinguished by enhanced anterior cingulate activity following the occurrence of an unexpected event and greater suppression of caudate activity following the omission of an expected event. These results suggest that neural activity within specific dopamine-rich brain regions can be modulated by violations in the expectation of nonrewarding events and that the direction of the modulation depends on the nature of the violations.

Use of noninvasive ventilation in patients with amyotrophic lateral sclerosis

INTRODUCTION: Noninvasive positive pressure ventilation (NIPPV) is associated with improved survival in amyotrophic lateral sclerosis (ALS) and has been widely recommended. The extent of NIPPV use in ALS patients and the factors associated with its use have not been studied. METHODS: A cross‐sectional study using the ALS Patient Care Database. Analyses were performed to assess the association of patient and care characteristics with use of ventilatory support. RESULTS: 1458 patients were studied. 15.6% used NIPPV and 2.1% used invasive mechanical ventilation. Patients who used NIPPV were significantly more likely to be male and have higher income than those who did not. They were also more likely to have a gastrostomy tube, lower vital capacity, more severe disease, bulbar involvement and poorer general health status as measured by the SF‐12 and Sickness Impact Profile. Multivariate analysis revealed that lower FVC, higher income and use of gastrostomy tube were independently associated with use of NIPPV. CONCLUSIONS: NIPPV is used more than seven times as frequently as invasive ventilation in ALS patients. Patients who use NIPPV have more severe disease than those who do not use any respiratory intervention. Patients with lower income are less likely to use NIPPV, which raises concerns about disparities in the care of patients with ALS.