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Adam R Aron

Publications and source records attributed to Adam R Aron.

13 recordsLinked to original sources
PubMed2006

Association between response inhibition and working memory in adult ADHD: a link to right frontal cortex pathology?

BACKGROUND: We sought to assess the relationship between response inhibition and working memory in adult patients with attention-deficit/hyperactivity disorder (ADHD) and neurosurgical patients with frontal lobe damage. METHODS: The stop-signal reaction time (SSRT) test and a spatial working memory (SWM) task were administered to 20 adult patients with ADHD and a group of matched controls. The same tasks were administered to 21 patients with lesions to right frontal cortex and 19 patients with left frontal lesions. RESULTS: The SSRT test, but not choice reaction time, was significantly associated with search errors on the SWM task in both the adult ADHD and right frontal patients. In the right frontal patients, impaired performance on both variables was correlated with the volume of damage to the inferior frontal gyrus. CONCLUSIONS: Response inhibition and working memory impairments in ADHD may stem from a common pathologic process rather than being distinct deficits. Such pathology could relate to right frontal-cortex abnormalities in ADHD, consistent with prior reports, as well as with the demonstration here of a significant association between SSRT and SWM in right frontal patients.

Adult↗
PubMed2006

Cortical and subcortical contributions to Stop signal response inhibition: role of the subthalamic nucleus.

Suppressing an already initiated manual response depends critically on the right inferior frontal cortex (IFC), yet it is unclear how this inhibitory function is implemented in the motor system. It has been suggested that the subthalamic nucleus (STN), which is a part of the basal ganglia, may play a role because it is well placed to suppress the "direct" fronto-striatal pathway that is activated by response initiation. In two experiments, we investigated this hypothesis with functional magnetic resonance imaging and a Stop-signal task. Subjects responded to Go signals and attempted to inhibit the initiated response to occasional Stop signals. In experiment 1, Going significantly activated frontal, striatal, pallidal, and motor cortical regions, consistent with the direct pathway, whereas Stopping significantly activated right IFC and STN. In addition, Stopping-related activation was significantly greater for fast inhibitors than slow ones in both IFC and STN, and activity in these regions was correlated across subjects. In experiment 2, high-resolution functional and structural imaging confirmed the location of Stopping activation within the vicinity of the STN. We propose that the role of the STN is to suppress thalamocortical output, thereby blocking Go response execution. These results provide convergent data for a role for the STN in Stop-signal response inhibition. They also suggest that the speed of Go and Stop processes could relate to the relative activation of different neural pathways. Future research is required to establish whether Stop-signal inhibition could be implemented via a direct functional neuroanatomic projection between IFC and STN (a "hyperdirect" pathway).

Adult↗
PubMed2005

Long-term test-retest reliability of functional MRI in a classification learning task.

Functional MRI is widely used for imaging the neural correlates of psychological processes and how these brain processes change with learning, development and neuropsychiatric disorder. In order to interpret changes in imaging signals over time, for example, in patient studies, the long-term reliability of fMRI must first be established. Here, eight healthy adult subjects were scanned on two sessions, 1 year apart, while performing a classification learning task known to activate frontostriatal circuitry. We show that behavioral performance and frontostriatal activation were highly concordant at a group level at both time-points. Furthermore, intra-class correlation coefficients (ICCs), which index the degree of correlation between subjects at different time-points, were high for behavior and for functional activation. ICC was significantly higher within the network recruited by learning than outside that network. We conclude that fMRI can have high long-term test-retest reliability, making it suitable as a biomarker for brain development and neurodegeneration.

Adult↗
PubMed2005

Deficits in response inhibition associated with chronic methamphetamine abuse.

Chronic methamphetamine (MA) abuse is associated with cerebral deficits, involving frontal/basal-ganglia regions that are important for inhibitory control. We used the Stop-Signal Task to measure response inhibition in 11 MA abusers (5-7 days abstinent) and two groups of control subjects who did not use MA (14 tobacco smokers and 29 non-smokers). Stop-signal reaction time (SSRT), which indicates the latency to inhibit an initiated motor response, was significantly longer for MA abusers than for either control group (p's<.01). In contrast, the MA abusers did not differ from either group on Go trial reaction time (RT) or number of discrimination errors, which reflect motor speed and decision-processes, respectively. MA abuse in this study was therefore associated with a specific deficit in inhibiting a pre-potent response. Future research could examine whether SSRT is different for MA abusers who respond to treatment compared to those who do not. If such differences are established then response inhibition may serve as a marker for investigating MA abuse in basic science and clinical trials.

Adult↗
PubMed2004

The cognitive neuroscience of response inhibition: relevance for genetic research in attention-deficit/hyperactivity disorder.

Psychological functions that are behaviorally and neurally well specified may serve as endophenotypes for attention-deficit/hyperactivity disorder (ADHD) research. Such endophenotypes, which lie between genes and symptoms, may relate more directly to relevant genetic variability than does the clinical ADHD syndrome itself. Here we review evidence in favor of response inhibition as an endophenotype for ADHD research. We show that response inhibition--operationalized by Go/NoGo or Stop-signal tasks--requires the prefrontal cortex (PFC), in particular the right inferior frontal cortex (IFC); that patients with ADHD have significant response inhibition deficits and show altered functional activation and gray matter volumes in right IFC; and that a number of studies indicate that response inhibition performance is heritable. Additionally, we review evidence concerning the role of the basal ganglia in response inhibition, as well as the role of neuromodulatory systems. All things considered, a combined right IFC structure/function/response inhibition phenotype is a particularly good candidate for future heritability and association studies. Moreover, a dissection of response inhibition into more basic components such as rule maintenance, vigilance, and target detection may provide yet better targets for association with genes for neuromodulation and brain development.

Animals↗
PubMed2004

A componential analysis of task-switching deficits associated with lesions of left and right frontal cortex.

Executive functions such as task-set switching are thought to depend on the frontal cortex. However, more precision is required in identifying which components of such high-level processes relate to which, if any, subregions of the brain. In a recent study of 19 patients with focal right frontal (RF) lesions and 17 with left frontal (LF) lesions, we found that response inhibition, as measured by the stop-signal task, was specifically disrupted by damage to the right inferior frontal gyrus (IFG). The present study examined task-switching performance in this same group of patients and in matched controls on the grounds that inhibitory mechanisms may also be required to switch task-set. Both RF and LF patients showed significantly larger switch costs (the difference, in reaction time and errors, between changing tasks and repeating the same task) than controls, but apparently for different reasons. For RF patients, a part of the switch deficit could be accounted for by impaired inhibition of inappropriate responses or task-sets triggered by stimuli, and one measure of the switch cost correlated reliably with damage to the IFG, specifically the pars opercularis (POp). For LF patients, a part of the switch deficit may have arisen from weak top-down control of task-set. The degree of top-down control correlated reliably with the extent of damage to the left middle frontal gyrus (MFG). This study localizes two components of the complex task-switching process (inhibition of task-sets and/or responses and top-down control of task-set) to the right IFG/POp and the left MFG respectively.

Case-Control Studies↗
PubMed2004

Inhibition and the right inferior frontal cortex.

It is controversial whether different cognitive functions can be mapped to discrete regions of the prefrontal cortex (PFC). The localisationist tradition has associated one cognitive function - inhibition - by turns with dorsolateral prefrontal cortex (DLPFC), inferior frontal cortex (IFC), or orbital frontal cortex (OFC). Inhibition is postulated to be a mechanism by which PFC exerts its effects on subcortical and posterior-cortical regions to implement executive control. We review evidence concerning inhibition of responses and task-sets. Whereas neuroimaging implicates diverse PFC foci, advances in human lesion-mapping support the functional localization of such inhibition to right IFC alone. Future research should investigate the generality of this proposed inhibitory function to other task domains, and its interaction within a wider network.

Animals↗
PubMed2003

Methylphenidate improves response inhibition in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: Response inhibition is an executive function that requires voluntary control over responses when there is a change of context. The right inferior frontal cortex is necessary for response inhibition, and a deficit in right frontostriatal circuitry might underlie attention-deficit/hyperactivity disorder (ADHD). Many studies of childhood ADHD have demonstrated impaired response inhibition and its amelioration by methylphenidate (MPH). The current study tested response inhibition and the effect of MPH in adult ADHD. METHODS: Response inhibition was assessed with the "tracking" stop-signal test in 13 adults with a diagnosis of ADHD, both while taking and while not taking medication, and 13 healthy, unmedicated, age- and intelligence quotient-matched control subjects. RESULTS: Stop-signal reaction time was significantly slower in unmedicated adults with ADHD relative to healthy control subjects, and this deficit was significantly ameliorated by medication. CONCLUSIONS: Adult ADHD patients had a response inhibition profile similar to that produced by lesions to the right inferior frontal cortex, which was remedied by stimulant medication.

Adolescent↗
PubMed2003

Task-set switching deficits in early-stage Huntington's disease: implications for basal ganglia function.

Executive functions are likely mediated by interconnected circuits including frontal lobe and basal ganglia structures. We assessed the executive function of task switching in patients with early-stage Huntington's disease (HD), a neurodegenerative disease affecting the basal ganglia. In two experiments, the HD patients had greater difficulty when switching than when repeating a task than matched controls, and this was true even when scaling for the overall slowing of the patients. In the first experiment, HD patients had a switching deficit even in a "pure" condition where they had to switch, predictably, and with substantial preparation time, between stimuli having only one possible response, indicating a switching deficit different from that for patients with Parkinson's disease or frontal lobe trauma, and possibly relating to inadequate activation of stimulus-response links or "response set." In the more elaborate second experiment, we could not account for the switching deficit of the patients in terms of inadequate preparation in advance of a switch, deficient suppression of task-set processing from the preswitch trial, or impaired suppression of interference due to the presence of a competing task set. Instead, we found that part of the switching deficit was due to elevated reaction time and errors on switch trials for a repeated response (same button press as on preswitch trial) relative to an alternated response (different button press from preswitch trial). We argue that this elevated "repetition effect" for the HD patients is due to excessive inhibition of the just-performed response in advance of a switch. Alterations in the "response-setting" process alone (Experiment 1) and both the response-setting and "response inhibition" process (Experiment 2) probably arise from striatal pathology in HD, thus accounting for the task-switching deficits and showing how basal ganglia implemented response processes may underpin executive function.

Adult↗
PubMed2003

Relative lack of cognitive effects of methylphenidate in elderly male volunteers.

RATIONALE: Methylphenidate, a dopaminergic and noradrenergic reuptake inhibitor, has been shown in young, healthy adult volunteers to produce pronounced effects on working memory and sustained attention. We were interested in assessing whether similar improvements could be conferred upon elderly volunteers in order to gain a more complete understanding of the effects of age on monoaminergic manipulations of working memory and attention, as well as to explore the potential for pharmacological intervention in attention and executive dysfunction disorders in this age group. OBJECTIVES: The main aim of the study was to characterise the dose-related effects of methylphenidate on a range of neuropsychological functions in elderly healthy volunteers. METHODS: Sixty healthy elderly adult male volunteers received either a single oral dose of placebo, 20 mg or 40 mg methylphenidate prior to performing a variety of tasks designed to assess memory, attention and executive function. A randomised double-blind, between-subjects design was used. RESULTS: Methylphenidate had significant cardiovascular and subjective effects. However, unlike in younger volunteers, no significant effects of drug on working memory (spatial span and spatial working memory), response inhibition (stop-signal) or sustained attention (rapid visual information processing) were seen. Subtle effects on latency similar to those in younger volunteers were identified: both doses of methylphenidate resulted in a slowing in response time during set-shifting and decision-making. CONCLUSIONS: The results of this study demonstrate that, in elderly subjects, the cognitive effects of methylphenidate are grossly attenuated and distinct from the profile previously described in younger volunteers. It is suggested that methylphenidate may not be appropriate as a pharmacological intervention in elderly patient groups, such as those reporting age-related cognitive decline.

Administration, Oral↗
PubMed2003

Distractibility during selection-for-action: differential deficits in Huntington's disease and following frontal lobe damage.

Selective attention can be measured through analysis of errors and reaction time (RT) for trials in which targets are presented alone compared with trials in which targets and distractors are presented. This study investigated selective attention using a reaching task, in which subjects made rapid reaches to targets. Thirty-seven patients with lesions of the prefrontal cortex (PFC) were compared with 19 healthy age- and IQ-matched volunteers and 18 patients with early-stage Huntington's disease (HD), a neurodegenerative disease primarily affecting the basal ganglia. It was hypothesised that, if fronto-striatal circuits as a whole support selection-for-action, then the pattern of behavioural performance of both patient groups would be similar. Alternatively, if the functional roles of PFC and basal ganglia in selection-for-action are dissociable, then two different patterns would emerge. It was found that that both HD and frontal groups were significantly more distractible than controls for RT, but they had a different pattern of errors. Frontal patients made significantly more touches of the distractor location itself than did controls, while this was not the case for HD. It is argued that a reactive-inhibition mechanism, required in the circumstance of strong distractor activation, is affected by frontal damage, while a lateral-inhibition mechanism, invoked during the recruitment of selective attention, is affected in HD. Additionally, there were significant correlations between the degree of distractibility for RT and the extent of lateral PFC damage, and between cue-generated preparation and lateral PFC damage, thus highlighting the critical importance of lateral, rather than orbital or medial, PFC for attention to action.

Attention↗
PubMed2002

Cognitive enhancing effects of modafinil in healthy volunteers.

RATIONALE: Modafinil, a novel wake-promoting agent, has been shown to have a similar clinical profile to that of conventional stimulants such as methylphenidate. We were therefore interested in assessing whether modafinil, with its unique pharmacological mode of action, might offer similar potential as a cognitive enhancer, without the side effects commonly experienced with amphetamine-like drugs. OBJECTIVES: The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests. METHODS: Sixty healthy young adult male volunteers received either a single oral dose of placebo, or 100 mg or 200 mg modafinil prior to performing a variety of tasks designed to test memory and attention. A randomised double-blind, between-subjects design was used. RESULTS: Modafinil significantly enhanced performance on tests of digit span, visual pattern recognition memory, spatial planning and stop-signal reaction time. These performance improvements were complemented by a slowing in latency on three tests: delayed matching to sample, a decision-making task and the spatial planning task. Subjects reported feeling more alert, attentive and energetic on drug. The effects were not clearly dose dependent, except for those seen with the stop-signal paradigm. In contrast to previous findings with methylphenidate, there were no significant effects of drug on spatial memory span, spatial working memory, rapid visual information processing or attentional set-shifting. Additionally, no effects on paired associates learning were identified. CONCLUSIONS: These data indicate that modafinil selectively improves neuropsychological task performance. This improvement may be attributable to an enhanced ability to inhibit pre-potent responses. This effect appears to reduce impulsive responding, suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder.

Adult↗