Adam Hampshire

Putting brain training to the test

‘Brain training’, or the goal of improved cognitive function through the regular use of computerized tests, is a multimillion-pound industry, yet in our view scientific evidence to support its efficacy is lacking. Modest effects have been reported in some studies of older individuals and preschool children, and video-game players outperform non-players on some tests of visual attention. However, the widely held belief that commercially available computerized brain-training programs improve general cognitive function in the wider population in our opinion lacks empirical support. The central question is not whether performance on cognitive tests can be improved by training, but rather, whether those benefits transfer to other untrained tasks or lead to any general improvement in the level of cognitive functioning. Here we report the results of a six-week online study in which 11,430 participants trained several times each week on cognitive tasks designed to improve reasoning, memory, planning, visuospatial skills and attention. Although improvements were observed in every one of the cognitive tasks that were trained, no evidence was found for transfer effects to untrained tasks, even when those tasks were cognitively closely related.

The role of the right inferior frontal gyrus: inhibition and attentional control

There is growing interest regarding the role of the right inferior frontal gyrus (RIFG) during a particular form of executive control referred to as response inhibition. However, tasks used to examine neural activity at the point of response inhibition have rarely controlled for the potentially confounding effects of attentional demand. In particular, it is unclear whether the RIFG is specifically involved in inhibitory control, or is involved more generally in the detection of salient or task relevant cues. The current fMRI study sought to clarify the role of the RIFG in executive control by holding the stimulus conditions of one of the most popular response inhibition tasks–the Stop Signal Task–constant, whilst varying the response that was required on reception of the stop signal cue. Our results reveal that the RIFG is recruited when important cues are detected, regardless of whether that detection is followed by the inhibition of a motor response, the generation of a motor response, or no external response at all.

Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives

Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviors associated with underlying dysregulation of frontostriatal circuitry. Central to neurobiological models of OCD is the orbitofrontal cortex, a neural region that facilitates behavioral flexibility after negative feedback (reversal learning). We identified abnormally reduced activation of several cortical regions, including the lateral orbitofrontal cortex, during reversal learning in OCD patients and their clinically unaffected close relatives, supporting the existence of an underlying previously undiscovered endophenotype for this disorder.

When thoughts become action: an fMRI paradigm to study volitional brain activity in non-communicative brain injured patients.

The assessment of voluntary behavior in non-communicative brain injured patients is often challenging due to the existence of profound motor impairment. In the absence of a full understanding of the neural correlates of consciousness, even a normal activation in response to passive sensory stimulation cannot be considered as proof of the presence of awareness in these patients. In contrast, predicted activation in response to the instruction to perform a mental imagery task would provide evidence of voluntary task-dependent brain activity, and hence of consciousness, in non-communicative patients. However, no data yet exist to indicate which imagery instructions would yield reliable single subject activation. The aim of the present study was to establish such a paradigm in healthy volunteers. Two exploratory experiments evaluated the reproducibility of individual brain activation elicited by four distinct mental imagery tasks. The two most robust mental imagery tasks were found to be spatial navigation and motor imagery. In a third experiment, where these two tasks were directly compared, differentiation of each task from one another and from rest periods was assessed blindly using a priori criteria and was correct for every volunteer. The spatial navigation and motor imagery tasks described here permit the identification of volitional brain activation at the single subject level, without a motor response. Volunteer as well as patient data [Owen, A.M., Coleman, M.R., Boly, M., Davis, M.H., Laureys, S., Pickard J.D., 2006. Detecting awareness in the vegetative state. Science 313, 1402] strongly suggest that this paradigm may provide a method for assessing the presence of volitional brain activity, and thus of consciousness, in non-communicative brain-injured patients.

Atomoxetine Modulates Right Inferior Frontal Activation During Inhibitory Control: A Pharmacological Functional Magnetic Resonance Imaging Study

BACKGROUND Atomoxetine, a selective noradrenaline reuptake inhibitor (SNRI) licensed for the treatment of attention-deficit/hyperactivity disorder (ADHD), has been shown to improve response inhibition in animals, healthy volunteers, and adult patients. However, the mechanisms by which atomoxetine improves inhibitory control have yet to be determined. METHODS The effects of atomoxetine (40 mg) were measured with a stop-signal functional magnetic resonance imaging (fMRI) paradigm in 19 healthy volunteers, in a within-subject, double-blind, placebo-controlled design. RESULTS Atomoxetine improved inhibitory control and increased activation in the right inferior frontal gyrus when volunteers attempted to inhibit their responses (irrespective of success). Plasma levels of drug correlated significantly with right inferior frontal gyrus activation only during successful inhibition. CONCLUSIONS These results show that atomoxetine exerts its beneficial effects on inhibitory control via modulation of right inferior frontal function, with implications for understanding and treating inhibitory dysfunction of ADHD and other disorders.

Catechol O-Methyltransferase val158met Genotype Influences Frontoparietal Activity during Planning in Patients with Parkinson's Disease

Cognitive dysfunction commonly occurs even in the early stages of Parkinsons disease (PD). Impairment on frontostriatally based executive tasks is particularly well described but affects only a proportion of early PD patients. Our previous work suggests that a common functional polymorphism (val158met) within the catechol O-methyltransferase (COMT) gene underlies some of this executive heterogeneity. In particular, an increasing number of methionine alleles, resulting in lower enzyme activity, is associated with impaired performance on the “Tower of London” planning task. The main objective of this study was to investigate the underlying neural basis of this genotype–phenotype effect in PD using functional magnetic resonance imaging. We scanned 31 patients with early PD who were homozygous for either valine (val) (n = 16) or methionine (met) (n = 15) at the COMT val158met polymorphism during performance of an executive task comprising both Tower of London (planning) and simple subtracting (“control”) problems. A cross-group comparison between genetic subgroups revealed that response times for planning problems were significantly longer in met compared with val homozygotes, whereas response times for control problems did not differ. Furthermore, imaging data revealed a significant reduction in blood oxygen level-dependent signal across the frontoparietal network involved in planning in met/met compared with val/val patients. Hence, we have demonstrated that COMT genotype impacts on executive function in PD through directly influencing frontoparietal activation. Furthermore, the directionality of the genotype–phenotype effect observed in this study, when interpreted in the context of the existing literature, adds weight to the hypothesis that the relationship between prefrontal function and dopamine levels follows as an inverted U-shaped curve.

Training the Emotional Brain: Improving Affective Control through Emotional Working Memory Training

Affective cognitive control capacity (e.g., the ability to regulate emotions or manipulate emotional material in the service of task goals) is associated with professional and interpersonal success. Impoverished affective control, by contrast, characterizes many neuropsychiatric disorders. Insights from neuroscience indicate that affective cognitive control relies on the same frontoparietal neural circuitry as working memory (WM) tasks, which suggests that systematic WM training, performed in an emotional context, has the potential to augment affective control. Here we show, using behavioral and fMRI measures, that 20 d of training on a novel emotional WM protocol successfully enhanced the efficiency of this frontoparietal demand network. Critically, compared with placebo training, emotional WM training also accrued transfer benefits to a “gold standard” measure of affective cognitive control–emotion regulation. These emotion regulation gains were associated with greater activity in the targeted frontoparietal demand network along with other brain regions implicated in affective control, notably the subgenual anterior cingulate cortex. The results have important implications for the utility of WM training in clinical, prevention, and occupational settings.

A functional network perspective on response inhibition and attentional control

Inferior frontal cortex (IFC) modules that inhibit dominant behaviours are a popular feature in theories of cognitive dysfunction. However, the paradigms on which these theories are based fail to distinguish between inhibitory and non-inhibitory cognitive demands. Here we use four novel fMRI variants of the classic stop-signal task to test whether the IFC houses unique inhibitory modules. Our results demonstrate that IFC sub-regions are not functionally unique in their sensitivities to inhibitory cognitive demands, but instead form components of spatially distributed networks. These networks are most strongly activated when infrequent stimuli are being processed, regardless of behavioural inhibitory demands, and when novel tasks are being acquired, as opposed to when routine responses must be suppressed. We propose that there are no inhibitory modules within the frontal lobes and that behavioural inhibition is an emergent property of spatially distributed functional networks, each of which supports a broader class of cognitive demands.

Adaptive coding of task-relevant information in human frontoparietal cortex.

Frontoparietal cortex is thought to be essential for flexible behavior, but the mechanism for control remains elusive. Here, we demonstrate a potentially critical property of this cortex: its dynamic configuration for coding of task-critical information. Using multivoxel pattern analysis of human functional imaging data, we demonstrate an adaptive change in the patterns of activation coding task-relevant stimulus distinctions. When task demands made perceptual information more difficult to discriminate, frontoparietal regions showed increased coding of this information. Visual cortices showed the opposite result: a weaker representation of perceptual information in line with the physical change in the stimulus. On a longer timescale, a rebalancing of coding was also seen after practice, with a diminished representation of task rules as they became familiar. The results suggest a flexible neural system, exerting cognitive control in a wide range of tasks by adaptively representing the task features most challenging for successful goal-directed behavior.

Extending Brain-Training to the Affective Domain: Increasing Cognitive and Affective Executive Control through Emotional Working Memory Training

So-called ‘brain-training’ programs are a huge commercial success. However, empirical evidence regarding their effectiveness and generalizability remains equivocal. This study investigated whether brain-training (working memory [WM] training) improves cognitive functions beyond the training task (transfer effects), especially regarding the control of emotional material since it constitutes much of the information we process daily. Forty-five participants received WM training using either emotional or neutral material, or an undemanding control task. WM training, regardless of training material, led to transfer gains on another WM task and in fluid intelligence. However, only brain-training with emotional material yielded transferable gains to improved control over affective information on an emotional Stroop task. The data support the reality of transferable benefits of demanding WM training and suggest that transferable gains across to affective contexts require training with material congruent to those contexts. These findings constitute preliminary evidence that intensive cognitively demanding brain-training can improve not only our abstract problem-solving capacity, but also ameliorate cognitive control processes (e.g. decision-making) in our daily emotive environments.