hot affective system

Brief Review of 2015-2016 Studies on Brain Training for Depression, Anxiety and Burnout

Here I review the latest peer-reviewed studies and meta-analyses that look at the benefits of working memory and executive control brain training for depression and anxiety.

For some quick definitions, working memory is our ‘mental workspace’ that stores and processes task-relevant information. It is the interface between the current focus of attention and long-term memories. Executive control is our ability to manage our attention and goal focus. Meta-analyses systematically assess all peer-reviewed, published studies meeting relevant criteria for a particular type of training. A meta-analysis, compared to a single peer reviewed paper enables us to draw much stronger conclusions about the effectiveness of brain training interventions. The most effective brain training interventions capitalize on the brain’s dynamic capacity to recover from brain disease – its neuroplasticity.

Depression

Depression is a condition in which a person feels discouraged, sad, hopeless, unmotivated or disinterested in life in general. Depressed individuals often suffer from insomnia. Loss of interest, apathy, and insomnia make it difficult to complete daily tasks.

Major depressive disorder is a common disorder among adults with a lifetime prevalence of 16.6% in the United States (1). In the UK a quarter of the population will experience some kind of mental health problem in the course of a year, with mixed anxiety and depression the most common disorder (2). The World Health Organisation forecasts that by 2020 depression will be the second leading contributor to the global burden of disease (3). It is estimated that only 37.5% of adults receive minimally adequate treatment (4).

Depression is associated with (5):

  • greater psychosocial disability
  • low productivity
  • missed work days,
  • greater risk of developing anxiety disorders
  • greater risk of developing cardiovascular diseases
  • higher rates of mortality

An estimated 7% of depressed adults commit suicide., largely in part due to lack of treatment or low treatment efficacy (6).

Cognitive Impairments from Depression

Depressed individuals have cognitive deficits associated with reduced quality of life. There are deficits in (7):

  • verbal fluency
  • working memory
  • attention
  • executive function
  • processing speed

While psychotherapy and antidepressants have proven efficacy for improving mood, cognitive deficits often remain when mood improves (8). And cognitive impairments are a risk factor for development of dementia.

Computerized Cognitive Training for Depression

Development of computerized cognitive training (CCT) to improve cognition in depressed people, and possibly improve antidepressant responses to other treatments can have a major public health benefit. Advantages of CCT as a treatment include:

  • Inexpensive
  • Noninvasive
  • Convenient (can be completed at home)
  • Can be tailored to meet specific cognitive needs of patient
  • No concern for medical side effects

 

Evidence for the Efficacy of CCT for Depression

Jeffrey Motter and his colleagues at Queens College/University of Columbia conducted a meta-analysis to look at the efficacy of CCT for depression, and have pre-published the results in their paper Computerized cognitive training and functional recovery in major depressive disorder: A meta-analysis (Jan 2016).

This meta-study systematically analysed 9 randomized trials of CCT for depression and found.

  • Improvement in Depressive Symptoms
  • Improved Global Functioning (including measures of IQ)
  • Improved Working Memory and Attention

The prevalent CCT training type was either executive control or working memory training such as dual n-back or ‘cognitive control’ training (see Table 1)

The outcome measures in this review were:

  • Symptom Severity (measures of mood and anxiety, such as the Beck Depression Inventory)
  • Daily Functioning (measures of social skills, work ability, and mobility)
  • Attention (tests for ability to maintain focus)
  • Working Memory (measures of the ability to maintain and update information while performing tasks)
  • Verbal Memory (the Hopkins Verbal Learning Test)
  • Executive Functioning (measures of task switching, inhibition and verbal fluency)
  • Global Functioning (general cognition measure, includes IQ test measures – the WAIS Verbal and Performance IQs)

The effect sizes for individual measures by study and domain (type of measure) are shown in this table below. ‘Favors CCT’ means the study supported the effectiveness of the brain training (CCT) for depression. ‘Favors CG’ means the study did not support brain training effectiveness, with no difference from the control group (CG). Standardized scores can be calculated by multiplying the ‘Hedges’ g’ by 15 (one standard deviation). So the first study reported a ~15 point improvement in Symptom Severity for depression (compared to the control group who did not do the brain training).
.

working memory and executive control training for depression

Effect sizes for different outcome measures are summarized in this table below:
.

brain training for depression

The mean effect sizes that were statistically significant are

  • Symptom Severity (0.43 = 6.5 points),
  • Daily Functioning (0.48 = 7 points),
  • Attention (0.67 = 10 points),
  • Working Memory (0.72 = 11 points)
  • Global Functioning (1.05 = 16 points)

(Note. The mean effect size for executive functioning was 0.20 was trending to significance. Executive Functioning was targeting in one study during the last two weeks of the training, and for only one session of psychoeducation in another, so the data are not sufficient to draw strong conclusions here. Verbal memory, targeted in half the studies, did not significantly improve with training.)

These are impressive results.

Not only is their cognitive improvement and reduction in the symptoms of depression, there is apparently good transfer to Daily Functioning – everyday life activities.

Compare symptom reduction from brain training with the effect sizes reported in FDA studies on the efficacy of antidepressant medication (compared to placebo) for symptom severity using the Hamilton Rating Scale of Depression (HRSD). Effect size is also Hedges g, as in the brain training studies (Figure 3).

Antidepressant drug effect sizes

The average overall estimated effect size for both published and unpublished studies is 0.26, compared to 0.43 for the brain training interventions. 

For potential limitations of this meta-analysis see Notes.

 

Brain Networks

Poor treatment response may be due in part to reduced functioning of the Cognitive Control Network (CCN) (9) a neural pathway that regulates higher-order cognitive processes (10). Brain training may enhance executive functioning, and strengthen functional connectivity in the CCN, in turn producing improvements in antidepressant response.

cognitive control network

The Cognitive Control Network

 


Building Resilience

It is known that both stress reactivity and brooding (a counterproductive type of rumination) are risk factors for developing depression.

In a recent study by Kristof Hoorelbeke and colleagues (2015) at-risk students performed 10 sessions of cognitive control or placebo (visual search) training. They found:

  • Increase in cognitive control was related to increased resilience.
  • The CCT group was more resilient when confronted with a lab stressor.
  • CCT reduced brooding in confrontation with a naturalistic stressor at follow-up.

Their conclusion was that cognitive control training forms a preventive intervention for depression.

The current experimental study provides evidence for the effectiveness of a working memory based cognitive control training (CCT) in increasing resilience to depression in an at risk population.

 


 

Anxiety

Anxiety disorders are characterized by exaggerated worry and tension, often expecting the worst even when there is no apparent reason for concern particularly with respect to money, work, health, and relationships. Individuals suffering from anxiety may suffer sleep disorders, feel on edge, and be constantly monitoring for potential threats.

Lifetime prevalence of anxiety disorders in the US is around 30% – almost a third of the population. Half of all lifetime cases start by age 14 years and three fourths by age 24 years (1).

Brain Networks

Impairment of attentional control in the face of threat-related distractors is well established for high-anxiety individuals. And high trait anxiety impairs cognitive processes that need attentional control  even in the absence of threat-related stimuli. In high-anxious individuals there is reduced coupling between regions of the Cognitive Control Network  (CCN) including the pre-frontal cortex and parietal cortex resulting in less neural efficiency (2). Even in non-anxious individuals negative distraction leads to relative deactivation in the CCN (also known as Dorsal Executive System) and its decoupling from emotional response centres involving the amygdala called the Ventral Affective System (3). These two systems are also known as the ‘cold executive’ and ‘hot emotional’ systems. In normal functioning the CNN maintains attentional focus by regulating the emotional reactivity of the VAS  in a tightly coupled way (4).

 

ventral affective system

Figure 1. Neural systems involved in cognitive/executive (dorsal) vs. emotional (ventral) processing. The dorsal system includes brain regions typically associated with “cold” executive (ColdEx; color-coded in blue) functions, such as the dorsolateral prefrontal cortex (dlPFC) and the lateral parietal cortex (LPC), which are critical to the active maintenance of goal-relevant information in working memory (WM). The ventral system includes brain regions involved in “hot” emotional (HotEmo; color-coded in red) processing, such as the amygdala (AMY), the ventrolateral PFC (vlPFC), and the medial PFC.  MTL MS, medial temporal lobe memory system; OFC, orbitofrontal cortex; OTC, occipitotemporal cortex.

Working memory and executive control brain training can result in functional strengthening of the ‘cold executive’ CCN and its regulation of the ‘hot emotional’ VAS system. This in turn can reduce symptoms of anxiety.

Evidence for Efficacy of Brain Training for Anxiety Disorders

There have been no systematic meta-reviews of the efficacy of working memory and executive control brain training for anxiety and anxiety disorders. But several studies suggest that this kind of training programmes can be a promising new approach for the treatment of various anxiety disorders (5).

Working Memory Training

This recently published study by Dr Sari and colleagues looked at the effects of just three weeks of working memory (n-back) training on attention control in high anxiety individuals.

They found that:

  • Training resulted in better attention control measured by a resting state EEG (theta/beta ratio – an index of attention control).
  • There was better inhibition of emotionally charged distractions.
  • These training-related gains were related to lower levels of trait anxiety after the brain training.

As with the depression studies, training effects were substantial:

“Our results showed that …training related gains were associated with lower levels of trait anxiety at post (vs pre) intervention. Our results demonstrate that adaptive working memory training in anxiety can have beneficial effects on attentional control and cognitive performance that may protect against emotional vulnerability in individuals at risk of developing clinical anxiety.”

More recently, Hadwin and Richards (2016) showed that for adolescents, working memory training (CogMed) led to positive changes in symptoms of trait and test anxiety, increased inhibitory control and reduced attention to threat. Results were maintained at follow-up 3-4 months after the intervention.

 

Executive Control Training

Cohen and her colleagues, in a study published on Oct 28, 2015, in the journal Neuroimage, found that executive control training can reduce the brain’s emotional reactivity by changing the brain’s ‘hot emotional’ VAS circuitry (see figure above) to make it less responsive to threatening information.

‘Emotional reactivity’ results when emotionally charged information grabs attention and slows down higher order cognitive functioning such as decision-making. Emotional reactivity is known to be heightened in individuals suffering from stress-related emotional dysregulation such as depression or anxiety.

We can measure how emotionally reactive someone is by flashing a picture of a threatening picture just before a colored square, and measuring the reaction time for naming the color. The more emotionally reactive, the slower the reaction time – because the ‘threat’ information draws attention and slows down the decision-making.

mj green

Cohen and her colleagues looked at how 6 days of brain training (45 minutes per day) affected emotional reactivity in this reaction time task. Using fMRI they also looked at brain activity doing this task – both before and after the brain training.

They found that participants who did the interference training showed reduced activation in the amygdala – a brain structure strongly linked to emotional reactivity and conditioning.

And the more the amygdala was calmed, the less decision-making was slowed by threatening pictures. In other words, the less participants were distracted by threatening information, the better their emotional regulation while getting on with the task at hand.

There was also evidence that, after the training there was increased connectivity between the amygdala and regions of the frontal cortex (vlPFC in diagram above) that interact strongly with the Cognitive Control Network (Dorsal Executive System).

The evidence suggests that executive control training can dampen emotional reactivity and serve as a short-term and easy-to-implement treatment for individuals suffering from disorders characterised by emotion dysregulation – including both anxiety and depression.

 


Burnout

Stress-related exhaustion – which can be associated with depression and/or anxiety – has been linked to  cognitive impairments including:

  • executive functioning
  • attention 
  • episodic memory (memory for specific personal experiences)

Gavelin and colleagues (2015) have recently looked at the additional benefits of cognitive control brain training to a standard stress-rehabilitation program for patients diagnosed with exhaustion disorder (ED).

Results showed pronounced training-related improvements on:

  • Updating task (executive functioning)
  • Episodic memory
  • Subjective memory complaints
  • Levels of burnout

Effect sizes for everyday memory problems on three measures are shown below:

brain training for burnout

The findings suggest that process-based cognitive training may be a cost-effective intervention for burn-out.

 


Mood & Prevention

It is known that dorso-lateral prefrontal cortex  (part of the frontoparietal control network) and other widespread lateral prefrontal and medial prefrontal regions are activated to control negative emotions (Phan et al., 2005Belden et al., 2014).

Tacheuchi and colleagues (2014) have looked at the effects of working memory training on emotional states and related brain mechanisms. They found that compared with controls who did no working memory training, those who did WM training for 4 weeks showed reduced anger, fatigue, and depression. And they found WM training reduced activity in the left frontoparietal network. They also found reduced activity in the left posterior insula during tasks evoking negative emotion, which was related to anger.

They concluded that WMT can reduce negative mood and provide new insight into the clinical applications of WMT, at least among subjects with preclinical-level conditions.


 References

Cohen, N. et al. (2015). Using Executive Control Training to Suppress Amygdala Reactivity to Aversive Information. NeuroImage. Online publication date: Oct-2015. Abstract.

Gavelin, H. M. (2015).  Effects of a process-based cognitive training intervention for patients with stress-related exhaustion. 18, 5. 578-588. Abstract.

Hadwin, Julie A and Field, Andy P, eds. (2010) Information processing biases and anxiety: a developmental perspective.Wiley-Blackwell.

Hadwin, J. A., & Richards, H. J. (2016). Working Memory Training and CBT Reduces Anxiety Symptoms and Attentional Biases to Threat: A Preliminary Study. Psychopathology, 47. Full article.

Hoorelbeke, K. et al. (2015). The influence of cognitive control training on stress reactivity and rumination in response to a lab stressor and naturalistic stress. Behaviour Research and Therapy, 69. 1-1. Full article.

Iordan, A. D., Dolcos, S. & Dolcos, F. (2013). Neural signatures of the response to emotional distraction: a review of evidence from brain imaging investigations. Front. Hum. Neurosci. 7, 200. Full article.

Motter, J. N. et al. (2016). Computerized cognitive training and functional recovery in major depressive disorder: A meta-analysis. Journal of Affective Disorders , 189 , 184 – 191. Full article.

Sari, B. A. et al. (2015) Training working memory to improve attentional control in anxiety: A proof-of-principle study using behavioral and electrophysiological measures. Biological Psychology. Online publication date: Sep-2015. Abstract.

Takeuchi, H., Taki, Y., Nouchi, R., Hashizume, H., Sekiguchi, A., Kotozaki, Y., … Kawashima, R. (2014). Working memory training improves emotional states of healthy individuals. Frontiers in Systems Neuroscience, 8, 200. Article.

Turner, E. H., Matthews, A. M., Linardatos, E., Tell, R. A., & Rosenthal, R. (2008). Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. New England Journal of Medicine, 358(3), 252–260. Article.

 

 


Notes

There are three limitations in Motter and colleagues’ meta-analysis, aside from the relatively small number of studies (9) with only partially overlapping outcome measures.

One – the similarity of the brain training in some cases to the outcome measures. Do we get ‘near transfer’ or ‘far transfer’ from training? But while this may be of concern for cognitive-ability outcomes such as attention, this is not relevant to depression Symptom Severity, Daily Functioning and Global Functioning measures. These are all ‘far transfer’ effects.

Two – the problem of ‘placebo effects’ (expectancy or motivation effects) due to lack of active controls as the comparison groups against which to judge the effectiveness of the brain training. Expectancy and motivation can contribute to differential performance between the training and control group if there is no equivalent to a ‘placebo group’ in antidepressant medication studies. However, only 4 of thee 9 studies had no intervening task or treatment (Table 1). Others were administered peripheral vision tasks, or a non-adaptive n-back tasks, or Transcranial Direct Current Stimulation or antidepressant medication and so on. Brain training was effective in these studies.

Three – in some of the studies additional antidepressant treatments (medication, psychotherapy, tDCS) were administered alongside the brain training. But these were also administered to the the control groups, and concurrent treatment did not account for a significant amount of variance in the results. Interactions with other treatments may be at work that partly explain the effectiveness of the brain training. As the authors state: “it is possible that positive changes in cognitive functioning directly improves mood, or indirectly by enhancing the effects of ongoing treatments”.

 


Working Memory and Executive Control Training Apps

The company CogMed also provides working memory training tools with a scientific basis.

My own working memory and executive functioning brain training software implements a combination of working memory training (e.g. n-back) and executive function training. (e.g. interference control and task-switching for cognitive flexibility). This can be found at this website. I am happy to provide this software free of charge for any research or education related projects.

A free app resource for dual n-back is Brain Workshop. This provides variations of the dual n-back.

 

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