From lost memories to brain drugs, a neuroscientist explains

Are we turning a corner in our understanding of the brain? Abode of Chaos, CC BY

The Conversation organised a public question-and-answer session on Reddit in which Barbara Sahakian, professor of Clinical Neuropsychology at Cambridge University, discussed subjects from depression to cognitive enhancing drugs. Here are the highlights.


How do nature and nurture interact in neurological disorders, especially depression?

Sahakian: Neuropsychiatric disorders can have high heritability, particularly, for example, Attention Deficit Hyperactivity Disorder (ADHD), schizophrenia and bipolar disorder. With Ian Goodyer and colleagues, we have been studying the genetic and environmental interactions in children which lead to cognitive changes, such as negative attentional bias and oversensitivity to negative feedback in adolescents who develop depression.

What are you currently working on that you are excited about?

Sahakian: Research on games that will improve cognition, such as memory, in people with schizophrenia or mild cognitive impairment, the very early stages of Alzheimer’s disease. There is also the Medical Research Council (MRC) deep and frequent phenotyping study, led by Simon Lovestone, where we are determining biomarkers, including cognitive ones such as CANTAB PAL for early detection of Alzheimer’s disease and for tracking disease progression. This will be very useful for assessing the efficacy of neuroprotective drug treatments. I am also excited by our Wellcome Trust research work … on understanding the neurobiological basis of Obsessive Compulsive Disorder and on using modafinil as an add-on to improve cognition in depression.

What is the most effective cognitive enhancing drug you know of?

Sahakian: Our studies have mainly examined methylphenidate, atomoxetine and modafinil. Earlier studies of ours also examined cholinesterase inhibitors in patients with Alzheimer’s disease. Recently, we have been conducting studies determining whether atomoxetine can improve cognitive and behavioural problems in patients with Parkinson’s disease. We are also looking at whether atomoxetine might prove a treatment for substance misuse. Modafinil has shown cognitive enhancing effects in Attention Deficit Hyperactivity Disorder (ADHD).

What is your opinion on the ethics of using drugs for cognitive enhancement?

Sahakian: I work on these drugs in order to improve cognition and functionality in patients with neuropsychiatric disorders. My first concern in regard to the increasing lifestyle use of cognitive enhancing drugs, such as modafinil and Ritalin, by healthy people are the safety issues. Many people are accessing these drugs via the internet, which is a very dangerous way to get hold of prescription only drugs, since you do not know what you are buying.

As a society, we do not think enough about the benefits and harms of increasing use of cognitive enhancing drugs. It reflects on our society that people may feel obliged to take drugs to keep up, rather than to enhance their cognition through lifelong learning or exercise. We should think about stress reduction, sleep, mindfulness and other activities that will help us with our cognition and well-being.

There are certainly many people who these drugs may be beneficial for … for example doctors working nights. We definitely need novel and more effective cognitive enhancing drugs for patients … for example, to treat the episodic memory problems in people with Alzheimer’s disease or schizophrenia.

How similar/dissimilar are we on a neurological level?

Sahakian: Our brains do show individual differences. Interestingly, this presents problems sometimes when conducting research studies or clinical treatments on the brain. It is important that individual differences are taken into account. You may be aware of the study of taxi drivers, by Eleanor Maguire and colleagues, where they demonstrated increases in the volume of the hippocampus, an area of the brain associated with navigation, depending on the length of time they had worked as a taxi driver.

What is the greatest challenge you faced along the path to professor and how did you overcome it?

Sahakian: I am frequently asked [this], particularly by women scientists. The most challenging, but also most rewarding, was balancing my career with children.

My 11 tips for young neuroscientists:
1. You are all different. You must live your life. You want different things in life to realise your potential.
2. Keep learning throughout life – develop a good skill base. Be open to new ideas.
3. Have confidence in yourself.
4. Focus on your achievements, not your failures – celebrate your successes.
5. Learn from your mistakes – you will make them (even when experienced) but do not be too harsh on yourself.
6. Do not be too harsh on others.
7. Be resilient; be positive.
8. Focus on the future, not on the past.
9. Be flexible.
10. Engage the public in science.
11. Have a vision of a better future for society – realise this through contributing to science and medicine policy development.

Army [veteran] here – how close are we to treating PTSD effectively?

Sahakian: There is, fortunately, currently a great deal of research around Post Traumatic Stress Disorder (PTSD). As you may know, Cognitive Behavioural Therapy (CBT) is recommended by the NHS for treating PTSD. There are also research studies using the drug propranolol as a treatment for PTSD. Also very exciting, but as yet not developed for use in humans, is the work on re-consolidation of memories. The idea is to bring the unwanted memories in to a labile state and then use a drug to erase them.

What does society need to do to promote brain health – pharmaceutical based enhancement/prevention, lifestyle changes?

Sahakian: Exercise and learning promotes new brain cells in an area of the brain called the hippocampus, which is very important for memory. This is one of the first areas in the brain to be damaged by Alzheimer’s disease. Therefore, it is important that we engage in exercise and learning throughout our life course to ensure that our brains function as best as possible.

Depression is a very common and debilitating disorder. In moderate to severe depression, antidepressant drugs are used as a treatment. These drugs will put people in the right state to recover from depression, but the person has to learn and re-learn that circumstances have changed and that they can become more positive about the present and the future. In other words, the person with depression has to take an active role in their treatment, and not a passive role. The drug will facilitate improvement, but it also requires an active effort on the individuals part.

Since we know that 75% of mental health disorders start before the age of 24, it is important that the government tries to identify mental health problems in children and adolescents. Ideally, we could prevent these using biomarkers.

What treatments are most effective for early-caught Alzheimer’s?

Sahakian: With others, I published some early proof of concept studies on the cholinesterase inhibitors which are now treatments for Alzheimer’s disease (AD). Aricept/Donepezil are used to improve the cognitive symptoms in AD. This class of drugs is particularly useful for treating concentration and attention problems. We need new effective drugs which will treat the episodic memory problems seen early on in AD. Currently in development are neuroprotective agents which will halt the underlying disease process. For this reason, it is important that we detect patients in the very earliest stages.

How plastic is the brain?

Sahakian: We know that young brains are plastic. In the adult human brain, the hippocampus shows plasticity. Cognitive training in people with schizophrenia increases not only cognition, but also psychosocial functioning.

Motivated behaviour is extremely important for carrying out activities of daily living. In neuropsychiatric disorders, motivation is frequently impaired, for example in patients with schizophrenia and negative symptoms. Modafinil as an add-on to the anti-psychotic medication improves cognition in patients with schizophrenia. We have shown that modafinil enhances task-related motivation in healthy people. These are very encouraging findings, as apathy can be a serious problem for functionality and well-being in patients with neuropsychiatric disorders.

How long will take until we can understand the brain from a biological perspective?

Sahakian: I am very optimistic about what we can achieve in the next 10 years. We have two very important human brain projects, one originating in the US (the BRAIN Initiative) and one in Europe – the Human Brain Project (HBP).

A very important delivery from the HBP will be methods for working with huge data sets and for connectome analysis. Connectomics, the study and production of connectomes (neural maps of the brain) will combine a number of techniques for mapping and studying connectivity within the brain. Understanding these connections could revolutionise our understanding of disorders where there is an abnormality within the connection of brain networks, including disorders such as autism and schizophrenia. As I have [pointed out before] there is not a single more important problem than understanding the brain in health and disease.

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