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Contents lists available at ScienceDirect

Neuroscience and Biobehavioral Reviews

jou rnal homepage: www.elsevier.com/locate/neubiorev

Commentary

What do experts think we should do to achieve brain health?

∗

Barbara J. Sahakian

University of Cambridge, Department of Psychiatry and MRC/Wellcome Trust Behavioural and Clinical Neuroscience Institute, Cambridge, UK

a r t i c l e i n f o

Article history:

Received 6 December 2013

Received in revised form 28 March 2014

Accepted 2 April 2014

Keywords:

Expert ideas in neuroscience, innovation,

technology and brain health

Neuropsychiatric disorders

The aim of this commentary is to discuss how we could achieve dementia in the UK (http://www.alzheimers.org.uk/). Due to an

brain health for a flourishing society within the next decade. This increase in the ageing population, institutionalized care costs for

will require integration and expertise from a number of different dementia is expected to rise. The rise in numbers of people cared

areas, including neuroscience, innovation and technology. Experts for in institutions will increase from 224,000 in 1998 to 365,000 in

from these fields have contributed their ideas which are presented 2031. There is a growing acknowledgement that as mental health

in Table 2. disorders become chronic and relapsing they may impact on the

There is not a single more important problem than understand- lifecourse and become difficult, if not impossible to treat. The same

ing the brain in health and disease. Mental ill health is the single is true for addiction where the behaviour of the drug addict has

largest cause of disability in the UK (http://www.dh.gov.uk/prod become habitual and compulsive. It will be essential to initiate

consum dh/groups/dh digitalassets/documents/digitalasset/dh any treatments early if they are to be successful. For example,

123993.pdf, No health without mental health; Fineberg et al., treatments for people with substance abuse will need to begin

2013). In addition to the distress and disability to the individual, before the transition to habitual, compulsive behaviour seen in

mental health disorders are also extremely expensive to society addiction, with its accompanying underlying neural changes.

and governments. For example, the wider costs of mental illness The Foresight Project on Mental Capital and Wellbeing empha-

in England are estimated at £105.2 billion each year with two sized biomarkers for prevention, early detection and early effective

common neuropsychiatric disorders, depression and dementia, treatment to enhance mental capital and wellbeing (Beddington

costing approximately £23.8 billion and £17 billion in total annual et al., 2008). Biomarkers include cognitive, neuroimaging, genetic,

costs, respectively. Indeed, recently neuroscience and mental cerebrospinal fluid and blood based measures. In the Prime Min-

health policy have emphasised the importance of early detection ister David Cameron’s outstanding speech on dementia, given in

and early effective treatment for people who develop a mental March 2012, he remarked on the importance of early detection

health problem (Collins et al., 2011; Insel et al., 2012; Beddington and early treatment stating that, “Only around 40 per cent of those

et al., 2008; Sahakian et al., 2010). One reason for this is that these with dementia know they have it.” He also noted that, “You can

problems are both common and are associated with large costs of help people live independently for longer or even put the brakes

disability. For example, 16% of adults in Britain have a common on their decline”. Early detection is cost-effective for the National

mental disorder, such as depression, at any one time (Jenkins Health Service (NHS). Each patient with Alzheimer’s disease who

et al., 2008). In England in 2007, lost earnings due to depression receives early assessment and treatment saves society £7741, com-

amounted to £5.8 billion and lower productivity accounts for a pared to no early assessment and treatment. Of this, £3600 is in

further £1.7–£2.8 billion. There are currently 800,000 people with direct healthcare costs (Getsios et al., 2012).

Cholinesterase inhibitors (e.g. donepezil) are currently avail-

able and approved by the National Institute for Clinical Excellence

∗ (NICE) for the treatment of patients within the mild and moderate

Tel.: +44 1223768506.

E-mail address: [email protected] stages of Alzheimer’s disease. Recent evidence has indicated that

http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

0149-7634/© 2014 Elsevier Ltd. All rights reserved.

Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

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2 B.J. Sahakian / Neuroscience and Biobehavioral Reviews xxx (2014) xxx–xxx

psychological stress combined with genetic risk can lead to a nega-

tive cognitive view of the world in adolescents which is consistent

with biomarkers seen in depression (Owens et al., 2012) and this

way of thinking may predispose to depression. It is not only for

depression that top down cognitive control is important but also

for a range of neuropsychiatric disorders, including attention deficit

hyperactivity disorder (ADHD) and schizophrenia. ADHD is a highly

heritable and disabling condition characterised by core cognitive

and behavioural symptoms of impulsivity, hyperactivity and/or

inattention. ADHD affects 5–6% of children worldwide and is the

most prevalent neuropsychiatric disorder of childhood. ADHD has

important implications for education provision, long-term social

outcomes and economic impact (Chamberlain and Sahakian, 2006;

Chamberlain et al., 2007a,b). For example, long-term studies indi-

cate that if not treated effectively, it is associated with poorer

long-term outcomes, including educational dropout, job dismissal,

increased accident rates, criminal activities and substance abuse

and other mental illness. Over 50% of people with childhood ADHD

still have symptoms as adults. In addition to problems in cognitive

control, ADHD children have deficits in working memory. Work-

ing memory is a core cognitive function that is used for any higher

Fig. 1. Neuroimages of normal brain development from 5 to 20 years of age. Our level ‘executive’ task such as planning or problem solving. It allows

brains are still in development through adolescence and young adulthood. Permis-

us to manipulate information and material in our mind while we

sion for use of this image was provided by Jay N Giedd MD, Chief, Brain Imaging

need it and then to discard it out of our working or ‘online’ space

Section, Child Psychiatry Branch, National Institute of Mental Health. This research

when it is no longer needed. Working memory is important for

work was conducted at the National Institute of Mental Health, NIH, USA. Source:

Provided by Jay N Giedd. at least four reasons. First, it has a strong relationship to fluid or

creative intelligence and also to crystallized intelligence or intel-

ligence quotient (IQ). Second, correlation studies support a close

this class of drugs may also prove beneficially in the more advanced, relationship between working memory and science achievement.

severe stage of the disease (Howard et al., 2012). This symptomatic Third, working memory measures at the start of formal education is

treatment improves attention and concentration (Eagger et al., a more powerful predictor of subsequent academic success than IQ

1991; Sahakian et al., 1993) but other novel symptomatic treat- (Alloway and Alloway, 2010). Finally, working memory is impaired

ments are needed which address the memory problems subserved in a number of neuropsychiatric disorders, including ADHD and

by neural networks which critically include the hippocampal for- schizophrenia. Therefore, improving working memory with phar-

mation. Recent cognitive enhancing drugs which target symptoms macological, psychological or cognitive treatments could have a

(such as episodic memory) rather than diagnostic categories (e.g. big impact on functionality and wellbeing. A shift to novel drug

Alzheimer’s disease or schizophrenia) represent a novel approach development for the treatment of neurobiologically based specific

to drug development which is likely to be successful since it is symptoms, such as working memory dysfunction or impulsivity,

instantiated in a neurobiological approach. Highly important is the rather than diagnostic categories, such as schizophrenia and ADHD,

recent development of neuroprotective drugs (e.g. Solanezumab, will be crucial. An effective treatment for impulsivity could be used

Lilly), now in phase three clinical trials, for the treatment of patients for ADHD, mania and substance abuse (Insel et al., 2012; Sahakian

with Alzheimer’s disease. These drugs will actually halt the disease et al., 2010).

process, rather than treat symptoms only. It is therefore essential Cognitive enhancing drugs, such as methylphenidate or

that people with mild cognitive impairment who are just devel- modafinil, can improve performance of healthy people as well

oping Alzheimer’s disease are detected so that they can be treated as those with ADHD or schizophrenia (http://royalsociety.org/

while they still maintain a good quality of life and their cognition, policy/projects/human-enhancement/workshop-report/; Lynch

wellbeing and functionality at work and at home are still intact. et al., 2013). In studies using positron emission tomography (PET),

They must receive effective neuroprotective treatment before there methylphenidate has also been shown to increase efficiency in

is extensive neuropathological damage to their brains. the brain network activated during performance of a working

Psychiatric disorders are disorders of cognition. Many psychi- memory task by healthy people (Mehta et al., 2000). This increased

atric disorders are of neurodevelopmental origin with an onset efficiency includes areas of prefrontal cortex known to be involved

or prodromal stage in childhood or adolescence. Indeed, mental in higher level ‘executive tasks’. Modafinil not only improves

disorders disproportionately affect the young, with 75% of illness performance on a working memory task in healthy people, but

having an onset before 24 years of age (Kessler et al., 2012). The also enhances task-related motivation (Muller et al., 2013). That

cognitive manifestations of mental health disorders include dis- is, people find doing the task more enjoyable. Therefore, drugs,

torted attentional biases, aberrant learning, memory impairments, such as modafinil, may promote motivation for completing tasks

dysfunctional reward systems and lack of top down cognitive con- that people have been putting off doing, for example studying

trol by prefrontal cortex. In recent years, studies based at the for exams, preparing long documents or dissertations. Modafinil

National Institute of Mental Health (NIH, USA) have shown that may also promote task-related motivation in patient groups with

our brains are still in development into late adolescence and early apathy or negative symptoms, such as schizophrenia (Scoriels

young adulthood (Fig. 1; Gogtay et al., 2004). It is perhaps not et al., 2012). These cognitive enhancing drugs act by affecting

surprising, therefore, that many neuropsychiatric disorders have chemicals in the brain that modulate cognition and behaviour.

symptoms of impaired top down cognitive control by prefrontal Another of these drugs is atomoxetine, which relatively selectively

cortex over behaviour. The brain, particularly, the prefrontal cor- increases the chemical in the brain noradrenaline.

tex is still developing late into adolescence and therefore especially Atomoxetine improves cognitive control in both healthy peo-

vulnerable to environmental insults and stressors. Indeed, early ple and those with ADHD (Chamberlain et al., 2007a,b, 2010).

Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

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Table 1

Important tools in neuroscience and mental health.

Technique Method and potential Reference

Modelling

iPS cell-derived models Induced pluripotent stem cells are an emerging tool for modelling Inoue, H., Yamanaka, S., 2011. Clin. Pharmacol. Ther., 89, (5) pp.

disease. These cells can recapitulate the disease process in the cells 55–61

of individual patients, and could also act as a screening mechanism

for therapeutic strategies. In this way, iPS technologies will be

important in personalised medicine.

Genetic techniques

New-generation Monoclonal antibodies are a class of therapeutic molecule that Buss, N.A., Henderson, S.J., McFarlane, M., Shenton, J.M., de Haan,

antibodies have revolutionised the treatment of oncology since their L., 2012. Monoclonal antibody therapeutics: history and future.

introduction in the 1980s. However, due to their size they are not Curr. Opin. Pharmacol., 12(5) pp. 615–622

able to pass the blood brain barrier and have therefore had little

impact in neuropsychology. Recently new generation antibodies,

such as fragments and bispecifics, have begun to be developed that

promise to finally open the door to this game changing class of

drugs for diseases such as Alzheimer’s and Multiple Sclerosis.

Gene therapy Viral based gene transfer systems are a useful tool in both research Coune, P.G., Schneider, B.L., Aebischer, P., 2012. Cold Spring Harb.

and gene therapy. Treatments for central nervous system disorders Perspect Med., 2, (4) doi: 10.1101/cshperspect.a009431

could be treated with viral vector approaches, such as in Palpant, N.J., Dudzinski, D. 2013. Zinc finger nucleases: looking

Huntington’s and Parkinson’s disease. New techniques for gene toward translation. Gene Ther., 20(2) pp. 121–127

editing such as zinc finger nucleases, TALENs and CRISPRS are

emerging with great potential for treating congenital diseases.

Engineered receptors Designer Receptors Exclusively Activated by Designer Drugs Ferguson, S.M., Neumaier, J.F., 2012. Grateful DREADDs:

(DREADDs) are engineered receptors, which are activated by Engineered Receptors Reveal How Neural Circuits Regulate

otherwise inert, small, drug-like molecules. DREADDs are Behavior. Neuropsychopharm. Rev., 37, pp. 296–297

currently used by many labs to remotely and non-invasively

control neuronal signalling. Although safe and effective viral

vectors for delivery of engineered receptors into humans still need

to be refined, DREADDs may one day provide an alternative

treatment option for neuropsychiatric disorders.

Stem cell therapy Stem cells in regenerative medicine are a rapidly growing field. Sinden, J.D., Muir, K.W., 2012. Stem cells in stroke treatment: the

The first successful clinical trials for stem cell implants in disease promise and the challenges. Int. J. Stroke., 7(5) pp. 426–434

have now occurred, such as the Pilot Investigation of Stem Cells in Cyranoski, D., 2013. Stem cells cruise to clinic. Nature, 494, pp. 413

Stroke. The first trial to transplant induced pluripotent stem cells Nakamura, M., Okano, H., 2013. Cell transplantation therapies for

into humans to treat macular degeneration are now underway and spinal cord injury focusing on induced pluripotent stem cells. Cell

may soon be starting for spinal cord injury. Res. 23, pp.70–80

Optogenetics Optogenetics has been used to study the neurotransmitter systems Tye, K.M, Deisseroth, K., 2012. Optogenetic investigation of neural

in the brain and understand the circuits involved in healthy brain circuits underlying brain disease in animal models. Nat. Rev.

and in animal models of disorders, such as in autism, depression Neurosci. 13(4) pp. 251–266

and addiction. Optogenetics can also be used alongside stem cell Tønnesen, J., Parish, C.L., Sørensen, A.T., Andersson, A., Lundberg,

studies, such as for Parkinson’s disease, to investigate whether the C., Deisseroth, K., et al., 2011. Functional integration of grafted

implanted stem cells that are altered to express a light sensitive neural stem cell-derived dopaminergic neurons monitored by

protein can release dopamine. optogenetics in an in vitro Parkinson model. PLoS ONE 6(3) pp. e17560

Imaging

Diffusion spectrum The development of DSI within the MRI field can measure diffusion Wedeen, V.J., Hagmann, P., Tseng, W.Y., Reese, T.G., Weisskoff,

imaging (DSI) directions from individual axonal tracts, allowing for mapping R.M., 2005. Mapping complex tissue architecture with diffusion

individual nerve fibres. This technique will be an important driving spectrum magnetic resonance imaging. Magn. Reson. Med. 54(6)

force for advancing connectome mapping. pp. 1377–1386

Magnetic resonance With 7 Tesla MRI equipment in use and these machines advancing Nishimoto, S., Vu, A.T., Naselaris, T., Benjamini, Y., Yu, B., Gallant,

imaging (MRI) up the Tesla scale, this technology can allow metabolic processes J.L., 2011. Reconstructing visual experiences from brain activity

to be studied at an individual neuron level. This could have great evoked by natural movies. Curr. Biol. 21(19) pp. 1641–1646

potential in developing and monitoring successful treatments.

fMRI has now been used by researchers to decode activity from the

visual cortex and reconstruct this into video sequences.

Positron emission PET is a widely used technique for measuring activity relating to Chien, D.T., Bahri, S., Szardenings, A.K., Walsh, J.C., Mu, F., Su, M.Y.,

tomography (PET) brain function, offering a method for early, non-invasive detection Shankle, W.R., Elizarov, A., Kolb, H.C., 2012. Early clinical PET

of disease. The development of novel radioligands could be imaging results with the novel PHF-Tau eadioligand [F-18]-T807. J.

important in diagnosing disease, such as Alzheimer’s disease. Alzheimers Dis., Doi: 10.3233/JAD-122059

‘Omics’

Connectomics Connectomics will combine a number of techniques for studying NIH, 2012. Human Connectome Project

connectivity within the brain. Understanding these connections http://www.humanconnectome.org/ [date accessed: 04/09/2012]

could revolutionise our understanding of how the brain functions Sporns, O., Tononi, G., Kotter, R., 2005. The human connectome: a

and the areas affected in ‘connectopathies’ including disorders structural description of the human brain. PLoS Comput. Biol. 1(4)

such as autism, schizophrenia and Alzheimer’s disease. e42

Genomics and Rapidly progressing genomic and proteomic techniques offer huge ENCODE Project Consortium, 2012. An integrated encyclopedia of

Proteomics potential for understanding brain disorders. These are essential for DNA elements in the human genome. Nature 489, 57–74.

understanding the changes in gene and protein expression that Geschwind, D.H., Konopka, G., 2009. Neuroscience in the era of

underlie the disease symptoms. However, due to the great power functional genomics and systems biology. Nature 461(7266) pp.

of these techniques they will be of greatest use when data 908–915

processing techniques catch up.

Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

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4 B.J. Sahakian / Neuroscience and Biobehavioral Reviews xxx (2014) xxx–xxx

Table 1 (Continued ).

Technique Method and potential Reference

Pharmacogenomics With rapid advances in genetic screening, iPS cell modelling and McMahon, F.J., Insel, T.R., 2012. Pharmacogenomics and

novel therapeutic developments, the potential for personalized medicine in neuropsychiatry. Neuron 74(5) pp.

pharmacogenomics may finally be realised. Effective treatments 773–776

could be tailored to groups or the individual reducing numbers of

nonresponders to treatment plans.

Neurotechnology

Bioinformatics With so many neuroscience techniques gathering large amounts of Geschwind, D.H., Konopka, G., 2009. Neuroscience in the era of

data, it is the storing, processing and analysis of these sets that is functional genomics and systems biology. Nature 461(7266) pp.

of vital importance to all fields. The harnessing and mining of these 908–915

large-scale data sets is progressing quickly but many other

techniques are still waiting on bioinformatic advances, such as

machine learning, to realise their power. Methods for network

analysis offer the promise of integrating data from different scales,

which will be essential for connectomics, genomics and linking

pathways in the brain to function and disease.

Brain–machine Brain–machine interfaces (BMIs) link the electronic signals in the Welberg, L., 2012. Brain–machine interfaces: restoring movement

interface brain to a computational device, decode them and then translate in a paralysed hand. Nat. Rev. Neurosci. 13, pp. 360–361

them into a command for a robotic device. Such technology has

existed for decades but recent advances in electrophysiological

techniques has permitted the simultaneous recording of over 2000

neurons, thus permitting the decoding of far more sophisticated

behaviours. This approach is now being developed to not only

control robotic prosthesis but also restore function to otherwise

paralysed muscles.

Mobile health The mobile phone is becoming one of the greatest tools in medical Luxton, D.D., McCann, R.A., Bush, N.E., Mishkind, M.C., Reger, G.M.,

research. Existing apps already permit the live monitoring of 2011. mHealth for mental health: Integrating smartphone

patients following treatment and with the development of every technology in behavioral healthcare. Professional Psychol. Res. Pract.

more sensitive and miniaturised sensors it is foreseeable that the 42(6) pp. 505–512

smart phone of the future will be able to monitor everything from

a person’s oxygen consumption to neural activity.

The most important advance will be the integration of many of these technologies.

Source: Jacqueline P Robbins, BSc, MRes, King’s College London and Martin Ducker, BSc, MPhil in Biosciences Enterprise, University of Cambridge.

Neuroimaging studies using pharmacological fMRI has shown that and new technology, such as mobile phones, the internet, the cloud

the site of action of atomoxetine critically involves the right inferior will be essential for detecting and monitoring of wellbeing and

frontal gyrus (Chamberlain et al., 2009). This brain area has been brain health. The same approach in terms of healthy diet, quality

shown to be important for cognitive control and stopping impulsive sleep and exercise is important for developing resilience in the face

actions. Impulsive actions include such behaviours as a child charg- of stress and as promotive factors for good brain ageing.

ing out into the street to retrieve a football rather than stopping by Education and new learning are known to enhance cognitive

the edge of the road to check whether a car is coming or contin- reserve and learning and exercise have been shown to increase neu-

uing to push another child in the lunch queue when the teacher rogenesis in the brain in important areas such as the hippocampus,

has asked the child to stop. Novel pharmacological, psychological an area key to memory and known to deteriorate in Alzheimer’s

and cognitive treatments are in development. We can check their disease (Olson et al., 2006; Eadie et al., 2005; Gould et al., 1999;

efficacy by observing changes in behaviour but also by detecting Orrell and Sahakian, 1995).

changes in the brain via neuroimaging techniques. For example, a Cognitive function is associated with better wellbeing

meta analysis of cognitive training in people with schizophrenia has (Beddington et al., 2008). Science, technology, higher levels

shown improvements in cognition and also psycho-social function- of cognitive ability and education are related to increased pros-

ing with a moderate effect size (Wykes et al., 2011). These benefits perity, such as gross domestic product (The Royal Society, 2010;

of cognitive training are important particularly as they impact on Rindermann, 2008). Importantly, investment in mental health

the functionality of these patients. Studies of the brains of healthy has provided substantial economic benefit in the past and should

people during cognitive training of working memory has shown continue to do so in the future (Health Economics Research Group,

both changes in brain activation and also in dopamine receptors Office of Health Economics, RAND Europe, 2008).

(Klingberg, 2010; Olesen et al., 2004; McNab et al., 2009). These Working on good brain health is something that should start

important studies illustrate the neurobiological basis to improve- with the nutrition and wellbeing of the mother prior to birth. Early

ments in cognitive function following training. Cognitive training environment has been shown to be crucial to good development.

using games which run on iPads or mobile phones will be an impor- At school, children should be taught about the factors that affect

tant new development to make training exciting and fun. The use of good brain health, such as healthy diet, exercise and learning for

‘serious’ games in people with schizophrenia and in the healthy to promoters and substance abuse and chronic and severe stress, for

improve forms of memory or to help promote social cognition and detractors.

social interaction in children with autism or Asperger’s syndrome It is especially important to develop resilience in those early

would be exciting new innovations. years. Since 75% of mental health illnesses start before 24 years

Realizing the future potential of neuroscience over the next 10 of age, it is crucial to detect the development of these illnesses

years will require a conceptual shift to focussing on good brain so they can be treated early and effectively (Kessler et al., 2012).

health. In the same way that we look after our bodies through Over the next 10 years, there will be significant advances in under-

healthy eating, exercise and monitoring and detecting physical ill- standing the neural basis of resilience. To date, the majority of

ness onset through health check ups and screening, individuals research effort has focussed on treatment of patients with chronic

need to be as attentive to their minds and wellbeing. Using current and relapsing mental health disorders. There is a great need to

Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

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G Model

NBR-1936; No. of Pages 19 ARTICLE IN PRESS

B.J. Sahakian / Neuroscience and Biobehavioral Reviews xxx (2014) xxx–xxx 7 to

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

G Model

NBR-1936; No. of Pages 19 ARTICLE IN PRESS

8 B.J. Sahakian / Neuroscience and Biobehavioral Reviews xxx (2014) xxx–xxx are the

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

G Model

NBR-1936; No. of Pages 19 ARTICLE IN PRESS

B.J. Sahakian / Neuroscience and Biobehavioral Reviews xxx (2014) xxx–xxx 9 a

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

G Model

NBR-1936; No. of Pages 19 ARTICLE IN PRESS

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

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G Model

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B.J. Sahakian / Neuroscience and Biobehavioral Reviews xxx (2014) xxx–xxx 11 all

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

G Model

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12 B.J. Sahakian / Neuroscience and Biobehavioral Reviews xxx (2014) xxx–xxx in of

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

G Model

NBR-1936; No. of Pages 19 ARTICLE IN PRESS

B.J. Sahakian / Neuroscience and Biobehavioral Reviews xxx (2014) xxx–xxx 13 the are

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

G Model

NBR-1936; No. of Pages 19 ARTICLE IN PRESS

14 B.J. Sahakian / Neuroscience and Biobehavioral Reviews xxx (2014) xxx–xxx of

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

G Model

NBR-1936; No. of Pages 19 ARTICLE IN PRESS

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

G Model

NBR-1936; No. of Pages 19 ARTICLE IN PRESS

16 B.J. Sahakian / Neuroscience and Biobehavioral Reviews xxx (2014) xxx–xxx It

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

G Model

NBR-1936; No. of Pages 19 ARTICLE IN PRESS

B.J. Sahakian / Neuroscience and Biobehavioral Reviews xxx (2014) xxx–xxx 17 M

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002

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18 B.J. Sahakian / Neuroscience and Biobehavioral Reviews xxx (2014) xxx–xxx

understand the healthy, creative brain and how new discoveries

and innovations are formed in the mind (see, e.g. Lawrence et al., Government Patient Advocacy Universities and

Groups Research Institutes

2008). Keeping a healthy mind is an active process and it will

(eg Alzheimer s (Academics)

Societ y)

require working at it everyday. It is far better to detect mental

health problems early than to let them slowly develop over time

UK Mental Health

without treatment. For example, the duration of untreated psy- Games Industry

Charity

chosis in schizophrenia is related to worsening of cognition and Good Brain Health

and Wellbeing

symptoms (Amminger et al., 2002; Chang et al., 2013; Joyce et al.,

for All of Society

2002). For those who do develop a mental health problem, early Cognition and

Wellcome Trust

effective treatments are needed. These may be pharmacological, Medical Devices

psychological, cognitive and combined. Patients will need to take

Com puting and

an active role in their treatments to ensure they retain good cog- Medical Research Communicatio n

Council Technology

nition and functionality and not respond passively to treatments,

Pharmaceutical Industries

as though they have no role in recovery. For example, learning Industry

and relearning in depression is important following both phar-

macological and cognitive behavioural treatments (Roiser et al.,

Fig. 2. The impact of neuroscience, innovation and technology: brain health in a

2011). Treatment resistance is relatively frequent in depression,

flourishing society.

whereby there is inadequate response following antidepressant

drug treatment (Fava, 2003; Fava and Davidson, 1996). By patients

innovation and technology spearheaded by Dr. John Williams aims

taking an active role in learning and relearning, it may be that

to stimulate engagement between those with expertise in neuro-

response to treatment improves. Antidepressant treatment in com-

science, bioinformatics and entrepreneurs and industries, including

bination with cognitive behavioural treatment (CBT) may facilitate

the pharmaceutical, games, computing and technology ones.

this learning process. Furthermore, novel fast acting antidepressant

In the UK, we have great expertise in a range of relevant disci-

drugs are in development (e.g. drugs altering NMDA receptor func-

plines that could be integrated to promote both good brain health

tion directly such as ketamine or indirectly; Zarate et al., 2006). In

and to stimulate the economy. Currently, we are not realizing the

addition, antidepressant drugs which improve depressive symp-

potential, but through policy makers engaging with relevant dis-

toms, cognition and functionality are also in development (e.g.

ciplines and key stakeholders, this could easily be achieved. There

multi-model activity profile). Given how common depression is in

are stakeholders keen to facilitate these developments within the

society, early detection and early effective treatment are key to pre-

entrepreneurial pockets of Silicon Fen in Cambridge, London-based

serving functionality, as chronicity and relapse are associated with

companies and also Oxford and Manchester, as well as elsewhere.

poorer cognition. The new concept of monitoring our brain health

Mental health, like good physical health, has to be worked at. It is

should reduce stigma in regard to mental health problems. In the

not something that can just be expected to happen without active

future, symptoms which are on a continuum in common disorders

participation by society and government. However, with the impact

such as depression and ADHD, for example sadness and impulsivity

of neuroscience, innovation and technology, brain health in a flour-

respectively, may be considered as problems of daily living.

ishing society can be achieved within the next 10 years.

Understanding the neurobiological basis of brain function in

health and disorder is essential. With our current and novel neu-

Disclosure statement

roscience innovations, tools and techniques (Table 1 ) and well

thought out concepts for how this can be achieved, great progress

Barbara Sahakian consults for Cambridge Cognition, Servier and

is possible within a 10 year framework (Table 2 ). These concepts

Lundbeck. She holds a grant from Janssen/J&J. She has share options

for rapid progress include understanding the neural basis of phar-

in Cambridge Cognition.

macological and psychological treatment, defining the underlying

neurobiology of disease processes, identifying new molecular tar-

gets for treatment and promoting knowledge of the neural basis Acknowledgements

of resilience. This research will require a mixed funding model of

large scale studies with extensive data sharing and smaller, creative I thank Sir John Beddington, previous Government Chief Sci-

and future-vision proof-of-concept studies. Novel training pro- entific Adviser, for inviting me to write this article and Sir Mark

grammes are needed which train young neuroscientists who can Walport, Government Chief Scientific Adviser, for permitting its

cross-talk and interact with other relevant disciplines to truly real- publication. I thank all those Experts who contributed to Table 2,

ize the potential of neuroscience to unlock brain health and create Jacqueline P Robbins and Martin Ducker for design and execution of

healthcare opportunities. Realization will rely on effective integra- Table 1 and Jay N Giedd for providing Fig. 1. I also thank Jacqueline

tion and collaboration between basic and clinical neuroscientists P Robbins, Martin Ducker, Clare Killikelly, Muzaffer Kaser, Joalice

in academia and industry and entrepreneurs in bioinformat- Stark, Andrew Blackwell and Jennifer Barnett for discussion.

ics, machine learning, brain–machine interface, games–industry,

mobile and tablet industries and nanotechnology (see Fig. 2). References

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Please cite this article in press as: Sahakian, B.J., What do experts think we should do to achieve brain health? Neurosci. Biobehav. Rev.

(2014), http://dx.doi.org/10.1016/j.neubiorev.2014.04.002