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Dr. Michael Merzenich: To harness Neuroplasticity for cognitive enhancement, we need to think “Fitness” more than “Games”

KavliPrize-Neuro(Edi­tor’s Note: In order to help read­ers famil­iar­ize them­selves with the work and think­ing of Dr. Michael Merzenich, one of the win­ners of the 2016 Kavli Prize in Neu­ro­science for ground­break­ing work on neu­ro­plas­tic­i­ty, we are con­dens­ing and repub­lish­ing the com­pre­hen­sive con­ver­sa­tion that Dr. Merzenich and Alvaro Fer­nan­dez had in 2009, in prepa­ra­tion for the inau­gur­al Sharp­Brains Vir­tu­al Sum­mit.)

Dr. Michael Merzenich, Emer­i­tus Pro­fes­sor at UCSF, is a lead­ing pio­neer in brain plas­tic­i­ty research. In the late 1980s, Dr. Merzenich was on the team that invent­ed the cochlear implant. In 1996, he was the found­ing CEO of Sci­en­tif­ic Learn­ing Cor­po­ra­tion, and in 2004 became co-founder and Chief Sci­en­tif­ic Offi­cer of Posit Sci­ence. He was elect­ed to the Nation­al Acad­e­my of Sci­ences in 1999 and to the Insti­tute of Med­i­cine in 2009.

(Alvaro Fer­nan­dez) There are many dif­fer­ent tech­nol­o­gy-free approach­es to harnessing/ enabling/ dri­ving neu­ro­plas­tic­i­ty. What is the val­ue that tech­nol­o­gy brings to the cog­ni­tive health table?

It’s all about effi­cien­cy, scal­a­bil­i­ty, per­son­al­iza­tion, and assured effec­tive­ness. Tech­nol­o­gy sup­ports the imple­men­ta­tion of near-opti­mal­ly-effi­cient brain-train­ing strate­gies. Through the Inter­net, it enables the low-cost dis­tri­b­u­tion of these new tools, any­where out in the world. Tech­nol­o­gy also enables the per­son­al­iza­tion of brain health train­ing, by pro­vid­ing sim­ple ways to mea­sure and address indi­vid­ual needs in each per­son­’s brain-health train­ing expe­ri­ence. It enables assess­ments of your abil­i­ties that can affirm that your own brain health issues have been effec­tive­ly addressed.

Of course sub­stan­tial gains could also be achieved by orga­niz­ing your every­day activ­i­ties that grow your neu­ro­log­i­cal abil­i­ties and sus­tain your brain health. Still, if the ordi­nary cit­i­zen is to have any real chance of main­tain­ing their brain fit­ness, they’re going to have to spend con­sid­er­able time at the brain gym!

One espe­cial­ly impor­tant con­tri­bu­tion of tech­nol­o­gy is the scal­a­bil­i­ty that it pro­vides for deliv­er­ing brain fit­ness help out into the world. Think about how effi­cient the drug deliv­ery sys­tem is today. Doc­tors pre­scribe drugs, insur­ance cov­ers them, and there is a drug store in every neigh­bor­hood in almost every city in the world so that every patient has access to them. Once neu­ro­plas­tic­i­ty-based tools and out­comes and stan­dard­ized, we can envi­sion a sim­i­lar sce­nario. And we don’t need all those drug stores, because we have the Inter­net!

Safe dri­ving seems to be one area where the ben­e­fits are more clear to see.

Yes, we see great poten­tial and inter­est among insur­ers for improv­ing dri­ving safe­ty, both for seniors and teens. Appro­pri­ate cog­ni­tive train­ing can low­er at-fault acci­dent rates. You can mea­sure clear ben­e­fits in rel­a­tive­ly short time frames, so it won’t take long for insur­ers to see an eco­nom­ic ratio­nale to not only offer pro­grams at low cost or for free but to incen­tivize dri­vers to com­plete them. All­state, AAA, State Farm and oth­er insur­ers are begin­ning to real­ize this poten­tial. It is impor­tant to note that typ­i­cal acci­dents among teens and seniors are dif­fer­ent, so that train­ing method­olo­gies will need to be dif­fer­ent for dif­fer­ent high-risk pop­u­la­tions.

Yet, most dri­ving safe­ty ini­tia­tives today still focus on edu­cat­ing dri­vers, rather that train­ing them neu­ro­log­i­cal­ly. We mea­sure vision, for exam­ple, but com­plete­ly ignore atten­tion­al con­trol abil­i­ties, or a dri­ver’s use­ful field of view. I expect this to change sig­nif­i­cant­ly over the next few years.

Can you sum­ma­rize what your recent research around brain train­ing sug­gests?

We have seen clear pat­terns in the appli­ca­tion of our train­ing pro­grams, some pub­lished (like IMPACT), some unpub­lished, some with healthy adults, and some with peo­ple with mild cog­ni­tive impair­ment or ear­ly Alzheimers Dis­ease (AD).

What we see in every case: 1) Despite one’s age, brain func­tion­ing can be improved, often with pret­ty impres­sive improve­ment in a short-time frame and lim­it­ed time invest­ed, 2) Basic neu­ro­log­i­cal abil­i­ties in 60–90 year olds that are direct­ly sub­ject to train­ing can be improved to the per­for­mance lev­el of the aver­age 20 or 30 or 40 year old, 3) Improve­ments gen­er­al­ize to broad­er cog­ni­tive mea­sures, and to indices of qual­i­ty of life, 4) Improve­ments are sus­tained over time…but that does not mean that they could not ben­e­fit from boost­er or refresh­er train­ing.

A major obsta­cle is that there is not enough research fund­ing for appro­pri­ate tri­als to address all of these issues, espe­cial­ly as they apply for the mild­ly cog­ni­tive­ly impaired (pre-AD) or the AD pop­u­la­tions. We’d wel­come not only more research dol­lars but also more FDA involve­ment, to help clar­i­fy the claims being made.

A key miss­ing ingre­di­ent is the wide­spread use of objec­tive assess­ments. What do you see in that area?

Unfor­tu­nate­ly, most researchers and pol­i­cy ini­tia­tives are still wed­ded to rel­a­tive­ly rudi­men­ta­ry assess­ments. For exam­ple, I recent­ly par­tic­i­pat­ed in meet­ings designed to help define a very-well-sup­port­ed EU ini­tia­tive on how cog­ni­tive sci­ence can con­tribute to drug devel­op­ment, in which most applied assess­ments and most assess­ments devel­op­ment were still paper-based. This is a major missed oppor­tu­ni­ty, giv­en the rapid­ly grow­ing devel­op­ment and avail­abil­i­ty of auto­mat­ed assess­ments.

I believe we will see more inde­pen­dent assess­ments but also embed­ded assessments…The FDA’s adop­tion of MATRICS as a stan­dard is a cru­cial step, because it pro­vides a clear set of bench­marks that apply for any drug or non-drug approach to treat­ment. We would like to see the FDA estab­lish sim­i­lar bench­marks for all major clin­i­cal indi­ca­tions in neu­ro­log­i­cal and psy­chi­atric med­i­cine.

It seems clear that neu­ro­plas­tic­i­ty-relat­ed tools will impact med­i­cine and men­tal health. Where and how do you think that may hap­pen first?

This may sur­prise peo­ple who haven’t been fol­low­ing the area close­ly, but I believe cog­ni­tive train­ing may well become a cru­cial part of the stan­dard of care in schiz­o­phre­nia over the next 3 or 4 years. With aca­d­e­m­ic part­ners at UCSF, Yale and Kon­stanz Uni­ver­si­ty, and through the devel­op­ment of pro­grams that effec­tive­ly address cog­ni­tive deficits that lim­it this patient pop­u­la­tion, we have already designed a train­ing pro­gram that is appro­pri­ate for eval­u­a­tion in a med­ical-device-direct­ed FDA tri­al. There is already agree­ment about the appli­ca­tion of the MATRICS neu­rocog­ni­tive assess­ment bat­tery for an FDA out­comes tri­al in this pop­u­la­tion, and NovaV­i­sion’s FDA approval of their stroke & TBI rehab strate­gies pro­vide any impor­tant FDA prece­dent.

If we talk about wider clin­i­cal prac­tice, we must rec­og­nize that many psy­chol­o­gists are attached to old­er forms of ther­a­py that don’t incor­po­rate con­tem­po­rary cog­ni­tive neu­ro­science find­ings, and that neu­rol­o­gists and psy­chi­a­trists are strong­ly phar­ma­ceu­ti­cal­ly ori­ent­ed, and in any event are great­ly pressed for time. Per­haps clin­i­cal prac­tice will only change once we have devel­oped the tools nec­es­sary to help pro­fes­sion­als mon­i­tor the brain func­tion and train­ing (treat­ment) sta­tus of the very large num­ber of patients that might typ­i­cal­ly be under their care.

That’s a very inter­est­ing point. How may remote mon­i­tor­ing and inter­ven­tions hap­pen?

We will prob­a­bly see hybrid mod­els emerge first. The clin­i­cian will, as usu­al, estab­lish a diag­no­sis and ini­ti­ate treat­ment in their office or clin­ic, prob­a­bly with the assis­tance of a trained ther­a­pist. At some point, the ther­a­py will con­tin­ue at home. The ther­a­pist and the super­vis­ing clin­i­cian would be able to remote­ly mon­i­tor the patien­t’s per­for­mance by the use of our Inter­net tools.

Only lat­er may full telemed­i­cine mod­els emerge, where per­haps a neu­rol­o­gist mon­i­tors the brain func­tion of sev­er­al patients using appro­pri­ate tools, and iden­ti­fies poten­tial per­son­al­ized pre­ven­tive inter­ven­tions with red flags that call for an office (or vir­tu­al) vis­it.

What else do you think will hap­pen over the next few years?

First, I believe we’ll need to focus on pub­lic edu­ca­tion, for peo­ple to under­stand the val­ue of tools with lim­it­ed face val­ue. One impor­tant aspect of this is the need to find bal­ance between what is fun and what has val­ue as a cog­ni­tive enhancer, which requires the activ­i­ties to be very tar­get­ed, repet­i­tive and slow­ly pro­gres­sive. Peo­ple need to think fit­ness as much or more than games.

Sec­ond, I believe the role of pro­vid­ing super­vi­sion, coach­ing, sup­port, will emerge to be a crit­i­cal one. Think about the need for hav­ing a piano teacher, if you want to learn how to play the piano and improve over  time. Tech­nol­o­gy may help fill this role, or empow­er and rich­ly sup­port real coach­es who do so.

My dream in all of this is to have stan­dard­ized and cred­i­ble tools to train the 5–6 main neu­rocog­ni­tive domains for cog­ni­tive health and per­for­mance through life, cou­pled with the right assess­ments to iden­ti­fy one’s indi­vid­ual needs and mea­sure progress. For exam­ple, I’d like to know what the 10 things are that I need to fix, and where to start. Assess­ments could either mea­sure the phys­i­cal sta­tus of the brain, such as the degree of myeli­na­tion, or mea­sure func­tions over time via auto­mat­ed neu­ropsych assess­ments, which is prob­a­bly going to be more effi­cient and scal­able and poten­tial­ly be self-admin­is­tered in a home health mod­el.

Mike, thank you very much once more for your time and insights.

My plea­sure.

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