
Modafinil-Induced Changes in Functional Connectivity of Healthy Elderly Subjects - LolWolf
http://journal.frontiersin.org/article/10.3389/fnagi.2017.00085/full
======
hashmymustache
Ah, resting state functional connectivity. Still not sure I believe most of
the broad-stroke conclusions, but an interesting area.

For those unfamiliar, a healthy brain has what is called neurovascular
coupling where the amount of blood flow into local clusters of neurons (order
of millimeters) is adjusted based on demand (order of seconds). Simple
optimization strategy. With MRI T2* imaging we are able to measure blood flow
because the ratio of oxy-/deoxy-hemoglobin subtly alters the magnetic field.
So if you take a picture of the brain every 2 seconds you get "blood flow" and
if the average signal in 2 areas have a similar shape, we say they are
"functionally connected." Just good to keep in mind because it's an area of
research particularly prone to misunderstanding.

~~~
marmaduke
> if the average signal in 2 areas have a similar shape, we say they are
> "functionally connected."

not so hard to understand:

The "functional" is because these analysis were usually applied to a specific
task condition, thus function specific.

"similar shape" or "connectivity" is operationalized by correlation, though
there are many other ways.

------
iandanforth
Warning personal anecdote. I briefly took this drug to help with excessive
sleep and sleepiness. It had a paradoxical effect where I felt more alert but
was actually experiencing micro-naps. This very nearly caused me to get into a
serious car accident. Please be careful if you're thinking about this drug as
part of a nootropic regimen.

~~~
davymac
Get yourself checked for sleep apnea

~~~
rhizome
Apnea more than narcolepsy?

------
golergka
A lot of people in this thread are exchanging advice about ibcreasing mental
capacity and alertness. I have a question about this.

Do you guys honestly feel that you're not smart or concentrated enough? Or are
you just trying to improve these traits to the max and beyond because they're
considered to be virtious in the culture around you?

~~~
teddyh
I am similarly baffled by the tolerance for (even illegally obtained) drugs
which apparently exist in this community. In another discussion here¹ about a
similar topic I wrote the following:

> If you have “ _an Everest of work_ ”, the solution is to _get less work_ ,
> not to take drugs. Be the person you are.

①
[https://news.ycombinator.com/item?id=8868035](https://news.ycombinator.com/item?id=8868035)

~~~
golergka
Even if the drugs are completely safe and don't have any drawabacks, my
question still stands.

------
et2o
> "Present findings provide functional data supporting the hypothesis that
> modafinil can modulate the cortico-cerebellar connectivity of the aging
> brain"

Did anyone doubt this at the start of the study? I bet Tylenol modulates
cortico-cerebellar connectivity. Pretty weak conclusion. I hate to be so
critical, but I'm not sure what is added. Drawing real-world implications is
likely impossible, which admittedly may not have been the authors' goal.

------
andy_ppp
Just as a counterpoint to all this "yay modafinil"; for me it's horrendous, I
get a headache feel queasy immediately. It's a chemical feeling like your
brain being coated in plastic. A lot like taking too much caffeine but without
some of the edginess and instead a feeling of dread replaces the caffeine
high.

Getting work done while feeling ill is more, not less difficult!

------
lnanek2
Considering on-label use is to combat sleepiness, would have been interesting
to see more than just a placebo control. E.g. vs. caffeine or vs. a good
night's rest vs. staying up all night. Maybe sleep vs. no sleep the night
before provides the same thing.

~~~
manarth
The fMRI happened 3 hours after the participants dose, so sleep vs. no sleep
wouldn't affect the results (you would reasonably expect the sleep vs. no
sleep to be randomly distributed between participants, without being unduly
biased to one cohort).

    
    
      Study participants received a single-dose of modafinil or a placebo pill.
      All subjects then underwent two fMRI scans, performed before and 3 h after
      drug (or placebo) administration.

~~~
johndubchak
When does Modafinil reach its full after taking a dose? I take it for sleep
apnea and I don't really feel 3 hours is a sufficient time to measure its
effects.

------
kyledrake
> "Present findings provide functional data supporting the hypothesis that
> modafinil can modulate the cortico-cerebellar connectivity of the aging
> brain"

I would love it if someone more knowledgeable of neuroscience explained what
this meant and what the potential implications could be.

~~~
jonnycomputer
Functional connectivity is just temporally correlated neural activation
(technically for fmri we are measuring blood oxygenation, but whatever). So we
might have regions a, b, c and d, and find that a and b tend to be co-
activated, but that c tends to de-activate when a or b are activated, while
d's activity is uncorrelated with any of the others. For example, insula and
dorsal anterior cingulate cortex are usually positively corellated with each
other, but negatively correlated with regions of the default mode network.
Modulation just means that the manipulation, in this case modafinil, changed
the correlation between neural activation in different brain regions, in this
case between cortical regions and the cerebellum.

------
jv0010
Modafinil has changed my life - I can't even explain how it helped me setup
and complete projects. I would say he best way to word the feeling is
'clarity' when one is using this. Worth a try

~~~
RyJones
I am 100% an unabashed fan of Provigil/modafinil. I think it should be
available OTC. Even though I have a prescription, it's $30/dose to fill it in
the states. I can buy it from India for ~$1/dose.

~~~
brookside
FYI - It's about a dollar a dose at Costco.

------
JumpCrisscross
N=24. Intriguing, but not evidence--taken alone--to effect behavioral changes
by.

~~~
coretx
Also: It's mentioning a chunk of the biochemical chain yet there is no clear
mention of causality regarding modafinil itself and that what is observed.

~~~
danielfoster
Surprisingly little is known about modafinil's activation chain,
unfortunately.

------
thepumpkin1979
I took Modafinil 200mg for a few weeks, definitely felt a boost but couldn't
stand the headaches. Also Modafinil made me more sharp during the day but my
work hours got too short, my brain was dead after 8 hrs of intense work. Then
I went to a psychiatrist and got diagnosed with ADD. Now I take
methylphenidate/ritalin 10mg, I split the tablet in two and take one starting
my day and one after lunch. It's magic. I can now work for 10+ hrs a day and
sometimes easily push for 14 hrs. It's really impressive.

~~~
ageofwant
Mate, you need to acquire a life. If you can't make do with absolutely maximum
7.5 hours of "work" a day you are entirely missing the point of living. You
are not excelling, or even succeeding, you are failing.

If you insist on being a slave, be sure to charge at max for the finite hours
you are selling, three to four times your normal rate beyond 7.5. And here is
something you think you knew but don't: Young time is more precious than old
time. Each hour before 35 is worth 3 hours after 35. This because experiences
are new, senses are heightened, live is intense.

Take it from a retired high priest: Don't burn your life on this altar of
bullshit.

~~~
Nav_Panel
> _Young time is more precious than old time. Each hour before 35 is worth 3
> hours after 35. This because experiences are new, senses are heightened,
> live is intense._

This is a depressing comment. Can you not have new, high intensity experiences
past age 35? Is losing this an inherent part of aging? Or do many just choose
to avoid new experiences after a certain point?

~~~
dwaltrip
I don't buy it. There is so much amazing shit in this universe, and it's so
difficult to get a proper perspective on it all. I honestly expect to enjoy
life more once I hit 35, as my understanding and perspective should be much
deeper, and I'll have made further progress on understanding how to live a
balanced and fulfilling life (at least, in a way that works for me).

I will also likely have acquired more financial resources and additional
connections with like minded folks, which should enable interesting projects
and adventures.

I'm basing this largely on how the past 5 years have gone, and the
understanding I have developed during that time (from age 22 to 27). I also
fully reserve the right to adjust this forecast 5 years from now :)

------
justlurkinNP
As an NP, I am glad someone shared this. My husband is a computer programmer,
saw this and thought, "oh this is your area of practice"

I have seen many good results with modafinil and elderly patients who are not
waking up well status post stroke. It doesn't always work, especially if the
stroke was huge, but there is something very heartwarming about worried family
members becoming ecstatic when their loved one wakes up and people are hugging
you in gratitude for prescribing it :' )

------
gotothedoctor
Protip: Modafinil is prescribed by doctors for ADD (& narcolepsy). Instead of
risking many things (examples: counterfeit or poisoned pills, being ripped
off, being arrested, or even just dealing with bitcoin), why not just go to
the doctor, get a legal prescription, and fill it at the pharmacy?

~~~
nommm-nommm
Lol. I had to fight my insurance for about six months through several levels
of appeals to get them to pay for it for off label use. And it costs, IIRC,
$700 a month out of pocket.

~~~
namlem
Modafinil is generic. If you have a prescription, you can just buy it for
cheap online from Canada.

~~~
fudged71
Which site do you recommend in Canada?

~~~
brookside
I've said said elsewhere in this thread, but the cost is about a dollar a pill
at Costco. (Costco is amazing.)

------
rebuilder
So my wife was on modafinil for a time, due to being very sleepy for unknown
reasons. The doctors figured it was better than whatever stims they had her on
before. Within a year or so of starting her on modafinil, they told her to
discontinue use because there are indications that long-term regular use
causes neurological damage.

I don't know what their sources were for that, and it seems likely the doctors
would be very conservative in prescribing experimental drugs, so there was
probably an abundance of caution in play there. That said, the long-term side
effects really are not well understood at all, so I'd think twice before
making a regular habit of modafinil use.

------
AJRF
I have been experimenting with moda for a few months. Started of on 100mg and
was smashing through my workload, just due to being generally less chatty or
interested in shooting the shit with co-workers.

My next batch I went for 200mg's to see how that affected me. Made me super
moody, fidgety and I would get agitated when something didn't go right for me
straight away. 100mg seems to be the right amount for me. Everyone else I
asked about 200mg said they had the same side effects.

I also don't use it much now, tending to take it once every 2 weeks to crush
out some work. Wary of dependence on it, and also what it's doing to my brain.

------
majormajor
To give another anecdote about focus-related chemicals, this one from a former
amphetamine (adderall)/ methylphenidate (ritalin) taker (by prescription) from
high school to the first year or so post-college.

In high school I tried caffeine to get focus, but it never worked well. This
was largely caffeine from soda. After seeing a therapist and a psychiatrist,
and doing a combo of stimulants for ADD + good-study/work-habit-building work
suggested by the therapist, was able to get through school much more
successfully than before. It gave a much clearer feeling, long-lasting (with
extended release variants of the drugs) focus than soda. Really quite
remarkable.

But I was never super thrilled with the tolerance building. A few days cold
turkey would reset things, but I was pretty useless for those days (of the
lying in bed watching TV and eating cheetos all day variety). This got harder
after college, when the only available times were weekends, and I wanted to be
more social. I had some concerns with some of the potential long-term health
effects, too.

I managed to wean myself off, and rely on the good habits it had helped me
built, but work was definitely more of a chore after that. Then I got into
coffee and green tea - at first, in fairly sweet sugar+creamer or latte form.
This was still sort of a jittery focus, similar to from soda. Eventually,
though, I started drinking black coffee and straight green tea (no rhyme or
reason to which one on a given day, just my two forms of caffeine of choice).

For me, the difference between "caffeine from straight coffee or tea" and
"caffeine from heavily sweetened sugary beverage" was enormous. My jitters
mostly came from the sugar levels. Couple that with more and more studies
suggesting potential positive health benefits from both straight coffee and
tea, and I'm feeling better overall for sure now. It's not _quite_ the same as
the magic productivity pill of amphetamines, but it's good enough for me now.

The other major thing that changed for me over the years was my interest in
the material. High school and first-few-years college work can be bland, and
good habits were supremely helpful here as well. Don't wait until the last
minute, don't do a few 14-hour day binges to get caught up or crank something
out quick and dirty, etc. Between learning that, and working my first few jobs
to find roles that had more natural appeal to me, I have much less need for
supplements than I used to anyway.

------
BuenosAir
I sometimes do Phenylpiracetam which is another nootropics to get works done
(for exams for example), but when I do it while programming, by the end of the
day I'm totally brain-dead, does this also happen with Modafinil ?

~~~
beaconstudios
Sometimes you can end up with energy debt after modafinil - if you get a lot
done while wired you may find yourself exhausted after it wears off.

------
mrcactu5
nope. I come from one of the world's producers of coffee, Puerto Rico.
Starbucks give me a break. I've seen better stuff at in the grocery aisle.

~~~
contrahax
congratulations

------
johnyzee
For an alternative to modafinil, I would like to take the opportunity to
recommend trying ginseng.

I take it as gelatine capsules (good quality from a serious vendor), one every
day. It takes a couple of weeks before it kicks in for me, but from then on it
has a distinct effect - I can think about programming problems with a lot more
clarity than usual, even when tired at the end of the day. Quite weird really.
Traditionally one would run a three month course, then stay off for a couple
of months before starting again.

There is always the possibility of placebo effect, but I've tried a lot of
things and this one feels real. There are also real scientific studies showing
enhanced mental acuity from using ginseng [1][2][3].

Of course is has the benefit of being a natural remedy (and legal, if you care
about that).

[1]
[https://www.ncbi.nlm.nih.gov/pubmed/20676609](https://www.ncbi.nlm.nih.gov/pubmed/20676609)

[2]
[https://www.ncbi.nlm.nih.gov/pubmed/16401645](https://www.ncbi.nlm.nih.gov/pubmed/16401645)

[3]
[https://www.ncbi.nlm.nih.gov/pubmed/20737519](https://www.ncbi.nlm.nih.gov/pubmed/20737519)

~~~
mrfusion
Can you recommend a brand?

~~~
johnyzee
The brand I use is from a local producer. Generally I would avoid anything
that is well-advertised, those brands seem to usually contain lower grade or
less active ingredient. You should look at the amount of ginsenosides. The one
I use contains 16 mg per capsule.

