Fletcher-Munson Curves, neurochemistry and drugs

[Survived Abortion]

First of all, this is not a question or discussion about how drugs change our perception of a the overall piece of music, but the fourier transform at the fundamental level.
Most people who have taken a variety of drugs will have noticed how some, if not all of them seem to affect how music sounds, to some degree.
Now, I studied psychoacoustics at university, amongst other music studies. The way we perceive the world through our senses is obviously a very tightly regulated system in the brain, encoded in our DNA/RNA.
However, we have the ability to temporarily or permanently alter those pathways in our brain responsible for how we make up reality in our heads. 'Equal-Loudness Curves' are the mathematical template which music producers, especially mastering engineers, use to get recorded music sounding spectrally balanced in a pleasing and realistic way when we listen to recorded sound...

My point - being so sensitive to these fluctuations as an engineer, I have noticed vast changes in Fletcher-Munson response during the use of certain drugs. In particular, Ketamine produces a vast spectral change in the perception of sound, a change which is actually more ear-fatiguing than normal. Benzodiazepines produce a beautifully sweetened fletcher-munson response. And so on and so forth.... Any neurochemist scholars or psychopharmacological peeps here - could you postulate any explanation for the changes at the bioneural level responsible for these alterations?

 

[wungchow]

I've noticed these effects too. I'm a music producer/composer. Cannabis tends to increase the euphoria produced by pleasing music. DXM/Ket drastically alter how the 'mix' of a song is perceived. Trazodone makes music seem much faster than it is!! When I listen to music I made on trazodone, it's always about 10 bpm slower than it should be.

 

[Survived Abortion]

^This speeding up/slowing down issue is intriguing. I've noticed that there are two variations on this. The first is as you said - the music actually sounds faster. The second is that the music plays at normal speed but seems to pass by much quicker or much slower.

I think maybe I should have generalized this thread more for all these audible anomalies, but I wanted to focus initially on this 'equal loudness' issue. Yes, DXM/Ket are definitely drugs that alter this, like as you said the mix of the song.

Could it be neurochemical, or is it all in the tention of the eardrums and other muscles in the ear canal etc.

 

[Survived Abortion]

I've not experienced DiPT, but from all the reports I have read, it sounds very much like the experience that one gets when going through heavy benzo withdrawal. (In that it totally screws with the way sound/music is interpreted, both tonally and temporally, and spectrally). So this is psychedelic...

Somebody must have an explanation for this. Surely...

 

[negrogesic]

I've noticed a "flattening" of notes after using 5-meo-dipt, DPT, and to a lesser extent LSD. With 5-meo-dipt this was nearly a full half-step, while with LSD it was slight but noticeable. After a large dose of 5-meo-dipt, my absolute sense of pitch was slightly off for well over a week, and I was worried it was permanently gone.

The timbre of music can be changed by many psychedelics, particularly in respect to the decay and sustain of a given note, but this can vary significantly by compound. For example, AMT appeared to reduce the sustain and increase the attack (with a short decay) of a given note, while 5-meo-dipt did almost the complete opposite.

I have no clue about the mechanism through which any of these things occur...

 

[Ham-milton]

With psilocybin and 4-HO-DIPT (which is nothing like DiPT, mind you) I notice that music seems to drop just about half an octave. I don't have perfect pitch, but I'm pretty good with this, and it seems like it's just about half an octave lower- which sounds really odd.

With DMT, though, notes seem to go up, but not nearly as dramatically as they go down. It also matters a lot less with DMT though, as I can rarely stand music under it's influence, everything sounds odd and kind of tinny.

Never used AMT, but I'm willing to bet that I'd experience music about the same as I do with DMT.

With THC though, well, it's odd. I don't know what changes, but something does. It's as if I'm able to find more depth to everything about the music. Sounds stupid, I know. I'm better able to pick out the various instruments and 'hold' each bit in my head seperate from the rest. I don't know that it increases euphoria, but it definitely changes something. What exactly, I don't know.

I'm gonna go play with fruity loops now.

 

[wungchow]

I think traditional euphoriants such as cannabis and alcohol simply make music sound more "awesome" then it really is. I think this is the sole explanation for why many recording artists make increasingly shitty music after their debut album. Too much drugs.

 

[MattPsy]

For a biochemical/pharmacological explanation, it doesn't require too big a stretch of the imagination to expect that signalling regulation of said Fourier-Transform neurons will result in altered frequency analysis. If the firing threshold of those neurons is altered, or their downstream signalling is boosted or inhibited etc, then you're going to get different output, and hence a different salient experience of sound.
I suppose this how DiPT might operate, it being more selective for this effect than others, perhaps because of different distribution of it in the brain or possibly even a difference in expressed receptors in the audio processing regions of the brain (so DiPT is a better agonist there than it is normally) ?
Things like functional selectivity and/or ligand dissociation rate may give rise to the ligand-selective effects ie. always an octave lower or whatever with ligand A and always an octave higher with ligand B.

 

[nuke]

I never noticed much in the way of sound perceptions on psychedelics or dissociatives oddly. Well, that is to say, my perception of music changes, but the music itself still sounds the same.

Things like functional selectivity and/or ligand dissociation rate may give rise to the ligand-selective effects ie. always an octave lower or whatever with ligand A and always an octave higher with ligand B.

From TiHKAL, the perception of sound and harmony caused by DiPT acts in a non-linear fashion. Things that would normally sound harmonic, like a major chord, not only sound lower but also cacophonious. I suspect something not so simple is going on, like the modulation of a yet to be discovered protein receptor by a small-molecule agonist/antagonist/partial agonist (in this case, DiPT), that is somehow involved in frequency perception between the ear and the auditory cortex.

A good question is: why does DiPT seem to cause this but MiPT doesn't?

 

[MattPsy]

Why does LSD cause hallucinations but lisuride doesn't? (rhetorical question)
Though yeah the difference between MiPT and DiPT is smaller.

Yeap I also agree that a heretofore unknown receptor may be involved. It seems pretty unlikely that the 5-HT2A receptor will be involved.

Also, just to clarify, are you thinking that the modulation that takes place will take place in the pathway of audio signals in between the ear and processing cortex? Or in the processing action itself? (all speculative, of course)

 

[Ham-milton]

Yeap I also agree that a heretofore unknown receptor may be involved. It seems pretty unlikely that the 5-HT2A receptor will be involved.

Why do you say this? High doses of 5HT2a agonists (4-ho-DMT especially) have had me talking to God, seeing cars melt and bugs covering everything- why is it any less likely that when I heard the Bishop's voice turn into Satans (on the day the pope died, no less) it was due to some other receptor?

 

[MattPsy]

Because there are lots of other 5-HT2A agonists that *don't* produce the marked and distinct audio modifying properties of DiPT?

 

[Survived Abortion]

For a biochemical/pharmacological explanation, it doesn't require too big a stretch of the imagination to expect that signalling regulation of said Fourier-Transform neurons will result in altered frequency analysis. If the firing threshold of those neurons is altered, or their downstream signalling is boosted or inhibited etc, then you're going to get different output, and hence a different salient experience of sound.
I suppose this how DiPT might operate, it being more selective for this effect than others, perhaps because of different distribution of it in the brain or possibly even a difference in expressed receptors in the audio processing regions of the brain (so DiPT is a better agonist there than it is normally) ?
Things like functional selectivity and/or ligand dissociation rate may give rise to the ligand-selective effects ie. always an octave lower or whatever with ligand A and always an octave higher with ligand B.

Wow. Thankyou, this is an excellent explanation. And very concisely put .
I really must look into this further. It could have made an excellent dissertation were I still at Uni.

 

[Survived Abortion]

Also, just to clarify, are you thinking that the modulation that takes place will take place in the pathway of audio signals in between the ear and processing cortex? Or in the processing action itself? (all speculative, of course)

The type of audio 'perception-distortion' occurring would dictate this, surely. To be more specific, if there is a marked alteration in the 'depth' of the music, i.e. the stereo image, emotional impact, and thought processes in reactions to specific instruments and tones, then it could reasonably be surmised that neuronal pathways responsible are further inward towards the emotional center of the brain - the amygdala and the limbic system.
However, if the properties of music perceived are changed on a surface level of pure fourier-transform, i.e. the music 'sounds' different, like frequency-band loudness has changed, or perhaps attacks, decays etc. are radically altered, - it's logical to assume that neural pathways which deal with sound before they reach emotional areas of the brain are involved. Therefore, they would be closer to the stages between the ear and the processing cortex.

This would be analogous to abberations in vision due to head trauma... Capgras Syndrome, which cut's off completely the emotional reaction from the fusiform-gyrus. If the emotional reaction were not severed, but altered, then reactions to familiar faces and objects would be very strange. But if it was the Fusiform Gyrus itself which was altered, then it would simply be a case of misinterpreting the raw image data.

Am I making sense?

 

[Ham-milton]

Because there are lots of other 5-HT2A agonists that *don't* produce the marked and distinct audio modifying properties of DiPT?

But we know that at high enough doses, all of them can do this. It seems much more likely to me that it's a distribution thing.

 

[leungkachong]

ON THE PRE-CORTICAL PARTS OF THE PATHWAY

Seems like you guys are missing some of the information in the lower parts of the pathways (pre-auditory cortex). Don't forget that there are only 3 neurons between the sensory source and the thalamus in most pathways (hearing has a couple extra). In the case of hearing:

1- Lower frequencies are recieved via spiral ganglion cells; upper frequencies by the cochlear hair cells.

2- From here, it's mono-synaptic/one neuron (CN VIII, cochlear nerve) to the cochlear nucleus in the medulla. Each neuron carries a single 'frequency', and the cochlear nucleus is tonotopically organized (one end is lowest frequency, other end is the highest frequency.. and its gradual in between).

3a- Next you get mono-synaptic projections to the ipsilateral (same-side) and contralateral (other-side) superior olivary nucleus. The time delay between getting to the ipsilateral and contralateral SON gives a lot of your sound localization ability.

(3b- Other projects from the cochlear nucleus go to the nucleus of the lateral lemniscus... don't worry abt this, these go to the same place as 3a anyways)

4- Another one-neuron path to the inferior colliculus, where you get a whole bunch of localization data integrated (vertical and horizontal get put together, and also a lil' mixing with visual data from the nearby superior colliculus)

5- From here it heads (one neuron) to the thalamus, which relays almost all sensory data to the cerebral cortex. Specific area, medial geniculate nucleus.

6- One neuron to the auditory cortex, where ALL that information kept it's tonotopic organization! One end of the auditory cortex is lowest frequency, and the other end highest. Impressive, eh?

Now the **POINT**: There's nooooo way you're going to have an effect on frequency/pitch perception (as it is not encoded by what the neuron SAYS, but actually by which neuron is FIRING) at the beginning of the auditory cortex or below. Tonotopic organization guaruntees this; and though the one neuron signalling only (next in path) one neuron is a bit simplified, it's good enough. Also, your also using GABA, Glu, NE, ACh in these neurons, so cut out any dreams of a serotonergic explanation down here.

All this above is just a relay station which is going to be essentially pharmacologically neutral until you get the the two cortices (right hemisphere more than left), with pitch encoded by which neuron(s) fire, and any other information still 'raw'... meaning only encoded by the rate/pattern of the firing neuron. You're on the right track thinking simple characteristics come from earlier stages of processing, but the processing you're interested in is happening *from the primary auditory cortex and above*.

------------------------------------------------------------------

ON THE CORTICAL PARTS OF THE PATHWAY (a basic intro on the parts of the brain you can't just dissect to understand, aka - the good stuff)

Now if I was not a pedagogous jerk, I would have pointed out the folly in logic before making you learn the entire pre-cortical auditory pathway.

The (tonotopically organized, to make analysis easier) primary auditory cortex first recieves the sound, and is necessary for you to be consciously aware you're hearing. The secondary auditory cortex is important in rhythm, understanding musical relationships and such... and the third is where you get the full musical experience that make you're limbic/insular cortices tingle with joy. (Note: Each area of cortex has generally 6 layers of neurons, horizontal projections within each single layer, and projections going in most any imaginable fashion. So don't expect to disentangle that mess). So you're interested in secondary and tertiary AC.

When imagining/hearing a song in your heard, you're looking at mostly tertiary auditory cortex activity, however primary AC activation produces real-life full-out hallucinations of actual sound being heard/percieved. Apparently, schizophrenics have marked primary AC activity (which will cause the secondary and tertiary to analyze/respond) while hallucinating.

Neat things I found: 1- Whichever neurons fire to signal that you recognize a sound causes a gamma activity on an EEG. 2- Extensive musical training doesn't just change the nature of processing in the AC, it actually produces more damned activity. 3- Parts of prefrontal cortex, which project to amygdala also respond to tones.

 

[MattPsy]

So for audio modifications in specific frequency ranges we're looking more at modification of the firing rate and behavior (threshold firing, refractory period maybe, et cetera - although the retention of audio modification after the psychedelic effects of DiPT have ended suggests some activity beyond simple receptor agonism - perhaps phosphorylation of receptors via secondary messengers or gene transcriptional changes...) of specific groupings of tonotopic neurons..? Interesting. I wonder why it affects some regions more than others, as what i've heard about DiPT is that it's not a simple modification (ie. not just a overall tone-shift).

 

[Survived Abortion]

ON THE PRE-CORTICAL PARTS OF THE PATHWAY

Seems like you guys are missing some of the information in the lower parts of the pathways (pre-auditory cortex). Don't forget that there are only 3 neurons between the sensory source and the thalamus in most pathways (hearing has a couple extra). In the case of hearing:

1- Lower frequencies are recieved via spiral ganglion cells; upper frequencies by the cochlear hair cells.

2- From here, it's mono-synaptic/one neuron (CN VIII, cochlear nerve) to the cochlear nucleus in the medulla. Each neuron carries a single 'frequency', and the cochlear nucleus is tonotopically organized (one end is lowest frequency, other end is the highest frequency.. and its gradual in between).

3a- Next you get mono-synaptic projections to the ipsilateral (same-side) and contralateral (other-side) superior olivary nucleus. The time delay between getting to the ipsilateral and contralateral SON gives a lot of your sound localization ability.

(3b- Other projects from the cochlear nucleus go to the nucleus of the lateral lemniscus... don't worry abt this, these go to the same place as 3a anyways)

4- Another one-neuron path to the inferior colliculus, where you get a whole bunch of localization data integrated (vertical and horizontal get put together, and also a lil' mixing with visual data from the nearby superior colliculus)

5- From here it heads (one neuron) to the thalamus, which relays almost all sensory data to the cerebral cortex. Specific area, medial geniculate nucleus.

6- One neuron to the auditory cortex, where ALL that information kept it's tonotopic organization! One end of the auditory cortex is lowest frequency, and the other end highest. Impressive, eh?

Now the **POINT**: There's nooooo way you're going to have an effect on frequency/pitch perception (as it is not encoded by what the neuron SAYS, but actually by which neuron is FIRING) at the beginning of the auditory cortex or below. Tonotopic organization guaruntees this; and though the one neuron signalling only (next in path) one neuron is a bit simplified, it's good enough. Also, your also using GABA, Glu, NE, ACh in these neurons, so cut out any dreams of a serotonergic explanation down here.

All this above is just a relay station which is going to be essentially pharmacologically neutral until you get the the two cortices (right hemisphere more than left), with pitch encoded by which neuron(s) fire, and any other information still 'raw'... meaning only encoded by the rate/pattern of the firing neuron. You're on the right track thinking simple characteristics come from earlier stages of processing, but the processing you're interested in is happening *from the primary auditory cortex and above*.

------------------------------------------------------------------

ON THE CORTICAL PARTS OF THE PATHWAY (a basic intro on the parts of the brain you can't just dissect to understand, aka - the good stuff)

Now if I was not a pedagogous jerk, I would have pointed out the folly in logic before making you learn the entire pre-cortical auditory pathway.

The (tonotopically organized, to make analysis easier) primary auditory cortex first recieves the sound, and is necessary for you to be consciously aware you're hearing. The secondary auditory cortex is important in rhythm, understanding musical relationships and such... and the third is where you get the full musical experience that make you're limbic/insular cortices tingle with joy. (Note: Each area of cortex has generally 6 layers of neurons, horizontal projections within each single layer, and projections going in most any imaginable fashion. So don't expect to disentangle that mess). So you're interested in secondary and tertiary AC.

When imagining/hearing a song in your heard, you're looking at mostly tertiary auditory cortex activity, however primary AC activation produces real-life full-out hallucinations of actual sound being heard/percieved. Apparently, schizophrenics have marked primary AC activity (which will cause the secondary and tertiary to analyze/respond) while hallucinating.

Neat things I found: 1- Whichever neurons fire to signal that you recognize a sound causes a gamma activity on an EEG. 2- Extensive musical training doesn't just change the nature of processing in the AC, it actually produces more damned activity. 3- Parts of prefrontal cortex, which project to amygdala also respond to tones.

I'm very grateful for this. Cheers bud.
So it seems my initial suspicions that some effects could be attributed to alterations in pre-auditory cortex activity are not blanket-wide. However, it could still account for GABAergic drug actions, and Na+ and K+ efficiency before it heads to the Auditory Cortex-amygdala complex. (Such as Carbamazepine effects, Benzo withdrawals, Ketamine - and so on).
Hmmm...

 

[psychedelicate]

i found this very interesting, props