Importantly, dopamine medications did not help with symptoms as much in these patients with more "off-target" effects...

...indicating that they may be contributing to variability in clinical response in patients with Parkinson's disease

(6/9)

We found that some patients had a strong "off-target" effect of dopamine medications - i.e., an increase in beta rhythms in dopamine-rich cortical regions

(5/9)

We hypothesized that these "off-target" effects of dopamine therapies may be reducing the effectiveness of the drug in some people

To test this, we developed a new approach that combines PLS and neuromaps to measure off-target medication effects with pharmaco-MEG

(4/9)

These changes were associated to one another: degeneration of the noradrenergic LC was reflected in alpha increases in fronto-motor areas

And(!!) This relationship was strongest in regions of the cortex that are most sensitive to norepinephrine - converging evidence for a noradrenergic basis

(6/n)

We used MEG to measure cortical alpha rhythms and neuromelanin-sensitive MRI to quantify degeneration of the LC

Mirroring previous research, we saw increased alpha oscillations and decreased LC neuromelanin in patients with PD

(5/n)

Final first-author paper from my postdoc w/ the brilliant @sylvainbaillet.bsky.social + crew!

We find converging evidence for a pathway b/w norepinephrine ➡️ cortical alpha rhythms ➡️ cognitive dysfunction in #Parkinson's disease

academic.oup.com/brain/advanc...

🧵👇

(1/n)

New pre-print! 🎉

www.medrxiv.org/content/10.1...

We use a MEG with a PLS-neuromaps "search" of off-target cortical effects of dopamine therapies in patients with #Parkinson's disease

A strong beta-rhythmic activation of dopamine-rich cortices in response to medication ▶️ worse clinical response

We'll be stationed on the Burnaby campus

Not exaggerating when I say it's one of the most beautiful campuses I've ever visited - on top of a mountain and surrounded by old forests

And with downtown Vancouver accessible by transit - what's not to love?!

New preprint! 📢

We combine MEG and neuromelanin-sensitive MRI of the locus coeruleus to show a noradrenergic basis for altered alpha rhythms in #Parkinson's disease

w/ Victoria Madge, Ted Fon, Alain Dagher, Louis Collins, and @sylvainbaillet.bsky.social

www.medrxiv.org/content/10.1...

In contrast, increased cortical thinning in norepinephrine transporter-rich brain regions intuitively signals *impaired* motor abilities

(6/8)

Changes in cortical neurophys are dependent on the densities of acetylcholine, serotonin, mu-opioid, and cannabinoid receptors/transporters

Interestingly, these alignments are related to *preserved* cognitive and psychiatric health across patients

(5/8)

Using a new approach to co-localization analysis, we test the alignment of PD-related alterations in cortical thickness and neurophys w/ the #neuromaps multi-atlas

Broadly, we find that cortical alterations in PD are *organized along neurochemical boundaries*

(4/8)

Via spatial contextualization w/ neuromaps, we show this gradient organizes along neurochemical and functional boundaries:

-slowing is compensatory in association regions in dopamine & serotonin

-slowing is impairing in sensory regions in GABA & norepinephrine

(7/8)

We developed a new approach to test for this spatial gradient effect using multiple regression and nonparametric permutations of the brain maps

This confirmed the spatial gradient effect, and showed that it is altered by key clinical features of PD

(4/8)

By applying specparam on the data before computing slowing, we show that this effect comprises both rhythmic and arrhythmic components

Rhythmic slowing related only to cognitive impairments, while arrhythmic slowing related to motor and cognitive scores

(2/8)

We show that cortical neurophysiology tends towards slower frequencies of activity in patients with Parkinson's disease

Unexpectedly, this slowing relates to both better *and* worse motor & cognitive function - depending on where in the 🧠 it is found

(1/8)

Excited to share our ongoing work linking #Alzheimer's disease proteinopathy to cortical neurophysiological change at #ASFNR2023 in Boston!