Just to my left, a woman in a walker rolled into the library, and promptly complained to the police officer on duty about chest pains. The library faces a square in the middle of Springfield where teenagers, shirtless hippies, skateboarders, and other non-mainstream people kill time in the warm afternoon. The library as such is a cool haven to read and access the internet -- several teenagers were playing WoW on the library computers, and I too am tapping into the resource. A possibly adrift artsy-type man of about my age similarly came to conduct his wayward business, having 'just ended up in Springfield', saying it as both and excuse and a badge of pride evincing his free spirit.

The woman is one of the classic types of hypochondriac, and though I'm only listening to them the EMT and police men know this, but they also know that on the off chance of being wrong, not taking the situation seriously could be a disaster. And so they administered simple blood pressure and pulse rate tests, both which seemed normal, then went about convincing her that she needed to be taken to the hospital to be completely checked out, thereby shifting the burden of liability to a place better protected by the standard operating procedure of a battery of tests.

The woman immediately protested, worried about the heavy cost of a ambulance ride, coupled with a paranoia that she would lose her walker. To this the EMT -- a short woman with her practical ponytail shoved through a baseball cap, as often they do -- let glints of irritation show through, asking her repeatedly to decide which hospital she wished to go to, and then asking her to arrange another means to the hospital. The woman protested, but the EMT could scarecly be blamed -- she is stuck in a system not of her design -- and somehow the smooth-souled librarian, who before had been placating library customers by putting holds on books, convinced both parties to go to the nearest hopsital. How exactly this was done I'll forever remain in ignorance, for another ambulance spun through the downtown circle at that instant, scattering sports cars, stopping sedans, and causing the skaters to pause their idling and look.

The incident vaguely reminds me when I had similar issues in Brooklyn, when i was sufficiently pained to drive my ass through the dirty orange-lit streets to a hospital in Williamsburg. They proceeded to do drug tests on me, despite my insistences, but everything checked out fine. In retrospect, the pain was likely heartburn antagonized by psychological isolation; this was before I really learned to listen to myself, and take care of the social and more basic physiological needs. The walker woman fell through these same cracks in a likely preventable but now very expensive way.

Meanwhile, a large black transsexual and a wrinkly white guy walk hurriedly past the plate glass windows of the library, talking animatedly. They may be in a fissure of sorts, but i doubt they consider it a fall...

So, a year and a half ago I bought a green 1995 900 SE convertible for $600. At that time, it didn't move or go in reverse. Since then, I've been fixing up random things here an there (or just straight modifying / breaking the car by other standards) and recently realized that I had better start keeping track of everything that's been done, in case my memory lapses or i need to know where some random part came from. I doubt this will be useful to anyone else - next time, pictures!

Things that I've done to the green convertible, in approximate chronological order:

1. replaced the clutch cable. previous owner says that the clutch was relatively new; verified when i swapped the transmission.
2. replaced the turbo transmission with one from a 900 S n/a; new transmission has slightly shorter final drive ratio, which is fun. Both transmissions have approximately the same number of miles on them (again, the original tranny had no reverse).
1. The subframe brace bolts were seized on this car - it took several weeks off and on + heat + rust solvent to remove both large 18mm bolts. I recommend replacing them with new ones if possible (these look fine, they are very heavy bolts).
2. In the process of doing this, I stripped one captive nut used for the transmission mount, and had to drill it out & replace it with a 3/8" grade 8 bolt & double nut affair from home cheapo. Be careful when threading these bolts in, or you'll have to do the same!
3. replaced the rubber boots on the control-arm ball joints, and in turn repacked the ball joints with grease. This takes a lot of patience.
4. installed a new gas filler hose from the plastic filler line to the gas tank. Previous one was held on with zip-ties. (yes, zip-ties: after i filled the damn thing up, i noticed that it was leaking excessively, and had to drive it around until the gas was burned through & unlikely to drip all over the ground once the car was parked.)
5. removed turbo silencer prior intercooler.
6. installed a new passenger side headlamp assembly.
7. replaced the thermostat.
8. replaced and gapped all 4 spark plugs.
9. reflashed the ECU to stage 2.5 or so - 1.4 bar peak boost @ 3k rpm, 1.2 bar above 4k rpm, no boost limit in 2nd gear. This was done via Trionic5 suite, available from http://ecuproject.com/
10. replaced both front struts & shocks with parts from a junkyard 1997 900 SE; previous ones had a loose / faulty wheel bearing. Very worthy upgrade.
11. replaced all brake pads + front brake rotors to fit the struts/shocks/bearing hubs from the 97 900 SE. (the hubs are incompatible with 1995 disc rotors - different internal flange diameter.)
12. added internal bracing / roll cage, though without the top hoop. removed most of the upholstery & seats in the back to fit this.
13. oil and filter changed at 161k.
14. adjusted some of the window seals - but they still need to be replaced eventually.
15. removed condenser and AC compressor.
16. replaced / changed the serpentine belt to a 71" / 1805mm 6-tooth duralast belt - aka AC delete belt ref. Water pump is only 25% engaged with the belt now, but seems to work just fine (and the internet verifies this.)
17. repainted some rust spots on the trunk lid.
18. installed plenty of grease on the upholstery -- oops :P
19. Got two used tires from America's discount tires; rear tires still shady. Will get around to replacing them; have already gotten around to destroying the front ones with second-gear burnouts to 60 :)
20. replaced both front brake calipers. The previous 1995-version calipers did not mate well with '97 struts and '97 discs. Initially bought used calipers off of ebay, but the damn bleeder valve was sheared off at the nut, so I took the pads off them and installed remaned ones. Brake feel is much, much better now.
21. Resurfaced flywheel, replaced clutch disc with one from a Jeep Wagoneer (though not the pressure plate -- it looked fine, no signs of cracking).
22. Replaced drivers side main crankcase seal.
23. Replaced drivers side transaxle output bushing + drivers and passengers transaxle output seals
24. Removed oil pan, cleaned pickup, and re-did oil pan seal.
25. Welded a new stud on the turbo, applied with anti-seize this time! always use anti-seize on exhaust parts, they get hot!
26. Removed head, had it ground to fix a minor valve leak and milled flat (increasing the compression ratio a bit). Cleaned the block top surface, intake manifold, fuel injectors, piston heads, and cylinders as best I could. Removed & replaced the broken stud underneath the power steering pump. In the course of having the head out, replaced the relevant seals:
1. Valve stem seals
2. Head gasket
3. Intake gasket
4. Exhaust gasket
27. Replaced upper and lower radiator hoses.
28. As of May 1, I no longer own the car -- I'm off to California, and can't take it with me. May the new owner enjoy it as much as I have!

Things that need to be done to the 'vert:

1. There is still a click in the rear drivers-side brake, should inspect it; likely brake pads.
2. New rear tires (!!).
3. hood gas springs are shot. Meh.

Now, wonders of wonders, I have another of these cars - though a sedan, not a convertible. It cost much more (about 8x as much), and is hence in much better shape. That said, I've had to do the following:

1. Replaced the rear drivers side brake caliper. In the rain; should have waited for a sunny day, as this took longer than expected. (Everything does.)
2. New front disc rotors & pads Dec 2008. As of July 2010, they should be replaced soon.
3. Replaced the clutch + throwout bearing. The latter was making terrible noises back when I drove to Atlanta fall 2008; I nearly didn't make it back.
4. Removed a "Saab saver" steering rack brace installed by a previous owner. To install this brace, you need to drill through the wheel well, which allows (possibly salty) water to touch the bare metal. As a result of this + stress upon metal that was not engineered to bear it, the wheel well cracked almost to the point where the shock mount was about to go through the hood! I'm glad I caught this while the car was parked, and not while i was going 70!
5. welded the wheel well back together with 2x1/4" steel strap. I tried to weld to the major braces of the unibody, and later covered everything with plenty of paint and spray-on rubber soundproofing compound. Still, I worry about the opposite side of the metal, where the heat from the welding undoubtably removed rust-preventing paint. Seems reliable so far.
6. replaced drivers side inner CV joint boot & of course repacked the CV joint grease. You need to take the CV joint completely apart to fit the thing - it won't stretch!
7. Built a tool for removing the differential output bushing from the transmission. As the output of the differential is only a bushing, and it's put under a lot of stress during hard acceleration (especially peel outs - one wheel spinning much faster than the other = lots of strain on difff), the bushing wears out quickly. It is a pressure fit sleeve, so I reasoned that it could be removed by pressure - not quite. It must be cut out, very tediously, using a single-ended hacksaw. To keep metal debris out of the diff housing, insert a rag into where the CV axle was, and flush the tranny throughly after installing a new bushing.
1. This is all rather difficult, so don't peel out!
2. The passengers side half-axle is supported by a bearing by the alternator, so it does not have the same levels of stress & does not wear as quickly.
8. Four new tires. $560 - beh.
9. Replaced front brake discs Nov 2010

And now the blue saab, to be sold to Joh:

1. Replaced front oxygen sensor
2. Replaced rear transmission mount (had to take off the subframe for this, yuck)
3. Fixed front passengers side window regulator
4. Adjusted clutch master cylinder. The linkage between the pedal and the master cylinder was plastic and badly worn, which was causing the clutch to never fully disengage, in turn gradually leading to third gear synchro wearing out. Adjusted the stop on the pedal to compensate for this; it should ultimately be replaced, though works fine now.
5. Replaced front drivers side headlight.

And the faculty of voluntarily bringing back a wandering attention over and over again is the very root of judgement, character, and will. No one is compos sui if he have it not. An education should improve this faculty would be education par excellence".

I highly agree with this philosophy / this deconstruction of the flow of information in human structures: http://www.lostgarden.com/2012/04/loops-and-arcs.html

On criticism as a meta-arc game:

"In the past I've discussed criticism as a game that attempts to revisit an arc repeatedly and embellish it with additional meaning. The game is to generate essays superficially based on some piece of existing art. In turn, other players generate additional essays based off the first essays. This acts as both a referee mechanism and judge. Score is accumulated via reference counts and by rising through an organization hierarchy. It is a deliciously political game of wit that is both impenetrable to outsiders and nearly independent of the actual source arcs. Here creating an arc becomes a move in the larger game. "

This morning hundreds of bees were swarming outside my front door -- a fact is not without reason, as my roommate makes honey, and her hive just today outgrew the apiary. Hence the hive split this morning, and one queen be left to wait on a branch outside while scouts searched for good places to build a new colony; meanwhile hundreds of non-scout workers were swarming around her.

Bees are amazing. Anyway, a friend sent a link to an article describing how to generate microwatts of energy off a flying insect, which led me to wonder how much energy those bees could have been producing instead of milling protectively about their queen.

• number of bees : 1000
• power, with direct connection to flight muscles: 400 uW
• total possible power: 400mW
• kCal in a tablespoon (21g) of honey: 64
• in joules: 270kJ
• Length of time it would take for 500 madly flapping bees (1) to generate the energy within a tablespoon of honey: 375 hours (15.6 days)
• Yield of honey from a large, productive hive: 150 lbs / year (2)
• in watts: 27.8 W
• number of bees: 20000 (2)
• factor better than energy harvesting: 3.5

Conclusion: let them make honey :-)

(1) Half the bees visible were resting on leaves, not madly flapping.

(2) Rough wiki-google estimate.

PMID-22448159 Spike sorting of heterogeneous neuron types by multimodality-weighted PCA and explicit robust variational Bayes.

• Cutting edge windowing-then-sorting method.
• projection multimodality-weighted principal component analysis (mPCA, novel).
• Multimodality of a feature is by checking the informativeness using the KS test of a given feature.
• Also investigate graph laplacian features (GLF), which projects high-dimensional data onto a low-dimensional space while preserving topological structure.
• Clustering based on variational Bayes for Student's T mixture model (SVB).
• Does not rely on MAP inference and works reliably over difficult-to sort data, e.g. bursting neurons and sparsely firing neurons.
• Wavelet preprocessing improves spike separation.
• 
• open-source, available at http://etos.sourceforge.net/

A frequent task in the lab is to sort spikes (extracellular neural action potentials) from background noise. In the lab we are working on doing this wirelessly; to minimize power consumption, spike sorting is done before the radio. In this way only times of spikes need be transmitted, saving bandwidth and power. (This necessitates a bidirectional radio protocol, but this is a worthy sacrifice).

In most sorting programs (e.g. Plexon), the raw signal is first thresholded, then waveform snippets (typically 32 samples long) are compared to a template to accept/reject them, or to sort them into different units. The comparison metric is usually the mean-squared error, MSE, aka the L2 norm. This makes sense, as the spike shapes are assumed to be stereotyped (they may very well not be), and the noise white / uncorrelated (another debatable assumption).

On the headstage we are working with for wireless neural recording, jumps and memory moves are expensive operations, hence we've elected to do no waveform extraction, and instead match continuously match. By using the built-in MPEG compression opcodes, we can compute the L1 norm at a rate of 4 samples / clock -- very efficient. However, this was more motivated by hardware considerations an not actual spike sorting practice. Literature suggests that for isolating a fixed-pattern signal embedded in noise, the best solution is instead a matched filter.

Hence, a careful study of spike-sorting was attempted in matlab, given the following assumptions: fixed spike shape (this was extracted from real data), and uncorrelated band-limited noise. The later was just white noise passed through a bandpass filter, e.g.

cheby1(3, 2, [500/15e3 7.5/15])

Where the passband edges are 500 Hz and 15kHz, at a sampling rate of 30kHz. (Actual rate is 31.25kHz). Since the spike times are known, we can rigorously compare the Receiver Operating Characteristic (ROC) and the area under curve (AUC) for different sorting algorithms. Four were tried: L1 (as mentioned above, motivated by the MPEG opcodes), L2 (Plexon), FIR matched filter, and IIR matched filter.

The latter was very much an experiment -- IIR filters are efficiently implemented on the blackfin processor, and they generally require fewer taps than their equivalent FIR implementation. To find an IIR equivalent to a given FIR matched filter (whose impulse response closely looks like the actual waveshape, just time-reversed), the filter parameters were simply optimized to match the two impulse responses. To facilitate the search, the denominator was specified in terms of complex conjugate pole locations (thereby constraining the form of the filter), while the numerator coefficients were individually optimized. Note that this is not optimizing given the objective to maximize sorting quality -- rather, it is to make the IIR filter impulse response as close as possible to the FIR matched filter, hence computationally light.

And yet: the IIR filter outperforms the FIR matched filter, even though the IIR filter has 1/3 the coefficients (10 vs 32)! Below is the AUC quality metric for the four methods.

And here are representative ROC curves at varying spike SNR ratios.

The remarkable thing is that even at very low SNR, the matched IIR filter can reliably sort cells from noise. (Note that the acceptable false positive here should be weighted more highly; in the present analysis true positive and false positive are weighted equally, which is decidedly non-Bayesian given most of the time there is no spike.) The matched IIR filter is far superior to the normal MSE to template / L2 norm method -- seems we've been doing it wrong all along?

As for reliably finding spikes / templates / filters when the SNR < 0, the tests above - which assume an equal number of spike samples and non-spike samples -- are highly biased; spikes are not normally sortable when the SNR < 0.

Upon looking at the code again, I realized three important things:

1. The false positive rate need to be integrated over all time where there is no spike, just the same as the true positive is over all time where there is a spike.
2. All methods need to be tested with 'distractors', or other spikes with a different shape.
3. The FIR matched filter was backwards!

Including #1 above, as expected, dramatically increased the false positive rate, which is to be expected and how the filters will be used in the real world. #2 did not dramatically impact any of the discriminators, which is good. #3 alleviated the gap between the IIR and FIR filters, and indeed the FIR matched filter performance now slightly exceeds the IIR matched filer.

Below, AUC metric for 4 methods.

And corresponding ROC for 6 different SNR ratios (note the SNRs sampled are slightly different, due to the higher false positive rate).

One thing to note: as implemented, the IIR filter requires careful matching of poles and zeros, and is may not work with 1.15 fixed-point math on the Blackfin. The method really deserves to be tested in vivo, which I shall do shortly.

See www.aicit.org/jcit/ppl/JCIT0509_05.pdf -- they add an 'adjustment' function to the matched filter due to variance in the amplitude of spikes, which adds a little performance at low SNRs.

$F(t)={\left[\frac{x(t)}{k\sigma }{\dot{e}}^{1-\frac{x(t)}{k\sigma }}\right]}^n$

Sigma is the standard deviation of x(t), n and k determine 'zoom intensity and zoom center'. The paper is not particularly well written - there are some typos, and their idea seems unjustified. Still the references are interesting:

• IEEE-238472 (pdf) Optimal detection, classification, and superposition resolution in neural waveform recordings.
• Their innovation: whitening filter before template matching, still use L2 norm.
• IEEE-568916 (pdf) Detection, classification, and superposition resolution of action potentials in multiunit single-channel recordings by an on-line real-time neural network
• Still uses thresholding / spike extraction and L2 norm. Inferior!
• IEEE-991160 (pdf) Parameter estimation of human nerve C-fibers using matched filtering and multiple hypothesis tracking
• They use a real matched filter to detect extracellular action potentials.

PMID-22017994[0] Closed-loop deep brain stimulation is superior in ameliorating parkinsonism.

• Also reviewed by Rui Costa: PMID-22017983[1]
• Good, brief review -- with appropriate minimal references.
• Partial goal of the work: parameter determination and optimization can take a long time, and are typically only done every 3-6 months initially. But the actually changes of activity / responsiveness occur on a faster timescale in the disease, even instantaneous; other studies have shown that updating the stimulation parameters more frequently helps patients. (of course, this is a different form of closed-loop).
• Pathology: intermittent neuronal oscillations in the basal ganglia and motor cortex commonly observed.
• In MPTP treated primates these oscillations occur in the tremor band (theta, 4-7Hz), and double-tremor band (9-15Hz, alpha) (Bergman et al 1994 {120}, Ras et al 2000 PMID-11069964 ).
• Actual pathology still inconclusive; talk about disruption of pathological patterns and 'focal inhibition', but this is no thorough review by any estimate.
• "In recent years, the role of pathological discharge patterns in the parkinsonian brain has emerged as pivotal in the disease pathology
• Eusebio and Brown, 2007;
• Hammond et al., 2007;
• Kuhn et al., 2009;
• Tass et al., 2010;
• Vitek, 2008;
• Weinberger et al., 2009;
• Wichmann and DeLong, 2006;
• Zaidel et al., 2009.
• Automatic systems should disrupt this pattern of discharge (Feng 2006, Tass 2003).
• However, the role of these oscillations as the neuronal correlate of PD motor symptoms is still debated (Hammond et al., 2007; Leblois et al., 2007; Lozano and Eltahawy, 2004; McIntyre et al., 2004; Tass et al., 2010; Vitek, 2002; Weinberger et al., 2009 {1089}).
• 2 african green monkeys, MPTP treatment.
• Recorded from GPi & M1 (127 and 210 neurons); stimulated GPi, 7 pulses at 130Hz, 80ms after spike from reference area (M1 or GPi).
• 80ms delay coincided with the next double-tremor oscillatory burst (12.5Hz)
• State of neuronal oscillatory discharge of cortico-BG loops often accompanied by synchronization btw cortex and BG (see also quote below)
• GPi following M1 activity superior (GP|M1 in their notation).
• single pulses did not work.
• Stimulation: 80uA 200us bipolar biphasic (small and short!).
• Stimiulus protocol (M1 trigger) abolishes oscillatory activity in recorded GPi neurons.
• Also reduced akinesia as measured with an accelerometer & decreased firing rate in the GPi.
• Both work better than constant 130Hz DBS.
• Also much more irregular: fewer stimulation pulses at longer latency.
• Open loop control (the control) did much less regarding FR oscillations & bursts and reduction in firing rate.
• Dorval et al 2010: increasing the stimulus irregularity of open-loop DBS decreases its beneficial clinical effectcs. (also Baker et. al 2011).
• GP train stimulation triggered on GP firing significantly worsened akinesia, despite the fact that the pallidial FR decreased.
• Treatment increased spike oscillation at double-tremor frequency in M1.
• Oscillations more important than firing rate changes (new vs. old hypothesis).
• pallidal oscillatory activity was not correlated to the pallidal discharge rate either before or during the application of standard DBS or GP|M1.
• In our data, may have double-frequency tremor effects. Heterodyne should detect this.
• "Studies on the dynamics of the entire cortico-basal ganglia loops have frequently reported the emergence of intra-and interloop component synchrony and oscillatory activity."
• "Nevertheless, the somewhat intuitive connection between neuronal oscillations and parkinsonian motor symptoms, which include rest and action tremors, has been challenged (Hammond et al., 2007 PMID-17532060 ; Leblois et al., 2007 {1146}; Lozano and Eltahawy, 2004; Tass et al., 2010 {1147}; Vitek, 2002; Weinberger et al., 2009). For instance, while the parkinsonian rest tremor occurs mainly at the 4–7 Hz frequency band, the oscillatory neuronal activity is observed in several characteristic frequency bands in both human PD patients (Hutchison et al., 2004) {1156} and animal models (Bergman et al 1994, Gubellini et al 2009) {1074}"
• This also has import to our heterodyne results!
• Synchrony between globus pallidus and M1 is dynamic and state-dependent (whatever that means -- have to check the refs, Levy et al 2002 {829}, Timmerman et al 2003 {1087})
• Quote: "... it suggests that reduction of the abnormal parkinsonian oscillatory activity could in fact be the underlying mechanism by which DBS exerts its action and brings about the associated clinical improvement."
• Neuronal oscillatory activity occurs as high as the beta-band, 15-35Hz, hence clinical app. would need a tuned antiphase lag.
• Suggest that the closed-loop treatment may be applicable to other diseases with characteristic firing patterns, like schizophrenia.
• Since synchonization and oscillations hend to coincide, .. we found this too.
• Heimer et al 2006 {1076}: oscillations and synchrony can exist independently.
• Figure suck. Text inconsistent and frequently too small.
• Wavelet spectrograms are nice tho.

Other thoughts:

• Somebody should measure the transfer function of the BG / cortical loop. H(z).
• This seems like adding a comb-filter or zero at a particular frequency: GP|GP stimluation exacerbated the effect, GP|M1 minimized the effect as there is a negation in there. (e.g. GP actviity decreases firing of M1, and vice versa).

____References____

PMID-15496658 Neuronal oscillations in the basal ganglia and movement disorders: evidence from whole animal and human recordings.

• This is a review / mini-symposium (only 3 pages)
• Cites other Hutchison papers: 1997, 1998.
• Critique classical hypothesis in that GPi firing does not increase that much, 10-22% in animal models. IT explains akinesia and bradykinesia, but not rigidity or tremor. (This was 8 years ago, remember!)
• Plus, most neurons have intrinsic pacemaker-like properties that sets the rate of firing in the absence of synaptic input. (Bevan et al 2002).
• Oscillations:
• Alpha band enhanced after MPTP treatment in green monkeys and in the STN of some PD patients with tremor at rest.
• Higher frequency oscillations (beta, 15-25Hz) can be observed in some patients without resting tremor.
• Much slower oscillations discovered by Judith Walters, 6 OHDA rat (0.3 - 2Hz).
• Also ultralow, multisecond oscillations, which appear in dopamine stimulated rats. (Ruskin et al 1999a,,b, 2003).
• Lesion of the STN was not found to change these ultralow oscillations, but did modify the connectivity between GP and SNr.
• Courtemanche et al 2003 studied the possible normal physiological function for oscillations in basal ganglia networks.
• Beta band decreased during saccadic eye movements.
• LFP syncronization showed task-related decrease, but only in sites engaged in the task, as evicenced by saccade-related activity.
• Boraud tested gradual small-dose administration of MPTP toxin:
• Minimal changes in the average firing rate of GPi neurons
• Oscillatory activity between 4-9 and 11-14 Hz, with differences between monkeys.
• Oscillations increased with symptom presentation.
• Goldberg et al 2004: analyzed coherence between EEG and BG LFP; surmise that in the PD condition the basal ganglia and cortex become more closely entrained by global brain dynamics, which are reflected in the widespread local field potentials.
• Peter Brown: oscillations in the beta band are enhanced to such an extent in Parkinson's disease that voluntary movements are not generated because motor command for initiation cannot override the enhanced oscillatory state.
• That is, movement initiation corresponds to beta-band desynchronization, and movement command cannot 'break through'.

PMID-21696996 The hippocampus: hub of brain network communication for memory

• Their hypothesis: memory encoding is dominated by theta oscillations 6-10 Hz; during inactivity, hippocampal neurons burst synchronously, creating sharp waves, theoretically supporting memory consolidation.
• (They claim): to date there is no generally accepted theoretical view on memory consolidation.
• Generally it seems to shift from hippocampus to neocortex, but still, evidence is equivocal. (Other than HM & other human evidence?)
• Posit a theory based on excitation ramps of reverse-replay, which seems a bit fishy to me (figure 3).
• Didn't know this: replay in visual and PFC can be so precise that it preserves detailed features of the crosscorrelograms between neurons. [58, 65, 81].

PMID-11832222 Theta Oscillations in the Hippocampus

• Theta-alpha oscillations have been found in 'all mammals to-date, including humans. (Hence conserved, hence possibly essential).
• Prevalent in REM sleep.
• Present in slices bathed in carbachol, too.
• As well as locomotor activities; but not usually when the animal is resting.
• Other reviews: Bland 1986, VAnderwolf 1988, Lopes da Silva et al 1990, Buzaki et al 1994 Stewart and Fox 1990, Vinogradova 1995, Vertex and Kocsis 1997.
• Modeling reviews used passive cable properties; actually, it seems neurons, and their dendrites are have active conductances & active oscillatory features.
• Theta oscillations most strongly present in CA1
• Along similar lamina, oscillations are similar.
• Osc. visible in cortical structures ...
• subicular complex, entorhinal cortex, perirhinal cortex, cingulate cortex, amygdala -- though none of these structures are capable of generating theta oscillations intrinsically.
• Also apparent in subcortical structures,
• Dorsal raphe nucleus, ventral tegmental nucleus, and anterior thalamic nuclei. None of these seem required for oscillation, however:
• Oscillations may emanate from the medial-septum-diagonal band of Broca (MS-DBB); lesion inactivates theta oscillations in all cortical areas, but the relative role is uncertain, as MS-DBB oscillations may require hippocampal and entorhinal afferents.
• EPSPs brought about by the MS-DBB cholinergic neurons on hippocampal pyramidal cells cannot be responsible for the atrophine-sensitive form of theta.
• That said, even though atrophine treatment only modestrly affects theta, it is reduced several-fold after selective neurotoxin elminiation of MS-DBB cholinergic cells -- maybe it's nicotinic synapses?
• Drugs:
• Theta can be blocked by GABA antagonist (picrotoxin, induces epilepsy) or agonist (pentoparbital anesthesia).
• Many other drugs affect oscillations.
• Broken down into atrophine-sensitive and atrophine-resistant oscillations.
• (Atrophine blocks muscarinic Ach receptors).
• Amplitude and frequency of theta does not appreciably change even after large doses of systematic muscarinic blockers.
• Same drugs abolish theta under anesthesia.
• The neurotransmitter and receptor causative in theta have never been clearly determined.
• Theta in CA3 is much smaller than in CA3:
• Distal dendritic arbor of CA3 pyramidal cells is considerably smaller than that of CA1 pyramidal neurons.
• CA3 pyramidal neurons receive perisomatic exitation near their somata from the large mossy terminals of granule cells.
• Regarding this, size of mossy fiber projection correlates well with spatial ability in mice, possibly causative. link (note: used the dryland radial maze, more appropriate for non-swimming mice!)
• Intrahippocampal oscillator (CA3?) can change its frequency and phase relatively independently from the extrahippocampal (entorhinal) theta inputs.
• CA1 interneurons discharge on the descenting phase of theta in the pyramidal cell layer, and are assumed to be responsible for the increased gamma of this phase.
• CA1 pyramidal cells discharge on the negative phase (makes sense) of theta as recorded from the CA1 pyramidal cell layer.
• Phase fluctuation of spikesis not random and correlates with behavioral varaibles.
• Stronger excitation = more spikes earlier in the theta negative phase.
• Firing of place cells varies systematically with animal position and theta phase -- there is a phase precession.
• Seems as though place is encoded in both which cell is firing as well as when in theta.
• alternately, this may be an effect of the CA3 oscillator running slightly faster than the extrinsic oscillator.
• 

Original model for theta oscillation creation (figure 2):

• Note that all oscillations require a dipole which periodically inverts along it's axis, as is required in a conductive solution.
• And yet there is no 'null' zone in theta oscillation, as dipole would imply. Rather, there is a gradual shift, more like a traveling wave.
• Dendrites are passive cables, LFP generated by summed activity of IPSP and EPSP on soma and dendrites.
• Excitation from perforant path,
• Inhibition from septum to feed-forward inhibitory neuron inputs.
• That said, the model is not completely consistent with experimental evidence:
• The highest probability of discharge in the behaving rat occurs around the positive peak of theta recorded at the level of the distal dendrites, corresponding to the negative phase in the pyramidal level. (Remember, spiking corresponds to sodium influx, hence decreased extracellular +)
• Cells may oscillate by themselves, without input.
• The cell connections within the hippocampus matter a lot, too.

LTP:

• Induction is present / optimal when the spacing between pulses is 200ms.
• Priming can be only one pulse!
• Not clear how this works - endogenous cannabanoids?
• Theta oscillation may provide a mechanism for bringing together time afferent inducing depolarization and dendritic invasion of fast spikes.

Conclusions:

• A theta cycle may be considered an information quantum, allowing the exchange of information among the linked members in a phase-locked manner. ...
• This discontinuous mode of operation may be a unique solution to temporally segregate and link neuronal assemblies to perform various operations.
• Notable support of this hypothesis:
• Theta cycle phase resets upon sensory stimulation
• Motor activity can become theta locked.

Misc:

• Ketamine blocks NMDA receptors.
• Granule cells can be eliminated by neonatal X-ray exposure. (why?)

http://web.cecs.pdx.edu/~greenwd/xmsnLine_notes.pdf -- Series termination will work, provided the impedance of the driver + series resistor is matched to the impedance of the transmission line being driven.

School has been so long ago, I've forgotten these essentials!

PMID-22388818 Corticostriatal plasticity is necessary for learning intentional neuroprosthetic skills.

• Trained a mouse to control an auditory cursor, as in Kipke's task {99}. Did not cite that paper, claimed it was 'novel'. oops.
• Summed neuronal firing rate of groups of 2 or 4 M1 neurons.
• One grou increased the frequenxy with increased firing rate; the other decreased tone with increasing FR.
• Removal of striatal NMDA receptors impairs the ability to learn neuroprosthetic skills.
• Hence, they argue, cortico-striatal plastciity is required to learn abstract skills, such as this tone to firing rate target acquisition task.
• Auditory feedback was essential for operant learning.
• Controlled by recording EMG of the vibrissae + injection of lidocane into the whisker pad.
• One reward was sucrose solution; the other was a food pellet. When the rat was satiated on one modality, they showed increased preference for the opposite reward. Clever control.
• Noticed pronounced oscillatory spike coupling, the coherence of which was increased in low-frequency bands in late learning relative to early learning (figure 3).
• Genetic manipulations: knockin line that expresses Cre recombinase in both striatonigral and striatopallidal medium spiny neurons, crossed with mice carrying a floxed allele of the NMDAR1 gene.
• These animals are relatively normal, and can learn to perform rapid sequential movements, but are unable to learn precise motor sequences.
• Acute pharmacological blockade of NMDAR did not affect performance of the neuroprosthetic skill.
• HEnce the deficits in the transgenic mice are due to an inability to perform the skill.

IEEE-4353634 (pdf) Optimal Operating Frequency in Wireless Power Transmission for Implantable Devices

• Key finding: biological tissue is remarkably transparent around 1 Ghz.
• Other work: you can propel a fluid in by putting current through it in a magnetic field, and which then subjects the device (something that can swim through blood!)
• See the press release: http://why.knovel.com/all-engineering-news/1276-overturning-old-assumptions-leads-to-breakthrough-in-implantable-medical-devices.html

PMID-12629196[0] Stimulation of the Subthalamic Nucleus Changes the Firing Pattern of Pallidal Neurons

• why does STN stim work? investigated the effects of STN HFS on neuronal activity of GPi and GPe.
• monkeys were treated with MPTP
• used a scaled-down version of human DBS stimulator (cool!)
• high frequency stimulation resulted in stimulus-synchronized regular firing pattern, plus an overall increase in pallidal firing rate.
• they think that this synchrony may underlie the beneficial effect of HFS in the STN
• only behavior was, apparently, what amplitude and frequency were required to alleviate parkinsonian symptoms.
• if i do DBS in normal monkeys, is there anything to say that the effect will be similar or comparable to treatment stimulation?
• they remind us that HFS = lesion in terms of alleviating symptoms of parkinsons.

____References____

PMID-19047633[0] Functional network reorganization during learning in a brain-computer interface paradigm.

• quote: For example, the tuning functions of neurons in the motor cortex can change when monkeys adapt to perturbations that interfere with the execution (5–7) or visual feedback (8–10) of their movements. Check these refs - have to be good!
• point out that only the BMI lets you see how the changes reflect changes in behavior.
• BMI also allows pertubactions to target a subset of neurons. apparently, they had the same idea as me.
• used the PV algorithm. yeck.
• perturbed a select subset of neurons by rotating their tuning by 90deg. about the Z-axis. pre - perturb - washout series of experiments.
• 3D BMI, center-out task, 8 targets at the corners of a cube.
• looked for the following strategies for compensating to the perturbation:
• re-aiming: to compensate for the deflected trajectory, aim at a rotated target.
• re-waiting: decrease the strength of the rotated neurons.
• re-mapping: use the new units based on their rotated tuning.
• modulation depths for the rotated neurons did in fact decrease.
• PD for the neurons that were perturbed rotated more than the control neurons.
• rotated neurons contributed to error parallel to perturbation, unrotated compensated for this, and contributed to 'errors' in the opposite direction.
• typical recording sessions of 3 hours - thus, the adaptation had to proceed quickly and only online. pre-perturb-washout each had about 8 * 20 trials.
• interesting conjecture: "Another possibility is that these neurons solve the “credit-assignment problem” described in the artificial intelligence literature (25–26). By using a form of Hebbian learning (27), each neuron could reduce its contribution to error independently of other neurons via noise-driven synaptic updating rules (28–30). "
• ref 25: Minsky - 1961;
• ref 26: Cohen PR, Feigenbaum EA (1982) The Handbook of Artificial Intelligence; 27 references Hebb driectly - 1949 ;
• ref 28: ALOPEX {695} ;
• ref 29: PMID-1903542[1] A more biologically plausible learning rule for neural networks.
• ref 30: PMID-17652414[2] Model of birdsong learning based on gradient estimation by dynamic perturbation of neural conductances. Fiete IR, Fee MS, Seung HS.

____References____

PMID-19744484 What can man do without basal ganglia motor output? The effect of combined unilateral subthalamotomy and pallidotomy in a patient with Parkinson's disease.

• Unilateral lesion of both STN and GPi in one patient. Hence, the patient was his own control.
• DRastically reduced the need for medication, indicating that it had a profound effect on BG output.
• Arm contralateral lesion showed faster reaction times and normal movement speeds; ipsilateral arm parkinsonian.
• Implicit sequence learning in a task was absent.
• In a go / no-go task when the percent of no-go trials increased, the RT speriority of contralateral hand was lost.
• " THe risk of persistent dyskinesias need not be viewed as a contraindication to subthalamotomy in PD patients since they can be eliminated if necessary by a subsequent pallidotomy without producting deficits that impair daily life.
• Subthalamotomy incurs persistent hemiballismus / chorea in 8% of patients; in many others chorea spontaneously disappears.
• This can be treated by a subsequent pallidotomy.
• Patient had Parkinsonian symptoms largely restricted to right side.
• Measured TMS ability to stimulate motor cortex -- which appears to be a common treatment. STN / GPi lesion appears to have limited effect on motor cortex exitability 9other things redulate it?).
• conclusion: interrupting BG output removes such abnormal signaling and allows the motor system to operate more normally.
• Bath DA presumably calms hyperactive SNr neurons.
• Yuo cannot distrupt output of the BG with compete imuntiy; the associated abnormalities may be too subtle to be detected in normal behaviors, explaniing the overall clinical improbement seen in PD patients after surgery and the scarcity fo clinical manifestations in people with focal BG lesions (Bhatia and Marsden, 1994; Marsden and Obeso 1994).
• Our results support the prediction that surgical lesions of the BG in PD would be associated with inflexibility or reduced capability for motor learning. (Marsden and Obeso, 1994).
• It is better to dispense with faulty BG output than to have a faulty one.

PMID-16271465 The basal ganglia: learning new tricks and loving it

• BG analogous to the anterior forebrain pathway (AFP), which is necessary for song learning in young birds. Requires lots of practice and feedback. Studies suggest e.g. that neural activity in the AFP is correlated with song variability, and that the AFP can adjust ongoing activity in effector motor pathways.
• LMAN = presumed homolog of cortex that receives basal ganglia outflow. Blockade of outflow from LMAN to RA creates stereotyped singing.
• To see accurately what is happening, it's necessary to record simultaneously, or in close temporal contiguity, striatal and cortical neurons during learning.
• Pasupathy and biller showed that changes occur in the striatum than cortex during learning.
• She cites lots of papers -- there has been a good bit of work on this, and the theories are coming together. I should be careful not to dismiss or negatively weight things.
• Person and Perkel [48] reports that in songbirds, the analogous GPi to thalamus pathway induces IPSPs as well as rebound spikes with highly selective timing.
• Reference Levenesque and Parent PMID-16087877 who find elaborate column-like arrays of striatonigral terminations in the SNr, not in the dopamine-containing SNpc.

PMID-21543839[0] A chronic generalized bi-directional brain-machine interface.

• Using a commercial neurostimulator package & battery etc.
• "A key goal of this research prototype is to help broaden the clinical scope and acceptance of NI techniques, particularly real-time brain state detection" Good purpose! good work!
• Augments the stimulator with 4 channels of ECoG/LFP + accelerometer + wireless telemetry.
• Can be used to detect parkinsons state or pre-epileptiform behavior.
• Much of this has been though of before, it just took the technology to catch up & a group to make it.
• Chronic data is needed from humans -- animal models are often inadequate.
• Tested in a primate for brain control of a cursor: 1D control using ECoG.
• Good Left/right ROC, actually.
• A large cost is simply the clinical testing; hence they piggy-back on an existing design.
• There should be more research-industry collaborations like this.
• impressive specs.
• 
• SVM classification algorithm (only consumed 10uW!) for data compression.
• short-time Fourier transform for extracting the power over a given band. This using a modified chopper-amplification scheme. Output data has a bandwidth of less than 5Hz, which greatly reduces processing requirements.
• Lots of processing on the BASIC chip, much like here.
• Also see the press release

____References____

see {1117}