[Hplusroadmap] An update and some notes on attention (was Fwd: Your Plastic Brain)

[Bryan Bishop]

On Tuesday 20 May 2008, Antonio Marcos wrote:
>  also most of them have aging brains (if not all =]) and all this
> cause anxiety, if they have to change, work because of it, worry that
> new people will take over their "jobs"/position/titles .. etc...

Although I have also thought that this might be the reason, I haven't 
really seen people *specifically* show that this is their line of 
reasoning for avoiding the topics. It's kind of a cognitive laziness. I 
could describe this best as the censorship and out-filtering that goes 
on when you don't want to click a link, when you don't want to search 
over the web for the meaning of a new word or new technique. I was 
doing some queries over Google Scholar this morning and found a good 
way to word this, it's apparently now being called 'attentional 
effort'. 
http://heybryan.org/mediawiki/index.php/Sustained_attention#More_attention_must_be_paid:_The_neurobiology_of_attentional_effort

Here's the abstract (with formatting/highlighting on the wiki):
> Increases in attentional effort are defined as the motivated
> activation of attentional systems in response to detrimental 
> challenges on attentional performance, such as the presentation of 
> distractors, prolonged time-on-task, changing target stimulus 
> characteristics and stimulus presentation parameters, circadian phase 
> shifts, stress or sickness. Increases in attentional effort are 
> motivated by the expected performance outcome; in the absence of such 
> motivation, attentional performance continues to decline or may cease 
> altogether. The beneficial effects of increased attentional effort are 
> due in part to the activation of top-down mechanisms that act to 
> optimize input detection and processing, thereby stabilizing or 
> recovering attentional performance in response to challenges. 
> Following a description of the psychological construct “attentional 
> effort”, evidence is reviewed indicating that increases in the 
> activity of cortical cholinergic inputs represent a major component of 
> the neuronal circuitry mediating increases in attentional effort. A 
> neuronal model describes how error detection and reward loss, 
> indicating declining performance, are integrated with motivational 
> mechanisms on the basis of neuronal circuits between 
> prefrontal/anterior cingulate and mesolimbic regions. The cortical 
> cholinergic input system is activated by projections of mesolimbic 
> structures to the basal forebrain cholinergic system. In prefrontal 
> regions, increases in cholinergic activity are hypothesized to 
> contribute to the activation of the anterior attention system and 
> associated executive functions, particularly the top-down optimization 
> of input processing in sensory regions. Moreover, and influenced in 
> part by prefrontal projections to the basal forebrain, increases in 
> cholinergic activity in sensory and other posterior cortical regions 
> contribute directly to the modification of receptive field properties 
> or the suppression of contextual information and, therefore, to the 
> mediation of top-down effects. The definition of attentional effort as 
> a cognitive incentive, and the description of a neuronal circuitry 
> model that integrates brain systems involved in performance 
> monitoring, the processing of incentives, activation of attention 
> systems and modulation of input functions, suggest that ‘attentional 
> effort’ represents a viable construct for cognitive neuroscience 
> research.                                    
(M Sarter, WJ Gehring, R Kozak)

I was looking up the neurological basis of attention earlier today in an 
effort to figure out how to integrate it within Markram's model of the 
intense world syndrome, which is based off of the neocortical columnar 
circuit, like the GABAergic inhibitory interneurons that modulate 
minicolumnar pyramidal cells. See here:

http://heybryan.org/intense_world_syndrome.html#minicolumnar_ecology
> Another component of minicolumns are various types of GABAergic
> inhibitory interneurons (i.e. neurons that produce GABA as their 
> neurotransmitter), which tend to be aligned one on top of the other 
> and modulate the activity of minicolumn pyramidal cells. Double 
> bouquet cells are present in all layers, but are most dense in layers 
> 2 and 3. The axon bundles (long projections that conduct electrical 
> impulses away from the cell body) of these cells are projected deep 
> into the cortex from layer 2 to layer 5, terminating on pyramidal 
> cells as well as other inhibitory interneurons. They create a narrow 
> vertical stream of inhibition through the cortex, as well as a 
> vertically directed disinhibition of those pyramidal cells upon which 
> the other inhibitory interneurons project. Other interneurons include 
> Chandelier cells [GABAergic fast spiking parvalbumin-containing 
> cortical interneurons with cartridge-shaped axons ' ... the cartridges 
> are immunoreactive to an isoform of the GABA membrane transporter, 
> GAT-1, and this serves as their identifying feature.[1][2] GAT-1 is 
> involved in the process of GABA reuptake into nerve terminals, thus 
> helping to terminate its synaptic activity.'], which synapse directly 
> onto the axon hillock (base of the axon projection from the cell body) 
> of pyramidal cells, modulating cell output and participating in 
> intra-columnar inhibition, and basket cells, which contacts the soma 
> and dendrites of pyramidal cells, modulating input to these cells. 
> Although these interneurons make up a small fraction of the total 
> number of minicolumn cells, they play a significant role in finely 
> tuning cortical information processing. A simplified representation of 
> a minicolumn is thus of a processing core surrounded by a GABAergic 
> interneuron circumferential zone of inhibitory and disinhibitory 
> activity.                           

Markram has been doing computational models [that work], he has 
simulations of neocortical columns running pretty well since 2005. 
http://heybryan.org/mediawiki/index.php/Henry_Markram
http://heybryan.org/mediawiki/index.php/Henry_Markram_computational_neurosci_imitation_project
http://heybryan.org/mediawiki/index.php/Human_cortex

Markram video (excellent, highly recommended):
http://video.google.com/videoplay?docid=-2874207418572601262&q=almaden+cognitive+computing

What this is all pointing towards is the control of 'attentional 
effort'. What happens if we pay attention to that attentional effort, 
if we can reduce the attentional effort?

Ultimately I see little difference between attentional effort and 
computational complexity. You voluntarily avoid computational 
complexity. By this I mean, will you rather process N items, or N+1 
items, if there is no difference other than N v. N+1? By this I mean, 
Big O-notation.

http://en.wikipedia.org/wiki/Computational_complexity
> Computational complexity theory, as a branch of the theory of
> computation in computer science, investigates the problems related to 
> the amounts of resources required for the execution of algorithms 
> (e.g., execution time), and the inherent difficulty in providing 
> efficient algorithms for specific computational problems.    
>
> A typical question of the theory is, "As the size of the input to an 
> algorithm increases, how do the running time and memory requirements 
> of the algorithm change and what are the implications and 
> ramifications of that change?" In other words, the theory, among other 
> things, investigates the scalability of computational problems and 
> algorithms. In particular, the theory places practical limits on what 
> computers can accomplish.      

	"The brain is not a computer: the brain is the brain."
			- saying of the cetics
http://heybryan.org/quotes.html

def: cetic; see by name: hallning, zazen, meditation, fugue, and the 
interface with the cybernetic spaces.

So I'm working on cutting out the 'attentional effort' stuff, down to a 
minimum, so that we don't have to keep on mentally booting up our 
attention systems, so that we don't have to crash in a focus-session:
http://heybryan.org/recursion.html
http://heybryan.org/2008-05-13_hyperfocusing.html
... and ultimately so that we don't do wasteful computational cycles.*

I'll say a few words about the recent literature research I've done.

So on 2008-05-13:
http://heybryan.org/2008-05-13_hyperfocusing.html (@bottom)
> Acetylcholine also has other effects on excitability of neurons. Its
> presence causes a slow depolarization by blocking a tonically-active 
> K+ current, which increases neuronal excitability. It appears to be a 
> paradox, however, that ACh increases spiking activity in inhibitory 
> interneurons while decreasing strength of synaptic transmission from 
> those cells. This decrease in synaptic transmission also occurs 
> selectively at some excitatory cells: For instance, it has an effect 
> on intrinsic and associational fibers in layer Ib of piriform cortex, 
> but has no effect on afferent fibers in layer Ia. Similar laminar 
> selectivity has been shown in dentate gyrus and region CA1 of the 
> hippocampus. One theory to explain this paradox interprets 
> acetylcholine neuromodulation in the neocortex as modulating the 
> estimate of expected uncertainty, acting counter to norepinephrine 
> (NE) signals for unexpected uncertainty. Both would then decrease 
> synaptic transition strength, but ACh would then be needed to counter 
> the effects of NE in learning, a signal understood to be 'noisy'.               

"Cholinergic modulation [via i.v. physostigmine] preferentially .. 
influenced maintenance of selective attention, with little influence on 
the shifting of attention."

That was a good research paper by Furey. Basically, it's known that 
images of faces 'steal attention' over images of houses, but Furey has 
isolated and localized that process in the brain and attenuated 
the 'stealing'ness of faces (it's not a modulation to the face, but to 
the brain, of course). It's not so much 'preferential encoding' but 
rather an ability for top-down processing [which can be related to the 
other information in this email, the 'cognitive cholinergic modulation 
of detection']. And earlier today I found a few more pieces of the 
puzzle to integrate, from M Sarter and JP Bruno. 

> Cortical cholinergic inputs mediating arousal, attentional processing
> and dreaming: differential afferent regulation of the basal forebrain 
> by telencephalic and brainstem afferents  

It's the signal-driven cholinergic modulation of detection system.

> Neurophysiological studies demonstrated that increases in cholinergic
> transmission in sensory areas enhance the cortical processing of 
> thalamic inputs. Cholinergic activity also suppresses the retrieval of 
> internal associations, thereby further promoting sensory input 
[not only that (cholinergic supression of internal-association 
retrieval), but long-distance connections are less numerous in autism, 
due to the metabolic demands of long axons and so on. It's an 
optimization problem.]
> processing. Behavioral studies documented the role of cortical 
> cholinergic inputs in attentional functions and capacities by 
> demonstrating, for example, that the integrity of the cortical 
> cholinergic input system is necessary for attentional performance, and 
> that the activity of cortical cholinergic inputs is selectively 
> enhanced during attentional performance. This review aims at 
> integrating the neurophysiological and behavioral evidence on the 
> functions of cortical cholinergic inputs and hypothesizes that the 
> cortical cholinergic input system generally acts to optimize the 
> processing of signals in attention-demanding contexts. Such 
> signals ‘recruit’, via activation of basal forebrain corticopetal 
> cholinergic projections, the cortical attention systems and thereby 
> amplify the processing of attention-demanding signals 
> (termed ‘signal-driven cholinergic modulation of detection’). The 
> activity of corticopetal cholinergic projections is also modulated by 
> direct prefrontal projections to the basal forebrain and, indirectly, 
> to cholinergic terminals elsewhere in the cortex; thus, cortical 
> cholinergic inputs are also involved in the mediation of top-down 
> effects, such as the knowledge-based augmentation of detection (see 
> Footnote 1) of signals and the filtering of irrelevant information 
> (termed ‘cognitive cholinergic modulation of detection’). Thus, 
> depending on the quality of signals and task characteristics, cortical 
> cholinergic activity reflects the combined effects of signal-driven 
> and cognitive modulation of detection. This hypothesis begins to 
> explain signal intensity or duration-dependent performance in 
> attention tasks, the distinct effects of cortex-wide versus prefrontal 
> cholinergic deafferentation on attention performance, and it generates 
> specific predictions concerning cortical acetylcholine (ACh) release 
> in attention task-performing animals. Finally, the consequences of 
> abnormalities in the regulation of cortical cholinergic inputs for the 
> manifestation of the symptoms of major neuropsychiatric disorders are 
> conceptualized in terms of dysregulation in the signal-driven and 
> cognitive cholinergic modulation of detection processes.                                    

From the same researchers:

> Basal forebrain corticopetal neurons participate in the mediation of
> arousal, specific attentional functions and rapid eye movement 
> sleep-associated dreaming. Recent studies on the afferent regulation 
> of basal forebrain neurons by telencephalic and brainstem inputs have 
> provided the basis for hypotheses which, collectively, propose that 
> the involvement of basal forebrain corticopetal projections in 
> arousal, attention and dreaming can be dissociated on the basis of 
> their regulation via major afferent projections. While the processing 
> underlying sustained, selective and divided attention performance 
> depends on the integrity of the telencephalic afferent regulation of 
> basal forebrain corticopetal neurons, arousal-induced attentional 
> processing (i.e. stimulus detection, selection and processing as a 
> result of a novel, highly salient, aversive or incentive stimuli) is 
> mediated via the ability of brainstem ascending noradrenergic 
> projections to the basal forebrain to activate or “recruit” these 
> telencephalic afferent circuits of the basal forebrain. In rapid eye 
> movement sleep, both the basal forebrain and thalamic cortiocopetal 
> projections are stimulated by cholinergic afferents originating mainly 
> from the pedunculopontine and laterodorsal tegmenta in the brainstem. 
> Rapid eye movement sleep-associated dreaming is described as a form of 
> hyperattentional processing, mediated by increased activity of 
> cortical cholinergic inputs and their cortical interactions with 
> activated thalamic efferents. In this context, long-standing 
> speculations about the similarities between dreaming and psychotic 
> cognition are substantiated by describing the role of an 
> over(re)active cortical cholinergic input system in either condition.                          
>
> Finally, while determination of the afferent regulation of basal
> forebrain corticopetal neurons in different behavioral/cognitive 
> states assists in defining the general cognitive functions of cortical 
> acetylcholine, this research requires a specification of the precise 
> anatomical organization of basal forebrain afferents and their 
> interactions in the basal forebrain. Furthermore, the present 
> hypotheses remain incomplete because of the paucity of data concerning 
> the regulation and role of basal forebrain non-cholinergic, 
> particularly GABAergic, efferents.        

I'm currently trying to track down some of the following:
* ways of increasing acetylcholine blood levels
* cortical acetylcholine (ACh) agonists 
*  intra-accumbens administration of D1 and, more potently, D2 receptor 
antagonists
* ACh reuptake inhibitors -> perhaps flood the brain with ACh
** this is to do sustained attention, remember
** anticholinesterase (surprisingly includes THC ...)
*** tacrine, donepezil, galanthamine, huperzine, heptylphysostigimine
* physostigmine (300 micrograms/kg), heptylphysostigmine (5 mg/kg) and 
tetrahydroaminoacridine (tacrine, 5 mg/kg), which all increase 
extracellular levels of ACh in the telencephalon
** acetylcholinesterase (AChE) inhibition, in other words

acytlcholinesterase: an enzyme present in nerve tissue, muscles and red 
blood cells that catalyzes the hydrolysis of acetylcholine to choline 
and acetic acid, allowing neural transmission across synapses to occur.

> Activation of AMPA/kainate receptors by intrabasalis perfusion of
> kainate (100 M) was sufficient to increase cortical ACh efflux even 
> under basal (nonstimulated) conditions. This effect of kainate was 
> blocked by coperfusion with the antagonist DNQX (0.1-5.0 mM).   

Kainate is *expensive*, at least at Sigma-Aldrich. I need a better 
chemical supplier. Anyway, kainate agonists are sort of like AMPA 
agonists [and in a sense are somewhat like taking pure glutamate?] and 
I suspect the *racetams will do the trick at least for the GABAergic 
inputs to the cortical cholinergic afferents. Also:

> Cortical acetylcholine efflux was stimulated by systemic
> administration of the benzodiazepine receptor partial inverse agonist 
> FG 7142. Administration of FG 7142 (8.0 mg/kg; i.p.) significantly 
> elevated acetylcholine efflux in both cortical regions (150–250% 
> relative to baseline) for 30 min after drug administration. The 
> ability of endogenous dopamine to regulate cortical acetylcholine 
> efflux under resting or stimulated conditions and the relative 
> contributions of D1- and D2-like dopamine receptor activation was also 
> assessed. In        

So once I go through this more thoroughly and do a few writeups, I'm 
thinking about splicing in some genes for these molecules into 
bacteria, purifying the results, then i.v.'ing the purified analytes 
into animal models of attention [possibly -- there's a few other ideas 
bouncing around, probably an organotypical neuron slice instead]. 

Then I get to work on this:
http://heybryan.org/mediawiki/index.php/Brainstate_augmentation_setup
http://heybryan.org/mediawiki/index.php/Neurofarm
http://heybryan.org/interfaces.html

- Bryan

* Be careful what you call 'waste'.
________________________________________
http://heybryan.org/