is novel in bringing together rigorous neuropsychology, current theories
of attentional control and computer modelling to bear upon the study of
Alzheimer's disease. Although models of dysmnesia have been developed in
AD, models of executive function have not. Rigorous neuropsychological
experiments are seldom used as a basis for modelling in AD.
novel and important is the use of dynamical systems theory to bridge the
informational and biological domains. This is crucial as neural activity
shows complex patterns, including oscillations, whose emergence is intimately
linked to the brain's information processing ability. On the other hand,
even simple psychological models have important, unexplored dynamical properties.
approach does not apply simply the minimal modifications that would fix
model shortcomings, without reference to the biological substrate. Lack
of such reference can be likened to trying to understand how a hummingbird
flies by building helicopters: both might be able to hover, but the biological
implementation may be fundamentally different to the engineering one. Models
are better developed by examining hitherto neglected biological data while
recognising that the relevant biology may be as yet unknown. Another objection
to the 'minimal modification' approach is that it is Kuhn's 'normal science'
par excellence (Notturno 1984), designed to avoid fundamental issues.
Critique of methods
dysfunction' in the dual task may not have the same origin or importance
as the impairment of ADL related functions. Hence it may not be the most
relevant starting point. The underlying attentional theory of Houghton
et al is not the only possible starting point for modelling either. The
information processing theory of EPIC (Meyer & Kieras, 1997) could
be a different one; The methodology of Cohen et al (1992) yet another,
particularly as a lot of work has examined the Stroop task in AD. The EPIC
model was not used as it has very coarse graining of the biological processes
involved. It involves however a detailed consideration of cognitive strategy,
which has been neglected in our study. The Baddeley experiments did not
consider differences in cognitive strategy and thus would be difficult
to reconcile with EPIC. It would not be surprising if AD patients had difficulties
inventing efficient strategies, and these would have to be considered in
the modelling of more complex tasks. This is relevant to the conjecture
that better strategies help the more educated preserve function in the
face of AD.
papers provide little detail into the particular ways in which performance
deteriorated under different conditions. They do not, for example, report
false-positive responses or evidence of strategy failure. Such information
could lead to more detailed modelling. Access to the original data might
help. In addition the conclusion of an 'Executive lesion' in AD reached
by Baddeley and assumed in this study is not the only possible one. An
alternative could be deficient automatization. Rather than AD impairing
executive control it could impair the process of automatisation (Cohen
et al, 1992), so that AD subjects find dual tasks harder because it is
harder to combine non-automatised tasks.
studies make many assumptions, which can be both a weakness and a strength.
Unproved assumptions used in the Houghton derived models which could reduce
the validity of our conclusions include that: 1. Performance is directly
related to level of activation of cortical areas 2. The most relevant cortical
areas are perceptual; 3. Diffuse influences (e.g. ACh) can be neglected;
4. Cortices can be treated in a 'lumped' manner; 5. Neural noise can be
neglected; 6. The way in which 'match' unit performance is impaired is
immaterial; 7. Cross-modality interference can be assumed to take place
via descending projections of the attentional mechanism 8. Parameter exploration
was adequate. The related strength of the approach is that such assumptions
are inherent in much thinking about attentional control, only they remain
hidden. On the other hand in this study they serve as incentives for meaningful
exploration. The manner in which some of these assumptions were dealt with
has been described in Methods. With respect to assumption 2., simulation
of variables more directly related to behavioural performance would be
highly desirable. Assumption 7 is of particular concern. It is adopted
on the grounds of consistency with imaging studies showing suppression
of non-attended modalities, of it providing a task-specific mechanism of
attentional control and of it being a priori unbiased with respect to the
study hypothesis. These assumptions will be discussed further.
Interpretation of findings
directly based on Houghton's theory
triad' proved a useful model. It is susceptible to attentional modulation,
easily allowing the implementation of excitatory and inhibitory attentional
control, including lateral inhibition and the match mechanism. It was,
however, found to have important shortcomings. First, it can show spuriously
excited states. Second, it is a lot more responsive to inhibitory rather
than excitatory modulation. Third, the 'gain' units alter the level of
activation but do not, in fact, change gain itself. These problems were
traced (fig. 7) to the steady-state input-output function of the specific
units involved. This curve has its maximum sensitivity at the resting state.
The use of excitation functions which are concave upwards at the origin
can solve these problems (fig. 8; section 3A of Results). This is an illustration
of why knowledge of dynamical properties of simple unit combinations can
the triad involves no conduction delays. More realistic, KI-like units
improve the points raised above, have physiological support and also address
the issue of time dependence in a more substantial way. They provide a
relatively well-explored avenue to the simulation of oscillatory cortical
dynamics. Objections can be raised: The KI equations have been derived
from archicortical rather than neocortical physiology; and the timescales
on which KI units operate do not relate to behavioural reaction times (their
response is still too fast). Therefore an indirect index of their response
would still have to be used to infer behavioural performance.
of the 'attentional triad' caused problems in dual-task simulations. If
cross-modality inhibition is used, then performance of each task has to
overcome inhibition by the other. This is difficult to achieve if excitatory
control is inherently weaker than inhibitory. It can result in attention
paradoxically decreasing performance during the dual task and in damage
to the attentional system dis-inhibiting perceptual units more than de-exciting
them. The result is a tendency for the AD condition to perform relatively
better in the dual task than normals, except within a limited parameter
range. This includes: 1. low stimulus intensities, which essentially linearise
perceptual unit response; 2. within-pathway, excitatory synapses from match
units to on-gain units much (e.g. four times) stronger than the cross-modality,
inhibitory ones. It can be seen that both these properties serve to offset
the tendency of the original ('Grossberg') units to saturate and to favour
inhibitory inputs. These considerations also explain why even successful
models showed quantitatively small effects.
drawback of the initial models is that progressive impairment of the 'match'
mechanism does not lead to the profound effects of advancing AD; rather,
impairment shows a floor effect. This can be understood if the positive
feedback loop formed by the perceptual-match connections is considered.
The participation of Grossberg-type units necessitates a low gain around
the loop to avoid spurious states. An improved high-gain loop (as in fig.
8) would be more suitable for the simulation of the profoundly deleterious
effect of AD.
On the other
hand, the Houghton-based model with suitable qualifications succeeded in
simulating qualitatively the overall pattern of the Baddeley results. It
seems that the essential features of this model include: 1. the matching
process 2. the presence of an active description of behavioural targets
and 3. change of responsiveness of perceptual units towards stimuli through
both inhibitory (decreasing responsiveness) and excitatory (increasing
it) attentional control. Shortcomings of the original models include use
of the Grossberg units and the symbolic implementation of the match / mismatch
mechanism. Features that do not keep with cortical physiology include the
zero transmission delays and system operation via point attractors.
success of lateral inhibition : Interpretation and novel predictions of
the augmented model.
of direct lateral inhibition and match-based attentional control provided
a strikingly robust model, simulating a number of results in a quantitative
manner. This is because it involves excitatory attentional control based
at the level of the match mechanism, with cross-modality inhibition at
a lower level, less prone to the ravages of AD. This model leads to some
novel predictions that are physiologically and psychologically testable.
Cross-modality inhibition is independent of attention for a given sensory
cortical activation. As in the Baddeley experiments it takes place between
procedurally unrelated tasks it is likely to operate in a general, non-specific
manner: different modalities laterally inhibit each other by default. Such
laterally inhibitory effects would be equivalent in AD and normals as long
as subjects attended to neither of the interfering modalities, performing
instead some third, neutral task. Such effects should be visible in human
imaging activation studies as well as in invasive animal experiments.
be the biological function of cross-modality interference effects observed
in the normal elderly, and more specifically of lateral inhibition? Cohen
and co-workers reach the conclusion in their discussion of automatic task
performance that tasks should interfere only to the extent that they utilise
overlapping brain modules, as opposed to some ill defined 'attentional
resource'. Similar principles underlie the dual task performance limitations
of the conceptually different EPIC (Meyer & Kieran, 1997). However,
Baddeley's experiments specifically minimise overlap between resources
required to perform the constituent tasks. Only then does the finding of
interference between the tasks, particularly between response-to-tones
and tracking, lend support to the theory of a 'central executive'. This
is considered as a shared resource, the homuncular manager of a limited
attentional 'budget'. There is, however, poor support for such a shared
so far modelled by direct lateral inhibition, could happen for a number
of reasons. First, the 'central executive' could be a brain processor which
can only deal in terms of serial procedures. The interference between increasingly
more demanding tasks would arise because the only way of multitasking this
serial processor is timesharing - and high performance biological serial
computation has not yet evolved. This is broadly consistent with the analysis
of H.A. Simon (1995), who claims that human thought is largely serial because
parallel processing becomes inefficient in a general purpose reasoning
device. Second, it may be that the organism doesn't know a priori that
two tasks won't clash. The default is mutual inhibition, as per the direct
lateral inhibition paradigm. Still, this isn't a good explanation for an
inhibitory setup. The cross-inhibitory 'setup' might be an example of a
synergy phenomenon. Synergies are ensembles of large numbers of biological
components (e.g. muscles, sensory organs, nerves, central circuits) which,
during a task, are coordinated and behave as a whole. As these are all
functionally bound together they lack freedom to behave relative to each
other except as prescribed by the pattern of coordination (Bernstein 1967,
as quoted in Kelso, 1995; Kelso et al, 1984). It may be that the ability
for coordination is a ubiquitous characteristic of behaving organisms.
This ability is achieved through couplings between all system levels and
components. In the presence of such couplings random relative component
activity (as is forced by the random relative timing of the two tasks in
the dual tasks paradigm) runs contrary to the general propensity for coordination.
Contrary to the dual task paradigm, organisms are good at multi-task performance
(e.g. walking, breathing and talking) if constraints of random relative
timing are lifted. This may be important in AD, where walking while talking
becomes difficult. Failure in this routine dual task may contribute to
some dangerous falls (Camicioli et al, 1997). In fact many behaviours can
be considered to involve multiple tasks having arbitrary but non-random
relations to each other. Cross-modality inhibition could be not necessarily
inhibition per se, but a vestige of cross-modality propensity for coordination.
Again, however, impaired dual task performance is just a side effect.
the lateral inhibition may have another function. In normal environments
animals utilise multi-sensory inputs. It would be disastrous for mice to
be impaired from hearing cats simply by looking for them. On the contrary,
cross-modality control could highlight in the 'interfered' modality features
of survival value in a context defined by the 'primary' modality, while
inhibiting known distractors. Irrelevant cross-modality stimuli would be
neither highlighted nor inhibited.
questions arise: What dual tasks show cooperative, and what neutral, effects
in normals ? and what happens in these tasks in AD ?
Next step models
It is important to run the whole series of simulations in this study, and particularly the MAS ones, by substituting units most compatible with cortical physiology for the Grossberg ones. These in the first instance should be KI sets. It is also important to simulate output processes including the 'binding' between perception and response selection. This would allow direct comparisons with experimental results such as reaction times and recall errors. It may be possible to simulate the digit-span experiments of Baddeley by using the successful models of Burgess & Hitch (1996) for short term memory for serial order (fig. 17).
Reflections in the light of other findings
As the discussion of the possible roles and biological substrates for cross-modality inhibition has shown, not only is it important to consider model development but also fundamental assumptions, while retaining successful general features of the present theory. This can be done by considering what ways of implementing these successful features would be most compatible with the current understanding of the neurophysiology of AD. Successful matching in the Houghton models involves an increase in activation of both the 'match / mismatch' and the perceptual neurons. While both sensory and frontal cortices are thought to be activated by attention and by concurrent tasks, it is not clear how the pattern of activation changes in AD.
Some important studies (Leuchter et al, 1992; Schreiter-Gasser et al, 1993) largely gave rise to the hypothesis that intercortical functional connectivity is especially impaired in AD and that it may account for 'dysexecutive' neuropsychological deficits. These studies influenced our modelling of AD as reducing the influence of the 'match' on the perceptual units. These studies however measured levels of EEG synchronisation of cortical oscillations, rather than levels of activation, between different cortical areas. It may therefore be that the matching process depends on such oscillatory processing.
lines of evidence, support this alternative view of matching. First, animal
data suggest that neural structures closer to the sensory receptors receive
bias, thus favouring some responses over others, through descending oscillatory
signals (Kay et al, 1996; Sillito et al, 1994). This is in addition to
the oscillatory signals of primary sensory cortex found during percept
recognition (Gray, 1994). Second, during visuomotor tasks human EEG shows
that successful trials are accompanied by increased synchronisation between
different but relevant brain areas. Gevins & Cutillo (1995) describe
increased evoked potential covariance between left prefrontal cortex and
the relevant motor and parietal cortices preceding successful responses.
Third, Bressler and coworkers (1993) showed how attention-demanding tasks
involve intermittent synchronisation of oscillatory activities among multiple
brain areas in the monkey. Synchronisation takes place very robustly, and
in discrete time frames, over cortical areas of obvious relevance. However
the findings are difficult to interpret because synchronisation epochs
do not map to information processing stages in an obvious way (unlike the
work of Kay et al in the olfactory system). Synchronisation may indicate
'consensual resolution of processing', whereby synchronous activity in
two or more areas allows amplification of the signal transmitted to common
targets that they project to (Bressler, 1995).
may involve synchronisation and AD could disrupt it through functional
disconnection, as demonstrated by the EEG studies. This could explain attentional
impairment in a general way. Cross-modality interference need not become
attenuated: Leuchter and coworkers (1992) clearly showed that coherence
of oscillatory activity between areas connected by broad, complex networks
is preserved. Most interestingly, imaging studies (Becker et al, 1996)
have shown that AD subjects activate cortical areas according to task demands
more diffusely than controls, activation 'spilling' into neighbouring areas.
Synaptic compensatory changes that account for the excess of false-positive
events during memory tasks in AD (Ruppin & Reggia, 1995) could also
account for this 'spill-over' effect. With respect to dual task performance,
such 'spill-over' would be consistent with a preserved or enhanced cross-task
a more satisfactory model of cross-modality interference could include
the physiological feature of oscillatory synchronisation and, in AD, an
impairment of the balance between long-range functional connectivity and
more local interference. This is in addition to the target units, the matching
mechanism based on recurrent connections and the perceptual mechanism modulated
by attention central to the successful psychological models.
New directions for further research
of a revised model
structure of the models used in this study (fig. 3) can be retained in
incorporating the above improvements. However, the cross-modality inhibitory
attentional projections are now omitted and local (between areas of the
same level) interference is postulated. The 'match' units are again identified
with association cortices. Each lumped cortical area is now capable of
oscillatory activity. Activation of motor schemata is through 'consensual
resolution of processing'. A diagram of the revised model is shown in fig
of the Baddeley results permits however drastic simplifications to be made.
In both all subjects the influence of the primary on the secondary task
was much greater than vice versa. We can therefore ignore the latter influence.
Also ignoring motor schema binding gives a preliminary model of only two
coupled oscillators. This bare bones model is shown in fig.
6b. Here the influence of the primary task is through a non-specific
broad band signal.
of the revised model
showed that the model is successful in simulating the overall pattern of
experimental results. Attentional activation improves its performance (indeed
for certain ranges of parametres attention is necessary for model response).
Simulation of AD by functional dysconnection of modules gradually impairs
performance, disproportionately so in the presence of an interfering task
(This is a summary of preliminary results. Please
email me for fuller info). In the normal case the presence of
interference does not greatly reduce performance.
information processing in the real brain involves a series of intermittent
synchronisations like the one successfully simulated here, the demonstrated
delays in synchronisation might be possible to directly link with prolongation
of reaction time. The problem here is that the broad band nature of cortical
oscillations does not clearly reveal a timescale with which the period
of oscillation of the simulated areas can be identified.
model is still inadequate in simulating physiology. Possible important
features that are omitted are the explicitly episodic nature of brain synchronisation;
the detailed description of the oscillators used; and most importantly,
all structure of information processing that the real episodic synchronisations
reflect. Another omitted feature is the non-negligible transmission delays
of real intercortical pathways. The model however captures enough of the
physiology to support the hypothesis in a preliminary manner.
& Alzheimer's disease
of AD related to executive function particularly lend themselves to modelling.
A most important example has to do with the possible effect of lack of
education, an independent risk factor for the development of AD (Orrell
& Sahakian, 1995). Functional imaging indicates greater deterioration
for a given degree of cognitive impairment in the brain areas subserving
attentional and executive functions of the better educated (Alexander et
al, 1997). This supports the hypothesis that better education is associated
with greater 'cognitive reserve'. The biological and psychological substrates
of the protective effect of education are however little understood and
could in the future be explored according to our paradigm. This might be
of preventative value.
Summary & Conclusion
dementia research has recently explored not only the memory but also the
so called 'dysexecutive' deficits (Baddeley et al, 1991). The latter are
thought to reflect difficulties in the coordination of daily activities
that compromise the independence of patients with AD at least as much as
memory deficits. The understanding of these executive deficits is thus
of great importance. Baddeley and co-workers (1991) postulated a Central
Executive System (CES) coordinating attention. Using the dual-task paradigm
they showed that the CES is particularly affected in DAT, accounting for
the severe attentional /executive deficits (Baddeley et al, 1991). These
experiments provided the necessary data to constrain the development of
rigorous models of executive control of attention.
and coworkers (Houghton & Tipper, 1994) have simulated successfully
many aspects of selective allocation of attention. We formulated the hypothesis
that "an application of the model of attentional control of Houghton et
al can account for the pattern of deficit observed by Baddeley in AD patients
during the performance of dual tasks". We aimed further to improve the
model heuristically but also on the basis of current neuroscientific findings.
control systems, one for each dual task modality, were combined (fig. 3).
The two systems were linked by cross modality inhibitory attentional control
(Houghton & Tipper, 1994). Damage due to AD was modelled as an impairment
of the influence of the attentional ('match') module on perceptual areas,
guided by the neuropathological finding that in early AD association areas
and corresponding long range projections are damaged (Morris, 1994).
It was found
that within a small parameter range the model could reproduce qualitatively
the general pattern of experimental results. However it had a tendency
to show spuriously activated states, lacked robustness, had difficulty
reproducing results in a quantitative way and failed to simulate the progressive
deterioration of executive function in AD. Dynamical analysis showed that
the units used to simulate individual cortical areas in the original models
were largely to blame for these failures. The model could be dramatically
improved by the introduction of lateral inhibition between sensory areas,
postulated to be largely unaffected by AD. Preliminary studies showed than
association function based on synchronisation of oscillations between different
brain areas, known to deteriorate in AD, could also account for Baddeley's
has contributed to the understanding of psychological mechanisms of executive
function particularly as involved in AD. It has demonstrated the importance
of dynamical understanding of psychological models. It brought together
rigorous neuropsychology and computer modelling, something not previously
attempted in this field but essential for the linking of the pathology
with the clinical features of AD. It has also indicated directions for
future research, mainly the investigation of the 'matching' function in
the context of oscillatory cortical dynamics and the disruption of intercortical
coordination of neuroactivity in AD.
This thesis would have been impossible without the help of Drs. Martin Orrell and George Houghton. I would further like to thank Dr. Ann Moutoussi and Dr. David Frost for precious glimpses into their world-views, and the staff of the Medical Education Centre, Whipp's Cross Hospital, Leytonstone for their help with literature searching and provision of reference papers.