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fMRI Analysis of Three
Concurrent Processing Pathways
Deborah Zelinsky
The Mind-Eye Connection,
USA
1. Introduction
Biomarkers are useful measurements to monitor ranges of neurological and biochemical
activity. They can be used as warning signs of poor adaptation to changes in either internal
or external environments. The eye is an apt structure to use for obtaining biomarkers, since
it interacts with multiple systems. For instance, pupil size and response during visual
scanning tasks is being touted as a potential biomarker for autism (Martineau, Hernandez et
al., 2011), the osmolarity in human corneal tear layer is thought to possibly be a biomarker
for dry eye severity (Suzuki, Massingale et al., 2010) and disruptions in rapid eye movement
during sleep is found to correlate with amounts of stress (Mellman, Bustamante et al., 2002).
This chapter proposes a use of functional magnetic resonance imaging (fMRI) to obtain a
visual stress biomarker in processing pathways. This hypothesized biomarker would use the
eye to indicate the relationship between internal adaptation (influenced by conscious and
non-conscious filtering and decision-making networks) and external environmental
changes. Section two of the chapter simplifies the big picture of brain function into cortical
and subcortical interconnected networks that have three concurrent movement pathways;
section three emphasizes the eye and how its complex circuitry connects with systems,
including motor, sensory and attentional networks linked with those three pathways.
Section four describes a proposed visual stress test that could show a dysfunction in the
synchrony among those three pathways, thus detecting disease states even before structural
changes occur. Implementation of this proposed test might be useful in assessing levels of
brain injury, or in early identification of diseases affecting brain circuitry, such as seizure
disorders, Alzheimer’s, Parkinson’s and multiple sclerosis.
Documentation of brain activity can be achieved by various methods, using both functional
and anatomical landmarks, which will help to account for individual patient differences. For
example, some methods quantify neuronal firing (via electrophysiological tools), others
measure oxygen levels in blood (via hemodynamic responses) and still others assess
metabolic changes (via optogenetic methods). (Optogenetic methods use genetically
engineered proteins to regulate activity of specific types of cells by turning neural circuits on
and off through light-activated channels. This new method observes and assesses local
networks within the framework of global circuitry.) Often, two or more testing methods are
used together to account for limitations in each (Dale and Sereno, 1993). For instance, fMRI
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maps where local neuronal activity is by measuring the hemodynamics of blood flow, and
electroencephalograms (EEG) map when electrical activity occurs by measuring frequency
oscillations of brainwaves. The fMRI and EEG together have high spatial resolution and
temporal resolutions respectively, providing more information than either method alone.
Combining optogenetics with fMRI technology into an optogenetic fMRI (ofMRI) allows
scientists to assess both neuronal activity and its metabolic sequellae, helping to identify,
and in some cases treat, underlying disease states (Lee, Durand et al., 2010; Zhang,
Gradinaru et al., 2010; Cardin, Carlen et al., 2010).
Although the fMRI is a wonderful diagnostic tool, one limitation is the restriction on patient
movement. To address this apparently unchangeable drawback, instead of the patient
moving, the external environment can be altered and the patient’s adaptation measured. The
alterations can be done through the eye by stimulating the retina with lenses, prisms, filters
and/or mirrors.
2. Survival functions to executive functions: Brain circuitry
Brain activation involves stimulation, modulation, feedback and feedforward mechanisms
in two main groupings: subcortical functions and cortical processing. Each grouping is
known to have multiple interconnections, with more pathways being discovered annually.
These extensive feedforward and feedback systems allow for interconnectivity of individual
structures as well as linkages between movements and thoughts.
Brain activity can be viewed in terms of arousal of, awareness of and attention to both the
internal and the external environment. Subcortical activity, such as survival functions
(circulation, digestion, respiration, etc.), remain beneath conscious awareness until altered
by suprathreshold sensory stimuli, causing distracting cortical activity. An individual with a
larger threshold of tolerance to sensory changes would not be burdened by those stimuli,
thus allowing more efficient brain function.
In 1973, Ralph Luria wrote about functional systems in the brain that were not in isolation.
(Luria, 1973) He proposed that the cortical brain was composed of both units and zones,
which, when functioning properly, work together to regulate behaviors, senses and
thinking. The units included information handling, tone and regulation of mental activity.
The zones included a primary, for information gathering, a secondary, for information
processing and programming, and a tertiary, for complex forms of integrated mental
activity. He hypothesized that sensation and perception were intimately involved with
movement, having afferent and efferent components. He also proposed that the eye, as an
extension of the brain, is never passive, and is always actively searching to pick out essential
clues from the environment. Now, almost forty years after Luria’s theory was first
presented, functional organization and anatomical connectivity of regions in the cerebral
cortex have been documented through neuroimaging and other techniques.
In the brain, structures are grouped to accomplish specific types of tasks. For instance, in
general movement networking, many interacting pathways are involved with the frontal
cortices, basal ganglia and cerebellum as the “main players.” The frontal cortices plan and
organize movement, generating motor programs (with the prefrontal and the premotor
regions contributing to different functions), the basal ganglia govern movement intention
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programs, and the cerebellum is involved in the coordinated adjustment (smoothing out) of
movement quality. The prefrontal cortex sends voluntary commands to the basal ganglia so
that appropriate movement is selected, and other cortical association areas send the basal
ganglia information for acquired (automatized) movement. Sensory signals from cortical
processing are sent to the matrix of the basal ganglia, while the striosomal portion of the
basal ganglia attaches an “emotional valence” to that sensory information for the purpose of
learning.
Fine motor tasks such as eye movements add more “players”. The brainstem’s oculomotor
system receives direct projections from the various eyefields located in their own brain
network. Frontal eye fields, parietal eye fields, prefrontal eye fields and supplementary eye
fields, each have a region involved in either saccadic or smooth eye movements (Lynch and
Tian, 2006; Cui, Yan et al., 2003). Neuroanatomical studies in non-human primates
determined that there are several distinct regions in the cerebral cortex (designated eye
fields) forming a cortico-cortical network guiding and executing decisions for voluntary,
visually guided saccadic and pursuit eye movements. Some of the subcortical structures
used in eye movement, for example, involve the superior colliculus and the frontal eye fields
integrating information received by the geniculate-striate pathway and contributing to more
thinking and movement decisions (Ding and Gold, 2011).
Anatomical patterns of new movements, from initial learning to automation, shift over time
as the movement is practiced and developed. The retention of movement schema
(praxicons) is in parietal/temporal-parietal circuits and connects with the cerebellum which
refines the praxicons and innervatory programs by comparing predicted movement
outcome with error. These comparisons are accomplished by the brain via two types of
procedures, described by theoretical control models. Forward models predict movement
outcomes by projecting signals to parietal and frontal motor regions, allowing for
automation and bypassing direct (slower) sensory input. Inverse cerebellar models are
initiated outside of conscious awareness and bypass premotor cortex commands, allowing
automatic movements. Speed and precise accuracy of intentionally guided actions and
predictions is thus developed (Imamizu and Kawato, 2009).
Movement is not in isolation from thoughts; it is one part of a network of functional circuits,
each with its own pathway, synchronizing like an orchestra. Concurrent pathways form
loops, including sensory stimuli, processing and motor reactions and responses. The
processing can be analytical and intentional, or intuitive and habitual, leading to various
brain networks, such as, visuo-spatial processing from the parietal lobe, visually guided
action from the premotor cortex and navigation, imagination and planning for the future in
the prefrontal cortex. (Kravitz, Saleem et al., 2011) Both the mind (cortical) and body
(subcortical) systems have to adapt to continual environmental changes, at either a
conscious or non-conscious level of awareness. Also, there is substantial integration between
subcortical and cortical structures as well as interrelationships and interactions at micro-
circuitry levels.
At any given moment, three movement types (reflex, developed and intentional) are the result
of three processing pathways, activated by different amounts of stimulation at different
speeds, capturing different amounts of attention. Figure 1 highlights the differences between
how these movement types are generated. The distinctions are important to our purposes
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because of the interrelationships among the three separate pathways. Developed movements
include learned-orienting and anticipatory pathways. However, orienting movements can also
be reflexive. It is possible that during an fMRI, the three processing pathways can be analyzed
to assess which one has more of an attentional demand at the expense of the others and
determine the location(s) of brain activity occurring.
The following diagram (Figure 1) has much more extensive integration of cortical and
subcortical structures than implied by the small arrow, but is a simplification in order to
describe the framework of subcortical to cortical shifts in brain activity. All cortical areas have
significant inputs and major feedforward and feedback connections to numerous subcortical
structures. Some functional networks share similar pathways. For instance, auditory and
visual reflexive spatial orienting are controlled by a common underlying neural substrate
(Santangelo, Olivetti Belardinelli et al., 2007) and there are subspecialized areas, such as the
middle temporal lobe (MT) which, in congenitally blind people, reacts to tactile motion, but in
sighted people, reacts to either visual or tactile motion. (Sani, Ricciardi et al., 2010).
Fig. 1. Simplified Diagram of Three Concurrent Movement Pathways
Many sensory signals lead to unconscious reflex
movements as shown by pathway 1. Remaining
signals from the thalamus and other subcortical
structures continue for futher processing in
various cortices (occipital, temporal, parietal
and frontal) eventually resulting in developed
(habitual) subconscious movements indicated
by pathway 2 and intentional, conscious
movements represented by pathway 3.
Anticipatory movements are grouped into the
developed (pathway 2) category.
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Whether the paradigm used is anatomical, physiological, psychological, neurological, etc,
there is only one brain with parallel systems in action. Below are some ways to view brain
activity. Each is a continuum, with a constant two-way exchange of information.
Stimulus Location Internal External
Processing Mode Ambient Where Am I* Ambient Where is It?* Focal What is It*
Physiological Pathways Magnocellular* Koniocellular* Parvocellular*
Anatomical Categories Subcortical Cortical
Functional Networks Survival Functions Executive Functions
Psychological Activity Non-conscious Conscious
Perceptual Activity Arousal Awareness Attention Intention
Brainwave Type delta theta alpha beta gamma
Table 1. Simplified continuums in brain function analysis (*discussed in section 3)
Visual, auditory and somatosensory signals are transmitted partly through the thalamus
and partly other subcortical regions. From the thalamus, auditory signals travel to the
temporal lobe, and visual signals to the occipital lobe, later combining with proprioceptive
and somatosensory information from the body in the parietal lobe for higher cortical
processing (Williams, 2010).
The integration of somatosensory, auditory and visual inputs is one aspect of determining
“Where am I?”. There are also cognitive systems operating to assist in spatial orientation
(Arthur, Philbeck et al., 2009). However when using MRI machines to assess brain activity and
functional circuitry in thinking and movement pathways, body movement cannot be used
because it is restricted. Similarly, auditory testing is difficult to use, because there is ambient
noise. Therefore, the obvious choice would be the eye -- easily accessible and directly
connected to the brain. It must be noted that recent studies suggest an effect upon the subject’s
vestibular system produced by the fMRI magnetic field (Roberts, Marcelli et al. 2011), which
could possibly influence eye movement findings. However, the effect was noted during a
resting state when the visual system was not provided any meaningful drive.
3. The mind-eye connection: Functional networks
Although eye movement is commonly assessed by fMRI, the complete depth of possibilities
has not fully been explored. As has been shown above, the eye is much more than a visual
sensory organ; it provides the entrance to a two-way street into the body and the mind. In
this chapter, for the sake of simplicity, only three subsystems -- motor, sensory and attention
-- will be addressed, while remaining aware that they are part of a much bigger, more
complex cortical/subcortical loop with multiple feedback and feedforward channels in a
continually adapting dynamic system of metabolic and neurological functional networks.
When the classically understood visual pathway from the eye to the visual cortex is engaged
in a conscious activity (i.e. seeing), reflexive and responsive networks are also in use. For
instance, the reading process comprises not only the cortical visual activity of seeing (letters
on the page), but also a concurrent process creating the foundation for visualization and
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interpretation. In addition, the mind is on the alert for external and internal sensory signals
which may shift mental attention. If a person is reading and a loud noise occurs, attention
will tend to shift as many events take place. The head reflexively turns toward the perceived
sound location, postural mechanisms maintain balance and respiration, digestion and
circulation systems are momentarily disrupted, to name a few. All in all, if processing is
disrupted, attention is often hindered.
There are numerous factors affecting visual processing such as internal health, attention,
spatial awareness, emotional state, etc., each affecting the functional networking of reflexive,
intuitive (developed) and analytical (intentional) processing pathways. If there is a problem
in one or more functional networks, the issue could be due to structural damage or
inefficient synchronization of systems. For instance, fMRI connectivity analysis
demonstrates that auditory and visual cortices are linked; altering one affects the other
(Eckert, Kamdar et al. 2008) . Recent studies propose that sensory systems might be able to
be used to regulate timing of brainwaves (Hughes, 2008), implying that visual interventions
could alter brain circuitry. fMRI testing revealed that in a resting state, activation in specific
cortical networks differs between patients with Alzheimer’s disease and healthy people.
This distinguishing factor of decreased metabolism in certain brain structures can be a
potential biomarker for Alzheimer’s disease. (Greicius, Srivastava et al. 2004)
Each individual has a unique filtering process that includes simultaneous and sequential
processing before decisions are made as to motor output. The mind continually filters external
and internal stimuli, choosing how to respond, with a complex series of conscious and non-
conscious thoughts and emotions, many of which affect brain networks connected with the
eye. (Reactions, on the other hand, are more automatic, occurring without those “decision-
making” processes). As will be shown, each of these decisions, reactions and responses can be
thought of in terms of “clues, cues and cruise control” and related to the three processing
pathways. Consciously used clues lead to intentional movements, inferences of cues accessed
beneath conscious awareness lead to habitual responses, and automatic reflex systems on
“Cruise Control” lead to reflex movements that function unconsciously.
(This is not a new concept. Dr. A.M Skeffington, the founding father of neuro-optometry,
understood that patients’ use of visual systems was not a simple, mechanical matter of
seeing but instead was a patient’s internal engagement with the external environment and
desire to explore a spatial world around them. This was extremely evident to him by
changes in the retinal reflex during optometric retinoscopy. Decades later, it was
demonstrated that conscious perception of the external world activated fast brainwaves,
different from the brain activity exhibited when perception of the external surroundings was
not high attentional priority (Hughes, 2008).)
Subsections, 3.1, 3.2 and 3.3. describe those processing channels in terms of 1) movements,
including eye movements, 2) sensory signal processing, including retinal signals, and 3)
attentional factors, modulated by external and internal elements.
3.1 Movement networks: Reactions and responses
There are many measureable motor outputs from the eye, including pupillary reactions,
ciliary body activity, eyelid and extraocular muscles (EOM) movement. The intraocular
(pupil and ciliary body) and extraocular muscles each use different circuitry (Muri, Iba-
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Zizen et al., 1996), often combining with feedback from eye muscle position
(proprioceptors) in the eye and neck muscles. Because the purpose is to discuss
intentional, habitual (developed) and reflexive movement pathways, this chapter is
limited to the related extraocular muscles which can be moved reflexively, habitually
(from developed skills) or intentionally. The eyelid will not be included because it is
innervated by both smooth and skeletal muscles, and is therefore controlled by different
functional networks.
Although the eyes can be moved voluntarily, most eye movements are reflexive (Weir, 2006).
Figure 2 shows reflexive reactions of extraocular muscles include the following, which share
many of the same neuronal pathways:
Vestibulo-Ocular Reflex (VOR) moves the eyes to counteract head movement, allowing
the eyes to maintain fixation – a function critical for stabilizing the eyes while the head
is moving.
Optokinetic Nystagmus Reflex (OKN) pathways help eye stabilization during an
involuntary fixation of moving objects (Swenson, 2006).
Reflexive Saccadic eye movements – when the superior colliculus sends signals
reflexively pointing the eyes to stimuli of interest, such as flashes of light or loud noises.
The superior colliculus contains a spatial mapping of the external environment and
receives visual, auditory and somatic sensation from many locations, including the
spinal cord, the cerebral cortex and basal ganglia.
Vestibular Colliculus Neck
Fig. 2. Reflex pathways of eye movements
Cortical responses of extraocular muscles based on sensory input and attention:
Non-reflexive saccadic eye movements
Vergence eye movements – convergence and divergence, aiming the eyes toward a
target on the z-axis.
Smooth Pursuit eye movements – require the eyes to be fixated on a moving external
target.
Fixation eye movements – maintain target in line of central eyesight.
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3.2 Sensory networks: Central and peripheral retinal signals
Other neurological sensory input in the visual system includes proprioceptors from the
EOM. There are also chemical pathways in the eye that have feedback and feedforward
input, such as the consistency of corneal tear layer which varies as the nervous system is
stressed, and the chemical gradients in the optic nerve which vary with retinal activity.
The retina itself functions constantly, extraordinarily busy with metabolic and neurological
activity, even during sleep. In fact, when eyelids are closed, regardless of the waking state,
photic stimulation caused by ambient lighting affects retinal (and brain) processing.
Concurrently, there is non-photic stimulation from metabolic activity. Of the multiple
sensory networks in the eye, this section will focus on central and peripheral retinal
stimulation. (Section 3.1 discussed retinal signals that were transmitted directly through the
midbrain’s superior colliculus to elicit reflex eye movements. This section emphasizes the
retinal signals that synapse at the thalamus’ lateral geniculate nucleus (LGN) and continue
to the occipital lobe.)
Retinal stimulation occurs in at least three ways: from extrinsic illumination (light or lack of
light), from intrinsic chemical changes via circadian rhythms (Tombran-Tink and Barnstable,
2008), or by mechanically induced pressure. The fact that extrinsic illumination stimulates
the retina, in easily manipulated ways, will help establish the visual stress biomarker
proposed in the beginning of the paper. During an fMRI, the visual stress test determines
when the peripheral retinal stimulation reaches its threshold and distracts central retinal
attention of details. Central stimulation occurs when the macular region receives light where
attention is placed.
Chemically and electrically, there is a monumental amount of internal processing occurring
in the retina via the main groups of retinal cells (bipolar, ganglion, horizontal, amacrine,
photoreceptor and Mueller), which are subdivided into over a hundred cell types, each
performing a different task. This cellular teamwork allows for such functions as luminous
efficiency, sensitivities to spectral frequencies and gated signaling channels.
Retinal processing begins at the photoreceptor level when a photon of light is absorbed by
the molecule rhodopsin, converting it into an activated state. Subsequently, a cascade of
chemical changes occurs in the outer retina, leading to various ion channels opening and
closing, eventually eliciting an electrical response in the inner retina, which is monitored by
action potentials and calcium regulation pathways. The traveling signals eventually arrive
in ganglion cells, continuing through the optic nerve and into the brain (Tombran-Tink and
Barnstable, 2008) (See Figure 3).
The superior, inferior, temporal, nasal and macular portions of the retina are developed
from completely different sets of chemical pathways and genetic codes, and each of those
five geographical sections in the retina is regulated by different transcription factors and
develops during different timeframes (DeGrip, Pugh et al., 2000; Tombran-Tink and
Barnstable, 2008). This is important, because patterned neuronal activity in the early retina
has a substantial influence on the retinotopic organization of the superior colliculus (Mrsic-
Flogel, Hofer et al., 2005). Therefore, stimulating selected retinal portions with visual
interventions can induce processing changes.
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Retinal pathways differ not only in development, but also in function. This has been
demonstrated by fMRI testing indicating that nasal and temporal regions vary in melatonin
suppression (Ruger, Gordijn et al., 2005). Binasal occlusion on eyeglasses has been used for
years to visually treat patients with crossed eyes and brain injuries. Perhaps this occlusion
alters the chemical pathways, indirectly affecting neurological circuitry in eye movement
control and thus perception of surrounding space (linking motor, sensory and attentional
circuitry). Processing also differs between the inferior and superior hemifields of external
space (Rubin, Nakayama et al., 1996). For instance, people are generally more attuned to
visual information entering from the lower portion of external space (light coming upward
stimulating the superior retina) than to light stimulating the inferior retina.
Alteration of retinal stimulation affects both subcortical and cortical processing. Visual
processing has been documented in several hundred functional feedback and feedforward
brain pathways encompassing almost fifty cortical regions (Klemm, 1996), and fMRI
allows for better three dimensional spatial resolution of these pathways. When activated
by light, the retina triggers activity at three concurrent levels of processing: analytical
(conscious, simultaneous or sequential), intuitive (subconscious) and autonomic
(unconscious). Eventually an fMRI database of normal functions can be accumulated so
that functional changes during disease processes could be compared to normed data.
fMRI usage can thus aid in the differentiation of pathways in concurrent systems during
mental activity.
Fig. 3. Central and peripheral light rays striking the retina, exiting the optic nerve.
©2011 Mind-Eye Connection Reprinted with permission. For simplification, the dendrites
are drawn in a line, but do vary in length.
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3.3 Attentional networks
Retinal stimulation is, of course, only one portion of sensory input to the eye. There are
many other sensory signals involved, such as proprioceptor information and signals from
corneal receptors. Consider the effect of a small eyelash rubbing against the cornea. During
the time when the eyelash is bothersome, reflex tearing occurs, the eyelid reflexively blinks,
the extraocular muscles reflexively point the eyes away from the pain, the auditory system’s
awareness of the surroundings constricts, the pupils change size, etc. If the person wishes to
continue to see, he must apply conscious effort. In a stressed condition or diseased state, the
need to apply conscious attention will occur sooner and more frequently than under normal
conditions. That painful sensory stimulus creates an attentional demand, diverting attention
away from the external environment and eyesight. The sensory system and motor systems
are not simply mechanical; they are inextricably linked with and influenced by attentional
networks.
This process of sensory input via light striking the retina does not take place in a vacuum.
Other events may influence the individual’s perception, including which details are
selectively filtered out from the available information at a given time. The level of awareness
an individual is able to experience is dependent not only on the proper functioning of the
retina and other structures of the eye, but also on the availability of the mind’s attentional
networks – neurological and chemical. This fact offers insight into patient function and
dysfunction and also presents many possibilities for designing tests to define the normal
parameters of conscious attention versus reflexive and habitual activity.
In 1911, an article commented on how retinal reflexes changed depending on attention
factors and the angle of the light (Wilson, 1911). A hundred years later, in 2011, a more
analytical research project demonstrated the validity of that concept in migraine sufferers
(Huang, Zong et al., 2011).
In the 1930’s, Dr. A.M. Skeffington, described “vision” as an emergent concept from four
intertwining circles (Where am I? Where is it? What is it? and Speech/Auditory). The
“Where am I?” relies mainly on subcortical processing, the “Where is it?” “What is it” and
“Speech/Auditory” rely mainly on cortical processing. Dr. Skeffington spent years
promoting his thoughts that the eye was part of the body, controlled by the brain, and that
changing information which entered the eye would affect the entire body (Skeffington,
1957). This pioneering optometrist believed that sensory systems should be evaluated in
total rather than in isolation. For instance, he believed that eye aiming and focusing be
evaluated together as a team, termed a visual reflex, rather than separately as convergence
and accommodation, since they are not separate. One responsibility of optometrists whose
work emphasizes neuro-optometry is to measure the function or dysfunction of retinal
circuitry. fMRI research demonstrates (decades after Dr. Skeffington’s proposals) that the
eyes do affect brain and body circuitry. (There is also interplay between an individual’s
genetic predisposition and their unique experiences, regulating brain circuitry.)
The sensory inputs of both eyes have magnocellular, koniocellular and parvocellular portions,
arising from peripheral and central retinal stimulation. The magnocelluar portion is further
divided into two smaller parts: non-conscious reflex and developed pathways. Testing the
mental shift in attention from ambient processing (magnocellular pathways) to focal
processing (parvocellular pathway) is important in differentiating movement pathways.
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Magnocellular (M) system provides answers to “Where am I?” and “Where is It?” at a
reflexive and a cortical level respectively, beneath conscious awareness, and the parvocellular
(P) system answers the meaningful question of “What is It?” at the cortical level.
The fastest retinal signal pathway is the reflexive “Where am I?” portion of the magnocellular
(M) pathway involving retinal signals that are processed subcortically. Of the retinal
signals continuing through the optic radiations before arriving at the occipital cortex, some
originate from macular stimulation (carrying information regarding color and detail) and
others from peripheral retinal activation (carrying information regarding such factors as speed,
location, size and shape). When entering the occipital lobe’s striate cortex, the information is
spatially based (externally controlled), with a point to point spatial representation of the
external world mapped with pinpoint precision. However, upon exiting the occipital lobe,
information is attentionally based (internally controlled), with the dorsal stream going on to the
parietal lobe (carrying “Where is It?” signals of background information) and the ventral
stream continuing to the temporal lobe (carrying “What is It?” signals of target information).
Signals from the dorsal and ventral streams integrate, eventually arriving in the frontal lobe.
From there, signals are transmitted to cranial nerves III, IV and VI which send signals to the
extraocular muscles, resulting in eye movement.
In 2011, it was determined that a Koniocelluar (K) pathway activity might be gating the
cortical circuits fed by the M and P pathways and hypothesized that the sensory streams can
be adjusted to modify brain rhythms via parallel visual pathways (Cheong, Tailby et al.,
2011). Also, each of the two cortical visual streams also have connections with subcortical
nuclei (Webster, Bachevalier et al., 1995). These studies seem to provide validity to the
concept of a visual stress biomarker.
In addition to the “Where am I?” (subcortical processing), “Where is It?” (dorsal stream) and
“What is It?” (ventral stream), hypotheses for When and Why pathways emerged in 2003
(Krekelberg, 2003). In 2011, a study found a “When” pathway and demonstrated its
connections between the visual cortex and the temporal lobe (Naya and Suzuki, 2011).
Sensory stimuli are filtered during processing, and decisions are made by the mind based on
arousal, attention, awareness, emotions and memories. Conscious attention and awareness
are often directed to different volumes of surrounding space which can be expanded or
constricted depending on other internal and external signals, including general health and
fatigue. Intra-cortical connections are responsible for routing information selectively to
progressively higher and higher levels of processing. There is top-down processing from
memory circuitry and bottom-up processing from retinal input, with the control of visual
attention thought to be found in the pulvinar (the back section of the thalamus) (Olshausen,
Anderson et al. 1993). The thalamus is also responsible for mediating the interaction
between attention and arousal during perceptual and cognitive tasks (Portas, Rees et al.,
1998; Saalmann and Kastner 2009, 2011). Dr. Selwyn Super, an optometrist whose work
emphasizes neuro-optometry, discusses intention as a top-down executive function with
feedforward and anticipatory circuitry and attention with both top-down and bottom-up
connections, competing with each other. In the case of patients with attentional neglect,
where internal awareness of surrounding space or of their body is not normal, some are
deemed sensory-attentional, others motor-intentional and still others as having
representational deficits (Super, 2005).
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It is clear that controlled, subtle continual change in retinal stimulation will eventually cause
shifts in attentional demands and brain activity as signals trigger shifts from arousal to
awareness to attention. This type of controlled change can be produced by optometric
methods.
Fig. 4. Magnocellular “Where is It?” pathway signals traveling in middle temporal (MT) and
medial superior temporal (MST) lobes.
Fig. 5. Parvocellular “What is It?” pathway Signals traveling through the inferior temporal
(IT) lobes.
4. Optometric changes to functional networks
Optometric tools, such as prisms, break light into frequencies and spatially distribute the
light onto the retina. Each tool stimulates different areas of the retina, and as the eye moves,
the optic flow sent to the brain is altered. By relying on the point to point brain mapping
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from the retina to the visual cortex, and the non-visual pathways from the retina to other
brain circuitry, visual intervention could affect fMRI findings.
The visual changes could be accomplished by using combinations of lenses, prisms and
filters (including occlusion) to alter entering light. The amount and direction of light input
can be a controlled variable, and the patient’s reactions to changing environmental stimuli
can be measured to determine how well, and in what areas, the subcortical and cortical
networks are interacting as well as its tipping point. Circuitry and pathways used for
information processing can be identified and modified.
The visual spectrum has more to offer than eyesight alone. For instance, prisms and mirrors
together are being developed to render objects invisible to the human eye (Zhang, Luo et al.,
2011), and mirrors are being used in rehabilitations in patients with neglect from brain
trauma (Ramachandran and Altschuler, 2009).
Intentional eye movements and retinal stimulation are often used to induce changes in brain
activity during fMRI testing. Equally as valuable, is an assessment of a patient’s adaptation
to environmental change. Disruption of mechanisms can lead to disease. If there is
significant variation from a normal database, eye movements can be used during fMRIs to
detect deviations in information processing, perhaps identifying disease states before
structural breakdowns occur.
Visual interventions can be in many forms, each stimulating the retina in a different way.
Lenses – dispersing light toward the edges or the center of the retina. This
change in light mainly alters the balance between central and peripheral
circuitry by having the target and background occupy different percentages of
the retinal input.
Yoked Prisms – angling light toward one edge of the retina. This initially affects
the body’s positional sense, because reflexive eye movements will point the
eyes toward the incoming light, triggering internal postural mechanisms in the
hips for stability of balance, to counteract the eye movement. Depending on the
stability of the person’s sense of balance, attention may be then shifted to
external targets.
Non-yoked prisms – angling light toward either nasal or temporal retinal
sensors. The eyes will also reflexively point toward the light, but this inward
and outward movement stimulates different visual and postural mechanisms
(shoulders rather than hips), pulling attention to the object location.
Filters – altering either spatial or temporal retinal input, thus affecting
processing.
Tints - filtering out specific wavelengths of light, stimulating specific retinal
cells, primarily altering internal sensations, via the autonomic nervous system.
Mirrors – make targets appear farther away than the mirror frame, creating a
sensory mismatch between the central (target) and peripheral (background).
©2010 Mind-Eye Connection Reprinted with permission
Table 2. Optometric tools for non-invasive visual interventions
Functional Magnetic Resonance Imaging – Advanced Neuroimaging Applications
96
Movements, sensory inputs and attention can be considered within a broader framework of
sensory integration. For instance, just because a person can hear and see does not mean he
can simultaneously watch and listen to a moving target such as a teacher in a classroom.
Using visual stress tolerated, as a biomarker for normal brain adjustments, will demonstrate
adaptation ability (as long as the patient’s individual tolerance level and overall physical
and mental state is considered).
Eye stimulation can be used for both diagnostic and therapeutic purposes. When a person
doesn’t appropriately adapt to environmental changes, this proposed biomarker will be
outside of a normal range. For instance, adaptation to specific spatial shifts in prisms led
researchers to the conclusion that prism adaptation was processed in motor parts of the
brain relating to action timing. Patients adapted to the prisms’ spatial displacement
independent of awareness of subjective timing (Tanaka, Homma et al., 2011).
5. Conclusion: A biomarker for usage of clues, cues and cruise control
The exploration of brain activity following changes in retinal inputs is fundamental for a
better understanding of the basic principles governing large-scale neuronal dynamics. The
hypo- and hypersensitivity of the retina, even through a closed eyelid, suggest a
neurological basis for the diagnostic and therapeutic effect of lenses to consciously and non-
consciously alter incoming sensory signals and influence brain processing.
Current functional magnetic resonance imaging vision research tends to focus on
perception, or on eyesight and damage in eye structures, such as optic neuritis and macular
degeneration. However, the eye offers much more. Its interactions and relationships within,
between and among motor, sensory and attentional networks (as well as emotional and
cognitive systems) can be documented by controlling external environmental changes and
measuring internal adaptation, thus differentiating among the three concurrent processing
pathways and movement outputs.
Assessment of the three different levels of eye movement and adaptation to change is
important for diagnosis of systems’ instability or dysfunction, with the ultimate goal to
measure shifts in attention and compare to a normed database. Thoughts and movements
are integrated via:
Consciously used clues, leading to intentional movements
Inferences of cues accessed beneath conscious awareness, leading to developed or
habitual actions
Automatic reflex systems on “Cruise Control” leading to movements that function
unconsciously
Thus, visual systems involve not solely what the eyes see, but the integration of neural
pathways. When observed during fMRI, eye motor responses offer insight into brain
activity and can be helpful to further categorize and appropriately treat the increasing
incidence of degenerative and other conditions. Specifically, a visual stress test can
influence brain circuitry via alterations of retinal input during an fMRI procedure (using
lenses, prisms, mirrors and/or filters) and can have the potential for revealing
dysfunction in such pathways as information processing, attention, movement and other
interconnected sensory systems. Imaging techniques are useful ways to demonstrate
fMRI Analysis of Three Concurrent Processing Pathways
97
dysfunctional circuitry, both in grey and white matter, but sometimes the dysfunction has
to be stressed before a breakdown can be observed. Clinical applications could include
assessments of functional breakdowns in disease states, e.g., seizure disorders, memory
deficits and visuo-cognitive abilities in patients with Alzheimer’s disease and eye
movement control and balance in patients with traumatic brain injuries or Parkinson’s
disease.
Retinal pathway changes and impairments have been noted in patients with epilepsy,
Parkinson’s and Alzheimer’s along with other diseases (van Baarsen, Porro et al., 2009;
Altintaş, Iseri, et al., 2008; Cubo,Tedeio, et al. 2010; Parisi V, 2003). Cortical atrophy in
Alzheimer’s patients can be seen years before cognitive impairment becomes evident
(Dickerson, Stoub et al. 2011), yet cognitive impairment is not always the first symptom of
Alzheimers disease (38% of people have vision, behavior or other warning signs (Balasa,
Gelpi, et. al. 2011) and that the default network brain activity differs in people with
Alzheimer’s (Shin J., Kepe, V. et al., 2011). This paper hypothesizes that shifts in cognitive
and attentional systems can be observed even earlier, using neuro-optometric
interventions during fMRI, in combination with other testing methods, to measure an
abnormal functional shift in either default attentional networks or cognitive networks,
before the structural atrophy occurs. A defect in functional connectivity would be a valuable
biomarker.
Embracing a viewpoint of brain circuitry and metabolism could shift optometry toward a
profession of selective neurological and biochemical pathway stimulation. Using the eye as
a portal to the nervous system, measurements of internal reactions and responses to external
changes can be made, in hopes of providing a useful visual stress biomarker for future
disease research and eventual interventions for preventive healthcare.
6. Acknowledgments
Credit must go to two optometrists who dedicate their lives to promoting neuro-optometric
concepts. Dr. Albert A. Sutton, who continually applies and teaches Dr. Skeffington’s
visionary viewpoint and has allowed me the privilege of learning from him for years. Dr.
Sutton’s way of stimulating thinking led to the integration of concepts discussed above.
Also, sincere thanks to Dr. Selwyn Super, practicing in California, for dedicating time to
thought-provoking discussions with me regarding his groundbreaking work on intention,
attention and inattention.
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