**1. Introduction**

The perception of light underlies the processes of cognitive brain function. However, the characterizations of the neuroadaptational processes that relates to the physical quality of light, particularly those implicated in color processing remains largely unknown. Simultaneous color contrast and color constancy have been identified as the memory processes associated with color processing [1-8]. Simultaneous color contrast is the phenomenon that surrounding colors profoundly influence perceived color [1,9]. The mechanism implicated in simultaneous color contrast has been described as wavelength-differencing, implying the ability to differ‐ entiate the dominant wavelength of the color of light [10]. Wavelength-differencing involves wavelength-encoding main effect at subcortical peaks, and energy-encoding effects at cortical peaks [11]. On the other hand, frequency-differencing refers to the ability to differentiate the dominant frequency (the inverse of wavelength) of the color of light, and involves energyencoding main effect at cortical and subcortical peaks [11, 12]. Genetic studies suggest genderrelated differences in color vision in primates. Whereas both trichromatic and dichromatic color vision occurs among female monkeys, males appear exclusively dichromatic [13]. It was proposed that, unlike humans, squirrel monkeys have only a single photopigment locus on the X chromosome [13].

Color constancy relates to the invariance of hue, or perceived color of a surface under variation in the spectral content of illumination [3, 14, 15]. In other words, color constancy refers to the unchanging nature of the perceived color of an object despite considerable variation in the wavelength composition of the light illuminating it [16]. It has been suggested that there may exist a color space comprising chromatic axes (red-green and blue-yellow) and achromatic

© 2013 Njemanze; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Njemanze; licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

(black-white) luminance axis [8]. However, the non-invasive physiologic measurements at the neural substrates to characterize the 'color space' in humans has not been feasible until now [17]. The anatomy of the main neural substrates for color processing have been characterized within the visual pathways and extrastriate cortex 'color centres' [18], which lie within the distribution territories of the posterior cerebral arteries (PCAs) [19-21] and middle cerebral arteries (MCAs) [19, 21, 22]. The superior parietal aspects of the optic radiation receive blood mainly from the MCA, whereas the inferior aspects are supplied by the PCAs [23]. The macular cortical region receives blood supply, from both the calcarine artery (a branch of the internal occipital artery of the PCA distribution), and branches of the MCA, which explains macular sparing with PCA occlusion [19]. Therefore, it is possible to characterize the 'color space' in the primary visual cortex and extrastriate areas using measurements of changes in blood flow velocity in the MCAs during color stimulation [22]. In prior studies in our laboratory for microgravity simulations, we applied non-invasive transcranial Doppler measurement of mean flow velocity (MFV) in the MCAs, to examine changes in color space in men during headdown rest, and demonstrated neuroplasticity over 25 hours of recordings [11], or more, if testing was continued. These findings have been related to formation of the phenomena of long term potentiation (LTP) and long-term depression (LTD), implicating role for NMDA receptors [11]. The phenomena of LTP [24] and LTD [25], have been applied to explain potential mechanisms of memory, primarily because they exhibit numerous properties expected of a synaptic associative memory mechanism, such as rapid induction, synapse specificity, associative interactions, persistence, and dependence on correlated synaptic activity. Given these important features, LTP and LTD remains only models of the synaptic and cellular events that may underlie memory formation.

wavelength-differencing processes in men [11], while in women, the underlying process was characterized as frequency-differencing [12]. This is the first hint that, there may be a genderrelated difference in color processing. This is a profound finding that may change our overall understanding of perceptive processes in men and women. It was therefore proposed that, the brain color processing mechanisms integrates within a three-dimensional 'color space', luminance effects in the left hemisphere, and wavelength-differencing effects in the right hemisphere in men, but frequency-differencing effects in the left hemisphere in women [17]. The latter finding led to the conclusion that, color processing followed the same rule of lateralization as other major cognitive functions, such as facial processing [26, 27] and general intelligence [30], which implicated the right hemisphere cognitive style in men, and left

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Furthermore, the functional integration in color space was mathematically modeled. It was shown that, the existence of wavelength-differencing in men and frequency-differencing in women, implemented inverse exponential and logarithmic functions, respectively. These gender-related differences that underlie cerebral asymmetry for color processing, has been hypothesized to be associated with the perception of the dual nature of light as a wave and as particulate energy referred to as quanta [11,12]. The presumed genetic and psychophysiologic effects of the physical qualities of light was the basis for the proposal of the light hypothesis of cerebral asymmetry [12]. The light hypothesis for cerebral asymmetry, posits that, the phenotypic neuroadaptation to environmental physical constraints of light as a wave and as quanta energy led to phenotypic evolution, and genetic variation of X-Y gene pairs that determine hemispheric asymmetry [12]. Hence, the evolutionary trend is towards optimiza‐ tion of perception of the 'whole' environment by functional coupling of the genes for comple‐ mentarity of both hemispheres within self, and between both genders [12]. More specifically, the basic tenant of the Light Hypothesis for cerebral asymmetry posits that, the right hemi‐ sphere is implicated in wavelength-differencing in men and the left hemisphere, in frequencydifferencing in women, with an overall gender complementarity in adaptive mechanisms for neuropsychophysiological processes. The latter has been characterized as gender-related

cognitive styles designed for coupled perceptual experience of the world around us.

of perception of faces has to be examined beyond the use of colors.

Overall, it has been documented that there is a gender-related difference in facial processing [26]. Facial perception occurred in the cortical region of the right hemisphere in men, but in the left in women. The results are similar to previous observations using transcranial Doppler [27], and agree with those made using electrophysiological techniques [28]. Similar genderrelated hemisphere differences have been observed at the amygdale for emotionally related stimuli [29], and for performance-related processing [30-32]. Men showed a right lateralization during object processing, but women showed a right tendency or bilateral activation. The effect

One presumption about the effects of color would be that, if the neuronal assemblies processing light information shared analogous topological organization as their blood flow supply, then dark would elicit the least effect, followed by colors and other stimuli on increasing complexity. This type of summation of responses related to stimulus complexity could be presumed as evidence for topological organization of these cortical areas was observed in men [26]. It was

hemisphere cognitive style in women.

Recently, we demonstrated using functional transcranial Doppler spectroscopy (*f*TCDS) technique, that color processing occurred within cortico-subcortical circuits [11, 12]. It was demonstrated that in men, wavelength-differencing of Yellow/Blue pairs occurred within the right hemisphere by processes of cortical long-term depression (CLTD) and subcortical longterm potentiation (SLTP). On the other hand, in women, frequency-differencing of Blue/Yellow pairs occurred within the left hemisphere by processes of cortical long-term potentiation (CLTP) and subcortical long-term depression (SLTD) [11, 12]. In both genders, there was luminance effect in the left hemisphere, while in men it was along an axis orthogonal to chromatic effect, in women it was along a parallel axis [11, 12]. It therefore, may be possible to describe mechanisms for color memory formation using *f*TCD and *f*TCDS techniques. In the present study, it was hypothesized that, the brain functionally integrates within a threedimensional physiologic 'color space', luminance effect in the left hemisphere with wave‐ length-differencing activity in the right hemisphere in men, but with frequency-differencing activity in the left hemisphere in women. This functional integration in color space could be mathematically modeled and could have potential applications in the study of color memory, adaptive neuroplasticity in stroke management and rehabilitation, as well as in neurodege‐ nerative diseases. There has not been any in-depth characterization of the neurophysiological processes involved in wavelength-differencing. However, effort has been made to apply the new modality of *f*TCDS, based on wave propagation theory to identify the neural processes implicated in color processing. It was suggested that, simultaneous color contrast implicated wavelength-differencing processes in men [11], while in women, the underlying process was characterized as frequency-differencing [12]. This is the first hint that, there may be a genderrelated difference in color processing. This is a profound finding that may change our overall understanding of perceptive processes in men and women. It was therefore proposed that, the brain color processing mechanisms integrates within a three-dimensional 'color space', luminance effects in the left hemisphere, and wavelength-differencing effects in the right hemisphere in men, but frequency-differencing effects in the left hemisphere in women [17]. The latter finding led to the conclusion that, color processing followed the same rule of lateralization as other major cognitive functions, such as facial processing [26, 27] and general intelligence [30], which implicated the right hemisphere cognitive style in men, and left hemisphere cognitive style in women.

(black-white) luminance axis [8]. However, the non-invasive physiologic measurements at the neural substrates to characterize the 'color space' in humans has not been feasible until now [17]. The anatomy of the main neural substrates for color processing have been characterized within the visual pathways and extrastriate cortex 'color centres' [18], which lie within the distribution territories of the posterior cerebral arteries (PCAs) [19-21] and middle cerebral arteries (MCAs) [19, 21, 22]. The superior parietal aspects of the optic radiation receive blood mainly from the MCA, whereas the inferior aspects are supplied by the PCAs [23]. The macular cortical region receives blood supply, from both the calcarine artery (a branch of the internal occipital artery of the PCA distribution), and branches of the MCA, which explains macular sparing with PCA occlusion [19]. Therefore, it is possible to characterize the 'color space' in the primary visual cortex and extrastriate areas using measurements of changes in blood flow velocity in the MCAs during color stimulation [22]. In prior studies in our laboratory for microgravity simulations, we applied non-invasive transcranial Doppler measurement of mean flow velocity (MFV) in the MCAs, to examine changes in color space in men during headdown rest, and demonstrated neuroplasticity over 25 hours of recordings [11], or more, if testing was continued. These findings have been related to formation of the phenomena of long term potentiation (LTP) and long-term depression (LTD), implicating role for NMDA receptors [11]. The phenomena of LTP [24] and LTD [25], have been applied to explain potential mechanisms of memory, primarily because they exhibit numerous properties expected of a synaptic associative memory mechanism, such as rapid induction, synapse specificity, associative interactions, persistence, and dependence on correlated synaptic activity. Given these important features, LTP and LTD remains only models of the synaptic and cellular events

Recently, we demonstrated using functional transcranial Doppler spectroscopy (*f*TCDS) technique, that color processing occurred within cortico-subcortical circuits [11, 12]. It was demonstrated that in men, wavelength-differencing of Yellow/Blue pairs occurred within the right hemisphere by processes of cortical long-term depression (CLTD) and subcortical longterm potentiation (SLTP). On the other hand, in women, frequency-differencing of Blue/Yellow pairs occurred within the left hemisphere by processes of cortical long-term potentiation (CLTP) and subcortical long-term depression (SLTD) [11, 12]. In both genders, there was luminance effect in the left hemisphere, while in men it was along an axis orthogonal to chromatic effect, in women it was along a parallel axis [11, 12]. It therefore, may be possible to describe mechanisms for color memory formation using *f*TCD and *f*TCDS techniques. In the present study, it was hypothesized that, the brain functionally integrates within a threedimensional physiologic 'color space', luminance effect in the left hemisphere with wave‐ length-differencing activity in the right hemisphere in men, but with frequency-differencing activity in the left hemisphere in women. This functional integration in color space could be mathematically modeled and could have potential applications in the study of color memory, adaptive neuroplasticity in stroke management and rehabilitation, as well as in neurodege‐ nerative diseases. There has not been any in-depth characterization of the neurophysiological processes involved in wavelength-differencing. However, effort has been made to apply the new modality of *f*TCDS, based on wave propagation theory to identify the neural processes implicated in color processing. It was suggested that, simultaneous color contrast implicated

that may underlie memory formation.

138 Advancements and Breakthroughs in Ultrasound Imaging

Furthermore, the functional integration in color space was mathematically modeled. It was shown that, the existence of wavelength-differencing in men and frequency-differencing in women, implemented inverse exponential and logarithmic functions, respectively. These gender-related differences that underlie cerebral asymmetry for color processing, has been hypothesized to be associated with the perception of the dual nature of light as a wave and as particulate energy referred to as quanta [11,12]. The presumed genetic and psychophysiologic effects of the physical qualities of light was the basis for the proposal of the light hypothesis of cerebral asymmetry [12]. The light hypothesis for cerebral asymmetry, posits that, the phenotypic neuroadaptation to environmental physical constraints of light as a wave and as quanta energy led to phenotypic evolution, and genetic variation of X-Y gene pairs that determine hemispheric asymmetry [12]. Hence, the evolutionary trend is towards optimiza‐ tion of perception of the 'whole' environment by functional coupling of the genes for comple‐ mentarity of both hemispheres within self, and between both genders [12]. More specifically, the basic tenant of the Light Hypothesis for cerebral asymmetry posits that, the right hemi‐ sphere is implicated in wavelength-differencing in men and the left hemisphere, in frequencydifferencing in women, with an overall gender complementarity in adaptive mechanisms for neuropsychophysiological processes. The latter has been characterized as gender-related cognitive styles designed for coupled perceptual experience of the world around us.

Overall, it has been documented that there is a gender-related difference in facial processing [26]. Facial perception occurred in the cortical region of the right hemisphere in men, but in the left in women. The results are similar to previous observations using transcranial Doppler [27], and agree with those made using electrophysiological techniques [28]. Similar genderrelated hemisphere differences have been observed at the amygdale for emotionally related stimuli [29], and for performance-related processing [30-32]. Men showed a right lateralization during object processing, but women showed a right tendency or bilateral activation. The effect of perception of faces has to be examined beyond the use of colors.

One presumption about the effects of color would be that, if the neuronal assemblies processing light information shared analogous topological organization as their blood flow supply, then dark would elicit the least effect, followed by colors and other stimuli on increasing complexity. This type of summation of responses related to stimulus complexity could be presumed as evidence for topological organization of these cortical areas was observed in men [26]. It was demonstrated that, the latter extends from the area implicated in color and object perception to a much greater area involved in facial perception. This agrees with the object form topology hypothesis proposed by Ishai and colleagues [33]. However, the relatedness of object, color and facial perception was process based, and appears to be associated with their common holistic processing strategy in the right hemisphere in men. Moreover, when the same men were presented with disarranged facial Paradigm requiring analytic processing, the left hemisphere was activated. This agrees in principle with the suggestion made by Gauthier that, the extrastriate cortex contains areas that are best suited for different computations, and described as the process-map model [34]. It has been proposed that the models of cognitive processing of colors and faces are not mutually exclusive, and this underscores the fact that color and facial processing do not impose any new constraints on the brain other than those used for other stimuli [26]. It may be suggested that each stimulus was mapped by category into color, face or non-face, and by process into holistic or analytic. Therefore, a unified category-specific process-mapping system was implemented for either right or left cognitive styles [26].

be expected to produce differences due to initial variations. In contrast, this limitation is overcome with Fourier-derived spectral density estimates, which assessed the periodicity during each stimulus condition independently, and lacked the properties of the original MFV signals. The absolute differences in MFV values would not affect the periodicity of the time series hence the Fourier transform would be equally sensitive for both men and women.

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The rationale for *f*TCDS has been discussed in detail elsewhere [26]. It has been demonstrated that, when measuring at the main stem of the middle cerebral artery (MCA) the origins of the peaks arise from a peripheral circulation reflection site such as the tip of the fingers, the terminal end of the lenticulostriate subcortical branches of the MCA and the terminal of the cortical branches of the MCA. The peaks designated as **F**- (fundamental or finger), **C**- (cortical), and **S**-(subcortical) peaks occurred at regular frequency intervals of 0.125, 0.25, and 0.375, respectively. These frequencies could be converted to cycles per second (Hz), assuming that the fundamental frequency of cardiac oscillation was the mean heart rate. The fundamental frequency *f* of the first harmonic was determined by the mean heart rate per second of for example, 74 bpm/60 seconds or 1.23 Hz. In other words, the **F**-, **C**-, and **S**-peaks occurred at multiples of the first harmonic, at second and third harmonics, respectively. The distance of

where *c* is the assumed wave propagation velocity of the peripheral arterial tree [38]. Consid‐ ering that there is vascular tortuosity, the estimated distance approximates that from the measurement site in the MCA main stem, to an imaginary site of summed reflections from the aorto-iliac junction [38] and the upper extremities, close to the finger tips when stretched sideways [26]. The **C**-peak occurred at the second harmonic, such that the estimated arterial

This length approximates the visible arterial length from the main stem of the MCA, through vascular tortuosity and around the cerebral convexity, to the end vessels at distal cortical sites such as the occipito-temporal junction on carotid angiograms of adults [26]. The **S**-peak

The latter is about the approximate visible arterial length of the lenticulostriate vessels from the main stem of the MCA on carotid angiograms [40]. Although it is not shown, the fourth harmonic would be expected to arise from the MCA bifurcation in closest proximity to the measurement site in the main stem of the MCA. The pre-bifurcation length from the meas‐

occurred at the third harmonic, and may have arisen from an estimated site at:

) [39] was given by:

D2= 1/8λ or c/8 \*2f, or 28 cm; and a frequency f2 of 2.46 Hz (2)

D3= 1/16 λ or c/16\*3f, or 9.3 cm; and a frequency f3 of 3.69 Hz (3)

D11 / <sup>4</sup>λ or c/4 f, or 6.15 (ms-1)/(4\*1.23 Hz) =125 cm (1)

the reflection site for **F**-peak could be presumed to emanate from a site at:

length (using common carotid *c* = 5.5 ms-1

urement point would be given by:

Another profound gender-related difference was related to the responsiveness to the dark condition. Studies in the dark condition were included to measure the effects of non-spectral stimuli, since it is known that, some of these can actually result in the production of color experience [35]. It was observed that, there was a tendency towards right lateralization in women but no lateralization in men in dark condition. The latter finding was difficult to interpret, and similar to observations made in previous studies [20]. These observations led to the suggestion that, scotopic visual information was processed in the right hemisphere in women [20]. However, in women data from spectral density estimates showed accentuation for dark responsiveness at the cortical (C-peaks) over those of light conditions. The latter may be an indication that greater neuronal assemblies were involved in processing scotopic vision in women compared to men. Furthermore, it was proposed that, in women the neuronal assemblies may not have the same orderly topological arrangement as in men; rather the neurons involved in processing cone and rod vision were segregated within the right hemi‐ sphere cortical region. Hence, in women the right hemisphere responded to luminance effect and object perception, but showed no category-specific face effect or color processing [12, 17, 26]. The latter arrangement explains the observed right lateralization for non-face Paradigm, but left lateralization for facial Paradigms and colors. In other words, similar to men, women employed the holistic mechanism for processing object stimulus in the right hemisphere, but preferred the analytic mechanism for facial and color perception in the left hemisphere. Therefore, one major observed gender-related difference was that, while men employed a category-specific process-mapping system for facial and color perception in the right hemi‐ sphere, women used same in the left hemisphere.

Another gender-related difference that has been consistently observed is the higher MFV in women than men [12, 17, 22, 26, 27, 36]. It is noteworthy that, the side differences appear to be related to cognitive changes rather than anatomic differences [37]. To cancel the effects of these initial variations in MFV, laterality index calculations were used [26, 27, 30]. However, if women differed from men in dark responsiveness, then LI calculations relative to dark would be expected to produce differences due to initial variations. In contrast, this limitation is overcome with Fourier-derived spectral density estimates, which assessed the periodicity during each stimulus condition independently, and lacked the properties of the original MFV signals. The absolute differences in MFV values would not affect the periodicity of the time series hence the Fourier transform would be equally sensitive for both men and women.

demonstrated that, the latter extends from the area implicated in color and object perception to a much greater area involved in facial perception. This agrees with the object form topology hypothesis proposed by Ishai and colleagues [33]. However, the relatedness of object, color and facial perception was process based, and appears to be associated with their common holistic processing strategy in the right hemisphere in men. Moreover, when the same men were presented with disarranged facial Paradigm requiring analytic processing, the left hemisphere was activated. This agrees in principle with the suggestion made by Gauthier that, the extrastriate cortex contains areas that are best suited for different computations, and described as the process-map model [34]. It has been proposed that the models of cognitive processing of colors and faces are not mutually exclusive, and this underscores the fact that color and facial processing do not impose any new constraints on the brain other than those used for other stimuli [26]. It may be suggested that each stimulus was mapped by category into color, face or non-face, and by process into holistic or analytic. Therefore, a unified category-specific process-mapping system was implemented for either right or left cognitive

Another profound gender-related difference was related to the responsiveness to the dark condition. Studies in the dark condition were included to measure the effects of non-spectral stimuli, since it is known that, some of these can actually result in the production of color experience [35]. It was observed that, there was a tendency towards right lateralization in women but no lateralization in men in dark condition. The latter finding was difficult to interpret, and similar to observations made in previous studies [20]. These observations led to the suggestion that, scotopic visual information was processed in the right hemisphere in women [20]. However, in women data from spectral density estimates showed accentuation for dark responsiveness at the cortical (C-peaks) over those of light conditions. The latter may be an indication that greater neuronal assemblies were involved in processing scotopic vision in women compared to men. Furthermore, it was proposed that, in women the neuronal assemblies may not have the same orderly topological arrangement as in men; rather the neurons involved in processing cone and rod vision were segregated within the right hemi‐ sphere cortical region. Hence, in women the right hemisphere responded to luminance effect and object perception, but showed no category-specific face effect or color processing [12, 17, 26]. The latter arrangement explains the observed right lateralization for non-face Paradigm, but left lateralization for facial Paradigms and colors. In other words, similar to men, women employed the holistic mechanism for processing object stimulus in the right hemisphere, but preferred the analytic mechanism for facial and color perception in the left hemisphere. Therefore, one major observed gender-related difference was that, while men employed a category-specific process-mapping system for facial and color perception in the right hemi‐

Another gender-related difference that has been consistently observed is the higher MFV in women than men [12, 17, 22, 26, 27, 36]. It is noteworthy that, the side differences appear to be related to cognitive changes rather than anatomic differences [37]. To cancel the effects of these initial variations in MFV, laterality index calculations were used [26, 27, 30]. However, if women differed from men in dark responsiveness, then LI calculations relative to dark would

styles [26].

140 Advancements and Breakthroughs in Ultrasound Imaging

sphere, women used same in the left hemisphere.

The rationale for *f*TCDS has been discussed in detail elsewhere [26]. It has been demonstrated that, when measuring at the main stem of the middle cerebral artery (MCA) the origins of the peaks arise from a peripheral circulation reflection site such as the tip of the fingers, the terminal end of the lenticulostriate subcortical branches of the MCA and the terminal of the cortical branches of the MCA. The peaks designated as **F**- (fundamental or finger), **C**- (cortical), and **S**-(subcortical) peaks occurred at regular frequency intervals of 0.125, 0.25, and 0.375, respectively. These frequencies could be converted to cycles per second (Hz), assuming that the fundamental frequency of cardiac oscillation was the mean heart rate. The fundamental frequency *f* of the first harmonic was determined by the mean heart rate per second of for example, 74 bpm/60 seconds or 1.23 Hz. In other words, the **F**-, **C**-, and **S**-peaks occurred at multiples of the first harmonic, at second and third harmonics, respectively. The distance of the reflection site for **F**-peak could be presumed to emanate from a site at:

$$\text{D}\_1\text{1/4}\lambda \text{ or } \text{c/4}\text{ f, or } 6.15 \text{ (ms}^{-1}\text{)/(4}\text{\*}1.23 \text{ Hz)} = 125 \text{ cm} \tag{1}$$

where *c* is the assumed wave propagation velocity of the peripheral arterial tree [38]. Consid‐ ering that there is vascular tortuosity, the estimated distance approximates that from the measurement site in the MCA main stem, to an imaginary site of summed reflections from the aorto-iliac junction [38] and the upper extremities, close to the finger tips when stretched sideways [26]. The **C**-peak occurred at the second harmonic, such that the estimated arterial length (using common carotid *c* = 5.5 ms-1 ) [39] was given by:

$$\text{D}\_2 = 1/8\lambda \text{ or } \text{c}/8 \text{ }^\circ \text{2f, or } 28 \text{ cm; and a frequency f}\_2 \text{ of } 2.46 \text{ Hz} \tag{2}$$

This length approximates the visible arterial length from the main stem of the MCA, through vascular tortuosity and around the cerebral convexity, to the end vessels at distal cortical sites such as the occipito-temporal junction on carotid angiograms of adults [26]. The **S**-peak occurred at the third harmonic, and may have arisen from an estimated site at:

$$\text{D}\_3 = 1/16 \,\lambda \text{ or } \text{c}/16 \,\text{°C} \text{; for 9.3 cm; and a frequency } \text{f}\_3 \text{ of 3.69 Hz} \tag{3}$$

The latter is about the approximate visible arterial length of the lenticulostriate vessels from the main stem of the MCA on carotid angiograms [40]. Although it is not shown, the fourth harmonic would be expected to arise from the MCA bifurcation in closest proximity to the measurement site in the main stem of the MCA. The pre-bifurcation length from the meas‐ urement point would be given by:

$$\mathbf{D\_4 = 1/32 \,\lambda \, or \, c/32^\*4f\_\circ \, or \, 3.5 \, cm; \, and \, a \, frequency \, f\_\circ \, of \, 4.92 \, Hz \tag{4}$$

**2.2. TCD scanning procedure**

at 30 degrees (Figure 1).

All *f*TCD procedures were performed using examination techniques previously described for cognitive studies [12, 17, 26, 27, 30, 46, 47, 48]. The *f*TCD scanning was performed using bilateral simultaneous *f*TCD instrument (Multi-Dop T, DWL, Sipplingen, Germany). *f*TCD studies were performed as follows: first, the participant was placed in a supine posture with their head up

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**Figure 1.** Shows the experimental setup with the subject supine with head-up at 30 degrees looking into the 3D-view‐ master for color stimulation with two 2MHz transcranial Doppler probes attached bilaterally for simultaneous meas‐ urements in both MCAs. (Source modified from Njemanze PC. United States Patent No. 8,152,727 April, 2012).

The Viewmaster *1* is placed in front of the subject where he/she could see clearly through it. The probe holder headgear *2* LAM-RAK (DWL, Sipplingen, Germany) was clamped with a base support the head *3* and on the nasal ridge, while the subject rested supine *4*. Two earplugs were affixed. Two 2-MHz probes connected via transducer cord *5* to the TCD device *6* were affixed in the probe holder and insonation was performed to determine the optimal position for continuous monitoring of both MCA main stems at 50 mm depth from the surface of the probe. The gain and power controls were kept constant for both MCAs in all participants. The headgear was placed comfortably on each participant prior to start of recording. Participants were instructed to remain mute and motionless throughout the short data acquisition time duration. They were informed that their thoughts and subjective feelings would be debriefed after the experimental data acquisition session. All participants were requested to refrain from internal or external verbalization and informed of the deleterious effects that might invalidate the data acquired. Environmental luminance was kept constant for all participants during the study. Effort was made to exclude the effects of environmental noise by sound shielding of the experimental room, and the participant wore earplugs that further reduced environmental noise levels. However, completely sensory deprivation of the participant was avoided. Vital signs were monitored using continuous recording of electrocardiography and respiration. A standard questionnaire was used for monitoring the self-perceived anxiety levels, as measured using state-trait anxiety inventory (STAI) in pre-test and posttest conditions. The STAI has been tested and validated by other investigators [49, 50]. In post-experimental debriefings was focused on what participants were ''thinking'' during task performance, and any relevance it might have to attention during the data acquisition process. The debriefings were cordial and voluntary to encourage participants to provide full disclosure of their thoughts during the

The calculated length approximates that of the segment of MCA main stem just after the carotid bifurcation, where probably the ultrasound sample volume was placed, to the MCA bifurca‐ tion or trifurcation, as the case may be. Thus, the latter estimates may approximate actual lengths. However, it has been suggested that the estimated distances may not correlate exactly with known morphometric dimensions of the arterial tree [41]. The *f*TCDS examines spectral density estimates of periodic processes induced during mental tasks, and hence offers a much more comprehensive picture of changes related to effects of a given mental stimulus. The spectral density estimates would be least affected by artifacts that lack periodicity, and filtering would reduce the effect of noise. Despite the outlined advantages of *f*TCDS, there are potential problems with the present studies which are conducted with relatively small sample size, which may create greater influence of outliers. However, statistical analysis did not reveal any extreme outliers in the present data set and exclusion of outliers did not alter the lateralization patterns. The choice of eight men and eight women for each of the two data sets for analysis, with a total of 48 points in each data set was ideal for Fourier analysis.

## **2. Methodological procedures**

#### **2.1. Subjects**

The study included 64 (32 men and 32 women) healthy subjects, divided in four groups of comprising each 8 men of mean ± SD age of 24.6 ± 2 years, and 8 women of mean ± SD age of 24 ± 2 years, all were right handed on hand preference questionnaire [42]. All subjects had normal sight and color vision, according to testing of visual acuity by Snellen chart, color vision by Ishihara pseudoisochromatic plates and color recognition [43]. Complete physical and mental examination revealed no abnormalities and routine evaluation of the cardiovascular, neurologic and respiratory systems were unremarka‐ ble. All were placed on the usual restrictions for cognitive studies [44]. All subjects gave written informed consent according to the Declaration of Helsinki; and the Institutional Ethics Board approved the study protocol. The experimental procedure including TCD scanning was similar for cognitive studies described in detail elsewhere [17, 22, 26]. In summary, TCD studies were performed using two 2 MHz probes of a bilateral simulta‐ neous TCD instrument (Multi-Dop T, DWL, Singen, Germany), with sample volume placed in the RMCA and LMCA main stems at a depth of 50 mm. The MCAs was chosen for measurements since it supplies about 80% of brain blood flow [45], and thus provides a global characterization of the color space than those from the PCAs. Moreover, complex processing of color occurs in the extrastriate cortex perfused by the MCAs, than in the primary visual cortex perfused by the PCAs. All participants were briefed on the protocol for the entire experiment, and all questions and practice sessions on what was required for the visual paradigms were explained prior to the start of the experimental data acquisition.

#### **2.2. TCD scanning procedure**

D4 = 1/32 λ or c/32\*4f, or 3.5 cm; and a frequency f<sup>4</sup> of 4.92 Hz (4)

The calculated length approximates that of the segment of MCA main stem just after the carotid bifurcation, where probably the ultrasound sample volume was placed, to the MCA bifurca‐ tion or trifurcation, as the case may be. Thus, the latter estimates may approximate actual lengths. However, it has been suggested that the estimated distances may not correlate exactly with known morphometric dimensions of the arterial tree [41]. The *f*TCDS examines spectral density estimates of periodic processes induced during mental tasks, and hence offers a much more comprehensive picture of changes related to effects of a given mental stimulus. The spectral density estimates would be least affected by artifacts that lack periodicity, and filtering would reduce the effect of noise. Despite the outlined advantages of *f*TCDS, there are potential problems with the present studies which are conducted with relatively small sample size, which may create greater influence of outliers. However, statistical analysis did not reveal any extreme outliers in the present data set and exclusion of outliers did not alter the lateralization patterns. The choice of eight men and eight women for each of the two data sets for analysis,

The study included 64 (32 men and 32 women) healthy subjects, divided in four groups of comprising each 8 men of mean ± SD age of 24.6 ± 2 years, and 8 women of mean ± SD age of 24 ± 2 years, all were right handed on hand preference questionnaire [42]. All subjects had normal sight and color vision, according to testing of visual acuity by Snellen chart, color vision by Ishihara pseudoisochromatic plates and color recognition [43]. Complete physical and mental examination revealed no abnormalities and routine evaluation of the cardiovascular, neurologic and respiratory systems were unremarka‐ ble. All were placed on the usual restrictions for cognitive studies [44]. All subjects gave written informed consent according to the Declaration of Helsinki; and the Institutional Ethics Board approved the study protocol. The experimental procedure including TCD scanning was similar for cognitive studies described in detail elsewhere [17, 22, 26]. In summary, TCD studies were performed using two 2 MHz probes of a bilateral simulta‐ neous TCD instrument (Multi-Dop T, DWL, Singen, Germany), with sample volume placed in the RMCA and LMCA main stems at a depth of 50 mm. The MCAs was chosen for measurements since it supplies about 80% of brain blood flow [45], and thus provides a global characterization of the color space than those from the PCAs. Moreover, complex processing of color occurs in the extrastriate cortex perfused by the MCAs, than in the primary visual cortex perfused by the PCAs. All participants were briefed on the protocol for the entire experiment, and all questions and practice sessions on what was required for the visual paradigms were explained prior to the start of the

with a total of 48 points in each data set was ideal for Fourier analysis.

**2. Methodological procedures**

142 Advancements and Breakthroughs in Ultrasound Imaging

experimental data acquisition.

**2.1. Subjects**

All *f*TCD procedures were performed using examination techniques previously described for cognitive studies [12, 17, 26, 27, 30, 46, 47, 48]. The *f*TCD scanning was performed using bilateral simultaneous *f*TCD instrument (Multi-Dop T, DWL, Sipplingen, Germany). *f*TCD studies were performed as follows: first, the participant was placed in a supine posture with their head up at 30 degrees (Figure 1).

**Figure 1.** Shows the experimental setup with the subject supine with head-up at 30 degrees looking into the 3D-view‐ master for color stimulation with two 2MHz transcranial Doppler probes attached bilaterally for simultaneous meas‐ urements in both MCAs. (Source modified from Njemanze PC. United States Patent No. 8,152,727 April, 2012).

The Viewmaster *1* is placed in front of the subject where he/she could see clearly through it. The probe holder headgear *2* LAM-RAK (DWL, Sipplingen, Germany) was clamped with a base support the head *3* and on the nasal ridge, while the subject rested supine *4*. Two earplugs were affixed. Two 2-MHz probes connected via transducer cord *5* to the TCD device *6* were affixed in the probe holder and insonation was performed to determine the optimal position for continuous monitoring of both MCA main stems at 50 mm depth from the surface of the probe. The gain and power controls were kept constant for both MCAs in all participants. The headgear was placed comfortably on each participant prior to start of recording. Participants were instructed to remain mute and motionless throughout the short data acquisition time duration. They were informed that their thoughts and subjective feelings would be debriefed after the experimental data acquisition session. All participants were requested to refrain from internal or external verbalization and informed of the deleterious effects that might invalidate the data acquired. Environmental luminance was kept constant for all participants during the study. Effort was made to exclude the effects of environmental noise by sound shielding of the experimental room, and the participant wore earplugs that further reduced environmental noise levels. However, completely sensory deprivation of the participant was avoided. Vital signs were monitored using continuous recording of electrocardiography and respiration. A standard questionnaire was used for monitoring the self-perceived anxiety levels, as measured using state-trait anxiety inventory (STAI) in pre-test and posttest conditions. The STAI has been tested and validated by other investigators [49, 50]. In post-experimental debriefings was focused on what participants were ''thinking'' during task performance, and any relevance it might have to attention during the data acquisition process. The debriefings were cordial and voluntary to encourage participants to provide full disclosure of their thoughts during the experimental data acquisition, and they were told that, there was no threat of any sanctions regardless of the outcome. Pre-experimental test runs in a different but selected group of participants provided insights into how participants understood the instructions and handled the stimulus used in the present study [22, 27]. The latter was used to modify and simplify the task design for easy comprehension and strict adherence. Baseline vital signs were recorded in full consciousness under normal resting conditions.

coil filament, of a general service lamp ran at a constant 24 V and 200 W, with a color temper‐ ature of about 2980 K and approximately 20 lumens/watt. Color stimulation was performed using optical homogenous filters placed on the reel of the Viewmaster, in the light path. Kodak Wratten filters: Deep Blue (No. 47B) with short dominant wavelength (l) of Sλ= 452.7 nm; and Deep Yellow (No. 12) with medium dominant wavelength (l) of Mλ = 510.7 nm were used. The Kodak manufacturer's manual for Wratten Filters provides the excitation purity and luminous transmittance for each filter [56]. During color stimulation the condition was identical to that of baseline, except for use of slides that were Blue, and Yellow, respectively. White light stimulation was considered as measurements with the left aperture on the reel open to white

A New Functional Transcranial Doppler Spectroscopy (fTCDS) Study of Cerebral Asymmetry During..

http://dx.doi.org/10.5772/54877

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**Figure 2.** Shows object (Paradigm 1) and facial stimuli (Paradigms 2-5). (Source: Njemanze PC. Aviat Space Environ

Paradigm 1: *Object perception* - Checkerboard square paradigm. The paradigm comprised black and white chequered square of alternating black and white square dots. This was a nonverbal passive viewing task of an object foveally presented from a slide projector onto a screen placed in front of the participant, which was inclined at 30 degrees from the horizontal plane at a distance of 80 cm from the nasal ridge. During the presentation, a continuous train of velocity waveform envelopes was recorded with the participant mute, still, with fixed gaze, and attention focused on the object. There were no mental or manual tasks to perform while

Paradigm 2: *Face encoding task* - whole neutral face. A novel whole male face expressing a neutral emotion was presented. The participant was instructed to commit the face to memory and told that their memory would be tested later. During the presentation, MFV was recorded

Paradigm 3: *Facial elements sorting task* – of disarranged face. This facial task comprised sorting elements of a disarranged face. Participants were instructed to sort the elements of the face and arrange them into a whole face, one element at a time, for 60 seconds. The task required a sophisticated perceptual mechanism capable of extraction of components of a face; analysis

Figure 2 shows that object and facial paradigms used in the present study.

viewing the object. MFV measurements were made for 60 seconds.

for 60 seconds while the participant viewed the face.

light reflected from the remote light source.

**2.5. Facial stimulation recordings**

Med, 2004, 75:800-805).

#### **2.3. Recordings under dark condition**

Measurements in dark condition were considered as light absent condition, as well as includ‐ ing background effects of scotopic vision [20, 51]. It is known that black may evoke a color experience [51]. Recording of a continuous train of velocity waveform envelopes was per‐ formed at rest with the participant mute, still, and attention-focused, in a dark visual field within a dark enclosed space with no mental or manual tasks to undertake. Although this had a similar effect to eye closure, but did not require eye muscle contractions and eye ball movements that could elicit motion artifacts. First, dark recording was obtained prior to stimuli administration for 60 seconds, and was used as reference for light stimulation conditions. An observer monitored the subject for movement artifacts, which were marked and removed from recordings.

#### **2.4. Color stimulation recordings**

The tasks were designed in our laboratory and the detailed rationale described elsewhere [22]. We have applied these tasks to show consistent and reliable recordings with TCD ultrasonog‐ raphy in prior studies [17, 22]. Briefly, specially adapted 3D-viewing device (Viewmaster, Portland, OR) was painted inside with black paint. The aperture on the right side of the device was closed to light, but the left side aperture was open, to be backlit from white light reflected from a remotely placed light source. In other words, there was left eye monocular vision, with light path from the left visual hemifield reaching the right side of the left eye retina, and crossing at chiasm to project contralaterally to the right visual cortex, while the light path from the right visual hemifield reaching the left side of the left eye retina, project ipsilaterally to the left visual cortex. The rationale for this design, relates to the fact that, in primates including humans, there is virtually total binocular vision; the left half of each retina project to the left visual cortex and the right half of each retina project to the right visual cortex. This means that the right visual cortex receives all its input from the left visual field and the left visual cortex receives all its inputs from the right visual field [52]. Color processing cells, receiving inputs from only one eye are grouped together within the same area of the striate cortex, extending from the upper to the lower cortical layers, and are referred to as ocular dominance columns (blobs) [15, 53, 54]. While those receiving inputs from both eyes are called hypercolumn [53, 55]. During binocular vision, there is binocular interaction due to stereopsis, the perception of depth [15]. Therefore, it is inappropriate to mix the inputs, from both retinas in a single neuron, before the information of color vision has been extracted [15]. The reflection from a light source was used, and projected onto a white surface flat screen, placed 125 cm from the lamp. The screen was positioned 80 cm from the nose ridge of the subject. The light source was a tungsten coil filament, of a general service lamp ran at a constant 24 V and 200 W, with a color temper‐ ature of about 2980 K and approximately 20 lumens/watt. Color stimulation was performed using optical homogenous filters placed on the reel of the Viewmaster, in the light path. Kodak Wratten filters: Deep Blue (No. 47B) with short dominant wavelength (l) of Sλ= 452.7 nm; and Deep Yellow (No. 12) with medium dominant wavelength (l) of Mλ = 510.7 nm were used. The Kodak manufacturer's manual for Wratten Filters provides the excitation purity and luminous transmittance for each filter [56]. During color stimulation the condition was identical to that of baseline, except for use of slides that were Blue, and Yellow, respectively. White light stimulation was considered as measurements with the left aperture on the reel open to white light reflected from the remote light source.
