**6. Results**

#### **6.1. Drawing qualities**

A total of only 10 hours of the Cognitive-Kinesthetic Drawing, spread out over 5 days, led to dramatic motor control changes in this *congenitally left-handed* blind participant, who was able for the first time to obtain a highly precise control of his *non-preferred right* hand.

done with the right (non-preferred) hand. Note, these are performed entirely *non-visually*, guided solely by the *memory from the haptic* exploration of the raised-line originals shown in the *left panel*.

**Figure 5.** Examples of drawings made by the left-handed blind participant, who underwent the Cognitive-Kinesthetic drawing training. **Left panel:** Raised-line originals used in the haptic exploration and memorization phase. The exploration was always done with the preferred/left hand. **Middle panel:** Drawing from memory with the *non-preferred/right* hand, showing the dramatic improvement *from pre-training to post-training*, despite the fact that this hand has never been used before for drawing, writing, or any other habitual motor activity. **Right panel:** Drawings with the *preferred/left* hand. These drawings are guided by the same memory that was guiding the other hand; the memory per se, however, was based always on the haptic exploration of the originals with the preferred/left hand. Note that the two hands seem to express

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After completing the training of the non-preferred/right hand, the participant had a session of practicing drawing with his all-life preferred (but untrained on the blind memory drawing) left hand. He was then asked to use the untrained left hand to draw the same images guided by the *already* acquired memory (**Figure 3**, *right panel*). Because the left hand had been the dominant one for almost six decades, and moreover, as the haptic exploration and memorization phase

Note that the exploration was always done with the *preferred/left* hand.

two different personalities.

The scope and quality of this unexpected new ability of the *non-preferred* hand is illustrated in **Figure 5**. The *central panel* shows a comparison of his pre-training versus post-training drawing Brain Reorganization in Late Adulthood: Rapid Left-to-Right Switch of Handedness… http://dx.doi.org/10.5772/intechopen.76317 75

We have conceptualized a system of *brain-change categories* and developed a novel type of voxel-wise parametric mapping that can provide the needed *multifaceted assessment of neuroplasticity* [37], and thus, bridge a major gap in this field. This is based on (1) assessing the activation (in each voxel of the brain) during an initial state (e.g., *before* training; *baseline*) and

**Figure 4.** Color coding for Categorical-Change mapping in the case of *positive baseline* activation. *Orange*: No significant change; *Red*: Reduced but still positive activation; *Yellow*: Increased positive activation; *Black*: Lost activation; *Blue*: BOLD

In the current study, we employed a subset of the categorical-change mapping to visualize **at once** *all five possible categories* of post-training change (or lack thereof) of any *positive baseline*

The color coding for novel type of maps is shown in **Figure 4**. If an activated region did not undergo any significant change relative to the initial state, it is visualized in orange; if its positive activation was increased—in yellow; if it was reduced but still positive—in red; if the activation was lost—in black; while if the sign of the BOLD signal was inverted from positive

Note that we have developed the categorical-change mapping to assess the *full spectrum of possible changes*, relative to a given pre-intervention state. In other words, this mapping tool can also be applied to brain regions that in the *baseline* state have *negative* BOLD signal, or have *no activation* at all. These two options are beyond the scope of the present analysis,

A total of only 10 hours of the Cognitive-Kinesthetic Drawing, spread out over 5 days, led to dramatic motor control changes in this *congenitally left-handed* blind participant, who was able

The scope and quality of this unexpected new ability of the *non-preferred* hand is illustrated in **Figure 5**. The *central panel* shows a comparison of his pre-training versus post-training drawing

for the first time to obtain a highly precise control of his *non-preferred right* hand.

into negative reflecting a changed in the nature of processing, it is shown in blue.

(2) the change in activation (e.g., *after* training) *relative* to that baseline.

activation prior to the state change or intervention.

signal inverted from positive into negative.

74 Neuroplasticity - Insights of Neural Reorganization

however.

**6. Results**

**6.1. Drawing qualities**

**Figure 5.** Examples of drawings made by the left-handed blind participant, who underwent the Cognitive-Kinesthetic drawing training. **Left panel:** Raised-line originals used in the haptic exploration and memorization phase. The exploration was always done with the preferred/left hand. **Middle panel:** Drawing from memory with the *non-preferred/right* hand, showing the dramatic improvement *from pre-training to post-training*, despite the fact that this hand has never been used before for drawing, writing, or any other habitual motor activity. **Right panel:** Drawings with the *preferred/left* hand. These drawings are guided by the same memory that was guiding the other hand; the memory per se, however, was based always on the haptic exploration of the originals with the preferred/left hand. Note that the two hands seem to express two different personalities.

done with the right (non-preferred) hand. Note, these are performed entirely *non-visually*, guided solely by the *memory from the haptic* exploration of the raised-line originals shown in the *left panel*. Note that the exploration was always done with the *preferred/left* hand.

After completing the training of the non-preferred/right hand, the participant had a session of practicing drawing with his all-life preferred (but untrained on the blind memory drawing) left hand. He was then asked to use the untrained left hand to draw the same images guided by the *already* acquired memory (**Figure 3**, *right panel*). Because the left hand had been the dominant one for almost six decades, and moreover, as the haptic exploration and memorization phase (*HE*) was always done with this hand, the expectation would be for these to provide definitive advantages for *left*-handed drawing.

hand (*baseline*), when the non-preferred/right hand instead performed the same memory

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The architecture of the *baseline network* (used as a mask) indicates that the movements of the *preferred/left* hand activated predominantly its *contralateral*/right hemisphere, as expected.

As also expected, the categorical-change mapping shows that *before* training, the drawing movements of the *non-preferred/right* hand resulted in a more *balanced inter-hemispheric* pattern of activation, indicating preservation of the greater involvement of the ipsilateral (right) hemisphere, consistent with previous studies on switching handedness (see Introduction). This result demonstrates that in its attempt to perform such a complex and precision-demanding motor task *before* training, the non-preferred/right hand continued to depend on the functional architecture of the preferred/left hand. Third, the figure shows that all motor, premotor, and sensorimotor regions in *both* hemispheres that were engaged by the preferred left hand were

**Figure 6.** Categorical changes in cortical activation relative to that for memory-guided drawing with the untrained left hand *(baseline)*. The *positive* activation in the brain network engaged by memory drawing with the *left hand* was used as the *baseline* for the comparisons in both panels. The differences from that *baseline* for the non-preferred/right-hand activation *before training* are shown in the top panel; *after training,* they are shown in the bottom panel. The voxel-wise changes are presented on inflated views of the lateral surfaces of the left and right hemispheres. Color coding as in **Figure 4**: *Orange—*No change relative to baseline; *Yellow*—Increased positive signal; *Red*—Decreased positive signal;

drawing task either *before* training (*top panel*) or *after* training (*bottom panel*).

engaged to an even higher degree by the non-preferred hand.

*Black*—Reduction to no significant signal; *Blue*—Negative signal.

*6.2.1.1. Pre-training (top panel)*

Conversely, in the main study (drawing with the non-preferred/right hand), the fact that the image information was gathered through exploration with the opposite (left) hand, sets the expectation that the *right*-hand drawing would be at a disadvantage. However, this seems to be the case only *before* the training. Note the rapidly achieved dramatic improvement *from pre-training to posttraining* for the right hand (**Figure 3**, *middle panel*) despite this disadvantage, and despite the fact that his right hand had never been used before for drawing, writing, or any other habitual motor activity. It is thus surprising, that the *post-training* reproductions with the right hand resembled the originals better than those done with the whole-life-preferred left hand (**Figure 5**, *right panel*). Note again that both phases of the process—*haptic memory encoding* and *retrieval for memory drawing*—were done without the involvement of any vision in this blind participant.

Although the drawing quality and similarity are evident to the human eye, we further assessed the drawing quality by *bi-dimensional regression analysis* [38]. First, for each original image, landmarks were set at unique points that could be easily identified by the naked eye in the original figures and the resulting drawings. Second, bi-dimensional analysis was run for the correspondence between landmarks on the original images and those available on their reproduction by drawing. The specific measure for analyzing the quality of drawings was the fit of an affine bi-dimensional regression (expressed as Fisher-Z values of the respective Rs). The number of landmarks depended on the complexity for each template image.

The bi-dimensional regression scores indicated an improvement averaging about a factor of six *from pre- to post-training* accuracy with the trained hand. Consistent with the perceptual evaluation done earlier, the *post-training* bi-dimensional regression values were significantly higher overall for the non-preferred (but Cognitive-Kinesthetically trained) right hand versus the preferred but untrained left hand, even though the left hand was the one used in acquiring the spatial memory that guided each of the hands along the drawing trajectories.

Interestingly, although the line stability, and image completeness produced by the preferred/ left hand were very good, the accuracy of reproduction with this preferred but untrained hand was lower by about a factor of two relative to the strong improvement with the training of the non-preferred/right hand. What was even more surprising was that, stylistically, it could be said that the two hands seemed to express two different personalities.

#### **6.2. Brain plasticity driven by the Cognitive-Kinesthetic Drawing Training**

#### *6.2.1. Baseline A: the activation in the brain network engaged by the left hand in memory drawing as baseline*

The fMRI recordings run *before* and *after* the training provided a measure of the neuroplastic functional changes underlying the behavioral improvements. To assess not simply *what* has been changed, but *how* was it changed and what specific *categories of change* had occurred in the cortex, we used our novel approach of Categorical-Change parametric brain mapping described earlier.

Using the categorical-change parametric mapping, **Figure 6** shows the types of changes that happened in the cortical network activated during memory drawing with the preferred/left hand (*baseline*), when the non-preferred/right hand instead performed the same memory drawing task either *before* training (*top panel*) or *after* training (*bottom panel*).

#### *6.2.1.1. Pre-training (top panel)*

(*HE*) was always done with this hand, the expectation would be for these to provide definitive

Conversely, in the main study (drawing with the non-preferred/right hand), the fact that the image information was gathered through exploration with the opposite (left) hand, sets the expectation that the *right*-hand drawing would be at a disadvantage. However, this seems to be the case only *before* the training. Note the rapidly achieved dramatic improvement *from pre-training to posttraining* for the right hand (**Figure 3**, *middle panel*) despite this disadvantage, and despite the fact that his right hand had never been used before for drawing, writing, or any other habitual motor activity. It is thus surprising, that the *post-training* reproductions with the right hand resembled the originals better than those done with the whole-life-preferred left hand (**Figure 5**, *right panel*). Note again that both phases of the process—*haptic memory encoding* and *retrieval for memory draw-*

Although the drawing quality and similarity are evident to the human eye, we further assessed the drawing quality by *bi-dimensional regression analysis* [38]. First, for each original image, landmarks were set at unique points that could be easily identified by the naked eye in the original figures and the resulting drawings. Second, bi-dimensional analysis was run for the correspondence between landmarks on the original images and those available on their reproduction by drawing. The specific measure for analyzing the quality of drawings was the fit of an affine bi-dimensional regression (expressed as Fisher-Z values of the respective Rs).

The bi-dimensional regression scores indicated an improvement averaging about a factor of six *from pre- to post-training* accuracy with the trained hand. Consistent with the perceptual evaluation done earlier, the *post-training* bi-dimensional regression values were significantly higher overall for the non-preferred (but Cognitive-Kinesthetically trained) right hand versus the preferred but untrained left hand, even though the left hand was the one used in acquiring

Interestingly, although the line stability, and image completeness produced by the preferred/ left hand were very good, the accuracy of reproduction with this preferred but untrained hand was lower by about a factor of two relative to the strong improvement with the training of the non-preferred/right hand. What was even more surprising was that, stylistically, it

The fMRI recordings run *before* and *after* the training provided a measure of the neuroplastic functional changes underlying the behavioral improvements. To assess not simply *what* has been changed, but *how* was it changed and what specific *categories of change* had occurred in the cortex, we used our novel approach of Categorical-Change parametric brain mapping described earlier. Using the categorical-change parametric mapping, **Figure 6** shows the types of changes that happened in the cortical network activated during memory drawing with the preferred/left

*ing*—were done without the involvement of any vision in this blind participant.

The number of landmarks depended on the complexity for each template image.

the spatial memory that guided each of the hands along the drawing trajectories.

could be said that the two hands seemed to express two different personalities.

**6.2. Brain plasticity driven by the Cognitive-Kinesthetic Drawing Training**

*6.2.1. Baseline A: the activation in the brain network engaged by the left hand in memory* 

advantages for *left*-handed drawing.

76 Neuroplasticity - Insights of Neural Reorganization

*drawing as baseline*

The architecture of the *baseline network* (used as a mask) indicates that the movements of the *preferred/left* hand activated predominantly its *contralateral*/right hemisphere, as expected.

As also expected, the categorical-change mapping shows that *before* training, the drawing movements of the *non-preferred/right* hand resulted in a more *balanced inter-hemispheric* pattern of activation, indicating preservation of the greater involvement of the ipsilateral (right) hemisphere, consistent with previous studies on switching handedness (see Introduction). This result demonstrates that in its attempt to perform such a complex and precision-demanding motor task *before* training, the non-preferred/right hand continued to depend on the functional architecture of the preferred/left hand. Third, the figure shows that all motor, premotor, and sensorimotor regions in *both* hemispheres that were engaged by the preferred left hand were engaged to an even higher degree by the non-preferred hand.

**Figure 6.** Categorical changes in cortical activation relative to that for memory-guided drawing with the untrained left hand *(baseline)*. The *positive* activation in the brain network engaged by memory drawing with the *left hand* was used as the *baseline* for the comparisons in both panels. The differences from that *baseline* for the non-preferred/right-hand activation *before training* are shown in the top panel; *after training,* they are shown in the bottom panel. The voxel-wise changes are presented on inflated views of the lateral surfaces of the left and right hemispheres. Color coding as in **Figure 4**: *Orange—*No change relative to baseline; *Yellow*—Increased positive signal; *Red*—Decreased positive signal; *Black*—Reduction to no significant signal; *Blue*—Negative signal.

#### *6.2.1.2. Post-training (bottom panel)*

Remarkably, after the Cognitive-Kinesthetic training, we observed a dramatic reorganization of motor architecture of the *non-preferred/right* hand toward a strongly expressed *contralateral* (left hemisphere) dominance. This previously unobserved reorganization is also clearly confirmed by the categorical-change map analysis in Section 6.2.2. below, where the *pre-training right-hand* network was used as baseline.

range of perceptual, cognitive, and precise motor functions, thus engaging widely *distributed networks* throughout the brain; their detailed analysis, however, is beyond the scope of this

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To quantitatively assess and compare the hemispheric patterns of activation across conditions, we applied the approach used in [1] of comparing the number of voxels, or—volume, activated in each condition. We, however, significantly expanded this approach by taking both positive and negative voxel activations and considering them separately. The voxel numbers were calculated for the conjunction of the motor, premotor, supplementary motor, and somatosensory cortices. The respective FreeSurfer ROIs were used to define the respec-

**Figure 8** shows that both the preferred/left hand (*left panel*) and the non-preferred/right hand pre-training (*middle panel*) conformed to pre-existing models: (1) the activation for the left hand was *predominantly contralateral* (right > left; see *left panel*), whereas (2) a more *balanced, bilateral* pattern of activation was observed for the drawing movements of the *right hand (mid-*

The *right panel* of **Figure 8**, on the other hand, reveals a radical reorganization in the motor control architecture of the right (non-preferred*)* hand as a result of the Cognitive-Kinesthetic drawing training. The bilateral pattern of (strongly positive) activation *before* training (*middle panel*) rapidly changed into a strongly contralateral (left hemispheric) pattern *after* training

**Figure 8.** Cognitive-Kinesthetic training effects on the pattern of inter-hemispheric interactions. Three distinct patterns of inter-hemispheric interaction were observed. The distributions of positive (*red*) and negative (*blue*) voxels per hemisphere (*L, left; R, right*) in the conjunction of the motor, premotor, supramotor, and somatosensory cortices during memory-guided drawing is shown for the preferred/left hand (*left panel*), the non-preferred/right hand *pre*-training

chapter.

(*right panel*).

**6.3. Patterns of hemispheric asymmetry**

tive cortical regions for quantitative analysis.

*dle panel)*, indicating a greater ipsilateral involvement.

(*middle panel*), and the non-preferred/right hand *post*-training (*right panel*).

#### *6.2.2. Baseline B: the activation in the brain network engaged by the non-preferred/right in memory drawing before training as a baseline*

In this section, the network activated by the non-preffered/right hand during MD was used as the basline in the analysis. Consistent with findings from Section 6.2.1. above (see **Figure 6**), the categorical-maps shown in **Figure 7** confirm both the *bilateral* pattern of (positive) activation of the *non-preferred* hand *before* training (used as the baseline mask) and the *transformation* of this *bilaterality* into a *strong contralaterality* as a result of training. Another striking finding from the categorical comparison in **Figure 7** was the *massive suppression* (blue) of the BOLD responses in the motor and premotor cortex of the *ipsilateral/*right hemisphere. Furthermore, contrary to what may be expected, this happened in conjunction not with an increase but with an almost *unchanged (orange) or even reduced (red)* activation in these motor control regions of the *contralateral/*left hemisphere relative to pre-training. In other words, the increased contralaterality (left hemisphere greater than right) was *not* caused by increased contralateral/left activation but by an *ipsilateral suppression*, in spite of the fact that this right hemisphere has been the dominant one for the *entire life* of this participant.

It is noteworthy that drawing, particularly if it is solely guided by memory as in the Cognitive-Kinesthetic training applied here, is a highly complex task *orchestrating* a wide

**Figure 7.** Rapid switch of handedness. To establish the categories of *training-induced* changes in the cortical network controlling the *non-preferred/right* hand during *MemoryDraw*, our categorical-change mapping was used with the *pre-training* activation pattern of the *right* hand as a *baseline* in a comparison with its activation *after* the right hand underwent the 10 hours of *training*. The *training-induced* categorical changes in the *functional architecture of the nonpreferred right* are shown on the lateral surfaces of the left and right hemisphere. Color coding as in **Figure 4**: *Orange* — No change relative to baseline; *Yellow* — Increased positive signal; *Red* — Decreased positive signal; *Black* — Reduction to no significant signal; *Blue* — Negative signal

range of perceptual, cognitive, and precise motor functions, thus engaging widely *distributed networks* throughout the brain; their detailed analysis, however, is beyond the scope of this chapter.

#### **6.3. Patterns of hemispheric asymmetry**

**Figure 7.** Rapid switch of handedness. To establish the categories of *training-induced* changes in the cortical network controlling the *non-preferred/right* hand during *MemoryDraw*, our categorical-change mapping was used with the *pre-training* activation pattern of the *right* hand as a *baseline* in a comparison with its activation *after* the right hand underwent the 10 hours of *training*. The *training-induced* categorical changes in the *functional architecture of the nonpreferred right* are shown on the lateral surfaces of the left and right hemisphere. Color coding as in **Figure 4**: *Orange* — No change relative to baseline; *Yellow* — Increased positive signal; *Red* — Decreased positive signal; *Black* — Reduction

Remarkably, after the Cognitive-Kinesthetic training, we observed a dramatic reorganization of motor architecture of the *non-preferred/right* hand toward a strongly expressed *contralateral* (left hemisphere) dominance. This previously unobserved reorganization is also clearly confirmed by the categorical-change map analysis in Section 6.2.2. below, where the *pre-training* 

In this section, the network activated by the non-preffered/right hand during MD was used as the basline in the analysis. Consistent with findings from Section 6.2.1. above (see **Figure 6**), the categorical-maps shown in **Figure 7** confirm both the *bilateral* pattern of (positive) activation of the *non-preferred* hand *before* training (used as the baseline mask) and the *transformation* of this *bilaterality* into a *strong contralaterality* as a result of training. Another striking finding from the categorical comparison in **Figure 7** was the *massive suppression* (blue) of the BOLD responses in the motor and premotor cortex of the *ipsilateral/*right hemisphere. Furthermore, contrary to what may be expected, this happened in conjunction not with an increase but with an almost *unchanged (orange) or even reduced (red)* activation in these motor control regions of the *contralateral/*left hemisphere relative to pre-training. In other words, the increased contralaterality (left hemisphere greater than right) was *not* caused by increased contralateral/left activation but by an *ipsilateral suppression*, in spite of the fact that this right hemisphere has

It is noteworthy that drawing, particularly if it is solely guided by memory as in the Cognitive-Kinesthetic training applied here, is a highly complex task *orchestrating* a wide

*6.2.2. Baseline B: the activation in the brain network engaged by the non-preferred/right in* 

to no significant signal; *Blue* — Negative signal

*6.2.1.2. Post-training (bottom panel)*

78 Neuroplasticity - Insights of Neural Reorganization

*right-hand* network was used as baseline.

*memory drawing before training as a baseline*

been the dominant one for the *entire life* of this participant.

To quantitatively assess and compare the hemispheric patterns of activation across conditions, we applied the approach used in [1] of comparing the number of voxels, or—volume, activated in each condition. We, however, significantly expanded this approach by taking both positive and negative voxel activations and considering them separately. The voxel numbers were calculated for the conjunction of the motor, premotor, supplementary motor, and somatosensory cortices. The respective FreeSurfer ROIs were used to define the respective cortical regions for quantitative analysis.

**Figure 8** shows that both the preferred/left hand (*left panel*) and the non-preferred/right hand pre-training (*middle panel*) conformed to pre-existing models: (1) the activation for the left hand was *predominantly contralateral* (right > left; see *left panel*), whereas (2) a more *balanced, bilateral* pattern of activation was observed for the drawing movements of the *right hand (middle panel)*, indicating a greater ipsilateral involvement.

The *right panel* of **Figure 8**, on the other hand, reveals a radical reorganization in the motor control architecture of the right (non-preferred*)* hand as a result of the Cognitive-Kinesthetic drawing training. The bilateral pattern of (strongly positive) activation *before* training (*middle panel*) rapidly changed into a strongly contralateral (left hemispheric) pattern *after* training (*right panel*).

**Figure 8.** Cognitive-Kinesthetic training effects on the pattern of inter-hemispheric interactions. Three distinct patterns of inter-hemispheric interaction were observed. The distributions of positive (*red*) and negative (*blue*) voxels per hemisphere (*L, left; R, right*) in the conjunction of the motor, premotor, supramotor, and somatosensory cortices during memory-guided drawing is shown for the preferred/left hand (*left panel*), the non-preferred/right hand *pre*-training (*middle panel*), and the non-preferred/right hand *post*-training (*right panel*).
