NeuroImage 19 (2003) 968 975

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Cross-modal plasticity for sensory and motor activation patterns in blind subjects
E.R. Gizewski,a,* T. Gasser,b A. de Greiff,c A. Boehm,a and M. Forstinga
a b

Department of Neuroradiology, University Hospital, Essen, Germany Department of Neurosurgery, University Hospital, Essen, Germany c Department of Neurology, University Hospital, Essen, Germany Received 22 November 2002; accepted 11 February 2003

Abstract Experimental data on cortical reorganization in blind subjects using H215O positron emission tomography and functional magnetic resonance imaging (fMRI) showed activation of the visual cortex related to Braille reading and tactile discrimination tasks in congenitally and early blind subjects. The purpose of our study was to differentiate whether occipital activation of blind subjects during Braille reading is task specic or only triggered by sensory or motor area activation. Twelve congenitally and early-onset blind subjects were studied with fMRI during Braille reading, discriminating nonsense dots, sensory stimulation with electromagnetic pulses, and nger tapping. All experiments were performed utilizing a block design with 6 active epochs alternating with 6 rest conditions lasting 34 s each. Echo-planar imaging sequences with 34 transversal slices were performed on a 1.5-T MR scanner. All blind individuals reading Braille and discriminating nonsense dots showed robust activation of the primary, secondary, and higher visual cortex. Application of peripheral electrical stimuli to the reading hand revealed expected sensory activation of the primary somatosensory cortex, but no activation in the visual cortex. Pure motor activation during nger tapping with the reading hand showed expected precentral activation and no activation of visual cortex. In conclusion, occipital activation during Braille reading and discrimination tasks is not due to plasticity of sensory or motor function; pure motor or sensory tasks do not lead to an activation of striate cortex. The brain learns to differentiate between nger touching and nger reading. Our results suggest that activation of the visual cortex in blind subjects is related to higher and more complex brain functions. 2003 Elsevier Science (USA). All rights reserved.

Introduction The rst experimental data on cortical reorganization in blind subjects were shown by Wanet-Defalque et al. (1988). They used uorodeoxyglucose-position emission tomography (18FDG-PET) to investigate the effects of early-onset blindness on cortical metabolism and observed an elevated glucose metabolism of the visual cortex. Since this time, the most interesting question is whether this activity is task dependent. With H215O-PET, a task-dependent occipital cortex activation related to tactile processing in congenitally

* Corresponding author. Department of Neuroradiology, University of Essen, Hufelandstr. 55, D-45127 Essen, Germany. Fax: 49-201-7235959. E-mail address: elke.gizewski@uni-essen.de (E.R. Gizewski).

and early-blind subjects was shown (Sadato et al., 1998; Buchel et al., 1998). Sadato et al. (2002) described primary and secondary visual cortex activation during Braille reading and discrimination tasks, whereas they found no activation during nondiscrimination tasks. Buchel et al. (1998b) described no activation in primary visual cortex in congenitally blind subjects during Braille reading but activation in this area in late-onset blindness. However, they found an activation of occipital areas during tactile reading tasks. The question arose about whether the occipital activation is necessary for Braille reading or an epiphenomenon related to an increased necessity for somatosensory input function. This issue has been addressed by an experiment using transcranial magnetic stimulation (TMS) to create a functional lesion in occipital brain areas during Braille reading (Cohen et al., 1997). TMS led to impairment of Braille

1053-8119/03/$ see front matter 2003 Elsevier Science (USA). All rights reserved. doi:10.1016/S1053-8119(03)00114-9

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Fig. 1. Setting of the electrical stimulation during functional magnetic resonance imaging measurements. The stimulus was generated using a standard stimulus generator outside the magnetic resonance cage. The stimulus was conducted to the electrodes using a ground-protected coaxial lead. The hand with the electrodes was placed in a ground-protected metal tube.

reading and even of perception of phantom dots. Therefore, occipital brain areas should be essential for Braille reading in blind subjects. However, the discussion about which part of the perception process is coded in primary and higher visual areas is still controversial.

The study was accepted by the local ethics committee (No. 02-1906). Experimental design All MR images were acquired using a 1.5-T MR (Sonata, Siemens, Erlangen, Germany) with a standard headcoil. A 3D FLASH sequence (TR 10 ms, TE 4.5 ms, ip angle 30, FOV 240 mm, matrix 512, slice-thickness 1.5 mm) was acquired for individual corregistration of functional and structural images. BOLD (blood oxygenation level dependant) contrast images were acquired by using an echoplanar technique (TR 100 ms, TE 50 ms, ip angle 90, FOV 240 mm, matrix 64) with 34 transversal slices with a thickness of 3 mm and a 0.3-mm slice gap. Three dummy scans were eliminated prior to data analysis. Each subject underwent four functional sessions. We demonstrated Braille words, senseless dots, and electrical sensible stimulation. A nger-tapping task was performed with the right hand opposing the thumb to every other nger after each acoustic cue. The stimuli were presented in a block design and alternated with resting periods every 34 s. Each run was divided into 6 epochs. Prior to the experiment all subjects got a check to ensure they could hear the auditory commands for start and stop within the scanner. To avoid unspecic activation subjects were asked not to make any sort of response or reading aloud during the experiment. The subjects were instructed to perform the tasks only with minimal movements. During activation, subjects had to read Braille and nonsense dots with their right hand. Standard Braille characters and nonsense dot were presented on hard paper that lay on the subjects abdomen and could be easily reached by

Subjects and method Subjects Six male and 6 female blind subjects (mean age, 53 years; range, 24 to 80 years) were studied. All subjects were right-handed and native German speakers; 9 were congenitally blind and 3 had minimal light perception prior to loss of sight early in life. Finally, all subjects were blind without residual light perception. They started to learn Braille between 6 and 15 years (mean age, 8 years) spending 2 8 h/day reading. The Braille reading skills were judged by each on a scale from 0 to 10, meaning 0 no Braille reading ability, and 10 excellent reading ability. The range in blind subjects was from 5 to 10. All blind subjects used the right hand to read Braille. As a control group 12 normal sighted right-handed subjects (5 men and 7 women with a mean age of 48 years; range, 20 to 72 years) were imaged under identical experimental conditions. No subject showed any brain tissue abnormality on magnetic resonance imaging (MRI). All blind volunteers had a history of peripheral blindness. Informed written consent was obtained prior to scanning.

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Fig. 2. (A) Statistical parametric maps of activation within the group of blind subjects reading Braille with their right hand compared with rest period. Task-related increase in magnetic resonance signal is superimposed on three orthogonal sections of three-dimensional T1-weighted standard brain. Statistical corrected threshold is P 0.05. Results show activation of visual cortex accompanied by activation of sensorimotor areas. (B) Statistical parametric maps of activation within the group of normal sighted subjects reading Braille with their right hand compared with rest period. Statistical corrected threshold is P 0.05. Results show expected activation of sensorimotor areas and no activation of visual cortex.

the reading hand. The subjects started reading after an acoustical cue. The factorial text consists of common nouns and words. No response was requested during scanning but the subjects had to give a summary of the read text after the scan. Nonsense dots were in lines in a randomised pattern according to real Braille word arrangement. During sensory stimulation subjects were asked to lie relaxed inside the scanner. The electrical stimulation on the right median nerve was performed with an average amplitude of 4 mA (3.5 to 7.2 mA), a frequency of 3 Hz, and a pulse length of 0.2 ms. This setting was below pain perception level in all subjects. Stimulus was generated by using a standard stimulus generator (Nicolet-Viking IVP, Madison, WI) outside the MR cage. Generator output strength and signal conguration were analysed and documented by a digital external oscilloscope (Hewlett Packard Innum, Colorado Springs, Colorado, USA).

The stimulus was conducted to the electrodes using a ground-protected coaxial lead. The hand with the electrodes was placed in a ground-protected metal tube to avoid imaging artefacts (Fig. 1). Data analysis For data analysis SPM 99 software (Wellcome Department of Cognitive Neurology, London, UK) was used. Prior to statistical analysis images were realigned utilizing the sinc interpolation and normalized to the standard stereotactic space corresponding to the template from the Montreal Neurological Institute (http://www.mrc-cbu. cam.ac.uk/imaging/mnispace.html). Bilinear interpolation was applied for normalization. The images were smoothed with an isotropic Gaussian kernel of 9 mm. A

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Fig. 3. (A) Statistical parametric maps of activation within the group of blind subjects during electrical stimulation of the right median nerve compared with rest period. Task-related increase in magnetic resonance signal is superimposed on three orthogonal sections of three-dimensional T1-weighted standard brain. Statistical corrected threshold was P 0.05. Results shows no activation of visual cortex. (B) Statistical parametric maps of activation within the group of normal sighted subjects during electrical stimulation of the right median nerve compared with rest period. Statistically corrected threshold is P 0.05. Results show expected activation of somatosensory area and no activation of visual cortex.

voxel-by-voxel comparison according to the general linear model was used to calculate differences of activation between active and resting condition. The model consisted of a boxcar function convolved with the hemodynamic response function and the corresponding temporal derivative. High-pass ltering with a cutoff frequency of 120 s and low-pass ltering with the hemodynamic response function was applied. For group analysis single-subject contrast images were entered into a random effects model. Signicant signal changes for each contrast were assessed by means of t statistics on a voxel-by-voxel basis (Friston et al., 1995). The resulting set of voxel values for each contrast constituted a statistical parametric mapping of the t statistic. The threshold was set to P 0.05 (corrected for multiple

comparisons). Additional small volume correction for the occipital cortex with a sphere of 20 mm radius diameter (center at 25; 90; 2 and 25; 90; 2) was done in sensory and motor tasks in blind and normal sighted volunteers. For analysis of specic activation in blind subjects during Braille reading and differences in sighted and blind subjects a random effects analysis of the four tasks (Braille blind, sensory blind, Braille sighted, and sensory sighted) was performed. We created individual contrasts for every blind and sighted subject (Braille reading median nerve stimulation). The resulting contrast images were taken to the second level analysis and entered into a two-sample t test. The threshold of the t statistic was set to P 0.05.

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Fig. 4. Statistical parametric maps of activation within the group of blind subjects during nger tapping with the right hand compared with rest period. Task-related increase in magnetic resonance signal is superimposed on three orthogonal sections of three-dimensional T1-weighted standard brain. Statistically corrected threshold is P 0.05. Results show no activation of visual cortex. (B) Statistical parametric maps of activation within the group of normal sighted subjects during nger tapping with their right hand compared with rest period. Statistically corrected threshold is P 0.05. Results show expected activation of sensorimotor areas and no activation of visual cortex.

Results Group analysis with random effects model Blind individuals reading Braille showed robust and signicant activation of the primary, secondary, and higher visual cortex. Fig. 2A shows the activated occipital lobe with cuneus, precuneus, and middle and inferior occipital gyrus bilateral. However, a slightly higher activation in the hemisphere contralateral to the reading hand was observed. In contrast, single-subject and group analysis of sighted subjects did not reveal any activation in visual cortex during reading Braille or nonsense dots (Fig. 2B). In all subjects expected activation of sensori-

motor brain areas was revealed. As described in former investigations we also found similar visual area activation in blind subjects during tactile discrimination tasks of nonsense dots. Application of a peripheral electrical stimulus to the reading hand showed the normal sensory activation of the primary somatosensory cortex in blind as well as in normal sighted subjects, but no activation in the visual cortex of the blind subjects. Fig. 3 shows the activated left postcentral gyrus in the hand area (A for the blind group and B for the sighted volunteers). Pure motor activation during nger tapping with the reading hand showed normal precentral activation in blind (Fig. 4A) as well as in normal sighted subjects (Fig. 4B), but no activation in the visual cortex in blind subjects. Table 1

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Results of single subject analysis of congenital and early blind subjects Individual statistical parametric mapping of all blind subjects did not reveal any occipital activation during motor and sensory tasks.

Discussion It is well known that blind people activate their visual cortex during Braille reading. This issue has been addressed by many PET and fMRI investigations of blind subjects and revealed occipital cortex activation during Braille reading and tactile discrimination tasks in congenitally and early blind subjects (Buchel et al., 1998; Sadato et al., 1996; De Volder et al., 1997; Burton et al., 2002). Our results during Braille reading with activation of visual cortical areas correspond to former investigations. Controversial discussions arise concerning V1 activation. Sadato et al. (2002) described primary and secondary visual cortex activation during Braille reading and discrimination tasks in early blind subjects, whereas Buchel et al. (1998) found V1 activation in late blind subjects. We also found an activation of V1 in our group of early and congenitally blind volunteers. Corresponding to Burton et al. (2002) we revealed a pronounced activation of occipital areas during Braille reading contralateral to the reading hand, which is postulated to be due to language-related areas in higher visual cortex areas. After all, early and congenital blind subjects show an activation of secondary and higher visual areas during Braille reading. Several studies addressed to clarify the task-specic activation. Cohen et al. (1997) showed disturbance of Braille reading and tactile perceptions during TMS stimulation of the occipital cortex in blind subjects whereas there was no effect on tactile perceptions in normal sighted volunteers. Some groups followed the aspect of task specicity using auditory instead of tactile input. Blind volunteers activated visual areas while using an ultrasonic echo-location device (De Volder et al., 1999) and

Fig. 5. Statistical parametric maps of areas more prominently activated in blind subjects during Braille reading compared with sighted subjects. For analysis of specic activation in blind subjects during Braille reading a random effects analysis of the four tasks (Braille blind, sensory blind, Braille sighted, and sensory sighted) was performed. The contrast images of interaction of both tasks in both groups were entered into a two sample t test. Interaction-related increase in magnetic resonance signal is superimposed on three orthogonal sections of three-dimensional T1-weighted standard brain. Statistically corrected threshold is P 0.05. Results show activation of visual cortex signicant for the blind group during Braille reading.

shows a summary of the local maxima in the blind group sorted by the performed task. Even small-volume correction for the occipital cortex did not reveal any signicant activation during nger tapping or electrical stimulation neither in blind nor in sighted volunteers. Analysis of differences in sighted and blind subjects in Braille reading and sensory activation in random effects analysis revealed the visual cortex activation as specic for the blind group during Braille reading (Fig. 5).

Table 1 Activated regions related to the performed stimuli Tasks Braille Talairach coordinates (mm) 9; 27; 27; 6; 6; 36; 62; 39; 99; 10 74; 34 97; 8 42; 69 3; 66 23; 56 1; 33 23; 56 Region (cortex) Middle occipital Superior occipital Cuneus Precentral Ventral premotor Precentral Postcentral Side L R R L L L R L Area of Activation (BA) 18 19 17 4 6 4 6 3 T value 19 7 6 7 9 20 7 6

Finger tapping Electrical stimulation

Overview over the activated areas during different active tasks: Braille reading, nger tapping, and sensory activation in blind subjects. Only statistically reliable areas (P 0.05) are included. Talairach coordinates are given in x, y, z direction.

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another group even presented occipital activation while listening to a sinus wave tone and discriminating sounds (Kujala et al., 1995a,b). But these results were discussed controversially. Buchel et al. (1998) could not nd occipital activation in blind subjects during an auditory task. Finally, for a tactile mental rotating task in blind subjects activation of visual cortex could be revealed (Roder et al., 1997). In our study, we decided to start a step before complex functions like discrimination and rotation tasks. We wanted to discriminate between occipital activation due to pure sensory or motor tasks and activation due to nger readingrelated tasks. As we did not nd any activation of visual areas in blind subjects during nger tapping and sensory electric stimulation, our results indicate that activation of the visual cortex in blind subjects is related to higher and complex brain functions and not to pure sensory or motor tasks. Even discriminating nonsense dots must be interpreted as a complex brain function, because the subject does not only feel the dots under his ngers but must also decide whether these dots are senseless or not. This might explain the activation of the visual cortex during discriminating tasks. Furthermore, some of the published discriminating tasks have been more complex; i.e., the subject additionally had to discriminate angle and width (Sadato et al., 1998). One further controversial nding is published by PascualLeone and Hamilton (2001). They describe visual cortex activation in blindfolded subjects during tactile stimulation consisting of a loofah brush. The authors argue that there might be as well some kind of visual imagery. Recent studies have revealed that blindfolded subjects performed better than sighted subjects in the Braille discrimination task. These results suggest that visual deprivation speeds up Braille learning and may be associated with a kind of neuroplastic change (Kauffman et al., 2002). There might be a clue to the recently started discussion about how occipital activation in blind subjects can be explained. Zangaladze et al. were able to show that visual cortical areas are involved in tactile discrimination of orientation in normal sighted subjects (Zangaladze et al., 1999; Sathian and Zangaladze, 2001). Additionally, Amedi et al. (2001) found an activation of occipitotemporal areas during object sensory recognition and Chen et al. (1998) during visual imagery. It is postulated that the neurons in the occipitotemporal region may constitute a multimodal object-related network. Therefore, our results are consistent with this theory of brain plasticity in blind subjects starting at an overlapping region of complex and higher brain functions and expanding to V2 and V1 in the absence of visual input. The postulated theory for crossmodal plasticity at the thalamic level indicates that information reaches the cortex through the somatosensory thalamus (Buchel, 1998; Rehkamper et al., 1994). According to this theory, pure sensory or motor tasks would be more likely to reach the occipital cortex in blind subjects. In conclusion, we were able to divide the complex

Braille reading task into two basic tasks and could show that only the complex task shows cross-modal plasticity. Further investigations in blind subjects with different onset ages of blindness and different abilities and learning strategies in Braille reading may lead to a more precise understanding of the way cross-modal plasticity occurs and can be trained.

Acknowledgments We thank J. Esser, M.D., Ph.D. (Department of Ophthalmology, University of Essen, Germany), for providing contact to organizations of blind people.

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