Abstract

Early blindness results in both structural and functional changes of the brain. However, these changes have rarely been studied in relation to each other. We measured alterations in cortical thickness (CT) caused by early visual deprivation and their relationship with cortical activity. Structural and functional magnetic resonance imaging was performed in 12 early blind (EB) humans and 12 sighted controls (SC). Experimental conditions included one-back tasks for auditory localization and pitch identification, and a simple sound-detection task. Structural and functional data were analyzed in a whole-brain approach and within anatomically defined regions of interest in sensory areas of the spared (auditory) and deprived (visual) modalities. Functional activation during sound-localization or pitch-identification tasks correlated negatively with CT in occipital areas of EB (calcarine sulcus, lingual gyrus, superior and middle occipital gyri, and cuneus) and in nonprimary auditory areas of SC. These results suggest a link between CT and activation and demonstrate that the relationship between cortical structure and function may depend on early sensory experience, probably via selective pruning of exuberant connections. Activity-dependent effects of early sensory deprivation and long-term practice are superimposed on normal maturation and aging. Together these processes shape the relationship between brain structure and function over the lifespan.

Introduction

It is well established that visual deprivation causes structural and functional reorganization in both the deprived and the intact sensory cortices (Rauschecker 1995; Bavelier and Neville 2002; Merabet and Pascual-Leone 2010). Although functional and structural changes after sensory deprivation have been studied extensively (Gilbert and Wiesel 1992), relatively little is known about how these changes relate to each other.

Sensory areas of the deprived modality have been shown consistently to adopt an important role in the processing of information from intact modalities during perceptual (Weeks et al. 2000; Pietrini et al. 2004; Kujala et al. 2005; Voss et al. 2008) and cognitive tasks (Sadato et al. 1996, 1998; Cohen et al. 1997; Büchel et al. 1998; Hamilton and Pascual-Leone 1998; Röder et al. 2002; Burton et al. 2003; Bedny et al. 2011; Striem-Amit et al. 2012). Recruitment of occipital cortex during nonvisual processing in the blind has been shown to be related to successful behavioral performance, since the degree of occipital involvement correlates positively with Braille reading abilities (Cohen et al. 1997), sound localization accuracy (Gougoux et al. 2005), and verbal memory performance (Amedi et al. 2003).

Increased cortical thickness (CT) within the occipital lobes in congenitally blind (CB) and early blind (EB) but not in late blind (LB) individuals compared with sighted controls (SC) is among the most consistently reported morphological changes caused by visual deprivation (Bridge et al. 2009; Jiang et al. 2009; Park et al. 2009; Voss and Zatorre 2011). Furthermore, it has recently been shown that occipital CT correlates positively with enhanced performance of the EB in a transposed melody discrimination task (Voss and Zatorre 2011). Thus, assuming that enhanced performance correlates positively with cortical activation (e.g., Cohen et al. 1997; Gougoux et al. 2005; Amedi et al. 2003; Karni et al. 1995), it would be logical to expect that CT within the occipital lobes of the EB also correlates positively with the magnitude of activation, that is, thicker cortex should be activated more strongly and vice versa.

On the other hand, it has been argued that greater thickness of occipital cortex in the EB may be caused by reduced pruning of exuberant connections (axon collaterals, dendritic arbors) and reduced elimination of ineffective synapses, which normally takes place during early development, with amount of pruning dependent on visual experience (Jiang et al. 2009). Although the initial connectivity of the visual pathway is nearly complete by the end of the gestation period, visual experience is still a key factor for synaptic refinement and increasing neurocomputational abilities (Innocenti and Frost 1979; Innocenti and Price 2005; Sanes et al. 2006). Deprived of visual stimulation, the occipital cortex of EB and CB individuals remains thicker compared with that of sighted. Owing to involvement of blind occipital areas in processing nonvisual information, however, these areas still undergo selective refinement by elimination of exuberant connections and stabilization of effective synapses (“Hebbian” plasticity; Rauschecker 1991). Therefore, within the group of EB, areas with a thinner cortex should be associated with more effective function, so negative correlations between CT and magnitude of activation might be expected. Consistent with this prediction, most studies in which relationships between cortical structure and function have been tested suggest a negative correlation between CT and activation in typically developing children and adults, that is, thinner cortex is activated more strongly (Rasser et al. 2005; Lu et al. 2009; Nunez et al. 2011). To our knowledge, only one study has shown a positive correlation between CT and functional activation in a limbic structure, the anterior cingulate cortex (Hegarty et al. 2012).

The present study was designed to resolve this ambiguity by measuring regional changes in CT caused by early blindness in relation to activation during functional magnetic resonance imaging (fMRI). Correlations between CT and magnitude of activation associated with auditory processing of sound identity and spatial location in both EB and SC were analyzed at the whole-brain level and within several anatomically defined regions of interest, including primary and nonprimary areas of visual and auditory cortex. This approach aimed to reveal whether and how the relationship between structure and function depends on early visual experience. Overall, we expected to find evidence for neuroplastic changes in cortical areas of EB subjects for both deprived (visual) and intact (auditory) modalities. We hypothesized that some occipital areas in EB would be activated particularly during demanding auditory tasks, similar to how nonprimary auditory areas are activated in SC. Consequently, we expected that relationships between anatomical structure and function typical for nonprimary auditory cortex in SC would also be observed in the reorganized “visual” cortex of the EB during auditory information processing. More specifically, we expected to find correlations between structure and function within equivalent cortical areas when attention is directed to spectral or spatial characteristics of the sounds. Two recent studies (Renier et al. 2010; Collignon et al. 2011), for instance, emphasized a specific role for the middle occipital gyrus (MOG), known to be involved in the processing of visual spatial information in the sighted, and of auditory spatial information in EB individuals. Based on these findings, we hypothesized that, in the EB, significant correlations between CT and functional activation during an auditory spatial task would be observed within the MOG.

Materials and Methods

Subjects

Anatomical and functional neuroimaging data were obtained from 12 EB (5 males, 10 right-handed, mean age ± standard deviation[S.D.]: 49 ± 9.2 years) and 12 age-, gender-, and handedness-matched sighted volunteers (mean age ± S.D.: 45 ± 10.9 years), which served as controls. All participants were healthy, with no history of neurological or psychiatric disorders. Nine of the blind participants were totally blind from birth and 3 became blind by the second year of life. Clinical characteristics of blind subjects are presented in Table 1. The study protocol was approved by Georgetown University's Institutional Review Board; written informed consent was obtained from all participants prior to the experiment.

Table 1

Clinical characteristics of EB subjects

Subject Sex Age (years) Handedness Cause of blindness Onset of blindness 
EB01 56 Right ROP Congenital 
EB02 45 Right Retinopathy <2 years 
EB03 56 Right Unknown Congenital 
EB04 38 Right Retinal detachment <2 years 
EB05 58 Right ROP Congenital 
EB06 53 Right ROP Congenital 
EB07 55 Right Retinal detachment Congenital 
EB08 34 Right Optic nerve hypoplasia <2 years 
EB09 34 Right ROP Congenital 
EB10 55 Left ROP Congenital 
EB11 55 Right ROP Congenital 
EB12 56 Left ROP Congenital 
Subject Sex Age (years) Handedness Cause of blindness Onset of blindness 
EB01 56 Right ROP Congenital 
EB02 45 Right Retinopathy <2 years 
EB03 56 Right Unknown Congenital 
EB04 38 Right Retinal detachment <2 years 
EB05 58 Right ROP Congenital 
EB06 53 Right ROP Congenital 
EB07 55 Right Retinal detachment Congenital 
EB08 34 Right Optic nerve hypoplasia <2 years 
EB09 34 Right ROP Congenital 
EB10 55 Left ROP Congenital 
EB11 55 Right ROP Congenital 
EB12 56 Left ROP Congenital 

ROP, retinopathy of prematurity; M, male; F, female.

Data Acquisition

All neuroimaging data were acquired at Georgetown University's Center for Functional and Molecular Imaging on a 3-Tesla Siemens Tim Trio scanner equipped with a 12-channel head coil. The fMRI data were acquired using an echo-planar imaging sequence (flip angle = 90°, TR = 3 s, TE = 60 ms). The FOV was 192 × 192 mm2 with a 64 × 64 matrix size; slice thickness was 2.8 mm with a 0.2-mm gap, resulting in an effective voxel resolution of 3 × 3 × 3 mm3. For each run, 184 volumes of 50 slices were acquired in a continuous sampling paradigm. At the end, a high-resolution 3D T1-weighted MPRAGE image (resolution 1 × 1 × 1 mm3) was acquired for each subject (TR = 1900 ms, TE = 2.52 ms, TI = 900 ms, flip angle = 9°). The volume consisted of 176 sagittal slices (FOV = 256 × 256 mm2, 256 × 256 matrix, slice thickness = 1 mm).

Stimuli and Experimental Design

The stimuli were 4 C-major piano chords over a range of 4 octaves originating from 4 different locations in virtual auditory space. The stimuli were presented via electrostatic MRI-compatible headphones (STAX, frequency transfer function 20 Hz to 20 kHz). Four sound source locations, ±90° (corresponding to the extreme left and right) and ±30°, were simulated by convolving the stimuli with standard head-related transfer functions provided by Amphiotik Synthesis. The stimulus duration was 1000 ms (including 10 ms rise/fall times); the interstimulus interval was 1s.

Subjects performed auditory identification (ID), localization (Loc), and simple sound-detection (SD) tasks. The experimental setup was the same as that used in Renier et al. (2010). For both auditory ID and Loc conditions, a one-back paradigm was employed. In this paradigm, subjects had to compare each new stimulus in the sequence with the previous one and categorize it as either the same or different regarding a certain stimulus attribute. During the ID task, subjects compared the chords in terms of pitch height, while, in the Loc task, they compared the chords' spatial locations. In matching trials, subjects pressed the left button of the MRI-compatible response pad with the left middle finger; in nonmatching trials, they pressed the right button with the left index finger. During the SD task, subjects pressed the left button every time they heard a stimulus. The SD task was used to control for perceptual and motor components of the experimental tasks (ID and Loc). In the ID task, spatial locations of the sounds were fixed within one condition, but varied among conditions. Conversely, in the Loc task, the same chord was presented from different locations, whereas the chord's height varied from one condition to another. In the SD task, both the chords' pitch and their spatial locations were fixed. The onset of each condition was announced through the headphones. Presentation of the stimuli and collection of behavioral data were controlled by Superlab software 4.0 (Cedrus Corp.). Sighted subjects were blindfolded during the scanning session. Before scanning, all participants were familiarized with the tasks during a brief practice session. Acquisition of functional data was performed using a block-design paradigm. Duration of 1 block was 18 s and corresponded to 9 presentations of stimuli. Blocks were separated by 12-s resting periods. Each of the 3 experimental conditions (ID, Loc, and SD) was repeated 6 times during a 9-min run. Thus, 1 run consisted of 18 blocks. Three runs were presented during the experiment. The order of the experimental conditions was counterbalanced across subjects.

Statistical Evaluation of Behavioral Data

Analysis of behavioral data (percent correct responses) was performed with a two-way mixed-design ANOVA with Group (EB vs. SC) as a between-subjects factor and Task (ID vs. Loc) as a within-subject factor. Detection scores were compared between the 2 groups using the two-tailed unpaired t-test.

Structural and Functional MRI Data Processing

Analysis of both structural (CT) and functional data was performed in surface space using Brain Voyager 2.1 (BVQX, Brain Innovation, Maastricht, the Netherlands).

Cortical Reconstruction and Intersubject Alignment

An intersubject cortical alignment procedure was employed in order to reduce the effect of anatomical variability and to improve the spatial correspondence of cortical areas between individual brains. Prior to surface reconstruction, the original T1-weighted MRIs were corrected for spatial intensity inhomogeneities and then converted into volumes with 1-mm isotropic voxels. After that, the volumes were further spatially transformed into standard Talairach space. Sinc interpolation was used at all steps of spatial transformation. For the normalized MRIs, an automatic segmentation of white-matter (WM) and gray-matter (GM) boundaries was applied. Topological errors such as “bridges” and remaining fragments of dura mater or cerebellum were corrected manually. The reconstructed cortical hemispheres were morphed into spherical representations of the folded cortex. Curvature information of individual brains was used for cortex-based intersubject alignment, which was carried out using the moving-target group averaging (Goebel et al. 2006) and resulted in creating averaged curvature maps. After the alignment procedure, averaged folded meshes were constructed for both hemispheres. Each mesh resulted from averaging 24 individual datasets (12 EB and 12 SC). These meshes were used for projecting both anatomical (CT) and functional (fMRI) datasets.

CT Analysis

CT analysis was carried out following a series of advanced segmentation steps. First, the Talairach-transformed individual MRIs were resampled to 0.5-mm isovoxel resolution space using sinc interpolation. Brains were segmented from the head tissue using an automatic brain-peeling tool. Peeling parameters were individually adjusted for each subject's MRI. Subcortical structures and cerebellum were removed using a default brain mask. Then, tissue contrast and homogeneity enhancement were followed by segmentation of WM/GM and GM/cerebrospinal fluid boundaries. After segmentation of the cortical layer was completed, CT was measured for each subject's hemisphere using the Laplace method (Jones et al. 2000; Geuze et al. 2008). Averaged CT maps were generated separately for each group of subjects. Whole-brain group differences in CT were evaluated using a two-tailed unpaired t-test in cortical surface space following cortical reconstruction and intersubject alignment. The results were corrected for multiple comparisons by cluster-size correction analysis, incorporated in Brain Voyager QX, using a Monte Carlo simulation procedure with 1000 iterations in order to define the cluster-size threshold corresponding to a familywise error rate of 0.05.

In a subsequent region-of-interest (ROI) analysis, we compared averaged thickness values from anatomically defined ROIs across subjects. Each ROI was determined on the basis of averaged meshes using anatomical landmarks. In the occipital lobes, ROIs were located within primary and nonprimary visual areas including bilateral calcarine sulcus (CS), lingual gyrus (LG), cuneus (Cu), and lateral occipital (LO) cortex. The LO region included the lateral surface of the occipital lobes (middle and inferior occipital gyri, MOG and IOG, respectively) bounded superiorly by the LO sulcus and anteriorly by the anterior occipital sulcus and temporo-occipital incisura (Fig. 2A). The ROIs within the temporal lobes included bilateral Heschl's gyrus (HG), and bilateral anterior and posterior parts of the lateral convexity of the superior temporal gyrus extending anteriorly and posteriorly to HG, respectively (aSTG, pSTG) (Fig. 2B). Statistical evaluations of CT were done separately for each pair of corresponding ROIs in the left and right hemispheres using a two-way analysis of variance (ANOVA) with Group (EB vs. SC) as a between-subjects factor and Hemisphere (left and right) as a within-subject factor. Mean CT values over each ROI were used as dependent variables. If significant main effects were observed (P < 0.05), post hoc analyses were performed using the Newman–Keuls test.

Analysis of Functional Data

The preprocessing of the functional data included slice-timing correction, correction for small interscan head movements, temporal high-pass filtering (removing frequencies lower than 3 cycles/run), and spatial smoothing using a 6-mm Gaussian filter. Data were transformed into Talairach space (Talairach and Tournoux 1988). For anatomical reference, the computed statistical maps were overlaid on the 3D T1-weighted scans. A general linear model (GLM) was used to analyze the blood oxygen level–dependent (BOLD) responses of each subject as a function of experimental condition. Regressors of interest consisted of boxcar functions convolved with the standard hemodynamic response function. A random-effects analysis of variance (RFX ANOVA) was employed in order to remove intersubject variability. The RFX ANOVA was applied in cortical surface space following the cortical reconstruction and intersubject alignment. The whole-brain analysis was done in 2 steps. First, BOLD responses associated with each experimental condition (ID, Loc, and SD) were compared between the 2 groups (EB vs. SC). Second, BOLD responses evoked by one-back tasks compared with the control task ((ID + Loc) vs. SD) were computed separately for each group. For all contrasts, the P values were corrected for false discovery rate (FDR) using a threshold of q < 0.05. The results of the direct contrast between the ID and Loc tasks were described in detail in an earlier paper from our group that focused on the differences between spatial and nonspatial processing in EB (Renier et al. 2010).

In the ROI analyses, statistical evaluations of the magnitude of the BOLD response were performed separately for each pair of corresponding ROIs in the left and right hemisphere using a three-way ANOVA with Group (EB vs. SC) as a between-subjects factor and Task (ID, Loc, and SD) and Hemisphere (left and right) as within-subject factors. The mean percentages of signal change over the ROI were used as dependent variables. The Greenhouse–Geisser correction was used for factors with more than 2 levels. If significant main effects were observed (P < 0.05), post hoc analyses were performed using the Newman–Keuls test.

Analysis of Correlations Between CT and Activation and Between CT and Age

First, in order to identify a general tendency in the relationships between CT and regional BOLD responses, we created a mixed-effects GLM, in which percent signal change within the ROIs during the ID, Loc, and SD tasks were used as dependent variables, CT and age as continuous predictors, and Group (EB vs. SC), ROI and Hemisphere (left vs. right) as categorical predictors. BOLD responses elicited during the ID, Loc, and SD tasks were tested separately. Wald-type statistics were applied to test the effects of CT and its interactions with other factors and their combinations. For tasks in which CT × Group × ROI × Hemisphere interactions produced significant main effects, the relationships between CT and activation were further tested using a GLM separately for each ROI (left and right) and each group of subjects. All statistical tests with subjects treated as random-effects were also controlled for Age. Finally, the ROIs where CT produced a significant effect on activation were submitted for the next step of analysis, in which relationships between the CT and BOLD response were tested using Pearson's correlations.

In addition to the GLM analysis in which mean values for the CT and percent signal change within each ROI were used, the relationships between CT and regional BOLD responses were examined at the whole-brain level in surface space using BVQX. Pearson's correlation coefficients (r) were calculated at each cortical surface point (vertex by vertex). The r-maps were corrected for multiple comparisons by cluster size using a Monte Carlo simulation.

Correlations between CT and age/duration of blindness were studied separately for each ROI and each group of subjects by using Pearson's correlation analyses.

Results

Differences between EB and SC participants were assessed in terms of 1) behavioral performance, 2) anatomy (CT), and 3) functional activation (BOLD response). Finally, a correlation between CT and activation data was performed.

Behavioral Data

Accuracy of one-back ID and Loc task performance did not differ between groups (F1,22 = 0.8, P = 0.37) or tasks (F1,22 = 1.1, P = 0.31). Both EB and SC participants managed pitch-identification and sound-localization tasks at high accuracy levels, though not at ceiling (EB, 87 ± 2% (mean ± standard error of mean) for the ID task and 85 ± 3% for the Loc task; SC, 89 ± 2% and 89 ± 3%, respectively). Detection scores in a sound-detection task (SD), which was used as a control task, were nearly perfect and did not differ between groups (99 ± 1% in EB and 97 ± 2% in SC; t(22) = 0.9, P = 0.38).

CT Analysis

CT Analysis of Whole-Brain Data

Comparison of CT data from EB and SC participants was first performed in a whole-brain analysis, followed by analysis of anatomically defined ROIs in occipital and superior temporal regions to specifically study effects in visual and auditory areas.

A t-test revealed significant group differences in CT between EB and SC (P < 0.05, corrected for multiple comparisons by cluster size) throughout a wide range of cortical areas (Fig. 1, Table 2). The most prominent differences were observed in occipital and frontal regions. Smaller clusters of group differences in CT were also detected within the right superior parietal lobe and in anterior cingulate gyrus. In all these areas, cortex was thicker in the EB group.

Table 2

Brain regions showing significant group differences in CT in a whole-brain analysis

Brain region BA x y z t value P value 
L LG 17 −4 −77 8.09 <0.000001 
L Cu 18 −5 −82 19 4.89 <0.0001 
L MOG 17/18 −15 −98 −3 7.32 <0.000001 
L IOG 18 −19 −94 −15 4.75 <0.0001 
L CS 17 −20 −62 3.95 <0.001 
L SFG 10 −22 53 10 5.94 <0.00001 
L MFG 10/46 −36 52 4.83 <0.0001 
L MFG −33 25 38 3.59 <0.005 
R LG 18 −76 −3 5.13 <0.00005 
R Cu 17 −84 5.03 <0.00005 
R IOG 18 28 −90 −3 6.64 <0.000001 
R SFG/SFS 10 18 55 5.12 <0.00005 
R ACG 32 45 −1 5.50 <0.00005 
R PoCeG/PoCeS 24 −37 54 3.92 <0.001 
Brain region BA x y z t value P value 
L LG 17 −4 −77 8.09 <0.000001 
L Cu 18 −5 −82 19 4.89 <0.0001 
L MOG 17/18 −15 −98 −3 7.32 <0.000001 
L IOG 18 −19 −94 −15 4.75 <0.0001 
L CS 17 −20 −62 3.95 <0.001 
L SFG 10 −22 53 10 5.94 <0.00001 
L MFG 10/46 −36 52 4.83 <0.0001 
L MFG −33 25 38 3.59 <0.005 
R LG 18 −76 −3 5.13 <0.00005 
R Cu 17 −84 5.03 <0.00005 
R IOG 18 28 −90 −3 6.64 <0.000001 
R SFG/SFS 10 18 55 5.12 <0.00005 
R ACG 32 45 −1 5.50 <0.00005 
R PoCeG/PoCeS 24 −37 54 3.92 <0.001 

BA, Brodmann area; x, y, z, peak Talairach coordinates; ACG, anterior cingulate gyrus; CS, calcarine sulcus; Cu, cuneus; IOG, inferior occipital gyrus; LG, lingual gyrus; MFG, middle frontal gyrus; MOG, middle occipital gyrus; PoCeG, postcentral gyrus; PoCeS, postcentral sulcus; SFG, superior frontal gyrus; SFS, superior frontal sulcus.

Figure 1.

Group differences in cortical thickness (EB > SC). Results are shown at P < 0.05, corrected by cluster size. Color scale codes t values. LH, left hemisphere; RH, right hemisphere; A, anterior; P, posterior. Occipital and frontal areas in EB were significantly thicker than in SC subjects (see Table 2).

Figure 1.

Group differences in cortical thickness (EB > SC). Results are shown at P < 0.05, corrected by cluster size. Color scale codes t values. LH, left hemisphere; RH, right hemisphere; A, anterior; P, posterior. Occipital and frontal areas in EB were significantly thicker than in SC subjects (see Table 2).

CT Analysis of ROI Data

A more detailed analysis of CT was performed for different anatomical regions in occipital and superior temporal regions, as defined in Materials and Methods (Fig. 2A,B).

Figure 2.

Anatomically defined ROIs in occipital (A) and superior temporal (B) cortices. (C) Cortical thickness within anatomically defined ROIs in EB (black bars) and SC (gray bars) subjects. Cu, cuneus; CS, calcarine sulcus; LG, lingual gyrus; LO, lateral occipital cortex; HG, Heschl's gyrus; aSTG, pSTG, anterior/posterior parts of the superior temporal gyrus; *P < 0.05, **P < 0.01. In occipital areas, cortex is consistently thicker in EB than in SC. In superior temporal areas, primary auditory cortex in the left HG was thicker, while nonprimary auditory cortex in the left aSTG was thinner in EB compared with SC.

Figure 2.

Anatomically defined ROIs in occipital (A) and superior temporal (B) cortices. (C) Cortical thickness within anatomically defined ROIs in EB (black bars) and SC (gray bars) subjects. Cu, cuneus; CS, calcarine sulcus; LG, lingual gyrus; LO, lateral occipital cortex; HG, Heschl's gyrus; aSTG, pSTG, anterior/posterior parts of the superior temporal gyrus; *P < 0.05, **P < 0.01. In occipital areas, cortex is consistently thicker in EB than in SC. In superior temporal areas, primary auditory cortex in the left HG was thicker, while nonprimary auditory cortex in the left aSTG was thinner in EB compared with SC.

In occipital ROIs, cortex was consistently thicker in EB than in SC subjects, confirming the results of whole-brain analysis. Using two-way ANOVA, a significant main effect of Group was observed within the CS (F1,22 = 5.5, P < 0.05), LG (F1,22 = 4.3, P < 0.05), Cu (F1,22 = 9.6, P < 0.01), and LO regions (F1,22 = 7.0, P < 0.05).

In superior temporal ROIs, corresponding to auditory regions, the effects of early blindness on CT were less uniform. A significant main effect of Group was found in anterior STG (aSTG) (F1,22 = 5.1, P < 0.05), where cortex was thinner in EB than in SC. In HG, corresponding to primary auditory areas, CT showed a Group–Hemisphere interaction (F1,22 = 4.3, P < 0.05) indicating that left HG was thicker in the group of EB than SC (P < 0.05). No significant effects of Group (F1,22 = 0.14, P = 0.71) and no Group–Hemisphere interactions (F1,22 = 0.01, P = 0.92) were detected for posterior STG (pSTG) (Fig. 2C).

Functional MRI Data Analysis

Whole-Brain fMRI Data

Group differences (EB vs. SC) in cortical functional activation corresponding to each experimental task (ID, Loc, SD) are presented in Figure 3 and Table 3.

Table 3

Brain regions showing significant group differences in activation by auditory stimuli across experimental tasks in a whole-brain analysis

Experimental task Brain region BA x y z t value P value 
ID Task (EB > SC) L Cu/SOG 18 −13 −90 18 6.44 <0.000001 
L Cu 17/18 −6 −82 12 4.66 <0.0005 
L IOG/MOG 18/19 −39 −78 6.15 <0.000005 
L FG 19 −33 −63 −13 5.08 <0.00005 
L CS 17 −10 −88 −3 4.23 <0.0005 
L LG 18 −14 −75 −9 4.11 <0.0005 
L PoCeS −18 −43 58 4.05 <0.0005 
R Cu 18 −82 24 5.09 <0.00005 
R SOG 18/19 18 −82 25 6.41 <0.000005 
R MOG 18 29 −83 5.33 <0.00005 
R IOG 18/19 43 −71 −1 7.72 <0.000001 
R CS 17 −82 4.52 <0.0005 
R LG 17 17 −62 4.91 <0.0001 
R FG 19 29 −66 −13 5.68 <0.00001 
R SPL 22 −63 45 4.51 <0.0005 
ID Task (EB < SC) L HG 41 −40 −22 −4.28 <0.0005 
R MTG 21 52 −21 −7 −4.72 <0.0001 
Loc Task (EB > SC) L Cu 17 −5 −84 10 6.20 <0.000005 
L SOG 19 −19 −82 27 7.74 <0.000001 
L MOG 19 −26 −85 6.56 <0.000001 
L CS 17 −7 −87 5.27 <0.00005 
L LG 18 −12 −80 −13 4.83 <0.0001 
L FG 19 −25 −63 −13 5.50 <0.00005 
L SFS −24 13 44 4.06 <0.0005 
L PrCeG −49 −11 43 4.34 <0.0005 
L CeS −27 −31 56 4.58 <0.0005 
L CeS −53 −6 22 4.34 <0.0005 
L PoCG/PoCS −14 −44 66 4.63 <0.0005 
L PCu 5/7 −8 −49 50 5.00 <0.00005 
R Cu 18 11 −85 20 6.82 <0.000001 
R SOG 18 18 −82 25 7.91 <0.000001 
R MOG 19 30 −82 7.13 <0.000001 
R IOG 19 43 −71 −1 7.91 <0.000001 
R CS 17 −86 −1 5.25 <0.00005 
R CS 17 15 −64 5.26 <0.00005 
R LG 18 −79 −2 4.92 <0.0001 
R FG 19 26 −55 −8 5.69 <0.00001 
R CeS 51 −12 28 4.37 <0.0005 
R PoCeG −36 65 5.45 <0.00005 
R PoCeG 25 −36 56 4.78 <0.0001 
R SPL 21 −64 43 5.79 <0.00001 
SD Task (EB > SC) R CeS 19 −32 56 4.76 <0.0001 
Experimental task Brain region BA x y z t value P value 
ID Task (EB > SC) L Cu/SOG 18 −13 −90 18 6.44 <0.000001 
L Cu 17/18 −6 −82 12 4.66 <0.0005 
L IOG/MOG 18/19 −39 −78 6.15 <0.000005 
L FG 19 −33 −63 −13 5.08 <0.00005 
L CS 17 −10 −88 −3 4.23 <0.0005 
L LG 18 −14 −75 −9 4.11 <0.0005 
L PoCeS −18 −43 58 4.05 <0.0005 
R Cu 18 −82 24 5.09 <0.00005 
R SOG 18/19 18 −82 25 6.41 <0.000005 
R MOG 18 29 −83 5.33 <0.00005 
R IOG 18/19 43 −71 −1 7.72 <0.000001 
R CS 17 −82 4.52 <0.0005 
R LG 17 17 −62 4.91 <0.0001 
R FG 19 29 −66 −13 5.68 <0.00001 
R SPL 22 −63 45 4.51 <0.0005 
ID Task (EB < SC) L HG 41 −40 −22 −4.28 <0.0005 
R MTG 21 52 −21 −7 −4.72 <0.0001 
Loc Task (EB > SC) L Cu 17 −5 −84 10 6.20 <0.000005 
L SOG 19 −19 −82 27 7.74 <0.000001 
L MOG 19 −26 −85 6.56 <0.000001 
L CS 17 −7 −87 5.27 <0.00005 
L LG 18 −12 −80 −13 4.83 <0.0001 
L FG 19 −25 −63 −13 5.50 <0.00005 
L SFS −24 13 44 4.06 <0.0005 
L PrCeG −49 −11 43 4.34 <0.0005 
L CeS −27 −31 56 4.58 <0.0005 
L CeS −53 −6 22 4.34 <0.0005 
L PoCG/PoCS −14 −44 66 4.63 <0.0005 
L PCu 5/7 −8 −49 50 5.00 <0.00005 
R Cu 18 11 −85 20 6.82 <0.000001 
R SOG 18 18 −82 25 7.91 <0.000001 
R MOG 19 30 −82 7.13 <0.000001 
R IOG 19 43 −71 −1 7.91 <0.000001 
R CS 17 −86 −1 5.25 <0.00005 
R CS 17 15 −64 5.26 <0.00005 
R LG 18 −79 −2 4.92 <0.0001 
R FG 19 26 −55 −8 5.69 <0.00001 
R CeS 51 −12 28 4.37 <0.0005 
R PoCeG −36 65 5.45 <0.00005 
R PoCeG 25 −36 56 4.78 <0.0001 
R SPL 21 −64 43 5.79 <0.00001 
SD Task (EB > SC) R CeS 19 −32 56 4.76 <0.0001 

CeS, central sulcus; FG, fusiform gyrus; HG, Heschl's gyrus; MTG, middle temporal gyrus; PCu, precuneus; PrCeG, precentral gyrus; SOG, superior occipital gyrus; SPL, superior parietal lobule. All other abbreviations as in Table 2.

Figure 3.

Group differences in cortical functional activation (EB > SC) during Identification versus Rest (ID), Localization versus Rest (Loc), and Sound Detection versus Rest (SD) tasks. Group differences are shown at P < 0.05, FDR-corrected. Color scale codes t values. ID and Loc auditory one-back tasks, but not SD, produce stronger activation in the occipital cortex in EB compared with SC.

Figure 3.

Group differences in cortical functional activation (EB > SC) during Identification versus Rest (ID), Localization versus Rest (Loc), and Sound Detection versus Rest (SD) tasks. Group differences are shown at P < 0.05, FDR-corrected. Color scale codes t values. ID and Loc auditory one-back tasks, but not SD, produce stronger activation in the occipital cortex in EB compared with SC.

In the auditory ID task, significant group differences were observed within medial and LO cortex, including the CS, LG, Cu, and inferior/middle occipital gyri (IOG/MOG). In all regions of occipital cortex, activation by the auditory ID task was stronger in the group of EB than in SC. Decreased activation in EB compared with SC was observed in the medial part of left HG, and within right superior temporal sulcus (STS).

In the auditory Loc task, enhanced activation in the EB group was observed within the same general regions of occipital cortex, within the superior parietal lobes bilaterally, and within the left middle frontal gyrus/sulcus.

In the SD task, group differences between EB and SC were confined to a small cluster within the right central sulcus (Table 3).

Contrasting cortical activation during the more demanding ID and Loc tasks with activation corresponding to the simple SD task revealed both similarities and differences between the EB and SC groups (Fig. 4, Table 4). Areas activated more strongly during the one-back tasks (compared with SD) included the fronto-parietal network in both groups, the medial and LO areas in the group of EB subjects, and nonprimary auditory cortex within pSTG for the group of SC. Task-induced deactivation was observed for both groups in areas of the “default-mode network” (Buckner et al. 2008), including medial frontal and parietal areas, anterior and posterior cingulate cortex, inferior parietal lobule, and lateral anterior temporal areas extending to the temporal pole. In addition, auditory one-back tasks induced deactivation within the right LO cortex in the group of SC, which was activated in the group of EB.

Table 4

Brain regions showing significant differences in activation between auditory one-back tasks (ID + Loc) and the sound-detection (SD) task in EB and SC in the whole-brain analysis

 Brain region BA x y z t value P value 
EB 
Activations L Cu 17 −4 −88 6.99 <0.000001 
L Cu 18 −12 −88 20 6.90 <0.000001 
L MOG 18 −23 −87 5.82 <0.00001 
L IOG 19 −39 −80 −4 5.63 <0.00001 
L CS 17 −9 −90 6.21 <0.000005 
L LG 18 −5 −83 −6 4.91 <0.0001 
L FG 19 −23 −65 −11 4.74 <0.0001 
L MeFG −7 47 6.29 <0.000005 
L MFG 46 −34 42 25 4.34 <0.0005 
L PrCeG −50 −2 33 6.92 <0.000001 
L PrCeS −19 −11 55 5.39 <0.00005 
L aINS 13 −29 14 10 5.39 <0.00005 
L IPS 7/40 −37 −42 37 5.74 <0.00001 
R Cu 17 −89 5.54 <0.00005 
R MOG 18 30 −80 4.70 <0.0001 
R IOG 19 43 −71 −1 5.19 <0.00005 
R CS 17 −86 −1 6.12 <0.000005 
R LG 18 −81 −4 5.90 <0.000005 
R MFG 9/46 35 27 31 4.46 <0.0005 
R MeFG 50 4.86 <0.0001 
R PrCeS 44 21 6.21 <0.000005 
R PrCeG/PrCeS 4/6 38 −8 46 5.37 <0.00005 
R aINS 13 30 14 12 5.46 <0.00005 
R SPL 20 −75 38 6.59 <0.000001 
R SMG 40 48 −40 40 5.33 <0.00005 
Deactivations L MeFG/ACG 32 −10 47 12 −5.71 <0.00001 
L PCG 30 −8 −58 16 −6.47 <0.000001 
L AG 39 −43 −65 27 −5.15 <0.00005 
L STS/MTG 21/22 −57 −12 −12 −5.36 <0.00005 
R SFG 19 23 48 −4.56 <0.0005 
R MeFG/ACG 32 10 54 11 −5.20 <0.00005 
R PCG 23/30 −56 20 −6.82 <0.000001 
R AG 39 44 −61 24 −5.00 <0.00005 
R STS/MTG 21/22 50 −2 −18 −4.98 <0.00005 
SC 
Activations L MeFG −8 52 5.38 <0.00005 
L PrCeG −43 −4 36 4.88 <0.0001 
L PrCeS −24 −15 51 4.68 <0.0005 
L aINS 13 −30 17 14 5.43 <0.00005 
L IPS 40 −49 −38 36 5.86 <0.00001 
L STG 22 −53 −40 14 4.52 <0.0005 
R MeFG 51 5.29 <0.00005 
R PrCeS 47 19 5.17 <0.00005 
R PrCeG/PrCeS 4/6 38 −8 47 6.29 <0.000005 
R aINS 13 29 19 12 6.21 <0.000005 
R IPS 7/40 34 −49 37 5.89 <0.000005 
R STG 42/40 56 −39 25 5.47 <0.00005 
R STS 22 44 −32 −1 4.85 <0.0001 
       
Deactivations L SFG −16 26 47 −4.66 <0.0005 
L ACG 24/32 −6 35 −5.49 <0.00005 
L PCG 23/30 −5 −50 18 −4.99 <0.00005 
L CeS −49 −13 29 −4.38 <0.0005 
L AG 39/19 −39 −71 23 −5.03 <0.00005 
L STG/STS 22/38 −48 −14 −5.19 <0.00005 
R MOG/IOG 19 39 −78 −2 −4.28 <0.0005 
R MeFG/ACG 24 36 −5.18 <0.00005 
R PCG 23 −42 30 −5.00 <0.00005 
R CeS 50 −13 31 −4.94 <0.0001 
R STG/STS 38 48 −15 −5.00 <0.00005 
 Brain region BA x y z t value P value 
EB 
Activations L Cu 17 −4 −88 6.99 <0.000001 
L Cu 18 −12 −88 20 6.90 <0.000001 
L MOG 18 −23 −87 5.82 <0.00001 
L IOG 19 −39 −80 −4 5.63 <0.00001 
L CS 17 −9 −90 6.21 <0.000005 
L LG 18 −5 −83 −6 4.91 <0.0001 
L FG 19 −23 −65 −11 4.74 <0.0001 
L MeFG −7 47 6.29 <0.000005 
L MFG 46 −34 42 25 4.34 <0.0005 
L PrCeG −50 −2 33 6.92 <0.000001 
L PrCeS −19 −11 55 5.39 <0.00005 
L aINS 13 −29 14 10 5.39 <0.00005 
L IPS 7/40 −37 −42 37 5.74 <0.00001 
R Cu 17 −89 5.54 <0.00005 
R MOG 18 30 −80 4.70 <0.0001 
R IOG 19 43 −71 −1 5.19 <0.00005 
R CS 17 −86 −1 6.12 <0.000005 
R LG 18 −81 −4 5.90 <0.000005 
R MFG 9/46 35 27 31 4.46 <0.0005 
R MeFG 50 4.86 <0.0001 
R PrCeS 44 21 6.21 <0.000005 
R PrCeG/PrCeS 4/6 38 −8 46 5.37 <0.00005 
R aINS 13 30 14 12 5.46 <0.00005 
R SPL 20 −75 38 6.59 <0.000001 
R SMG 40 48 −40 40 5.33 <0.00005 
Deactivations L MeFG/ACG 32 −10 47 12 −5.71 <0.00001 
L PCG 30 −8 −58 16 −6.47 <0.000001 
L AG 39 −43 −65 27 −5.15 <0.00005 
L STS/MTG 21/22 −57 −12 −12 −5.36 <0.00005 
R SFG 19 23 48 −4.56 <0.0005 
R MeFG/ACG 32 10 54 11 −5.20 <0.00005 
R PCG 23/30 −56 20 −6.82 <0.000001 
R AG 39 44 −61 24 −5.00 <0.00005 
R STS/MTG 21/22 50 −2 −18 −4.98 <0.00005 
SC 
Activations L MeFG −8 52 5.38 <0.00005 
L PrCeG −43 −4 36 4.88 <0.0001 
L PrCeS −24 −15 51 4.68 <0.0005 
L aINS 13 −30 17 14 5.43 <0.00005 
L IPS 40 −49 −38 36 5.86 <0.00001 
L STG 22 −53 −40 14 4.52 <0.0005 
R MeFG 51 5.29 <0.00005 
R PrCeS 47 19 5.17 <0.00005 
R PrCeG/PrCeS 4/6 38 −8 47 6.29 <0.000005 
R aINS 13 29 19 12 6.21 <0.000005 
R IPS 7/40 34 −49 37 5.89 <0.000005 
R STG 42/40 56 −39 25 5.47 <0.00005 
R STS 22 44 −32 −1 4.85 <0.0001 
       
Deactivations L SFG −16 26 47 −4.66 <0.0005 
L ACG 24/32 −6 35 −5.49 <0.00005 
L PCG 23/30 −5 −50 18 −4.99 <0.00005 
L CeS −49 −13 29 −4.38 <0.0005 
L AG 39/19 −39 −71 23 −5.03 <0.00005 
L STG/STS 22/38 −48 −14 −5.19 <0.00005 
R MOG/IOG 19 39 −78 −2 −4.28 <0.0005 
R MeFG/ACG 24 36 −5.18 <0.00005 
R PCG 23 −42 30 −5.00 <0.00005 
R CeS 50 −13 31 −4.94 <0.0001 
R STG/STS 38 48 −15 −5.00 <0.00005 

AG, angular gyrus; aINS, anterior insula; PCG, posterior cingulate gyrus; IPS, intraparietal sulcus; MeFG, medial frontal gyrus; PrCeG, precentral gyrus; PrCeS, precentral sulcus; SMG, supramarginal gyrus; STG, superior temporal gyrus; STS, superior temporal sulcus. All other abbreviations as in Tables 2–3.

Figure 4.

Differences between activation elicited during one-back tasks (ID + Loc) versus control task (SD) in EB and SC subjects. Differences are shown at P < 0.05, FDR-corrected. Color scale codes t values. In EB, auditory one-back tasks produced stronger activation in bilateral occipital cortex compared with the SD task. In SC, auditory one-back tasks produced stronger activation in nonprimary auditory cortex (left and right pSTG) than the SD task.

Figure 4.

Differences between activation elicited during one-back tasks (ID + Loc) versus control task (SD) in EB and SC subjects. Differences are shown at P < 0.05, FDR-corrected. Color scale codes t values. In EB, auditory one-back tasks produced stronger activation in bilateral occipital cortex compared with the SD task. In SC, auditory one-back tasks produced stronger activation in nonprimary auditory cortex (left and right pSTG) than the SD task.

Region-of-Interest fMRI Data

Results of the ROI analysis of the fMRI data are presented in detail as Supplementary Material. In brief, in the group of EB, occipital cortex was activated consistently more strongly than in SC during auditory ID and Loc one-back tasks, confirming the results of whole-brain analysis (Supplementary Fig. 1).

In auditory areas, a group difference in the magnitude of activation was observed in the ID task only: for the group of SC, HG was activated significantly more strongly than for EB. Furthermore, as might be expected, HG activation was not significantly modulated by the type of task in either of the groups. In contrast, activity within nonprimary auditory areas was task dependent for SC: aSTG was activated more strongly during the ID than Loc task, and pSTG was activated more strongly during both ID and Loc tasks than during simple SD. In EB, activity within anterior and pSTG was less specific.

Correlation Between Cortical Thickness and fMRI Activation

For studying the relationship between CT and functional activation, we employed a mixed-effects GLM and looked specifically for [CT × Group × ROI] and [CT × Group × ROI × Hemisphere] interactions. Significant effects of such interactions imply that activation in different ROIs (or pairs of symmetrical ROIs) may be affected by CT in one group but not another, or CT may have a different effect on activation in the EB and SC. Using the GLM revealed significant [CT × Group × ROI] and [CT × Group × ROI × Hemisphere] interactions in all 3 experimental tasks (Loc task: F6,125 = 12.8, P < 0.0001 and F12,125 = 3.0, P < 0.001; ID task: F6,125 = 10.2, P < 0.0001 and F12,125 = 2.2, P < 0.05; SD task: F6,125 = 3.1, P < 0.01 and F12,125 = 2.3, P < 0.01, respectively). In the SD, but not in the Loc or ID tasks, activation was significantly affected by the age of subjects (F1,21 = 12.2, P < 0.01, F1,21 = 0.5, P = 0.50 and F1,21 = 2.1, P = 0.16, respectively).

As a next step, relationships between CT and activation were further tested separately for each ROI and each group of subjects. In the group of EB, CT had a significant main effect on regional BOLD responses in the left CS (F1,8 = 10.1, P < 0.05) during the ID task, and in the left Cu (F1,8 = 7.5, P < 0.05) and left LO (F1,8 = 5.4, P < 0.05) during the Loc task. In the group of SC, a significant effect of CT on regional BOLD responses was detected in the left and right pSTG (F1,8 = 13.6, P < 0.01 and F1,8 = 5.9, P < 0.05, respectively) during the Loc task. In none of these regions was activation significantly affected by age, which rules out the possibility that age contributed to the relationship between CT and regional BOLD responses during the ID and Loc tasks. In contrast, activation during the SD task was significantly affected by age but not by CT in either group. In EB, age had a main effect on activation solely within left aSTG. In SC, a main effect of age was found within several occipital regions and left aSTG (Supplementary Table 1).

On the basis of the GLM results, the 5 ROIs in which CT had a significant main effect on activation during ID and Loc tasks were submitted for the next step of analysis using Pearson's correlations, in order to detect the direction of correlation between CT and activation and to calculate the correlation coefficient. In the EB group, CT correlated negatively with the magnitude of the BOLD response in several occipital regions, that is, thinner cortical regions produced stronger activation during auditory one-back tasks (Fig. 5). During the ID task, CT correlated negatively with activity in the left CS (r = −0.67, P < 0.05), whereas, during the Loc task, CT correlated negatively with activity in the left Cu (r = −0.68, P < 0.05) and left LO (r = −0.58, P < 0.05). In the group of SC, CT within the bilateral pSTG regions correlated negatively with activity during the Loc task (left and right, r = −0.65, P < 0.05).

Figure 5.

Correlations between cortical thickness and magnitude of BOLD response within anatomically defined ROIs, as shown above each plot. Data points for EB subjects are represented with red diamonds, for SC with blue diamonds. r: correlation coefficient; *P < 0.05. In all ROIs shown, CT but not Age produced a significant effect on activation.

Figure 5.

Correlations between cortical thickness and magnitude of BOLD response within anatomically defined ROIs, as shown above each plot. Data points for EB subjects are represented with red diamonds, for SC with blue diamonds. r: correlation coefficient; *P < 0.05. In all ROIs shown, CT but not Age produced a significant effect on activation.

Finally, correlations between CT and regional BOLD responses were examined at the whole-brain level (vertex by vertex). The analysis was performed for the Loc and ID tasks, in which functional activation was significantly affected by CT but not by Age, implying that Age was not a contributing factor to the relationship between CT and activation. In the group of EB, all significant correlations between CT and BOLD responses found during either ID or Loc tasks were negative and were observed mainly within the occipital lobes. Areas of significant correlation between CT and BOLD response during the ID task included left CS, LG, SOG, right Cu, and left middle frontal gyrus (MFG). During the Loc task, CT correlated negatively with the BOLD response in CS, LG, MOG, and SOG in the left hemisphere and Cu in the right hemisphere (Table 5, Fig. 6). In SC, negative correlations between CT and BOLD responses during the Loc task were found in the temporal and frontal lobes of the left hemisphere. Clusters of significant correlations were located in the STG, STS, temporal pole, and inferior frontal gyrus (IFG). During the ID task, CT correlated negatively with the BOLD response in left IFG and positively in right lingual/fusiform gyri on the ventral surface of the occipital lobes. Taking into account that visual cortex in SC tended to be deactivated by auditory one-back tasks, the latter positive correlation implies that thinner cortex may be suppressed more effectively.

Table 5

Brain regions showing significant correlations between CT and functional activation in EB and SC in the whole-brain analysis

Brain region BA x y z r value P value 
EB, ID task 
 L CS 17 −10 −87 −0.73 <0.01 
 L LG 18 −5 −85 −7 −0.79 <0.005 
 L SOG 19 −28 −81 15 −0.83 <0.001 
 L MFG −33 19 44 −0.90 <0.0001 
 R Cu 18 −63 12 −0.79 <0.005 
EB, Loc task 
 L CS 17 −9 −87 −3 −0.77 <0.005 
 L LG 18 −5 −85 −7 −0.84 <0.001 
 L MOG 18 −29 −90 −0.79 <0.005 
 L SOG 19 −22 −80 21 −0.84 <0.001 
 R Cu 19 12 −80 35 −0.81 <0.005 
SC, ID task 
 R LG/FG 18 22 −86 −12 0.84 <0.001 
 L IFG 45 −45 34 −1 −0.85 <0.0005 
SC, Loc task 
 L IFG 45 −47 37 −0.90 <0.0001 
 L STG 22 −54 −6 −4 −0.86 <0.0005 
 L STS 21 −52 −28 −5 −0.84 <0.001 
 L Temp Pole 38 −46 −1 −26 −0.87 <0.0005 
Brain region BA x y z r value P value 
EB, ID task 
 L CS 17 −10 −87 −0.73 <0.01 
 L LG 18 −5 −85 −7 −0.79 <0.005 
 L SOG 19 −28 −81 15 −0.83 <0.001 
 L MFG −33 19 44 −0.90 <0.0001 
 R Cu 18 −63 12 −0.79 <0.005 
EB, Loc task 
 L CS 17 −9 −87 −3 −0.77 <0.005 
 L LG 18 −5 −85 −7 −0.84 <0.001 
 L MOG 18 −29 −90 −0.79 <0.005 
 L SOG 19 −22 −80 21 −0.84 <0.001 
 R Cu 19 12 −80 35 −0.81 <0.005 
SC, ID task 
 R LG/FG 18 22 −86 −12 0.84 <0.001 
 L IFG 45 −45 34 −1 −0.85 <0.0005 
SC, Loc task 
 L IFG 45 −47 37 −0.90 <0.0001 
 L STG 22 −54 −6 −4 −0.86 <0.0005 
 L STS 21 −52 −28 −5 −0.84 <0.001 
 L Temp Pole 38 −46 −1 −26 −0.87 <0.0005 

Temp Pole, temporal pole; IFG, inferior frontal gyrus. All other abbreviations as in Tables 2–4.

Figure 6.

Whole-brain correlations between cortical thickness and magnitude of BOLD response during ID (A) and Loc tasks (B). Results are shown at P < 0.05, corrected by cluster size. The color scale codes r values. In SC, negative correlation between CT and magnitude of cortical activation during auditory one-back Loc task was observed in nonprimary auditory areas in the left temporal lobe. In EB, in contrast, clusters of significant negative correlation between CT and magnitude of cortical activation during auditory ID and Loc tasks were located in the occipital lobes.

Figure 6.

Whole-brain correlations between cortical thickness and magnitude of BOLD response during ID (A) and Loc tasks (B). Results are shown at P < 0.05, corrected by cluster size. The color scale codes r values. In SC, negative correlation between CT and magnitude of cortical activation during auditory one-back Loc task was observed in nonprimary auditory areas in the left temporal lobe. In EB, in contrast, clusters of significant negative correlation between CT and magnitude of cortical activation during auditory ID and Loc tasks were located in the occipital lobes.

Correlation Between Cortical Thickness and Age

In the EB group, CT correlated negatively with both age (Supplementary Fig. 2) and duration of blindness in the left HG (age: r = −0.63, P < 0.05; duration of blindness: r = −0.63, P < 0.05) and the right aSTG (age: r = −0.77, P < 0.01; duration of blindness: r = −0.75, P < 0.01). In the SC group, a significant correlation between CT and age was found only in primary visual cortex within the right CS (r = −0.59, P < 0.05).

Summary of Results

In occipital cortex, the group of EB subjects (compared with SC) showed greater CT and stronger functional activation by auditory one-back tasks (Tables 2, 3, and 6). In superior temporal cortex, these effects were mixed: left HG (which includes primary auditory cortex) was thicker in EB than SC, while nonprimary auditory cortex in left aSTG was thinner in EB than SC (Table 6). Finally, for both groups, functional activation in areas that were preferentially involved during auditory one-back tasks (occipital cortex [CS, LG, SOG, MOG, and Cu] for EB and nonprimary auditory cortex [aSTG and pSTG] for SC) correlated negatively with CT. This similarity between occipital areas in EB and nonprimary auditory areas in SC confirms our hypothesis that these areas are performing the same types of operation during demanding auditory information processing.

Table 6

Summary of results

ROI
 
Analysis Left hemisphere
 
Right hemisphere
 
   CT Activation Correlation CT Activation Correlation 
Occipital cortex CS Whole-brain EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
EB: negative (ID, Loc) n.s. EB > SC (ID, Loc)
EB: ID + Loc > SD 
n.s. 
ROI EB > SC EB > SC (ID, Loc)
EB: ID > SD, Loc > SD 
EB: negative (ID) n.s. EB > SC (ID, Loc)
EB: ID > SD, Loc > SD 
n.s. 
LG Whole-brain EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
EB: negative (ID, Loc) EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
SC: positive (ID) 
ROI EB > SC EB > SC (ID, Loc)
EB: ID > SD, Loc > SD 
n.s. n.s. EB > SC (ID, Loc)
EB: ID > SD, Loc > SD 
n.s. 
Cu Whole-brain EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
n.s. EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
EB: negative (ID, Loc) 
ROI EB > SC EB > SC (ID, Loc)
EB: ID > SD, Loc > SD
SC: ID<SD, Loc <SD, Loc <ID 
EB: negative (Loc) EB > SC EB > SC (ID, Loc)
EB: ID > SD, Loc > SD
SC: Loc <SD 
n.s. 
LO Whole-brain EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
EB: negative (Loc) EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
n.s. 
ROI EB > SC EB > SC (ID, Loc)
EB: ID > SD, Loc > SD
SC: ID<SD, Loc <SD 
EB: negative (Loc) EB > SC EB > SC (ID, Loc)
EB: ID > SD, Loc > SD
SC: ID<SD, Loc <SD 
n.s. 
Superior temporal cortex HG Whole-brain n.s. EB < SC (ID) n.s. n.s. n.s. n.s. 
ROI EB > SC EB < SC (ID) n.s. n.s. n.s. n.s. 
STGa Whole-brain n.s. n.s. SC: negative (Loc) n.s. n.s. n.s. 
ROI EB < SC EB > SC n.s. n.s. SC: ID > Loc n.s. 
STGp Whole-brain n.s. SC: ID + Loc > SD n.s. n.s. SC: ID + Loc > SD n.s. 
ROI n.s. SC: ID > SD, Loc > SD SC: negative (Loc) n.s. SC: ID > SD, Loc > SD SC: negative (Loc) 
ROI
 
Analysis Left hemisphere
 
Right hemisphere
 
   CT Activation Correlation CT Activation Correlation 
Occipital cortex CS Whole-brain EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
EB: negative (ID, Loc) n.s. EB > SC (ID, Loc)
EB: ID + Loc > SD 
n.s. 
ROI EB > SC EB > SC (ID, Loc)
EB: ID > SD, Loc > SD 
EB: negative (ID) n.s. EB > SC (ID, Loc)
EB: ID > SD, Loc > SD 
n.s. 
LG Whole-brain EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
EB: negative (ID, Loc) EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
SC: positive (ID) 
ROI EB > SC EB > SC (ID, Loc)
EB: ID > SD, Loc > SD 
n.s. n.s. EB > SC (ID, Loc)
EB: ID > SD, Loc > SD 
n.s. 
Cu Whole-brain EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
n.s. EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
EB: negative (ID, Loc) 
ROI EB > SC EB > SC (ID, Loc)
EB: ID > SD, Loc > SD
SC: ID<SD, Loc <SD, Loc <ID 
EB: negative (Loc) EB > SC EB > SC (ID, Loc)
EB: ID > SD, Loc > SD
SC: Loc <SD 
n.s. 
LO Whole-brain EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
EB: negative (Loc) EB > SC EB > SC (ID, Loc)
EB: ID + Loc > SD 
n.s. 
ROI EB > SC EB > SC (ID, Loc)
EB: ID > SD, Loc > SD
SC: ID<SD, Loc <SD 
EB: negative (Loc) EB > SC EB > SC (ID, Loc)
EB: ID > SD, Loc > SD
SC: ID<SD, Loc <SD 
n.s. 
Superior temporal cortex HG Whole-brain n.s. EB < SC (ID) n.s. n.s. n.s. n.s. 
ROI EB > SC EB < SC (ID) n.s. n.s. n.s. n.s. 
STGa Whole-brain n.s. n.s. SC: negative (Loc) n.s. n.s. n.s. 
ROI EB < SC EB > SC n.s. n.s. SC: ID > Loc n.s. 
STGp Whole-brain n.s. SC: ID + Loc > SD n.s. n.s. SC: ID + Loc > SD n.s. 
ROI n.s. SC: ID > SD, Loc > SD SC: negative (Loc) n.s. SC: ID > SD, Loc > SD SC: negative (Loc) 

n.s., no significant difference; ROI, region of interest.

Discussion

We analyzed structural and functional changes in the cerebral cortex of EB subjects. To understand the relationship between structure and function, we combined measurements of CT and functional activation (regional BOLD responses). Negative correlations between CT and functional activation (i.e., stronger activation in thinner cortex) during attention-demanding auditory tasks were found in occipital cortex of EB and in nonprimary auditory cortex of sighted controls (SC). Based on classical animal studies on the effects of visual deprivation, we conclude that activity-dependent pruning and changes of synaptic efficacy are the main causes for the observed structure–function relationships in blind humans. However, other forms of plasticity, including those related to long-term practice, may contribute to these correlations as well.

Structural Correlates of Plasticity

Reduced Pruning with Early Visual Deprivation

In the group of EB, a thicker cortex (compared with SC) was found bilaterally within the LO and Cu regions of the occipital lobe, and in the left CS and LG. These results are in line with previous observations of a thicker visual cortex in early and CB individuals (Bridge et al. 2009; Jiang et al. 2009; Park et al. 2009; Voss and Zatorre 2011). Importantly, no thickening of occipital cortex was found in LB subjects, which suggests that the thickness of occipital cortex depends on early visual experience. Consistently, in PET studies, high levels of glucose metabolism related to synaptic activity were also observed in the occipital cortex of early but not LB subjects during the resting state (Veraart et al. 1990; De Volder et al. 1997). Thus, the increased thickness in EB compared with SC may result from reduced pruning of exuberant connections during the early stages of ontogeny (Innocenti 2007; Jiang et al. 2009; Park et al. 2009; Voss and Zatorre 2011).

Results from a classical series of microscopic neuroanatomical studies in rhesus monkeys by Rakic and colleagues (Rakic et al. 1986, 1994; Bourgeois et al. 1989, 1994; Zecevic et al. 1989; Zecevic and Rakic 1991; Bourgeois and Rakic 1993, 1996), and from similar studies in humans (Huttenlocher et al. 1982; Garey 1984; Huttenlocher 1984, 1990; Huttenlocher and de Courten 1987; Huttenlocher and Dabholkar 1997) have demonstrated that the early stages of ontogeny (from the prenatal period through infancy) are characterized by an initial overproduction of synaptic contacts followed by pruning of inactive synapses. In human visual cortex, synaptogenesis is most rapid between the ages of 2–4 months and occurs concurrently with dendritic and axonal growth and with myelination of the subcortical WM (Huttenlocher and de Courten 1987; Huttenlocher and Dabholkar 1997). The initial concurrent synaptic overproduction in different cortical layers and areas (Rakic et al. 1986; Huttenlocher 1990; Huttenlocher and Dabholkar 1997) may be a prerequisite for the subsequent refinement of connections within neural circuits by mechanism of competitive interactions between extrinsic afferents (Rakic et al. 1986; Zecevic and Rakic 1991; Bourgeois et al. 1994). Maximum synaptic density in the human visual cortex is reached by age 8 months to 1 year (Garey 1984; Huttenlocher 1984).

The rapid phase of synaptogenesis is followed by a subsequent longer period of pruning, during which synapses are eliminated by about 40% to reach mature levels at about 11 years of age in humans (Huttenlocher et al. 1982; Garey 1984; Huttenlocher 1984, 1990; Huttenlocher and de Courten 1987). While the first phase of synapse formation is independent of retinal input (Bourgeois et al. 1989; Bourgeois and Rakic 1996), synaptic pruning in the retino-geniculo-striate pathway is controlled by sensory experience (Rakic et al. 1986; Stryker and Harris 1986) or, more generally, by patterned neural activity in the retinal ganglion cells (Meister et al. 1991; Wong et al. 1993). Neural activity causes not only selective survival of active synapses, but also further strengthening of synaptic efficacy, which is essential for full functional maturation of the brain (Rakic et al. 1986). Thus, the increased CT in EB compared with SC may, in large part, be due to greater survival of exuberant cortico-cortical and thalamo-cortical connections, which fail to get pruned under conditions of early sensory deprivation (Hyvärinen et al. 1981; Rauschecker and Korte 1993; Kingsbury et al. 2002; Karlen et al. 2006).

Changes of Cell Morphology with Visual Deprivation

A further source of intergroup differences in CT between EB and SC might be alteration of cellular morphology in visually deprived individuals. Results of a recent developmental study suggest that binocular enucleation in newborn ferrets causes a reduction in the proportion of stellate cells in layer IV of primary visual cortex (the main target of thalamic afferents), and a concomitant increase in the size of their basal dendrites when compared with neurons within the same layer of normally developing controls (Callaway and Borrell 2011). In sighted animals, the stellate cells of layer IV were shown to initially develop as pyramidal cells and, thereafter, transform their dendritic arborization to stellate appearance by a process of active retraction of apical dendrites paralleled by an increase in the number of basal dendrites (Vercelli et al. 1992; Callaway and Borrell 2011). In enucleated ferrets, a large proportion of neurons failed to cease growth of apical dendrites, and even neurons that eliminated their apical dendrites developed excessively large basal dendrites (Callaway and Borrell 2011). In agreement with this finding, an experiment on rabbits showed that neonatal deafening increased the nonpyramidal dendrite length in layers III/IV of primary auditory cortex by 27% relative to normally hearing controls (McMullen et al. 1988). The process of dendritic development is regulated by several neurotrophic factors, for example, brain-derived neurotrophic factor and neurotrophin 3 (McAllister et al. 1996; Callaway and Borrell 2011). The growth-promoting influence of these factors can, in turn, be affected by neuronal firing activity (McAllister et al. 1996). Consequently, congenital or early sensory deprivation may result in major remodeling of the cortical fine structure.

Structural Changes in the Auditory Cortex of the Early Blind

In auditory cortex, group differences in CT were observed in left HG, where cortex was thicker in EB than in SC, and in left aSTG, where cortex was thinner in EB. The latter finding is in line with a study by Park et al. (2009) showing a thinner nonprimary auditory cortex in CB compared with SC. Histological and neuroimaging studies suggest that the development of brain structures is heterochronous, with frontal and temporal association areas maturing last (Huttenlocher and Dabholkar 1997; Giedd et al. 1999; Gogtay et al. 2004; Sowell et al. 2004). For this reason, synaptic pruning of nonprimary auditory cortex may have a greater impact on its ultimate fine organization, resulting in greater synaptic efficacy, as reflected by higher activation levels in EB individuals compared with SC.

The Effect of Training on Cortical Thickness

In contrast to the above effects of early sensory deprivation, studies on brain plasticity in adult humans related to extensive training have reported increases in both GM volume and CT (Sluming et al. 2002; Gaser and Schlaug 2003; Draganski et al. 2004; Cannonieri et al. 2007; Bermudez et al. 2009; Jacini et al. 2009; Engvig et al. 2010; Foster and Zatorre 2010; Wei et al. 2011). This may be explained by, for example, axonal sprouting (Darian-Smith and Gilbert 1994; Gilbert and Li 2012) and increased spine density (Yuste and Bonhoeffer 2004) in structures critical for a certain skill or task performance. Left auditory cortex plays a crucial role in auditory temporal processing (Zatorre and Belin 2001; Jamison et al. 2006; Warrier et al. 2009), and the thickening of left HG observed here may be related to the acquisition of skills important for social communication in EB, for instance, comprehension of ultra-fast speech exploited in assistive devices (Moos et al. 2008; Hertrich et al. 2009).

Functional Correlates of Plasticity

In line with several neuroimaging and electrophysiological studies (Kujala et al. 1995, 2005; Sadato et al. 1996, 1998; Weeks et al. 2000; Amedi et al. 2003; Bedny et al. 2011), functional reorganization of occipital areas in EB was reflected in the consistent involvement of these areas during tasks requiring auditory selective attention and working memory, whereas simple sound detection elicited less reliable activation within occipital cortex. These findings are also in line with a recent study on congenitally deaf subjects, which demonstrated that more demanding, bimodal tasks elicited stronger activation of the deprived auditory cortex than less demanding unimodal tasks (Karns et al. 2012).

While activity within nonprimary auditory areas of SC was modulated by the type of task and varied across experimental conditions, blind subjects showed less differentiation. Higher level functions of auditory cognition, normally accomplished by nonprimary auditory areas (Rauschecker and Scott 2009), may be taken on by occipital regions in EB. Results from several recent studies in CB and EB subjects demonstrate that occipital areas in the deprived dorsal “visual” where-pathway remain specialized for the processing of spatial characteristics (Renier et al. 2010; Collignon et al. 2011) and motion in space (Poirier et al. 2006; Bedny et al. 2010; Wolbers et al. 2011), while switching their modality to the auditory domain. In the context of the present study, this suggests that large regions of occipital cortex may in fact be innately multisensory and, in EB, take over functions of nonprimary auditory areas in auditory cognitive tasks. These functions are specified, however, by the computational algorithms that each area has built in regardless of sensory modality.

The above cross-modal organizational principles may be generalized to other sensory modalities (Renier et al. 2013). This is strongly supported by recent animal studies on congenital and early deafness (Lomber et al. 2010, 2011; Meredith et al. 2011). The authors demonstrated superior visual spatial abilities in early deaf cats. Reversible cooling of the posterior auditory field, which is normally involved in sound localization in hearing animals (Lomber and Malhotra 2008), selectively eliminated the superior visual localization abilities of the deaf animals, whereas deactivation of the dorsal zone of “auditory” cortex disrupted their superior visual motion detection abilities. Thus, in very general terms, the original functions of nonprimary sensory areas seem to be preserved after sensory deprivation, although the modalities driving the neurons in the reorganized areas are altered (Lomber et al. 2010, 2011; Renier et al. 2010, 2013; Kok et al. 2014).

Correlation Between Structure and Age

We found negative correlations between CT and age in both groups: In SC within primary visual cortex and in EB in both primary and nonprimary auditory cortex. CT in the CS of primary visual cortex has been shown to decrease during the lifespan; moreover, CS is among the cortical areas that are thinning most rapidly with age (Salat et al. 2004). In EB, however, no significant correlations between CT and either age or duration of blindness were found in any of the occipital ROIs.

In a recent study by Voss and Zatorre (2011), CT in the occipital lobe was shown to correlate positively with the duration of blindness in a joint group of EB and LB subjects, implying that exuberant connections might be utilized and strengthened to compensate for the vision loss through experience-dependent plasticity. A stable CT of the occipital lobes in our quite homogenous group of EB subjects may reflect the superposition of two opposing trends: a decrease of CT due to developmental maturation and aging, and an increase due to experience-dependent plasticity and training, which results in thickening of cortex and thus compensates for age-related thinning.

On the other hand, the thickness of auditory cortex in EB did correlate negatively with age. This suggests that cortical areas corresponding to the ecologically most important input channel in the blind, carrying, for example, distance information, may be affected more strongly by individual experience.

Correlation Between Structure and Function

The main finding of the present study is a consistent negative correlation between the magnitude of activation and CT in EB subjects, that is, stronger activations are generally found in thinner cortex. This is in line with recent developmental studies (Lu et al. 2009; Nunez et al. 2011) demonstrating a similar relationship in fronto-parietal areas of children of various ages performing linguistic tasks. Both sets of results suggest that pruning of exuberant connections during development increases selectivity and effectiveness of synaptic activity and, therefore, leads to stronger activation.

From this perspective, it is noteworthy that negative correlations between CT and functional activation were observed for both EB as for SC during the Loc (but not the ID) task in areas known to be involved in auditory spatial processing: pSTG in the sighted (as revealed by ROI analysis) and MOG in the blind volunteers (as revealed by both ROI and whole-brain analyses). This finding suggests that the aforementioned areas are adapted for optimal processing of auditory spatial features and further supports a specific role of the MOG in auditory localization following congenital or early blindness.

Individual experience may also affect structure–function relationship, but these effects are not uniform. Long-term practice may increase CT and reduce activation (Meister et al. 2005; Haier et al. 2009) leading again to negative correlations between the two measures. However, long-term training may also result in increases of activation (Koelsch et al. 2005), as demonstrated for musicians in areas that were thicker in musicians than nonmusicians (Bermudez et al. 2009). Thus, intense training may sometimes result in the opposite structure–function relationships, masking the effects of pruning to a certain extent.

Effects of Age

What complicates matters further is that experience-dependent changes are superimposed on regular aging-related changes, such as cellular shrinkage and reduction in dendritic arborization (Morrison and Hof 1997). Thus, age per se also contributes to negative correlations between CT and activation. Sensory cortical areas have been shown to undergo relatively linear thinning throughout the lifespan (Salat et al. 2004; Sowell et al. 2007). At the same time, functional neuroimaging studies have consistently shown that senior subjects produce overactivations in a wide range of perceptual, motoric, mnemonic, and verbal tasks, apparently in an effort to compensate for age-related decline (Cabeza 2001; Reuter-Lorenz and Cappell 2008). Although overactivations in the older group were predominantly confined to the fronto-parietal network, some authors also reported additional overactivations in nonprimary visual and auditory areas (Grady et al. 1994; Townsend et al. 2006).

In the present study, analysis of the relationship between CT and functional activation was controlled for age by using age as a continuous predictor in a mixed-effects GLM. Since age did not affect magnitude of BOLD responses during either ID or Loc tasks, the possibility that it contributed significantly to the relationship between CT and activation during working memory processing of auditory attributes can be discounted.

Conclusions

The present study provides evidence for both structural and functional reorganization of the visual and auditory cortex in EB individuals. In addition, our results demonstrate negative correlations between CT and BOLD response magnitude in areas involved in demanding processing of auditory information: occipital cortex in EB and pSTG in SC. The findings of the present study imply an important role of occipital cortex as a substrate for higher order processing of auditory information in visually deprived individuals. In addition, both primary and nonprimary auditory areas, with their potential for multisensory integration (Hackett and Schroeder 2009), provide an extended capacity in EB for detailed sensory processing of sounds. Together, these mechanisms may underlie the superior performance of blind individuals in perceptually difficult tasks.

Supplementary Material

Supplementary material can be found at: http://www.cercor.oxfordjournals.org/.

Funding

This work was supported by grants from the U.S. National Institutes of Health (R01EY018923 to J.P.R.), the National Science Foundation of the USA (PIRE-OISE-0730255 to J.P.R.), the Academy of Finland (Grant number 123044 to I.A., 259752 to S.C.; National Centers of Excellence Program 2006–2011 to S.C., I.A.; a Finland Distinguished Professorship [FiDiPro] award to J.P.R.), and the aivoAALTO project of Aalto University (to S.C.).

Notes

Conflict of Interest: None declared.

References

Amedi
A
Raz
N
Pianka
P
Malach
R
Zohary
E
.
2003
.
Early “visual” cortex activation correlates with superior verbal memory performance in the blind
.
Nat Neurosci
 .
6
:
758
766
.
Bavelier
D
Neville
HJ
.
2002
.
Cross-modal plasticity: where and how?
Nat Rev Neurosci
 .
3
:
443
452
.
Bedny
M
Konkle
T
Pelphrey
K
Saxe
R
Pascual-Leone
A
.
2010
.
Sensitive period for a multimodal response in human visual motion area MT/MST
.
Curr Biol
 .
20
:
1900
1906
.
Bedny
M
Pascual-Leone
A
Dodell-Feder
D
Fedorenko
E
Saxe
R
.
2011
.
Language processing in the occipital cortex of congenitally blind adults
.
Proc Natl Acad Sci USA
 .
108
:
4429
4434
.
Bermudez
P
Lerch
JP
Evans
AC
Zatorre
RJ
.
2009
.
Neuroanatomical correlates of musicianship as revealed by cortical thickness and voxel-based morphometry
.
Cereb Cortex
 .
19
:
1583
1596
.
Bridge
H
Cowey
A
Ragge
N
Watkins
K
.
2009
.
Imaging studies in congenital anophthalmia reveal preservation of brain architecture in ‘visual’ cortex
.
Brain
 .
132
:
3467
3480
.
Büchel
C
Price
C
Friston
K
.
1998
.
A multimodal language region in the ventral visual pathway
.
Nature
 .
394
:
274
277
.
Buckner
RL
Andrews-Hanna
JR
Schacter
DL
.
2008
.
The brain's default network: anatomy, function, and relevance to disease
.
Ann N Y Acad Sci
 .
1124
:
1
38
.
Burton
H
Diamond
JB
McDermott
KB
.
2003
.
Dissociating cortical regions activated by semantic and phonological tasks: a fMRI study in blind and sighted people
.
J Neurophysiol
 .
90
:
1965
1982
.
Bourgeois
JP
Goldman-Rakic
PS
Rakic
P
.
1994
.
Synaptogenesis in the prefrontal cortex of rhesus monkeys
.
Cereb Cortex
 .
4
:
78
96
.
Bourgeois
JP
Jastreboff
PJ
Rakic
P
.
1989
.
Synaptogenesis in visual cortex of normal and preterm monkeys: evidence for intrinsic regulation of synaptic overproduction
.
Proc Natl Acad Sci USA
 .
86
:
4297
4301
.
Bourgeois
JP
Rakic
P
.
1993
.
Changes of synaptic density in the primary visual cortex of the macaque monkey from fetal to adult stage
.
J Neurosci
 .
13
:
2801
2820
.
Bourgeois
JP
Rakic
P
.
1996
.
Synaptogenesis in the occipital cortex of macaque monkey devoid of retinal input from early embryonic stages
.
Eur J Neurosci
 .
8
:
942
950
.
Cabeza
R
.
2001
.
Cognitive neuroscience of aging: contributions of functional neuroimaging
.
Scand J Psychol
 .
42
:
277
286
.
Callaway
EM
Borrell
V
.
2011
.
Developmental sculpting of dendritic morphology of layer 4 neurons in visual cortex: influence of retinal input
.
J Neurosci
 .
31
:
7456
7470
.
Cannonieri
GC
Bonilha
L
Fernandes
PT
Cendes
F
Li
LM
.
2007
.
Practice and perfect: length of training and structural brain changes in experienced typists
.
Neuroreport
 .
18
:
1063
1066
.
Cohen
LG
Celnik
P
Pascual-Leone
A
Corwell
B
Falz
L
Dambrosia
J
Honda
M
Sadato
N
Gerloff
C
Catala
MD
et al
1997
.
Functional relevance of cross-modal plasticity in blind humans
.
Nature
 .
389
:
180
183
.
Collignon
O
Vandewalle
G
Voss
P
Albouy
G
Charbonneau
G
Lassonde
M
Lepore
F
.
2011
.
Functional specialization for auditory-spatial processing in the occipital cortex of congenitally blind humans
.
Proc Natl Acad Sci USA
 .
108
:
4435
4440
.
Darian-Smith
C
Gilbert
CD
.
1994
.
Axonal sprouting accompanies functional reorganization in adult cat striate cortex
.
Nature
 .
368
:
737
740
.
De Volder
AG
Bol
A
Blin
J
Robert
A
Arno
P
Grandin
C
Michel
C
Veraart
C
.
1997
.
Brain energy metabolism in early blind subjects: neural activity in the visual cortex
.
Brain Res
 .
750
:
235
244
.
Draganski
B
Gaser
C
Busch
V
Schuierer
G
Bogdahn
U
May
A
.
2004
.
Neuroplasticity: changes in grey matter induced by training
.
Nature
 .
427
:
311
312
.
Engvig
A
Fjell
AM
Westlye
LT
Moberget
T
Sundseth
O
Larsen
VA
Walhovd
KB
.
2010
.
Effects of memory training on cortical thickness in the elderly
.
Neuroimage
 .
52
:
1667
1676
.
Foster
NE
Zatorre
RJ
.
2010
.
Cortical structure predicts success in performing musical transformation judgments
.
Neuroimage
 .
53
:
26
36
.
Garey
LJ
.
1984
.
Structural development of the visual system of man
.
Hum Neurobiol
 .
3
:
75
80
.
Gaser
C
Schlaug
G
.
2003
.
Brain structures differ between musicians and non-musicians
.
J Neurosci
 .
23
:
9240
9245
.
Geuze
E
Westenberg
HG
Heinecke
A
de Kloet
CS
Goebel
R
Vermetten
E
.
2008
.
Thinner prefrontal cortex in veterans with posttraumatic stress disorder
.
Neuroimage
 .
41
:
675
681
.
Giedd
JN
Blumenthal
J
Jeffries
NO
Castellanos
FX
Liu
H
Zijdenbos
A
Paus
T
Evans
AC
Rapoport
JL
.
1999
.
Brain development during childhood and adolescence: a longitudinal MRI study
.
Nat Neurosci
 .
2
:
861
863
.
Gilbert
CD
Li
W
.
2012
.
Adult visual cortical plasticity
.
Neuron
 .
75
:
250
264
.
Gilbert
CD
Wiesel
TN
.
1992
.
Receptive field dynamics in adult primary visual cortex
.
Nature
 .
356
:
150
152
.
Goebel
R
Esposito
F
Formisano
E
.
2006
.
Analysis of functional image analysis contest (FIAC) data with brainvoyager QX: from single-subject to cortically aligned group general linear model analysis and self-organizing group independent component analysis
.
Hum Brain Mapp
 .
27
:
392
401
.
Gogtay
N
Giedd
JN
Lusk
L
Hayashi
KM
Greenstein
D
Vaituzis
AC
Nugent
TF
3rd
Herman
DH
Clasen
LS
Toga
AW
et al
2004
.
Dynamic mapping of human cortical development during childhood through early adulthood
.
Proc Natl Acad Sci USA
 .
101
:
8174
8179
.
Gougoux
F
Zatorre
RJ
Lassonde
M
Voss
P
Lepore
F
.
2005
.
A functional neuroimaging study of sound localization: visual cortex activity predicts performance in early-blind individuals
.
PLoS Biol
 .
3
:
e27
.
Grady
CL
Maisog
JM
Horwitz
B
Ungerleider
LG
Mentis
MJ
Salerno
JA
Pietrini
P
Wagner
E
Haxby
JV
.
1994
.
Age-related changes in cortical blood flow activation during visual processing of faces and location
.
J Neurosci
 .
14
:
1450
1462
.
Hackett
TA
Schroeder
CE
.
2009
.
Multisensory integration in auditory and auditory-related areas of cortex
.
Hear Res
 .
258
:
1
3
.
Haier
RJ
Karama
S
Leyba
L
Jung
RE
.
2009
.
MRI assessment of cortical thickness and functional activity changes in adolescent girls following three months of practice on a visual-spatial task
.
BMC Res Notes
 .
2
:
174
.
Hamilton
RH
Pascual-Leone
A
.
1998
.
Cortical plasticity associated with Braille learning
.
Trends Cogn Sci
 .
2
:
168
174
.
Hegarty
CE
Foland-Ross
LC
Narr
KL
Townsend
JD
Bookheimer
SY
Thompson
PM
Altshuler
LL
.
2012
.
Anterior cingulate activation relates to local cortical thickness
.
Neuroreport
 .
23
:
420
424
.
Hertrich
I
Dietrich
S
Moos
A
Trouvain
J
Ackermann
H
.
2009
.
Enhanced speech perception capabilities in a blind listener are associated with activation of fusiform gyrus and primary visual cortex
.
Neurocase
 .
15
:
163
170
.
Huttenlocher
PR
.
1990
.
Morphometric study of human cerebral cortex development
.
Neuropsychologia
 .
28
:
517
527
.
Huttenlocher
PR
.
1984
.
Synapse elimination and plasticity in developing human cerebral cortex
.
Am J Ment Defic
 .
88
:
488
496
.
Huttenlocher
PR
Dabholkar
AS
.
1997
.
Regional differences in synaptogenesis in human cerebral cortex
.
J Comp Neurol
 .
387
:
167
178
.
Huttenlocher
PR
de Courten
C
.
1987
.
The development of synapses in striate cortex of man
.
Hum Neurobiol
 .
6
:
1
9
.
Huttenlocher
PR
de Courten
C
Garey
LJ
Van der Loos
H
.
1982
.
Synaptogenesis in human visual cortex—evidence for synapse elimination during normal development
.
Neurosci Lett
 .
33
:
247
252
.
Hyvärinen
J
Carlson
S
Hyvärinen
L
.
1981
.
Early visual deprivation alters modality of neuronal responses in area 19 of monkey cortex
.
Neurosci Lett
 .
26
:
239
243
.
Innocenti
GM
.
2007
.
Subcortical regulation of cortical development: some effects of early, selective deprivations
.
Prog Brain Res
 .
164
:
23
37
.
Innocenti
GM
Frost
DO
.
1979
.
Effects of visual experience on the maturation of the efferent system to the corpus callosum
.
Nature
 .
280
:
231
234
.
Innocenti
GM
Price
DJ
.
2005
.
Exuberance in the development of cortical networks
.
Nat Rev Neurosci
 .
6
:
955
965
.
Jacini
WF
Cannonieri
GC
Fernandes
PT
Bonilha
L
Cendes
F
Li
LM
.
2009
.
Can exercise shape your brain? Cortical differences associated with judo practice
.
J Sci Med Sport
 .
12
:
688
690
.
Jamison
HL
Watkins
KE
Bishop
DV
Matthews
PM
.
2006
.
Hemispheric specialization for processing auditory nonspeech stimuli
.
Cereb Cortex
 .
16
:
1266
1275
.
Jiang
J
Zhu
W
Shi
F
Liu
Y
Li
J
Qin
W
Li
K
Yu
C
Jiang
T
.
2009
.
Thick visual cortex in the early blind
.
J Neurosci
 .
29
:
2205
2211
.
Jones
SE
Buchbinder
BR
Aharon
I
.
2000
.
Three-dimensional mapping of cortical thickness using Laplace's equation
.
Hum Brain Mapp
 .
11
:
12
32
.
Karlen
SJ
Kahn
DM
Krubitzer
L
.
2006
.
Early blindness results in abnormal corticocortical and thalamocortical connections
.
Neuroscience
 .
142
:
843
858
.
Karni
A
Meyer
G
Jezzard
P
Adams
MM
Turner
R
Ungerleider
LG
.
1995
.
Functional MRI evidence for adult motor cortex plasticity during motor skill learning
.
Nature
 .
377
:
155
158
.
Karns
CM
Dow
MW
Neville
HJ
.
2012
.
Altered cross-modal processing in the primary auditory cortex of congenitally deaf adults: a visual-somatosensory fMRI study with a double-flash illusion
.
J Neurosci
 .
32
:
9626
9638
.
Kingsbury
MA
Lettman
NA
Finlay
BL
.
2002
.
Reduction of early thalamic input alters adult corticocortical connectivity
.
Brain Res Dev Brain Res
 .
138
:
35
43
.
Koelsch
S
Fritz
T
Schulze
K
Alsop
D
Schlaug
G
.
2005
.
Adults and children processing music: an fMRI study
.
Neuroimage
 .
25
:
1068
1076
.
Kok
MA
Chabot
N
Lomber
SG
.
2014
.
Crossmodal reorganization of cortical afferents to dorsal auditory cortex following early- and late-onset deafness
.
J Comp Neurol
 .
522
:
654
675
.
Kujala
T
Huotilainen
M
Sinkkonen
J
Ahonen
AI
Alho
K
Hämäläinen
MS
Ilmoniemi
RJ
Kajola
M
Knuutila
JE
Lavikainen
J
et al
1995
.
Visual cortex activation in blind humans during sound discrimination
.
Neurosci Lett
 .
183
:
143
146
.
Kujala
T
Palva
MJ
Salonen
O
Alku
P
Huotilainen
M
Jarvinen
A
Näätänen
R
.
2005
.
The role of blind humans’ visual cortex in auditory change detection
.
Neurosci Lett
 .
379
:
127
131
.
Lomber
SG
Malhotra
S
.
2008
.
Double dissociation of ‘what’ and ‘where’ processing in auditory cortex
.
Nat Neurosci
 .
11
:
609
616
.
Lomber
SG
Meredith
MA
Kral
A
.
2011
.
Adaptive crossmodal plasticity in deaf auditory cortex: areal and laminar contributions to supranormal vision in the deaf
.
Prog Brain Res
 .
191
:
251
270
.
Lomber
SG
Meredith
MA
Kral
A
.
2010
.
Cross-modal plasticity in specific auditory cortices underlies visual compensations in the deaf
.
Nat Neurosci
 .
13
:
1421
1427
.
Lu
LH
Dapretto
M
O'Hare
ED
Kan
E
McCourt
ST
Thompson
PM
Toga
AW
Bookheimer
SY
Sowell
ER
.
2009
.
Relationships between brain activation and brain structure in normally developing children
.
Cereb Cortex
 .
19
:
2595
2604
.
McAllister
AK
Katz
LC
Lo
DC
.
1996
.
Neurotrophin regulation of cortical dendritic growth requires activity
.
Neuron
 .
17
:
1057
1064
.
McMullen
NT
Goldberger
B
Suter
CM
Glaser
EM
.
1988
.
Neonatal deafening alters nonpyramidal dendrite orientation in auditory cortex: a computer microscope study in the rabbit
.
J Comp Neurol
 .
267
:
92
106
.
Meister
I
Krings
T
Foltys
H
Boroojerdi
B
Muller
M
Topper
R
Thron
A
.
2005
.
Effects of long-term practice and task complexity in musicians and nonmusicians performing simple and complex motor tasks: implications for cortical motor organization
.
Hum Brain Mapp
 .
25
:
345
352
.
Meister
M
Wong
RO
Baylor
DA
Shatz
CJ
.
1991
.
Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina
.
Science
 .
252
:
939
943
.
Merabet
LB
Pascual-Leone
A
.
2010
.
Neural reorganization following sensory loss: the opportunity of change
.
Nat Rev Neurosci
 .
11
:
44
52
.
Meredith
MA
Kryklywy
J
McMillan
AJ
Malhotra
S
Lum-Tai
R
Lomber
SG
.
2011
.
Crossmodal reorganization in the early deaf switches sensory, but not behavioral roles of auditory cortex
.
Proc Natl Acad Sci USA
 .
108
:
8856
8861
.
Moos
A
Hertrich
I
Dietrich
S
Trouvain
J
Ackermann
H
.
2008
.
Perception of ultra-fast speech by a blind listener—does he use his visual system?
8th International Speech Production Seminar (ISSP 2008)
,
8–12 December, Strasbourg, France
, pp.
297
300
.
Morrison
JH
Hof
PR
.
1997
.
Life and death of neurons in the aging brain
.
Science
 .
278
:
412
419
.
Nunez
SC
Dapretto
M
Katzir
T
Starr
A
Bramen
J
Kan
E
Bookheimer
S
Sowell
ER
.
2011
.
fMRI of syntactic processing in typically developing children: structural correlates in the inferior frontal gyrus
.
Dev Cogn Neurosci
 .
1
:
313
323
.
Park
HJ
Lee
JD
Kim
EY
Park
B
Oh
MK
Lee
S
Kim
JJ
.
2009
.
Morphological alterations in the congenital blind based on the analysis of cortical thickness and surface area
.
Neuroimage
 .
47
:
98
106
.
Pietrini
P
Furey
ML
Ricciardi
E
Gobbini
MI
Wu
WH
Cohen
L
Guazzelli
M
Haxby
JV
.
2004
.
Beyond sensory images: object-based representation in the human ventral pathway
.
Proc Natl Acad Sci USA
 .
101
:
5658
5663
.
Poirier
C
Collignon
O
Scheiber
C
Renier
L
Vanlierde
A
Tranduy
D
Veraart
C
De Volder
AG
.
2006
.
Auditory motion perception activates visual motion areas in early blind subjects
.
Neuroimage
 .
31
:
279
285
.
Rakic
P
Bourgeois
JP
Eckenhoff
MF
Zecevic
N
Goldman-Rakic
PS
.
1986
.
Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex
.
Science
 .
232
:
232
235
.
Rakic
P
Bourgeois
JP
Goldman-Rakic
PS
.
1994
.
Synaptic development of the cerebral cortex: implications for learning, memory, and mental illness
.
Prog Brain Res
 .
102
:
227
243
.
Rasser
PE
Johnston
P
Lagopoulos
J
Ward
PB
Schall
U
Thienel
R
Bender
S
Toga
AW
Thompson
PM
.
2005
.
Functional MRI BOLD response to Tower of London performance of first-episode schizophrenia patients using cortical pattern matching
.
Neuroimage
 .
26
:
941
951
.
Rauschecker
JP
.
1995
.
Compensatory plasticity and sensory substitution in the cerebral cortex
.
Trends Neurosci
 .
18
:
36
43
.
Rauschecker
JP
.
1991
.
Mechanisms of visual plasticity: Hebb synapses, NMDA receptors, and beyond
.
Physiol Rev
 .
71
:
587
615
.
Rauschecker
JP
Korte
M
.
1993
.
Auditory compensation for early blindness in cat cerebral cortex
.
J Neurosci
 .
13
:
4538
4548
.
Rauschecker
JP
Scott
SK
.
2009
.
Maps and streams in the auditory cortex: nonhuman primates illuminate human speech processing
.
Nat Neurosci
 .
12
:
718
724
.
Renier
LA
Anurova
I
De Volder
AG
Carlson
S
VanMeter
J
Rauschecker
JP
.
2010
.
Preserved functional specialization for spatial processing in the middle occipital gyrus of the early blind
.
Neuron
 .
68
:
138
148
.
Renier
L
De Volder
AG
Rauschecker
JP
.
2013
.
Cortical plasticity and preserved function in early blindness
.
Neurosci Biobehav Rev
 .
.
Reuter-Lorenz
PA
Cappell
KA
.
2008
.
Neurocognitive aging and the compensation hypothesis
.
Curr Dir Psychol Sci
 .
17
:
177
182
.
Röder
B
Stock
O
Bien
S
Neville
H
Rosler
F
.
2002
.
Speech processing activates visual cortex in congenitally blind humans
.
Eur J Neurosci
 .
16
:
930
936
.
Sadato
N
Pascual-Leone
A
Grafman
J
Deiber
MP
Ibanez
V
Hallett
M
.
1998
.
Neural networks for Braille reading by the blind
.
Brain
 .
121
:
1213
1229
.
Sadato
N
Pascual-Leone
A
Grafman
J
Ibanez
V
Deiber
MP
Dold
G
Hallett
M
.
1996
.
Activation of the primary visual cortex by Braille reading in blind subjects
.
Nature
 .
380
:
526
528
.
Salat
DH
Buckner
RL
Snyder
AZ
Greve
DN
Desikan
RS
Busa
E
Morris
JC
Dale
AM
Fischl
B
.
2004
.
Thinning of the cerebral cortex in aging
.
Cereb Cortex
 .
14
:
721
730
.
Sanes
DH
Reh
TA
Harris
WA
.
2006
.
The development of the nervous system. 2nd ed
 .
Burlington
(
MA
):
Elsevier Academic Press
.
Sluming
V
Barrick
T
Howard
M
Cezayirli
E
Mayes
A
Roberts
N
.
2002
.
Voxel-based morphometry reveals increased gray matter density in Broca's area in male symphony orchestra musicians
.
Neuroimage
 .
17
:
1613
1622
.
Sowell
ER
Peterson
BS
Kan
E
Woods
RP
Yoshii
J
Bansal
R
Xu
D
Zhu
H
Thompson
PM
Toga
AW
.
2007
.
Sex differences in cortical thickness mapped in 176 healthy individuals between 7 and 87 years of age
.
Cereb Cortex
 .
17
:
1550
1560
.
Sowell
ER
Thompson
PM
Leonard
CM
Welcome
SE
Kan
E
Toga
AW
.
2004
.
Longitudinal mapping of cortical thickness and brain growth in normal children
.
J Neurosci
 .
24
:
8223
8231
.
Striem-Amit
E
Cohen
L
Dehaene
S
Amedi
A
.
2012
.
Reading with sounds: sensory substitution selectively activates the visual word form area in the blind
.
Neuron
 .
76
:
640
652
.
Stryker
MP
Harris
WA
.
1986
.
Binocular impulse blockade prevents the formation of ocular dominance columns in cat visual cortex
.
J Neurosci
 .
6
:
2117
2133
.
Talairach
G
Tournoux
P
.
1988
.
Co-planar stereotaxic atlas of the human brain
 .
Stuttgart
(
NY
):
Georg Thieme /Thieme Medical Publishers
.
Townsend
J
Adamo
M
Haist
F
.
2006
.
Changing channels: an fMRI study of aging and cross-modal attention shifts
.
Neuroimage
 .
31
:
1682
1692
.
Veraart
C
De Volder
AG
Wanet-Defalque
MC
Bol
A
Michel
C
Goffinet
AM
.
1990
.
Glucose utilization in human visual cortex is respectively elevated and decreased in early versus late blindness
.
Brain Res
 .
510
:
115
121
.
Vercelli
A
Assal
F
Innocenti
GM
.
1992
.
Emergence of callosally projecting neurons with stellate morphology in the visual cortex of the kitten
.
Exp Brain Res
 .
90
:
346
358
.
Voss
P
Gougoux
F
Zatorre
RJ
Lassonde
M
Lepore
F
.
2008
.
Differential occipital responses in early- and late-blind individuals during a sound-source discrimination task
.
Neuroimage
 .
40
:
746
758
.
Voss
P
Zatorre
RJ
.
2011
.
Occipital cortical thickness predicts performance on pitch and musical tasks in blind individuals
.
Cereb Cortex
 .
22
:
2455
2465
.
Warrier
C
Wong
P
Penhune
V
Zatorre
R
Parrish
T
Abrams
D
Kraus
N
.
2009
.
Relating structure to function: Heschl's gyrus and acoustic processing
.
J Neurosci
 .
29
:
61
69
.
Weeks
R
Horwitz
B
Aziz-Sultan
A
Tian
B
Wessinger
CM
Cohen
LG
Hallett
M
Rauschecker
JP
.
2000
.
A positron emission tomographic study of auditory localization in the congenitally blind
.
J Neurosci
 .
20
:
2664
2672
.
Wei
G
Zhang
Y
Jiang
T
Luo
J
.
2011
.
Increased cortical thickness in sports experts: a comparison of diving players with the controls
.
PLoS One
 .
6
:
e17112
.
Wolbers
T
Zahorik
P
Giudice
NA
.
2011
.
Decoding the direction of auditory motion in blind humans
.
Neuroimage
 .
56
:
681
687
.
Wong
RO
Meister
M
Shatz
CJ
.
1993
.
Transient period of correlated bursting activity during development of the mammalian retina
.
Neuron
 .
11
:
923
938
.
Yuste
R
Bonhoeffer
T
.
2004
.
Genesis of dendritic spines: insights from ultrastructural and imaging studies
.
Nat Rev Neurosci
 .
5
:
24
34
.
Zatorre
RJ
Belin
P
.
2001
.
Spectral and temporal processing in human auditory cortex
.
Cereb Cortex
 .
11
:
946
953
.
Zecevic
N
Bourgeois
JP
Rakic
P
.
1989
.
Changes in synaptic density in motor cortex of rhesus monkey during fetal and postnatal life
.
Brain Res Dev Brain Res
 .
50
:
11
32
.
Zecevic
N
Rakic
P
.
1991
.
Synaptogenesis in monkey somatosensory cortex
.
Cereb Cortex
 .
1
:
510
523
.