Abstract

In functional neuroimaging studies, task-related activity refers to the signal difference between the stimulation and rest conditions. We asked whether long-term changes in the sensory environment may affect brain activity at rest. To answer this question, we compared regional cerebral blood flow between a group of normally hearing controls and a group of cochlear-implanted (CI) deaf patients. Here we present evidence that long-term alteration of auditory experience, such as profound deafness followed by partial auditory recuperation through cochlear implantation, leads to functional cortical reorganizations at rest. Without any visual or auditory stimulation, CI subjects showed changes of cerebral blood flow in the visual, auditory cortex, Broca area, and in the posterior temporal cortex with an increment of activity in these areas from the time of activation of the implant to less than a year after the implantation.

Introduction

Psychophysical and neuroimaging studies in both animal and human subjects have clearly demonstrated that cortical plasticity following sensory deprivation from early developmental stages leads to the functional reorganization of the brain that favors the spared modalities (Rauschecker 1995). Abnormal metabolic levels are observed in the deprived primary sensory areas (Veraart et al. 1990; Wanet-Defalque et al. 1988) reflecting the appropriation by the remaining sensory modalities (Lee et al. 2001; Lee, Truy, et al. 2007). Consequently, numerous reports have described auditory or somatosensory activations in the visual cortex of congenital blind patients (Kujala et al. 1995; Sadato et al. 1996; Buchel et al. 1998; Weeks et al. 2000) as well as responses to visual stimulation in the auditory cortex of patients deaf from birth (Calvert et al. 1997; Nishimura et al. 1999; Petitto et al. 2000; Finney et al. 2001).

Brain functioning at rest (Mazoyer et al. 2001), or its default-mode activity (Raichle and Snyder 2007), is attracting increasing attention because task-related changes in the brain's electrical activity, cerebral blood flow, glucose, and oxygen consumption are relatively small compared with the values of these parameters at rest (Giove et al. 2003; Kenet et al. 2003; Fiser et al. 2004). Thus, most of the energy is consumed by the brain for neural information-related processes (glutamate cycling) during conscious resting-state activity (Shulman et al. 2004). A possible explanation for this is that the brain activity at rest may serve to monitor the current status of the individual relative to the environment and to predict possible changes in this environment (Raichle 2006; Raichle and Snyder 2007); this monitoring would allow the system to track any deviance in the flow of incoming information from its predictive coding (Strelnikov 2007). In this view, the resting activity might represent the intrinsic functional organization of the brain (Gusnard and Raichle 2001; Raichle and Snyder 2007).

We hypothesize that cortical reorganization linked to long-term adaptive processes and induced by a long period of deafness should impact intrinsic brain activity at rest.

Cochlear-implanted (CI) deaf patients offer a unique opportunity to test such a hypothesis. A cochlear implant is a neuroprosthesis that allows postlingually deaf patients to understand speech through long-term adaptive processes that lead to coherent percepts from the coarse information delivered by the implant. As a result of a long period of deafness and because of the crude information provided by the implant (Zeng 2004), CI users have developed compensatory strategies for speech comprehension favoring lip-reading and visuo-auditory interactions (Rouger et al. 2007). Neuroimaging studies have reported that their network involved in sensory and speech processing presents different patterns and/or levels of activation compared with normal-hearing subjects (Giraud, Truy, et al. 2001). As modern neuroimaging techniques are mostly based on the changes of regional cerebral blood flow (rCBF) between a stimulated condition relative to a reference or resting-state condition, here, using H215O positron emission tomography (PET) we asked whether differences in brain activity level could be identified at rest between CI users and controls. To further analyze the role of the sensory input, we compared the level of activity at rest for patients at the time of the implant activation and after several months postimplantation when they have achieved the maximum recovery of speech comprehension (Rouger et al. 2007).

Materials and Methods

Nine CI deaf subjects of various etiology (mean age 50.9 years, see Table 1) and 6 normally hearing subjects (mean age 34.2 years) participated in the study. The mean age difference between CI patients and controls in our study is about 16 years which could potentially be a confounding factor. Normal-hearing controls (6 subjects) were physically healthy and free of neurological disease, head injury, psychiatric disorders, and hearing deficit on tonal audiometry. Due to the progressive nature of deafness, its duration before cochlear implantation could not be precisely estimated but constituted more than 3 years. We measured brain activity of postlingually deaf patients with unilateral cochlear implants within 1–22 days (mean 7.6) after the implant activation, and within the period of 3–11 months postimplantation (mean 7.0, see Table 1). Patients present a significant recovery of speech comprehension as soon as the implant is activated (see Table 1) the performance of word recognition being of 50% which is close to that reported from a large sample (Rouger et al. 2007). Experienced CI subjects had significantly higher word-recognition scores than inexperienced ones (mean difference 17 ± 8, P < 0.01), see Table 1 for the word-recognition scores per patient. Performance was collected during regular visits to the ear–nose–throat department following a standard rehabilitation program. The word-recognition test included French disyllabic words derived from French word lists specifically designed for speech rehabilitation therapies. The words were presented by a female French speech therapist, who pronounced each word with even intonation, tempo, and vocal intensity.

Table 1

Characteristics of patients in the study

Cochlear-implanted patients
 
Auditory word recognition %
 
No. Age Sex Implant Side Onset T0 T1 Pre-op T0 T1 
CI02 81 Nucleus CI24 31d 2d 11m 20 50 70 
CI03 39 Nucleus CI24 36d 22d 10m 30 65 75 
CI04 39 Nucleus CI24 35d 8d 4m 50 45 85 
CI06 57 Nucleus CI24 27d 2d 3m 20 15 35 
CI07 69 Medel 29d 5d 10m 25 80 90 
CI08 39 Nucleus CI24 32d 9d 20 — 
CI09 62 Clarion 34d 3d 4m 55 70 90 
CI10 64 Advanced bionics 33d 9d 9m 45 60 
CI11 54 Nucleus CI24 33d 15d 6m 45 50 60 
CI12 35 Nucleus CI24 31d 1d 6m 10 60 60 
Mean      7.6d 7.0m 25.5 50.0 69.5 
Cochlear-implanted patients
 
Auditory word recognition %
 
No. Age Sex Implant Side Onset T0 T1 Pre-op T0 T1 
CI02 81 Nucleus CI24 31d 2d 11m 20 50 70 
CI03 39 Nucleus CI24 36d 22d 10m 30 65 75 
CI04 39 Nucleus CI24 35d 8d 4m 50 45 85 
CI06 57 Nucleus CI24 27d 2d 3m 20 15 35 
CI07 69 Medel 29d 5d 10m 25 80 90 
CI08 39 Nucleus CI24 32d 9d 20 — 
CI09 62 Clarion 34d 3d 4m 55 70 90 
CI10 64 Advanced bionics 33d 9d 9m 45 60 
CI11 54 Nucleus CI24 33d 15d 6m 45 50 60 
CI12 35 Nucleus CI24 31d 1d 6m 10 60 60 
Mean      7.6d 7.0m 25.5 50.0 69.5 

Note: T0—the time of the first PET examination, from implant activation, in days; T1—the time of the second PET examination from implant activation, in months.

All subjects were scanned in a darkened shielded room, their head was immobilized, and the head position was checked before each acquisition to ensure that it was aligned transaxially to the orbitomeatal line, as determined using a laser beam. Subjects lay calmly in a silent dark room, with their eyes closed and no task was administered.

Measurements of the regional distribution of radioactivity were obtained with an ECAT HR+ (Siemens, Erlangen, Germany) PET camera with full volume acquisition (63 planes, thickness 2.4 mm, axial field-of-view 158 mm, in-plane resolution ≈4.2 mm). The duration of each scan was 80 s; approximately 6 mCi of H2O15 was administered to each subject.

Neuroimaging data were analyzed with statistical parametric mapping (SPM) 2 including the standard procedures of images preprocessing (realignment, spatial normalization to the Montreal Neurological Institute brain template, smoothing with 8-mm isotropic Gaussian kernel), defining the models and their statistical assessment.

Comparisons (contrasts) between the groups were performed using t statistics. Global normalization was performed using proportional scaling with global flow scaled to 50 mL/dL/min. The proportional threshold masking of the images was at 80% of the mean global value. Voxels which did not reach a threshold of the overall mean/8 were masked out and the mean of the remaining voxels was calculated with the resulting voxel values being ratios of the normalized value for this voxel to the global mean.

The ensuing comparison images (SPM-t maps) were estimated using voxel-level t- and z-values which corresponded to P < 0.05 for the false positive probability with family-wise error correction for multiple nonindependent comparisons.

We analyzed our data in the following way: we first identified regions that differed significantly between control subjects and CI patients. Within the regions identified we tested for orthogonal differences between the experienced and inexperienced CI patients. To protect against false positives we used a corrected level of significance for the first contrast, which then provided a spatial constraint for tests of the longitudinal differences, within the CI patients. For completeness, we provide the estimates of resting flow for all 3 groups in regions showing a significant difference between control and CI subjects.

All participants gave their full-informed consent prior to their participation in this study in accordance with the Declaration of Helsinki (1975). The reported data on the rest condition were collected during a study on word/nonword discrimination task approved by the local research ethics committee (N° 2-03-34/Avis n°2, Toulouse, France).

Results

Compared with controls, areas showing significantly either higher or lower activity were determined for the inexperienced and experienced CI users (Tables 2–3, Fig. 1). These regions included frontal and temporal areas involved in the speech processing network (Hickok and Poeppel 2007) as well as associative sensory areas in the temporal and occipital cortices possibly reflecting cross-modal compensation in the form of visually based strategies (Bavelier and Neville 2002).

Table 2

Increased rCBF in CI patients, relative to normal-hearing subjects

Brain region P corr N voxels z-Value x y z 
CI inexperienced > controls 
    R middle occipital gyrus 0.005 471 5.34 40 −66 −12 
    R precuneus 0.042 85 4.86 26 −86 44 
    L cuneus 0.047 (clust) 178 4.57 −16 −104 −2 
    L middle occipital gyrus   4.15 −20 −102 10 
    L inferior occipital gyrus   3.52 −26 −94 −8 
    R precentral gyrus, sup 0.043 485 4.86 16 −24 56 
    R parahippocampal gyrus 0.033 (clust) 195 4.45 32 −8 −18 
    L posterior cingulate gyrus 0.023 289 5.01 −26 −70 10 
    R inferior temporal gyrus, post   4.33 44 −16 −20 
    R middle temporal gyrus, post 0.027 (clust) 205 4.29 48 −42 −14 
    R fusiform gyrus   4.14 42 −46 −10 
    R fusiform gyrus   3.48 36 −44 −16 
    R cerebellum 0.004 (clust) 314 4.40 24 −42 −38 
    R cerebellum   4.40 26 −50 −42 
CI experienced > controls 
    R inferior occipital gyrus 0.030 259 4.95 42 −74 −12 
    L posterior cingulate gyrus 0.015 251 5.11 −26 −70 10 
    L middle temporal gyrus, post 0.003 (clust) 313 4.48 −52 −38 −8 
    L middle temporal gyrus, middle  3.77 −52 −16 −18 
Brain region P corr N voxels z-Value x y z 
CI inexperienced > controls 
    R middle occipital gyrus 0.005 471 5.34 40 −66 −12 
    R precuneus 0.042 85 4.86 26 −86 44 
    L cuneus 0.047 (clust) 178 4.57 −16 −104 −2 
    L middle occipital gyrus   4.15 −20 −102 10 
    L inferior occipital gyrus   3.52 −26 −94 −8 
    R precentral gyrus, sup 0.043 485 4.86 16 −24 56 
    R parahippocampal gyrus 0.033 (clust) 195 4.45 32 −8 −18 
    L posterior cingulate gyrus 0.023 289 5.01 −26 −70 10 
    R inferior temporal gyrus, post   4.33 44 −16 −20 
    R middle temporal gyrus, post 0.027 (clust) 205 4.29 48 −42 −14 
    R fusiform gyrus   4.14 42 −46 −10 
    R fusiform gyrus   3.48 36 −44 −16 
    R cerebellum 0.004 (clust) 314 4.40 24 −42 −38 
    R cerebellum   4.40 26 −50 −42 
CI experienced > controls 
    R inferior occipital gyrus 0.030 259 4.95 42 −74 −12 
    L posterior cingulate gyrus 0.015 251 5.11 −26 −70 10 
    L middle temporal gyrus, post 0.003 (clust) 313 4.48 −52 −38 −8 
    L middle temporal gyrus, middle  3.77 −52 −16 −18 

Note: P values are presented with correction for multiple nonindependent comparisons, those marked as (clust) are assessed at cluster level, others at voxel level.

Table 3

Decreased rCBF in CI patients, relative to normal-hearing subjects

Brain region P corr N voxels z-Value x y z 
Controls > CI inexperienced 
    L anterior cingulate gyrus 0.000 2157 5.78 −2 44 
    R anterior cingulate gyrus 0.002  5.46 42 −6 
    R medial frontal gyrus, ant 0.006  5.23 54 10 
    L superior temporal gyrus, middle 0.001 1640 5.71 −48 −16 
    L inferior frontal gyrus, triang 0.019  4.99 −54 12 
    L insula 0.096  4.59 −44 −6 
    L inferior temporal gyrus, ant 0.006 218 5.23 −50 −2 −42 
    R superior temporal gyrus, middle 0.096 477 4.59 52 −18 
    R insula 0.195  4.39 42 −12 −4 
Controls > CI experienced 
    R medial frontal gyrus, ant 0.003 1508 5.37 52 12 
    L inferior frontal gyrus, triang 0.042 359 4.80 −54 16 
    L anterior cingulate gyrus 0.005  5.26 −4 44 
    R anterior cingulate gyrus 0.502  4.07 28 18 
    L superior temporal gyrus, middle 0.039 342 4.81 −50 −14 
    L insula 0.160  4.45 −44 −6 
    L insula 0.998  3.37 −38 −10 −2 
    L inferior temporal gyrus, ant 0.007 (clust) 300 4.60 −50 −2 −42 
    L middle temporal gyrus, ant   4.31 −34 −50 
    L superior temporal gyrus, ant   3.97 −34 12 −44 
Brain region P corr N voxels z-Value x y z 
Controls > CI inexperienced 
    L anterior cingulate gyrus 0.000 2157 5.78 −2 44 
    R anterior cingulate gyrus 0.002  5.46 42 −6 
    R medial frontal gyrus, ant 0.006  5.23 54 10 
    L superior temporal gyrus, middle 0.001 1640 5.71 −48 −16 
    L inferior frontal gyrus, triang 0.019  4.99 −54 12 
    L insula 0.096  4.59 −44 −6 
    L inferior temporal gyrus, ant 0.006 218 5.23 −50 −2 −42 
    R superior temporal gyrus, middle 0.096 477 4.59 52 −18 
    R insula 0.195  4.39 42 −12 −4 
Controls > CI experienced 
    R medial frontal gyrus, ant 0.003 1508 5.37 52 12 
    L inferior frontal gyrus, triang 0.042 359 4.80 −54 16 
    L anterior cingulate gyrus 0.005  5.26 −4 44 
    R anterior cingulate gyrus 0.502  4.07 28 18 
    L superior temporal gyrus, middle 0.039 342 4.81 −50 −14 
    L insula 0.160  4.45 −44 −6 
    L insula 0.998  3.37 −38 −10 −2 
    L inferior temporal gyrus, ant 0.007 (clust) 300 4.60 −50 −2 −42 
    L middle temporal gyrus, ant   4.31 −34 −50 
    L superior temporal gyrus, ant   3.97 −34 12 −44 

Note: P values are presented with correction for multiple nonindependent comparisons, those marked as (clust) are assessed at cluster level, others at voxel level.

Figure 1.

Differences in rCBF at rest between CI patients and normal-hearing subjects (for the purpose of better illustration, an uncorrected P < 0.00001 voxel level threshold was used for the figure). Yellow–red scale reflects increased activity, green–blue scale reflects decreased activity in CI patients compared with controls. For the abbreviations V, A, T, B, and rCBF levels in these areas, see Figure 2.

Figure 1.

Differences in rCBF at rest between CI patients and normal-hearing subjects (for the purpose of better illustration, an uncorrected P < 0.00001 voxel level threshold was used for the figure). Yellow–red scale reflects increased activity, green–blue scale reflects decreased activity in CI patients compared with controls. For the abbreviations V, A, T, B, and rCBF levels in these areas, see Figure 2.

Inexperienced CI patients elicited more resting-state activity than controls in the associative visual cortex, in the right precentral and parahippocampal cortex, in the basal parts of the right temporal cortex and in the right cerebellum.

Normally hearing controls presented more resting-state activity than inexperienced implanted patients (i.e., deactivations in patients) for the auditory cortex bilaterally extending to the insulas, for the triangular part of the left inferior frontal gyrus (Broca's area), for the basal parts of the left temporal lobes and for the anterior cingulum.

Experienced CI patients showed more resting-state activity than controls in the right inferior occipital gyrus with an extension to the inferior temporal region, in the posterior and middle parts of the middle temporal gyrus and in the left posterior cingulate gyrus.

Normally hearing controls showed more resting-state activity than experienced implanted patients in Broca's area, in the middle part of the left superior temporal gyrus extending to the left insula and in the anterior part of the left middle and inferior temporal gyri, in the anterior cingulate cortex bilaterally and in the right medial frontal cortex.

Diagrams in Figure 2 present an inverse relationship between the activity of audiovisual and fronto-temporal speech-related areas in CI patients and normally hearing controls. Visual areas exhibit more activity in experienced CI patients than in controls but auditory areas elicit less activity than in controls. Posterior temporal areas show more activity but Broca's area shows less activity in CI subjects than in controls. Thus, in CI patients at rest there is a reorganization of activity toward more posterior parts of the brain: from temporal to occipital areas for sensory processing and from frontal to temporal areas for speech processing.

Figure 2.

Changes of rCBF in the regions of interest. Left: Experienced and inexperienced CI patients compared with the group of normally hearing controls. Right: Individual differences of CI patients between the inexperienced and experienced stages. A, auditory cortex (the left superior temporal gyrus, middle part); V, visual cortex (the right inferior occipital gyrus); B, Broca's area (the left inferior frontal gyrus, triangular part); T, temporal area (the left middle temporal gyrus, posterior part). Activity level is presented in arbitrary units, which reflect the deviation of rCBF from the mean activity for 3 groups together, confidence intervals at P < 0.05. T0 represents inexperienced and T1 experienced CI users.

Figure 2.

Changes of rCBF in the regions of interest. Left: Experienced and inexperienced CI patients compared with the group of normally hearing controls. Right: Individual differences of CI patients between the inexperienced and experienced stages. A, auditory cortex (the left superior temporal gyrus, middle part); V, visual cortex (the right inferior occipital gyrus); B, Broca's area (the left inferior frontal gyrus, triangular part); T, temporal area (the left middle temporal gyrus, posterior part). Activity level is presented in arbitrary units, which reflect the deviation of rCBF from the mean activity for 3 groups together, confidence intervals at P < 0.05. T0 represents inexperienced and T1 experienced CI users.

It is interesting that inexperienced CI patients present more widely distributed differences from controls than experienced patients. There is a trend suggesting that brain functioning in experienced CI users is closer to controls.

To further examine the role of sensory inputs through CI on brain activity at rest, we calculated the difference between the experienced stage of CI users (less than 1 year) and the inexperienced stage (at the time of the cochlear implant activation) in the regions of interest where controls are different from experienced CI patients: the right occipital visual cortex, the left posterior middle temporal gyrus, the left superior temporal gyrus, “Broca's area” and the left anterior temporal cortex. ANOVA analysis of controls, inexperienced and experienced implanted patients yielded a significant group effect for each of the 4 areas (F2,46 = 6.3–16.9, P < 0.01) (Fig. 2). The patients demonstrated significantly higher activity in the experienced compared with the inexperienced stage in the right occipital visual cortex (P < 0.05), in the left middle temporal gyrus, posterior part (P < 0.05), in the left superior temporal gyrus, middle part (P < 0.01), and in “Broca's area” (P < 0.05). This shows that the differences observed at rest between controls and experienced CI patients are progressive and depend on the amount of experience with the cochlear implant.

It should be noted (Fig. 2, left) that the reported effects are statistical, calculated at the group level. Though the majority of subjects demonstrate these effects, they are not present in some of the subjects due to interindividual variability.

The “rest” scans analysis were based on 2 separate acquisitions, one preceding and one terminating a series of 6 scans during which the patient had to perform a visuo-motor task (respond to the normally positioned or to the upside-down face) and a visual or visuo-auditory words/nonwords discrimination task. The interval between different scans was about 10 min when no task was administered and consequently, the 2 “rest scans” were separated by a period of about 90 min at least. However, to check whether differential rest activity was stable, we analyzed the differences between the 2 rest scans. No significant difference was observed in neither of the 3 groups of subjects with no significant group interaction (P > 0.01). Even at the threshold of P = 0.1 no differential activity corresponded to the reported in Tables 2 and 3 areas. This means that the activity level we observed is not directly induced by the preceding task.

However, as the main task in the scanner was identification of words, we were able to test correlations of audiovisual scores with brain activity at rest in the areas were differences between patients and controls were observed. Significant correlations (P < 0.01) were found for the auditory areas of the middle part of the left superior temporal gyrus (r = 0.64) and for the posterior part of the left middle temporal gyrus (r = 0.63) (Fig. 3). Correlations in the other areas did not reach the level of significance. We also performed correlation analysis for these areas only with the first rest scan before any stimulation—in spite in of a limited number of observations in this case, correlations with the first scan survived the level of significance (P < 0.05) for both areas.

Figure 3.

Correlation analysis of behavior performance and brain activity at rest. In CI patients, the activity observed at rest in the auditory and posterior temporal cortices (labeled, respectively, A and T in Fig. 1) presents a positive correlation with the performances on the audiovisual identification of words in inexperienced (T0) and experienced (T1) CI subjects.

Figure 3.

Correlation analysis of behavior performance and brain activity at rest. In CI patients, the activity observed at rest in the auditory and posterior temporal cortices (labeled, respectively, A and T in Fig. 1) presents a positive correlation with the performances on the audiovisual identification of words in inexperienced (T0) and experienced (T1) CI subjects.

Discussion

Sensory deprivation from birth or during adulthood leads to the reorganization of cortical functions (Kral and Eggermont 2007) that may modify auditory recovery in CI patients (Lee, Giraud, et al. 2007). On the other hand, in postlingually deaf patients, cochlear implantation yields a progressive recovery of auditory functions and speech comprehension during the first months after surgery (Rouger et al. 2007), which is associated with adaptive changes in the speech processing network (Giraud, Truy, et al. 2001).

Thus, cochlear implantation offers a unique insight into the cortical mechanisms that underlie adult functional plasticity due to the lost sensory modality because we can precisely evaluate progressive changes during auditory recovery. As cochlear implants provide a distorted signal, patients develop specific compensatory strategies that lead to the reattribution of functional specificity to the cortical areas involved in speech comprehension. This reorganization can be expressed as different levels of activation in auditory areas involved in semantic and/or phonological speech processing (Giraud et al. 2000) as well as the implication of visual or visuo-auditory areas (Giraud, Price, et al. 2001) which are linked to the visuo-auditory speech intelligibility strategies developed by the patients (Rouger et al. 2007, 2008; Desai et al. 2008). The present results show evidence that at rest, compared with normal-hearing subjects, CI deaf patients elicit specific regions of lower or higher activity that closely match the known reorganized network involved in speech comprehension after cochlear implantation.

In CI patients, the increased activity at rest observed in the left posterior and middle temporal region may be related to the previously reported higher activation of this region in CI users during phonological processing (Giraud, Truy, et al. 2001; Ito et al. 2004). Defined as a “sound-meaning interface” (Hickok and Poeppel 2007), this area is believed to merge perceptual and semantic information. Its higher activity in CI users at rest could reflect a certain adaptation and predictive coding needed to map the impoverished information provided by the implant onto semantic representations. This is why the activity is higher in experienced than in inexperienced CI patients.

Furthermore, we found that in the resting state, the CI patients present a higher level of activity in the inferior occipital gyrus (visual cortex) compared with controls. In previous studies, it has been demonstrated that CI users present a specific higher activity in the visual areas in response to auditory words (Giraud, Truy, et al. 2001). Such activation, not observed in hearing controls, follows the progressive recovery of auditory functions and is probably related to the cross-modal compensation induced by the deafness. The present observation of higher activity in visual areas at rest may correspond to the higher capacities for visual and audiovisual integration of speech shown in CI patients (Rouger et al. 2007; Desai et al. 2008). We have shown that despite considerable recovery of auditory performance during the first year postimplantation, CI patients maintain a much higher level of word recognition in speech-reading conditions compared with controls (Rouger et al. 2007; Strelnikov et al. 2008), a result that may explain the higher level of activity in the visual cortex even for the experienced CI patients.

The left inferior frontal region (Broca's area) is known to be involved in phonological processing (Demonet et al. 1992; Vigneau et al. 2006), among other functions. It was recently shown that in CI users, the activation of Broca's area during speech processing depends upon the auditory recovery and is negatively correlated with the duration of deafness (Lee et al. 2001; Green et al. 2005; Mortensen et al. 2006; Lee, Giraud, et al. 2007). Here, when comparing CI and normal hearing subjects at rest, we observed a significant lower level of activity in the left inferior frontal cortex in CI patients. Broca's area is implicated in an auditory–motor loop of crucial importance for language acquisition during development (Hickok and Poeppel 2007) and in intrinsic generation of words (Friston et al. 1991), a process that, according to the present results, might also be critical during the recovery of speech comprehension after implantation. We can infer that the decreased level of activity in the left frontal cortex in CI patients might originate from the lack of sensory inputs to this area from the auditory cortex.

Further support for such a suggestion is the hypoactivity we observed in CI users at rest within the middle part of the left superior temporal gyrus extending to the left insula. A similar difference between controls and CI patients has been reported in response to auditory speech stimulation (Ito et al. 2004). This decreased activity in the auditory cortex of CI patients could reflect the diminished (although progressively increasing with time), recruitment of the auditory areas by the stimulation through the implant as well as the reduced accessibility to fine acoustic details resulting from the impoverished auditory signals (Giraud, Truy, et al. 2001; Green et al. 2005).

We also observed a differential level of activity at rest in a restricted set of areas including the inferior temporal gyrus and the cingulate cortex, the latter presenting an increased level in its posterior part in CI patients. The posterior cingulate cortex is considered the key structure for the “default-mode” brain network which has been related to self-consciousness, general alertness, and arousal (Fiset et al. 1999). Although the present results do not address the issue of the default-mode network as previously defined (Raichle et al. 2001), the increased activity at rest in this specific region in CI compared with controls might reflect a compensatory mechanism in our patients so that their auditory handicap is alleviated by enhanced awareness of perceptual cues from alternative sensory channels, especially visual cues that can help deciphering speech via lip-reading.

We did not find any differences between the 2 analyzed rest scans suggesting that the effect we observed cannot be explained by a direct effect of the previous task onto the resting scan stimulation, as reported in functional magnetic resonance imaging studies (Waites et al. 2005) in which the time intervals separating successive acquisition periods are much shorter that in our present protocol. However, as all the subjects were in the same conditions and were given the same instructions before the study, this may have produced a certain effect of set (Sidtis 2007). From this viewpoint, our results indicate that there is a different effect of set or context between CI patients and controls. We argue that this difference is caused by the long-term changes in sensory input where brain plasticity after sensory deprivation is further modified by the crude sensory information from cochlear implants. As a result, the different patterns of brain activity at rest reflect the compensatory adaptive strategies needed to maximize speech comprehension. This hypothesis is reinforced by the presence of significant positive correlations with performances on audiovisual word identification in the auditory cortex and in the posterior temporal integrative cortex. Such a correlation between the resting state and the speech comprehension performances of the patients is observed exclusively in these 2 auditory areas that present a progressive increase at rest in the activity level after implantation. This proves once again that the resting state reflects an adaptation of the brain to facilitate information processing in a given context. Thus, brain activity at rest reflects cognitive predictions which are considered an important mechanism of brain functioning because the brain employs memory of past experiences to interpret new incoming information and to predict some general features of the relevant informational input in future (Kveraga et al. 2007).

Conclusion

Here we show that the level of cortical activity of CI patient during rest presents regional disparities compared with controls that match the dissimilarities previously reported in neuroimaging experiments involving active stimulation with speech stimuli. We propose that these differences at rest reflect adaptive processes of 2 origins: long-term adaptive mechanisms induced by the long period of hearing loss and comparatively short-term adaptive processes corresponding to the reactivation of the auditory system because the magnitude of these differences depends on the sensory experience provided by the neuroprosthesis. Reorganization of the resting-state activity may happen not only due to the progressive reactivation of the sensory network of speech processing after cochlear implantation, but also due to the development of new speech comprehension strategies by CI patients, as speech reading is no longer the unique reliable sensory channel.

Altogether, our data suggest that adaptive changes associated with the functional compensation due to cochlear implantation can be observed in stimulation-independent cortical activities during the resting state, and these distributed activities correspond to a coherent functional neuro-anatomical network. The presence of a differential level of activity in CI patients at rest may reflect a facilitatory mechanism whereby cortical areas that become crucial for speech processing are maintained efficiently active. The fact that the differential patterns of activity are specifically linked to speech processing by the visuo-auditory network suggests that even only partially restored, auditory sensory input is able to trigger speech-related activity in the brain.

Funding

ACI Neurosciences Intégratives et Computationnelles grant to O.D., P.B., J.R.; La Fondation de l'Avenir grant to O.D., S.L.; la Fondation pour la Recherche Médicale grant to S.L., J.R.; BQR Université Paul Sabatier grant to B.P., J.F.D., O.D.; ANR Hearing Loss grant, (ANR-06-Neuro-021-04) to O.D., P.B.; and the CNRS Atip+ program grant to B.P. and K.S.

We thank C. Marlot for help in bibliography, J. Foxton for correcting the manuscript, M.-L. Labordes, and the technical staff of the PET centre of the Toulouse University Hospital, G. Viallard and H. Gros-Dagnac.

Conflict of Interest: None declared.

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