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Pharmacological Enhancement of Aural Habilitation in Adult Cochlear Implant Users

Tobey, Emily A.; Devous, Michael D. Sr; Buckley, Kristi; Overson, Gary; Harris, Thomas; Ringe, Wendy; Martinez-Verhoff, Julie

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Objective: The purpose of this report was to examine the preliminary data collected under a larger on-going feasibility study conducted with cochlear implant patients exploring the potential benefit of pharmacologically-enhanced aural rehabilitation therapy as a means of increasing speech tracking skills.

Design: Eight adult cochlear implant participants participated in a randomized, double-blind study and received either 10 mg d-amphetamine (Treatment group, N = 4) or a placebo (Placebo group, N = 4) 60 minutes prior to a 1.5 hour intensive aural rehabilitation session occurring twice a week for two months. Treatment consisted of a multi-step rehabilitation program individualized for each participant to develop auditory-only speech tracking skills. Prior to and at the conclusion of the therapy sessions, SPECT rCBF imaging and speech tracking assessments were conducted.

Results: Speech tracking scores of the placebo and treatment groups were similar before the aural habilitation intervention. In the placebo group, speech tracking performance increased 13.5% for visual plus auditory and auditory only presentations as a function of aural habilitation alone. The 10 mg d-amphetamine-facilitated program resulted in minimal increases in visual plus auditory tracking scores (2%) but led to a 43% increase for auditory-only speech tracking. Regional cerebral blood flow measures indicated no substantial improvement of brain activation in the placebo group while both the extent and magnitude of primary and associative auditory cortex activations increased significantly with the pharmacologically enhanced treatment program.

Conclusions: These data support previous studies indicating an accelerated acquisition of speech and language abilities in stroke patients receiving traditional speech therapy in combination with d-amphetamine. Data, however, are preliminary and further study is warranted.

This paper examined the speech tracking performance and regional cerebral blood flow (rBF) responses of eight adult cochlear implant users before and after an 8-week, twice-a-week for 1.5 hours aural habilitation program. Half of the subjects were randomly assigned in a double-blinded fashion to a placebo group (aural habilitation training only), and half of the subjects were assigned to a pharmacologically enhanced program (10 mg of d-amphetamine plus aural habilitation program). Auditory-only speech tracking scores improved on average 12% in the placebo group and 43% for the pharmacologically enhanced group. Increases in rCBF were noted for both groups; however, the extent and amount of activation post-intervention were greater for the pharmacologically enhanced group.

Callier Advanced Hearing Research Center, The University of Texas at Dallas, Dallas, TX (E.T., K.B., G.O., J.M.V.); Nuclear Medicine Center, The University of Texas Southwestern Medical Center, Dallas, TX (M.D., T.H., W.R.); Department of Otolaryngology—Head and Neck Surgery, The University of Texas Southwestern Medical Center, Dallas, TX (E.T.)

Address for correspondence: Emily A. Tobey, Ph.D., Callier Advanced Hearing Research Center, 1966 Inwood Road, Dallas, TX 75235.

Received January 10, 2005; accepted February 14, 2005.

One of the major consequences of long-term deafness is a change in the neural architecture of the central nervous system (CNS). Alterations to the CNS following long-term deafness are observed in both animals and humans. Cochlear implants provide restoration of some aspects of hearing in individuals with severe-to-profound hearing losses by using electrodes implanted in the cochlea to stimulate the auditory nerve directly. Electrical stimulation of the auditory nerve enhances or preserves CNS structure and function allowing many individuals with long-standing deafness to consider cochlear implantation as a therapeutic avenue. However, a great deal of variation exists in the post-implantation speech perception performance of adults using cochlear implants. Some individuals experience substantial benefit while other individuals receive less benefit from cochlear implants.

Compromises to auditory CNS architecture as a function of profound hearing loss are extensive. Degenerative effects are observed for the spiral ganglion and brainstem auditory neurons following periods of auditory deprivation (Clopton et al., 1978; Webster & Webster, 1977). Several investigators report the degenerative effects of profound hearing loss extend to the cortex (Kral, Tillein, Heid, Hartmann, & Klinke, 2004). Studies using functional magnetic resonance imaging (fMRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT) reveal depressed neuronal activity in post-lingually deaf subjects, generally observed bilaterally in primary and association cortices (Morita et al., 2004; Naito et al., 1995; Naito et al., 1997; Okazawa et al., 1996; Truy et al., 1995). In contrast, persons with residual hearing or deafness of short periods demonstrate more nearly normal resting cortical metabolism/perfusion in primary and secondary auditory cortices (Jancke, Gaab, Wustenberg, Scheich, & Heinze, 2001; Shiomi, et al., 1999).

Stimulation of the auditory CNS via cochlear implants results in changes to cortical responses that suggests the auditory neural architecture following periods of auditory deprivation remains relatively plastic and responsive to “bottom-up” influences (Nishimura et al., 2000). Metabolic changes are observed in adults using multichannel cochlear implants when listening to spectrally simple signals (i.e., pure tones) or to spectrally complex signals (i.e., running speech) (Giraud & Truy, 2002; Herzog et al., 1991; Ito, Sakakibara, Iwasaki, & Yonekura, 1993; Naito et al., 1997; Naito, et al., 2000a; Nishimura, et al., 2000; Okazawa, et al., 1996; Wong, Miyamoto, Pisoni, Sehgal & Hutchins,1999). Although functional brain imaging studies use different imaging techniques, stimuli and analyses procedures, a consistent pattern of blunted cortical activations is observed in cochlear implant users relative to normal hearing control subjects. Blunted responses improve toward normal values following implantation relative to values noted prior to implantation but the values do not reach normal levels even in subjects with high levels of speech perception performance. Typically, the greatest activations occur contralateral to the ear of implantation in primary and associative auditory cortices with similar but smaller activations occurring ipsilateral to the ear of implantation (Fujiki et al., 1999; Fujiki, et al., 2000; Giraud et al., 2000; Naito et al., 2000b; Okazawa et al., 1996). Cochlear implant patients with minimal open-set speech perception abilities demonstrate the greatest blunting of cortical activation. Cortical activations in these individuals reveal blunted responses contralateral to the ear of implantation and minimal, if any, responses ipsilateral to the ear of implantation.

While our research and that of many other investigators is aimed at documenting the response of neural architecture underlying normal and impaired speech perception (Roland, Tobey, & Devous, Sr., 2001; Okazawa et al., 1996; Naito, et al. 2000b; Giraud, et al., 2000; Fujiki et al., 1999; Fujiki et al., 2000), we are unaware of any research that directly focuses on “repairing” neural architecture abnormalities in cochlear implant patients. However, there are suggestions in the literature as to how this might be accomplished. For example, aphasic patients following stroke demonstrate a significant improvement in recovery of language function if classic therapeutic measures are combined with the administration of low dosages of d-amphetamine in order to stimulate injured but noninfarcted speech and language areas (Wertz et al., 1986; Walker-Batson., 2000; Hurwitz et al., 1991; Feeney, Gonzalez & Law, 1982; Boyeson & Feeney, 1990).

Modification of synaptic plasticity is poorly understood, though several approaches to block plasticity processes are known. The N methyl-D-aspartate (NMDA) receptor has been implicated in synaptic plasticity (Nicoll & Malenka, 1995), and it has been shown that plasticity is blocked with drugs that block NMDA receptors, such as memantine (Dinse et al., 2003). Unfortunately, less is known about drugs that enhance cortical plasticity and the pharmacological mechanisms underlying perceptual learning. Thus, the cortical reorganization in humans in response to changes in perceptual learning remains to be clarified. As mentioned above, in aphasia following stroke, small doses of D-amphetamine effectively stimulate peri-infarct and contralateral homologous regions to become receptive to speech and language interventions. It is unknown whether the less responsive auditory cortices in cochlear implant users could be similarly activated.

Several mechanisms have been ascribed to d-amphetamine responses. For example, the modulatory role of d-amphetamine may be related to the enhancing effects of amphetamine on long-term potentiation (Delanoy, Tucci, & Gold,1983). D-amphetamine increases the CNS levels of dopamine, serotonin, and noradrenaline by one of four possible mechanisms: 1) as a partial antagonist, mimicking the action of norepinephrine at the receptor; 2) inhibiting catecholamine reuptake; 3) inhibiting monoamine oxidase; or 4) displacing norepinephrine by releasing it onto receptors (Wertz et al., 1986; Walker-Batson et al. 2000; Hurwitz et al., 1991; Feeney, Gonzalez, & Law 1982; Boyeson & Feeney 1990). Monoamines modify long-term changes in synaptic function, with serotonin being more potent than noradrenaline (Lacaille & Harley, 1985). Also, ventral tegmental neurons are believed to provide reinforcement signals for learning-related reorganization (Montague, Dayan, Sejnowski, 1996). Amphetamine-induced release of dopamine may work in aphasia (or cochlear implantation) in a manner similar to that reported after ventral tegmental stimulation is paired with auditory stimuli (Bao, Chan, Merzenich, 2001). Regardless of the exact mechanism of action of d-amphetamine on speech-language centers and pathways in the brain, we will acquire important information regarding the cortical responsiveness of individuals with cochlear implants with regard to adrenergic systems, if adult cochlear implant users respond to a d-amphetamine enhanced treatment with greater increases in speech tracking performance than individuals receiving similar aural habilitation training without pharmacologic enhancement.

The purpose of this report is to report on the data obtained in a descriptive, feasibility study conducted with adult cochlear implant patients to explore the potential benefit of pharmacologically enhanced aural rehabilitation therapy as a means of increasing speech tracking skills. A structured auditory rehabilitation program was developed to be used in parallel with either a placebo or 10 mg of d-amphetamine. This initial report asked:

a) Are speech tracking performances in adult cochlear implant users improved with aural habilitation?

b) To what extent, are speech tracking performances in adult cochlear implant users further enhanced with pharmacological management?

c) Do objective measures of cortical activity acquired via functional brain imaging reflect positive alterations to brain metabolism as a function of aural habilitation alone (i.e., with placebo) or pharmacologically enhanced aural habilitation (i.e., with 10 mg d-amphetamine)?

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Methods

Overview

Subjects underwent speech perception and rCBF assessment both before and after an 8 week aural rehabilitation experience that consisted of two, 1.5 hour sessions per week. Imaging was assessed during an experimental task involving auditory plus visual processing and during a control task involving visual only processing, conducted on separate days. Each rehabilitation session consisted of the administration of either placebo or 10 mg d-amphetamine 60 min prior to speech therapy. Monitoring of heart rate and general physical status was monitored before and after the individual intervention sessions.

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Subjects

The first eight adult cochlear implant volunteers for the study are included in this report. All participants were enrolled in a randomized, double-blind intervention study approved by the Institutional Review Boards of the University of Texas at Dallas and the University of Texas Southwestern Medical Center. Half of the participants were randomly assigned to the placebo group and half were assigned to the treatment group. Table 1 describes the demographic characteristics of the subjects. The average age of the placebo group was 69 years (ranging from 65 to 74 years) and the average age of the treatment group was 52 years (ranging in age from 44 to 59 years). Average length of cochlear implant experience was 3.5 years for the placebo group and 3.2 years for the treatment group. Four of the participants used Cochlear Corporation devices, two used Advanced Bionics Corporation devices and two used Med-El Corporation devices. Two of the participants were bilaterally implanted, one participant was implanted in the right ear and five participants were implanted in the left ear. Average consonant-vowel-consonant (CVC) performance was 56.5% (ranging from 20 to 72%) for the placebo group and 52.5% (ranging from 8 - 92%) for the treatment group. Performance on the Hearing In Noise Test (HINT) sentences (Nilsson, Soli, & Sullivan, 1994) presented at 60 dB in quiet was 74% for the placebo group and 67% for the treatment group.

TABLE 1

TABLE 1

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Functional Brain Imaging Procedures

Regional cerebral blood flow (rCBF) was measured via SPECT during speech perception tasks delivered under an experimental and control condition, each imaged on separate days. The experimental auditory condition consisted of subjects listening to and watching a 15 minute segment of an adolescent novel video-taped by single female speaker. Auditory signals were presented monaurally with the opposite ear plugged. In the case of the binaurally implanted participants, rCBF was measured for each ear monaurally and a combined binaural conditions on different test days. For the purposes of this paper, only the monaural left responses will be reported for the bilaterally implanted participants. The control condition was composed of a segment of a different story presented as a visual signal only. The two stories were randomly assigned to the participants as either the experimental or control condition. At least 48 hours separated the two test sessions.

All participants were individually tested by inserting a 22-gauge Quick-Cath needle into the left forearm that was connected to polyethylene tubing extending out of the participant’s visual field (allowing for the radiotracer to be delivered without the subject’s knowledge). Participants were seated in a dimly lit room with their eyes open and auditory state controlled by the stimulus conditions. Five minutes into a given task, the rCBF tracer (99mTc-HMPAO) was administered without the subject’s knowledge. Radiotracer uptake was completed over the 2 minutes following the injection. Imaging with a PRISM 3000 scanner commenced following a 1.5 hour delay (although the tracer is extracted by the brain within 2 minutes after injection and after wards is unchanged in its distribution, this delay permits clearance of background scalp and blood pool radiotracer activity from subsequent imaging). Subjects received instructions to pay close attention to the video tape under the various conditions because they would be asked to answer 5 open-ended questions regarding the content of the video at its conclusion.

Image analyses consisted of three different activities: normalization, coregistration, and subtraction. SPECT images were co-registered to Talairach space and normalized to whole brain counts. Analyses of change in rCBF were measured relative to global cerebral blood flow. Images were smoothed from their original resolution of 6.5 mm to a final resolution of 10mm. For this feasibility study, only left ear responses were examined in the two bilaterally implanted subjects and the responses of the participant with a right implant were flipped in order to examine group data as a function of contralateral and ipsilateral responses. Areas activated were overlaid on an rCBF model in Talairach space (Talairach & Tournoux, 1988). Voxel-wise analyses of treatment induced effects on rCBF were analyzed using Statistical Parametric Mapping (SPM 99) (Friston, 1994).

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Speech Tracking Procedures

In this descriptive, feasibility study, measures of discourse tracking were obtained at three time intervals: before, during, and after intervention following the procedures outlined by DeFillipo and Scott (De Filippo & Scott, 1978). All materials were rated using the Flesch-Kincaid Reading Index to determine and control for reading level and difficulty. Pretreatment discourse tracking measures consisted of words-per-minute scores obtained under three conditions. First, a 10-minute ceiling discourse measure determined the words-per-minute score for a “ceiling” trial. This trial consisted of allowing the participant to have access to the written text, listen to the text and watch the face of the tester. The second condition eliminated access to the written text and consisted of a visual plus auditory measure (V+A) consisting of tracking a passage with visual and auditory cues from the examiner. The third condition consisted of an auditory-only tracking condition (A-only) in which text and visual cues were eliminated. Data are reported as words-per-minute scores. Two measures, V+A and A-only, were obtained post-intervention.

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Intervention Procedures

The aural habilitation program was held twice a week for 1.5 hour individual sessions for a total of 8-weeks. In order to properly monitor vital signs as a function of the pharmacological treatment, each session lasted approximately 3 hours. In the following paragraphs, we will briefly describe the make-up of the initial session (which parallels the final session) and describe the intervening sessions constituting the aural habilitation program.

During the initial and final sessions, the session consisted of greetings (approximately 5 minutes), followed by a 5-minute baseline measure of heart-rate, blood pressure, affect and general emotional states that were logged as vital statistics in the participant’s file. The three measures of speech tracking scores were obtained in ten minute segments. A “ceiling” measure of speech tracking was acquired, followed by a 10-minute pre-treatment baseline measure of V+A and A-only (30 minutes total of speech tracking). Participants then were administered the placebo or d-amphetamine (10 mg dose) and given an hour break to allow a period of “ramp-up” for the medications. Measures of “medicated” heart-rate, blood pressure, affect, and general emotional state were again acquired and logged as vital statistics (5 minutes). Auditory rehabilitation training began with a half hour session of single words in isolation using the Common Words Lists 1, 2, 3, 4 with 25 words per list delivered with full V+A cues and written text. A five minute break was given before commencing with a 20 minute period of speech tracking practice consisting of the lowest reading grade-level materials (materials not used in pre- or post-testing). The mode of presentation of discourse was varied individually for the participant based on their levels of performance. All participants started with V+A presentations and moved to A-only presentations over the course of treatment. Participants were then given a 5-minute speech tracking session using new materials presented under V+A or A-only conditions (a total of 10 minutes). Vital statistics were again gathered and entered into the participants’ records (5 minutes). Times for breaks were extended for the participants, as needed. In addition, all participants were asked to remain in the clinic for an hour after the initial intervention session to insure they experienced no residual effects from the medications.

During subsequent sessions, the initial portion of the session consisted of greetings (5 minutes), un-medicated vital statistics, (5 minutes), administration of placebo or treatment (1 minute), a 1-hour break to allow “ramp-up” of the medications, and measures of “medicated” vital statistics (5 minutes). Thirty minutes of intensive training consisting of single words in isolation were given followed by a 5 minute break. One-half hour of speech tracking practice commenced by starting with the lowest reading-grade materials and moving upward in reading complexity. Based on individual performances during a given session, intervention sessions concluded with a speech tracking performance test acquired with V + A and A-only, as well as a 5-minute medicated vital statistic acquisition period. Participants were allowed to leave these sessions when hemodynamic and affective states returned to baseline.

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Results

Table 2 depicts the “ceiling,” V + A, and A-only speech tracking scores for the individual subjects in the Placebo and Treatment groups. The mean “ceiling” performance for materials averaging a 5.4 reading grade level for the Placebo and Treatment groups was 81.7 and 81.2 words per minute, respectively. Prior to intervention, the Placebo group achieved 59.1 words-per-minute in V + A condition (standard deviation 4.8 words-per-minute) and 50.0 words-per-minute in the A-only condition (standard deviation 13.3 words-per-minute). The Treatment group scored 66.9 words-per-minute (standard deviation 16.5 words-per-minute) and 43.3 words-per-minute (standard deviation 15.3 words-per-minute) in the V + A and A-only conditions, respectively. Following the 8-week intervention program, the Placebo group achieved 67.5 words-per-minute during V + A conditions (standard deviation 12 words-per-minute) and 55.4 words-per-minute in the A-only condition (standard deviation 9.5 words-per-minute). Scores for the Treatment group were 67.6 words-per-minute (standard deviation 13.8 words-per-minute) and 59.0 words-per-minute (standard deviation 14.9 words-per-minute) for the V + A and A-only conditions, respectively.

TABLE 2

TABLE 2

Figure 1 depicts the percent changes in speech tracking performance for the two groups. The scores resulted in a percent change in performance ((Pre values - Post values)/ Pre-Values) * 100) of 13.5% for speech tracking under V + A (standard deviation of 13%) and 13.5% for A-only (standard deviation of 20.3%) conditions for the Placebo group. Calculations of percent change in speech tracking performance for the Treatment group were 2.0% for the V + A condition (standard deviation 6.2%) and 43% for the A-only condition (standard deviation 26.8%; p = .007). Figure 2 shows the percent changes in speech tracking scores for the individual participants in the Placebo (left panel) and Treatment (right panel) groups, respectively (note the raw scores used to calculate these values are shown in Table 2). As shown in Figure 2, half of the Placebo participants demonstrated changes greater than 10% in performance for A-only speech tracking as a function of the intervention program (Subjects P2 and P4 did not). As indicated in Table 1, subject P2 achieved scores of 66 and 73% correct identification of CVC and HINT stimuli, respectively. Subject P4 achieved performance levels of 72 and 94% correct identification on CVC and HINT sentences in quiet. Similarly, two out of the four Placebo subjects demonstrated increases of greater than 10% in V + A speech tracking scores (Subjects P1 and P2 did not). Subject P1 achieved scores of 20% and 35% for CVC and HINT sentences prior to participating in the intervention program.

Fig. 1. Percent change scores are indicated for the placebo (clear bars) and treatment group (solid bars) for speech tracking words-per-minute acquired under visual + auditory and auditory-only conditions.

Fig. 1. Percent change scores are indicated for the placebo (clear bars) and treatment group (solid bars) for speech tracking words-per-minute acquired under visual + auditory and auditory-only conditions.

Fig. 2. Percent change scores are indicated for the individual subjects in the placebo group on the left panel. Percent change scores are indicated for the individual subjects in the treatment group are in the right panel. Visual plus auditory speech tracking scores are indicated by the clear bars and auditory-only scores are indicated by the solid bars.

Fig. 2. Percent change scores are indicated for the individual subjects in the placebo group on the left panel. Percent change scores are indicated for the individual subjects in the treatment group are in the right panel. Visual plus auditory speech tracking scores are indicated by the clear bars and auditory-only scores are indicated by the solid bars.

The right panel of Figure 2 illustrates the individual percent change speech tracking scores for the Treatment group. Only one subject (T4) demonstrated changes greater than 10% in the V+ A speech tracking scores. This subject achieved scores of 44 and 37% correct on CVC and HINT stimuli prior to intervention. The remaining three participants showed essentially no change in V+A speech tracking performance (ranging from -0.5% to -1.6%). All four participants in the Treatment group achieved increases of A-only speech tracking scores greater than 10% with scores ranging from 22.3% to 79.7% changes.

Figure 3 illustrates the speech tracking scores for the individual test sessions during the intervention program for each of the participants in the Placebo and Treatment groups. The four panels on the left represent the speech tracking scores as a function of individual intervention session for the Placebo group and the panels on the right represent those of the Treatment group. Although considerable variation appears across subjects within and across the groups, V+ A speech tracking scores typically were higher than speech tracking scores obtained in the A-only conditions throughout the intervention program.

Fig. 3. Speech tracking scores are shown for the individual therapy sessions for the individual subjects. Panels located on the left represent scores from the placebo group and panels on the right represent scores from the treatment group. Individual subjects are in ascending order from the top of the page (i.e., subject 1 is at the top of the page and subject 4 is at the bottom of the page). Visual plus auditory scores are indicated by the small, light line and auditory-only scores are indicated by the thick, dark line.

Fig. 3. Speech tracking scores are shown for the individual therapy sessions for the individual subjects. Panels located on the left represent scores from the placebo group and panels on the right represent scores from the treatment group. Individual subjects are in ascending order from the top of the page (i.e., subject 1 is at the top of the page and subject 4 is at the bottom of the page). Visual plus auditory scores are indicated by the small, light line and auditory-only scores are indicated by the thick, dark line.

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Functional Brain Imaging Data

Table 3 illustrates the comprehension scores acquired under the two SPECT brain imaging conditions before and after intervention. Following intervention, comprehension improved 19% for the Placebo group for the V+A condition and 27.5% for the visual-only condition. In the Treatment group, comprehension improved 45% for the V+A condition and 12.5% for the visual-only condition following intervention.

TABLE 3

TABLE 3

Figure 4 depicts the SPECT images acquired prior to, and following, intervention in the Placebo group. Prior to intervention, small but significant activations were observed in the superior and middle temporal gyri in the hemisphere contralateral to the ear of implantation (Brodmann areas 41, 21, 22, and 38) (p < .0001). Ipsilateral to the ear of implantation, cortical activations were reliably observed in the superior temporal gyrus (Brodmann areas 41 and 22) (p < .0001). Following the intervention program, significant activations were found in the Transverse and Superior Temporal Gyri bilaterally to the ear of implantation (Brodmann areas 42 and 22) (p < .0001).

Fig. 4. The panels display 10 consecutive MRI slices moving from inferior to superior cortex going from left to right. More inferior slices represent auditory association cortices and more superior slices represent primary auditory cortices. Anterior is at the top of the slices and left is indicated on left side of the images. The top panel represents the average data from 4 placebo subjects receiving stimulation to the left ear prior to aural habilitation training. The bottom panel represents the average data from 4 placebo subjects receiving stimulation to the left ear following aural habilitation training. The colors superimposed on the images represent areas of significant rCBF activation under the conditions of listening to monaural signals (

Fig. 4. The panels display 10 consecutive MRI slices moving from inferior to superior cortex going from left to right. More inferior slices represent auditory association cortices and more superior slices represent primary auditory cortices. Anterior is at the top of the slices and left is indicated on left side of the images. The top panel represents the average data from 4 placebo subjects receiving stimulation to the left ear prior to aural habilitation training. The bottom panel represents the average data from 4 placebo subjects receiving stimulation to the left ear following aural habilitation training. The colors superimposed on the images represent areas of significant rCBF activation under the conditions of listening to monaural signals (

Figure 5 illustrates the areas of significant activation acquired before and after intervention in the Treatment group. Prior to intervention, significant activations were observed in the inferior, middle and superior temporal gyri (Brodmann areas 41,20, 21, 22, 38) of the hemisphere contralateral to the ear of implantation (p < .0001). Following the intervention program, substantial activations were observed in the superior temporal gyrus in the hemisphere ipsilateral to the ear of implantation (Brodmann areas 41, 42, 22 and 38) (p < .0001). In addition, even larger activations occurred contralateral to the ear of implantation in the middle and superior temporal gyri (Brodmann areas 41, 42, and 21) (p < .0001).

Fig. 5. The panels display 10 consecutive MRI slices moving from inferior to superior cortex going from left to right. More inferior slices represent auditory association cortices and more superior slices represent primary auditory cortices. Anterior is at the top of the slices and left is indicated on left side of the images. The top panel represents the average data from 4 treatment subjects receiving stimulation to the left ear prior to aural habilitation training. The bottom panel represents the average data from 4 treatment subjects receiving stimulation to the left ear following aural habilitation training paired with d-amphetamine. The colors superimposed on the images represent areas of significant rCBF activation under the conditions of listening to monaural signals (

Fig. 5. The panels display 10 consecutive MRI slices moving from inferior to superior cortex going from left to right. More inferior slices represent auditory association cortices and more superior slices represent primary auditory cortices. Anterior is at the top of the slices and left is indicated on left side of the images. The top panel represents the average data from 4 treatment subjects receiving stimulation to the left ear prior to aural habilitation training. The bottom panel represents the average data from 4 treatment subjects receiving stimulation to the left ear following aural habilitation training paired with d-amphetamine. The colors superimposed on the images represent areas of significant rCBF activation under the conditions of listening to monaural signals (

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Discussion

Overall, data from the placebo group suggest speech tracking scores in adult cochlear implant users improve on average 13% as a function of an 8-week aural habilitation program designed to enhance speech tracking abilities. These improvements are evident in both V+A and A-only speech tracking conditions suggesting aural habilitation provides a positive benefit for adult cochlear implant users. Considerable variation, however, occurred in the individual speech tracking performance of the placebo group with one subject achieving minimal performance changes for V+A and A-only presentations, two participants achieving increases in performance for V+A and A-only stimuli, and one subject increasing performance for V + A stimuli but not A-only stimuli.

Variability in the placebo group may be related to several factors including the demographic characteristics of the group which were intentionally not controlled, as part of the larger feasability study. For example, the two subjects demonstrating the greatest changes in V+ A speech tracking scores were bilaterally implanted. One of the bilaterally implanted subjects (Subject P4) also demonstrated substantial increases in A-only speech tracking performance whereas the second subject (Subject P3) did not. Inspection of the individual session speech tracking performance for subject P3 indicates their performance hovered around 70 and 60 words-per-minute for V+A and A-only presentations, respectively. Similarly, high performance levels are evident in the individual session data for subject P4 who achieves approximately 80 words-per-minute scores in V+A conditions and 70 words-per-minute under A-only conditions. Changes in speech tracking scores for V+A and A-only presentations were poorest for Subject P2 whose V+A and A-only performance hovered around 50 words-per-minute. However, subject P2 also had the least experience using their implant (.92 years). Subject P1 who had the lowest CVC and HINT performance demonstrated V+A speech tracking scores during the individual sessions of around 70 words-per-minute while A-only tracking hovered at 30 words-per-minute.

Comparisons of the speech tracking intervention sessions relative to the “ceiling” performances achieved when participants were allowed to also read the stimuli, as well as listen and see the examiner, are also revealing regarding sources of individual variability. During the intervention program, the two bilaterally implanted participants preformed nearly at ceiling levels for both V+A and A-only stimuli. Subject P2 appeared to be slightly below ceiling levels during the intervention program. Subject P1 remained substantially below ceiling levels for A-only stimuli. Although his V+A tracking scores were higher than his A-only scores during the intervention program, they, too, remained below his ceiling level. These observations suggest the intervention program designed with reading materials of approximately a fifth grade level allowed the majority of subjects to practice speech tracking at a fairly high level of success; thus, reducing frustration. However, it is not clear if higher performance levels would be achieved if the program was longer than 8-weeks, more intensive than two, 1.5 hour sessions per week, or designed to use more difficult reading materials. Manipulations of these variables may reduce the overall variance associated with aural habilitation as indicated by this small group of participants.

In contrast, the Treatment group displayed minimal changes in V+A speech tracking performance accompanied by substantial changes in A-only speech tracking scores following the intervention program. The percent change of A-only speech tracking performances was over three times as high as that observed for the placebo group, ranging from 22 to 79% across the individual participants in the treatment group. Interestingly, the two participants with the lowest CVC and HINT scores (subjects T2 and T4) demonstrated the greatest gains in A-only speech tracking scores (46.1% and 79.7%, respectively).

The speech tracking scores acquired across the treatment sessions relative to the ceiling levels acquired under conditions combining text, visual and auditory cues resemble the placebo group. For example, V+A speech tracking was typically higher than A-only tracking performance for all subjects across all sessions. As in the case of the placebo group, most of the subjects in the treatment group preformed below their ceiling performance again confirming fifth grade reading materials provided a reasonable stimulus for practicing speech tracking. Variability in speech tracking was evident in the measures acquired across treatment sessions in manners paralleling the placebo group, with some individuals achieving high levels of performance (i.e., subject T2) and others achieving fewer words-per-minute tracking scores (i.e., subject T4).

Differences between the groups were further confirmed by the functional brain imaging measures. Prior to intervention, the two groups demonstrated small reliable activations of the superior and middle temporal gyrus contralateral to the ear of implantation. Ipsilateral activation of the superior temporal gyrus also was evident in the two groups. Following the intervention program, no substantial improvement in brain activation occurred in the Placebo group, while both the extent and magnitude of primary auditory and association cortex increased significantly in the Treatment group. Increased responses were noted both contralateral and ipsilateral to the ear of implantation. These data support previous studies indicating SPECT rCBF is a sensitive measure of changes in cortical activity associated with adult cochlear implant users.

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Caveats That Must Be Considered

Administration of d-amphetamine appears to enhance recovery of motor function, sensorimotor integration and binocular depth perception (Jonason, Lauber, Robbins, Meyer, & Meyer, 1970; Hurwitz, et al., 1991; Feeney, Gonzalez, & Law, 1982; Feeney & Hovda, 1985; Dietrich, et al., 1990; Crisostomo, Duncan, Propst, Dawson, & Davis, 1988). D-amphetamine-facilitated recovery appears to be greater when the pharmacologic treatment is paired with practice or training than when the drug is administered in isolation (Walker-Batson, 2000). Increase rate and extent of recovery is evident in hemiplegic patients following strokes when low dosages are administered during physical therapy conducted in the subacute recovery period (Crisostomo, Duncan, Propst, Dawson, & Davis, 1988). Administration of d-amphetamine paired with speech/language treatment during the subacute recovery period also accelerates communication abilities in stroke patients (Walker-Batson, 2000). Our data based on the preliminary reports of the first few participants enrolled in our feasibility study suggest d-amphetamine facilitates the development of A-only speech tracking scores in adult cochlear implant users. Although it is not entirely clear why greater changes are observed in the A-only conditions relative to the V + A conditions in the Treatment group, one can speculate that these differences reflect the emphasis of the intervention program on A-only speech tracking skills and may reflect the ability of the Treatment group to reach auditory-only speech tracking abilities more quickly than the placebo group. Achievement of these abilities, in turn, assures the group will receive a greater amount of practice in these skills during the intervention. Future studies with larger N’s will allow us to investigate these factors more clearly in order to specify the underlying relationships of factors contributing to these observations.

Although these initial observations are exciting and suggest new avenues for exploring how to enhance auditory performance in adult cochlear implant users, many questions remain to be addressed. For example, it is not clear precisely what dosage of d-amphetamine constitutes the ideal amount to enhance performance. Nor is it clear how long the treatment should last. When one considers the large increases in speech tracking performance acquired over 16 therapy sessions for 24 hours of aural habilitation, one must question if different dosages and a greater number of therapy sessions would further enhance performance. For example, the aphasia literature suggests a significant clinical change is indicated by a 15 point change in the Porch Index for Communication Disorders (Walker-Batson, 2000). One study reports a 16.7 point change when therapy is paired with d-amphetamine across 10 drug treatment sessions and 33 hours of therapy delivered in a 5-week period (Walker-Batson, 2000). Another study indicates patients made a 18.2 point recovery after 12 weeks of d-amphetamine-paired therapy that provided between 96 to 120 hours of therapy (Wertz et al., 1986). These issues will need to be carefully explored to determine the optimal habilitation intervals for adult cochlear implant users.

The composition and level of difficulty for tasks contained within the aural habilitation also needs to be explored to determine the ideal components necessary to increase performance in adult cochlear implant users. Several studies examining the treatment of phonological problems in young children suggest targeting more complex sounds results in a generalization of benefit to less complex sounds. It is not clear if such a concept can be applied to the development of effective aural habilitation programs for adult cochlear implant users.

Additionally, with the very small sample of participants described here, it is not yet possible to determine what type of patient will receive the most benefit. The subjects in this preliminary report used a variety of different implant devices, different speech processing strategies and different implantation characteristics (i.e., unilateral versus bilateral). Although the two bilateral patients (subjects P3 and P4) demonstrated the greatest percent change in performance for the placebo group, the percent changes in performance for two of the unilaterally implanted subjects in the treatment group with roughly similar lengths of implant experience (subjects T2 and T4) was higher. These four subjects also pinpoint another confounding issue, the chronological age of the subjects. Subjects in the placebo group are older than subjects in the treatment group. It remains unclear if the performance differences are related to the age and cognitive conditions of the groups. Finally, it is not clear how generalizable and long-lasting these findings may be. Future studies will attempt to more carefully match important demographic characteristics of subjects and to include a wide range of performance measures in order to better characterize the speech perception abilities of individuals participating in the intervention sessions. We intend to continue following these subjects to examine the stability of performance over time while we increase our pool of participants further examining these issues (Constable et al., 1978).

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Acknowledgments

Portions of this work were presented at the International Meeting on Cochlear Implants held in Indianapolis, IN. Work on this project is sponsored by the Charles A. Dana Foundation Clinical Hypotheses Program in Imaging. (M. Devous, Sr., Principal Investigator) and the National Institute of Deafness and Other Communication Disorders (R01 DC04558, E. Tobey, Principal Investigator). We appreciate the assistance of Drs. Pam Kruger, Nathan Schwade and Peter Roland.

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