1. Table 2. Mean (±SEM) percent BOLD signal change for tones relative to silent trials in PAC. ControlsPatientsSignificance Left ear stimulation L. PAC0.7% (0.10)0.8% (0.08)n.s. R. PAC0.5% (0.09)0.5% (0.09)n.s. Right ear stimulation L. PAC0.9% (13.4)0.9% (0.20)n.s. R. PAC 0.3% (0.10)0.6% (0.12)p<0.08 zIn non-primary auditory cortex, there were no significant differences between the HL patients and the normal controls. CHL patients SNHL patients Patient mean (±SEM) Lateralized plastic changes in unilateral hearing loss J. T. Devlin 1, K. Lanary 1, J. Raley 1, E. Tunbridge 1, A. Floyer-Lea 1, C. Narain 1, P. Jezzard 1, M. Burton 2, D. R. Moore 3, P. M. Matthews 1 1 Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, U. K. 2 ENT Department, Radcliffe Infirmary, Oxford, U. K. 3 MRC Institute of Hearing Research, Nottingham, U. K. Unilateral deafness by cochlear ablation in animals produces a dramatic increase in the level of neural activity in the inferior colliculus and auditory cortex on the side of the intact ear to acoustic stimulation of that ear. Previous fMRI studies 1 appear to confirm this finding in humans who have unilateral sensorineural hearing loss. Here we asked whether long term unilateral hearing loss in humans changes the symmetry of pure tone BOLD activation in the supratemporal plane. In primary auditory cortex there was a clear laterality effect. Relative to silence, tones presented to the left ear led to greater left hemisphere activity, as seen previously in normals 2. Right ear stimulation, on the other hand, led to more bilateral activation – a reduction of the normal left hemisphere advantage – and this was due to an increase in ipsilateral activation. In non-primary auditory cortex unilateral hearing loss did not change the normal contralateral dominance. Summary zThe current study used sparse sampling 3 to measure cortical auditory responses to monaurally presented tones zParticipants discriminated between high (4000Hz) and low (250Hz) frequency tones (90db SPL) by pressing one of two buttons as quickly as possible after the tone onset. zHalf of all trials had a silent stimulus. zThe purpose of the task was simply to control attention by forcing participants to attend to the tones throughout the scanning. Current Study Figure 3: Laterality indices in PAC Laterality calculations Discussion Like previous studies, we observed a reduction in the normal contralateral advantage for auditory processing in patients with unilateral hearing loss 1,5. The current study, however, qualifies these findings in two important ways: 1. Plastic changes were limited to primary auditory cortex and not found in the adjacent non-primary regions, and 2. Only right ear stimulation led to a reduced laterality effect and this was due to an increase in ipsilateral activation rather than a reduction in contralateral activity. If BOLD signal primarily reflects synaptic metabolic demands 6, then the observed changes are consistent with animal studies showing substantial sub-cortical activation increases on the side of the stimulated ear. Unlike other species, however, in humans this effect is only present for right ear stimulation. This may be due to the fact that humans appear to be unique in that they display a left hemisphere dominance for processing simple monaurally presented auditory stimuli 2. In other words, a strong sub-cortical path already exists in humans leading from the left ear to left PAC which may not need to be strengthened in the event of hearing loss in the right ear. Expected BOLD signal Stimulation Paradigm Tone Scanner Tone Scanner 0 5 10 15 20 25 30 35 Time (seconds) Figure 1: Sparse sampling paradigm zTo assess relative laterality of auditory cortex responses, we computed a Laterality Index (LI): (Contralateral - Ipsilateral BOLD signal change) (Contralateral + Ispilateral BOLD signal change) +100 indicates completely contralateral activation -100 indicates completely ipsilateral activation zUsing mean signal change avoided biasing the laterality calculation through (1) an arbitrary statistical threshold for counting active voxels, or (2) differences in the volume of the ROIs across hemispheres (i.e. partial volume effects). LI = × 100 Primary auditory cortex zThe majority of primary auditory cortex (PAC) is located on Heschls gyrus and was therefore identified on each participants structural scan as an anatomic correlate of PAC. 50 30 10 -10 -30 -50 R Laterality index Left ear stimulation Right ear stimulation 50 30 10 -10 -30 -50 n.s. zFor right ear stimulation, HL patients showed a significant reduction in the normal contralateral dominance. In fact, there was no significant laterality effect in these patients. zThere were no significant differences between the HL patients and the normal controls for left ear stimulation. Both groups showed a strong ipsilateral (i.e. left hemisphere) dominance. Non-primary auditory cortex zDefined as areas adjacent to PAC which were activated by the tone vs. silence comparison in the group 123 Step 1: Tones vs. silence in RFX (cluster stats: Z>2.3, p<0.05) Step 2: Anatomically masked to include coordinates of human non-primary areas 4 Step 3: Removed individual subjects HG Masked HG removed Figure 4: Laterality indices in non-primary areas Laterality index 20 10 0 -10 -30 20 10 0 -10 -20 #1561 E.g.: * (n.s.) (p<0.05) References 1. Bilecen, D., Seifritz, E., Radu, E. W., Schmid, N., Wetzel, S., Probst, R., & Scheffler, K. (2000). Cortical reorganization after acute unilateral hearing loss traced by fMRI. Neurology, 54(3), 765-767. 2. Devlin, J. T., Raley, J., Tunbridge, E., Lanary, K., Floyer-Lea, A., Narain, C., Cohen, I., Behrens, T. E. J., Jezzard, P., Matthews, P. M., & Moore, D. R. (in submission). Functional asymmetry for auditory processing in human primary auditory cortex. (See also Poster #1448.) 3. Hall, D. A., Haggard, M. P., Akeroyd, M. A., Palmer, A. R., Summerfield, A. Q., Elliot, M. R., Gurney, E. M., & Bowtell, R. W. (1999). "Sparse" temporal sampling in auditory fMRI. Human Brain Mapping, 7, 213-223. 4. Rivier, F., & Clarke, S. (1997). Cytochrome oxidase, acetylcholinesterase, and NADPH-diaphorase staining in human supratemporal and insular cortex: Evidence for multiple auditory areas. NeuroImage, 6, 288-304. 5. Scheffler, K., Bilecen, D., Schmid, N., Tschopp, K., & Seelig, J. (1998). Auditory cortical responses in hearing subjects and unliateral deaf patients as detected by functional magnetic resonance imaging. Cerebral Cortex, 8, 156-163. 6. Logothetis, N. K., Pauls, J., Augath, M., Trinath, T., & Oeltermann, A. (2001). Neurophysiological investigation of the basis of the fMRI signal. Nature, 412(6843), 150-157. Left ear stimulation Right ear stimulation Results HG MTG PT PP STG STS Insula TP CS PreCS IFS PTr IPS SMG PreCS Right hemisphereLeft hemisphere Left ear stimulation Right ear stimulation p<0.01 p<10 -7 zMonaural tones relative to silence activated Heschls gyrus and adjacent non-primary areas bilaterally Figure 2: Auditory cortex activations TP PT PP HG Insula SMG CS IPS PreCS PTr STG STS MTG The upper panels display lateral views of the inflated left and right hemisphere surfaces with sulci and gyri shown in dark and light grey, respectively. The middle and bottom panels show activation in cortical auditory fields due to left and right ear stimulation. Participants z11 patients with long term unilateral hearing loss z7 sensorineural hearing loss (SNHL) z5 conductive hearing loss (CHL) z12 normal hearing controls Table 1. Patient details Type of AffectedDurationSeverity Hearing loss GenderEar(yrs)(threshold)Etiology SNHLFR23Mod.-Sev.Possibly mumps (65-75dB) SNHLML20ProfoundPossibly mumps (>90dB) SNHLFR16 ProfoundPossibly mumps (>95dB) SNHLMR12 ProfoundUnknown (>95dB) SNHLMR12 ProfoundUnknown (>95dB) SNHLFL9 ProfoundPossibly maternal (>95dB)rubella SNHLML8 ProfoundPossibly viral (>95dB) CHLFL2MildOtosclerosis (36.25dB) CHLMR6Mild-Mod.Perforated ear (46.25dB)drum CHLFL20ModerateOtosclerosis (57.5dB) CHLMR18ModerateCongenital atresia (60dB)of external canal The threshold value represents the patients average for 500Hz, 1kHz, 2kHz, and 4kHz pure tone audiometry. Normal group means * zThus the reduction in laterality in patients with unilateral hearing loss in their left ear was due to an increase in activation in PAC ipsilateral to the stimulated (i.e. right) ear.