Cochlear implant electrode configuration effects on activation threshold and tonotopic selectivity

Objective. The conductive nature of the fluids and tissues of the cochlea can lead to broad activation of spiral ganglion neurons using contemporary cochlear implant stimulation configurations such as monopolar (MP) stimulation. The relatively poor spatial selectivity is thought to limit implant performance, particularly in noisy environments. Several current focusing techniques have been proposed to reduce the spread of activation with the aim towards achieving improved clinical performance. Approach. The present research evaluated the efficacy of focused multipolar (FMP) stimulation, a relatively new focusing technique in the cochlea, and compared its efficacy to both MP stimulation and tripolar (TP) stimulation. The spread of neural activity across the inferior colliculus (IC), measured by recording the spatial tuning curve, was used as a measure of spatial selectivity. Adult cats (n = 6) were acutely deafened and implanted with an intracochlear electrode array before multi-unit responses were recorded across the cochleotopic gradient of the contralateral IC. Recordings were made in response to acoustic and electrical stimulation using the MP, TP and FMP configurations. Main results. FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation. However, thresholds were significantly higher (p < 0.001) for FMP and TP stimulation compared to MP stimulation. There were no differences found in spatial selectivity and threshold between FMP and TP stimulation. Significance. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance. However, further research will be required to demonstrate the efficacy of these modes of stimulation after longer durations of deafness.

To compare the effects of Monopole (Mono), Tripole (Tri), and "Virtual channel" (Vchan) electrode configurations on spectral resolution and speech perception in a crossover design. Nine experienced adults who received an Advanced Bionics CII/90K cochlear implant participated in a crossover design using three experimental strategies for 2 wk each. Three strategies were compared: (1) Mono; (2) Tri with current partly returning to adjacent electrodes and partly (25 or 75%) to the extracochlear reference; and (3) a monopolar "Vchan" strategy creating seven intermediate channels between two contacts. Each strategy was a variant of the standard "HiRes" processing strategy using 14 channels and 1105 pulses/sec/ channel, and a pulse duration of 32 microsec/phase. Spectral resolution was measured using broadband noise with a sinusoidally rippled spectral envelope with peaks evenly spaced on a logarithmic frequency scale. Speech perception was measured for monosyllables in quiet and in steady-state and fluctuating noises. Subjective comments on music experience and preferences in everyday use were assessed through questionnaires. Thresholds and most comfortable levels with Mono and Vchan were both significantly lower than levels with Tri. Spectral resolution was significantly higher with Tri than with Mono; spectral resolution with Vchan did not differ significantly from the other configurations. Moderate but significant correlations between word recognition and spectral resolution were found in speech in quiet and fluctuating noise. For speech in quiet, word recognition was best with Mono and worst with Vchan; Tri did not significantly differ from the other configurations. Pooled across the noise conditions, word recognition was best with Tri and worst with Vchan (Mono did not significantly differ from the other configurations). These differences were small and insufficient to result in a clear increase in performance across subjects if the result from the best configuration per subject was compared with the result from Mono. Across all subjects, music appreciation and satisfaction in everyday use did not clearly differ between configurations. (1) Although spectral resolution was improved with the tripolar configuration, differences in speech performance were too small in this limited group of subjects to justify clinical introduction. (2) Overall spectral resolution remained extremely poor compared with normal hearing; it remains to be seen whether further manipulations of the electrical field will be more effective.

Spatial mapping of sound frequencies along the auditory pathway is refined by sound-evoked activity during early development. However, the extent to which neonatal auditory deprivation alters this organization remains unclear. This study uniquely examined frequency-specific spatial representations in the inferior colliculus (IC) using targeted low-frequency (apical) and high-frequency (basal) cochlear stimulation, enabling the direct evaluation of low-frequency pathway integrity after neonatal deafness. Sixteen Sprague-Dawley rats (8 normal-hearing [NH] and 8 neonatally deafened [ND] rats) were studied. Neonatal deafness was induced by daily kanamycin injections from postnatal days 4 to 17. At 8-10 weeks of age, the animals underwent unilateral cochlear implantation with bipolar electrode pairs positioned in the apical and basal cochlear regions to activate low- and high-frequency pathways. Multiunit responses were recorded from the contralateral IC using a multichannel linear electrode array. Spatial tuning curves (STCs) based on cumulative discriminability were used to assess the thresholds, spread of excitation, and tonotopic precision. Spiral ganglion neuron (SGN) density was histologically assessed. Despite 48-67 % SGN loss across cochlear turns, electrically evoked auditory brainstem response and IC thresholds were comparable between groups, indicating preserved peripheral excitability. However, ND rats showed significantly broader STCs (p = 0.002) and reduced dorsoventral separation of apical and basal best sites (1.18 ± 0.24 mm vs 1.80 ± 0.30 mm, p = 0.039), reflecting degraded central tonotopic precision. These effects were most pronounced for apical (low-frequency) stimulation, consistent with the selective vulnerability of lowfrequency pathways to early auditory deprivation. These findings provide direct physiological evidence that early auditory experience is critical for refining the frequency-organized connectivity in the auditory midbrain. The preferential degradation of apical (low-frequency) spatial tuning offers translational insights for optimizing stimulation strategies in early-onset deafness.

Contemporary cochlear implants with multiple electrode stimulation can produce good speech perception but poor music perception. Hindered by the lack of a gold standard to quantify electric pitch, relatively little is known about the nature and extent of the electric pitch abnormalities and their impact on cochlear implant performance. Here we overcame this obstacle by comparing acoustic and electric pitch perception in 3 unilateral cochlear-implant subjects who had functionally usable acoustic hearing throughout the audiometric frequency range in the non-implant ear. First, to establish a baseline, we measured and found slightly impaired pure tone frequency discrimination and nearly perfect melody recognition in all 3 subjects’ acoustic ear. Second, using pure tones in the acoustic ear to match electric pitch induced by an intra-cochlear electrode, we found that the frequency-electrode function was not only 1–2 octaves lower, but also 2 times more compressed in frequency range than the normal cochlear frequency-place function. Third, we derived frequency difference limens in electric pitch and found that the equivalent electric frequency discrimination was 24 times worse than normal-hearing controls. These 3 abnormalities are likely a result of a combination of broad electric field, distant intra-cochlear electrode placement, and non-uniform spiral ganglion cell distribution and survival, all of which are inherent to the electrode-nerve interface in contemporary cochlear implants. Previous studies emphasized on the “mean” shape of the frequency-electrode function, but the present study indicates that the large “variance” of this function, reflecting poor electric pitch discriminability, is the main factor limiting contemporary cochlear implant performance.

Modeling the electrode–neuron interface of cochlear implants: Effects of neural survival, electrode placement, and the partial tripolar configuration

Human aging is characterized by reductions in the ability to remember associations between items, despite intact memory for single items. Older adults also show less selectivity in task-related brain activity, such that patterns of activation become less distinct across multiple experimental tasks. This reduced selectivity or dedifferentiation has been found for episodic memory, which is often reduced in older adults, but not for semantic memory, which is maintained with age. We used fMRI to investigate whether there is a specific reduction in selectivity of brain activity during associative encoding in older adults, but not during item encoding, and whether this reduction predicts associative memory performance. Healthy young and older adults were scanned while performing an incidental encoding task for pictures of objects and houses under item or associative instructions. An old/new recognition test was administered outside the scanner. We used agnostic canonical variates analysis and split-half resampling to detect whole-brain patterns of activation that predicted item versus associative encoding for stimuli that were later correctly recognized. Older adults had poorer memory for associations than did younger adults, whereas item memory was comparable across groups. Associative encoding trials, but not item encoding trials, were predicted less successfully in older compared with young adults, indicating less distinct patterns of associative-related activity in the older group. Importantly, higher probability of predicting associative encoding trials was related to better associative memory after accounting for age and performance on a battery of neuropsychological tests. These results provide evidence that neural distinctiveness at encoding supports associative memory and that a specific reduction of selectivity in neural recruitment underlies age differences in associative memory.

Meditation has been shown to improve creativity in some situation. However, little is known about the brain systems underling insight into a problem when the person fails to solve the problem. Here, we examined the neural correlation using Chinese Remote Association Test, as a measure of creativity. We provide a solution following the failure of the participant to provide one. We examine how meditation in comparison with relaxation influences the reaction of the participant to a correct solution. The event-related functional magnetic resonance imaging showed greater activity, mainly distributed in the right cingulate gyrus (CG), insula, putamen, inferior frontal gyrus (IFG), and the bilateral middle frontal gyrus (MFG), the inferior parietal lobule (IPL) and the superior temporal gyrus (STG). This pattern of activation was greater following 5 h of meditation training than the same amount of relaxation. Based on prior research, we speculate on the function of this pattern of brain activity: (i) CG may be involved in detecting conflict and breaking mental set, (ii) MFG/IFG may play an important role in restructuring of the problem representation, (iii) insula, IPL and STG may be associated with error detection, problem understanding or general attentive control and (iv) putamen may be activated by 'Aha' feeling.

The purpose of functional brain mapping is to localize patterns of neuronal activity associated with sensory, motor, and cognitive functions, or with disease processes. To be complete, an imaging modality needs near millimeter precision in localizing regions of activated tissue and sub-second temporal precision for characterizing changes in patterns of activation over time. Increasingly fine anatomical resolution is available with functional magnetic resonance imaging (fMRI). However, fMRI is an indirect measure of neuronal electrical activity whose temporal resolution is too gross to resolve the rapidly shifting patterns of activity that are characteristic of actual neurophysiological processes. In contrast, electroencephalography (EEG) and event-related potential (ERP) methods have a temporal resolution typically in the one to five millisecond range, depending on the AID rate. For simplicity the term EEG is used here in a general sense to refer both to recordings of brain electrical activity and, except where noted, to recordings of brain magnetic activity called magnetoencephalograms or MEGs. The nature of MEG recording technology and the relative strengths and weaknesses of EEG versus MEG approaches have been reviewed elsewhere (Cohen & Cuffin, 1991; Leahy et al., 1998; Williamson & Kaufman, 1987). From a broad perspective that considers all neuroimaging modalities, the differences between EEG and MEG are slight relative to their similarities.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Treatments against ALL might lead to later cognitive effects and alterations in brain structure in survivors but to the authors' knowledge the observed variability in the severity of neurocognitive deficits is not fully understood. The objective of the current study was to investigate abnormalities in visual short-term memory (VSTM) brain activation in survivors of childhood ALL using magnetoencephalography. A VSTM task was completed by 40 survivors of ALL and 26 controls. VSTM capacity (Cowan K) and brain activation were assessed during the retention period of the task (400-1400milliseconds) using a standard minimum norm source localization method. Performance (Cowan K) was found to be similar between survivors of ALL and controls. Atypical brain activation was found in survivors of ALL during the task, including overactivation of regions usually involved in VSTM (lateral occipital, precentral gyrus, and postcentral gyrus), recruitment of regions that typically are not involved in VSTM (superior/middle temporal gyrus and supramarginal gyrus), and lower activation of frontal brain regions (inferior frontal gyrus). These patterns of activation were modulated by the age at the time of cancer onset (P=.01) because activity was found to be reduced in participants who were younger at diagnosis. The results of the current study suggest a pattern of neural inefficiency and compensatory activity during VSTM in survivors of ALL.

Psychosis is characterized by a diminished ability of the brain to distinguish externally driven activity patterns from self-generated activity patterns. Antipsychotic drugs are a class of small molecules with relatively broad binding affinity for a variety of neuromodulator receptors that, in humans, can prevent or ameliorate psychosis. How these drugs influence the function of cortical circuits, and in particular their ability to distinguish between externally and self-generated activity patterns, is still largely unclear. To have experimental control over self-generated sensory feedback, we used a virtual reality environment in which the coupling between movement and visual feedback can be altered. We then used widefield calcium imaging to determine the cell type-specific functional effects of antipsychotic drugs in mouse dorsal cortex under different conditions of visuomotor coupling. By comparing cell type-specific activation patterns between locomotion onsets that were experimentally coupled to self-generated visual feedback and locomotion onsets that were not coupled, we show that deep cortical layers were differentially activated in these two conditions. We then show that the antipsychotic drug clozapine disrupted visuomotor integration at locomotion onsets also primarily in deep cortical layers. Given that one of the key components of visuomotor integration in cortex is long-range cortico-cortical connections, we tested whether the effect of clozapine was detectable in the correlation structure of activity patterns across dorsal cortex. We found that clozapine as well as two other antipsychotic drugs, aripiprazole and haloperidol, resulted in a strong reduction in correlations of layer 5 activity between cortical areas and impaired the spread of visuomotor prediction errors generated in visual cortex. Our results are consistent with the interpretation that a major functional effect of antipsychotic drugs is a selective alteration of long-range layer 5-mediated communication.

Spectral ripple discrimination thresholds were measured in 15 cochlear-implant users with broadband (350-5600 Hz) and octave-band noise stimuli. The results were compared with spatial tuning curve (STC) bandwidths previously obtained from the same subjects. Spatial tuning curve bandwidths did not correlate significantly with broadband spectral ripple discrimination thresholds but did correlate significantly with ripple discrimination thresholds when the rippled noise was confined to an octave-wide passband, centered on the STC's probe electrode frequency allocation. Ripple discrimination thresholds were also measured for octave-band stimuli in four contiguous octaves, with center frequencies from 500 Hz to 4000 Hz. Substantial variations in thresholds with center frequency were found in individuals, but no general trends of increasing or decreasing resolution from apex to base were observed in the pooled data. Neither ripple nor STC measures correlated consistently with speech measures in noise and quiet in the sample of subjects in this study. Overall, the results suggest that spectral ripple discrimination measures provide a reasonable measure of spectral resolution that correlates well with more direct, but more time-consuming, measures of spectral resolution, but that such measures do not always provide a clear and robust predictor of performance in speech perception tasks.

A key characteristic of eating disorders is atypical activity in the amygdala. However, risk factors for the development of eating disorder symptomology (EDS) and their underlying neural mechanisms are not well understood in non-clinical populations. We examined the role of amygdala reactivity to negative facial emotions in anorexia nervosa symptomology (ANS) and bulimia nervosa symptomology (BNS) using a classical face-matching task and an inter-subject representational similarity analysis (IS-RSA). Behavioral analyses showed a sequential-mediation effect, tracing a path from greed personality trait → depression → body dysmorphic disorder → EDS/ANS. Imaging analyses revealed that individuals with high EDS had decreased amygdala reactivity and altered activation patterns in the amygdala and visual pathways when processing angry faces. We found that variations in amygdala activation and its connectivity with the visual pathway mediated the effect of depression on EDS/ANS, but not BNS. Individuals with similar EDS showed similar spontaneous brain activity patterns, especially in regions associated with the default mode network, frontal-parietal network, visual network (VIS), and attention network. We also observed sequence-mediation effects, e.g., depression → VIS → body dysmorphic disorder → EDS/ANS, but not BNS. These findings highlight the role of amygdala activation in understanding eating disorders and the potential influence of greed personality traits and depression on disordered eating symptoms through the amygdala-visual pathway connection in non-clinical populations.

Brain Organization Underlying Superior Mathematical Abilities in Children with Autism

The distribution of stimulus-evoked 14C-2-deoxyglucose (2DG) labeling in primary somatosensory cortex (SI) of monkey (Macaca fascicularis) and cat was investigated. Reconstructions of the global pattern of labeling reveal that discrete skin stimuli evoke activity within an extensive region of SI, and that the activation pattern typically consists of multiple, elongated regions of above-background labeling ("modules," typically 0.5-1.0 mm wide, and 1-4 mm long). Evidence obtained using recently developed methods (Tommerdahl, 1989) for quantitative analysis of 2DG activity patterns is shown to be consistent with the idea (Whitsel et al., 1991) that SI modules typically are bounded by zones dominated by stimulus-evoked inhibition. The labeling pattern within individual 2DG modules in SI of both cats and monkeys is analyzed quantitatively (in the frequency domain). Within-module spatial activation patterns are demonstrated to be periodic, consisting of radially oriented profiles of above-background labeling separated from each other by less strongly labeled radial profiles. The spectral characteristics of within-module 2DG labeling change systematically with location along the module's long axis: spatial frequencies between 18 and 35 cycles/mm are prominent in the labeling that occupies both the middle and upper layers at central locations in the module, but are a less obvious component of the labeling in both the middle and upper layers at locations remote to the module center. Since the radially oriented periodic variation both (1) in 2DG labeling in regions of SI outside modules and (2) in optical density in images of Nissl-stained sections of SI consists predominantly of spatial frequencies in the range of 18-35 cycles/mm, it is concluded that the radial profiles of labeling within individual 2DG modules correspond to groupings of minicolumns distinguishable from their neighbors on the basis of labeling intensity. The findings raise the possibility that highly structured, within-module spatial patterns of SI minicolumnar activation encode information about the physical properties of tactile stimuli.

Denervation due to amputation is known to induce cortical reorganization in the sensorimotor cortex. Although there is evidence that reorganization does not lead to a complete loss of the representation of the phantom limb, it is unclear to what extent detailed, finger-specific activation patterns are preserved in motor cortex, an issue that is also relevant for development of brain-computer interface solutions for paralysed people. We applied machine learning to obtain a quantitative measure for the functional organization within the motor and adjacent cortices in amputees, using high resolution functional MRI and attempted hand gestures. Subjects with above-elbow arm amputation (n = 8) and non-amputated controls (n = 9) made several gestures with either their right or left hand. Amputees attempted to make gestures with their amputated hand. Images were acquired using 7 T functional MRI. The sensorimotor cortex was divided into four regions, and activity patterns were classified in individual subjects using a support vector machine. Classification scores were significantly above chance for all subjects and all hands, and were highly similar between amputees and controls in most regions. Decodability of phantom movements from primary motor cortex reached the levels of right hand movements in controls. Attempted movements were successfully decoded from primary sensory cortex in amputees, albeit lower than in controls but well above chance level despite absence of somatosensory feedback. There was no significant correlation between decodability and years since amputation, or age. The ability to decode attempted gestures demonstrates that the detailed hand representation is preserved in motor cortex and adjacent regions after denervation. This encourages targeting sensorimotor activity patterns for development of brain-computer interfaces.