Auditory cortical processing : Binaural interaction in healthy and ROBO1-deficient subjects

Two functioning ears provide clear advantages over monaural listening. During natural binaural listening, robust brain-level interaction occurs between the slightly different inputs from the left and the right ear. Binaural interaction requires convergence of inputs from the two ears somewhere in the auditory system, and it therefore relies on midline crossing of auditory pathways, a fundamental property of the mammalian central nervous system. Binaural interaction plays a significant role in sound localization and other auditory functions, e.g. speech comprehension in a noisy environment. However, the neural mechanisms and significance of binaural interaction and the development of crossed auditory pathways are poorly known. This thesis aimed to expand, by means of magnetoencephalography (MEG), knowledge about binaural cortical processing and midline crossing of auditory pathways in subjects with the defective dyslexia susceptibility gene ROBO1 and in healthy individuals. Study I demonstrated that in dyslexic individuals who carry a weakly expressing haplotype of the ROBO1 gene, binaural interaction is strongly impaired as compared with healthy, age- and sex-matched controls. Moreover, the observed impairment correlated with the expression level of the ROBO1 gene: the weaker the expression, the more abnormal was the binaural interaction. On the basis of previous animal studies and the quite well known anatomy of the subcortical auditory system, we suggest that the normally extensive crossing of auditory pathways is defective in ROBO1-deficient dyslexic subjects. All auditory illusions emerging in healthy individuals rely on normal neurophysiology, and thus illusions elicited by binaural sounds can be valuable in revealing auditory binaural processing. Studies II and III examined the neural basis of peculiar pitch perception and sound localization during the auditory octave illusion originally described by Diana Deutsch in 1974. In the octave illusion, dichotic tones separated by an octave alternate rapidly between the ears so that when the left ear receives the low tone, the right ear receives the high tone and vice versa. Study II demonstrated that transient 100-ms responses (N100m), generated in the auditory cortices, follow the sound location perceived during the illusion. Study III further showed that modifications in normal binaural interactions contribute to the illusory pitch perception. Currently, binaural interaction can be studied non-invasively in detail by means of cortical steady-state responses and MEG-based frequency-tagging. Steady-state responses have also been used in clinical settings to evaluate hearing in non-collaborative patients. Until now, only simple acoustic stimuli have been used to elicit steady-state responses, although in our daily lives we communicate with physically much more complex sounds, such as speech and music. Study IV demonstrated that natural sounds with carefully selected sound parameters can also be used as reliable stimuli in future steady-state studies, and therefore to scrutinize the role and mechanisms of binaural interaction. This thesis links the dyslexia susceptibility gene, ROBO1, to neurodevelopment of auditory system and binaural processing, reveals the sound localization and pitch perception mechanisms during the octave illusion, and provides knowledge about steady-state responses to natural sounds, thereby advancing future binaural interactions studies.Kahdesta toimivasta korvasta on selvää hyötyä ihmiselle, vaikka monien äänien havaitseminen onnistuukin varsin hyvin yhden korvan avulla. Esimerkiksi äänten paikallistaminen sekä puheen ymmärtäminen meluisassa ja kaikuvassa ympäristössä pohjautuvat pitkälti vasemmasta ja oikeasta korvasta tulevien hieman erilaisten viestien väliseen vuorovaikutukseen aivoissa. Tämän ns. binauraalisen vuorovaikutuksen merkitys ja hermostollinen perusta tunnetaan toistaiseksi kuitenkin varsin huonosti. Tässä väitöskirjassa tutkittiin aivoissa tapahtuvaa binauraalista vuorovaikutusta sekä vuorovaikutukselle välttämätöntä kuuloratojen risteämistä aivojen keskilinjan yli magnetoenkefalografian (MEG) avulla. Tutkimuksiin osallistui sekä lukivaikeudesta kärsiviä henkilöitä, joilla kaikilla on sama heikosti toimiva, lukivaikeudelle altistava ROBO1-geenin muutos, että terveitä henkilöitä. Tutkimustulokset osoittivat, että lukivaikeudesta kärsivillä henkilöillä, joilla ROBO1-geeni toimii heikosti, binauraalinen vuorovaikutus on merkittävästi heikompaa kuin terveillä verrokkihenkilöillä. Lisäksi havaittiin, että binauraalinen vuorovaikutus oli sitä heikompaa, mitä heikommin ROBO1-geeni toimi. Aiemmat eläinkokeet ovat osoittaneet, että ihmisen ROBO1-geeniä vastaavat geenit säätelevät banaanikärpäsillä ja hiirillä monien hermoratojen risteämistä aivojen keskilinjan yli puolelta toiselle. Toisaalta normaali binauraalinen vuorovaikutus perustuu kuuloratojen osittaiseen risteämiseen aivoissa. Näin ollen tutkimuksessa havaittu poikkeavan heikko binauraalinen vuorovaikutus johtunee kuuloratojen puutteellisesta risteämisestä. Terveiden henkilöiden binauraalisia mekanismeja tutkittiin lisäksi ns. oktaavi-illuusion avulla. Koska terveillä henkilöillä esiintyvät illuusiot pohjautuvat normaaliin aivotoimintaan, binauraaliseen vuorovaikutukseen liittyvät illuusiot voivat olla hyödyllisiä aivomekanismien selvittämisessä. Oktaavi-illuusiossa vasempaan ja oikeaan korvaan annetaan yhtä aikaa erilaiset, oktaavin päässä toisistaan olevat äänet, jotka sen jälkeen vaihtavat nopeasti paikkaa puolelta toiselle. Tyypillisesti sekä havaitun äänen korkeus että paikka ovat osittain ristiriidassa annettujen äänten kanssa. Tulosten perusteella aivojen nopea 100-ms vaste liittyy havaittuun paikkaan ja poikkeava binauraalinen vuorovaikutus havaittuun äänen korkeuteen. Tutkimustulokset tuovat lisää tietoa äänten havaitsemisesta ja paikantamisesta aivoissa. Toistaiseksi binauraalista vuorovaikutusta on tutkittu tarkasti vain puhtailla äänillä. Neljännessä osatyössä havaittiin, että myös luonnolliset äänet, kuten musiikki ja puhe synnyttävät MEG:llä mitattavissa olevia jatkuvaisvasteita, joita voitaneen käyttää binauraalisen vuorovaikutuksen tutkimiseen sekä mahdollisesti myös erilaisten kuulo-ongelmien tutkimisessa

Acute epiglottitis after COVID-19 infection

In patients with acute epiglottitis, the possibility of COVID-19 should be ruled out. Repeated nasofiberoscopy examinations or a tracheostomy, which may produce infectious aerosols, may be required.Peer reviewe

Investigating the association of electrically-evoked compound action potential thresholds with inner-ear dimensions in pediatric cochlear implantation

Objectives: A narrow bony cochlear nerve canal (BCNC), as well as a hypoplastic and aplastic cochlear nerve (CN) have been associated with increased electrically-evoked compound action potential (eCAP) thresholds in some studies, suggesting poorer neural excitability in cochlear implantation. Also, in large cochleae the extent of activated spiral ganglion neurons with electrical stimulation is less than in smaller ones. However, a detailed description of the relationship between eCAP thresholds for a lateral-wall electrode array and dimensions of the inner-ear structures and internal auditory canal (IAC) is missing. Design: The study subjects were 52 pediatric patients with congenital severe-to-profound hearing loss (27 females and 25 males; ages 0.7-2.0 years; 1.0 +/- 0.3 years, mean +/- SD) implanted bilaterally with Cochlear Nucleus CI422, CI522, or CI622 implants with full insertion of the Slim Straight electrode array. Diameters of the cochlea and the BCNC as well as the widths and heights of the IAC and the CN were evaluated from preoperative computed tomography and magnetic resonance images. These anatomical dimensions were compared with each other and with the patients' intraoperative eCAP thresholds. Results: The eCAP thresholds increased from the apical to basal direction (r = 0.89, p < 0.001). After sorting the cochleae into four size categories, higher eCAP thresholds were found in larger than in smaller cochleae (p < 0.001). With similar categorization, the eCAP thresholds were higher in cochleae with a larger BCNC than in cochleae with a smaller BCNC (p < 0.001). Neither IAC nor CN cross-sectional areas affected the eCAP thresholds. Correlations were found between cochlea and BCNC diameters and between IAC and CN cross-sectional areas (r = 0.39 and r = 0.48, respectively, p < 0.001 for both). Conclusions: In the basal part of the electrode array, higher stimulation levels to elicit measurable neural responses (eCAP thresholds) were required than in the apical part. Increased eCAP thresholds associated with a larger cochlear diameter, but contrary to the earlier studies, not with a small size of the BCNC or the CN. Instead, the BCNC diameter correlated significantly with the cochlea diameter.Peer reviewe

Binaural interaction and the octave illusion

The auditory octave illusion arises when dichotically presented tones, one octave apart, alternate rapidly between the ears. Most subjects perceive an illusory sequence of monaural tones: A high tone in the right ear (RE) alternates with a low tone, incorrectly localized to the left ear (LE). Behavioral studies suggest that the perceived pitch follows the RE input, and the perceived location the higher-frequency sound. To explore the link between the perceived pitches and brain-level interactions of dichotic tones, magnetoencephalographic responses were recorded to 4 binaural combinations of 2-min long continuous 400- and 800-Hz tones and to 4 monaural tones. Responses to LE and RE inputs were distinguished by frequency-tagging the ear-specific stimuli at different modulation frequencies. During dichotic presentation, ipsilateral LE tones elicited weaker and ipsilateral RE tones stronger responses than when both ears received the same tone. During the most paradoxical stimulus—high tone to LE and low tone to RE perceived as a low tone in LE during the illusion—also the contralateral responses to LE tones were diminished. The results demonstrate modified binaural interaction of dichotic tones one octave apart, suggesting that this interaction contributes to pitch perception during the octave illusion.Peer reviewe

Gaze-Direction-Based MEG Averaging During Audiovisual Speech Perception

To take a step towards real-life-like experimental setups, we simultaneously recorded magnetoencephalographic (MEG) signals and subject's gaze direction during audiovisual speech perception. The stimuli were utterances of /apa/ dubbed onto two side-by-side female faces articulating /apa/ (congruent) and /aka/ (incongruent) in synchrony, repeated once every 3 s. Subjects (N = 10) were free to decide which face they viewed, and responses were averaged to two categories according to the gaze direction. The right-hemisphere 100-ms response to the onset of the second vowel (N100m’) was a fifth smaller to incongruent than congruent stimuli. The results demonstrate the feasibility of realistic viewing conditions with gaze-based averaging of MEG signals

Improvements in Hearing and in Quality of Life after Sequential Bilateral Cochlear Implantation in a Consecutive Sample of Adult Patients with Severe-to-Profound Hearing Loss

Bilateral cochlear implantation is increasing worldwide. In adults, bilateral cochlear implants (BICI) are often performed sequentially with a time delay between the first (CI1) and the second (CI2) implant. The benefits of BICI have been reported for well over a decade. This study aimed at investigating these benefits for a consecutive sample of adult patients. Improvements in speech-in-noise recognition after CI2 were followed up longitudinally for 12 months with the internationally comparable Finnish matrix sentence test. The test scores were statistically significantly better for BICI than for either CI alone in all assessments during the 12-month period. At the end of the follow-up period, the bilateral benefit for co-located speech and noise was 1.4 dB over CI1 and 1.7 dB over CI2, and when the noise was moved from the front to 90 degrees on the side, spatial release from masking amounted to an improvement of 2.5 dB in signal-to-noise ratio. To assess subjective improvements in hearing and in quality of life, two questionnaires were used. Both questionnaires revealed statistically significant improvements due to CI2 and BICI. The association between speech recognition in noise and background factors (duration of hearing loss/deafness, time between implants) or subjective improvements was markedly smaller than what has been previously reported on sequential BICI in adults. Despite the relatively heterogeneous sample, BICI improved hearing and quality of life.Peer reviewe

Spiritual well-being correlates with quality of life of both cancer and non-cancer patients in palliative care - further validation of EORTC QLQ-SWB32 in Finnish

Publisher Copyright: © 2023. The Author(s).BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) has developed the Spiritual Well-being Questionnaire (EORTC QLQ-SWB32), a measure of spiritual well-being validated with people receiving palliative care for cancer, although its usefulness is not restricted to that population. We aimed to translate and validate this tool in Finnish and to study the relationship between spiritual well-being (SWB) and quality of life (QOL). METHODS: A Finnish translation was produced according to the guidelines of EORTC and included forward- and back-translations. Face, content, construct and convergence/divergence validity and reliability were studied in a prospective manner. QOL was assessed with EORTC QLQ-C30 and 15D questionnaires. Sixteen individuals participated in the pilot testing. 101 cancer patients drawn from oncology units, and 89 patients with other chronic diseases drawn from religious communities in different parts of the country participated in the validation stage. Retest was obtained from 16 individuals (8 cancer and 8 non-cancer patients). Inclusion criteria included patients with either a well-defined palliative care plan, or who would benefit from palliative care, as well as the capacity to understand and communicate in Finnish. RESULTS: The translation appeared understandable and acceptable. Factorial analysis identified four scoring scales with high Cronbach alfa values: Relationship with Self (0.73), Relationship with Others (0.84), Relationship with Something Greater (0.82), Existential (0.81), and, additionally, a scale on Relationship with God (0.85). There was a significant correlation between SWB and QOL in all participants. CONCLUSIONS: The Finnish translation of EORTC QLQ-SWB32 is a valid and reliable measure both for research and clinical practice. SWB is correlated with QOL in cancer and non-cancer patients undergoing palliative care or who are eligible for it.Peer reviewe

Improvements in Hearing and in Quality of Life after Sequential Bilateral Cochlear Implantation in a Consecutive Sample of Adult Patients with Severe-to-Profound Hearing Loss

Bilateral cochlear implantation is increasing worldwide. In adults, bilateral cochlear implants (BICI) are often performed sequentially with a time delay between the first (CI1) and the second (CI2) implant. The benefits of BICI have been reported for well over a decade. This study aimed at investigating these benefits for a consecutive sample of adult patients. Improvements in speech-in-noise recognition after CI2 were followed up longitudinally for 12 months with the internationally comparable Finnish matrix sentence test. The test scores were statistically significantly better for BICI than for either CI alone in all assessments during the 12-month period. At the end of the follow-up period, the bilateral benefit for co-located speech and noise was 1.4 dB over CI1 and 1.7 dB over CI2, and when the noise was moved from the front to 90 degrees on the side, spatial release from masking amounted to an improvement of 2.5 dB in signal-to-noise ratio. To assess subjective improvements in hearing and in quality of life, two questionnaires were used. Both questionnaires revealed statistically significant improvements due to CI2 and BICI. The association between speech recognition in noise and background factors (duration of hearing loss/deafness, time between implants) or subjective improvements was markedly smaller than what has been previously reported on sequential BICI in adults. Despite the relatively heterogeneous sample, BICI improved hearing and quality of life

Effect of remdesivir post hospitalization for COVID-19 infection from the randomized SOLIDARITY Finland trial

We report the first long-term follow-up of a randomized trial (NCT04978259) addressing the effects of remdesivir on recovery (primary outcome) and other patient-important outcomes one year after hospitalization resulting from COVID-19. Of the 208 patients recruited from 11 Finnish hospitals, 198 survived, of whom 181 (92%) completed follow-up. At one year, self-reported recovery occurred in 85% in remdesivir and 86% in standard of care (SoC) (RR 0.94, 95% CI 0.47-1.90). We infer no convincing difference between remdesivir and SoC in quality of life or symptom outcomes (p > 0.05). Of the 21 potential long-COVID symptoms, patients reported moderate/major bother from fatigue (26%), joint pain (22%), and problems with memory (19%) and attention/concentration (18%). In conclusion, after a one-year follow-up of hospitalized patients, one in six reported they had not recovered well from COVID-19. Our results provide no convincing evidence of remdesivir benefit, but wide confidence intervals included possible benefit and harm.Peer reviewe