Cortical hemispheric asymmetries are present at young ages and further develop into adolescence.

Specialization of the auditory cortices for pure tone listening may develop with age. In adults, the right hemisphere dominates when listening to pure tones and music; we thus hypothesized that (a) asymmetric function between auditory cortices increases with age and (b) this development is specific to tonal rather than broadband/non-tonal stimuli. Cortical responses to tone-bursts and broadband click-trains were recorded by multichannel electroencephalography in young children (5.1 ± 0.8 years old) and adolescents (15.2 ± 1.7 years old) with normal hearing. Peak dipole moments indicating activity strength in right and left auditory cortices were calculated using the Time Restricted, Artefact and Coherence source Suppression (TRACS) beamformer. Monaural click-trains and tone-bursts in young children evoked a dominant response in the contralateral right cortex by left ear stimulation and, similarly, a contralateral left cortex response to click-trains in the right ear. Responses to tone-bursts in the right ear were more bilateral. In adolescents, peak activity dominated in the right cortex in most conditions (tone-bursts from either ear and to clicks from the left ear). Bilateral activity was evoked by right ear click stimulation. Thus, right hemispheric specialization for monaural tonal stimuli begins in children as young as 5 years of age and becomes more prominent by adolescence. These changes were marked by consistent dipole moments in the right auditory cortex with age in contrast to decreases in dipole activity in all other stimulus conditions. Together, the findings reveal increasingly asymmetric function for the two auditory cortices, potentially to support greater cortical specialization with development into adolescence.

Early unilateral cochlear implantation promotes mature cortical asymmetries in adolescents who are deaf.

Unilateral cochlear implant (CI) stimulation establishes hearing to children who are deaf but compromises bilateral auditory development if a second implant is not provided within ∼ 1.5 years. In this study we asked: 1) What are the cortical consequences of missing this early sensitive period once children reach adolescence? 2) What are the effects of unilateral deprivation on the pathways from the opposite ear? Cortical responses were recorded from 64-cephalic electrodes within the first week of bilateral CI activation in 34 adolescents who had over 10 years of unilateral right CI experience and in 16 normal hearing peers. Cortical activation underlying the evoked peaks was localized to areas of the brain using beamformer imaging. The first CI evoked activity which was more strongly lateralized to the contralateral left hemisphere than normal, with abnormal recruitment of the left prefrontal cortex (involved in cognition/attention), left temporo-parietal-occipital junction (multi-modal integration), and right precuneus (visual processing) region. CI stimulation in the opposite deprived ear evoked atypical cortical responses with abnormally large and widespread dipole activity across the cortex. Thus, using a unilateral CI to hear beyond the period of cortical maturation causes lasting asymmetries in the auditory system, requires recruitment of additional cortical areas to support hearing, and does little to protect the unstimulated pathways from effects of auditory deprivation. The persistence of this reorganization into maturity could signal a closing of a sensitive period for promoting auditory development on the deprived side.

Electroconvulsive therapy for the acute management of severe agitation in dementia (ECT-AD): A modified study protocol.

OBJECTIVE: This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented. METHODS: Initially, the RCT randomized participants 1:1 to either ECT plus usual care or simulated ECT plus usual care (S-ECT) groups. As patients were enrolled, data were collected from both ECT and simulated ECT (S-ECT) patients. The study now continues in an open-label study design where all patients receive actual ECT, reducing the targeted sample size from 200 to 50 participants. RESULTS: Study is ongoing and open to enrollment. CONCLUSION: The transition of the ECT-AD study design from an RCT to open-label design exemplifies adaptive research methodologies in response to real-world challenges. Data from both the RCT and open-label phases of the study will provide a unique perspective on the role of ECT in managing severe treatment-refractory agitation in dementia, potentially influencing future clinical practices and research approaches.

Modifiable Risk Factors in Alzheimer Disease and Related Dementias: A Review.

PURPOSE: Although Alzheimer disease and related dementias (ADRDs) have long been considered nonpreventable and even an inevitable consequence of aging, recent findings from longitudinal studies indicate a downtrend in age-adjusted incidence and prevalence of ADRDs in Western countries. This remarkable trend might be the result of improved management of so-called modifiable risk factors. The aim of this review is to present evidence of modifiable factors of ADRDs in a life-course approach. METHODS: A PubMed database search was conducted between November and December 2020 to identify relevant studies evaluating the role of modifiable risk factors in the development of ADRDs. Key words (Alzheimer's disease and modifiable risk factors) were used and specific inclusion and exclusion criteria applied. FINDINGS: This review identifies modifiable factors for ADRDs divided into early-life, middle-life, and late-life risk factors, depending on the available window of preventive action. According to life course exposure, factors can be protective or deleterious for ADRDs that participate in the underlying pathophysiologic complexity of these diseases as well as the complexity for public health measures implementations. IMPLICATIONS: The available evidence derived from epidemiologic, preclinical, interventional studies suggest that modifiable risk factors for ADRDs offer opportunities for therapeutic and preventive actions.

Effects of long-term unilateral cochlear implant use on large-scale network synchronization in adolescents.

Unilateral cochlear implantation (CI) limits deafness-related changes in the auditory pathways but promotes abnormal cortical preference for the stimulated ear and leaves the opposite ear with little protection from auditory deprivation. In the present study, time-frequency analyses of event-related potentials elicited from stimuli presented to each ear were used to determine effects of unilateral CI use on cortical synchrony. CI-elicited activity in 34 adolescents (15.4±1.9 years of age) who had listened with unilateral CIs for most of their lives prior to bilateral implantation were compared to responses elicited by a 500Hz tone-burst in normal hearing peers. Phase-locking values between 4 and 60Hz were calculated for 171 pairs of 19-cephalic recording electrodes. Ear specific results were found in the normal hearing group: higher synchronization in low frequency bands (theta and alpha) from left ear stimulation in the right hemisphere and more high frequency activity (gamma band) from right ear stimulation in the left hemisphere. In the CI group, increased phase synchronization in the theta and beta frequencies with bursts of gamma activity were elicited by the experienced-right CI between frontal, temporal and parietal cortical regions in both hemispheres, consistent with increased recruitment of cortical areas involved in attention and higher-order processes, potentially to support unilateral listening. By contrast, activity was globally desynchronized in response to initial stimulation of the naïve-left ear, suggesting decoupling of these pathways from the cortical hearing network. These data reveal asymmetric auditory development promoted by unilateral CI use, resulting in an abnormally mature neural network.

Premenstrual Psychosis in an Adolescent: A Case Report.

Premenstrual psychosis is a rare phenomenon initiating during or preceding menses, often lasting one to two weeks after the onset of menses. Previous literature shows links between the estrogen decline of the menstrual cycle's late luteal phase and the worsening of preexisting symptomatology in psychosis. There is thought to be a similar etiology in premenstrual psychosis. Current literature describes mostly clinical cases showing successful treatment using oral contraceptives and/or atypical antipsychotics. We present an adolescent who suffered from a new episode of psychosis beginning just before the onset of menses. Her symptoms abated after the completion of menses and with the initiation of combined oral contraceptives and olanzapine.

Central auditory development after long-term cochlear implant use.

OBJECTIVE: We aimed to determine whether long-term cortical auditory development is altered or delayed in children using cochlear implants relative to their normal hearing peers. We hypothesized that cortical development in children using unilateral cochlear implants follows a normal trajectory with long-term auditory input when the duration of bilateral auditory deprivation in childhood is limited. METHODS: Electrically-evoked cortical responses were recorded in 79 children who received one cochlear implant within 2.03 ± 1.36 years of bilateral deafness and had up to ∼16 years of time-in-sound experience, and in 58 peers with normal hearing. Amplitude differences between the responses from children using cochlear implants and with normal hearing were calculated between 0 and 300 ms. RESULTS: Responses from cochlear implant users remain different from those of their normal hearing peers. These differences decreased over time, but were not eliminated even after 10 years of time-in-sound. Specifically, the P(1)-N(1)-P(2)-N(2) complex, typical of a normally mature response, began to emerge by 10 years of time-in-sound experience, but the amplitudes of peaks P(2) and N(2) became abnormally large. CONCLUSION: Mature-like cortical responses emerge in children after long-term unilateral cochlear implant use, however, differences from normal persist. SIGNIFICANCE: Maturation of cortical responses with long-term cochlear implant use potentially underlies functional improvements in hearing. Persistent differences from normal could reflect an increase in attention or multi-sensory processing during listening.

Benefits and detriments of unilateral cochlear implant use on bilateral auditory development in children who are deaf.

We have explored both the benefits and detriments of providing electrical input through a cochlear implant in one ear to the auditory system of young children. A cochlear implant delivers electrical pulses to stimulate the auditory nerve, providing children who are deaf with access to sound. The goals of implantation are to restrict reorganization of the deprived immature auditory brain and promote development of hearing and spoken language. It is clear that limiting the duration of deprivation is a key factor. Additional considerations are the onset, etiology, and use of residual hearing as each of these can have unique effects on auditory development in the pre-implant period. New findings show that many children receiving unilateral cochlear implants are developing mature-like brainstem and thalamo-cortical responses to sound with long term use despite these sources of variability; however, there remain considerable abnormalities in cortical function. The most apparent, determined by implanting the other ear and measuring responses to acute stimulation, is a loss of normal cortical response from the deprived ear. Recent data reveal that this can be avoided in children by early implantation of both ears simultaneously or with limited delay. We conclude that auditory development requires input early in development and from both ears.

Speech detection in noise and spatial unmasking in children with simultaneous versus sequential bilateral cochlear implants.

OBJECTIVES: To measure speech detection in noise performance for children with bilateral cochlear implants (BiCI), to compare performance in children with simultaneous implant versus those with sequential implant, and to compare performance to normal-hearing children. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary academic pediatric center. PATIENTS: Children with early-onset bilateral deafness and 2-year BiCI experience, comprising the "sequential" group (>2 yr interimplantation delay, n = 12) and "simultaneous group" (no interimplantation delay, n = 10) and normal-hearing controls (n = 8). INTERVENTION: Thresholds to speech detection (at 0-degree azimuth) were measured with noise at 0-degree azimuth or ± 90-degree azimuth. MAIN OUTCOME MEASURES: Spatial unmasking (SU) as the noise condition changed from 0-degree azimuth to ± 90-degree azimuth and binaural summation advantage (BSA) of 2 over 1 CI. RESULTS: Speech detection in noise was significantly poorer than controls for both BiCI groups (p < 0.0001). However, the SU in the simultaneous group approached levels found in normal controls (7.2 ± 0.6 versus 8.6 ± 0.6 dB, p > 0.05) and was significantly better than that in the sequential group (3.9 ± 0.4 dB, p < 0.05). Spatial unmasking was unaffected by the side of noise presentation in the simultaneous group but, in the sequential group, was significantly better when noise was moved to the second rather than the first implanted ear (4.8 ± 0.5 versus 3.0 ± 0.4 dB, p < 0.05). This was consistent with a larger BSA from the sequential group's second rather than first CI. CONCLUSION: Children with simultaneously implanted BiCI demonstrated an advantage over children with sequential implant by using spatial cues to improve speech detection in noise.