Rate of Correction and All-Cause Mortality in Patients With Severe Hypernatremia.

Importance: Hypernatremia is common among hospitalized patients and is associated with high mortality rates. Current guidelines suggest avoiding fast correction rates but are not supported by robust data. Objective: To investigate whether there is an association between hypernatremia correction rate and patient survival. Design, Setting, and Participants: This retrospective cohort study examined data from all patients admitted to the Tel Aviv Medical Center between 2007 and 2021 who were diagnosed with severe hypernatremia (serum sodium ≥155 mmol/L) at admission or during hospitalization. Statistical analysis was performed from April 2022 to August 2023. Exposure: Patients were grouped as having fast correction rates (>0.5 mmol/L/h) and slow correction rates (≤0.5 mmol/L/h) in accordance with current guidelines. Main Outcomes and Measures: All-cause 30-day mortality. Results: A total of 4265 patients were included in this cohort, of which 2621 (61.5%) were men and 343 (8.0%) had fast correction rates; the median (IQR) age at diagnosis was 78 (64-87) years. Slow correction was associated with higher 30-day mortality compared with fast correction (50.7% [1990 of 3922] vs 31.8% [109 of 343]; P < .001). These results remained significant after adjusting for demographics (age, gender), Charlson comorbidity index, initial sodium, potassium, and creatinine levels, hospitalization in an ICU, and severe hyperglycemia (adjusted odds ratio [aOR], 2.02 [95% CI, 1.55-2.62]), regardless of whether hypernatremia was hospital acquired (aOR, 2.19 [95% CI, 1.57-3.05]) or documented on admission (aOR, 1.64 [95% CI, 1.06-2.55]). There was a strong negative correlation between absolute sodium correction during the first 24 hours following the initial documentation of severe hypernatremia and 30-day mortality (Pearson correlation coefficient, -0.80 [95% CI, -0.93 to -0.50]; P < .001). Median (IQR) hospitalization length was shorter for fast correction vs slow correction rates (5.0 [2.1-14.9] days vs 7.2 [3.5-16.1] days; P < .001). Prevalence of neurological complications was comparable for both groups, and none were attributed to fast correction rates of hypernatremia. Conclusions and Relevance: This cohort study of patients with severe hypernatremia found that rapid correction of hypernatremia was associated with shorter hospitalizations and significantly lower patient mortality without any signs of neurologic complications. These results suggest that physicians should consider the totality of evidence when considering the optimal rates of correction for patients with severe hypernatremia.

The Temporal Association Cortex Plays a Key Role in Auditory-Driven Maternal Plasticity.

Mother-infant bonding develops rapidly following parturition and is accompanied by changes in sensory perception and behavior. Here, we study how ultrasonic vocalizations (USVs) are represented in the brain of mothers. Using a mouse line that allows temporally controlled genetic access to active neurons, we find that the temporal association cortex (TeA) in mothers exhibits robust USV responses. Rabies tracing from USV-responsive neurons reveals extensive subcortical and cortical inputs into TeA. A particularly dominant cortical source of inputs is the primary auditory cortex (A1), suggesting strong A1-to-TeA connectivity. Chemogenetic silencing of USV-responsive neurons in TeA impairs auditory-driven maternal preference in a pup-retrieval assay. Furthermore, dense extracellular recordings from awake mice reveal changes of both single-neuron and population responses to USVs in TeA, improving discriminability of pup calls in mothers compared with naive females. These data indicate that TeA plays a key role in encoding and perceiving pup cries during motherhood.

Neural Correlates of Learning Pure Tones or Natural Sounds in the Auditory Cortex.

Associative learning of pure tones is known to cause tonotopic map expansion in the auditory cortex (ACx), but the function this plasticity sub-serves is unclear. We developed an automated training platform called the "Educage," which was used to train mice on a go/no-go auditory discrimination task to their perceptual limits, for difficult discriminations among pure tones or natural sounds. Spiking responses of excitatory and inhibitory parvalbumin (PV+) L2/3 neurons in mouse ACx revealed learning-induced overrepresentation of the learned frequencies, as expected from previous literature. The coordinated plasticity of excitatory and inhibitory neurons supports a role for PV+ neurons in homeostatic maintenance of excitation-inhibition balance within the circuit. Using a novel computational model to study auditory tuning curves, we show that overrepresentation of the learned tones does not necessarily improve discrimination performance of the network to these tones. In a separate set of experiments, we trained mice to discriminate among natural sounds. Perceptual learning of natural sounds induced "sparsening" and decorrelation of the neural response, consequently improving discrimination of these complex sounds. This signature of plasticity in A1 highlights its role in coding natural sounds.