Purpose The biological mechanisms underlying developmental stuttering remain unclear. In a previous investigation, we showed that there is significant spatial correspondence between regional gray matter structural anomalies and the expression of genes linked to energy metabolism. In the current study, we sought to further examine the relationship between structural anomalies in the brain in children with persistent stuttering and brain regional energy metabolism. Method High-resolution structural MRI scans were acquired from 26 persistent stuttering and 44 typically developing children. Voxel-based morphometry was used to quantify the between-group gray matter volume (GMV) differences across the whole brain. Group differences in GMV were then compared with published values for the pattern of glucose metabolism measured via F 18 fluorodeoxyglucose uptake in the brains of 29 healthy volunteers using positron emission tomography. Results A significant positive correlation between GMV differences and F 18 fluorodeoxyglucose uptake was found in the left hemisphere (ρ = .36, p < .01), where speech-motor and language processing are typically localized. No such correlation was observed in the right hemisphere (ρ = .05, p = .70). Conclusions Corroborating our previous gene expression studies, the results of the current study suggest a potential connection between energy metabolism and stuttering. Brain regions with high energy utilization may be particularly vulnerable to anatomical changes associated with stuttering. Such changes may be further exacerbated when there are sharp increases in brain energy utilization, which coincides with the developmental period of rapid speech/language acquisition and the onset of stuttering during childhood. Supplemental Material https://doi.org/10.23641/asha.14110454

Early-life blindness causes lasting visual impairment, for which the circuit basis is only partially understood. Degradation of visual connections as well as the network dynamics supporting neural oscillations and arousal states are likely contributors. To define how blindness affects dynamics, we examined the effects of two forms of blindness, bilateral loss of retinal input (enucleation) and degradation of visual input (eyelid-suture), on emergent network properties and their state-dependence in the visual cortex of awake head-fixed mice. Neither form of early visual deprivation fundamentally altered the state-dependent regulation of firing-rates or local field potential oscillations. However, each form of deprivation did cause a unique set of changes in network behavior. Enucleation caused a loss of low-frequency synchronization specifically during movement, suggesting a mouse model for human alpha oscillations. Neurons were also less correlated and fired more regularly, with no change in mean firing rates. Chronic lid-suture decreased firing rates during quiet-wakefulness, but not during movement, and had no effect on neural correlations or firing regularity. Sutured animals also had a broadband increase in LFP power and increased occurrence, but reduced central frequency, of narrowband gamma oscillations. The complementary, rather than additive, effects of lid-suture vs.enucleation suggest that the development of these emergent network properties does not require vision but is plastic to modified input. Our results suggest that the etiology of human blindness will be a crucial determinant of circuit pathology and its capacity to respond to clinical interventions.

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Background Fear learning is an adaptive response to traumatic events and gradual decline of fear response on repeated exposure to stimuli can lead to fear extinction. However, a single presentation of a cue threat can reactive the fear memory through an alternative process called reconsolidation. Here we sought to investigate the role of the renin angiotensin systems (RAS) in reconsolidation to determine whether recent findings from RAS extinction studies in rodents and humans might also be explained by interference with reconsolidation. Methods Using Pavlovian auditory fear conditioning, a single retrieval tone was presented to initiate memory recall. It has been previously shown that fear memories, after retrieval, are in a labile state for a time‐limited window of six hours and require protein synthesis for consolidation. Without any pharmacological intervention, mRNA levels at early (40mins) and late (4hr) phases of reconsolidation were compared to examine gene expression pattern changes in common RAS and plasticity genes in different brain regions during memory reconsolidation. Results To validate our behavior model of single retrieval presentation, we compared the expression of immediate early genes (IEGs) ‐ cfos, Egr‐1 and Arc in the basolateral amygdala (BLA) – critical for fear learning and memory. These IEG’s were induced rapidly at 40mins with 2–3‐fold (p<0.001; n=12) increases in mRNA expression and returned to the baseline within 4hrs comparable to animals which did not receive the retrieval tone. The RAS distribution in the brain follows a distinct pattern which we confirmed in our lab by measuring the expression level of angiotensinogen (Agt) in telencephalon (forebrain) and diencephalon (mid and hindbrain) relative to liver. There is a 3‐fold increase in Agt (p=0.025, n=6) mRNA levels at 40mins. Angiotensin converting enzyme (Ace) mRNA levels decreased by half (p = 0.0169, n=6) and consequently Ace2 levels increased 2‐fold at early reconsolidation phase in BLA. The angiotensin type1 receptor (Agtr1) showed increased expression (p=0.0213, n=10) at 4hrs whereas angiotensin type 2 receptor (Agtr2) had steady rise at both 40mins and 4hrs (p=0.0016, n=10). The BLA mRNA levels for tachykinin receptor 3 (Tac3r), previously shown to modulate fear memory and angiotensin II, was elevated by 3‐fold at both 40mins and 4hrs. We also examined the CA1 hippocampal region, but unlike the BLA, there was no significant change in the expression levels of these. Conclusion Here we identified two distinct pathways for brain RAS in the BLA during a time course of memory reconsolidation, including early phase activation of Ace2 and a later phase increase in angiotensin receptors (Agtr1 and Agtr2) mRNA levels. These data suggest that, similar to transcriptional regulation of IEGs in the BLA, angiotensin‐related genes undergo dynamic regulation during reconsolidation following fear memory retrieval. Support or Funding Information NIH1R01HL137103‐01, AHA15CSA24340001 Evaluation of brain angiotensin and plasticity related ge...