Generalization and discrimination of inhibitory avoidance differentially engage anterior and posterior retrosplenial subregions.

Introduction: In a variety of behavioral procedures animals will show selective fear responding in shock-associated contexts, but not in other contexts. However, several factors can lead to generalized fear behavior, where responding is no longer constrained to the conditioning context and will transfer to novel contexts. Methods: Here, we assessed memory generalization using an inhibitory avoidance paradigm to determine if generalized avoidance behavior engages the retrosplenial cortex (RSC). Male and female Long Evans rats received inhibitory avoidance training prior to testing in the same context or a shifted context in two distinct rooms; one room that had fluorescent lighting (Light) and one that had red LED lighting (Dark). Results: We found that animals tested in a light context maintained context-specificity; animals tested in the same context as training showed longer latencies to cross and animals tested in the shifted context showed shorter latencies to cross. However, animals tested in the dark generalized their avoidance behavior; animals tested in the same context and animals tested in the shifted context showed similarly-high latencies to cross. We next examined expression of the immediate early gene zif268 and perineuronal nets (PNNs) following testing and found that while activity in the basolateral amygdala corresponded with overall levels of avoidance behaviors, anterior RSC (aRSC) activity corresponded with learned avoidance generally, but posterior RSC (pRSC) activity seemed to correspond with generalized memory. PNN reduction in the RSC was associated with memory formation and retrieval, suggesting a role for PNNs in synaptic plasticity. Further, PNNs did not reduce in the RSC in animals who showed a generalized avoidance behavior, in line with their hypothesized role in memory consolidation. Discussion: These findings suggest that there is differential engagement of retrosplenial subregions along the rostrocaudal axis to generalization and discrimination.

Diffusion-Weighted Imaging in Mild Traumatic Brain Injury: A Systematic Review of the Literature.

There is evidence that diffusion-weighted imaging (DWI) is able to detect tissue alterations following mild traumatic brain injury (mTBI) that may not be observed on conventional neuroimaging; however, findings are often inconsistent between studies. This systematic review assesses patterns of differences in DWI metrics between those with and without a history of mTBI. A PubMed literature search was performed using relevant indexing terms for articles published prior to May 14, 2020. Findings were limited to human studies using DWI in mTBI. Articles were excluded if they were not full-length, did not contain original data, if they were case studies, pertained to military populations, had inadequate injury severity classification, or did not report post-injury interval. Findings were reported independently for four subgroups: acute/subacute pediatric mTBI, acute/subacute adult mTBI, chronic adult mTBI, and sport-related concussion, and all DWI acquisition and analysis methods used were included. Patterns of findings between studies were reported, along with strengths and weaknesses of the current state of the literature. Although heterogeneity of sample characteristics and study methods limited the consistency of findings, alterations in DWI metrics were most commonly reported in the corpus callosum, corona radiata, internal capsule, and long association pathways. Many acute/subacute pediatric studies reported higher FA and lower ADC or MD in various regions. In contrast, acute/subacute adult studies most commonly indicate lower FA within the context of higher MD and RD. In the chronic phase of recovery, FA may remain low, possibly indicating overall demyelination or Wallerian degeneration over time. Longitudinal studies, though limited, generally indicate at least a partial normalization of DWI metrics over time, which is often associated with functional improvement. We conclude that DWI is able to detect structural mTBI-related abnormalities that may persist over time, although future DWI research will benefit from larger samples, improved data analysis methods, standardized reporting, and increasing transparency.

Surface-based abnormalities of the executive frontostriatial circuit in pediatric TBI.

Childhood traumatic brain injury (TBI) is one of the most common causes of acquired disability and has significant implications for executive functions (EF), such as impaired attention, planning, and initiation that are predictive of everyday functioning. Evidence has suggested attentional features of executive functioning require behavioral flexibility that is dependent on frontostriatial circuitry. The purpose of this study was to evaluate surface-based deformation of a specific frontostriatial circuit in pediatric TBI and its role in EF. Regions of interest included: the dorsolateral prefrontal cortex (DLPFC), caudate nucleus, globus pallidus, and the mediodorsal nucleus of the thalamus (MD). T1-weighted magnetic resonance images were obtained in a sample of children ages 8-13 with complicated mild, moderate, or severe TBI (n = 32) and a group of comparison children with orthopedic injury (OI; n = 30). Brain regions were characterized using high-dimensional surface-based brain mapping procedures. Aspects of EF were assessed using select subtests from the Test of Everyday Attention for Children (TEA-Ch). General linear models tested group and hemisphere differences in DLPFC cortical thickness and subcortical shape of deep-brain regions; Pearson correlations tested relationships with EF. Main effects for group were found in both cortical thickness of the DLPFC (F1,60 = 4.30, p = 0.042) and MD mean deformation (F1,60 = 6.50, p = 0.01) all with lower values in the TBI group. Statistical surface maps revealed significant inward deformation on ventral-medial aspects of the caudate in TBI relative to OI, but null results in the globus pallidus. No significant relationships between EF and any region of interest were observed. Overall, findings revealed abnormalities in multiple aspects of a frontostriatial circuit in pediatric TBI, which may reflect broader pathophysiological mechanisms. Increased consideration for the role of deep-brain structures in pediatric TBI can aid in the clinical characterization of anticipated long-term developmental effects of these individuals.