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Some auditory discriminations cannot be acquired by the cat after large bilateral ablations of auditory cortex at maturity. However, if such ablations are sustained during infancy, these discriminations are readily learned. The function of the cortex in auditory discrimination depends on the age of the nervous system at the time of injury.

ObjectiveIdentifying persons with HIV (PWH) at increased risk for Alzheimer's disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.DesignWe examined 92 PWH from the CHARTER Program, ages 45-68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).ResultsAt baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.ConclusionsEpisodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

Associating different aspects of experience with discrete events is critical for human memory. A potential mechanism for linking memory components is phase precession, during which neurons fire progressively earlier in time relative to theta oscillations. However, no direct link between phase precession and memory has been established. Here we recorded single-neuron activity and local field potentials in the human medial temporal lobe while participants (n = 22) encoded and retrieved memories of movie clips. Bouts of theta and phase precession occurred following cognitive boundaries during movie watching and following stimulus onsets during memory retrieval. Phase precession was dynamic, with different neurons exhibiting precession in different task periods. Phase precession strength provided information about memory encoding and retrieval success that was complementary with firing rates. These data provide direct neural evidence for a functional role of phase precession in human episodic memory.

Early stages of Alzheimer's disease (AD) are associated with volume reductions in specific subregions of the medial temporal lobe (MTL). Using a manual segmentation method-the Olsen-Amaral-Palombo (OAP) protocol-previous work in healthy older adults showed that reductions in grey matter volumes in MTL subregions were associated with lower scores on the Montreal Cognitive Assessment (MoCA), suggesting atrophy may occur prior to diagnosis of mild cognitive impairment, a condition that often progresses to AD. However, current "gold standard" manual segmentation methods are labour intensive and time consuming. Here, we examined the utility of Automatic Segmentation of Hippocampal Subfields (ASHS) to detect volumetric differences in MTL subregions of healthy older adults who varied in cognitive status as determined by the MoCA. We trained ASHS on the OAP protocol to create the ASHS-OAP atlas and then examined how well automated segmentation replicated manual segmentation. Volumetric measures obtained from the ASHS-OAP atlas were also contrasted against those from the ASHS-PMC atlas, a widely used atlas provided by the ASHS team. The pattern of volumetric results was similar between the ASHS-OAP atlas and manual segmentation for anterolateral entorhinal cortex and perirhinal cortex, suggesting that ASHS-OAP is a viable alternative to current manual segmentation methods for detecting group differences based on cognitive status. Although ASHS-OAP and ASHS-PMC produced varying volumes for most regions of interest, they both identified early signs of neurodegeneration in CA2/CA3/DG and identified marginal differences in entorhinal cortex. Our findings highlight the utility of automated segmentation methods but still underscore the need for a unified and harmonized MTL segmentation atlas.

IntroductionAlthough frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype.MethodsRetrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments.ResultsCommon symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations.DiscussionThis study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients.HighlightsThis project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

A central assumption of neuroscience is that long-term memories are represented by the same brain areas that encode sensory stimuli1. Neurons in inferotemporal (IT) cortex represent the sensory percept of visual objects using a distributed axis code2-4. Whether and how the same IT neural population represents the long-term memory of visual objects remains unclear. Here we examined how familiar faces are encoded in the IT anterior medial face patch (AM), perirhinal face patch (PR) and temporal pole face patch (TP). In AM and PR we observed that the encoding axis for familiar faces is rotated relative to that for unfamiliar faces at long latency; in TP this memory-related rotation was much weaker. Contrary to previous claims, the relative response magnitude to familiar versus unfamiliar faces was not a stable indicator of familiarity in any patch5-11. The mechanism underlying the memory-related axis change is likely intrinsic to IT cortex, because inactivation of PR did not affect axis change dynamics in AM. Overall, our results suggest that memories of familiar faces are represented in AM and perirhinal cortex by a distinct long-latency code, explaining how the same cell population can encode both the percept and memory of faces.

Self-concept develops during adolescence, but little is known about self-concept in adolescents with autism. This behavioral neuroimaging study investigated (1) self-concept positivity across three domains (academic, physical appearance, and prosocial) and (2) from the perspective of self (direct self-concept) and the perceived perspective of peers (reflected self-concept) in 12- to 16-year-old adolescent males with (n = 35) and without autism (n = 34). These behavioral and neural measures of self-concept were additionally related to autism traits and alexithymia traits across groups. Results showed no general group differences, but more autism traits were related to less positive self-concept ratings in the physical appearance and prosocial domains. More autism traits were also associated with less similarity between direct and reflected prosocial self-concept ratings. Lower self-esteem was additionally explained by alexithymia, specifically the difficulty to identify ones feelings. Participants showed medial prefrontal cortex activation in response to evaluating self-traits in both groups. Region-of-interest analyses revealed that medial prefrontal cortex and right temporal–parietal junction activation were differentially related to alexithymia traits. Together, this study provides a comprehensive understanding of self-concept and self-esteem in adolescents with varying levels autism and alexithymia traits. Developing a positive view of the self is important for maintaining a good mental health, as feeling negative about the self increases the risk of developing internalizing symptoms such as feelings of depression and anxiety. Even though autistic individuals regularly struggle with these internalizing feelings, and both self-concept and internalizing feelings are known to develop during adolescence, there is a lack of studies investigating the development of positive self-concept and self-esteem in autistic adolescents. Here, we studied academic, physical, and prosocial self-concept as well as self-esteem in adolescent males with and without autism on both the behavioral and neural level. We additionally focused on similarities in one's own and peers' perspectives on the self, and we assessed a potential role of alexithymia (i.e. having trouble identifying and describing one's feelings) in developing a more negative view of the self. Results showed that there were no group differences in self-esteem, self-concept, or underlying neural activation. This shows that autistic adolescent males use the same neural processes when they evaluate their traits. However, regardless of clinical diagnosis, a higher number of autism traits was related to a less positive physical and prosocial self-concept, whereas more difficulty identifying one's feelings was related to lowered self-esteem and less activation in medial prefrontal cortex during self-evaluations. Therefore, in treatment of autistic adolescents with low self-esteem, it is important to take into account and possibly aim to improve alexithymic traits as well. [ABSTRACT FROM AUTHOR]

IntroductionMagnetic resonance imaging (MRI) research has advanced our understanding of neurodegeneration in sporadic early-onset Alzheimer's disease (EOAD) but studies include small samples, mostly amnestic EOAD, and have not focused on developing an MRI biomarker.MethodsWe analyzed MRI scans to define the sporadic EOAD-signature atrophy in a small sample (n = 25) of Massachusetts General Hospital (MGH) EOAD patients, investigated its reproducibility in the large longitudinal early-onset Alzheimer's disease study (LEADS) sample (n = 211), and investigated the relationship of the magnitude of atrophy with cognitive impairment.ResultsThe EOAD-signature atrophy was replicated across the two cohorts, with prominent atrophy in the caudal lateral temporal cortex, inferior parietal lobule, and posterior cingulate and precuneus cortices, and with relative sparing of the medial temporal lobe. The magnitude of EOAD-signature atrophy was associated with the severity of cognitive impairment.DiscussionThe EOAD-signature atrophy is a reliable and clinically valid biomarker of AD-related neurodegeneration that could be used in clinical trials for EOAD.HighlightsWe developed an early-onset Alzheimer's disease (EOAD)-signature of atrophy based on magnetic resonance imaging (MRI) scans. EOAD signature was robustly reproducible across two independent patient cohorts. EOAD signature included prominent atrophy in parietal and posterior temporal cortex. The EOAD-signature atrophy was associated with the severity of cognitive impairment. EOAD signature is a reliable and clinically valid biomarker of neurodegeneration.

Individuals with high emotional granularity make fine-grained distinctions between their emotional experiences. To have greater emotional granularity, one must acquire rich conceptual knowledge of emotions and use this knowledge in a controlled and nuanced way. In the brain, the neural correlates of emotional granularity are not well understood. While the anterior temporal lobes, angular gyri, and connected systems represent conceptual knowledge of emotions, inhibitory networks with hubs in the inferior frontal cortex (i.e., posterior inferior frontal gyrus, lateral orbitofrontal cortex, and dorsal anterior insula) guide the selection of this knowledge during emotions. We investigated the structural neuroanatomical correlates of emotional granularity in 58 healthy, older adults (ages 62-84 years), who have had a lifetime to accrue and deploy their conceptual knowledge of emotions. Participants reported on their daily experience of 13 emotions for 8 weeks and underwent structural magnetic resonance imaging. We computed intraclass correlation coefficients across daily emotional experience surveys (45 surveys on average per participant) to quantify each participant's overall emotional granularity. Surface-based morphometry analyses revealed higher overall emotional granularity related to greater cortical thickness in inferior frontal cortex (pFWE < 0.05) in bilateral clusters in the lateral orbitofrontal cortex and extending into the left dorsal anterior insula. Overall emotional granularity was not associated with cortical thickness in the anterior temporal lobes or angular gyri. These findings suggest individual differences in emotional granularity relate to variability in the structural neuroanatomy of the inferior frontal cortex, an area that supports the controlled selection of conceptual knowledge during emotional experiences.

IntroductionWe tested sex-dependent associations of variation in the SNAP-25 gene, which encodes a presynaptic protein involved in hippocampal plasticity and memory, on cognitive and Alzheimer's disease (AD) neuroimaging outcomes in clinically normal adults.MethodsParticipants were genotyped for SNAP-25 rs1051312 (T > C; SNAP-25 expression: C-allele > T/T). In a discovery cohort (N = 311), we tested the sex by SNAP-25 variant interaction on cognition, Aβ-PET positivity, and temporal lobe volumes. Cognitive models were replicated in an independent cohort (N = 82).ResultsIn the discovery cohort, C-allele carriers exhibited better verbal memory and language, lower Aβ-PET positivity rates, and larger temporal volumes than T/T homozygotes among females, but not males. Larger temporal volumes related to better verbal memory only in C-carrier females. The female-specific C-allele verbal memory advantage was evidenced in the replication cohort.ConclusionsIn females, genetic variation in SNAP-25 is associated with resistance to amyloid plaque formation and may support verbal memory through fortification of temporal lobe architecture.HighlightsThe SNAP-25 rs1051312 (T > C) C-allele results in higher basal SNAP-25 expression. C-allele carriers had better verbal memory in clinically normal women, but not men. Female C-carriers had higher temporal lobe volumes, which predicted verbal memory. Female C-carriers also exhibited the lowest rates of amyloid-beta PET positivity. The SNAP-25 gene may influence female-specific resistance to Alzheimer's disease (AD).

Memory consolidation during sleep is thought to depend on the coordinated interplay between cortical slow waves, thalamocortical sleep spindles and hippocampal ripples, but direct evidence is lacking. Here, we implemented real-time closed-loop deep brain stimulation in human prefrontal cortex during sleep and tested its effects on sleep electrophysiology and on overnight consolidation of declarative memory. Synchronizing the stimulation to the active phases of endogenous slow waves in the medial temporal lobe (MTL) enhanced sleep spindles, boosted locking of brain-wide neural spiking activity to MTL slow waves, and improved coupling between MTL ripples and thalamocortical oscillations. Furthermore, synchronized stimulation enhanced the accuracy of recognition memory. By contrast, identical stimulation without this precise time-locking was not associated with, and sometimes even degraded, these electrophysiological and behavioral effects. Notably, individual changes in memory accuracy were highly correlated with electrophysiological effects. Our results indicate that hippocampo-thalamocortical synchronization during sleep causally supports human memory consolidation.

Prior studies in Social Neuroeconomics have consistently reported activation in social cognition regions during interactive economic games, suggesting mentalizing during economic choice. Such mentalizing occurs during active participation in the game, as well as during passive observation of others' interactions. We designed a novel version of the classic false-belief task (FBT) in which participants read vignettes about interactions between agents in the ultimatum and trust games and were subsequently asked to infer the agents' beliefs. We compared activation patterns during the economic games FBT to those during the classic FBT using conjunction analyses. We find significant overlap in the left temporoparietal junction (TPJ) and dorsal medial prefrontal cortex, as well as the temporal pole (TP) during two task phases: belief formation and belief inference. Moreover, generalized Psychophysiological Interaction (gPPI) analyses show that during belief formation, the right TPJ is a target of both the left TPJ and the right TP seed regions, whereas during belief inferences all seed regions show interconnectivity with each other. These results indicate that across different task types and phases, mentalizing is associated with activation and connectivity across central nodes of the social cognition network. Importantly, this is the case for both the novel economic games and the classic FBTs.

Attaching semantic meaning to sensory information received from both inside and outside our bodies is a fundamental function of the human brain. The theory of Controlled Semantic Cognition (CSC) proposes that the formation of semantic knowledge relies on connections between spatially distributed modality-specific spoke-nodes, and a modality-general hub in the anterior temporal lobes (ATLs). This theory can also be applied to social semantic knowledge, though certain domain-specific spoke-nodes may make a disproportionate contribution to the understanding of social concepts. The ATLs have strong connections with spoke-node structures such as the subgenual ACC (sgACC) and the orbitofrontal cortex (OFC) that play an important role in predicting the hedonic value of stimuli. We hypothesized that in addition to the ATL semantic hub, a social semantic task would also require input from hedonic evaluation structures. We used voxel based morphometry (VBM) to examine structural brain-behavior relationships in 152 patients with neurodegeneration (Alzheimer's disease [N = 12], corticobasal syndrome (N = 18], progressive supranuclear palsy [N = 13], behavioral variant frontotemporal dementia [N = 56], and primary progressive aphasia (PPA) [N = 53]) using the Social Interaction Vocabulary Task (SIVT). This task measures the ability to correctly match a social term (e.g. "gossiping") with a visual depiction of that social interaction. As predicted, VBM showed that worse SIVT scores corresponded with volume loss in bilateral ATL semantic hub regions, but also in the sgACC, OFC, caudate and putamen (pFWE

Converging evidence from studies of human and nonhuman animals suggests that the hippocampus contributes to sequence learning by using temporal context to bind sequentially occurring items. The fornix is a white matter pathway containing the major input and output pathways of the hippocampus, including projections from medial septum and to diencephalon, striatum, lateral septum and prefrontal cortex. If the fornix meaningfully contributes to hippocampal function, then individual differences in fornix microstructure might predict sequence memory. Here, we tested this prediction by performing tractography in 51 healthy adults who had undertaken a sequence memory task. Microstructure properties of the fornix were compared with those of tracts connecting medial temporal lobe regions but not predominantly the hippocampus: the Parahippocampal Cingulum bundle (PHC) (conveying retrosplenial projections to parahippocampal cortex) and the Inferior Longitudinal Fasciculus (ILF) (conveying occipital projections to perirhinal cortex). Using principal components analysis, we combined Free-Water Elimination Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging measures obtained from multi-shell diffusion MRI into two informative indices: the first (PC1) capturing axonal packing/myelin and the second (PC2) capturing microstructural complexity. We found a significant correlation between fornix PC2 and implicit reaction-time indices of sequence memory, indicating that greater fornix microstructural complexity is associated with better sequence memory. No such relationship was found with measures from the PHC and ILF. This study highlights the importance of the fornix in aiding memory for objects within a temporal context, potentially reflecting a role in mediating inter-regional communication within an extended hippocampal system.

Background and aimsAbout 1/3 of youth spend more than four hours/day engaged in screen media activity (SMA). This investigation utilized longitudinal brain imaging and mediation analyses to examine relationships among SMA, brain patterns, and internalizing problems.MethodsData from Adolescent Brain Cognitive Development (ABCD) participants with baseline and two-year follow-up structural imaging data that passed quality control (N = 5,166; 2,385 girls) were analyzed. Joint and Individual Variation Explained (JIVE) identified a brain co-development pattern among 221 brain features (i.e., differences in surface area, thickness, or cortical and subcortical gray-matter volume between baseline and two-year-follow-up data). Generalized linear mixed-effect models investigated associations between baseline SMA, structural co-development and internalizing and externalizing psychopathology at two-year follow-up.ResultsSMA at baseline was related to internalizing psychopathology at year 2 (β=0.020,SE=0.008,P=0.014) and a structural co-development pattern (β=0.015,SE=0.007,P=0.029), where the co-development pattern suggested that rates of change in gray-matter volumes of the brainstem, gray-matter volumes and/or cortical thickness measures of bilateral superior frontal, rostral middle frontal, inferior parietal, and inferior temporal regions were more similar than those in other regions. This component partially mediated the relationship between baseline SMA and future internalizing problems (indirect effect = 0.020, P-value = 0.043, proportion mediated: 2.24%).Discussion and conclusionsGreater youth engagement in SMA at ages 9-10 years statistically predicted higher levels of internalizing two years later. This association was mediated by cortical-brainstem circuitry, albeit with relatively small effect sizes. The findings may help delineate processes contributing to internalizing behaviors and assist in identifying individuals at greater risk for such problems.

Recent psychology and neuroscience studies have used tactile stimuli in patients, concluding after their experiments that touch is a sense tightly linked to emotions. In parallel, a new way of seeing films, 4D cinema, has added new stimuli to the traditional audiovisual via, including the tactile vibration. In this work, we have studied the brain activity of audience while viewing a scene filmed and directed by us and with an emotional content, under two different conditions: 1) image + sound, 2) image + sound + vibro-tactile stimulation. We have designed a glove where pulse trains are generated in coin motors at specific moments and recorded 35 viewers' electroencephalograms (EEGs) to evaluate the impact of the vibro-tactile stimulation during the film projection. Hotelling's T-squared results show higher brain intensity if the tactile stimulus is received during the viewing than if no tactile stimulus is injected. Condition 1 participants showed activation in left and right orbitofrontal areas, whereas Condition 2 they also showed activities in right superior frontal and right-medial frontal areas. We conclude that the addition of vibrotactile stimulus increases the brain activity in areas linked with attentional processes, while producing a higher intensity in those related to emotional processes. [ABSTRACT FROM AUTHOR]

Cognitive control deficits are associated with impaired executive functioning in schizophrenia. The Dual Mechanisms of Control framework suggests that proactive control requires sustained dorsolateral prefrontal activity, whereas reactive control marshals a larger network. However, primate studies suggest these processes are maintained by dual-encoding regions. To distinguish between these theories, we compared the distinctiveness of proactive and reactive control functional neuroanatomy. In a reanalysis of data from a previous study, 47 adults with schizophrenia and 56 controls completed the Dot Pattern Expectancy task during an fMRI scan examining proactive and reactive control in frontoparietal and medial temporal regions. Areas suggesting specialized control or between-group differences were tested for association with symptoms and task performance. Elastic net models additionally explored these areas' predictive abilities regarding performance. Most regions were active in both reactive and proactive control. However, evidence of specialized proactive control was found in the left middle and superior frontal gyri. Control participants showed greater proactive control in the left middle and right inferior frontal gyri. Elastic net models moderately predicted task performance and implicated various frontal gyri regions in control participants, with additional involvement of anterior cingulate and posterior parietal regions for reactive control. Elastic nets for patient participants implicated the inferior and superior frontal gyri, and posterior parietal lobe. Specialized cognitive control was unassociated with either performance or schizophrenia symptomatology. Future work is needed to clarify the distinctiveness of proactive and reactive control, and its role in executive deficits in severe psychopathology.

Epileptogenic seizures, or status epilepticus (SE), leads to excitotoxic injury in hippocampal and limbic neurons in the kainic acid (KA) animal model of temporal lobe epilepsy (TLE). Here, we have further characterized neural activity regulated methylaminoisobutryic acid (MeAIB)/glutamine transport activity in mature rat hippocampal neurons in vitro that is inhibited by riluzole (IC50 = 1 μM), an anti-convulsant benzothiazole agent. We screened a library of riluzole derivatives and identified SKA-41 followed by a second screen and synthesized several novel chlorinated aminothiazoles (SKA-377, SKA-378, SKA-379) that are also potent MeAIB transport inhibitors in vitro, and brain penetrant following systemic administration. When administered before KA, SKA-378 did not prevent seizures but still protected the hippocampus and several other limbic areas against SE-induced neurodegeneration at 3d. When SKA-377 - 379, (30 mg/kg) were administered after KA-induced SE, acute neural injury in the CA3, CA1 and CA4/hilus was also largely attenuated. Riluzole (10 mg/kg) blocks acute neural injury. Kinetic analysis of SKA-378 and riluzoles' blockade of Ca2+-regulated MeAIB transport in neurons in vitro indicates that inhibition occurs via a non-competitive, indirect mechanism. Sodium channel NaV1.6 antagonism blocks neural activity regulated MeAIB/Gln transport in vitro (IC50 = 60 nM) and SKA-378 is the most potent inhibitor of NaV1.6 (IC50 = 28 μM) compared to NaV1.2 (IC50 = 118 μM) in heterologous cells. However, pharmacokinetic analysis suggests that sodium channel blockade may not be the predominant mechanism of neuroprotection here. Riluzole and our novel aminothiazoles are agents that attenuate acute neural hippocampal injury following KA-induced SE and may help to understand mechanisms involved in the progression of epileptic disease.

The piriform cortex (PC) is part of the olfactory system, principally receiving input from the lateral olfactory tract and projecting to downstream components of the olfactory network, including the amygdala. Based on preclinical studies, PC is vulnerable to injury and can be easily kindled as an onset site for seizures. While the role of PC in human epilepsy has been studied indirectly and the subject of speculation, cases of demonstrated PC seizure onset from direct intracranial recording are rare. We present a pediatric patient with drug-resistant focal reflex epilepsy and right mesial temporal sclerosis with habitual seizures triggered by coconut aroma. The patient underwent stereoelectroencephalography with implantation of olfactory cortices including PC, through which we identified PC seizure onset, mapped high-frequency activity associated with presentation of olfactory stimuli and performance on cognitive tasks, and reproduced habitual seizures via cortical stimulation of PC. Coconut odor did not trigger seizures in our work with the patient. Surgical workup resulted in resection of the patient's right amygdala, PC, and mesial temporal pole, following which she has been seizure free for 20 months without functional decline in cognition or smell. Histological findings from resected tissue showed astrogliosis and subpial gliosis.

In semantic dementia (SD), asymmetric degeneration of the anterior temporal lobes is associated with loss of semantic knowledge and alterations in socioemotional behavior. There are two clinical variants of SD: semantic variant primary progressive aphasia (svPPA), which is characterized by predominant atrophy in the anterior temporal lobe and insula in the left hemisphere, and semantic behavioral variant frontotemporal dementia (sbvFTD), which is characterized by predominant atrophy in those structures in the right hemisphere. Previous studies of behavioral variant frontotemporal dementia, an associated clinical syndrome that targets the frontal lobes and anterior insula, have found impairments in baseline autonomic nervous system activity that correlate with left-lateralized frontotemporal atrophy patterns and disruptions in socioemotional functioning. Here, we evaluated whether there are similar impairments in resting autonomic nervous system activity in SD that also reflect left-lateralized atrophy and relate to diminished affiliative behavior. A total of 82 participants including 33 people with SD (20 svPPA and 13 sbvFTD) and 49 healthy older controls completed a laboratory-based assessment of respiratory sinus arrhythmia (RSA; a parasympathetic measure) and skin conductance level (SCL; a sympathetic measure) during a two-minute resting baseline period. Participants also underwent structural magnetic resonance imaging, and informants rated their current affiliative behavior on the Interpersonal Adjective Scale. Results indicated that baseline RSA and SCL were lower in SD than in healthy controls, with significant impairments present in both svPPA and sbvFTD. Voxel-based morphometry analyses revealed left-greater-than-right atrophy related to diminished parasympathetic and sympathetic outflow in SD. While left-lateralized atrophy in the mid-to-posterior insula correlated with lower RSA, left-lateralized atrophy in the ventral anterior insula correlated with lower SCL. In SD, lower baseline RSA, but not lower SCL, was associated with lower gregariousness/extraversion. Neither autonomic measure related to warmth/agreeableness, however. Through the assessment of baseline autonomic nervous system physiology, the present study contributes to expanding conceptualizations of the biological basis of socioemotional alterations in svPPA and sbvFTD.

BackgroundIn Alzheimer's disease (AD), the gradual accumulation of amyloid-β (Aβ) and tau proteins may underlie alterations in empathy.ObjectiveTo assess whether tau aggregation in the medial temporal lobes related to differences in cognitive empathy (the ability to take others' perspectives) and emotional empathy (the ability to experience others' feelings) in AD.MethodsOlder adults (n = 105) completed molecular Aβ positron emission tomography (PET) scans. Sixty-eight of the participants (35 women) were Aβ positive and symptomatic with diagnoses of mild cognitive impairment, dementia of the Alzheimer's type, logopenic variant primary progressive aphasia, or posterior cortical atrophy. The remaining 37 (22 women) were asymptomatic Aβ negative healthy older controls. Using the Interpersonal Reactivity Index, we compared current levels of informant-rated cognitive empathy (Perspective-Taking subscale) and emotional empathy (Empathic Concern subscale) in the Aβ positive and negative participants. The Aβ positive participants also underwent molecular tau-PET scans, which were used to investigate whether regional tau burden in the bilateral medial temporal lobes related to empathy.ResultsAβ positive participants had lower perspective-taking and higher empathic concern than Aβ negative healthy controls. Medial temporal tau aggregation in the Aβ positive participants had divergent associations with cognitive and emotional empathy. Whereas greater tau burden in the amygdala predicted lower perspective-taking, greater tau burden in the entorhinal cortex predicted greater empathic concern. Tau burden in the parahippocampal cortex did not predict either form of empathy.ConclusionsAcross AD clinical syndromes, medial temporal lobe tau aggregation is associated with lower perspective-taking yet higher empathic concern.

Speech processing requires extracting meaning from acoustic patterns using a set of intermediate representations based on a dynamic segmentation of the speech stream. Using whole brain mapping obtained in fMRI, we investigate the locus of cortical phonemic processing not only for single phonemes but also for short combinations made of diphones and triphones. We find that phonemic processing areas are much larger than previously described: they include not only the classical areas in the dorsal superior temporal gyrus but also a larger region in the lateral temporal cortex where diphone features are best represented. These identified phonemic regions overlap with the lexical retrieval region, but we show that short word retrieval is not sufficient to explain the observed responses to diphones. Behavioral studies have shown that phonemic processing and lexical retrieval are intertwined. Here, we also have identified candidate regions within the speech cortical network where this joint processing occurs.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and atrophy in the medial temporal lobe (MTL) and subsequent brain regions. Structural magnetic resonance imaging (sMRI) has been widely used in research and clinical care for diagnosis and monitoring AD progression. However, atrophy patterns are complex and vary by patient. To address this issue, researchers have made efforts to develop more concise metrics that can summarize AD-specific atrophy. Many of these methods can be difficult to interpret clinically, hampering adoption. In this study, we introduce a novel index which we call an "AD-NeuroScore," that uses a modified Euclidean-inspired distance function to calculate differences between regional brain volumes associated with cognitive decline. The index is adjusted for intracranial volume (ICV), age, sex, and scanner model. We validated AD-NeuroScore using 929 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study, with a mean age of 72.7 years (SD = 6.3; 55.1-91.5) and cognitively normal (CN), mild cognitive impairment (MCI), or AD diagnoses. Our validation results showed that AD-NeuroScore was significantly associated with diagnosis and disease severity scores (measured by MMSE, CDR-SB, and ADAS-11) at baseline. Furthermore, baseline AD-NeuroScore was associated with both changes in diagnosis and disease severity scores at all time points with available data. The performance of AD-NeuroScore was equivalent or superior to adjusted hippocampal volume (AHV), a widely used metric in AD research. Further, AD-NeuroScore typically performed as well as or sometimes better when compared to other existing sMRI-based metrics. In conclusion, we have introduced a new metric, AD-NeuroScore, which shows promising results in detecting AD, benchmarking disease severity, and predicting disease progression. AD-NeuroScore differentiates itself from other metrics by being clinically practical and interpretable.

BackgroundSocial and language abilities are closely intertwined during early typical development. In autism spectrum disorder (ASD), however, deficits in social and language development are early-age core symptoms. We previously reported that superior temporal cortex, a well-established social and language region, shows reduced activation to social affective speech in ASD toddlers; however, the atypical cortical connectivity that accompanies this deviance remains unknown.MethodsWe collected clinical, eye tracking, and resting-state fMRI data from 86 ASD and non-ASD subjects (mean age 2.3 ± 0.7 years). Functional connectivity of left and right superior temporal regions with other cortical regions and correlations between this connectivity and each child's social and language abilities were examined.ResultsWhile there was no group difference in functional connectivity, the connectivity between superior temporal cortex and frontal and parietal regions was significantly correlated with language, communication, and social abilities in non-ASD subjects, but these effects were absent in ASD subjects. Instead, ASD subjects, regardless of different social or nonsocial visual preferences, showed atypical correlations between temporal-visual region connectivity and communication ability (r(49) = 0.55, p

White matter hyperintensities are a marker of small vessel cerebrovascular disease that are strongly related to cognition in older adults. Similarly, medial temporal lobe atrophy is well-documented in aging and Alzheimer's disease and is associated with memory decline. Here, we assessed the relationship between lobar white matter hyperintensities, medial temporal lobe subregional volumes, and hippocampal memory in older adults. We collected MRI scans in a sample of 139 older adults without dementia (88 females, mean age (SD) = 76.95 (10.61)). Participants were administered the Rey Auditory Verbal Learning Test (RAVLT). Regression analyses tested for associations among medial temporal lobe subregional volumes, regional white matter hyperintensities and memory, while adjusting for age, sex, and education and correcting for multiple comparisons. Increased occipital white matter hyperintensities were related to worse RAVLT delayed recall performance, and to reduced CA1, dentate gyrus, perirhinal cortex (Brodmann area 36), and parahippocampal cortex volumes. These medial temporal lobe subregional volumes were related to delayed recall performance. The association of occipital white matter hyperintensities with delayed recall performance was fully mediated statistically only by perirhinal cortex volume. These results suggest that white matter hyperintensities may be associated with memory decline through their impact on medial temporal lobe atrophy. These findings provide new insights into the role of vascular pathologies in memory loss in older adults and suggest that future studies should further examine the neural mechanisms of these relationships in longitudinal samples.

Studies of interictal EEG functional connectivity in the epileptic brain seek to identify abnormal interactions between brain regions involved in generating seizures, which clinically often is defined by the seizure onset zone (SOZ). However, there is evidence for abnormal connectivity outside the SOZ (NSOZ), and removal of the SOZ does not always result in seizure control, suggesting, in some cases, that the extent of abnormal connectivity indicates a larger seizure network than the SOZ. To better understand the potential differences in interictal functional connectivity in relation to the seizure network and outcome, we computed event connectivity in the theta (4-8 Hz, ThEC), low-gamma (30-55 Hz, LGEC), and high-gamma (65-95 Hz, HGEC) bands from interictal depth EEG recorded in surgical patients with medication-resistant seizures suspected to begin in the temporal lobe. Analysis finds stronger LGEC and HGEC in SOZ than NSOZ of seizure-free (SF) patients (p = 1.10e-9, 0.0217), but no difference in not seizure-free (NSF) patients. There were stronger LGEC and HGEC between mesial and lateral temporal SOZ of SF than NSF patients (p = 0.00114, 0.00205), and stronger LGEC and ThEC in NSOZ of NSF than SF patients (p = 0.0089, 0.0111). These results show that event connectivity is sensitive to differences in the interactions between regions in SOZ and NSOZ and SF and NSF patients. Patients with differential strengths in event connectivity could represent a well-localized seizure network, whereas an absence of differences could indicate a larger seizure network than the one localized by the SOZ and higher likelihood for seizure recurrence.

ObjectiveEpisodic memory impairment and hippocampal pathology are hallmark features of both temporal lobe epilepsy (TLE) and amnestic mild cognitive impairment (aMCI). Pattern separation (PS), which enables the distinction between similar but unique experiences, is thought to contribute to successful encoding and retrieval of episodic memories. Impaired PS has been proposed as a potential mechanism underling episodic memory impairment in aMCI, but this association is less established in TLE. In this study, we examined behavioral PS in patients with TLE and explored whether profiles of performance in TLE are similar to aMCI.MethodPatients with TLE, aMCI, and age-matched, healthy controls (HCs) completed a modified recognition task that relies on PS for the discrimination of highly similar lure items, the Mnemonic Similarity Task (MST). Group differences were evaluated and relationships between clinical characteristics, California Verbal Learning Test-Second Edition scores, and MST performance were tested in the TLE group.ResultsPatients with TLE and aMCI demonstrated poorer PS performance relative to the HCs, but performance did not differ between the two patient groups. Neither the side of seizure focus nor having hippocampal sclerosis affected performance in TLE. However, TLE patients with clinically defined memory impairment showed the poorest performance.ConclusionMemory performance on a task that relies on PS was disrupted to a similar extent in TLE and aMCI. The MST could provide a clinically useful tool for measuring hippocampus-dependent memory impairments in TLE and other neurological disorders associated with hippocampal damage.

Individuals with left temporal lobe epilepsy (TLE) have a higher rate of atypical (i.e., bilateral or right hemisphere) language lateralization compared to healthy controls. In addition, bilinguals have been observed to have a less left-lateralized pattern of language representation. We examined the combined influence of bilingual language experience and side of seizure focus on language lateralization profiles in TLE to determine whether bilingualism promotes re-organization of language networks. Seventy-two monolingual speakers of English (21 left TLE; LTLE, 22 right TLE; RTLE, 29 age-matched healthy controls; HC) and 24 English-dominant bilinguals (6 LTLE, 7 RTLE, 11 HC) completed a lexical-semantic functional MRI task and standardized measures of language in English. Language lateralization was determined using laterality indices based on activations in left vs right homologous perisylvian regions-of-interest (ROIs). In a fronto-temporal ROI, LTLE showed the expected pattern of weaker left language lateralization relative to HC, and monolinguals showed a trend of weaker left language lateralization relative to bilinguals. Importantly, these effects were qualified by a significant group by language status interaction, revealing that bilinguals with LTLE had greater rightward language lateralization relative to monolingual LTLE, with a large effect size particularly in the lateral temporal region. Rightward language lateralization was associated with better language scores in bilingual LTLE. These preliminary findings suggest a combined effect of bilingual language experience and a left hemisphere neurologic insult, which may together increase the likelihood of language re-organization to the right hemisphere. Our data underscore the need to consider bilingualism as an important factor contributing to language laterality in patients with TLE. Bilingualism may be neuroprotective pre-surgically and may mitigate post-surgical language decline following left anterior temporal lobectomy, which will be important to test in larger samples.

Background/Introduction: Widespread network disruption has been hypothesized to be an important predictor of outcomes in patients with refractory temporal lobe epilepsy (TLE). Most studies examining functional network disruption in epilepsy have largely focused on the symmetric bidirectional metrics of the strength of network connections. However, a more complete description of network dysfunction impacts in epilepsy requires an investigation of the potentially more sensitive directional metrics of information flow. Methods: This study describes a whole-brain magnetoencephalography-imaging approach to examine resting-state directional information flow networks, quantified by phase-transfer entropy (PTE), in patients with TLE compared with healthy controls (HCs). Associations between PTE and clinical characteristics of epilepsy syndrome are also investigated. Results: Deficits of information flow were specific to alpha-band frequencies. In alpha band, while HCs exhibit a clear posterior-to-anterior directionality of information flow, in patients with TLE, this pattern of regional information outflow and inflow was significantly altered in the frontal and occipital regions. The changes in information flow within the alpha band in selected brain regions were correlated with interictal spike frequency and duration of epilepsy. Conclusions: Impaired information flow is an important dimension of network dysfunction associated with the pathophysiological mechanisms of TLE.

Decades of research studying the behavioral effects of damage to structures in medial temporal lobe of rhesus monkeys have documented that such damage, particularly damage to the amygdala, causes animals to become hyporesponsive to threat and hyper-social. This phenotype, a subset of the behaviors known as "Klüver-Bucy Syndrome," is one of the most well-known phenomena in behavioral neuroscience. Carrying on the tradition of evaluating hyposensitivity to threat in monkeys with temporal lobe lesions, we evaluated the responses of rhesus monkeys with bilateral ibotenic acid lesions of the amygdala or hippocampus and procedure-matched control animals to the presentation of an unfamiliar human intruder and threatening objects of varying complexity. All animals behaved as expected-calibrating their responses to the ostensible threat value of the stimuli such that they were most responsive to the most potent stimuli and least responsive to the least potent stimuli. Contrary to an earlier report (Mason et al., 2006), lesion status did not impact the pattern of responses across multiple dependent measures (overt behaviors, position in cage, etc.). The only lesion induced difference consistent with hyposensitivity to threat was that monkeys with amygdala lesions retrieved food rewards placed near reptile-like objects more rapidly than did control animals. These findings call into question the assumption that amygdala damage causes robust, stereotyped changes to affective behavior. They also highlight the importance of replication in neuroscientific studies using nonhuman primates. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Human speech perception results from neural computations that transform external acoustic speech signals into internal representations of words. The superior temporal gyrus (STG) contains the nonprimary auditory cortex and is a critical locus for phonological processing. Here, we describe how speech sound representation in the STG relies on fundamentally nonlinear and dynamical processes, such as categorization, normalization, contextual restoration, and the extraction of temporal structure. A spatial mosaic of local cortical sites on the STG exhibits complex auditory encoding for distinct acoustic-phonetic and prosodic features. We propose that as a population ensemble, these distributed patterns of neural activity give rise to abstract, higher-order phonemic and syllabic representations that support speech perception. This review presents a multi-scale, recurrent model of phonological processing in the STG, highlighting the critical interface between auditory and language systems.

ObjectiveEmerging research highlights the importance of basal-temporal cortex, centered on the fusiform gyrus, to both pre-surgical naming ability and post-surgical naming outcomes in temporal lobe epilepsy (TLE). In this study, we investigate whether integrity of the white matter network that interconnects this basal region to the distributed language network affects naming ability and risk for post-surgical naming decline.MethodsPatients with drug-resistant TLE were recruited from two epilepsy centers in a prospective longitudinal study. The pre-surgical dataset included 50 healthy controls, 47 left TLE (L-TLE), and 41 right TLE (R-TLE) patients. All participants completed pre-surgical T1- and diffusion-weighted MRI (dMRI), as well as neuropsychological tests of auditory and visual naming. Nineteen L-TLE and 18 R-TLE patients underwent anterior temporal lobectomy (ATL) and also completed post-surgical neuropsychological testing. Pre-surgical fractional anisotropy (FA) of the white matter directly beneath the fusiform neocortex (i.e., superficial white matter; SWM) and of deep white matter tracts with connections to the basal-temporal cortex [inferior longitudinal fasciculus (ILF) and inferior frontal occipital fasciculus (IFOF)] was calculated. Clinical variables, hippocampal volume, and FA of each white matter tract or region were examined in linear regressions with naming scores, or change in naming scores, as the primary outcomes.ResultsPre-surgically, higher FA in the bilateral ILF, bilateral IFOF, and left fusiform SWM was associated with better visual and auditory naming scores (all ps

Roughly two-thirds of all people report having experienced déjà vu-the odd feeling that a current experience is both novel and a repeat or replay of a previous, unrecalled experience. Reports of an association between déjà vu and seizure aura symptomatology have accumulated for over a century, and frequent déjà vu is also now known to be associated with focal seizures, particularly those of a medial temporal lobe (MTL) origin. A longstanding question is whether seizure-related déjà vu has the same basis and is the same subjective experience as non-seizure déjà vu. Survey research suggests that people who experience both seizure-related and non-seizure déjà vu can often subjectively distinguish between the two. We present a case of a person with a history of focal MTL seizures who reports having experienced both seizure-related and non-seizure common déjà vu, though the non-seizure type was more frequent during this person's youth than it is currently. The patient was studied with a virtual tour paradigm that has previously been shown to elicit déjà vu among non-clinical, young adult participants. The patient reported experiencing déjà vu of the common non-seizure type during the virtual tour paradigm, without associated abnormalities of the intracranial EEG. We situate this work in the context of broader ongoing projects examining the subjective correlates of seizures. The importance for memory research of virtual scenes, spatial tasks, virtual reality (VR), and this paradigm for isolating familiarity in the context of recall failure are discussed.

Naming of nouns and verbs can be selectively impaired in neurological disorders, but the specificity of the neural and cognitive correlates of such dissociation remains unclear. Functional imaging and stroke research sought to identify cortical regions selectively recruited for nouns versus verbs, yet findings are inconsistent. The present study investigated this issue in neurodegenerative diseases known to selectively affect different brain networks, thus providing new critical evidence of network specificity. We examined naming performances on nouns and verbs in 146 patients with different neurodegenerative syndromes (Primary Progressive Aphasia - PPA, Alzheimer's disease - AD, and behavioral variant Frontotemporal Dementia - FTD) and 30 healthy adults. We then correlated naming scores with MRI-derived cortical thickness values as well as with performances in semantic and syntactic tasks, across all subjects. Results indicated that patients with the semantic variant PPA named significantly fewer nouns than verbs. Instead, nonfluent/agrammatic PPA patients named fewer verbs than nouns. Across all subjects, performance on nouns (adjusted for verbs) specifically correlated with cortical atrophy in left anterior temporal regions, and performance on verbs (adjusted for nouns) with atrophy in left inferior and middle frontal, inferior parietal and posterior temporal regions. Furthermore, lower lexical-semantic abilities correlated with deficits in naming both nouns and verbs, while lower syntactic abilities only correlated with naming verbs. Our results show that different neural and cognitive mechanisms underlie naming of specific grammatical categories in neurodegenerative diseases. Importantly, our findings showed that verb processing depends on a widespread perisylvian networks, suggesting that some regions might be involved in processing different types of action knowledge. These findings have important implications for early differential diagnosis of neurodegenerative disorders.

BackgroundProsopagnosia is a rare neurological condition characterized by the impairment of face perception with preserved visual processing and cognitive functioning and is associated with injury to the fusiform gyrus and inferior longitudinal fasciculus (ILF). Reports of this clinical impairment following resection of right temporal lobe diffuse gliomas in the absence of contralateral injury are exceedingly scarce and not expected as a complication of surgery.ObservationsThe authors describe the case of a young female patient found to have an incidental diffuse glioma in the right inferior temporal lobe despite evidence of preoperative ILF disruption by the tumor. Following resection of the lesion, despite the preoperative disruption to the ILF by the tumor, the patient developed prosopagnosia. There was no evidence of contralateral, left-sided ILF injury.LessonsGiven the significant functional impairment associated with prosopagnosia, neurosurgeons should be aware of the exceedingly rare possibility of a visual-processing deficit following unilateral and, in this case, right-sided inferior temporal lobe glioma resections. More investigation is needed to determine whether preoperative testing can determine dominance of facial-processing networks for patients with lesions in the right inferior posterior temporooccipital lobe and whether intraoperative mapping could help prevent this complication.

Pattern separation, the ability to differentiate new information from previously experienced similar information, is highly sensitive to hippocampal structure and function and declines with age. Functional MRI studies have demonstrated hippocampal hyperactivation in older adults compared to young, with greater task-related activation associated with worse pattern separation performance. The current study was designed to determine whether pattern separation was sensitive to differences in task-free hippocampal cerebral blood flow (CBF) in 130 functionally intact older adults. Given prior evidence that apolipoprotein E e4 (APOE e4) status moderates the relationship between CBF and episodic memory, we predicted a stronger negative relationship between hippocampal CBF and pattern separation in APOE e4 carriers. An interaction between APOE group and right hippocampal CBF was present, such that greater right hippocampal CBF was related to better lure discrimination in noncarriers, whereas the effect reversed directionality in e4 carriers. These findings suggest that neurovascular changes in the medial temporal lobe may underlie memory deficits in cognitively normal older adults who are APOE e4 carriers.

Aging entails a multifaceted complex of changes in macro- and micro-structural properties of human brain gray matter (GM) and white matter (WM) tissues, as well as in intellectual abilities. To better capture tissue-specific brain aging, we combined volume and distribution properties of diffusivity indices to derive subject-specific age scores for each tissue. We compared age-related variance between younger and older adults for GM and WM age scores, and tested whether tissue-specific age scores could explain different effects of aging on fluid (Gf) and crystalized (Gc) intelligence in younger and older adults. Chronological age was strongly associated with GM (R2 = 0.73) and WM (R2 = 0.57) age scores. The GM age score accounted for significantly more variance in chronological age in younger relative to older adults (p

Objective we evaluated whether memory recall following an extended (1 week) delay predicts cognitive and brain structural trajectories in older adultsMethodClinically normal older adults (52-92 years old) were followed longitudinally for up to 8 years after completing a memory paradigm at baseline [Story Recall Test (SRT)] that assessed delayed recall at 30 min and 1 week. Subsets of the cohort underwent neuroimaging (N = 134, mean age = 75) and neuropsychological testing (N = 178-207, mean ages = 74-76) at annual study visits occurring approximately 15-18 months apart. Mixed-effects regression models evaluated if baseline SRT performance predicted longitudinal changes in gray matter volumes and cognitive composite scores, controlling for demographics.ResultsWorse SRT 1-week recall was associated with more precipitous rates of longitudinal decline in medial temporal lobe volumes (p = .037), episodic memory (p = .003), and executive functioning (p = .011), but not occipital lobe or total gray matter volumes (demonstrating neuroanatomical specificity; p > .58). By contrast, SRT 30-min recall was only associated with longitudinal decline in executive functioning (p = .044).ConclusionsMemory paradigms that capture longer-term recall may be particularly sensitive to age-related medial temporal lobe changes and neurodegenerative disease trajectories. (JINS, 2020, xx, xx-xx).

Decades of electrophysiological research on top-down control converge on the role of the lateral frontal cortex in facilitating attention to behaviorally relevant external inputs. However, the involvement of frontal cortex in the top-down control of attention directed to the external versus internal environment remains poorly understood. To address this, we recorded intracranial electrocorticography while subjects directed their attention externally to tones and responded to infrequent target tones, or internally to their own thoughts while ignoring the tones. Our analyses focused on frontal and temporal cortices. We first computed the target effect, as indexed by the difference in high frequency activity (70-150 Hz) between target and standard tones. Importantly, we then compared the target effect between external and internal attention, reflecting a top-down attentional effect elicited by task demands, in each region of interest. Both frontal and temporal cortices showed target effects during external and internal attention, suggesting this effect is present irrespective of attention states. However, only the frontal cortex showed an enhanced target effect during external relative to internal attention. These findings provide electrophysiological evidence for top-down attentional modulation in the lateral frontal cortex, revealing preferential engagement with external attention.

Hippocampal circuit alterations that differentially affect hippocampal subfields are associated with age-related memory decline. Additionally, functional organization along the longitudinal axis of the hippocampus has revealed distinctions between anterior and posterior (A-P) connectivity. Here, we examined the functional connectivity (FC) differences between young and older adults at high-resolution within the medial temporal lobe network (entorhinal, perirhinal, and parahippocampal cortices), allowing us to explore how hippocampal subfield connectivity across the longitudinal axis of the hippocampus changes with age. Overall, we found reliably greater connectivity for younger adults than older adults between the hippocampus and parahippocampal cortex (PHC) and perirhinal cortex (PRC). This drop in functional connectivity was more pronounced in the anterior regions of the hippocampus than the posterior ones, consistent for each of the hippocampal subfields. Further, intra-hippocampal connectivity also reflected an age-related decrease in functional connectivity within the anterior hippocampus in older adults that was offset by an increase in posterior hippocampal functional connectivity. Interestingly, the anterior-posterior dysfunction in older adults between hippocampus and PHC was predictive of lure discrimination performance on the Mnemonic similarity task (MST), suggesting a role in memory performance. While age-related dysfunction within the hippocampal subfields has been well-documented, these results suggest that the age-related dysfunction in hippocampal connectivity across the longitudinal axis may also contribute significantly to memory decline in older adults.

Introduction: One of the most challenging symptoms of aphasia is an impairment in auditory comprehension. The inability to understand others has a direct impact on a person's quality of life and ability to benefit from treatment. Despite its importance, limited research has examined the recovery pattern of auditory comprehension and instead has focused on aphasia recovery more generally. Thus, little is known about the time frame for auditory comprehension recovery following stroke, and whether specific neurologic and demographic variables contribute to recovery and outcome. Methods: This study included 168 left hemisphere chronic stroke patients stroke patients with auditory comprehension impairments ranging from mild to severe. Univariate and multivariate lesion-symptom mapping (LSM) was used to identify brain regions associated with auditory comprehension outcomes on three different tasks: Single-word comprehension, yes/no sentence comprehension, and comprehension of sequential commands. Demographic variables (age, gender, and education) were also examined for their role in these outcomes. In a subset of patients who completed language testing at two or more time points, we also analyzed the trajectory of recovery in auditory comprehension using survival curve-based time compression. Results: LSM analyses revealed that poor single-word auditory comprehension was associated with lesions involving the left mid- to posterior middle temporal gyrus, and portions of the angular and inferior-middle occipital gyri. Poor yes/no sentence comprehension was associated almost exclusively with the left mid-posterior middle temporal gyrus. Poor comprehension of sequential commands was associated with lesions in the left posterior middle temporal gyrus. There was a small region of convergence between the three comprehension tasks, in the very posterior portion of the left middle temporal gyrus. The recovery analysis revealed that auditory comprehension scores continued to improve beyond the first year post-stroke. Higher education was associated with better outcome on all auditory comprehension tasks. Age and gender were not associated with outcome or recovery slopes. Conclusions: The current findings suggest a critical role for the posterior left middle temporal gyrus in the recovery of auditory comprehension following stroke, and that spontaneous recovery of auditory comprehension can continue well beyond the first year post-stroke.

Recent work has conceptualized the brain as a network comprised of groups of sub-networks or modules. "Flexibility" of brain network(s) indexes the dynamic reconfiguration of comprising modules. Using novel techniques from dynamic network neuroscience applied to high-resolution resting-state functional magnetic resonance imaging (fMRI), the present study investigated the effects of an aerobic exercise intervention on the dynamic rearrangement of modular community structure-a measure of neural flexibility-within the medial temporal lobe (MTL) network. The MTL is one of the earliest brain regions impacted by Alzheimer's disease. It is also a major site of neuroplasticity that is sensitive to the effects of exercise. In a two-group non-randomized, repeated measures and matched control design with 34 healthy older adults, we observed an exercise-related increase in flexibility within the MTL network. Furthermore, MTL network flexibility mediated the beneficial effect aerobic exercise had on mnemonic flexibility, as measured by the ability to generalize past learning to novel task demands. Our results suggest that exercise exerts a rehabilitative and protective effect on MTL function, resulting in dynamically evolving networks of regions that interact in complex communication patterns. These reconfigurations may underlie exercise-induced improvements on cognitive measures of generalization, which are sensitive to subtle changes in the MTL.

We report neuropsychological and neuropathological findings for a patient (A.B.), who developed memory impairment after a cardiac arrest at age 39. A.B. was a clinical psychologist who, although unable to return to work, was an active participant in our neuropsychological studies for 24 y. He exhibited a moderately severe and circumscribed impairment in the formation of long-term, declarative memory (anterograde amnesia), together with temporally graded retrograde amnesia covering ∼5 y prior to the cardiac arrest. More remote memory for both facts and autobiographical events was intact. His neuropathology was extensive and involved the medial temporal lobe, the diencephalon, cerebral cortex, basal ganglia, and cerebellum. In the hippocampal formation, there was substantial cell loss in the CA1 and CA3 fields, the hilus of the dentate gyrus (with sparing of granule cells), and the entorhinal cortex. There was also cell loss in the CA2 field, but some remnants remained. The amygdala demonstrated substantial neuronal loss, particularly in its deep nuclei. In the thalamus, there was damage and atrophy of the anterior nuclear complex, the mediodorsal nucleus, and the pulvinar. There was also loss of cells in the medial and lateral mammillary nuclei in the hypothalamus. We suggest that the neuropathology resulted from two separate factors: the initial cardiac arrest (and respiratory distress) and the recurrent seizures that followed, which led to additional damage characteristic of temporal lobe epilepsy.

PurposeAlthough magnetic resonance imaging (MRI) and 18F-2-fluorodeoxyglucose-positron emission tomography (FDG-PET) are used for pre-surgical assessment of focal cortical dysplasia (FCD), they often disagree. This study aimed to identify factors that contribute to discrepancies in FCD imaging between MRI and FDG-PET.MethodsSixty-two patients (mean age, 18.9 years) with a FCD type I or II were retrospectively selected. These patients were visually categorized into two groups: 1) extent of PET abnormality larger than MRI abnormality and 2) vice versa or equivalent. Predictive factors of these two groups were analyzed by multivariate logistic regression. The extent of hypometabolic transient zone surrounding FCDs and their mean standardized uptake values were measured and compared by the Mann-Whitney U-test.ResultsFCDs were detected on MRI and PET in 46 and 55 patients, respectively, whereas no abnormality was detected in 4 patients. The PET hypometabolic areas were larger than the MRI abnormal areas in 26 patients (88 % in the temporal lobe), whereas the PET hypometabolic areas were equivalent or smaller than the MRI abnormal areas in 32 patients (69 % in the frontal lobe). The temporal lobe location was an independent predictor for differentiating the two groups (OR = 35.2, 95 % CI = 6.81-168.0, P < .001). The temporal lobe lesions had significantly wider transient zones and lower standardized uptake values than those in the other lobes (P < .001, both).ConclusionThe discrepancies between MRI and FDG-PET findings of FCD were associated with temporal lobe location.