Rhinal Regions Research Articles

Association of Loneliness with Functional Connectivity MRI, Amyloid-β PET, and Tau PET Neuroimaging Markers of Vulnerability for Alzheimer's Disease.

Loneliness has been declared an "epidemic" associated with negative physical, mental, and cognitive health outcomes such as increased dementia risk. Less is known about the relationship between loneliness and advanced neuroimaging correlates of Alzheimer's disease (AD). To assess whether loneliness was associated with advanced neuroimaging markers of AD using neuroimaging data from Framingham Heart Study (FHS) participants without dementia. In this cross-sectional observational analysis, we used functional connectivity MRI (fcMRI), amyloid-β (Aβ) PET, and tau PET imaging data collected between 2016 and 2019 on eligible FHS cohort participants. Loneliness was defined as feeling lonely at least one day in the past week. The primary fcMRI marker was Default Mode Network intra-network connectivity. The primary PET imaging markers were Aβ deposition in precuneal and FLR (frontal, lateral parietal and lateral temporal, retrosplenial) regions, and tau deposition in the amygdala, entorhinal, and rhinal regions. Of 381 participants (mean age 58 [SD 10]) who met inclusion criteria for fcMRI analysis, 5% were classified as lonely (17/381). No association was observed between loneliness status and network changes. Of 424 participants (mean age 58 [SD = 10]) meeting inclusion criteria for PET analyses, 5% (21/424) were lonely; no associations were observed between loneliness and either Aβ or tau deposition in primary regions of interest. In this cross-sectional study, there were no observable associations between loneliness and select fcMRI, Aβ PET, and tau PET neuroimaging markers of AD risk. These findings merit further investigation in prospective studies of community-based cohorts.

Association of Neurotrophic Factors at Midlife With In Vivo Measures of β-Amyloid and Tau Burden 15 Years Later in Dementia-Free Adults.

Neurotrophic factors (NTFs) play an important role in Alzheimer disease (AD) pathophysiology. Brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) are important NTFs. However, a direct link of BDNF and VEGF circulating levels with in vivo measures of amyloid-β (Aβ) and tau burden remains to be elucidated. We explored the relationship of BDNF and VEGF serum levels with future brain Aβ and tau pathology in a cohort of cognitively healthy, predominantly middle-aged adults and tested for possible effect modifications by sex and menopausal status. This cross-sectional analysis was conducted using data from the Framingham Heart Study (FHS), a community-based cohort study. The study sample included cognitively healthy participants from the FHS Offspring and Third-generation cohorts. BDNF and VEGF were measured in the third-generation cohort during examination cycles 2 (2005-2008) and 1 (2002-2005), respectively, and in the offspring cohort during examination cycle 7 (1998-2001). Participants underwent 11C-Pittsburgh compound B amyloid and 18F-Flortaucipir tau-PET imaging (2015-2021). Linear regression models were used to assess the relationship of serum BDNF and VEGF levels with regional tau and global Aβ, adjusting for potential confounders. Interactions with sex and menopausal status were additionally tested. The sample included 414 individuals (mean age = 41 ± 9 years; 51% female). Continuous measures of BDNF and VEGF were associated with tau signal in the rhinal region after adjustment for potential confounders (β = -0.15 ± 0.06, p = 0.018 and β = -0.19 ± 0.09, p = 0.043, respectively). High BDNF (≥32,450 pg/mL) and VEGF (≥488 pg/mL) levels were significantly related to lower rhinal tau (β = -0.27 ± 0.11, p = 0.016 and β = -0.40 ± 0.14, p = 0.004, respectively) and inferior temporal tau (β = -0.24 ± 0.11, p = 0.028 and β = -0.26 ± 0.13, p = 0.049, respectively). The BDNF-rhinal tau association was observed only among male individuals. Overall, BDNF and VEGF were not associated with global amyloid; however, high VEGF levels were associated with lower amyloid burden in postmenopausal women (β = -1.96 ± 0.70, p = 0.013, per 1 pg/mL). This study demonstrates a robust association between BDNF and VEGF serum levels with in vivo measures of tau almost 2 decades later. These findings add to mounting evidence from preclinical studies suggesting a role of NTFs as valuable blood biomarkers for AD risk prediction.

Neural Correlates of Confidence during Item Recognition and Source Memory Retrieval: Evidence for Both Dual-process and Strength Memory Theories

Although the medial-temporal lobes (MTL), PFC, and parietal cortex are considered primary nodes in the episodic memory network, there is much debate regarding the contributions of MTL, PFC, and parietal subregions to recollection versus familiarity (dual-process theory) and the feasibility of accounts on the basis of a single memory strength process (strength theory). To investigate these issues, the current fMRI study measured activity during retrieval of memories that differed quantitatively in terms of strength (high vs. low-confidence trials) and qualitatively in terms of recollection versus familiarity (source vs. item memory tasks). Support for each theory varied depending on which node of the episodic memory network was considered. Results from MTL best fit a dual-process account, as a dissociation was found between a right hippocampal region showing high-confidence activity during the source memory task and bilateral rhinal regions showing high-confidence activity during the item memory task. Within PFC, several left-lateralized regions showed greater activity for source than item memory, consistent with recollective orienting, whereas a right-lateralized ventrolateral area showed low-confidence activity in both tasks, consistent with monitoring processes. Parietal findings were generally consistent with strength theory, with dorsal areas showing low-confidence activity and ventral areas showing high-confidence activity in both tasks. This dissociation fits with an attentional account of parietal functions during episodic retrieval. The results suggest that both dual-process and strength theories are partly correct, highlighting the need for an integrated model that links to more general cognitive theories to account for observed neural activity during episodic memory retrieval.

Slow Potentials in the Rhinal Region of the Cat Brain Cortex Related to Visual Recognition Memory

We examined correlation between the development of slow potentials in the rhinal cortical region of cats and results of behavioral testing of visual recognition memory of these animals in the “delayed nonmatching-to-sample” (DNMS) selection version. Among different types of cognitive memory, the recognition memory occupies a special position because the process of taking off (retrieval) of a memory trace from the “stores” can be completely and effectively controlled by the experimenter (this process is initiated only after repetitive presentation of a stimulus identical to that whose trace should be subjected to retrieval or after presentation of an absolutely new stimulus whose trace had not been formed earlier). Recording of the field potentials was performed from the surface of the rhinal cortex using stereotaxically implanted mono- or bipolar Ag-AgCl electrodes after the experimental animals reached a sufficiently high level of successful performance of the test for recognition memory. Analysis of relations between negative slow potentials in the rhinal cortex and the correctness of performance (according to Spearman’s nonparametric test) demonstrated the existence of significant correlation between the electrophysiological and behavioral indices of visual recognition memory only within a late portion (final 10 sec but not initial 10 ones) of the retention interval for memorizing the trace of single presentation of a visual stimulus. The data obtained are interpreted as a confirmation of the existence of correlation between generation of negative slow potentials in the rhinal cortical region and the process of retrieval of the sample from the visual memory stores.

Sensory gating in the human hippocampal and rhinal regions: Regional differences

To further explore the roles of medial temporal structures in mediating sensory gating of incoming irrelevant or redundant auditory input, twenty-seven patients with intractable epilepsy with depth electrodes implanted in the medial temporal lobe for presurgery evaluation underwent evoked response recording to auditory paired-stimuli (S1-S2). Seventeen subjects were diagnosed with left medial temporal lobe epilepsy (MTLE) and 10 with right MTLE. Only data from the nonlesion side were included. Twenty-three records from rhinal and anterior hippocampal regions, and 21 from posterior hippocampal regions were included in the analysis. The rhinal region had two prominent components (a negativity peaking around 200 ms followed by a positivity peaking around 400 ms). Both the anterior and posterior hippocampal regions exhibited a dominant negative potential peaking around 400 ms. These components were all composed predominantly of slower frequencies. In contrast, a negativity in the posterior hippocampus at around 100 ms was composed of slow and fast frequencies. All components but the early rhinal negativity were attenuated by stimulus repetition. This is the first report documenting that different regions of the medial temporal area are differentially involved in the processing of auditory input, most likely reflecting separate steps of processing. The data support the need for further exploration of the contribution of these regions to sensory gating. This information helps to increase our understanding of this basic but important and complex function.

Triple Dissociation in the Medial Temporal Lobes: Recollection, Familiarity, and Novelty

Memory for past events may be based on retrieval accompanied by specific contextual details (recollection) or on the feeling that an item is old (familiarity) or new (novelty) in the absence of contextual details. There are indications that recollection, familiarity, and novelty involve different medial temporal lobe subregions, but available evidence is scarce and inconclusive. Using functional magnetic resonance imaging (MRI), we isolated retrieval-related activity associated with recollection, familiarity, and novelty by distinguishing between linear and nonlinear oldness functions derived from recognition confidence levels. Within the medial temporal lobes (MTLs), we found a triple dissociation among the posterior half of the hippocampus, which was associated with recollection, the posterior parahippocampal gyrus, which was associated with familiarity, and anterior half of the hippocampus and rhinal regions, which were associated with novelty. Furthermore, multiple regression analyses based on individual trial activity showed that all three memory signals, i.e., recollection, familiarity, and novelty, make significant and independent contributions to recognition memory performance. Finally, functional dissociations among recollection, familiarity, and novelty were also found in posterior midline, left parietal cortex, and prefrontal cortex regions. This is the first study to reveal a triple dissociation within the MTL associated with distinct retrieval processes. This finding has direct implications for current memory models.

Sensory gating in the human hippocampal and rhinal regions

Objective: The objective of this work was to ascertain if sensory gating can be demonstrated within the human medial temporal lobe Methods: Eight patients with intractable epilepsy with depth electrodes implanted in the medial temporal lobe for presurgery evaluation underwent evoked response recording to auditory paired-stimuli (S1–S2). Each of the eight subjects had a diagnosis of left medial temporal lobe epilepsy (MTLE) Results: Data from the non-focal right hippocampi revealed a large negative response on S1 (starting at about 190 ms and lasting for approximately 300 ms from stimulus onset). Rhinal region recordings revealed a positive response (starting at about 240 ms with a rapid incline, followed by a long-lasting decline). A significant attenuation of both responses to S2 stimuli was observed. Conclusions: Data are suggestive of an involvement of the human medial temporal lobe in the processing of simple auditory information which occurs in a time frame later than the neocortical auditory evoked components. The exact role of these anatomical structures in the sensory gating process remains to be defined. Significance: This study provides the first evidence of an activation of the rhinal cortex after simple auditory stimulation and provides new evidence that the activation of the medial temporal lobe structures occurs at a later stage than that of the neocortex.

Extensive cytotoxic lesions involving both the rhinal cortices and area TE impair recognition but spare spatial alternation in the rat.

Rats with cytotoxic lesions of the perirhinal, postrhinal, and TE cortices (Rh+TE, n = 7) were compared with surgical control animals (n = 7) on a series of spontaneous object recognition tests. The Rh+TE group was associated with a failure to select the novel object. This recognition deficit contrasted with the apparently normal ability of the same animals to learn and perform a spatial working memory test (T-maze alternation). The animals were also tested on the acquisition of an automated visual discrimination task in which the stimuli were presented on a visual display unit (VDU) equipped with a touch screen. The animals with Rh+TE lesions showed only a borderline deficit on this task. These findings are consistent with other evidence implicating the rhinal region in recognition memory. More importantly, they also provide a dissociation between spatial working memory and object recognition and, hence, show that extensive rhinal lesions are not sufficient to disconnect the hippocampus functionally.