Previous research has investigated how the perirhinal cortex (PRC), hippocampus (HC) and temporal pole (TP) are involved in complex visual discrimination using a variety of stimuli. Results from these studies have shown that the PRC activates to a greater extent for object stimuli relative to scene stimuli and that familiar stimuli elicit greater activation than do novel stimuli. In contrast, the HC shows greater activation for scene stimuli relative to objects and has also been reported to show greater activation for familiar relative to novel stimuli. To our knowledge, however, no studies in humans have replicated the stimulus specificity findings reported for PRC and HC. Additionally, no studies have used a combination of perceptual difficulty and familiarity/novelty to investigate how varying these factors affects activation in PRC, HC and TP during visual discrimination tasks. Chapter 2 describes an fMRI study performed to investigate the PRC's and HC's involvement in object and scene visual discrimination. The results of this study showed that the PRC was activated similarly by scenes and objects and that the HC was activated similarly for objects and scenes. Chapter 3 describes an fMRI experiment that manipulated both familiarity and difficulty, measuring how this affected PRC, HC and TP activation. In PRC the results showed a significant interaction between novelty and level of difficulty, such that novel objects with high levels of overlapping features showed greater activation compared to all other conditions. In contrast, the HC only showed a main effect of difficulty, indicating that the stimuli with high, relative to low, levels of difficulty elicited greater activation regardless of familiarity. Cumulatively, the evidence above suggests that the involvement of the PRC and HC in visual discrimination is complex. We propose that PRC is engaged whenever visual discrimination is required for any stimuli with overlapping features not just objects, and is activated to a greater extent when stimuli are novel, while HC appears to respond to stimuli with overlapping features, regardless of familiarity.

Convergent evidence suggests that the perirhinal cortex (PRC) is involved in perception, in addition to long-term memory, by representing higher-order object feature conjunctions. Recent functional magnetic resonance imaging (fMRI) investigations have shown greater PRC activity during the processing of objects with a higher versus lower degree of features in common, but notably, these studies have been limited to examining only two levels of feature overlap. To address this, we scanned neurologically healthy participants with fMRI during a 1-back working memory task for objects that possessed a very low, low, medium or high degree of feature overlap. Somewhat consistent with previous findings, trends towards greater PRC activity for high versus medium feature overlap objects, and for semantically identical compared to semantically different objects were observed. However, other aspects of our data, including diminished PRC activity during medium versus low feature overlap objects, are difficult to interpret and require further investigation.

Convergent evidence suggests that the perirhinal cortex (PRC) is involved in perception, in addition to long-term memory, by representing higher-order object feature conjunctions. Recent functional magnetic resonance imaging (fMRI) investigations have shown greater PRC activity during the processing of objects with a higher versus lower degree of features in common, but notably, these studies have been limited to examining only two levels of feature overlap. To address this, we scanned neurologically healthy participants with fMRI during a 1-back working memory task for objects that possessed a very low, low, medium or high degree of feature overlap. Somewhat consistent with previous findings, trends towards greater PRC activity for high versus medium feature overlap objects, and for semantically identical compared to semantically different objects were observed. However, other aspects of our data, including diminished PRC activity during medium versus low feature overlap objects, are difficult to interpret and require further investigation.

Two amnesic patients with MTL damage that included the hippocampus and perirhinal cortex were tested along controls on a series of “oddity” discrimination tasks, in which they had to select an odd item from a visual array. Participants’ eye moments were monitored while they performed these tasks. Three types of stimuli were used: greebles, scenes, and faces. Results revealed that patients were impaired on tasks that required them to discriminate between items that shared features in common and tasks that required processing items from different viewpoints. An analysis of their eye movements revealed that their impaired performance was linked with decreased viewing times of target items compared to controls, when discriminating between greebles and scenes; their poor performance on the faces task could not be explained by the same token.

Two amnesic patients with MTL damage that included the hippocampus and perirhinal cortex were tested along controls on a series of “oddity” discrimination tasks, in which they had to select an odd item from a visual array. Participants’ eye moments were monitored while they performed these tasks. Three types of stimuli were used: greebles, scenes, and faces. Results revealed that patients were impaired on tasks that required them to discriminate between items that shared features in common and tasks that required processing items from different viewpoints. An analysis of their eye movements revealed that their impaired performance was linked with decreased viewing times of target items compared to controls, when discriminating between greebles and scenes; their poor performance on the faces task could not be explained by the same token.

The hippocampus, a brain region that is part of the limbic system in the medial temporal lobe, is critical to episodic memory, or the memory of autobiographical events. The hippocampus plays an important role in the consolidation of information from short-term memory into more permanent long-term memory and spatial memory which enables navigation. Hippocampal damage in humans has been linked to memory loss, such as in Alzheimer’s disease and other dementias, as well as in amnesia such as in the case of patient H.M. The role of the hippocampus has been well characterized in humans but is less understood in rodents due to contradictory findings. While rodents have served well as model organisms in developing our understanding of the cognitive map that is critical for spatial navigation, there has been substantial contention over the degree to which the rodent hippocampus supports non-spatial memory, specifically the memory for items or objects previously encountered. The overall objective of this research is to gain a better understanding of how neuronal circuits involving the hippocampus and perirhinal cortex function to support object memory in the brain. Chemogenetic technologies such as DREADDs (designer receptor exclusively activated by designer drugs) have proven to be effective tools in remote manipulation of neuronal activity. First, a series of behavioral tasks was used to validate the effects of DREADD inactivation in the CA1 region of dorsal hippocampus in C57BL/6J male mice. DREADD inhibition resulted in significant impairment in the spontaneous object recognition (SOR) task and of spatial memory in the Morris water maze. In conjunction, mice were implanted with bilateral perirhinal cortex guide cannulae to allow for temporary muscimol inactivation during distinct time points in the SOR task to further investigate the nature of its relationship with the hippocampus. The results reveal an unexpected role for the perirhinal cortex in the retrieval of strong object memory. Finally, Arc mRNA expression was quantified in CA1 of dorsal hippocampus and perirhinal cortex following both weak and strong object memory formation. The results indicate that the perirhinal cortex and hippocampus have distinct, yet complementary roles in object recognition memory and that distinction is gated by memory strength. Understanding the neural mechanisms supporting the weak-strong object memory distinction in mice is an important step not only in validating mice as a suitable model system to study episodic memory in humans, but also in developing treatments and understanding the underlying causes of diseases affecting long-term memory such as Alzheimer’s disease. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection

Behavioral data in individuals with Down syndrome (DS) and mouse models of the syndrome suggest impaired object processing. In this study we examined the component processes that may contribute to object memory deficits. A neuropsychological test battery was administered to individuals with DS (n=28), including tests targeting perirhinal cortex (PRC) and prefrontal cortex (PFC) function, tests of perception (i.e., convexity based figure ground perception), and tests of memory (object recognition and object-in-place learning). To compare to individuals with DS, the same number of typically developing chronological age (CA, n=28) and mental age-matched (MA, n=28) controls were recruited. We observed object memory deficits in DS (p<0.001). In contrast, the DS group showed relatively intact use of convexity when making figure-ground judgments and spared PRC-dependent function, as compared to MA control. In addition, measures of PFC function seemed to be related to performance on object recognition tasks. These findings suggest that the inputs into the MTL from low and high level perceptual processing streams may be intact in DS. The object memory deficits we observed might reflect impaired PFC function.

The perirhinal cortex (PRC) is a medial temporal lobe (MTL) structure known to be involved in assessing whether an object is familiar (i.e., meaningful) or novel. Recent evidence shows that the PRC is sensitive to the familiarity of both whole object configurations and their parts, and suggests the PRC may modulate part familiarity responses in V2. Here, using functional magnetic resonance imaging (fMRI), we investigated age-related decline in the PRC's sensitivity to part/configuration familiarity and assessed its functional connectivity to visual cortex in young and older adults. Participants categorized peripherally presented silhouettes as familiar ("real-world") or novel. Part/configuration familiarity was manipulated via three silhouette configurations: Familiar (parts/configurations familiar), Control Novel (parts/configurations novel), and Part-Rearranged Novel (parts familiar, configurations novel). "Real-world" judgments were less accurate than "novel" judgments, although accuracy did not differ between age groups. The fMRI data revealed differential neural activity, however: In young adults, a linear pattern of activation was observed in left hemisphere (LH) PRC, with Familiar > Control Novel > Part-Rearranged Novel. Older adults did not show this pattern, indicating age-related decline in the PRC's sensitivity to part/configuration familiarity. A functional connectivity analysis revealed a significant coupling between the PRC and V2 in the LH in young adults only. Older adults showed a linear pattern of activation in the temporopolar cortex (TPC), but no evidence of TPC-V2 connectivity. This is the first study to demonstrate age-related decline in the PRC's representations of part/configuration familiarity and its covariance with visual cortex.

BACKGROUND: Mild cognitive impairment (MCI) is a clinical condition that is characterized by mild changes in cognition. The amnestic form of MCI (aMCI) primarily affects memory and is thought to represent a stage between healthy aging and Alzheimer’s disease (AD). The medial temporal lobe (MTL) and the limbic system are two areas of the brain that have been implicated in the amnestic form of MCI. While MCI represents a risk factor for AD, it does not always lead to dementias. Being a carrier of the APOE Ɛ4 allele has also shown to increase chances of progression from MCI to AD. OBJECTIVE: To determine whether the subnuclei of the amygdala, along with other specific regions within the MTL, can differentiate between cognitively normal individuals and age-matched subjects with aMCI. METHODS: T1-weighted magnetic resonance imaging (MRI) data from two sources, the Boston University Alzheimer’s Disease Center (BU-ADC) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), was compiled for cross-sectional analysis. 95 scans in total from 45 cognitively normal participants and 50 diagnosed with aMCI were analyzed and the volumes of interest were automatically generated by the developmental version of FreeSurfer v6.0. To evaluate how well the volumes could predict either group membership (i.e. control group or MCI group) or APOE Ɛ4 status (i.e. carrier or noncarrier), the variables were assessed by nominal logistic regression models. RESULTS: Six of the nine nuclei of the amygdala had significantly reduced volumes in the aMCI group compared to controls. The whole amygdala and the perirhinal cortex also demonstrated reduced volumes in the aMCI group compared to the control group. The whole amygdala was a good predictor of group membership (R2 = 0.1386, whole model test chi square = 18.21558, p = 0.0004), but none of the subnuclei were good predictors individually. A model containing the 9 nuclei, the entorhinal cortex, and the perirhinal cortex provided a good fit for predicting APOE Ɛ4 status fit (R2 = 0.3000, whole model test chi square = 36.29563, p = 0.0002) and the best predictor was the corticoamygdaloid transition area of the amygdala. CONCLUSIONS: The results of our study confirm previous findings of reduced whole amygdala volume and add to the limited literature of reduced perirhinal cortex and amygdaloid nuclei volumes in MCI compared to healthy controls. To the best of our knowledge, this was the first time the automatic segmentation atlas was used to analyze the volumes of nine subnuclei of the amygdala in a population of aMCI. Our model testing the volume of the whole amygdala accurately predicted aMCI subjects with 58% accuracy and controls with 70% accuracy; the accuracy rose to 69% when the entorhinal cortex and the perirhinal cortex were added to the model to predict aMCI subjects from controls. Additionally, the model for predicting APOE Ɛ4 status identified noncarriers of the allele at 85% accuracy. Future studies should consider increasing the sample size to better assess small ROIs and assess for differences in the separate hemispheres.

Memory impairments are common in individuals with temporal lobe epilepsy (TLE). This is understandable given that temporal lobe brain structures involved in TLE play a central role in encoding memories. It is widely accepted that individuals whose seizure focus is in the left temporal lobe (LTLE) tend to have verbal memory impairments, whereas individuals whose seizure focus is in the right temporal lobe (RTLE) tend to have visuospatial memory impairments. However, evidence of functional subdivisions within the left and right temporal lobes in both the animal and human literature suggest that more specific subtypes of memory impairment may exist in TLE based on differences in seizure foci. The aim of this study was to identify more specific subtypes of memory-impairments in patients with intractable TLE using several measures of memory functioning and cluster analysis. Identification of more specific memory subtypes in TLE could have prognostic significance for patients and contribute to our knowledge about the organization of memory systems of the human brain. Four memory subtypes were identified in this sample: 1) patients with mild to moderate figural memory deficits; 2) patients with moderate to severe figural memory deficits, mild facial recognition deficits, and mild attention/concentration deficits; 3) patients with severe figural memory deficits and mild verbal episodic memory deficits; and 4) patients with no episodic or semantic memory deficits. Unexpectedly, the subtypes found did not exhibit the expected pattern of verbal memory impairments with left temporal lobe damage/dysfunction or visuospatial memory impairments with right temporal lobe damage/dysfunction. However, consistent with the literature, there was a trend towards some clusters with better verbal memory having higher left hippocampal volumes; and a trend towards one cluster with facial recognition deficits having lower anterior temporal lobe volumes. Small sample sizes in this study limited the ability to clearly validate many of the cluster differences, particularly differences in brain volumes. Nevertheless, the results of this study support the hypothesis that subtypes of memory impairment do exist in patients with TLE. With larger sample sizes, it is plausible that additional subtypes may be found, or the characteristics of the subtypes found may become clearer.