Self-concept is a mental representation of the self—an internal sense of personal identity. This complex representation is unique to the human mind. Behavioral studies on self-concept have demonstrated that self-relevant information is remembered better than other types of information, a phenomenon commonly known as the “self-reference effect” (SRE). However, the underlying neural mechanisms of SRE remain largely unknown.

Here, we recorded neural activity from ∼600 neurons from 15 neurosurgical epilepsy patients, who were implanted with depth electrodes for seizure monitoring. The SRE paradigm consisted of an incidental learning (encoding) task and subsequent memory recognition test. During the incidental learning task, participants were asked to rate various personality traits in three distinct encoding conditions: the self, a friend, and a celebrity. In the recognition part of the task, participants were asked to distinguish between traits that were presented during the encoding phase (old) and traits that were not presented (new).

Our behavioral findings showed the highest memory accuracy on the recognition test for traits that were associated with the “self” condition, which is consistent with previous studies on SRE. Additionally, we found that traits associated with the “friend” category were more accurately recognized than those associated with a celebrity, indicating that personally familiar information—even if not self-related— improves memory recognition. Through single-unit analyses from target brain regions, including the medial temporal lobe (MTL) and medial prefrontal cortex (mPFC), we identified unique patterns of neural activity during the memory encoding phase, specifically increased responses during self-referential encoding in a subset of the neuronal population.

Future analyses will explore the relationship between increased MTL activity during self-referential encoding and improved memory recognition of traits rated in relation to the self, and network interactions between MTL and mPFC in self-oriented memory processes.

Behavior is the product of interconnected brain regions that work together as networks. This case study examines whether there are differences between a participant with a large congenital left temporal lobe cyst, which impacted the volume of structures in the region, and control subjects of similar age on cognitive tasks and network connectivity as measured by resting-state functional magnetic resonance imaging (rs-fMRI).

The case participant (CP; 71 year old female) and controls (CON; n = 25; 48% female) were recruited as part of a larger aging study. CON were chosen from the larger study population by age (+/- 10 years from CP; Range = 68-86 years). Cognitive tasks included: Shopping list memory task, Montreal Cognitive Assessment, WAIS-IV subtests: Digit Span, Digit-Symbol, Symbol Span, and Letter-Number Sequencing. For rs-fMRI, we administered four blood-oxygen level dependent (BOLD) functional connectivity (rs-fMRI) scans at 6 minutes each. Image processing was conducted using the CONN toolbox. Independent sample t-tests evaluated differences between CP and CON. Segregation was evaluated in the Auditory (Au), Cerebellar-basal ganglia (CBBG), Cingulo-Opercular Task Control (COTC), Dorsal Attention (DA), Default Mode (DMN), Fronto-Parietal Task Control (FPTC), Salience (Sa), Sensory Somatomotor Hand (SSH), Sensory Somatomotor Mouth (SSM), Visual (Vi), and Ventral Attention (VA) networks to assess CP’s functional segregation by network throughout the brain. Bonferroni correction was applied to account for multiple comparisons in cognitive testing (.05/7 for significance at p < 0.007) and network segregation (.05/11 for significance at p < .005).

Independent samples t-tests did not reveal significant differences across cognitive tasks (t(24) <1.04, p > .05). Network segregation did not reveal significant differences between CP and CON across networks examined (t(24) < 1.269, p > .005). However, DMN and DA segregation trended toward significance (t(24) = -2.724, p = .006 and t(24) =-2.006, p = .028), respectively) with CP demonstrating lower segregation as compared to CON.

CP performed similarly on cognitive testing to CON, indicating that the congenital presence of a large temporal lobe cyst did not impact global cognition, list learning and memory, working memory, or processing speed. CP did not demonstrate significantly different segregation across networks of interest after Bonferroni correction. Our cognitive performance results are consistent with a similar case-study examining language, which revealed intact linguistic abilities (Tuckete et al., 2022). The lack of differences in cognitive performance and segregation highlight the capacity for plasticity in the human brain, even in the presence of a large structural abnormality. This also suggests that the processes of aging in this case are not markedly different from controls. In future research we intend to expand on this case study by evaluating right temporal to hippocampal seeds and language network seeds to delve deeper into memory and language functioning.

Set-shifting/switching tasks, among other measures of executive functioning, are typically thought to represent frontal lobe functioning. However, the neuroanatomical correlates of these tests are not fully established. The aim of this study was to examine associations between individual measures of set-shifting/switching and cortical thickness. We hypothesized that performance on each switching measure would strongly correlate with aggregated cortical thickness within the frontal lobe.

Measures of interest included set-shifting subtests of the Delis-Kaplan Executive Function System (DKEFS): Color-Word Inhibition Switching, Category Switching, and Trail Making Test Number-Letter Switching. Archival data from an outpatient memory disorders clinic were reviewed to identify individuals whose neuropsychological evaluations included the measures of interest and had quality-assessed, volumetric MRI data available (n=243; 53.1% male, 81.9% Caucasian, Mage=72.4, SDage=6.7). Cortical thickness values were generated by FreeSurfer and averages were calculated for both frontal and temporal lobes, separately. Using partial correlations, controlling for age, we explored associations between each switching trial separately with right and left, frontal and temporal cortical thickness. The strength of associations within each lobe were then compared using Fisher's r-to-z transformations.

Category Switching was significantly correlated with left and right hemisphere temporal thickness (r=0.38 and 0.31, respectively), but was not significantly correlated with left or right frontal lobe cortical thickness (r=.12 and .07, respectively). Fisher's r-to-z transformations revealed significantly stronger relationships between Category Switching and temporal thickness, rather than frontal thicknesses. Trails Switching was also significantly correlated with left and right temporal cortical thickness (r=-0.28, and =-0.23, respectively) and bore weaker associations with frontal cortical thickness (r=-.13 and r = -.14 for left and right hemispheres, respectively). In contrast, Color-Word Inhibition-Switching did not show a significant relationship with frontal or temporal cortical thickness.

Contrary to our hypothesis, stronger associations were observed with temporal lobe cortical thickness for Category Switching. Category Switching involves a language production component which could explain the strong association with temporal cortical thickness compared to frontal cortical thickness. Additionally, the pattern of associations between Trails Switching and frontal and temporal thickness was non-specific. Perhaps most striking is the lack of association between each switching measure and frontal cortical thickness, which was unexpected, given that these measures are used to assess executive functioning, broadly localized to the frontal lobe. Future directions involve examining the associations of these measure with subcortical structures and replicating these findings in larger datasets.

Semantic fluency measures comprise a differing number of trials depending on the test battery and/or normative data used. Using semantic fluency trials from the Delis Kaplan Executive Function System (D-KEFS; Animals and Boys’ names), we sought to examine whether: 1) there was incremental benefit of multiple trials in associations with aggregated temporal cortical thickness and 2) patterns of neuroanatomical associations with specific temporal lobe structures differed between Animals and Boys’ names trials.

Archival records of adults who completed a neuropsychological evaluation which included the semantic fluency measures of interest and had undergone structural MRI were identified (n=243, Mage=72.35 years, SDage=6.74, Female=46.9%). Cortical thickness values were obtained using FreeSurfer and averaged across sub-regions, separately for the left and right temporal lobe, per recommendations from the FreeSurfer group. Multiple linear regression models were fit to examine separate and incremental contribution of both Animals and Boys’ names, on temporal lobe thickness, including age, sex, and education in the models. Zero order correlations with each of the temporal cortical thickness areas (inferior, middle, and superior temporal; banks of the superior temporal sulcus, fusiform, transverse temporal, entorhinal, temporal pole, and parahippocampal cortices) were also computed to identify more focal neuroanatomical correlates.

Animals and Boys’ names trials individually accounted for a significant proportion of variance when predicting temporal cortical thickness over and above demographics, but Animals was a considerably stronger predictor for left temporal cortical thickness (Left: Animals AR2 =.127*, Boys’ names AR2 = .067*; Right: Animals AR2 =.074*, Boys’ names AR2 = .065*). The variance accounted for by Boys’ names incrementally over Animals was not significant (AR2 = .004 for left and .015 for right hemispheres, respectively). Similarly, though the composite Category fluency index accounted for a significant proportion of the variance independently, it did not add incrementally over and above Animals alone when predicting cortical thickness in either hemisphere. When examining simple correlations with specific temporal cortices, Animals consistently had correlations of a greater magnitude than Boys’ names within the left hemisphere (Animals r>.3 for superior, middle, inferior, and fusiform gyri; Boys’ names r< .3 for all cortical thickness regions). Greater variability was noted for associations with right temporal thickness but Animals continued to show associations of a greater magnitude of associations than Boys’ names for several sub-regions. * denotes significance at p < .01.

The additional Boys’ names trial does not confer significant benefit over Animals alone, when predicting cortical thickness in either temporal lobe. Additionally, overall category fluency provided little incremental utility over and above the Animals trial alone in predicting temporal thickness. Psychometrically, it is expected that composites derived from multiple trials are more robust. However, this study demonstrates that it is important to examine whether the administration of additional trials is truly beneficial, particularly in a climate where brevity of neuropsychological assessment is critically desired. Further, psychometric tests have historically been validated against other neuropsychological measures, but it is critical we also validate measures against neuroanatomical correlates.

The purpose of this investigation was to examine neuropsychological functioning after frontal (FL) or temporal lobectomy (ATL) in patients with localization related epilepsy. Few studies have compared cognitive changes following FL and ATL. Past research found improvement on measures of verbal and visual memory along with confrontation naming after FL (Busch et al., 2017). In contrast, a number of studies have reported verbal memory and naming decline in those undergoing left ATL. The current study examined post-operative cognitive changes in epilepsy patients who underwent either a left or right FL or ATL.

Subjects include 430 patients (204 men, 225 women, 1 gender not specified), who underwent surgical resection; Right FL = 25, Left FL = 26, Right ATL = 211, Left ATL = 168. Patients had a mean FSIQ = 90, ages ranging from 18 to 71 (mean age = 37 years), right (n=359), left (n=50), or mixed (n=18) handedness, and education ranging from 3 to 22 years (mean = 12.9 years of education). Change from pre- to post FL and ATL was examined in the following domains: learning and memory [Long Term Storage for Selective Reminding Tests (SRT), Wechsler’s Memory Scale (WMS): Logical Memory Delayed Recall (LM) and Visual Reproduction Delayed Recall (VR)], and language [Boston Naming Test (BNT)].

A one-way ANOVA was used to examine changes in language and memory. Our findings revealed statistically significant differences between resection groups for LM, SRT, and BNT. There were significant declines (p<.001) for left ATL when compared to right ATL for LM, SRT, and BNT. There were significant declines for left ATL, when compared to the gains in both left (p<.001; p=.002) and right (p=.018; p=.008) FL for LM and BNT. Left ATL also had significant declines when compared to gains in SRT (p<.001) for right FL. There were significant declines for left FL when compared to right ATL for SRT (p=.007). Lastly, there were significant gains for right FL when compared to left FL for SRT (p=.020).

The pre- to post-surgical neuropsychological change in learning, memory, and language is understudied in frontal lobe epilepsy (FLE); although several investigators reported some learning and memory impairments in FLE at either pre- or post-surgical time points (Johnson-Markve et al., 2011; Incisa Della Rocchetta et al., 1993). The current study suggests that resections of the frontal lobes are associated with better outcomes for naming and verbal memory (LM) when compared to left ATLs. Interestingly, verbal list learning declined more in left than right FL and right ATL patients suggesting a possible language based executive functioning component to this memory measure. As expected, our study further supports that left ATLs are associated with material specific memory declines. This pattern was not seen for those undergoing a right ATL (i.e., nonverbal memory did not decline in patients with right ATL).

The brain is reliant on mitochondria to carry out a host of vital cellular functions (e.g., energy metabolism, respiration, apoptosis) to maintain neuronal integrity. Clinically relevant, dysfunctional mitochondria have been implicated as central to the pathogenesis of Alzheimer’s disease (AD). Phosphorous magnetic resonance spectroscopy (31p MRS) is a non-invasive and powerful method for examining in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. At least one prior 31p MRS study found temporal-frontal differences for high energy phosphates in persons with mild AD. The goal of the current study was to examine regional (i.e., frontal, temporal) 31p MRS ratios of mitochondrial function in a sample of older adults at-risk for AD. Given the high energy consumption in temporal lobes (i.e., hippocampus) and preferential age-related changes in frontal structure-function, we predicted 31p MRS ratios of mitochondrial function would be greater in temporal as compared to frontal regions.

The current study leveraged baseline neuroimaging data from an ongoing multisite study at the University of Florida and University of Arizona. Participants were older adults with memory complaints and a first-degree family history of AD [N = 70; mean [M] age [years] = 70.9, standard deviation [SD] =5.1; M education [years] = 16.2, SD = 2.2; M MoCA = 26.5, SD = 2.4; 61.4% female; 91.5% non-latinx white]. To achieve optimal sensitivity, we used a single voxel method to examine 31p MRS ratios (bilateral prefrontal and left temporal). Mitochondrial function was estimated by computing 5 ratios for each voxel: summed adenosine triphosphate to total pooled phosphorous (ATP/TP; momentary energy), ATP to inorganic phosphate (ATP/Pi; energy consumption), phosphocreatine to ATP (PCr/ATP; energy reserve), phosphocreatine to inorganic phosphate (PCr/Pi; oxidative phosphorylation), and phosphomonoesters to phosphodiesters (PME/PDE; cellular membrane turnover rate). All ratios were corrected for voxel size and cerebrospinal fluid fraction. Separate repeated measures analyses of variance controlling for scanner site differences (RM ANCOVAs) were performed.

31p MRS ratios were unrelated to demographic characteristics and were not included as additional covariates in analyses. Results of separate RM ANCOVAs revealed all 31p MRS ratios of mitochondrial function were greater in left temporal relative to bilateral prefrontal voxel: ATP/TP (p < .001), ATP/Pi (p = .001), PCr/ATP (p = .004), PCr/Pi (p = .004), and PME/PDE (p = .017). Effect sizes (partial eta squared) ranged from 0.6-.20.

Consistent and extending one prior study, all 31p MRS ratios of mitochondrial function were greater in temporal as compared to frontal regions in older adults at-risk for AD. This may in part be related to the intrinsically high metabolic rate of the temporal region and preferential age-related changes in frontal structure-function. Alternatively, findings may reflect the influence of unaccounted factors (e.g., hemodynamics, auditory stimulation). Longitudinal study designs may inform whether patterns of mitochondrial function across different brain regions are present early in development, occur across the lifespan, or some combination. In turn, this may inform future studies examining differences in mitochondrial function (as measured using 31p MRS) in AD.