Motor imagery is defined as a dynamic state during which a subject mentally simulates a given action without overt movements. Our aim was to use near-infrared spectroscopy to investigate differences in cerebral hemodynamic during motor imagery of self-feeding with chopsticks using the dominant or non-dominant hand.

Twenty healthy right-handed people participated in this study. The motor imagery task involved eating sliced cucumber pickles using chopsticks with the dominant (right) or non-dominant (left) hand. Activation of regions of interest (pre-supplementary motor area, supplementary motor area, pre-motor area, pre-frontal cortex, and sensorimotor cortex was assessed.

Motor imagery vividness of the dominant hand tended to be significantly higher than that of the non-dominant hand. The time of peak oxygenated hemoglobin was significantly earlier in the right pre-frontal cortex than in the supplementary motor area and left pre-motor area. Hemodynamic correlations were detected in more regions of interest during dominant-hand motor imagery than during non-dominant-hand motor imagery.

Hemodynamic might be affected by differences in motor imagery vividness caused by variations in motor manipulation.

Individuals with Autism Spectrum Disorder (ASD) or Early-Onset Psychosis (EOP) both experience substantial difficulties with social cognition (Spek et al. 2012; Lanillos et al. 2020); however, the impact of therapy and medication use on their social cognition has not yet been examined (Lai et al. 2014; Schiffman et al. 2018). This project will explore the effects of the history of therapy and medication use as moderating variables between neural architecture and social cognition performance.

T1-weighted imaging data were acquired on a 3T Siemens scanner for 51 ASD and EOP participants (Mean Age = 16.33), with 41 individuals endorsing history of therapy and 23 endorsing history of medication use across groups. Cortical thickness was calculated using FreeSurfer imaging analysis software (v5.3; Fischel et al., 2002) for social brain regions including inferior parietal lobe (IPL), middle temporal lobe (MPL), caudal anterior cingulate cortex (cACC), rostral anterior cingulate cortex (rACC), fusiform gyrus, precuneus cortex, and insular cortex. The Awareness of Social Inference Test (TASIT; McDonald et al., 2006) was administered to assess social cognition performance. After controlling for individuals that had a history of both therapy and medication use, Pearson's correlations were utilized to examine the relationship between cortical thickness and social cognition performance in ASD and EOP patients. The PROCESS Procedure moderation analysis in SPSS was utilized to determine if history of therapy or medication use moderated the relationship between cortical thickness and social cognition performance (Hayes, 2018).

Across groups, there was a negative association between an individual's cACC thickness and TASIT Do score (r = -.415, p = .005) as well as the total TASIT score (r = -.325, p = .031). Additionally, there was a positive association between an individual's precuneus cortical thickness and their TASIT Say score (r = .440, p = .003). Results of the moderation analyses revealed that lack of medication use was associated with greater rACC thickness and higher TASIT Say score (R2 Change = .1281 mm, p = .0191). Additionally, lack of past therapy experience was associated with greater insular thickness and higher TASIT Think scores (R2 Change = .1957 mm, p = .0033). Conversely, past therapy history was associated with greater fusiform gyrus thickness and higher TASIT Say score (R2 Change = .1115 mm, p =.0262).

Our results suggest that for individuals without a history of therapy or medication use, higher cortical thickness of the rACC and insula support better social cognition performance; whereas for individuals with past therapy experience, higher cortical thickness of the fusiform cortex underlies better social cognition performance. Collectively, these findings suggest that an individual's history of therapy or medication use may be relevant variables to consider when examining the relationship between neural cortical thickness and social cognition performance in these neuropsychiatric conditions.

Glioblastomas, Grade 4 astrocytomas, comprise about 60% of all astrocytomas and have a median survival rate between 14 and 16 months. The extent of resection impacts the prognosis, with an eloquent balance of preserving the patient's functional status. As preoperative imaging and intraoperative techniques improve to maximize safe operative resection, thorough neuropsychological evaluation can aid in assessing cognitive decline and quality of life pre- and post-treatment. In light of the tumors' progressive nature and potential presence in precarious brain locations, it is imperative that the functional burden of the various presentations of glioblastomas be understood. Given the limited data on cognitive presentations of glioblastomas, we present a case study describing a neuropsychological and neuroradiologic profile of a Grade 4 astrocytoma in a patient with a left temporal glioblastoma.

The patient signed consent for clinical evaluation and research. At the time of evaluation, he was 68 years old with a master's degree and was working at multiple start-up companies. He began noticing subtle cognitive functioning changes approximately two months prior with difficulty understanding information. His challenges progressed to difficulty composing emails, word-finding issues, and some slurring and mispronunciations. He was diagnosed with a brain tumor after an emergency MRI was performed. He participated in a neuropsychological evaluation just prior to surgery. The evaluation included a battery of neuropsychological tests examining attention, processing speed, executive functioning, learning and memory, language functioning, visuospatial functioning, motor functioning, and mood.

The imaging results revealed a non-enhancing intra-axial mass in the left superior temporal lobe with surrounding edema. Also noted were rare scattered nonspecific T2 hyperintensities. The scores showed variable motor functioning and deficits within attention for complex information, executive functioning abilities (i.e., motor planning and sequencing, phonemic fluency), language functioning, visuospatial functioning, and learning and memory of information relative to his premorbid level of functioning, indicating total brain involvement consistent with imaging findings of edema.

Taken together, the results of the evaluation and imaging were suggestive of a level of cognitive decline that is more than expected with normal aging. Moreover, there was a lack of evidence representative of a lateralized profile. Notably, the evaluation was conducted before resection surgery, and therefore, the patient continued to experience significant brain edema due to the tumor. Although medication may have contributed to dysfunction, particularly with motor and cognitive slowing, it is not likely that it explained his presentation entirely. As such, the evaluation results were suggestive of neurocognitive dysfunction, which was partially attributable to the tumor and edema displacing neuronal tissue. Given the potential for improvement following tumor resection and secondary decline resulting from recurrence or treatment, it is crucial to have a baseline and the ability to map out higher order functioning, including frontal and temporal lobe functioning. Ultimately, as the field continues to look toward long-term survival for patients with currently lethal brain tumors, the goal is to achieve maximum resection with minimal neurocognitive loss.

Neurodegeneration in Alzheimer’s disease (AD) is typically assessed through brain MRI, and proprietary software can provide normative quantification of regional atrophy. However, proprietary software can be cost-prohibitive for research settings. Thus, we used the freely available software NOrmative Morphometry Image Statistics (NOMIS) which generates normative z-scores of segmented T1-weighted images from FreeSurfer to determine if these scores replicate established patterns of neurodegeneration in the context of amnestic mild cognitive impairment (aMCI), and whether these measures correlate with episodic memory test performance.

Patients with aMCI (n = 25) and cognitively normal controls (CN; n = 74) completed brain MRI and two neuropsychological tests of episodic memory (the Rey Auditory Verbal Learning Test and the Wechsler Logical Memory Tests I & II), from which a single composite of normed scores was computed. A subset returned for follow-up (aMCI n = 11, CN n = 52) after ∼15 months and completed the same procedures. T1-weighted images were segmented using FreeSurfer v6.0 and the outputs were submitted to NOMIS to generate normative morphometric estimates for AD-relevant regions (i.e., hippocampus, parahippocampus, entorhinal cortex, amygdala) and control regions (i.e., cuneus, lingual gyrus, pericalcarine gyrus), controlling for age, sex, head size, scanner manufacturer, and field strength. Baseline data were used to test for differences in ROI volumes and memory between groups and to assess the within-group associations between ROI volumes and memory performance. We also evaluated changes in ROI volumes and memory over the follow-up interval by testing the main effects of time, group, and the group X time interactions. Lastly, we tested whether change in volume was associated with declines in memory.

At baseline, the aMCI group performed 2 SD below the CN group on episodic memory and exhibited smaller volumes in all AD-relevant regions (volumes 0.4 - 1.2 SD below CN group, ps < .041). There were no group differences in control region volumes. Memory performance was associated with volumes of the AD-relevant regions in the aMCI group (average rho = .51) but not with control regions. ROI volumes were not associated with memory in the CN group. At follow-up, the aMCI group continued to perform 2 SD below the CN group on episodic memory tests; however, change of performance over time did not differ between groups. The aMCI group continued to exhibit smaller volumes in all AD-relevant regions than the CN group, with greater declines in hippocampal volume (17% annual decline vs. 8% annual decline) and entorhinal volume (54% annual decline vs. 5% annual decline). There was a trending Group X Time interaction such that decrease in hippocampal volume was marginally associated with decline in memory for the aMCI group but not the CN group.

Normative morphometric values generated from freely available software demonstrated expected patterns of group differences in AD-related volumes and associations with memory. Significant effects were localized to AD-relevant brain regions and only occurred in the aMCI group. These findings support the validity of these free tools as reliable and cost-effective alternatives to proprietary software.

Obesity is associated with adverse effects on brain health, including increased risk for neurodegenerative diseases. Changes in cerebral metabolism may underlie or precede structural and functional brain changes. While bariatric surgery is known to be effective in inducing weight loss and improving obesity-related medical comorbidities, few studies have examined whether it may be able to improve brain metabolism. In the present study, we examined change in cerebral metabolite concentrations in participants with obesity who underwent bariatric surgery.

35 patients with obesity (BMI > 35 kg/m2) were recruited from a bariatric surgery candidate nutrition class. They completed single voxel 1H-proton magnetic resonance spectroscopy at baseline (pre-surgery) and within one year post-surgery. Spectra were obtained from a large medial frontal brain region. Tissue-corrected absolute concentrations for metabolites including choline-containing compounds (Cho), myo-inositol (mI), N-acetylaspartate (NAA), creatine (Cr), and glutamate and glutamine (Glx) were determined using Osprey. Paired t-tests were used to examine within-subject change in metabolite concentrations, and correlations were used to relate these changes to other health-related outcomes, including weight loss and glycemic control.

Bariatric surgery was associated with a reduction in cerebral Cho (f[34j = -3.79, p < 0.001, d = -0.64) and mI (f[34] = -2.81, p < 0.01, d = -0.47) concentrations. There were no significant changes in NAA, Glx, or Cr concentrations. Reductions in Cho were associated with greater weight loss (r = 0.40, p < 0.05), and reductions in mI were associated with greater reductions in HbA1c (r = 0.44, p < 0.05).

Participants who underwent bariatric surgery exhibited reductions in cerebral Cho and mI concentrations, which were associated with improvements in weight loss and glycemic control. Given that elevated levels of Cho and mI have been implicated in neuroinflammation, reduction in these metabolites after bariatric surgery may reflect amelioration of obesity-related neuroinflammatory processes. As such, our results provide evidence that bariatric surgery may improve brain health and metabolism in individuals with obesity.

The stria terminalis (ST) is a white matter tract with connections to limbic and autonomic brain structures that is implicated in affective functioning. Recent works suggests that ST functional integrity and connectivity is associated with faster responses to emotional cues (Dzafic et al., 2019) and may be influenced by environmental factors including socioeconomic status (SES) and childhood adversity (Banihashemi et al., 2020). The role of the ST in the experience of more daily affective experiences, such as depressive symptoms, remains unexplored. Therefore, the present study examined the role of the ST and SES, as assessed by household income, in the relationship between age and depressive symptoms in typically developing children and adolescents.

Participants include 64 typically developing children and adolescents age 8-21 (Mage=13.27, SD=3.15) who participated in an ongoing study of development of neurocognitive and social-cognitive skills. Participants completed imaging on a 3Tesla MR Siemens PRISMA scanner. Tractography was executed via ENIGMA tract-based spatial statistics to quantify WM integrity and provided values for mean fractional anisotropy (mFA) of the ST. Depressive symptoms were measured with the Behavior Assessment Scale for Children-Third Edition (BASC-3) parent report scale, and annual family income was obtained per parent report. Mediation and moderation analyses were conducted using Process version 4.1 (Hayes, 2022) in SPSS version 28. As depression symptoms are often higher in early adolescence than later, we examined the indirect effect of age on depressive symptoms through ST mFA and evaluated this relationship at different levels of family income.

Age was associated with lower levels of depressive symptoms (b=-.98, t=-2.18, p<.05), whereas greater right ST mFA was associated with higher levels of depressive symptoms (b=42.05, t=2.50, p<.05). Right ST mFA explained significant variance in the relationship between age and parent-reported depression (ab=.13, 95% CI [.02, .29]). The conditional indirect effect of family income was significant for children with annual family incomes between 25-50k (effect=.16, 95% CI [.01, .38]) and 75-100k (effect=.13, 95% CI [.001, .31]), but not for 100k+ (effect=.11, 95% CI [-.05, .33]).

The present study revealed a significant, positive relationship between white matter integrity in the right ST and parent-reported depressive symptoms in healthy children and young adults. Finding extend on prior work implicating the ST in threat responsivity (Dzafic et al., 2019). Moreover,results suggest the role of the ST in the relationship between age and depression depends on level of family income, such that ST mFA explains more variance at lower income levels, and is no longer significant for children from families with income greater than 100k. These findings support the notion that environmental stressors (such as lower family income) may strengthen ST pathways via activity-dependent plasticity and repeated, coordinated activation (Rinaman et al., 2011). Future studies should examine these brain-behavior associations, as they may replicate in a larger sample, with more nuanced indicators of environmental stress.

Functional magnetic resonance imaging (fMRI) research has generally focused on drawing conclusions from average brain activation patterns. Importantly, the brain is inherently variable; growing literature has found that within-individual blood oxygen level-dependent (BOLD) signal variability may be meaningful, and not just “noise.” For example, recent research has identified increased BOLD signal variability in healthy younger and older adults during more effortful/complex task loads of n-back paradigms, commonly used tasks that involve important elements of executive function (e.g., attention, working memory, planning, inhibition, etc.). Verbal fluency is a complex cognitive domain that also involves similar processes to generate words given certain rules. As a result, the current study builds on existing literature to investigate within-individual BOLD signal variability patterns in peak coordinates of a verbal fluency network during different loads of a letter n-back task. Due to greater executive demands, greater variability was expected during more effortful/complex n-back task loads in regions of a verbal fluency network.

Forty-eight healthy young adults (Mage(SD) = 22.41(4.47), 25 females) from the Atlanta area completed a letter n-back task in an MRI scanner. After standard processing in AFNI, images were corrected for motion and physiological artifacts, which may be confounding sources of variability. Volumes associated with each load of the letter n-back task (0-back, 1-back, 2-back, 3-back, crosshair) were identified. Task runs were normalized and respective run means were subtracted prior to concatenating all runs for each load type. Standard deviations were calculated across this mean-run corrected time series. Ten peak regions of interest (ROIs) were identified from a verbal fluency network generated from 84 peer-reviewed publications for this domain gathered on NeuroSynth. Paired samples t-tests with Benjamini-Hochberg correction for multiple comparisons were conducted to explore differences in variability during n-back task loads.

In several of the verbal fluency network ROIs, within-individual BOLD signal variability was significantly greater for 2-back versus 0-back loads with medium to large effect sizes (p’s < .001 - < .01, Cohen’s d range: .53-.93). Variability was also significantly greater for 3-back versus 0-back loads with small to medium effect sizes (p’s < .001 - < .01, Cohen’s d range: .48-.74). Specific regions that evidenced this pattern included ROIs in the left inferior frontal gyrus, left cingulate, right inferior frontal gyrus, left middle frontal gyrus, and left superior parietal lobule. Only two regions demonstrated increased variability in the 1-back load versus crosshair (left middle frontal gyrus, p < .001, d = .63; left lentiform nucleus, p < .05, d = .42). No regions demonstrated a significant difference in variability in the 0-back load versus crosshair.

This study contributes to growing literature examining within-individual BOLD signal variability in healthy individuals by exploring variability patterns in a verbal fluency network. The observed pattern of results supports the hypothesis and is in line with previous research, demonstrating that greater variability occurs with greater executive task demands. Future research can use an inscanner task of verbal fluency and can extend variability findings during this in-scanner task to out-of-scanner measures of verbal fluency.

Chronic musculoskeletal pain is associated with neurobiological, physiological, and cellular measures. Importantly, we have previously demonstrated that a biobehavioral and psychosocial resilience index appears to have a protective relationship on the same biomarkers. Less is known regarding the relationships between chronic musculoskeletal pain, protective factors, and brain aging. This study investigates the relationships between clinical pain, a resilience index, and brain age. We hypothesized that higher reported chronic pain would correlate with older appearing brains, and the resilience index will attenuate the strength of the relationship between chronic pain and brain age.

Participants were drawn from an ongoing observational multisite study and included adults with chronic pain who also reported knee pain (N = 135; age = 58.3 ± 8.1; 64% female; 49% non-Hispanic Black, 51% non-Hispanic White; education Mdn = some college; income level Mdn = $30,000 - $40,000; MoCA M = 24.27 ± 3.49). Measures included the Graded Chronic Pain Scale (GCPS), characteristic pain intensity (CPI) and disability, total pain body sites; and a cognitive screening (MoCA). The resilience index consisted of validated biobehavioral (e.g., smoking, waist/hip ratio, and active coping) and psychosocial measures (e.g., optimism, positive affect, negative affect, perceived stress, and social support). T1-weighted MRI data were obtained. Surface area metrics were calculated in FreeSurfer using the Human Connectome Project's multi-modal cortical parcellation scheme. We calculated brain age in R using previously validated and trained machine learning models. Chronological age was subtracted from predicted brain age to generate a brain age gap (BAG). With higher scores of BAG indicating predicated age is older than chronological age. Three parallel hierarchical regression models (each containing one of three pain measures) with three blocks were performed to assess the relationships between chronic pain and the resilience index in relation to BAG, adjusting for covariates. For each model, Block 1 entered the covariates, Block 2 entered a pain score, and Block 3 entered the resilience index.

GCPS CPI (R2 change = .033, p = .027) and GCPS disability (R2 change = 0.038, p = 0.017) significantly predicted BAG beyond the effects of the covariates, but total pain sites (p = 0.865) did not. The resilience index was negatively correlated and a significant predictor of BAG in all three models (p < .05). With the resilience index added in Block 3, both GCPS CPI (p = .067) and GCPS disability (p = .066) measures were no longer significant in their respective models. Additionally, higher education/income (p = 0.016) and study site (p = 0.031) were also significant predictors of BAG.

In this sample, higher reported chronic pain correlated with older appearing brains, and higher resilience attenuated this relationship. The biobehavioral and psychosocial resilience index was associated with younger appearing brains. While our data is cross-sectional, findings are encouraging that interventions targeting both chronic pain and biobehavioral and psychosocial factors (e.g., coping strategies, positive and negative affect, smoking, and social support) might buffer brain aging. Future directions include assessing if chronic pain and resilience factors can predict brain aging over time.

Functional near infrared spectroscopy (fNIRS) is a form of non-invasive neuroimaging that uses light to measure changes in oxygenated and deoxygenated hemoglobin (Yucel et. al., 2021). Relative to fMRI, fNIRS is significantly cheaper and less susceptible to motion artifacts thereby enabling researchers to acquire data in more ecologically valid environments and has a higher temporal resolution that makes it well-suited for connectivity analyses (Tak and Ye, 2014). fNIRS is, however, uniquely limited by cortical anatomy. With a typical probe array having a penetrance depth of up to 3cm, the benefits of fNIRS may be limited by the neocortical atrophy that is characteristic in those with neurodegeneration. We present preliminary findings comparing fNIRS probe sensitivity in older adults diagnosed with posterior cortical atrophy (PCA) relative to cognitively intact older adults using Monte Carlo (MC) simulations. MC simulations offer probabilistic models that simulate photon movement through tissues of interest. We were particularly interested in fNIRS' sensitivity in the occipitoparietal cortices since these are regions characteristically affected in PCA.

We acquired high resolution structural (T1) MRI on 3 cognitively intact older adults and 3 individuals who received a clinical diagnosis of PCA according to Crutch et al. (2017) criteria. Individual T1 scans were preprocessed and transformed into a twodimensional (2D) surface using FreeSurfer. This continuous 2D surface was then segmented into its main tissue priors, as well as its pial surfaces. Segmented MRIs were then imported into AtlasViewer software and registered to our full head fNIRS probe array via an affine transformation. We embedded the GPU-accelerated Monte Carlo Extreme 3D light transport simulator software (Fang and Boas, 2009) into AtlasViewer which enabled us to launch 10 million photons from each optode, compared to the 1 million that AtlasViewer is set to by default, thereby providing more accurate results (Aasted et. al., 2015). We then assessed the sensitivity profile (log units), a mathematical estimate of optical density, of the inferior and superior occipital gyri, middle occipital gyrus, the superior and inferior parietal lobules, and left and right precunei.

Among the regions interrogated, five channels on our fNIRS probe were markedly different between the controls and those with PCA. Specifically, sensitivity values for channels covering the right inferior (hedges g = 8.04) and left superior occipital gyrus (hedges g = 2.46), the right inferior parietal lobule (hedges g = 8.89), and the right (hedges g = 9.43) and left (hedges g = 14.83) precunei were all markedly lower in those with PCA.

We provided preliminary evidence that the sensitivity of fNIRS appears to be markedly reduced in those with PCA. This is especially relevant for researchers using fNIRS in populations with neurodegeneration. Future work will evaluate these findings in a larger sample as well as in other neurologic conditions with the goal of helping researchers appropriately power their studies and interpret their results.

Executive function is known to decline in later life, largely attributed to structural and functional changes in the prefrontal cortex. However, other regions of the brain are integral to executive functioning, including the hippocampus. The hippocampus plays a large role in memory but its intricate connections to limbic regions including the prefrontal cortex likely underlies associations between the hippocampus and executive functions. Due to the hippocampus’ complex structure, hippocampal subregions may be differentially associated with executive function, but this possibility remains largely unexplored. Therefore, we examined the association between volume of the hippocampus and its subregions with executive function to understand these relationships across the adult lifespan.

The study included 32 healthy, community-dwelling participants (age range = 18-81, mean age = 51.06 ± 20.98, 91% white, 72% female) who received a 3-Tesla magnetic resonance imaging (MRI) scan and completed a cognitive battery. We calculated an executive composite based on Trail Making Test Part B and the interference score from the Stroop Color and Word Test. Freesurfer (version 5.3) as used to quantify total hippocampal volume and subfield volumes for CA1, CA2-3, CA4-dentate gyrus, subiculum, and presubiculum. We conducted mixed-effects regression analyses with total hippocampal and subfield volume, age group (young, middle-aged, and older), and their interaction predicting the executive function composite, controlling for total intracranial volume.

Larger hippocampal subregion volumes in CA1 (p = 0.03), the subiculum (p = 0.01), and the CA4-dentate gyrus (p = 0.04) predicted better executive function. Total hippocampal volume and the presubiculum were not significantly associated with the executive function composite. The age group interaction was not significant for any of the models. Follow-up analyses by hemisphere showed that the effects were right lateralized in CA1and CA4-dentate gyrus, and bilateral in the subiculum.

These data support the literature demonstrating the involvement of the hippocampus in executive function and demonstrates variation across hippocampal subfields. The lack of significant age interactions suggests these relationships may not differ across the lifespan, although this finding would need to be replicated in larger samples. These findings support previous literature showing CA4-dentate gyrus’ association with neurogenesis may facilitate better executive function by increasing connection strength among CA1, CA2-3, and the frontal cortex. This study contributes to our understanding of how specific hippocampal subregions relate to executive function, which has both clinical and research implications.

Improving the timeline for intervention in Alzheimer's disease (AD) has considerable potential to delay and mitigate disability and suffering. Neuropsychological assessment is useful for distinguishing AD from normal aging and other dementias but is less useful in preclinical detection due to its limited sensitivity. The N400 (N4), a language-based EEG event-related potential (ERP) related to semantic functioning, is a promising candidate marker of AD with potential to improve early detection and monitoring of AD. For example, studies have shown that individuals with AD show a reduced N4 "effect"—a smaller difference in the size of the N4 to semantically congruent vs. incongruent word-pairs. The goal of this study is to assess the presence of the N4 effect in healthy seniors, and those with amnestic mild cognitive impairment (MCI) or mild AD, and to evaluate associations between performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the N4 across these samples.

Fifty older adults (intact=27, combined MCI/mild AD group=23; "impaired") completed neuropsychological testing, including the RBANS, as part of a larger study. Participants were re-contacted and returned for EEG assessment between several weeks to one year later. During EEG recording, participants completed a word-pair judgement paradigm, which involved distinguishing between semantically congruent and incongruent word-pairs. Data was collected and analyzed according to customized N4 analysis scripts provided as part of ERPCORE, an online resource for acquiring and analyzing common ERP components (Kappenman et al., 2021; https://osf.io/thsqg/). The change in N4 amplitude between congruent and incongruent trials (the N4 effect) was used as an index of participants' semantic functioning. Participants' N4 effect was quantified using the mean amplitude from 300-550 milliseconds poststimulus at electrode Cz.

Repeated measures ANOVAs indicated a significant effect of trial type on the N400 amplitude in the intact individuals (F(1, 26)=77.66, p<.001), which remained significant in the sample as a whole (F(1, 48)=65.18, p<.001). Although intact participants numerically showed a larger N4 effect (intact: M=-4.02, SD=2.37; impaired: M=-2.60, SD=3.40), the expected group-by-trial interaction was not significant (F(1, 48)=3.01, p=.089). Correlational analyses revealed no significant associations between the N4 effect and the RBANS Total Scale scores (r=-.14, p=.32), nor for the Immediate Memory (r=-.002, p=.99), Visuospatial/Constructional (r=-.069, p=.63), Language (r=-.15, p=.30) Attention (r=-.21, p=.14), or Delayed Memory (r=-.18 p=.58) indexes.

Results confirmed the presence of the N4 effect in intact participants and in the sample as a whole. Although the N4 effect was numerically smaller in the impaired group as expected, this difference was not significant in the present sample. Likewise, we observed no evidence for associations between the size of N4 effect and performance on RBANS indexes. Overall, the present study provides mixed evidence for the utility of the N4 as a biomarker in mild AD. Factors that may have contributed to the lack of associations between the N4 effect and the RBANS include the limited sample size and variable lengths of time between participants' initial cognitive assessments and EEG testing.

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.

Attention is the backbone of cognitive systems and is requisite for many cognitive processes vital to everyday functioning, including memory, problem solving, and the cognitive control of behavior. Attention is commonly impaired following traumatic brain injury and is a critical focus of rehabilitation efforts. The development of reliable methods to assess rehabilitation-related changes are paramount. The Attention Network Test (ANT) has been used previously to identify 3 independent, yet interactive attention networks—alerting, orienting, and executive control (EC). We examined the behavioral and neurophysiological robustness and temporal stability of these networks across multiple sessions to assess the ANT’s potential utility as an effective measure of change during attention rehabilitative interventions.

15 healthy young adults completed 4 sessions of the ANT (1 session/7-day period). ANT networks were assessed within the task by contrasting opposing stimulus conditions: cued vs. non-cued trials probed alerting, valid vs. invalid spatial cues probed orienting, and congruent vs. incongruent targets probed EC. Differences in median correct-trial reaction times (RTs) and error rates (ERs) between the condition pairs were assessed to determine attention network scores; robustness of networks effects, as determined by one-sample t-tests at each session, against a mean of 0, determining the presence of significant network effects at each session. Sixty-four-channel electroencephalography (EEG) data were acquired concurrently and processed using Matlab to create condition-related event-related potentials (ERPs)—particularly the cue- and probe-related P1, N1, and P3 deflection amplitudes, measured by using signed-area calculation in regions of interest (ROIs) determined by observation of spherical-spline voltages. This enabled us to examine the robustness of cue- and probe-attention-network ERPs.

All three attention networks showed robust effects. However, only the EC RT and ER network scores remained significantly robust [t(14)s>13.9,ps<.001] across all sessions, indicating that EC is robust in the face of repeated exposure. Session 1 showed the greatest EC-RT robustness effect which became smaller during the subsequent sessions per ANOVAs on Session x Congruency [F(3,42)=10.21,p<.0001], reflecting persistence despite practice effects. RT robustness of the other networks varied across sessions. Alerting and EC ERs were similarly robust across all 4 sessions, but were more variable for the orienting network. ERP results: The cue-locked P1-orienting (valid vs. invalid) was generally larger to valid- than invalid-cues, but the robustness across sessions was variable (significant in only sessions 1 and 4 [t(14)s>2.13,ps<.04], as reflected in a significant main effect of session [p=.0042]. Next, target-locked EC P3s were generally smaller to congruent than incongruent targets [F(1,14)=9.40,p=.0084], showing robust effects only in sessions 3 and 4 [ps<.005].

The EC network RT and ER scores were consistently robust across all sessions, suggesting that this network may be less vulnerable to practice effects across session than the other networks and may be the most reliable probe of attentional rehabilitation. ERP measures were more variable across attention networks with respect to robustness. Behavioral measures of EC-network may be most reliable for assessing progress related to attentional-rehabilitation efforts.

Timing, or the decision of when to act, is essential to mammalian behaviors from escaping predators to driving a car. It requires cognitive functions such as working memory for time-based rules and attention to the passing of time. Thus, it can be used as a proxy for higher order executive functions that are difficult to measure but are impaired in many neurological disorders. Therefore, insights from studies of interval timing, tasks which require estimating time intervals of several seconds, have great value for our understanding of human disease. Crucial to timing is the basal ganglia, which integrates cortical activity with midbrain dopamine signals and sends out signals to the spinal cord that regulate movement, motivation, and other behaviors. We have previously found that within the basal ganglia, medium spiny neurons of the striatum exhibit ramping activity in time-related tasks. In other words, they gradually increase or decrease firing frequency across a timed interval, and this is thought to encode time. Yet it is still unknown how the encoding of time is translated into time-based motor responses. To answer this question, we turned to the external globus pallidus (GPe) because it is a regulatory hub within the basal ganglia and is thus well positioned to regulate timing behavior. We sought to examine how the GPe functions in response to time-based demands.

We recorded from neuronal ensembles using 16 channel electrode arrays implanted in the GPe of five mice while they performed an interval timing task called the switch interval timing task. Spike sorting was then used to identify signal from individual neurons.

Data were compiled from 43 neurons over several trials. Principal component analysis of neural firing activity was then conducted and revealed a downward ramping pattern in GPe neurons during interval timing trials. Data were then separated based on trials in which mice made correct decisions and those in which mice made a mistake. We found that when mice make correct timing decisions, there is downward ramping activity in the GPe, yet when mice make timing mistakes, this ramping pattern is lost.

Our findings suggest that the GPe processes timing signals through ramping activity, before projecting to the output nuclei of the basal ganglia. This is a novel finding and contributes to a growing understanding of the temporal code of the basal ganglia. The full extent of this code is still unknown, but this insight contributes to a better understanding of how the globus pallidus represents cognition. If we can better explain the neural correlates of timing, we can use this knowledge to inform therapeutic interventions for basal ganglia dysfunction, which could have profound implications for diseases like Parkinson’s disease, which affects millions around the world.

Epilepsy includes recurrent, unprovoked seizures and affects 470,000 children in the US, of which 7% have drug-resistant epilepsy due to failing two or more antiseizure medication trials. For some patients with drug-resistant epilepsy, surgery has been successful in reducing seizure burden. Functional MRI (fMRI) and intracranial mapping of neurocognitive functions, especially language, are increasingly done to assess potential functional loss from epilepsy surgery. However, these procedures vary by medical institute. The purpose of this review was to examine published literature on fMRI and intracranial mapping procedures for pediatric epilepsy surgery workup toward development of a standardized protocol that can be used across institutes as a guide to standard-of-care best practices for predicting loss of function associated with epilepsy surgery.

Our literature review includes information from 8 electronic databases for peer-reviewed, English language studies of evaluation for pediatric epilepsy surgery candidacy. Thirty-one studies were selected based on inclusion criteria. Only studies including fMRI and intracranial mapping conducted with pediatric patients being worked up for epilepsy surgery were selected.

Our review revealed that the most common task used in fMRI and intracranial mapping procedures is visual-object naming, but type of naming tasks and the way they are administered varies widely across medical institutes and includes published measures and those created on site. Variability makes examining findings across studies and designing best practice for these procedures challenging.

Creating gold-standard procedures for fMRI and intracranial mapping administration for epilepsy surgery evaluations is critical in optimizing treatment and functional outcomes for our pediatric patients. Our review is an initial step in this process.

Concurrent electroencephalography (EEG) during neuropsychological assessment offers a promising method to understand realtime neural and cognitive processes during task performance. For example, previous studies using experimental tasks suggest that midline-frontal theta power (MFT) could serve as a measure of mental exertion and subjective difficulty. The RBANS provides an opportunity to examine this issue in neuropsychological assessment, as a widely-used screening battery that was explicitly developed with subtests that vary according to difficulty within its five domains. This study investigated the effects of task difficulty, cognitive domain, and age on elicitation of MFT during rest and RBANS administration.

EEG was recorded during eyes-closed and eyes-open resting periods and RBANS administration in a sample of 45 healthy younger adults (n = 21; mean age = 23.29, SD = 3.27, range = 19-33; 48% female) and older adults (n = 24; mean age = 70.58, SD = 5.77, range = 59-83; 83% female). MFT was defined as the highest peak above the overall power spectrum within 4-8Hz from electrode Fz, and operationalized as a binary variable (present/absent). A multilevel generalized logistic regression model was run to assess the main effects of Age (Younger, Older), Difficulty (Easy, Hard), Domain (Rest, Immediate Memory, Visuospatial/Constructional, Language, Attention, Delayed Memory), and their potential interactions, on the presence of MFT.

In the full sample, the Coding, Figure Recall, and Picture Naming subtests were numerically most likely to elicit MFT (71.1%, 66.7%, and 62.2%, respectively), whereas Semantic Fluency, Eyes-Closed Rest, and List Recall had the lowest likelihoods (37.7%, 31%, 28.9%). Older adults were also numerically less likely to exhibit MFT (37.50% present) compared to younger adults (62.24% present). An analysis of deviance revealed a significant effect of Age (F(1,43) = 7.22, p = .01) and a significant interaction between Difficulty and Domain (F(5,220) = 4.78, p < .001). Specifically, Hard subtests in the Visuospatial/Constructional (Figure Copy; b = -2.63, p < .05) and Language (Semantic Fluency; b = -2.92, p < .01) Domains were less likely to elicit MFT than the Easy subtests (i.e., Line Orientation and Picture Naming, respectively).

Results indicated that MFT can be reliably measured during neuropsychological assessment, and varies in relation to both age and task-related factors. Consistent with previous studies, older adults exhibited less MFT than younger adults in general, possibly suggesting a failure to recruit the relevant networks. Further, present findings suggest that the presence of MFT varies not only by the type of task but also by the level of difficulty. Future research with larger samples can clarify whether and how the amount of MFT elicited during specific subtests relates to objective and subjective difficulty. Overall, MFT can reliably be elicited by cognitive tasks and bears further study as a measure of real-time neural expenditure.

Functional near-infrared spectroscopy (fNIRS) is a non-invasive functional neuroimaging method that takes advantage of the optical properties of hemoglobin to provide an indirect measure of brain activation via task-related relative changes in oxygenated hemoglobin (HbO). Its advantage over fMRI is that fNIRS is portable and can be used while walking and talking. In this study, we used fNIRS to measure brain activity in prefrontal and motor region of interests (ROIs) during single- and dual-task walking, with the goal of identifying neural correlates.

Nineteen healthy young adults [mean age=25.4 (SD=4.6) years; 14 female] engaged in five tasks: standing single-task cognition (serial-3 subtraction); single-task walking at a self-selected comfortable speed on a 24.5m oval-shaped course (overground walking) and on a treadmill; and dual-task cognition+walking on the same overground course and treadmill (8 trials/condition: 20 seconds standing rest, 30 seconds task). Performance on the cognitive task was quantified as the number of correct subtractions, number of incorrect subtractions, number of self-corrected errors, and percent accuracy over the 8 trials. Walking speed (m/sec) was recorded for all walking conditions. fNIRS data were collected on a system consisting of 16 sources, 15 detectors, and 8 short-separation detectors in the following ROIs: right and left lateral frontal (RLF, LLF), right and left medial frontal (RMF, LMF), right and left medial superior frontal (RMSF, LMSF), and right and left motor (RM, LM). Lateral and medial refer to ROIs’ relative positions on lateral prefrontal cortex. fNIRS data were analyzed in Homer3 using a spline motion correction and the iterative weighted least squares method in the general linear model. Correlations between the cognitive/speed variables and ROI HbO data were applied using a Bonferroni adjustment for multiple comparisons.

Subjects with missing cognitive data were excluded from analyses, resulting in sample sizes of 18 for the single-task cognition, dual-task overground walking, and dual-task treadmill walking conditions. During dual-task overground walking, there was a significant positive correlation between walking speed and relative change in HbO in RMSF [r(18)=.51, p<.05] and RM [r(18)=.53, p<.05)]. There was a significant negative correlation between total number of correct subtractions and relative change in HbO in LMSF ([r(18)=-.75, p<.05] and LM [r(18)=-.52, p<.05] during dual-task overground walking. No other significant correlations were identified.

These results indicate that there is lateralization of the cognitive and motor components of overground dual-task walking. The right hemisphere appears to be more active the faster people walk during the dual-task. By contrast, the left hemisphere appears to be less active when people are working faster on the cognitive task (i.e., serial-3 subtraction). The latter results suggest that automaticity of the cognitive task (i.e., more total correct subtractions) is related to decreased brain activity in the left hemisphere. Future research will investigate whether there is a change in cognitive automaticity over trials and if there are changes in lateralization patterns in neurodegenerative disorders that are known to differentially affect the hemispheres (e.g., Parkinson’s disease).

High-definition transcranial direct current stimulation (HD-tDCS) is a non-invasive form of brain stimulation used to modulate neuronal activity in a brain region of interest. Growing research has shown that HD-tDCS is a promising treatment for cognitive decline in neurodegenerative disease. Most HD-tDCS studies have used amplitudes of 2mA or less, with little investigation into tolerability at greater intensities since anecdotal lore generally suggests them to be poorly tolerated. Therefore, we examined the tolerability of HD-tDCS and common side effect profile in older adults who received total amplitudes of 3mA to 10mA (delivered using multiple electrodes delivering 2-4mA). We developed a series of methods (e.g., participant instructions, task engagement, techniques to lower impedance) and hypothesized they would equate the experience between active and sham HD-tDCS. We also compared symptom endorsement between those receiving active stimulation at 3mA+ total versus those receiving 2mA or lower; again, hypothesizing no difference in reported symptoms.

295 older adults (Mage = 71.12±9.42) (Normal Cognition = 75, Amnestic MCI [aMCI] = 172, Dementia of the Alzheimer's Type [DAT] = 27, Other = 21) were enrolled across six HD-tDCS studies. All participants received one to thirty 20- to 30-minute sessions of active or sham stimulation at total amplitudes between 2mA and 10mA. All participants completed a standardized side effect questionnaire after each session asking whether they experienced burning, tingling, itching, scalp pain, trouble concentrating, sleepiness, headache, mood changes, neck pain, skin redness, or any other symptoms. When symptoms were endorsed, participants rated the severity of the symptom (mild, moderate, severe).

We used Fisher's Exact tests to compare the frequency and severity of side effects in active (3mA or higher) vs. sham stimulation. Those receiving sham were significantly more likely to report tingling than those receiving active HD-tDCS. Conversely, those receiving active stimulation more frequently endorsed mood changes and skin redness relative to the sham group, though moderate-severe ratings were endorsed in only 2.9% and 0.4% of the sessions, respectively. Relative to those receiving 2mA, participants receiving higher intensities of active stimulation experienced skin redness more frequently, whereas the 2mA reported higher frequencies of itching and scalp pain. A burning sensation was endorsed at equal rates between these groups; however, the higher intensity active group reported it as moderate or severe more frequently than the 2mA active group. Despite these minor differences, most side effects following 3mA+ were reported at low frequencies and were typically mild when endorsed.

Our findings demonstrate that HD-tDCS is well-tolerated for total amplitudes up to 10mA in older adults with little tangible difference in the reported experience relative to sham. Findings support the use of higher HD-tDCS amplitudes, at least when key methodological procedures are followed.

High-definition transcranial direct current stimulation (HD-tDCS) is a non-invasive brain stimulation technique shown to modulate neuronal networks. In order for HD-tDCS to be used in randomized, placebo-controlled clinical trials, it is critical to have methods that enable blinding. Some research has shown that sham stimulation is an effective blind in tDCS. However, few studies have investigated the double-blinding of HD-tDCS, especially at intensities greater than 2mA. We address this knowledge gap by examining the blinding and double-blinding of HD-tDCS among a mixed neurologic sample of older adults.

A sample of 240 older adults (Mage = 72.21±8.94) with various clinical diagnoses (Normal Cognition = 34, Amnestic MCI [aMCI] = 172, Dementia-Alzheimer’s Type [DAT] = 27, Other = 7) were recruited through five double-blind, randomized controlled trials. All participants were stimulation naive at their first session and received one to thirty sessions of 20- or 30-minutes of active (n=1472) or sham (n=681) stimulation at total amplitudes of 2mA, 4mA, or 6mA. At the start of each stimulation session, a study team member entered a code into the tDCS unit, and the electrical current was gradually ramped up to the specified (blinded) amplitude over a period of 30 seconds. The current remained at this level for the specified amount of time in the active condition (e.g., 20-minutes) but was ramped down over the next 30 seconds for those in the sham condition. This ramp up/down process was repeated in the final minute (e.g., 20th minute) in the sham session to provide both primacy and recency effects. After each active or sham session, participants were asked whether they received 'real’ or sham stimulation. One study also asked a study team member if they believed the participant received real or sham stimulation at two primary outcome endpoints.

We used Fisher’s Exact tests to evaluate the efficacy of our blinding and double-blinding procedures. In stimulation naive participants receiving their first session, there were no differences in accuracy, suggesting adequate blinding. We also examined participant blinding across all sessions to determine whether repeated HD-tDCS exposure might impact blinding. Across all sessions, participants in the sham condition were more likely to endorse being in the 'real’ (active) condition, again suggesting adequate blinding. There were no significant group differences for active versus sham in the frequency of the study team correctly stating the participant’s condition, suggesting sufficient double-blinding. No significant differences were found in study team blinding when data from the 2mA versus 4mA to 6mA were analyzed separately.

These results suggest that the HD-tDCS sham method is an effective blind and double-blind for HD-tDCS in clinical trials, even at total amplitudes as high as 6mA.

Episodic memory functioning is distributed across two brain circuits, one of which courses through the dorsal anterior cingulate cortex (dACC). Thus, delivering non-invasive neuromodulation technology to the dACC may improve episodic memory functioning in patients with memory problems such as in amnestic mild cognitive impairment (aMCI). This preliminary study is a randomized, double-blinded, sham-controlled clinical trial to examine if high definition transcranial direct current stimulation (HD-tDCS) can be a viable treatment in aMCI.

Eleven aMCI participants, of whom 9 had multidomain deficits, were randomized to receive 1 mA HD-tDCS (N=7) or sham (N=4) stimulation. HD-tDCS was applied over ten 20-minute sessions targeting the dACC. Neuropsychological measures of episodic memory, verbal fluency, and executive function were completed at baseline and after the last HD-tDCS session. Changes in composite scores for memory and language/executive function tests were compared between groups (one-tailed t-tests with a = 0.10 for significance). Clinically significant change, defined as > 1 SD improvement on at least one test in the memory and non-memory domains, was compared between active and sham stimulation based on the frequency of participants in each.

No statistical or clinically significant change (N-1 X2; p = 0.62) was seen in episodic memory for the active HD-tDCS (MDiff = 4.4; SD = 17.1) or sham groups (MDiff = -0.5; SD = 9.7). However, the language and executive function composite showed statistically significant improvement (p = 0.04; MDiff = -15.3; SD = 18.4) for the active HD-tDCS group only (Sham MDiff = -5.8; SD = 10.7). Multiple participants (N=4) in the active group had clinically significant enhancement in language and executive functioning tests, while nobody in the sham group did (p = 0.04).

HD-tDCS targeting the dACC had no direct benefit for episodic memory deficits in aMCI based on preliminary findings for this ongoing clinical trial. However, significant improvement in language and executive function skills occurred in response to HD-tDCS, suggesting HD-tDCS in this configuration has promising potential as an intervention for language and executive function deficits in MCI.