The purpose of this invited paper was to summarize my clinical research on disturbances of higher order consciousness (i.e., primarily on self-awareness but including anosognosia and impaired awareness of another person’s cognitive/emotional state) that contributed to my receiving the Distinguished Career Award from the International Neuropsychology Society.

I reviewed my early clinical encounters with disturbances in higher order consciousness and then a series of studies performed with various colleagues over the last 45 years to better understand the nature of these disturbances. The findings obtained are also discussed within the context of other researchers’ observations during this time frame.

Disturbances in higher order consciousness include classic anosognosia, impaired self-awareness, denial of disability, and denial of ability. Proposed diagnostic features of each of these disturbances are outlined and a model for understanding their complex relationships suggested. Different treatment/rehabilitation approaches for these disturbances are also summarized.

Disturbances in higher order consciousness are often revealed when exploring with the person their subjective experiences of their neurological and neuropsychological functioning following different brain disorders. These subjective experiences have diagnostic value and lead to different rehabilitation approaches. The neuropsychological investigation of disturbances in higher order consciousness should include integrating knowledge from the neurosciences with nonbiological understandings of how cultural and personality features of the person may also influences their subjective experiences associated with a known or suspected brain disorder.

Traumatic brain injury (TBI), mental health conditions (e.g., posttraumatic stress disorder [PTSD]), and vascular comorbidities (e.g., hypertension, diabetes) are highly prevalent in the Veteran population and may exacerbate age-related changes to cerebral white matter (WM). Our study examined (1) relationships between health conditions—TBI history, PTSD, and vascular risk—and cerebral WM micro- and macrostructure, and (2) associations between WM measures and cognition.

We analyzed diffusion tensor images from 183 older male Veterans (mean age = 69.18; SD = 3.61) with (n = 95) and without (n = 88) a history of TBI using tractography. Generalized linear models examined associations between health conditions and diffusion metrics. Total WM hyperintensity (WMH) volume was calculated from fluid-attenuated inversion recovery images. Robust regression examined associations between health conditions and WMH volume. Finally, elastic net regularized regression examined associations between WM measures and cognitive performance.

Veterans with and without TBI did not differ in severity of PTSD or vascular risk (p’s >0.05). TBI history, PTSD, and vascular risk were independently associated with poorer WM microstructural organization (p’s <0.5, corrected), however the effects of vascular risk were more numerous and widespread. Vascular risk was positively associated with WMH volume (p = 0.004, β=0.200, R2 = 0.034). Higher WMH volume predicted poorer processing speed (R2 = 0.052).

Relative to TBI history and PTSD, vascular risk may be more robustly associated with WM micro- and macrostructure. Furthermore, greater WMH burden is associated with poorer processing speed. Our study supports the importance of vascular health interventions in mitigating negative brain aging outcomes in Veterans.

Higher white matter hyperintensity (WMH) volume is a marker of cardiovascular disease (CVD) risk. CVD risk factors increase risk for Alzheimer’s disease and related dementias (ADRD). Mexican Americans (MA) and individuals of other Hispanic/Latino heritages have higher risk for CVD and ADRD. However, knowledge of associations between WMH volume and cognition in these groups remains limited.

We conducted a cross-sectional study of associations between WMH volume and neuropsychological performance (attention/executive functioning, memory) in MA (n = 851) and non-Hispanic White (NHW; n = 747) adults in the Health and Aging Brain Study: Health Disparities.

The MA group (mean age = 63.72 ± 7.90 years; 66.3% female) had higher rates of consensus diagnoses of hypertension and diabetes, whereas the NHW group (mean age = 69.18 ± 8.65 years; 55.2% female) had higher rates of diagnosed CVD (ps < .01). WMH volumes were higher among individuals with CVD risk factors/conditions (ps < .01). There were differential associations between WMH and neuropsychological performance across ethnoracial groups (ps < .001), wherein associations were steeper in the NHW group than in the MA group. Lower educational level was associated with higher WMH volume in the NHW group (p < .001), but no association was seen in the MA group (p > .05).

Negative effects of pathological changes in the form of WMH on cognition may be less robust or consistent for MA adults than NHW adults. Furthermore, the impact of WMH on cognition in NHW adults may be mitigated by cognitive reserve related to educational attainment.

To establish quick-reference criteria regarding the frequency of statistically rare changes in seven neuropsychological measures administered to older adults.

Data from 935 older adults examined over a two-year interval were obtained from the Alzheimer’s Disease Neuroimaging Initiative. The sample included 401 cognitively normal older adults whose scores were used to determine the natural distribution of change scores for seven cognitive measures and to set change score thresholds corresponding to the 5th percentile. The number of test scores that exceeded these thresholds were counted for the cognitively normal group, as well as 381 individuals with mild cognitive impairment (MCI) and 153 individuals with dementia. Regression analyses examined whether the number of change scores predicted diagnostic group membership beyond demographic covariates.

Only 4.2% of cognitively normal participants obtained two or more change scores that fell below the 5th percentile of change scores, compared to 10.6% of the stable MCI participants and 38.6% of those who converted to dementia. After adjusting for age, gender, race/ethnicity, and premorbid estimates, the number of change scores below the 5th percentile significantly predicted diagnostic group membership.

It was uncommon for older adults to have two or more change scores fall below the 5th percentile thresholds in a seven-test battery. Higher change counts may identify those showing atypical cognitive decline.

Neuropsychological assessment through VideoTeleConferencing (VTC) can help improve access to diagnostic and follow-up care in memory clinics. This study investigated the stability of performance on VTC assessment in relation to in-person assessment using a test-retest design and explored user experiences of VTC assessment.

Thirty-one patients (62 ± 6.7 years, 45% female, 58% Subjective Cognitive Decline, 42% Mild Cognitive Impairment/dementia diagnosis) were included from the Amsterdam Dementia Cohort between August 2020 and February 2021. Patients underwent a face-to-face neuropsychological assessment followed by a VTC assessment using the same test protocol within 4 months. Reliability coefficients were calculated using intraclass correlation coefficients (ICC). For each test, the proportion of clinically relevant differences in performances between assessment modalities was calculated. User experiences of patients and neuropsychologists were assessed with questionnaires (User Satisfaction and Ease of use [USE] questionnaire and System Usability Scale [SUS]). Neuropsychologists also participated in a focus group.

ICC values were moderate to excellent (0.63-0.93) for all test measures in the total sample. On all tests, most patients did not show clinically relevant performance differences between modalities. Patients and neuropsychologists reported overall positive VTC system usability, although neuropsychologists indicated in the focus group that patients without cognitive impairment required less training for the system and were more independent.

VTC assessment showed adequate to excellent test-retest reliability for a broad range of neuropsychological tests commonly used in practice. Assessment through VTC may be a user friendly method in the memory clinic, especially to monitor individuals at risk for future cognitive decline.

Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.

We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).

At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.

Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.

Pediatric-onset multiple sclerosis (POMS) accounts for approximately 2 to 5% of all individuals with MS and is associated with an increased risk for cognitive impairment. In recent years, neuropsychological screening questionnaires have been increasingly utilized for pediatric populations in multidisciplinary settings. This study examines the clinical utility of the Colorado Learning Difficulties Questionnaire (CLDQ) and Pediatric Perceived Cognitive Functioning (Peds PCF) screening measures for identifying cognitive impairment in persons with POMS during a target neuropsychological evaluation.

Retrospective data was gathered from electronic medical records at a single pediatric hospital.

Forty-nine participants were included (69% female; 43% Hispanic/Latinx; mean age = 16.1 years old, range = 9.9 to 20.6 years old). Correlation analyses demonstrated strong interrelatedness between caregiver ratings on screening measures and performance on traditional neuropsychological measures. Effect sizes were medium across comparisons (CLDQ: Spearman’s rho = −.321 to −.563; PedsPCF: Spearman’s rho = .308 to .444). Exploratory cut-points using receiver operating characteristic analysis and Youden indices are also discussed.

Comparison of scores across caregiver rating questionnaires and on a targeted neuropsychological battery suggests that the screening surveys alone may not be sensitive enough to identify children with cognitive impairments, but ratings may provide qualitatively meaningful information along with neuropsychological testing. This study illustrates how pediatric neuropsychologists can leverage screening tools to focus consultative interviews and effectively triage referrals for evaluation within an academic medical setting.

This study examined the validity of a visual inspection time (IT) task as a measure of processing speed (PS) in a sample of children with and without cerebral palsy (CP). IT tasks measure visualization speed without focusing on the motor response time to indicate decision making about the properties of those stimuli.

Participants were 113 children ages 8–16, including 45 with congenital CP, and 68 typically developing peers. Measures were a standard visual IT task that required dual key responding and a modified version using an assistive technology button with response option scanning. Performance on these measures was examined against traditional Wechsler PS measures (Coding, Symbol Search).

IT performance shared considerable variance with traditional paper-pencil PS measures for the group with CP, but not necessarily in the typically developing group. Concurrent validity was found for both IT task versions with traditional PS measures in the group with CP. IT classification accuracy for lowered PS showed modest sensitivity and good specificity particularly for the modified IT task.

As measures of PS in children with CP who are unable to validly participate in traditional PS tasks, IT tasks demonstrate adequate concurrent validity and may serve as a beneficial alternative measure of PS in this population.

To introduce the Emory 10-element Complex Figure (CF) scoring system and recognition task. We evaluated the relationship between Emory CF scoring and traditional Osterrieth CF scoring approach in cognitively healthy volunteers. Additionally, a cohort of patients undergoing deep brain stimulation (DBS) evaluation was assessed to compare the scoring methods in a clinical population.

The study included 315 volunteers from the Emory Healthy Brain Study (EHBS) with Montreal Cognitive Assessment (MoCA) scores of 24/30 or higher. The clinical group consisted of 84 DBS candidates. Scoring time differences were analyzed in a subset of 48 DBS candidates.

High correlations between scoring methods were present for non-recognition components in both cohorts (EHBS: Copy r = 0.76, Immediate r = 0.86, Delayed r = 0.85, Recognition r = 47; DBS: Copy r = 0.80, Immediate r = 0.84, Delayed Recall r = 0.85, Recognition r = 0.37). Emory CF scoring times were significantly shorter than Osterrieth times across non-recognition conditions (all p < 0.00001, individual Cohen’s d: 1.4–2.4), resulting in an average time savings of 57%. DBS patients scored lower than EHBS participants across CF memory measures, with larger effect sizes for Emory CF scoring (Cohen’s d range = 1.0–1.2). Emory CF scoring demonstrated better group classification in logistic regression models, improving DBS candidate classification from 16.7% to 32.1% compared to Osterrieth scoring.

Emory CF scoring yields results that are highly correlated with traditional Osterrieth scoring, significantly reduces scoring time burden, and demonstrates greater sensitivity to memory decline in DBS candidates. Its efficiency and sensitivity make Emory CF scoring well-suited for broader implementation in clinical research.

To evaluate the impact of receptive vocabulary versus years of education on neuropsychological performance of Black and White older adults.

A community-based prospectively enrolled cohort (n = 1,007; 130 Black, 877 White) in the Emory Healthy Brain Study were administered the NIH Toolbox Picture Vocabulary Test and neuropsychological measures. Group differences were evaluated with age, sex, and education or age, sex, and Toolbox Vocabulary scores as covariates to determine whether performance differences between Black versus White participants were attenuated or eliminated.

With vocabulary as a covariate, the main effect of race was no longer significant for the MoCA, Phonemic Fluency, Rey Auditory Verbal Learning Test, and Rey Complex Figure Test immediate and delayed recall. Although still significantly different between groups, the effect sizes for Animal Fluency, Trails B-A, Symbol Digit Modalities Test, and Rey Copy were attenuated, with the greatest reductions occurring for the Multilingual Naming Test and Judgment of Line Orientation.

Findings support the value of using receptive vocabulary as a proxy for premorbid ability level when comparing the cognitive performance of Black and White older adults. The results extend investigations using measures of single word reading to encompass measures assessing word meaning.

Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation technique, has shown some promise as a novel treatment approach for a range of mental health disorders, including OCD. This study provides a systematic review of the literature involving randomized controlled trials of tDCS for OCD and evaluates the quality of reporting using the CONSORT (Consolidating Standards of Reporting Trials) statement. This study also examined the outcomes of tDCS as a therapeutic tool for OCD.

This systematic review was prospectively registered with PROSPERO (CRD42023426005) and the data collected in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The quality of reporting of included studies was evaluated in accordance with the CONSORT statement.

Eleven randomized controlled trials were identified. Evaluation of the reviewed studies revealed low levels of overall compliance with the CONSORT statement highlighting the need for improved reporting. Key areas included insufficient information about - the intervention (for replicability), participant flow, recruitment, and treatment effect sizes. Study discussions did not fully consider limitations and generalizability, and the discussion/interpretation of the findings were often incongruent with the results and therefore misleading. Only two studies reported a significant difference between sham and active tDCS for OCD outcomes, with small effect sizes noted.

The variability in protocols, lack of consistency in procedures, combined with limited significant findings, makes it difficult to draw any meaningful conclusions about the effectiveness of tDCS for OCD. Future studies need to be appropriately powered, empirically driven, randomized sham-controlled clinical trials.

High-definition transcranial direct current stimulation (HD-tDCS) has the potential to improve cognitive functioning following neurological injury and in neurodegenerative conditions. In this case report, we present the first use of HD-tDCS in a person with severe anterograde amnesia following carbon monoxide poisoning.

The participant underwent two rounds of HD-tDCS that were separated by 3 months (Round 1 = 30 sessions; Round 2 = 31 sessions). We used finite element modeling of the participant’s structural MRI to develop an individualized montage that targeted multiple brain regions involved in memory encoding, as identified by Neurosynth.

Overall, the participant’s objective cognitive functioning improved significantly following Round 1, declined during the 2 months without HD-tDCS, and again improved following Round 2. Subjective informant reports from family and medical personnel followed this same pattern of improvement following each round with a decline in between rounds. We also provide preliminary evidence of altered brain activity during a learning/memory task using functional near-infrared spectroscopy, which may help establish the physiological effects of HD-tDCS in future work.

Overall, these findings reinforce the potential value of HD-tDCS as a user-friendly method of enhancing cognition following anoxic/hypoxic brain injury.