Frontal Systems Behavior Scale Research Articles

A-163 APOE ε4 Alters Self-Awareness of Executive Function in Cognitively Intact Middle Aged and Older Adults

Abstract Objective Subjective cognitive complaints (SCC) may be an early indicator of future cognitive decline. Although early executive function (EF) decline in Alzheimer’s disease (AD) may be a sensitive predictor, the predicative utility of SCCs specific to EF is unknown. Thus, this study examined whether EF performance predicts SCCs of EF in healthy, well-educated middle aged and older adults, and whether carrying of APOE ε4 alters that prediction. Method Fifty-five cognitively intact middle aged to older adults (Mage = 64.1, range = 48–84, 19 e4+) completed the Frontal Systems Behavior Scale (FrSBe) Executive Dysfunction Scale (EXECDYS) to measure SCCs and an EF battery (Trail-making A&B, Symbol-digit Modalities Test, verbal fluency (letter, category), which principal components analysis (varimax rotation) reduced to a single EF factor. We examined whether SCCs (EXECDYS) were predicted by EF performance (age, depression covaried), and whether ε4 moderated that prediction (PROCESS 3.0). Results The model was significant (R2 = 0.31; p = 0.002), with a significant EXECDYS X ε4 interaction (ß = 4.24, t(55) = 2.37; p = .02), indicating that EF performance predicted EXECDYS, but in ε4-carriers only, those with poorer EF were less aware of that dysfunction. Conclusions Amongst APOE ε4-carriers, a group with high risk for AD, those with poorer EF had less accurate self-awareness of their EF, suggesting earlier formal assessment is needed in ε4-carriers to detect decline. Furthermore, as our study examined healthy, well-educated, cognitively intact adults from middle age, these findings suggest ε4-carriers are at particularly high risk for AD if their self-awareness and performance of EF are both low. Combining EF assessment with self-appraisal of EF may aid AD diagnostics.

Association of HIV serostatus and metabolic syndrome with neurobehavioral disturbances.

Metabolic syndrome (MetS), a constellation of related metabolic risk factors, is a common comorbidity associated with cognitive difficulty in people living with HIV (PLWH). Neurobehavioral disturbances (e.g., behavioral manifestations of frontal-subcortical dysfunction) are also prevalent in HIV, yet the role MetS might play in HIV-associated neurobehavioral disturbances is unknown. Thus, we examined the link between MetS and neurobehavioral disturbances in PLWH. Participants included 215 adults (117 PLWH, 98 HIV-uninfected), aged 36 to 65years, from a cohort study at the University of California San Diego. Using the Frontal Systems Behavior Scale, we captured neurobehavioral disturbances (apathy, disinhibition, and executive dysfunction). MetS was defined by the National Cholesterol Education Program's Adult Treatment Panel-III criteria. Covariates examined included demographic, neurocognitive impairment, and psychiatric characteristics. When controlling for relevant covariates, both HIV serostatus and MetS were independently associated with greater apathy and executive dysfunction. HIV, but not MetS, was associated with greater disinhibition. The present findings suggest an additive effect of HIV and MetS on specific neurobehavioral disturbances (apathy and executive dysfunction), underscoring the importance of identifying and treating both HIV and MetS to lessen central nervous system burden among PLWH.

The Neurological Predictor Scale Predicts Adaptive Functioning via Executive Dysfunction in Young Adult Survivors of Childhood Brain Tumor.

Survivors of childhood brain tumors experience neurological sequelae that disrupt everyday adaptive functioning (AF) skills. The Neurological Predictor Scale (NPS), a cumulative measure of tumor treatments and sequelae, predicts cognitive outcomes, but findings on its relation to informant-reported executive dysfunction (ED) and AF are mixed. Given known effects of frontal-subcortical system disruptions on AF, this study assessed the NPS' relationship with AF as mediated by frontal systems dysfunction, measured by the Frontal Systems Behavior Scale (FrSBe). 75 participants (Mage = 23.5, SDage = 4.5) were young adult survivors of childhood brain tumors at least 5 years past diagnosis. FrSBe and Scales of Independent Behavior-Revised (SIB-R), a measure of AF, were administered to informants. Parallel multiple mediator models included Apathy and ED as mediators, and age at diagnosis and time between diagnosis and assessment as covariates. More complex treatment and sequelae were correlated with poorer functioning. Mediation models were significant for all subscales: Motor Skills (MS), p=.0001; Social Communication (SC), p=.002; Personal Living (PL), p=.004; Community Living (CL), p=.007. The indirect effect of ED on SC and CL was significant; the indirect effect of Apathy was not significant for any subscales. More complex tumor treatment and sequelae were associated with poorer long-term AF via increased ED. Cognitive rehabilitation programs may focus on the role of executive function and initiation that contribute to AF, particularly SC and CL skills, to help survivors achieve comparable levels of independence in everyday function as their peers.

Response inhibition in Veterans with a history of mild traumatic brain injury: The role of self-reported complaints in objective performance

ABSTRACT Introduction Although objective deficits in response inhibition (RI) have been detected in civilians with mild traumatic brain injury (mTBI), it remains unclear whether objective RI is worse in military Veterans with mTBI despite the prevalence of self-reported disinhibition. Assessing RI in Veterans is critical due to their unique characteristics, including combat and blast exposure, in addition to the prevalence of psychiatric comorbidity. Therefore, the aims of this study were to (1) examine RI performance in Veterans with mTBI compared to non-mTBI Veterans and (2) compare RI performance in well-defined subgroups of mTBI Veterans with and without self-reported complaints of disinhibition to non-mTBI Veterans. Method 53 mTBI Veterans and 37 non-mTBI Veterans completed a Go/No-Go RI task and measures of self-reported disinhibition (Frontal Systems Behavior Scale) and psychiatric symptoms. ANCOVAs covarying for mood and demographics compared RI performances of the non-mTBI Veterans to (1) the total sample of mTBI Veterans (n= 53) and to (2) mTBI Veterans with elevated (t-score ≥ 60; mTBI-SubjDis; n= 23) and low (t-score < 60; mTBI-NoSubjDis; n= 30) levels of self-reported disinhibition. Results There were no significant differences in RI between the mTBI group as a whole and the non-mTBI Veterans group. However, when Veterans with mTBI were divided into groups by clinically-significant concern about their disinhibition, the mTBI-SubjDis group demonstrated significantly worse RI than the mTBI-NoSubjDis and non-mTBI Veteran groups. No significant differences in RI performance were observed between the mTBI-NoSubjDis and non-mTBI Veteran groups. Conclusions Results indicate that mTBI Veterans with elevated levels of self-reported disinhibition show diminished performance on objective measures of RI, independent of mood. Findings highlight the unique contribution of subjective complaints on executive functioning in mTBI, and they underscore the importance of assessing cognitive complaints in order to identify those most at risk for poor-long term outcomes.

Apathy and its impact on carer burden and psychological wellbeing in primary progressive aphasia

ObjectiveWhile patients with primary progressive aphasia (PPA) typically present with predominant language impairment, behavioural symptoms, such as apathy, are often under-recognised. We aimed to systematically characterise apathy across the three recognised subtypes of PPA, plus atypical right-lateralised presentations of semantic dementia, and to evaluate the impact of apathy on carer burden and psychological wellbeing. MethodsBaseline assessments from 114 PPA patients were included: 31 left semantic dementia (left SD) 16 right semantic dementia (right SD), 30 progressive nonfluent aphasia (PNFA) and 37 logopenic progressive aphasia (LPA). Clinician (Neuropsychiatric Inventory; NPI) and carer rated (Cambridge Behavioural Inventory; CBI, Frontal Systems Behaviour Scale; FrSBe) measures were used to quantify symptoms of apathy, and carer burden and psychological wellbeing were determined using the Zarit Burden Interview and Depression, Anxiety and Stress Scale. ResultsOn the NPI, symptoms of apathy were present in 39% left SD, 56% right SD, 33% PNFA and 43% LPA patients. Multiple regression analysis revealed that 17.9% of the variance in carer burden was uniquely explained by scores on carer rated measures of apathy (CBI, FrSBe), even after accounting for diagnosis, disease duration, and cognitive and language impairment. ConclusionsApathy is much more common than current diagnostic criteria for PPA would suggest, though the severity of apathy is similar across patient groups. Increased awareness and routine assessments of apathy symptoms are needed, together with targeted pharmacological and behavioural interventions. Moreover, as apathy substantially contributes to carer burden in PPA, psychoeducation addressing behavioural symptoms may be beneficial.

Frontal Behavior Syndromes in Idiopathic Normal Pressure Hydrocephalus as a Function of Alzheimer's Disease Biomarker Status.

Cognitive impairment and apathy are well-documented features of idiopathic normal pressure hydrocephalus (iNPH). However, research examining other neuropsychiatric manifestations of iNPH is scant, and it is unknown whether the neuropsychiatric presentation differs for iNPH patients with comorbid Alzheimer's disease (AD) versus iNPH without AD. This study aims to advance our understanding of neuropsychiatric syndromes associated with iNPH. Fifty patients from Butler Hospital's Normal Pressure Hydrocephalus Clinic met inclusion criteria. Caregiver ratings on the Frontal Systems Behavior Scale (FrSBe) were examined to appraise changes in apathy, executive dysfunction, and disinhibition. Patients also completed cognitive tests of global cognition, psychomotor speed, and executive functioning. AD biomarker status was determined by either amyloid-beta (Aβ) positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) total tau to Aβ-42 ratio. Results revealed clinically significant elevations on the FrSBe's apathy and executive dysfunction scales and modest correlations among these scales and cognitive measures. Of the 44 patients with available neuroimaging or CSF draw data, 14 presented with comorbid AD. Relative to the iNPH-only group, the iNPH + AD group showed a larger increase from pre-illness to current informant ratings on the executive dysfunction scale, but not the apathy or disinhibition scales. These results replicate and extend prior research by identifying apathy and executive dysfunction as prominent neuropsychiatric symptoms of iNPH and suggest comorbid AD exacerbates dysexecutive behaviors. Future research is warranted to examine the effects of comorbid AD pathology in response to shunt surgery for iNPH, neuropsychiatric symptom changes, and resultant caregiver burden.

Apathy is Associated with Critical Psychological Determinants of Medication Adherence in HIV Disease.

Apathy is common in HIV, separable from depression, and has been associated with non-adherence to antiretroviral therapy (ART). We examined the associations between apathy and critical psychological determinants of ART adherence, as per the information-motivation-behavioral model, in 85 persons living with HIV. Apathy was measured using a composite of the apathy subscale of the Frontal Systems Behavioral Scale and the vigor-activation scale of the Profile of Mood States. Independent of major depressive disorder, apathy was related at small-to-medium effect sizes with motivation to adhere and self-efficacy for health-relateddecision-making and medication management, but not with HIV knowledge or medication management skills. These findings suggest that apathy plays a unique role in several critical health adherence determinants and support the importance of assessment and management of apathy to maximize health outcomes among individuals with HIV disease.

Cognitive process scores associated with self-reported behavioral dysfunction on the Frontal Systems Behavior Scale (FrSBe) in chronic traumatic brain injury

ABSTRACTIntroduction: Individuals with traumatic brain injury (TBI) often experience long-term cognitive impairment that affects daily functioning, but neuropsychological tests are often not associated with functional outcomes in chronic TBI. To identify better neuropsychological test predictors of functional outcomes, we identified process-oriented neuropsychological test scores associated with behavioral dysfunction in chronic TBI.Method: Adults (N = 65, age = 49.9 years, education = 14.6 years, 80% male, 97% white) with a > 6-month (median = 55 months) history of TBI (31% complicated mild, 20% moderate, 49% severe) completed the self-reported Frontal Systems Behavior Scale (FrSBe) and a battery of neuropsychological tests. Cognitive scores significantly associated with FrSBe domain scores (Apathy, Disinhibition, Executive Dysfunction) were included in hierarchical linear regression analyses.Results: Pearson correlations were significant (|r| = .25 – .41, p < .05) between FrSBe Disinhibition and Executive Dysfunction domains and numerous cognitive scores, particularly cognitive process scores, including California Verbal Learning Test II (CVLT-II) and Letter (FAS) Fluency Intrusions and Repetitions. In the regression analyses, gender, injury severity, premorbid intelligence, time since injury, self-awareness, and depression status accounted for less than 1% (Disinhibition) and 6.1% (Executive Dysfunction) of the total adjusted variance in respective FrSBe domains. Cognitive process scores were the strongest factors associated with behavioral dysfunction, explaining an additional 22.9% of the total adjusted variance in Disinhibition [F(3, 50) = 6.28, p = .001]. For Executive Dysfunction, traditional scores explained 2.6% added variance on top of the base model, with cognitive process scores explaining an additional 17.2% [F(4, 48) = 6.79, p = .003] of the total adjusted variance.Conclusions: Less frequently utilized cognitive process scores from well-known neuropsychological tests may be better predictors of behavioral dysfunction in chronic TBI, as measured by the FrSBe. Future prospective study is required to validate these findings and test the sensitivity and specificity of these cognitive process scores for identifying risk for behavioral dysfunction.

The Prevalence and Determinants of Return to Work in Nasopharyngeal Carcinoma Survivors

To assess the employment status in working-age survivors of nasopharyngeal carcinoma (NPC) and explore clinical, treatment, and sociodemographic factors that may facilitate or impede successful return to work (RTW). This Canadian study was part of a larger cross-sectional study assessing late toxicities in 107 disease-free survivors of NPC who received curative-intent intensity modulated radiation therapy ≥4 years earlier. For this substudy, eligible participants were employed at diagnosis and were of working age (<65 years) at study enrollment. Patient-reported work status (modified Radiation Therapy Oncology Group Work Status Questionnaire), quality of life (Functional Assessment of Cancer Therapy-Head and Neck questionnaire), symptom burden (MD Anderson Symptom Inventory for head and neck cancer), anxiety and depression (Hospital Anxiety and Depression Scale), neurobehavioral functioning (Frontal Systems Behavior Scale), and neurocognitive function (Montreal Cognitive Assessment) were assessed. Univariable and multivariable logistic regression models were used to explore the impact of variables on RTW status. Among 73 eligible patients, the median age was 53 years (range, 32-64) and median time from intensity modulated radiation therapy completion was 7.3 years (range, 4.2-11.1). At enrollment, 45 (62%) were working, of whom 14 (31%) had reduced work hours from diagnosis by a median of 12 h/wk (range, 4-30). Overall, mean work hours decreased from 41.6 to 37.8 h/wk (P = .005). Currently employed (vs unemployed) patients were younger (P = .017) and reported better performance status (P = .013). They had higher quality of life (P = .044), lower symptom burden (P = .03), less significant change from their baseline neurobehavioral function (P = .008), and disability (P = .0025) or private health benefits (P= .035). Anxiety, depression, occupation type, income, and Montreal Cognitive Assessment score were not significantly associated with RTW in the univariable analysis. Age, change in baseline neurobehavioral function, and having private health benefits were all independent predictors of RTW. The majority of long-term survivors of NPC do RTW, although almost one-third report working fewer hours. Prospective research is needed to better understand and facilitate successful RTW in survivors of NPC.

Phase I trial of caudate deep brain stimulation for treatment-resistant tinnitus.

The objective of this open-label, nonrandomized trial was to evaluate the efficacy and safety of bilateral caudate nucleus deep brain stimulation (DBS) for treatment-resistant tinnitus. Six participants underwent DBS electrode implantation. One participant was removed from the study for suicidality unrelated to brain stimulation. Participants underwent a stimulation optimization period that ranged from 5 to 13 months, during which the most promising stimulation parameters for tinnitus reduction for each individual were determined. These individual optimal stimulation parameters were then used during 24 weeks of continuous caudate stimulation to reach the endpoint. The primary outcome for efficacy was the Tinnitus Functional Index (TFI), and executive function (EF) safety was a composite z-score from multiple neuropsychological tests (EF score). The secondary outcome for efficacy was the Tinnitus Handicap Inventory (THI); for neuropsychiatric safety it was the Frontal Systems Behavior Scale (FrSBe), and for hearing safety it was pure tone audiometry at 0.5, 1, 2, 3, 4, and 6 kHz and word recognition score (WRS). Other monitored outcomes included surgery- and device-related adverse events (AEs). Five participants provided full analyzable data sets. Primary and secondary outcomes were based on differences in measurements between baseline and endpoint. The treatment effect size of caudate DBS for tinnitus was assessed by TFI [mean (SE), 23.3 (12.4)] and THI [30.8 (10.4)] scores, both of which were statistically significant (Wilcoxon signed-rank test, 1-tailed; alpha = 0.05). Based on clinically significant treatment response categorical analysis, there were 3 responders determined by TFI (≥ 13-point decrease) and 4 by THI (≥ 20-point decrease) scores. Safety outcomes according to EF score, FrSBe, audiometric thresholds, and WRS showed no significant change with continuous caudate stimulation. Surgery-related and device-related AEs were expected, transient, and reversible. There was only one serious AE, a suicide attempt unrelated to caudate neuromodulation in a participant in whom stimulation was in the off mode for 2 months prior to the event. Bilateral caudate nucleus neuromodulation by DBS for severe, refractory tinnitus in this phase I trial showed very encouraging results. Primary and secondary outcomes revealed a highly variable treatment effect size and 60%-80% treatment response rate for clinically significant benefit, and no safety concerns. The design of a phase II trial may benefit from targeting refinement for final DBS lead placement to decrease the duration of the stimulation optimization period and to increase treatment effect size uniformity.Clinical trial registration no.: NCT01988688 (clinicaltrials.gov).

C-29 Sleep and Cognition Among Older Adults: Objective Performance versus Subjective Complaint

Abstract Objective Although poor sleep has been hypothesized to contribute to cognitive difficulties, a review by Scullin &amp; Bliwise (2015) suggested that poor sleep has little impact on older adults’ cognition. Nevertheless, older adults express subjective concerns about both their sleep and cognition. The purpose of this study was to test associations between self-reported sleep, cognitive performance, and subjective cognitive concerns. Method Twenty-three women and 18 men, aged 55 to 83 (M = 68), completed a 3-hour test battery that included global, memory, executive, and verbal measures. Sleep was assessed using the Pittsburgh Sleep Quality Index (PSQI). Subjective cognitive complaints were measured using the Frontal Systems Behavior Scale (FrSBe), which provided a total and three subscale scores (Apathy, Disinhibition, Executive Dysfunction). Results PSQI scores were consistent with means of older non-diagnosed older adults (Bush et al., 2012; M = 6.34, SD = 3.70). Cognitive test scores did not correlate with PSQI scores or FrSBe scores; however, Total PSQI correlated with Total FrSBe (r = .397; CI = .099 to .741) and two of the three FrSBe subscales: Apathy (r = .472; CI = .190 to .683) and Executive Dysfunction (r = .395; CI = .097 to .629), but not Disinhibition (r = .231; CI = -.086 to .505). Conclusions As previously found, cognitive test scores were unrelated to sleep measures; however, associations were found between poor sleep and subjective cognitive concerns, particularly avolition and executive dysfunction. Findings may indicate distress characteristic among older adults that involves sleep disturbance and cognitive worry.

C-21 Emotional Predictors of Self-Reported Frontal Behavior Disruption in Older Adults

Abstract Objective Behavioral manifestations of executive dysfunction (e.g., apathy) include internal experiences subject to informant misinterpretation. Self-reports of these functions, however, may be influenced by subjective cognitive concerns (SCC). The purpose of this study was to assess emotional distress and SCC as predictors of self-reported frontal behavior disruption. Method Twenty-one women and 18 men aged 55 to 83 (M = 66), completed measures of emotional functioning and SCC. The Frontal Systems Behavior Scale (FrSBe) measured frontal behavior concerns, which provided three subscales (Apathy, Disinhibition, Executive Function) and a total score. Emotional functioning was measured with the Patient Health Questionnaire, 9-item (PHQ-9), Generalized Anxiety Disorder, 7-item (GAD-7), and the Dementia Worry Scale (DWS). SCCs were measured using the Cognitive Function- Short-Form 6a (CFSF). Results FrSBe scores were regressed on PHQ-9, GAD-7, CFSF, and DWS. Apathy was predicted by PHQ (B = 1.02, CI: .49 to 1.55, sr2 = .151), CFSF (B = -.42, CI: -.75 to -.10, sr2 = .071), and DWS (B = .14, CI: .02 to .26, sr2 = .052). Disinhibition was predicted by CFSF (B = -.61, CI: -1.06 to -.15, sr2 = .134). Executive dysfunction was predicted by DWS (B = .22, CI: .02 to .41, sr2 = .080). Trends were found for PHQ and CFSF to predict Executive Dysfunction. Conclusions Depression, dementia worry, and SCC predicted aspects of perceived frontal behavior disruption, particularly apathy. Subjective cognitive concern predicted perceived apathy ad disinhibition; dementia worry predicted perceived apathy and executive dysfunction. Depression was only predictive of perceived apathy. These findings support the relationship between depression, dementia worry, SCC, and self-reported behavioral disruption emphasizing the importance of emotions and SCC in self-reported behavioral functioning.

Neuroanatomical correlates of apathy and disinhibition in behavioural variant frontotemporal dementia.

Neuroanatomical correlates of apathy and disinhibition, behavioral abnormalities in behavioral variant Frontotemporal dementia (bvFTD) remain unclear. In this study 45 participants (25 bvFTD patients and 20 controls) provided data on clinical, neuropsychological, behavioral (on Frontal Systems Behavior (FrSBe) Scale), cortical volume (on voxel-based morphometry (VBM)) and tract based spatial fractional anisotropy ((FA) on magnetic resonance imaging (MRI), allowing examination of the neural correlates of apathy and disinhibition. The patients with bvFTD had predominant grey matter loss and corresponding white matter fractional anisotropy reduction in the frontal and temporal lobe compared to the controls. Grey matter loss in frontal, temporal and limbic structures correlated with apathy and degeneration in temporal limbic brain areas correlated with disinhibition. FA changes in inferior fronto-occipital fasciculus and forceps minor correlated with apathy and fibre integrity changes in the superior longitudinal fasciculus correlated with disinhibition. The current study suggests that apathy and disinhibition arises due to changes in the frontal, temporal and limbic brain areas in bvFTD.

ERPs predict symptomatic distress and recovery in sub-acute mild traumatic brain injury

Mild traumatic brain injury (mTBI) can affect high-level executive functioning long after somatic symptoms resolve. We tested if simple EEG responses within an oddball paradigm could capture variance relevant to this clinical problem. The P3a and P3b components reflect bottom-up and top-down processes driving engagement with exogenous stimuli. Since these features are related to primitive decision abilities, abnormal amplitudes following mTBI may account for problems in the ability to exert executive control. Sub-acute (<2 weeks) mTBI participants (N = 38) and healthy controls (N = 24) were assessed at an initial session as well as a two-month follow-up (sessions 1 and 2). We contrasted the initial assessment to a comparison group of participants with chronic symptomatology following brain injury (N = 23). There were no group differences in P3a or P3b amplitudes. Yet in the sub-acute mTBI group, higher symptomatology on the Frontal Systems Behavior scale (FrSBe), a questionnaire validated as measuring symptomatic distress related to frontal lobe injury, correlated with lower P3a in session 1. This relationship was replicated in session 2. These findings were distinct from chronic TBI participants, who instead expressed a relationship between increased FrSBe symptoms and a lower P3b component. In the sub-acute group, P3b amplitudes in the first session correlated with the degree of symptom change between sessions 1 and 2, above and beyond demographic predictors. Controls did not show any relationship between FrSBe symptoms and P3a or P3b. These findings identify symptom-specific alterations in neural systems that vary along the time course of post-concussive symptomatology.

Reduction in apathy following epilepsy surgery.

IntroductionSurgical treatment for patients with epilepsy who do not respond to antiepileptic medication can lead to changes in behavior, including new onset of neuropsychiatric symptoms such as depression and anxiety. In other cases, neuropsychiatric symptoms present before surgery may be alleviated. Because application of diagnostic criteria for primary psychiatric disorders may not be valid in assessing behavior in epilepsy populations, we sought to determine the feasibility of measuring behaviors associated with frontal-subcortical dysfunction using the Frontal Systems Behavior Scale (FrSBe) in patients who had received surgical intervention for medically refractory epilepsy.Materials and methodsTwenty-three patients who had previously undergone epilepsy surgery and their family member informants completed the FrSBe. The FrSBe includes separate forms for patients and informants to rate symptoms associated with three frontal lobe syndromes – executive dysfunction, disinhibition, and apathy – prior to and following a neurological condition. Patients and informants were asked to rate frontal lobe behaviors before and after epilepsy surgery using the FrSBe.ResultsInformants rated patients as showing a significantly greater reduction in apathy on the FrSBe compared to either disinhibition or executive dysfunction subscales. A trend in reduction of apathy following right hemisphere resection was found.ConclusionsPatients who have undergone epilepsy surgery show a reduction in apathy but it is unclear whether this behavioral change is directly related to the surgical intervention. We suggest that these preliminary findings support the utility of implementing dimensional scales such as the FrSBe to study behavioral changes following epilepsy surgery.

Variables associated with subjective cognitive change among Iraq and Afghanistan war Veterans with blast-related mild traumatic brain injury

ABSTRACTIntroduction: This study investigated variables associated with subjective decline in executive function among Veterans of Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND) following a history of blast-related mild traumatic brain injury (mTBI).Method: Fifty-six male U.S. Veterans (MAge = 35.3 ± 8.8 years) with a history of blast-related mTBI (6.6 ± 3.2 years post injury) completed a battery of self-report questionnaires and neuropsychological measures. Participants rated current and retrospectively estimated pre-mTBI executive function difficulties on the Frontal Systems Behavior Scale (FrSBe). A difference score (post- minus pre-mTBI ratings) was the dependent variable (∆FrSBe). Linear regression models examined variables predicting ∆FrSBe, including: pre-injury characteristics (education, premorbid intelligence), injury-related characteristics (number of blast exposures, losses of consciousness), post-injury clinical symptoms (PTSD Checklist–Military version; Pittsburgh Sleep Quality Index), and post-injury neuropsychological performances on executive function measures (Trail Making Test Part B; Controlled Oral Word Association Test; Auditory Consonant Trigrams; Wisconsin Card Sorting Test).Results: While 11% of participants had a clinically elevated pre-injury FrSBe total score, 82% had a clinically elevated post-injury FrSBe total score. Only self-reported PTSD symptom severity independently predicted perceived change in executive function.Conclusions: Many OEF/OIF/OND Veterans with a history of blast-related mTBI experience subjective decline in executive function following injury. Perceived executive function decline was associated with higher PTSD symptom severity, aligning with previous research associating PTSD with cognitive complaints. Results did not support a correspondence between perceived cognitive change and neuropsychological performances.

Frontal-subcortical behaviors during Alzheimer's disease in individuals with Down syndrome

There is evidence that frontal-subcortical circuits play an important role in the initial presentation of dementia in Down syndrome (DS), including changes in behavior, a decline in working memory and executive dysfunction. We evaluated 92 individuals with DS (≥30 years of age), divided into 3 groups by diagnosis—stable cognition, prodromal dementia, and Alzheimer's disease. Each individual was evaluated with an executive protocol developed for people with intellectual disabilities and was rated for behaviors related to frontal lobe dysfunction (disinhibition, executive dysfunction, and apathy) by an informant using the Frontal Systems Behavior Scale. Informant-reported behaviors related to frontal lobe dysfunction were found to correlate negatively with executive function performance. Disinhibition and executive dysfunction were associated with the clinical stage of dementia. The odds of having Alzheimer's disease increased in parallel with increases in the domain and total Frontal Systems Behavior Scale scores (p ≤ 0.5). Disinhibition, executive dysfunction and apathy should be taken into consideration during the clinical evaluation of adults with DS, and future studies should consider the intersection of neuropathology, brain connectivity, and behavior.

3551 Intermittent Theta Burst Stimulation to Relieve Depression and Executive Function impairment in older adults

OBJECTIVES/SPECIFIC AIMS: The objective of the study is to examine the ability of iTBS to improve depression and executive impairment in depressed older adults. If effective, this treatment will have the potential to improve the quality of life in LLD. METHODS/STUDY POPULATION: From 12- 2016 to date older adults (60 – 85 y/o) in a major depressive episode, with evidence of executive dysfunction (on the NIH Tool Box battery) were enrolled. iTBS protocol: This brief paradigm (3 min 9 seconds duration) was administered on weekdays for four weeks (20 sessions total). Stimulation intensity was set up to 120% of the observed motor threshold. Depression primary outcome: Change in the Montgomery Asberg Depression Rating Scale (MADRS) from baseline to the end of iTBS course. Executive function primary outcome: Change in executive measures from the electronic NIH Tool Box cognitive domain battery8. Executive secondary outcome: Change in scores from baseline to the end of iTBS on the Frontal Systems Behavior Scale (FrSBe), this self reported instrument measures dys-executive behavior. Statistical Analysis: paired t-test examined changes in depression and executive variables from baseline to post iTBS. Pearson correlation examined the association between degree of mood improvement and degree of improvement in executive function. SPSS v 24 was used for all analyses. RESULTS/ANTICIPATED RESULTS: We examined 11 subjects. Primary outcomes: Patients showed a significant decrease in scores on the Montgomery Asberg Depression Rating Scale (MADRS) from baseline Mean (M) = 27.73, Standard Deviation (SD) 8.2 to the end of 4 weeks of iTBS: M = 15.91, SD = 10.05, t = 7.4, p &lt; .001. The Flanker Inhibitory Control and attention test significantly improved from baseline M = 91.0, SD = 7 to the end of iTBS M = 98.7, SD = 12.8, t = −2.9, p = .014 (higher scores at week 4 denote improvement). The List Sorting Working Memory test and the Dimensional Change Card sort a measure of cognitive flexibility improved but did not reach statistical significance. The self reported executive measure improved from baseline M = 48.6, SD = 9.4 to post iTBS M = 39.4, SD = 8.5, t = 3.8, p = .003 (lower scores at week 4 denote improvement). We also examined whether the degree of improvement in depression related to the degree of improvement in executive function. We found positive correlations between change in mood scores with iTBS with change in executive scores with iTBS, with a strong relationship with working memory r = 0.34. Tolerability and Side effects: Common side effects were twitching in facial muscles during the stimulation (n =11), headaches (n =10) and pain or discomfort at the stimulation site and face (n =4). One participant withdrew due to intolerance to the stimulation. DISCUSSION/SIGNIFICANCE OF IMPACT: The iTBS paradigm was effective in improving mood and executive function in older adults. Both the psychometric measure and the self reported executive function measure (indicative of dysexecutive behavior) reflected improvements post iTBS. Improvement in executive function was correlated with depression improvement. We targeted the Dorso Lateral Prefrontal cortex, which exhibits decreased connectivity with the dorsal anterior cingulate in depressed elderly and is a key in orchestration of executive function. Our findings are consistent with the conceptualization of depression as a circuit level disorder affecting interconnected networks involving mood and cognition. Although we demonstrated potential therapeutic effects, the mechanism of action of iTBS remains unknown. We are presently conducting a randomized controlled trial to examine the effects of iTBS on brain connectivity using functional MRI. Results of this study underway will hopefully demonstrate engagement of the TMS target and contribute to a neurocircuitry based approach treatment of geriatric depression.

Cognitive Decline Influences Emotional Creativity in the Elderly

Little is known about the relationship between emotional creativity and age-related cognitive decline. This study explored how deficits in some cognitive abilities are related to emotional creativity, i.e., cognitive abilities relating to originality and appropriateness in emotional experience. One hundred and eighty-seven older adults (mean age = 63.2; 58.4% females) were administered the Emotional Creativity Inventory, the Frontal Systems Behavior Scale, and the Cognitive Complaint Interview. As hypothesized, emotional creativity was negatively related to apathy and positively to disinhibition/emotional dysregulation. Several processes, such as apathy-related loss of interest, unconcern, subjective lack of energy, and changed perception of one’s disinhibited emotional reactions, may explain the observed results.

Evaluación de la Función Ejecutiva en Usuarios con Dependencia de Pasta Base de Cocaína Mediante una Batería Neuropsicológica

La adiccion a la pasta base de cocaina (PBC) representa un serio problema de salud en Chile. La adiccion a las drogas se relaciona con deficit en las funciones ejecutivas, asociadas a regiones prefrontales del cerebro. El proposito del estudio fue comparar el rendimiento neuropsicologico de un grupo de dependientes de PBC que se atendian en 4 centros de tratamiento publico (n = 27), respecto de un grupo control (n = 16). Se empleo un diseno transversal comparativo y se administro el Test de Colores y Palabras de Stroop, el Test de Clasificacion de Tarjetas de Wisconsin, el Juego de Azar de Iowa, el Test del Trazado de un Camino, el Test de Aprendizaje Verbal, el Test de Fluencia Verbal y la Escala de Comportamiento Frontal. Mediante analisis multivariado de la varianza, controlando el nivel de depresion, se hallo que el grupo con dependencia tenia un rendimiento menor en la curva de aprendizaje y mayores puntajes en las subescalas de desinhibicion y disfuncion ejecutiva de la Escala de Comportamiento Frontal. Los resultados generales son coherentes con los de la literatura revisada.