Telemedicine-Based Cognitive Examinations During COVID-19 and Beyond: Perspective of the Massachusetts General Hospital Behavioral Neurology & Neuropsychiatry Group.

Telehealth and telemedicine have encountered explosive growth since the beginning of the COVID-19 pandemic, resulting in increased access to care for patients located far from medical centers and clinics. Subspecialty clinicians in behavioral neurology & neuropsychiatry (BNNP) have implemented the use of telemedicine platforms to perform cognitive examinations that were previously office based. In this perspective article, BNNP clinicians at Massachusetts General Hospital (MGH) describe their experience performing cognitive examinations via telemedicine. The article reviews the goals, prerequisites, advantages, and potential limitations of performing a video- or telephone-based telemedicine cognitive examination. The article shares the approaches used by MGH BNNP clinicians to examine cognitive and behavioral areas, such as orientation, attention and executive functions, language, verbal learning and memory, visual learning and memory, visuospatial function, praxis, and abstract abilities, as well as to survey for neuropsychiatric symptoms and assess activities of daily living. Limitations of telemedicine-based cognitive examinations include limited access to and familiarity with telecommunication technologies on the patient side, limitations of the technology itself on the clinician side, and the limited psychometric validation of virtual assessments. Therefore, an in-person examination with a BNNP clinician or a formal in-person neuropsychological examination with a neuropsychologist may be recommended. Overall, this article emphasizes the use of standardized cognitive and behavioral assessment instruments that are either in the public domain or, if copyrighted, are nonproprietary and do not require a fee to be used by the practicing BNNP clinician.

Multimodal Neural and Behavioral Data Predict Response to Rehabilitation in Chronic Poststroke Aphasia.

BACKGROUND: Poststroke recovery depends on multiple factors and varies greatly across individuals. Using machine learning models, this study investigated the independent and complementary prognostic role of different patient-related factors in predicting response to language rehabilitation after a stroke. METHODS: Fifty-five individuals with chronic poststroke aphasia underwent a battery of standardized assessments and structural and functional magnetic resonance imaging scans, and received 12 weeks of language treatment. Support vector machine and random forest models were constructed to predict responsiveness to treatment using pretreatment behavioral, demographic, and structural and functional neuroimaging data. RESULTS: The best prediction performance was achieved by a support vector machine model trained on aphasia severity, demographics, measures of anatomic integrity and resting-state functional connectivity (F1=0.94). This model resulted in a significantly superior prediction performance compared with support vector machine models trained on all feature sets (F1=0.82, P<0.001) or a single feature set (F1 range=0.68-0.84, P<0.001). Across random forest models, training on resting-state functional magnetic resonance imaging connectivity data yielded the best F1 score (F1=0.87). CONCLUSIONS: While behavioral, multimodal neuroimaging data and demographic information carry complementary information in predicting response to rehabilitation in chronic poststroke aphasia, functional connectivity of the brain at rest after stroke is a particularly important predictor of responsiveness to treatment, both alone and combined with other patient-related factors.

Common and distinct neural substrates of sentence production and comprehension.

Functional neuroimaging and lesion-symptom mapping investigations implicate a left frontal-temporal-parietal network for sentence processing. The majority of studies have focused on sentence comprehension, with fewer in the domain of sentence production, which have not fully elucidated overlapping and/or unique brain structures associated with the two domains, particularly for sentences with noncanonical word order. Using voxel-based lesion symptom mapping (VLSM) we examined the relationship between lesions within the left hemisphere language network and both sentence comprehension and production of simple and complex syntactic structures in 76 participants with chronic stroke-induced aphasia. Results revealed shared regions across domains in the anterior and posterior superior temporal gyri (aSTG, pSTG), and the temporal pole (adjusted for verb production/comprehension). Additionally, comprehension was associated with lesions in the anterior and posterior middle temporal gyri (aMTG, pMTG), the MTG temporooccipital regions, SMG/AG, central and parietal operculum, and the insula. Subsequent VLSM analyses (production versus comprehension) revealed critical regions associated with each domain: anterior temporal lesions were associated with production; posterior temporo-parietal lesions were associated with comprehension, implicating important roles for regions within the ventral and dorsal stream processing routes, respectively. Processing of syntactically complex, noncanonical (adjusted for canonical), sentences was associated with damage to the pSTG across domains, with additional damage to the pMTG and IPL associated with impaired sentence comprehension, suggesting that the pSTG is crucial for computing noncanonical sentences across domains and that the pMTG, and IPL are necessary for re-analysis of thematic roles as required for resolution of long-distance dependencies. These findings converge with previous studies and extend our knowledge of the neural mechanisms of sentence comprehension to production, highlighting critical regions associated with both domains, and further address the mechanism engaged for syntactic computation, controlled for the contribution of verb processing.

Reliability of BOLD signals in chronic stroke-induced aphasia.

Investigating the neurobiology of language impairment and treatment in chronic stroke aphasia using fMRI requires an understanding of measurement variability within and between participants. In this multicenter study, we evaluated the scan-rescan reliability of an auditory and visual (written) story comprehension paradigm in stroke participants with aphasia (N = 65) and healthy controls (N = 22). The multi-modal task was conducted twice (~1 week apart) on separate visits upon study enrolment and twice again at completion three months later. A non-language visuomotor task was studied in the aphasia group only, which was conducted once per time point (3 months apart). While participants were asked to make responses during the comprehension task, these in-scanner responses were not recorded. Reliability was assessed using intraclass correlation coefficient (ICC) at both group and individual participant levels. The visual story comprehension condition had higher reliability than the auditory condition in both groups, with participants with aphasia exhibiting lower reliability than controls in both conditions (stroke ICC = .43, healthy ICC = .81). Differences in reliability within the group of participants with aphasia were found to be partially explained by overall language impairment as well as greater head motion. In the participants with aphasia, the visuomotor paradigm was found to have greater reliability than the story comprehension task at equivalent interscan intervals (visuomotor = 0.50, comprehension = 0.34), and its reliability was not associated with language impairment. This work highlights the importance of considering the reliability of fMRI tasks in aphasia research, provides strategies to improve reliability and has potential implications for the field of clinical neuroimaging in general.

Pain Catastrophizing and Limiting Behavior Mediate the Association Between Anxiety and Postconcussion Symptoms.

BACKGROUND: Despite growing evidence that anxiety is critical in the development and maintenance of postconcussion symptoms after mild traumatic brain injury (mTBI), little is known about potential mechanisms through which anxiety may affect these symptoms. OBJECTIVE: To test the strength and reliability of cognitive (pain catastrophizing) and behavioral (limiting behaviors) pathways mediating the relationship between anxiety and postconcussion symptoms among patients with mTBI. METHOD: Patients with mTBI (N = 57) completed self-report measures of anxiety, postconcussion symptoms, pain catastrophizing, and limiting behavior. After preliminary simple-mediation models (for pain catastrophizing and limiting behavior separately), we ran a multiple-mediation model (pathways modeled simultaneously). Bootstrapping with 10,000 resampling iterations assessed mediation reliability. RESULTS: In preliminary simple mediation models, both pain catastrophizing (ß = 0.24, 95% confidence interval [CI] = 0.03-0.44, P = 0.02) and limiting behaviors (ß = 0.14, 95% CI = 0.03-0.26, P = 0.01) partially mediated the relationship between anxiety and postconcussion symptoms. In the multiple mediation model, pain catastrophizing was a less reliable but numerically stronger mediator (ß = 0.19, 95% CI = -0.01 to 0.38; P = 0.05) and explained more variance in postconcussion symptoms (R2 = 0.41) than limiting behavior (ß = 0.10, 95% CI = 0.02-0.21, P = 0.03; R2 = 0.22), although mediators did not significantly differ in strength (ß = 0.08, 95% CI = -0.16 to 0.32; P = 0.49). Results provide novel evidence for the role of pain catastrophizing and limiting behaviors in explaining the association between anxiety and postconcussion symptoms. Addressing both factors may improve the recovery trajectory of individuals with mTBI. Emphasizing limiting behavior may yield more consistent and reliable effects. CONCLUSION: Results support developing interventions to directly target anxiety, for pain catastrophizing, and for activity engagement despite symptoms, to decrease symptom severity among patients with mTBI.

Telemedicine in Behavioral Neurology-Neuropsychiatry: Opportunities and Challenges Catalyzed by COVID-19.

Coronavirus 2019 (COVID-19) has profoundly impacted the well-being of society and the practice of medicine across health care systems worldwide. As with many other subspecialties, the clinical paradigm in behavioral neurology and neuropsychiatry (BN-NP) was transformed abruptly, transitioning to real-time telemedicine for the assessment and management of the vast majorities of patient populations served by our subspecialty. In this commentary, we outline themes from the BN-NP perspective that reflect the emerging lessons we learned using telemedicine during the COVID-19 pandemic. Positive developments include the ability to extend consultations and management to patients in our high-demand field, maintenance of continuity of care, enhanced ecological validity, greater access to a variety of well-reimbursed telemedicine options (telephone and video) that help bridge the digital divide, and educational and research opportunities. Challenges include the need to adapt the mental state examination to the telemedicine environment, the ability to perform detailed motor neurologic examinations in patients where motor features are important diagnostic considerations, appreciating nonverbal cues, managing acute safety and behavioral concerns in less controlled environments, and navigating intervention-based (neuromodulation) clinics requiring in-person contact. We hope that our reflections help to catalyze discussions that should take place within the Society for Behavioral and Cognitive Neurology, the American Neuropsychiatric Association, and allied organizations regarding how to optimize real-time telemedicine practices for our subspecialty now and into the future.

Neural networks for sentence comprehension and production: An ALE-based meta-analysis of neuroimaging studies.

Comprehending and producing sentences is a complex endeavor requiring the coordinated activity of multiple brain regions. We examined three issues related to the brain networks underlying sentence comprehension and production in healthy individuals: First, which regions are recruited for sentence comprehension and sentence production? Second, are there differences for auditory sentence comprehension vs. visual sentence comprehension? Third, which regions are specifically recruited for the comprehension of syntactically complex sentences? Results from activation likelihood estimation (ALE) analyses (from 45 studies) implicated a sentence comprehension network occupying bilateral frontal and temporal lobe regions. Regions implicated in production (from 15 studies) overlapped with the set of regions associated with sentence comprehension in the left hemisphere, but did not include inferior frontal cortex, and did not extend to the right hemisphere. Modality differences between auditory and visual sentence comprehension were found principally in the temporal lobes. Results from the analysis of complex syntax (from 37 studies) showed engagement of left inferior frontal and posterior temporal regions, as well as the right insula. The involvement of the right hemisphere in the comprehension of these structures has potentially important implications for language treatment and recovery in individuals with agrammatic aphasia following left hemisphere brain damage.

Comparison of Measures to Predict Mortality and Length of Stay in Hospitalized Patients.

BACKGROUND: Patient risk adjustment is critical for hospital benchmarking and allocation of healthcare resources. However, considerable heterogeneity exists among measures. OBJECTIVES: The performance of five measures was compared to predict mortality and length of stay (LOS) in hospitalized adults using claims data; these include three comorbidity composite scores (Charlson/Deyo age-comorbidity score, V W Elixhauser comorbidity score, and V W Elixhauser age-comorbidity score), 3 M risk of mortality (3 M ROM), and 3 M severity of illness (3 M SOI) subclasses. METHODS: Binary logistic and zero-truncated negative binomial regression models were applied to a 2-year retrospective dataset (2013-2014) with 123,641 adult inpatient admissions from a large hospital system in New York City. RESULTS: All five measures demonstrated good to strong model fit for predicting in-hospital mortality, with C-statistics of 0.74 (95% confidence interval [CI] [0.74, 0.75]), 0.80 (95% CI [0.80, 0.81]), 0.81(95% CI [0.81, 0.82]), 0.94 (95% CI [0.93, 0.94]), and 0.90 (95% CI [0.90, 0.91]) for Charlson/Deyo age-comorbidity score, V W Elixhauser comorbidity score, V W Elixhauser age-comorbidity score, 3 M ROM, and 3 M SOI, respectively. The model fit statistics to predict hospital LOS measured by the likelihood ratio index were 0.3%, 1.2%, 1.1%, 6.2%, and 4.3%, respectively. DISCUSSION: The measures tested in this study can guide nurse managers in the assignment of nursing care and coordination of needed patient services and administrators to effectively and efficiently support optimal nursing care.

A Study of the Longitudinal Patterns of Stimulant and Amyl Nitrite Use and Sexual Behavior Pre- and Post-HIV Seroconversion Among MSM.

The use of stimulant drugs alone or in combination with amyl nitrites (stimulant/nitrites) has been associated with higher rates of risky sexual behavior and predictive of HIV infection among men who have sex with men. However, the temporal pattern of stimulant/nitrite use pre- and post-seroconversion has not been well established. This study assessed changes in stimulant/nitrite use and risky sexual behavior among seroconverting MSM over time. Data were collected in the Baltimore-Washington, DC; Pittsburgh; Chicago; and Los Angeles sites of the Multicenter AIDS Cohort Study (MACS), a longitudinal study of the natural history of HIV infection among MSM. We used propensity scores to select 1044 MSM from 7087 MACS participants composed of 348 seroconverting, 348 seronegative, and 348 seroprevalent participants matched on demographics, recruitment cohort, and study visits. We centered up to four-years of semi-annual data around the seroconversion visit of the seroconverting case within each matched group of participants. Mixed effects regressions estimated the effects of serostatus, recruitment cohort, and time on self-reported stimulant/nitrite use, numbers of male intercourse partners, and numbers of unprotected receptive anal intercourse (URAI) partners. Covariates included demographics, binge drinking, and marijuana use. Seroconverters had the highest odds of stimulant/inhaled nitrite use (AOR 10.3, CI 4.8-22.0), incident rates of intercourse (IRR 1.6, CI 1.3-2.1), and URAI partners (IRR 5.1, CI 3.5-7.3). All participants decreased drug use and sexual risk behavior over time. However, the decreases were largest for seroconverters who nevertheless maintained the highest rates of stimulant/nitrite use and sexual risk. Cohort-related effects were associated with sharp reductions in stimulant/nitrite use and URAI in the early 1990s that rebounded considerably within the first decade of the 2000s. Although all participants decreased risky sexual behavior and stimulant and/or nitrite use over time, seroconverters had the largest decreases. There was no evidence for abrupt or substantial increases in drug use or risky sex post-seroconversion. However, there was substantial variation at the individual level, with the factors underlying this variation not well understood and worth further study. Moreover, stimulant/nitrite use and risky sexual behavior appear to have been strongly influenced by contextual historical and socio-cultural effects. The manner in which contextual factors influence individual behavior is also not well understood and also warrants further study.

Neuropsychiatric Associations With Gender, Illness Duration, Work Disability, and Motor Subtype in a U.S. Functional Neurological Disorders Clinic Population.

The assessment of functional neurological disorders (FND) requires an interdisciplinary approach. The authors retrospectively reviewed charts for 100 outpatients with FND and used univariate and regression analyses to investigate neuropsychiatric associations with gender, illness duration, and work disability; secondary analyses evaluated for differences across motor FND subtypes. Men reported higher rates of cognitive complaints and functional weakness, whereas women endorsed increased past physical/sexual trauma. Number of self-reported medication allergies/sensitivities positively correlated with illness duration. Individuals with functional weakness compared with other motor FND subtypes exhibited lower rates of past psychiatric hospitalization and head trauma. This study supports the feasibility of integrating FND research.

Right Hemisphere Grey Matter Volume and Language Functions in Stroke Aphasia.

The role of the right hemisphere (RH) in recovery from aphasia is incompletely understood. The present study quantified RH grey matter (GM) volume in individuals with chronic stroke-induced aphasia and cognitively healthy people using voxel-based morphometry. We compared group differences in GM volume in the entire RH and in RH regions-of-interest. Given that lesion site is a critical source of heterogeneity associated with poststroke language ability, we used voxel-based lesion symptom mapping (VLSM) to examine the relation between lesion site and language performance in the aphasic participants. Finally, using results derived from the VLSM as a covariate, we evaluated the relation between GM volume in the RH and language ability across domains, including comprehension and production processes both at the word and sentence levels and across spoken and written modalities. Between-subject comparisons showed that GM volume in the RH SMA was reduced in the aphasic group compared to the healthy controls. We also found that, for the aphasic group, increased RH volume in the MTG and the SMA was associated with better language comprehension and production scores, respectively. These data suggest that the RH may support functions previously performed by LH regions and have important implications for understanding poststroke reorganization.

Intrahemispheric Perfusion in Chronic Stroke-Induced Aphasia.

Stroke-induced alterations in cerebral blood flow (perfusion) may contribute to functional language impairments and recovery in chronic aphasia. Using MRI, we examined perfusion in the right and left hemispheres of 35 aphasic and 16 healthy control participants. Across 76 regions (38 per hemisphere), no significant between-subjects differences were found in the left, whereas blood flow in the right was increased in the aphasic compared to the control participants. Region-of-interest (ROI) analyses showed a varied pattern of hypo- and hyperperfused regions across hemispheres in the aphasic participants; however, there were no significant correlations between perfusion values and language abilities in these regions. These patterns may reflect autoregulatory changes in blood flow following stroke and/or increases in general cognitive effort, rather than maladaptive language processing. We also examined blood flow in perilesional tissue, finding the greatest hypoperfusion close to the lesion (within 0-6 mm), with greater hypoperfusion in this region compared to more distal regions. In addition, hypoperfusion in this region was significantly correlated with language impairment. These findings underscore the need to consider cerebral perfusion as a factor contributing to language deficits in chronic aphasia as well as recovery of language function.

"Cat-gras" delusion: a unique misidentification syndrome and a novel explanation.

ABSRACT Capgras syndrome is a distressing delusion found in a variety of neurological and psychiatric diseases where a patient believes that a family member, friend, or loved one has been replaced by an imposter. Patients recognize the physical resemblance of a familiar acquaintance but feel that the identity of that person is no longer the same. Here we describe a 73-year-old male with right posterior frontal and bilateral anterior-medial frontal damage from prior brain trauma with a similar delusion of an imposter replacing his pet cat. Misidentification syndromes for animals, as opposed to humans, have been rarely reported. Neuropsychological testing showed deficits in executive processing and memory retrieval with prominent intrusions and false positive responses. The delusional belief content in Capgras syndrome has been hypothesized to result from loss of an emotional or autonomic response to familiar stimuli, from theory of mind deficits, or from loss of self-environment distinctions. We instead propose that Capgras delusions result from a dysfunction in linking external stimuli with retrieved internal autobiographical memories pertaining to that object. This leads to an erroneously learned identity that persists as a specific delusional belief.

Preliminary Predictors of Initial Attendance, Symptom Burden, and Motor Subtype in a US Functional Neurological Disorders Clinic Population.

BACKGROUND AND OBJECTIVE: Although many patients present with functional neurological symptoms (FNS), few US clinics offer specialized FNS care, and data on clinic attendees remain limited. We determined predictors of initial attendance, symptom burden, and FNS subtype in the first patients referred to our Functional Neurological Disorders Clinic for suspected FNS. METHODS: We reviewed the charts of 62 consecutive patients (46 women, 16 men). Regression analyses investigated predictors of keeping the first scheduled clinic appointment. For the 49 patients who did keep that appointment, regression analyses examined neuropsychiatric factors associated with symptom burden and motor FNS subtypes. RESULTS: The odds of not keeping the first appointment were 10.4 times greater for patients referred from the emergency department than from other sources. The patients who kept their appointment reported a symptom burden that was significantly associated with a past FNS-related emergency department visit and a diagnosis of another medically unexplained somatic syndrome. The number of FNS findings on neurological examination also correlated with a history of an FNS-related emergency department visit. Patients with psychogenic non-epileptic seizures reported cognitive complaints and prior psychiatric hospitalizations significantly more often than did patients with other FNS. One fourth of all patients had two or more motor FNS. CONCLUSIONS: In our FNS cohort, patients were less likely to keep an initial clinic appointment if they were referred from the emergency department than from other sources. Patients with psychogenic non-epileptic seizures were more likely to report cognitive symptoms and past psychiatric hospitalizations than patients with other FNS.

Mechanisms underlying syntactic comprehension deficits in vascular aphasia: new evidence from self-paced listening.

Sixty-one people with aphasia (pwa) and 41 matched controls were tested for the ability to understand sentences that required the ability to process particular syntactic elements and assign particular syntactic structures. Participants paced themselves word-by-word through 20 examples of 11 spoken sentence types and indicated which of two pictures corresponded to the meaning of each sentence. Sentences were developed in pairs such that comprehension of the experimental version of a pair required an aspect of syntactic processing not required in the corresponding baseline sentence. The need for the syntactic operations required only in the experimental version was triggered at a "critical word" in the experimental sentence. Listening times for critical words in experimental sentences were compared to those for corresponding words in the corresponding baseline sentences. The results were consistent with several models of syntactic comprehension deficits in pwa: resource reduction, slowed lexical and/or syntactic processing, abnormal susceptibility to interference from thematic roles generated non-syntactically. They suggest that a previously unidentified disturbance limiting the duration of parsing and interpretation may lead to these deficits, and that this mechanism may lead to structure-specific deficits in pwa. The results thus point to more than one mechanism underlying syntactic comprehension disorders both across and within pwa.

Challenges Associated With Using Large Data Sets for Quality Assessment and Research in Clinical Settings.

The rapidly expanding use of electronic records in health-care settings is generating unprecedented quantities of data available for clinical, epidemiological, and cost-effectiveness research. Several challenges are associated with using these data for clinical research, including issues surrounding access and information security, poor data quality, inconsistency of data within and across institutions, and a paucity of staff with expertise to manage and manipulate large clinical data sets. In this article, we describe our experience with assembling a data-mart and conducting clinical research using electronic data from four facilities within a single hospital network in New York City. We culled data from several electronic sources, including the institution's admission-discharge-transfer system, cost accounting system, electronic health record, clinical data warehouse, and departmental records. The final data-mart contained information for more than 760,000 discharges occurring from 2006 through 2012. Using categories identified by the National Institutes of Health Big Data to Knowledge initiative as a framework, we outlined challenges encountered during the development and use of a domain-specific data-mart and recommend approaches to overcome these challenges.

MSM and drug use: A latent class analysis of drug use and related sexual risk behaviors.

This study examined patterns of drug use among gay men and other men who have sex with men (MSM) to identify sub-categories of men whose drug use and sexual behavior place them at especially high risk for HIV. A latent class analysis of a sample of MSM yielded a four-class model with two distinct high drug use sub-groups: one whose drug use concentrated on "sex-drugs" (SDU); and a distinct polydrug use class that showed higher probabilities of using all other drugs assessed. Comparative follow-up analyses indicated the SDU group was also more likely to engage in particular potentially high-risk sexual behaviors, be older, and to be HIV positive. Implications of distinguishing between patterns of drug use for HIV-risk prevention efforts with MSM are discussed.

Neuroimaging in aphasia treatment research: issues of experimental design for relating cognitive to neural changes.

The design of functional neuroimaging studies investigating the neural changes that support treatment-based recovery of targeted language functions in acquired aphasia faces a number of challenges. In this paper, we discuss these challenges and focus on experimental tasks and experimental designs that can be used to address the challenges, facilitate the interpretation of results and promote integration of findings across studies.

Scalable modulator for frequency shift keying in free space optical communications.

Frequency shift keyed (FSK) modulation formats are well-suited to deep space links and other high loss links. FSK's advantage comes from its use of bandwidth expansion. I.e., FSK counteracts power losses in the link by using an optical bandwidth that is greater than the data rate, just as pulse position modulation (PPM) does. Unlike PPM, increasing FSK's bandwidth expansion does not require increased bandwidth in electronic components. We present an FSK modulator whose component count rises logarithmically with the bandwidth expansion. We tested it with four-fold bandwidth expansion at 5 and 20 Gbit/s. When paired with a pre-amplified receiver, the required received power was about 4 and 5 dB from the theoretical best for such receivers. We also tested the FSK transmitter with a photon counting receiver.