Clinical presentation and neural correlates of stroke-associated spatial delusions.

BACKGROUND AND PURPOSE: Incongruent beliefs about self-localization in space markedly disturb patients' behavior. Spatial delusions, or reduplicative paramnesias, are characterized by a firm conviction of place reduplication, transformation, or mislocation. Evidence suggests they are frequent after right hemisphere lesions, but comprehensive information about their clinical features is lacking. METHODS: We prospectively screened 504 acute right-hemisphere stroke patients for the presence of spatial delusions. Their behavioral and clinical features were systematically assessed. Then, we analyzed the correlation of their duration with the magnitude of structural disruption of belief-associated functional networks. Finally, we described the syndrome subtypes and evaluated whether the clinical categorization would be predicted by the structural disruption of familiarity-associated functional networks using an unsupervised k-means clustering algorithm. RESULTS: Sixty patients with spatial delusions were identified and fully characterized. Most (93%) localized the misidentified places closer to home than the hospital. The median time duration was 3 days (interquartile range = 1-7 days), and it was moderately correlated with the magnitude of structural-functional decoupling of belief-associated functional networks (r = 0.39, p = 0.02; beta coefficient regressing for lesion volume = 3.18, p = 0.04). Each clinical subtype had characteristic response patterns, which were reported, and representative examples were provided. Clustering based on structural disruption of familiarity- and unfamiliarity-associated functional networks poorly matched the clinical categorization (lesion: Rand index = 0.47; structural disconnection: Rand index = 0.51). CONCLUSIONS: The systematic characterization of the peculiar clinical features of stroke-associated spatial delusions may improve the syndrome diagnosis and clinical approaches. The novel evidence about their neural correlates fosters the clarification of the pathophysiology of delusional misidentifications.

Unravelling the Neural Basis of Spatial Delusions After Stroke.

OBJECTIVE: Knowing explicitly where we are is an interpretation of our spatial representations. Reduplicative paramnesia is a disrupting syndrome in which patients present a firm belief of spatial mislocation. Here, we studied the largest sample of patients with delusional misidentifications of space (ie, reduplicative paramnesia) after stroke to shed light on their neurobiology. METHODS: In a prospective, cumulative, case-control study, we screened 400 patients with acute right-hemispheric stroke. We included 64 cases and 233 controls. First, lesions were delimited and normalized. Then, we computed structural and functional disconnection maps using methods of lesion-track and network-mapping. The maps were compared, controlling for confounders. Second, we built a multivariate logistic model, including clinical, behavioral, and neuroimaging data. Finally, we performed a nested cross-validation of the model with a support-vector machine analysis. RESULTS: The most frequent misidentification subtype was confabulatory mislocation (56%), followed by place reduplication (19%), and chimeric assimilation (13%). Our results indicate that structural disconnection is the strongest predictor of the syndrome and included 2 distinct streams, connecting right fronto-thalamic and right occipitotemporal structures. In the multivariate model, the independent predictors of reduplicative paramnesia were the structural disconnection map, lesion sparing of right dorsal fronto-parietal regions, age, and anosognosia. Good discrimination accuracy was demonstrated (area under the curve = 0.80 [0.75-0.85]). INTERPRETATION: Our results localize the anatomic circuits that may have a role in the abnormal spatial-emotional binding and in the defective updating of spatial representations underlying reduplicative paramnesia. This novel data may contribute to better understand the pathophysiology of delusional syndromes after stroke. ANN NEUROL 2021;89:1181-1194.

Signal quality and power spectrum analysis of remote ultra long-term subcutaneous EEG.

OBJECTIVE: Ultra long-term subcutaneous electroencephalography (sqEEG) monitoring is a new modality with great potential for both health and disease, including epileptic seizure detection and forecasting. However, little is known about the long-term quality and consistency of the sqEEG signal, which is the objective of this study. METHODS: The largest multicenter cohort of sqEEG was analyzed, including 14 patients with epilepsy and 12 healthy subjects, implanted with a sqEEG device (24/7 EEG™ SubQ), and recorded from 23 to 230 days (median 42 days), with a median data capture rate of 75% (17.9 hours/day). Median power spectral density plots of each subject were examined for physiological peaks, including at diurnal and nocturnal periods. Long-term temporal trends in signal impedance and power spectral features were investigated with subject-specific linear regression models and group-level linear mixed-effects models. RESULTS: sqEEG spectrograms showed an approximate 1/f power distribution. Diurnal peaks in the alpha range (8-13Hz) and nocturnal peaks in the sigma range (12-16Hz) were seen in the majority of subjects. Signal impedances remained low, and frequency band powers were highly stable throughout the recording periods. SIGNIFICANCE: The spectral characteristics of minimally invasive, ultra long-term sqEEG are similar to scalp EEG, whereas the signal is highly stationary. Our findings reinforce the suitability of this system for chronic implantation on diverse clinical applications, from seizure detection and forecasting to brain-computer interfaces.

Brain state monitoring for the future prediction of migraine attacks.

BACKGROUND: Migraine attacks are unpredictable, precluding preemptive interventions and leading to lack of control over individuals' lives. Although there are neurophysiological changes 24-48 hours before migraine attacks, so far, they have not been used in patients' management. This study evaluates the applicability and the ability to identify pre-attack changes of daily "at home" electroencephalography obtained with a portable system for migraine patients. METHODS: Patients with episodic migraine fulfilling ICHD-3 beta criteria used a mobile system composed of a wireless EEG device (BrainStation®, Neuroverse®, Inc., USA) and mobile application (BrainVitalsM®, Neuroverse®, Inc., USA) to self-record their neural activity daily at home while resting and while performing an attention task, over the course of 2 weeks. Standard EEG spectral analysis and event-related brain potentials (ERP) methods were used and recordings were grouped by time from migraine attacks (i.e. "Interictal day", "24 h Before Migraine", "Migraine day" and "Post Migraine"). RESULTS: Twenty-four patients (22 women) recorded an average of 13.3 ± 1.9 days and had 2 ± 0.9 attacks. Twenty-four hours before attack onset, there was a statistically significant modulation of relative power in the delta (decrease) and beta (increase) frequency bands, at rest, and a significant reduction of the amplitude and inter-trial coherence measures of an attention event-related brain potential (P300). CONCLUSIONS: This proof-of-concept study shows that brain state monitoring, utilising an easy-to-use wearable EEG system to track neural modulations at home, can identify physiological changes preceding a migraine attack enabling valuable pre-symptom prediction and subsequent early intervention.

Aura status: a not so frequent aura.

BACKGROUND: Migraine aura status is a variety of migraine aura with unvalidated research criteria. AIM AND METHODS: We conducted a systematic review of published cases and a retrospective analysis of 500 cases of migraine with aura to evaluate the applicability and clinical features of ICHD-III beta criteria, compared to a more liberal definition for its diagnosis: ≥3 aura episodes for up to three consecutive days. RESULTS: Many publications under this title correspond to persistent or formerly designated prolonged auras. Nine cases fulfilled ICHD-III beta status criteria. In our series, either 1.7% or 4.2% cases fulfilled ICDH-III beta or our definition, respectively. Regardless of the criteria, aura status patients were older at onset of status than those with typical aura, had a predominance of visual symptoms, normal neuroimaging and no sequelae. Status recurred in a few. CONCLUSION: Both criteria identify a similar population in terms of age, gender, main symptoms, imaging and outcome. Since patients with closely recurring auras might raise the same approach independently of the criteria, the use of more liberal criteria will allow more cases for detailed diagnosis and therapeutic analysis, eventually leading to the identification of subtypes.

Mapping delusions of space onto a structural disconnectome that decouples familiarity and place networks.

Interpretation of space is an important determinant of human behaviour. Delusions of space, or reduplicative paramnesias, are a particularly disturbing form of spatial disorientation characterized by the patients' strong belief of place reduplication, transformation or mislocation. Their occurrence following focal brain damage provides a unique opportunity to unveil the structural-functional basis of space misinterpretations. First, we identified reports of lesion-associated reduplicative paramnesias with brain images available through a systematic review of the literature (n = 24). Each lesion was matched with 4 stroke controls and the sample was randomly split in an exploratory (n = 60) and in a validation (n = 60) dataset. Second, we used 178 7T tractographies to compute structural disconnectome maps and analysed lesion topography and disconnection patterns. Delusions of space were significantly associated with structural disconnection of right ventrolateral prefrontal and right temporal regions, and this finding was replicated in the validation sample. Third, we performed a functional meta-analysis of syndrome-related terms. We demonstrated that the structural disconnectomes of delusions of space were spatially correlated with the functional meta-analytic maps of familiarity and place, and replicated the previous evidence that the lesion topography maps are spatially correlated with belief-related functional networks. No association was found with control terms. These results reveal that structural disconnection putatively mediates functional changes associated with reduplicative paramnesias and provide a possible neural basis for the content specificity for places that characterizes these delusional beliefs.

Sensitivity to expressions of pain in schizophrenia patients.

Patients with schizophrenia tend to neglect their own pain and are known to have impairments in the processing of facial expressions. However, the sensitivity to dynamic expressions of pain has not been studied in these patients. Our goal was to test this ability in schizophrenia and to probe the underlying cognitive processes. We hypothesized that patients would have a reduced sensitivity to expressions of pain and that this impairment would correlate with deficits in attention, working memory, basic emotions recognition and with positive symptoms. We applied a battery of tests composed of the Comprehensive Affect Testing System (CATS), Sensitivity to Expressions of Pain (STEP), Toulouse-Pierón, Stroop and Digit Span tests to two groups of individuals, 27 patients with the diagnosis of schizophrenia and 27 healthy volunteers, matched on age, education and gender. Symptoms were assessed using Brief Psychiatric Rating Scale. The sensitivity to expressions of pain was found to be impaired in schizophrenia and a bias to attribute lower pain intensities may be present at some discrimination levels. STEP performance was correlated with working memory but not with Affect Naming or attention. These findings may contribute to the improvement of cognitive remediation strategies.

230 days of ultra long-term subcutaneous EEG: seizure cycle analysis and comparison to patient diary.

We describe the longest period of subcutaneous EEG (sqEEG) monitoring to date, in a 35-year-old female with refractory epilepsy. Over 230 days, 4791/5520 h of sqEEG were recorded (86%, mean 20.8 [IQR 3.9] hours/day). Using an electronic diary, the patient reported 22 seizures, while automatically-assisted visual sqEEG review detected 32 seizures. There was substantial agreement between days of reported and recorded seizures (Cohen's kappa 0.664), although multiple clustered seizures remained undocumented. Circular statistics identified significant sqEEG seizure cycles at circadian (24-hour) and multidien (5-day) timescales. Electrographic seizure monitoring and analysis of long-term seizure cycles are possible with this neurophysiological tool.

Memory malingering: evaluating WMT criteria.

The Word Memory Test (WMT) has been considered one of the best assessment tools for assessing memory malingering in spite of some reported false-positive results. Our goal was to examine the sensitivity and specificity of Green's 2003 criteria for memory malingering using a Portuguese adaptation of the WMT. We applied the WMT to three groups of participants, including 20 healthy subjects asked to simulate memory impairment, 29 healthy adults asked to produce their best performance, and 21 patients with the diagnosis of mild cognitive impairment (MCI). Using Green's 2003 criteria, based on scores below cutoffs on the easy subtests, 67% of the MCI patients were classified as "poor effort." However, the sensitivity and specificity of the diagnosis could be raised to 95% using an alternative set of criteria, relying on comparisons between easy and hard subtest scores. We conclude that Green's original criteria based on easy subtest scores alone seem to be of low specificity for the diagnosis of memory impairment simulation, but the WMT is a good instrument for identifying simulation if the alternative criteria are applied.

The serial use of child neurocognitive tests: development versus practice effects.

When serial neurocognitive assessments are performed, 2 main factors are of importance: test-retest reliability and practice effects. With children, however, there is a third, developmental factor, which occurs as a result of maturation. Child tests recognize this factor through the provision of age-corrected scaled scores. Thus, a ready-made method for estimating the relative contribution of developmental versus practice effects is the comparison of raw (developmental and practice) and scaled (practice only) scores. Data from a pool of 507 Portuguese children enrolled in a study of dental amalgams (T. A. DeRouen, B. G. Leroux, et al., 2002; T. A. DeRouen, M. D. Martin, et al., 2006) showed that practice effects over a 5-year period varied on 8 neurocognitive tests. Simple regression equations are provided for calculating individual retest scores from initial test scores.

A longitudinal factor analytic study of children's neurocognitive abilities.

The neurocognitive abilities of 503 Portuguese children aged 8-11.9 years at onset of the study were assessed annually for 8 years in 3 functional domains: memory, motor and visual motor functions, and attention. A series of exploratory principal axis factor analyses, with varimax rotation, revealed seven factors: Divided Attention, Selective Attention, Verbal Learning and Recall, Visual Learning and Recall, Motor Speed, Visual-Motor Speed, and Working Memory. The same factors emerged across the 8-year period, suggesting that children's neurocognitive structures are articulated and stable throughout this period of development. From these exploratory analyses a small set of cost-effective neuropsychological tests were found to characterize children's functioning consistently throughout the 8-year period.

Neurological outcomes in children with and without amalgam-related mercury exposure: seven years of longitudinal observations in a randomized trial.

BACKGROUND: Although large-scale, randomized trials involving children have been completed and their results demonstrate an absence of neurobehavioral effects from clinical exposure to mercury amalgam, neurological findings from such studies have not been reported. METHODS: The authors conducted a randomized, prospective trial examining the safety of dental amalgam in which 507 children aged 8 through 12 years were assigned to treatment with either amalgam or resin-based composite. During seven years of follow-up, the authors performed annual clinical neurological examinations, including an evaluation of neurological hard signs (NHSs), presence of tremor and neurological soft signs (NSSs). RESULTS: The authors found no significant differences between treatment groups in any of the neurological measures. Groups did not differ with respect to the presence or absence of NHSs or tremor, nor the presence or absence or severity of NSSs at any point. As expected, NSS severity scores diminished with increasing age. CONCLUSIONS: Even at the levels of amalgam exposure in this study (a mean of 7.7-10.7 amalgam surfaces per subject across the seven years of follow-up), the authors conclude that exposure to mercury from dental amalgam does not adversely affect neurological status. CLINICAL IMPLICATIONS: The current evidence is that potential neurobehavioral or neurological effects from dental amalgam mercury exposure in children are inconsequential.

Age differences in neural correlates of feedback processing after economic decisions under risk.

This study examines age-related differences in behavioral responses to risk and in the neurophysiological correlates of feedback processing. Our sample was composed of younger, middle-aged, and older adults, who were asked to decide between 2 risky options, in the gain and loss domains, during an EEG recording. Results evidenced group-related differences in early and later stages of feedback processing, indexed by differences in the feedback-related negativity (FRN) and P3 amplitudes. Specifically, in the loss domain, younger adults showed higher FRN amplitudes after non-losses than after losses, whereas middle-aged and older adults had similar FRN amplitudes after both. In the gain domain, younger and middle-aged adults had higher P3 amplitudes after gains than after non-gains, whereas older adults had similar P3 amplitudes after both. Behaviorally, older adults had higher rates of risky decisions than younger adults in the loss domain, a result that was correlated with poorer performance in memory and executive functions. Our results suggest age-related differences in the outcome-related expectations, as well as in the affective relevance attributed to the outcomes, which may underlie the group differences found in risk-aversion.

Neurobehavioral effects of dental amalgam in children: a randomized clinical trial.

CONTEXT: Dental (silver) amalgam is a widely used restorative material containing 50% elemental mercury that emits small amounts of mercury vapor. No randomized clinical trials have determined whether there are significant health risks associated with this low-level mercury exposure. OBJECTIVE: To assess the safety of dental amalgam restorations in children. DESIGN: A randomized clinical trial in which children requiring dental restorative treatment were randomized to either amalgam for posterior restorations or resin composite instead of amalgam. Enrollment commenced February 1997, with annual follow-up for 7 years concluding in July 2005. SETTING AND PARTICIPANTS: A total of 507 children in Lisbon, Portugal, aged 8 to 10 years with at least 1 carious lesion on a permanent tooth, no previous exposure to amalgam, urinary mercury level <10 microg/L, blood lead level <15 microg/dL, Comprehensive Test of Nonverbal Intelligence IQ > or =67, and with no interfering health conditions. INTERVENTION: Routine, standard-of-care dental treatment, with one group receiving amalgam restorations for posterior lesions (n = 253) and the other group receiving resin composite restorations instead of amalgam (n = 254). MAIN OUTCOME MEASURES: Neurobehavioral assessments of memory, attention/concentration, and motor/visuomotor domains, as well as nerve conduction velocities. RESULTS: During the 7-year trial period, children had a mean of 18.7 tooth surfaces (median, 16) restored in the amalgam group and 21.3 (median, 18) restored in the composite group. Baseline mean creatinine-adjusted urinary mercury levels were 1.8 microg/g in the amalgam group and 1.9 microg/g in the composite group, but during follow-up were 1.0 to 1.5 microg/g higher in the amalgam group than in the composite group (P<.001). There were no statistically significant differences in measures of memory, attention, visuomotor function, or nerve conduction velocities (average z scores were very similar, near zero) for the amalgam and composite groups over all 7 years of follow-up, with no statistically significant differences observed at any time point (P values from .29 to .91). Starting at 5 years after initial treatment, the need for additional restorative treatment was approximately 50% higher in the composite group. CONCLUSIONS: In this study, children who received dental restorative treatment with amalgam did not, on average, have statistically significant differences in neurobehavioral assessments or in nerve conduction velocity when compared with children who received resin composite materials without amalgam. These findings, combined with the trend of higher treatment need later among those receiving composite, suggest that amalgam should remain a viable dental restorative option for children. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00066118.

Cluster headache without autonomic symptoms: why is it different?

BACKGROUND: Some patients with otherwise typical cluster headache (CH) have persistent attacks free of cranial autonomic symptoms (CAS). The factors responsible for this atypical presentation are not known. OBJECTIVES: To identify factors associated to the absence of CAS in patients with CH. METHODS: A prospective series of 157 patients with the diagnosis of CH was analyzed, comparing 148 typical CH patients with 9 CH patients without CAS. RESULTS: Patients without CAS reported significantly less intense attacks (P = .003) when compared to those with CAS. There was also a tendency (not reaching statistical significance) for a higher frequency of females and chronic CH among those without CAS. Otherwise, there were no differences between the two groups (in age, duration of illness, follow-up time, attack duration or frequency, nor side or site of pain). A logistic regression analysis showed that only pain intensity could explain the difference between the two groups, since the other explanatory variables were also associated with different intensity of attacks. CONCLUSIONS: These results support the hypothesis that CH without cranial autonomic symptoms represents a milder form of CH.