Assessing the feasibility of digital keypress statistics to detect seizures and capture cognitive impairment in patients with epilepsy: A pilot study.

BACKGROUND: Efficient, non-invasive monitoring may provide a more accurate and comprehensive understanding of seizure frequency and the development of some comorbidities in people with epilepsy. Novel keyboard technology measuring digital keypress statistics has demonstrated its practical value for neurodegenerative diseases including Parkinson's Disease and Dementia. Smartphones integrated into daily life may serve as a low-burden longitudinal monitoring system for patients with epilepsy. OBJECTIVE: This study aimed to assess the feasibility of keyboard statistics as an objective measure of seizure frequency for patients with epilepsy, in addition to tracking differences between cognitively normal and cognitively impaired patients. METHODS: Six adult patients admitted to the Epilepsy Monitoring Unit (EMU) at Mayo Clinic in Rochester, Minnesota were studied. The keyboard was installed on the patient's smartphone. In the EMU, typing statistics were correlated to electroencephalogram (EEG) confirmed seizures. After discharge, participants continued using their keyboards and kept a seizure log. We also analyzed the key press/release times and usage of participants' keyboards for adherence. RESULTS: Keyboard sessions during and after seizures assessed for key press/release differences versus baseline showed no statistically significant difference (p = 0.44). Using one-way ANOVA, cognitive impairment's potential impact on keyboard statistics was explored in patients who had neuropsychological testing (N = 3). Significant differences were found between patients with and without cognitive impairment (p < 0.001). No significant difference was noted between patients with mild intellectual disability and normal cognitive function (p = 0.55).

High and low frequency anterior nucleus of thalamus deep brain stimulation: Impact on memory and mood in five patients with treatment resistant temporal lobe epilepsy.

High frequency anterior nucleus of the thalamus deep brain stimulation (ANT DBS) is an established therapy for treatment resistant focal epilepsies. Although high frequency-ANT DBS is well tolerated, patients are rarely seizure free and the efficacy of other DBS parameters and their impact on comorbidities of epilepsy such as depression and memory dysfunction remain unclear. The purpose of this study was to assess the impact of low vs high frequency ANT DBS on verbal memory and self-reported anxiety and depression symptoms. Five patients with treatment resistant temporal lobe epilepsy were implanted with an investigational brain stimulation and sensing device capable of ANT DBS and ambulatory intracranial electroencephalographic (iEEG) monitoring, enabling long-term detection of electrographic seizures. While patients received therapeutic high frequency (100 and 145 Hz continuous and cycling) and low frequency (2 and 7 Hz continuous) stimulation, they completed weekly free recall verbal memory tasks and thrice weekly self-reports of anxiety and depression symptom severity. Mixed effects models were then used to evaluate associations between memory scores, anxiety and depression self-reports, seizure counts, and stimulation frequency. Memory score was significantly associated with stimulation frequency, with higher free recall verbal memory scores during low frequency ANT DBS. Self-reported anxiety and depression symptom severity was not significantly associated with stimulation frequency. These findings suggest the choice of ANT DBS stimulation parameter may impact patients' cognitive function, independently of its impact on seizure rates.

A platform for brain network sensing and stimulation with quantitative behavioral tracking: Application to limbic circuit epilepsy.

Temporal lobe epilepsy is a common neurological disease characterized by recurrent seizures. These seizures often originate from limbic networks and people also experience chronic comorbidities related to memory, mood, and sleep (MMS). Deep brain stimulation targeting the anterior nucleus of the thalamus (ANT-DBS) is a proven therapy, but the optimal stimulation parameters remain unclear. We developed a neurotechnology platform for tracking seizures and MMS to enable data streaming between an investigational brain sensing-stimulation implant, mobile devices, and a cloud environment. Artificial Intelligence algorithms provided accurate catalogs of seizures, interictal epileptiform spikes, and wake-sleep brain states. Remotely administered memory and mood assessments were used to densely sample cognitive and behavioral response during ANT-DBS. We evaluated the efficacy of low-frequency versus high-frequency ANT-DBS. They both reduced seizures, but low-frequency ANT-DBS showed greater reductions and better sleep and memory. These results highlight the potential of synchronized brain sensing and behavioral tracking for optimizing neuromodulation therapy.

Drug-resistant temporal lobe epilepsy with temporal encephaloceles: How far to resect.

PURPOSE: This study sought to evaluate the impact of surgical extent on seizure outcome in drug-resistant temporal lobe epilepsy (DR-TLE) with temporal encephaloceles (TE). METHODS: This was a single-institution retrospective study of patients who underwent surgery for DR-TLE with TE between January 2008 and December 2020. The impact of surgical extent on seizure outcome was evaluated. In a subset with dominant DR-TLE, the impact of surgical extent on neuropsychometric outcome was evaluated. RESULTS: Thirty-four patients were identified (female, 56%; median age at surgery, 43 years). TE were frequently overlooked on initial magnetic resonance imaging (MRI), with encephaloceles only detected after repeat or expert re-review of MRI, additional multi-modal imaging, or intra-operatively in 31 (91%). Sixteen (47%) underwent limited resections, including encephalocele resection only (n = 5) and encephalocele resection with more extensive temporal corticectomy sparing the amygdala and hippocampus (n = 11). The remainder (n = 18, 53%) underwent standard anterior temporal lobectomy and amygdalohippocampectomy (ATLAH). Limited resection was performed more frequently on the left (12/17 vs. 4/17, p = 0.015). Twenty-seven patients (79%) had a favourable outcome (Engel I/II), and 17 (50%) were seizure-free at the last follow-up (median seizure-free survival of 27.3 months). There was no statistically significant difference in seizure-free outcomes between limited resection and ATLAH. In dominant DR-TLE, verbal memory decline was more likely after ATLAH than limited resection (3/4 vs. 0/9, p = 0.014). CONCLUSION: Expert re-review of imaging and multi-modal advanced imaging improved TE identification. There was no statistical difference in seizure-free outcomes based on surgical extent. Preservation of verbal memory supports limited resection in dominant temporal cases.

Laser Interstitial Thermal Therapy for Epilepsy.

Laser interstitial thermal therapy is an important new technique with a diverse use in epilepsy. This article gives an up-to-date evaluation of the current use of the technique within epilepsy, as well as provides some guidance to novice users appropriate clinical cases for its use.

Multimodal approach leads to seizure-freedom in a case of highly refractory drug-resistant focal epilepsy.

Drug-resistant, nonlesional, extratemporal lobe focal epilepsy can be difficult to treat and may require a high degree of multidisciplinary teamwork to localize the seizure onset zone for resective surgery. Here, we describe a patient with longstanding drug-resistant, nonlesional, extratemporal focal epilepsy with a high seizure burden who became seizure-free after prolonged evaluation and eventual left frontal cortical resection. Prior evaluations included magnetoencephalography, invasive video-EEG monitoring, and implantation of a responsive neurostimulation (RNS) device for ongoing intracranial stimulation. Highly sophisticated techniques were utilized including stereotactic localization of prior evaluations to guide repeat stereo-EEG (SEEG), electrical stimulation mapping, SEEG-guided radiofrequency ablation, and awake resection with language and motor mapping using a cognitive testing platform . Incorporating a wide array of data from multiple centers and evaluation time periods was necessary to optimize seizure control and minimize the risk of neurological deficits from surgery.

Mayo normative studies: A conditional normative model for longitudinal change on the Auditory Verbal Learning Test and preliminary validation in preclinical Alzheimer's disease.

Introduction: The aim of this study was to develop a conditional normative model for Rey's Auditory Verbal Learning Test (AVLT) that accounts for practice effects. Methods: In our normative sample, robust conditional norms were derived from 1001 cognitively unimpaired (CU) adults ages 50 to 89 who completed the AVLT up to eight times. Linear mixed-effects models adjusted for baseline performance, prior test exposures, time, demographics, and interaction terms. In our preliminary validation, mean performance on conditional and typical normative scores across two to four completed follow-up tests in preclinical Alzheimer's disease participants at baseline with positive amyloid and tau positron emission (n = 27 CU amyloid [A]+tau[T]+) was compared to biomarker negative individuals (n = 269 CU A-T-). Results: AVLT performance using typical norms did not differ across A+T+ and A-T- groups. Conditional norms z-scores were lower in the A+T+ relative to the A-T- group for 30-minute recall (P = .033) and sum of trials (P = .030). Discussion: Conditional normative methods that account for practice effects show promise for identifying longitudinal cognitive decline.

Shape features of working memory-related deep-brain regions differentiate high and low community functioning in schizophrenia.

We have previously shown that schizophrenia (SCZ) participants with high community functioning demonstrate better verbal working memory (vWM) performance relative to those with low community functioning. In the present study, we investigated whether neuroanatomical differences in regions supporting vWM also exist between schizophrenia groups that vary on community functioning. Utilizing magnetic resonance imaging, shape features of deep-brain nuclei known to be involved in vWM were calculated in samples of high functioning (HF-SCZ, n = 23) and low functioning schizophrenia participants (LF-SCZ, n = 18), as well as in a group of healthy control participants (CON, n = 45). Large deformation diffeomorphic metric mapping was employed to characterize surface anatomy of the caudate nucleus, globus pallidus, hippocampus, and thalamus. Statistical analyses involved linear mixed-effects models and vertex-wise contrast mapping to assess between-group differences in structural shape features, and Pearson correlations to evaluate relationships between shape metrics and vWM performance. We found significant between-group main effects in deep-brain surface anatomy across all structures. Post-hoc comparisons revealed HF-SCZ and LF-SCZ groups significantly differed on both caudate and hippocampal shape, however, significant correlations with vWM were only observed in hippocampal shape for both SCZ groups. Specifically, more abnormal hippocampal deformation was associated with lower vWM suggesting hippocampal shape is both a neural substrate for vWM deficits and a potential biomarker to predict or monitor the efficacy of cognitive rehabilitation. These findings add to a growing body of literature related to functional outcomes in schizophrenia by demonstrating unique shape patterns across the spectrum of community functioning in SCZ.

Failed Performance on the Test of Memory Malingering and Misdiagnosis in Individuals with Early-Onset Dysexecutive Alzheimer's Disease.

OBJECTIVE: Individuals with early-onset dysexecutive Alzheimer's disease (dAD) have high rates of failed performance validity testing (PVT), which can lead to symptom misinterpretation and misdiagnosis. METHOD: The aim of this retrospective study is to evaluate rates of failure on a common PVT, the test of memory malingering (TOMM), in a sample of clinical patients with biomarker-confirmed early-onset dAD who completed neuropsychological testing. RESULTS: We identified seventeen patients with an average age of symptom onset at 52.25 years old. Nearly fifty percent of patients performed below recommended cut-offs on Trials 1 and 2 of the TOMM. Four of six patients who completed outside neuropsychological testing were misdiagnosed with alternative etiologies to explain their symptomatology, with two of these patients' performances deemed unreliable based on the TOMM. CONCLUSIONS: Low scores on the TOMM should be interpreted in light of contextual and optimally biological information and do not necessarily rule out a neurodegenerative etiology.

Diagnostic accuracy of the Cogstate Brief Battery for prevalent MCI and prodromal AD (MCI A+ T+ ) in a population-based sample.

INTRODUCTION: This study evaluated the diagnostic accuracy of the Cogstate Brief Battery (CBB) for mild cognitive impairment (MCI) and prodromal Alzheimer's disease (AD) in a population-based sample. METHODS: Participants included adults ages 50+ classified as cognitively unimpaired (CU, n = 2866) or MCI (n = 226), and a subset with amyloid (A) and tau (T) positron emission tomography who were AD biomarker negative (A-T-) or had prodromal AD (A+T+). RESULTS: Diagnostic accuracy of the Learning/Working Memory Composite (Lrn/WM) for discriminating all CU and MCI was moderate (area under the curve [AUC] = 0.75), but improved when discriminating CU A-T- and MCI A+T+ (AUC = 0.93) and when differentiating MCI participants without AD biomarkers from those with prodromal AD (AUC = 0.86). Conventional cut-offs yielded lower than expected sensitivity for both MCI (38%) and prodromal AD (73%). DISCUSSION: Clinical utility of the CBB for detecting MCI in a population-based sample is lower than expected. Caution is needed when using currently available CBB normative data for clinical interpretation.

Mayo Normative Studies: Regression-Based Normative Data for the Auditory Verbal Learning Test for Ages 30-91 Years and the Importance of Adjusting for Sex.

OBJECTIVE: Rey's Auditory Verbal Learning Test (AVLT) is a widely used word list memory test. We update normative data to include adjustment for verbal memory performance differences between men and women and illustrate the effect of this sex adjustment and the importance of excluding participants with mild cognitive impairment (MCI) from normative samples. METHOD: This study advances the Mayo's Older Americans Normative Studies (MOANS) by using a new population-based sample through the Mayo Clinic Study of Aging, which randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. Regression-based normative T-score formulas were derived from 4428 cognitively unimpaired adults aged 30-91 years. Fully adjusted T-scores correct for age, sex, and education. We also derived T-scores that correct for (1) age or (2) age and sex. Test-retest reliability data are provided. RESULTS: From raw score analyses, sex explained a significant amount of variance in performance above and beyond age (8-10%). Applying original age-adjusted MOANS norms to the current sample resulted in significantly fewer-than-expected participants with low delayed recall performance, particularly in women. After application of new T-scores adjusted only for age, even in normative data derived from this sample, these age-adjusted T-scores showed scores <40 T occurred more frequently among men and less frequently among women relative to T-scores that also adjusted for sex. CONCLUSIONS: Our findings highlight the importance of using normative data that adjust for sex with measures of verbal memory and provide new normative data that allow for this adjustment for the AVLT.

Pick's disease: clinicopathologic characterization of 21 cases.

BACKGROUND: Pick's disease (PiD) is a unique subtype of frontotemporal lobar degeneration characterized pathologically by aggregates of 3-Repeat tau. Few studies have examined the clinical variability and disease progression in PiD. We describe the clinical features, neuropsychological profiles and coexistent pathologies in 21 cases of autopsy-confirmed PiD. METHODS: This study was a retrospective analysis of patients with Pick's disease evaluated at Mayo Clinic, Rochester or Jacksonville (1995-2018), and identified through an existing database. RESULTS: Twenty-one cases with sufficient clinical data were identified. Behavioral variant FTD (bvFTD; 12/21) was the most common phenotype, followed by primary progressive aphasia (PPA; 7/21), corticobasal syndrome (CBS; 1/21) and amnestic dementia (1/21). Median age at disease onset was 54 years, with PPA cases (median = 52 years) presenting earlier than bvFTD (median = 59). Median disease duration (onset-death) overall was 10 years and did not differ significantly between bvFTD (median = 9.5 years) and PPA (median = 13). Age at death was not significantly different in PPA (median = 66) compared to bvFTD (median = 68.5). A third of the cases (n = 7/21) demonstrated pure PiD pathology, while the remainder showed co-existent other pathologies including Alzheimer's type (n = 6), cerebral amyloid angiopathy (n = 3), combined Alzheimer's and amyloid angiopathy (n = 4), and Lewy body disease (n = 1). CONCLUSIONS: Our study shows that bvFTD and PPA are the most common clinical phenotypes associated with PiD, although rare presentations such as CBS were also seen. Coexisting non-Pick's pathology was also present in many cases. Our study highlights the clinical and pathologic heterogeneity in PiD.

Recent Self-Reported Cannabis Use Is Associated With the Biometrics of Delta-9-Tetrahydrocannabinol.

OBJECTIVE: Research typically characterizes cannabis use by self-report of cannabis intake frequency. In an effort to better understand relationships between measures of cannabis use, we evaluated if Δ-9-tetrahydrocannabinol (THC) and metabolite concentrations (biometrics) were associated with a calibrated timeline followback (TLFB) assessment of cannabis use. METHOD: Participants were 35 young adult male cannabis users who completed a calibrated TLFB measure of cannabis use over the past 30 days, including time of last use. The calibration required participants handling four plastic bags of a cannabis substitute (0.25, 0.5, 1.0, and 3.5 grams) to quantify cannabis consumed. Participants provided blood and urine samples for analysis of THC and metabolites, at two independent laboratories. Participants abstained from cannabis use on the day of sample collection. We tested Pearson correlations between the calibrated TLFB measures and cannabis biometrics. RESULTS: Strong correlations were seen between urine and blood biometrics (all r > .73, all p < .001). TLFB measures of times of use and grams of cannabis consumed were significantly related to each biometric, including urine 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) and blood THC, 11-hydroxy-THC (11-OH-THC), THCCOOH, THCCOOH-glucuronide (times of use: r > .48-.61, all p < .05; grams: r > .40-.49, all p < .05). CONCLUSIONS: This study extends prior work to show TLFB methods significantly relate to an extended array of cannabis biometrics. The calibration of cannabis intake in grams was associated with each biometric, although the simple TLFB measure of times of use produced the strongest relationships with all five biometrics. These findings suggest that combined self-report and biometric data together convey the complexity of cannabis use, but allow that either the use of calibrated TLFB measures or biometrics may be sufficient for assessment of cannabis use in research.

Neural correlates of preserved facial affect perception in high functioning schizophrenia.

Individuals with 'high functioning' schizophrenia (HF-SCZ) may have preserved facial affect perception (FAP) compared to individuals with 'low functioning' schizophrenia (LF-SCZ). The neural mechanisms supporting preserved FAP in HF-SCZ have yet to be evaluated. This study compared brain activation during FAP performance in HF-SCZ, LF-SCZ, and controls. Results demonstrated greater activation in the precuneus in CON compared to both SCZ groups, while HF-SCZ activated this region intermediate to controls and LF-SCZ. These preliminary findings suggest greater precuneus activation may be related to preserved FAP in HF-SCZ compared to LF-SCZ, though future research is needed to further evaluate differences between groups.

Cortical thickness of neural substrates supporting cognitive empathy in individuals with schizophrenia.

BACKGROUND: Cognitive empathy is supported by the medial prefrontal cortex (mPFC), inferior frontal gyrus (IFG), anterior mid-cingulate cortex (aMCC), insula (INS), supplementary motor area (SMA), right temporo-parietal junction (TPJ), and precuneus (PREC). In healthy controls, cortical thickness in these regions has been linked to cognitive empathy. As cognitive empathy is impaired in schizophrenia, we examined whether reduced cortical thickness in these regions was associated with poorer cognitive empathy in this population. METHODS: 41 clinically-stable community-dwelling individuals with schizophrenia and 46 healthy controls group-matched on demographic variables completed self-report empathy questionnaires, a cognitive empathy task, and structural magnetic resonance imaging. We examined between-group differences in study variables using t-tests and analyses of variance. Next, we used Pearson correlations to evaluate the relationship between cognitive empathy and cortical thickness in the mPFC, IFG, aMCC, INS, SMA, TPJ, and PREC in both groups. RESULTS: Individuals with schizophrenia demonstrated cortical thinning in the IFG, INS, SMA, TPJ, and PREC (all p<0.05) and impaired cognitive empathy across all measures (all p<0.01) relative to controls. While cortical thickness in the mPFC, IFC, aMCC, and INS (all p<0.05) was related to cognitive empathy in controls, we did not observe these relationships in individuals with schizophrenia (all p>0.10). CONCLUSIONS: Individuals with schizophrenia have reduced cortical thickness in empathy-related neural regions and significant impairments in cognitive empathy. Interestingly, cortical thickness was related to cognitive empathy in controls but not in the schizophrenia group. We discuss other mechanisms that may account for cognitive empathy impairment in schizophrenia.

High functioning individuals with schizophrenia have preserved social perception but not mentalizing abilities.

Social perception and mentalizing are fundamental social cognitive abilities that are related to functioning and are impaired in schizophrenia. A novel approach to examine the relationship between social cognition and community functioning is to first functionally categorize individuals with schizophrenia and then evaluate social cognitive performance. We evaluated differences in social perception and mentalizing among controls (CON, n=45), high functioning individuals with schizophrenia (HF-SCZ, n=36), and individuals with low functioning schizophrenia (LF-SCZ, n=24). Analyses revealed that HF-SCZ had preserved social perceptual abilities compared to LF-SCZ. Both schizophrenia groups had impaired mentalizing abilities compared to CON, but did not differ from each other. These results suggest that HF-SCZ and LF-SCZ are characterized by differences in the perceptual aspects of social cognition and encourage future research to evaluate the neural basis underlying this preserved ability.

Cluster analysis differentiates high and low community functioning in schizophrenia: Subgroups differ on working memory but not other neurocognitive domains.

BACKGROUND: Schizophrenia is characterized by impairment in multiple aspects of community functioning. Available literature suggests that community functioning may be enhanced through cognitive remediation, however, evidence is limited regarding whether specific neurocognitive domains may be treatment targets. We characterized schizophrenia subjects based on their level of community functioning through cluster analysis in an effort to identify whether specific neurocognitive domains were associated with variation in functioning. METHODS: Schizophrenia (SCZ, n=60) and control (CON, n=45) subjects completed a functional capacity task, social competence role-play, functional attainment interview, and a neuropsychological battery. Multiple cluster analytic techniques were used on the measures of functioning in the schizophrenia subjects to generate functionally-defined subgroups. MANOVA evaluated between-group differences in neurocognition. RESULTS: The cluster analysis revealed two distinct groups, consisting of 36 SCZ characterized by high levels of community functioning (HF-SCZ) and 24 SCZ with low levels of community functioning (LF-SCZ). There was a main group effect for neurocognitive performance (p<0.001) with CON outperforming both SCZ groups in all neurocognitive domains. Post-hoc tests revealed that HF-SCZ had higher verbal working memory compared to LF-SCZ (p≤0.05, Cohen's d=0.78) but the two groups did not differ in remaining domains. CONCLUSION: The cluster analysis classified schizophrenia subjects in HF-SCZ and LF-SCZ using a multidimensional assessment of community functioning. Moreover, HF-SCZ demonstrated rather preserved verbal working memory relative to LF-SCZ. The results suggest that verbal working memory may play a critical role in community functioning, and is a potential cognitive treatment target for schizophrenia subjects.

The 40-item Monell Extended Sniffin' Sticks Identification Test (MONEX-40).

BACKGROUND: Most existing olfactory identification (ID) tests have the primary aim of diagnosing clinical olfactory dysfunction, thereby rendering them sub-optimal for experimental settings where the aim is to detect differences in healthy subjects' odor ID abilities. MATERIALS AND METHODS: We have developed an extended version of the olfactory ID subtest of the Sniffin' Sticks test battery to better assess the variability in ID scores and thereby olfactory abilities of healthy, adult individuals. Twenty-four odorants, corresponding cue labels, and distractor labels were added to the existing 16-item Sniffin' Sticks ID test to create the 40-item Monell Extended Sniffin' Sticks Identification Test (MONEX-40). The MONEX-40 was administered to 259 healthy young subjects, of which 72 were retested on an average of 212 days (SD 112 days) later. RESULTS: The added odor items demonstrated good validity, as shown by a significant correlation of the results with the original 16-item ID test. In addition, the MONEX-40 achieved a significant test-retest and split-half reliability. CONCLUSIONS: Taken together, these results suggest that the MONEX-40 is a reliable method for experimental assessment of odor ID ability in healthy, young individuals. Moreover, its use of a wider range of odors allows the experimenter to present subsets of the MONEX-40 within the same experiment while maintaining statistical power.

The spectrin-based membrane skeleton stabilizes mouse megakaryocyte membrane systems and is essential for proplatelet and platelet formation.

Megakaryocytes generate platelets by remodeling their cytoplasm first into proplatelets and then into preplatelets, which undergo fission to generate platelets. Although the functions of microtubules and actin during platelet biogenesis have been defined, the role of the spectrin cytoskeleton is unknown. We investigated the function of the spectrin-based membrane skeleton in proplatelet and platelet production in murine megakaryocytes. Electron microscopy revealed that, like circulating platelets, proplatelets have a dense membrane skeleton, the main fibrous component of which is spectrin. Unlike other cells, megakaryocytes and their progeny express both erythroid and nonerythroid spectrins. Assembly of spectrin into tetramers is required for invaginated membrane system maturation and proplatelet extension, because expression of a spectrin tetramer-disrupting construct in megakaryocytes inhibits both processes. Incorporation of this spectrin-disrupting fragment into a novel permeabilized proplatelet system rapidly destabilizes proplatelets, causing blebbing and swelling. Spectrin tetramers also stabilize the "barbell shapes" of the penultimate stage in platelet production, because addition of the tetramer-disrupting construct converts these barbell shapes to spheres, demonstrating that membrane skeletal continuity maintains the elongated, pre-fission shape. The results of this study provide evidence for a role for spectrin in different steps of megakaryocyte development through its participation in the formation of invaginated membranes and in the maintenance of proplatelet structure.

Methods for building an inexpensive computer-controlled olfactometer for temporally-precise experiments.

Many human olfactory experiments call for fast and stable stimulus-rise times as well as exact and stable stimulus-onset times. Due to these temporal demands, an olfactometer is often needed. However, an olfactometer is a piece of equipment that either comes with a high price tag or requires a high degree of technical expertise to build and/or to run. Here, we detail the construction of an olfactometer that is constructed almost exclusively with "off-the-shelf" parts, requires little technical knowledge to build, has relatively low price tags, and is controlled by E-Prime, a turnkey-ready and easily-programmable software commonly used in psychological experiments. The olfactometer can present either solid or liquid odor sources, and it exhibits a fast stimulus-rise time and a fast and stable stimulus-onset time. We provide a detailed description of the olfactometer construction, a list of its individual parts and prices, as well as potential modifications to the design. In addition, we present odor onset and concentration curves as measured with a photo-ionization detector, together with corresponding GC/MS analyses of signal-intensity drop (5.9%) over a longer period of use. Finally, we present data from behavioral and psychophysiological recordings demonstrating that the olfactometer is suitable for use during event-related EEG experiments.