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Objective: The primary aim of the research was to compare the impact of postischemic and hemorrhagic stroke on brain connectivity and recovery using resting-state functional magnetic resonance imaging. Methods and Procedures: We serially imaged 20 stroke patients, 10 with ischemic stroke (IS) and 10 with intracerebral hemorrhage (ICH), at 1, 3, and 12 months (1M, 3M, and 12M) after ictus. Data from 10 healthy volunteers were obtained from a publically available imaging data set. All functional and structural images underwent standard processing for brain extraction, realignment, serial registration, unwrapping, and denoising using SPM12. A seed-based group analysis using CONN software was used to evaluate the default mode network and the sensorimotor network connections by applying bivariate correlation and hemodynamic response function weighting. Results: In comparison with healthy controls, both IS and ICH exhibited disrupted interactions (decreased connectivity) between these two networks at 1M. Interactions then increased by 12M in each group. Temporally, each group exhibited a minimal increase in connectivity at 3M compared with 12M. Overall, the ICH patients exhibited a greater magnitude of connectivity disruption compared with IS patients, despite a significant intrasubject reduction in hematoma volume. We did not observe any significant correlation between change in connectivity and recovery as measured on the National Institutes of Health Stroke Scale (NIHSS) at any time point. Conclusions: These findings demonstrate that the largest changes in functional connectivity occur earlier (3M) rather than later (12M) and show subtle differences between IS and ICH during recovery and should be explored further in larger samples.

Introduction: Working memory (WM) is an essential component of executive functions which depend on maintaining task-related information online for brief periods in both the presence and absence of interfering stimuli. Active maintenance occurs during the WM delay period, the time between stimulus encoding and subsequent retrieval. Previous studies have extensively documented prefrontal and posterior parietal cortex activity during the WM delay period, but the role of subcortical structures including the thalamus remains to be fully elucidated, especially in humans., Methods: Using a simultaneous electroencephalogram (EEG)-functional magnetic resonance imaging (fMRI) approach, we investigated the role of the thalamus during the WM delay period in a modified Sternberg paradigm following low and high memory load encoding of naturalistic scenes. During the delay, participants passively viewed scrambled scenes containing similar color and spatial frequency to serve as a perceptual baseline. Individual source estimation was weighted by the location of the thalamic fMRI signal relative to the WM delay period onset., Results: The effects memory load on maintenance were observed bilaterally in thalamus with higher EEG source amplitudes in the low compared to high load condition occurring 160-390 ms after the onset of the delay period., Conclusion: The main finding that thalamic activation was elevated during the low compared to high condition despite similar duration of perceptual input and upcoming motor requirements suggests a capacity-limited role for sensory filtering of the thalamus during consolidation of stimuli into WM, where the highest activity occurs when fewer stimuli need to be maintained in the presence of interfering perceptual stimuli during the delay. The results are discussed in the context of theories regarding the role of the thalamus in sensory gating during working memory., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gomes, Plaska, Ortega and Ellmore.)

Introduction: Motor classifications of Parkinson's Disease (PD) have been widely used. This paper aims to update a subtype classification using the MDS-UPDRS-III and determine if cerebrospinal neurotransmitter profiles (HVA and 5-HIAA) differ between these subtypes in a cohort from the Parkinson's Progression Marker Initiative (PPMI)., Methods: UPDRS and MDS-UPDRS scores were collected for 20 PD patients. Akinetic-rigid (AR), Tremor-dominant (TD), and Mixed (MX) subtypes were calculated using a formula derived from UPDRS, and a new ratio was developed for subtyping patients with the MDS-UPDRS. This new formula was subsequently applied to 95 PD patients from the PPMI dataset, and subtyping was correlated to neurotransmitter levels. Data were analyzed using receiver operating characteristic models and ANOVA., Results: Compared to previous UPDRS classifications, the new MDS-UPDRS TD/AR ratios produced significant areas under the curve (AUC) for each subtype. The optimal sensitivity and specificity cutoff scores were ≥0.82 for TD, ≤0.71 for AR, and >0.71 and <0.82 for Mixed. Analysis of variance showed that the AR group had significantly lower HVA and 5-HIAA levels than the TD and HC groups. A logistic model using neurotransmitter levels and MDS-UPDRS-III could predict the subtype classification., Conclusions: This MDS-UPDRS motor classification system provides a method to transition from the original UPDRS to the new MDS-UPDRS. It is a reliable and quantifiable subtyping tool for monitoring disease progression. The TD subtype is associated with lower motor scores and higher HVA levels, while the AR subtype is associated with higher motor scores and lower 5-HIAA levels., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Abstract Introduction: One manipulation used to study the neural basis of working memory (WM) is to vary the information load at encoding, then measure activity and connectivity during maintenance in the delay period. A hallmark finding is increased delay activity and connectivity between frontoparietal brain regions with increased load. Most WM studies, however, employ simple stimuli during encoding and unfilled intervals during the delay. In this study, we asked how delay period activity and connectivity change during low and high load maintenance of complex stimuli. Methods: Twenty-two participants completed a modified Sternberg WM task with two or five naturalistic scenes as stimuli during scalp electroencephalography (EEG). On each trial, the delay was filled with phase-scrambled scenes to provide a visual perceptual control with similar color and spatial frequency as presented during encoding. Functional connectivity during the delay was assessed by the phase-locking value (PLV). Results: Results showed reduced theta/alpha delay activity amplitude during high compared with low WM load across frontal, central, and parietal sources. A network with higher connectivity during low load consisted of increased PLV between (1) left frontal and right posterior temporal sources in the theta/alpha bands, (2) right anterior temporal and left central sources in the alpha and lower beta bands, and (3) left anterior temporal and posterior temporal sources in the theta, alpha, and lower beta bands. Discussion: The findings suggest a role for interhemispheric connectivity during WM maintenance of complex stimuli with load modulation when limited attentional resources are essential for filtering. Impact statement The patterns of brain connectivity subserving working memory (WM) have largely been investigated to date using simple stimuli, including letters, digits, and shapes and during unfilled WM delay intervals. Fewer studies describe functional connectivity changes during the maintenance of more naturalistic stimuli in the presence of distractors. In the present study, we employed a scene-based WM task during electroencephalography in healthy humans and found that during low-load WM maintenance with distractors increased interhemispheric connectivity in frontotemporal networks. These findings suggest a role for increased interhemispheric connectivity during maintenance of complex stimuli when attentional resources are essential for filtering.

Humans have a remarkably high capacity and long duration memory for complex scenes. Previous research documents the neural substrates that allow for efficient categorization of scenes from other complex stimuli like objects and faces, but the spatiotemporal neural dynamics underlying scene memory at timescales relevant to working and longer-term memory are less well understood. In the present study, we used high density EEG during a visual continuous recognition task in which new, old, and scrambled scenes consisting of color outdoor photographs were presented at an average rate 0.26 Hz. Old scenes were single repeated presentations occurring within either a short-term (< 20 s) or longer-term intervals of between 30 s and 3 min or 4 and 10 min. Overall recognition was far above chance, with better performance at shorter- than longer-term intervals. Sensor-level ANOVA and post hoc pairwise comparisons of event related potentials (ERPs) revealed three main findings: (1) occipital and parietal amplitudes distinguishing new and old from scrambled scenes; (2) frontal amplitudes distinguishing old from new scenes with a central positivity highest for hits compared to misses, false alarms and correct rejections; and (3) frontal and parietal changes from ∼300 to ∼600 ms distinguishing among old scenes previously encountered at short- and longer-term retention intervals. These findings reveal how distributed spatiotemporal neural changes evolve to support short- and longer-term recognition of complex scenes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ellmore, Reichert Plaska, Ng and Mei.)

Spontaneous eye blink rate (sEBR) has been linked to attention and memory, specifically working memory (WM). sEBR is also related to striatal dopamine (DA) activity with schizophrenia and Parkinson's disease showing increases and decreases, respectively, in sEBR. A weakness of past studies of sEBR and WM is that correlations have been reported using blink rates taken at baseline either before or after performance of the tasks used to assess WM. The goal of the present study was to understand how fluctuations in sEBR during different phases of a visual WM task predict task accuracy. In two experiments, with recordings of sEBR collected inside and outside of a magnetic resonance imaging bore, we observed sEBR to be positively correlated with WM task accuracy during the WM delay period. We also found task-related modulation of sEBR, including higher sEBR during the delay period compared to rest, and lower sEBR during task phases (e.g., stimulus encoding) that place demands on visual attention. These results provide further evidence that sEBR could be an important predictor of WM task performance with the changes during the delay period suggesting a role in WM maintenance. The relationship of sEBR to DA activity and WM maintenance is discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ortega, Plaska, Gomes and Ellmore.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. It is one of the leading sources of morbidity and mortality in the aging population AD cardinal symptoms include memory and executive function impairment that profoundly alters a patient's ability to perform activities of daily living. People with mild cognitive impairment (MCI) exhibit many of the early clinical symptoms of patients with AD and have a high chance of converting to AD in their lifetime. Diagnostic criteria rely on clinical assessment and brain magnetic resonance imaging (MRI). Many groups are working to help automate this process to improve the clinical workflow. Current computational approaches are focused on predicting whether or not a subject with MCI will convert to AD in the future. To our knowledge, limited attention has been given to the development of automated computer-assisted diagnosis (CAD) systems able to provide an AD conversion diagnosis in MCI patient cohorts followed longitudinally. This is important as these CAD systems could be used by primary care providers to monitor patients with MCI. The method outlined in this paper addresses this gap and presents a computationally efficient pre-processing and prediction pipeline, and is designed for recognizing patterns associated with AD conversion. We propose a new approach that leverages longitudinal data that can be easily acquired in a clinical setting (e.g., T1-weighted magnetic resonance images, cognitive tests, and demographic information) to identify the AD conversion point in MCI subjects with AUC = 84.7. In contrast, cognitive tests and demographics alone achieved AUC = 80.6, a statistically significant difference ( n = 669, p < 0.05). We designed a convolutional neural network that is computationally efficient and requires only linear registration between imaging time points. The model architecture combines Attention and Inception architectures while utilizing both cross-sectional and longitudinal imaging and clinical information. Additionally, the top brain regions and clinical features that drove the model's decision were investigated. These included the thalamus, caudate, planum temporale, and the Rey Auditory Verbal Learning Test. We believe our method could be easily translated into the healthcare setting as an objective AD diagnostic tool for patients with MCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pena, Suescun, Schiess, Ellmore, Giancardo and the Alzheimer’s Disease Neuroimaging Initiative.)

Background: Neuroinflammation plays a key role in PD pathogenesis, and allogeneic bone marrow-derived mesenchymal stem cells can be used as an immunomodulatory therapy., Objective: The objective of this study was to prove the safety and tolerability of intravenous allogeneic bone marrow-derived mesenchymal stem cells in PD patients., Methods: This was a 12-month single-center open-label dose-escalation phase 1 study of 20 subjects with mild/moderate PD assigned to a single intravenous infusion of 1 of 4 doses: 1, 3, 6, or 10 × 10 6 allogeneic bone marrow-derived mesenchymal stem cells/kg, evaluated 3, 12, 24, and 52 weeks postinfusion. Primary outcome safety measures included transfusion reaction, study-related adverse events, and immunogenic responses. Secondary outcomes included impact on peripheral markers, PD progression, and changes in brain perfusion., Results: There were no serious adverse reactions related to the infusion and no responses to donor-specific human leukocyte antigens. Most common treatment-emergent adverse events were dyskinesias (20%, n = 4) with 1 emergent and 3 exacerbations; and hypertension (20%, n = 4) with 3 transient episodes and 1 requiring medical intervention. One possibly related serious adverse event occurred in a patient with a 4-year history of lymphocytosis who developed asymptomatic chronic lymphocytic leukemia. Peripheral inflammation markers appear to be reduced at 52 weeks in the highest dose including, tumor necrosis factor-α (P < 0.05), chemokine (C-C motif) ligand 22 (P < 0.05), whereas brain-derived neurotrophic factor (P < 0.05) increased. The highest dose seems to have demonstrated the most significant effect at 52 weeks, reducing the OFF state UPDRS motor, -14.4 (P < 0.01), and total, -20.8 (P < 0.05), scores., Conclusion: A single intravenous infusion of allogeneic bone marrow-derived mesenchymal stem cells at doses of 1, 3, 6, or 10 × 10 6 allogeneic bone marrow-derived mesenchymal stem cells/kg is safe, well tolerated, and not immunogenic in mild/moderate PD patients. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Rehearsal during working memory (WM) maintenance is assumed to facilitate retrieval. Less is known about how rehearsal modulates WM delay activity. In the present study, 44 participants completed a Sternberg Task with either intact novel scenes or phase-scrambled scenes, which had similar color and spatial frequency but lacked semantic content. During the rehearsal condition participants generated a descriptive label during encoding and covertly rehearsed during the delay period. During the suppression condition participants did not generate a label during encoding and suppressed (repeated "the") during the delay period. This was easy in the former (novel scenes) but more difficult in the later condition (phase-scrambled scenes) where scenes lacked semantic content. Behavioral performance and EEG delay activity was analyzed as a function of maintenance strategy. Performance during WM revealed a benefit of rehearsal for phase-scrambled but not intact scenes. Examination of the absolute amplitude revealed three underlying sources of activity for rehearsal, including the left anterior temporal (ATL) and left and midline parietal regions. Increases in alpha and theta activity in ATL were correlated with improvement in performance on WM with rehearsal only when labeling was not automatic (e.g., phase-scrambled scenes), which may reflect differences in labeling and rehearsal (i.e., semantic associations vs. shallow labels). We conclude that rehearsal only benefits memory for visual stimuli that lack semantic information, and that this is correlated with changes in alpha and theta rhythms., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Low levels of the natural antioxidant uric acid (UA) and the presence of REM sleep behavior disorder (RBD) are both associated with an increased likelihood of developing Parkinson's disease (PD). RBD and PD are also accompanied by basal ganglia dysfunction including decreased nigrostriatal and nigrocortical resting state functional connectivity. Despite these independent findings, the relationship between UA and substantia nigra (SN) functional connectivity remains unknown. In the present study, voxelwise analysis of covariance was used in a cross-sectional design to explore the relationship between UA and whole-brain SN functional connectivity using the eyes-open resting state fMRI method in controls without RBD, patients with idiopathic RBD, and PD patients with and without RBD. The results showed that controls exhibited a positive relationship between UA and SN functional connectivity with left lingual gyrus. The positive relationship was reduced in patients with RBD and PD with RBD, and the relationship was found to be negative in PD patients. These results are the first to show differential relationships between UA and SN functional connectivity among controls, prodromal, and diagnosed PD patients in a ventral occipital region previously documented to be metabolically and structurally altered in RBD and PD. More investigation, including replication in longitudinal designs with larger samples, is needed to understand the pathophysiological significance of these changes., (Copyright © 2020 Ellmore, Suescun, Castriotta and Schiess.)

Parkinson's disease is the second most prevalent neurodegenerative disorder in the Western world. It is estimated that the neuronal loss related to Parkinson's disease precedes the clinical diagnosis by more than 10 years (prodromal phase) which leads to a subtle decline that translates into non-specific clinical signs and symptoms. By leveraging diffusion magnetic resonance imaging brain (MRI) data evaluated longitudinally, at least at two different time points, we have the opportunity of detecting and measuring brain changes early on in the neurodegenerative process, thereby allowing early detection and monitoring that can enable development and testing of disease modifying therapies. In this study, we were able to define a longitudinal degenerative Parkinson's disease progression pattern using diffusion magnetic resonance imaging connectivity information. Such pattern was discovered using a de novo early Parkinson's disease cohort ( n = 21), and a cohort of Controls ( n = 30). Afterward, it was tested in a cohort at high risk of being in the Parkinson's disease prodromal phase ( n = 16). This progression pattern was numerically quantified with a longitudinal brain connectome progression score. This score is generated by an interpretable machine learning (ML) algorithm trained, with cross-validation, on the longitudinal connectivity information of Parkinson's disease and Control groups computed on a nigrostriatal pathway-specific parcellation atlas. Experiments indicated that the longitudinal brain connectome progression score was able to discriminate between the progression of Parkinson's disease and Control groups with an area under the receiver operating curve of 0.89 [confidence interval (CI): 0.81-0.96] and discriminate the progression of the High Risk Prodromal and Control groups with an area under the curve of 0.76 [CI: 0.66-0.92]. In these same subjects, common motor and cognitive clinical scores used in Parkinson's disease research showed little or no discriminative ability when evaluated longitudinally. Results suggest that it is possible to quantify neurodegenerative patterns of progression in the prodromal phase with longitudinal diffusion magnetic resonance imaging connectivity data and use these image-based patterns as progression markers for neurodegeneration.

Repetitive saccades benefit memory when executed before retrieval, with greatest effects for episodic memory in consistent-handers. Questions remain including how saccades affect scene memory, an important visual component of episodic memory. The present study tested how repetitive saccades affect working and recognition memory for novel scenes. Handedness direction (left-right) and degree (strong/consistent vs. mixed/inconsistent) was measured by raw and absolute laterality quotients respectively from an 8-question handedness inventory completed by 111 adults. Each then performed either 30 s of repetitive horizontal saccades or fixation before or after tasks of scene working memory and scene recognition. Regression with criterion variables of overall percent correct accuracy and d -prime sensitivity showed that when saccades were made before working memory, there was better overall accuracy as a function of increased direction but not degree of handedness. Subjects who made saccades before working memory also performed worse during subsequent recognition memory, while subjects who fixated or made saccades after the working memory task performed better. Saccades made before recognition resulted in recognition accuracy that was better (Cohen's d  = 0.3729), but not significantly different from fixation before recognition. The results demonstrate saccades and handedness interact to affect scene memory with larger effects on encoding than recognition. Saccades before scene encoding in working memory are detrimental to short- and long-term memory, especially for those who are not consistently right-handed, while saccade execution before scene recognition does not appear to benefit recognition accuracy. The findings are discussed with respect to theories of interhemispheric interaction and control of visuospatial attention., Competing Interests: The authors declare there are no competing interests.

There is growing interest in understanding how specific neural events that occur during sleep, including characteristic spindle oscillations between 10 and 16 Hz (Hz), are related to learning and memory. Neural events can be recorded during sleep using the well-known method of scalp electroencephalography (EEG). While publicly available sleep EEG datasets exist, most consist of only a few channels collected in specific patient groups being evaluated overnight for sleep disorders in clinical settings. The dataset described in this Data in Brief includes 22 participants who each participated in EEG recordings on two separate days. The dataset includes manual annotation of sleep stages and 2528 manually annotated spindles. Signals from 64-channels were continuously recorded at 1 kHz with a high-density active electrode system while participants napped for 30 or 60 min inside a sound-attenuated testing booth after performing a high- or low-load visual working memory task where load was randomized across recording days. The high-density EEG datasets present several advantages over single- or few-channel datasets including most notably the opportunity to explore spatial differences in the distribution of neural events, including whether spindles occur locally on only a few channels or co-occur globally across many channels, whether spindle frequency, duration, and amplitude vary as a function of brain hemisphere and anterior-posterior axis, and whether the probability of spindle occurrence varies as a function of the phase of ongoing slow oscillations. The dataset, along with python source code for file input and signal processing, is made freely available at the Open Science Framework through the link https://osf.io/chav7/.

Understanding events requires interplaying cognitive processes arising in neural networks whose organisation and connectivity remain subjects of controversy in humans. In the present study, by combining diffusion tensor imaging and functional interaction analysis, we aim to provide new insights on the organisation of the structural and functional pathways connecting the multiple nodes of the identified semantic system -shared by vision and language (Jouen et al., 2015). We investigated a group of 19 healthy human subjects during experimental tasks of reading sentences or seeing pictures. The structural connectivity was realised by deterministic tractography using an algorithm to extract white matter fibers terminating in the selected regions of interest (ROIs) and the functional connectivity by independent component analysis to measure correlated activities among these ROIs. The major connections link ventral neural stuctures including the parietal and temporal cortices through inferior and middle longitudinal fasciculi, the retrosplenial and parahippocampal cortices through the cingulate bundle, and the temporal and prefrontal structures through the uncinate fasciculus. The imageability score provided when the subject was reading a sentence was significantly correlated with the factor of anisotropy of the left parieto-temporal connections of the middle longitudinal fasciculus. A large part of this ventrally localised structural connectivity corresponds to functional interactions between the main parietal, temporal and frontal nodes. More precisely, the strong coactivation both in the anterior temporal pole and in the region of the temporo-parietal cortex suggests dual and cooperating roles for these areas within the semantic system. These findings are discussed in terms of two semantics-related sub-systems responsible for conceptual representation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Sustained and elevated activity during the working memory delay period has long been considered the primary neural correlate for maintaining information over short time intervals. This idea has recently been reinterpreted in light of findings generated from multiple neural recording modalities and levels of analysis. To further investigate the sustained or transient nature of activity, the temporal-spectral evolution (TSE) of delay period activity was examined in humans with high density EEG during performance of a Sternberg working memory paradigm with a relatively long six second delay and with novel scenes as stimuli. Multiple analyses were conducted using different trial window durations and different baseline periods for TSE computation. Sensor level analyses revealed transient rather than sustained activity during delay periods. Specifically, the consistent finding among the analyses was that high amplitude activity encompassing the theta range was found early in the first three seconds of the delay period. These increases in activity early in the delay period correlated positively with subsequent ability to distinguish new from old probe scenes. Source level signal estimation implicated a right parietal region of transient early delay activity that correlated positively with working memory ability. This pattern of results adds to recent evidence that transient rather than sustained delay period activity supports visual working memory performance. The findings are discussed in relation to synchronous and desynchronous intra- and inter-regional neural transmission, and choosing an optimal baseline for expressing temporal-spectral delay activity change.

Researchers classify critical neural events during sleep called spindles that are related to memory consolidation using the method of scalp electroencephalography (EEG). Manual classification is time consuming and is susceptible to low inter-rater agreement. This could be improved using an automated approach. This study presents an optimized filter based and thresholding (FBT) model to set up a baseline for comparison to evaluate machine learning models using naïve features, such as raw signals, peak frequency, and dominant power. The FBT model allows us to formally define sleep spindles using signal processing but may miss examples most human scorers would agree are spindles. Machine learning methods in theory should be able to approach performance of human raters but they require a large quantity of scored data, proper feature representation, intensive feature engineering, and model selection. We evaluate both the FBT model and machine learning models with naïve features. We show that the machine learning models derived from the FBT model improve classification performance. An automated approach designed for the current data was applied to the DREAMS dataset [1]. With one of the expert's annotation as a gold standard, our pipeline yields an excellent sensitivity that is close to a second expert's scores and with the advantage that it can classify spindles based on multiple channels if more channels are available. More importantly, our pipeline could be modified as a guide to aid manual annotation of sleep spindles based on multiple channels quickly (6-10 s for processing a 40-min EEG recording), making spindle detection faster and more objective., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Decades of research identify the hippocampal formation as central to memory storage and recall. Events are stored via distributed population codes, the parameters of which (e.g., sparsity and overlap) determine both storage capacity and fidelity. However, it remains unclear whether the parameters governing information storage are similar between species. Because episodic memories are rooted in the space in which they are experienced, the hippocampal response to navigation is often used as a proxy to study memory. Critically, recent studies in rodents that mimic the conditions typical of navigation studies in humans and nonhuman primates (i.e., virtual reality) show that reduced sensory input alters hippocampal representations of space. The goal of this study was to quantify this effect and determine whether there are commonalities in information storage across species. Using functional molecular imaging, we observe that navigation in virtual environments elicits activity in fewer CA1 neurons relative to real-world conditions. Conversely, comparable neuronal activity is observed in hippocampus region CA3 and the dentate gyrus under both conditions. Surprisingly, we also find evidence that the absolute number of neurons used to represent an experience is relatively stable between nonhuman primates and rodents. We propose that this convergence reflects an optimal ensemble size for episodic memories. SIGNIFICANCE STATEMENT One primary factor constraining memory capacity is the sparsity of the engram, the proportion of neurons that encode a single experience. Investigating sparsity in humans is hampered by the lack of single-cell resolution and differences in behavioral protocols. Sparsity can be quantified in freely moving rodents, but extrapolating these data to humans assumes that information storage is comparable across species and is robust to restraint-induced reduction in sensory input. Here, we test these assumptions and show that species differences in brain size build memory capacity without altering the structure of the data being stored. Furthermore, sparsity in most of the hippocampus is resilient to reduced sensory information. This information is vital to integrating animal data with human imaging navigation studies., (Copyright © 2017 the authors 0270-6474/17/372795-07$15.00/0.)

Purpose: Our previous retrospective analysis of clinically referred breast cancer survivors' performance on learning and memory measures found a primary weakness in initial encoding of information into working memory with intact retention and recall of this same information at a delay. This suggests that survivors may misinterpret cognitive lapses as being due to forgetting when, in actuality, they were not able to properly encode this information at the time of initial exposure. Our objective in this study was to replicate and extend this pattern of performance to a research sample to increase the generalizability of this finding in a sample in which subjects were not clinically referred for cognitive issues., Methods: We contrasted learning and memory performance between breast cancer survivors on endocrine therapy 2 to 6 years post-treatment with age- and education-matched healthy controls. We then stratified lower- and higher-performing breast cancer survivors to examine specific patterns of learning and memory performance. Contrasts were generated for four aggregate visual and verbal memory variables from the California Verbal Learning Test-2 (CVLT-2) and the Brown Location Test (BLT): Single-trial Learning: Trial 1 performance, Multiple-trial Learning: Trial 5 performance, Delayed Recall: Long-delay Recall performance, and Memory Errors: False-positive errors., Results: As predicted, breast cancer survivors' performance as a whole was significantly lower on Single-trial Learning than the healthy control group but exhibited no significant difference in Delayed Recall. In the secondary analysis contrasting lower- and higher-performing survivors on cognitive measures, the same pattern of lower Single-trial Learning performance was exhibited in both groups, with the additional finding of significantly weaker Multiple-trial Learning performance in the lower-performing breast cancer group and intact Delayed Recall performance in both groups., Conclusions: As with our earlier finding of weaker initial encoding with intact recall in a cohort of clinically referred breast cancer survivors, our results indicate this same profile in a research sample of breast cancer survivors. Further, when the breast cancer group was stratified by lower and higher performance, both groups exhibited significantly lower performance on initial encoding, with more pronounced encoding weakness in the lower-performing group. As in our previous research, survivors did not lose successfully encoded information over longer delays, either in the lower- or higher-performing group, again arguing against memory decay in survivors. The finding of weaker initial encoding of information together with intact delayed recall in survivors points to specific treatment interventions in rehabilitation of cognitive dysfunction., Implications for Cancer Survivors: The finding of weaker initial encoding of information together with intact delayed recall in survivors points to specific treatment interventions in rehabilitation of cognitive dysfunction and is discussed.

Background and Objectives: The anterior cingulate cortex (ACC) is hypothesized to be involved in decision making and emotion regulation. Previous observations of drug dependent individuals indicate that substance dependence may be associated with cingulum white matter abnormalities. The present study evaluated cingulum white matter in cigarette smokers., Methods: Diffusion tensor imaging (DTI) in adult tobacco smokers and healthy non-smoker controls (total N = 70) was performed in a 3T Siemens Trio MRI scanner., Results: Analyses of DTI tractography of the cingulum in tobacco-smoking individuals and controls indicated that tobacco abusers have significantly reduced fractional anisotropy (FA) in the right cingulum. In addition, FA in the left cingulum white matter was negatively associated with the number of cigarettes smoked per day and the Fagerstrom test for nicotine dependence, a self-report measure of tobacco dependence severity., Conclusions: The white matter of the cingulum is altered in a non-symmetrical way in tobacco smokers. An inverse relationship between FA and reported number of cigarettes per day was observed. Previous studies have also noted altered neural connectivity in cigarette smokers using similar methods. Similar white matter differences in the cingulum have been observed in methamphetamine dependent individuals and patients with dementia, which suggests that the cingulum may be altered by mechanisms not specific to tobacco exposure., Scientific Significance: By better understanding the effects of tobacco abuse on the brain, we hope to gain insight into how drug dependence influences the neurological foundations of behavior., (© 2016 American Academy of Addiction Psychiatry.)

There is accumulating evidence that sleep as well as awake offline processing is important for the transformation of new experiences into long-term memory (LTM). Yet much remains to be understood about how various cognitive factors influence the efficiency of awake offline processing. In the present study we investigated how changes in attention and context in the immediate period after exposure to new visual information influences LTM consolidation. After presentation of multiple naturalistic scenes within a working memory paradigm, recognition was assessed 30 min and 24 h later in three groups of subjects. One group of subjects engaged in a focused attention task [the Revised Attentional Network Task (R-ANT)] in the 30 min after exposure to the scenes. Another group of subjects remained in the testing room during the 30 min after scene exposure and engaged in no goal- or task-directed activities. A third group of subjects left the testing room and returned 30 min later. A signal detection analysis revealed no significant differences among the three groups in hits, false alarms, or sensitivity on the 30-min recognition task. At the 24-h recognition test, the group that performed the R-ANT made significantly fewer hits compared to the group that left the testing room and did not perform the attention ask. The group that performed the R-ANT and the group that remained in the testing room during the 30-min post-exposure interval made significantly fewer false alarms on the 24-h recognition test compared to the group that left the testing room. The group that stayed in the testing room and engaged in no goal- or task-directed activities exhibited significantly higher sensitivity (d') compared to the group that left the testing room and the group that performed the R-ANT task. Staying in the same context after exposure to new information and resting quietly with minimal engagement of attention results in the best ability to distinguish old from novel visual stimuli after 24 h. These findings suggest that changes in attentional demands and context during an immediate post-exposure offline processing interval modulate visual memory consolidation in a subtle but significant manner.

This research tests the hypothesis that comprehension of human events will engage an extended semantic representation system, independent of the input modality (sentence vs. picture). To investigate this, we examined brain activation and connectivity in 19 subjects who read sentences and viewed pictures depicting everyday events, in a combined fMRI and DTI study. Conjunction of activity in understanding sentences and pictures revealed a common fronto-temporo-parietal network that included the middle and inferior frontal gyri, the parahippocampal-retrosplenial complex, the anterior and middle temporal gyri, the inferior parietal lobe in particular the temporo-parietal cortex. DTI tractography seeded from this temporo-parietal cortex hub revealed a multi-component network reaching into the temporal pole, the ventral frontal pole and premotor cortex. A significant correlation was found between the relative pathway density issued from the temporo-parietal cortex and the imageability of sentences for individual subjects, suggesting a potential functional link between comprehension and the temporo-parietal connectivity strength. These data help to define a "meaning" network that includes components of recently characterized systems for semantic memory, embodied simulation, and visuo-spatial scene representation. The network substantially overlaps with the "default mode" network implicated as part of a core network of semantic representation, along with brain systems related to the formation of mental models, and reasoning. These data are consistent with a model of real-world situational understanding that is highly embodied. Crucially, the neural basis of this embodied understanding is not limited to sensorimotor systems, but extends to the highest levels of cognition, including autobiographical memory, scene analysis, mental model formation, reasoning and theory of mind., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The capacity for semantic memory-the ability to acquire and store knowledge of the world-is highly developed in the human brain. In particular, semantic memory assimilated through an auditory route may be a uniquely human capacity. One method of obtaining neurobiological insight into memory mechanisms is through the study of experts. In this work, we study a group of Hindu Vedic priests, whose religious training requires the memorization of vast tracts of scriptural texts through an oral tradition, recalled spontaneously during a lifetime of subsequent spiritual practice. We demonstrate focal increases of cortical thickness in regions of the left prefrontal lobe and right temporal lobe in Vedic priests, in comparison to a group of matched controls. The findings are relevant to current hypotheses regarding cognitive processes underlying storage and recall of long-term declarative memory.

Diffusion tensor imaging (DTI) is a form of MRI that has been used extensively to map in vivo the white matter architecture of the human brain. It is also used for mapping subcortical nuclei because of its general sensitivity to tissue orientation differences and effects of iron accumulation on the diffusion signal. While DTI provides excellent spatial resolution in individual subjects, a challenge is visualizing consistent patterns of diffusion orientation across subjects. Here we present a simple method for averaging direction-encoded color anisotropy maps in standard space, explore this technique for visualizing the substantia nigra (SN) in relation to other midbrain structures, and show with signal-to-noise analysis that averaging improves the direction-encoded color signature. SN is distinguished on averaged maps from neighboring structures, including red nucleus (RN) and cerebral crus, and is proximal to SN location from existing brain atlases and volume of interest (VOI) delineation on individual scans using two blinded raters., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Neuroimaging has uncovered both long-range and short-range connectivity abnormalities in the brains of individuals with autism spectrum disorders (ASD). However, the precise connectivity abnormalities and the relationship between these abnormalities and cognition and ASD symptoms have been inconsistent across studies. Indeed, studies find both increases and decreases in connectivity, suggesting that connectivity changes in the ASD brain are not merely due to abnormalities in specific connections, but rather, due to changes in the structure of the network in which the brain areas interact (i.e., network topology). In this study, we examined the differences in the network topology between high-functioning ASD patients and age and gender matched typically developing (TD) controls. After quantitatively characterizing the whole-brain connectivity network using diffusion tensor imaging (DTI) data, we searched for brain regions with different connectivity between ASD and TD. A measure of oral language ability was then correlated with the connectivity changes to determine the functional significance of such changes. Whole-brain connectivity measures demonstrated greater local connectivity and shorter path length in ASD as compared to TD. Stronger local connectivity was found in ASD, especially in regions such as the left superior parietal lobule, the precuneus and angular gyrus, and the right supramarginal gyrus. The relationship between oral language ability and local connectivity within these regions was significantly different between ASD and TD. Stronger local connectivity was associated with better performance in ASD and poorer performance in TD. This study supports the notion that increased local connectivity is compensatory for supporting cognitive function in ASD., (Copyright © 2012 Wiley Periodicals, Inc.)

Study Objectives: Rapid eye movement sleep behavior disorder (RBD) is a condition closely associated with Parkinson disease (PD). RBD is a sleep disturbance that frequently manifests early in the development of PD, likely reflecting disruption in normal functioning of anatomical areas affected by neurodegenerative processes. Although specific neuropathological aspects shared by RBD and PD have yet to be fully documented, further characterization is critical to discovering reliable biomarkers that predict PD onset. In the current study, we tested the hypothesis of altered functional connections of the substantia nigra (SN) in patients in whom RBD was diagnosed., Design: Between-groups, single time point imaging., Setting: UTHSC-H 3 telsa MRI center., Participants: Ten patients with RBD, 11 patients with PD, and 10 age-matched controls., Interventions: NA., Measurements and Results: We measured correlations of SN time series using resting state blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) in patients with idiopathic RBD who were at risk for developing PD, patients in whom PD was diagnosed, and age-matched controls. Using voxelwise analysis of variance, different correlations (P < 0.01, whole-brain corrected) between left SN and left putamen were found in patients with RBD compared with controls and patients with PD. SN correlations with right cuneus/precuneus and superior occipital gyrus were significantly different for patients with RBD compared with both controls and patients with PD., Conclusions: The results suggest that altered nigrostriatal and nigrocortical connectivity characterizes rapid eye movement sleep behavior disorder before onset of obvious motor impairment. The functional changes are discussed in the context of degeneration in dopaminergic and cognition-related networks.

Recovery from aneurysmal subarachnoid hemorrhage (SAH) is often incomplete and accompanied by subtle but persistent cognitive deficits. Previous neuropsychological reports indicate these deficits include most prominently memory impairment, with working memory particularly affected. The neural basis of these memory deficits remains unknown and unexplored by functional magnetic resonance imaging (fMRI). In the present study, patients who experienced (SAH) underwent fMRI during the performance of a verbal working memory paradigm. Behavioral results indicated a subtle but statistically significant impairment relative to healthy subjects in working memory performance accuracy, which was accompanied by relatively increased blood-oxygen level dependent signal in widespread left and right hemisphere cortical areas during periods of encoding, maintenance, and retrieval. Activity increases remained after factoring out inter-individual differences in age and task performance, and included most notably left hemisphere regions associated with phonological loop processing, bilateral sensorimotor regions, and right hemisphere dorsolateral prefrontal cortex. We conclude that deficits in verbal working memory following recovery from (SAH) are accompanied by widespread differences in hemodynamic correlates of neural activity. These differences are discussed with respect to the immediate and delayed focal and global brain damage that can occur following (SAH), and the possibility that this damage induces subcortical disconnection and subsequent decreased efficiency in neural processing.

Content-specific sub-systems of visual working memory (VWM) have been explored in many neuroimaging studies with inconsistent findings and procedures across experiments. The present study employed functional magnetic resonance imaging (fMRI) and a change detection task using a high number of trials and matched stimulus displays across object and location change (what vs. where) conditions. Furthermore, individual task periods were studied independently across conditions to identify differences corresponding to each task period. Importantly, this combination of task controls has not previously been described in the fMRI literature. Composite results revealed differential frontoparietal activation during each task period. A separation of object and location conditions yielded a distributed system of dorsal and ventral streams during the encoding of information corresponding to bilateral inferior parietal lobule (IPL) and lingual gyrus activation, respectively. Differential activity was also shown during the maintenance of information in middle frontal structures bilaterally for objects and the right IPL and left insula for locations. Together, these results reflect a domain-specific dissociation spanning several cortices and task periods. Furthermore, differential activations suggest a general caudal-rostral separation corresponding to object and location memory, respectively.

Hearing and feeling both rely upon the transduction of physical events into frequency-based neural codes, suggesting that the auditory system may be intimately related to the somatosensory system. Here, we provide evidence that the neural substrates for audition and somatosensation are anatomically linked. Using diffusion tensor imaging with both deterministic and probabilistic tractography to measure white matter connectivity, we show that there are extensive ipsilateral connections between the primary auditory cortex and the primary and secondary somatosensory regions in the human cerebral cortex. We further show that these cross-modal connections are exaggerated between the auditory and secondary somatosensory cortex in the lesioned hemisphere of a patient (SR) with acquired auditory-tactile synesthesia, in whom sounds alone produce bodily sensations. These results provide an anatomical basis for multisensory interactions between audition and somatosensation and suggest that cross-talk between these regions may explain why some sounds, such as nails screeching down a chalkboard or an audible mosquito, can induce feelings of touch, especially on the contralesional body surface of patient SR.

Altered brain connectivity accompanies autism spectrum disorders (ASD), but the relationship between connectivity and intellectual abilities, which often differs within ASD, and between ASD and typically developing (TD) children, is not understood. Here, diffusion tensor imaging (DTI) was used to explore the relationship between white matter integrity and non-verbal intelligence quotients (IQ) in children with ASD and in age- and gender-matched TD children. Tract-based spatial statistical analyses (TBSS) of DTI fractional anisotropy (FA) revealed altered relationships between white matter and IQ. Different relationships were found using within-group analyses, where regions of significant (p < .05, corrected) correlations in ASD overlapped minimally with regions of FA-IQ correlations in TD subjects. An additional between-groups analysis revealed significant correlation differences in widespread cortical and subcortical areas. These preliminary findings suggest altered brain connectivity may underlie some differences in intellectual abilities of ASD, and should be investigated further in larger samples as a function of development.

Understanding a word requires mapping sounds to a word-form and then identifying its correct meaning, which in some cases necessitates the recruitment of cognitive control processes to direct the activation of semantic knowledge in a task appropriate manner (i.e., semantic control). Neuroimaging and neuropsychological studies identify a fronto-temporal network important for word comprehension. However, little is known about the connectional architecture subserving controlled retrieval and selection of semantic knowledge during word comprehension. We used diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI) in aphasic individuals with varying degrees of word comprehension deficits to examine the role of three white matter pathways within this network: the uncinate fasciculus (UF), inferior longitudinal fasciculus (ILF), and inferior fronto-occipital fasciculus (IFOF). Neuroimaging data from a group of age-matched controls were also collected in order to establish that the patient group had decreased structural and functional connectivity profiles. We obtained behavioral data from aphasic participants on two measures of single word comprehension that involve semantic control, and assessed pathway functional significance by correlating patients' performance with indices of pathway structural integrity and the functional connectivity profiles of regions they connect. Both the structural integrity of the UF and the functional connectivity strength of regions it connects predicted patients' performance. This result suggests the semantic control impairment in word comprehension resulted from poor neural communication between regions the UF connects. Inspections of other subcortical and cortical structures revealed no relationship with patients' performance. We conclude that the UF mediates semantic control during word comprehension by connecting regions specialized for cognitive control with those storing word meanings. These findings also support a relationship between structural and functional connectivity measures, as the rs-fMRI results provide converging evidence with those obtained using DTI., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We explored the diagnostic value of oxygen-enhanced MRI, a novel technique for measuring regional brain metabolism, in a set of normal adult volunteers and temporal lobe epilepsy patients. Eight right-handed adult normal volunteers and ten right-handed patients with temporal lobe epilepsy were studied. Six patients had lesions concordant with their epilepsy on high-resolution (3T) structural MRI. Four patients were nonlesional. Hyperoxia (oxygen enhancement, OE) was carried out by administering 100% O(2) in epochs by mask or cannula interleaved with breathing of normal atmospheric air. The T2* (blood oxygen level dependent, BOLD) signal was recorded in continuously acquired echo-planar images. Data from nine temporal lobe subregions were subjected to spectral analysis and statistical testing. OE resulted in unambiguous concordant positive T2* signal change in all subjects. Analysis of the distribution of spectral power within the temporal lobe revealed a significant (p<0.025, one-sided) group difference between normals and epilepsy patients, with seven patients exhibiting large deviations from normalcy that lateralized their disease. Two such patients had nonlesional MRIs. Oxygen-enhanced MRI is a promising metabolic imaging modality for the diagnosis and lateralization of oxidative metabolic derangement associated with lesional and nonlesional temporal lobe epilepsy., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Electrocorticography (ECoG) allows for measurement of task-related local field potentials directly from cortex in neurosurgical patients. Diffusion tensor imaging (DTI) tractography is an MRI technique that allows for reconstruction of brain white matter tracts, which can be used to infer structural connectivity. This paper reports a novel merger of these two modalities. A processing stream is described in which fiber tracts near intracranial macroelectrodes showing task-related functional responses are isolated to explore structural networks related to working memory maintenance. Results show that ECoG-constrained tractography is useful for revealing structural connectivity patterns related to spatially- and temporally-specific functional responses., (2010 Elsevier Ltd. All rights reserved.)

Here we present a novel multimodal analysis of network connectivity in the language system. We assessed connectivity of Broca's area using tractography with diffusion tensor imaging (DTI), and with cortico-cortical evoked potentials (CCEPs) to measure the spread of artificial currents applied directly to human cortex. We found that both the amplitude and latency of CCEP currents significantly correlates (r(2)=0.41, p<10(-16)) with the number of DTI pathways connecting the stimulation and recording loci. This strategy of relating electrical information flow with the neural architecture will likely yield new insights into cognitive processes., (2011 Elsevier Ltd. All rights reserved.)

This article has been withdrawn at the request of the authors. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy. This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy., (Copyright © 2011. Published by Elsevier Inc. All rights reserved.)

Background: The application of advanced 3T MRI imaging techniques to study recovery after subarachnoid hemorrhage (SAH) is complicated by the presence of image artifacts produced by implanted aneurysm clips. To characterize the effect of these artifacts on image quality, we sought to: 1) quantify extent of image artifact in SAH patients with implanted aneurysm clips across a range of MR sequences typically used in studies of volumetry, blood oxygen level dependent signal change (BOLD-fMRI), and diffusion-weighted imaging (DW-MRI) and 2) to explore the ability to reconstruct white matter pathways in these patients., Methods: T1- and T2-weighted structural, BOLD-fMRI, and DW-MRI scans were acquired at 3T in two patients with titanium alloy clips in ACOM and left ACA respectively. Intensity-based planimetric contouring was performed on aligned image volumes to define each artifact. Artifact volumes were quantified by artifact/clip length and artifact/brain volume ratios and analyzed by two-way (scan-by-rater) ANOVAs. Tractography pathways were reconstructed from DW-MRI at varying distances from the artifacts using deterministic methods., Results: Artifact volume varied by MR sequence for length (p = 0.007) and volume (p < 0.001) ratios: it was smallest for structural images, larger for DW-MRI acquisitions, and largest on fMRI images. Inter-rater reliability was high (r = 0.9626, p < 0.0001), and reconstruction of white matter connectivity characteristics increased with distance from the artifact border. In both patients, reconstructed white matter pathways of the uncinate fasciculus and inferior fronto-occipital fasciculus were clearly visible within 2 mm of the artifact border., Conclusions: Advanced 3T MR can successfully image brain tissue around implanted titanium aneurysm clips at different spatial ranges depending on sequence type. White matter pathways near clip artifacts can be reconstructed and visualized. These findings provide a reference for designing functional and structural neuroimaging studies of recovery in aSAH patients after clip placement.

The relationship between blood oxygenation level-dependent (BOLD) functional MRI (fMRI) signal and the underlying neural electrical activity in humans is a topic of intense interest to systems neuroscience. This relationship has generally been assumed to be invariant regardless of the brain region and the cognitive task being studied. We critically evaluated these assumptions by comparing the BOLD-fMRI response with local field potential (LFP) measurements during visually cued common noun and verb generation in 11 humans in whom 1210 subdural electrodes were implanted. As expected, power in the mid-gamma band (60-120 Hz) correlated positively (r(2) = 0.16, p < 10(-16)) and power in the beta band (13-30 Hz) correlated negatively (r(2) = 0.09, p < 10(-16)) with the BOLD signal change. Beta and mid-gamma band activity independently explain different components of the observed BOLD signal. Importantly, we found that the location (i.e., lobe) of the recording site modulates the relationship between the electrocorticographic (ECoG) signal and the observed fMRI response (p < 10(-16), F(21,1830) = 52.7), while the type of language task does not. Across all brain regions, ECoG activity in the gamma and beta bands explains 22% of the fMRI response, but if the lobar location is considered, 28% of the variance can be explained. Further evaluation of this relationship at the level of individual gyri provides additional evidence of differences in the BOLD-LFP relationship by cortical locus. This spatial variability in the relationship between the fMRI signal and neural activity carries implications for modeling of the hemodynamic response function, an essential step for interregional fMRI comparisons.

Electrocorticography (ECoG) and functional MRI (BOLD-fMRI) have been used previously to measure brain activity during working memory delay periods. These studies have separately reported oscillation changes in the theta (4-8 Hz) band and BOLD-fMRI increases during delay periods when information is maintained in memory. However, it is not known how intracranial cortical field potential (CFP) changes relate to BOLD-fMRI responses during delay periods. To answer this question, fMRI was obtained from six epilepsy patients during a visual working memory task. Then, following subdural macroelectrode implant, continuous ECoG was used to record CFPs during the same task. Time-frequency analyses showed delay period gamma band oscillation amplitude increases on electrodes located near fMRI activity, while in the theta band changes were higher for electrodes located away from fMRI activation. The amplitude of the ECoG gamma band response was significantly positively correlated with the fMRI response, while a negative correlation was found for the theta band. The findings are consistent with previous reports of local field potential (LFP) coupling in the gamma band with BOLD-fMRI responses during visual stimulation in monkeys, but are novel in that the relationship reported here persists after the disappearance of visual stimuli while information is being maintained in memory. We conclude that there is a relationship between BOLD-fMRI increases and human working memory delay period gamma oscillation increases and theta decreases. The spectral profile change provides a basis for comparison of working memory delay period BOLD-fMRI with field potential recordings in animals and other human intracranial EEG studies., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Mesial temporal lobe epilepsy (MTLE) is hypothesized to involve derangement of long-range limbic connectivity, but in vivo evidence is lacking. We used diffusion tractography to investigate the relationship between hippocampal atrophy and connectivity in MTLE patients with hippocampal sclerosis (HS). Atrophy was correlated with relatively decreased connectivity density but increased connectivity strength, suggesting that HS is accompanied by relatively sparse but strong connections as measured by diffusion anisotropy., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: The purpose of this study was to quantify volumes of specific subcortical gray matter nuclei implicated in Parkinson's disease (PD) as a preliminary step for identifying a non-invasive clinical biomarker for PD. We hypothesized that REM sleep behavior disorder (RBD) patients, at risk for developing PD, will demonstrate a pattern of neuronal degeneration reflected in reduced striatal volumes on T1-weighted MRI., Methods: We compared measures of RBD patients confirmed by polysomnography (PSG) with groups of age/gender-matched Control subjects and early PD (EPD) patients (Hoehn & Yahr < 2). Clinical measurements included the Unified Parkinson's disease Rating Scales (UPDRS), timed gait and finger tapping tasks, the Parkinson's Disease Questionnaire (PDQ-39), and a time-synchronized video recorded single-night PSG. Volumetric measurements were derived from high-resolution T1-weighted 3 T MRI images., Results: The matched Control and EPD groups were statistically similar to the RBD group in age, gender, handedness, and total brain volumes. The RBD group had smaller bilateral putamen volumes (both raw and normalized by brain tissue volume), in addition to some clinical impairment on the UPDRS and PDQ-39., Conclusions: Reduced putamen volumes may be a structural marker for RBD and reflect a pattern of neurodegeneration that predicts the development of PD., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Excessive and abnormal accumulation of alpha-synuclein (α-synuclein) is a factor contributing to pathogenic cell death in Parkinson's disease. The purpose of this study, based on earlier observations of Parkinson's disease cerebrospinal fluid (PD-CSF) initiated cell death, was to determine the effects of CSF from PD patients on the functionally different microglia and astrocyte glial cell lines. Microglia cells from human glioblastoma and astrocytes from fetal brain tissue were cultured, grown to confluence, treated with fixed concentrations of PD-CSF, non-PD disease control CSF, or control no-CSF medium, then photographed and fluorescently probed for α-synuclein content by deconvolution fluorescence microscopy. Outcome measures included manually counted cell growth patterns from day 1-8; α-synuclein density and distribution by antibody tagged 3D model stacked deconvoluted fluorescent imaging., Results: After PD-CSF treatment, microglia growth was reduced extensively, and a non-confluent pattern with morphological changes developed, that was not evident in disease control CSF and no-CSF treated cultures. Astrocyte growth rates were similarly reduced by exposure to PD-CSF, but morphological changes were not consistently noted. PD-CSF treated microglia showed a significant increase in α-synuclein content by day 4 compared to other treatments (p ≤ 0.02). In microglia only, α-synuclein aggregated and redistributed to peri-nuclear locations., Conclusions: Cultured microglia and astrocytes are differentially affected by PD-CSF exposure compared to non-PD-CSF controls. PD-CSF dramatically impacts microglia cell growth, morphology, and α-synuclein deposition compared to astrocytes, supporting the hypothesis of cell specific susceptibility to PD-CSF toxicity.

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral left- and right-hemisphere language dominant subjects may be predicted by hemispheric asymmetry in the relative density of three white matter pathways terminating in the temporal lobe implicated in different aspects of language function: the arcuate (AF), uncinate (UF), and inferior longitudinal fasciculi (ILF). Laterality indices computed from asymmetry of high anisotropy AF pathways, but not the other pathways, classified the majority (19 of 23) of patients using the Wada results as the standard. A logistic regression model incorporating information from DTI of the AF, fMRI activity in Broca's area, and handedness was able to classify 22 of 23 (95.6%) patients correctly according to their Wada score. We conclude that evaluation of highly anisotropic components of the AF alone has significant predictive power for determining language laterality, and that this markedly asymmetric distribution in the dominant hemisphere may reflect enhanced connectivity between frontal and temporal sites to support fluent language processes. Given the small sample reported in this preliminary study, future research should assess this method on a larger group of patients, including subjects with bi-hemispheric dominance., (Copyright (c) 2009 Elsevier Inc. All rights reserved.)

Inappropriate response tendencies may be stopped via a specific fronto/basal ganglia/primary motor cortical network. We sought to characterize the functional role of two regions in this putative stopping network, the right inferior frontal gyrus (IFG) and the primary motor cortex (M1), using electocorticography from subdural electrodes in four patients while they performed a stop-signal task. On each trial, a motor response was initiated, and on a minority of trials a stop signal instructed the patient to try to stop the response. For each patient, there was a greater right IFG response in the beta frequency band ( approximately 16 Hz) for successful versus unsuccessful stop trials. This finding adds to evidence for a functional network for stopping because changes in beta frequency activity have also been observed in the basal ganglia in association with behavioral stopping. In addition, the right IFG response occurred 100-250 ms after the stop signal, a time range consistent with a putative inhibitory control process rather than with stop-signal processing or feedback regarding success. A downstream target of inhibitory control is M1. In each patient, there was alpha/beta band desynchronization in M1 for stop trials. However, the degree of desynchronization in M1 was less for successfully than unsuccessfully stopped trials. This reduced desynchronization on successful stop trials could relate to increased GABA inhibition in M1. Together with other findings, the results suggest that behavioral stopping is implemented via synchronized activity in the beta frequency band in a right IFG/basal ganglia network, with downstream effects on M1.

Object: Maps produced using either electrical stimulation or functional imaging have demonstrated a distributed network of cortical regions involved in expressive and receptive language tasks. The pattern of connectivity among components of this network has begun to be explored with diffusion tensor (DT) imaging, but has yet to be completely characterized. In this study the authors used DT imaging-based tractography to examine the interrelationship between cortical areas found to be essential for language by intraoperative electrical stimulation., Methods: The authors localized the arcuate fasciculus (AF), a white matter fiber system connecting frontal and parietotemporal areas in 10 patients, 9 of whom subsequently underwent left hemispheric language mapping., Results: The authors found that 81 (79%) of 102 essential language sites (ELSs) were closely related to the AF. Of all ELSs, 59% were located within 7.5 mm of AF fiber pathway terminations, and another 20% contained pathways terminating closer to the AF than would be expected by chance (p < 0.05). Additionally, direct subcortical stimulation of the AF following focal cerebral resections produced transient language deficits. The close spatial relationship found between ELSs and the AF suggests that tractography data alone may be used for localization of ELSs., Conclusions: The deficits evoked by subcortical stimulation validate and demonstrate the utility of this AF localization technique, and provide further evidence that the AF is an important pathway for fluent language. Taken together, these results demonstrate that DT imaging of the AF may be used to predict the location of brain areas that will be eloquent by the standards of stimulation mapping.

Consolidation theory assumes that as time passes, some memories are strengthened and become resistant to change while other memories are weakened and forgotten. Recent demonstrations that implicit, or procedural, memories are retrieved more efficiently after learning and retention are consistent with the idea that these particular memory traces have strengthened with time, and therefore may be accessed faster. However, it is not clear whether the process of explicit memory retrieval also becomes more efficient with time. In two experiments, we explored 1) how much time is required for retrieval of separate explicit and implicit components of hippocampal-dependent visuomotor associative memories after variable retention intervals, and 2) how the explicit and implicit processing times change when the associations are rehearsed after initial retrieval. We found that after learning and retention, explicit and implicit processing times diverged: 1) the time taken to retrieve successfully the explicit component increased relative to a pre-retention baseline but, after spaced rehearsal, decreased, although not to a level significantly below that obtained at the end of learning, and 2) the implicit, or procedural, component processing times continued to gradually decrease after retention, and with continued rehearsal, reached a level significantly below the pre-retention baseline. We conclude that the observed divergence in post-retention reaction times suggests that explicit and implicit memory systems may reorganize differently after learning, and that as a consequence, different amounts of processing time may be required for retrieval of these different memory components.