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Green spaces are integral to urban landscape, serving ecological, health, and recreational functions. During the pandemic, urban green spaces were crucial for enabling safe social distancing and enhancing well-being. This study delves into the perception, accessibilities, and qualities of urban green spaces in Wrocław during and after the pandemic. A survey was conducted to understand causes and effects of diverse usage of the urban green space, assessing changes in usage frequency before, during, and after lockdown, as well as public awareness of benefits associated with green spaces. Proximity to green spaces emerges as a key factor as people prefer easily and quick access to these areas. The study also noted a partial modification of social behaviour and increased social and ecological awareness. The results reveal evident development of new daily habits. Although the beginning of the pandemic led to discomfort, adaptive behaviours soon followed, changing daily routines and previous leisure activities. Given the findings on availability and adequacy of green spaces, it is advisable to rearrange these areas to meet the diverse needs of inhabitants.

Perumahan hadir dengan kemudahan-kemudahan yang ditawarkan, adanya sistem kredit, penawaran bunga rendah, booking fee dengan harga murah dan lain sebagainya untuk menarik minat konsumen. Kantor Perumahan Asri Residence yang bertempat di Jakabaring, berupaya dalam menarik minat beli customer agar penjualan unit rumah maupun properti tersebut sesuai dengan sasaran perusahaan. iklan yang di rancang oleh perusahaan belum tepat sasaran dapat dilihat dengan seringnya menyebarkan seperti brosur kepada orang yang tidak membutuhkan rumah. Untuk zaman sekarang yang serba digital seharusnya dimaksimalkan dalam pemasaran melalui media sosial dengan postingan yang menarik dan rutin. Jika iklan yang akan berhasil dalam mempengaruhi perilaku konsumen, mereka harus terlebih dahulu memimpin konsumen melalui serangkaian tahap penerimaan. Selain periklanan untuk meningkatkan penjualan ada juga promosi penjualan (sales promotion). Alat promosi penjualan yang digunakan oleh Perumahan Asri Residence diantaranya voucher, hadiah dan diskon.

Objectives: The purpose of this study was to compare data obtained from the reticulocyte channel (RET channel) heated to 41 °C with those obtained from impedance channel (I-Channel) at room temperature in the samples with the mean corpuscular hemoglobin concentration (MCHC) 370 g/L, in the presence of cold agglutinins. Methods: In this study, 60 blood samples (group 1) with the MCHC 370 g/L (with cold agglutinins) were used to compare the two analytical channels of the XN-9000 analyzer in different preanalytical conditions. The parameters evaluated in both groups were the following: red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT), mean cell volume (MCV), RBC-most frequent volume (R-MFV), mean hemoglobin concentration (MCH) and mean cellular hemoglobin concentration (MCHC). Results: The results of this study showed an excellent correlation with both channels of the XN-9000 analyzer in samples with and without cold agglutinins, except for the MCHC. The bias between the values obtained in the I-channel and those obtained in the RET channel of both groups was insignificant and remained within the limits of acceptability, as reported by Ricos et al. for all considered parameters, except for MCHC. Conclusions: The presence of cold agglutinins in blood samples can be detected by a spurious lowering of the RBC count and by a spurious increase in the MCHC. The RET channel represents a great opportunity to correct the RBC count in a rapid manner without preheating. However, neither methodology can completely solve the residual presence of cold agglutinins in all samples, despite the MCHC values being < 370 g/L.

Background: High systolic blood pressure in young individuals with normal central pressure has been described as “Spureous Systolic Hypertension” and there is a strong controversy if it is a normal or pathologic condition. Objective: To compare young adult patients (20–40 y.o.) with isolated systolic hypertension (ISH) with elderly patients (60 to 80 y.o.) with the same condition and analyze the vascular and hemodynamic patterns to find out if the spureous hypertension is truly a hypertensive phenotype and deserves to be treated. Material and Methods: To analyze the vascular pattern we evaluated the database of NIVE (Phillips IU22® and CAP with Arteriograph®) with 2890 first ever evaluated patients, and analyzed 55 young controls (A), 56 young with ISH (B), 19 elderly controls (C) and 51 elderly with ISH (D). For the Hemodynamic analysis (Impedance Cardiography, Exxer®) the same groups with (A) 115, (B) 59, (C) 50 and (D) 148. Results: Most of the vascular and hemodynamic findings as expected by age but Group B was similar in terms of the central stiffness (PWV, Ao PP and total Compliance) to the group C meaning EVA. The proportion of p with increased IMT, abnormal PWV and endothelial dysfunction were higher in the B group compared with A and the elderly (Comparison between same age intervals by “t” test and ANOVA for the whole sample. Signification

Background: US is a simple, reproducible and economic technique for vascular evaluation. New technologies using radiofrequency and multidimensional Doppler plus computer development allow to evaluate parameters like shear stress, Flow profile and vascular remodeling no invasively. Objective: To compare the “regional” carotid evaluation with the accepted parameters of vascular disease like remodeling, arterial stiffness and endothelial function in hypertensive patients. Methods: We evaluated 43 consecutive patients (18 healthy referent, 12 controlled HTN y 6 non controlled HTN) derived for NIVE (IMT, Plaques, PWV c-f and Endothelial Function) (“systemic parameters”) and using a new US machine Resona 7® with radiofrequency and multidimensional Doppler (VFlow) we obtained “regional parameters” of the common carotid artery like remodeling, arterial stiffness, wall shear stress and hemodynamic data like instantaneous speed and flow and speed gradient. The protocol was approved by LEC. Results: All the systemic parameters (IMT, %Plaques, PWV c-f and Endothelial Function) were significantly abnormal (p < 0.05) independently of BP control. The regional parameters and the regional hemodynamics showed an abnormal tendency without statistical significance. Correlation, regression and concordance tests showed that these parameters are concordant but not interchangeable. Conclusion: The systemic and regional parameters where altered in hypertensive patients indicating the presence of associated vascular disease, independently of BP control. However, they were not interchangeable. These findings are limited due to the sample size and heterogeneity to yield a clinical application. Maybe, this pattern of regional vascular abnormalities, clearly different in hypertensives, could open a new field of investigation of vascular disease in hypertension.

Introduction: Globally, medical schools are trying to widen access and to increase the diversity of their student body to be more representative of the population and to meet the future heath care needs of society. Selection methods must not disadvantage the applicants from priority groups. In Memorial University’s Faculty of Medicine, rural applicants and applicants from low socioeconomic status are priority groups. Methods: Since 2013, Memorial University has used a combination of traditional panel interviews and MMIs to interview candidates for medical school. We wondered whether applicants who participate in this medical school interview process perform differently on the MMIs compared to the traditional panel interview process and whether performance differs on either of the two interview processes based on age, sex, origin(urban or rural), or socioeconomic status. Results: The mean score on the traditional panel interview was higher than that on the MMI. Females scored higher than males on both the traditional panel interview and the MMI. Applicants aged 22 and younger performed worse on both the traditional panel interview and the MMI than the other age groups. Neighborhood socioeconomic status, and urban/rural living status were not significantly related with applicants’ performance on the traditional panel interview or MMI. Discussion: The type of interview is not disadvantaging applicants from Memorial University’s priority areas.

Environment There seems to be a common abnormality of the healing process in several diseases as COPD, liver esteatosis, and arterial stiffening. Objective: To asses the association of frequency between liver esteatosis and aortic stiffness by means of c-f PWV in patients included in a CV prevention programme. Methods: 43 patients underwent a simultaneous evaluation including antropometry, biochemistry, cardiac, vascular and abdominal ultrasonography. Results: Mean age was 53,4 ± 11 y.o, 67% male, SBP 137 ± 17, DBP 87 ± 10 PP 50,3 ± 11 mmHg, BMi 29 ± 4. CVRF: HTN 74%, DLP 69%, DBT 7%, TBQ 28%, OBS 42%, OVWT 28%, SED 71%.CV Drugs: 63%. Nine (21%) presented abnormal PWV and esteatosis and 17 (39,5%) none of them. Whereas 4 (9,5%) presented abnormal PWV with normal liver and 13 (30%) the opposite. (Fisher NS, Cochran’s

Autoimmune diseases are caused by an immune response against some autoantigens. This response, characterized by the presence of autoantibodies, causes an inflammatory disease, which can cause a damage of specific organ (organ-specific autoimmune diseases) or systemic (systemic autoimmune diseases). The presence of these autoantibodies in the serum can therefore be a useful parameter for the diagnosis and/or monitoring of autoimmune diseases In this paper we describe a flow chart about laboratory tests in the diagnosis of systemic autoimmune diseases so as to maintain appropriateness of the request and contain costs.

Closed-loop direct brain stimulation is a promising tool for modulating neural activity and behavior. However, it remains unclear how to optimally target stimulation to modulate brain activity in particular brain networks that underlie particular cognitive functions. Here, we test the hypothesis that stimulation's behavioral and physiological effects depend on the stimulation target's anatomical and functional network properties. We delivered closed-loop stimulation as 47 neurosurgical patients studied and recalled word lists. Multivariate classifiers, trained to predict momentary lapses in memory function, triggered the stimulation of the lateral temporal cortex (LTC) during the study phase of the task. We found that LTC stimulation specifically improved memory when delivered to targets near white matter pathways. Memory improvement was largest for targets near white matter that also showed high functional connectivity to the brain's memory network. These targets also reduced low-frequency activity in this network, an established marker of successful memory encoding. These data reveal how anatomical and functional networks mediate stimulation's behavioral and physiological effects, provide further evidence that closed-loop LTC stimulation can improve episodic memory, and suggest a method for optimizing neuromodulation through improved stimulation targeting., (© The Author(s) 2023. Published by Oxford University Press.)

Traumatic brain injury (TBI) is a leading cause of cognitive disability in adults, often characterized by marked deficits in episodic memory and executive function. Prior studies have found that direct electrical stimulation of the temporal cortex yielded improved memory in epilepsy patients, but it is not clear if these results generalize to patients with a specific history of TBI. Here we asked whether applying closed-loop, direct electrical stimulation to lateral temporal cortex could reliably improve memory in a TBI cohort. Among a larger group of patients undergoing neurosurgical evaluation for refractory epilepsy, we recruited a subset of patients with a history of moderate-to-severe TBI. By analyzing neural data from indwelling electrodes as patients studied and recalled lists of words, we trained personalized machine-learning classifiers to predict momentary fluctuations in mnemonic function in each patient. We subsequently used these classifiers to trigger high-frequency stimulation of the lateral temporal cortex (LTC) at moments when memory was predicted to fail. This strategy yielded a 19% boost in recall performance on stimulated as compared with non-stimulated lists (P = 0.012). These results provide a proof-of-concept for using closed-loop stimulation of the brain in treatment of TBI-related memory impairment., Competing Interests: Declaration of competing interest B.C.J. receives research funding from NeuroPace, Inc. and Harvard Pilgrim, Inc. not relating to this research. R.E.G. serves as a consultant to Medtronic, which was previously a subcontractor on this project, and receives compensation for these services. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. M.J.K. holds a greater than 5% equity interest in Nia Therapeutics Inc., a company intended to develop and commercialize brain stimulation therapies for memory restoration. R.E.G. holds a less than 5% equity interest in Nia Therapeutics, Inc. P.A.W. is employed by Blackrock Microsystems Europe GmbH. E.A.S. has served as a compensated technical consultant to Nia Therapeutics Inc., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL microwire recordings from 20 patients (9 female, 11 male) navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings. The array of local field potentials in the MTL contains sufficient information for above-chance decoding of subjects' instantaneous location in the environment. Closer examination revealed that as subjects gain experience with the environment the field potentials come to represent both the subjects' locations in virtual space and in high-dimensional semantic space. Similarly, we observe a learning effect on temporal sequence coding. Over time, field potentials come to represent future locations, even after controlling for spatial proximity. This predictive coding of future states, more so than the strength of spatial representations per se, is linked to variability in subjects' navigation performance. Our results thus support the conceptualization of the MTL as a memory space, representing both spatial- and nonspatial information to plan future actions and predict their outcomes. SIGNIFICANCE STATEMENT Using rare microwire recordings, we studied the representation of spatial, semantic, and temporal information in the human MTL. Our findings demonstrate that subjects acquire a cognitive map that simultaneously represents the spatial and semantic relations between landmarks. We further show that the same learned representation is used to predict future states, implicating MTL cell assemblies as the building blocks of prospective memory functions., (Copyright © 2023 the authors.)

Objective: The medial temporal lobe (MTL) encodes and recalls memories and can be a predominant site for interictal spikes (IS) in patients with focal epilepsy. It is unclear whether memory deficits are due to IS in the MTL producing a transient decline. Here, we investigated whether IS in the MTL subregions and lateral temporal cortex impact episodic memory encoding and recall., Methods: Seventy-eight participants undergoing presurgical evaluation for medically refractory focal epilepsy with depth electrodes placed in the temporal lobe participated in a verbal free recall task. IS were manually annotated during the pre-encoding, encoding, and recall epochs. We examined the effect of IS on word recall using mixed-effects logistic regression., Results: IS in the left hippocampus (odds ratio [OR] = .73, 95% confidence interval [CI] = .63-.84, p < .001) and left middle temporal gyrus (OR = .46, 95% CI = .27-.78, p < .05) during word encoding decreased subsequent recall performance. Within the left hippocampus, this effect was specific for area CA1 (OR = .76, 95% CI = .66-.88, p < .01) and dentate gyrus (OR = .74, 95% CI = .62-.89, p < .05). IS in other MTL subregions or inferior and superior temporal gyrus and IS occurring during the prestimulus window did not affect word encoding (p > .05). IS during retrieval in right hippocampal (OR = .22, 95% CI = .08-.63, p = .01) and parahippocampal regions (OR = .24, 95% CI = .07-.8, p < .05) reduced the probability of recalling a word., Significance: IS in medial and lateral temporal cortex contribute to transient memory decline during verbal episodic memory., (© 2022 International League Against Epilepsy.)

Background: Brain stimulation has emerged as a powerful tool in human neuroscience, becoming integral to next-generation psychiatric and neurologic therapeutics. Theta-burst stimulation (TBS), in which electrical pulses are delivered in rhythmic bouts of 3-8 Hz, seeks to recapitulate neural activity seen endogenously during cognitive tasks. A growing literature suggests that TBS can be used to alter or enhance cognitive processes, but little is known about how these stimulation events influence underlying neural activity., Objective: Our study sought to investigate the effect of direct electrical TBS on mesoscale neural activity in humans by asking (1) whether TBS evokes persistent theta oscillations in cortical areas, (2) whether these oscillations occur at the stimulated frequency, and (3) whether stimulation events propagate in a manner consistent with underlying functional and structural brain architecture., Methods: We recruited 20 neurosurgical epilepsy patients with indwelling electrodes and delivered direct cortical TBS at varying locations and frequencies. Simultaneous iEEG was recorded from non-stimulated electrodes and analyzed to understand how TBS influences mesoscale neural activity., Results: We found that TBS rapidly evoked theta rhythms in widespread brain regions, preferentially at the stimulation frequency, and that these oscillations persisted for hundreds of milliseconds post stimulation offset. Furthermore, the functional connectivity between recording and stimulation sites predicted the strength of theta response, suggesting that underlying brain architecture guides the flow of stimulation through the brain., Conclusions: By demonstrating that cortical TBS induces frequency-specific oscillatory responses, our results suggest this technology can be used to directly and predictably influence the activity of cognitively-relevant brain networks., Competing Interests: Declaration of competing interest M.J.K. and D. S. R. have co-founded a company, Nia Therapeutics (“Nia”), intended to develop and commercialize brain stimulation therapies for memory restoration. E.A.S has served as a compensated technical consultant for Nia. P.A.W is employed by Blackrock Microsystems Europe GmbH., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The role of the left ventral lateral parietal cortex (VPC) in episodic memory is hypothesized to include bottom-up attentional orienting to recalled items, according to the dual-attention model (Cabeza et al., 2008). However, its role in memory encoding could be further clarified, with studies showing both positive and negative subsequent memory effects (SMEs). Furthermore, few studies have compared the relative contributions of sub-regions in this functionally heterogeneous area, specifically the anterior VPC (supramarginal gyrus/BA40) and the posterior VPC (angular gyrus/BA39), on a within-subject basis. To elucidate the role of the VPC in episodic encoding, we compared SMEs in the intracranial EEG across multiple frequency bands in the supramarginal gyrus (SmG) and angular gyrus (AnG), as twenty-four epilepsy patients with indwelling electrodes performed a free recall task. We found a significant SME of decreased theta power and increased high gamma power in the VPC overall, and specifically in the SmG. Furthermore, SmG exhibited significantly greater spectral tilt SME from 0.5 to 1.6 s post-stimulus, in which power spectra slope differences between recalled and unrecalled words were greater than in the AnG (p = 0.04). These results affirm the contribution of VPC to episodic memory encoding, and suggest an anterior-posterior dissociation within VPC with respect to its electrophysiological underpinnings., Competing Interests: Declaration of Competing Interest MRS is a consultant/advisor for Medtronic (fee to institution); is a consultant for NeurologyLive; received research support (to institution) from Eisai, Engage, Medtronic, Neurelis, Pfizer, SK Life Science, Inc., Takeda, UCB, and Xenon; and has been a speaker for Eisai., (Copyright © 2020. Published by Elsevier Inc.)

Traumatic brain injury is a leading cause of cognitive disability and is often associated with significant impairment in episodic memory. In traumatic brain injury survivors, as in healthy controls, there is marked variability between individuals in memory ability. Using recordings from indwelling electrodes, we characterized and compared the oscillatory biomarkers of mnemonic variability in two cohorts of epilepsy patients: a group with a history of moderate-to-severe traumatic brain injury ( n  = 37) and a group of controls without traumatic brain injury ( n  = 111) closely matched for demographics and electrode coverage. Analysis of these recordings demonstrated that increased high-frequency power and decreased theta power across a broad set of brain regions mark periods of successful memory formation in both groups. As features in a logistic-regression classifier, spectral power biomarkers effectively predicted recall probability, with little difference between traumatic brain injury patients and controls. The two groups also displayed similar patterns of theta-frequency connectivity during successful encoding periods. These biomarkers of successful memory, highly conserved between traumatic brain injury patients and controls, could serve as the basis for novel therapies that target disordered memory across diverse forms of neurological disease., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Researchers have used direct electrical brain stimulation to treat a range of neurological and psychiatric disorders. However, for brain stimulation to be maximally effective, clinicians and researchers should optimize stimulation parameters according to desired outcomes., Objective: The goal of our large-scale study was to comprehensively evaluate the effects of stimulation at different parameters and locations on neuronal activity across the human brain., Methods: To examine how different kinds of stimulation affect human brain activity, we compared the changes in neuronal activity that resulted from stimulation at a range of frequencies, amplitudes, and locations with direct human brain recordings. We recorded human brain activity directly with electrodes that were implanted in widespread regions across 106 neurosurgical epilepsy patients while systematically stimulating across a range of parameters and locations., Results: Overall, stimulation most often had an inhibitory effect on neuronal activity, consistent with earlier work. When stimulation excited neuronal activity, it most often occurred from high-frequency stimulation. These effects were modulated by the location of the stimulating electrode, with stimulation sites near white matter more likely to cause excitation and sites near gray matter more likely to inhibit neuronal activity., Conclusion: By characterizing how different stimulation parameters produced specific neuronal activity patterns on a large scale, our results provide an electrophysiological framework that clinicians and researchers may consider when designing stimulation protocols to cause precisely targeted changes in human brain activity., Competing Interests: Declaration of competing interest M.K. and D.R. have started a company, Nia Therapeutics, Inc., intended to develop and commercialize brain stimulation therapies for memory restoration. Each of them holds >5% equity interest in Nia. R.E.G. serves as a consultant to Medtronic, which was a subcontractor on the RAM project. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies. B.J. receives research funding from NeuroPace and Medtronic not relating to this research. G.W. has rights to receive future royalties from the licensing of brain stimulation technology. Mayo Clinic has a financial interest related to brain stimulation technology, and is co-owner of Cadence Neuroscience Inc, the development of which has been assisted by G.W. The remaining authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Patients with medically refractory epilepsy often undergo intracranial electroencephalography (iEEG) monitoring to identify a seizure focus and determine their candidacy for surgical intervention. This clinically necessary monitoring period provides an increasingly utilized research opportunity to study human neurophysiology, however ethical concerns demand a thorough appreciation of the associated risks. We measured the incidence of research stimulation-associated seizures in a large multi-institutional dataset in order to determine whether brain stimulation was statistically associated with seizure incidence and identify potential risk factors for stimulation-associated seizures., Approach: 188 subjects undergoing iEEG monitoring across ten institutions participated in 770 research stimulation sessions over 3.5 yr. Seizures within 30 min of a stimulation session were included in our retrospective analysis. We analyzed stimulation parameters, seizure incidence, and typical seizure patterns, to assess the likelihood that recorded seizures were stimulation-induced, rather than events that occurred by chance in epilepsy patients prone to seizing., Main Results: In total, 14 seizures were included in our analysis. All events were single seizures, and no adverse events occurred. The mean amplitude of seizure-associated stimulation did not differ significantly from the mean amplitude delivered in sessions without seizures. In order to determine the likelihood that seizures were stimulation induced, we used three sets of analyses: visual iEEG analysis, statistical frequency, and power analyses. We determined that three of the 14 seizures were likely stimulation-induced, five were possibly stimulation-induced, and six were unlikely stimulation-induced. Overall, we estimate a rate of stimulation-induced seizures between 0.39% and 1.82% of sessions., Significance: The rarity of stimulation-associated seizures and the fact that none added morbidity or affected the clinical course of any patient are important findings for understanding the feasibility and safety of intracranial stimulation for research purposes.

Whereas numerous findings support a distinction between episodic and semantic memory, it is now widely acknowledged that these two forms of memory interact during both encoding and retrieval. The precise nature of this interaction, however, remains poorly understood. To examine the role of semantic organization during episodic encoding and retrieval, we recorded intracranial encephalographic signals as 69 neurosurgical patients studied and subsequently recalled categorized and unrelated word lists. Applying multivariate classifiers to neural recordings, we were able to reliably predict encoding success, retrieval success, and temporal and categorical clustering during recall. By assessing how these classifiers generalized across list types, we identified specific retrieval processes that predicted recall of categorized lists and distinguished between recall transitions within and between category clusters. These results particularly implicate retrieval (rather than encoding) processes in the categorical organization of episodic memories. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1-3-Hz "low theta" band increases when viewing subsequently remembered object-location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition.

The medial temporal lobe (MTL) is widely implicated in supporting episodic memory and navigation, but its precise functional role in organizing memory across time and space remains elusive. Here we examine the specific cognitive processes implemented by MTL structures (hippocampus and entorhinal cortex) to organize memory by using electrical brain stimulation, leveraging its ability to establish causal links between brain regions and features of behavior. We studied neurosurgical patients of both sexes who performed spatial-navigation and verbal-episodic memory tasks while brain stimulation was applied in various regions during learning. During the verbal memory task, stimulation in the MTL disrupted the temporal organization of encoded memories such that items learned with stimulation tended to be recalled in a more randomized order. During the spatial task, MTL stimulation impaired subjects' abilities to remember items located far away from boundaries. These stimulation effects were specific to the MTL. Our findings thus provide the first causal demonstration in humans of the specific memory processes that are performed by the MTL to encode when and where events occurred. SIGNIFICANCE STATEMENT Numerous studies have implicated the medial temporal lobe (MTL) in encoding spatial and temporal memories, but they have not been able to causally demonstrate the nature of the cognitive processes by which this occurs in real-time. Electrical brain stimulation is able to demonstrate causal links between a brain region and a given function with high temporal precision. By examining behavior in a memory task as subjects received MTL stimulation, we provide the first causal evidence demonstrating the role of the MTL in organizing the spatial and temporal aspects of episodic memory., (Copyright © 2018 the authors 0270-6474/18/384471-11$15.00/0.)

Memory failures are frustrating and often the result of ineffective encoding. One approach to improving memory outcomes is through direct modulation of brain activity with electrical stimulation. Previous efforts, however, have reported inconsistent effects when using open-loop stimulation and often target the hippocampus and medial temporal lobes. Here we use a closed-loop system to monitor and decode neural activity from direct brain recordings in humans. We apply targeted stimulation to lateral temporal cortex and report that this stimulation rescues periods of poor memory encoding. This system also improves later recall, revealing that the lateral temporal cortex is a reliable target for memory enhancement. Taken together, our results suggest that such systems may provide a therapeutic approach for treating memory dysfunction.

Every movement we make represents one of many possible actions. In reaching tasks with multiple targets, dorsal premotor cortex (PMd) appears to represent all possible actions simultaneously. However, in many situations we are not presented with explicit choices. Instead, we must estimate the best action based on noisy information and execute it while still uncertain of our choice. Here we asked how both primary motor cortex (M1) and PMd represented reach direction during a task in which a monkey made reaches based on noisy, uncertain target information. We found that with increased uncertainty, neurons in PMd actually enhanced their representation of unlikely movements throughout both planning and execution. The magnitude of this effect was highly variable across sessions, and was correlated with a measure of the monkeys' behavioral uncertainty. These effects were not present in M1. Our findings suggest that PMd represents and maintains a full distribution of potentially correct actions.

Humans readily learn to move through direct physical practice and by watching the movements of others. Some researchers have proposed that action observation can inform subsequent changes in control through the acquisition of a neural representation of the novel dynamics, but to date learning following observation has been described by kinematic metrics. Here we designed an experiment to consider the specificity of adaptation to novel dynamic perturbations at the level of force generation. We measured changes in temporal patterns of force output following either the performance or observation of movements perturbed by either position- or velocity-dependent dynamic environments to 1) establish whether previously described observational motor learning effects were attributable to changes in predictive limb control and 2) determine whether such adaptation reflected a learned dependence on limb states appropriate to the haptic environment. We found that subjects who observed perturbed movements produced significant compensatory changes in their lateral force output, despite never directly experiencing force perturbations firsthand while performing the motor task. The time series of observers' adapted force outputs suggested that the state dependence of observed dynamics shapes adaptation. We conclude that the brain can transform observation of kinematics into state-dependent adaptation of reach dynamics.

We have exposed human participants to both full-movement and pulsatile viscous force perturbations to study the effect of force duration on the incremental transformation of sensation into adaptation. Traditional views of movement biomechanics could suggest that pulsatile forces would largely be attenuated as stiffness and viscosity act as a natural low-pass filter. Sensory transduction, however, tends to react to changes in stimuli and therefore could underlie heightened sensitivity to briefer, pulsatile forces. Here, participants adapted within perturbation duration conditions in a manner proportionate to sensed force and positional errors. Across perturbation conditions, we found participants had greater adaptive sensitivity when experiencing pulsatile forces rather than full-movement forces. In a follow-up experiment, we employed error-clamped, force channel trials to determine changes in predictive force generation. We found that while participants learned to closely compensate for the amplitude and breadth of full-movement forces, they exhibited a persistent mismatch in amplitude and breadth between adapted motor output and experienced pulsatile forces. This mismatch could generate higher salience of error signals that contribute to heightened sensitivity to pulsatile forces.