fNIRS is sensitive to leg activity in the primary motor cortex after systemic artifact correction.

BACKGROUND: functional near-infrared spectroscopy (fNIRS) is an increasingly popular tool to study cortical activity during movement and gait that requires further validation. This study aimed to assess (1) whether fNIRS can detect the difficult-to-measure leg area of the primary motor cortex (M1) and distinguish it from the hand area; and (2) whether fNIRS can differentiate between automatic (i.e., not requiring one's attention) and non-automatic movement processes. Special attention was attributed to systemic artifacts (i.e., changes in blood pressure, heart rate, breathing) which were assessed and corrected by short channels, i.e., fNIRS channels which are mainly sensitive to superficial scalp hemodynamics. METHODS: Twenty-three seated, healthy participants tapped four fingers on a keyboard or tapped the right foot on four squares on the floor in a specific order given by a 12-digit sequence (e.g., 434141243212). Two different sequences were executed: a beforehand learned (i.e., automatic) version and a newly learned (i.e., non-automatic) version. A 36-channel fNIRS device including 12 short channels covered multiple motor-related cortical areas including M1. The fNIRS data were analyzed with a general linear model (GLM). Correlation between the expected functional hemodynamic responses (i.e. task regressor) and the short channels (i.e. nuisance regressors), necessitated performing a separate short channel regression instead of integrating them in the GLM. RESULTS: Consistent with the M1 somatotopy, we found significant HbO increases of very large effect size in the lateral M1 channels during finger tapping (Cohen's d = 1.35, p<0.001) and significant HbO increases of moderate effect size in the medial M1 channels during foot tapping (Cohen's d = 0.8, p<0.05). The cortical activity differences between automatic and non-automatic tasks were not significantly different. Importantly, leg movements produced large systemic fluctuations, which were adequately removed by the use of all available short channels. DISCUSSION: Our results indicate that fNIRS is sensitive to leg activity in M1, though the sensitivity is lower than for finger activity and requires rigorous correction for systemic fluctuations. We furthermore highlight that systemic artifacts may result in an unreliable GLM analysis when short channels show signals that are similar to the expected hemodynamic responses.

Dealing with the heterogeneous presentations of freezing of gait: how reliable are the freezing index and heart rate for freezing detection?

BACKGROUND: Freezing of gait (FOG) is an unpredictable gait arrest that hampers the lives of 40% of people with Parkinson's disease. Because the symptom is heterogeneous in phenotypical presentation (it can present as trembling/shuffling, or akinesia) and manifests during various circumstances (it can be triggered by e.g. turning, passing doors, and dual-tasking), it is particularly difficult to detect with motion sensors. The freezing index (FI) is one of the most frequently used accelerometer-based methods for FOG detection. However, it might not adequately distinguish FOG from voluntary stops, certainly for the akinetic type of FOG. Interestingly, a previous study showed that heart rate signals could distinguish FOG from stopping and turning movements. This study aimed to investigate for which phenotypes and evoking circumstances the FI and heart rate might provide reliable signals for FOG detection. METHODS: Sixteen people with Parkinson's disease and daily freezing completed a gait trajectory designed to provoke FOG including turns, narrow passages, starting, and stopping, with and without a cognitive or motor dual-task. We compared the FI and heart rate of 378 FOG events to baseline levels, and to stopping and normal gait events (i.e. turns and narrow passages without FOG) using mixed-effects models. We specifically evaluated the influence of different types of FOG (trembling vs akinesia) and triggering situations (turning vs narrow passages; no dual-task vs cognitive dual-task vs motor dual-task) on both outcome measures. RESULTS: The FI increased significantly during trembling and akinetic FOG, but increased similarly during stopping and was therefore not significantly different from FOG. In contrast, heart rate change during FOG was for all types and during all triggering situations statistically different from stopping, but not from normal gait events. CONCLUSION: When the power in the locomotion band (0.5-3 Hz) decreases, the FI increases and is unable to specify whether a stop is voluntary or involuntary (i.e. trembling or akinetic FOG). In contrast, the heart rate can reveal whether there is the intention to move, thus distinguishing FOG from stopping. We suggest that the combination of a motion sensor and a heart rate monitor may be promising for future FOG detection.

Dynamics of a Mutual Inhibition Circuit between Pyramidal Neurons Compared to Human Perceptual Competition.

Neural competition plays an essential role in active selection processes of noisy and ambiguous input signals, and it is assumed to underlie emergent properties of brain functioning, such as perceptual organization and decision-making. Despite ample theoretical research on neural competition, experimental tools to allow neurophysiological investigation of competing neurons have not been available. We developed a "hybrid" system where real-life neurons and a computer-simulated neural circuit interacted. It enabled us to construct a mutual inhibition circuit between two real-life pyramidal neurons. We then asked what dynamics this minimal unit of neural competition exhibits and compared them with the known behavioral-level dynamics of neural competition. We found that the pair of neurons shows bistability when activated simultaneously by current injections. The addition of modeled synaptic noise and changes in the activation strength showed that the dynamics of the circuit are strikingly similar to the known properties of bistable visual perception: The distribution of dominance durations showed a right-skewed shape, and the changes of the activation strengths caused changes in dominance, dominance durations, and reversal rates as stated in the well-known empirical laws of bistable perception known as Levelt's propositions.SIGNIFICANCE STATEMENT Visual perception emerges as the result of neural systems actively organizing visual signals that involves selection processes of competing neurons. While the neural competition, realized by a "mutual inhibition" circuit has been examined in many theoretical studies, its properties have not been investigated in real neurons. We have developed a "hybrid" system where two real-life pyramidal neurons in a mouse brain slice interact through a computer-simulated mutual inhibition circuit. We found that simultaneous activation of the neurons leads to bistable activity. We investigated the effect of noise and the effect of changes in the activation strength on the dynamics. We observed that the pair of neurons exhibit dynamics strikingly similar to the known properties of bistable visual perception.

Orthostatic Blood Pressure Recovery Measured Using a Sphygmomanometer Is Not Associated with Physical Performance or Number of Falls in Geriatric Outpatients.

BACKGROUND: Orthostatic hypotension (OH) and impaired OH recovery derived from beat-to-beat blood pressure (BP) measurements are associated with detrimental clinical outcome, but the clinical relevance of OH recovery assessed using the widely available sphygmomanometer is still unclear. METHOD: 635 geriatric outpatients underwent comprehensive geriatric assessment, including orthostatic BP measurements using a sphygmomanometer, during supine rest and 1 and 3 min after standing up and assessment of physical performance (i.e., the timed up and go test and the Short Physical Performance Battery) and the number of falls in the past year. The association between BP recovery, defined as BP at 3 min minus BP at 1 min after standing up, with physical performance and falls was assessed using regression analyses, adjusting for age and sex, both in the entire cohort and after stratifying for the presence of OH at 1 min after standing up. RESULTS: BP recovery was not associated with physical performance or number of falls, neither in the entire cohort, nor in subpopulations with or without OH. CONCLUSION: The clinical relevance of BP recovery between 1 and 3 min after standing up could not be demonstrated. The results suggest that sphygmomanometer measurements have an inadequate time resolution to record the clinically relevant dynamics of orthostatic BP recovery.

End-to-end optimization of prosthetic vision.

Neural prosthetics may provide a promising solution to restore visual perception in some forms of blindness. The restored prosthetic percept is rudimentary compared to normal vision and can be optimized with a variety of image preprocessing techniques to maximize relevant information transfer. Extracting the most useful features from a visual scene is a nontrivial task and optimal preprocessing choices strongly depend on the context. Despite rapid advancements in deep learning, research currently faces a difficult challenge in finding a general and automated preprocessing strategy that can be tailored to specific tasks or user requirements. In this paper, we present a novel deep learning approach that explicitly addresses this issue by optimizing the entire process of phosphene generation in an end-to-end fashion. The proposed model is based on a deep auto-encoder architecture and includes a highly adjustable simulation module of prosthetic vision. In computational validation experiments, we show that such an approach is able to automatically find a task-specific stimulation protocol. The results of these proof-of-principle experiments illustrate the potential of end-to-end optimization for prosthetic vision. The presented approach is highly modular and our approach could be extended to automated dynamic optimization of prosthetic vision for everyday tasks, given any specific constraints, accommodating individual requirements of the end-user.

Real-world indoor mobility with simulated prosthetic vision: The benefits and feasibility of contour-based scene simplification at different phosphene resolutions.

Neuroprosthetic implants are a promising technology for restoring some form of vision in people with visual impairments via electrical neurostimulation in the visual pathway. Although an artificially generated prosthetic percept is relatively limited compared with normal vision, it may provide some elementary perception of the surroundings, re-enabling daily living functionality. For mobility in particular, various studies have investigated the benefits of visual neuroprosthetics in a simulated prosthetic vision paradigm with varying outcomes. The previous literature suggests that scene simplification via image processing, and particularly contour extraction, may potentially improve the mobility performance in a virtual environment. In the current simulation study with sighted participants, we explore both the theoretically attainable benefits of strict scene simplification in an indoor environment by controlling the environmental complexity, as well as the practically achieved improvement with a deep learning-based surface boundary detection implementation compared with traditional edge detection. A simulated electrode resolution of 26 × 26 was found to provide sufficient information for mobility in a simple environment. Our results suggest that, for a lower number of implanted electrodes, the removal of background textures and within-surface gradients may be beneficial in theory. However, the deep learning-based implementation for surface boundary detection did not improve mobility performance in the current study. Furthermore, our findings indicate that, for a greater number of electrodes, the removal of within-surface gradients and background textures may deteriorate, rather than improve, mobility. Therefore, finding a balanced amount of scene simplification requires a careful tradeoff between informativity and interpretability that may depend on the number of implanted electrodes.

Cerebral autoregulation assessed by near-infrared spectroscopy: validation using transcranial Doppler in patients with controlled hypertension, cognitive impairment and controls.

PURPOSE: Cerebral autoregulation (CA) aims to attenuate the effects of blood pressure variation on cerebral blood flow. This study assessed the criterion validity of CA derived from near-infrared spectroscopy (NIRS) as an alternative for Transcranial Doppler (TCD). METHODS: Measurements of continuous blood pressure (BP), oxygenated hemoglobin (O2Hb) using NIRS and cerebral blood flow velocity (CBFV) using TCD (gold standard) were performed in 82 controls, 27 patients with hypertension and 94 cognitively impaired patients during supine rest (all individuals) and repeated sit to stand transitions (cognitively impaired patients). The BP-CBFV and BP-O2Hb transfer function phase shifts (TFφ) were computed as CA measures. Spearman correlations (ρ) and Bland Altman limits of agreement (BAloa) between NIRS- and TCD-derived CA measures were computed. BAloa separation < 50° was considered a high absolute agreement. RESULTS: NIRS- and TCD-derived CA estimates were significantly correlated during supine rest (ρ = 0.22-0.30, N = 111-120) and repeated sit-to-stand transitions (ρ = 0.46-0.61, N = 19-32). BAloa separation ranged between 87° and 112° (supine rest) and 65°-77° (repeated sit to stand transitions). CONCLUSION: Criterion validity of NIRS-derived CA measures allows for comparison between groups but was insufficient for clinical application in individuals.

Validation of Soft Multipin Dry EEG Electrodes.

Current developments towards multipin, dry electrodes in electroencephalography (EEG) are promising for applications in non-laboratory environments. Dry electrodes do not require the application of conductive gel, which mostly confines the use of gel EEG systems to the laboratory environment. The aim of this study is to validate soft, multipin, dry EEG electrodes by comparing their performance to conventional gel EEG electrodes. Fifteen healthy volunteers performed three tasks, with a 32-channel gel EEG system and a 32-channel dry EEG system: the 40 Hz Auditory Steady-State Response (ASSR), the checkerboard paradigm, and an eyes open/closed task. Within-subject analyses were performed to compare the signal quality in the time, frequency, and spatial domains. The results showed strong similarities between the two systems in the time and frequency domains, with strong correlations of the visual (ρ = 0.89) and auditory evoked potential (ρ = 0.81), and moderate to strong correlations for the alpha band during eye closure (ρ = 0.81-0.86) and the 40 Hz-ASSR power (ρ = 0.66-0.72), respectively. However, delta and theta band power was significantly increased, and the signal-to-noise ratio was significantly decreased for the dry EEG system. Topographical distributions were comparable for both systems. Moreover, the application time of the dry EEG system was significantly shorter (8 min). It can be concluded that the soft, multipin dry EEG system can be used in brain activity research with similar accuracy as conventional gel electrodes.

Bistability and Stabilization of Human Visual Perception under Ambiguous Stimulation.

We discuss a computational model that describes stabilization of percept choices under intermittent viewing of an ambiguous visual stimulus at long stimulus intervals. Let T_off and T_on be the time that the stimulus is off and on, respectively. The behavior was studied by direct numerical simulation in a grid of (T_off, T_on) values in a 2007 paper of Noest, van Ee, Nijs, and van Wezel. They found that both alternating and repetitive sequences of percepts can appear stably, sometimes even for the same values of T_off and T_on. Longer T_off, however, always leads to a situation where, after transients, only repetitive sequences of percepts exist. We incorporate T_off and T_on explicitly as bifurcation parameters of an extended mathematical model of the perceptual choices. We elucidate the bifurcations of periodic orbits responsible for switching between alternating and repetitive sequences. We show that the stability borders of the alternating and repeating sequences in the (T_off, T_on) -parameter plane consist of curves of limit point and period-doubling bifurcations of periodic orbits. The stability regions overlap, resulting in a wedge with bistability of both sequences. We conclude by comparing our modeling results with the experimental results obtained by Noest, van Ee, Nijs, and van Wezel.

Opto-locomotor reflexes of mice to reverse-phi stimuli.

In a reverse-phi stimulus, the contrast luminance of moving dots is reversed each displacement step. Under those conditions, the direction of the moving dots is perceived in the direction opposite of the displacement direction of the dots. In this study, we investigate if mice respond oppositely to phi and reverse-phi stimuli. Mice ran head-fixed on a Styrofoam ball floating on pressurized air at the center of a large dome. We projected random dot patterns that were displaced rightward or leftward, using either a phi or a reverse-phi stimulus. For phi stimuli, changes in direction caused the mice to reflexively compensate and adjust their running direction in the direction of the displaced pattern. We show that for reverse-phi stimuli mice compensate in the direction opposite to the displacement direction of the dots, in accordance with the perceived direction of displacement in humans for reverse-phi stimuli.

Monocular and binocular opto-locomotor reflex biases for random dot motion in mice.

We investigated the relationship between eyes receiving visual input of large field translating random dot motion and subsequent reflexive changes in running direction in mice. The animals were head-fixed running on a Styrofoam ball and the opto-locomotor reflex (OLR) was measured in response to 2 s of dots patterns moving horizontally to the left or right. We measured the OLR in conditions with both eyes open (binocular) and one eye closed (monocular). When we covered the right or left eye in the monocular condition, we found reflexive behavior to be delayed for a few hundred milliseconds to leftward or rightward motion, respectively. After this delay, the bias disappeared and reflexive behavior was similar to responses to motion under binocular conditions. These results might be explained by different contributions of subcortical and cortical visual motion processing pathways to the OLR. Furthermore, we found no evidence for nonlinear interactions between the two eyes, because the sum of the OLR of the two monocular conditions was equal in amplitude and temporal characteristics to the OLR under binocular conditions.

Sensitivity and reliability of cerebral oxygenation responses to postural changes measured with near-infrared spectroscopy.

PURPOSE: Cerebral oxygenation as measured by near-infrared spectroscopy (NIRS) might be useful to discriminate between physiological and pathological responses after standing up in individuals with orthostatic hypotension. This study addressed the physiological sensitivity of the cerebral oxygenation responses as measured by NIRS to different types and speeds of postural changes in healthy adults and assessed the reliability of these responses. METHODS: Cerebral oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb) and tissue saturation index (TSI) were measured bilaterally on the forehead of 15 healthy individuals (12 male, age range 18-27) using NIRS. Participants performed three repeats of sit to stand, and slow and rapid supine to stand movements. Responses were defined as the difference between mean, minimum and maximum O2Hb, HHb and TSI values after standing up and baseline. Test-retest, interobserver and intersensor reliabilities were addressed using intraclass correlation coefficients (ICCs). RESULTS: The minimum O2Hb response was most sensitive to postural changes and showed significant differences (- 4.09 µmol/L, p < 0.001) between standing up from sitting and supine position, but not between standing up at different speeds (- 0.31 µmol/L, p = 0.70). The minimum O2Hb response was the most reliable parameter (ICC > 0.6). CONCLUSIONS: In healthy individuals, NIRS-based cerebral oxygenation parameters are sensitive to postural change and discriminate between standing up from supine and sitting position with minimum O2Hb response as the most sensitive and reliable parameter. The results underpin the potential value for future clinical use of NIRS in individuals with orthostatic hypotension.

Sparse pallidal connections shape synchrony in a network model of the basal ganglia.

Neural synchrony in the basal ganglia, especially in the beta frequency band (13-30 Hz), is a hallmark of Parkinson's disease and considered as antikinetic. In contrast, the healthy basal ganglia show low levels of synchrony. It is currently unknown where synchrony and oscillations arise in the parkinsonian brain and how they are transmitted through the basal ganglia, as well as what makes them dependent on dopamine. The external part of the globus pallidus has recently been identified as a hub nucleus in the basal ganglia, possessing intrinsic inhibitory connections and possibly also gap junctions. In this study, we show that in a conductance-based network model of the basal ganglia, the combination of sparse, high-conductance inhibitory synapses and sparse, low-conductance gap junctions in the external part of the globus pallidus could effectively desynchronize the whole network. However, when gap junction coupling became strong enough, the effect was impeded and activity synchronized. In particular, sustained periods of beta coherence occurred between some neuron pairs. As gap junctions can change their conductance with the dopamine level, we suggest pallidal gap junction coupling as a mechanism contributing to the development of beta synchrony in the parkinsonian basal ganglia.

Patterns of resting state connectivity in human primary visual cortical areas: a 7T fMRI study.

The nature and origin of fMRI resting state fluctuations and connectivity are still not fully known. More detailed knowledge on the relationship between resting state patterns and brain function may help to elucidate this matter. We therefore performed an in depth study of how resting state fluctuations map to the well known architecture of the visual system. We investigated resting state connectivity at both a fine and large scale within and across visual areas V1, V2 and V3 in ten human subjects using a 7Tesla scanner. We found evidence for several coexisting and overlapping connectivity structures at different spatial scales. At the fine-scale level we found enhanced connectivity between the same topographic locations in the fieldmaps of V1, V2 and V3, enhanced connectivity to the contralateral functional homologue, and to a lesser extent enhanced connectivity between iso-eccentric locations within the same visual area. However, by far the largest proportion of the resting state fluctuations occurred within large-scale bilateral networks. These large-scale networks mapped to some extent onto the architecture of the visual system and could thereby obscure fine-scale connectivity. In fact, most of the fine-scale connectivity only became apparent after the large-scale network fluctuations were filtered from the timeseries. We conclude that fMRI resting state fluctuations in the visual cortex may in fact be a composite signal of different overlapping sources. Isolating the different sources could enhance correlations between BOLD and electrophysiological correlates of resting state activity.

Pallidal gap junctions-triggers of synchrony in Parkinson's disease?

Although increased synchrony of the neural activity in the basal ganglia may underlie the motor deficiencies exhibited in Parkinson's disease (PD), how this synchrony arises, propagates through the basal ganglia, and changes under dopamine replacement remains unknown. Gap junctions could play a major role in modifying this synchrony, because they show functional plasticity under the influence of dopamine and after neural injury. In this study, confocal imaging was used to detect connexin-36, the major neural gap junction protein, in postmortem tissues of PD patients and control subjects in the putamen, subthalamic nucleus (STN), and external and internal globus pallidus (GPe and GPi, respectively). Moreover, we quantified how gap junctions affect synchrony in an existing computational model of the basal ganglia. We detected connexin-36 in the human putamen, GPe, and GPi, but not in the STN. Furthermore, we found that the number of connexin-36 spots in PD tissues increased by 50% in the putamen, 43% in the GPe, and 109% in the GPi compared with controls. In the computational model, gap junctions in the GPe and GPi strongly influenced synchrony. The basal ganglia became especially susceptible to synchronize with input from the cortex when gap junctions were numerous and high in conductance. In conclusion, connexin-36 expression in the human GPe and GPi suggests that gap junctional coupling exists within these nuclei. In PD, neural injury and dopamine depletion could increase this coupling. Therefore, we propose that gap junctions act as a powerful modulator of synchrony in the basal ganglia.

Gaze-contingent processing improves mobility, scene recognition and visual search in simulated head-steered prosthetic vision.

Objective.The enabling technology of visual prosthetics for the blind is making rapid progress. However, there are still uncertainties regarding the functional outcomes, which can depend on many design choices in the development. In visual prostheses with a head-mounted camera, a particularly challenging question is how to deal with the gaze-locked visual percept associated with spatial updating conflicts in the brain. The current study investigates a recently proposed compensation strategy based on gaze-contingent image processing with eye-tracking. Gaze-contingent processing is expected to reinforce natural-like visual scanning and reestablished spatial updating based on eye movements. The beneficial effects remain to be investigated for daily life activities in complex visual environments.Approach.The current study evaluates the benefits of gaze-contingent processing versus gaze-locked and gaze-ignored simulations in the context of mobility, scene recognition and visual search, using a virtual reality simulated prosthetic vision paradigm with sighted subjects.Main results.Compared to gaze-locked vision, gaze-contingent processing was consistently found to improve the speed in all experimental tasks, as well as the subjective quality of vision. Similar or further improvements were found in a control condition that ignores gaze-dependent effects, a simulation that is unattainable in the clinical reality.Significance.Our results suggest that gaze-locked vision and spatial updating conflicts can be debilitating for complex visually-guided activities of daily living such as mobility and orientation. Therefore, for prospective users of head-steered prostheses with an unimpaired oculomotor system, the inclusion of a compensatory eye-tracking system is strongly endorsed.

Home-based monitoring of cerebral oxygenation in response to postural changes using near-infrared spectroscopy.

Orthostatic hypotension (OH) is prevalent in older adults and can cause falls and hospitalization. Diagnostic intermittent blood pressure (BP) measurements are only a proxy for cerebral perfusion and do not reflect daily-life BP fluctuations. Near-infrared spectroscopy (NIRS)-measured cerebral oxygenation potentially overcomes these drawbacks. This study aimed to determine feasibility, face validity, and reliability of NIRS in the home environment. Ten participants with OH (2 female, mean age 77, SD 3.7) and 11 without OH (5 female, mean age 78, SD 6.7) wore a NIRS sensor at home on two different days for 10-11 h per day. Preceded by a laboratory-situated test, cerebral oxygenation was measured during three standardized supine-stand tests per day and during unsupervised daily life activities. Data availability, quality, and user experience were assessed (feasibility), as well as differences in posture-related oxygenation responses between participants with and without OH and between symptomatic (dizziness, light-headedness, blurred vision) and asymptomatic postural changes (face validity). Reliability was assessed through repetitive supine-stand tests. Up to 80% of the standardized home-based supine-stand tests could be analyzed. Oxygenation recovery values were lower for participants with OH (p = 0 .03-0.15); in those with OH, oxygenation showed a deeper maximum drop for symptomatic than asymptomatic postural changes (p = 0.04). Intra-class correlation coefficients varied from 0.07 to 0.40, with no consistent differences over measurements. This proof-of-concept study shows feasibility and face validity of at-home oxygenation monitoring using NIRS, confirming its potential value for diagnosis and monitoring in OH and OH-related symptoms. Further data are needed for conclusions about reliability.

The effect of a change in antihypertensive treatment on orthostatic hypotension in older adults: A systematic review and meta-analysis.

BACKGROUND: Orthostatic hypotension (OH) is common in older adults with hypertension. Antihypertensive treatment (AHT) prevents cardio- and cerebrovascular events. However, physicians are concerned to cause OH, making them hesitant to initiate or augment AHT in older adults with hypertension. METHODS: We systematically researched electronic databases for trials with older participants (≥65 years) with hypertension and OH assessment after initiating, discontinuing, or augmenting AHT. Study quality was assessed using the ROBINS-I tool. Meta-analyses on OH prevalence and postural blood pressure (BP) drop were performed. RESULTS: Twenty-five studies (26,695 participants) met inclusion criteria, of which fifteen could be included in the meta-analyses. OH prevalence decreased after AHT initiation or augmentation (risk ratio 0.39 (95 % CI = 0.21-0.72; I2 = 47 %; p < 0.01), n = 6 studies), but also after AHT discontinuation (risk ratio 0.39 (95 % CI = 0.28-0.55; I2 = 0 %; p < 0.01), n = 2 studies). Postural BP drop did not change after initiation or augmentation of AHT (mean difference 1.07 (95 % CI = -0.49-2.64; I2 = 92 %; p = 0.18), n = 11 studies). The main reason for ten studies not to be included in the meta-analyses was absence of baseline OH data. Most of these studies reported OH incidences between 0 and 2 %. Studies were heterogeneous in OH assessment methods (postural change, timing of BP measurements, and OH definition). Risk of bias was moderate to serious in twenty studies. CONCLUSION: Results suggest that AHT initiation or augmentation decreases OH prevalence, implying that the risk of inducing OH may be overestimated in current AHT decision-making in older adults. However, the overall low level of evidence and the finding that AHT discontinuation reduces OH prevalence limit firm conclusions at present and highlight an important research gap. Future AHT trials in older adults should measure OH in a standardized protocol, adhering to consensus guidelines to overcome these limitations.