Investigating the neural mechanisms of transcranial direct current stimulation effects on human cognition: current issues and potential solutions.

Transcranial direct current stimulation (tDCS) has been studied extensively for its potential to enhance human cognitive functions in healthy individuals and to treat cognitive impairment in various clinical populations. However, little is known about how tDCS modulates the neural networks supporting cognition and the complex interplay with mediating factors that may explain the frequently observed variability of stimulation effects within and between studies. Moreover, research in this field has been characterized by substantial methodological variability, frequent lack of rigorous experimental control and small sample sizes, thereby limiting the generalizability of findings and translational potential of tDCS. The present manuscript aims to delineate how these important issues can be addressed within a neuroimaging context, to reveal the neural underpinnings, predictors and mediators of tDCS-induced behavioral modulation. We will focus on functional magnetic resonance imaging (fMRI), because it allows the investigation of tDCS effects with excellent spatial precision and sufficient temporal resolution across the entire brain. Moreover, high resolution structural imaging data can be acquired for precise localization of stimulation effects, verification of electrode positions on the scalp and realistic current modeling based on individual head and brain anatomy. However, the general principles outlined in this review will also be applicable to other imaging modalities. Following an introduction to the overall state-of-the-art in this field, we will discuss in more detail the underlying causes of variability in previous tDCS studies. Moreover, we will elaborate on design considerations for tDCS-fMRI studies, optimization of tDCS and imaging protocols and how to assure high-level experimental control. Two additional sections address the pressing need for more systematic investigation of tDCS effects across the healthy human lifespan and implications for tDCS studies in age-associated disease, and potential benefits of establishing large-scale, multidisciplinary consortia for more coordinated tDCS research in the future. We hope that this review will contribute to more coordinated, methodologically sound, transparent and reproducible research in this field. Ultimately, our aim is to facilitate a better understanding of the underlying mechanisms by which tDCS modulates human cognitive functions and more effective and individually tailored translational and clinical applications of this technique in the future.

Cortical processes of multisensory plausibility modulation of vibrotactile perception in virtual environments in middled-aged and older adults.

Digital technologies, such as virtual or augmented reality, can potentially support neurocognitive functions of the aging populations worldwide and complement existing intervention methods. However, aging-related declines in the frontal-parietal network and dopaminergic modulation which progress gradually across the later periods of the adult lifespan may affect the processing of multisensory congruence and expectancy based contextual plausibility. We assessed hemodynamic brain responses while middle-aged and old adults experienced car-riding virtual-reality scenarios where the plausibility of vibrotactile stimulations was manipulated by delivering stimulus intensities that were either congruent or incongruent with the digitalized audio-visual contexts of the respective scenarios. Relative to previous findings observed in young adults, although highly plausible vibrotactile stimulations confirming with contextual expectations also elicited higher brain hemodynamic responses in middle-aged and old adults, this effect was limited to virtual scenarios with extreme expectancy violations. Moreover, individual differences in plausibility-related frontal activity did not correlate with plausibility violation costs in the sensorimotor cortex, indicating less systematic frontal context-based sensory filtering in older ages. These findings have practical implications for advancing digital technologies to support aging societies.

Brain oscillatory processes related to sequence memory in healthy older adults.

Sequence memory is subject to age-related decline, but the underlying processes are not yet fully understood. We analyzed electroencephalography (EEG) in 21 healthy older (60-80 years) and 26 young participants (20-30 years) and compared time-frequency spectra and theta-gamma phase-amplitude-coupling (PAC) during encoding of the order of visually presented items. In older adults, desynchronization in theta (4-8 Hz) and synchronization in gamma (30-45 Hz) power did not distinguish between subsequently correctly and incorrectly remembered trials, while there was a subsequent memory effect for young adults. Theta-gamma PAC was modulated by item position within a sequence for older but not young adults. Specifically, position within a sequence was coded by higher gamma amplitude for successive theta phases for later correctly remembered trials. Thus, deficient differentiation in theta desynchronization and gamma oscillations during sequence encoding in older adults may reflect neurophysiological correlates of age-related memory decline. Furthermore, our results indicate that sequences are coded by theta-gamma PAC in older adults, but that this mechanism might lose precision in aging.

Neural correlates of home-based intervention effects on value-based sequential decision-making in healthy older adults.

Older adults demonstrate difficulties in sequential decision-making, which is partly attributed to under-recruitment of prefrontal networks. It is, therefore, important to understand the mechanisms that may improve this ability. This study investigated the effectiveness of an 18-sessions, home-based cognitive intervention and the neural mechanisms that underpin individual differences in intervention effects. Participants were required to learn sequential choices in a 3-stage Markov decision-making task that would yield the most rewards. Participants were assigned to better or worse responders group based on their performance at the last intervention session (T18). Better responders improved significantly starting from the fifth intervention session while worse responders did not improve across all training sessions. At post-intervention, only better responders showed condition-dependent modulation of the dorsolateral prefrontal cortex (DLPFC) as measured by fNIRS, with higher DLPFC activity in the delayed condition. Despite large individual differences, our data showed that value-based sequential-decision-making and its corresponding neural mechanisms can be remediated via home-based cognitive intervention in some older adults; moreover, individual differences in recruiting prefrontal activities after the intervention are associated with variations in intervention outcomes. Intervention-related gains were also maintained at three months after post-intervention. However, future studies should investigate the potential of combining other intervention methods such as non-invasive brain stimulation with cognitive intervention for older adults who do not respond to the intervention, thus emphasizing the importance of developing individualized intervention programs for older adults.

Cognitive training and brain stimulation in patients with cognitive impairment: a randomized controlled trial.

BACKGROUND: Repeated sessions of training and non-invasive brain stimulation have the potential to enhance cognition in patients with cognitive impairment. We hypothesized that combining cognitive training with anodal transcranial direct current stimulation (tDCS) will lead to performance improvement in the trained task and yield transfer to non-trained tasks. METHODS: In our randomized, sham-controlled, double-blind study, 46 patients with cognitive impairment (60-80 years) were randomly assigned to one of two interventional groups. We administered a 9-session cognitive training (consisting of a letter updating and a Markov decision-making task) over 3 weeks with concurrent 1-mA anodal tDCS over the left dorsolateral prefrontal cortex (20 min in tDCS, 30 s in sham group). Primary outcome was trained task performance (letter updating task) immediately after training. Secondary outcomes included performance in tasks testing working memory (N-back task), decision-making (Wiener Matrices test) and verbal memory (verbal learning and memory test), and resting-state functional connectivity (FC). Tasks were administered at baseline, at post-assessment, and at 1- and 7-month follow-ups (FU). MRI was conducted at baseline and 7-month FU. Thirty-nine participants (85%) successfully completed the intervention. Data analyses are reported on the intention-to-treat (ITT) and the per-protocol (PP) sample. RESULTS: For the primary outcome, no difference was observed in the ITT (ß = 0.1, 95%-CI [- 1.2, 1.3, p = 0.93] or PP sample (ß = - 0.2, 95%-CI [- 1.6, 1.2], p = 0.77). However, secondary analyses in the N-back working memory task showed that, only in the PP sample, the tDCS outperformed the sham group (PP: % correct, ß = 5.0, 95%-CI [- 0.1, 10.2], p = 0.06, d-prime ß = 0.2, 95%-CI [0.0, 0.4], p = 0.02; ITT: % correct, ß = 3.0, 95%-CI [- 3.9, 9.9], p = 0.39, d-prime ß = 0.1, 95%-CI [- 0.1, 0.3], p = 0.5). Frontoparietal network FC was increased from baseline to 7-month FU in the tDCS compared to the sham group (pFDR < 0.05). Exploratory analyses showed a correlation between individual memory improvements and higher electric field magnitudes induced by tDCS (ρtDCS = 0.59, p = 0.02). Adverse events did not differ between groups, questionnaires indicated successful blinding (incidence rate ratio, 1.1, 95%-CI [0.5, 2.2]). CONCLUSIONS: In sum, cognitive training with concurrent brain stimulation, compared to cognitive training with sham stimulation, did not lead to superior performance enhancements in patients with cognitive impairment. However, we observed transferred working memory benefits in patients who underwent the full 3-week intervention. MRI data pointed toward a potential intervention-induced modulation of neural network dynamics. A link between individual performance gains and electric fields suggested dosage-dependent effects of brain stimulation. Together, our findings do not support the immediate benefit of the combined intervention on the trained function, but provide exploratory evidence for transfer effects on working memory in patients with cognitive impairment. Future research needs to explore whether individualized protocols for both training and stimulation parameters might further enhance treatment gains. TRIAL REGISTRATION: The study is registered on ClinicalTrials.gov (NCT04265378). Registered on 7 February 2020. Retrospectively registered.

Coming in handy: CeTI-Age - A comprehensive database of kinematic hand movements across the lifespan.

The Tactile Internet aims to advance human-human and human-machine interactions that also utilize hand movements in real, digitized, and remote environments. Attention to elderly generations is necessary to make the Tactile Internet age inclusive. We present the first age-representative kinematic database consisting of various hand gesturing and grasping movements at individualized paces, thus capturing naturalistic movements. We make this comprehensive database of kinematic hand movements across the adult lifespan (CeTI-Age-Kinematic-Hand) publicly available to facilitate a deeper understanding of intra-individual-focusing especially on age-related differences-and inter-individual variability in hand kinematics. The core of the database contains participants' hand kinematics recorded with wearable resistive bend sensors, individual static 3D hand models, and all instructional videos used during the data acquisition. Sixty-three participants ranging from age 20 to 80 years performed six repetitions of 40 different naturalistic hand movements at individual paces. This unique database with data recorded from an adult lifespan sample can be used to advance machine-learning approaches in hand kinematic modeling and movement prediction for age-inclusive applications.

Levodopa suppresses grid-like activity and impairs spatial learning in novel environments in healthy young adults.

Accumulated evidence from animal studies suggests a role for the neuromodulator dopamine in memory processes, particularly under conditions of novelty or reward. Our understanding of how dopaminergic modulation impacts spatial representations and spatial memory in humans remains limited. Recent evidence suggests age-specific regulation effects of dopamine pharmacology on activity in the medial temporal lobe, a key region for spatial memory. To which degree this modulation affects spatially patterned medial temporal representations remains unclear. We reanalyzed recent data from a pharmacological dopamine challenge during functional brain imaging combined with a virtual object-location memory paradigm to assess the effect of Levodopa, a dopamine precursor, on grid-like activity in the entorhinal cortex. We found that Levodopa impaired grid cell-like representations in a sample of young adults (n = 55, age = 26-35 years) in a novel environment, accompanied by reduced spatial memory performance. We observed no such impairment when Levodopa was delivered to participants who had prior experience with the task. These results are consistent with a role of dopamine in modulating the encoding of novel spatial experiences. Our results suggest that dopamine signaling may play a larger role in shaping ongoing spatial representations than previously thought.

Phantom Illusion based Vibrotactile Rendering of Affective Touch Patterns.

Physically accurate (authentic) reproduction of affective touch patterns on the forearm is limited by actuator technology. However, in most VR applications a direct comparison with actual touch is not possible. Here, the plausibility is only compared to the user's expectation. Focusing on the approach of plausible instead of authentic touch reproduction enables new rendering techniques, like the utilization of the phantom illusion to create the sensation of moving vibrations. Following this idea, a haptic armband array (4x2 vibrational actuators) was built to investigate the possibilities of recreating plausible affective touch patterns with vibration. The novel aspect of this work is the approach of touch reproduction with a parameterized rendering strategy, enabling the integration in VR. A first user study evaluates suitable parameter ranges for vibrational touch rendering. Duration of vibration and signal shape influence plausibility the most. A second user study found high plausibility ratings in a multimodal scenario and confirmed the expressiveness of the system. Rendering device and strategy are suitable for a various stroking patterns and applicable for emerging research on social affective touch reproduction.

Neural correlates of valence-dependent belief and value updating during uncertainty reduction: An fNIRS study.

Selective use of new information is crucial for adaptive decision-making. Combining a gamble bidding task with assessing cortical responses using functional near-infrared spectroscopy (fNIRS), we investigated potential effects of information valence on behavioral and neural processes of belief and value updating during uncertainty reduction in young adults. By modeling changes in the participants' expressed subjective values using a Bayesian model, we dissociated processes of (i) updating beliefs about statistical properties of the gamble, (ii) updating values of a gamble based on new information about its winning probabilities, as well as (iii) expectancy violation. The results showed that participants used new information to update their beliefs and values about the gambles in a quasi-optimal manner, as reflected in the selective updating only in situations with reducible uncertainty. Furthermore, their updating was valence-dependent: information indicating an increase in winning probability was underweighted, whereas information about a decrease in winning probability was updated in good agreement with predictions of the Bayesian decision theory. Results of model-based and moderation analyses showed that this valence-dependent asymmetry was associated with a distinct contribution of expectancy violation, besides belief updating, to value updating after experiencing new positive information regarding winning probabilities. In line with the behavioral results, we replicated previous findings showing involvements of frontoparietal brain regions in the different components of updating. Furthermore, this study provided novel results suggesting a valence-dependent recruitment of brain regions. Individuals with stronger oxyhemoglobin responses during value updating was more in line with predictions of the Bayesian model while integrating new information that indicates an increase in winning probability. Taken together, this study provides first results showing expectancy violation as a contributing factor to sub-optimal valence-dependent updating during uncertainty reduction and suggests limitations of normative Bayesian decision theory.

Functional Connectivity and Microstructural Network Correlates of Interindividual Variability in Distinct Executive Functions of Healthy Older Adults.

Executive functions, essential for daily life, are known to be impaired in older age. Some executive functions, including working memory updating and value-based decision-making, are specifically sensitive to age-related deterioration. While their neural correlates in young adults are well-described, a comprehensive delineation of the underlying brain substrates in older populations, relevant to identify targets for modulation against cognitive decline, is missing. Here, we assessed letter updating and Markov decision-making task performance to operationalize these trainable functions in 48 older adults. Resting-state functional magnetic resonance imaging was acquired to quantify functional connectivity (FC) in task-relevant frontoparietal and default mode networks. Microstructure in white matter pathways mediating executive functions was assessed with diffusion tensor imaging and quantified by tract-based fractional anisotropy (FA). Superior letter updating performance correlated with higher FC between dorsolateral prefrontal cortex and left frontoparietal and hippocampal areas, while superior Markov decision-making performance correlated with decreased FC between basal ganglia and right angular gyrus. Furthermore, better working memory updating performance was related to higher FA in the cingulum bundle and the superior longitudinal fasciculus. Stepwise linear regression showed that cingulum bundle FA added significant incremental contribution to the variance explained by fronto-angular FC alone. Our findings provide a characterization of distinct functional and structural connectivity correlates associated with performance of specific executive functions. Thereby, this study contributes to the understanding of the neural correlates of updating and decision-making functions in older adults, paving the way for targeted modulation of specific networks by modulatory techniques such as behavioral interventions and non-invasive brain stimulation.

Shorter planning depth and higher response noise during sequential decision-making in old age.

Forward planning is crucial to maximize outcome in complex sequential decision-making scenarios. In this cross-sectional study, we were particularly interested in age-related differences of forward planning. We presumed that especially older individuals would show a shorter planning depth to keep the costs of model-based decision-making within limits. To test this hypothesis, we developed a sequential decision-making task to assess forward planning in younger (age < 40 years; n = 25) and older (age > 60 years; n = 27) adults. By using reinforcement learning modelling, we inferred planning depths from participants' choices. Our results showed significantly shorter planning depths and higher response noise for older adults. Age differences in planning depth were only partially explained by well-known cognitive covariates such as working memory and processing speed. Consistent with previous findings, this indicates age-related shifts away from model-based behaviour in older adults. In addition to a shorter planning depth, our findings suggest that older adults also apply a variety of heuristical low-cost strategies.

Dopamine differentially modulates medial temporal lobe activity and behavior during spatial navigation in young and older adults.

Aging is associated with changes in spatial navigation behavior. In addition to an overall performance decline, older adults tend to rely more on proximal location cue information than on environmental boundary information during spatial navigation compared to young adults. The fact that older adults are more susceptible to errors during spatial navigation might be partly attributed to deficient dopaminergic modulation of hippocampal and striatal functioning. Hence, elevating dopamine levels might differentially modulate spatial navigation and memory performance in young and older adults. In this work, we administered levodopa (L-DOPA) in a double-blind within-subject, placebo-controlled design and recorded functional neuroimaging while young and older adults performed a 3D spatial navigation task in which boundary geometry or the position of a location cue were systematically manipulated. An age by intervention interaction on the neural level revealed an upregulation of brain responses in older adults and a downregulation of responses in young adults within the medial temporal lobe (including hippocampus and parahippocampus) and brainstem, during memory retrieval. Behaviorally, L-DOPA had no effect on older adults' overall memory performance; however, older adults whose spatial memory improved under L-DOPA also showed a shift towards more boundary processing under L-DOPA. In young adults, L-DOPA induced a decline in spatial memory performance in task-naïve participants. These results are consistent with the inverted-U-shaped hypothesis of dopamine signaling and cognitive function and suggest that increasing dopamine availability improves hippocampus-dependent place learning in some older adults.

Digitally embodied lifespan neurocognitive development and Tactile Internet: Transdisciplinary challenges and opportunities.

Mechanisms underlying perceptual processing and inference undergo substantial changes across the lifespan. If utilized properly, technologies could support and buffer the relatively more limited neurocognitive functions in the still developing or aging brains. Over the past decade, a new type of digital communication infrastructure, known as the "Tactile Internet (TI)," is emerging in the fields of telecommunication, sensor and actuator technologies and machine learning. A key aim of the TI is to enable humans to experience and interact with remote and virtual environments through digitalized multimodal sensory signals that also include the haptic (tactile and kinesthetic) sense. Besides their applied focus, such technologies may offer new opportunities for the research tapping into mechanisms of digitally embodied perception and cognition as well as how they may differ across age cohorts. However, there are challenges in translating empirical findings and theories about neurocognitive mechanisms of perception and lifespan development into the day-to-day practices of engineering research and technological development. On the one hand, the capacity and efficiency of digital communication are affected by signal transmission noise according to Shannon's (1949) Information Theory. On the other hand, neurotransmitters, which have been postulated as means that regulate the signal-to-noise ratio of neural information processing (e.g., Servan-Schreiber et al., 1990), decline substantially during aging. Thus, here we highlight neuronal gain control of perceptual processing and perceptual inference to illustrate potential interfaces for developing age-adjusted technologies to enable plausible multisensory digital embodiments for perceptual and cognitive interactions in remote or virtual environments.

Neural evidence for age-related deficits in the representation of state spaces.

Under high cognitive demands, older adults tend to resort to simpler, habitual, or model-free decision strategies. This age-related shift in decision behavior has been attributed to deficits in the representation of the cognitive maps, or state spaces, necessary for more complex model-based decision-making. Yet, the neural mechanisms behind this shift remain unclear. In this study, we used a modified 2-stage Markov task in combination with computational modeling and single-trial EEG analyses to establish neural markers of age-related changes in goal-directed decision-making under different demands on the representation of state spaces. Our results reveal that the shift to simpler decision strategies in older adults is due to (i) impairments in the representation of the transition structure of the task and (ii) a diminished signaling of the reward value associated with decision options. In line with the diminished state space hypothesis of human aging, our findings suggest that deficits in goal-directed, model-based behavior in older adults result from impairments in the representation of state spaces of cognitive tasks.

Congruence-based contextual plausibility modulates cortical activity during vibrotactile perception in virtual multisensory environments.

How congruence cues and congruence-based expectations may together shape perception in virtual reality (VR) still need to be unravelled. We linked the concept of plausibility used in VR research with congruence-based modulation by assessing brain responses while participants experienced vehicle riding experiences in VR scenarios. Perceptual plausibility was manipulated by sensory congruence, with multisensory stimulations confirming with common expectations of road scenes being plausible. We hypothesized that plausible scenarios would elicit greater cortical responses. The results showed that: (i) vibrotactile stimulations at expected intensities, given embedded audio-visual information, engaged greater cortical activities in frontal and sensorimotor regions; (ii) weaker plausible stimulations resulted in greater responses in the sensorimotor cortex than stronger but implausible stimulations; (iii) frontal activities under plausible scenarios negatively correlated with plausibility violation costs in the sensorimotor cortex. These results potentially indicate frontal regulation of sensory processing and extend previous evidence of contextual modulation to the tactile sense.

L-DOPA enhances neural direction signals in younger and older adults.

Previous studies indicate a role of dopamine in spatial navigation. Although neural representations of direction are an important aspect of spatial cognition, it is not well understood whether dopamine directly affects these representations, or only impacts other aspects of spatial brain function. Moreover, both dopamine and spatial cognition decline sharply during age, raising the question which effect dopamine has on directional signals in the brain of older adults. To investigate these questions, we used a double-blind cross-over L-DOPA/Placebo intervention design in which 43 younger and 37 older adults navigated in a virtual spatial environment while undergoing functional magnetic resonance imaging (fMRI). We studied the effect of L-DOPA, a dopamine precursor, on fMRI activation patterns that encode spatial walking directions that have previously been shown to lose specificity with age. This was done in predefined regions of interest, including the early visual cortex, retrosplenial cortex, and hippocampus. Classification of brain activation patterns associated with different walking directions was improved across all regions following L-DOPA administration, suggesting that dopamine broadly enhances neural representations of direction. No evidence for differences between regions was found. In the hippocampus these results were found in both age groups, while in the retrosplenial cortex they were only observed in younger adults. Taken together, our study provides evidence for a link between dopamine and the specificity of neural responses during spatial navigation. SIGNIFICANCE STATEMENT: The sense of direction is an important aspect of spatial navigation, and neural representations of direction can be found throughout a large network of space-related brain regions. But what influences how well these representations track someone's true direction? Using a double-blind cross-over L-DOPA/Placebo intervention design, we find causal evidence that the neurotransmitter dopamine impacts the fidelity of direction selective neural representations in the human hippocampus and retrosplenial cortex. Interestingly, the effect of L-DOPA was either equally present or even smaller in older adults, despite the well-known age related decline of dopamine. These results provide novel insights into how dopamine shapes the neural representations that underlie spatial navigation.

Older adults process the probability of winning sooner but weigh it less during lottery decisions.

Empirical evidence has shown that visually enhancing the saliency of reward probabilities can ease the cognitive demands of value comparisons and improve value-based decisions in old age. In the present study, we used a time-varying drift diffusion model that includes starting time parameters to better understand (1) how increasing the saliency of reward probabilities may affect the dynamics of value-based decision-making and (2) how these effects may interact with age. We examined choices made by younger and older adults in a mixed lottery choice task. On a subset of trials, we used a color-coding scheme to highlight the saliency of reward probabilities, which served as a decision-aid. The results showed that, in control trials, older adults started to consider probability relative to magnitude information sooner than younger adults, but that their evidence accumulation processes were less sensitive to reward probabilities than that of younger adults. This may indicate a noisier and more stochastic information accumulation process during value-based decisions in old age. The decision-aid increased the influence of probability information on evidence accumulation rates in both age groups, but did not alter the relative timing of accumulation for probability versus magnitude in either group.

Incentive motivation improves numerosity discrimination in children and adolescents.

We recently showed that incentive motivation improves the precision of the Approximate Number System (ANS) in young adults. To shed light on the development of incentive motivation, the present study investigated whether this effect and its underlying mechanisms may also be observed in younger samples. Specifically, seven-year-old children (n = 23; 12 girls) and 14-year-old adolescents (n = 30; 15 girls) performed a dot comparison task with monetary reward incentives. Both age groups showed higher accuracy in a reward compared to a neutral condition and, similarly, higher processing efficiency as revealed by the drift rate parameter of the EZ-diffusion model. Furthermore, in line with the Incentive Salience Hypothesis, phasic pupil dilations-indicating the activation of the brain's salience network-were greater in incentivized trials in both age groups. Together these finding suggest that incentive modulation improves numerosity discrimination in children and adolescents by enhancing the perceptual saliency of numerosity information. However, the observed reward anticipation effects were less pronounced in children relative to adolescents. Furthermore, unlike previous findings regarding young adults, the decision thresholds of children and adolescents were not raised by the monetary reward, which may indicate a more protracted development of incentive regulation of response caution than perceptual evidence accumulation.

Analysis of the Clinical Significance and Safety of Interferon in the Treatment of Chronic Myeloproliferative Tumors.

Objective: To investigate the clinical significance and safety of interferon in the treatment of chronic myeloproliferative tumors (MPN). Methods: In this prospective study, a total of 120 patients with advanced chronic MPN admitted to our hospital between April 2016 and August 2020 were assessed for eligibility and recruited, including 62 patients with JAK2V617F mutation-positive ET (ET group) and 58 patients with JAK2V617F mutation-positive PV (PV group). 62 patients with JAK2V617F mutation-positive ET were assigned (1 : 1) to receive interferon-α (IFN-α) or hydroxyurea (HU). A similar subgrouping method for treatment of IFN-α and HU was introduced to patients with JAK2V617F mutation-positive PV. Outcome measures included efficacy and adverse reactions. Results: For patients with JAK2V617F mutation-positive ET and PV, there were no significant differences in the overall response rate between the groups treated with IFN-α or HU (P > 0.05); however, the patients treated with IFN-α had a significantly higher 5-year progression-free survival (PFS) than those treated with HU (P < 0.05). IFN-α was associated with a significantly lower incidence of disease progression, thrombotic events, splenomegaly, myelofibrosis, nausea, and vomiting and a higher incidence of hematological adverse reactions and flu-like symptoms versus HU (P < 0.05). After six months of treatment, the PV group had 12 cases of hematological response both in the IFN-α subgroup and the HU subgroup and fewer PV patients treated with IFN-α required phlebotomy versus those treated with HU (P < 0.05), in which 4 patients in the IFN-α subgroup had no hematological response and 6 patients in the HU subgroup had no hematological response. There was no significant difference in the number of cases with phlebotomy between the two subgroups of PV patients without hematological response (P > 0.05). Conclusion: The use of IFN in the treatment of JAK2V617F mutation-positive ET and PV patients yields a prominent clinical effect by prolonging PFS and avoiding phlebotomy for JAK2V617F mutation-positive PV patients.