Prefrontal Gamma Research Articles

Causal functional maps of brain rhythms in working memory

Human working memory is a key cognitive process that engages multiple functional anatomical nodes across the brain. Despite a plethora of correlative neuroimaging evidence regarding the working memory architecture, our understanding of critical hubs causally controlling overall performance is incomplete. Causal interpretation requires cognitive testing following safe, temporal, and controllable neuromodulation of specific functional anatomical nodes. Such experiments became available in healthy humans with the advance of transcranial alternating current stimulation (tACS). Here, we synthesize findings of 28 placebo-controlled studies (in total, 1,057 participants) that applied frequency-specific noninvasive stimulation of neural oscillations and examined working memory performance in neurotypical adults. We use a computational meta-modeling method to simulate each intervention in realistic virtual brains and test reported behavioral outcomes against the stimulation-induced electric fields in different brain nodes. Our results show that stimulating anterior frontal and medial temporal theta oscillations and occipitoparietal gamma rhythms leads to significant dose-dependent improvement in working memory task performance. Conversely, prefrontal gamma modulation is detrimental to performance. Moreover, we found distinct spatial expression of theta subbands, where working memory changes followed orbitofrontal high-theta modulation and medial temporal low-theta modulation. Finally, all these results are driven by changes in working memory accuracy rather than processing time measures. These findings provide a fresh view of the working memory mechanisms, complementary to neuroimaging research, and propose hypothesis-driven targets for the clinical treatment of working memory deficits.

Inhibition of fatty acid amide hydrolase reverses aberrant prefrontal gamma oscillations in the sub-chronic PCP model for schizophrenia.

Hypofunctioning of NMDA receptors, and the resulting shift in the balance between excitation and inhibition, is considered a key process in the pathophysiology of schizophrenia. One important manifestation of this phenomenon is changes in neural oscillations, those above 30Hz (i.e., gamma-band oscillations), in particular. Although both preclinical and clinical studies observed increased gamma activity following acute administration of NMDA receptor antagonists, the relevance of this phenomenon has been recently questioned given the reduced gamma oscillations typically observed during sensory and cognitive tasks in schizophrenia. However, there is emerging, yet contradictory, evidence for increased spontaneous gamma-band activity (i.e., at rest or under baseline conditions). Here, we use the sub-chronic phencyclidine (PCP) rat model for schizophrenia, which has been argued to model the pathophysiology of schizophrenia more closely than acute NMDA antagonism, to investigate gamma oscillations (30-100Hz) in the medial prefrontal cortex of anesthetized animals. While baseline gamma oscillations were not affected, oscillations induced by train stimulation of the posterior dorsal CA1 (pdCA1) field of the hippocampus were enhanced in PCP-treated animals (5mg/kg, twice daily for 7days, followed by a 7-day washout period). This effect was reversed by pharmacological enhancement of endocannabinoid levels via systemic administration of URB597 (0.3mg/kg), an inhibitor of the catabolic enzyme of the endocannabinoid anandamide. Intriguingly, the pharmacological blockade of CB1 receptors by AM251 unmasked a reduced gamma oscillatory activity in PCP-treated animals. The findings are consistent with the observed effects of URB597 and AM251 on behavioral deficits reminiscent of the symptoms of schizophrenia and further validate the potential for cannabinoid-based drugs as a treatment for schizophrenia.

Behavioral State-Dependent Modulation of Prefrontal Cortex Activity by Respiration.

Respiration-rhythmic oscillations in the local field potential emerge in the mPFC, a cortical region with a key role in the regulation of cognitive and emotional behavior. Respiration-driven rhythms coordinate local activity by entraining fast γ oscillations as well as single-unit discharges. To what extent respiration entrainment differently engages the mPFC network in a behavioral state-dependent manner, however, is not known. Here, we compared the respiration entrainment of mouse PFC local field potential and spiking activity (23 male and 2 female mice) across distinct behavioral states: during awake immobility in the home cage (HC), during passive coping in response to inescapable stress under tail suspension (TS), and during reward consumption (Rew). Respiration-driven rhythms emerged during all three states. However, prefrontal γ oscillations were more strongly entrained by respiration during HC than TS or Rew. Moreover, neuronal spikes of putative pyramidal cells and putative interneurons showed significant respiration phase-coupling throughout behaviors with characteristic phase preferences depending on the behavioral state. Finally, while phase-coupling dominated in deep layers in HC and Rew conditions, TS resulted in the recruitment of superficial layer neurons to respiration. These results jointly suggest that respiration dynamically entrains prefrontal neuronal activity depending on the behavioral state.SIGNIFICANCE STATEMENT The mPFC, through its extensive connections (e.g., to the amygdala, the striatum, serotoninergic and dopaminergic nuclei), flexibly regulates cognitive behaviors. Impairment of prefrontal functions can lead to disease states, such as depression, addiction, or anxiety disorders. Deciphering the complex regulation of PFC activity during defined behavioral states is thus an essential challenge. Here, we investigated the role of a prefrontal slow oscillation that has recently attracted rising interest, the respiration rhythm, in modulating prefrontal neurons during distinct behavioral states. We show that prefrontal neuronal activity is differently entrained by the respiration rhythm in a cell type- and behavior-dependent manner. These results provide first insight into the complex modulation of prefrontal activity patterns by rhythmic breathing.

Neuronal selectivity for stimulus information determines prefrontal LFP gamma power regardless of task execution

Local field potential (LFP) power in the gamma frequency is modulated by cognitive variables during task execution. We sought to examine whether such modulations only emerge when task rules are established. We therefore analyzed neuronal firing and LFPs in different prefrontal subdivisions before and after the same monkeys were trained to perform cognitive tasks. Prior to task rule learning, sites containing neurons selective for stimuli already exhibited increased gamma power during and after the passive viewing of stimuli compared to the baseline period. Unexpectedly, when the same monkeys learned to maintain these stimuli in working memory, the elevation of gamma power above the baseline was diminished, despite an overall increase in firing rate. Learning and executing the task further decoupled LFP power from single neuron firing. Gamma power decreased at the time when subjects needed to make a judgment about whether two stimuli were the same or not, and differential gamma power was observed for matching and nonmatching stimuli. Our results indicate that prefrontal gamma power emerges spontaneously, not necessarily tied to a cognitive task being executed.

The role of optogenetic stimulations of parvalbumin-positive interneurons in the prefrontal cortex and the ventral hippocampus on an acute MK-801 model of schizophrenia-like cognitive inflexibility

Schizophrenia research has increased in recent decades and focused more on its neural basis. Decision-making and cognitive flexibility are the main cognitive functions that are impaired and considered schizophrenia endophenotypes. Cognitive impairment was recently connected with altered functions of N-methyl-d-aspartate (NMDAR) glutamatergic receptors, which increased cortical activity. Selective NMDAR antagonists, such as MK-801, have been used to model cognitive inflexibility in schizophrenia. Decreased GABAergic inhibitory activity has been shown elsewhere with enhanced cortical activity. This imbalance in the excitatory/inhibitory may reduce the entrainment of prefrontal gamma and hippocampal theta rhythms and result in gamma/theta band de-synchronization.The current study established an acute MK-801 administration model of schizophrenia-like cognitive inflexibility in rats and used the attentional set-shifting task in which rats learned to switch/reverse the relevant rule. During the task, we used in vivo optogenetic stimulations of parvalbumin-positive interneurons at specific light pulses in the prefrontal cortex and ventral hippocampus.The first experiments showed that acute dizocilpine in rats produced schizophrenia-like cognitive inflexibility. The second set of experiments demonstrated that specific optogenetic stimulation at specific frequencies of parvalbumin-positive interneurons in the prefrontal cortex and ventral hippocampus rescued the cognitive flexibility rats that received acute MK-801.These findings advance our knowledge of the pivotal role of parvalbumin interneurons in schizophrenia-like cognitive impairment and may guide further research on this severe psychiatric disorder.

The Relation Between the Power of Prefrontal Gamma in Rest-state EEG Under Normal Sleep and Reactive Aggression Behaviour After Sleep Deprivation.

Whether sleep deprivation affects aggressive behaviour is still under debate. The present study examined the influence of individual differences in reactive aggressive behaviour after sleep deprivation and preliminarily explored an electrophysiological marker to identify individuals with more aggressive behaviour after sleep deprivation. Thirty participants performed the Taylor Aggression Paradigm task under two sleep conditions: normal sleep (NS, one night of regular sleep) and total sleep deprivation (SD, 30h of wakefulness), and 5-minute resting-state electroencephalogram (EEG) acquisition was completed under the NS condition. The results found that although sleep deprivation did not have significant effects on aggressive behaviour in the overall analysis, the participants can be classified as an increased group (n = 16) and a no-increased group (n = 14) by different changes in the two sleep conditions (SD-NS). In addition, prefrontal gamma (γ) power was significantly lower in the increased group than in the no-increased group, which may reflect the difference in ability on inhibition. Furthermore, more critical is that γ power was significantly negatively correlated with change in the reactive aggressive behaviour. These results indicate that the effect of SD on reactive aggression varies between individuals, and prefrontal γ power may be an effective electrophysiological marker for identifying people at risk of aggressive behaviour after SD.

Gamma Transcranial Alternating Current Stimulation Improves Craving and Cognition in Patients with Alcohol Use Disorder: An Open Label Pilot Study

Objective: Alcohol use disorder (AUD) is one of the most common psychiatric disorders worldwide. It often shows a chronic course, and pharmacological treatment is rather ineffective for maintaining abstinence. New non-invasive brain stimulation techniques could help to improve AUD symptoms by rebalancing and synchronizing the disturbed prefrontal brain function and thus reduce craving. This study aims at evaluating the use of gamma transcranial alternating current stimulation to improve clinical und neuropsychological symptoms in patients with AUD.
 Methods: In this small open label study, six patients suffering from AUD for several years underwent treatment with prefrontal gamma transcranial alternating current stimulation for 10 min twice daily respectively 20 min once per day for 10 days. Clinical and neuropsychological tests as well as craving were assessed over the course of treatment.
 Results: Scores of the Alcohol Craving Questionnaire decreased in all patients and cognitive functions assessed by word fluency and computer-based n-back test improved.
 Conclusions: This new non-invasive brain stimulation technique could be of interest in treating craving symptoms and in maintaining abstinence.

Synaptic Variability and Cortical Gamma Oscillation Power in Schizophrenia.

Cognitive impairments in schizophrenia are associated with lower gamma oscillation power in the prefrontal cortex (PFC). Gamma power depends in part on excitatory drive to fast-spiking parvalbumin interneurons (PVIs). Excitatory drive to cortical neurons varies in strength, which could affect how these neurons regulate network oscillations. The authors investigated whether variability in excitatory synaptic strength across PVIs could contribute to lower prefrontal gamma power in schizophrenia. In postmortem PFC from 20 matched pairs of comparison and schizophrenia subjects, levels of vesicular glutamate transporter 1 (VGlut1) and postsynaptic density 95 (PSD95) proteins were quantified to assess variability in excitatory synaptic strength across PVIs. A computational model network was then used to simulate how variability in excitatory synaptic strength across fast-spiking (a defining feature of PVIs) interneurons (FSIs) regulates gamma power. The variability of VGlut1 and PSD95 levels at excitatory inputs across PVIs was larger in schizophrenia relative to comparison subjects. This alteration was not influenced by schizophrenia-associated comorbid factors, was not present in monkeys chronically exposed to antipsychotic medications, and was not present in calretinin interneurons. In the model network, variability in excitatory synaptic strength across FSIs regulated gamma power by affecting network synchrony. Finally, greater synaptic variability interacted synergistically with other synaptic alterations in schizophrenia (i.e., fewer excitatory inputs to FSIs and lower inhibitory strength from FSIs) to robustly reduce gamma power. The study findings suggest that greater variability in excitatory synaptic strength across PVIs, in combination with other modest synaptic alterations in these neurons, can markedly lower PFC gamma power in schizophrenia.

Investigating the Effects of Auditory and Vibrotactile Rhythmic Sensory Stimulation on Depression: An EEG Pilot Study.

BackgroundMajor depressive disorder (MDD) is a persistent psychiatric condition and one of the leading causes of global disease burden. In a previous study, we investigated the effects of a five-week intervention consisting of rhythmic gamma frequency (30-70 Hz) vibroacoustic stimulation in 20 patients formally diagnosed with MDD. In that study, the findings suggested a significant clinical improvement in depression symptoms as measured using the Montgomery-Asberg Depression Rating Scale (MADRS), with 37% of participants meeting the criteria for clinical response. The goal of the present research was to examine possible changes from baseline to posttreatment in resting-state electroencephalography (EEG) recordings using the same treatment protocol and to characterize basic changes in EEG related to treatment response.Materials and methodsThe study sample consisted of 19 individuals aged 18-70 years with a clinical diagnosis of MDD. The participants were assessed before and after a five-week treatment period, which consisted of listening to an instrumental musical track on a vibroacoustic device, delivering auditory and vibrotactile stimulus in the gamma-band range (30-70 Hz, with particular emphasis on 40 Hz). The primary outcome measure was the change in Montgomery-Asberg Depression Rating Scale (MADRS) from baseline to posttreatment and resting-state EEG.ResultsAnalysis comparing MADRS score at baseline and post-intervention indicated a significant change in the severity of depression symptoms after five weeks (t = 3.9923, df = 18, p = 0.0009). The clinical response rate was 36.85%. Resting-state EEG power analysis revealed a significant increase in occipital alpha power (t = -2.149, df = 18, p = 0.04548), as well as an increase in the prefrontal gamma power of the responders (t = 2.8079, df = 13.431, p = 0.01442).ConclusionsThe results indicate that improvements in MADRS scores after rhythmic sensory stimulation (RSS) were accompanied by an increase in alpha power in the occipital region and an increase in gamma in the prefrontal region, thus suggesting treatment effects on cortical activity in depression. The results of this pilot study will help inform subsequent controlled studies evaluating whether treatment response to vibroacoustic stimulation constitutes a real and replicable reduction of depressive symptoms and to characterize the underlying mechanisms.

Prefrontal gamma power and LFP tuning in working memory decrease during monkey adolescent development

Prefrontal gamma power and LFP tuning in working memory decrease during monkey adolescent development

Synaptic Variability Regulates Cortical Gamma Oscillation Power in Schizophrenia

Cortical neurons receive excitatory drive of variable strength, which could affect how these neurons regulate network behavior during oscillatory activity. Prefrontal gamma oscillations require excitatory drive to parvalbumin interneurons and alterations in these synaptic inputs might contribute to lower prefrontal gamma power in schizophrenia. Here, we utilized computational modeling and empirical measures in human prefrontal cortex to investigate how variability in excitatory synaptic strength across parvalbumin interneurons could contribute to lower gamma power in schizophrenia.

The Effectiveness of a Video Intervention According to Distress Levels - Differences in Psychophysiological Indicators -

본 연구는 디스트레스 수준에 따른 영상 처치의 심리적 안정화 효과성 차이를 검증하였다. 이를 위해 대학생 21명을 단일경관과 복합경관 영상 집단에 무선할당하고 영상 처치 후 심리생리적 지표(정적 및 부적정서, 상태불안, EEG)를 측정하였다. 이후 각 영상 주제 내 디스트레스 수준에 따라 영상 처치에 따른 심리생리적 반응 변화가 유의한지 통계검증하였다. 그 결과 모든 영상 집단 내고 디스트레스군은 처치에 따른 부적정서가 감소하였고 상태불안은 복합경관 처치 후 감소하였다. 반면 저 디스트레스 군에서는 정서 변화가 유의하지 않았다. 단일경관 고 디스트레스군의 경우, 우측 전두엽, 측두엽, 좌측 전전두엽의 감마파가 증가했지만 우측 전전두엽 감마파는 감소했다. 복합경관고 디스트레스군의 좌측 전전두엽 베타파는 증가, 우측 전두엽 세타파는 감소했다. 이로써 영상 처치후 모든 디스트레스 수준에서 인지적 처리수준이 증가했다. 이에 따라 높은 디스트레스 수준에서 영상에 따른 부정적 정서조절의 효과성이 검증되었다.This study is to examine if the populations with different distress levels can gain different psychological stabilization benefits from the video intervention. The study randomly assigned 21 university students to two intervention arms(Only and Mix) and psychophysiological indicators were measured before and after video stimuli. Then, psychophysiological responses were analyzed to verify if there are any significant changes in the key variables. The analysis discovered that the negative affect decreased in the high-distress population of the Only and Mix arms and state anxiety dropped after the Mix intervention. However, the low-distress populations in both arms did not show significant changes in affect. In the high-distress population of the Only arm, gamma waves at the left prefrontal, right frontal and temporal lobe increased, while right prefrontal gamma waves decreased. The high-distress subjects of the Mix arm showed an increase in beta waves at the left prefrontal, while the right frontal theta waves decreased. In conclusion, it was verified that the video interventions can boost cognitive processing regardless of the distress level, and the video invention can be effective in regulating the negative affect in the high-distress population.

Gamma activity accelerates during prefrontal development.

Gamma oscillations are a prominent activity pattern in the cerebral cortex. While gamma rhythms have been extensively studied in the adult prefrontal cortex in the context of cognitive (dys)functions, little is known about their development. We addressed this issue by using extracellular recordings and optogenetic stimulations in mice across postnatal development. We show that fast rhythmic activity in the prefrontal cortex becomes prominent during the second postnatal week. While initially at about 15 Hz, fast oscillatory activity progressively accelerates with age and stabilizes within gamma frequency range (30-80 Hz) during the fourth postnatal week. Activation of layer 2/3 pyramidal neurons drives fast oscillations throughout development, yet the acceleration of their frequency follows similar temporal dynamics as the maturation of fast-spiking interneurons. These findings uncover the development of prefrontal gamma activity and provide a framework to examine the origin of abnormal gamma activity in neurodevelopmental disorders.

Frontal Brain Asymmetry and Willingness to Pay.

Consumers frequently make decisions about how much they are willing to pay (WTP) for specific products and services, but little is known about the neural mechanisms underlying such calculations. In this study, we were interested in testing whether specific brain activation—the asymmetry in engagement of the prefrontal cortex—would be related to consumer choice. Subjects saw products and subsequently decided how much they were willing to pay for each product, while undergoing neuroimaging using electroencephalography. Our results demonstrate that prefrontal asymmetry in the gamma frequency band, and a trend in the beta frequency band that was recorded during product viewing was significantly related to subsequent WTP responses. Frontal asymmetry in the alpha band was not related to WTP decisions. Besides suggesting separate neuropsychological mechanisms of consumer choice, we find that one specific measure—the prefrontal gamma asymmetry—was most strongly related to WTP responses, and was most coupled to the actual decision phase. These findings are discussed in light of the psychology of WTP calculations, and in relation to the recent emergence of consumer neuroscience and neuromarketing.

Locus coeruleus phasic discharge is essential for stimulus-induced gamma oscillations in the prefrontal cortex.

The locus coeruleus (LC) noradrenergic (NE) neuromodulatory system is critically involved in regulation of neural excitability via its diffuse ascending projections. Tonic NE release in the forebrain is essential for maintenance of vigilant states and increases the signal-to-noise ratio of cortical sensory responses. The impact of phasic NE release on cortical activity and sensory processing is less explored. We previously reported that LC microstimulation caused a transient desynchronization of population activity in the medial prefrontal cortex (mPFC), similar to noxious somatosensory stimuli. The LC receives nociceptive information from the medulla and therefore may mediate sensory signaling to its forebrain targets. Here we performed extracellular recordings in LC and mPFC while presenting noxious stimuli in urethane-anesthetized rats. A brief train of foot shocks produced a robust phasic response in the LC and a transient change in the mPFC power spectrum, with the strongest modulation in the gamma (30-90 Hz) range. The LC phasic response preceded prefrontal gamma power increase, and cortical modulation was proportional to the LC excitation. We also quantitatively characterized distinct cortical states and showed that sensory responses in both LC and mPFC depend on the ongoing cortical state. Finally, cessation of the LC firing by bilateral local iontophoretic injection of clonidine, an α2-adrenoreceptor agonist, completely eliminated sensory responses in the mPFC without shifting cortex to a less excitable state. Together, our results suggest that the LC phasic response induces gamma power increase in the PFC and is essential for mediating sensory information along an ascending noxious pathway. NEW & NOTEWORTHY Our study shows linear relationships between locus coeruleus phasic excitation and the amplitude of gamma oscillations in the prefrontal cortex. Results suggest that the locus coeruleus phasic response is essential for mediating sensory information along an ascending noxious pathway.

Language Prediction Is Reflected by Coupling between Frontal Gamma and Posterior Alpha Oscillations.

Readers and listeners actively predict upcoming words during language processing. These predictions might serve to support the unification of incoming words into sentence context and thus rely on interactions between areas in the language network. In the current magnetoencephalography study, participants read sentences that varied in contextual constraints so that the predictability of the sentence-final words was either high or low. Before the sentence-final words, we observed stronger alpha power suppression for the highly compared with low constraining sentences in the left inferior frontal cortex, left posterior temporal region, and visual word form area. Importantly, the temporal and visual word form area alpha power correlated negatively with left frontal gamma power for the highly constraining sentences. We suggest that the correlation between alpha power decrease in temporal language areas and left prefrontal gamma power reflects the initiation of an anticipatory unification process in the language network.

Organization of prefrontal network activity by respiration-related oscillations

The medial prefrontal cortex (mPFC) integrates information from cortical and sub-cortical areas and contributes to the planning and initiation of behaviour. A potential mechanism for signal integration in the mPFC lies in the synchronization of neuronal discharges by theta (6–12 Hz) activity patterns. Here we show, using in vivo local field potential (LFP) and single-unit recordings from awake mice, that prominent oscillations in the sub-theta frequency band (1–5 Hz) emerge during awake immobility in the mPFC. These oscillation patterns are distinct from but phase-locked to hippocampal theta activity and occur synchronized with nasal respiration (hence termed prefrontal respiration rhythm [PRR]). PRR activity modulates the amplitude of prefrontal gamma rhythms with greater efficacy than theta oscillations. Furthermore, single-unit discharges of putative pyramidal cells and GABAergic interneurons are entrained by prefrontal PRR and nasal respiration. Our data thus suggest that PRR activity contributes to information processing in the prefrontal neuronal network.

Sex differences in learned fear expression and extinction involve altered gamma oscillations in medial prefrontal cortex

Sex differences in learned fear expression and extinction involve the medial prefrontal cortex (mPFC). We recently demonstrated that enhanced learned fear expression during auditory fear extinction and its recall is linked to persistent theta activation in the prelimbic (PL) but not infralimbic (IL) cortex of female rats. Emerging evidence indicates that gamma oscillations in mPFC are also implicated in the expression and extinction of learned fear. Therefore we re-examined our in vivo electrophysiology data and found that females showed persistent PL gamma activation during extinction and a failure of IL gamma activation during extinction recall. Altered prefrontal gamma oscillations thus accompany sex differences in learned fear expression and its extinction. These findings are relevant for understanding the neural basis of post-traumatic stress disorder, which is more prevalent in women and involves impaired extinction and mPFC dysfunction.

Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons.

SummaryAbnormalities in prefrontal GABAergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to maternal immune activation, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders.

Individual differences and specificity of prefrontal gamma frequency-tACS on fluid intelligence capabilities

Emerging evidence suggests that transcranial alternating current stimulation (tACS) is an effective, frequency-specific modulator of endogenous brain oscillations, with the potential to alter cognitive performance. Here, we show that reduction in response latencies to solve complex logic problem indexing fluid intelligence is obtained through 40 Hz-tACS (gamma band) applied to the prefrontal cortex. This improvement in human performance depends on individual ability, with slower performers at baseline receiving greater benefits. The effect could have not being explained by regression to the mean, and showed task and frequency specificity: it was not observed for trials not involving logical reasoning, as well as with the application of low frequency 5 Hz-tACS (theta band) or non-periodic high frequency random noise stimulation (101–640 Hz). Moreover, performance in a spatial working memory task was not affected by brain stimulation, excluding possible effects on fluid intelligence enhancement through an increase in memory performance. We suggest that such high-level cognitive functions are dissociable by frequency-specific neuromodulatory effects, possibly related to entrainment of specific brain rhythms. We conclude that individual differences in cognitive abilities, due to acquired or developmental origins, could be reduced during frequency-specific tACS, a finding that should be taken into account for future individual cognitive rehabilitation studies.