Oscillatory Activity In Beta Band Research Articles

D2 receptor antagonist raclopride regulates glutamatergic neuronal activity in the pedunculopontine nucleus in a rat model of Parkinson's disease

Parkinson disease (PD) is defined by the loss of dopamine (DA). Changes in the pedunculopontine nucleus (PPN), particularly in local field potential (LFP), can be attributed to deficits in DA and DA receptor expression levels. PPN is a heterogeneous nucleus consisting of cholinergic, γ-aminobutyric acid (GABAergic), and glutamatergic neurons. However, it is unclear whether low levels of DA receptors affect the activity of different PPN neuron types. We record the neuronal activity of PPN by administering the selective dopamine D1 and D2 receptor antagonists, SCH23390 and Raclopride, respectively. This study discover that the firing rates of glutamatergic neurons could be normalized, and their firing patterns were more consistent in lesioned rats treated with raclopride. Raclopride administration could correct the increased coherence and phase locking between glutamatergic spikes and beta-band oscillatory activity in lesioned rats. Raclopride administration correct the increased coherence and phase locking between glutamatergic spikes and beta-band oscillatory activity in lesioned rats.

Modality-specific frequency band activity during neural entrainment to auditory and visual rhythms.

Rhythm perception depends on the ability to predict the onset of rhythmic events. Previous studies indicate beta band modulation is involved in predicting the onset of auditory rhythmic events (Fujioka et al., 2009, 2012; Snyder & Large, 2005). We sought to determine if similar processes are recruited for prediction of visual rhythms by investigating whether beta band activity plays a role in a modality-dependent manner for rhythm perception. We looked at electroencephalography time-frequency neural correlates of prediction using an omission paradigm with auditory and visual rhythms. By using omissions, we can separate out predictive timing activity from stimulus-driven activity. We hypothesized that there would be modality-independent markers of rhythm prediction in induced beta band oscillatory activity, and our results support this hypothesis. We find induced and evoked predictive timing in both auditory and visual modalities. Additionally, we performed an exploratory-independent components-based spatial clustering analysis, and describe all resulting clusters. This analysis reveals that there may be overlapping networks of predictive beta activity based on common activation in the parietal and right frontal regions, auditory-specific predictive beta in bilateral sensorimotor regions, and visually specific predictive beta in midline central, and bilateral temporal/parietal regions. This analysis also shows evoked predictive beta activity in the left sensorimotor region specific to auditory rhythms and implicates modality-dependent networks for auditory and visual rhythm perception.

Self-Tuning Deep Brain Stimulation Controller for Suppression of Beta Oscillations: Analytical Derivation and Numerical Validation.

Closed-loop control strategies for deep brain stimulation (DBS) in Parkinson's disease offer the potential to provide more effective control of patient symptoms and fewer side effects than continuous stimulation, while reducing battery consumption. Most of the closed-loop methods proposed and tested to-date rely on controller parameters, such as controller gains, that remain constant over time. While the controller may operate effectively close to the operating point for which it is set, providing benefits when compared to conventional open-loop DBS, it may perform sub-optimally if the operating conditions evolve. Such changes may result from, for example, diurnal variation in symptoms, disease progression or changes in the properties of the electrode-tissue interface. In contrast, an adaptive or “self-tuning” control mechanism has the potential to accommodate slowly varying changes in system properties over a period of days, months, or years. Such an adaptive mechanism would automatically adjust the controller parameters to maintain the desired performance while limiting side effects, despite changes in the system operating point. In this paper, two neural modeling approaches are utilized to derive and test an adaptive control scheme for closed-loop DBS, whereby the gain of a feedback controller is continuously adjusted to sustain suppression of pathological beta-band oscillatory activity at a desired target level. First, the controller is derived based on a simplified firing-rate model of the reciprocally connected subthalamic nucleus (STN) and globus pallidus (GPe). Its efficacy is shown both when pathological oscillations are generated endogenously within the STN-GPe network and when they arise in response to exogenous cortical STN inputs. To account for more realistic biological features, the control scheme is then tested in a physiologically detailed model of the cortical basal ganglia network, comprised of individual conductance-based spiking neurons, and simulates the coupled DBS electric field and STN local field potential. Compared to proportional feedback methods without gain adaptation, the proposed adaptive controller was able to suppress beta-band oscillations with less power consumption, even as the properties of the controlled system evolve over time due to alterations in the target for beta suppression, beta fluctuations and variations in the electrode impedance.

A Population Model of Deep Brain Stimulation in Movement Disorders From Circuits to Cells.

For more than 30 years, deep brain stimulation (DBS) has been used to target the symptoms of a number of neurological disorders and in particular movement disorders such as Parkinson’s disease (PD) and essential tremor (ET). It is known that the loss of dopaminergic neurons in the substantia nigra leads to PD, while the exact impact of this on the brain dynamics is not fully understood, the presence of beta-band oscillatory activity is thought to be pathological. The cause of ET, however, remains uncertain, however pathological oscillations in the thalamocortical-cerebellar network have been linked to tremor. Both of these movement disorders are treated with DBS, which entails the surgical implantation of electrodes into a patient’s brain. While DBS leads to an improvement in symptoms for many patients, the mechanisms underlying this improvement is not clearly understood, and computational modeling has been used extensively to improve this. Many of the models used to study DBS and its effect on the human brain have mainly utilized single neuron and single axon biophysical models. We have previously shown in separate models however, that the use of population models can shed much light on the mechanisms of the underlying pathological neural activity in PD and ET in turn, and on the mechanisms underlying DBS. Together, this work suggested that the dynamics of the cerebellar-basal ganglia thalamocortical network support oscillations at frequency range relevant to movement disorders. Here, we propose a new combined model of this network and present new results that demonstrate that both Parkinsonian oscillations in the beta band and oscillations in the tremor frequency range arise from the dynamics of such a network. We find regions in the parameter space demonstrating the different dynamics and go on to examine the transition from one oscillatory regime to another as well as the impact of DBS on these different types of pathological activity. This work will allow us to better understand the changes in brain activity induced by DBS, and allow us to optimize this clinical therapy, particularly in terms of target selection and parameter setting.

The impact of body posture on intrinsic brain activity: The role of beta power at rest.

Tying the hands behind the back has detrimental effects on sensorimotor perceptual tasks. Here we provide evidence that beta band oscillatory activity in a resting state condition might play a crucial role in such detrimental effects. EEG activity at rest was measured from thirty young participants (mean age = 24.03) in two different body posture conditions. In one condition participants were required to keep their hands freely resting on the table. In the other condition, participants’ hands were tied behind their back. Increased beta power was observed in the left inferior frontal gyrus during the tied hands condition compared to the free hands condition. A control experiment ruled out alternative explanations for observed change in beta power, including muscle tension. Our findings provide new insights on how body postural manipulations impact on perceptual tasks and brain activity.

Altered modulation of beta band oscillations during memory encoding is predictive of lower subsequent recognition performance in post-traumatic stress disorder.

We studied the relationship between electrophysiological markers of memory encoding, subsequent recognition performance, and severity of PTSD symptoms in service members with combat exposure (n=40, age: 41.2±7.2 years) and various levels of PTSD symptom severity assessed using the PTSD Check List for DSM V version (PCL-5). Brain activity was recorded using magnetoencephalography during a serial presentation of 86 images of outdoor scenes that were studied by participants for an upcoming recognition test. In a second session, the original images were shown intermixed with an equal number of novel images while participants performed the recognition task. Participants recognized 76.0%±12.1% of the original images and correctly categorized as novel 89.9%±7.0% of the novel images. A negative correlation was present between PCL-5 scores and discrimination performance (Spearman rs=-0.38, p=0.016). PCL-5 scores were also negatively correlated with the recognition accuracy for original images (rs=-0.37, p=0.02). Increases in theta and gamma power and decreases in alpha and beta power were observed over distributed brain networks during memory encoding. Higher PCL-5 scores were associated with less suppression of beta band power in bilateral ventral and medial temporal regions and in the left orbitofrontal cortex. These regions also showed positive correlations between the magnitude of suppression of beta power during encoding and subsequent recognition accuracy. These findings indicate that the lower recognition performance in participants with greater PTSD symptom severity may be due in part to ineffective encoding reflected in altered modulation of beta band oscillatory activity.

Theta-alpha oscillations characterize emotional subregion in the human ventral subthalamic nucleus.

Therapeutic outcomes of STN-DBS for movement and psychiatric disorders depend on electrode location within the STN. Electrophysiological and functional mapping of the STN has progressed considerably in the past years, identifying beta-band oscillatory activity in the dorsal STN as a motor biomarker. It also has been suggested that STN theta-alpha oscillations, involved in impulse control and action inhibition, have a ventral source. However, STN local field potential mapping of motor, associative, and limbic areas is often limited by poor spatial resolution. Providing a high-resolution electrophysiological map of the motor, associative and limbic anatomical sub-areas of the subthalamic nucleus. We have analyzed high-spatial-resolution STN microelectrode electrophysiology recordings of PD patients (n = 303) that underwent DBS surgery. The patients' STN intraoperative recordings of spiking activity (933 electrode trajectories) were combined with their imaging data (n = 83 patients, 151 trajectories). We found a high theta-alpha (7-10 Hz) oscillatory area, located near the STN ventromedial border in 29% of the PD patients. Theta-alpha activity in this area has higher power and lower central frequency in comparison to theta-alpha activity in more dorsal subthalamic areas. When projected on the DISTAL functional atlas, the theta-alpha oscillatory area overlaps with the STN limbic subarea. We suggest that theta-alpha oscillations can serve as an electrophysiological marker for the ventral subthalamic nucleus limbic subarea. Therefore, theta-alpha oscillations can guide optimal electrode placement in neuropsychiatric STN-DBS procedures and provide a reliable biomarker input for future closed-loop DBS device. © 2019 International Parkinson and Movement Disorder Society.

Beta-Band Resonance and Intrinsic Oscillations in a Biophysically Detailed Model of the Subthalamic Nucleus-Globus Pallidus Network.

Increased beta-band oscillatory activity in the basal ganglia network is associated with Parkinsonian motor symptoms and is suppressed with medication and deep brain stimulation (DBS). The origins of the beta-band oscillations, however, remains unclear with both intrinsic oscillations arising within the subthalamic nucleus (STN)—external globus pallidus (GPe) network and exogenous beta-activity, originating outside the network, proposed as potential sources of the pathological activity. The aim of this study was to explore the relative contribution of autonomous oscillations and exogenous oscillatory inputs in the generation of pathological oscillatory activity in a biophysically detailed model of the parkinsonian STN-GPe network. The network model accounts for the integration of synaptic currents and their interaction with intrinsic membrane currents in dendritic structures within the STN and GPe. The model was used to investigate the development of beta-band synchrony and bursting within the STN-GPe network by changing the balance of excitation and inhibition in both nuclei, and by adding exogenous oscillatory inputs with varying phase relationships through the hyperdirect cortico-subthalamic and indirect striato-pallidal pathways. The model showed an intrinsic susceptibility to beta-band oscillations that was manifest in weak autonomously generated oscillations within the STN-GPe network and in selective amplification of exogenous beta-band synaptic inputs near the network's endogenous oscillation frequency. The frequency at which this resonance peak occurred was determined by the net level of excitatory drive to the network. Intrinsic or endogenously generated oscillations were too weak to support a pacemaker role for the STN-GPe network, however, they were considerably amplified by sparse cortical beta inputs and were further amplified by striatal beta inputs that promoted anti-phase firing of the cortex and GPe, resulting in maximum transient inhibition of STN neurons. The model elucidates a mechanism of cortical patterning of the STN-GPe network through feedback inhibition whereby intrinsic susceptibility to beta-band oscillations can lead to phase locked spiking under parkinsonian conditions. These results point to resonance of endogenous oscillations with exogenous patterning of the STN-GPe network as a mechanism of pathological synchronization, and a role for the pallido-striatal feedback loop in amplifying beta oscillations.

Oscillation dynamics in an extended model of thalamic-basal ganglia

The increase in oscillations in beta-band (13–30 Hz) of the basal ganglia (BG) is a hallmark neural dynamic feature of Parkinson’s disease (PD). Physiological studies have shown that striatum microcircuits also play an important role in the pathogenesis of this disease, but the relevant biophysical mechanism still remains unclear. Based on the previous striatal inhibitory model, we propose an extended thalamic-basal ganglia model containing medium spine neurons (MSNs) and fast-spiking interneurons (FSIs). Using this model, we demonstrate here that decreasing M-current conductance of the MSNs results in beta oscillations in the striatum and is transmitted to the globus pallidus pars interna (GPi) neurons through direct and indirect channels. Spectral power of local field potential shows that increased inhibition of GPi and globus pallidus pars externa by striatum also causes oscillatory activity in beta-band of BG, and leads to the bursting oscillations of the GPi neurons. In addition, beta-band oscillations in GPi can emerge because of dopamine depletion. And also, gap junction (GJ) between FSIs regulates the peak activity of GPi neurons through the striatum. Especially, in the Parkinson’s state, removal of GJ can reduce the energy of the beta-band slightly. These results not only highlight the roles of the striatum in controlling but also provide new ideas for studying PD in the future.

Disruption of the Prefrontal Cortex Improves Implicit Contextual Memory-Guided Attention: Combined Behavioral and Electrophysiological Evidence.

Many studies have shown that the dorsolateral prefrontal cortex (DLPFC) plays an important role in top-down cognitive control over intentional and deliberate behavior. However, recent studies have reported that DLPFC-mediated top-down control interferes with implicit forms of learning. Here we used continuous theta-burst stimulation (cTBS) combined with electroencephalography to investigate the causal role of DLPFC in implicit contextual memory-guided attention. We aimed to test whether transient disruption of the DLPFC would interfere with implicit learning performance and related electrical brain activity. We applied neuronavigation-guided cTBS to the DLPFC or to the vertex as a control region prior to the performance of an implicit contextual learning task. We found that cTBS applied over the DLPFC significantly improved performance during implicit contextual learning. We also noted that beta-band (13-19Hz) oscillatory power was reduced at fronto-central channels about 140 to 370ms after visual stimulus onset in cTBS DLPFC compared with cTBS vertex. Taken together, our results provide evidence that DLPFC-mediated top-down control interferes with contextual memory-guided attention and beta-band oscillatory activity.

The Degree of Modulation of Beta Band Activity During Motor Planning Is Related to Trait Impulsivity.

Impulsivity is a prominent personality trait, and a key modulating component of neurologic and psychiatric disorders. How impulsivity is related to the brain mechanisms associated with action planning is poorly understood. Here, we investigated the relation between impulsivity and the modulation of beta band oscillatory activity associated with action planning and execution. Given that beta power decreases during action planning and decreases further during action execution, we hypothesized that during planning the level of beta band power of more impulsive individuals would be closer to the level reached during execution than that of less impulsive individuals. This could explain the tendency to “jump the gun” (commission errors) in high impulsivity. To test this hypothesis, we recruited healthy volunteers (50 participants analyzed) and used the Barratt Impulsiveness Scale questionnaire to evaluate their impulsivity as high or low. We then recorded their brain neuromagnetic signals while they performed an instructed-delay task that induced different levels of action planning by varying the number of spatial cues, hence the uncertainty, about the location of the upcoming target. During the early cue period of the task, we found a posterior (source localized in the occipito-parietal areas) and a left fronto-central group of channels (source localized in the left sensorimotor areas) where beta power was modulated by number of cues, whereas during the late cue period only the left fronto-central group was modulated. We found that the decrease of relative beta band power during action planning in the left fronto-central group of channels was more pronounced in the high impulsivity group than in the low impulsivity group. In addition, we found that the beta band-mediated functional connectivity between the posterior and the left fronto-central groups of channels was weaker in the high impulsivity group than in the low impulsivity group during the early cue period. Furthermore, high impulsives made more commission and movement errors in the task than low impulsives. These results reveal neural mechanisms through which impulsivity affects action planning and open the way for further study of the role of beta band activity in impulsivity, especially in the context of disease and therapeutics.

The Value of Homework: Exposure to Odors in the Home Cage Enhances Odor-Discrimination Learning in Mice.

Perceptual learning is an enhancement in discriminability of similar stimuli following experience with those stimuli. Here, we examined the efficacy of adding additional active training following a standard training session, compared with additional stimulus exposure in the absence of associated task performance. Mice were trained daily in an odor-discrimination task, and then, several hours later each day, received 1 of 3 different manipulations: 1) a second active-training session, 2) non-task-related odor exposure in the home cage, or 3) no second session. For home-cage exposure, odorants were presented in small tubes that mice could sniff and investigate for a similar period of time as in the active discrimination task each day. The results demonstrate that daily home-cage exposure was equivalent to active odor training in supporting improved odor discrimination. Daily home-cage exposure to odorants that did not match those used in the active task did not improve learning, yielding outcomes similar to those obtained with no second session. Piriform cortical local field potential recordings revealed that both sampling in the active learning task and investigation in the home cage evoked similar beta band oscillatory activity. Together the results suggest that odor-discrimination learning can be significantly enhanced by addition of odor exposure outside of the active training task, potentially because of the robust activity evoked in the olfactory system by both exposure paradigms. They further suggest that odorant exposure alone could enhance or maintain odor-discrimination abilities in conditions associated with olfactory impairment, such as aging or dementia.

Striatal Microstimulation Induces Persistent and Repetitive Negative Decision-Making Predicted by Striatal Beta-Band Oscillation

Persistent thoughts inducing irrationally pessimistic and repetitive decisions are often symptoms of mood and anxiety disorders. Regional neural hyperactivities have been associated with these disorders, but it remains unclear whether there is a specific brain region causally involved in these persistent valuations. Here, we identified potential sources of such persistent states by microstimulating the striatum of macaques performing a task by which we could quantitatively estimate their subjective pessimistic states using their choices to accept or reject conflicting offers. We found that this microstimulation induced irrationally repetitive choices with negative evaluations. Local field potentials recorded in the same microstimulation sessions exhibited modulations of beta-band oscillatory activity that paralleled the persistent negative states influencing repetitive decisions. These findings demonstrate that local striatal zones can causally affect subjective states influencing persistent negative valuation and that abnormal beta-band oscillations can be associated with persistency in valuation accompanied by an anxiety-like state.

Spontaneous sensorimotor cortical activity is suppressed by deep brain stimulation in patients with advanced Parkinson’s disease

Advanced Parkinson's disease (PD) is characterized by an excessive oscillatory beta band activity in the subthalamic nucleus (STN). Deep brain stimulation (DBS) of STN alleviates motor symptoms in PD and suppresses the STN beta band activity. The effect of DBS on cortical sensorimotor activity is more ambiguous; both increases and decreases of beta band activity have been reported. Non-invasive studies with simultaneous DBS are problematic due to DBS-induced artifacts. We recorded magnetoencephalography (MEG) from 16 advanced PD patients with and without STN DBS during rest and wrist extension. The strong magnetic artifacts related to stimulation were removed by temporal signal space separation. MEG oscillatory activity at 5–25 Hz was suppressed during DBS in a widespread frontoparietal region, including the sensorimotor cortex identified by the cortico-muscular coherence. The strength of suppression did not correlate with clinical improvement. Our results indicate that alpha and beta band oscillations are suppressed at the frontoparietal cortex by STN DBS in PD.

Neuronal beta band oscillatory activity in the basal ganglia reflecting rigidity in Parkinson’s disease patients

Neuronal beta band oscillatory activity in the basal ganglia reflecting rigidity in Parkinson’s disease patients

A platform for long-term monitoring the deep brain rhythms

Deep brain stimulation (DBS) provides a valuable platform for recording local field potentials (LFP) during surgery for studying the mechanisms of brain diseases and DBS therapy. Long-term neural activity monitoring remains a necessity for research on some neurodegenerative disorders and closed-loop DBS systems. A neurostimulator with recording ability has been developed as a research tool and a medical device. This study investigates the feasibility of chronic electrophysiological studies using neurostimulator (model G102RS) for recording LFP. Recent studies have suggested that oscillatory beta band activity can be used as a biomarker of Parkinson’s disease (PD). Here, subthalamic LFP recordings were obtained from (i) a group of PD patients undergoing DBS therapy, (ii) the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned monkey model of PD, and (iii) a PD patient with an implanted neurostimulator. A total of 55/60 LFP datasets measured from the PD patients at rest during the operation contained spectral peaks in beta band as pathophysiological oscillations. These oscillations were strongly suppressed during DBS. The long-term animal experiment and the clinical implant demonstrated that the G102RS can adequately record the long-term frequency band-specific amplitude fluctuations such as the beta band activity. The device could identify the suppression of the beta band activity during DBS. Together, these data demonstrate the use of this medical device for chronic electrophysiological studies.

Beta- and gamma-band activity reflect predictive coding in the processing of causal events.

In daily life, complex events are perceived in a causal manner, suggesting that the brain relies on predictive processes to model them. Within predictive coding theory, oscillatory beta-band activity has been linked to top-down predictive signals and gamma-band activity to bottom-up prediction errors. However, neurocognitive evidence for predictive coding outside lower-level sensory areas is scarce. We used magnetoencephalography to investigate neural activity during probability-dependent action perception in three areas pivotal for causal inference, superior temporal sulcus, temporoparietal junction and medial prefrontal cortex, using bowling action animations. Within this network, Granger-causal connectivity in the beta-band was found to be strongest for backward top-down connections and gamma for feed-forward bottom-up connections. Moreover, beta-band power in TPJ increased parametrically with the predictability of the action kinematics-outcome sequences. Conversely, gamma-band power in TPJ and MPFC increased with prediction error. These findings suggest that the brain utilizes predictive-coding-like computations for higher-order cognition such as perception of causal events.

Deep Brain Recordings Using an Implanted Pulse Generator in Parkinson's Disease.

Recent studies suggest that oscillatory beta activity could be used as a state biomarker in patients with Parkinson's disease for subthalamic closed-loop stimulation with the intention of improving clinical benefit. Here we investigate the feasibility of subthalamic recordings via a novel chronically implanted pulse generator. Subthalamic local field potential recordings were obtained from eight patients before and during deep brain stimulation (DBS). All data were analyzed in the frequency domain using Fourier transform-based methods and compared between ON and OFF stimulation conditions. Distinct peaks of oscillatory beta band activity were found in 12 of 15 electrodes. DBS induced a significant frequency specific suppression of oscillatory beta activity (p = 0.002). The results of the study suggest that oscillatory beta band synchronization and its modulation by DBS is recordable with a system suitable for chronic implantation and may serve as a biomarker for subthalamic closed-loop stimulation in patients with Parkinson's disease.

V44. Spatially distinct cortico-thalamic networks identified by parallel iEEG and MEG recordings in patients with tremor

Question The ventral intermediate nucleus region (VIMr) of the ventrolateral thalamus and the caudal Zona Incerta (cZi) are established targets for deep brain stimulation (DBS) therapy of medication refractory tremor. While the mechanism of action of DBS remains elusive, evidence points to a modulation of a coordinated network of oscillations. Distinct oscillatory activity patterns may allow large scale interactions between different neural structures. Aberrant activity patterns in these oscillatory networks can lead to the manifestation of specific symptoms, such as tremor, that can be treated with DBS. To characterize the oscillatory cortico-thalamic network we performed simultaneous magnetoencephalographic (MEG) and local field potential (LFP) recordings from the VIMr and cZi DBS electrodes in 10 patients (age: 59 ± 2.7 years) with tremor (6 Parkinson’s disease, 3 essential tremor, 1 orthostatic tremor). Methods Simultaneous MEG-LFP recordings were conducted with the patients at rest with eyes open. LFPs were recorded bipolarly from adjacent contact pairs of the DBS electrodes. The lowermost contact pair was targeted at the cZi (01), while the two upper (12, 23) contact pairs targeted at the VIMr. Dynamic imaging of coherent sources (DICS) beamforming was utilized to visualize peaks of frequency specific cortico-thalamic coherence in Montreal Neurological Institute (MNI) space. Significant clusters were identified using Statistical Parametric Mapping (SPM, FWE corrected threshold p Results Two spatially distinct beta band (13–30 Hz) clusters of cortico-subcortical oscillatory network activity were found for the cZi and VIMr contact pairs, respectively. Coupling of oscillatory beta band activity from the cZi was focally localized in the central cerebellum. In contrast, cortico-thalamic beta band coupling was localized in the motor cortex. No significant clusters were found for the alpha band (7–13 Hz). Conclusions Our results suggest a motor network characterized by beta band coherence between the VIMr and motor cortex and between the cZi and the Cerebellum. These findings extend previous reports on cortico-thalamic LFP-EEG coherence from patients with tremor to a cerebellar connection with the cZi. The reported results are in line with findings from cortico-muscular coherence, FDG-PET and resting state fMRI studies that propose the motor cortex, cerebellum and VIMr as key structures in the tremor network.

Modulation of Beta-Band Activity in the Subgenual Anterior Cingulate Cortex during Emotional Empathy in Treatment-Resistant Depression.

Deep brain stimulation (DBS) is a promising approach in treatment-resistant depression (TRD). TRD is associated with problems in interpersonal relationships, which might be linked to impaired empathy. Here, we investigate the influence of DBS in the subgenual anterior cingulate cortex (sgACC) on empathy in patients with TRD and explore the pattern of oscillatory sgACC activity during performance of the multifaceted empathy test. We recorded local field potential activity directly from sgACC via DBS electrodes in patients. Based on previous behavioral findings, we expected disrupted empathy networks. Patients showed increased empathic involvement ratings toward negative stimuli as compared with healthy subjects that were significantly reduced after 6 months of DBS. Stimulus-related oscillatory activity pattern revealed a broad desynchronization in the beta (14-35 Hz) band that was significantly larger during patients' reported emotional empathy for negative stimuli than when patients reported to have no empathy. Beta desynchronization for empathic involvement correlated with self-reported severity of depression. Our results indicate a "negativity bias" in patients that can be reduced by DBS. Moreover, direct recordings show activation of the sgACC area during emotional processing and propose that changes in beta-band oscillatory activity in the sgACC might index empathic involvement of negative emotion in TRD.