If humans are faced with difficult choices when making decisions, the ability to slow down responses becomes critical in order to avoid suboptimal choices. Current models of decision making assume ...that the subthalamic nucleus (STN) mediates this function by elevating decision thresholds, thereby requiring more evidence to be accumulated before responding 1–9. However, direct electrophysiological evidence for the exact role of STN during adjustment of decision thresholds is lacking. Here, we show that trial-by-trial variations in STN low-frequency oscillatory activity predict adjustments of decision thresholds before subjects make a response. The relationship between STN activity and decision thresholds critically depends on the subjects’ level of cautiousness. While increased oscillatory activity of the STN predicts elevated decision thresholds during high levels of cautiousness, it predicts decreased decision thresholds during low levels of cautiousness. This context-dependent relationship may be mediated by increased influence of the medial prefrontal cortex (mPFC)-STN pathway on decision thresholds during high cautiousness. Subjects who exhibit a stronger increase in phase alignment of low-frequency oscillatory activity in mPFC and STN before making a response have higher decision thresholds and commit fewer erroneous responses. Together, our results demonstrate that STN low-frequency oscillatory activity and corresponding mPFC-STN coupling are involved in determining how much evidence subjects accumulate before making a decision. This finding might explain why deep-brain stimulation of the STN can impair subjects’ ability to slow down responses and can induce impulsive suboptimal decisions.
•Subjects make a choice when the integrated evidence crosses a “decision threshold”•Such thresholds are reflected by 2- to 8-Hz oscillations in the subthalamic nucleus•The relationship between decision thresholds and STN activity is context dependent•This is mediated by altered prefrontal-STN coupling during high cautiousness
In this article, Herz et al. show that decision thresholds in humans are modulated by subthalamic low-frequency oscillatory activity. This relationship depends on the subjects’ level of cautiousness, which is mediated by increased influence of the medial prefrontal cortex-subthalamic pathway on decision thresholds when caution is required.
Objective
Brain–computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide ...proof‐of‐principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS.
Methods
We tested BCI‐controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale.
Results
Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation.
Interpretation
BCI‐controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Ann Neurol 2013;74:449–457
Making the right decision from conflicting information takes time. Recent computational, electrophysiological, and clinical studies have implicated two brain areas as being crucial in assuring ...sufficient time is taken for decision-making under conditions of conflict: the medial prefrontal cortex and the subthalamic nucleus (STN). Both structures exhibit an elevation of activity at low frequencies (<10 Hz) during conflict that correlates with the amount of time taken to respond. This suggests that the two sites could become functionally coupled during conflict. To establish the nature of this interaction we recorded from deep-brain stimulation electrodes implanted bilaterally in the STN of 13 Parkinson's disease patients while they performed a sensory integration task involving randomly moving dots. By gradually increasing the number of dots moving coherently in one direction, we were able to determine changes in the STN associated with response execution. Furthermore, by occasionally having 10% of the dots move in the opposite direction as the majority, we were able to identify an independent increase in STN theta-delta activity triggered by conflict. Crucially, simultaneous midline frontal electroencephalographic recordings revealed an increase in the theta-delta band coherence between the two structures that was specific to high-conflict trials. Activity over the midline frontal cortex was Granger causal to that in STN. These results establish the cortico-subcortical circuit enabling successful choices to be made under conditions of conflict and provide support for the hypothesis that the brain uses frequency-specific channels of communication to convey behaviorally relevant information.
How the prefrontal cortex and subthalamic nucleus coordinate their activity during decision-making is unclear. By recording simultaneously from the two structures, Zavala et al. show that ...within-trial cognitive control involves theta oscillations, whereas across-trial adaptations involve beta oscillations. The two structures participate in separate, complementary stages of the decision-making process.
Abstract
There is increasing evidence that the medial prefrontal cortex participates in conflict and feedback monitoring while the subthalamic nucleus adjusts actions. Yet how these two structures coordinate their activity during cognitive control remains poorly understood. We recorded from the human prefrontal cortex and the subthalamic nucleus simultaneously while participants (n = 22) performed a novel task involving high conflict trials, complete response inhibition trials, and trial-to-trial behavioural adaptations to conflict and errors. Overall, we found that within-trial adaptions to both conflict and complete response inhibition involved changes in the theta band while across-trial behavioural adaptations to both conflict and errors involved changes in the beta band (P < 0.05). Yet the role each region's theta and beta oscillations played during the task differed significantly between the two sites. Trials that involved either within-trial conflict or complete response inhibition were associated with increased theta phase synchrony between the medial prefrontal cortex and the subthalamic nucleus (P < 0.05). Despite increased synchrony, however, increases in prefrontal theta power were associated with response inhibition, while increases in subthalamic theta power were associated with response execution (P < 0.05). In the beta band, post-response increases in prefrontal beta power were suppressed when the completed trial contained either conflict or an erroneous response (P < 0.05). Subthalamic beta power, on the other hand, was only modified during the subsequent trial that followed a conflict or error trial. Notably, these adaptation trials exhibited slower response times (P < 0.05), suggesting that both brain regions contribute to across-trial adaptations but do so at different stages of the adaptation process. Taken together, our data shed light on the mechanisms underlying within-trial and across-trial cognitive control and how disruption of this network can negatively impact cognition. More broadly, however, our data also demonstrate that the specific role of a brain region, rather than the frequency being utilized, governs the behavioural correlates of oscillatory activity.
Recent studies have implicated the subthalamic nucleus (STN) in decisions that involve inhibiting movements. Many of the decisions that we make in our daily lives, however, do not involve any motor ...actions. We studied non-motor decision making by recording intraoperative STN and prefrontal cortex (PFC) electrophysiology as participants perform a novel task that required them to decide whether to encode items into working memory. During all encoding trials, beta band (15-30 Hz) activity decreased in the STN and PFC, and this decrease was progressively enhanced as more items were stored into working memory. Crucially, the STN and lateral PFC beta decrease was significantly attenuated during the trials in which participants were instructed not to encode the presented stimulus. These changes were associated with increase lateral PFC-STN coherence and altered STN neuronal spiking. Our results shed light on why states of altered basal ganglia activity disrupt both motor function and cognition.
The medial prefrontal cortex (mPFC) is thought to control the shift from automatic to controlled action selection when conflict is present or when mistakes have been recently committed. Growing ...evidence suggests that this process involves frequency specific communication in the theta (4–8Hz) band between the mPFC and the subthalamic nucleus (STN), which is the main target of deep brain stimulation (DBS) for Parkinson's disease. Key in this hypothesis is the finding that DBS can lead to impulsivity by disrupting the correlation between higher mPFC oscillations and slower reaction times during conflict. In order to test whether theta band coherence between the mPFC and the STN underlies adjustments to conflict and to errors, we simultaneously recorded mPFC and STN electrophysiological activity while DBS patients performed an arrowed flanker task. These recordings revealed higher theta phase coherence between the two sites during the high conflict trials relative to the low conflict trials. These differences were observed soon after conflicting arrows were displayed, but before a response was executed. Furthermore, trials that occurred after an error was committed showed higher phase coherence relative to trials that followed a correct trial, suggesting that mPFC–STN connectivity may also play a role in error related adjustments in behavior. Interestingly, the phase coherence we observed occurred before increases in theta power, implying that the theta phase and power may influence behavior at separate times during cortical monitoring. Finally, we showed that pre-stimulus differences in STN theta power were related to the reaction time on a given trial, which may help adjust behavior based on the probability of observing conflict during a task.
•During conflict STN theta phase synchronizes with that of the mesial frontal cortex.•The increased synchrony is associated with stimulus induced phase locking.•Increased synchrony was also observed in trials that followed an error.•Pre-stimulus STN theta power correlated with reaction time but only during conflict.
Indications for deep brain stimulation (DBS) are rapidly growing within functional neurosurgery. The objective of this study was to characterize national trends in demographics and complications ...across distinct populations of DBS patients.
We identified patients from the 2008–2018 American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Participant Use Data File (PUF) who underwent an implantation or revision procedure for DBS. Summary statistics for postoperative infection rate, noninfectious complication rate, total hospital length of stay, discharge disposition, mortality, reoperation or readmission, and time from operation to readmission were obtained. Patients were categorized by diagnosis for DBS treatment. Outcomes for each diagnosis group were compared to outcomes for the total study population.
DBS patients who underwent primary implantation procedures had low rates of postoperative infections (1.2%), noninfectious complications (0.8%), and mortality (0.1%) and a high likelihood of discharge home (97.6%). In addition, a large percentage of patients presented for revision or removal of neurostimulators (34.2% of cases) or treatment of long-term hardware infection (4.5%). Compared with patients with other diagnoses, patients with Parkinson disease experienced lower rates of noninfectious complications (odds ratio 0.32; 95% CI, 0.15–0.63; p = 0.002) and fewer unplanned reoperations (odds ratio 0.60; 95% CI, 0.39–0.92; p = 0.02).
Analysis of a national database suggests that DBS is a relatively safe treatment across several different patient populations. These overall favorable results support the continued practice of DBS surgery and provide encouraging validation for increasing access to DBS therapy for new indications that are being actively investigated.
Use-dependent forms of synaptic plasticity have been extensively characterized at chemical synapses, but a relationship between natural activity and strength at electrical synapses remains elusive. ...The thalamic reticular nucleus (TRN), a brain area rich in gap-junctional (electrical) synapses, regulates cortical attention to the sensory surround and participates in shifts between arousal states; plasticity of electrical synapses may be a key mechanism underlying these processes. We observed long-term depression resulting from coordinated burst firing in pairs of coupled TRN neurons. Changes in gap-junctional communication were asymmetrical, indicating that regulation of connectivity depends on the direction of use. Modification of electrical synapses resulting from activity in coupled neurons is likely to be a widespread and powerful mechanism for dynamic reorganization of electrically coupled neuronal networks.
INTRODUCTION: Although neuroradiological techniques have expanded, stereotactic needle biopsy is a simple, ubiquitous,and immediate strategy for established or potential brain tumor patients with ...atypical clinical and/or radiographic findings. METHODS: Outpatient stereotactic needle biopsies performed by a single surgeon from August 2020 through November 2022 were retrospectively reviewed. Electronic medical records were queried for clinical, perioperative, and tumor demographics. Financial records were queried for insurance and payment reports. Descriptive statistics were used to characterize comparisons among collected variables. RESULTS: 107 consecutive stereotactic needle biopsy procedures were conducted in adult brain tumor patients. All biopsies were performed using a single needle-pass in the outpatient setting, targeting supratentorial lesions in 89.7% of cases. Tissue diagnosis was established in 96% of procedures, with glioma being the most common histology. No intraoperative or perioperative complications occurred. Four patients (3.7%) were admitted overnight due to urinary retention (n = 2) and asymptomatic tract hemorrhage (n = 2), respectively. Insurance approval was sought preoperatively from non-commercial (31.7%) and commercial (68.3%) payors and approved in all cases. Postoperatively, 30.8% of patients received an experimental therapeutic on the basis of tissue analysis. CONCLUSIONS: We report the largest experience to date with outpatient stereotactic needle biopsy in newly-diagnosed and recurrent brain tumor patients. Our findings identify this strategy as a cost-effective alternative to advanced imaging that facilitates clinical trial accrual through tissue acquisition.
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