Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference^1,2. However, how cognitive control regulates working memory storage is unclear. Here we show that interactions of frontal control and hippocampal persistent activity are coordinated by theta–gamma phase–amplitude coupling (TG-PAC). We recorded single neurons in the human medial temporal and frontal lobe while patients maintained multiple items in their working memory. In the hippocampus, TG-PAC was indicative of working memory load and quality. We identified cells that selectively spiked during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons was coordinated with frontal theta activity when cognitive control demand was high. By introducing noise correlations with persistently active neurons in the hippocampus, PAC neurons shaped the geometry of the population code. This led to higher-fidelity representations of working memory content that were associated with improved behaviour. Our results support a multicomponent architecture of working memory^1,2, with frontal control managing maintenance of working memory content in storage-related areas^3–5. Within this framework, hippocampal TG-PAC integrates cognitive control and working memory storage across brain areas, thereby suggesting a potential mechanism for top-down control over sensory-driven processes.

Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer’s Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neural circuits. To investigate this, we performed a post-hoc analysis on a multi-center cohort of 46 patients with DBS to the fornix (NCT00658125, NCT01608061). Using normative structural and functional connectivity data, we found that stimulation of the circuit of Papez and stria terminalis robustly associated with cognitive improvement (R = 0.53,p < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48,p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48,p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming.

Neural responses recorded from auditory cortex exhibit adaptation, a stimulus-specific decrease that occurs when the same sound is presented repeatedly. Stimulus-specific adaptation is thought to facilitate perception in noisy environments. Although adaptation is assumed to arise independently from cortex, this has been difficult to validate directly in vivo. In this study, we used a neural network model of auditory cortex with multicompartmental cell modeling to investigate cortical adaptation. We found that repetitive, non-adapted inputs to layer IV neurons in the model elicited frequency-specific decreases in simulated single neuron, population-level and local field potential (LFP) activity, consistent with stimulus-specific cortical adaptation. Simulated recordings of LFPs, generated solely by excitatory post-synaptic inputs and recorded from layers II/III in the model, showed similar waveform morphologies and stimulus probability effects as auditory evoked responses recorded from human cortex. We tested two proposed mechanisms of cortical adaptation, neural fatigue and neural sharpening, by varying the strength and type of inter- and intra-layer synaptic connections (excitatory, inhibitory). Model simulations showed that synaptic depression modeled in excitatory (AMPA) synapses was sufficient to elicit a reduction in neural firing rate, consistent with neural fatigue. However, introduction of lateral inhibition from local layer II/III interneurons resulted in a reduction in the number of responding neurons, but not their firing rates, consistent with neural sharpening. These modeling results demonstrate that adaptation can arise from multiple neural mechanisms in auditory cortex.

Background: Brain-computer interfaces (BCIs) can restore communication for movement- and/or speech-impaired individuals by enabling neural control of computer typing applications. Single command click detectors provide a basic yet highly functional capability. Methods: We sought to test the performance and long-term stability of click decoding using a chronically implanted high density electrocorticographic (ECoG) BCI with coverage of the sensorimotor cortex in a human clinical trial participant (ClinicalTrials.gov, NCT03567213) with amyotrophic lateral sclerosis. We trained the participant’s click detector using a small amount of training data (<44 min across 4 days) collected up to 21 days prior to BCI use, and then tested it over a period of 90 days without any retraining or updating. Results: Using a click detector to navigate a switch scanning speller interface, the study participant can maintain a median spelling rate of 10.2 characters per min. Though a transient reduction in signal power modulation can interrupt usage of a fixed model, a new click detector can achieve comparable performance despite being trained with even less data (<15 min, within 1 day). Conclusions: These results demonstrate that a click detector can be trained with a small ECoG dataset while retaining robust performance for extended periods, providing functional text-based communication to BCI users.

Radiosurgery to the right fifth cranial nerve was performed with the Gamma Knife on a 39- year-old patient who presented with classic symptoms of trigeminal neuralgia (TN), but was found on imaging studies to harbour a small intrinsic vascular malformation within the nerve. Based on size and drainage, the arteriovenous malformation (AVM) was Spetzler-Martin Grade III and no previous history of bleeding was reported. The patient had failed a trial of carbamazepine, and no surgical procedures had been performed. A decrease in symptoms was reported by the 6-month follow- up. A review of the literature on microAVM-induced TN is provided as well as a discussion of management.