Intracranial Recordings Demonstrate Both Cortical and Medial Temporal Lobe Engagement in Visual Search in Humans.

Visual search is a fundamental human behavior, providing a gateway to understanding other sensory domains as well as the role of search in higher-order cognition. Search has been proposed to include two component processes: inefficient search (Search) and efficient search (Pop-out). According to extant research, these two processes map onto two separable neural systems located in the frontal and parietal association cortices. In this study, we use intracranial recordings from 23 participants to delineate the neural correlates of Search and Pop-out with an unprecedented combination of spatiotemporal resolution and coverage across cortical and subcortical structures. First, we demonstrate a role for the medial temporal lobe in visual search, on par with engagement in frontal and parietal association cortex. Second, we show a gradient of increasing engagement over anatomical space from dorsal to ventral lateral frontal cortex. Third, we confirm previous intracranial work demonstrating nearly complete overlap in neural engagement across cortical regions in Search and Pop-out. We further demonstrate Pop-out selectivity, manifesting as activity increase in Pop-out as compared to Search, in a distributed set of sites including frontal cortex. This result is at odds with the view that Pop-out is implemented in low-level visual cortex or parietal cortex alone. Finally, we affirm a central role for the right lateral frontal cortex in Search.

Spatiotemporal dynamics of word retrieval in speech production revealed by cortical high-frequency band activity.

Word retrieval is core to language production and relies on complementary processes: the rapid activation of lexical and conceptual representations and word selection, which chooses the correct word among semantically related competitors. Lexical and conceptual activation is measured by semantic priming. In contrast, word selection is indexed by semantic interference and is hampered in semantically homogeneous (HOM) contexts. We examined the spatiotemporal dynamics of these complementary processes in a picture naming task with blocks of semantically heterogeneous (HET) or HOM stimuli. We used electrocorticography data obtained from frontal and temporal cortices, permitting detailed spatiotemporal analysis of word retrieval processes. A semantic interference effect was observed with naming latencies longer in HOM versus HET blocks. Cortical response strength as indexed by high-frequency band (HFB) activity (70-150 Hz) amplitude revealed effects linked to lexical-semantic activation and word selection observed in widespread regions of the cortical mantle. Depending on the subsecond timing and cortical region, HFB indexed semantic interference (i.e., more activity in HOM than HET blocks) or semantic priming effects (i.e., more activity in HET than HOM blocks). These effects overlapped in time and space in the left posterior inferior temporal gyrus and the left prefrontal cortex. The data do not support a modular view of word retrieval in speech production but rather support substantial overlap of lexical-semantic activation and word selection mechanisms in the brain.

Infection and Erosion Rates in Trials of a Cranially Implanted Neurostimulator Do Not Increase with Subsequent Neurostimulator Placements.

BACKGROUND/AIMS: The RNS® System utilizes a cranially implanted neurostimulator attached to leads placed at the seizure focus to provide brain responsive stimulation for the treatment of medically intractable partial onset epilepsy. Infection and erosion rates related to the cranial implant site were assessed overall and by neurostimulator procedure to determine whether rates increased with additional procedures. METHODS: Infection and erosion rates were calculated as (1) chance per neurostimulator procedure, (2) incidence per patient implant year, and (3) rates for initial and each subsequent neurostimulator implant (generalized estimating equation). RESULTS: In 256 patients followed for an average of 7 years, the infection rate was 3.7% per neurostimulator procedure (n = 31/840), and the rate of erosions was 0.8% per neurostimulator procedure (n = 7/840). Rates did not increase with subsequent neurostimulator procedures (p = 0.66, infection; p = 0.70, erosion). A prior infection or erosion at the implant site did not significantly increase the risk at a later procedure (p ≥ 0.05 for all combinations). CONCLUSION: These data indicate that the risk for infection compares favorably to other neurostimulation devices and suggest that rates of infection and erosion do not increase with subsequent neurostimulator replacements.

Surface-Guided Formation of an Organocobalt Complex.

Organocobalt complexes represent a versatile tool in organic synthesis as they are important intermediates in Pauson-Khand, Friedel-Crafts, and Nicholas reactions. Herein, a single-molecule-level investigation addressing the formation of an organocobalt complex at a solid-vacuum interface is reported. Deposition of 4,4'-(ethyne-1,2-diyl)dibenzonitrile and Co atoms on the Ag(111) surface followed by annealing resulted in genuine complexes in which single Co atoms laterally coordinated to two carbonitrile groups undergo organometallic bonding with the internal alkyne moiety of adjacent molecules. Alternative complexation scenarios involving fragmentation of the precursor were ruled out by complementary X-ray photoelectron spectroscopy. According to density functional theory analysis, the complexation with the alkyne moiety follows the Dewar-Chatt-Duncanson model for a two-electron-donor ligand where an alkyne-to-Co donation occurs together with a strong metal-to-alkyne back-donation.

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography.

OBJECTIVE: Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. METHODS: Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded. RESULTS: Eighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0-376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording. SIGNIFICANCE: About one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions.

A rapid theta network mechanism for flexible information encoding.

Flexible behavior requires gating mechanisms that encode only task-relevant information in working memory. Extant literature supports a theoretical division of labor whereby lateral frontoparietal interactions underlie information maintenance and the striatum enacts the gate. Here, we reveal neocortical gating mechanisms in intracranial EEG patients by identifying rapid, within-trial changes in regional and inter-regional activities that predict subsequent behavioral outputs. Results first demonstrate information accumulation mechanisms that extend prior fMRI (i.e., regional high-frequency activity) and EEG evidence (inter-regional theta synchrony) of distributed neocortical networks in working memory. Second, results demonstrate that rapid changes in theta synchrony, reflected in changing patterns of default mode network connectivity, support filtering. Graph theoretical analyses further linked filtering in task-relevant information and filtering out irrelevant information to dorsal and ventral attention networks, respectively. Results establish a rapid neocortical theta network mechanism for flexible information encoding, a role previously attributed to the striatum.

Left hemisphere dominance for bilateral kinematic encoding in the human brain.

Neurophysiological studies in humans and nonhuman primates have revealed movement representations in both the contralateral and ipsilateral hemispheres. Inspired by clinical observations, we ask if this bilateral representation differs for the left and right hemispheres. Electrocorticography was recorded in human participants during an instructed-delay reaching task, with movements produced with either the contralateral or ipsilateral arm. Using a cross-validated kinematic encoding model, we found stronger bilateral encoding in the left hemisphere, an effect that was present during preparation and was amplified during execution. Consistent with this asymmetry, we also observed better across-arm generalization in the left hemisphere, indicating similar neural representations for right and left arm movements. Notably, these left hemisphere electrodes were centered over premotor and parietal regions. The more extensive bilateral encoding in the left hemisphere adds a new perspective to the pervasive neuropsychological finding that the left hemisphere plays a dominant role in praxis.

The brain is split into two hemispheres, each playing the leading role in coordinating movement for the opposite side of the body: lesions on the left hemisphere therefore often result in difficulties moving the right arm or leg, and vice versa. In fact, very few anatomical connections exist between a given hemisphere and the body parts on the same (or 'ipsilateral') side. Yet, movements produced with only one limb still engage both sides of the brain, with the hemisphere which does not control the action production, still encoding the direction and speed of the movement. Previous evidence also indicate that the two hemispheres may not have equal roles when coordinating ipsilateral movements. Merrick et al. aimed to shed light on these processes; to do so, they measured electrical activity from the surface of the brain of six patients as they moved their arms to reach a screen. The results revealed that, while the right hemisphere only encoded information about the opposite arm, the left hemisphere contained information about both arms. Finer analyses showed that, for both hemispheres, moving the opposite arm was strongly associated with activity in the primary motor cortex, a region which helps to execute movements. However, in the left hemisphere, movements from the ipsilateral arm were related to activity in brain areas involved in planning and integrating different types of sensory information. These findings contribute to a better understanding of how the motor system works, which could ultimately help with the development of brain-machine interfaces for patients who need a neuroprosthetic limb.

Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy.

OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS: Of 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04-9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER: NCT00572195. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

A role for PKC-epsilon in Fc gammaR-mediated phagocytosis by RAW 264.7 cells.

Protein kinase C (PKC) plays a prominent role in immune signaling, and the paradigms for isoform selective signaling are beginning to be elucidated. Real-time microscopy was combined with molecular and biochemical approaches to demonstrate a role for PKC- epsilon in Fc gamma receptor (Fc gammaR)-dependent phagocytosis. RAW 264.7 macrophages were transfected with GFP-conjugated PKC isoforms, and GFP movement was followed during phagocytosis of fluorescent IgG-opsonized beads. PKC- epsilon, but not PKC-delta, concentrated around the beads. PKC- epsilon accumulation was transient; apparent as a "flash" on target ingestion. Similarly, endogenous PKC- epsilon was specifically recruited to the nascent phagosomes in a time-dependent manner. Overexpression of PKC- epsilon, but not PKC-alpha, PKC-delta, or PKC-gamma enhanced bead uptake 1.8-fold. Additionally, the rate of phagocytosis in GFP PKC- epsilon expressors was twice that of cells expressing GFP PKC-delta. Expression of the regulatory domain ( epsilon RD) and the first variable region ( epsilon V1) of PKC- epsilon inhibited uptake, whereas the corresponding PKC-delta region had no effect. Actin polymerization was enhanced on expression of GFP PKC- epsilon and epsilon RD, but decreased in cells expressing epsilon V1, suggesting that the epsilon RD and epsilon V1 inhibition of phagocytosis is not due to effects on actin polymerization. These results demonstrate a role for PKC- epsilon in Fc gammaR-mediated phagocytosis that is independent of its effects on actin assembly.