Human periventricular nodular heterotopia shows several interictal epileptic patterns and hyperexcitability of neuronal firing.

Periventricular nodular heterotopia (PNH) is a malformation of cortical development that frequently causes drug-resistant epilepsy. The epileptogenicity of ectopic neurons in PNH as well as their role in generating interictal and ictal activity is still a matter of debate. We report the first in vivo microelectrode recording of heterotopic neurons in humans. Highly consistent interictal patterns (IPs) were identified within the nodules: (1) Periodic Discharges PLUS Fast activity (PD+F), (2) Sporadic discharges PLUS Fast activity (SD+F), and (3) epileptic spikes (ES). Neuronal firing rates were significantly modulated during all IPs, suggesting that multiple IPs were generated by the same local neuronal populations. Furthermore, firing rates closely followed IP morphologies. Among the different IPs, the SD+F pattern was found only in the three nodules that were actively involved in seizure generation but was never observed in the nodule that did not take part in ictal discharges. On the contrary, PD+F and ES were identified in all nodules. Units that were modulated during the IPs were also found to participate in seizures, increasing their firing rate at seizure onset and maintaining an elevated rate during the seizures. Together, nodules in PNH are highly epileptogenic and show several IPs that provide promising pathognomonic signatures of PNH. Furthermore, our results show that PNH nodules may well initiate seizures.

Long-term deep intracerebral microelectrode recordings in patients with drug-resistant epilepsy: Proposed guidelines based on 10-year experience.

PURPOSE: Human neuronal activity, recorded in vivo from microelectrodes, may offer valuable insights into physiological mechanisms underlying human cognition and pathophysiological mechanisms of brain diseases, in particular epilepsy. Continuous and long-term recordings are necessary to monitor non predictable pathological and physiological activities like seizures or sleep. Because of their high impedance, microelectrodes are more sensitive to noise than macroelectrodes. Low noise levels are crucial to detect action potentials from background noise, and to further isolate single neuron activities. Therefore, long-term recordings of multi-unit activity remains a challenge. We shared here our experience with microelectrode recordings and our efforts to reduce noise levels in order to improve signal quality. We also provided detailed technical guidelines for the connection, recording, imaging and signal analysis of microelectrode recordings. RESULTS: During the last 10 years, we implanted 122 bundles of Behnke-Fried hybrid macro-microelectrodes, in 56 patients with pharmacoresistant focal epilepsy. Microbundles were implanted in the temporal lobe (74%), as well as frontal (15%), parietal (6%) and occipital (5%) lobes. Low noise levels depended on our technical setup. The noise reduction was mainly obtained after electrical insulation of the patient's recording room and the use of a reinforced microelectrode model, reaching median root mean square values of 5.8 µV. Seventy percent of the bundles could record multi-units activities (MUA), on around 3 out of 8 wires per bundle and for an average of 12 days. Seizures were recorded by microelectrodes in 91% of patients, when recorded continuously, and MUA were recorded during seizures for 75 % of the patients after the insulation of the room. Technical guidelines are proposed for (i) electrode tails manipulation and protection during surgical bandage and connection to both clinical and research amplifiers, (ii) electrical insulation of the patient's recording room and shielding, (iii) data acquisition and storage, and (iv) single-units activities analysis. CONCLUSIONS: We progressively improved our recording setup and are now able to record (i) microelectrode signals with low noise level up to 3 weeks duration, and (ii) MUA from an increased number of wires . We built a step by step procedure from electrode trajectory planning to recordings. All these delicate steps are essential for continuous long-term recording of units in order to advance in our understanding of both the pathophysiology of ictogenesis and the neuronal coding of cognitive and physiological functions.

Kv1.1 channels inhibition in the rat motor cortex recapitulates seizures associated with anti-LGI1 encephalitis.

Autoimmune encephalitis associated with antibodies directed against the leucine-rich glioma inactivated 1 (LGI1) protein is responsible for specific tonic-dystonic motor seizures. Although dysfunctions in neuronal excitability have been associated with anti-LGI1 autoantibodies, their relation to seizures remain inconclusive. We developed a new in vivo experimental rat model to determine whether inhibition of Kv1.1 channels by dentrotoxin-K (DTX) in the primary motor cortex (M1) could recapitulate the human seizures and to elucidate their subtending cortical mechanisms. Comparing electro-clinical features of DTX-induced seizures in rats with those recorded from a cohort of anti-LGI1 encephalitis patients revealed striking similarities in their electroencephalographic (EEG) signature, frequency of recurrence and semiology. By combining multi-site extracellular and intracellular recordings of M1 pyramidal neurons in DTX rats, we demonstrated that the blockade of Kv1.1 channels induced a sequence of changes in neuronal excitability and synaptic activity, leading to massive suprathreshold membrane depolarizations underlying the paroxysmal EEG activity. Our results suggest the central role of Kv1.1 channels disruption in the emergence of anti-LGI1-associated seizures and suggest that this new rodent model could serve future investigations on ictogenesis in autoimmune encephalitis.

Neuronal correlates of the subjective experience of attention.

The effect of top-down attention on stimulus-evoked responses and alpha oscillations and the association between arousal and pupil diameter are well established. However, the relationship between these indices, and their contribution to the subjective experience of attention, remains largely unknown. Participants performed a sustained (10-30 s) attention task in which rare (10%) targets were detected within continuous tactile stimulation (16 Hz). Trials were followed by attention ratings on an 8-point visual scale. Attention ratings correlated negatively with contralateral somatosensory alpha power and positively with pupil diameter. The effect of pupil diameter on attention ratings extended into the following trial, reflecting a sustained aspect of attention related to vigilance. The effect of alpha power did not carry over to the next trial and furthermore mediated the association between pupil diameter and attention ratings. Variations in steady-state amplitude reflected stimulus processing under the influence of alpha oscillations but were only weakly related to subjective ratings of attention. Together, our results show that both alpha power and pupil diameter are reflected in the subjective experience of attention, albeit on different time spans, while continuous stimulus processing might not contribute to the experience of attention.

Benchmarking for On-Scalp MEG Sensors.

OBJECTIVE: We present a benchmarking protocol for quantitatively comparing emerging on-scalp magnetoencephalography (MEG) sensor technologies to their counterparts in state-of-the-art MEG systems. METHODS: As a means of validation, we compare a high-critical-temperature superconducting quantum interference device (high Tc SQUID) with the low- Tc SQUIDs of an Elekta Neuromag TRIUX system in MEG recordings of auditory and somatosensory evoked fields (SEFs) on one human subject. RESULTS: We measure the expected signal gain for the auditory-evoked fields (deeper sources) and notice some unfamiliar features in the on-scalp sensor-based recordings of SEFs (shallower sources). CONCLUSION: The experimental results serve as a proof of principle for the benchmarking protocol. This approach is straightforward, general to various on-scalp MEG sensors, and convenient to use on human subjects. The unexpected features in the SEFs suggest on-scalp MEG sensors may reveal information about neuromagnetic sources that is otherwise difficult to extract from state-of-the-art MEG recordings. SIGNIFICANCE: As the first systematically established on-scalp MEG benchmarking protocol, magnetic sensor developers can employ this method to prove the utility of their technology in MEG recordings. Further exploration of the SEFs with on-scalp MEG sensors may reveal unique information about their sources.

Metacognition of attention during tactile discrimination.

The ability to monitor the success of cognitive processing is referred to as metacognition. Studies of metacognition typically probe post-decision judgments of confidence, showing that we can report on the success of wide range of cognitive processes. Much less is known about our ability to monitor and report on the degree of top-down attention, an ability of paramount importance in tasks requiring sustained attention. However, it has been repeatedly shown that the degree and locus of top-down attention modulates alpha (8-14Hz) power in sensory cortices. In this study we investigated whether self-reported ratings of attention are reflected by sensory alpha power, independent from confidence and task difficulty. Subjects performed a stair-cased tactile discrimination task requiring sustained somatosensory attention. Each discrimination response was followed by a rating of their attention at the moment of stimulation, or their confidence in the discrimination response. MEG was used to estimate trial-by-trial alpha power preceding stimulation. Staircasing of task-difficulty successfully equalized performance between conditions. Both attention and confidence ratings reflected subsequent discrimination performance. Task difficulty specifically influenced confidence ratings. As expected, specifically attention ratings, but not confidence ratings, correlated negatively with contralateral somatosensory alpha power preceding tactile stimuli. Taken together, these results demonstrate that the degree of attention can be subjectively experienced and reported accurately, independent from task difficulty and knowledge about task performance.

Reliable recording and analysis of MEG-based corticokinematic coherence in the presence of strong magnetic artifacts.

OBJECTIVE: Corticokinematic coherence (CKC) is the coupling between magnetoencephalographic (MEG) signals and limb kinematics during fast movements. Our objective was to assess the robustness of CKC-based identification of the primary sensorimotor (SM1) cortex of subjects producing strong magnetic artifacts when the MEG signals were cleaned with temporal signal space separation (tSSS). METHODS: We recorded MEG during active and passive forefinger movements and during median-nerve stimulation in the following conditions: (1) artifact-free, (2) a magnetic wire attached to the scalp at C3 location, and (3) a magnetic wire attached behind the lower central incisors. Data were pre-processed with tSSS and analyzed using standard CKC methods, somatosensory evoked fields (SEFs), and dipole modeling. RESULT: Artifacts were effectively suppressed by tSSS, enabling successful identification of the SM1 cortex in all subjects based on CKC and SEFs. The sources were in artifact conditions ∼5 mm away from the sources identified in artifact-free conditions. CONCLUSION: tSSS suppressed artifacts strongly enough to enable reliable identification of the SM1 cortex on the basis of CKC mapping, with localization accuracy comparable to SEF-based mapping. SIGNIFICANCE: The results suggest that CKC can be used for SM1 cortex identification and for studies of proprioception even in patients implanted with magnetic material.

Metacognitive awareness of covert somatosensory attention corresponds to contralateral alpha power.

Studies on metacognition have shown that participants can report on their performance on a wide range of perceptual, memory and behavioral tasks. We know little, however, about the ability to report on one's attentional focus. The degree and direction of somatosensory attention can, however, be readily discerned through suppression of alpha band frequencies in EEG/MEG produced by the somatosensory cortex. Such top-down attentional modulations of cortical excitability have been shown to result in better discrimination performance and decreased response times. In this study we asked whether the degree of attentional focus is also accessible for subjective report, and whether such evaluations correspond to the amount of somatosensory alpha activity. In response to auditory cues participants maintained somatosensory attention to either their left or right hand for intervals varying randomly between 5 and 32 seconds, while their brain activity was recorded with MEG. Trials were terminated by a probe sound, to which they reported their level of attention on the cued hand right before probe-onset. Using a beamformer approach, we quantified the alpha activity in left and right somatosensory regions, one second before the probe. Alpha activity from contra- and ipsilateral somatosensory cortices for high versus low attention trials were compared. As predicted, the contralateral somatosensory alpha depression correlated with higher reported attentional focus. Finally, alpha activity two to three seconds before the probe-onset was correlated with attentional focus. We conclude that somatosensory attention is indeed accessible to metacognitive awareness.

Mindfulness reduces habitual responding based on implicit knowledge: evidence from artificial grammar learning.

Participants were unknowingly exposed to complex regularities in a working memory task. The existence of implicit knowledge was subsequently inferred from a preference for stimuli with similar grammatical regularities. Several affective traits have been shown to influence AGL performance positively, many of which are related to a tendency for automatic responding. We therefore tested whether the mindfulness trait predicted a reduction of grammatically congruent preferences, and used emotional primes to explore the influence of affect. Mindfulness was shown to correlate negatively with grammatically congruent responses. Negative primes were shown to result in faster and more negative evaluations. We conclude that grammatically congruent preference ratings rely on habitual responses, and that our findings provide empirical evidence for the non-reactive disposition of the mindfulness trait.

Sensorimotor Alpha Activity is Modulated in Response to the Observation of Pain in Others.

The perception-action account of empathy states that observation of another person's state automatically activates a similar state in the observer. It is still unclear in what way ongoing sensorimotor alpha oscillations are involved in this process. Although they have been repeatedly implicated in (biological) action observation and understanding communicative gestures, less is known about their role in vicarious pain observation. Their role is understood as providing a graded inhibition through functional inhibition, thereby streamlining information flow through the cortex. Although alpha oscillations have been shown to have at least visual and sensorimotor origins, only the latter are expected to be involved in the empathetic response. Here, we used magnetoencephalography, allowing us to spatially distinguish and localize oscillatory components using beamformer source reconstruction. Subjects observed realistic pictures of limbs in painful and no-pain (control) conditions. As predicted, time-frequency analysis indeed showed increased alpha suppression in the pain condition compared to the no-pain condition. Although both pain and no-pain conditions suppressed alpha- and beta-band activity at both posterior and central sensors, the pain condition suppressed alpha more only at central sensors. Source reconstruction localized these differences along the central sulcus. Our results could not be accounted for by differences in the evoked fields, suggesting a unique role of oscillatory activity in empathetic responses. We argue that alpha oscillations provide a unique measure of the underlying functional architecture of the brain, suggesting an automatic disinhibition of the sensorimotor cortices in response to the observation of pain in others.