Richard Selway

Frontal and temporal functional connections of the living human brain

Connections between human temporal and frontal cortices were investigated by intracranial electroencephalographic responses to electrical stimulation with 1‐ms single pulses in 51 patients assessed for surgery for treatment of epilepsy. The areas studied were medial temporal, entorhinal, lateral temporal, medial frontal, lateral frontal and orbital frontal cortices. Findings were assumed to be representative of human brain as no differences were found between epileptogenic and non‐epileptogenic hemispheres. Connections between intralobar temporal and frontal regions were common (43–95%). Connections from temporal to ipsilateral frontal regions were relatively uncommon (seen in 0–25% of hemispheres). Connections from frontal to ipsilateral temporal cortices were more common, particularly from orbital to ipsilateral medial temporal regions (40%). Contralateral temporal connections were rare (< 9%) whereas contralateral frontal connections were frequent and faster, particularly from medial frontal to contralateral medial frontal (61%) and orbital frontal cortices (57%), and between both orbital cortices (67%). Orbital cortex receives profuse connections from the ipsilateral medial (78%) and lateral (88%) frontal cortices, and from the contralateral medial (57%) and orbital (67%) frontal cortices. The high incidence of intralobar temporal connections supports the presence of temporal reverberating circuits. Frontal cortex projects within the lobe and beyond, to ipsilateral and contralateral structures.

Single-pulse electrical stimulation identifies epileptogenic frontal cortex in the human brain.

Objective: To assess the value of single-pulse electrical stimulation (SPES) to identify frontal epileptogenic cortex during presurgical assessment. Methods: SPES (1-millisecond pulses, 4 to 8 mA, 0.1 Hz) has been used during chronic recordings in 30 patients with intracranial electrodes in the frontal lobes. As a result of presurgical assessment, 17 patients were considered to have frontal epilepsy and 13 extrafrontal epilepsy. Results: Two types of responses to SPES were seen: 1) early responses: starting immediately after the stimulus and considered as normal responses; 2) late responses: two types of responses seen in some areas after the initial early response: a) delayed responses: spikes or sharp waves occurring between 100 milliseconds and 1 second after stimulation. Frontal delayed responses were seen in 11 frontal patients and 1 extrafrontal patient, whereas extrafrontal delayed responses were seen in 1 frontal and 10 extrafrontal patients. b) Repetitive responses: two or more consecutive sharp-and-slow-wave complexes, each resembling the initial early response. Repetitive responses were seen only when stimulating the frontal lobes of 10 frontal patients. Among the 17 frontal patients, 13 had late responses exclusively in the epileptogenic frontal lobe, whereas only 3 showed them in both frontal lobes. Frontal late responses were associated with neuropathologic abnormalities, and complete resection of abnormal SPES areas was associated with good postsurgical seizure outcome. Conclusions: Single-pulse electrical stimulation (SPES) could be an important additional investigation during presurgical assessment to identify frontal epileptogenicity. SPES can be useful in patients who have widespread or multiple epileptogenic areas, normal neuroimaging, or few seizures during telemetry.

Single pulse electrical stimulation of the hippocampus is sufficient to impair human episodic memory.

We have used the single pulse electrical stimulation (SPES) technique to investigate whether more localized stimulation of the hippocampus can affect human episodic memory. A recognition memory test including words, object drawings, abstract drawings and unfamiliar faces was performed without stimulation (baseline) or synchronized with single 1 ms electrical pulses applied to the left, right or both hippocampi in 12 epileptic patients investigated with bilateral depth electrodes. No differences were found in memory performance between baseline and unilateral stimulation, either in the total score or in material-specific scores. In contrast, bilateral stimulation was associated with a pronounced decrease in the median of total memory scores (57%), and of material-specific sub-scores for words (38%), geometrical drawings (81%) and faces (100%). Additional study of stimulation at presentation of stimuli (encoding) versus the recognition memory (retrieval) test phase, showed reduction in memory only at encoding. The results provide causal evidence that the hippocampi are necessary for supporting episodic memory. The induction of memory deficits by bilateral stimulation with parameters that do not induce effects when applied unilaterally suggests that recognition memory can be processed independently by the hippocampus on either hemisphere.

Cross-frequency coupling within and between the human thalamus and neocortex

There is currently growing interest in, and increasing evidence for, cross-frequency interactions between electrical field oscillations in the brains of various organisms. A number of theories have linked such interactions to crucial features of neuronal function and cognition. In mammals, these interactions have mostly been reported in the neocortex and hippocampus, and it remains unexplored whether similar patterns of activity occur in the thalamus, and between the thalamus and neocortex. Here we use data recorded from patients undergoing thalamic deep-brain stimulation for epilepsy to demonstrate the existence and prevalence, across a range of frequencies, of both phase–amplitude (PAC) and amplitude–amplitude coupling (AAC) both within the thalamus and prefrontal cortex (PFC), and between them. These cross-frequency interactions may play an important role in local processing within the thalamus and neocortex, as well as information transfer between them.

Mortality and SUDEP in epilepsy patients treated with vagus nerve stimulation.

The risk of premature death is increased in patients with intractable epilepsy. The effect of vagus nerve stimulation (VNS) on mortality remains unclear. In a previous study by Annegers et al., mortality was raised, comparable to similar intractable cohorts. Our aim was to calculate standardized mortality ratios (SMRs), identify epilepsy‐related deaths, and estimate sudden unexpected death in epilepsy (SUDEP) rates in patients treated with VNS for epilepsy.