Neuronal activity in the human amygdala and hippocampus enhances emotional memory encoding

Emotional events are often easier to recall, and comprise our most valuable memories. Here, as subjects performed a memory task in which they recalled emotional stimuli more readily than neutral stimuli, we used direct brain recording and stimulation in the hippocampus and amygdala to identify how the brain prioritizes emotional information for memory encoding. High-frequency activity (HFA), a correlate of local neuronal spiking, increased in both hippocampus and amygdala when subjects successfully encoded emotionally arousing stimuli. Direct electrical stimulation applied to these regions during encoding decreased HFA and selectively impaired retrieval for emotional stimuli. Finally, depressed subjects' memory was biased more by valence than arousal, and they exhibited a congruent increase in HFA as a function of valence. Our findings thus provide evidence that emotional stimuli up-regulate activity in the amygdala--hippocampus circuit to enhance memory for emotional information, and suggest that targeted modulation of this circuit alters emotional memory processes.

Understanding Variable Motor Responses to Direct Electrical Stimulation of the Human Motor Cortex During Brain Surgery

Direct electrical stimulation of the brain is the gold standard technique used to define functional-anatomical relationships during neurosurgical procedures. Areas that respond to stimulation are considered “critical nodes” of circuits that must remain intact for the subject to maintain the ability to perform certain functions, like moving and speaking. Despite its routine use, the neurophysiology underlying downstream motor responses to electrical stimulation of the brain, such as muscle contraction or movement arrest, is poorly understood. Furthermore, varying and sometimes counterintuitive responses can be seen depending on how and where the stimulation is applied, even within the human primary motor cortex. Therefore, here we review relevant neuroanatomy of the human motor system, provide a brief historical perspective on electrical brain stimulation, explore mechanistic variations in stimulation applications, examine neurophysiological properties of different parts of the motor system, and suggest areas of future research that can promote a better understanding of the interaction between electrical stimulation of the brain and its function.

P03.06 Boolean logic puzzles as a neurosurgical mapping tool to preserve programming skill

BACKGROUND In glioma surgery, awake craniotomy with Direct Electrical Stimulation (DES) is increasingly becoming the gold standard treatment to preserve language, cognition and motor function and to optimize extent of resection. Computer programming is historically seen as an integration of cognition, language, and mathematics but an intraoperative task to monitor computer programming does not exist yet. In this study we describe a new task for intraoperative monitoring, using visual Boolean Logic Puzzles. MATERIAL AND METHODS We describe a computer programmer who underwent awake craniotomy to resect an anaplastic astrocytoma in the left superior frontal gyrus. At the request of the patient we tested programming language. We developed a new task and set of logic puzzle visual stimuli to monitor underlying cognitive function used for programming language. This test was used during preoperative functional MRI (fMRI), direct electrical stimulation (DES) and ongoing monitoring during resection. RESULTS In fMRI this task showed bilateral activation in Brodmann area 6 and 8 and for left hemisphere in Brodmann area 10. These areas are below and lateral of the tumor. Monitoring of language, motor skills and Boolean mapping was performed during DES and while resection was performed. No deficits in programming ability could be identified intra- and postoperatively. CONCLUSION Boolean Logic Puzzles may be a useful intraoperative task to preserve programming skills.

Unilateral Blinking: Insights from Stereo-EEG and Tractography

To study the neuroanatomical correlate of involuntary unilateral blinking in humans, using the example of patients with focal epilepsy. Patients with drug resistant focal epilepsy undergoing presurgical evaluation with stereotactically implanted EEG-electrodes (sEEG) were recruited from the local epilepsy monitoring unit. Only patients showing ictal unilateral blinking or unilateral blinking elicited by direct electrical stimulation were included (n = 16). MRI and CT data were used for visualization of the electrode positions. In two patients, probabilistic tractography with seeding from the respective electrodes was additionally performed. Three main findings were made: (1) involuntary unilateral blinking was associated with activation of the anterior temporal region, (2) tractography showed widespread projections to the ipsilateral frontal, pericentral, occipital, limbic and cerebellar regions and (3) blinking was observed predominantly in female patients with temporal lobe epilepsies. Unilateral blinking was found to be associated with an ipsilateral activation of the anterior temporal region. We suggest that the identified network is not part of the primary blinking control but might have modulating influence on ipsilateral blinking by integrating contextual information.

Two Different Subcortical Networks of Language System: Morphogram and Phonogram, Through the Analysis of Unique Japanese Characters

Language systems worldwide are based on morphograms or phonograms, and Japanese is a unique language that uses a complicated combination of kanji (morphogram) and kana (phonogram) characters. The white matter networks associated with reading have been investigated previously but remain unclear. In this study, we performed intraoperative language mapping under local anesthesia and postoperative language assessments of 65 consecutive patients who underwent surgical resection for cerebral glioma within the dominant temporal or parietal lobe. The cases showing intraoperative dyslexia elicited by direct electrical stimulation (DES) or postoperative kanji and/or kana dyslexia were extracted. Five patients showed transient kanji or kana dyslexia intraoperatively, and 8 patients showed kanji or kana dyslexia postoperatively. During intraoperative mapping, kanji or kana dyslexia were indeed reproduced by DES. We investigated the maximal overlapping lesions of the resection cavity that were associated with kanji or kana dyslexia, and then determined the subcortical elicited points that evoked kanji or kana dyslexia. These areas were localized near three white matter bundles: the arcuate fascicle, posterior superior longitudinal fascicle, and inferior longitudinal fascicle (ILF). The intraoperative DES distributions for kanji dyslexia were especially associated with the anterior-inferior side of the ILF. On the other hand, the DES point associated with kana dyslexia was localized on the posterior-superior side of the complex of these three tracts. These results suggested the presence of specific non-interfering networks that subserved the reading process for morphograms and phonograms.

Biomarker-guided neuromodulation aids memory in traumatic brain injury

Traumatic brain injury (TBI) is a leading cause of cognitive disability in adults, often characterized by marked deficits in episodic memory and executive function. Prior studies have found that direct electrical stimulation of the temporal cortex yielded improved memory in epilepsy patients, but it is not clear if these results generalize to patients with a specific history of TBI. Here we asked whether applying closed-loop, direct electrical stimulation to lateral temporal cortex could reliably improve memory in a TBI cohort. Among a larger group of patients undergoing neurosurgical evaluation for refractory epilepsy, we recruited a subset patients with a history of moderate-to-severe TBI. By analyzing neural data from indwelling electrodes as patients studied and recalled lists of words, we trained personalized machine-learning classifiers to predict momentary fluctuations in mnemonic function in each patient. We subsequently used these classifiers to trigger high-frequency stimulation of the lateral temporal cortex (LTC) at moments when memory was predicted to fail. This strategy yielded a 19% boost in recall performance on stimulated as compared with non-stimulated lists (P = 0.012). These results provide a proof-of-concept for using closed-loop stimulation of the brain in treatment of TBI-related memory impairment.

Intraoperative Cognitive Mapping Tasks for Direct Electrical Stimulation in Clinical and Neuroscientific Contexts

Direct electrical stimulation (DES) has been widely applied in both guidance of lesion resection and scientific research; however, the design and selection of intraoperative cognitive mapping tasks have not been updated in a very long time. We introduce updated mapping tasks for language and non-language functions and provide recommendations for optimal design and selection of intraoperative mapping tasks. In addition, with DES becoming more critical in current neuroscientific research, a task design that has not been widely used in DES yet (subtraction and conjunction paradigms) was introduced for more delicate mapping of brain functions especially for research purposes. We also illustrate the importance of designing a common task series for DES and other non-invasive mapping techniques. This review gives practical updated guidelines for advanced application of DES in clinical and neuroscientific research.