Single-neuron correlate of epilepsy-related cognitive deficits in visual recognition memory in right mesial temporal lobe.

OBJECTIVE: Impaired memory is a common comorbidity of refractory temporal lobe epilepsy (TLE) and often perceived by patients as more problematic than the seizures themselves. The objective of this study is to understand what the relationship of these behavioral impairments is to the underlying pathophysiology, as there are currently no treatments for these deficits, and it remains unknown what circuits are affected. METHODS: We recorded single neurons in the medial temporal lobes (MTLs) of 62 patients (37 with refractory TLE) who performed a visual recognition memory task to characterize the relationship between behavior, tuning, and anatomical location of memory selective and visually selective neurons. RESULTS: Subjects with a seizure onset zone (SOZ) in the right but not left MTL demonstrated impaired ability to recollect as indicated by the degree of asymmetry of the receiver operating characteristic curve. Of the 1973 recorded neurons, 159 were memory selective (MS) and 366 were visually selective (VS) category cells. The responses of MS neurons located within right but not left MTL SOZs were impaired during high-confidence retrieval trials, mirroring the behavioral deficit seen both in our task and in standardized neuropsychological tests. In contrast, responses of VS neurons were unimpaired in both left and right MTL SOZs. Our findings show that neuronal dysfunction within SOZs in the MTL was specific to a functional cell type and behavior, whereas other cell types respond normally even within the SOZ. We show behavioral metrics that detect right MTL SOZ-related deficits and identify a neuronal correlate of this impairment. SIGNIFICANCE: Together, these findings show that single-cell responses can be used to assess the causal effects of local circuit disruption by an SOZ in the MTL, and establish a neural correlate of cognitive impairment due to epilepsy that can be used as a biomarker to assess the efficacy of novel treatments.

Value-Related Neuronal Responses in the Human Amygdala during Observational Learning.

The amygdala plays an important role in many aspects of social cognition and reward learning. Here, we aimed to determine whether human amygdala neurons are involved in the computations necessary to implement learning through observation. We performed single-neuron recordings from the amygdalae of human neurosurgical patients (male and female) while they learned about the value of stimuli through observing the outcomes experienced by another agent interacting with those stimuli. We used a detailed computational modeling approach to describe patients' behavior in the task. We found a significant proportion of amygdala neurons whose activity correlated with both expected rewards for oneself and others, and in tracking outcome values received by oneself or other agents. Additionally, a population decoding analysis suggests the presence of information for both observed and experiential outcomes in the amygdala. Encoding and decoding analyses suggested observational value coding in amygdala neurons occurred in a different subset of neurons than experiential value coding. Collectively, these findings support a key role for the human amygdala in the computations underlying the capacity for learning through observation.SIGNIFICANCE STATEMENT Single-neuron studies of the human brain provide a unique window into the computational mechanisms of cognition. In this study, epilepsy patients implanted intracranially with hybrid depth electrodes performed an observational learning (OL) task. We measured single-neuron activity in the amygdala and found a representation for observational rewards as well as observational expected reward values. Additionally, distinct subsets of amygdala neurons represented self-experienced and observational values. This study provides a rare glimpse into the role of human amygdala neurons in social cognition.

Management of Intracranial Stenotic Disease in Cancer Patients Treated With Vasotoxic Agents.

OBJECTIVE: To summarize the characteristics of and therapeutic options for cancer patients whose treatments may be vasotoxic and cause intracranial arterial stenotic disease and stroke. METHODS: We describe 3 patients with symptomatic cerebrovascular pathology that were being actively treated for cancer. RESULTS: Two of the patients were being treated with tyrosine kinase inhibitors (TKIs); and the third was being treated with 2 monoclonal antibodies, one of which was targeting an endothelial growth factor. These agents have been associated with vascular adverse events. Surgical revascularization was done in the first 2 patients, as they were suffering from cerebral ischemia. The third patient had suffered a significant brain hemorrhage, and therapeutic options were limited. In the first 2 patients, treatments also included antiplatelet agents and stopping/changing the TKI. In one of these patients we demonstrated regression of arterial stenosis after changing the TKI. CONCLUSIONS: Possibilities for treatment in this population, beyond the usual medical and surgical administrations, may include stopping or changing cancer drugs that may be related to the development of arterial pathology. Collaboration with oncologists is essential in this subset of patients. While aware of the potential for vascular toxicity, oncologists are often not fully appreciative of the fact that their therapeutic agents can cause stroke.

Embolization of a cavernous carotid fistula through the vein of Labbé: a new alternative transvenous access route.

Endovascular treatment of carotid cavernous fistulas (CCFs) via a transvenous approach is standard, but in rare cases this approach is challenging due to absence or thrombosis of the commonly used venous routes. A 61-year-old woman presented with a symptomatic CCF with all but one of the venous access routes to the CCF thrombosed, leaving an engorged superficial middle cerebral vein (SMCV) as the only venous outflow from the cavernous sinus. Access to the CCF was made possible after careful navigation of the sigmoid sinus, the vein of Labbé and the SMCV, bypassing the need for surgical access to the SMCV or for a direct transorbital puncture. The CCF was completely occluded by coiling and Onyx embolization. The patient made an uneventful recovery, with resolution of her symptoms. To the best of our knowledge, this access route has not been previously reported in the treatment of CCFs.

Embolization of a cavernous carotid fistula through the vein of Labbé: a new alternative transvenous access route.

Endovascular treatment of carotid cavernous fistulas (CCFs) via a transvenous approach is standard, but in rare cases this approach is challenging due to absence or thrombosis of the commonly used venous routes. A 61-year-old woman presented with a symptomatic CCF with all but one of the venous access routes to the CCF thrombosed, leaving an engorged superficial middle cerebral vein (SMCV) as the only venous outflow from the cavernous sinus. Access to the CCF was made possible after careful navigation of the sigmoid sinus, the vein of Labbé and the SMCV, bypassing the need for surgical access to the SMCV or for a direct transorbital puncture. The CCF was completely occluded by coiling and Onyx embolization. The patient made an uneventful recovery, with resolution of her symptoms. To the best of our knowledge, this access route has not been previously reported in the treatment of CCFs.

The human amygdala parametrically encodes the intensity of specific facial emotions and their categorical ambiguity.

The human amygdala is a key structure for processing emotional facial expressions, but it remains unclear what aspects of emotion are processed. We investigated this question with three different approaches: behavioural analysis of 3 amygdala lesion patients, neuroimaging of 19 healthy adults, and single-neuron recordings in 9 neurosurgical patients. The lesion patients showed a shift in behavioural sensitivity to fear, and amygdala BOLD responses were modulated by both fear and emotion ambiguity (the uncertainty that a facial expression is categorized as fearful or happy). We found two populations of neurons, one whose response correlated with increasing degree of fear, or happiness, and a second whose response primarily decreased as a linear function of emotion ambiguity. Together, our results indicate that the human amygdala processes both the degree of emotion in facial expressions and the categorical ambiguity of the emotion shown and that these two aspects of amygdala processing can be most clearly distinguished at the level of single neurons.

Mechanical Thrombectomy in Wake-Up Strokes: A Case Series Using Alberta Stroke Program Early CT Score (ASPECTS) for Patient Selection.

BACKGROUND: There is lack of published studies on mechanical thrombectomy with stent retrievers for wake-up stroke (WUS). OBJECTIVE: To report the outcomes of WUS patients with large vessel occlusions, selected for intervention based on Alberta Stroke Program Early CT Score (ASPECTS) and treated with stent retrievers or primary aspiration thrombectomy. METHODS: Data were collected retrospectively for each consecutive WUS patient undergoing mechanical thrombectomy with a stent retriever or primary aspiration catheter between February 2015 and September 2016. ASPECTS ≥ 6 was used as the primary imaging criterion for offering thrombectomy in these WUS patients. Main outcomes were the in-hospital improvement in the National Institutes of Health Stroke Scale (NIHSS) and the occurrence of symptomatic hemorrhage. RESULTS: Twelve patients were included in this study; 11 were treated with stent retrievers and 1 was treated with primary aspiration thrombectomy alone. Successful recanalization was achieved in 100% of the patients (33% thrombolysis in cerebral infarction [TICI] 2B and 67% TICI 3). Every patient experienced a reduction in the NIHSS during hospitalization, with a mean NIHSS decrease of 11.1 ± 5.1 points. There was a trend for a larger reduction in the NIHSS in patients with TICI 3 compared to TICI 2B recanalization. There was no symptomatic intracranial hemorrhage in our cohort. CONCLUSIONS: For patients with WUS, careful selection of patients using ASPECTS may allow for safe interventions, with low risk of clinical deterioration, and no-periprocedural mortality. All our patients demonstrated a reduction in their NIHSS after the thrombectomy and clinical improvement.

Persistently active neurons in human medial frontal and medial temporal lobe support working memory.

Persistent neural activity is a putative mechanism for the maintenance of working memories. Persistent activity relies on the activity of a distributed network of areas, but the differential contribution of each area remains unclear. We recorded single neurons in the human medial frontal cortex and medial temporal lobe while subjects held up to three items in memory. We found persistently active neurons in both areas. Persistent activity of hippocampal and amygdala neurons was stimulus-specific, formed stable attractors and was predictive of memory content. Medial frontal cortex persistent activity, on the other hand, was modulated by memory load and task set but was not stimulus-specific. Trial-by-trial variability in persistent activity in both areas was related to memory strength, because it predicted the speed and accuracy by which stimuli were remembered. This work reveals, in humans, direct evidence for a distributed network of persistently active neurons supporting working memory maintenance.

Transarterial Embolization of a Spontaneous Intraorbital Arteriovenous Fistula With n-BCA Glue.

Arteriovenous fistulae of the orbit are exceedingly rare. They are high-flow vascular malformations involving a fistula from the ophthalmic artery to one of the draining ophthalmic veins. Presenting symptoms can mimic those of carotid cavernous fistulae or of ophthalmic venous varices, and include diplopia, proptosis, chemosis, decreased visual acuity, and retro-orbital pain. Very few case reports are published on the treatment of this aggressive vascular malformation, and they uniformly describe techniques involving a transvenous access for the embolization of the fistula. To the best of authors' knowledge, they report the first case of transarterial embolization of an intraorbital AVF.

Representation of retrieval confidence by single neurons in the human medial temporal lobe.

Memory-based decisions are often accompanied by an assessment of choice certainty, but the mechanisms of such confidence judgments remain unknown. We studied the response of 1,065 individual neurons in the human hippocampus and amygdala while neurosurgical patients made memory retrieval decisions together with a confidence judgment. Combining behavioral, neuronal and computational analysis, we identified a population of memory-selective (MS) neurons whose activity signaled stimulus familiarity and confidence, as assessed by subjective report. In contrast, the activity of visually selective (VS) neurons was not sensitive to memory strength. The groups further differed in response latency, tuning and extracellular waveforms. The information provided by MS neurons was sufficient for a race model to decide stimulus familiarity and retrieval confidence. Together, our results indicate a trial-by-trial relationship between a specific group of neurons and declared memory strength in humans. We suggest that VS and MS neurons are a substrate for declarative memories.

Neurons in the human amygdala selective for perceived emotion.

The human amygdala plays a key role in recognizing facial emotions and neurons in the monkey and human amygdala respond to the emotional expression of faces. However, it remains unknown whether these responses are driven primarily by properties of the stimulus or by the perceptual judgments of the perceiver. We investigated these questions by recording from over 200 single neurons in the amygdalae of 7 neurosurgical patients with implanted depth electrodes. We presented degraded fear and happy faces and asked subjects to discriminate their emotion by button press. During trials where subjects responded correctly, we found neurons that distinguished fear vs. happy emotions as expressed by the displayed faces. During incorrect trials, these neurons indicated the patients' subjective judgment. Additional analysis revealed that, on average, all neuronal responses were modulated most by increases or decreases in response to happy faces, and driven predominantly by judgments about the eye region of the face stimuli. Following the same analyses, we showed that hippocampal neurons, unlike amygdala neurons, only encoded emotions but not subjective judgment. Our results suggest that the amygdala specifically encodes the subjective judgment of emotional faces, but that it plays less of a role in simply encoding aspects of the image array. The conscious percept of the emotion shown in a face may thus arise from interactions between the amygdala and its connections within a distributed cortical network, a scheme also consistent with the long response latencies observed in human amygdala recordings.

Single-neuron correlates of atypical face processing in autism.

People with autism spectrum disorder (ASD) show abnormal processing of faces. A range of morphometric, histological, and neuroimaging studies suggest the hypothesis that this abnormality may be linked to the amygdala. We recorded data from single neurons within the amygdalae of two rare neurosurgical patients with ASD. While basic electrophysiological response parameters were normal, there were specific and striking abnormalities in how individual facial features drove neuronal response. Compared to control patients, a population of neurons in the two ASD patients responded significantly more to the mouth, but less to the eyes. Moreover, we found a second class of face-responsive neurons for which responses to faces appeared normal. The findings confirm the amygdala's pivotal role in abnormal face processing by people with ASD at the cellular level and suggest that dysfunction may be traced to a specific subpopulation of neurons with altered selectivity for the features of faces.

Regarding the possibility of anterior vascular injury from the posterior approach to the lumbar disc space: an anatomical study.

STUDY DESIGN: Anatomical study with magnetic resonance imaging data. OBJECTIVE: To document the distances between the major retroperitoneal vessels and the anterior lumbar disc spaces; to determine the effect of patient positioning on these relationships; and to discuss ways to deal with vascular injury. SUMMARY OF BACKGROUND DATA: It is well known that there are major vascular structures anterior to the lower lumbar spine. Vascular injury during posterior approaches, however, remains a problem. These anatomical relationships have not been determined in vivo, and there are no data on the effect of turning the patient prone, and onto bolsters. METHODS: A random sampling of 49 women and 48 men was made. All examinations were performed in magnetic resonance scanners operating at 1.5 T. Measurements were made using electronic calipers on axial T2-weighted images. Post hoc studies were done on a smaller number of patients, to determine the effect of prone positioning. RESULTS: At the L4-L5 level, 66% of the common iliac arteries in women and 49% of those in men were within 5 mm of the anterior aspect of the disc space. At L5-S1, these numbers dropped to 23% for women and 19% for men. No relationship between the age of the patient and the distance from disc space to blood vessel was found. There was little change in these measurements between the supine and prone positions. The use of bolsters to decompress the abdominal contents in the prone position did not significantly alter the disc-artery distances. Venous relationships were also documented. CONCLUSION: The lower lumbar spine is confirmed to frequently be very close to the major retroperitoneal vessels. Turning the patient prone and placing the patient on bolsters does not change this relationship. This is part of the reason why vascular injuries may occur during routine lumbar spine surgery. Spine surgeons should be able to recognize and initiate treatment of such injuries.

Single-unit responses selective for whole faces in the human amygdala.

The human amygdala is critical for social cognition from faces, as borne out by impairments in recognizing facial emotion following amygdala lesions [1] and differential activation of the amygdala by faces [2-5]. Single-unit recordings in the primate amygdala have documented responses selective for faces, their identity, or emotional expression [6, 7], yet how the amygdala represents face information remains unknown. Does it encode specific features of faces that are particularly critical for recognizing emotions (such as the eyes), or does it encode the whole face, a level of representation that might be the proximal substrate for subsequent social cognition? We investigated this question by recording from over 200 single neurons in the amygdalae of seven neurosurgical patients with implanted depth electrodes [8]. We found that approximately half of all neurons responded to faces or parts of faces. Approximately 20% of all neurons responded selectively only to the whole face. Although responding most to whole faces, these neurons paradoxically responded more when only a small part of the face was shown compared to when almost the entire face was shown. We suggest that the human amygdala plays a predominant role in representing global information about faces, possibly achieved through inhibition between individual facial features.

Human memory strength is predicted by theta-frequency phase-locking of single neurons.

Learning from novel experiences is a major task of the central nervous system. In mammals, the medial temporal lobe is crucial for this rapid form of learning. The modification of synapses and neuronal circuits through plasticity is thought to underlie memory formation. The induction of synaptic plasticity is favoured by coordinated action-potential timing across populations of neurons. Such coordinated activity of neural populations can give rise to oscillations of different frequencies, recorded in local field potentials. Brain oscillations in the theta frequency range (3-8 Hz) are often associated with the favourable induction of synaptic plasticity as well as behavioural memory. Here we report the activity of single neurons recorded together with the local field potential in humans engaged in a learning task. We show that successful memory formation in humans is predicted by a tight coordination of spike timing with the local theta oscillation. More stereotyped spiking predicts better memory, as indicated by higher retrieval confidence reported by subjects. These findings provide a link between the known modulation of theta oscillations by many memory-modulating behaviours and circuit mechanisms of plasticity.

Embolization of the middle meningeal artery for the treatment of epidural hematoma.

Epidural hematomas (EDHs) are sometimes treated nonoperatively. Decision making, however, is not always perfect, and some hematomas chosen for observation later deteriorate and require surgical clot removal. With the current endovascular technology it is possible to embolize meningeal arteries to stop epidural bleeding. In this study, the author presents his experience in the treatment of a patient with a troublesome postoperative EDH successfully controlled with embolization therapy. This treatment is also useful in posttraumatic EDH and may obviate the need for surgery in some patients with EDHs who present early after injury and without significant mass effect.

Endovascular treatment of distally located giant aneurysms.

OBJECTIVE: Because giant aneurysms (GAs) can be technically difficult to clip, the endovascular approach is becoming increasingly popular. Endovascular treatment of distally located GAs, which often requires parent vessel occlusion, is particularly challenging because limited pathways are available for collateral flow. We aimed to determine the outcomes of endovascular attempts to treat GAs downstream from the circle of Willis. METHODS: Between 1991 and 1998, 27 patients with 27 distally located very large aneurysms or GAs were evaluated for possible endovascular treatment. Ten underwent selective embolization and 9 were treated with primary parent vessel occlusion, with or without distal bypass. Eight patients could not be treated endovascularly. RESULTS: Selective embolization resulted in only one cure. Two patients died as a result of subarachnoid hemorrhage during the follow-up period. One coil-treated patient, who underwent subsequent spontaneous parent vessel occlusion, and all nine patients treated primarily with parent vessel occlusion were considered cured after their treatments. Only two patients treated with parent vessel occlusion experienced periprocedural ischemia, which did not result in a major deficit in either case. Of the eight patients who could not be treated endovascularly, one succumbed to surgery, four died while being treated conservatively, and three were lost to follow-up monitoring. CONCLUSION: Selective aneurysm embolization is usually not curative in these situations. For selected patients, however, endovascular parent vessel occlusion is usually safe and effective in preventing the progression of symptoms and bleeding.