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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Direct access to the carotid circulation by cut down for endovascular neuro-interventions.

BACKGROUND: Not all vascular lesions of the brain that are amenable to endovascular treatment are safely accessible via the transfemoral route. We describe our technique of carotid cut down for endovascular access and present a couple of illustrative cases. The increasing number of neurosurgeons performing endovascular procedures, or collaborating with interventional neuroradiologists, suggests that this technique should be revived. METHODS: Through a small transverse neck incision at the level of the thyroid cartilage, the CCA, ICA, and external carotid artery are exposed. After obtaining vascular control with vessel loupes, a purse-string suture is placed in the CCA. Puncture of the artery in the center of the purse string is followed by navigation of a wire, and then a sheath, into the ICA. The neurointervention is then carried out. At the conclusion of the procedure, the sheath is removed from the CCA and the purse string tied to secure the artery. RESULTS: This technique has allowed us to successfully access the intracranial circulation in 6 patients with challenging anatomy. We present here 2 of the original cases leading to our increasing use of this technique. CONCLUSION: Carotid cut down for direct puncture of the CCA is a viable option to gain access to the intracranial circulation when the transfemoral route seems difficult or dangerous.

Balloon assistance as a routine adjunct to the endovascular treatment of cerebral aneurysms.

BACKGROUND: The technique of BAC is attractive because the balloon theoretically allows for (1) "control" of blood flow in the vessel; (2) improved stability of the microcatheter in the aneurysm; (3) denser packing with coils; and (4) improved delineation of the neck of the aneurysm. The purpose of this communication is to document our outcomes with this technique and help determine if this technique is of benefit. METHODS: Data on all endovascularily treated aneurysms have been gathered prospectively at our institution since March 2000. The first case of BAC was in November 2000. We have become very liberal in our indications, to the point where all aneurysms are considered for BAC. We document here our results obtained over a 1-year period, during which we treated 56 patients with 60 aneurysms in 58 coiling sessions using only bare platinum coils. RESULTS: Balloon-assisted coiling was attempted in 50 (86%) of the 58 coiling sessions. Successful embolizations were achieved in all but 1 patient in whom BAC was attempted. There was one technique-related complication. The packing density for the BAC cases was, on average, 35.7% (median, 34.6%; SD, 14.1%). Follow-up angiography revealed a 13% class 3 recurrence rate. CONCLUSION: With experience, BAC can be used in the endovascular treatment of most cerebral aneurysms. Although complications are associated with its use, we feel that the risk/benefit ratio is favorable. Excellent coil packing density with bare coils is achievable with this technique.

Complications of endovascular treatment of cerebral aneurysms.

BACKGROUND: The International Subarachnoid Aneurysm Trial has indicated that endovascular management of acutely ruptured aneurysms may be superior to surgery. Clearly poor results ensue from both forms of treatment, and some of these are because of technical complications (not just poor patient status). This observational study was performed to determine the complications associated with the endovascular treatment of ruptured and unruptured cerebral aneurysms. METHODS: Prospective data were gathered on 118 patients undergoing 126 endovascular treatment sessions for 126 nontraumatic cerebral aneurysms (30% unruptured) over a 3-year period. The average age was 51 years (range, 12-85 years). Females comprised 75% of the population treated. RESULTS: Good outcomes were achieved with 71% of the procedures (59% for subarachnoid hemorrhage [SAH]; 97% for unruptured). No bleeding or rebleeding occurred from treated aneurysms. Vessel or aneurysm perforation occurred in 11 cases and led to adverse outcome in 3 (3%). Thromboembolic complications were felt to cause cerebral infarction in 8 cases (6%). The risk of vessel/aneurysm rupture or thromboembolic stroke was greater in patients with SAH. Eight attempts to coil (6%) were initially unsuccessful. Two of these were later successfully coiled and others had surgery. None of the failed attempts led to clinical deterioration. Balloon-assisted coiling (BAC) was not associated with an increased complication rate. CONCLUSIONS: Vessel perforation and thromboembolic stroke are significant risks of endovascular treatment, especially after SAH. In our hands, however, BAC does not add to this risk.

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.

Ventriculostomy-related cerebral hemorrhages after endovascular aneurysm treatment.

BACKGROUND AND PURPOSE: Recent evidence suggests that endovascular treatment of acutely ruptured aneurysms is equivalent, if not superior, to surgical treatment. Not all patients who undergo endovascular treatment do well, however. We have identified ventriculostomy-related hemorrhage to be a potential source of morbidity and mortality. METHODS: Prospectively gathered data on patients (n = 51) admitted to a hospital for the endovascular treatment of acutely ruptured aneurysms during a 2.5-year period was analyzed. RESULTS: Twenty-four patients had drains inserted, and three suffered symptomatic ventriculostomy-related cerebral hemorrhages. Two of the three patients were being treated with heparin, one of whom also received clopidogrel, and the third was being treated with low molecular weight heparin at the time. The latter had a normal platelet count, prothrombin time, and activated partial thromboplastin time. All cerebral hemorrhages were deemed to have occurred as a result of drain manipulation. CONCLUSION: The risk of hemorrhage must be considered when using anticoagulation and antiplatelet therapy in patients requiring ventriculostomy. Interventionalists must not only work closely with neurosurgeons when it is anticipated that a ventriculostomy may be needed but also ensure that there is good communication with the neurosurgical team during the postprocedural period.

Surgical handling characteristics of an ethylene vinyl alcohol copolymer compared with N-butyl cyanoacrylate used for embolization of vessels in an arteriovenous malformation resection model in swine.

OBJECT: There have been significant improvements in neurovascular technology and implants over the past decade. One such material, N-butyl cyanoacrylate (NBCA), is now commercially available for cerebral arteriovenous malformation (AVM) embolization in the US. An ethylene vinyl alcohol copolymer preparation, Onyx, which is currently being evaluated, is approved for use outside North America. Although reports indicate that Onyx may be superior to NBCA from an endovascular perspective, little information exists about its surgical handling characteristics. The purpose of this study was to compare the surgical handling characteristics of Onyx-treated vessels with those of NBCA-embolized vessels in an AVM resection model. METHODS: Fourteen pigs (two groups of seven) were anesthetized. A femoral artery was cannulated, followed by selective catheterization of the ascending pharyngeal arteries. Nidal rete mirabile (RM) embolizations were performed using either 6% Onyx or 20% NBCA. After angiographically confirmed obliteration of flow in the right RM, microsurgical resection of this structure was performed. Surgical handling characteristics of the embolized RM were rated on a scale of 1 to 5 and blood loss was recorded. Different surgeons performed the embolizations and resections. The surgeon who performed resections was blinded to the embolization agent used, and the data analysis was also performed in a blinded fashion. The surgical handling scores were superior (p < 0.05) in the Onyx-treated group. Although there was also less blood loss in this group, the difference was not significant. Subjectively, the surgeon who performed the resections believed that Onyx was softer and handled better than NBCA. CONCLUSIONS: Onyx, which may offer endovascular advantages, also seems to provide benefits for the surgeon.

Therapeutic effect of caspase inhibitors in the prevention of apoptosis and reversal of chronic cerebral vasospasm.

One of the important histological changes in cerebral vasospasm after subarachnoid hemorrhage (SAH) is endothelial cell damage, which involves apoptosis. The current study was undertaken to determine whether anti-apoptosis therapy prevents apoptosis and reverses vasospasm in a dog SAH model. Twenty-three mongrel dogs of either sex, weighing 17-25 kg, were subjected to autologous arterial blood injection into the cisterna magna on day 0 and day 2, and sacrificed on day 7. Angiography was performed on day 0 before blood injection and on day 7 before sacrifice. Caspase-2 (Z-VDVAD-FMK, 10 microM) inhibitor, caspase-3 (Z-DEVD-FMK, 10 microM) inhibitor, or vehicle (DMSO) were injected intrathecally from day 2 to day 6. The effects of caspase inhibitors on apoptosis and vasospasm were evaluated by angiography and transmission electron microscopy. The residual diameter of the basilar artery on day 7 in SAH dogs without treatment was 53.4+/-5.5% of the day 0 diameter. Marked damage to the endothelial cells, including apoptotic like changes, was observed in these arteries. Both caspase inhibitors prevented apoptosis in the endothelial cells. Only caspase-3 inhibitor, however, had a near-significant effect on reducing 13.3% of angiographic vasospasm. Higher doses and early treatment, as well as other more potent apoptosis inhibitors, are recommended for future studies.