The amygdala is a key structure mediating emotional processing. Few studies have used direct electrical stimulation of the amygdala in humans to examine stimulation-elicited physiological and ...emotional responses, and the nature of such effects remains unclear. Determining the effects of electrical stimulation of the amygdala has important theoretical implications for current discrete and dimensional neurobiological theories of emotion, which differ substantially in their predictions about the emotional effects of such stimulation. To examine the effects of amygdala stimulation on physiological and subjective emotional responses we examined epilepsy patients undergoing intracranial EEG monitoring in which depth electrodes were implanted unilaterally or bilaterally in the amygdala. Nine subjects underwent both sham and acute monopolar electrical stimulation at various parameters in electrode contacts located in amygdala and within lateral temporal cortex control locations. Stimulation was applied at either 50 Hz or 130 Hz, while amplitudes were increased stepwise from 1 to 12 V, with subjects blinded to stimulation condition. Electrodermal activity (EDA), heart rate (HR), and respiratory rate (RR) were simultaneously recorded and subjective emotional response was probed after each stimulation period. Amygdala stimulation (but not lateral control or sham stimulation) elicited immediate and substantial dose-dependent increases in EDA and decelerations of HR, generally without affecting RR. Stimulation elicited subjective emotional responses only rarely, and did not elicit clinical seizures in any subject. These physiological results parallel stimulation findings with animals and are consistent with orienting/defensive responses observed with aversive visual stimuli in humans. In summary, these findings suggest that acute amygdala stimulation in humans can be safe and can reliably elicit changes in emotion physiology without significantly affecting subjective emotional experience, providing a useful approach for investigation of amygdala-mediated modulatory effects on cognition.
•Increasing amplitudes of amygdala stimulation elicited dose-dependent increases in EDA and decreases in heart rate.•In one patient, amygdala stimulation caused subjective experiences of fear and anxiety, accompanied by increased heart rate.•Amygdala stimulation reliably elicits changes in autonomic activity in a dose-dependent and safe manner.•At the amplitudes of stimulation delivered, amygdala stimulation elicits subjective emotional experiences only infrequently.
A monosynaptic projection from the cortex to the subthalamic nucleus is thought to have an important role in basal ganglia function and in the mechanism of therapeutic subthalamic deep-brain ...stimulation, but in humans the evidence for its existence is limited. We sought physiological confirmation of the cortico-subthalamic hyperdirect pathway using invasive recording techniques in patients with Parkinson's disease (9 men, 1 woman). We measured sensorimotor cortical evoked potentials using a temporary subdural strip electrode in response to low-frequency deep-brain stimulation in patients undergoing awake subthalamic or pallidal lead implantations. Evoked potentials were grouped into very short latency (<2 ms), short latency (2-10 ms), and long latency (10-100 ms) from the onset of the stimulus pulse. Subthalamic and pallidal stimulation resulted in very short-latency evoked potentials at 1.5 ms in the primary motor cortex accompanied by EMG-evoked potentials consistent with corticospinal tract activation. Subthalamic, but not pallidal stimulation, resulted in three short-latency evoked potentials at 2.8, 5.8, and 7.7 ms in a widespread cortical distribution, consistent with antidromic activation of the hyperdirect pathway. Long-latency potentials were evoked by both targets, with subthalamic responses lagging pallidal responses by 10-20 ms, consistent with orthodromic activation of the thalamocortical pathway. The amplitude of the first short-latency evoked potential was predictive of the chronic therapeutic stimulation contact.
This is the first physiological demonstration of the corticosubthalamic hyperdirect pathway and its topography at high spatial resolution in humans. We studied cortical potentials evoked by deep-brain stimulation in patients with Parkinson's disease undergoing awake lead implantation surgery. Subthalamic stimulation resulted in multiple short-latency responses consistent with activation of hyperdirect pathway, whereas no such response was present during pallidal stimulation. We contrast these findings with very short latency, direct corticospinal tract activations, and long-latency responses evoked through polysynaptic orthodromic projections. These findings underscore the importance of incorporating the hyperdirect pathway into models of human basal ganglia function.
Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4-10 Hz rhythm that coordinates brain-wide neural ...activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in theta's function. To characterize human hippocampal theta, we examine the properties of theta oscillations throughout the anterior-posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observe hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently displays oscillations at ~8-Hz and the precise frequency of these oscillations correlates with the speed of movement, implicating these signals in spatial navigation. We also observe slower ~3 Hz oscillations, but these signals are more prevalent in the anterior hippocampus and their frequency does not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high- and low-frequency theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes.
Graded decisions in the human brain Xie, Tao; Adamek, Markus; Cho, Hohyun ...
Nature communications,
05/2024, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Decision-makers objectively commit to a definitive choice, yet at the subjective level, human decisions appear to be associated with a degree of uncertainty. Whether decisions are definitive (i.e., ...concluding in all-or-none choices), or whether the underlying representations are graded, remains unclear. To answer this question, we recorded intracranial neural signals directly from the brain while human subjects made perceptual decisions. The recordings revealed that broadband gamma activity reflecting each individual's decision-making process, ramped up gradually while being graded by the accumulated decision evidence. Crucially, this grading effect persisted throughout the decision process without ever reaching a definite bound at the time of choice. This effect was most prominent in the parietal cortex, a brain region traditionally implicated in decision-making. These results provide neural evidence for a graded decision process in humans and an analog framework for flexible choice behavior.
Summary
Objective
Magnetic resonance (MR) thermography–guided laser interstitial thermal therapy, or stereotactic laser ablation (SLA), is a minimally invasive alternative to open surgery for focal ...epilepsy caused by cerebral cavernous malformations (CCMs). We examined the safety and effectiveness of SLA of epileptogenic CCMs.
Methods
We retrospectively analyzed 19 consecutive patients who presented with focal seizures associated with a CCM. Each patient underwent SLA of the CCM and adjacent cortex followed by standard clinical and imaging follow‐up.
Results
All but one patient had chronic medically refractory epilepsy (median duration 8 years, range 0.5‐52 years). Lesions were located in the temporal (13), frontal (five), and parietal (one) lobes. CCMs induced magnetic susceptibility artifacts during thermometry, but perilesional cortex was easily visualized. Fourteen of 17 patients (82%) with >12 months of follow‐up achieved Engel class I outcomes, of which 10 (59%) were Engel class IA. Two patients who were not seizure‐free from SLA alone became so following intracranial electrode‐guided open resection. Delayed postsurgical imaging validated CCM involution (median 83% volume reduction) and ablation of surrounding cortex. Histopathologic examination of one previously ablated CCM following open surgery confirmed obliteration. SLA caused no detectable hemorrhages. Two symptomatic neurologic deficits (visual and motor) were predictable, and neither was permanently disabling.
Significance
In a consecutive retrospective series, MR thermography–guided SLA was an effective alternative to open surgery for epileptogenic CCM. The approach was free of hemorrhagic complications, and clinically significant neurologic deficits were predictable. SLA presents no barrier to subsequent open surgery when needed.
Abstract
Approximately one-third of patients with epilepsy do not achieve adequate seizure control through medical management alone. Mesial temporal lobe epilepsy (MTLE) is one of the most common ...forms of medically refractory epilepsy referred for surgical management. Stereotactic laser amygdalohippocampotomy using magnetic resonance-guided laser interstitial thermal therapy (MRg-LITT) is an important emerging therapy for MTLE. Initial published reports support MRg-LITT as a less invasive surgical option with a shorter hospital stay and fewer neurocognitive side effects compared with craniotomy for anterior temporal lobectomy with amygdalohippocampectomy and selective amygdalohippocampectomy. We provide a historical overview of laser interstitial thermal therapy development and the technological advancements that led to the currently available commercial systems. Current applications of MRg-LITT for MTLE, reported outcomes, and technical issues of the surgical procedure are reviewed. Although initial reports indicate that stereotactic laser amygdalohippocampotomy may be a safe and effective therapy for medically refractory MTLE, further research is required to establish its long-term effectiveness and its cost/benefit profile.
Objective
To evaluate the outcomes 1 year and longer following stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy in a large series of patients treated over a 5‐year period ...since introduction of this novel technique.
Methods
Surgical outcomes of a consecutive series of 58 patients with mesial temporal lobe epilepsy who underwent the surgery at our institution with at least 12 months of follow‐up were retrospectively evaluated. A subgroup analysis was performed comparing patients with and without mesial temporal sclerosis.
Results
One year following stereotactic laser amygdalohippocampotomy, 53.4% (95% confidence interval CI = 40.8–65.7%) of all patients were free of disabling seizures (Engel I). Three of 9 patients became seizure‐free following repeat ablation. Subgroup analysis showed that 60.5% (95% CI = 45.6–73.7%) of patients with mesial temporal sclerosis were free of disabling seizures as compared to 33.3% (95% CI = 15.0–58.5%) of patients without mesial temporal sclerosis. Quality of Life in Epilepsy‐31 scores significantly improved at the group level, few procedure‐related complications were observed, and verbal memory outcome was better than historical open resection data.
Interpretation
In an unselected consecutive series of patients, stereotactic laser amygdalohippocampotomy yielded seizure‐free rates for patients with mesial temporal lobe epilepsy lower than, but comparable to, the outcomes typically associated with open temporal lobe surgery. Analogous to results from open surgery, patients without mesial temporal sclerosis fared less well. This novel procedure is an effective minimally invasive alternative to resective surgery. In the minority of patients not free of disabling seizures, laser ablation presents no barrier to additional open surgery. Ann Neurol 2018;83:575–587
Stereotactic laser amygdalohippocampotomy (SLAH) uses laser interstitial thermal therapy guided by magnetic resonance thermography. This novel intervention can achieve seizure freedom while ...minimizing collateral damage compared to traditional open surgery, in patients with mesial temporal lobe epilepsy. An algorithm is presented to guide treatment decisions for initial and repeat procedures in patients with and without mesial temporal sclerosis. SLAH may improve access by medication-refractory patients to effective surgical treatments and thereby decrease medical complications, increase productivity, and minimize socioeconomic consequences in patients with chronic epilepsy.
ABSTRACT
BACKGROUND:
Open surgery effectively treats mesial temporal lobe epilepsy, but carries the risk of neurocognitive deficits, which may be reduced with minimally invasive alternatives.
...OBJECTIVE:
To describe technical and clinical outcomes of stereotactic laser amygdalohippocampotomy with real-time magnetic resonance thermal imaging guidance.
METHODS:
With patients under general anesthesia and using standard stereotactic methods, 13 adult patients with intractable mesial temporal lobe epilepsy (with and without mesial temporal sclerosis MTS) prospectively underwent insertion of a saline-cooled fiberoptic laser applicator in amygdalohippocampal structures from an occipital trajectory. Computer-controlled laser ablation was performed during continuous magnetic resonance thermal imaging followed by confirmatory contrast-enhanced anatomic imaging and volumetric reconstruction. Clinical outcomes were determined from seizure diaries.
RESULTS:
A mean 60% volume of the amygdalohippocampal complex was ablated in 13 patients (9 with MTS) undergoing 15 procedures. Median hospitalization was 1 day. With follow-up ranging from 5 to 26 months (median, 14 months), 77% (10/13) of patients achieved meaningful seizure reduction, of whom 54% (7/13) were free of disabling seizures. Of patients with preoperative MTS, 67% (6/9) achieved seizure freedom. All recurrences were observed before 6 months. Variances in ablation volume and length did not account for individual clinical outcomes. Although no complications of laser therapy itself were observed, 1 significant complication, a visual field defect, resulted from deviated insertion of a stereotactic aligning rod, which was corrected before ablation.
CONCLUSION:
Real-time magnetic resonance-guided stereotactic laser amygdalohippocampotomy is a technically novel, safe, and effective alternative to open surgery. Further evaluation with larger cohorts over time is warranted.
Modulating brain oscillations has strong therapeutic potential. Interventions that both non-invasively modulate deep brain structures and are practical for chronic daily home use are desirable for a ...variety of therapeutic applications. Repetitive audio-visual stimulation, or sensory flicker, is an accessible approach that modulates hippocampus in mice, but its effects in humans are poorly defined. We therefore quantified the neurophysiological effects of flicker with high spatiotemporal resolution in patients with focal epilepsy who underwent intracranial seizure monitoring. In this interventional trial (NCT04188834) with a cross-over design, subjects underwent different frequencies of flicker stimulation in the same recording session with the effect of sensory flicker exposure on local field potential (LFP) power and interictal epileptiform discharges (IEDs) as primary and secondary outcomes, respectively. Flicker focally modulated local field potentials in expected canonical sensory cortices but also in the medial temporal lobe and prefrontal cortex, likely via resonance of stimulated long-range circuits. Moreover, flicker decreased interictal epileptiform discharges, a pathological biomarker of epilepsy and degenerative diseases, most strongly in regions where potentials were flicker-modulated, especially the visual cortex and medial temporal lobe. This trial met the scientific goal and is now closed. Our findings reveal how multi-sensory stimulation may modulate cortical structures to mitigate pathological activity in humans.