Theta mediated dynamics of human hippocampal-neocortical learning systems in memory formation and retrieval.

Episodic memory arises as a function of dynamic interactions between the hippocampus and the neocortex, yet the mechanisms have remained elusive. Here, using human intracranial recordings during a mnemonic discrimination task, we report that 4-5 Hz (theta) power is differentially recruited during discrimination vs. overgeneralization, and its phase supports hippocampal-neocortical when memories are being formed and correctly retrieved. Interactions were largely bidirectional, with small but significant net directional biases; a hippocampus-to-neocortex bias during acquisition of new information that was subsequently correctly discriminated, and a neocortex-to-hippocampus bias during accurate discrimination of new stimuli from similar previously learned stimuli. The 4-5 Hz rhythm may facilitate the initial stages of information acquisition by neocortex during learning and the recall of stored information from cortex during retrieval. Future work should further probe these dynamics across different types of tasks and stimuli and computational models may need to be expanded accordingly to accommodate these findings.

Theta mediated dynamics of human hippocampal-neocortical learning systems in memory formation and retrieval.

Episodic memory arises as a function of dynamic interactions between the hippocampus and the neocortex, yet the mechanisms have remained elusive. Here, using human intracranial recordings during a mnemonic discrimination task, we report that 4-5 Hz (theta) power is differentially recruited during discrimination vs. overgeneralization, and its phase supports hippocampal-neocortical when memories are being formed and correctly retrieved. Interactions were largely bidirectional, with small but significant net directional biases; a hippocampus-to-neocortex bias during acquisition of new information that was subsequently correctly discriminated, and a neocortex-to-hippocampus bias during accurate discrimination of new stimuli from similar previously learned stimuli. The 4-5 Hz rhythm may facilitate the initial stages of information acquisition by neocortex during learning and the recall of stored information from cortex during retrieval. Future work should further probe these dynamics across different types of tasks and stimuli and computational models may need to be expanded accordingly to accommodate these findings.

An orexigenic subnetwork within the human hippocampus.

Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive processing1-4. This function has been reported to be mediated at least in part by lateral hypothalamic inputs, including those involving orexigenic lateral hypothalamic neuropeptides, such as melanin-concentrating hormone5,6. This circuit, however, remains elusive in humans. Here we combine tractography, intracranial electrophysiology, cortico-subcortical evoked potentials, and brain-clearing 3D histology to identify an orexigenic circuit involving the lateral hypothalamus and converging in a hippocampal subregion. We found that low-frequency power is modulated by sweet-fat food cues, and this modulation was specific to the dorsolateral hippocampus. Structural and functional analyses of this circuit in a human cohort exhibiting dysregulated eating behaviour revealed connectivity that was inversely related to body mass index. Collectively, this multimodal approach describes an orexigenic subnetwork within the human hippocampus implicated in obesity and related eating disorders.

A rodent obstacle course procedure controls delivery of enrichment and enhances complex cognitive functions.

Enrichment in rodents affects brain structure, improves behavioral performance, and is neuroprotective. Similarly, in humans, according to the cognitive reserve concept, enriched experience is functionally protective against neuropathology. Despite this parallel, the ability to translate rodent studies to human clinical situations is limited. This limitation is likely due to the simple cognitive processes probed in rodent studies and the inability to control, with existing methods, the degree of rodent engagement with enrichment material. We overcome these two difficulties with behavioral tasks that probe, in a fine-grained manner, aspects of higher-order cognition associated with deterioration with aging and dementia, and a new enrichment protocol, the 'Obstacle Course' (OC), which enables controlled enrichment delivery, respectively. Together, these two advancements will enable better specification (and comparisons) of the nature of impairments in animal models of complex mental disorders and the potential for remediation from various types of intervention (e.g., enrichment, drugs). We found that two months of OC enrichment produced substantial and sustained enhancements in categorization memory, perceptual object invariance, and cross-modal sensory integration in mice. We also tested mice on behavioral tasks previously shown to benefit from traditional enrichment: spontaneous object recognition, object location memory, and pairwise visual discrimination. OC enrichment improved performance relative to standard housing on all six tasks and was in most cases superior to conventional home-cage enrichment and exercise track groups.

Proximal CA1 20-40 Hz power dynamics reflect trial-specific information processing supporting nonspatial sequence memory.

The hippocampus is known to play a critical role in processing information about temporal context. However, it remains unclear how hippocampal oscillations are involved, and how their functional organization is influenced by connectivity gradients. We examined local field potential activity in CA1 as rats performed a nonspatial odor sequence memory task. We found that odor sequence processing epochs were characterized by distinct spectral profiles and proximodistal CA1 gradients of theta and 20-40 Hz power than track running epochs. We also discovered that 20-40 Hz power was predictive of sequence memory performance, particularly in proximal CA1 and during the plateau of high power observed in trials in which animals had to maintain their decision until instructed to respond. Altogether, these results provide evidence that dynamics of 20-40 Hz power along the CA1 axis are linked to trial-specific processing of nonspatial information critical to order judgments and are consistent with a role for 20-40 Hz power in gating information processing.

Second opinion in spine surgery: A scoping review.

BACKGROUND: As a growing number of patients seek consultations for increasingly complex and costly spinal surgery, it is of both clinical and economic value to investigate the role for second opinions (SOs). Here, we summarized and focused on the shortcomings of 14 studies regarding the role and value of SOs before proceeding with spine surgery. METHODS: Utilizing PubMed, Google Scholar, and Scopus, we identified 14 studies that met the inclusion criteria that included: English, primary articles, and studies published in the past 20 years. RESULTS: We identified the following findings regarding SO for spine surgery: (1) about 40.6% of spine consultations are SO cases; (2) 61.3% of those received a discordant SO; (3) 75% of discordant SOs recommended conservative management; and (4) SO discordance applied to a variety of procedures. CONCLUSION: The 14 studies reviewed regarding SOs in spine surgery showed that half of the SOs differed from those given in the initial consultation and that SOs in spine surgery can have a substantial impact on patient care. Absent are prospective studies investigating the impact of following a first versus second opinion. These studies are needed to inform the potential benefit of universal implementation of SOs before major spine operations to potentially reduce the frequency and type/extent of surgery.

The insulo-opercular cortex encodes food-specific content under controlled and naturalistic conditions.

The insulo-opercular network functions critically not only in encoding taste, but also in guiding behavior based on anticipated food availability. However, there remains no direct measurement of insulo-opercular activity when humans anticipate taste. Here, we collect direct, intracranial recordings during a food task that elicits anticipatory and consummatory taste responses, and during ad libitum consumption of meals. While cue-specific high-frequency broadband (70-170 Hz) activity predominant in the left posterior insula is selective for taste-neutral cues, sparse cue-specific regions in the anterior insula are selective for palatable cues. Latency analysis reveals this insular activity is preceded by non-discriminatory activity in the frontal operculum. During ad libitum meal consumption, time-locked high-frequency broadband activity at the time of food intake discriminates food types and is associated with cue-specific activity during the task. These findings reveal spatiotemporally-specific activity in the human insulo-opercular cortex that underlies anticipatory evaluation of food across both controlled and naturalistic settings.

Getting Down to the Bare Bones: Does laminoplasty or laminectomy With Fusion Provide Better Outcomes for Patients With Multilevel Cervical Spondylotic Myelopathy?

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is a degenerative disorder leading to progressive decline in spinal cord function. Cervical laminoplasty (CLP) and cervical laminectomy with fusion (CLF) are standard treatments for multilevel CSM. However, it is still unclear whether one procedure over the other provides better outcomes. Here, we performed a comprehensive review of published articles that compare the clinical outcomes and costs between CLP and CLF for CSM. METHODS: A literature search was performed using PubMed, Web of Science, and Cochrane databases. Strict exclusion criteria were applied, and included articles were then assessed for publication year, study design, and significant differences in outcome variables. RESULTS: From 519 studies identified with search terms, 38 studies were included for the qualitative analysis. Statistically significant differences in the clinical outcomes and costs were found in 18 studies. Eleven studies were prospective or retrospective, and 8 studies were meta-analyses. For the outcome variables of interest, results were reported by classifying into prospective studies, retrospective studies, and meta-analyses. CONCLUSION: CLP and CLF are 2 of the most commonly performed surgical procedures for the treatment of CSM. Although CLP and CLF each provide satisfactory clinical outcomes for patients with CMS, CLP may result in better cervical range of motion and less cost, length of stay, operation time, blood loss, paraspinal muscular atrophy, and rate of nerve palsies as compared to CLF. The major limitation of CLP versus CLF comparison studies includes the heterogeneity in techniques and preoperative criteria. Thus, further validation and investigations in larger cohorts will be required.

Epidural electrical stimulation for spinal cord injury.

A long-standing goal of spinal cord injury research is to develop effective repair strategies, which can restore motor and sensory functions to near-normal levels. Recent advances in clinical management of spinal cord injury have significantly improved the prognosis, survival rate and quality of life in patients with spinal cord injury. In addition, a significant progress in basic science research has unraveled the underlying cellular and molecular events of spinal cord injury. Such efforts enabled the development of pharmacologic agents, biomaterials and stem-cell based therapy. Despite these efforts, there is still no standard care to regenerate axons or restore function of silent axons in the injured spinal cord. These challenges led to an increased focus on another therapeutic approach, namely neuromodulation. In multiple animal models of spinal cord injury, epidural electrical stimulation of the spinal cord has demonstrated a recovery of motor function. Emerging evidence regarding the efficacy of epidural electrical stimulation has further expanded the potential of epidural electrical stimulation for treating patients with spinal cord injury. However, most clinical studies were conducted on a very small number of patients with a wide range of spinal cord injury. Thus, subsequent studies are essential to evaluate the therapeutic potential of epidural electrical stimulation for spinal cord injury and to optimize stimulation parameters. Here, we discuss cellular and molecular events that continue to damage the injured spinal cord and impede neurological recovery following spinal cord injury. We also discuss and summarize the animal and human studies that evaluated epidural electrical stimulation in spinal cord injury.

Anticipatory human subthalamic area beta-band power responses to dissociable tastes correlate with weight gain.

The availability of enticing sweet, fatty tastes is prevalent in the modern diet and contribute to overeating and obesity. In animal models, the subthalamic area plays a role in mediating appetitive and consummatory feeding behaviors, however, its role in human feeding is unknown. We used intraoperative, subthalamic field potential recordings while participants (n = 5) engaged in a task designed to provoke responses of taste anticipation and receipt. Decreased subthalamic beta-band (15-30 Hz) power responses were observed for both sweet-fat and neutral tastes. Anticipatory responses to taste-neutral cues started with an immediate decrease in beta-band power from baseline followed by an early beta-band rebound above baseline. On the contrary, anticipatory responses to sweet-fat were characterized by a greater and sustained decrease in beta-band power. These activity patterns were topographically specific to the subthalamic nucleus and substantia nigra. Further, a neural network trained on this beta-band power signal accurately predicted (AUC ≥ 74%) single trials corresponding to either taste. Finally, the magnitude of the beta-band rebound for a neutral taste was associated with increased body mass index after starting deep brain stimulation therapy. We provide preliminary evidence of discriminatory taste encoding within the subthalamic area associated with control mechanisms that mediate appetitive and consummatory behaviors.

The market landscape of online second opinion services for spine surgery.

BACKGROUND: The aim of this study was to identify patient interest in second opinion services online and identify the options patients have in obtaining second opinions from spine surgeons in the United States. METHODS: We utilized Google Trends (i.e., search data since 2010) to ascertain the level of interest in receiving second opinions for spinal surgery. In addition, we contacted the top 30 hospitals for neurology and neurosurgery in the U.S. News rankings by phone to obtain information regarding when/how and at what cost they provide second opinions for spine surgery. RESULTS: The cost of the second surgical opinions averaged $493 (±$343) USD (range $90-$1,300); the time to receive a second opinion averaged 20 (±19) days (range 1 day-5 months). Remote or "online second opinion" programs charged an average of $643 (±$259) USD (range $100-$850), and the time to receive an "online second opinion" averaged 14 (±7) days (range 1-4 weeks). CONCLUSION: Although second opinions have been shown to be beneficial to patients, ambiguous or high costs and long wait times may serve as barriers for certain groups (i.e., uninsured or underinsured) and potentially diminish the quality of care.

Back pain outcomes after minimally invasive anterior lumbar interbody fusion: a systematic review.

OBJECTIVE: Minimally invasive anterior lumbar interbody fusion surgery (MIS ALIF) is a technique that restores disc height and lumbar lordosis through a smaller exposure and less soft-tissue trauma compared to open approaches. The mini-open and laparoscopic assistance techniques are two main forms of MIS ALIF. The authors conducted a systematic review that sought to critically summarize the literature on back pain following MIS ALIF. METHODS: In March 2020, the authors searched the PubMed, Web of Science, and Cochrane Library databases for studies describing back pain visual analog scale (VAS) outcomes after MIS ALIF. The following exclusion criteria were applied to studies evaluated in full text: 1) the study included fewer than 20 patients, 2) the mean follow-up duration was shorter than 12 months, 3) the study did not report back pain VAS score as an outcome measure, and 4) MIS ALIF was not studied specifically. The methodology for the included studies were evaluated for potential biases and assigned a level of evidence. RESULTS: There were a total of 552 patients included from 13 studies. The most common biases were selection and interviewer bias. The majority of studies were retrospective. The mean sample size was 42.3 patients. The mean follow-up duration was approximately 41.8 months. The mean postoperative VAS reduction was 5.1 points. The mean VAS reduction for standalone grafts was 5.9 points, and 5.0 points for those augmented with posterior fixation. The most common complications included bladder or urinary dysfunction, infection, and hardware-related complications. CONCLUSIONS: This was a systematic review of back pain outcomes following MIS ALIF. Back pain VAS score was reduced postoperatively across all studies. The complication rates were low overall. MIS ALIF is safe and effective at reducing back pain in appropriate patient populations.

Electrophysiology and Structural Connectivity of the Posterior Hypothalamic Region: Much to Learn From a Rare Indication of Deep Brain Stimulation.

Cluster headache (CH) is among the most common and debilitating autonomic cephalalgias. We characterize clinical outcomes of deep brain stimulation (DBS) to the posterior hypothalamic region through a novel analysis of the electrophysiological topography and tractography-based structural connectivity. The left posterior hypothalamus was targeted ipsilateral to the refractory CH symptoms. Intraoperatively, field potentials were captured in 1 mm depth increments. Whole-brain probabilistic tractography was conducted to assess the structural connectivity of the estimated volume of activated tissue (VAT) associated with therapeutic response. Stimulation of the posterior hypothalamic region led to the resolution of CH symptoms, and this benefit has persisted for 1.5-years post-surgically. Active contacts were within the posterior hypothalamus and dorsoposterior border of the ventral anterior thalamus (VAp). Delta- (3 Hz) and alpha-band (8 Hz) powers increased and peaked with proximity to the posterior hypothalamus. In the posterior hypothalamus, the delta-band phase was coupled to beta-band amplitude, the latter of which has been shown to increase during CH attacks. Finally, we identified that the VAT encompassing these regions had a high proportion of streamlines of pain processing regions, including the insula, anterior cingulate gyrus, inferior parietal lobe, precentral gyrus, and the brainstem. Our unique case study of posterior hypothalamic region DBS supports durable efficacy and provides a platform using electrophysiological topography and structural connectivity, to improve mechanistic understanding of CH and this promising therapy.

Spatiotemporal patterns of neocortical activity around hippocampal sharp-wave ripples.

A prevalent model is that sharp-wave ripples (SWR) arise 'spontaneously' in CA3 and propagate recent memory traces outward to the neocortex to facilitate memory consolidation there. Using voltage and extracellular glutamate transient recording over widespread regions of mice dorsal neocortex in relation to CA1 multiunit activity (MUA) and SWR, we find that the largest SWR-related modulation occurs in retrosplenial cortex; however, contrary to the unidirectional hypothesis, neocortical activation exhibited a continuum of activation timings relative to SWRs, varying from leading to lagging. Thus, contrary to the model in which SWRs arise 'spontaneously' in the hippocampus, neocortical activation often precedes SWRs and may thus constitute a trigger event in which neocortical information seeds associative reactivation of hippocampal 'indices'. This timing continuum is consistent with a dynamics in which older, more consolidated memories may in fact initiate the hippocampal-neocortical dialog, whereas reactivation of newer memories may be initiated predominantly in the hippocampus.

Mapping human temporal and parietal neuronal population activity and functional coupling during mathematical cognition.

Brain areas within the lateral parietal cortex (LPC) and ventral temporal cortex (VTC) have been shown to code for abstract quantity representations and for symbolic numerical representations, respectively. To explore the fast dynamics of activity within each region and the interaction between them, we used electrocorticography recordings from 16 neurosurgical subjects implanted with grids of electrodes over these two regions and tracked the activity within and between the regions as subjects performed three different numerical tasks. Although our results reconfirm the presence of math-selective hubs within the VTC and LPC, we report here a remarkable heterogeneity of neural responses within each region at both millimeter and millisecond scales. Moreover, we show that the heterogeneity of response profiles within each hub mirrors the distinct patterns of functional coupling between them. Our results support the existence of multiple bidirectional functional loops operating between discrete populations of neurons within the VTC and LPC during the visual processing of numerals and the performance of arithmetic functions. These findings reveal information about the dynamics of numerical processing in the brain and also provide insight into the fine-grained functional architecture and connectivity within the human brain.