Explore the vast range of titles available.

In this randomized, sham-controlled trial, MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor who had not had a response to medication. Adverse effects of the procedure included sensory deficits and gait disturbances. Essential tremor, the most common movement disorder, 1 is characterized by a distinctive postural and intention tremor typically affecting the hands more than the legs, trunk, head, or voice. 2 , 3 Essential tremor does not shorten life expectancy, but it can affect quality of life, functional activities, mood, and socialization. 4 – 6 Class I evidence exists for propranolol and primidone as first-line medications that reduce tremor by approximately 60% in 50% of patients. 7 – 11 If resistance to medications develops or side effects are unacceptable, neurosurgical intervention is considered, primarily targeting the nucleus ventralis intermedius of the thalamus, a component of tremor circuitry that . . .

Neuroimaging evidence suggests that the default mode network (DMN) exhibits antagonistic activity with dorsal attention (DAN) and salience (SN) networks. Here we use human intracranial electroencephalography to investigate the behavioral relevance of fine-grained dynamics within and between these networks. The three networks show dissociable profiles of task-evoked electrophysiological activity, best captured in the high-frequency broadband (HFB; 70–170 Hz) range. On the order of hundreds of milliseconds, HFB responses peak fastest in the DAN, at intermediate speed in the SN, and slowest in the DMN. Lapses of attention (behavioral errors) are marked by distinguishable patterns of both pre- and post-stimulus HFB activity within each network. Moreover, the magnitude of temporally lagged, negative HFB coupling between the DAN and DMN (but not SN and DMN) is associated with greater sustained attention performance and is reduced during wakeful rest. These findings underscore the behavioral relevance of temporally delayed coordination between antagonistic brain networks. Brain imaging studies suggest that specific, large-scale, cortical networks show antagonistic activity with one another. Here, the authors studied the dynamics of these networks using implanted electrodes in the human brain, revealing that the coordination of inter-network dynamics on fast time scales relates to fluctuations in attention.

Everyday tasks in social settings require humans to encode neural representations of not only their own spatial location, but also the location of other individuals within an environment. At present, the vast majority of what is known about neural representations of space for self and others stems from research in rodents and other non-human animals 1 – 3 . However, it is largely unknown how the human brain represents the location of others, and how aspects of human cognition may affect these location-encoding mechanisms. To address these questions, we examined individuals with chronically implanted electrodes while they carried out real-world spatial navigation and observation tasks. We report boundary-anchored neural representations in the medial temporal lobe that are modulated by one’s own as well as another individual’s spatial location. These representations depend on one’s momentary cognitive state, and are strengthened when encoding of location is of higher behavioural relevance. Together, these results provide evidence for a common encoding mechanism in the human brain that represents the location of oneself and others in shared environments, and shed new light on the neural mechanisms that underlie spatial navigation and awareness of others in real-world scenarios. In real-world spatial navigation and observation tasks, oscillatory activity in the human brain encodes representations of self and others, with oscillatory power increasing at locations near the boundaries of the room.

Hedonic feeding is driven by the “pleasure” derived from consuming palatable food and occurs in the absence of metabolic need. It plays a critical role in the excessive feeding that underlies obesity. Compared to other pathological motivated behaviors, little is known about the neural circuit mechanisms mediating excessive hedonic feeding. Here, we show that modulation of prefrontal cortex (PFC) and anterior paraventricular thalamus (aPVT) excitatory inputs to the nucleus accumbens (NAc), a key node of reward circuitry, has opposing effects on high fat intake in mice. Prolonged high fat intake leads to input- and cell type-specific changes in synaptic strength. Modifying synaptic strength via plasticity protocols, either in an input-specific optogenetic or non-specific electrical manner, causes sustained changes in high fat intake. These results demonstrate that input-specific NAc circuit adaptations occur with repeated exposure to a potent natural reward and suggest that neuromodulatory interventions may be therapeutically useful for individuals with pathologic hedonic feeding. Hedonic feeding occurs in the absence of metabolic need and plays a critical role in the excessive feeding that underlies obesity. The authors show that optogenetic manipulation of NAc inputs from the prefrontal cortex versus inputs from the anterior paraventricular nucleus of the thalamus has opposite effects on high fat intake.

The authors show that postsynaptic deletion of neuroligin-3 from parvalbumin interneurons causes a decrease in NMDA-receptor-mediated excitatory postsynaptic currents and an increase in presynaptic glutamate release probability linked to a deficit in presynaptic Group III metabotropic glutamate receptor function. This selective disruption of excitatory transmission on parvalbumin interneurons leads to abnormal hippocampal network activity and a decrease in contextual fear extinction. Hippocampal network activity is generated by a complex interplay between excitatory pyramidal cells and inhibitory interneurons. Although much is known about the molecular properties of excitatory synapses on pyramidal cells, comparatively little is known about excitatory synapses on interneurons. Here we show that conditional deletion of the postsynaptic cell adhesion molecule neuroligin-3 in parvalbumin interneurons causes a decrease in NMDA-receptor-mediated postsynaptic currents and an increase in presynaptic glutamate release probability by selectively impairing the inhibition of glutamate release by presynaptic Group III metabotropic glutamate receptors. As a result, the neuroligin-3 deletion altered network activity by reducing gamma oscillations and sharp wave ripples, changes associated with a decrease in extinction of contextual fear memories. These results demonstrate that neuroligin-3 specifies the properties of excitatory synapses on parvalbumin-containing interneurons by a retrograde trans-synaptic mechanism and suggest a molecular pathway whereby neuroligin-3 mutations contribute to neuropsychiatric disorders.

Reward hypersensitization is a common feature of neuropsychiatric disorders, manifesting as impulsivity for anticipated incentives. Temporally specific changes in activity within the nucleus accumbens (NAc), which occur during anticipatory periods preceding consummatory behavior, represent a critical opportunity for intervention. However, no available therapy is capable of automatically sensing and therapeutically responding to this vulnerable moment in time when anticipation-related neural signals may be present. To identify translatable biomarkers for an off-the-shelf responsive neurostimulation system, we record local field potentials from the NAc of mice and a human anticipating conventional rewards. We find increased power in 1- to 4-Hz oscillations predominate during reward anticipation, which can effectively trigger neurostimulation that reduces consummatory behavior in mice sensitized to highly palatable food. Similar oscillations are present in human NAc during reward anticipation, highlighting the translational potential of our findings in the development of a treatment for a major unmet need.

Over the past decade, deaths attributable to opioid and stimulant use have risen dramatically. While the U.S. Food and Drug Administration (FDA) has approved three medications for opioid use disorder, there is currently no FDA-approved treatment for stimulant use disorder. Despite the availability of medications for opioid use disorder, the rates of relapse and overdose, particularly in the time of widespread fentanyl use, remain distressingly high. There is an urgent need for more effective treatment options for these debilitating disorders. This article provides an overview of the current standard of care for opioid use disorder and stimulant use disorder. New and emerging neuromodulation approaches with a particular focus on deep brain stimulation are then discussed.

Mounting evidence demonstrates that the central nervous system (CNS) orchestrates glucose homeostasis by sensing glucose and modulating peripheral metabolism. Glucose responsive neuronal populations have been identified in the hypothalamus and several corticolimbic regions. However, how these CNS gluco-regulatory regions modulate peripheral glucose levels is not well understood. To better understand this process, we simultaneously measured interstitial glucose concentrations and local field potentials in 3 human subjects from cortical and subcortical regions, including the hypothalamus in one subject. Correlations between high frequency activity (HFA, 70–170 Hz) and peripheral glucose levels are found across multiple brain regions, notably in the hypothalamus, with correlation magnitude modulated by sleep-wake cycles, circadian coupling, and hypothalamic connectivity. Correlations are further present between non-circadian (ultradian) HFA and glucose levels which are higher during awake periods. Spectro-spatial features of neural activity enable decoding of peripheral glucose levels both in the present and up to hours in the future. Our findings demonstrate proactive encoding of homeostatic glucose dynamics by the CNS. How human brain activity relates to peripheral metabolism is not known. Here, the authors find that intracranial activity is strongly coupled to peripheral glucose variations across multiple brain regions and is sufficient for decoding of glucose levels.

Abstract BACKGROUND Parkinson disease (PD) impairs daily functioning for an increasing number of patients and has a growing national economic burden. Deep brain stimulation (DBS) may be the most broadly accepted procedural intervention for PD, but cost-effectiveness has not been established. Moreover, magnetic resonance image-guided focused ultrasound (FUS) is an emerging incisionless, ablative treatment that could potentially be safer and even more cost-effective. OBJECTIVE To (1) quantify the utility (functional disability metric) imparted by DBS and radiofrequency ablation (RF), (2) compare cost-effectiveness of DBS and RF, and (3) establish a preliminary success threshold at which FUS would be cost-effective compared to these procedures. METHODS We performed a meta-analysis of articles (1998-2018) of DBS and RF targeting the globus pallidus or subthalamic nucleus in PD patients and calculated utility using pooled Unified Parkinson Disease Rating Scale motor (UPDRS-3) scores and adverse events incidences. We calculated Medicare reimbursements for each treatment as a proxy for societal cost. RESULTS Over a 22-mo mean follow-up period, bilateral DBS imparted the most utility (0.423 quality-adjusted life-years added) compared to (in order of best to worst) bilateral RF, unilateral DBS, and unilateral RF, and was the most cost-effective (expected cost: $32 095 ± $594) over a 22-mo mean follow-up. Based on this benchmark, FUS would need to impart UPDRS-3 reductions of ∼16% and ∼33% to be the most cost-effective treatment over 2- and 5-yr periods, respectively. CONCLUSION Bilateral DBS imparts the most utility and cost-effectiveness for PD. If our established success threshold is met, FUS ablation could dominate bilateral DBS’s cost-effectiveness from a societal cost perspective. Graphical Abstract Graphical Abstract

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. Animal studies have shown that insulo-opercular network function is critical in gustation and in behaviour based on anticipated food availability. The authors describe activities within the human insulo-opercular cortex which underlie anticipatory food evaluation in both controlled and naturalistic settings.