Neuroscience

Shared neural coding for social hierarchy and reward value in primate amygdala

Nature Neuroscience - 19 February 2018 - 12:00am

Shared neural coding for social hierarchy and reward value in primate amygdala

Shared neural coding for social hierarchy and reward value in primate amygdala, Published online: 19 February 2018; doi:10.1038/s41593-018-0082-8

New data reveal that the amygdala—a brain area specialized for emotion—also signals the hierarchical rank of peers in a social group. These neural signals likely mediate appropriate social and emotional behavior in many social settings.
Categories: Neuroscience

Single excitatory axons form clustered synapses onto CA1 pyramidal cell dendrites

Nature Neuroscience - 19 February 2018 - 12:00am

Single excitatory axons form clustered synapses onto CA1 pyramidal cell dendrites

Single excitatory axons form clustered synapses onto CA1 pyramidal cell dendrites, Published online: 19 February 2018; doi:10.1038/s41593-018-0084-6

Bloss et al. show single axons form clustered inputs onto the dendrites of hippocampal pyramidal cells in a projection-specific manner. The spatial and temporal features inherent in these connections efficiently drive dendritic depolarization.
Categories: Neuroscience

Predicting Recovery in Acute Post-stroke Aphasia

Annals of Neurology - 16 February 2018 - 1:40pm
Abstract

Objective: Many stroke patients show remarkable recovery of language after initial severe impairment, but it is difficult to predict which patients will show good recovery. We aimed to identify patient and lesion characteristics that together predict the best naming outcome in four studies.

Methods: We report two longitudinal studies that identified two variables at onset that were strongly associated with good recovery of naming (the most common residual deficit in aphasia) in the first six months after stroke: damage to left posterior superior temporal gyrus (pSTG) and/or superior longitudinal fasciculus/arcuate fasciculus (SLF/AF) and selective serotonin reuptake inhibitor (SSRI) use. We then tested these variables in two independent cohorts of chronic left hemisphere stroke patients, using chi squared tests and multivariable logistic regression for dichotomous outcomes and t-tests for continuous outcomes.

Results: Lesion load in left pSTG and SLF/AF was associated with poorer naming outcome. Preservation of these areas and use of SSRIs were associated with naming recovery, independent of lesion volume, time since stroke, and depression. Patients with damage to these critical areas showed better naming outcome if they took SSRIs for three months after stroke. Those with preservation of these critical areas achieved good recovery of naming regardless of SSRI use.

Interpretation: Lesion load in left pSTG and SLF/AF at onset predicts later naming performance. Although based on a small number of patients, our preliminary results suggest outcome might be modulated by SSRIs, but these associations need to be confirmed in a larger randomized controlled trial. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

[18F]AV-1451 tau-PET and primary progressive aphasia

Annals of Neurology - 16 February 2018 - 11:50am
Abstract

Objectives: To assess [18F]AV-1451 tau-PET uptake patterns across the primary progressive aphasia (PPA) variants (logopenic, semantic and agrammatic), examine regional uptake patterns of [18F]AV-1451 independent of clinical diagnosis, and compare the diagnostic utility of [18F]AV-1451, [18F]-fluorodeoxygluclose (FDG)-PET and MRI to differentiate the PPA variants.

Methods: We performed statistical parametric mapping of [18F]AV-1451 across 40 PPA patients (logopenic-PPA=14, semantic-PPA=13 and agrammatic-PPA=13) compared to 80 cognitively normal, PiB-negative controls, age and gender matched 2:1. Principal component analysis of regional [18F]AV-1451 tau-PET SUVR was performed to understand underlying patterns of [18F]AV-1451 uptake independent of clinical diagnosis. Penalized multinomial regression analyses were utilized to assess diagnostic utility.

Results: Logopenic-PPA showed striking uptake throughout neocortex, particularly temporoparietal, compared to controls, semantic-PPA and agrammatic-PPA. Semantic-PPA and agrammatic-PPA showed milder patterns of focal [18F]AV-1451 uptake. Semantic-PPA showed elevated uptake (left>right) in anteromedial temporal lobes, compared to controls and agrammatic-PPA. Agrammatic-PPA showed elevated uptake (left>right) throughout prefrontal white matter and in subcortical grey matter structures, compared to controls and semantic-PPA. The principal component analysis of regional [18F]AV-1451 indicated two primary dimensions, a severity dimension that distinguished logopenic-PPA from agrammatic-PPA and semantic-PPA, and a frontal-versus-temporal contrast that distinguishes agrammatic-PPA and semantic-PPA cases. Diagnostic utility of [18F]AV-1451was superior to MRI and at least equal to FDG-PET.

Interpretation: [18F]AV-1451binding characteristics differ across the PPA variants, and were excellent at distinguishing between the variants. [18F]AV-1451binding characteristics were as good or better than other brain imaging modalities utilized in clinical practice, suggesting that [18F]AV-1451 may have clinical diagnostic utility in PPA. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

Control of synaptic plasticity in deep cortical networks

Nature Rev. Neurosc. - 16 February 2018 - 12:00am

Control of synaptic plasticity in deep cortical networks

Control of synaptic plasticity in deep cortical networks, Published online: 16 February 2018; doi:10.1038/nrn.2018.6

How are synapses optimally strengthened or weakened to improve network performance? Roelfsema and Holtmaat provide an overview of factors that influence synaptic plasticity, particularly in deep, multilayered biological networks, and present a specific framework in which neuromodulators and feedback connections may interact to selectively potentiate synapses responsible for rewarded action.
Categories: Neuroscience

Behavioural neuroscience: In hunt mode

Nature Rev. Neurosc. - 16 February 2018 - 12:00am

Behavioural neuroscience: In hunt mode

Behavioural neuroscience: In hunt mode, Published online: 16 February 2018; doi:10.1038/nrn.2018.18

Two studies characterize inputs to the periaqueductal grey that regulate hunting behaviour in mice.
Categories: Neuroscience

Imaging structural and functional brain development in early childhood

Nature Rev. Neurosc. - 16 February 2018 - 12:00am

Imaging structural and functional brain development in early childhood

Imaging structural and functional brain development in early childhood, Published online: 16 February 2018; doi:10.1038/nrn.2018.1

The human brain undergoes rapid development during the first 2 years of life. Here, Gilmore and colleagues give an overview of recent neuroimaging studies of the developmental trajectories of brain structure and function in the first years after birth.
Categories: Neuroscience

Neuroimmunology: Dietary salt-induced deficits

Nature Rev. Neurosc. - 16 February 2018 - 12:00am

Neuroimmunology: Dietary salt-induced deficits

Neuroimmunology: Dietary salt-induced deficits, Published online: 16 February 2018; doi:10.1038/nrn.2018.15

In mice, consumption of a high-salt diet induces accumulation of T helper 17 lymphocytes in the gut, leading to a rise in plasma interleukin-17 levels as well as neurovascular dysfunction and cognitive deficits.
Categories: Neuroscience

Leptin and brain–adipose crosstalks

Nature Rev. Neurosc. - 16 February 2018 - 12:00am

Leptin and brain–adipose crosstalks

Leptin and brain–adipose crosstalks, Published online: 16 February 2018; doi:10.1038/nrn.2018.7

The brain regulates adipose tissue metabolism through sympathetic efferent pathways; in turn, adipose tissues relay energy-status information to the brain. This Review gives an overview of interactions between the brain and adipose tissues, with a particular focus on leptin as a regulator of these communications.
Categories: Neuroscience

Effects of adolescent alcohol consumption on the brain and behaviour

Nature Rev. Neurosc. - 15 February 2018 - 12:00am

Effects of adolescent alcohol consumption on the brain and behaviour

Effects of adolescent alcohol consumption on the brain and behaviour, Published online: 15 February 2018; doi:10.1038/nrn.2018.10

The prevalence of adolescent alcohol use in some countries is high and is associated with various changes in brain function and behaviour. In this Review, Linda Spear examines the contributors to and consequences of alcohol use during adolescence, covering findings in humans and rodent models of this developmental period.
Categories: Neuroscience

Synaptic transmission: A hare as well as a tortoise

Nature Rev. Neurosc. - 15 February 2018 - 12:00am

Synaptic transmission: A hare as well as a tortoise

Synaptic transmission: A hare as well as a tortoise, Published online: 15 February 2018; doi:10.1038/nrn.2018.17

Axons of striatal dopaminergic neurons are shown to release dopamine in a RIM-dependent manner and with a high release probability from axonal active zone-like structures.
Categories: Neuroscience

Diabetic neuropathy differs between type 1 and type 2 diabetes Insights from magnetic resonance neurography

Annals of Neurology - 14 February 2018 - 5:30pm
Abstract

Objective: To visualize and quantify differences of microstructural nerve damage in distal symmetric diabetic neuropathy (DPN) between type 1 diabetes (T1D) and type 2 diabetes (T2D), and to detect correlations between neuropathic symptoms and serological risk factors.

Methods: 3T magnetic resonance neurography of the sciatic nerve was performed in 120 patients (T1D n=35; T2D n=85) with either DPN (n=84) or no DPN (NDPN; n=36). Results were subsequently correlated with clinical, serological, and electrophysiological patient data.

Results: T2-weighted (T2w) hyperintense lesions correlated negatively with tibial compound motor action potential (r=-0.58; p<0.0001) and peroneal nerve conduction (r=0.51; p=0.0002), and positively with neuropathy disability (NDS; r=-0.54; p<0.0001) and severity score (NSS; r=0.52; p<0.0001), and HbA1c levels (r=0.23; p=0.014). T2w-hypointense lesions correlated positively with NDS, NSS (r=0.28; p=0.002; r=0.36; p<0.0001), and serum triglycerides (r=0.34; p=0.0003), and negatively with serum HDL (r=-0.48; p<0.0001). For DPN in T1D, elevated values of T2w-hyperintense lesions (19.67%±4.13 vs. 12.49%±1.23; p=0.027) and HbA1c (8.74%±0.29 vs. 7.11%±0.16; p<0.0001) were found when compared to T2D. For DPN in T2D, elevated T2w-hypointense lesions (23.41mm3±2.69 vs. 11.43mm3±1.74; p=0.046), triglycerides (220.70mg/dl±23.70 vs. 106.60mg/dl±14.51; p<0.0001), and lower serum HDL (51.29mg/dl±3.02 vs. 70.79mg/dl±4.65; p<0.0001) were found when compared to T1D.

Interpretation: The predominant type of nerve lesions in DPN differs between T1D and T2D. Correlations found between lesion type and serological parameters indicate that predominant nerve lesions in T1D are associated with poor glycemic control and loss of nerve conduction, whereas predominant lesions in T2D are associated with changes in lipid metabolism. These findings may be helpful for future studies on the underlying pathophysiological pathways and possible treatments for DPN in T1D and T2D. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

Memory formation depends on both synapse-specific modifications of synaptic strength and cell-specific increases in excitability

Nature Neuroscience - 12 February 2018 - 12:00am

Memory formation depends on both synapse-specific modifications of synaptic strength and cell-specific increases in excitability

Memory formation depends on both synapse-specific modifications of synaptic strength and cell-specific increases in excitability, Published online: 12 February 2018; doi:10.1038/s41593-018-0076-6

The authors discuss newly emerging evidence for the role of the transcription factor CREB in memory, including its role in modulating changes in excitability that are critical for neural assembly formation and linking of memories across time.
Categories: Neuroscience

Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation

Nature Neuroscience - 12 February 2018 - 12:00am

Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation

Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation, Published online: 12 February 2018; doi:10.1038/s41593-018-0079-3

This study describes single-nucleus ATAC-seq, a method to profile open chromatin in individual nuclei from frozen tissues. It is used to examine gene regulation in 15,000 nuclei comprising 20 distinct cell types in the developing mouse forebrain.
Categories: Neuroscience

Bidirectional and long-lasting control of alcohol-seeking behavior by corticostriatal LTP and LTD

Nature Neuroscience - 12 February 2018 - 12:00am

Bidirectional and long-lasting control of alcohol-seeking behavior by corticostriatal LTP and LTD

Bidirectional and long-lasting control of alcohol-seeking behavior by corticostriatal LTP and LTD, Published online: 12 February 2018; doi:10.1038/s41593-018-0081-9

Addiction-related behaviors are believed to result from drug-evoked synaptic changes, but their causality is unclear. The authors show that bidirectional optogenetic modifications of synaptic strength distinctly alter alcohol-seeking behavior.
Categories: Neuroscience

Amygdala stimulation-induced apnea is attention and nasal-breathing dependent

Annals of Neurology - 8 February 2018 - 10:10pm
Abstract

Objective:

Evidence suggests disordered breathing is critically involved in Sudden unexplained death in epilepsy (SUDEP). To that end, evaluating structures that are activated by seizures and can activate brain regions that produce cardiorespiratory changes can further our understanding of the pathophysiology of SUDEP. Prior preclinical studies have shown that electrical stimulation of the human amygdala induces apnea, suggesting a role for the amygdala in controlling respiration. In this study, we aimed to both confirm these findings in a larger group of patients with intractable temporal lobe epilepsy (TLE) and also further explore the anatomical and cognitive properties of this effect.

Methods:

Seven surgical TLE patients had depth electrodes implanted in the amygdala that were used to deliver electrical stimulation during functional mapping prior to resection. Real-time respiratory monitoring was performed in each patient to confirm apnea.

Results:

Our data confirm that amygdala stimulation reliably induces apnea (occurring in all seven patients) and further suggest that apnea can be overcome by instructing the patient to inhale, and can be prevented entirely by breathing through the mouth prior to electrical stimulation. Finally, stimulation induced apnea occurred only when stimulating the medial most amygdalar contacts located in the central nucleus.

Interpretation:

These findings confirm a functional connection between the amygdala and respiratory control in humans. Moreover, they suggest specific amygdalar nuclei may be critical in mediating this effect and that attentional state is critical to apnea mediated by amygdala activation - perhaps alluding to future development of strategies for the prevention of SUDEP. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

Do subjects with minimal motor features have prodromal PD?

Annals of Neurology - 8 February 2018 - 10:06pm
ABSTRACT

Background: Understanding the pathological changes underlying mild motor features of the eldery and defining a patient population with prodromal Parkinson's disease (PD) are of great clinical importance. It remains unclear, however, how to accurately and specifically diagnose prodromal PD. We examined whether older adults with minimal parkinsonian motor features have nigrostriatal degeneration and α-synuclein pathology consistent with prodromal PD.

Methods: Brain sections were obtained from older adults with a clinical diagnosis of PD (N=21) and without a clinical diagnosis of PD (N=27) who underwent motor examination proximate to death. Cases without PD were further dichotomized into no motor deficit (n=9) or minimal motor features (n-18) groups using a modified Unified Parkinson's Disease Rating Scale. We performed quantitative unbiased stereological analyses of dopaminergic neurons/terminals and α-synuclein accumulation in the nigrostriatal system.

Results: In all subjects with minimal motor features, there were significant reductions in dopaminergic neurons and terminals in the substantia nigra and putamen that was intermediate between subjects with no motor deficit and PD. Phosphorylated α-synuclein inclusions were observed in the substantia nigra that were of similar density to what was seen in PD. Furthermore, there was greater Lewy neuritic pathology in the putamen relative to PD patients. Lastly, neurons with α-synuclein inclusions displayed reductions in tyrosine hydroxylase expression that was comparable in subjects with both minimal motor features and PD.

Interpretation: Minimal motor features in older adults may represent prodromal PD and identify at risk individuals for testing putative neuroprotective interventions that could slow or prevent PD progression. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

Stereotactic Laser Amygdalohippocampotomy for Mesial Temporal Lobe Epilepsy

Annals of Neurology - 8 February 2018 - 10:06pm
Abstract

Objective: To evaluate the outcomes one-year and longer following stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy in a large series of patients treated over a five-year period since introduction of this novel technique.

Methods: Surgical outcomes of a consecutive series of fifty-eight patients with mesial temporal lobe epilepsy who underwent the surgery at our institution with at least 12-months 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: 40.8%-65.7%) of all patients were free of disabling seizures (Engel 1). Three of nine patients became seizure free following repeat ablation. Subgroup analysis showed that 60.5% (95% confidence interval: 45.6%-73.7%) of patients with mesial temporal sclerosis were free of disabling seizures as compared to 33.3% (95% confidence interval: 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. This article is protected by copyright. All rights reserved.

Categories: Neuroscience

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