Isolated Inflammatory Necrosis of the Falciform Ligament: A Case Report with Review of Literature.

Inflammatory necrosis of the falciform ligament is an extremely rare cause of acute right upper quadrant pain. Due to overlapping symptoms with pathologies affecting the gall bladder and liver, this poses a diagnostic challenge with limited existing literature. Here, we report a case of a 62-year-old female patient presenting in the accident and emergency department with right upper quadrant pain. The patient underwent ultrasonography and revealed thickened and echogenic falciform ligament. Further, a computed tomography revealed swollen falciform ligament with associated fat stranding. The patient was kept under conservative management and improved over 2 weeks.

A Novel Biophysical Model for the Generation of Sharp Wave Ripples in CA1 Hippocampus.

Synchronous activities among neurons in the brain generate emergent network oscillations such as the hippocampal Sharp-wave ripples (SPWRs) that facilitate information processing during memory formation. However, how neurons and circuits are functionally organized to generate oscillations remains unresolved. Biophysical models of neuronal networks can shed light on how thousands of neurons interact in intricate circuits to generate such emergent SPWR network events. Here we developed a large-scale biophysically realistic neural network model of CA1 hippocampus with functionally organized circuit modules containing distinct types of neurons. Model simulations reproduced synaptic, cellular and network aspects of physiological SPWRs. The model provided insights into the role of neuronal types and their microcircuit motifs in generating SPWRs in the CA1 region. The model also suggests experimentally testable predictions including the role of specific neuron types in the genesis of hippocampal SPWRs.

Transcriptomic characterization of Trichoderma harzianum T34 primed tomato plants: assessment of biocontrol agent induced host specific gene expression and plant growth promotion.

In this study, we investigated the intricate interplay between Trichoderma and the tomato genome, focusing on the transcriptional and metabolic changes triggered during the late colonization event. Microarray probe set (GSE76332) was utilized to analyze the gene expression profiles changes of the un-inoculated control (tomato) and Trichoderma-tomato interactions for identification of the differentially expressed significant genes. Based on principal component analysis and R-based correlation, we observed a positive correlation between the two cross-comaparable groups, corroborating the existence of transcriptional responses in the host triggered by Trichoderma priming. The statistically significant genes based on different p-value cut-off scores [(padj-values or q-value); padj-value < 0.05], [(pcal-values); pcal-value < 0.05; pcal < 0.01; pcal < 0.001)] were cross compared. Through cross-comparison, we identified 156 common genes that were consistently significant across all probability thresholds, and showing a strong positive corelation between p-value and q-value in the selected probe sets. We reported TD2, CPT1, pectin synthase, EXT-3 (extensin-3), Lox C, and pyruvate kinase (PK), which exhibited upregulated expression, and Glb1 and nitrate reductase (nii), which demonstrated downregulated expression during Trichoderma-tomato interaction. In addition, microbial priming with Trichoderma resulted into differential expression of transcription factors related to systemic defense and flowering including MYB13, MYB78, ERF2, ERF3, ERF5, ERF-1B, NAC, MADS box, ZF3, ZAT10, A20/AN1, polyol sugar transporter like zinc finger proteins, and a novel plant defensin protein. The potential bottleneck and hub genes involved in this dynamic response were also identified. The protein-protein interaction (PPI) network analysis based on 25 topmost DEGS (pcal-value < 0.05) and the Weighted Correlation Gene Network Analysis (WGCNA) of the 1786 significant DEGs (pcal-value < 0.05) we reported the hits associated with carbohydrate metabolism, secondary metabolite biosynthesis, and the nitrogen metabolism. We conclude that the Trichoderma-induced microbial priming re-programmed the host genome for transcriptional response during the late colonization event and were characterized by metabolic shifting and biochemical changes specific to plant growth and development. The work also highlights the relevance of statistical parameters in understanding the gene regulatory dynamics and complex regulatory networks based on differential expression, co-expression, and protein interaction networks orchestrating the host responses to beneficial microbial interactions.

40-Hz optogenetic stimulation rescues functional synaptic plasticity after stroke.

Evoked brain oscillations in the gamma range have been shown to assist in stroke recovery. However, the causal relationship between evoked oscillations and neuroprotection is not well understood. We have used optogenetic stimulation to investigate how evoked gamma oscillations modulate cortical dynamics in the acute phase after stroke. Our results reveal that stimulation at 40 Hz drives activity in interneurons at the stimulation frequency and phase-locked activity in principal neurons at a lower frequency, leading to increased cross-frequency coupling. In addition, 40-Hz stimulation after stroke enhances interregional communication. These effects are observed up to 24 h after stimulation. Our stimulation protocol also rescues functional synaptic plasticity 24 h after stroke and leads to an upregulation of plasticity genes and a downregulation of cell death genes. Together these results suggest that restoration of cortical dynamics may confer neuroprotection after stroke.

Locating causal hubs of memory consolidation in spontaneous brain network in male mice.

Memory consolidation after learning involves spontaneous, brain-wide network reorganization during rest and sleep, but how this is achieved is still poorly understood. Current theory suggests that the hippocampus is pivotal for this reshaping of connectivity. Using fMRI in male mice, we identify that a different set of spontaneous networks and their hubs are instrumental in consolidating memory during post-learning rest. We found that two types of spatial memory training invoke distinct functional connections, but that a network of the sensory cortex and subcortical areas is common for both tasks. Furthermore, learning increased brain-wide network integration, with the prefrontal, striatal and thalamic areas being influential for this network-level reconfiguration. Chemogenetic suppression of each hub identified after learning resulted in retrograde amnesia, confirming the behavioral significance. These results demonstrate the causal and functional roles of resting-state network hubs in memory consolidation and suggest that a distributed network beyond the hippocampus subserves this process.

A protocol to investigate neural coupling of brain oscillations in rodents using in vivo electrophysiological recordings.

Memory processes are highly dependent on a cross-talk between brain regions via synchronized neural oscillations. Here, we present a protocol to perform multi-site electrophysiological recordings in vivo in freely moving rodents to investigate functional connectivity across brain regions during memory processes. We describe steps for recording local field potentials (LFPs) during behavior, extracting LFP bands, and analyzing synchronized LFP activity across brain regions. This technique also provides the potential to simultaneously assess single unit activity using tetrodes. For complete details on the use and execution of this protocol, please refer to Wang et al.1.

Reverse engineering information processing in lateral amygdala during auditory tones.

Learning in the mammalian lateral amygdala (LA) during auditory fear conditioning (tone - foot shock pairing), one form of associative learning, requires N-methyl-D-aspartate (NMDA) receptor-dependent plasticity. Despite this fact being known for more than two decades, the biophysical details related to signal flow and the involvement of the coincidence detector, NMDAR, in this learning, remain unclear. Here we use a 4000-neuron computational model of the LA (containing two types of pyramidal cells, types A and C, and two types of interneurons, fast spiking FSI and low-threshold spiking LTS) to reverse engineer changes in information flow in the amygdala that underpin such learning; with a specific focus on the role of the coincidence detector NMDAR. The model also included a Ca2s based learning rule for synaptic plasticity. The physiologically constrained model provides insights into the underlying mechanisms that implement habituation to the tone, including the role of NMDARs in generating network activity which engenders synaptic plasticity in specific afferent synapses. Specifically, model runs revealed that NMDARs in tone-FSI synapses were more important during the spontaneous state, although LTS cells also played a role. Training trails with tone only also suggested long term depression in tone-PN as well as tone-FSI synapses, providing possible hypothesis related to underlying mechanisms that might implement the phenomenon of habituation.

Ethnobotanical uses and phytochemical, biological, and toxicological profiles of Datura metel L.: A review.

Datura metel L., a recognized poisonous plant in the Solanaceae family, is widely distributed in the world. Traditionally, D. metel is used in many diseases, including neurological and heart diseases; fever; catarrh; pain; diarrhea; skin diseases; chronic bronchitis; asthma; digestive disorders; and so on. It possesses many important phytochemicals that can be used to treat various types of diseases. This review aims at summarizing the traditional uses, phytochemical, biological, and toxicological profiles of D. metel based on the database reports. For this, an up-to-date (till March 20, 2023) search was made in the databases: PubMed, Google Scholar, Science Direct, Scopus, and MedLine, with relevant keywords for the published evidence. Findings suggest that the plant has many traditional uses, such as a cure for madness, epilepsy, psoriasis, heart diseases, diarrhea, mad dog bites, indigestion, etc. It possesses various important phytochemicals, including withanolides, daturaolone, datumetine, daturglycosides, ophiobolin A, baimantuoluoline A, and many others. D. metel has many important biological activities, including antioxidant, anti-inflammatory, anti-microbial, insecticidal, anti-cancer, anti-diabetic, analgesic, anti-pyretic, neurological, contraceptive, and wound healing capacity. In conclusion, the toxic plant, D. metel, can be considered a potential source of phyto-therapeutic lead compounds.

Insights into the encoding of memories through the circuitry of fear.

Associative learning induces physical changes to a network of cells, known as the memory engram. Fear is widely used as a model to understand the circuit motifs that underpin associative memories. Recent advances suggest that the distinct circuitry engaged by different conditioned stimuli (e.g. tone vs. context) can provide insights into what information is being encoded in the fear engram. Moreover, as the fear memory matures, the circuitry engaged indicates how information is remodelled after learning and hints at potential mechanisms for consolidation. Finally, we propose that the consolidation of fear memories involves plasticity of engram cells through coordinated activity between brain regions, and the inherent characteristics of the circuitry may mediate this process.

The PPN and motor control: Preclinical studies to deep brain stimulation for Parkinson's disease.

The pedunculopontine nucleus (PPN) is the major part of the mesencephalic locomotor region, involved in the control of gait and locomotion. The PPN contains glutamatergic, cholinergic, and GABAergic neurons that all make local connections, but also have long-range ascending and descending connections. While initially thought of as a region only involved in gait and locomotion, recent evidence is showing that this structure also participates in decision-making to initiate movement. Clinically, the PPN has been used as a target for deep brain stimulation to manage freezing of gait in late Parkinson's disease. In this review, we will discuss current thinking on the role of the PPN in locomotor control. We will focus on the cytoarchitecture and functional connectivity of the PPN in relationship to motor control.

Theta coupling within the medial prefrontal cortex regulates fear extinction and renewal.

Fear learning, and its extinction, are fundamental learning processes that allow for a response adaptation to aversive events and threats in the environment. Thus, it is critical to understand the neural mechanism that underpins fear learning and its relapse following extinction. The neural dynamics within the subregions of the medial prefrontal cortex, including the prelimbic cortex (PL) and the infralimbic (IL) cortex, and functional connectivity between them during fear extinction and its relapse, are not well understood. Using in-vivo electrophysiological recordings in awake behaving rats, we identified increased theta activity in the PL during fear learning and in the IL following extinction. Importantly, the PL-IL theta coupling is significantly enhanced throughout fear learning and extinction, but not in fear relapse. Together, our results provide evidence for the importance of synchronized PL-IL activity to regulate context-dependent retrieval of a fear extinction memory.

Development of saline loaded mask materials, evaluation of the antimicrobial efficacy and survivability of selected bacteria on these mask materials.

Objective: Surgical face masks have been recommended by World Health Organization (WHO) during the COVID-19 pandemic. Nowadays wearing masks have become a norm and lifestyle around the globe. The present investigation was carried out to evaluate the feasibility of developing masks loaded with analytical grade sodium chloride (NaCl), Iodized salts (IS) and Omani sea salt (OSS) with or without sodium bicarbonate (NaHCO3). Methods: The saline loaded masks were prepared by soaking the middle layer of the mask in 30% (w/v) saline solutions (NaCl, IS, OSS) with or without 10% NaHCO3 for 24 h followed by drying at room temperature. The prepared saline solutions and its combinations were evaluated for antimicrobial efficacy against the bacteria like Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Salmonella typhi, and Staphylococcus aureus, and antifungal activity against the Penicillium spp. and Rhizopus spp. by agar diffusion. Optical microscopy was employed to observe the formation of salt crystal in the mask material. Survivability of S. aureus and P. aeruginosa was tested on the mask material loaded with 30% OSS + 10% NaHCO3 at particular time intervals. Results: The results showed that a combination of 30% OSS + 10% NaHCO3 exhibited promising antimicrobial activity against all the bacteria as well as Rhizopus spp. compared to the 30% IS + 10% NaHCO3. Moreover, the middle layer of the mask loaded with saline solutions of 30% OSS + 10% NaHCO3 or 30% IS + 10% NaHCO3 have antibacterial activity, particularly for oral microbiome. On dehydration, the masks materials showed the presence of a significant amount of salt crystals. Survivability tests showed that both S. aureus and P. aeruginosa were killed within 3 h of contact with the salt crystals on the mask materials. Conclusions: A combination of 30% OSS + 10% NaHCO3 possessed significant antimicrobial activities on the tested microorganisms. Presence of a significant amount of salt crystals on dehydration of the saline loaded masks can be used as an effective protective barrier to infectious respiratory agents.

A midbrain-thalamus-cortex circuit reorganizes cortical dynamics to initiate movement.

Motor behaviors are often planned long before execution but only released after specific sensory events. Planning and execution are each associated with distinct patterns of motor cortex activity. Key questions are how these dynamic activity patterns are generated and how they relate to behavior. Here, we investigate the multi-regional neural circuits that link an auditory "Go cue" and the transition from planning to execution of directional licking. Ascending glutamatergic neurons in the midbrain reticular and pedunculopontine nuclei show short latency and phasic changes in spike rate that are selective for the Go cue. This signal is transmitted via the thalamus to the motor cortex, where it triggers a rapid reorganization of motor cortex state from planning-related activity to a motor command, which in turn drives appropriate movement. Our studies show how midbrain can control cortical dynamics via the thalamus for rapid and precise motor behavior.

Changes in pallidal neural activity following long-term symptom improvement from botulinum toxin treatment in DYT6 dystonia: a case report.

BACKGROUND: The globus pallidus internus is the main target for the treatment of dystonia by deep brain stimulation. Unfortunately, for some genetic etiologies, the therapeutic outcome of dystonia is less predictable. In particular, therapeutic outcomes for deep brain stimulation in craniocervical and orolaryngeal dystonia in DYT6-positive patients are poor. Little is known about the neurophysiology of the globus pallidus internus in DYT6-positive dystonia, and how symptomatic treatment affects the neural activity of this region. CASE PRESENTATION: We present here the case of a 55-year-old Caucasian female DYT6-dystonic patient with blepharospasm, spasmodic dysphonia, and oromandibular dystonia where single-unit and local field potential activity was recorded from the globus pallidus internus during two deep brain stimulation revision surgeries 4 years apart with no symptomatic improvement. Botulinum toxin injections consistently improved dysphonia, while some of the other symptoms were only inconsistently or marginally improved. Neural activity in the globus pallidus internus during both revision surgeries were compared with previously published results from an idiopathic dystonic cohort. Single-cell firing characteristics and local field potential from the first revision surgery showed no differences with our control group. However, during the second revision surgery, the mean firing rate of single units and local field potential power in the gamma range were lower than those present during the first revision surgery or the control group. CONCLUSIONS: Symptoms related to facial movements were greatly improved by botulinum toxin treatment between revision surgeries, which coincided with lower discharge rate and changes in gamma local field oscillations.

A protocol to investigate cellular and circuit mechanisms generating sharp wave ripple oscillations in rodent basolateral amygdala using ex vivo slices.

Basolateral amygdala circuits generate oscillatory network activity to process and remember emotion-tagged events. Ex vivo preparations that recapitulate network activities seen in vivo provide an ideal system to investigate the mechanisms driving these network oscillations. Here we describe an ex vivo preparation of basolateral amygdala slices from rodents for measuring the generated sharp wave ripple oscillations (SWs) using local field potential recording and targeted recording from chandelier neurons that initiate SWs. For complete details on the use and execution of this protocol, please refer to Perumal et al. (2021).

Proceedings of the 10th annual deep brain stimulation think tank: Advances in cutting edge technologies, artificial intelligence, neuromodulation, neuroethics, interventional psychiatry, and women in neuromodulation.

The deep brain stimulation (DBS) Think Tank X was held on August 17-19, 2022 in Orlando FL. The session organizers and moderators were all women with the theme women in neuromodulation. Dr. Helen Mayberg from Mt. Sinai, NY was the keynote speaker. She discussed milestones and her experiences in developing depression DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging DBS technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank X speakers was that DBS has continued to expand in scope however several indications have reached the "trough of disillusionment." DBS for depression was considered as "re-emerging" and approaching a slope of enlightenment. DBS for depression will soon re-enter clinical trials. The group estimated that globally more than 244,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia, and Australia; cutting-edge technologies, closed loop DBS, DBS tele-health, neuroethics, lesion therapy, interventional psychiatry, and adaptive DBS.

Hippocampus-Prefrontal Coupling Regulates Recognition Memory for Novelty Discrimination.

Recognition memory provides the ability to distinguish familiar from novel objects and places, and is important for recording and updating events to guide appropriate behavior. The hippocampus (HPC) and medial prefrontal cortex (mPFC) have both been implicated in recognition memory, but the nature of HPC-mPFC interactions, and its impact on local circuits in mediating this process is not known. Here we show that novelty discrimination is accompanied with higher theta activity (4-10 Hz) and increased c-Fos expression in both these regions. Moreover, theta oscillations were highly coupled between the HPC and mPFC during recognition memory retrieval for novelty discrimination, with the HPC leading the mPFC, but not during initial learning. Principal neurons and interneurons in the mPFC responded more strongly during recognition memory retrieval compared with learning. Optogenetic silencing of HPC input to the mPFC disrupted coupled theta activity between these two structures, as well as the animals' (male Sprague Dawley rats) ability to differentiate novel from familiar objects. These results reveal a key role of monosynaptic connections between the HPC and mPFC in novelty discrimination via theta coupling and identify neural populations that underlie this recognition memory-guided behavior.SIGNIFICANCE STATEMENT Many memory processes are highly dependent on the interregional communication between the HPC and mPFC via neural oscillations. However, how these two brain regions coordinate their oscillatory activity to engage local neural populations to mediate recognition memory for novelty discrimination is poorly understood. This study revealed that the HPC and mPFC theta oscillations and their temporal coupling is correlated with recognition memory-guided behavior. During novel object recognition, the HPC drives mPFC interneurons to effectively reduce the activity of principal neurons. This study provides the first evidence for the requirement of the HPC-mPFC pathway to mediate recognition memory for novelty discrimination and describes a mechanism for how this memory is regulated.

Energy-Level Manipulation in Novel Indacenodithiophene-Based Donor-Acceptor Polymers for Near-Infrared Organic Photodetectors.

Organic photodetectors (OPDs) are promising candidates for next-generation digital imaging and wearable sensors due to their low cost, tuneable optoelectrical properties combined with high-level performance, and solution-processed fabrication techniques. However, OPD detection is often limited to shorter wavelengths, whereas photodetection in the near-infrared (NIR) region is increasingly being required for wearable electronics and medical device applications. NIR sensing suffers from low responsivity and high dark currents. A common approach to enhance NIR photon detection is lowering the optical band gap via donor-acceptor (D-A) molecular engineering. Herein, we present the synthesis of two novel indacenodithiophene (IDT)-based D-A conjugated polymers, namely, PDPPy-IT and PSNT-IT via palladium-catalyzed Stille coupling reactions. These novel polymers exhibit optical band gaps of 1.81 and 1.27 eV for PDPPy-IT and PSNT-IT, respectively, with highly desirable visible and NIR light detection through energy-level manipulation. Moreover, excellent materials' solubility and thin-film processability allow easy incorporation of these polymers as an active layer into OPDs for light detection. In the case of PSNT-IT devices, a photodetection up to 1000 nm is demonstrated with a peak sensitivity centered at 875 nm, whereas PDPPy-IT devices are efficient in detecting the visible spectrum with the highest sensitivity at 660 nm. Overall, both OPDs exhibit spectral responsivities up to 0.11 A W-1 and dark currents in the nA cm-2 range. With linear dynamic ranges exceeding 140 dB and fast response times recorded below 100 µs, the use of novel IDT-based polymers in OPDs shows great potential for wearable optoelectronics.

Saturated free fatty acids and association with memory formation.

Polyunsaturated free fatty acids (FFAs) such as arachidonic acid, released by phospholipase activity on membrane phospholipids, have long been considered beneficial for learning and memory and are known modulators of neurotransmission and synaptic plasticity. However, the precise nature of other FFA and phospholipid changes in specific areas of the brain during learning is unknown. Here, using a targeted lipidomics approach to characterise FFAs and phospholipids across the rat brain, we demonstrated that the highest concentrations of these analytes were found in areas of the brain classically involved in fear learning and memory, such as the amygdala. Auditory fear conditioning led to an increase in saturated (particularly myristic and palmitic acids) and to a lesser extent unsaturated FFAs (predominantly arachidonic acid) in the amygdala and prefrontal cortex. Both fear conditioning and changes in FFA required activation of NMDA receptors. These results suggest a role for saturated FFAs in memory acquisition.

Low-intensity ultrasound restores long-term potentiation and memory in senescent mice through pleiotropic mechanisms including NMDAR signaling.

Advanced physiological aging is associated with impaired cognitive performance and the inability to induce long-term potentiation (LTP), an electrophysiological correlate of memory. Here, we demonstrate in the physiologically aged, senescent mouse brain that scanning ultrasound combined with microbubbles (SUS+MB), by transiently opening the blood-brain barrier, fully restores LTP induction in the dentate gyrus of the hippocampus. Intriguingly, SUS treatment without microbubbles (SUSonly), i.e., without the uptake of blood-borne factors, proved even more effective, not only restoring LTP, but also ameliorating the spatial learning deficits of the aged mice. This functional improvement is accompanied by an altered milieu of the aged hippocampus, including a lower density of perineuronal nets, increased neurogenesis, and synaptic signaling, which collectively results in improved spatial learning. We therefore conclude that therapeutic ultrasound is a non-invasive, pleiotropic modality that may enhance cognition in elderly humans.