Rostral and caudal BLA engage distinct circuits in the prelimbic and infralimbic PFC

Connections from the basolateral amygdala (BLA) to medial prefrontal cortex (PFC) regulate memory and emotion and become disrupted in neuropsychiatric disorders. We hypothesized that the diverse roles attributed to interactions between the BLA and PFC reflect multiple circuits nested within a wider network. To assess these circuits, we first used anatomy to show that the rostral BLA (rBLA) and caudal BLA (cBLA) differentially project to prelimbic (PL) and infralimbic (IL) subregions of the PFC, respectively. We then combined in vivo silicon probe recordings and optogenetics to show that rBLA primarily engages PL, whereas cBLA mainly influences IL. Using ex vivo whole-cell recordings and optogenetics, we then assessed which neuronal subtypes are targeted, showing that rBLA preferentially drives layer 2 (L2) cortico-amygdalar (CA) neurons in PL, whereas cBLA drives layer 5 (L5) pyramidal tract (PT) cells in IL. Lastly, we used soma-tagged optogenetics to explore the local circuits linking superficial and deep layers of PL, showing how rBLA can also impact L5 PT cells. Together, our findings delineate how subregions of the BLA target distinct networks within the PFC to have different influence on prefrontal output.

STMO-12 Efforts for safe malignant brain tumor surgery at our hospital

Although maximal safe resection is the current standard for glioblastoma surgery, its safety and removal rate conflict with each other. Electrophysiological monitoring, such as motor evoked potential monitoring and awake craniotomy, can be utilized as safety measures; not all facilities can perform them. Herein, we present a representative case report on our efforts for a safe malignant brain tumor surgery. Case: A 77-year-old woman with glioblastoma in the premotor cortex presented with seizure of the upper left lower limb. Her pyramidal tract ran from the medial bottom to the posterior of the tumor. We performed excision from the site using the lowest gamma entropy. We then removed all parts of the tumor, with the exception of the pyramidal tract infiltration, and no paralysis was observed. She was definitively diagnosed with glioblastoma and is currently on maintenance chemotherapy. As a preoperative examination, we performed cerebrovascular angiography. We then performed various other tests to ascertain the patient’s condition. Considering lesions that affect language, Wada tests were performed regardless of laterality. For all patients with epilepsy onset, preoperative 256-channel electroencephalogram measurement and intraoperative the gamma entropy analysis were performed to confirm epileptogenicity. Considering lesions that affect eloquence, subdural electrodes were placed and brain function mapping was performed the next day. Based on the results, the safest cortical incision site and excision range were determined, and excision was performed on the following day. Of the 14 operated glioblastoma cases after November 2018, more than 85% of the contrast-enhanced lesions were completely removed in 7 cases, partially removed in 5 cases, and underwent biopsy in 2 cases. Postoperative Karnofsky performance status scores remained unchanged in 11 cases, improved in 1 case, and deteriorated in 2 cases. Our efforts have resulted in safe and sufficient removal of malignant brain tumors during surgery.

Cholinergic deficits selectively boost cortical intratelencephalic control of the striatum in Huntington’s disease

Huntington’s disease (HD) is a progressive, neurodegenerative disease caused by a CAG triplet expansion in the huntingtin gene. Although corticostriatal dysfunction has long been implicated in HD, the determinants and pathway specificity of this pathophysiology remain a matter of speculation. To help fill this gap, the zQ175+/- knockin mouse model of HD was studied using approaches that allowed optogenetic interrogation of intratelencephalic (IT) and pyramidal tract (PT) connections with principal striatal spiny projection neurons (SPNs). These studies revealed that the connectivity of IT, but not PT, neurons with direct and indirect pathway SPNs increased in early symptomatic zQ175+/- HD mice. This enhancement was attributable to reduced inhibitory control of IT terminals by striatal cholinergic interneurons (ChIs). Lowering mutant huntingtin selectively in ChIs with a virally-delivered zinc finger repressor protein normalized striatal acetylcholine release and IT functional connectivity – revealing a novel node in the network underlying corticostriatal pathophysiology in HD.

Diverse operant control of different motor cortex populations during learning

During motor learning, as well as during neuroprosthetic learning, animals learn to control motor cortex activity in order to generate behavior. Two different population of motor cortex neurons, intra-telencephalic (IT) and pyramidal tract (PT) neurons, convey the resulting cortical signals within and outside the telencephalon. Although a large amount of evidence demonstrates contrasting functional organization among both populations, it is unclear whether the brain can equally learn to control the activity of either class of motor cortex neurons. To answer this question, we used a Calcium imaging based brain-machine interface (CaBMI) and trained different groups of mice to modulate the activity of either IT or PT neurons in order to receive a reward. We found that animals learn to control PT neuron activity faster and better than IT neuron activity. Moreover, our findings show that the advantage of PT neurons is the result of characteristics inherent to this population as well as their local circuitry and cortical depth location. Taken together, our results suggest that motor cortex is optimized to control the activity of pyramidal track neurons, embedded deep in cortex, and relaying motor commands outside of the telencephalon.

Abdominal tendon reflexes in lesions of the pyramidal tract

Abdominal tendon reflexes were studied in Th. Dosuzkov and Fr. Bodlakova (Revue v. Neurologii i psychiatrii, 1928, no. 4). They find the reflex of the rectus abdominis muscles described by Astvatsaturov not only in paraplegia (and hemiplegia) with the lower limbs in the extension position (Erb'a type), but also in the flexion position (Babinsky type).

Thalamus gates active dendritic computations in cortex during sensory processing

Perception is causally linked to a calcium-dependent spiking mechanism that is built into the distal dendrites of layer 5 pyramidal tract neurons – the major output cell type of the cerebral cortex. It is yet unclear which circuits activate this cellular mechanism upon sensory stimulation. Here we found that the same thalamocortical axons that relay sensory signals to layer 4 also densely target the dendritic domain by which pyramidal tract neurons initiate calcium spikes. Distal dendritic inputs, which normally appear greatly attenuated at the cell body, thereby generate bursts of action potentials in cortical output during sensory processing. Our findings indicate that thalamus gates an active dendritic mechanism to facilitate the combination of sensory signals with top-down information streams into cortical output. Thus, in addition to being the central hub for sensory signals, thalamus is also likely to ensure that the signals it relays to cortex are perceived by the animal.

Sensitivity of brain MRI and neurological examination for detection of upper motor neurone degeneration in amyotrophic lateral sclerosis

ObjectivesTo investigate sensitivity of brain MRI and neurological examination for detection of upper motor neuron (UMN) degeneration in patients with amyotrophic lateral sclerosis (ALS).MethodsWe studied 192 patients with ALS and 314 controls longitudinally. All patients visited our centre twice and underwent full neurological examination and brain MRI. At each visit, we assessed UMN degeneration by measuring motor cortex thickness (CT) and pyramidal tract fibre density (FD) corresponding to five body regions (bulbar region and limbs). For each body region, we measured degree of clinical UMN and lower motor neuron (LMN) symptom burden using a validated scoring system.ResultsWe found deterioration over time of CT of motor regions (p≤0.0081) and progression of UMN signs of bulbar region and left arm (p≤0.04). FD was discriminative between controls and patients with moderate/severe UMN signs (all regions, p≤0.034), but did not change longitudinally. Higher clinical UMN burden correlated with reduced CT, but not lower FD, for the bulbar region (p=2.2×10−10) and legs (p≤0.025). In the arms, we found that severe LMN signs may reduce the detectability of UMN signs (p≤0.043). With MRI, UMN degeneration was detectable before UMN signs became clinically evident (CT: p=1.1×10−10, FD: p=6.3×10−4). Motor CT, but not FD, deteriorated more than UMN signs during the study period.ConclusionsMotor CT is a more sensitive measure of UMN degeneration than UMN signs. Motor CT and pyramidal tract FD are discriminative between patients and controls. Brain MRI can monitor UMN degeneration before signs become clinically evident. These findings promote MRI as a potential biomarker for UMN progression in clinical trials in ALS.

Characteristic Magnetic Resonance Image Features of Acute Network Injury in Young Patients

Cerebral infarction is known to cause secondary degeneration of the areas connected to the primarily damaged regions. This has been named as acute network injury and is usually recognized in newborns or babies by high signal intensity on diffusion-weighted imaging (DWI). In this article, we present 2 cases demonstrating several characteristics of network injury. Some features are comparable to previous studies and others are distinctive to our cases. The patients not only showed secondary injury in the thorough pyramidal tract along the longitudinal extensions of neural tracts as expected but also followed transverse connections to reach the contralateral hemisphere. The location of network injury varied according to the initial lesion and projected in an omnidirectional manner as long as the brain parts are interconnected. In addition, the cases well demonstrated the temporal changes on brain imaging. Network injury appeared on DWI around a week after major damage and then subsequently disappeared. The overall process of appearance to disappearance was completed within 2 weeks from the symptom onset. As ominous neurological outcomes are thought to be related to acute network injuries, a comprehensive understanding of the phenomenon is pivotal in improving diagnosis and management.

Recurrent Lobar Hemorrhages and Multiple Cortical Superficial Siderosis in a Patient of Alzheimer's Disease With Homozygous APOE ε2 Allele Presenting Hypobetalipoproteinemia and Pathological Findings of 18F-THK5351 Positron Emission Tomography: A Case Report

In Alzheimer's disease, the apolipoprotein E gene (APOE) ε2 allele is a protective genetic factor, whereas the APOE ε4 allele is a genetic risk factor. However, both the APOE ε2 and the APOE ε4 alleles are genetic risk factors for lobar intracerebral hemorrhage. The reasons for the high prevalence of lobar intracerebral hemorrhage and the low prevalence of Alzheimer's disease with the APOE ε2 allele remains unknown. Here, we describe the case of a 79-year-old Japanese female with Alzheimer's disease, homozygous for the APOE ε2 allele. This patient presented with recurrent lobar hemorrhages and multiple cortical superficial siderosis. The findings on the 11C-labeled Pittsburgh Compound B-positron emission tomography (PET) were characteristic of Alzheimer's disease. 18F-THK5351 PET revealed that the accumulation of 18F-THK 5351 in the right pyramidal tract at the pontine level, the cerebral peduncle of the midbrain, and the internal capsule, reflecting the lesions of the previous lobar intracerebral hemorrhage in the right frontal lobe. Moreover, 18F-THK5351 accumulated in the bilateral globus pallidum, amygdala, caudate nuclei, and the substantia nigra of the midbrain, which were probably off-target reaction, by binding to monoamine oxidase B (MAO-B). 18F-THK5351 were also detected in the periphery of prior lobar hemorrhages and a cortical subarachnoid hemorrhage, as well as in some, but not all, areas affected by cortical siderosis. Besides, 18F-THK5351 retentions were observed in the bilateral medial temporal cortices and several cortical areas without cerebral amyloid angiopathy or prior hemorrhages, possibly where tau might accumulate. This is the first report of a patient with Alzheimer's disease, carrying homozygous APOE ε2 allele and presenting with recurrent lobar hemorrhages, multiple cortical superficial siderosis, and immunohistochemically vascular amyloid β. The 18F-THK5351 PET findings suggested MAO-B concentrated regions, astroglial activation, Waller degeneration of the pyramidal tract, neuroinflammation due to CAA related hemorrhages, and possible tau accumulation.

Impairment and Compensation in Dexterous Upper-Limb Function After Stroke. From the Direct Consequences of Pyramidal Tract Lesions to Behavioral Involvement of Both Upper-Limbs in Daily Activities

Impairments in dexterous upper limb function are a significant cause of disability following stroke. While the physiological basis of movement deficits consequent to a lesion in the pyramidal tract is well demonstrated, specific mechanisms contributing to optimal recovery are less apparent. Various upper limb interventions (motor learning methods, neurostimulation techniques, robotics, virtual reality, and serious games) are associated with improvements in motor performance, but many patients continue to experience significant limitations with object handling in everyday activities. Exactly how we go about consolidating adaptive motor behaviors through the rehabilitation process thus remains a considerable challenge. An important part of this problem is the ability to successfully distinguish the extent to which a given gesture is determined by the neuromotor impairment and that which is determined by a compensatory mechanism. This question is particularly complicated in tasks involving manual dexterity where prehensile movements are contingent upon the task (individual digit movement, grasping, and manipulation…) and its objective (placing, two step actions…), as well as personal factors (motivation, acquired skills, and life habits…) and contextual cues related to the environment (presence of tools or assistive devices…). Presently, there remains a lack of integrative studies which differentiate processes related to structural changes associated with the neurological lesion and those related to behavioral change in response to situational constraints. In this text, we shall question the link between impairments, motor strategies and individual performance in object handling tasks. This scoping review will be based on clinical studies, and discussed in relation to more general findings about hand and upper limb function (manipulation of objects, tool use in daily life activity). We shall discuss how further quantitative studies on human manipulation in ecological contexts may provide greater insight into compensatory motor behavior in patients with a neurological impairment of dexterous upper-limb function.