Brain substrates for automatic retrieval of value memory in the primate basal ganglia

Our behavior is often carried out automatically. Automatic behavior can be guided by past experiences, such as learned values associated with objects. Passive-viewing and free-viewing tasks with no immediate outcomes provide a testable condition in which monkeys and humans automatically retrieve value memories and perform habitual searching. Interestingly, in these tasks, caudal regions of the basal ganglia structures are involved in automatic retrieval of learned object values and habitual gaze. In contrast, rostral regions do not participate in these activities but instead monitor the changes in outcomes. These findings indicate that automatic behaviors based on the value memories are processed selectively by the caudal regions of the primate basal ganglia system. Understanding the distinct roles of the caudal basal ganglia may provide insight into finding selective causes of behavioral disorders in basal ganglia disease.

Volumetric MRI-Based Biomarkers in Huntington's Disease: An Evidentiary Review

Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder that is caused by expansion of a CAG-repeat tract in the huntingtin gene and characterized by motor impairment, cognitive decline, and neuropsychiatric disturbances. Neuropathological studies show that disease progression follows a characteristic pattern of brain atrophy, beginning in the basal ganglia structures. The HD Regulatory Science Consortium (HD-RSC) brings together diverse stakeholders in the HD community—biopharmaceutical industry, academia, nonprofit, and patient advocacy organizations—to define and address regulatory needs to accelerate HD therapeutic development. Here, the Biomarker Working Group of the HD-RSC summarizes the cross-sectional evidence indicating that regional brain volumes, as measured by volumetric magnetic resonance imaging, are reduced in HD and are correlated with disease characteristics. We also evaluate the relationship between imaging measures and clinical change, their longitudinal change characteristics, and within-individual longitudinal associations of imaging with disease progression. This analysis will be valuable in assessing pharmacodynamics in clinical trials and supporting clinical outcome assessments to evaluate treatment effects on neurodegeneration.

Distinct population code for movement kinematics and changes of ongoing movements in human subthalamic nucleus

The subthalamic nucleus (STN) is theorized to globally suppress movement through connections with downstream basal ganglia structures. Current theories are supported by increased STN activity when subjects withhold an uninitiated action plan, but a critical test of these theories requires studying STN responses when an ongoing action is replaced with an alternative. We perform this test in subjects with Parkinson's disease using an extended reaching task where the movement trajectory changes mid-action. We show that STN activity decreases during action switches, contrary to prevalent theories. Further, beta oscillations in the STN local field potential, which are associated with movement inhibition, do not show increased power or spiking entrainment during switches. We report an inhomogeneous population neural code in STN, with one sub-population encoding movement kinematics and direction and another encoding unexpected action switches. We suggest an elaborate neural code in STN that contributes to planning actions and changing the plans.

Anatomical aspects of the insula, opercula and peri-insular white matter for a transcortical approach to insular glioma resection

The insula is a lobe located deep in each hemisphere of the brain and is surrounded by eloquent cortical, white matter, and basal ganglia structures. The aim of this study was to provide an anatomical description of the insula and white matter tracts related to surgical treatment of gliomas through a transcortical approach. The study also discusses surgical implications in terms of intraoperative brain mapping. Five adult brains were prepared according to the Klingler technique. Cortical anatomy was evaluated with the naked eye, whereas white matter dissection was performed with the use of a microscope. The widest exposure of the insular surface was noted through the temporal operculum, mainly in zones III and IV according to the Berger-Sanai classification. By going through the pars triangularis in all cases, the anterior insular point and most of zone I were exposed. The narrowest and deepest operating field was observed by going through the parietal operculum. This method provided a suitable approach to zone II, where the corticospinal tract is not covered by the basal ganglia and is exposed just under the superior limiting sulcus. At the subcortical level, the identification of the inferior frontoocipital fasciculus at the level of the limen insulae is critical in terms of preserving the lenticulostriate arteries. Detailed knowledge of the anatomy of the insula and subcortical white matter that is exposed through each operculum is essential in preoperative planning as well as in the intraoperative decision-making process in terms of intraoperative brain mapping.

Secondary parkinsonism caused by chronic subdural hematomas owing to compressed cortex and a disturbed cortico–basal ganglia–thalamocortical circuit: illustrative case

BACKGROUND Chronic subdural hematoma (CSDH) is a commonly encountered condition in neurological and neurosurgical practice, but the presence of concomitant parkinsonism is extremely rare. Basal ganglia disturbance is a well-known underlying mechanism; however, few cases present with cerebral cortex compression as the cause of symptoms. OBSERVATIONS A 52-year-old man was referred to the authors’ hospital with a 5-week history of gait disturbance and suspected Parkinson’s disease. Neurological examination revealed a mask-like face, stooped posture, left-predominant rigidity, and postural instability. The authors initiated dopamine agonist administration, and brain magnetic resonance imaging (MRI) was scheduled. One week later, MRI showed bilateral CSDHs. The hematomas markedly compressed the bilateral cerebral cortex, whereas the midbrain and basal ganglia structures were intact. The patient underwent burr hole drainage and was discharged after 9 days without sequelae. LESSONS CSDH can cause parkinsonism by compressing the cerebral cortex, which is a part of the cortico–basal ganglia–thalamocortical circuit. Surgery leads to positive outcomes, as illustrated by this case, in which cerebral cortex compression caused parkinsonism.

Understanding the Role of Sensorimotor Beta Oscillations

Beta oscillations have been predominantly observed in sensorimotor cortices and basal ganglia structures and they are thought to be involved in somatosensory processing and motor control. Although beta activity is a distinct feature of healthy and pathological sensorimotor processing, the role of this rhythm is still under debate. Here we review recent findings about the role of beta oscillations during experimental manipulations (i.e., drugs and brain stimulation) and their alteration in aging and pathology. We show how beta changes when learning new motor skills and its potential to integrate sensory input with prior contextual knowledge. We conclude by discussing a novel methodological approach analyzing beta oscillations as a series of transient bursting events.

Whole-brain mapping of monosynaptic inputs to midbrain cholinergic neurons

The cholinergic midbrain is involved in a wide range of motor and cognitive processes. Cholinergic neurons of the pedunculopontine (PPN) and laterodorsal tegmental nucleus (LDT) send long-ranging axonal projections that target sensorimotor and limbic areas in the thalamus, the dopaminergic midbrain and the striatal complex following a topographical gradient, where they influence a range of functions including attention, reinforcement learning and action-selection. Nevertheless, a comprehensive examination of the afferents to PPN and LDT cholinergic neurons is still lacking, partly due to the neurochemical heterogeneity of this region. Here we characterize the whole-brain input connectome to cholinergic neurons across distinct functional domains (i.e. PPN vs LDT) using conditional transsynaptic retrograde labeling in ChAT::Cre male and female rats. We reveal that input neurons are widely distributed throughout the brain but segregated into specific functional domains. Motor related areas innervate preferentially the PPN, whereas limbic related areas preferentially innervate the LDT. The quantification of input neurons revealed that both PPN and LDT receive similar substantial inputs from the superior colliculus and the output of the basal ganglia (i.e. substantia nigra pars reticulata). Notably, we found that PPN cholinergic neurons receive preferential inputs from basal ganglia structures, whereas LDT cholinergic neurons receive preferential inputs from limbic cortical areas. Our results provide the first characterization of inputs to PPN and LDT cholinergic neurons and highlight critical differences in the connectome among brain cholinergic systems thus supporting their differential roles in behavior.

Anatomical aspects of the insula, opercula and peri-insular white matter for a transcortical approach to insular glioma resection

Introduction: The insula is a lobe located deep in each hemisphere of the brain and is surrounded by eloquent cortical, white matter and basal ganglia structures. The aim of this study was to provide an anatomical description of the insula and white matter tracts related to surgical treatment of gliomas through a transcortical approach. The study also discusses surgical implications in terms of intraoperative brain mapping. Methods Five adult brains were prepared according to the Klingler technique. Cortical anatomy was evaluated with the naked eye, whereas white matter dissection was performed with the use of a microscope. Results The widest exposure of the insular surface was noted through the temporal operculum, mainly in Zones III and IV according to the Berger-Sanai classification. By going through the pars triangularis in all cases, the anterior insular point and most of Zone I were exposed. The narrowest and deepest operating field was observed by going through the parietal operculum. This method provided a suitable approach to Zone II, where the corticospinal tract is not covered by the basal ganglia and is exposed just under the superior limiting sulcus. At the subcortical level, the identification of the inferior frontoocipital fasciculus at the level of the limen insulae is critical in terms of preserving the lenticulostriate arteries. Conclusion Detailed knowledge of the anatomy of the insula and subcortical white matter that is exposed through each operculum is essential in preoperative planning as well as in the intraoperative decision-making process in terms of intraoperative brain mapping.

Real time and delayed effects of subcortical low intensity focused ultrasound

Deep brain nuclei are integral components of large-scale circuits mediating important cognitive and sensorimotor functions. However, because they fall outside the domain of conventional non-invasive neuromodulatory techniques, their study has been primarily based on neuropsychological models, limiting the ability to fully characterize their role and to develop interventions in cases where they are damaged. To address this gap, we used the emerging technology of non-invasive low-intensity focused ultrasound (LIFU) to directly modulate left lateralized basal ganglia structures in healthy volunteers. During sonication, we observed local and distal decreases in blood oxygenation level dependent (BOLD) signal in the targeted left globus pallidus (GP) and in large-scale cortical networks. We also observed a generalized decrease in relative perfusion throughout the cerebrum following sonication. These results show, for the first time using functional MRI data, the ability to modulate deep-brain nuclei using LIFU while measuring its local and global consequences, opening the door for future applications of subcortical LIFU.

Thalamic Volume Mediates Associations Between Cardiorespiratory Fitness and Memory in People With Parkinson’s

Cognitive deficits occur in patients with Parkinson’s disease (PD), and cardiorespiratory fitness (CRF) is associated with both current and future cognitive decline in this disease. The underlying neurobiological factors explaining this relationship, however, are not well known. In this cross-sectional study we examined the associations between CRF and cognitive performance and whether such associations were mediated by grey matter volumes of basal ganglia structures. A total of 33 individuals with PD underwent structural magnetic resonance imaging (sMRI), CRF evaluation (VO2max), and neuropsychological assessment. Composite scores of episodic memory, executive functioning, attention, language, and visuospatial functioning were generated. Brain MRI morphological measurements was performed with the Freesurfer image analysis suite. Structural equation models were constructed to examine whether sMRI volume estimates of basal ganglia structures, specifically the thalamus and pallidum, mediated associations between VO2 max and cognitive performance while adjusting for age, education, PD disease duration, sex, and intracranial volume. Higher VO2max was associated with better episodic memory (Standardized β=0.390; p=0.009), executive functioning (Standardized β=0.263; p=0.021), and visuospatial performance (β=0.408; p=0.004). Higher VO2max was associated with larger thalamic (Standardized β=0.602; p<0.001) and pallidum (Standardized β=0.539; p<0.001) volumes. Thalamic volume significantly mediated the association between higher VO2max and better episodic memory (indirect effect=0.209) and visuospatial ability (indirect effect=0.178) performance (p<.05). The pallidum did not significantly mediate associations between VO2 max and cognitive outcomes. These results suggest the thalamus plays an important role in the association between CRF episodic memory and visuospatial functioning in individuals with PD.