Topographic organization of connections between prefrontal cortex and mediodorsal thalamus: Evidence for a general principle of indirect thalamic pathways between directly connected cortical areas.
ABSTRACT: Our ability to act flexibly, according to goals and context, is known as cognitive control. Hierarchical levels of control, reflecting different levels of abstraction, are represented across prefrontal cortex (PFC). Although the mediodorsal thalamic nucleus (MD) is extensively interconnected with PFC, the role of MD in cognitive control is unclear. Tract tracer studies in macaques, involving subsets of PFC areas, have converged on coarse MD-PFC connectivity principles; but proposed finer-grained topographic schemes, which constrain interactions between MD and PFC, disagree in many respects. To investigate a unifying topographic scheme, we performed probabilistic tractography on diffusion MRI data from eight macaque monkeys, and estimated the probable paths connecting MD with each of all 19 architectonic areas of PFC. We found a connectional topography where the orderly progression from ventromedial to anterior to posterolateral PFC was represented from anteromedial to posterolateral MD. The projection zones of posterolateral PFC areas in MD showed substantial overlap, and those of ventral and anteromedial PFC areas in MD overlapped. The exception was cingulate area 24: its projection zone overlapped with projections zones of all other PFC areas. Overall, our data suggest that nearby, functionally related, directly connected PFC areas have partially overlapping projection zones in MD, consistent with a role for MD in coordinating communication across PFC. Indeed, the organizing principle for PFC projection zones in MD appears to reflect the flow of information across the hierarchical, multi-level PFC architecture. In addition, cingulate area 24 may have privileged access to influence thalamocortical interactions involving all other PFC areas.
Project description:We examined the extent of the ferret prefrontal cortex (PFC) and its reciprocal connections with the mediodorsal nucleus of the thalamus (MD) by anterograde and retrograde labeling in 6- to 14-week-old male ferrets. Our results indicate that in the ferret, as in other species, MD projects heavily to the PFC although it also projects to other cortical and subcortical structures. The MD projection to PFC terminates largely in layer IV with lighter innervation of layers II, III, V, and VI. The cells projecting back to MD are mostly in layer VI. The parvocellular component of MD projects to and receives projections from the more caudal and dorsomedial component of the PFC, whereas the magnocellular portion of MD projects to and receives projections from the more rostral and lateral component of the PFC. With these results we have localized the ferret PFC, defined as a frontal cortical region with heavy reciprocal connections with the MD.
Project description:A careful review of the literature suggests that a significant number of patients undergoing anterior cruciate ligament (ACL) reconstruction have less-than-optimal results. Although overall outcomes of ACL reconstruction are favorable, there remains considerable room for improvement. Anatomically, the ACL consists of 2 major functional bundles, the anteromedial bundle and the posterolateral bundle. Biomechanically, both bundles contribute significantly to the anterior and rotational stability of the knee. Therefore anatomic double-bundle ACL reconstruction techniques may further improve the outcomes in ACL surgery. This article presents a technique for arthroscopic double-bundle ACL reconstruction that includes the use of 2 femoral and 2 tibial tunnels to restore both the anteromedial and posterolateral bundles of the ACL with minimal hardware for fixation.
Project description:To understand how the information derived from different motor cortical areas representing different body parts is organized in the basal ganglia, we examined the neuronal responses in the subthalamic nucleus (STN), and the external (GPe) and internal (GPi) segments of the globus pallidus (input, relay and output nuclei, respectively) to stimulation of the orofacial, forelimb and hindlimb regions of the primary motor cortex (MI) and supplementary motor area (SMA) in macaque monkeys under the awake state. Most STN and GPe/GPi neurons responded exclusively to stimulation of either the MI or SMA, and one-fourth to one-third of neurons responded to both. STN neurons responding to the hindlimb, forelimb and orofacial regions of the MI were located along the medial-lateral axis in the posterolateral STN, while neurons responding to the orofacial region of the SMA were located more medially than the others in the anteromedial STN. GPe/GPi neurons responding to the hindlimb, forelimb and orofacial regions of the MI were found along the dorsal-ventral axis in the posterolateral GPe/GPi, and neurons responding to the corresponding regions of the SMA were similarly but less clearly distributed in more anteromedial regions. Moreover, neurons responding to the distal and proximal forelimb MI regions were found along the lateral-medial axis in the STN and the ventral-dorsal axis in the GPe/GPi. Most STN and GPe/GPi neurons showed kinaesthetic responses with similar somatotopic maps. These observations suggest that the somatotopically organized inputs from the MI and SMA are well preserved in the STN and GPe/GPi with partial convergence.
Project description:Major depressive disorder (MDD) is associated with structural and functional alterations in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Enhanced ACC activity at rest (measured using various imaging methodologies) is found in treatment-responsive patients and is hypothesized to bolster treatment response by fostering adaptive rumination. However, whether structural changes influence functional coupling between fronto-cingulate regions and ACC regional homogeneity (ReHo) and whether these functional changes are related to levels of adaptive rumination and treatment response is still unclear. Cortical thickness and ReHo maps were calculated in 21 unmedicated depressed patients and 35 healthy controls. Regions with reduced cortical thickness defined the seeds for the subsequent functional connectivity (FC) analyses. Patients completed the Response Style Questionnaire, which provided a measure of adaptive rumination associated with better response to psychotherapy. Compared with controls, depressed patients showed thinning of the right anterior PFC, increased prefrontal connectivity with the supragenual ACC (suACC), and higher ReHo in the suACC. The suACC clusters of increased ReHo and FC spatially overlapped. In depressed patients, suACC ReHo scores positively correlated with PFC thickness and with FC strength. Moreover, stronger fronto-cingulate connectivity was related to higher levels of adaptive rumination. Greater suACC ReHo and connectivity with the right anterior PFC seem to foster adaptive forms of self-referential processing associated with better response to psychotherapy, whereas prefrontal thinning impairs the ability of depressed patients to engage the suACC during a major depressive episode. Bolstering the function of the suACC may represent a potential target for treatment.
Project description:<h4>Background</h4>Psychological conditions affect pain responses in the human anterior cingulate cortex (ACC) according to brain imaging analysis. The rodent prefrontal cortex (PFC) including cingulate areas is also related to the affective dimension of pain. We previously reported PFC nociceptive responses inhibited by inputs from the amygdala, such as with dopamine (DA) D2 receptor (D2R) blockers, to show decreased effect on amygdala projections. In this study, we examined whether direct projections from the ventral tegmental area (VTA) to the PFC affect nociceptive responses in the PFC.<h4>Results</h4>High frequency stimulation (HFS, 50 Hz, 30 s) delivered to the VTA produced long-lasting suppression (LLS) of nociceptive responses in the rat PFC including cingulate and prelimbic areas. Nociceptive responses evoked by mechanical pressure stimulation (2 s duration at 500 g constant force) applied to the tails of urethane-anesthetized rats were recorded using extracellular unit recording methods in the PFC. HFS delivered to the VTA, which has been reported to increase DA concentrations in the PFC, significantly suppressed nociceptive responses. The LLS of nociceptive responses persisted for about 30 minutes and recovered to the control level within 60 min after HFS. We also demonstrated local microinjection of a selective D2 agonist of DA receptors to induce LLS of mechanical nociceptive responses, while a D2 but not a D1 antagonist impaired the LLS evoked by HFS. In contrast, DA depletion by a 6-hydroxydopamine injection or a low concentration of DA induced by a ?-opiate receptor agonist injected into the VTA had minimal effect on nociceptive responses in the PFC.<h4>Conclusion</h4>HFS delivered to VTA inhibited nociceptive responses for a long period in PFC. DA D2R activation mediated by local D2 agonist injection also induced LLS of mechanical nociceptive responses. The mesocortical DA system may modify PFC nociceptive responses via D2 activity.
Project description:PURPOSE:Thalamic hemorrhage breaking into ventricles (THBIV) is a devastating disease with high morbidity and mortality rates. Endoscopic surgery (ES) may improve outcomes, although there is no consensus on its superiority. We investigated the efficacy and safety of ES and compared the outcomes of different management strategies by ES, hematoma puncture and drainage (HPD), and external ventricular drainage (EVD) in patients with THBIV. METHODS:We retrospectively analyzed patients with THBIV treated by ES, HPD, or EVD at our hospital from June 2015 to June 2018. Patients were categorized into anteromedial and posterolateral groups based on THBIV location, and then the two groups were further divided into ES, HPD, and EVD subgroups. Individualized surgical approach was adopted according to the location of the hematoma in the ES subgroups. Patient characteristics and surgical outcomes were investigated. RESULTS:We analyzed 211 consecutive patients. There were no significant differences in clinical characteristics or incidence of perioperative procedure-related complications (postoperative rebleeding and intracranial infection) in either anteromedial or posterolateral groups. Compared with other therapeutic methods, the ES subgroups had the highest hematoma evacuation rate, shortest drainage time, and lowest incidence of chronic ventricular dilatation (all p < 0.05). Among the three anteromedial subgroups, ES subgroup had the best clinical outcomes which was assessed by the modified Rankin Scale, followed by HPD and EVD subgroups (p < 0.01); while in the posterolateral subgroups, clinical outcomes in the ES and HPD subgroups were similar and better than that in the EVD subgroup (p = 0.037). CONCLUSION:Individualized surgical ES approach for removal of thalamic and ventricular hematomas is a minimally invasive, safe, and effective strategy for the treatment of THBIV with a thalamic hematoma volume of 10-30 mL.
Project description:Zone-to-zone projection of olfactory and vomeronasal sensory axons underlies the topographic and functional mapping of chemoreceptor expression zones of the sensory epithelia onto zonally arranged glomeruli in the main and accessory olfactory bulbs. Here we identified OCAM (R4B12 antigen), an axonal surface glycoprotein expressed by subsets of both olfactory and vomeronasal axons in a zone-specific manner. OCAM is a novel homophilic adhesion molecule belonging to the immunoglobulin superfamily with striking structural homology to neural cell adhesion molecule. In both the main and accessory olfactory systems, OCAM mRNA is expressed by sensory neurons in restricted chemoreceptor expression zones, and OCAM protein-expressing axons project to the glomeruli in the corresponding zones of the main and accessory bulbs. OCAM protein is expressed on subsets of growing sensory axons in explant cultures even in the absence of the target bulb. These results demonstrate a precisely coordinated zonal expression of chemoreceptors and OCAM and suggest that OCAM may play important roles in selective fasciculation and zone-to-zone projection of the primary olfactory axons.
Project description:Conventional single-bundle anterior cruciate ligament (ACL) reconstruction cannot improve the rotational stability of the knee. Traditional double-bundle ACL reconstruction requires is demanding, complex, time- and implant consuming, and associated with a high incidence of complications. Double-bundle ACL reconstruction using a free quadriceps tendon autograft through 3 independent tunnels provides some advantage, but the antegrade graft passage, tibial tunnel confluence, and graft site morbidity represent disadvantages. This Technical Note describes a modification of double-bundle ACL reconstruction using the hamstring tendon autograft through a single branched tibial tunnel and a single femoral tunnel using 2 interference screws (Arthrex, Naples, FL). The gracilis tendon autograft is passed through tibial tunnel stem to the posterolateral tibial tunnel branch to the posterolateral position in the femoral tunnel. The semitendinosus tendon autograft is passed through the tibial tunnel stem to the anteromedial tibial tunnel branch to the anteromedial position in the femoral tunnel. Both grafts are fixed by 2 interference screws: 1 at the femoral tunnel and 1 at the tibial tunnel stem with the knee at 20° flexion.
Project description:The D?/D? receptor agonist pramipexole has clinical efficacy as an antidepressant, but its neural mechanisms are unknown. We used ¹?FDG-PET to investigate the cerebral metabolic effects of pramipexole augmentation of mood stabilizers in bipolar II depression. Fifteen bipolar II depressed patients on mood stabilizers were imaged at baseline and following 6 wk of pramipexole (n=7) or placebo (n=8) augmentation. Relative to placebo, pramipexole treatment was associated with reductions in normalized metabolism in bilateral orbitofrontal cortex, left ventrolateral prefrontal cortex (PFC), and right anteromedial PFC. Voxel-wise analyses additionally showed decreased normalized metabolism in the left inferior parietal cortex and medial frontopolar cortical (BA 10P) area of the anteromedial PFC following pramipexole treatment. These pramipexole-induced effects on regional metabolism suggest a mechanism of antidepressant action distinct from that previously reported under serotonin reuptake inhibitor treatment and appear compatible with evidence that the central dopaminergic system plays a role in the pathophysiology of bipolar depression.