Medial Subregions Research Articles

Mapping Patterns of Ipsilateral Supraclavicular Nodal Metastases in Breast Cancer: Rethinking the Clinical Target Volume for High-risk Patients

To map the location of metastatic supraclavicular (SCV) lymph nodes (LNMs) in breast cancer patients with SCV node involvement and determine whether and where the radiation therapy clinical target volume (CTV) of this region could be modified in high-risk subsets. Fifty-five patients with metastatic SCV LNMs were eligible for geographic mapping and atlas coverage analysis. All LNMs and their epicenters were registered proportionally by referencing the surrounding landmarks onto simulation computed tomography images of a standard patient. CTVs based on selected SCV atlases, including the one by the Radiation Therapy Oncology Group (RTOG) were contoured. A modified SCV CTV was tried and shown to have better involved-node coverage and thus theoretically improved prophylaxis in this setting. A total of 50 (91%) and 45 (81.8%) patients had LNMs in the medial and lateral SCV subregions, respectively. Also, 36 patients (65.5%) had LNMs located at the junction of the jugular-subclavian veins. All nodes were covered in only 25.5% to 41.8% of patients by different atlases. The RTOG atlas covered all nodes in 25.5% of patients. Stratified by the nodes in all the patients as a whole, 49.2% to 81.3% were covered, and the RTOG atlas covered 62.6%. The lateral and posterior borders were the most overlooked locations. Modification by extending the borders to natural anatomic barriers allowed the new CTV to cover all the nodes in 81.8% of patients and encompass 96.1% of all the nodes. According to the distribution of SCV LNMs, the extent of existing atlases might not be adequate for potential metastatic sites in certain groups of patients. The extension of the lateral and posterior CTV borders in high-risk or recurrent patients might be a reasonable approach for increasing coverage. However, additional data in more homogeneous populations with localized disease are needed before routine application.

Temporally Dissociable Contributions of Human Medial Prefrontal Subregions to Reward-Guided Learning.

Multiple subregions of the medial prefrontal cortex are known to be involved in decision making and learning, and expose similar response patterns in fMRI. Here, we used a novel approach to analyzing simultaneous EEG-fMRI that allows to dissociate the individual time courses of brain regions. We find that vmPFC and dmPFC have distinguishable time courses and time-frequency patterns.

Gender moderates the association between dorsal medial prefrontal cortex volume and depressive symptoms in a subclinical sample

Major depressive disorder is associated with lower medial prefrontal cortex volumes. The role that gender might play in moderating this relationship and what particular medial prefrontal cortex subregion(s) might be implicated is unclear. Magnetic resonance imaging was used to assess dorsal, ventral, and anterior cingulate regions of the medial prefrontal cortex in a normative sample of male and female adults. The Depression, Anxiety, and Stress Scale (DASS) was used to measure these three variables. Voxel-based morphometry was used to test for correlations between medial prefrontal gray matter volume and depressive traits. The dorsal medial frontal cortex was correlated with greater levels of depression, but not anxiety and stress. Gender moderates this effect: in males greater levels of depression were associated with lower dorsal medial prefrontal volumes, but in females no relationship was observed. The results indicate that even within a non-clinical sample, male participants with higher levels of depressive traits tend to have lower levels of gray matter volume in the dorsal medial prefrontal cortex. Our finding is consistent with low dorsal medial prefrontal volume contributing to the development of depression in males. Future longitudinal work is needed to substantiate this possibility.

Comparison of T2 Values in the Lateral and Medial Portions of the Weight-Bearing Cartilage of the Hip for Patients With Symptomatic Femoroacetabular Impingement and Asymptomatic Volunteers

To develop a simplified method to define a clinically relevant subregion in the course of arthroscopic treatment of femoroacetabular impingement (FAI) using T2 mapping in patients and asymptomatic volunteers. Additionally, we sought to compare the lateral and medial subregion values in asymptomatic volunteers and in patients presenting with FAI. Finally, we wanted to investigate possible associations between patients' T2 mapping values and demographic variables-i.e., alpha angle, age, sex, and body mass index (BMI). Twenty-five asymptomatic volunteers and 23 consecutive symptomatic patients with FAI (cam or mixed type) were prospectively enrolled and evaluated with a sagittal T2 mapping sequence. The weight-bearing region of the acetabular and femoral cartilage was manually segmented and divided into medial and lateral subregions. Median T2 values were determined, and patient characteristics were assessed as potential predictors of T2 values. T2 values in the lateral portion of the acetabulum were lower than in the medial portion for both asymptomatic volunteers (43 v 53 ms; P < .001) and patients with FAI (42 v 49 ms; P=.016). The medial acetabulum (MA) of asymptomatic volunteers had higher T2 values than those of the FAI group (53 v 49 ms; P= .040). The lateral-minus-medial difference was significantly larger among asymptomatic volunteers than in patients with FAI (P= .047). Patients with FAI had higher alpha angles than those of the asymptomatic volunteers, but no other associations with patient characteristics were observed. This study's findings suggest that there are differences in cartilage T2 mapping values between medial and lateral weight-bearing aspects of the hip and may expand the application and usefulness of biochemical magnetic resonance imaging (MRI) techniques, specifically T2 mapping, in the diagnosis of hip cartilage damage with the evaluation of clinically relevant subregions. When comparing asymptomatic volunteers and patients with FAI presenting with cam or mixed type deformity, we observed a significant contrast between the T2 mapping values of the lateral and medial portions of the weight-bearing zone of the acetabular cartilage, whereas such contrast was not observed when zone 3 was analyzed as a whole. Level III, development of diagnostic criteria on the basis of consecutive patients with a universally applied reference gold standard.

Minimal change multiple system atrophy: an aggressive variant?

Glial cytoplasmic inclusions containing α-synuclein are the pathological hallmark of multiple system atrophy (MSA). Minimal change (MC-MSA) is an unusual MSA subtype with neuronal loss largely restricted to the substantia nigra and locus coeruleus. Immunohistochemistry on selected brain regions and semiquantitative assessment were performed on six MC-MSA and eight MSA control cases. More neuronal cytoplasmic inclusions were seen in the caudate and substantia nigra in MC-MSA than in MSA controls (P = 0.002), without any statistical difference in glial cytoplasmic inclusion load in any region. Severe glial cytoplasmic inclusion load was found in the ventrolateral medulla (P = 1.0) and nucleus raphe obscurus (P = 0.4) in both groups. When compared with MSA controls, the three MC-MSA cases who had died of sudden unexpected death had an earlier age of onset (mean: 38 vs. 57.6 y, P = 0.02), a numerically shorter disease duration (mean: 5.3 vs. 8 y, P = 0.2) and a more rapid clinical progression with most of the clinical milestones reached within 3 y of presentation, suggesting an aggressive variant of MSA. Another three MC-MSA cases, who had died of unrelated concurrent diseases, had an age of onset (mean: 57.7 y) and temporal course similar to controls, had less severe neuronal loss and gliosis in the medial and dorsolateral substantia nigra subregions (P < 0.05) than in MSA controls, and could be considered as a unique group with interrupted pathological progression. Significant respiratory dysfunction and early orthostatic hypotension were observed in all MC-MSA cases. Our findings could suggest that α-synuclein-associated oligodendroglial pathology may lead to neuronal dysfunction sufficient to cause clinical symptoms before overt neuronal loss in MSA. © 2015 International Parkinson and Movement Disorder Society.

Brief report: symmetricity of radiographic and MRI-detected structural joint damage in persons with knee pain – the Joints on Glucosamine (JOG) Study

Most MRI-based osteoarthritis (OA) studies have focused on a single knee per person and thus, data on bilaterality is sparse. Study aim was to describe symmetricity of MRI-detected OA features in a cohort of subjects with knee pain. Participants were 169 subjects with chronic knee pain who had 3 T MRI of both knees using the same protocol as in the Osteoarthritis Initiative. Knees were read for cartilage damage, bone marrow lesions (BMLs), and meniscal damage according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. Chi(2) tests were used to compare the proportion of knees with unilateral tissue pathology to the proportion what would be expected if both knees were independent. We further used percent agreement and linear weighted kappa statistics to describe agreement of cartilage damage and BMLs in the same articular plates. 51.2% of participants were men, mean age was 52.1 (±6.2), mean BMI was 29.0 kg/m(2) (±4.1). All plates showed a significant higher degree of symmetricity for cartilage damage as evidenced by weighted kappas ranging from 0.32 to 0.59. For BMLs the degree of symmetricity was higher for the patella, trochlea, medial tibia, lateral femur, and medial femur; for meniscal damage the degree of unilaterality was lower for all medial meniscal subregions but not all lateral. Kappas ranged between 0.52 and 0.68 for cartilage and 0.30 and 0.55 for BMLs for the four subregions with highest agreement. A higher degree of symmetricity of tissue damage than expected by chance was observed in this cohort of subjects with knee pain.

Consistent delayed unilateral neuronal death after modified transient focal cerebral ischemia in mice that mimics neuronal injury after transient global cerebral ischemia.

Numerous studies have attempted to reveal the pathophysiology of ischemic neuronal injury using a representative transient global cerebral ischemia (tGCI) model in rodents; however, most of them have used gerbil or rat models. Recent advances in transgene and gene-knockout technology have enabled the precise molecular mechanisms of ischemic brain injury to be investigated. Because the predominant species for the study of genetic mutations is the mouse, a representative mouse model of tGCI is of particular importance. However, simple mouse models of tGCI are less reproducible; therefore, a more complex process or longer duration of ischemia, which causes a high mortality rate, has been used in previous tGCI models in mice. In this study, the authors aimed to overcome these problems and attempted to produce consistent unilateral delayed hippocampal CA1 neuronal death in mice. C57BL/6 mice were subjected to short-term unilateral cerebral ischemia using a 4-mm silicone-coated intraluminal suture to obstruct the origin of the posterior cerebral artery (PCA), and regional cerebral blood flow (rCBF) of the PCA territory was measured using laser speckle flowmetry. The mice were randomly assigned to groups of different ischemic durations and histologically evaluated at different time points after ischemia. The survival rate and neurological score of the group that experienced 15 minutes of ischemia were also evaluated. Consistent neuronal death was observed in the medial CA1 subregion 4 days after 15 minutes of ischemia in the group of mice with a reduction in rCBF of < 65% in the PCA territory during ischemia. Morphologically degenerated cells were mostly positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and cleaved caspase 3 staining 4 days after ischemia. The survival rates of the mice 24 hours (n = 24), 4 days (n = 15), and 7 days (n = 7) after being subjected to 15 minutes of ischemia were 95.8%, 100%, and 100%, respectively, and the mice had slight motor deficits. The authors established a model of delayed unilateral hippocampal neuronal death in C57BL/6 mice by inducing ischemia in the PCA territory using an intraluminal suture method and established inclusion criteria for PCAterritory rCBF monitored by laser speckle flowmetry. This model may be useful for investigating the precise molecular mechanisms of ischemic brain injury.

Influence of motivation on control hierarchy in the human frontal cortex.

The frontal cortex mediates cognitive control and motivation to shape human behavior. It is generally observed that medial frontal areas are involved in motivational aspects of behavior, whereas lateral frontal regions are involved in cognitive control. Recent models of cognitive control suggest a rostro-caudal gradient in lateral frontal regions, such that progressively more rostral (anterior) regions process more complex aspects of cognitive control. How motivation influences such a control hierarchy is still under debate. Although some researchers argue that both systems work in parallel, others argue in favor of an interaction between motivation and cognitive control. In the latter case it is yet unclear how motivation would affect the different levels of the control hierarchy. This was investigated in the present functional MRI study applying different levels of cognitive control under different motivational states (low vs high reward anticipation). Three levels of cognitive control were tested by varying rule complexity: stimulus-response mapping (low-level), flexible task updating (mid-level), and sustained cue-task associations (high-level). We found an interaction between levels of cognitive control and motivation in medial and lateral frontal subregions. Specifically, flexible updating (mid-level of control) showed the strongest beneficial effect of reward and only this level exhibited functional coupling between dopamine-rich midbrain regions and the lateral frontal cortex. These findings suggest that motivation differentially affects the levels of a control hierarchy, influencing recruitment of frontal cortical control regions depending on specific task demands.

Activation of the mouse primary visual cortex by medial prefrontal subregion stimulation is not mediated by cholinergic basalo-cortical projections.

The medial prefrontal cortex (mPFC) exerts top-down control of primary visual cortex (V1) activity. As there is no direct neuronal projection from mPFC to V1, this functional connection may use an indirect route, i.e., via basalo-cortical cholinergic projections. The cholinergic projections to V1 originate from neurons in the horizontal limb of the diagonal band of Broca (HDB), which receive neuronal projections from the ventral part of the mPFC, composed of prelimbic (PrL) and infralimbic cortices (IL). Therefore, the objective of this study was to determine whether electrical stimulation of mice mPFC subregions activate (1) V1 neurons; and (2) HDB cholinergic neurons, suggesting that the HDB serves as a relay point in the mPFC-V1 interaction. Neuronal activation was quantified using c-Fos immunocytochemistry or thallium autometallography for each V1 layer using automated particle analysis tools and optical density measurement. Stimulation of IL and PrL induced significantly higher c-Fos expression or thallium labeling in layers II/III and V of V1 in the stimulated hemisphere only. A HDB cholinergic neuron-specific lesion by saporin administration reduced IL-induced c-Fos expression in layers II/III of V1 but not in layer V. However, there was no c-Fos expression or thallium labeling in the HDB neurons, suggesting that this area was not activated by IL stimulation. Stimulation of another mPFC subarea, the anterior cingulate cortex (AC), which is involved in attention and receives input from V1, activated neither V1 nor HDB. The present results indicate that IL and PrL, but not AC, stimulation activates V1 with the minor involvement of the HDB cholinergic projections. These results suggest a functional link between the ventral mPFC and V1, but this function is only marginally supported by HDB cholinergic neurons and may involve other brain regions.

Differential roles of medial prefrontal subregions in the regulation of drug seeking

The prefrontal cortex plays an important role in shaping cognition and behavior. Many studies have shown that medial prefrontal cortex (mPFC) plays a key role in seeking, extinction, and reinstatement of cocaine seeking in rodent models of relapse. Subregions of mPFC appear to play distinct roles in these behaviors, such that the prelimbic cortex (PL) is proposed to drive cocaine seeking and the infralimbic cortex (IL) is proposed to suppress cocaine seeking after extinction. This dichotomy of mPFC function may be a general attribute, as similar dorsal–ventral distinctions exist for expression vs. extinction of fear conditioning. However, other results indicate that the role of mPFC neurons in reward processing is more complex than a simple PL-seek vs. IL-extinguish dichotomy. Both PL and IL have been shown to drive and inhibit drug seeking (and other types of behaviors) depending on a range of factors including the behavioral context, the drug-history of the animal, and the type of drug investigated. This heterogeneity of findings may reflect multiple subcircuits within each of these PFC areas supporting unique functions. It may also reflect the fact that the mPFC plays a multifaceted role in shaping cognition and behavior, including those overlapping with cocaine seeking and extinction. Here we discuss research leading to the hypothesis that dorsal and ventral mPFC differentially control drug seeking and extinction. We also present recent results calling the absolute nature of a PL vs. IL dichotomy into question. Finally, we consider alternate functions for mPFC that correspond less to response execution and inhibition and instead incorporate the complex cognitive behavior for which the mPFC is broadly appreciated.This article is part of a Special Issue entitled Addiction circuits.

Oxytocin microinjected into the central amygdaloid nuclei exerts anti-aggressive effects in male rats

We recently demonstrated that acute and chronic intracerebroventricular enhancement of brain OXT levels induces potent anti-aggressive and pro-social explorative effects during social challenges. However, the exact anatomical location in the brain where OXT exerts its action is still elusive. In the present study, we targeted two critical brain areas, i.e. the central amygdala (CeA) and the dorsal raphe (DR), both containing high levels of OXT receptors (OXTRs) and constituting important nodes of the neural circuitry related to aggression. Behavioral effects of local micro-infusion of OXT and OXTR antagonist, L368.899, (alone and combined) were evaluated in resident male rats during confrontations with an unfamiliar male intruder. Our results show that OXT microinjected into the CeA markedly reduced resident's offensive behavior and facilitated social exploration, without affecting other non-aggressive behaviors. The receptor specificity of the behavioral effects was verified when a micro-infusion of a selective OXTR antagonist nullified the changes. Pharmacological blockade of CeA OXTRs per se was without clear behavioral effects suggesting that endogenous OXT within the CeA does not play a major inhibitory role on offensiveness. Anatomical specificity was also supported by the absence of relevant behavioral effects when OXT was microinjected into more medial sub-regions of the amygdala. Likewise, within the DR neither OXT nor OXTR exerted significant effects on offensive aggression, while microinjection of the 5-HT1A autoreceptor agonist in this region significantly suppressed aggression.In conclusion, our results point at the CeA as an important brain site of action for the anti-aggressive and pro-social explorative effects induced by exogenous enhancement of brain OXT levels.

Frontostriatal systems comprising connections between ventral medial prefrontal cortex and nucleus accumbens subregions differentially regulate motor impulse control in rats.

Deficits in impulse control are prevalent in several neuropsychiatric disorders that are based on impaired frontostriatal communication. The ventral medial prefrontal cortex (vmPFC) and the nucleus accumbens (NAc) are key substrates of impulse control in rats. The NAc core and shell are considered to be differentially involved suggesting a functional distinction between the connections of the vmPFC and particular NAc subregions concerning impulse control. In the present study, simultaneous inactivation of the rats' vmPFC and NAc core or shell by contralateral microinfusion of the GABAA receptor agonist muscimol was used to investigate their relevance for impulse control in the five-choice serial reaction time task (5-CSRTT). Disconnection of the vmPFC and NAc shell produced specific impairments in inhibitory control, indicated by significantly increased premature responding and an enhanced number of time-out responses, closely resembling the effects of bilateral inactivation of either the vmPFC or NAc shell previously reported using the same task. In contrast, disconnection of the vmPFC and NAc core only slightly increased the rate of omissions and latency of reward collection indicating attentional and motivational deficits. Our results extend previous findings indicating the functional specialisation of frontostriatal networks and show a differential contribution of specific vmPFC-NAc connections to behavioural control depending on the NAc subregion. We conclude that the regulation of impulse control in rats requires an intact connection between the vmPFC and the NAc shell, while the vmPFC-NAc core projection seems to be of minor importance.

Parcellation of the human orbitofrontal cortex based on gray matter volume covariance.

The human orbitofrontal cortex (OFC) is an enigmatic brain region that cannot be parcellated reliably using diffusional and functional magnetic resonance imaging (fMRI) because there is signal dropout that results from an inherent defect in imaging techniques. We hypothesise that the OFC can be reliably parcellated into subregions based on gray matter volume (GMV) covariance patterns that are derived from artefact-free structural images. A total of 321 healthy young subjects were examined by high-resolution structural MRI. The OFC was parcellated into subregions-based GMV covariance patterns; and then sex and laterality differences in GMV covariance pattern of each OFC subregion were compared. The human OFC was parcellated into the anterior (OFCa), medial (OFCm), posterior (OFCp), intermediate (OFCi), and lateral (OFCl) subregions. This parcellation scheme was validated by the same analyses of the left OFC and the bilateral OFCs in male and female subjects. Both visual observation and quantitative comparisons indicated a unique GMV covariance pattern for each OFC subregion. These OFC subregions mainly covaried with the prefrontal and temporal cortices, cingulate cortex and amygdala. In addition, GMV correlations of most OFC subregions were similar across sex and laterality except for significant laterality difference in the OFCl. The right OFCl had stronger GMV correlation with the right inferior frontal cortex. Using high-resolution structural images, we established a reliable parcellation scheme for the human OFC, which may provide an in vivo guide for subregion-level studies of this region and improve our understanding of the human OFC at subregional levels.

Olfactory tubercle neurons exhibit slow-phasic firing patterns during cocaine self-administration

Olfactory tubercle neurons exhibit slow-phasic firing patterns during cocaine self-administration

MRI T2 mapping of the asymptomatic supraspinatus tendon by age and imaging plane using clinically relevant subregions

PurposeDiagnosis of partial rotator cuff tears and tendonopathy using conventional MRI has proven variable. Quantitative T2 mapping may have application for assessing rotator cuff health. In order to evaluate the usefulness of T2 mapping for the rotator cuff, methods must be refined for mapping the supraspinatus tendon, and normative T2 values must first be acquired. Materials and methodsThis study was IRB approved. Thirty asymptomatic volunteers (age: 18–62) were evaluated with sagittal and coronal T2 mapping sequences. Manual segmentation of tendon and muscle as a unit and tendon alone was performed twice by two independent raters. Segmentations were divided into medial, middle and lateral subregions and mean T2 values calculated. ResultsAnatomic comparison of mean T2 values illustrated highest values in the medial region, lowest values in the lateral region, and intermediate values for the middle region upon coronal segmentation (p<0.001). In sagittal segmentations, there were higher values in the medial region and no significant differences between the lateral and middle subregions. No significant differences were found with comparison across age groups. Inter and intra-rater segmentation repeatability was excellent, with coefficients ranging from 0.85 to 0.99. ConclusionT2 mapping illustrated anatomic variation along the supraspinatus muscle-tendon unit with low standard deviations and excellent repeatability, suggesting that changes in structure due to degeneration or changes associated with healing after repair may be detectable.

Activity in prelimbic cortex subserves fear memory reconsolidation over time

The prelimbic cortex has been implicated in the consolidation of previously learned fear. Herein, we report that temporarily inactivating this medial prefrontal cortex subregion with the GABAA agonist muscimol (4.0 nmol in 0.2 μL per hemisphere) was able to equally disrupt 1-, 7-, and 21-d-old contextual fear memories after their brief retrieval in rats. In all cases, this effect was prevented when memory reactivation was omitted. These results indicate that recent and remote fear memories are susceptible to reconsolidation blockade induced by prelimbic cortex inactivation. It was also demonstrated that the disrupting effect of prelimbic cortex inactivation on fear memory persisted over 11 d, and did not show extinction-related features, such as reinstatement. Infusing the same dose and volume of muscimol bilaterally into the infralimbic cortex after brief retrieval/reactivation of the fear memory did not disrupt it, as seen in prelimbic cortex-inactivated animals. The expression of Zif268/Egr1, the product of an immediate early gene related to memory reconsolidation, was also less pronounced in the infralimbic cortex than in prelimbic cortex following memory retrieval/reactivation. Altogether, the present findings highlight that activity in the prelimbic cortex may reestablish reactivated aversive memories and, therefore, contribute to their maintenance over time.

T1rho MRI of menisci in patients with osteoarthritis at 3 Tesla: A preliminary study

To compare and assess subregional, compartmental, and whole T1rho values of menisci in patients with doubtful-minimal (Kellgren-Lawrence [KL] grade 1-2) as compared to moderate-severe (KL3-4) osteoarthritis (OA) and healthy controls at 3 Tesla (T). Forty-six subjects were included in the study and subdivided into three subgroups: 16 healthy controls (4 females, 12 males; mean age = 34.4 ± 10.2 years; age range, 24-63 years), 20 patients with doubtful-minimal (KL1-2) OA (9 females, 11 males; mean age = 61.9 ± 10.8 years; age range, 40-80 years), and 10 patients with moderate-severe (KL3-4) OA (4 females, 6 males; mean age = 71.1 ± 9.6 years; age range, 58-89 years). All subjects were evaluated on a 3T MR scanner using a spin-lock-based three-dimensional GRE sequence for T1rho mapping. Clinical proton density (PD)-weighted fast spin echoes (FSE) images in the sagittal (without fat saturation), axial, and coronal (fat-saturated) planes were acquired for cartilage Whole-Organ MR Imaging Score (WORMS) grading. Analysis of covariance was performed to determine whether there were any statistically significant differences between subregional, compartmental, and whole T1rho values of meniscus among healthy controls, OA patients with KL1-2 and with KL3-4. Lateral anterior (median ± interquartile range: 26 ± 3 ms) and medial posterior (29 ± 6 ms) meniscus subregions in healthy controls had significantly lower T1rho values (P < 0.05) than the corresponding meniscus subregions in both KL1-2 (29 ± 7 ms and 35 ± 8 ms, respectively) and KL3-4 (30 ± 12 ms and 40 ± 13 ms, respectively) OA subjects. Significantly lower meniscus T1rho values (P < 0.05) were also identified in the medial compartment in healthy controls (28 ± 5 ms) relative to both KL1-2 OA subjects and KL3-4 OA subjects (32 ± 7 ms and 37 ± 7 ms, respectively). The entire meniscus T1rho values in healthy controls (28 ± 4 ms) were significantly lower than those of both KL1-2 and KL3-4 OA subjects (33 ± 6 ms and 34 ± 6 ms, respectively). Significant elevations of T1rho values in specific regions of menisci in both KL1-2 and KL3-4 OA patients indicate that T1rho mapping may be sensitive to meniscus degeneration. The preliminary results suggest that damage in the medial posterior subregion and medial compartment of menisci may possibly be associated with osteoarthritis.

Pre-radiographic osteoarthritic changes are highly prevalent in the medial patella and medial posterior femur in older persons: Framingham OA study

To determine which subregions of the knee joint have a high prevalence of pre-radiographic osteoarthritic changes, i.e., cartilage damage and osteophytes that can only be detected by magnetic resonance imaging (MRI), in radiographically normal knees. Institutional Review Board approval and written informed consent from all participants was obtained. Data was collected from a community cohort in Framingham, MA, involving people aged 50-79. Participants underwent weight-bearing posteroanterior and lateral knee radiography with the fixed-flexion protocol, and 1.5 T MRI. Knees without radiographic osteoarthritis (Kellgren Lawrence grade 0 for the tibiofemoral joint and absence of any osteophytes or joint space narrowing in the patellofemoral joint) were included. The knee joint was divided into 14 subregions for cartilage and 16 subregions for osteophytes, and prevalence and severity of cartilage damage (grade 0-6) and osteophytes (grade 0-7) were semiquantitatively assessed using the Whole Organ Magnetic Resonance Imaging Score (WORMS). The mean age of 696 participants was 62.3 ± 8.4 years, and the mean body mass index was 27.9 ± 5.1 kg/m2. Women comprised 55.2% of the study sample (384/696). Prevalence of cartilage damage (grade ≥2) was 47.7% (332/696) in the medial patellar and 29.9% (208/696) in patellar lateral (PL) subregions, and 24.0% (167/696) in femoral medial anterior (FMA) and 26.5% (184/696) in femoral medial central (FMC) subregions. Prevalence of osteophytes (grade ≥2) was highest at 60.8% (423/696) in the medial femoral posterior subregion, followed by 34.0% (237/696) in PL and 24.6% (171/696) in patellar medial (PM) subregions. For all other subregions, prevalence of these lesions was lower than the aforementioned percentages. MRI-detected cartilage damage and osteophytes are highly prevalent in the medial patellofemoral and medial posterior tibiofemoral joints in radiographically normal knees in persons aged 50-79.

Deep brain stimulation of the nucleus accumbens shell attenuates cocaine reinstatement through local and antidromic activation.

Accumbal deep brain stimulation (DBS) is a promising therapeutic modality for the treatment of addiction. Here, we demonstrate that DBS in the nucleus accumbens shell, but not the core, attenuates cocaine priming-induced reinstatement of drug seeking, an animal model of relapse, in male Sprague Dawley rats. Next, we compared DBS of the shell with pharmacological inactivation. Results indicated that inactivation using reagents that influenced (lidocaine) or spared (GABA receptor agonists) fibers of passage blocked cocaine reinstatement when administered into the core but not the shell. It seems unlikely, therefore, that intrashell DBS influences cocaine reinstatement by inactivating this nucleus or the fibers coursing through it. To examine potential circuit-wide changes, c-Fos immunohistochemistry was used to examine neuronal activation following DBS of the nucleus accumbens shell. Intrashell DBS increased c-Fos induction at the site of stimulation as well as in the infralimbic cortex, but had no effect on the dorsal striatum, prelimbic cortex, or ventral pallidum. Recent evidence indicates that accumbens DBS antidromically stimulates axon terminals, which ultimately activates GABAergic interneurons in cortical areas that send afferents to the shell. To test this hypothesis, GABA receptor agonists (baclofen/muscimol) were microinjected into the anterior cingulate, and prelimbic or infralimbic cortices before cocaine reinstatement. Pharmacological inactivation of all three medial prefrontal cortical subregions attenuated the reinstatement of cocaine seeking. These results are consistent with DBS of the accumbens shell attenuating cocaine reinstatement via local activation and/or activation of GABAergic interneurons in the medial prefrontal cortex via antidromic stimulation of cortico-accumbal afferents.

Connectivity-Based Parcellation of the Human Temporal Pole Using Diffusion Tensor Imaging

The temporal pole (TP) is an association cortex capable of multisensory integration and participates in various high-order cognitive functions. However, an accepted parcellation of the human TP and its connectivity patterns have not yet been well established. Here, we sought to present a scheme for the parcellation of human TP based on anatomical connectivity and to reveal its subregional connectivity patterns. Three distinct subregions with characteristic fiber pathways were identified, including the dorsal (TAr), the medial (TGm), and lateral (TGl) subregions, which are located ventrally. According to the connectivity patterns, a dorsal/ventral sensory segregation of auditory and visual processing and the medial TGm involved in the olfactory processing were observed. Combined with the complementary resting-state functional connectivity analysis, the connections of the TGm with the orbitofrontal cortex and other emotion-related areas, the TGl connections with the MPFC and major default mode network regions, and the TAr connections with the perisylvian language areas were observed. To the best of our knowledge, the present study represents the first attempt to parcel the human TP based on its anatomical connectivity features, which may help to improve our understanding of its connectional anatomy and to extend the available knowledge in TP-related clinical research.