Association of Normal vs Abnormal Meary Angle With Hindfoot Malalignment and First Metatarsal Rotation: A Short Report.

BACKGROUND: Recent work has reported a significant association between first metatarsal (M1) rotation and hindfoot alignment, with the finding of a moderate association between the calcaneal moment arm (CMA) and 2 M1 pronation angular measures: Saltzman (r = 0.641, P < .01) and Kim (r = 0.615, P < .01). The aim of the current post hoc investigation was to determine if this association is related with Meary angle. METHODS: We reanalyzed previously published data set separating patients into 2 groups: (1) those with normal Meary angle (n = 128) and (2) those with abnormal Meary angle (n = 147). Hindfoot alignment and M1 rotation were measured on weightbearing computed tomography. Statistical analyses were performed to evaluate for association between these variables among the groups. RESULTS: The correlation between CMA and M1 rotation of the entire cohort was r = 0.577 (Saltzman ankle) and r = 0.540 (Kim angle). For the subset with a normal Meary angle, this association was negligible (Saltzman and Kim angles, r = 0.194 and 0.240, respectively). Conversely, for the abnormal Meary angle subset, the association was substantial (Saltzman and Kim angles, r = 0.733 and 0.675, respectively). CONCLUSION: Patients presenting with an abnormal Meary angle and hindfoot deformity have a high likelihood of manifesting a proportionate degree of M1 rotation. LEVEL OF EVIDENCE: Level III, Retrospective Cohort Study.

Association Between Hindfoot Alignment and First Metatarsal Rotation.

BACKGROUND: The association between forefoot and hindfoot position for planus and cavus feet is fundamental to the treatment of these deformities. However, no studies have evaluated the association between hindfoot alignment and first metatarsal (M1) axial rotation. Understanding this possible relationship may help to understand the deformity and improve patient care. The purpose of this study is to determine a correlation between hindfoot alignment and metatarsal rotation as assessed by weightbearing computed tomography (WBCT). METHODS: Patients who underwent weightbearing plain radiography (WBPR) and WBCT between 2015 and 2018 were evaluated. Hindfoot alignment was measured with the calcaneal moment arm (CMA). M1 rotation was measured using the Kim and Saltzman angles. Patient subgroups were created according to the severity of valgus/varus hindfoot alignment. Statistical analyses were performed to evaluate for association between variables. RESULTS: Among the 196 patient feet included in the study, the average CMA was 6.0 ± 16.2 mm. The average Kim and Saltzman angles were 7.7 ± 12.9 degrees and 2.8 ± 13.1 degrees, respectively. The average Meary angle was 182.0 ± 11.9 degrees. A moderately strong association was found between the CMA and the Saltzman (r = 0.641, P < .01) and Kim angles (r = 0.615, P < .01). Hindfoot valgus was associated with M1 pronation and hindfoot varus with M1 supination. Additionally, inverse relationships between the Meary angle and the Saltzman (r = -0.600, P < .01) and Kim angles (r = -0.529, P < .01) were identified. CONCLUSION: In this well-defined cohort, we found substantial correlation between hindfoot alignment and M1 rotation. Hindfoot valgus was associated with M1 pronation, and hindfoot varus was associated with M1 supination. Surgeons correcting cavovarus/planovalgus deformities should be aware of this association and evaluate the need for first-ray derotation. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Percutaneous Fixation of a Fifth Metatarsal Base Fracture.

SUMMARY: Owing to a vascular watershed, zone II and III fifth metatarsal base fractures commonly progress to nonunion without operative intervention. This article and the accompanying video demonstrate the use of intramedullary screw fixation for a fifth metatarsal base fracture and review treatment decisions involved with management of these injuries.

Normative Distribution of First Metatarsal Axial Rotation.

BACKGROUND: First metatarsal (M1) axial rotation is recognized as a clinically relevant component of hallux valgus deformity. Methods to realign the M1 in 3 dimensions have been developed. One goal of these operations is to restore normal rotation of the first ray. The aim of this study is to provide estimates for the normal distribution of M1 rotation in patients without relevant anatomic pathology. METHODS: Using stringent clinical and radiographic criteria, we evaluated a set of plain radiograph and weightbearing computed tomography (WBCT) images of 62 feet from a consecutive patient database. Subjects included had normal foot alignment without bunion symptoms. M1 rotation of each foot was measured using 2 unique methods (Saltzman et al and Kim et al methods). Measurement of rotation was performed by 2 observers from coronal WBCT images. Mean values and confidence intervals (CIs) of M1 rotation were calculated for each method. Inter- and intraobserver reliability values were also reported. RESULTS: Mean M1 rotation values of 2.1 degrees (95% CI: 0.9-3.4) and 6.1 degrees (95% CI: 4.4-7.8) were identified using the Saltzman et al and Kim et al methods, respectively. Inter- and intraobserver reliability values were interpreted as excellent for both methods. CONCLUSION: In this study, we describe the natural distribution of the M1 axial rotation in subjects without bunion or other identifiable bony foot deformities. This information should provide a normative reference for surgeons correcting rotational issues of the first metatarsal. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Clinical Outcomes and Quality of Literature Addressing Glenohumeral Internal Rotation Deficit: A Systematic Review.

BACKGROUND: Glenohumeral internal rotation deficit (GIRD) can negatively impact shoulder function particularly in the throwing athlete. QUESTIONS/PURPOSE: This study aimed to systematically evaluate recent trends in clinical outcomes and quality of published evidence pertaining to GIRD. METHODS: A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, MEDLINE, PubMed Central, and Embase were searched from January 1, 2011, through April 23, 2017, for all articles evaluating GIRD. Two reviewers independently screened articles for eligibility and extracted data for analysis. RESULTS: Eighty-two articles were included in the final review. In general, the overall number of articles published increased over time. Two-thirds of all studies were conducted in the USA. Seventy-eight percent (N = 64) of included studies were level-III to level-V evidence, with no level-I study performed during the study period. Eighty-five percent of studies were either epidemiologic, review, or imaging articles, and only 12% were clinical studies. Significant variability in the clinical definition of GIRD was identified. All studies evaluating non-operative management of GIRD demonstrated significant improvements in internal rotation of the affected extremity. CONCLUSION: Current trends in GIRD-related literature demonstrate limited focus on clinical, therapeutic, or patient-reported outcomes and mostly consist of low-level evidence. There is a lack of consensus in the literature on what clinically constitutes GIRD.

Ankle Arthrodesis Through an Anterior Approach.

Ankle arthritis occurs primarily because of trauma and has a huge impact on patient's quality of life. Ankle arthrodesis is indicated for patients with end-stage ankle arthritis who fail conservative management. High rates of fusion can be achieved through an anterior approach. This video demonstrates an ankle arthrodesis using an anterior approach to the ankle in a patient with posttraumatic ankle arthritis.

Current Workload Recommendations in Baseball Pitchers: A Systematic Review.

BACKGROUND: Several recommendations have been made regarding pitch counts and workload for baseball players of different levels, including Little League, high school, collegiate, and professional baseball. However, little consensus is found in the literature regarding the scientific basis for many of these recommendations. PURPOSE: The primary purpose of this study was to summarize the evidence regarding immediate and long-term musculoskeletal responses to increasing pitching workload in baseball pitchers of all levels. A secondary purpose of this review was to evaluate the extent to which workload influences injury and/or performance in baseball pitchers. STUDY DESIGN: Systematic review. METHODS: We performed a systematic search in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies addressing physiologic and/or pathologic musculoskeletal changes in response to a quantifiable pitching workload. We included studies examining the effects of pitching workload on performance, injury rate, and musculoskeletal changes in Little League, high school, collegiate, and professional baseball players. RESULTS: We identified 28 studies that met our inclusion and exclusion criteria: 16 studies regarding Little League and high school pitchers and 12 studies regarding collegiate and professional pitchers. The current evidence presented suggests that increased pitching workload may be associated with an increased risk of pain, injury, and arm fatigue in Little League and high school pitchers. However, little consensus was found in the literature regarding the association between pitching workload and physiologic or pathologic changes in collegiate and professional pitchers. CONCLUSION: Evidence, although limited, suggests the use of pitch counts to decrease injury rates and pain in Little League and high school baseball pitchers. However, further research must be performed to determine the appropriate number of pitches (or throws) for players of different ages. This systematic review reported conflicting evidence regarding the use of pitch counts in college and professional baseball. Future high-quality research is required to determine the role, if any, of pitch counts for collegiate and professional pitchers.

Whole-Body Cryotherapy in Sports Medicine.

Cryotherapy has gained popularity among athletes across many sports. The main goals of cryotherapy, and specifically whole-body cryotherapy, are for injury prevention and counteracting negative inflammatory symptoms following athletic performance in hopes of improving recovery.

The Overhead Athletes Shoulder.

The overhead athlete places tremendous forces across the shoulder which result in necessary adaptive, but also potentially pathologic structural change. In this chapter we aim to review the biomechanics of throwing, the mechanisms of injury with overhead sports, the detailed history, and physical examination in this population, and concluding with specific diagnoses and the various treatment options.

A Clinical Comparison of Linear- and Surface Area-Based Methods of Measuring Glenoid Bone Loss.

BACKGROUND: The purpose of this study was to determine whether linear-based measurement significantly overestimates glenoid bone loss in comparison with surface area-based measurement in patients with recurrent anterior shoulder instability and glenoid bone loss. HYPOTHESIS: Linear-based measurement will significantly overestimate glenoid bone loss in comparison with surface area-based measurement in patients with anterior shoulder instability and glenoid bone loss. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: Thirty patients with anterior shoulder instability underwent preoperative bilateral shoulder computed tomography (CT) scans. Three-dimensional CT (3D-CT) reconstruction with humeral head subtraction was performed to obtain an en face view of the 3D-CT glenoid. Glenoid bone loss was measured with the surface area and linear methods of measurement. Statistical analysis was performed with a paired 2-tailed t test. RESULTS: Twenty-eight patients (5 female and 23 male; mean age, 25.1 years; age range, 15-58 years) were included in the study; 17 patients underwent a glenoid augmentation procedure, and 11 underwent arthroscopic Bankart repair. The mean percentage glenoid bone loss calculated with the surface area and linear methods was 12.8% ± 8.0% and 17.5% ± 9.7% ( P < .0001), respectively. For the 17 patients who underwent glenoid augmentation, mean percentage bone loss with the surface area and linear methods was 16.6% ± 7.9% and 23.0% ± 8.0% ( P < .0001), respectively. CONCLUSION: Linear measurement of glenoid bone loss significantly overestimates bone loss compared with surface area measurement in patients with anterior glenoid bony defects. These results indicate that these different methods cannot be used interchangeably and cannot be used with the same critical thresholds for glenoid bone loss.

Return to Play After Multiligament Knee Injuries in National Football League Athletes.

BACKGROUND:: Return to play (RTP) of National Football League (NFL) athletes after isolated anterior cruciate ligament (ACL) tears has been reported. However, no studies have reported on RTP of NFL athletes after multiligament knee injuries. HYPOTHESES:: NFL athletes with multiligament knee injuries have lower RTP rates and longer recoveries than athletes with isolated ACL tears. Second, athletes with ACL and medial collateral ligament (MCL) injuries will have higher RTP rates and shorter time to RTP than athletes with an ACL tear and posterolateral corner involvement. STUDY DESIGN:: Retrospective cohort study. LEVEL OF EVIDENCE:: Level 4. METHODS:: Publicly available NFL injury data were reviewed for all multiligament knee injuries incurred between 2000 and 2016 with RTP information. Athletes were excluded if RTP was limited for reasons unrelated to the injury. Extracted data included type of injury, RTP, time to RTP (days), number and percentage of games played, and performance. RESULTS:: A total of 50 NFL athletes with multiligament knee injuries met inclusion and exclusion criteria. The overall RTP rate was 64.0%. Athletes with ACL/MCL tears had an RTP rate of 70.8%, whereas athletes with ACL and posterior collateral ligament/lateral collateral ligament (PCL/LCL) tears had an RTP rate of 55.6% ( P = 0.26). Mean time to RTP for all 50 athletes was 388.71 ± 198.52 days. The mean time to RTP for athletes with ACL/MCL injuries was 305.1 ± 58.9 days, compared with 459.2 ± 245.1 days ( P = 0.004) and 609.3 ± 183.1 days ( P < 0.0001) for those with combined ACL and PCL/LCL injuries and frank knee dislocations, respectively. Athletes with ACL/MCL injuries were more likely to return to prior performance level (43.5%) than those with ACL and PCL/LCL injuries (18.5%) ( P < 0.001). CONCLUSION:: The RTP rate for athletes with multiligament knee injuries is significantly less than the RTP rate for athletes with isolated ACL tears. In addition, athletes with ACL and MCL tears have a higher RTP rate, a significantly shorter time to RTP, and a greater likelihood of returning to prior performance than athletes with ACL and PCL/LCL tears. CLINICAL RELEVANCE:: Multiligament knee injuries significantly affect the ability of a football player to return to sport. ACL and MCL tears are associated with better RTP prognosis compared with ACL and PCL/LCL tears.

Humeral Retroversion and Capsule Thickening in the Overhead Throwing Athlete: A Systematic Review.

PURPOSE: To investigate the humeral and soft-tissue adaptations, including humeral retroversion, range of motion, and posterior capsule changes, in overhead throwing athletes. METHODS: We performed a systematic review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Embase were searched from January 1, 2011, through April 23, 2017, by 2 reviewers independently and in duplicate. The methodologic quality of all included articles was assessed using the Methodological Index for Non-randomized Studies criteria. Interobserver agreement for assessments of eligibility was calculated with the Cohen κ statistic. Descriptive statistics and raw counts were used to summarize data. RESULTS: We identified 14 studies (6 Level IV and 8 Level III) including 1,152 overhead throwing athletes. The mean age of the included athletes was 18.37 years (standard deviation, 1.52 years), with 59% of the athletes being pitchers and 41% being position players. Significantly greater humeral retroversion was found across all studies evaluating bony morphology in the dominant arm of overhead throwing athletes (range of mean differences, 9.6°-25.8°). Each of these studies also found decreased internal rotation in the dominant arm (range of mean internal rotation differences, -28° to -7.8°). Five studies found a significant negative correlation between the difference in humeral retroversion between the 2 arms and the difference in internal rotation (range of Pearson correlation coefficients, -0.56 to -0.35). Soft-tissue adaptations were assessed in 5 studies, with 4 identifying significantly thicker posterior capsules and 2 identifying significantly stiffer posterior capsules (P < .05). CONCLUSIONS: Overhead throwing athletes consistently show several distinct changes in their dominant shoulder. These include increased humeral retroversion and the presence of a thickened and stiff posterior capsule. Concomitantly, there is often reduced internal rotation and increased external rotation of the dominant arm. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and IV studies.

The Effect of Capsulectomy on Hip Joint Biomechanics.

BACKGROUND: Capsulectomy is performed during hip arthroscopic surgery in young adult patients with hip pain to improve intraoperative visualization. The stability of the hip joint after anterior capsulectomy is relatively unknown. PURPOSE: To evaluate anterior hip stability in capsular sectioned states with a labral injury to test whether the load required for anterior translation would decrease with greater capsular injuries. STUDY DESIGN: Controlled laboratory study. METHODS: Sixteen hips from 8 of 10 human cadaveric pelvises (mean age, 54.25 years) were prepared/mounted onto a custom-built fixture and tested in 5 states: intact capsule, intact labrum (all intact); sutured capsule, intact labrum (sutured intact); sutured capsule, 1-cm partial labrectomy (sutured labrectomy); partial capsulectomy, 1-cm partial labrectomy (partial capsulectomy); and total capsulectomy, 1-cm partial labrectomy (total capsulectomy). Each hip was tested in a neutral position with a 20-N compressive force. The load at 12 mm of anterior translation was recorded for each state after 2 preconditioning trials. RESULTS: A repeated-measures analysis of variance with Bonferroni adjustment showed no difference between the all-intact versus sutured-intact states and demonstrated no significant difference between the sutured-intact and sutured-labrectomy states. There were significant differences between the sutured-labrectomy and partial capsulectomy (P = .01), sutured-labrectomy and total capsulectomy (P < .001), and partial capsulectomy and total capsulectomy (P = .04) states. CONCLUSION: The findings demonstrate that the capsule/labrum plays an important role in anterior hip stability and that the iliofemoral ligament is crucial for preventing anterior translation in labral-injured states. In addition, the ischiofemoral and pubofemoral ligaments provide resistance to anterior translation in iliofemoral- and labral-deficient states. Intraoperative capsulectomy should be avoided in patients with large, irreparable labral tears to prevent postoperative anterior hip instability. CLINICAL RELEVANCE: This study quantifies the roles of the capsulolabral structures in anterior hip stability and demonstrates the importance of maintaining/repairing them during hip arthroscopic surgery.

Does Repair of a Hill-Sachs Defect Increase Stability at the Glenohumeral Joint?

BACKGROUND: The effect of osteoallograft repair of a Hill-Sachs lesion and the effect of allograft fit on glenohumeral translations in response to applied force are poorly understood. PURPOSE: To compare the impact of a 25% Hill-Sachs lesion, a perfect osteoallograft repair (PAR) of a 25% Hill-Sachs lesion, and an "imperfect" osteoallograft repair (IAR) of a 25% Hill-Sachs lesion on glenohumeral translations in response to a compressive load and either an anterior or posterior load in 3 clinically relevant arm positions. STUDY DESIGN: Controlled laboratory study. METHODS: A robotic/universal force-moment sensor testing system was used to apply joint compression (22 N) and an anterior or posterior load (44 N) to cadaveric shoulders (n = 9) with the skin and deltoid removed (intact) at 3 glenohumeral joint positions (abduction/external rotation): 0°/0°, 30°/30°, and 60°/60°. The 25% bony defect state, PAR state, and IAR state were created and the loading protocol was performed. Translational motion was measured in each position for each shoulder state. A nonparametric repeated-measures Friedman test with a Wilcoxon signed-rank post hoc test was performed to compare the biomechanical parameters (P < .05). RESULTS: Compared with the defect shoulder, the PAR shoulder had significantly less anterior translation with an anterior load in the 0°/0° (15.3 ± 8.2 vs 16.6 ± 9.0 mm, P = .008) and 30°/30° (13.6 ± 7.1 vs 14.2 ± 7.0 mm, P = .021) positions. Compared with IAR, the PAR shoulder had significantly less anterior translation with an anterior load in the 0°/0° (15.3 ± 8.2 vs 16.6 ± 9.0 mm, P = .008) and 30°/30° (13.6 ± 7.1 vs 14.4 ± 7.1 mm, P = .011) positions, and the defect shoulder had significantly less anterior translation with an anterior load in the 30°/30° (14.2 ± 7.0 vs 14.4 ± 7.0 mm, P = .038) position. CONCLUSION: PAR resulted in the least translational motion at the glenohumeral joint. The defect shoulder had significantly less translational motion at the joint compared with the IAR. An IAR resulted in the most translational motion at the glenohumeral joint. This demonstrates the biomechanical importance of performing an osteoallograft repair in which the allograft closely matches the Hill-Sachs defect and fully restores the preinjury state of the humeral head. CLINICAL RELEVANCE: This study demonstrates the importance of performing an osteoallograft repair of a Hill-Sachs defect that closely matches the preinjury state and restores normal humeral head anatomy.

The Influence of Surgical Stabilization on Glenohumeral Abduction Using 3-Dimensional Computed Tomography in Patients With Shoulder Instability.

PURPOSE: This study compared the amount of glenohumeral abduction during arm abduction in the affected and unaffected shoulders of 3 groups of patients with shoulder instability: failed surgical stabilization, successful surgical stabilization, and unstable shoulder with no prior surgical intervention. METHODS: All patients underwent bilateral shoulder computed tomography scans in 3 positions: 0° of abduction and 0° of external rotation (0-0 position), 30° of abduction and 30° of external rotation (30-30 position), and arms maximally abducted (overhead position). Three-dimensional computed tomography reconstruction was performed for both shoulders in all 3 positions. A specialized coordinate system marked specific points and directions on the humerus and glenoid of each model. These coordinates were used to calculate the glenohumeral abduction for the normal and affected sides in the 0-0, 30-30, and overhead positions. RESULTS: Thirty-nine patients with shoulder instability were included, of whom 14 had failed surgical repairs, 10 had successful surgical repairs, and 15 had unstable shoulders with no prior surgical intervention. In the overhead position, patients with failed surgical intervention had significantly less glenohumeral abduction in the failed shoulder (95.6° ± 12.7°) compared with the normal shoulder (101.5° ± 12.4°, P = .02). Patients with successfully stabilized shoulders had significantly less glenohumeral abduction in the successfully stabilized shoulder (93.6° ± 10.8°) compared with the normal shoulder (102.1° ± 12.5°, P = .03). Unstable shoulders with no prior surgical intervention (102.1° ± 10.3°) did not differ when compared with the normal shoulders (101.9° ± 10.9°, P = .95). CONCLUSIONS: Surgical intervention, regardless of its success, limits the amount of abduction at the glenohumeral joint. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Comparison of 3-Dimensional Computed Tomography-Based Measurement of Glenoid Bone Loss With Arthroscopic Defect Size Estimation in Patients With Anterior Shoulder Instability.

PURPOSE: The purpose of this study was to compare four 3-dimensional (3D) computed tomography (CT) methods of measuring glenoid bone loss with the arthroscopic estimation of glenoid bone loss. METHODS: Twenty patients with recurrent anterior shoulder instability underwent bilateral shoulder CT scans and were found to have glenoid bone loss. Arthroscopic estimation of glenoid bone loss was performed in all patients. Three-dimensional CT reconstruction was performed on the CT scans of each patient. The glenoid bone loss of each patient was measured using the surface area, Pico, ratio, and anteroposterior distance-from-bare area methods. The mean percent loss calculated with each method was compared with arthroscopy to determine the reliability of arthroscopy in the measurement of glenoid bone loss. RESULTS: The mean percent bone loss calculated with arthroscopic estimation, surface area, Pico, ratio, and anteroposterior distance-from-bare area methods was 18.13% ± 11.81%, 12.15% ± 8.50% (P = .005), 12.77% ± 8.17% (P = .002), 9.50% ± 8.74% (P < .001), and 12.44% ± 10.68% (P = .001), respectively. Repeated-measures analysis of variance showed that the 3D CT methods and arthroscopy were significantly different (F4,76 = 13.168, P = .02). The estimate using arthroscopy is 55% greater than the average of the 3D CT methods. CONCLUSIONS: Our findings suggest that arthroscopy significantly overestimates glenoid bone loss compared with CT and call into question its validity as a method of measurement. A more internally consistent and accurate method for the measurement of glenoid bone loss is necessary to appropriately diagnose and treat shoulder instability. LEVEL OF EVIDENCE: Level IV, case series.

Dysfunction and Dysconnection in Cortical-Striatal Networks during Sustained Attention: Genetic Risk for Schizophrenia or Bipolar Disorder and its Impact on Brain Network Function.

Abnormalities in the brain's attention network may represent early identifiable neurobiological impairments in individuals at increased risk for schizophrenia or bipolar disorder. Here, we provide evidence of dysfunctional regional and network function in adolescents at higher genetic risk for schizophrenia or bipolar disorder [henceforth higher risk (HGR)]. During fMRI, participants engaged in a sustained attention task with variable demands. The task alternated between attention (120 s), visual control (passive viewing; 120 s), and rest (20 s) epochs. Low and high demand attention conditions were created using the rapid presentation of two- or three-digit numbers. Subjects were required to detect repeated presentation of numbers. We demonstrate that the recruitment of cortical and striatal regions are disordered in HGR: relative to typical controls (TC), HGR showed lower recruitment of the dorsal prefrontal cortex, but higher recruitment of the superior parietal cortex. This imbalance was more dramatic in the basal ganglia. There, a group by task demand interaction was observed, such that increased attention demand led to increased engagement in TC, but disengagement in HGR. These activation studies were complemented by network analyses using dynamic causal modeling. Competing model architectures were assessed across a network of cortical-striatal regions, distinguished at a second level using random-effects Bayesian model selection. In the winning architecture, HGR were characterized by significant reductions in coupling across both frontal-striatal and frontal-parietal pathways. The effective connectivity analyses indicate emergent network dysconnection, consistent with findings in patients with schizophrenia. Emergent patterns of regional dysfunction and dysconnection in cortical-striatal pathways may provide functional biological signatures in the adolescent risk-state for psychiatric illness.

Fronto-parietal hypo-activation during working memory independent of structural abnormalities: conjoint fMRI and sMRI analyses in adolescent offspring of schizophrenia patients.

Adolescent offspring of schizophrenia patients (HR-S) are an important group in whom to study impaired brain function and structure, particularly of the frontal cortices. Studies of working memory have suggested behavioral deficits and fMRI-measured hypoactivity in fronto-parietal regions in these subjects. Independent structural MRI (sMRI) studies have suggested exaggerated frontal gray matter decline. Therefore the emergent view is that fronto-parietal deficits in function and structure characterize HR-S. However, it is unknown if fronto-parietal sub-regions in which fMRI-measured hypo-activity might be observed are precisely those regions of the cortex in which gray matter deficits are also observed. To investigate this question we conducted conjoint analyses of fronto-parietal function and structure in HR-S (n=19) and controls (n=24) with no family history of psychoses using fMRI data during a continuous working memory task (2 back), and sMRI collected in the same session. HR-S demonstrated significantly reduced BOLD activation in left dorso-lateral prefrontal cortex (BA 9/46) and bilateral parietal cortex (BA 7/40). Sub-regions of interest were created from the significant fronto-parietal functional clusters. Analyses of gray matter volume from volume-modulated gray matter segments in these clusters did not reveal significant gray matter differences between groups. The results suggest that functional impairments in adolescent HR-S can be independent of impairments in structure, suggesting that the relationship between impaired function and structure is complex. Further studies will be needed to more closely assess whether impairments in function and structure provide independent or interacting pathways of vulnerability in this population.

Inefficiently increased anterior cingulate modulation of cortical systems during working memory in young offspring of schizophrenia patients.

BACKGROUND: Children and adolescent offspring of schizophrenia patients are at increased risk for schizophrenia and are also characterized by impairments in brain structure and function. To date, few studies have investigated whether functional interactions between brain regions are intact or altered. Using an established verbal working memory paradigm with variable levels of memory load, we investigated the modulatory effect of activity in cognitive control regions of the brain (specifically the dorsal anterior cingulate cortex) on activity in core working memory regions, in particular the dorsal prefrontal cortex and the parietal lobe. METHODS: Forty four subjects participated. An n-back task with two levels of working memory load (1- and 2-back) was employed during fMRI (4 T Bruker MedSpec system). Data were processed with SPM5 and the modulatory effects of the anterior cingulate were investigated using psycho-physiological interaction (PPI). RESULTS: In spite of only subtle activation differences, and no significant differences in performance accuracy, a significant group x memory load interaction in the parietal lobe, indicated aberrantly increased modulatory inputs to this region under conditions of high working memory load in schizophrenia offspring. DISCUSSION: Increased modulatory inputs from a central control region like the anterior cingulate presumably reflect relative inefficiency in intra-cortical interactions in the vulnerable brain. This inefficiency may reflect a developmentally mediated impairment in functional brain interactions in this important vulnerable population. It is highly plausible that the resultant effect of these altered interactions is an increased vulnerability to impaired brain development, and therefore to psychiatric disorders including schizophrenia.