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Background Low grade fibromyxoid sarcoma (LGFMS) is a rare and benign mesenchymal tumor with indolent course, most commonly found in young or middle-aged men. The majority of the LGFMSs are located in the trunk and deep soft tissue of the lower extremities. They appear as well circumscribed, although not encapsulated, which often leads to incomplete surgical resection. Despite their seemingly benign appearance, these tumors have aggressive behavior with high metastatic and recurrence rates. Accurate histopathologic examination of the specimen and its immunohistochemical analysis are mandatory for a precise diagnosis. Case summary We report a case of a 38 year-old-man who presented with jaundice and upper abdominal discomfort. Multi-detector computed tomography and magnetic resonance imaging showed a large left liver tumor mass, extending to the hepatoduodenal ligament. Left hepatectomy was performed with resection and reconstruction of hepatic artery and preservation of middle hepatic vein. Histopathologic examination confirmed the tumor being a low-grade fibromyxoid sarcoma. Three and a half years after surgery, the patient died after being diagnosed with spine metastasis. Conclusion Due to poor response to all modalities of adjuvant treatment, we consider that the focus of treatment should be on surgery as the only option for curing the disease.

Background: Sac regression after Endovascular Aneurysm Repair (EVAR) of Abdominal Aortic Aneurysms (AAA) has been proposed as a marker of successful response to treatment. Several variables related to AAA morphology are reported to influence sac behavior post-EVAR yet little is known about the pre-operative [for full text, please go to the a.m. URL]

It remains difficult to predict when which patients with abdominal aortic aneurysm (AAA) will require surgery. The aim was to study the accuracy of geometric and biomechanical analysis of small AAAs to predict reaching the threshold for surgery, diameter growth rate and rupture or symptomatic aneurysm. 189 patients with AAAs of diameters 40–50 mm were included, 161 had undergone two CTAs. Geometric and biomechanical variables were used in prediction modelling. Classifications were evaluated with area under receiver operating characteristic curve (AUC) and regressions with correlation between observed and predicted growth rates. Compared with the baseline clinical diameter, geometric-biomechanical analysis improved prediction of reaching surgical threshold within four years (AUC 0.80 vs 0.85, p = 0.031) and prediction of diameter growth rate (r = 0.17 vs r = 0.38, p = 0.0031), mainly due to the addition of semiautomatic diameter measurements. There was a trend towards increased precision of volume growth rate prediction (r = 0.37 vs r = 0.45, p = 0.081). Lumen diameter and biomechanical indices were the only variables that could predict future rupture or symptomatic AAA (AUCs 0.65–0.67). Enhanced precision of diameter measurements improves the prediction of reaching the surgical threshold and diameter growth rate, while lumen diameter and biomechanical analysis predicts rupture or symptomatic AAA.

Objective: Limb graft occlusion (LGO) is a serious complication after endovascular aneurysm repair (EVAR) and while device development enables treatment of increasingly complex aortic anatomy, little is known about how endograft type affects the risk of occlusion. This observational study aimed to explore the incidence of LGO after EVAR for three major endograft systems. Methods: All patients with standard EVAR as the primary intervention for infrarenal abdominal aortic aneurysm (AAA), between January 2012 and December 2018, at five Swedish vascular surgery centres, were included in this multicentre retrospective cohort study. LGO was defined as a total limb occlusion regardless of symptoms, or a treated significant stenosis. A nested case control (NCC) design with incidence density sampling of 1:3 was used for analysis of potential per-operative and morphological risk factors. Conditional logistic regression was used to estimate multivariable odds ratios (OR) with 95% confidence intervals (CI) Results: A total of 924 patients were included. The majority were male (84%), the mean age was 76 years (+/- 7.5 SD), and median AAA diameter was 59 mm (IQR 55, 67). Patients were treated with Zenith Alpha (n = 315, ZISL limbs), Excluder (n = 152, PLC/PXC limbs), and Endurant (n = 457, ETLW/ ETEW limbs). During median follow up of 37 months (IQR 21, 62), 55 occlusions occurred (5.9%); 39 with Zenith Alpha (12.4%), one with Excluder (0.7%), and 15 with Endurant (3.3%). In the NCC analysis, the Zenith Alpha device (OR 5.31, 95% CI 1.97 - 14.3), external iliac artery (EIA) landing (OR 5.91, 95% CI 1.30 - 26.7), and EIA diameter < 10 mm (OR 4.99, 95% CI 1.46 - 16.9) were associated with an increased risk of LGO. Conclusion: Endograft device type is an independent risk factor for LGO after EVAR. Specifically, the Zenith Alpha demonstrated an increased risk of LGO compared with the Endurant and Excluder devices. In addition, a narrow EIA and landing zone in EIA are also risk factors for LGO. Funding Agencies|Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation [20180596]; Swedish Society of Medicine [SLS-174151]; Futurum Jonkoping county; Swedish Research CouncilSwedish Research CouncilEuropean Commission [12660, 20180867, 20180072]

Abdominal aortic aneurysms (AAAs) primarily affect elderly men. The effect of sex on aneurysm development has been associated with the effects of sex hormones through mechanisms that are not fully understood. The present study examined the association between the levels of sex hormones and the occurrence of AAAs in elderly men.A prospective case-control study was conducted of 452 men aged 65 years participating in screening for AAAs from 2013 to 2019. Of the 452 men, 230 had an AAA and 222 an aortic diameter of 30 mm (control group). Questionnaires and blood samples were collected and stored consecutively. The serum levels of total testosterone, estradiol, progesterone, luteinizing hormone, and sex hormone-binding globulin were analyzed using electrochemiluminescent immunoassays. Multivariable logistic regression analysis was used to assess the association between sex hormones and AAA.The median aneurysm diameter was 33 mm. Men with AAA had greater estradiol (93 pmol/L vs 84 pmol/L; P =.003) and progesterone (0.41 nmol/L vs 0.17 nmol/L; P .001) levels compared with the controls. The testosterone levels were lower in the AAA group than in the control group (13 nmol/L vs 14 nmol/L; P = .026). AAA was associated with detectable levels of progesterone (odds ratio [OR], 6.69; 95% confidence interval [CI], 3.86-11.47), smoking (OR, 5.26; 95% CI, 3.12-8.85), coronary heart disease (OR, 4.06; 95% CI, 1.92-8.58), and a body mass index25 kg/mThe observed higher estradiol and progesterone levels in men with an AAA suggest an effect of sex hormones on aneurysm development. The association between progesterone levels and the aortic diameter stresses the importance of focusing on the potential effect of this unconsidered female sex hormone on aneurysm formation.

BackgroundDisorders of gait are a very common feature of Parkinson’s Disease. We examined how deep brain stimulation of the subthalamic nucleus (STN DBS) and dopaminergic medication affect gait and more specifically its rhythmicity.ObjectivesWe accurately quantified multiple gait parameters in Parkinson’s patients during on and off stages of their treatment (levodopa or STN DBS) to compare and contrast the treatment-induced changes in gait.MethodsWe studied 11 patients with STN DBS, 15 patients on levodopa and 42 healthy controls. They all completed the MDS-UPDRS part III along with a gait assessment protocol while wearing six nine-axis inertial measurement units (lumbar, sternal, and all four extremities).ResultsBoth medication and stimulation significantly improved stride length, while medication further significantly increased gait speed. In the lower limbs, both medication and stimulation had a normalising effect on lower limb angles, significantly increasing the foot strike angle and toe-off angle.ConclusionsSTN DBS reduced the step to step variability in a range of lower limb gait parameters in PD, while antiparkinsonian medication had no significant effect. This suggests that STN stimulation, but not dopaminergic medication, has access to circuits that control gait rhythm, and that the resulting effect of stimulation on gait is beneficial. However, the results we observed for movement of the trunk and upper limbs were strikingly different to those seen in the lower limbs. We propose a hypothesis to explain why we observe these results, focusing on cholinergic pedunculopontine projections.

Objective: Predicting which abdominal aortic aneurysms (AAA) will require surgery and which may remain stable remains a challenge. We set out to evaluate whether semi-automatic diameter measurements and finite element analysis (FEA) might predict the four-year prognosis of AAAs more precisely than standard diameter measurements. Methods: From a retrospective dataset of 97 patients with aneurysm baseline diameter of 40-50 mm, 39 AAAs remained below 55 mm in diameter for four years whilst 58 expanded beyond 54 mm within four years, or were treated surgically. Standard diameters, measured by radiologists or vascular surgeons, were recorded at baseline and at follow-up. Maximal external and luminal diameters as well as total and luminal volume were semi-automatically re-measured from 3D models based on CT images. FEA, estimating the peak wall rupture index (PWRI), was subsequently performed. Further, in 94 patients from the dataset, standard diameter growth rates between baseline and follow-up were calculated. Results: Aneurysms that would require surgery within four years were identified with 100% specificity by semi-automatic diameter, n=13 (22%), luminal diameter, n=14 (24%), PWRI, n=7 (12%), and luminal volume, n=5 (8.6%). Neither standard diameter nor total volume could reach 100% specificity. AAA diameter growth rate correlated with baseline semi-automatic diameter (r=0.39, p=9.2e-5), luminal diameter (r=0.29, p=0.005) and luminal volume (r=0.23, p=0.027) but not with PWRI (r=0.17, p=0.094), total volume (r=0.16, p=0.13), nor standard diameter (r=0.14, p=0.17). Conclusion: In AAAs with small diameters, precise, semiautomatic measurement of the maximal external and luminal diameter is able to specifically identify aneurysms requiring surgery within four years.

The primary aim of this study was to evaluate the benefit of extended lymphadenectomy in pancreaticoduodenectomy (PD) and to estimate its impact on long-term survival in patients with pancreatic head carcinoma. Secondary endpoints included perioperative mortality, postoperative morbidity and predictors of survival in patients undergoing standard versus extended lymphadenectomy for pancreatic head carcinoma.From January 2007 to December 2010, 60 patients with potentially resectable pancreatic head carcinoma were operated using pylorus-preserving pancreatoduodenectomy (PPPD) at the Clinic for Digestive Surgery, Clinical Center of Serbia, Belgrade. Intraoperatively patients were randomly stratified into two groups: the first group (N1=30) underwent PPPD with standard lymphadenectomy whilst the second group (N2=30) was operated with PPPD with extended lymphadenectomy. None of the patients received adjuvant treatments.The number of retrieved lymph nodes, mean operating time and postoperative hospital stay were greater in patients with extended lymphadenectomy . Cox regression analysis showed that stage and lymph node metastasis were independent prognostic factors for survival.Extended lymphadenectomy in PPPD did not improve long-term survival in patients with resectable pancreatic head carcinoma and led to comparable and similar morbidity and mortality rates to those after standard lymphadenectomy.

Background and Purpose— The mechanisms underlying motor recovery after stroke are not fully understood. Several studies used functional MRI longitudinally to relate brain activity changes with performance gains of the upper limb after therapy, but research into training-induced recovery of lower limb function has been relatively neglected thus far. Methods— We investigated functional reorganization after 4 weeks of treadmill training with partial body weight support in 18 chronic patients (mean age, 59.9±13.5 years) with mild to moderate paresis (Motricity Index affected leg: 77.7±10.5; range, 9 to 99) and gait impairment (Functional Ambulation Category: 4.4±0.6; range, 3 to 5) due to a single subcortical ischemic stroke using repeated 3.0-T functional MRI and an ankle-dorsiflexion paradigm. Results— Walking endurance improved after training (2-minute timed walking distance: 121.5±39.0 versus pre: 105.1±38.1 m; P =0.0001). For active movement of the paretic foot versus rest, greater walking endurance correlated with increased brain activity in the bilateral primary sensorimotor cortices, the cingulate motor areas, and the caudate nuclei bilaterally and in the thalamus of the affected hemisphere. Conclusions— Despite the strong subcortical contributions to gait control, rehabilitation-associated walking improvements are associated with cortical activation changes. This is similar to findings in upper limb rehabilitation with some differences in the involved cortical areas. We observed bihemispheric activation increases with greater recovery both in cortical and subcortical regions with movement of the paretic foot. However, although the dorsal premotor cortex appears to play an important role in recovery of hand movements, evidence for the involvement of this region in lower extremity recovery was not found.

The neural substrates that enable individuals to achieve their fastest and strongest motor responses have long been enigmatic. Importantly, characterization of such activities may inform novel therapeutic strategies for patients with hypokinetic disorders, such as Parkinson's disease. Here, we ask whether the basal ganglia may play an important role, not only in the attainment of maximal motor responses under standard conditions but also in the setting of the performance enhancements known to be engendered by delivery of intense stimuli. To this end, we recorded local field potentials from deep brain stimulation electrodes implanted bilaterally in the subthalamic nuclei of 10 patients with Parkinson's disease, as they executed their fastest and strongest handgrips in response to a visual cue, which was accompanied by a brief 96-dB auditory tone on random trials. We identified a striking correlation between both theta/alpha (5-12Hz) and high-gamma/high-frequency (55-375 Hz) subthalamic nucleus activity and force measures, which explained close to 70 of interindividual variance in maximal motor responses to the visual cue alone, when patients were ON their usual dopaminergic medication. Loud auditory stimuli were found to enhance reaction time and peak rate of development of force still further, independent of whether patients were ON or OFF l-DOPA, and were associated with increases in subthalamic nucleus power over a broad gamma range. However, the contribution of this broad gamma activity to the performance enhancements observed was only modest (13). The results implicate frequency-specific subthalamic nucleus activities as substantial factors in optimizing an individual's peak motor responses at maximal effort of will, but much less so in the performance increments engendered by intense auditory stimuli. © 2012 The Author. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

We present a 19-year-old woman with severe encephalitis and raised intracranial pressure requiring decompressive craniectomy. Her clinical features were consistent with encephalitis in the context of acute primary Epstein-Barr virus (EBV) infection (infectious mononucleosis). Serology, bone marrow aspirate and PCR of blood and cerebrospinal fluid confirmed the diagnosis. She was treated with corticosteroids and aciclovir. She was critically unwell for 3 weeks, requiring artificial ventilation but eventually made a good recovery. EBV encephalitis is uncommon, making the diagnosis and decisions about clinical management challenging.

The pedunculopontine nucleus, a component of the reticular formation, is topographically organized in animal models and implicated in locomotor control. In Parkinson's disease, pedunculopontine nucleus stimulation is an emerging treatment for gait freezing. Local field potentials recorded from pedunculopontine nucleus electrodes in such patients have demonstrated oscillations in the alpha and beta frequency bands, reactive to self-paced movement. Whether these oscillations are topographically organized or relevant to locomotion is unknown. Here, we recorded local field potentials from the pedunculopontine nucleus in parkinsonian patients during rest and unconstrained walking. Relative gait speed was assessed with trunk accelerometry. Peaks of alpha power were present at rest and during gait, when they correlated with gait speed. Gait freezing was associated with attenuation of alpha activity. Beta peaks were less consistently observed across rest and gait, and did not correlate with gait speed. Alpha power was maximal in the caudal pedunculopontine nucleus region and beta power was maximal rostrally. These results indicate a topographic distribution of neuronal activity in the pedunculopontine nucleus region and concur with animal data suggesting that the caudal subregion has particular relevance to gait. Alpha synchronization, proposed to suppress 'task irrelevant' distraction, has previously been demonstrated to correlate with performance of cognitive tasks. Here, we demonstrate a correlation between alpha oscillations and improved gait performance. The results raise the possibility that stimulation of caudal and rostral pedunculopontine nucleus regions may differ in their clinical effects. © 2011 The Author.

© BMJ Publishing Group Limited 2017. Background: Evidence for longer term exercise delivery for people with Parkinson's disease (PwP) is deficient. Aim: Evaluate safety and adherence to a minimally supported community exercise intervention and estimate effect sizes (ES). Methods: 2-arm parallel phase II randomised controlled trial with blind assessment. PwP able to walk ≥100 m and with no contraindication to exercise were recruited from the Thames valley, UK, and randomised (1:1) to intervention (exercise) or control (handwriting) groups, via a concealed computer-generated list. Groups received a 6-month, twice weekly programme. Exercise was undertaken in community facilities (30 min aerobic and 30 min resistance) and handwriting at home, both were delivered through workbooks with monthly support visits. Primary outcome was a 2 min walk, with motor symptoms (Movement Disorder Society Unified Parkinson's Disease Rating Scale, MDS-UPDRS III), fitness, health and well-being measured. Results: Between December 2011 and August 2013, n=53 (n=54 analysed) were allocated to exercise and n=52 (n=51 analysed) to handwriting. N=37 adhered to the exercise, most attending ≥1 session/week. Aerobic exercise was performed in 99% of attended sessions and resistance in 95%. Attrition and adverse events (AEs) were similar between groups, no serious AEs (n=2 exercise, n=3 handwriting) were related, exercise grouprelated AEs (n=2) did not discontinue intervention. Largest effects were for motor symptoms (2 min walk ES=0.20 (95% CI -0.44 to 0.45) and MDS-UPDRS III ES=-0.30 (95% CI 0.07 to 0.54)) in favour of exercise over the 12-month follow-up period. Some small effects were observed in fitness and well-being measures (ES>0.1). Conclusions: PwP exercised safely and the possible long-term benefits observed support a substantive evaluation of this community programme.

Gait freezing and postural instability are disabling features of Parkinsonian disorders, treatable with pedunculopontine nucleus stimulation. Both features are considered deficits of proximal and axial musculature, innervated predominantly by reticulospinal pathways and tend to manifest when gait and posture require adjustment. Adjustments to gait and posture are amenable to pre-preparation and rapid triggered release. Experimentally, such accelerated release can be elicited by loud auditory stimuli--a phenomenon known as 'StartReact'. We observed StartReact in healthy and Parkinsonian controls. However, StartReact was absent in Parkinsonian patients with severe gait freezing and postural instability. Pedunculopontine nucleus stimulation restored StartReact proximally and proximal reaction times to loud stimuli correlated with gait and postural disturbance. These findings suggest a relative block to triggered, pre-prepared movement in gait freezing and postural instability, relieved by pedunculopontine nucleus stimulation.

Introduction. Autoimmune cholangitis or immunoglobulin G4-associated cholangitis (IAC) has been recently regarded as a new clinical and histopathological entity and is a part of a complex autoimmune disorder - IgG4-related systemic disease (ISD). ISD is an autoimmune disease with multi-organic involvement, characterized with IgG4-positive plasmocytic infiltration of various tissues and organs with a consequent sclerosis, which responds well to steroid therapy. Most commonly affected organs are the pancreas (autoimmune pancreatitis, [AIP]) and the common bile duct (IAC). IAC and cholangiocarcinoma (CCA) share many clinical, laboratory and imaging findings. Case Outline. We present a case of a 60-year-old male with a biliary stricture of a common bile duct, which was clinically considered as a bile duct carcinoma and treated surgically. Definite histopathological findings and immunohistochemistry revealed profound chronic inflammation, showing lymphoplasmacytic IgG-positive infiltration of a resected part of a common bile duct, highly suggestive for the diagnosis of IAC. In addition, postoperative IgG4 serum levels were also increased. Conclusion. It is of primary clinical importance to make a difference between IAC and CCA, in order to avoid unnecessary surgical intervention. Therefore, IAC should be considered in differential diagnosis in similar cases.

Objectives: Rest tremor is a cardinal symptom of Parkinson's disease (PD), and is readily suppressed by deep brain stimulation (DBS) of the subthalamic nucleus (STN). The therapeutic effect of the latter on bradykinesia and rigidity has been associated with the suppression of exaggerated beta (13-30 Hz) band synchronization in the vicinity of the stimulating electrode, but there is no correlation between beta suppression and tremor amplitude. In the present study, we investigate whether tremor suppression is related to suppression of activities at other frequencies.Materials and Methods: We recorded hand tremor and contralateral local field potential (LFP) activity from DBS electrodes during stimulation of the STN in 15 hemispheres in 11 patients with PD. DBS was applied with increasing voltages starting at 0.5 V until tremor suppression was achieved or until 4.5 V was reached.Results: Tremor was reduced to 48.9% +/- 10.9% of that without DBS once stimulation reached 2.5-3 V (t14 = -4.667, p Conclusions: Our findings support a relationship between low gamma oscillations and PD tremor, and reinforce the principle that the subthalamic LFP is a rich signal that may contain information about the severity of multiple different Parkinsonian features.

ObjectivesTo investigate the acute and adaptation cardiovascular and metabolic training responses in people with Parkinson’s disease (pwP).Design(1) A cross-sectional study of exercise response of pwP compared with sedentary controls and (2) an interventional study of exercise training in pwP.SettingCommunity leisure facilities.ParticipantspwP (n=83) and sedentary controls (n=55).InterventionsStudy 1 included participants from a two-arm-parallel single-blind phase II randomised controlled trial (RCT), that undertook a baseline maximal incremental exercise test and study 2 included those randomised to the exercise group in the RCT, who completed a 6-month weekly exercise programme (n=37). The intervention study 2 was a prescribed exercise program consisting of sessions lasting 60 min, two times a week over a 6-month period. The control group followed the same protocol which derived the same cardiorespiratory parameters, except that they were instructed to aim for a cadence of ~60 revolutions per minute and the unloaded phase lasted 3 min with an initial step of 25 W.Primary and secondary outcome measuresStepwise incremental exercise test to volitional exhaustion was the primary outcome measure.ResultsStudy 1 showed higher maximum values for heart rate (HR), VO2L/min, VCO2L/min and ventilation L/min for the control group; respiratory exchange ratio (RER), perceived exertion and O2pulse (VO2L/min/HR) did not differ between groups. In study 2, for pwP who adhered to training (n=37), RER increased significantly and although there was no significant change in aerobic capacity or HR response, reduced blood pressure was found.ConclusionsAn abnormal cardiovascular response to exercise was observed in pwP compared to controls. After the exercise programme, metabolic deficiencies remained for pwP. These observations add to the pathogenic understanding of PD, acknowledge an underling metabolic contribution and support that certain cardiovascular symptoms may improve as a result of this type of exercise.

The basal ganglia may play an important role in the control of motor scaling or effort. Recently local field potential (LFP) recordings from patients with deep brain stimulation electrodes in the basal ganglia have suggested that local increases in the synchronisation of neurons in the gamma frequency band may correlate with force or effort. Whether this feature uniquely codes for effort and whether such a coding mechanism holds true over a range of efforts is unclear. Here we investigated the relationship between frequency-specific oscillatory activities in the subthalamic nucleus (STN) and manual grips made with different efforts. The latter were self-rated using the 10 level Borg scale ranging from 0 (no effort) to 10 (maximal effort). STN LFP activities were recorded in patients with Parkinson's Disease (PD) who had undergone functional surgery. Patients were studied while motor performance was improved by dopaminergic medication. In line with previous studies we observed power increase in the theta/alpha band (4–12 Hz), power suppression in the beta band (13–30 Hz) and power increase in the gamma band (55–90 Hz) and high frequency band (101–375 Hz) during voluntary grips. Beta suppression deepened, and then reached a floor level as effort increased. Conversely, gamma and high frequency power increases were enhanced during grips made with greater effort. Multiple regression models incorporating the four different spectral changes confirmed that the modulation of power in the beta band was the only independent predictor of effort during grips made with efforts rated, Highlights • Changes in motor effort are associated with changes in oscillatory synchronisation in the STN. • The precise pattern of changes in STN activity depends on the degree of effort. • Failure of these changes may contribute to impairment in effort in Parkinson's Disease.

Background and Purpose— Although knowledge concerning cortical reorganization related to upper limb function after ischemic stroke is growing, similar data for lower limb movements are limited. Previous studies with hand movement suggested increasing recruitment of motor areas in the unlesioned hemisphere with increasing disability. We used ankle movement as a lower limb analog to test for similarities and differences in recovery patterns. Methods— Eighteen subjects were selected with chronic residual gait impairment due to a single subcortical ischemic stroke. Functional MRI scans were obtained at 3.0 T during active and passive ankle dorsiflexion in the patients (8 females, 10 males; mean age, 59.9±13.5 years; range, 32 to 74 years) and 18 age-matched healthy control subjects. Results— We observed substantial neocortical activity associated with foot movement both in the patients with stroke and in the healthy control subjects. Our primary finding was increased cortical activation with increasing functional impairment. The extent of activation (particularly in the primary sensorimotor cortex and the supplementary motor area of the unlesioned hemisphere) increased with disability. The changes were most prominent with the active movement task. Conclusions— Using ankle movement, we observed increased activation in the unlesioned hemisphere associated with worse function of the paretic leg, consistent with studies on movement of paretic upper limbs. We interpret this finding as potentially adaptive recruitment of undamaged ipsilateral motor control pathways from the supplementary motor area and (possibly maladaptive) disinhibition of the ipsilateral sensorimotor cortex.

Movement of an affected hand after stroke is associated with increased activation of ipsilateral motor cortical areas, suggesting that these motor areas in the undamaged hemisphere may adaptively compensate for damaged or disconnected regions. However, this adaptive compensation has not yet been demonstrated directly. Here we used transcranial magnetic stimulation (TMS) to interfere transiently with processing in the ipsilateral primary motor or dorsal premotor cortex (PMd) during finger movements. TMS had a greater effect on patients than controls in a manner that depended on the site, hemisphere, and time of stimulation. In patients with right hemiparesis (but not in healthy controls), TMS applied to PMd early (100 ms) after the cue to move slowed simple reaction-time finger movements by 12% compared with controls. The relative slowing of movements with ipsilateral PMd stimulation in patients correlated with the degree of motor impairment, suggesting that functional recruitment of ipsilateral motor areas was greatest in the more impaired patients. We also used functional magnetic resonance imaging to monitor brain activity in these subjects as they performed the same movements. Slowing of reaction time after premotor cortex TMS in the patients correlated inversely with the relative hemispheric lateralization of functional magnetic resonance imaging activation in PMd. This inverse correlation suggests that the increased activation in ipsilateral cortical motor areas during movements of a paretic hand, shown in this and previous functional imaging studies, represents a functionally relevant, adaptive response to the associated brain injury.

Local field potential recordings made from the basal ganglia of patients undergoing deep brain stimulation have suggested that frequency specific activity is involved in determining the rate of force development and the peak force at the outset of a movement. However, the extent to which the basal ganglia might be involved in motor performance later on in a sustained contraction is less clear. We therefore recorded from the subthalamic nucleus region (STNr) in patients with Parkinson's disease (PD) as they made maximal voluntary grips. Relative to age-matched controls they had more rapid force decrement when contraction was meant to be sustained and prolonged release reaction time and slower rate of force offset when they were supposed to release the grip. These impairments were independent from medication status. Increased STNr power over 5–12Hz (in the theta/alpha band) independently predicted better performance—reduced force decrement, shortened release reaction time and faster rate of force offset. In contrast, lower mean levels and progressive reduction of STNr power over 55–375Hz (high gamma/high frequency) over the period when contraction was meant to be sustained were both strongly associated with greater force decrement over time. Higher power over 13–23Hz (low beta) was associated with more rapid force decrement during the period when grip should have been sustained, and with a paradoxical shortening of the release reaction time. These observations suggest that STNr activities at 5–12Hz and 55–375Hz are necessary for optimal grip performance and that deficiencies of such activities lead to motor impairments. In contrast, increased levels of 13–25Hz activity both promote force decrement and shorten the release reaction time, consistent with a role in antagonising (and terminating) voluntary movement. Frequency specific oscillatory activities in the STNr impact on motor performance from the beginning to the end of a voluntary grip.