Order of Treatment Matters in Ischemic Stroke: Mechanical Thrombectomy First, Then Carotid Artery Stenting for Tandem Lesions of the Anterior Circulation.

BACKGROUND: One endovascular treatment option of acute ischemic stroke due to tandem occlusion (TO) comprises intracranial thrombectomy and acute extracranial carotid artery stenting (CAS). In this setting, the order of treatment may impact the clinical outcome in this stroke subtype. METHODS: Retrospective analysis was performed on data prospectively collected in 4 international stroke centers between 2013 and 2017. One hundred sixty-five patients with anterior TO were treated by endovascular therapy. Clinical and procedural data were evaluated. Favorable clinical outcome was defined as modified Rankin Scale (mRS) ≤2 at 90 days. Propensity score matching was performed for different treatment strategies. RESULTS: Patients' mean age was 65 ± 11 years and 118 were male (69%). The median admission National Institutes of Health Stroke Scale was 15 (interquartile range 8). In 59% of the patients (n = 101), the antegrade strategy (first stenting, then thrombectomy) was -performed, in 41% (n = 70) retrograde treatment (first thrombectomy, then stenting). Successful reperfusion (mTICI ≥2b) was achieved in 128 patients (75%). Fifty-nine patients (39%) showed a favorable clinical outcome after 90 days. After propensity score matching, data of 100 patients could be analyzed. Analysis revealed that the retrograde strategy yielded a significantly higher rate of successful reperfusion compared to the antegrade strategy (92 vs. 56%; p < 0.001). The rate of favorable clinical outcome after 90 days (mRS ≤2) was consistently higher (44 vs. 30%; p < 0.05) in the retrograde strategy group. CONCLUSION: Mechanical thrombectomy prior to acute CAS in TO is a predictive factor for favorable clinical outcome at 90 days.

Carotid Artery Stenosis Contralateral to Acute Tandem Occlusion: An Independent Predictor of Poor Clinical Outcome after Mechanical Thrombectomy with Concomitant Carotid Artery Stenting.

BACKGROUND AND PURPOSE: Cerebral ischemic strokes due to extra-/intracranial tandem occlusions (TO) of the anterior circulation are responsible for causing mechanical thrombectomy (MT). The impact of concomitant contralateral carotid stenosis (CCS) upon outcome remains unclear in this stroke subtype. METHODS: Retrospective analysis of prospectively collected data of 4 international stroke centers between 2011 and 2017. One hundred ninety-seven consecutive patients with anterior TO were treated with MT and acute carotid artery stenting (CAS). Clinical (including demographics and National Institutes of Health Stroke Scale [NIHSS]), imaging (including angiographic evaluation of CCS) and procedural data were evaluated. Favorable clinical outcome was defined as modified Rankin Scale (mRS) ≤2 at 90 days. RESULTS: In 186 out of 197 TO patients preinterventional CT angiography was available for analysis, thereof 49 patients (26%) presented with CCS. Median admission NIHSS and procedural timings did not differ between groups. Reperfusion was successful in 38 out of 49 patients (78%) vs. 113 out of 148 patients (76%) without CCS. In stark contrast, rate of favorable outcome at 90 days differed significantly between groups (22 vs. 44%; p < 0.05). The presence of CCS in TO was associated with an unfavorable clinical outcome independent of age and NIHSS in multivariate logistic regression (p < 0.05). Final infarct volume was significantly larger in CCS patients (100 ± 127 vs. 63 ± 77 cm3; p < 0.05). Neither all-cause mortality rates (25 vs. 17%) nor frequency of peri-interventional symptomatic intracranial hemorrhage differed between groups (7 vs. 6%). CONCLUSION: For patients with anterior TO undergoing MT with concomitant CAS the presence of CCS >50% is an independent predictor of poor clinical outcome. This most likely cause is due to poorer collateral flow to the affected tissue.

Incomplete Large Vessel Occlusions in Mechanical Thrombectomy: An Independent Predictor of Favorable Outcome in Ischemic Stroke.

BACKGROUND AND PURPOSE: Cerebral large vessel occlusion (LVO) in acute ischemic stroke (AIS) may be complete (CLVO) or incomplete (ILVO). The influence of ILVO on clinical outcome after mechanical thrombectomy (MT) remains unclear. We investigated primarily the clinical outcome in patients with AIS due to ILVO or CLVO. METHODS: Five hundred three consecutive AIS patients with LVO treated with stent-retriever or direct aspiration-based MT between 2010 and 2016 were analyzed. The primary endpoint was favorable clinical outcome (modified Rankin Scale ≤2) at 90 days; secondary endpoints were periprocedural parameters. RESULTS: Forty-nine patients (11.3%) with a median National Institutes of Health Stroke Scale (NIHSS) of 11 presented with ILVO and the remainder presented with CLVO and median NIHSS of 15 (p < 0.001). The median groin puncture-to-reperfusion time was 30 vs. 67 min, respectively (p < 0.001). Successful reperfusion was reached in 47 out of 49 ILVO (95.9%) vs. 298 out of 381 CLVO (78.2%; p < 0.005) with less retrieval maneuvers (1.7 ± 2.2 vs. 3.0 ± 2.5; p < 0.001). The favorable outcome at 90 days was 81% in patients with ILVO vs. 29.1% in CLVO (p < 0.001); respective all-cause mortality rates were 6.4 vs. 28.5% (p < 0.001). Periprocedural complications (6.9%) occurred exclusively in CLVO patients (p < 0.05). ILVO was associated with favorable clinical outcome independent of age and NIHSS in multivariate logistic regression both in the anterior (OR 3.6; 95% CI 1.8-6.9; p < 0.001) and posterior circulation (OR 3.5; 95% CI 1.8-6.9; p < 0.001). CONCLUSIONS: AIS due to ILVO is frequent and is associated with a nearly threefold higher chance of favorable clinical outcome at 90 days, independent of age and initial NIHSS compared to CLVO.

The relevance of 'mixed anxiety and depression' as a diagnostic category in clinical practice.

According to ICD-10 criteria, mixed anxiety and depressive disorder (MADD) is characterized by co-occurring, subsyndromal symptoms of anxiety and depression, severe enough to justify a psychiatric diagnosis, but neither of which are clearly predominant. MADD appears to be very common, particularly in primary care, although prevalence estimates vary, often depending on the diagnostic criteria applied. It has been associated with similarly pronounced distress, impairment of daily living skills, and reduced health-related quality of life as fully syndromal depression and anxiety. Although about half of the patients affected remit within a year, non-remitting patients are at a high risk of transition to a fully syndromal psychiatric disorder. The validity and clinical usefulness of MADD as a diagnostic category are under debate. It has not been included in the recently released DSM-5 since the proposed diagnostic criteria turned out to be not sufficiently reliable. Moreover, reviewers have disputed the justification of MADD based on divergent results regarding its prevalence and course, diagnostic stability over time, and nosological inconsistencies between subthreshold and threshold presentations of anxiety and depressive disorders. We review the evidence in favor and against MADD and argue that it should be included into classification systems as a diagnostic category because it may enable patients to gain access to appropriate treatment early. This may help to reduce patients' distress, prevent exacerbation to a more serious psychiatric disorder, and ultimately reduce the societal costs of this very common condition.

DSM-5 reviewed from different angles: goal attainment, rationality, use of evidence, consequences­part 2: bipolar disorders, schizophrenia spectrum disorders, anxiety disorders, obsessive-compulsive disorders, trauma- and stressor-related disorders, personality disorders, substance-related and addictive disorders, neurocognitive disorders.

Part 1 of this paper discussed several more general aspects of Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and offered a detailed, paradigmatic analysis of changes made to the chapter on depressive disorders. This second part focusses on several other disorders, including bipolar and schizophrenia spectrum disorders. The respective changes and their possible consequences are discussed under consideration of traditional psychiatric classification, particularly from the perspective of European traditions and on the basis of a PubMed search and review papers. The general conclusion is that even seemingly small changes such as the introduction of the mixed feature specifier can have far-reaching consequences. Contrary to the original plans, DSM-5 has not radically changed to become a primarily dimensional diagnostic system but has preserved the categorical system for most disorders. The ambivalence of the respective decision-making becomes apparent from the last minute decision to change the classification of personality disorders from dimensional back to categorical. The advantages and disadvantages of the different approaches are discussed in this context. In DSM-5, only the chapter on addictive disorders has a somewhat dimensional structure. Also in contrast to the original intentions, DSM-5 has not used a more neurobiological approach to disorders by including biological markers to increase the objectivity of psychiatric diagnoses. Even in the most advanced field in terms of biomarkers, the neurocognitive disorders, the primarily symptom-based, descriptive approach has been preserved and the well-known amyloid-related and other biomarkers are not included. This is because, even after so many years of biomarker research, the results are still not considered to be robust enough to use in clinical practice.

DSM-5 reviewed from different angles: goal attainment, rationality, use of evidence, consequences--part 1: general aspects and paradigmatic discussion of depressive disorders.

DSM-5 was published in 2013 after about 10 years of preparation. Part 1 of this paper discusses several more general aspects of DSM-5 and offers a detailed, paradigmatic analysis of changes made to the chapter on depressive disorders. The background for the changes is analysed on the basis of a PubMed search and review papers on the classification of mental disorders in general and on empirical knowledge about individual disorders. Contrary to the original plans, DSM-5 has not introduced a primarily dimensional diagnostic system but has widely preserved the categorical system of disorders. Also, it has not adopted a more neurobiological approach to disorders by including biological markers to increase the objectivity of psychiatric diagnoses but has maintained the primarily symptom-based, descriptive approach. The criteria for some disorders have been changed, including affective, schizophrenic and addiction disorders, and a few new disorders have been added. A minimal version of the dimensional approach was realised through the introduction of several transnosological specifiers and the option to make symptom- or syndrome-related severity and dimensional assessments. These specifiers and assessments might allow a more individualised description of a patient's psychopathological state and more personalised treatment. However, most of the symptom- and syndrome-related assessments are not mandatory and therefore may not be used in clinical practice.

Coordinated reset neuromodulation for Parkinson's disease: proof-of-concept study.

BACKGROUND: The discovery of abnormal synchronization of neuronal activity in the basal ganglia in Parkinson's disease (PD) has prompted the development of novel neuromodulation paradigms. Coordinated reset neuromodulation intends to specifically counteract excessive synchronization and to induce cumulative unlearning of pathological synaptic connectivity and neuronal synchrony. METHODS: In this prospective case series, six PD patients were evaluated before and after coordinated reset neuromodulation according to a standardized protocol that included both electrophysiological recordings and clinical assessments. RESULTS: Coordinated reset neuromodulation of the subthalamic nucleus (STN) applied to six PD patients in an externalized setting during three stimulation days induced a significant and cumulative reduction of beta band activity that correlated with a significant improvement of motor function. CONCLUSIONS: These results highlight the potential effects of coordinated reset neuromodulation of the STN in PD patients and encourage further development of this approach as an alternative to conventional high-frequency deep brain stimulation in PD.

[The Use of Artificial Intelligence in Alzheimer's Disease - Personalized Diagnostics and Therapy]. / Der Einsatz von Künstlicher Intelligenz bei Alzheimer-Krankheit ­ Personalisierte Diagnostik und Therapie.

Using the example of dementia in Alzheimer's disease, it is shown which opportunities but also risks are posed by newer methodological approaches of artificial intelligence (AI) for the diagnosis and treatment of Alzheimer's dementia (AD). In addition, AI is examined in the context of an ethical-philosophical critique of technology.

Clinical presentation of posterior cerebral artery occlusions - Clinical rationale for a more aggressive therapeutic strategy?

INTRODUCTION: A proximal occlusion of the posterior cerebral artery (PCA) can affect patients severely and clinical outcome might be poor. Aim of this paper is to describe clinical presentation, diagnostic findings and outcome of patients suffering from ischemia in the PCA territory. METHODS: We conducted a retrospective analysis of clinically affected patients with imaging-based evidence of ischemia within in the PCA territory at a comprehensive stroke center over a six-year period. Clinical (including demographics, National Institutes of Health Stroke Scale, NIHSS, modified Rankin Sclae, mRS), imaging (including occlusion site and brain infarction) and therapeutic data were evaluated. A favorable outcome was defined as an mRS ≤2. RESULTS: Two hundred thirty-five patients were clinically affected with evidence of PCA ischemia detected by cross-sectional imaging. One-hundred fourty-five patients demonstrated an occlusion of the PCA including 43/145 (30%) with P1 occlusion, 80/145 (55%) with P2 and 22/145 (15%) with P3 occlusion. The most frequent symptom was hemi-/ quadrantanopsia (181/235, 77%). Sixty-eight patients (29%) suffered from hemiparesis. The occurrence of a hemiparesis was associated with a P1 occlusion (27/43, 63% vs. 41/192, 21%; p < 0.0001). Hemi-/quadrantanopsia was less frequently associated with a P1 occlusion (26/43, 61% vs. 155/192, 81%; p = 0.0043). P1 occlusions more frequently showed thalamic infarction (28/43, 65% vs. 65/192, 34%; p < 0.0001). At discharge, patients with P1 occlusion more often showed a poor outcome (mRS > 2, 30/43, 70% vs. 55/192, 29%; p < 0.0001). CONCLUSION: Hemiparesis due to P1 occlusion is a common phenomenon in stroke patients and associated with a poor clinical outcome.

Correction to: Mechanical Thrombectomy in Basilar Artery Occlusion : Presence of Bilateral Posterior Communicating Arteries is a Predictor of Favorable Clinical Outcome.

Correction to: Clin Neuroradiol 2017 https://doi.org/10.1007/s00062-017-0651-3 The original version of this article unfortunately contained a mistake. The presentation of Fig. 2 was incorrect. The corrected figure is given ….

Mechanical Thrombectomy in Basilar Artery Occlusion : Presence of Bilateral Posterior Communicating Arteries is a Predictor of Favorable Clinical Outcome.

BACKGROUND: Mechanical thrombectomy (MT) of basilar artery occlusions (BAO) is a subject of debate. We investigated the clinical outcome of MT in BAO and predictors of a favorable outcome. MATERIAL AND METHODS: A total of 104 MTs of BAO (carried out between 2010 and 2016) were analyzed. Favorable outcome as a modified Rankin scale (mRS) ≤ 2 at 90 days was the primary endpoint. The influence of the following variables on outcome was investigated: number of detectable posterior communicating arteries (PcoAs), patency of basilar tip, completeness of BAO and posterior circulation Alberta Stroke Program early computed tomography score (PC-ASPECTS). Secondary endpoints were technical periprocedural parameters including symptomatic intracranial hemorrhage (sICH). RESULTS: The favorable clinical outcome at 90 days was 25% and mortality was 43%. The rate of successful reperfusion, i.e. modified thrombolysis in cerebral infarction (mTICI) ≥ 2b was 82%. Presence of bilateral PcoAs (area under the curve, AUC: 0.81, odds ratio, OR: 4.2, 2.2-8.2; p < 0.0001), lower National Institute of Health Stroke Scale (NIHSS) on admission (AUC: 0.74, OR: 2.6, 1.3-5.2; p < 0.01), PC-ASPECTS ≥ 9 (AUC: 0.72, OR: 4.2, 1.5-11.9; p < 0.01), incomplete BAO (AUC: 0.66, OR: 2.6, 1.4-4.8; p < 0.001), and basilar tip patency (AUC: 0.66, OR: 2.5, 1.3-4.8; p < 0.01) were associated with a favorable outcome. Stepwise logistic regression analysis revealed that the strongest predictors of favorable outcome at 90 days were bilateral PcoAs, low NIHSS on admission, and incomplete BAO (AUC: 0.923, OR: 7.2, 3-17.3; p < 0.0001). CONCLUSION: The use of MT for BAO is safe with high rates of successful reperfusion. Aside from baseline NIHSS and incomplete vessel occlusion, both known predictors of favorable outcome in anterior circulation events, we found that collateral flow based on the presence or absence of PcoAs had a decisive prognostic impact.

Clinical Outcome After Mechanical Thrombectomy in Patients with Diabetes with Major Ischemic Stroke of the Anterior Circulation.

BACKGROUND: Among patients with acute ischemic stroke treated with mechanical thrombectomy (MT), patients with diabetes (DP) show a poorer outcome compared with patients without diabetes (NDP). This study aims to provide a comprehensive analysis of factors associated with unfavorable outcome in DP receiving MT for stroke of the anterior circulation. METHODS: This study included 317 of 498 consecutive patients who received interventional treatment for acute ischemic stroke in the terminal internal carotid artery and/or middle cerebral artery, including 46 DP. The study data included pre- and posttreatment stroke computed tomography, including perfusion data, collateral status, treatment data including treatment times, pre-existing cardiovascular risk factors, cerebrovascular events, comorbidities, laboratory parameters, and medication. Neurologic status was assessed at baseline (National Institute of Health Stroke Scale [NIHSS]/modified Rankin Scale [mRS]) and after 90 days (mRS 90). RESULTS: Compared with NDP, DP showed a significantly poorer outcome (mRS90 >2) (P < 0.05). Collateralization and infarct core size did not differ between groups, whereas the penumbra was significantly smaller in DP than in NDP (P < 0.05). The poorer mRS90 outcome (mRS90 > 2) in DP was associated with poor collaterals (P = 0.01) and hyperglycemia on admission (P < 0.05). Shorter time to reperfusion was associated with favorable mRS90 in the NDP (P < 0.001) but not the DP (P = 0.49) group. In univariate logistic regression, the following parameters were significantly associated with mRS90: diabetes, hyperglycemia at admission, time to reperfusion, and the NIHSS score (P < 0.05 each). In multivariate analyses and partition regression models of all variables, DP with admission hyperglycemia (≥132 mg/dL) and older age (≥66 years) showed a particularly poor outcome. CONCLUSIONS: The main factors for an unfavorable outcome of DP after MT are admission hyperglycemia, age, and NIHSS score.

The Use of Flow Diverter in Ruptured, Dissecting Intracranial Aneurysms of the Posterior Circulation.

OBJECTIVE: Acute dissecting aneurysms of the posterior circulation are a rare cause of subarachnoid hemorrhage. Established endovascular treatment options include parent artery occlusion and stent-assisted coiling, but appear to be associated with an increased risk of ischemic stroke. Vessel reconstruction with flow diverters is an alternative treatment option; however, its safety and efficacy in the acute stage remains unclear. METHODS: This is a multicentric retrospective analysis of 15 consecutive acutely ruptured dissecting posterior circulation aneurysms treated with flow diverters. The primary end point was favorable aneurysm occlusion, defined as OKM C1-3 and D (O'Kelly Marotta scale). Secondary end points were procedure-related complications and clinical outcome. RESULTS: Nine of 15 aneurysms (60%) arose from the intradural portion of the vertebral artery, 3 were located on the posterior inferior cerebellar artery and 1 each on the anterior inferior cerebellar artery, posterior cerebral artery, and basilar artery. Flow diverter placement was technically successful in 14 of 15 cases (93%). After endovascular treatment, none of the ruptured aneurysms rebled. Median clinical follow-up was 217 days and median angiographic follow-up was 203 days. Favorable occlusion was observed in 7 of 14 aneurysms (50%) directly after flow diverter placement; of those, 5 were completely occluded (36%). Seven patients (47%) with poor-grade subarachnoid hemorrhage died in the acute phase. Favorable clinical outcome (modified Rankin scale ≤2) was observed in 4 of 15 patients (27%) and a moderate outcome (modified Rankin scale 3/4) was observed in 5 of 15 patients (33%). All aneurysms showed complete occlusion at follow-up. CONCLUSIONS: Flow diverters might be a feasible, alternative treatment option for acutely ruptured dissecting posterior circulation aneurysms and may effectively prevent rebleeding. Larger cohort studies are required to validate these results.

The causal relationship between subcortical local field potential oscillations and Parkinsonian resting tremor.

To study the dynamical mechanism which generates Parkinsonian resting tremor, we apply coupling directionality analysis to local field potentials (LFP) and accelerometer signals recorded in an ensemble of 48 tremor epochs in four Parkinsonian patients with depth electrodes implanted in the ventro-intermediate nucleus of the thalamus (VIM) or the subthalmic nucleus (STN). Apart from the traditional linear Granger causality method we use two nonlinear techniques: phase dynamics modelling and nonlinear Granger causality. We detect a bidirectional coupling between the subcortical (VIM or STN) oscillation and the tremor, in the theta range (around 5 Hz) as well as broadband (>2 Hz). In particular, we show that the theta band LFP oscillations definitely play an efferent role in tremor generation, while beta band LFP oscillations might additionally contribute. The brain-->tremor driving is a complex, nonlinear mechanism, which is reliably detected with the two nonlinear techniques only. In contrast, the tremor-->brain driving is detected with any of the techniques including the linear one, though the latter is less sensitive. The phase dynamics modelling (applied to theta band oscillations) consistently reveals a long delay in the order of 1-2 mean tremor periods for the brain-->tremor driving and a small delay, compatible with the neural transmission time, for the proprioceptive feedback. Granger causality estimation (applied to broadband signals) does not provide reliable estimates of the delay times, but is even more sensitive to detect the brain-->tremor influence than the phase dynamics modelling.

Tremor entrainment by patterned low-frequency stimulation.

High-frequency test stimulation for tremor suppression is a standard procedure for functional target localization during deep brain stimulation. This method does not work in cases where tremor vanishes intraoperatively, for example, due to general anaesthesia or due to an insertional effect. To overcome this difficulty, we developed a stimulation technique that effectively evokes tremor in a well-defined and quantifiable manner. For this, we used patterned low-frequency stimulation (PLFS), i.e. brief high-frequency pulse trains administered at pulse rates similar to neurons' preferred burst frequency. Unlike periodic single-pulse stimulation, PLFS enables one to convey effective and considerably greater integral charge densities without violation of safety requirements. In a computational investigation of an oscillatory neuronal network temporarily rendered inactive, we found that PLFS evokes synchronized activity, phase locked to the stimulus. While a stronger increase in the amount of synchrony in the neuronal population requires higher stimulus intensities, the portion of synchronously active neurons nevertheless becomes strongly phase locked to PLFS already at weak stimulus intensities. The phase entrainment effect of PLFS turned out to be robust against variations in the stimulation frequency, whereas enhancement of synchrony required precisely tuned stimulation frequencies. We applied PLFS to a patient with spinocerebellar ataxia type 2 (SCA2) with pronounced tremor that disappeared intraoperatively under general anaesthesia. In accordance with our computational results, PLFS evoked tremor, phase locked to the stimulus. In particular, weak PLFS caused low-amplitude, but strongly phase-locked tremor. PLFS test stimulations provided the only functional information about target localization. Optimal target point selection was confirmed by excellent post-operative tremor suppression.

Subthalamic-thalamic DBS in a case with spinocerebellar ataxia type 2 and severe tremor-A unusual clinical benefit.

This is a single case report of a patient with spinocerebellar ataxia type 2 (SCA2) and severe tremor. Whereas disease progression with prevailing ataxia and dysmetria was slow over the first symptomatic 6 years, 6 months prior to operation were characterized by the development of a severe, debilitating postural tremor rendering the patient unable to independently sit, stand, speak, or swallow. Deep brain stimulation (DBS) at a subthalamic-thalamic electrode position almost completely arrested her tremor. The patient regained the functional state prior to her rapid disease progression allowing a restricted range of daily activities. Her condition has remained approximately stable over the two postoperative years to date. In addition to the efficacy of DBS on cerebellar tremor, the results illustrate a remarkable improvement of the patient's general condition and independence.

Timing of V1/V2 and V5+ activations during coherent motion of dots: an MEG study.

In order to study the temporal activation course of visual areas V1 and V5 in response to a motion stimulus, a random dots kinematogram paradigm was applied to eight subjects while magnetic fields were recorded using magnetoencephalography (MEG). Sources generating the registered magnetic fields were localized with Magnetic Field Tomography (MFT). Anatomical identification of cytoarchitectonically defined areas V1/V2 and V5 was achieved by means of probabilistic cytoarchitectonic maps. We found that the areas V1/V2 and V5+ (V5 and other adjacent motion sensitive areas) exhibited two main activations peaks at 100-130 ms and at 140-200 ms after motion onset. The first peak found for V1/V2, which corresponds to the visual evoked field (VEF) M1, always preceded the peak found in V5+. Additionally, the V5+ peak was correlated significantly and positively with the second V1/V2 peak. This result supports the idea that the M1 component is generated not only by the visual area V1/V2 (as it is usually proposed), but also by V5+. It reflects a forward connection between both structures, and a feedback projection to V1/V2, which provokes a second activation in V1/V2 around 200 ms. This second V1/V2 activation (corresponding to motion VEF M2) appeared earlier than the second V5+ activation but both peaked simultaneously. This result supports the hypothesis that both areas also generate the M2 component, which reflects a feedback input from V5+ to V1/V2 and a crosstalk between both structures. Our study indicates that during visual motion analysis, V1/V2 and V5+ are activated repeatedly through forward and feedback connections and both contribute to m-VEFs M1 and M2.

Pattern reversal visual evoked responses of V1/V2 and V5/MT as revealed by MEG combined with probabilistic cytoarchitectonic maps.

Pattern reversal stimulation provides an established tool for assessing the integrity of the visual pathway and for studying early visual processing. Numerous magnetoencephalographic (MEG) and electroencephalographic (EEG) studies have revealed a three-phasic waveform of the averaged pattern reversal visual evoked potential/magnetic field, with components N75(m), P100(m), and N145(m). However, the anatomical assignment of these components to distinct cortical generators is still a matter of debate, which has inter alia connected with considerable interindividual variations of the human striate and extrastriate cortex. The anatomical variability can be compensated for by means of probabilistic cytoarchitectonic maps, which are three-dimensional maps obtained by an observer-independent statistical mapping in a sample of ten postmortem brains. Transformed onto a subject's brain under consideration, these maps provide the probability with which a given voxel of the subject's brain belongs to a particular cytoarchitectonic area. We optimize the spatial selectivity of the probability maps for V1 and V2 with a probability threshold which optimizes the self- vs. cross-overlap in the population of postmortem brains used for deriving the probabilistic cytoarchitectonic maps. For the first time, we use probabilistic cytoarchitectonic maps of visual cortical areas in order to anatomically identify active cortical generators underlying pattern reversal visual evoked magnetic fields as revealed by MEG. The generators are determined with magnetic field tomography (MFT), which reconstructs the current source density in each voxel. In all seven subjects, our approach reveals generators in V1/V2 (with a greater overlap with V1) and in V5 unilaterally (right V5 in three subjects, left V5 in four subjects) and consistent time courses of their stimulus-locked activations, with three peak activations in V1/V2 (contributing to C1m/N75m, P100m, and N145m) and two peak activations in V5 (contributing to P100m and N145m). The reverberating V1/V2 and V5 activations demonstrate the effect of recurrent activation mechanisms including V1 and extrastriate areas and/or corticofugal feedback loops. Our results demonstrate that the combined investigation of MEG signals with MFT and probabilistic cytoarchitectonic maps significantly improves the anatomical identification of active brain areas.