Production of Sentential Negation in German and Italian Non-fluent Aphasia.

The ability of persons with non-fluent aphasia (PWAs) to produce sentential negation has been investigated in several languages, but only in small samples. Accounts of (morpho)syntactic impairment in PWAs have emphasized various factors, such as whether the negative marker blocks or interferes with verb movement, the position of the Negation Phrase in the syntactic hierarchy or the interpretability of negation. This study investigates the ability of German- and Italian-speaking PWAs to construct negative sentences, as well as the role of verbal working memory (WM) capacity and education in task performance and production of sentential negation. German and Italian differ in the syntactic properties of the negative markers that are relevant here (nicht and non, respectively). A sentence anagram task tapping into the construction of negative and affirmative declarative sentences was administered to 9 German- and 7 Italian-speaking PWAs, and to 14 German- and 11 Italian-speaking age- and education-matched healthy volunteers. We fitted generalized linear mixed-effects models to the datasets. There was no significant difference between negative and affirmative sentences in either group of PWAs. There was a main effect of verbal WM capacity on task performance, but no interaction between verbal WM capacity and production of negative vs. affirmative sentences. Education did not affect task performance. The results are discussed in light of different linguistically-informed accounts of (morpho)syntactic impairment in non-fluent aphasia.

Language Assessment in Multilingualism and Awake Neurosurgery.

Multilingualism has become a worldwide phenomenon that poses critical issues about the language assessment in patients undergoing awake neurosurgery in eloquent brain areas. The accuracy and sensitivity of multilingual perioperative language assessment procedures is crucial for a number of reasons: they should be appropriate to detect deficits in each of the languages spoken by the patient; they should be suitable to identify language-specific cortical regions; they should ensure that each of the languages of a multilingual patient is tested at an adequate and comparable level of difficulty. In clinical practice, a patient-tailored approach is generally preferred. This is a necessary compromise since it is impossible to predict all the possible language combinations spoken by individuals and thus the availability of standardized testing batteries is a potentially unattainable goal. On the other hand, this leads to high inconsistency in how different neurosurgical teams manage the linguistic features that determine similarity or distance between the languages spoken by the patient and that may constrain the neuroanatomical substrate of each language. The manuscript reviews the perioperative language assessment methodologies adopted in awake surgery studies on multilingual patients with brain tumor published from 1991 to 2021 and addresses the following issues: (1) The language selected for the general neuropsychological assessment of the patient. (2) The procedures adopted to assess the dimensions that may constrain language organization in multilingual speakers: age and type of acquisition, exposure, proficiency, and use of the different languages. (3) The type of preoperative language assessment used for all the languages spoken by the patient. (4) The linguistic tasks selected in the intraoperative setting. The reviewed data show a great heterogeneity in the perioperative clinical workup with multilingual patients. The only exception is the task used during language mapping, as the picture naming task is highly preferred. The review highlights that an objective and accurate description of both the linguistic profile of multilingual patients and the specific properties of the languages under scrutiny can profitably support clinical management and decision making in multilingual awake neurosurgery settings.

Modelling picture naming in aphasia: The relationship between consistency and predictability of responses.

OBJECTIVE: Two aspects of aphasic picture naming were examined: response consistency, that is, the extent to which the accuracy of the response to the same stimulus is replicated in a successive examination, and response predictability, that is, the extent to which accuracy depends on the characteristics of each stimulus. METHODS: Thirty-eight aphasic participants were examined twice. The response pattern was the same across the 2 presentations (response stability) for 36 participants, who were classified into 3 groups according to the prevailing error-type (lexical-semantic, phonological, or a balance between the two error-types): Their item-consistency was quantified with Cohen's kappa. In each case the roles played by lexical frequency, precocity of acquisition and length of the target word, and visual complexity and image agreement of the stimulus picture were examined; the ability to predict response accuracy of a model simultaneously including these 5 variables was quantified by means of the McFadden index. Finally, the relationship between predictability (McFadden index) and consistency (Cohen's kappa) was analyzed. RESULTS: For 34 of 36 participants, consistency was higher than chance. Consistency was directly correlated to the prevalence of lexical-semantic errors. On regression analysis, the relationship between consistency and predictability was significant. CONCLUSIONS: Response consistency reflects the existence of a clear difficulty gradient within the items of a battery. The significant relationship between consistency and error type suggests that, in principle, lexical-semantic errors might be more predictable than phonological errors based on the characteristics of each stimulus. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Time reference in nonfluent and fluent aphasia: a cross-linguistic test of the PAst DIscourse LInking Hypothesis.

Recent studies by Bastiaanse and colleagues found that time reference is selectively impaired in people with nonfluent agrammatic aphasia, with reference to the past being more difficult to process than reference to the present or to the future. To account for this dissociation, they formulated the PAst DIscourse LInking Hypothesis (PADILIH), which posits that past reference is more demanding than present/future reference because it involves discourse linking. There is some evidence that this hypothesis can be applied to people with fluent aphasia as well. However, the existing evidence for the PADILIH is contradictory, and most of it has been provided by employing a test that predominantly taps retrieval processes, leaving largely unexplored the underlying ability to encode time reference-related prephonological features. Within a cross-linguistic approach, this study tests the PADILIH by means of a sentence completion task that 'equally' taps encoding and retrieval abilities. This study also investigates if the PADILIH's scope can be extended to fluent aphasia. Greek- and Italian-speaking individuals with aphasia participated in the study. The Greek group consisted of both individuals with nonfluent agrammatic aphasia and individuals with fluent aphasia, who also presented signs of agrammatism. The Italian group consisted of individuals with agrammatic nonfluent aphasia only. The two Greek subgroups performed similarly. Neither language group of participants with aphasia exhibited a pattern of performance consistent with the predictions of the PADILIH. However, a double dissociation observed within the Greek group suggests a hypothesis that may reconcile the present results with the PADILIH.

Pure word deafness following left temporal damage: Behavioral and neuroanatomical evidence from a new case.

Pure Word Deafness (PWD) is a rare disorder, characterized by selective loss of speech input processing. Its most common cause is temporal damage to the primary auditory cortex of both hemispheres, but it has been reported also following unilateral lesions. In unilateral cases, PWD has been attributed to the disconnection of Wernicke's area from both right and left primary auditory cortex. Here we report behavioral and neuroimaging evidence from a new case of left unilateral PWD with both cortical and white matter damage due to a relatively small stroke lesion in the left temporal gyrus. Selective impairment in auditory language processing was accompanied by intact processing of nonspeech sounds and normal speech, reading and writing. Performance on dichotic listening was characterized by a reversal of the right-ear advantage typically observed in healthy subjects. Cortical thickness and gyral volume were severely reduced in the left superior temporal gyrus (STG), although abnormalities were not uniformly distributed and residual intact cortical areas were detected, for example in the medial portion of the Heschl's gyrus. Diffusion tractography documented partial damage to the acoustic radiations (AR), callosal temporal connections and intralobar tracts dedicated to single words comprehension. Behavioral and neuroimaging results in this case are difficult to integrate in a pure cortical or disconnection framework, as damage to primary auditory cortex in the left STG was only partial and Wernicke's area was not completely isolated from left or right-hemisphere input. On the basis of our findings we suggest that in this case of PWD, concurrent partial topological (cortical) and disconnection mechanisms have contributed to a selective impairment of speech sounds. The discrepancy between speech and non-speech sounds suggests selective damage to a language-specific left lateralized network involved in phoneme processing.

The dissociability of lexical retrieval and morphosyntactic processes for nouns and verbs: A functional and anatomoclinical study.

Nouns and verbs can dissociate following brain damage, at both lexical retrieval and morphosyntactic processing levels. In order to document the range and the neural underpinnings of behavioral dissociations, twelve aphasics with disproportionate difficulty naming objects or actions were asked to apply phonologically identical morphosyntactic transformations to nouns and verbs. Two subjects with poor object naming and 2/10 with poor action naming made no morphosyntactic errors at all. Six of 10 subjects with poor action naming showed disproportionate or no morphosyntactic difficulties for verbs. Morphological errors on nouns and verbs correlated at the group level, but in individual cases a selective impairment of verb morphology was observed. Poor object and action naming with spared morphosyntax were associated with non-overlapping lesions (inferior occipitotemporal and fronto-temporal, respectively). Poor verb morphosyntax was observed with frontal-temporal lesions affecting white matter tracts deep to the insula, possibly disrupting the interaction of nodes in a fronto-temporal network.

Neural bases of orthographic long-term memory and working memory in dysgraphia.

Spelling a word involves the retrieval of information about the word's letters and their order from long-term memory as well as the maintenance and processing of this information by working memory in preparation for serial production by the motor system. While it is known that brain lesions may selectively affect orthographic long-term memory and working memory processes, relatively little is known about the neurotopographic distribution of the substrates that support these cognitive processes, or the lesions that give rise to the distinct forms of dysgraphia that affect these cognitive processes. To examine these issues, this study uses a voxel-based mapping approach to analyse the lesion distribution of 27 individuals with dysgraphia subsequent to stroke, who were identified on the basis of their behavioural profiles alone, as suffering from deficits only affecting either orthographic long-term or working memory, as well as six other individuals with deficits affecting both sets of processes. The findings provide, for the first time, clear evidence of substrates that selectively support orthographic long-term and working memory processes, with orthographic long-term memory deficits centred in either the left posterior inferior frontal region or left ventral temporal cortex, and orthographic working memory deficits primarily arising from lesions of the left parietal cortex centred on the intraparietal sulcus. These findings also contribute to our understanding of the relationship between the neural instantiation of written language processes and spoken language, working memory and other cognitive skills.

Thematic role assignment in the posterior parietal cortex: A TMS study.

Verbs denote relations between entities acting a role in an event. Thematic roles are essential to the correct use of verbs and involve both semantic and syntactic aspects. We used repetitive Transcranial Magnetic Stimulation (rTMS) to study the involvement of three different left parietal sites in the understanding of thematic roles. In a sentence-to-picture matching task, twelve participants were asked to judge whether or not a given picture matched with a written sentence. Pictures represented simple reversible actions, and sentences were in the active or passive diathesis. Whereas both active and passive sentences require the correct encoding of thematic roles, passives also imply thematic reanalysis, as the canonical order of thematic roles is systematically reversed. The experiment was divided in three sessions. In each session a different parietal site (anterior, middle, posterior) was stimulated at 5 Hz in an event-related fashion, time-locked to the presentation of visual stimuli. Results showed increased accuracy for passive sentences following posterior parietal stimulation. The effect appeared to be (a) TMS-related, as no effect was observed in a control, no-TMS experiment with eighteen new participants; (b) independent from semantic processes involved in word-picture association, as no TMS-related effects were observed in a picture-word matching task. We interpret the results as showing that the posterior parietal site is specifically involved in the assignment of thematic roles, in particular when the correct interpretation of a sentence requires reanalysis of temporarily encoded thematic roles, as in passive reversible sentences.

Verb production tasks in the measurement of communicative abilities in aphasia.

BACKGROUND: The neurofunctional correlates of verbs and nouns have been the focus of many theoretically oriented studies. In clinical practice, however, more attention is typically paid to nouns, and the relative usefulness of tasks probing nouns and verbs is unclear. The routine administration of tasks that use verbs could be a relevant addition to current batteries. Evaluating performance on both noun and verb tasks may provide a more reliable account of everyday language abilities than an evaluation restricted to nouns. AIMS: To assess the benefits of administering verb tasks in addition to noun tasks, and their relation to three functional measures of language. METHOD AND PROCEDURE: Twenty-one subjects with poststroke language disorders completed four picture-naming tasks and a role-playing test (Communicative Abilities in Daily Living, Second Edition, CADL-2), commonly used as measure of everyday language abilities. Two questionnaires (Communicative Effectiveness Index, CETI, and Communicative Activity Log, CAL) were completed by caregivers. Picture-naming tasks were matched for psycholinguistic variables to avoid lexicosemantic and morphosyntactic confounds. RESULTS: No significant differences emerged across picture-naming tasks. Scores on the role-playing test and the two questionnaires differed; scores between the two questionnaires did not. The four naming tasks correlated significantly with CADL-2, CETI, and CAL. The strength of the correlation with CADL-2 was significantly greater for Naming Finite Verbs than for Object Naming. Thirteen participants showed no differences in performance between tasks, 6 fared significantly worse on verb tasks than on Object Naming, 1 fared better at Naming Finite Verbs though his performance was poor overall, and 1 was significantly more impaired on verbs. CONCLUSIONS: Performance on tasks that use verbs, and especially Naming Finite Verbs, may provide a more accurate estimate of language abilities in daily living than Object Naming alone. Administering both verb and noun tasks may be recommended in clinical practice.

Can tDCS enhance item-specific effects and generalization after linguistically motivated aphasia therapy for verbs?

BACKGROUND: Aphasia therapy focusing on abstract properties of language promotes both item-specific effects and generalization to untreated materials. Neuromodulation with transcranial Direct Current Stimulation (tDCS) has been shown to enhance item-specific improvement, but its potential to enhance generalization has not been systematically investigated. Here, we test the efficacy of ACTION (a linguistically motivated protocol) and tDCS in producing item-specific and generalized improvement in aphasia. METHOD: Nine individuals with post-stroke aphasia participated in this study. Participants were pre-tested with a diagnostic language battery and a cognitive screening. Experimental tasks were administered over multiple baselines. Production of infinitives, of finite verbs and of full sentences were assessed before and after each treatment phase. Nonword repetition was used as a control measure. Each subject was treated in two phases. Ten daily 1-h treatment sessions were provided per phase, in a double-blind, cross-over design. Linguistically-motivated language therapy focusing on verb inflection and sentence construction was provided in both phases. Each session began with 20 min of real or sham tDCS. Stimulation site was determined individually, based on MRI scans. RESULTS: Group data showed improved production of treated and untreated verbs, attesting the efficacy of behavioral treatment, and its potential to yield generalization. Each individual showed significant item-specific improvement. Generalization occurred in the first phase of treatment for all subjects, and in the second phase for two subjects. Stimulation effects at the group level were significant for treated and untreated verbs altogether, but a ceiling effect for Sham cannot be excluded, as scores between real tDCS and Sham differed only before treatment. CONCLUSION: Our data demonstrate the efficacy of ACTION and suggest that tDCS may enhance both item-specific effects and generalization.

Awake surgery between art and science. Part II: language and cognitive mapping.

Direct cortical and subcortical stimulation has been claimed to be the gold standard for exploring brain function. In this field, efforts are now being made to move from intraoperative naming-assisted surgical resection towards the use of other language and cognitive tasks. However, before relying on new protocols and new techniques, we need a multi-staged system of evidence (low and high) relating to each step of functional mapping and its clinical validity. In this article we examine the possibilities and limits of brain mapping with the aid of a visual object naming task and various other tasks used to date. The methodological aspects of intraoperative brain mapping, as well as the clinical and operative settings, were discussed in Part I of this review.

Distinguishable neurofunctional effects of task practice and item practice in picture naming: a BOLD fMRI study in healthy subjects.

Practice of language tasks results in improved performance and BOLD signal changes. We distinguish changes correlated with repeated exposure to a picture naming task, from changes associated with naming specific items trained during practice. Task practice affected trained and untrained items, yielding left-sided BOLD deactivations in extrastriate, prefrontal and superior temporal areas (consistent with their putative role in perceptual priming, articulatory planning and phonological lexical retrieval, respectively). Item practice effects were restricted to trained words. There was deactivation in left posterior fusiform (supporting its role in accessing structural object representations), anterior cingulate and left insular/inferior frontal cortices (consistent with their role in processing low-frequency words). Central precuneus and posterior cingulate were hyperactivated (consistent with their putative role in episodic memory for trained items, probably due to functional connections with language areas). In healthy subjects, naming practice modifies stored linguistic representations, but mostly affects ease of access to trained words.

The role of Broca's area in speech perception: evidence from aphasia revisited.

Motor theories of speech perception have been re-vitalized as a consequence of the discovery of mirror neurons. Some authors have even promoted a strong version of the motor theory, arguing that the motor speech system is critical for perception. Part of the evidence that is cited in favor of this claim is the observation from the early 1980s that individuals with Broca's aphasia, and therefore inferred damage to Broca's area, can have deficits in speech sound discrimination. Here we re-examine this issue in 24 patients with radiologically confirmed lesions to Broca's area and various degrees of associated non-fluent speech production. Patients performed two same-different discrimination tasks involving pairs of CV syllables, one in which both CVs were presented auditorily, and the other in which one syllable was auditorily presented and the other visually presented as an orthographic form; word comprehension was also assessed using word-to-picture matching tasks in both auditory and visual forms. Discrimination performance on the all-auditory task was four standard deviations above chance, as measured using d', and was unrelated to the degree of non-fluency in the patients' speech production. Performance on the auditory-visual task, however, was worse than, and not correlated with, the all-auditory task. The auditory-visual task was related to the degree of speech non-fluency. Word comprehension was at ceiling for the auditory version (97% accuracy) and near ceiling for the orthographic version (90% accuracy). We conclude that the motor speech system is not necessary for speech perception as measured both by discrimination and comprehension paradigms, but may play a role in orthographic decoding or in auditory-visual matching of phonological forms.

Temporal stability and representational distinctiveness: key functions of orthographic working memory.

A primary goal of working memory research has been to understand the mechanisms that permit working memory systems to effectively maintain the identity and order of the elements held in memory for sufficient time as to allow for their selection and transfer to subsequent processing stages. Based on the performance of two individuals with acquired dysgraphia affecting orthographic working memory (WM; the graphemic buffer), we present evidence of two distinct and dissociable functions of orthographic WM. One function is responsible for maintaining the temporal stability of letters held in orthographic WM, while the other is responsible for maintaining their representational distinctiveness. The failure to maintain temporal stability and representational distinctiveness gives rise, respectively, to decay and interference effects that manifest themselves in distinctive error patterns, including distinct serial position effects. The findings we report have implications beyond our understanding of orthographic WM, as the need to maintain temporal stability and representational distinctiveness in WM is common across cognitive domains.

A computer-aided evaluation of error patterns in aphasic speech.

The objective of this research is to provide an improved automated computational tool to study aphasic production. Using the speech production of Italian aphasic patients, the present study demonstrates the possibility of applying an integrated algorithm to automatically assess and generate error patterns typical of aphasic speech. Philological studies and aphasia studies share one common point: errors (or variants) are informative, and the intention of the authors (in the case of philology) or of the patients (in the case of aphasiology) is to be established. For this precise reason, the present study adapts a tool, originally used in computational philology for the alignment of textual variants (Boschetti, 2007, 2008), and puts it to use for assessing aphasic patient's speech error patterns. As is demonstrated, this tool is effective and analytical. The authors expect this to be beneficial for the use of analysing aphasic production in both clinical and academic settings.

Reversed concreteness effect for nouns in a subject with semantic dementia.

Selective sparing of abstract relative to concrete words has been documented only exceptionally in aphasia, following bilateral temporal damage. In this paper we present a new case with sparing of abstract word processing and impairment of concrete words due to selective atrophy of the left anterior temporal regions.In our subject, the reversal of the concreteness effect was restricted to nouns. Performance on nouns was not homogeneous. Proper names (people and landmarks) were very severely damaged. Among common names, living entities were selectively impaired in comparison to non-living entities. Category-specific damage for living beings resulted from widespread loss of conceptual information, and perceptual information was less impaired than associative knowledge. This observation challenges theories explaining the reversal of concreteness effect with a selective loss of perceptual information. Also the alternative account, namely a different representational architecture for abstract as opposed to concrete terms, with an advantage for concrete words accruing from an impairment of categorical information, fails to account for the data.Most subjects showing preserved knowledge of abstract words, relative to concrete words, suffer from diseases affecting anterior temporal regions (semantic dementia, herpes encephalitis), and frequently present with greater, or unilateral involvement of the left hemisphere. Our case converges with similar previous reports and with some neuroimaging studies in suggesting that the right temporal lobe and probably the left inferior prefrontal gyrus play a crucial role in the representation of abstract concepts.

Posterior cerebral artery infarcts and semantic category dissociations: a study of 28 patients.

In this study we analysed the relationship between damage in the territory of the posterior cerebral artery and semantic knowledge, with special reference to category dissociations. Twenty-eight posterior cerebral artery stroke patients (18 left, 8 right and 2 bilateral posterior cerebral artery infarctions) completed a neuropsychological battery aimed at assessing semantic knowledge. The battery included picture naming, word-picture matching, a verbal semantic questionnaire and a picture reality decision task. For each participant, the lesion was reconstructed on the basis of MRI images, and was classified according to the involvement of the areas supplied by posterior cerebral artery. Defective naming scores were observed in 12 of 18 left posterior cerebral artery cases (67%), four of eight right posterior cerebral artery cases (50%), and one of two bilateral posterior cerebral artery cases (50%). Only in the bilateral posterior cerebral artery lesion case did we observe the pattern expected in pure visual agnosia, i.e. poor picture naming, poor picture reality decision, and normal verbal semantic questionnaire. Nine left posterior cerebral artery cases and two right posterior cerebral artery cases presented with poor performance on both the picture naming task and the verbal semantic questionnaire, thus suggesting semantic impairment. For 5 of the 12 left posterior cerebral artery patients who fared poorly on the naming task, biological stimuli (overall) were significantly more impaired than artifacts. In three of these five subjects, performance on plant-life stimuli was significantly less accurate than that on animals. A further left posterior cerebral artery patient presented a disproportionate impairment on plant-life stimuli only on the word-picture matching and on the questionnaire. The patterns of performance in these subjects suggest that the observed dissociations originated at the semantic level. Among left posterior cerebral artery patients, a naming deficit only occurred when damage to the fusiform gyrus extended anterior to Talairach's y-coordinate -50, and a disproportionate impairment of biological categories only when the lesion extended anterior to y = -32.5. Results show that the semantic deficit for the category of plant life is a genuine cognitive pattern, and does not depend on loss of colour knowledge. The contrast of left posterior cerebral artery strokes and herpes simplex encephalitis cases shows that the neural substrates for the semantic representation of plant life and animals are, at least in part, distinct. Middle and posterior portions of the left fusiform are crucial for the representation of plant-life knowledge, whereas left anterior temporal areas are more crucial than left posterior and basal temporal areas for the representation of knowledge about animals.

The effect of a silybin-vitamin e-phospholipid complex on nonalcoholic fatty liver disease: a pilot study.

Oxidative stress leads to chronic liver damage. Silybin has been conjugated with vitamin E and phospholipids to improve its antioxidant activity. Eighty-five patients were divided into 2 groups: those affected by nonalcoholic fatty liver disease (group A) and those with HCV-related chronic hepatitis associated with nonalcoholic fatty liver disease (group B), nonresponders to treatment. The treatment consisted of silybin/vitamin E/phospholipids. After treatment, group A showed a significant reduction in ultrasonographic scores for liver steatosis. Liver enzyme levels, hyperinsulinemia, and indexes of liver fibrosis showed an improvement in treated individuals. A significant correlation among indexes of fibrosis, body mass index, insulinemia, plasma levels of transforming growth factor-beta, tumor necrosis factor-alpha, degree of steatosis, and gamma-glutamyl transpeptidase was observed. Our data suggest that silybin conjugated with vitamin E and phospholipids could be used as a complementary approach to the treatment of patients with chronic liver damage.

Spelling and dysgraphia.

Early cognitive models of spelling assumed that orthographic word representations are linear, ordered sequences of abstract letter identities (graphemes), activated only by word meaning information, and in some cases proposed that activating phonological information is a necessary stage of the spelling process. Over the past 20 years, studies on dysgraphia have shown that orthographic representations are autonomous from phonological representations and, just like the latter, are directly activated from semantics. The selection of an orthographic form for output relies on the convergence of activation from lexical-semantic information and from sublexical phoneme-grapheme conversion procedures. In addition, it is increasingly clear that orthographic representations are multidimensional objects that separately represent the graphosyllabic structure (or perhaps the nucleus/non-nucleus positions) of the target, and the identity, the CV status, and the quantity (doubling) of each grapheme. In spelling, the structure of orthographic knowledge and the mechanisms involved in processing serial order interact in complex ways and constrain performance accuracy. Further research is needed to clarify some critical issues: We need to specify in greater detail the mechanisms involved in the interaction between meaning and sublexical information; we must consider the possibility that orthographic representations have texture, in addition to structure; we must provide explicit hypotheses on the mechanisms that process orthographic knowledge; and we must gain a better understanding of the interaction between structure and serial order.

Hyperproduction of fibrin and inefficacy of antithrombin III and alpha2 macroglobulin in the presence of bacterial porins.

Bacterial porins enhance the thrombin activity upon chromogen substrate chromozym. Should porin-dependent enhancement of thrombin activity take place also upon fibrinogen in vivo, this might greatly increase the fibrin production which, in turn, might lead to blood vessel obstruction. In this study, we demonstrate fibrin hyperproduction in a simplified coagulative system, consisting of fibrinogen and thrombin-pure molecules, in the presence of bacterial porins. In particular, bacterial porins, in the presence of thrombin, significantly increased the fibrin production compared with thrombin alone. Also, fibrin hyperproduction took place even in the presence of the thrombin inhibitors antithrombin III (AT III) or alpha2 macroglobulin (alpha2M). However, the thrombin-fibrinogen reaction in the presence of AT III or alpha2M did not generate fibrin, unless porins were present. In conclusion, porins not only enhance thrombin activity but also inhibit the antithrombin activity exerted by AT III or alpha2M. We hypothesize that, because of porins activity, fibrin is largely generated due to thrombin hyperactivation. Moreover, further fibrin is produced by thrombin, which is not blocked by two serpins for the presence of porins. These results might be relevant as to the occurrence of disseminated intravascular coagulation in sepsis by gram-negative bacteria, which are known to produce porins.