Assuntos
Comparação Transcultural , Reflexo de Sobressalto , Transtornos de Tique/etnologia , Adolescente , Adulto , Idade de Início , Criança , Feminino , França/etnologia , Humanos , Maine/epidemiologia , Masculino , Quebeque/epidemiologia , Síndrome , Transtornos de Tique/diagnóstico , Transtornos de Tique/epidemiologia , Gravação de VideoteipeRESUMO
The symptoms and signs associated with all stages of a temporal lobe seizure may be helpful in determining both the localization and lateralization of seizure onset. Auras, when present, may be very suggestive of temporal lobe onset and may further localize to a mesiobasal or lateral temporal lobe site of onset. During the ictus, automatisms and motor phenomena may be highly indicative of temporal lobe seizure activity and may even help lateralize the discharge. In the post-ictal period, motor paresis and aphasia are helpful in lateralization. Video E.E.G. data has provided extensive information on the utility of ictal symptomatology in seizure localization. Thus, the seizure semiology provides important adjunctive information in evaluating patients for epilepsy surgery and should be concordant with information obtained from ictal EEG, neuroimaging and neuropsychology.
Assuntos
Encéfalo/fisiopatologia , Epilepsia do Lobo Temporal/fisiopatologia , Automatismo/fisiopatologia , Epilepsia/fisiopatologia , Humanos , Atividade MotoraRESUMO
BACKGROUND: We examined the lateralizing value of postictal language and motor deficits and studied their underlying mechanisms. PATIENTS AND METHODS: The total sample consisted of 35 patients (26 temporals, 8 frontals, 1 parietal) with a good postsurgical outcome (Engel's class I and II). Postictal examination was blindly reviewed on videotapes. In 15 cases (29 seizures), postictal language manifestations were analyzed in relation with the diffusion of the epileptic discharge recorded by intracerebral EEG. Language dominance was determined by the intracarotid amobarbital test. RESULTS: Postictal aphasia was observed only when (1) seizure originated in the dominant hemisphere and (2) ictal activity spread to language areas (Wernicke and/or Broca areas). When the epileptic focus was in the nondominant hemisphere, no postictal aphasia was observed even if there was secondary generalization of ictal activity affecting the language areas of the dominant hemisphere. Postictal motor deficits also had a strong lateralizing value even when seizures were secondarily generalized. CONCLUSION: Postictal aphasia in temporal epilepsies and postical motor deficits in temporal and extra temporal epilepsies provided excellent lateralizing information. Postictal deficits appear to be the result of inhibitory mechanisms induced by previous ictal activity of the structures related to these functions.
Assuntos
Afasia/etiologia , Epilepsia/complicações , Destreza Motora , Paresia/etiologia , Adolescente , Adulto , Criança , Eletroencefalografia , Epilepsia/fisiopatologia , Epilepsia/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Clinical features that may help to differentiate medial temporal lobe epilepsy (MTLE) from neocortical temporal lobe epilepsy (NTLE) are lacking. OBJECTIVE: To investigate the localizing and lateralizing value of the association of ipsilateral motor automatisms and contralateral dystonic posturing in patients with medically refractory temporal lobe epilepsy. PATIENTS AND METHODS: Videotapes of 60 patients with well-defined MTLE, NTLE, or both were reviewed to assess the presence and the localizing value of unilateral dystonic posturing associated with motor automatisms. RESULTS: Twenty-eight of the 60 patients exhibited unilateral dystonic posturing. This sign was observed in patients with MTLE and NTLE. It was mostly contralateral to the seizure focus in patients with MTLE and exclusively ipsilateral in patients with NTLE. Unilateral motor automatisms occurred in 26 of the 60 patients with MTLE or NTLE. It was predominantly ipsilateral to the seizure focus in patients with MTLE and exclusively contralateral in patients with NTLE. The association of ipsilateral motor automatisms and contralateral dystonic posturing was found in 14 patients with MTLE but in none of the patients with NTLE. Two patients who had medial and neocortical seizure onset also exhibited this clinical feature. This association was not significantly correlated with the postoperative outcome in patients with MTLE. CONCLUSIONS: The association of ipsilateral motor automatisms and contralateral dystonic posturing may help to differentiate MTLE from NTLE with a reliable lateralizing value. This clinical association may reflect a specific pattern in the spread of the ictal discharge.
Assuntos
Automatismo/complicações , Distonia/complicações , Epilepsia do Lobo Temporal/complicações , Lateralidade Funcional/fisiologia , Postura , Desempenho Psicomotor/fisiologia , Adulto , Atrofia/patologia , Atrofia/cirurgia , Automatismo/diagnóstico , Distonia/diagnóstico , Eletroencefalografia , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/cirurgia , Feminino , Seguimentos , Hipocampo/patologia , Hipocampo/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Estudos Retrospectivos , Índice de Gravidade de Doença , Lobo Temporal/metabolismo , Gravação em VídeoRESUMO
7 cases of pure multiple subpial transection (MST) without associated cortical resection, for treatment of pharmaco-resistant partial epilepsy localized in highly functional cortical area, are reported. The transections were performed following the technique described by Morrell. The follow-up period ranged from 1 to 4 years. MST induced no significant neurological handicap: only 2 patients experiencing a transitory sensory-motor deficit and with total recovery within 1 month. With respect to seizures, 5 patients were improved with a decrease in seizure frequency of 100, 95, 75, 60 and 40%, respectively. Complex partial seizures changed postoperatively into simple partial seizures in 1 case. In conclusion, this procedure seems to be adequate, although no statistically significant results are available at this time. In our series, we believe failures could be attributed to either a very restricted area of transection or to an incorrect delimitation of the epileptic focus.
Assuntos
Epilepsias Parciais/cirurgia , Pia-Máter/cirurgia , Adulto , Criança , Resistência a Medicamentos , Eletroencefalografia , Feminino , Seguimentos , Humanos , MasculinoRESUMO
Quantitative analysis of hippocampal formations (HF) by magnetic resonance imaging (MRI) was correlated with depth electrode recordings in 18 patients with partial epilepsy. All had seizures of mesiotemporal origin. Electrodes explored three HF segments: amygdala and HF head and anterior and posterior HF body. Corresponding HF measurements were made on coronal MRI sequences, and atrophy was quantified by one global and three segmental indexes of asymmetry per patient. HF from which seizure originated showed global atrophy in 15 patients. Segmental analysis demonstrated discrete tissue damage in 1 patient; thus, 16 patients (88%) had significant hippocampal atrophy ipsilateral to the mesial focus. The existence of more pronounced atrophy in segments giving rise to ictal onset than in segments without ictal onset was not statistically significant. Nevertheless, in posterior HF, all segments (four) with seizure onset were atrophied and none of the nonatrophied posterior segments (four) were at seizure origin. These findings confirm that MRI-detected hippocampal atrophy is a powerful indicator of a mesiotemporal focus and strongly contributes to consideration of resective surgery without intracerebral EEG monitoring. Study of the distribution of maximal tissue damage may add some information, and help surgeons decide on the posterior extent of hippocampus removal. As illustrated by 3 patients who had multiple sites of seizure onset, however, the presence of this marker should not be interpreted systematically as evidence of pure mesiotemporal epilepsy.
Assuntos
Eletroencefalografia , Epilepsia do Lobo Temporal/diagnóstico , Hipocampo/patologia , Imageamento por Ressonância Magnética , Adolescente , Adulto , Criança , Eletrodos Implantados , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose , Técnicas EstereotáxicasRESUMO
We examined the prognostic value of spatial and temporal characteristics of intracerebral propagation of seizures during temporal lobe epilepsy (TLE) surgery. Seven TLE patients resistant to standard anterotemporal lobectomy who had no known causes of resistance [e.g., extratemporal (ET), lesions, multifocal epilepsy] were matched with 7 seizure-free patients and 7 others who were almost seizure-free after operation. Intracerebral ictal propagation pathways were not different in the three groups. Propagation was multidirectional, most frequently to the frontal lobes and sometimes to the contralateral temporal lobe (CTL). ET propagation delays were significantly shorter in resistant patients than in markedly improved patients. The resistant group also had more frequent propagation delays < 1.0 s, but propagation times > 1.0 s were equally likely in all groups. The extent of ET propagation and frequency of focal onsets were not different among the groups. Results suggest that very short propagation times predict reduced efficacy of operation, and that long propagation times are not related to surgical success.
Assuntos
Eletroencefalografia , Epilepsia do Lobo Temporal/cirurgia , Lobo Frontal/fisiopatologia , Lateralidade Funcional/fisiologia , Complicações Pós-Operatórias/fisiopatologia , Lobo Temporal/cirurgia , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/etiologia , Epilepsias Parciais/fisiopatologia , Epilepsia do Lobo Frontal/diagnóstico , Epilepsia do Lobo Frontal/etiologia , Epilepsia do Lobo Frontal/fisiopatologia , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Humanos , Masculino , Vias Neurais/fisiopatologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Lobo Temporal/fisiopatologiaRESUMO
OBJECTIVE: To determine the occurrence of magnetic resonance imaging-detected hippocampal atrophy (HA) in patients with partial epilepsy (temporal and extratemporal, cryptogenic, or symptomatic). Magnetic resonance imaging-detected HA has been demonstrated to be both sensitive and specific for hippocampal sclerosis in cryptogenic temporal lobe epilepsy. DESIGN: Patients' hippocampal formations were measured on a computerized system using T1-weighted, 5-mm contiguous magnetic resonance coronal images made perpendicular to the hippocampus long axis. Hippocampal atrophy was defined on the basis of a normative asymmetry index and correlated with the epileptogenic focus defined by clinical, electroencephalographic, and magnetic resonance imaging (apart from HA) localizing data. PATIENTS AND CONTROL SUBJECTS: Seventy patients with intractable complex partial seizures of temporal, extratemporal, or undefined origin and 21 healthy control subjects. RESULTS: Hippocampal atrophy was present in 70% of patients with cryptogenic temporal lobe epilepsy (TLE) (n = 40), 44% of patients with symptomatic TLE (n = 9), 29% of patients with extratemporal epilepsy (n = 14), and 6% of unclassified patients (n = 16). In the cryptogenic TLE category, HA was marked and usually concordant (93%) with electroencephalographic lateralization. Hippocampal atrophy was often mild in the extratemporal epilepsy category. With the use of a wider confidence interval (+/- 3.1 SD instead of +/- 2.2 SD), HA specificity for TLE increased to 93%, HA specificity for lateralizing cryptogenic TLE reached 96%, and HA sensitivity for cryptogenic TLE stood almost unchanged (68%). We found a link between early convulsions and HA occurrence. CONCLUSIONS: Hippocampal atrophy is a marker for TLE. Dual pathologic findings are detected in 44% of symptomatic TLE cases. Mild HA is rarely associated with extratemporal epilepsy. Magnetic resonance imaging-based hippocampal volumetric analysis is a useful method to localize the origin of partial complex seizures.
Assuntos
Epilepsias Parciais/diagnóstico , Hipocampo/patologia , Imageamento por Ressonância Magnética , Adulto , Atrofia , Eletroencefalografia , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/cirurgia , Hipocampo/fisiopatologia , Humanos , Pessoa de Meia-IdadeRESUMO
We examined the hypothesis of dorsomedial frontal lobe involvement in target detection through the effects of distractor interference and multiple target interference on unilateral lobectomy patients. Seven patients who underwent a unilateral frontal lobectomy for epilepsy involving dorsomedial cortex and variable amounts of lateral cortex were compared to 10 patients with a unilateral temporal lobectomy and to 10 normal adults on a visual character cancellation task. The task involved detecting occurrences of target characters embedded in rows of characters under three conditions: detection of one target character in the absence of distractors, detection of one target character among distractors, and detection of three targets among distractors. Visual detection performance was compared to that in the Stroop reading interference task. Frontals were predictably slower than the other groups in the baseline conditions of the character cancellation task and the Stroop task. After partialing out baseline detection performance in the character cancellation task, frontals showed an almost normal detection in the presence of distractors but were distinctly slower and made more errors than the other groups in multiple target detection. Frontals were also slower on the Stroop even after partialing out baseline naming performance. Temporals were normal on all tasks. Results suggest that frontal damage can affect selectivity in target detection as well as the Stroop and that this deficit is independent of the general psychomotor slowing observed in these patients.
Assuntos
Encefalopatias/fisiopatologia , Lobo Frontal/cirurgia , Adolescente , Adulto , Criança , Feminino , Lobo Frontal/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Desempenho Psicomotor , Psicocirurgia , Campos Visuais , Percepção VisualRESUMO
We examined the somatosensory perceptions evoked by stimulation of rolandic and parietal brain regions in 40 epileptic patients undergoing a presurgical investigation with intracerebral electrodes. Bipolar stimulation trains were delivered in an incremental sequence at medial and/or lateral contact pairs of stereotaxically implanted, multi-contact electrodes, while monitoring stimulus after discharge propagation with electrodes in frontal and temporal lobes. Rolandic stimulation evoked contralateral sensations, whereas sensations from either side were evoked in the opercular region. Stimulation of lateral posterior parietal cortex evoked only few sensations and these were restricted to the supramarginal gyrus. Contralateral sensations were evoked in the posterior cingulate gyrus, whereas ipsilateral sensations were evoked in the vicinity of the cingulate sulcus. Complex proprioceptive sensations in the form of bilateral feelings of levitation were elicited in a medial parietal region around the subparietal sulcus and not at any other site. These perceptions were not accompanied by any movement, tactile, or vestibular sensations, suggesting that the human sub-parietal sulcus region is linked to the proprioceptive processing system.
Assuntos
Córtex Somatossensorial/fisiologia , Tato/fisiologia , Eletrodos , Epilepsia/fisiopatologia , Humanos , Processos Mentais/fisiologia , Estimulação Física , Propriocepção/fisiologia , Técnicas EstereotáxicasAssuntos
Epilepsia do Lobo Frontal/fisiopatologia , Adolescente , Adulto , Córtex Cerebral/fisiopatologia , Estimulação Elétrica , Eletroencefalografia , Epilepsia Parcial Complexa/fisiopatologia , Epilepsia do Lobo Frontal/psicologia , Epilepsia do Lobo Frontal/cirurgia , Feminino , Humanos , Masculino , Córtex Motor/fisiopatologiaAssuntos
Epilepsia do Lobo Frontal/diagnóstico , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Frontal/fisiopatologia , Epilepsia do Lobo Temporal/fisiopatologia , Lobo Frontal/anatomia & histologia , Lobo Frontal/fisiologia , Humanos , Córtex Motor/anatomia & histologia , Córtex Motor/fisiologiaRESUMO
The currently available surgical procedures for the treatment of epilepsy, from fundamental data to therapeutic results, including various means of investigation are reported. The work is based on a review of the literature and on the cases studied by the two teams from the Universities of Montreal and Bordeaux who share the same concept of epilepsy surgery. The patient groups of the two teams include 316 S.E.E.G., 214 cortectomies, 39 callosotomies and 2 multiple sub-pial transsections. In the first part, the authors attempt to demonstrate that the epileptic focus corresponds to the region where the seizures arise, that this focus is not directly comparable to the region where inter-ictal spikes are recorded and sometimes becomes autonomous from the causal lesion. The epileptic phenomenon has a definite harmful effect on cerebral functions and a probable self-aggravating potential. The second chapter summarizes the clinical data on which the indications and contraindications are based. These obviously depend on whether the intervention is intended to be curative or palliative. Various non-invasive and invasive investigations are then reviewed, according to their relative importance and the experience of each team. The main points developed are: the electroclinical correlations during seizures, the symptomatological data for differentiating between temporal and frontal lobe seizures, the contribution of M.R.I. in demonstrating the epileptogenic and epileptic lesions, the electrophysiological information suggesting that S.E.E.G. remains the most informative mean of investigation. The various methods of investigation of assessing electrical, functional (cerebral blood flow, metabolism) and morphological aspects of epilepsy, supply non-redondant findings about the localisation of the epileptic focus. The chapter on surgical techniques mainly discusses the various modes of implantation of subdural and intracerebral electrodes and reports the same rate of morbidity in both cases. Orthogonal teleradiography is still perfectly suited to the implantation of intracerebral electrodes. S.E.E.G. is still the most anatomically precise technique. However, in certain conditions, extraoperative E.Co.G. is more adequate. New surgical modalities have recently appeared such as the multiple subpial transsections which allow treatment of epileptic foci unapproachable by cortectomy and such as modified techniques of hemispherectomy, which by decreasing morbidity, renew interest in them. In the chapter on surgical results, the authors emphasize the methodological problems of evaluation that partly account for their wide variability. The results obtained with the various surgical modalities are reviewed. The outcome in cortectomies is discussed at length in terms of the data from the literature as well as the results reported by both teams.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Epilepsia/cirurgia , Adolescente , Adulto , Encéfalo/cirurgia , Criança , Pré-Escolar , Epilepsia/diagnóstico , Epilepsia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We have compared the relative localizing value of common tests in the presurgical evaluation of epilepsy in 73 patients with depth electrode (SEEG) confirmed epileptogenic foci and excellent surgical outcome. We found the tests of abnormality (CT, amytal, neuropsychology) to be frequently non-informative and often discordant with SEEG. The EEG was concordant with the SEEG in 38% of cases and provided lateralization in 78%. EEG was less localizing than ictal behavior in frontals but not in temporals. The need for SEEG is rather evident in these results but could become attenuated by the development of the localizing power of scalp EEG.
Assuntos
Epilepsia/diagnóstico , Eletroencefalografia , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/cirurgia , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Epilepsia do Lobo Frontal/diagnóstico , Epilepsia do Lobo Frontal/diagnóstico por imagem , Epilepsia do Lobo Frontal/cirurgia , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/cirurgia , Humanos , Cuidados Pré-Operatórios , Tomografia Computadorizada por Raios XRESUMO
The effects of physiological noise and modelling procedure on spatio-temporal source modelling (STSM) solutions were examined by adding EEG noise (3-4% of total energy) to synthetic signals from 3 dipoles producing topographies that partially cancelled at the surface of an homogeneous sphere. Three patterns of source activation profiles were each associated with two EEG records. The STSM solutions were subjected to statistical tests that detect signal left in the residuals. All models substantially accounted for noise. Essentially correct models left no consistent signal in the residuals, but other statistically acceptable models were also occasionally found. Unambiguous correct solutions were found for moderately correlated source activations. Statistically adequate 2-source and 3-source models were found for the 4 data sets incorporating nearly parallel activations of 2 sources. When all 3 sources had comparable amplitudes, the 2-source models represented compromises containing gross mislocalizations but correct 3-source models were found. When one of the parallel sources was attenuated by 75%, only 2-source models satisfactorily approximated the 2 main sources. The localization errors in the "correct" models ranged from 2.5% to 13% of the sphere radius. Thus, even with a perfect signal propagation model, STSM could at best claim approximate localizations from data containing structured noise.
Assuntos
Encéfalo/fisiologia , Eletroencefalografia , Modelos Neurológicos , HumanosRESUMO
Visual phenomena evoked by direct electrical stimulation of extrastriate cortex were observed in 30 epileptic patients as part of a presurgical investigation. An incremental sequence of low-level bipolar stimulation trains was delivered at medial and lateral pairs of contacts of stereotaxically-implanted multilead intracerebral electrodes in parietal, occipital and posterior temporal regions. Diffusion of stimulus afterdischarges was monitored by electrodes in temporal and frontal lobes and by the non-stimulated contacts of the stimulated electrode. Localized stimulations evoked few visual phenomena. The strongest anatomo-perceptual correlation was found for stimulation in the medial parieto-occipital fissure which evoked visual motion phenomena in all three patients stimulated in that region. The evoked motion perceptions were not associated with eye movements or any particular localization of the epileptic focus. These perceptions were only evoked once outside of the medial PO region at the 61 sites examined. The results suggest that the medial parieto-occipital region is closely linked to the human visual motion processing system.
Assuntos
Epilepsia/fisiopatologia , Percepção de Movimento/fisiologia , Lobo Occipital/fisiologia , Lobo Parietal/fisiologia , Mapeamento Encefálico , Estimulação Elétrica , Epilepsia/cirurgia , Humanos , Imageamento por Ressonância Magnética , Lobo Occipital/patologia , Lobo Occipital/fisiopatologia , Lobo Parietal/patologia , Lobo Parietal/fisiopatologia , Valores de ReferênciaRESUMO
The concordance between the epileptogenic area as determined by intracranially recorded spontaneous seizure onset and that determined by electrically induced auras or seizures in 126 patients with medically intractable epilepsy was studied. Four to 11 multicontact depth electrodes were chronically implanted in patients as part of a preoperative investigation procedure. Localization of the epileptic area was obtained from the recording of three spontaneous seizures and from stimulation data including self-reported auras, seizures, and intracranial EEG afterdischarges recorded during an incremental stimulation sequence at all cortical pairs of contacts. Positive responses to stimulation were obtained in 63% of patients. Concordance between spontaneous and induced auras or seizures was greater than 90% with single unilateral foci and less with multiple foci. Stimulation data reliably predicted the resection area in unilateral and bilateral temporal foci but not in other locations. Afterdischarge thresholds were not reliable predictors of the spontaneous seizure focus. The intracranial stimulation procedure used appears to provide useful confirmatory and complementary localizing information in relation to that obtained from spontaneous seizures.
Assuntos
Encéfalo/fisiopatologia , Epilepsia/fisiopatologia , Limiar Diferencial , Estimulação Elétrica , Eletroencefalografia , Eletrofisiologia , Previsões , HumanosRESUMO
The indications of surgery for epilepsy are: 1) resistance to medical treatment; 2) well-localized cortical focus, and 3) possibility of removing the focus without creating a significant functional deficit. Presurgical evaluation is initially clinical: correlations between the clinical manifestations recorded on videotapes and EEG tracings, neurological and neuropsychological examinations, intra-carotid amytal test. Interictal and, preferably, ictal EEG recording on the scalp and in depth is the fundamental procedure used to locate epileptogenic areas. The most reliable locating examination is the recording of a spontaneous seizure by means of implanted electrodes. Recent or old lesions responsible for epilepsy can be detected by arteriography, ventriculography, CT scans and, more recently, nuclear magnetic resonance. PET scan and SPECT are not commonly used. The ideal operation is cortectomy which gives the best long-term results (87 p. 100 in temporal lobe epilepsy). When cortectomy is not feasible, complete or partial (anterior two-thirds) callosotomy can be of considerable help in some forms of epilepsy with frequent falls and generalized seizures. On the whole, it seems that the surgical treatment of epilepsy is grossly underused.
Assuntos
Eletroencefalografia , Epilepsia/cirurgia , Cuidados Pré-Operatórios/métodos , Córtex Cerebral/cirurgia , Corpo Caloso/cirurgia , Eletrodos Implantados , HumanosRESUMO
To test the three main hypotheses of the human amnesic syndrome (encoding, consolidation, retrieval), we designed an original protocol for memory assessment under Amytal that included, in addition to a retrograde memory measure, both short-term and long-term anterograde memory measures. Twenty epileptic patients with SEEG-confirmed unilateral temporal lobe foci were given right and left injections on successive days. Only the long-term memory measure for material presented under Amytal was significantly related to the presence of a temporal contralateral epileptogenic focus, even if it was assessed when the hemisphere had completely recovered from the effect of Amytal. Short-term memory deficits were observed equally often after injections ipsilateral and contralateral to the epileptogenic focus, and no retrograde amnesia was observed. These results are consistent with the consolidation hypothesis.