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Background: QEEG cordance and low-resolution electromagnetic tomography (LORETA) are relatively new applications of QEEG. Four small-scale studies have shown that decreases of QEEG prefrontal theta cordance after the first week on new antidepressants predict clinical response to treatment in patients with unipolar depression., Methods: We calculated prefrontal theta cordance and changes in 3D distribution of brain electrical activity using LORETA in the case of a 54-year old man experiencing his third depressive episode., Results: We did not detect a decrease of prefrontal theta cordance after one week of new treatment and the patient did not respond to this therapy after four weeks. However, we observed a decrease of prefrontal theta cordance after the first week of clomipramine therapy. Manic symptoms emerged after two weeks of clomipramine treatment. A decrease of prefrontal theta cordance preceded the clomipramine induced switch to hypomania during the next episode of depression also. LORETA before and during clomipramine therapies detected a significant increase of theta in the right postcentralis gyrus in the parietal lobe, and a borderline increase of alfa2 in the right middle frontal gyrus., Discussion: In a patient with bipolar spectrum disorder we found that a treefold change in theta prefrontal cordance preceded mood changes in a similar way as in patients with unipolar depression. We speculate that the changes detected by LORETA can attributed to the anticholinergic activity of clomipramine and the specific effects of a mood switch. Our data suggest that the new applications of QEEG can be sensitive to mood changes and have potential in bipolar disorder research.

The present study tested the hypothesis that functional cortico-muscular coupling is a putative physiological mechanism by which Brodmann area 10 (BA10) of anterior prefrontal cortex controls subjects' behavior. Intracerebral stereo electroencephalographic (SEEG) data were recorded from BA10 of epilepsy subjects in the course of pre-surgical monitoring. During the SEEG recordings, these subjects were engaged in three conditions: the execution of intentional hand muscle contractions as triggered by auditory stimuli ("EXE"); the execution of the same muscle contractions as an imitation of a person seated in front of the subject ("IMI"); and the mere observation of the hand muscle contractions performed by that person ("OBS"). SEEG frequency bands of interest were theta (4-7 Hz), alpha (8-12 Hz), beta 1 (13-21 Hz), beta 2 (22-30 Hz), and gamma (31-45 Hz). Results showed that functional cortico-muscular coupling at gamma band was higher in amplitude during the intentional muscle contraction ("EXE") than the other conditions ("IMI" and "OBS"). Instead, cortico-muscular coupling at theta band was higher in amplitude during the imitative muscle contraction ("IMI") than the other conditions ("EXE" and "OBS"). In parallel, there was an increase of SEEG gamma band power during the intentional muscle contraction and an increase of SEEG theta band power during its imitation. The present results suggest that anterior prefrontal cortex (BA10) might control subjects' behavior by means of functional cortico-muscular coupling at selective frequency bands (theta and wide gamma rhythms).

We were interested to know if chronic l-DOPA treatment in Parkinson's disease (PD) patients could restore impairment of the intracortical excitability, when this difference could occur, and if it was related to the total daily dose of l-DOPA. Twelve patients with early PD were studied using paired transcranial magnetic stimulation before the administration of l-DOPA, and then after 3, 6, and 12 months of l-DOPA treatment. The level of disturbed intracortical excitability strongly correlated with the total daily dose of l-DOPA. The level of cortical excitability in PD patients seems to be indirectly related to the nigro-striatal functioning.

Miller Fisher syndrome (MFS) is a localized variant of Guillain-Barré syndrome (GBS), characterized by ophthalmoplegia, areflexia, and ataxia. Recent neurophysiological studies have suggested that abnormal terminal axon dysfunction occurs in some cases of Miller Fisher syndrome and Guillain-Barrd syndrome. We present a rare case report of recurrent MFS with abnormal terminal axon dysfunction. To the best of our knowledge, this is the first case report of recurrent MFS with terminal axon dysfunction that persisted up to nine months after the initial presentation of the second attack with positive antiganglioside antibodies and full clinical recovery.

Background: The aim of our study was to evaluate the efficacy of electroconvulsive (ECT) and venlafaxine therapy from the patient's point of view., Methods: We used a retrospective chart review from 22 inpatients who underwent ECT and 22 patients treated with venlafaxine due to resistant unipolar or bipolar depression. We used bilateral ECT in a median of 8 (IQR 7-9.7) sessions and venlafaxine therapy with a median daily dosage of 225 mg (IQR 150-225 mg) for a median of 4 (IQR 4-5) weeks. The main outcome was change in a self-evaluation scale - Short Form of the Beck Depression Inventory (BDI-SF). The response was defined as the decreasing of the BDI-SF score by >or=50%, remission as decreasing of BDI-SF score

This study concerns the question of how task modification affects the frequency occurrence of event-related potentials (ERP) inside the active cortical areas. In 13 candidates for epilepsy surgery, 156 sites in the temporal (74), frontal (73), and parietal (9) cortices were recorded by means of depth and subdural electrodes. Four modifications of the somatosensory evoked P3-like potentials were performed; (i) an oddball paradigm with silent counting of target stimuli (P3c); (ii) an oddball paradigm with a hand movement in response to target stimuli (P3m); (iii) an S1-S2 paradigm, ERP in the P300 time window after the S2 stimulus, with silent counting of target stimuli (S2c), and (iv) an S1-S2 paradigm with a hand movement in response to target stimuli (S2m). In comparing the oddball paradigms with the S1-S2 (contingent negative variation, CNV) paradigms, four regions emerge that are significantly linked with the oddball P3; the prefrontal cortex, the cingulate, the amygdalo-hippocampal complex, and the lateral temporal cortex. A prominent role of the cingulate and the fronto-orbital cortex in the cognitive processing of movement was supported when tasks with identical cognitive loads but different required responses were compared. Even relatively simple cognitive tasks activate many cortical regions. The investigated areas were activated in all tests; however, small regions in each field were active or inactive in relation to the nature of the task. The study indicates a variable and task-dependent internal organization of a highly complex and widely distributed system of active cortical areas.

We present a case report of a 37-year old woman diagnosed with depressive disorder, first episode, who was admitted into a psychiatric hospital after a failed suicidal attempt. She responded to antidepressant therapy, as evidenced by a >50% reduction in MADRS total score. She was discharged after 4 weeks of treatment, denying any suicidal ideations. The following day the patient committed suicide; she burned herself to death. It is very likely that the patient dissimulated her symptoms and ideations. Subsequently, her quantitative EEG records were retrospectively analyzed. An increase of prefrontal theta cordance value after the first week of mirtazapine therapy was found. Recently three small studies have revealed that decrease of prefrontal theta cordance after 1 week of antidepressant administration can predict clinical response in patients with unipolar depression. In our previous study the absence of a decreased theta prefrontal cordance was associated with lack of treatment response with NPV 1.0 (Bares et al., 2007). Thus, we hypothesize that prefrontal theta cordance could become an objective marker of change of depressive symptoms, independent of patients' compliance and symptom dissimulation, more precise than objective and self-rated depression rating scales.

The ability to precisely time events is essential for both perception and action. There is evidence that the cerebellum is important for the neural representation of time in a variety of behaviors including time perception, the tapping of specific time intervals, and eye-blink conditioning. It has been difficult to assess the contribution of the cerebellum to timing during more dynamic motor behavior because the component movements themselves may be abnormal or any motor deficit may be due to an inability to combine the component movements into a complete action rather than timing per se. Here we investigated the performance of subjects with cerebellar disease in predictive motor timing using a task that involved mediated interception of a moving target, and we tested the effect of movement type (acceleration, deceleration, constant), speed (slow, medium, fast), and angle (0 degrees , 15 degrees and 30 degrees) on performance. The subjects with cerebellar damage were significantly worse at interception than healthy controls even when we controlled for basic motor impairments such as response time. Our data suggest that subjects with damage to the cerebellum have a fundamental problem with predictive motor timing and indicate that the cerebellum plays an essential role in integrating incoming visual information with motor output when making predictions about upcoming actions. The findings demonstrate that the cerebellum may have properties that would facilitate the processing or storage of internal models of motor behavior.

Introduction: Previous studies of patients with unipolar depression have shown that early decreases of EEG cordance (a new quantitative EEG method) can predict clinical response. We examined whether early QEEG decrease represents a phenomenon associated with response to treatment with different antidepressants in patients with treatment resistant depression., Method: The subjects were 17 inpatients with treatment resistant depression. EEG data and response to treatment were monitored at baseline and after 1 and 4 weeks on an antidepressant treatment. QEEG cordance was computed at three frontal electrodes in theta frequency band. The prefrontal cordance combines complementary information from absolute and relative power of EEG spectra. Recent studies have shown that cordance correlates with cortical perfusion. Depressive symptoms were assessed using Montgomery-Asberg Depression Rating Scale (MADRS)., Results: All 17 patients completed the 4-week study. All five responders showed decreases in prefrontal cordance after the first week of treatment. Only 2 of the 12 nonresponders showed early prefrontal cordance decrease. The decrease of prefrontal QEEG cordance after week 1 in responders as well as the increase in nonresponders were both statistically significant (p-value 0.03 and 0.01, respectively) and the changes of prefrontal cordance values were different between both groups (p-value 0.001)., Conclusion: Our results suggest that decrease in prefrontal cordance may indicate early changes of prefrontal activity in responders to antidepressants. QEEG cordance may become a useful tool in the prediction of response to antidepressants.

Background: Transcranial magnetic stimulation (rTMS) can modulate cortical activity. The goal of our study was to assess whether rTMS would facilitate effect of serotonin reuptake inhibitors in patients with panic disorder., Method: Fifteen patients suffering from panic disorder resistant to serotonin reuptake inhibitor (SRI) therapy were randomly assigned to either active or to sham rTMS. The aim of the study was to compare the 2 and 4 weeks efficacy of the 10 sessions 1 Hz rTMS with sham rTMS add on SRI therapy. We use 1 Hz, 30 minutes rTMS, 110% of motor threshold administered over the right dorso-lateral prefrontal cortex (DLPFC). The same time schedule was used for sham administration. Fifteen patients finished the study,. Psychopathology was assessed using the rating scales CGI, HAMA, PDSS and BAI before the treatment, immediately after the experimental treatment and 2 weeks after the experimental treatment by an independent reviewer., Results: Both groups improved during the study period but the treatment effect did not differ between groups in any of the instruments., Conclusion: Low frequency rTMS administered over the right dorso-lateral prefrontal cortex after 10 sessions did not differ from sham rTMS add on serotonin reuptake inhibitors in patients with panic disorder.

Objective: Previous surface CNV studies including a hand motor output have suggested that the late phase of the CNV reflects the preparation of the sensorimotor cortices involved in the motor output given the same similarity in scalp potential distribution with readiness potential. However, the poor spatial resolution of the scalp recorded CNV data prevented a definitive conclusion. This intracerebral study allowed us to test this hypothesis using a CNV paradigm in which a non-motor task is used as a reference. This study concerned the intracerebrally located generators of the Contingent Negative Variation in two different paradigm settings: (i) motor output required, (ii) silent counting required (non-motor control condition)., Methods: Stereoelectroencephalography (SEEG) recordings of the contingent negative variation (CNV) in a somato-somatosensory stimulation paradigm with a motor or counting task were taken from nine patients with drug-resistant epilepsy. The intracerebral recordings were taken from 25 cortical areas in both hemispheres (supplementary motor area-SMA; the cingulate gyrus; the orbitofrontal, premotor and dorsolateral prefrontal cortices; lateral temporal cortex, amygdalohippocampal complex; and the parietooccipital cortex)., Results: The slow waves were generated in the SMA, the premotor, dorsolateral, and orbitofrontal cortices, the cingulate gyrus, and parts of the lateral temporal, mesial temporal structures and parietal cortex. We found a significant difference between the two tasks in the CNV potential generation. The task with the motor output produced significantly higher numbers of CNV potential generators when compared to the task with silent counting., Conclusions: The CNV potential generators varied between motor and non-motor tasks. The intracerebral distribution of the potentials linked with expectation is task dependent. Our main conclusion is that the executive network is more active during the motor task than during counting task.

Objective: Risperidone in antipsychotic doses induces hyperprolactinemia. The aim of this study was to verify whether the same is true for low doses of risperidone (0.5-2 mg per day) added to antidepressants or anxiolytics., Methods: Prolactin levels were measured in 4 men (mean age 49.5+/-19.1 years) and 8 women (mean age 31.3+/-8.2 years) inpatients with depressive and anxiety disorders who were treated with risperidone (median doses per day 1.25 mg) for median 15.5 days as an augmentation treatment to antidepressants (n=8), anxiolytics (n=6) and mood stabilizers (n=2)., Results: 11 of 12 patients had hyperprolactinemia. Median plasma prolactin level was 1598 mIU/ml, 95% CI 1 040-2 661 mIU/ml. Significant correlation between risperidone daily dose and plasma prolactin level (Spearman's R=0.655, p=0.02) was detected. Two women suffered from galactorrhea and one from amenorrhea., Conclusions: Even low doses of risperidone used as an augmentation to antidepressants or benzodiazepines are associated with hyperprolactinemia and can induce endocrinological side effects. The co-medication of antidepressants and benzodiazepines can potentially increase intensity of prolactinemia.

Background: The goal of our study is to assess whether transcranial magnetic stimulation (rTMS) would facilitate the effect of antidepressant in OCD patients., Method: The aim of the randomized, double-blind, sham controlled study was to compare the 2 and 4 week efficacy of the 10 sessions rTMS with sham rTMS in serotonin reuptake inhibitor resistant OCD patient. Thirty three right-handed patients were randomly assigned to either active rTMS or to sham rTMS. Active rTMS with the frequency of 1 Hz at 110% of motor threshold (MT) was administered over the left dorso-lateral prefrontal cortex. The same time schedule was used for sham administration. Thirty patients finished the study, three patients' dropped out at the beginning. Psychopathology was assessed by CGI, HAMA, Y-BOCS and BAI before the treatment, immediately after the experimental treatment, and 2 weeks after the experimental treatment by an independent reviewer., Results: Both groups improved during the study period but the treatment effect did not differ between them in any of the instruments., Conclusion: Low frequency rTMS administered over the left dorso-lateral prefrontal cortex during 10 daily sessions did not differ from sham rTMS in facilitating the effect of serotonin reuptake inhibitors in OCD patients.

Fourteen male patients suffering from Parkinson's disease, each of whom had been treated with L-DOPA, and in whom additional treatment with oral dopamine agonist (DA) was needed, were followed for a period of one year. Pergolide mesylate (Permax) was given to each patient, and titrated to a total daily dose of 3 mg. All of the patients were taking L-DOPA. The assessments performed before the start of pergolide treatment consisted of neurological examination, unified Parkinson's disease rating scale (UPDRS) III and IV subscales scoring, mini mental state examination (MMSE) scoring, the neuropsychological examination including Zung scale scoring, biochemical and hematological examinations including prolactine serum levels; and a sexological examination during which the patients filled-in the international index of erectile function (IIEF) questionnaire. These examinations were repeated during the control assessments at months 1, 3, 6 and 12. ANOVA, non-parametric Friedmann's ANOVA and Tukey post hoc tests were used for the statistical analysis. There were statistically significant differences between the values of UPDRS III motor subscale and all subscales of IIEF when months 0 and 1 were compared with the results obtained at months 3, 6 and 12. Pergolide mesylate, when added to L-DOPA, significantly improved all sexual functions in younger male Parkinsonian patients who were still interested in sexual activities. The treatment with pergolide in these cases might be more beneficial than with short-acting PDE-5 inhibitor sildenafile. Nevertheless, the relationship between pergolide treatment and incidence of restrictive valvular heart disease must be considered.

Purpose: Dropped head syndrome is characterized by a gradual forward sagging of the head due to the isolated weakness of the neck extensor muscles. The syndrome has a relatively benign clinical course. To date, there have been no reports of dropped head syndrome in epileptic patients., Methods: Nine patients with intractable epilepsy (mean age, 33.6+/-9.91 years), each presenting with apparent dropped head, were evaluated. The duration of the drooping head symptom varied from 3 to 15 years (mean, 7.4+/-4.06 years), with a slowly progressing weakness in most of the patients. In all of the patients, extensive clinical, laboratory, electrophysiological, histopathological, and neuroimaging examinations were performed., Results: The weakness in all of the subjects was strictly limited to the cervical paraspinal muscles. Laboratory studies produced normal results from all subjects. EMG and muscle biopsy were normal or revealed subtle nonspecific myopathic changes without inflammation in the cervical paraspinal muscles. Polymyographic investigation revealed that none of the patients had convincing dystonic spasms of the anterior neck muscles. No atrophy or fatty changes of the neck extensor muscles were observed on CT or MRI. In most of the patients (7/9), altered L-carnitine concentrations were observed (four patients displayed a marked decrease in plasma carnitine concentrations, and three other patients showed abnormalities in urinary excretion of carnitine)., Conclusions: These findings seem to suggest that a secondary carnitine deficiency, induced by antiepileptic drugs (principally valproic acid), represents a plausible pathogenetic mechanism for the development of dropped head in some epileptic patients.

Sources of potentials evoked by cognitive processing of sensory and motor activities were studied in 9 epilepsy surgery candidates with electrodes implanted in the basal ganglia (BG), mostly in the putamen. Several contacts were also located in the pallidum and the caudate. The recorded potentials were related to a variety of cognitive and motor activities (attentional, decisional, time estimation, sensory processing, motor preparation, and so on). In five different tests, we recorded P3-like potentials evoked by auditory and visual stimuli and sustained potential shifts in the Bereitschaftspotential and Contingent Negative Variation protocols. All of the studied potentials were generated in the BG. They were recorded from all over the putamen. Various potentials on the same lead or nearby contacts were recorded. A functional topography in the BG was not displayed. We presume that the cognitive processes we studied were produced in clusters of neurons that are organized in the basal ganglia differently than the known functional organization, e.g., of motor functions. The basal ganglia, specifically the striatum, may play an integrative role in cognitive information processing, in motor as well as in nonmotor tasks. This role seems to be nonspecific in terms of stimulus modality and in terms of the cognitive context of the task., (Copyright 2005 Movement Disorder Society.)

Objectives: Second-generation antipsychotics presumably lack the typical side effects of conventional antipsychotics., Methodology: A 34 year old Caucasian woman with ICD-10 diagnosis of Recurrent depressive disorder with current moderate symptoms, and with a history of repeated self-injury was treated with lithium, clonazepam and ziprasidone., Results: On the ninth day of ziprasidone administration, galactorrhea appeared. After 36 days of ziprasidone therapy, galactorrhea persisted. The prolactin plasma level was 28 ng/ml. Thyroid tests (TSH,T3,T4) and the lithium plasma level were within the normal range during ziprasidone treatment. Two weeks after the ziprasidone withdrawal, galactorrhea disappeared and the prolactin level decreased down to 18 ng/ml., Conclusion: Psychiatrists should be aware that even second-generation antipsychotics, including ziprasidone, have a propensity to cause side-effects associated with the dopamine D2 receptor blockade, such as galactorrhea.

Objectives: Amisulpride in antipsychotic doses can induce hyperprolactinemia. The aim of this study was to prove whether the same is true for low doses of amisulpride., Methodology: Plasma prolactin levels were measured in 5 males and 5 females with depressive symptoms who were treated with 50 mg of amisulpride per day as an augmentation to antidepressants (n=5), benzodiazepine anxiolytics (n=8) or in monotherapy (n=1). Six of these patients were assessed prior to onset of amisulpride treatment and after 10 days of amisulpride use. Four patients had been using amisulpride for more than a month., Results: There was a significant increase of prolactin levels from mean 16+/-6 ng/ml to 113+/-65 ng/ml (median 14.5 ng/ml to median 92 ng/ml; Wilcoxon matched pair test, p=0.027). All patients had hyperprolactinemia (30-200 ng/ml). The prolactinemia was significantly higher in females (mean 160+/-50 ng/ml; median 198 ng/ml) than in males (mean 48+/-12 ng/ml; median 48 ng/ml; Mann-Whitney U test, p=0.041)., Conclusion: Even low doses of amisulpride used as an augmentation to antidepressant treatment, benzodiazepines or in monotherapy seem to be associated with hyperprolactinemia. The co-medication of antidepressants and benzodiazepines can potentially increase intensity of prolactinemia.

We studied cognitive functions related to processing sensory and motor activities in the basal ganglia (BG), specifically in the putamen and in cortical structures forming the BG-frontocortical circuits. Intracerebral recordings were made from 160 brain sites in 32 epilepsy surgery candidates. We studied P3-like potentials in five different tests evoked by auditory and visual stimuli, and two sustained potentials that are related to cognitive activities linked with movement preparation: BP (Bereitschaftspotential) and CNV (contingent negative variation). We compared the presence of a potential with a phase reversal or an amplitude gradient to the absence of a generator. All of the studied cognitive potentials were generated in the BG; the occurrence in frontal cortical areas was more selective. The frequency of all but one potential was significantly higher in the BG than in the prefrontal and in the cingulate cortices. The P3-like potentials elicited in the oddball paradigm were also more frequent in the BG than in the motor/premotor cortex, while the occurrence of potentials elicited in motor tasks (BP, CNV, and P3-like potentials in the CNV paradigm) in the motor cortex did not significantly differ from the occurrence in the BG. The processing of motor tasks fits with the model by Alexander et al. of segregated information processing in the motor loop. A variable and task-dependent internal organisation is more probable in cognitive sensory information processing. Cognitive potentials were recorded from all over the putamen. The BG may play an integrative role in cognitive information processing.

Do recency processes associated with repetitive sensorimotor events modulate the magnitude and functional coupling of brain rhythmicity in human temporal cortex? Intracranial stereo electroencephalographic activity (SEEG; 256 Hz sampling rate) was recorded from hippocampus, and inferior (BA20) and middle (BA21) temporal cortex in four epilepsy patients. The repetitive events were represented by predicted imperative somatosensory stimuli (CNV paradigm) triggering hand movements ("repetitive visuomotor") or counting ("repetitive counting"). The non-repetitive events were "rare" (P3 paradigm) somatosensory stimuli triggering hand movements ("non-repetitive visuomotor") or counting ("non-repetitive counting"). Brain rhythmicity was indexed by event-related desynchronization/synchronization (ERD/ERS) of SEEG data, whereas the functional coupling was evaluated by spectral SEEG coherence between pairs of the mentioned areas. The frequency bands of interest were theta (4-8 Hz), alpha (8-12 Hz), beta (14-30 Hz), and gamma (32-46 Hz). Compared to the non-repetitive events, the "repetitive visuomotor" events showed a significant beta and gamma ERS in the hippocampus and a significant theta ERD in the inferior temporal cortex. Furthermore, the "repetitive visuomotor" events induced a task-specific significant gamma coherence among the examined areas. These results suggest that recency processes do modulate the magnitude and functional coupling of brain rhythmicity (especially gamma) in the human temporal cortex.

Objective: The Catalan Health Interview Survey Follow-up Study analyzed survival differences according to comorbidity, using an adaptation of the Charlson's index., Study Design and Setting: Vital status was ascertained by record linkage with death certificates 5 years after interview. Three thousand one hundred five men and 3,536 women aged 40-84 years old were included in the analysis. Proportional hazards models with age as time scale were used to calculate relative risk (RR) and 95% confidence interval adjusted for potential confounders., Results: The adjusted RR of death in men was 1.02 (0.73-1.41) for a comorbidity index of 1-2; the RR was 1.51 (1-2.30) for an index of 3-4, and 2.64 (1.43-4.89) for an index of >4 composed to an index of 0. In women, for the same comorbidity index categorization, the RR of death were 0.83 (0.55-1.24), 1.71 (1.09-2.72) and 2.65 (1.47-4.77)., Conclusion: This result confirms the relation between comorbidity and the risk of death based on a comorbidity index that takes into account severity and number of self-declared chronic diseases with mortality.

Objective: This study concerned sensory processing (post-stimulus late evoked potential components) in different parts of the human brain as related to a motor task (hand movement) in a cognitive paradigm (Contingent Negative Variation). The focus of the study was on the time and space distribution of middle and late post-stimulus evoked potential (EP) components, and on the processing of sensory information in the subcortical-cortical networks., Methods: Stereoelectroencephalography (SEEG) recordings of the contingent negative variation (CNV) in an audio-visual paradigm with a motor task were taken from 30 patients (27 patients with drug-resistant epilepsy; 3 patients with chronic thalamic pain). The intracerebral recordings were taken from 337 cortical sites (primary sensorimotor area (SM1); supplementary motor area (SMA); the cingulate gyrus; the orbitofrontal, premotor and dorsolateral prefrontal cortices; the temporal cortex, including the amygdalohippocampal complex; the parietooccipital lobes; and the insula) and from subcortical structures (the basal ganglia and the posterior thalamus). The concurrent scalp recordings were obtained from 3 patients in the thalamic group. In 4 patients in the epilepsy group, scalp recordings were taken separately from the SEEG procedure. The middle and long latency evoked potentials following an auditory warning (S1) and a visual imperative (S2) stimuli were analyzed. The occurrences of EPs were studied in two time windows (200-300 ms; and over 300 ms) following S1 and S2., Results: Following S1, a high frequency of EP with latencies over 200 ms was observed in the primary sensorimotor area, the supplementary motor area, the premotor cortex, the orbitofrontal cortex, the cingulate gyrus, some parts of the temporal lobe, the basal ganglia, the insula, and the posterior thalamus. Following S2, a high frequency of EP in both of the time windows over 200 ms was observed in the SM1, the SMA, the premotor and dorsolateral prefrontal cortex, the orbitofrontal cortex, the cingulate gyrus, the basal ganglia, the posterior thalamus, and in some parts of the temporal cortex. The concurrent scalp recordings in the thalamic group of patients twice revealed potentials peaking approximately at 215 ms following S1. Following S2, EP occurred with latencies of 215 and 310 ms, respectively. Following S1, separate scalp recordings in 4 patients in the epilepsy group displayed EP 3 times in the 'over 300 ms' time window. Following S2, EP were presented once in the '200-300 ms' time window and 3 times in the 'over 300 ms' time window., Conclusions: The SM1, the SMA, multiple sites of the frontal lobe, some parts of the temporal lobe, the cingulate gyrus, the basal ganglia, the insula, and the posterior thalamus all participate in a cortico-subcortical network that is important for the parallel cognitive processing of sensory information in a movement related task.

The P3 wave of event-related potentials was recorded with intracranial electrodes in 24 epileptic patients during the pre-surgical evaluation of epilepsy surgery. Three different cognitive auditory paradigms were used: (1) odd-ball paradigm with no output required (PGI) where patients had simply to recognize target tones, (2) odd-ball with motor response (PGII), where patients had to press a button in response to target tones, and (3) odd-ball with both counting task and motor response (PGIII), where patients had to recognize target tones, press a button in response to them, and count their number. The occurrence of P3 potential, its latency and amplitude, and the dependence of P3 latency on the task complexity were calculated. Identifiable P3 potentials in all the three paradigms were recorded from locations in mesial cortex (18 locations mesial temporal, eight locations mesial frontal, two locations mesial parietal) and lateral sites (eight sites lateral temporal, five lateral frontal, and two lateral parietal). P3 latency values ranged from 257 to 320 ms in all explored cortical areas when PGI was used; they significantly increased or decreased during PGII and PGIII, depending on the task and structure explored. In the mesial temporal cortex, the changes of P3 latency between paradigms were minimal. In the mesial parietal cortex, there was significant P3 delay in both PGII and PGIII relative to PGI. In the mesial frontal cortex, there was a significant latency decrease in PGII, and practically identical mean latency in PGI and PGIII. In all lateral cortices (temporal, frontal and parietal), there was always a P3 latency increase in PGII and PGIII relative to PGI, the most significant results being observed in the parietal and frontal lateral areas. The results support the multi-generator theory of P3. Prolongation of the mean P3 latency in lateral frontal and parietal cortices when the paradigm involved the execution of a motor task might reflect specific gating in this area during active movements, while the absence of modification in the temporal lobe may reflect minimal involvement of this region in motor planning or processing. The prolongation of mean P3 latency in practically all lateral structures in PGIII suggests that most cortical areas were involved in the cognitive functions needed for this test. The finding of reduction and subsequent prolongation of P3 latency in the mesial frontal cortex might reflect the unique specialization of this area and its specific involvement in motor processing.

An 8-month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin) and pergolide (PRG; Permax) as add-on to L-dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non-demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self - Rating Depression Scale by Zung were evaluated in an open-label design. The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L-dopa decreased significantly but the decrease was statistically more pronounced in the PRG group. Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG.

Twelve patients with early Parkinson's disease (PD), none of whom had received any previous L-DOPA treatment, but using other antiparkinsonian drugs, were studied using transcranial magnetic stimulation (TMS). Contralateral and ipsilateral hemispheres were examined, with a focus on the more pronounced parkinsonian symptoms. The conditioning-test TMS paradigm (with a subthreshold conditioning stimulus and a suprathreshold test stimulus) was used through a stimulating round coil. Paired stimuli of short (3, 5 and 7 ms), medium (10, 15 and 20 ms), and long (100, 150, 200 and 250 ms) interstimulus intervals (ISI) were pseudo-randomly mixed with a single stimulus. The first interosseus muscle was used for the motor-evoked potential recordings. Ten healthy subjects (age and sex matched) were studied in the same manner to obtain normative data. When both groups were compared, the significant difference (reduction of the intracortical inhibition and facilitation) between the PD patients and the control group was found at the short and the medium ISI (3, 5, 7, 10, 15 and 20 ms) in both hemispheres (P < 0.05). The longer ISI produced non-significant differences between the two groups in intracortical excitability. There was a non-significant difference in the motor threshold. In conclusion, it can be supposed that both intracortical inhibition and facilitation are impaired in patients with early PD using other antiparkinsonian treatments than L-DOPA or dopamine agonists.

Objective: The somatosensory evoked potentials of the median nerve (SEP) were registered intracerebrally in 12 subjects to elucidate the origin of N30 component and its behavior in the motor 'gating' tasks., Methods: The recordings were done from the electrodes which were inserted within the cortex of frontal lobe in the pre-surgical phase of epilepsy surgery. The registrations focused on the precentral N30 SEP component and its behaviour under the 'gating' paradigms. Two different 'gating' paradigms, motor and mental, were used and the SEP then were recorded in 3 conditions: (1) normal (N) paradigm, during which the subjects were instructed not to perform any movement by the stimulated hand, or to mentally simulate the movement; (2) active movement (AM) paradigm, during which the subjects were instructed to perform the active movement as the internal motor sequence test by the fingers of the hand of the stimulated limb; (3) mental movement simulation (MMS), during which the subjects were instructed to only mentally simulate the movements performed in the previous paradigm, and this 'virtual' movement also involved the hand of the stimulated limb. The recordings were done at least twice in each paradigm and averaged runs of 2000 artefact-free sweeps were used for the analysis., Results: The results demonstrated that the precentral N30 component of SEP is generated only in the pre-motor area, either dorsolaterally or mesially, which consists of Brodmann's areas 6 and 8, and their borders. Only the N30 potentials recorded there in 7 subjects had a shape and character of 'near-field' potential. The behaviour of the N30 component when recorded in the AM and MMS paradigms was different depending on the fact of whether they were recorded dorsolaterally or mesially. When there was a clear 'near-field' N30 potential recorded mesially, there was a certain gating present during the AM paradigm, i.e. during the performance of movement. However, the gating caused by the mental movement simulation in the MMS paradigm was substantially more expressed, and the N30 wave practically disappeared in some cases. On the contrary, the gating of the N30 wave, recorded in the frontal dorsolateral premotor cortex (DLPC), was almost complete when the AM (active movement) paradigm was employed, and it was only partial when the MMS paradigm (mental movement simulation) was employed., Conclusions: The results of N30 registrations in our group of patients strongly support the theory of separate generator (or generators) of the N30 wave within the premotor cortex. They also brought forward evidence that the dorsolateral premotor cortex (Brodmann's areas 6 and 8) serves as the substrate of the 'motor execution' process, and the mesial frontal cortex (Brodmann's area 6) serves as the substrate of the 'motor planning' process. Further research should focus on the mutual registration of neurophysiological phenomena and imaging phenomena to obtain new data, which will be able to more precisely elucidate the workings of the premotor cortex during the whole process of motor performance.

Three patients with advanced Parkinson's disease, all of whom developed excessive daytime sleepiness and 'sleep attacks' after the administration of entacapone, are described. This is another demonstration that inappropriate daytime sleep episodes are not exclusive to dopamine agonists.

Electrooculography (EOG) recordings in 21 L-DOPA-naive patients suffering from Parkinson's disease (PD) were made before and after apomorphine subcutaneous administration (ASA). The effect of apomorphine on smooth pursuit eye movements (SPEM) was studied. Age-matched healthy subjects, who underwent SPEM recordings without the ASA procedure, were examined in order to compare baseline SPEM. EOG recordings were used to compare the patient group and the control group, and to compare the SPEM before and after ASA within the patient group. Significant differences in SPEM were found between both groups, as well as in the SPEM before and after ASA. The theory that SPEM is disturbed in early PD patients was confirmed. The dopaminergic control of horizontal SPEM is supposed.

Cortical excitability and cortico-cortical inhibition were examined in twenty-one patients suffering from idiopathic rotational cervical dystonia. Polymyography of cervical muscles, somatosensory evoked potential recordings, and paired transcranial magnetic stimulation were used to assess the dystonic disorder. The results were compared with those obtained in a group of sixteen healthy age-matched volunteers. Statistically significant differences between the patient group and the control group were found when the amplitude values of the mean P22/N30 component measured at F [3, 4] and C[3, 4]' electrode positions were compared. The mean amplitude of P22/N30 in both of these electrode positions contralaterally to the direction of head deviation was significantly higher in the patient group (p

Results from a dose-ranging study in a selected group of de novo patients with rotational cervical dystonia (CD) suggest that 500 units of Dysport (Clostridium botulinum toxin type A haemaglutinin complex) is the optimal starting dose. The present study aimed to confirm the efficacy and safety profile of this dose in a population of CD patients more representative of those seen in a typical dystonia clinic. A total of 68 patients with moderate to severe CD (Tsui score > or = 9) were randomly assigned to receive placebo or Dysport 500 units. Treatment was administered according to the clinical pattern of head deviation, using a standardised injection protocol. A total of 21 patients (11 Dysport, 10 placebo) had not previously received botulinum toxin type A (BtxA) injections, and 47 patients (24 Dysport, 23 placebo) had received BtxA more than 12 weeks previously. Assessments were performed at baseline and weeks 4, 8 and 16. Patients defined as non-responders at week 4 were re-treated in an open phase with 500 units of Dysport at week 6, and were followed up at week 10. Significant between-group differences in Tsui scores were present at weeks 4 (p=0.001) and 8 (p=0.002). Similarly, there were significant between-group differences (p < 0.001) in patient and investigator assessments of response in favour of Dysport at weeks 4 and 8. Also, more Dysport (49%) than placebo (33%) patients were pain-free at week 4 (p=0.02). Overall, 30/35 (86 %) Dysport patients and 14/33 (42%) placebo patients were classified as responders at week 4. Adverse events were reported by 15/35 Dysport patients and 9/33 placebo patients. Open phase treatment produced improvements in Tsui (p < 0.001) and pain scores (p=0.011), and 23/24 patients were classified as responders. Although individual dose titration and muscle selection is desirable, this study demonstrated that a dose of 500 units of Dysport injected into clinically identified neck muscles without electromyographic guidance is safe and effective in the treatment of patients with the major clinical types of cervical dystonia.

Objective: Intracranial recordings were taken from the basal ganglia (BG) in order to explore the possible role of the BG in the cognitive processing of sensory information., Methods: Ten patients with intractable temporal lobe epilepsy, who were candidates for epilepsy surgery, underwent intracranial recordings with depth electrodes. A frontal approach was used for the insertion of diagonal depth electrodes into the amygdalo-hippocampal complex (AH complex). These electrodes passed through the BG. The putamen was explored in 8 patients; the nucleus caudatus and pallidum were explored in two patients. The contingent negative variation (CNV) paradigm was tested using auditory warning stimuli and visual imperative stimuli followed by a hand flexion. The auditory and visual middle and late latency potentials evoked by the warning and imperative stimuli were analyzed., Results: (1) Auditory evoked potentials (EPs): the amplitude potential gradient was observed with latencies of (a) 150-195ms (9 patients); (b) 215-290ms (9 patients); and (c) 350-600ms (10 patients). Negative potentials, with latencies of 100 and 110ms were observed in two patients. (2) Visual EPs: (a) 160-195ms (9 patients); (b) 210-295ms (9 patients); and (c) 330-550ms (7 patients). Negative potentials with latencies between 100 and 120ms were observed in 4 patients. CNV was obtained from the BG in 8 patients; a phase reversal was observed twice., Conclusions: (1) The BG generate middle and late latency EPs in a cognitive paradigm linked to the motor task. (2) The BG generate CNV. (3) The BG could play an integrative role in the processing of sensory, cognitive, and motor information.

Objectives: The brain potentials preceding and accompanying self-paced acral limb movements (Bereitschaftspotential/readiness potential (RP) paradigm) were studied in 12 patients., Methods: Intracranial electrodes were implanted in order to explore intractable epilepsy. The electrodes were introduced into sites corresponding to the electroclinical characteristics of each patient's epileptic seizures. In 7 patients, several depth electrodes were implanted orthogonally, in the temporal, fronto-orbital and prefrontal cortex. In 4 patients, subdural strip electrodes were used for the exploration of the fronto-temporal convexity. There were no RPs recorded in these areas. No contacts were placed in the central region known to generate cortical RP. In all the patients, one or two diagonal electrodes passed through or touched the basal ganglia to reach the amygdala and the hippocampus. The putamen was explored in 11 patients (in 3 of them bilaterally); the caudate head was explored in two patients, and the pallidum was explored in two patients., Results: RP with a clear amplitude gradient was present in all explored structures, however a phase reversal was never observed. RP was observed in the caudate in all recordings, and in the pallidum in one patient. It was recorded in the putamen in 8 out of the 11 explored patients. RPs were displayed contralaterally to the movement 9 times in 13 explorations, and ipsilaterally 4 times in 9 explorations. The shape of RP resembled the RP shape in the cortex and on the scalp. Movement accompanying potentials (MAPs) were also present in all 3 explored structures. The electrophysiological characteristics of MAP differed from RP, indicating separate generators. In the basal ganglia, RPs preceded the onset of movement by 500-1500 ms, at an average of 1080 (+/-330) ms. It seems that the RP in the basal ganglia starts slightly later than the RP in the motor cortices. That should be definitely demonstrated in patients with simultaneous recordings from cortical and subcortical structures. RP and MAP were displayed synchronously in the cortex and in the basal ganglia during most of the premovement period, as well as during the execution of movement. RP generators were reported by several authors in other deeply located structures, i.e. in the thalamus and in the brain-stem., Conclusions: Based on all these recordings, we presume that the RPs recorded on the scalp are generated simultaneously in several cortical as well as subcortical structures.

Intracranial recordings were obtained from three patients with intractable chronic pain who underwent analgesic electrical stimulation of the contralateral thalamus. Multilead electrode made it possible to record from several thalamic nuclei. The electrode was targeted into the ventroposterolateral (VPL) nucleus of the thalamus. During separate recording sessions, the following tests were performed: somatosensory evoked potentials (SEP) of the median or posterior tibial nerve, event-related cognitive potentials (auditory oddball P3 wave), readiness potential (RP) and contingent negative variation (CNV) using auditory warning (S1) and visual imperative (S2) stimuli. The movement accompanying potential (MAP), which was present in the VPL in all but one of the recordings, behaved as a far-field potential. Recordings obtained from the VPL confirmed its established role as a relay nucleus, processing somatosensory information to the primary somatosensory cortex. The VPL generated the 'thalamic' SEP, which was the only potential regularly recorded in this nucleus. In the recordings from one patient (No. 3), auditory and visual evoked potentials of the CNV protocol, peaking at approximately 300 ms, were obtained from the VPL and appeared to be generated in situ. Neither RP, CNV nor 'oddball' ERPs appeared in the VPL. From the pulvinar, only a visually evoked potential was recorded. Oddball P3, RP, CNV, and middle and long latency auditory and visual potentials (evoked in the CNV paradigm) appeared to be generated 'dorsally' to the VPL, probably in the nucleus posterolateralis (PL). This structure may therefore be involved in both the processing of afferent information and in cognitive operations.

While exploring 11 epileptic patients with intracerebral electrodes, we recorded readiness potential (RP) preceding a complex motor task. Multilead depth electrodes were positioned stereotactically into the cortex. In three patients, it was also possible to record RP from the putamen. The movement triggering the recording was the turning of a page in an architectural book. The movement was performed under two conditions: in the first condition, without looking at the pictures on the page (typical self-pacing); and in the second condition, following the inspection of the pictures. There were no significant differences in the appearance of RP under these two conditions, neither in duration nor in amplitude. That could be explained by the fact that "self-paced" does not mean "spontaneous," but covers the internal non-conscious program related to a given task. RP were present in the contralateral primary sensorimotor cortex and the bilateral supplementary motor area (SMA), and in the anterior caudal cingulate cortex. No difference between the cortical topography of RP preceding a simple motor task and the topography of RP occurring in connection with complex movement was observed., (Copyright 2001 Movement Disorder Society.)

Efficiency and safety of amantadine sulfate (AMS) infusions were investigated in late stage complications of Parkinson's disease (PD). In an open-label study, 21 PD patients suffering from motor fluctuations and/or dyskinesias were administered AMS infusions (PK-Merz, 400 mg per day) during seven days. Oral AMS treatment followed. Significant improvement of UPDRS motor scores was observed between day 0 and day 7, remaining improved until day 21. Based on patients' diary notes, both severity and occurrence of hypokinetic "off" state significantly decreased (from 6.6 to 3.1 hours, p < 0.001, average "off" time per day) as well as dopaminergic-induced dyskinesias (from 2.5 to 1.3 hours, p < 0.05, average duration of dyskinesias per day). AMS infusions followed by oral administration appeared as a safe method for improvement of both motor fluctuations and dyskinesias in advanced PD. In advantage to simple oral therapy, AMS infusions allowed fast introduction of a profound and durable treatment effect.