Electrical stimulation is a less-invasive alternative for treating drug-resistant epilepsy compared to surgical resection of the epileptogenic area. Different stimulation protocols have been practiced to suppress seizures either in-vivo, in-vitro and in-silico. In this work we have controlled rapid discharges occurring at electrical onset of seizure in an in-silico model of epilepsy using backstepping technique.

In this study of 23 patients with premenstrual dysphoric disorder (PMDD) and 18 normal comparison (NC) subjects, we examined sleep EEG measures during baseline midfollicular (MF) and late luteal (LL) menstrual cycle phases and after early sleep deprivation (ESD), in which subjects slept from 03.00 to 07.00 h, and late sleep deprivation (LSD), in which subjects slept from 21.00 to 01.00 h. Each sleep deprivation night was followed by a night of recovery sleep (ESD-R, LSD-R) (sleep 22.30–06.30 h) and was administered in the late luteal phase of separate menstrual cycles. During baseline studies, sleep EEG measures differed significantly by menstrual cycle phase, but not group. Both PMDD and NC groups showed longer REM latencies and less REM sleep (minutes and percent) during the luteal compared with the follicular menstrual cycle phase. PMDD subjects, however, did not show sleep architecture changes similar to those of patients with major depressive disorders. Sleep quality was better during recovery nights of sleep in PMDD compared with NC subjects. REM sleep measures changed in association with clinical improvement in responders to sleep deprivation. Both early and late sleep deprivation may help to correct underlying circadian rhythm disturbances during sleep in PMDD, although differential sleep changes during ESD vs. LSD did not correlate with clinical response. Further sleep studies addressing additional circadian variables may serve to elucidate mechanisms mediating the therapeutic effects of sleep deprivation in PMDD.

This study examined neuropsychological performance across the menstrual cycle in women with varying levels of premenstrual symptomatology. Following a 2-month period of prospective symptom documentation, there were 19 women who met DSM-IV criteria for Premenstrual Dysphoric Disorder (PMDD group) and 18 women with mild to moderate symptoms. Neuropsychological functioning was evaluated at the late follicular (pre-ovulatory) and late luteal (premenstrual) phases across the domains of psychomotor speed, attention, and verbal learning and memory. Repeated measures analysis of variance yielded significant group×phase differences on the psychomotor index, with women in the PMDD group demonstrating significant psychomotor slowing in the late luteal phase. This psychomotor slowing was subtle, however, and scores remained within the normal range across testing sessions. No group or phase differences were found on indices of attention or verbal learning and memory. These results suggest that with the exception of subtle psychomotor slowing in the late follicular relative to the late luteal phase, there is no discernible difference in cognitive functioning between women with and without PMDD.

Patients with premenstrual dysphoric disorder (PMDD) respond therapeutically to sleep deprivation and light therapy. They have blunted circadian rhythms of melatonin. The authors sought to test the hypothesis that these disturbances are a reflection of a disturbance in the underlying circadian pacemaker or, alternatively, that they reflect a disturbance in the input pathways to the clock. To test these hypotheses, after a 2-month diagnostic evaluation, 8 patients who met DSM-IV criteria for PMDD and 5 normal control (NC) subjects underwent two studies to determine whether PMDD subjects showed (1) altered melatonin sensitivity to light suppression (Study 1) and (2) altered phase-shift responses to morning light as a measure of the functional capacity of the underlying pacemaker (Study 2). In both studies, measurements were made during asymptomatic follicular and symptomatic luteal menstrual cycle phases in PMDD patients. The results of Study 1 showed no significant effect of group or menstrual cycle phase on the amount or percentage of suppression of melatonin by light. The results of Study 2 showed that with respect to the variable of offset time, PMDD subjects, when symptomatic, showed a reduced and directionally altered melatonin phase-shift response to a morning bright light stimulus ; in 4 of 5 NC subjects, melatonin offset was advanced by bright morning light, whereas in PMDD subjects, it was delayed (3 subjects) or not shifted (5 subjects) (group effect, p = .045). Study 2 also revealed that area under the curve also changed differentially in PMDD versus NC subjects. In summary, the primary findings from this pilot study suggest that in PMDD there is a maladaptive (directionally altered and blunted) response to light in the symptomatic luteal phase. Because the suppressive effects of light were similar in PMDD and NC subjects, the previously observed low melatonin levels in this disorder do not likely represent a disturbance in pineal reactivity to suprachiasmatic nucleus efferents. Instead, the findings support a possible disturbance in PMDD in the clock itself or its coupling mechanisms.

The aim of this study was to replicate and extend previous work in which the authors observed lower, shorter, and advanced nocturnal melatonin secretion patterns in premenstrually depressed patients compared to those in healthy control women. The authors also sought to test the hypothesis that the therapeutic effect of bright light in patients was associated with corrective effects on the phase, duration, and amplitude of melatonin rhythms. In 21 subjects with premenstrual dysphoric disorder (PMDD) and 11 normal control (NC) subjects, the authors measured the circadian profile of melatonin during follicular and luteal menstrual cycle phases and after 1 week of light therapy administered daily, in a randomized crossover design. During three separate luteal phases, the treatments were either (1) bright (> 2500 lux) white morning (AM; 06:30 to 08:30 h), (2) bright white evening (PM;19:00 to 21:00 h), or (3) dim (< 10 lux) red evening light (RED). In PMDD subjects, during the luteal phase compared to the follicular menstrual cycle phase, melatonin onset time was delayed, duration was com pressed, and area under the curve, amplitude, and mean levels were decreased. In NC subjects, melatonin rhythms did not change significantly during the menstrual cycle. After AM light in PMDD subjects, onset and offset times were advanced and both duration and midpoint concentration were decreased as compared to RED light. After PM light in PMDD subjects, onset and offset times were delayed, midpoint concentration was increased, and duration was de creased as compared to RED light. By contrast, after light therapy in NC subjects, duration did not change; onset, offset, and midpoint concentration changed as they did in PMDD subjects. When the magnitude of advance and delay phase shifts in onset versus offset time with AM, PM, or RED light were compared, the authors found that in PMDD subjects light shifted offset time more than onset time and that AM light had a greater effect on shifting melatonin offset time (measured the following night in RED light), whereas PM light had a greater effect in shifting melatonin onset time. These findings replicate the authors' previous observation that nocturnal melatonin concentrations are decreased in women with PMDD and suggest specific effects of light therapy on melatonin

The aim of this study was to test the hypothesis that the circadian rhythm of core body temperature is altered in premenstrual dysphoric disorder (PMDD) subjects compared to that in normal comparison (NC) subjects and that it is normalized in PMDD subjects after treatment with early night partial sleep deprivation (ESD) or late night partial sleep deprivation (LSD). A total of 23 subjects meeting DSM-IV criteria for PMDD and 18 NC subjects had 24-h core body temperature recordings taken during the following conditions: (1) baseline midfollicular (preovulatory) and (2) late luteal (postovulatory) menstrual cycle phases and after a randomized crossover trial in subsequent luteal phases of (3) ESD, in which subjects slept from 03:00 to 07:00 h, followed by (4) a night of recovery sleep (ESD-R: sleep 22:30 to 06:30 h), and (5) LSD, in which subjects slept from 21:00 to 01:00 h, also followed by (6) a night of recovery sleep (LSD-R: sleep 22:30 to 06:30 h). Temperature amplitudes were significantly decreased in the luteal phase compared to those in the follicular menstrual cycle phase and increased after nights of recovery sleep. Compared to the baseline late luteal phase, during LSD, temperature amplitude increased in PMDD subjects but decreased in NC subjects. During ESD, the temperature acrophase was delayed in PMDD subjects but was advanced in NC subjects; during LSD, the tempera ture acrophase was advanced in PMDD subjects but was delayed in NC subjects compared to the late luteal baseline. Nocturnal temperature and temperature maxima and mesors tended to be higher in PMDD subjects than in NC subjects; when not reduced during sleep deprivation interventions, these were not asso ciated with therapeutic effects. Alterations in both phase and amplitude of temperature circadian rhythms characterize PMDD subjects as contrasted with NC subjects in response to sleep deprivation. The changes in phase reflected more shifts in temperature acrophase in response to shifts in sleep in PMDD subjects. This realignment of the timing of sleep and temperature in addition to the enhancement of blunted amplitude rhythms during recovery nights of sleep may provide corrective mechanisms that contribute to the therapeutic effects of sleep deprivation.

Synopsis In 15 women with Late Luteal Phase Dysphoric Disorder (LLPDD) and in 15 normal control subjects, personality traits were assessed using the Millon Clinical Multiaxial Inventory (MCMI) during follicular and luteal menstrual-cycle phases. Compared with controls, LLPDD subjects had less compulsive but more passive/aggressive and borderline/cycloid traits, and more depression and hypomania. Menstrual-cycle phase did not significantly affect personality variables in either group. In particular, depression and hypomania in LLPDD subjects suggests a relationship with affective disorders.

The present study extended previous work by examining whether disturbances in the circadian rhythms of prolactin (PRL) and thyroid-stimulating hormone (TSH) distinguish patients with premenstrual dysphoric disorder (PMDD) from normal volunteers. In addition, the effects of therapeutic interventions with early and late partial sleep deprivation were explored. Both PRL and TSH levels were measured every 30 min from 18:00 h to 09:00 h during midfollicular and late luteal menstrual cycle phases in 23 PMDD patients and 18 normal volunteers. Hormone levels were measured again after a randomized crossover trial of early (sleep 03:00-07:00 h) versus late (sleep 21:00-01:00 h) partial sleep deprivation administered in two separate luteal phases. Compared with normal volunteers, PMDD patients had higher PRL concentrations, consistent with previous findings. TSH rhythms occurred earlier in PMDD than in normal subjects. PRL levels decreased and TSH levels increased with sleep deprivation compared with baseline conditions. The timing of PRL secretion shifted earlier with late sleep deprivation and later with early sleep deprivation. Although circadian disturbances of PRL and TSH were found in PMDD patients compared with normal volunteers, the therapeutic effects of early and late sleep deprivation do not appear to be mediated by correcting these disturbances.

OBJECTIVE:The aim of this study was to compare the clinical effects of early-night and late-night partial sleep deprivation in patients with premenstrual dysphoric disorder and normal comparison subjects.METHOD:In the premenstrual phase of two menstrual cycles, 23 subjects with DSM-IV premenstrual dysphoric disorder and 18 normal comparison subjects underwent a randomized crossover trial of 1) early-night sleep deprivation, in which subjects slept from 3:00 a.m. to 7:00 a.m., followed by a night of recovery sleep (11:00 p.m. to 7:00 a.m.), and 2) late-night sleep deprivation, in which subjects slept from 9:00 p.m. to 1:00 a.m., followed by a night of recovery sleep.RESULTS:For the subjects with premenstrual dysphoric disorder, in both partial sleep deprivation conditions the Hamilton and Beck depression ratings were significantly lower after recovery sleep than at baseline. Ratings on the day after early or late partial sleep deprivation tended to be lower than at baseline but were not statistically different. The normal comparison subjects showed no clinically important mood changes. A factor analytic approach used with the Hamilton depression scores showed that depressive retardation symptoms were the most responsive to sleep deprivation in the premenstrual dysphoric disorder subjects.CONCLUSIONS:These results are consistent with the reported efficacy of sleep deprivation for major depressive disorder. However, the premenstrual dysphoric disorder subjects improved after the recovery sleep rather than directly after partial sleep deprivation. That late-night sleep deprivation did not have greater benefit than did the hypothesized sham treatment, early-night sleep deprivation, also suggests that placebo effects cannot be ruled out.

In 20 late luteal phase dysphoric disorder (LLPDD) and in 11 normal control (NC) subjects, circadian profiles of cortisol, prolactin, thyrotropin-stimulating hormone (TSH), and core body temperature were measured during midfollicular (MF) and late luteal (LL) menstrual cycle phases and after 1 week of light therapy either with (1) bright (tau 2500 lux) white morning (6:30 AM to 8:30 AM), (2) bright white evening (7 PM to 9 PM) or (3) dim (< 10 lux) red evening light, randomly administered in three separate luteal phases. In NC but not PMDD subjects, the cortisol peak significantly delayed in the LL compared with the MF phase. In PMDD, prolactin peak and amplitude were higher, prolactin acrophase earlier, and temperature amplitude higher during both the MF and LL phases. After light treatment, prolactin amplitude remained higher in LLPDD than in controls. In both groups, bright light shifted the cortisol acrophase, and AM light increased the prolactin nadir. Bright PM light increased the TSH nadir in LLPDD, but decreased it in controls. Thus, menstrual cycle phase, diagnosis, and light therapy may differentially affect neuroendocrine systems.

Nineteen patients with late luteal phase dysphoric disorder (LLPDD) and 11 healthy comparison subjects underwent a 3-month crossover trial of bright (more than 2500 lux) white morning, bright white evening, and placebo dim (less than 10 lux) red evening light, administered daily for 1 week during the premenstrual phase of the menstrual cycle. All light treatments significantly reduced depressive ratings from baseline levels.

Six women with late luteal phase dysphoric disorder had a significant reduction in depression ratings after treatment with evening, but not morning, bright light. Bright light may offer an alternative to the pharmacologic treatment of premenstrual mood disorders.