Prevalence, characteristics, and treatment of fatigue in oncological cancer patients in Italy: a cross-sectional study of the Italian Network for Supportive Care in Cancer (NICSO).

BACKGROUND: Fatigue is one of the most distressing symptoms of cancer patients. Its characteristics and impact on quality of life have not been fully explored and treatment of cancer-related fatigue in Italian oncological centers has not been codified. METHODS: A cross-sectional study was carried out on all patients attending for any reason the 24 participating centers in two non-consecutive days. Patients with fatigue filled out the Brief Fatigue Inventory (BFI) questionnaire and reported any pharmacological or non-pharmacological treatment for fatigue. RESULTS: From October 2014 to May 2015, 1394 cancer patients agreed to participate in the study. Fatigue was referred by 866 (62.1%) of patients; its duration was > 4 months in 441 patients (50.9%). In the investigators' opinion, the most important (probable or almost sure) determinants of fatigue were reduced physical activity (271 patients), anxiety (149), pain (131), insomnia (125), anemia (123), and depression (123). Fatigue of moderate/severe intensity was reported by 43%/29.2% of patients, while usual fatigue in the last 24 h by 45%/33.1%, and the worst fatigue in the last 24 h by 33%/54.8%, respectively. Concerning the impact on quality of life, fatigue interfered moderately/severely with general activity in 30.8%/38.6% of patients, with mood in 26.1%/32.8%, with the ability to work in 27.9%/35.6%, with normal work in 26.7%/38.9%, with relationships with others in 21%/23.4% and with the ability to amuse themselves in 22.2%/33.1%. Only 117/866 patients (13.5%) received a pharmacological treatment represented by a corticosteroid in 101 patients (86.3%) while 188 patients (21.7%) received a non-pharmacological treatment such as physical exercise (120 patients, 63.8%) and various alimentary supplements (52 patients, 27.6%). CONCLUSIONS: Cancer-related fatigue is frequently reported by oncological patients; its intensity and impact on quality of life is relevant.

Brains "in concert": frontal oscillatory alpha rhythms and empathy in professional musicians.

Playing music in ensemble represents a unique human condition/performance where musicians should rely on empathic relationships. Recent theories attribute to frontal Brodmann areas (BAs) 44/45 and 10/11 a neural basis for "emotional" and "cognitive" empathy. We hypothesized that activity of these structures reflects empathy trait in professional musicians playing in ensemble. Simultaneous electroencephalographic (EEG) alpha rhythms (8-12 Hz) were recorded in three saxophone quartets during music performance in ensemble (EXECUTION), video observation of their own performance (OBSERVATION), a control task (CONTROL), and resting state (RESTING). EEG source estimation was performed. Results showed that the higher the empathy quotient test score, the higher the alpha desynchronization in right BA 44/45 during the OBSERVATION referenced to RESTING condition. Empathy trait score and alpha desynchronization were not correlated in other control areas or in EXECUTION/CONTROL conditions. These results suggest that alpha rhythms in BA 44/45 reflect "emotional" empathy in musicians observing own performance.

Resting state cortical electroencephalographic rhythms in subjects with normal and abnormal body weight.

It is well known that resting state regional cerebral blood flow is abnormal in obese when compared to normal-weight subjects but the underlying neurophysiological mechanisms are poorly known. To address this issue, we tested the hypothesis that amplitude of resting state cortical electroencephalographic (EEG) rhythms differ among underweight, normal-weight, and overweight/obese subjects as a reflection of the relationship between cortical neural synchronization and regulation of body weight. Eyes-closed resting state EEG data were recorded in 16 underweight subjects, 25 normal-weight subjects, and 18 overweight/obese subjects. All subjects were psychophysically healthy (no eating disorders or major psychopathologies). EEG rhythms of interest were delta (2-4Hz), theta (4-8Hz), alpha 1 (8-10.5Hz), alpha 2 (10.5-13Hz), beta 1 (13-20Hz), beta 2 (20-30Hz), and gamma (30-40Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography (LORETA). Statistical results showed that parietal and temporal alpha 1 sources fitted the pattern underweight>normal-weight>overweight/obese (p<0.004), whereas occipital alpha 1 sources fitted the pattern normal-weight>underweight>overweight/obese (p<0.00003). Furthermore, amplitude of the parietal, occipital, and temporal alpha 2 sources was stronger in the normal-weight subjects than in the underweight and overweight/obese subjects (p<0.0007). These results suggest that abnormal weight in healthy overweight/obese subjects is related to abnormal cortical neural synchronization at the basis of resting state alpha rhythms and fluctuation of global brain arousal.

An art therapy group intervention for cancer patients to counter distress before chemotherapy.

Background: The aim of this study was to investigate the feasibility and effectiveness of a single group session based on art therapy (AT) for adult cancer patients to reduce anxiety and distress before anticancer treatment. Methods: A non-randomized pre-post study design was adopted. Sixty-two patients took part in one of twenty-seven "one-off" sessions held over a four-month period. Sixty-six patients, who simply received routine medical treatment, served as the control group (CG). Results: The intervention was appropriate to patients' needs and feasible in the context of their routine medical care. In contrast to the CG, the intervention group(IG) participants demonstrated a decrease in symptoms of anxiety, drowsiness and tiredness. Conclusions: The intervention proved suitable to the medical routine of patients' care. The clinical implications of the AT protocol and future research aimed at testing it vs. a different type of psychosocial intervention in a randomized controlled study are discussed.

Experience-optimised fast track improves outcomes and decreases complications in total knee arthroplasty.

PURPOSE: The aim of this study was to describe an advanced total knee arthroplasty (TKA) fast-track programme and determine discharge parameters during hospitalisation, as well as patient satisfaction, outcomes and complications within the first 12 months after surgery. METHODS: This prospective study was based on patients selected consecutively for primary elective TKA, undergoing surgery between 2014 and 2017 in an established fast-track setting. Hospitalisation-related parameters were collected: demographics, body mass index (BMI), surgical time, ischaemia time, haemoglobin values, blood transfusions, length of stay, weight-bearing and stair-climbing time, opioid administration, preoperative and discharge loss of extension and maximum active flexion of the knee, visual analogue scale (VAS), 12-month follow-up satisfaction rate and range of motion, any complications, hospital re-admission and re-operation within the first 12 months. Differences were determined using t-tests. RESULTS: A total of 704 total knee replacements implanted in 481 patients were included in the study and 223 patients had a bilateral TKA. Their mean age was 69.8 years (range 57-88 years). At the 12-month follow-up, 623 patients (88.5%) reported being satisfied or very satisfied and 15 (2.1%) were dissatisfied with their TKA, mean active flexion and loss of extension were 104.4° and 2.3°, respectively. A total of 15 complications occurred (two percent): five painful knees, three knee stiffness, three haematomas, two infections, one hospital re-admission and one deep venous thrombosis. No cases of pulmonary embolism and death related to surgery were reported. CONCLUSION: The study reports on an advanced fast-track programme for TKA with a low incidence of surgery- and hospitalisation-related issues and complications and without any severe adverse events during the first year. On average, the fast-track programme had a short length of stay, an early recovery of weight-bearing, knee mobility, pain control and a high satisfaction rate, accompanied with an acceptable 12 month range of motion.

Judgment of actions in experts: a high-resolution EEG study in elite athletes.

The present study tested the two following hypotheses: (i) compared to non-athletes, elite athletes are characterized by a reduced cortical activation during the judgment of sporting observed actions; (ii) in elite athletes, a good judgment of observed sporting actions is related to a low cortical activation. To address these issues, electroencephalographic (EEG) data were recorded in 15 elite rhythmic gymnasts and 13 non-gymnasts. They observed a series of 120 rhythmic gymnastic videos. At the end of each video, the subjects had to judge the artistic/athletic level of the exercise by a scale from 0 to 10. The mismatch between their judgment and that of the coach indexed the degree of action judgment. The EEG cortical sources were estimated by sLORETA. With reference to a pre-stimulus period, the power decrease of alpha (8-12 Hz) rhythms during the videos indexed the cortical activation (event related desynchronization, ERD). Regarding the hypothesis (i), low- and high-frequency alpha ERD was lower in amplitude in the elite rhythmic gymnasts compared to the non-gymnasts in occipital and temporal areas (ventral pathway) and in dorsal pathway. Regarding the hypothesis (ii), in the elite rhythmic gymnasts high-frequency alpha ERD was higher in amplitude with the videos characterized by a high judgment error than those characterized by a low judgment error; this was true in inferior posterior parietal and ventral premotor areas ("mirror" pathway). These results globally suggest that the judgment of observed sporting actions is related to low amplitude of alpha ERD, as a possible index of spatially selective cortical activation ("neural efficiency").

Visuo-attentional and sensorimotor alpha rhythms are related to visuo-motor performance in athletes.

This study tested the two following hypotheses: (i) compared with non-athletes, elite athletes are characterized by a reduced cortical activation during the preparation of precise visuo-motor performance; (ii) in elite athletes, an optimal visuo-motor performance is related to a low cortical activation. To this aim, electroencephalographic (EEG; 56 channels; Be Plus EB-Neuro) data were recorded in 18 right-handed elite air pistol shooters and 10 right-handed non-athletes. All subjects performed 120 shots. The EEG data were spatially enhanced by surface Laplacian estimation. With reference to a baseline period, power decrease/increase of alpha rhythms during the preshot period indexed the cortical activation/deactivation (event-related desynchronization/synchronization, ERD/ERS). Regarding the hypothesis (i), low- (about 8-10 Hz) and high-frequency (about 10-12 Hz) alpha ERD was lower in amplitude in the elite athletes than in the non-athletes over the whole scalp. Regarding the hypothesis (ii), the elite athletes showed high-frequency alpha ERS (about 10-12 Hz) larger in amplitude for high score shots (50%) than for low score shots; this was true in right parietal and left central areas. A control analysis confirmed these results with another indicator of cortical activation (beta ERD, about 20 Hz). The control analysis also showed that the amplitude reduction of alpha ERD for the high compared with low score shots was not observed in the non-athletes. The present findings globally suggest that in elite athletes (experts), visuo-motor performance is related to a global decrease of cortical activity, as a possible index of spatially selective cortical processes ("neural efficiency").

Is there a "neural efficiency" in athletes? A high-resolution EEG study.

"Neural efficiency" hypothesis posits that cortical activity is spatially focused in experts. Here we tested the hypothesis that compared to non-athletes, elite athletes are characterized by a reduced cortical activation during visuo-motor tasks related to the field of expertise, as a function of movement side. EEG data (56 channels; EB-Neuro) were continuously recorded in the following right-handed subjects: 11 non-athletes, 11 elite fencing athletes, and 11 elite karate athletes. During the EEG recordings, they observed pictures with fencing and karate attacks, and had to quickly click a right (left) keyboard button for the attacks at right (left) monitor side. The EEG data were averaged with respect to the movement onset, and were spatially enhanced by surface Laplacian estimation. The potentials related to the preparation (readiness potential) and initiation (motor potential) of the movements were measured. For the right movement, the potentials overlying supplementary motor and contralateral sensorimotor areas were higher in amplitude in the non-athletes than in the elite karate and fencing athletes. Furthermore, the amplitude of the motor potential over ipsilateral sensorimotor area was higher in the elite karate than fencing athletes, and its distribution over bilateral sensorimotor areas was less asymmetrical in the karate than in the other two groups. For the left movement, these potentials showed no difference between the groups. The present results suggest that "neural efficiency" hypothesis does not fully account for the organization of motor systems in elite athletes. "Neural efficiency" would depend on several factors including side of the movement, hemisphere, and kind of athletes.

Functional cortico-muscular coupling during upright standing in athletes and nonathletes: a coherence electroencephalographic-electromyographic study.

We tested the hypothesis that functional cortico-muscular coupling of brain rhythms is implied in the control of lower limb muscles for upright standing. Electroencephalographic (EEG; Be-plus Eb-Neuro) and electromyographic (EMG) data were recorded in 18 fencing and 19 karate elite athletes, 14 karate amateurs, and 9 non-athletes, during quiet upright standing with open and closed eyes conditions. Cortico-muscular coupling was evaluated by computing EEG-EMG spectral coherence and directed transfer function (DTF). Body sway area did not differ among the groups. In non-athletes, the EEG-EMG coherence (gastrocnemius lateralis) at centro-parietal and parasylvian alpha rhythms (about 8-12 Hz) was higher during the open than closed eyes condition. This was not true in the elite athletes. At the same alpha rhythms, the sport amateurs presented values halfway between the non-athletes and elite athletes. Finally, the DTF was higher for cortico-muscular than muscular-cortical direction. These results suggest that visual information affects cortico-muscular coherence at 8-12 Hz in non-athletes and amateur athletes but not in elite athletes. In elite athletes, this might be due to a long training for the control of equilibrium based on proprioceptive and tactile inputs.

Pre-stimulus alpha power affects vertex N2-P2 potentials evoked by noxious stimuli.

It is well known that scalp potentials evoked by nonpainful visual and auditory stimuli are enhanced in amplitude when preceded by pre-stimulus low-amplitude alpha rhythms. This study tested the hypothesis that the same holds for the amplitude of vertex N2-P2 potentials evoked by brief noxious laser stimuli, an issue of interest for clinical perspective. EEG data were recorded in 10 subjects from 30 electrodes during laser noxious stimulation. The artifact-free vertex N2-P2 complex was spatially enhanced by surface Laplacian transformation. Pre-stimulus alpha power was computed at three alpha sub-bands according to subject's individual alpha frequency peak (i.e. about 6-8Hz for alpha 1, 8-10Hz for alpha 2 and 10-12Hz for alpha 3 sub-band). Individual EEG single trials were divided in two sub-groups. The strong-alpha sub-group (high band power) included halfway of all EEG single trials, namely those having the highest pre-stimulus alpha power. Weak-alpha sub-group (low band power) included the remaining trials. Averaging procedure provided laser evoked potentials for both trial sub-groups. No significant effect was found for alpha 1 and alpha 2 sub-bands. Conversely, compared to strong-alpha 3 sub-group, weak-alpha 3 sub-group showed vertex N2-P2 potentials having significantly higher amplitude (p<0.05). These results extend to the later phases of pain processing systems the notion that generation mechanisms of pre-stimulus alpha rhythms and (laser) evoked potentials are intrinsically related and subjected to fluctuating "noise". That "noise" could explain the trial-by-trial variability of laser evoked potentials and perception.

Adaptability and reproducibility of a memory disruption rTMS protocol in the PharmaCog IMI European project.

Transcranial magnetic stimulation (TMS) can interfere with cognitive processes, such as transiently impairing memory. As part of a multi-center European project, we investigated the adaptability and reproducibility of a previously published TMS memory interfering protocol in two centers using EEG or fMRI scenarios. Participants were invited to attend three experimental sessions on different days, with sham repetitive TMS (rTMS) applied on day 1 and real rTMS on days 2 and 3. Sixty-eight healthy young men were included. On each experimental day, volunteers were instructed to remember visual pictures while receiving neuronavigated rTMS trains (20 Hz, 900 ms) during picture encoding at the left dorsolateral prefrontal cortex (L-DLPFC) and the vertex. Mixed ANOVA model analyses were performed. rTMS to the L-DLPFC significantly disrupted recognition memory on experimental day 2. No differences were found between centers or between fMRI and EEG recordings. Subjects with lower baseline memory performances were more susceptible to TMS disruption. No stability of TMS-induced memory interference could be demonstrated on day 3. Our data suggests that adapted cognitive rTMS protocols can be implemented in multi-center studies incorporating standardized experimental procedures. However, our center and modality effects analyses lacked sufficient statistical power, hence highlighting the need to conduct further studies with larger samples. In addition, inter and intra-subject variability in response to TMS might limit its application in crossover or longitudinal studies.

Pre-stimulus alpha rhythms are correlated with post-stimulus sensorimotor performance in athletes and non-athletes: a high-resolution EEG study.

OBJECTIVE: In this study, we tested the hypothesis that a pre-stimulus brief (1 min) 10-Hz audio-visual flickering stimulation modulates alpha EEG rhythms and cognitive-motor performance in elite athletes and in non-athletes during visuo-spatial demands. METHODS: Electroencephalographic (EEG) data were recorded (56 channels; EB-Neuro) in 14 elite fencing athletes and in 14 non-athletes during visuo-spatial-motor demands (i.e. subjects had to react to pictures of fencing and karate attacks). The task was performed after pre-stimulus 15- (placebo) or 10-Hz (experimental) flickering audio-visual stimulation lasting 1 min and after no stimulation (baseline). RESULTS: With reference to the baseline condition, only the 10-Hz stimulation induced a negative correlation between pre-stimulus alpha power and reaction time in the fencing athletes and non-athletes as a single group. The higher the enhancement of alpha power before the pictures, the stronger the improvement of the reaction time. The maximum effects were observed in right posterior parietal area (P4 electrode) overlying sensorimotor integrative cortex. Similar results were obtained in a control experiment in which eight elite karate subjects had to react to pictures of karate and basket attacks. CONCLUSIONS: The present results suggest that a preliminary 10-Hz sensory stimulation can modulate EEG alpha rhythms and sensorimotor performance in both elite athletes and non-athletes engaged in visuo-spatial-motor demands. SIGNIFICANCE: Identification of the EEG state of sporting experts prior to their performance provides a plausible rationale for the modulation of alpha rhythms to enhance sporting performance in athletes and sensorimotor performance in patients to be rehabilitated.

Visual event-related potentials in elite and amateur athletes.

In the present study, we tested the hypothesis that the neural synchronization estimated in visual cortex during visuo-spatial demands shows different features in elite karate athletes when compared to amateur karate athletes and non-athletes. EEG recordings (56 channels; EB-Neuro) were performed from 17 elite karate athletes, 14 amateur karate athletes, and 15 non-athletes, during the observation of pictures with basket and karate attacks. They clicked a right (left) keyboard button for basket or karate attacks at right (left) monitor side. Results pointed to no difference of late occipital VEPs/ERPs after basket versus karate attacks in the non-athletes (300-800 ms post-stimulus). In the amateur karate athletes, occipital VEPs/ERPs at 300-450 ms post-stimulus (P3-P4 components) were lower in amplitude for the karate than basket attacks. In the elite karate athletes, the occipital VEPs/ERPs further declined in amplitude at 300-450 ms post-stimulus (P3 and P4 components) and enhanced at about 800 ms post-stimulus ("N2" component) for the karate than basket attacks. A control study showed that in 10 elite fencers, the same was true for the fencing compared to the karate attacks. These results support the hypothesis that peculiar mechanisms of occipital neural synchronization can be observed in elite athletes during visuo-spatial demands, possibly to underlie sustained visuo-spatial attention and self-control.

Stop Flow in abdominal and pelvic cancer relapses.

To determinate MTD, DLT and safe doses for phase II study, a dose finding study with Mitomycin and Adriamycin Stop-Flow administration was carried out. A phase II study focused on resectability of pelvic colorectal relapses is in progress. From November 1995, 84 pts, 52 male and 32 female (94 treatments), with advanced not resectable abdominal (14 pts) or pelvic (70 pts) relapses, and resistant to previous systemic chemotherapy, were enrolled in the study. 46 pts entered the phase I-early phase II study, while subsequently 38 pts were recruited in ongoing phase II study. Safe dose were: MMC 20 mg/mq and ADM 75 mg/mq. The phase II study focused on colorectal relapses registered very promising responses: 90% pain control, 1 pCR and 26 PR / 63 (OR 43%), 8 NC (13%) 9/27 responder patients (33%) obtained a complete resectability of colorectal relapses. Stop-Flow is a safe and feasible technique very useful as a palliation treatment.

Cortical Neural Synchronization Underlies Primary Visual Consciousness of Qualia: Evidence from Event-Related Potentials.

This article reviews three experiments on event-related potentials (ERPs) testing the hypothesis that primary visual consciousness (stimulus self-report) is related to enhanced cortical neural synchronization as a function of stimulus features. ERP peak latency and sources were compared between "seen" trials and "not seen" trials, respectively related and unrelated to the primary visual consciousness. Three salient features of visual stimuli were considered (visuospatial, emotional face expression, and written words). Results showed the typical visual ERP components in both "seen" and "not seen" trials. There was no statistical difference in the ERP peak latencies between the "seen" and "not seen" trials, suggesting a similar timing of the cortical neural synchronization regardless the primary visual consciousness. In contrast, ERP sources showed differences between "seen" and "not seen" trials. For the visuospatial stimuli, the primary consciousness was related to higher activity in dorsal occipital and parietal sources at about 400 ms post-stimulus. For the emotional face expressions, there was greater activity in parietal and frontal sources at about 180 ms post-stimulus. For the written letters, there was higher activity in occipital, parietal and temporal sources at about 230 ms post-stimulus. These results hint that primary visual consciousness is associated with an enhanced cortical neural synchronization having entirely different spatiotemporal characteristics as a function of the features of the visual stimuli and possibly, the relative qualia (i.e., visuospatial, face expression, and words). In this framework, the dorsal visual stream may be synchronized in association with the primary consciousness of visuospatial and emotional face contents. Analogously, both dorsal and ventral visual streams may be synchronized in association with the primary consciousness of linguistic contents. In this line of reasoning, the ensemble of the cortical neural networks underpinning the single visual features would constitute a sort of multi-dimensional palette of colors, shapes, regions of the visual field, movements, emotional face expressions, and words. The synchronization of one or more of these cortical neural networks, each with its peculiar timing, would produce the primary consciousness of one or more of the visual features of the scene.

Brain neural synchronization and functional coupling in Alzheimer's disease as revealed by resting state EEG rhythms.

Alzheimer's disease (AD) is the most common type of neurodegenerative disorder, typically causing dementia along aging. AD is mainly characterized by a pathological extracellular accumulation of amyloid-beta peptides that affects excitatory and inhibitory synaptic transmission, inducing aberrant patterns in neuronal circuits. Growing evidence shows that AD targets cortical neuronal networks related to cognitive functions including episodic memory and visuospatial attention. This is partially reflected by the abnormal mechanisms of cortical neural synchronization and coupling that generate resting state electroencephalographic (EEG) rhythms. The cortical neural synchronization is typically indexed by EEG power density. The EEG coupling between electrode pairs probes functional (inter-relatedness of EEG signals) and effective (casual effect from one over the other electrode) connectivity. The former is typically indexed by synchronization likelihood (linear and nonlinear) or spectral coherence (linear), the latter by granger causality or information theory indexes. Here we reviewed literature concerning EEG studies in condition of resting state in AD and mild cognitive impairment (MCI) subjects as a window on abnormalities of the cortical neural synchronization and functional and effective connectivity. Results showed abnormalities of the EEG power density at specific frequency bands (<12Hz) in the MCI and AD populations, associated with an altered functional and effective EEG connectivity among long range cortical networks (i.e. fronto-parietal and fronto-temporal). These results suggest that resting state EEG rhythms reflect the abnormal cortical neural synchronization and coupling in the brain of prodromal and overt AD subjects, possibly reflecting dysfunctional neuroplasticity of the neural transmission in long range cortical networks.

Resting state Rolandic mu rhythms are related to activity of sympathetic component of autonomic nervous system in healthy humans.

We tested the hypothesis of a relationship between heart rate variability (HRV) and Rolandic mu rhythms in relaxed condition of resting state. Resting state eyes-closed electroencephalographic (EEG) and electrocardiographic (ECG) data were recorded (10-20 System) in 42 healthy adults. EEG rhythms of interest were high-frequency alpha (10.5-13Hz) and low-frequency beta (13-20Hz), which are supposed to form Rolandic mu rhythms. Rolandic and occipital (control) EEG sources were estimated by LORETA software. Results showed a statistically significant (p<0.05, corrected) negative correlation across all subjects between Rolandic cortical sources of low-frequency beta rhythms and the low-frequency band power (LF, 0.04-0.15Hz) of tachogram spectrum as an index of HRV. The lower the amplitude of Rolandic sources of low-frequency beta rhythms (as a putative sign of activity of somatomotor cortex), the higher the LF band power of tachogram spectrum (as a putative sign of sympathetic activity). This effect was specific as there was neither a similar correlation between these EEG rhythms and high-frequency band power of tachogram spectrum (as a putative sign of parasympathetic vagal activity) neither between occipital sources of low-frequency beta rhythms (as a putative sign of activity of visual cortex) and LF band power of tachogram spectrum. These results suggest that Rolandic low-frequency beta rhythms are related to sympathetic activity regulating heart rate, as a dynamic neurophysiologic oscillatory mechanism sub-serving the interaction between brain neural populations involved in somatomotor control and brain neural populations regulating ANS signals to heart for on-going homeostatic adaptations.

Cortical sources of resting state EEG rhythms are related to brain hypometabolism in subjects with Alzheimer's disease: an EEG-PET study.

Cortical sources of resting state electroencephalographic (EEG) delta (2-4 Hz) and low-frequency alpha (8-10.5 Hz) rhythms show abnormal activity (i.e., current density) in patients with dementia due to Alzheimer's disease (AD). Here, we hypothesized that abnormality of this activity is related to relevant disease processes as revealed by cortical hypometabolism typically observed in AD patients by fluorodeoxyglucose positron emission tomography. Resting state eyes-closed EEG data were recorded in 19 AD patients with dementia and 40 healthy elderly (Nold) subjects. EEG frequency bands of interest were delta and low-frequency alpha. EEG sources were estimated in these bands by low-resolution brain electromagnetic tomography (LORETA). Fluorodeoxyglucose positron emission tomography images were recorded only in the AD patients, and cortical hypometabolism was indexed by the so-called Alzheimer's discrimination analysis tool (PALZ) in the frontal association, ventromedial frontal, temporoparietal association, posterior cingulate, and precuneus areas. Results showed that compared with the Nold group, the AD group pointed to higher activity of delta sources and lower activity of low-frequency alpha sources in a cortical region of interest formed by all cortical areas of the PALZ score. In the AD patients, there was a positive correlation between the PALZ score and the activity of delta sources in the cortical region of interest (p < 0.05). These results suggest a relationship between resting state cortical hypometabolism and synchronization of cortical neurons at delta rhythms in AD patients with dementia.

Neurophysiological assessment of Alzheimer's disease individuals by a single electroencephalographic marker.

Here we presented a single electroencephalographic (EEG) marker for a neurophysiological assessment of Alzheimer's disease (AD) patients already diagnosed by current guidelines. The ability of the EEG marker to classify 127 AD individuals and 121 matched cognitively intact normal elderly (Nold) individuals was tested. Furthermore, its relationship to AD patients' cognitive status and structural brain integrity was examined. Low-resolution brain electromagnetic tomography (LORETA) freeware estimated cortical sources of resting state eyes-closed EEG rhythms. The EEG marker was defined as the ratio between the activity of parieto-occipital cortical sources of delta (2-4 Hz) and low-frequency alpha (8-10.5 Hz) rhythms. Results showed 77.2% of sensitivity in the recognition of the AD individuals; 65% of specificity in the recognition of the Nold individuals; and 0.75 of area under the receiver-operating characteristic curve. Compared to the AD subgroup with the EEG maker within one standard deviation of the Nold mean (EEG-), the AD subgroup with EEG+ showed lower global cognitive status, as revealed by Mini-Mental State Evaluation score, and more abnormal values of white-matter and cerebrospinal fluid normalized volumes, as revealed by structural magnetic resonance imaging. We posit that cognitive and functional status being equal, AD patients with EEG+ should receive special clinical attention due to a neurophysiological "frailty". EEG+ label can be also used in clinical trials (i) to form homogeneous groups of AD patients diagnosed by current guidelines and (ii) as end-point to evaluate intervention effects.

Occipital sources of resting-state alpha rhythms are related to local gray matter density in subjects with amnesic mild cognitive impairment and Alzheimer's disease.

Occipital sources of resting-state electroencephalographic (EEG) alpha rhythms are abnormal, at the group level, in patients with amnesic mild cognitive impairment (MCI) and Alzheimer's disease (AD). Here, we evaluated the hypothesis that amplitude of these occipital sources is related to neurodegeneration in occipital lobe as measured by magnetic resonance imaging. Resting-state eyes-closed EEG rhythms were recorded in 45 healthy elderly (Nold), 100 MCI, and 90 AD subjects. Neurodegeneration of occipital lobe was indexed by weighted averages of gray matter density, estimated from structural MRIs. EEG rhythms of interest were alpha 1 (8-10.5 Hz) and alpha 2 (10.5-13 Hz). EEG cortical sources were estimated by low-resolution brain electromagnetic tomography. Results showed a positive correlation between occipital gray matter density and amplitude of occipital alpha 1 sources in Nold, MCI, and AD subjects as a whole group (r = 0.3, p = 0.000004, N = 235). Furthermore, there was a positive correlation between the amplitude of occipital alpha 1 sources and cognitive status as revealed by Mini Mental State Examination score across all subjects (r = 0.38, p = 0.000001, N = 235). Finally, amplitude of occipital alpha 1 sources allowed a moderate classification of individual Nold and AD subjects (sensitivity: 87.8%; specificity: 66.7%; area under the receiver operating characteristic curve: 0.81). These results suggest that the amplitude of occipital sources of resting-state alpha rhythms is related to AD neurodegeneration in occipital lobe along pathologic aging.