Brain and cognitive functions in two groups of naïve HIV patients selected for a different plan of antiretroviral therapy: A qEEG study.

OBJECTIVE: Cortical sources of electroencephalographic (EEG) rhythms were investigated in two sub-populations of naïve HIV subjects, grouped based on clinical criteria to receive different combination anti-retroviral therapies (cARTs). These EEG sources were hypothesized to reflect beneficial effects of both regimes. METHODS: Eyes-closed resting state EEG data were collected in 19 (Group A) and 39 (Group B) naïve HIV subjects at baseline (i.e. pre-treatment; T0) and after 5months of cART (T5). Compared with the Group A, the Group B was characterized by slightly worse serological parameters and higher cardiovascular risk. At T0, mean viral load (VL) and CD4 count were 87,694copies/ml and 435cells/µl in the Group A and 187,370copies/ml and 331cells/µl in the Group B. The EEG data were also collected in 50 matched control HIV-negative subjects. Cortical EEG sources were assessed by LORETA software. RESULTS: Compared to the Control Group, the HIV Groups showed lower alpha (8-12Hz) source activity at T0 while the Group B also exhibited higher delta source activity. The treatment partially normalized alpha and delta source activity in the Group A and B, respectively, in association with improved VL, CD4, and cognitive functions. CONCLUSIONS: Different cART regimens induced diverse beneficial effects in delta or alpha source activity in the two naïve HIV Groups. SIGNIFICANCE: These sources might unveil different neurophysiological effects of diverse cART on brain function in naïve HIV Groups as a function of clinical status and/or therapeutic compounds.

Antiretroviral therapy affects the z-score index of deviant cortical EEG rhythms in naïve HIV individuals.

OBJECTIVE: Here we tested the effect of combined antiretroviral therapy (cART) on deviant electroencephalographic (EEG) source activity in treatment-naïve HIV individuals. METHODS: Resting state eyes-closed EEG data were recorded before and after 5 months of cART in 48 male HIV subjects, who were naïve at the study start. The EEG data were also recorded in 59 age- and sex-matched healthy subjects as a control group. Frequency bands of interest included delta, theta, alpha1, alpha2 and alpha3, based on alpha frequency peak specific to each individual. They also included beta1 (13-20 Hz) and beta2 (20-30 Hz). Low-resolution brain electromagnetic tomography (LORETA) estimated EEG cortical source activity in frontal, central, temporal, parietal, and occipital regions. RESULTS: Before the therapy, the HIV group showed greater parietal delta source activity and lower spatially diffuse alpha source activity compared to the control group. Thus, the ratio of parietal delta and alpha3 source activity served as an EEG marker. The z-score showed a statistically deviant EEG marker (EEG +) in 50% of the HIV individuals before therapy (p < 0.05). After 5 months of cART, delta source activity decreased, and alpha3 source activity increased in the HIV subjects with EEG + (about 50% of them showed a normalized EEG marker). CONCLUSIONS: This procedure detected a deviant EEG marker before therapy and its post-therapy normalization in naïve HIV single individuals. SIGNIFICANCE: The parietal delta/alpha3 EEG marker may be used to monitor cART effects on brain function in such individuals.

Abnormal cortical sources of resting state electroencephalographic rhythms in single treatment-naïve HIV individuals: A statistical z-score index.

OBJECTIVE: This study tested a simple statistical procedure to recognize single treatment-naïve HIV individuals having abnormal cortical sources of resting state delta (<4 Hz) and alpha (8-13 Hz) electroencephalographic (EEG) rhythms with reference to a control group of sex-, age-, and education-matched healthy individuals. Compared to the HIV individuals with a statistically normal EEG marker, those with abnormal values were expected to show worse cognitive status. METHODS: Resting state eyes-closed EEG data were recorded in 82 treatment-naïve HIV (39.8 ys.±1.2 standard error mean, SE) and 59 age-matched cognitively healthy subjects (39 ys.±2.2 SE). Low-resolution brain electromagnetic tomography (LORETA) estimated delta and alpha sources in frontal, central, temporal, parietal, and occipital cortical regions. RESULTS: Ratio of the activity of parietal delta and high-frequency alpha sources (EEG marker) showed the maximum difference between the healthy and the treatment-naïve HIV group. Z-score of the EEG marker was statistically abnormal in 47.6% of treatment-naïve HIV individuals with reference to the healthy group (p<0.05). Compared to the HIV individuals with a statistically normal EEG marker, those with abnormal values exhibited lower mini mental state evaluation (MMSE) score, higher CD4 count, and lower viral load (p<0.05). CONCLUSIONS: This statistical procedure permitted for the first time to identify single treatment-naïve HIV individuals having abnormal EEG activity. SIGNIFICANCE: This procedure might enrich the detection and monitoring of effects of HIV on brain function in single treatment-naïve HIV individuals.

Cortical sources of resting state electroencephalographic rhythms differ in relapsing-remitting and secondary progressive multiple sclerosis.

OBJECTIVE: Resting state electroencephalographic (EEG) rhythms are abnormal in multiple sclerosis (MS) patients, but it is unclear if they can reflect different neurophysiologic abnormalities in MS sub-types (phenotypes) such as relapsing-remitting (RR) and secondary progressive (SP). METHODS: We tested whether cortical sources of resting state EEG rhythms are abnormal in MS patients and differ between MS phenotypes. Resting state eyes-closed EEG activity was recorded in 36 RR, 23 SP, and 41 matched healthy subjects. EEG bands of interest were individually identified based on Transition frequency (TF), Individual alpha frequency (IAF), and Individual beta frequency (IBF). LORETA freeware estimated cortical EEG sources. RESULTS: Widespread TF -4Hz (delta) and IAF (alpha) cortical sources were abnormal in the MS sub-groups compared to the control group. Furthermore, TF -4Hz sources in central, parietal, and limbic regions were higher in amplitude in the SP compared to the RR sub-group. CONCLUSION: Cortical sources of resting state EEG rhythms are abnormal in MS patients at group level and differ between RR and SP sub-groups. SIGNIFICANCE: Future studies should test the utility of these EEG markers in the diagnosis and management of MS clinical phenotypes and in the therapy evaluation.

Antiretroviral therapy effects on sources of cortical rhythms in HIV subjects: responders vs. mild responders.

OBJECTIVE: We tested the hypothesis that 5months of combined anti-retroviral therapy (cART) affect cortical sources of resting state cortical electroencephalographic (EEG) rhythms in naïve HIV subjects. METHODS: Eyes-closed resting state EEG data were recorded at baseline (i.e. pre-treatment; T0), T1 (after 4weeks of cART), T2 (after 8weeks of cART), and T5 (after 5months of cART) in 38 naïve HIV subjects. EEG data were also recorded in 40 age-matched cognitively normal subjects for control purposes. 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), and beta 2 (20-30Hz). Cortical EEG sources were estimated by LORETA software. RESULTS: Compared to the control group, the HIV group at T0 showed greater delta sources and lower widespread alpha sources. cART induced a global improvement of biological (viral load, CD4 count) and EEG (delta, alpha) markers, remarkable even after 4weeks. Compared to HIV Responders (>100cells/µl at 5-month follow up), the HIV Mild Responders (<100cells/µl) showed greater parietal delta sources at baseline and lower occipital alpha sources at 5-month follow up. CONCLUSIONS: In naïve HIV subjects, 5months of successful cART affect brain synchronization mechanisms at the basis of the generation of delta and alpha rhythms. SIGNIFICANCE: The present EEG markers may be useful secondary neurophysiological end points for pharmacological clinical trials in naïve HIV subjects.

Cortical sources of resting-state EEG rhythms in "experienced" HIV subjects under antiretroviral therapy.

OBJECTIVE: Treatment-naïve patients with human immunodeficiency virus (HIV) are characterized by diffuse abnormalities of resting-state cortical electroencephalographic (EEG) rhythms (Babiloni et al., 2012a). Here, we tested the hypothesis that these EEG rhythms vary as a function of the systemic immune activity and antiretroviral therapy (ART) in HIV patients. METHODS: Resting-state eyes-closed EEG data were recorded in 68 ART-HIV patients (mini mental state evaluation (MMSE) of 27.5 ± 0.3 SEM), in 60 treatment-naïve HIV subjects (MMSE of 27.5 ± 0.4 SEM) and in 75 age-matched cognitively normal subjects (MMSE of 29.3 ± 0.1 SEM). Based on the CD4 lymphocytes' count, we divided ART-HIV subjects into two subgroups: those with CD4>500 cells/µl (ART-HIV+) and those with CD4<500 cells/µl (ART-HIV-). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-12 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Cortical EEG sources were estimated by LORETA software. RESULTS: Widespread theta, alpha, and beta sources were lower in ART-HIV subjects than in control subjects. Furthermore, occipital and temporal alpha 1 sources were lower in treatment-naïve HIV than in ART-HIV subjects. Moreover, the opposite was true for widespread pathological delta sources. Finally, parietal, occipital, and temporal alpha 1 sources were lower in ART-HIV- than in ART-HIV+ subjects. CONCLUSIONS: In ART-HIV subjects, cortical sources of resting-state alpha rhythms are related to systemic immune activity and cART. SIGNIFICANCE: This EEG procedure may produce biomarkers of treatment response in patients' brain compartments for longitudinal clinical studies.

Cortical sources of resting-state EEG rhythms are abnormal in naïve HIV subjects.

OBJECTIVE: The aim of the study was to test the hypothesis that cortical sources of resting-state electroencephalographic (EEG) rhythms show peculiar frequency/spatial features in naïve human subjects with human immunodeficiency virus (HIV) compared to healthy control subjects. METHODS: Resting-state eyes-closed EEG data were recorded in 18 naïve HIV subjects (15 males; mean age 39 years±2.0 standard error of mean, SEM) and in 18 age-matched cognitively normal subjects (15 males; 38.7years±2.2 SEM). EEG rhythms of interest were delta (2-4Hz), theta (4-8Hz), alpha1 (8-10Hz), alpha2 (10-12Hz), beta1 (13-20Hz) and beta2 (20-30Hz). Cortical EEG sources were estimated by normalised, low-resolution electromagnetic tomography (LORETA). RESULTS: Mini Mental State Evaluation (MMSE) score was lower in HIV (26.5 ± 0.7 SEM) than in healthy (29.2 ± 0.5 SEM) subjects (p<0.05). Central and parietal delta sources showed higher amplitude in the HIV than in control subjects. Furthermore, topographically widespread, cortical sources of resting-state alpha rhythms were lower in amplitude in HIV subjects than in control subjects. CONCLUSIONS: The present results suggest that topography and frequency of the cortical sources of resting-state EEG rhythms can distinguish groups of HIV and control subjects. SIGNIFICANCE: These results encourage future studies in an enlarged cohort of HIV subjects to test the hypothesis that the present methodological approach provides clinically useful information for an early detection of the effect of HIV infection on brain and cognitive functions.

Cortical sources of resting state EEG rhythms are abnormal in dyslexic children.

OBJECTIVE: Previous studies have been inconclusive whether dominant resting state alpha rhythms differ in amplitude in dyslexic subjects when compared to control subjects, being these rhythms considered as a reflection of effective cortical neural synchronization and cognition. Here we used a validated EEG source estimation to test the hypothesis that resting state alpha rhythms are abnormal in dyslexic subjects and are related to reading deficits. METHODS: Eyes-closed resting state electroencephalographic (EEG) data were recorded in 26 dyslexics (12 males, mean age of 11 years ± 0.5 standard error of mean, SEM) and 11 age-matched normal control subjects (8 males, mean age of 11 years ± 0.7 SEM). EEG rhythms of interest, based on individual alpha frequency peak, were the following: about 2-4 Hz (delta), 4-6 Hz (theta), 6-8 Hz (alpha 1), 8-10 Hz (alpha 2), and 10-12 Hz (alpha 3). For the higher frequencies, we selected beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz). Cortical EEG sources were estimated by low resolution electromagnetic tomography (LORETA). LORETA solutions were normalized across all voxels and frequencies. RESULTS: Compared to the control children, the dyslexics showed lower amplitude of parietal, occipital, and temporal alpha 2 and alpha 3 sources. In the dyslexics, some of these sources were correlated to reading time of pseudo-words (parietal alpha 2, r=-0.56, p=0.02; parietal alpha 3, r=-0.58, p=0.02; temporal alpha 3, r=-0.57, p=0.02); the higher the alpha power, the shorter the reading time. CONCLUSIONS: Dyslexic children are characterized by limited abnormalities of resting state EEG rhythms as to topography (posterior regions) and frequency (alpha), which were related to phonological encoding (pseudo-words reading). SIGNIFICANCE: Dyslexia may be associated to some functional impairment of cortical neuronal synchronization mechanisms involved in the resting state condition.

Cortical sources of EEG rhythms are abnormal in down syndrome.

OBJECTIVE: Previous studies have been inconclusive whether dominant resting state alpha rhythms are greater or lower in amplitude in subjects with Down syndrome (DS) when compared to control subjects, ample resting alpha rhythms being considered as a reflection of good mechanisms of cortical neural synchronization. Here we tested the hypothesis that when the effects of head volume conduction are taken into account by the normalization of the cortical sources of resting alpha rhythms, these sources are lower in amplitude in DS subjects than in controls in line with typical findings in Alzheimer's disease patients. METHODS: Eyes-closed resting electroencephalographic (EEG) data were recorded in 45 DS subjects (25 males; mean age of 22.8years+/-0.7 standard error of mean (SEM)) and in 45 age-matched cognitively normal subjects (25 males; mean age of 22.4years+/-0.5 SEM). 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). Cortical EEG sources were estimated by low resolution electromagnetic tomography (LORETA) and normalized across all voxels and frequencies. RESULTS: Central, parietal, occipital, and temporal cortical sources of resting alpha and beta rhythms were lower in amplitude in the DS than control subjects, whereas the opposite was true for occipital delta cortical sources. A control analysis on absolute source values showed that they were globally larger in amplitude across several frequency bands in DS than control subjects. CONCLUSIONS: These results suggest that normalized cortical sources of alpha rhythms are lower in amplitude in DS than control subjects, as it is typically found in Alzheimer's disease. SIGNIFICANCE: DS is accompanied by a functional impairment of cortical neuronal synchronization mechanisms in the resting state condition.