A. Versari

Correlations of Topographical EEG Features with Clinical Severity in Mild and Moderate Dementia of Alzheimer Type

Quantitative electroencephalography (qEEG) and the Folstein Mini Mental State examination (MMSE) were obtained from 31 patients affected by probable dementia of Alzheimers type (DAT). qEEG data were examined both by spectral analysis (Fast Fourier Transformation) and by single frequency band topographical centroid, and compared with those of 24 healthy subjects of the same age group. DAT patients were found to have higher absolute power in the slow (delta and theta) frequency bands. Quantitative topographical assessment showed significantly more anteriorly located centers of gravity for the alpha and beta activity. Only alpha anteriorization was correlated with the degree of cognitive impairment as measured by the global deterioration scale and MMSE. It is concluded that quantitative topographical assessment was successful for the statistical handling of the EEG power maps, and to identify a potential parameter for the functional staging of the disease.

The effects on auditory neurocognitive evoked responses and contingent negative variation activity of frontal cortex lesions or ablations in man: three new case studies

Our previous research in patients with extensive surgical ablations of the prefrontal cortex contradict the hypothesis of some authors that the generators of several auditory event-related potentials (ERPs) (N100; P200; N200; P300; SW), recordable in humans with depth/scalp electrodes and MEG over the prefrontal dorsolateral cortical areas, are essentially located in medial prefrontal and anterior cingulate-limbic cortices. Using a standard CNV paradigm, 21 EEG electrodes and topographic mapping analysis, the post-warning (S1) auditory N100a b c, P200, P300 (binaural clicks) and CNV activity were recorded in three additional patients after extensive dorsolateral and/or medial prefrontal cortex ablations, verified through CT/MRI examinations. No true post-S1/CNV components were recordable over the ablated frontal areas, only sporadic volume-conducted ERPs probably generated in the temporo-parietal lobes or posterior cingulate gyrus. For one of these patients, after excision of a vast right frontal epileptogenic cortical region (including extensive dorsolateral areas, but sparing the fronto-medial cortex and anterior/middle cingulate gyrus), no post-S1/CNV components were recordable over the ablated regions. These latest observations again indicate that independent neuronal generators of several post-S1 auditory and CNV components are located in the dorsolateral supramodal premotor/prefrontal cortical areas which are directly, ipsilaterally connected to the uni/multimodal temporo-parieto-occipital sensory and associative regions through the long, two-way, fairly superficial, superior arcuate-longitudinal and deeper superior and inferior occipito-frontal bundles. Clear and almost constant differences in the latency of some post-S1 N100 subcomponents (especially the time-lapses between onset and the highest amplitude of the N100 a and c) over various posterior, central and anterior cortical areas sequentially involved, roughly measured in 10 normal subjects along the scalp and with MRI cerebral imaging, may probably be accounted for by the transcortical homohemispheric conduction time, which varies in our scalp recordings from 1 cm/0.74-1.28 ms, mean approximately 1 cm/1.02 ms ( approximately 9.8 ms).

Topographic CNV activity mapping, presenile mild primary cognitive decline and Alzheimer-type dementia.

The CNV complex evoked with a standard paradigm (S1-2 sec-S2-motor response) and reaction time (RT) to the imperative signal (S2) were recorded and measured in 12 patients with initial presenile idiopathic cognitive decline (PICD), 12 with presenile Alzheimer-type dementia (PAD) and 10 healthy age-matched controls. Significant group differences were obtained for measures of some CNV components, particularly of the late pre-S2 CNV. No significant CNV activity, very prolonged RTs and sometimes characteristic post-imperative negative variations (PINV) were observed in the majority of patients with PAD. These results suggest that similar CNV complex and RT changes to those observed in our patients may constitute a valuable clue in the study of pathophysiological brain functioning in the early stages of presenile idiopathic mental deterioration.

Cognitive potentials: ipsilateral corticocortical interconnections in prefrontal human cortex ablations

The research deals with the possible role of the essentially monosynaptic bidirectional corticocortical connections between occipito-temporo-parietal association cortical areas and frontal areas in the genesis of some contingent negative variation (CNV) components, especially on the supramodal dorsolateral prefrontal regions. With standard and topographic mapping methods of analysis, the multicomponent CNV complex formation was examined in 7 patients with extensive frontal cortex ablations exactly identified through CT/MRI examinations, and in 10 normal subjects. On the scalp over the ablated frontocortical areas, no consistent post-warning auditory N100 a-b-c, P200, P300, early and late CNV components were recordable. The hypothesis is proposed that the bidirectional ipsilateral long-distance pathways which interconnect uni-polymodal occipito-temporo-parietal cortical areas to prefrontal ones, in particular the arcuate-superior longitudinal and superior/inferior occipito-frontal fasciculi, play an important role in the genesis of several CNV complex components, especially the multicomponent post-S1 auditory N100. The posteroanterior sequential latency differences of these neurocognitive components, roughly measured along the scalp or on MRI imagings, is probably accounted for by the transcortical ipsilateral conduction time of about 1 cm/ms (10 m/s).

Changes in bit-mapped contingent negative variation (CNV) activity due to initial normal involutional processes of the human brain

Bit-color mapped multicomponent CNV complexes and RTs to S2 evoked with a simple warned CNV/RT paradigm were recorded and measured in 20 selected right-handed very healthy volunteers (10 young adults and 10 presenile subjects, mean age 28.3 and 59.6, respectively). EEG and CNV components (post S1, N1, P2, P3; early CNV; N1200; late CNV; CNV resolution) were recorded from Fz, C3, Cz, C4, P3, Pz, and P4 referenced to linked mastoid electrodes. EOG, RT and stimuli were also recorded. The presenile group differed significantly from the younger group in the auditory post-S1 N1 and early (O-wave) and late (P-wave) CNV complex components. A progressive amplitude reduction limited to frontal leads between O-wave and P-wave, the lowest point being reached in the P-wave, was characteristic in the presenile group. Moreover, presenile subjects showed relatively flat CNV waveshapes of low amplitude and, on the whole, performed a little less well than young ones. This finding suggests that the statistically significant changes in auditory post-S1 N1 and CNV activity recorded in our presenile subjects, without any appreciable deficits in behavioral or mental performance, could be alerting signs of early brain involutional processes related to minimal and subclinical decline in orienting, attentiveness and response preparation capabilities. If such is the case, and it could be confirmed in a larger sample of very healthy subjects, these age-related changes in the presenium might prove to be of considerable practical importance for clinical research.

Contingent negative variation and reaction time in patients with presenile idiopathic cognitive decline and presenile Alzheimer-type dementia. Preliminary report on long-term nicergoline treatment

Up to date 6 patients with initial presenile idiopathic cognitive decline (PICD) and 5 suffering from a presenile Alzheimer-type dementia (PAD) with a mean age of 59.5 were admitted to the trial. The 6 PICD patients were assigned to a double-blind nicergoline/placebo 6-month course with an oral dose of 30 mg twice a day. PAD patients were treated in an open design (nicergoline oral dose 30 mg twice a day) for at least 6 months. Until now only 4 PICD and 3 PAD patients have been treated regularly for 6 months. Two of 4 PICD patients showed a progressive enhancement of contingent negative variation (CNV), shorter reaction time (RT) and an improvement of clinical status. The other 2 PICD patients, on the contrary, showed a progressive mild worsening of CNV-RT and clinical patterns. The double-blind trial is not yet completed. CNV activity, RTs and clinical patterns progressively improved also in 2 PAD patients while in the 3rd they remained nearly unchanged or minimally worse during the 6-month treatment. The positive nicergoline effect on CNV-RT and clinical status noted in our patients appeared similar to that observed by other authors with DHEMT in patients with senile dementia of Alzheimer type. No adverse drug-related reactions were seen.