Since the mid-1960s, essentially using electrophysiological methods, our research group has examined the effects of different brain diseases in humans, both on first- and second-order conditioned responses and on some types of neurocognitive potentials of the CNV complex. This didactic lecture will focus on our various attempts to identify and understand the neuroanatomical and neurophysiological substrates involved in cognitive information processing followed by the conception and execution of sensory-motor and behavioural responses evoked by significant acoustic stimuli, in both pathological situations and normal control subjects. Great interest was, e.g. aroused in the early 1970s by the rare, fortunately unrepeatable, opportunity of examining the CNV patterns in various psychiatric patients treated with psychosurgical Freeman–Watts bilateral prefrontal ‘radical’ lobotomy, also with repeated recordings (The Responsive Brain (1976) 158; Multidisciplinary Perspectives in Event-Related Brain-Potentials Research (1978) 376) or bimedial bifrontal cingulotomy (Multidisciplinary Perspectives in Event-Related Brain Potential Research (1978) 383). In the same period, investigations into CNV activity recorded in patients submitted to complete callosotomy (‘split brain’: Attention and Performance, vol. IV (1972) 221; Electroenceph. Clin. Neurophysiol. Suppl. 33 (1973) 161) were also begun and were continued into the 1980s, also with regard to other types of ERP (Brain 111 (1988) 553; J. Cog. Neurosci. 2 (1990) 258). All these data furnished unique information about the sub-second dynamics of unilateral or bihemispheric cortico-cortical and cortico-subcortical interconnections in humans. In recent years, with a classic method of analysis based on sequential scalp-topographic bidimensional neuroelectric mapping and 21/19 electrodes connected to three different references, and binaural/monaural clicks as warning signals (S1), we have repeatedly examined the CNV activity of 11 selected patients submitted to complete ablation of the damaged cortical areas, with uni- or bilateral lesions restricted to the prefrontal or associative parieto-temporal areas. We have always used the standard CNV paradigm (S1–S2 motor-response) which evokes a complex of neurocognitive potentials, including the P300 from S1, which are well-known, since they are certainly among the most studied ERPs in the various ages and races of normal subjects, psychiatric patients and subjects with different brain diseases. The most important results have been, (1) In normal subjects the MRI and the latency differences of CNV component measurements along the bidirectional pathways functionally interconnecting ipsilateral distant associative cortical areas (e.g. the arcuate-superior longitudinal complex bundle) were accounted for by the transcortical conduction time, which varies in our scalp recordings from 1 cm/0.74 to 1.28 ms (∼9.8 m/s). (2) Constantly, no true auditory S1-elicited N1a, b, c, P2, N2, P300 components or CNV slow waves (O- and E-wave) were recordable over the whole of the ablated cortical areas, but only clearly identifiable volume-conducted EP/ERPs generated in other hemispheric structures. (3) The post-S1 ERP/CNV complexes on the intact hemisphere were found to be within the normal limits. (4) Effects of severe disruption on the S1 ERP/CNV complexes evocable on the site and on remote ipsilateral apparently normal anatomo-functionally interconnected brain regions were observed in 5 patients, 4 of whom had extensive frontocortical ablations. In two of the latter the distant disruptive action on the CNV components over the neuroradiologically normal ipsilateral two-way connected post-rolandic sensory and association areas was seen to be partially reversible, showing aspects of a probable slowly evolving diaschisis-like effect. Similar deactivation of some ERP components was observed in reverse on the ipsilateral dorsolateral frontocortical region in the fifth patient with a large parieto-temporal cortex ablation. These data require confirmation, and when this phenomenon is observable, it must be appropriately monitored with different methods of functional neuroimaging. This will serve not only for medical and neuropsychophysiological diagnosis purposes, but also particularly for a correct and really useful planning of neuro-rehabilitation activities in selected cases.