431
differently in schizophrenia. Thought disorder in
disorganized schizophrenics (i.e. without psycho-
motor poverty or reality distortion) shows a posi-
tive correlation with increased blood flow (rCBF)
in the mediodorsal thalamus and frontal Brodmann
areas 9, 10, 24, 32 and a negative correlation with
areas 39, 44, 45, 47 (Liddle et al. 1992).
As we progress from Nl events, information is
relayed to appropriate association areas of the cor-
tex allowing for conscious∕controlled processing.
Relays via subcortical nuclei (e.g. pulvinar) allow
for automatic processing (cf. blindsight). The lat-
ter type of processing may well be illustrated by
P2 components, often associated with inhibitory
processes essential for the rejection of common
events in oddball discriminations (Alho et al.
1987). The influence of stimulus features on this
process, particularly in primary sensory cortex,
may well incur 5HT activity (Hegerl and Juckel
1993).
For processes associated with events around the
P3 latency there are at least 3 other classes of sub-
cortical comparison necessary (see wavy arrows,
Fig. 3). These may be listed as three checks:
1. What are the needs? (state, motivation), use of
the uncinate fasiculus (orbito-frontal-amygdala-
hypothalamus);
2. What are the stimulus associations? (target, land-
mark, shock); use of parahippocampal gyrus;
3. Is an appropriate response pattern available? use
of basal ganglia.
The first system shows hypoperfusion in disorgan-
ized schizophrenics, the second a left-right asym-
metry in reality-distorted subjects and the third
hyperperfusion in those with the poverty syndrome
(Liddle et al. 1992). It is thus no wonder that if P3
reflects such a range of neural activity that it is
weakly or variably expressed in schizophrenics and
other patients with mental disturbance.
One implication of the distributed processing
indicated by the wavey arrows in Fig. 3 is that there
is much cross-talk between widely separated parts
of the brain and that the outcome, expressed as
ERP generators may also be widely distributed.
Thus it should be no surprise that temporal lesions
may interfere with negative components usually
maximal in frontal regions (Woods et al. 1987) and
that frontal damage may interfere with P3, usually
maximal at parietal sites (Nasman and Dorio 1992).
(For a recent discussion on multiple P3 generators
see Johnson 1993.)
The generators are per se temporary represen-
tations of the stage of stimulus processing and re-
flect the outcome of neural interactions. This is a
phenomenon reminiscent of long-term potentiation
(LTP) —a facilitation of neural activity dependent
on amino-acid transmitters (e.g. Asp and Gly) and
enhanced by rhythmic burst firing, especially at
theta frequencies (Bliss and Collingridge 1993).
As theta frequencies are more common in man than
was thought until recently (e.g. Michel et al. 1992)
and have long been associated with attention-
related function in animals (see below) it is rel-
evant that significant components such as the Nl,
N2, P3 and late negative wave tend to occur in
phase with a theta rhythm. Others have also re-
ported enhanced theta frequencies during increased
attentional demands in ERP-Oddball studies
(Basar-Eroglu et al. 1992). The hippocampal com-
plex, one source of theta waves, figures promi-
nently in analyses of rCBF designed to find ‘the
common factor’ among schizophrenics with dif-
ferent symptoms (Friston et al. 1992) and in theo-
ries of the schizophrenic process (Gray et al. 1991).
Subtraction and comparison in the physiology
of attention
The rCBF measures from the Hammersmith cyclo-
tron unitjust mentioned emphasized the left medial
temporal lobe for an association with the psycho-
pathology of schizophrenia. This is also the region
where McCarley and colleagues (1993) have
elegantly shown reduced volume on magnetic reso-
nance images, a reduced P3 in auditory discrimi-
nation and an association with thought disorder in
schizophrenic patients. The link to attention is
brought even closer by the report from Posner et
al. (1988) that schizophrenic subjects with active
symptoms were relatively slow to detect targets in
the right visual field, reflecting left-hemisphere
function. This task places demands on the ability
to switch attention, a putative role of DA activity
(see below) — a transmitter also reported to be