When doors of perception close: bottom-up models of disrupted cognition in schizophrenia

Abstract

Schizophrenia is a major mental disorder that affects approximately 1% of the population worldwide. Cognitive deficits are a key feature of schizophrenia and a primary cause of long-term disability. Current neurophysiological models of schizophrenia focus on distributed brain dysfunction with bottom-up as well as top-down components. Bottom-up deficits in cognitive processing are driven by impairments in basic perceptual processes that localize to primary sensory brain regions. Within the auditory system, deficits are apparent in elemental sensory processing, such as tone matching following brief delay. Such deficits lead to impairments in higher-order processes such as phonological processing and auditory emotion recognition. Within the visual system, deficits are apparent in functioning of the magnocellular visual pathway, leading to higher-order deficits in processes such as perceptual closure, object recognition, and reading. In both auditory and visual systems, patterns of deficit are consistent with underlying impairment of brain N-methyl-d-aspartate receptor systems.

Figure 1

Evolving conceptual models of the interactions between sensory and attentional systems in brain. (a) Linear model proposed by Broadbent in 1958, postulating direct effects of attention on sensory stores. (b) Modified model proposed by Cowan et al. in 1988, illustrating both pre- and postattentional stages of sensory/perceptual processing. (From Cowan 1995, pp. 9 and 31.)

Figure 2

Schematic diagram of mismatch negativity (MMN) generators in schizophrenia. (a) MMN is elicited in an auditory oddball paradigm in which a sequence of repetitive standard stimuli (blue boxes) is interrupted by stimuli that differ in a physical stimulus dimension such as pitch or duration ( green boxes). The deviant probability equals the number of deviants divided by the total number of stimuli. MMN reflects N-methyl-D-aspartate (NMDA)-dependent processing of stimulus deviance within the auditory sensory cortex. (b) Schematic diagram of MMN generators within the auditory cortex (located in the superior temporal lobe, shown in red ). Because of the orientation of MMN generators, the MMN reverses in polarity between the frontal midline electrode (Fz) and the left (LM) and right (RM) mastoids. Because pitch deviance can be detected at stimulus onset, but duration deviance can only be detected at the time of standard stimulus offset, duration MMN ( pale blue line) is delayed relative to pitch (frequency) MMN ( pink line). The dashed arrow indicates the orientation of the electrical field originating from the auditory cortex. Activity from auditory cortex characteristically inverts between the central midline electrode (Fz) and the mastoids (RM, LM) relative to a nose reference (not shown). (c) Characteristic waveforms at Fz from patients with recent onset or chronic schizophrenia versus controls. Peak MMN responses (arrows) are significantly reduced in patients with schizophrenia relative to controls, for both pitch (top line) and duration (bottom line). Dashed lines illustrate the latency shift in response to pitch versus duration to deviant stimuli. (From Javitt et al. 2008, p. 73.)

Figure 3

Relationship between tone matching and voice emotion discrimination in schizophrenia. (a) Factor analysis showing separate clustering of auditory versus visual affective discrimination tests, and interrelationship among impairments in a tone matching task (TMT), distorted tunes task (DTT), voice emotion discrimination (VOICE-DISCRIM), and voice emotion identification (VOICE-ID) in schizophrenia, with separate clustering of face emotion discrimination (FACE-DIS) and face emotion identification (FACE-ID) tasks. Values are correlation coefficients (r); * = p < 0.05, ** p < 0.01. (From Leitman et al. 2005.) Scatter plots show relationship between (b) tone matching and voice emotion identification and (c) voice emotion identification and global outcome, as reflected by the Independent Living Scale. (From Leitman et al. 2008.) (d ) Schematic diagram of bottom-up relationships between impaired auditory sensory processing.

Figure 4

(a) Schematic model of visual system showing projections of the magnocellular (M) and parvocellular (P) pathways, which project preferentially through lateral geniculate nucleus (LGN) to primary visual cortex (V1) and then to dorsal (“where”) and ventral (“what”) streams. (b) Illustrations of anatomic arrangements of visual regions (cartoon source: Google commons). (inset) Relative properties of magnocellular and parvocellular neurons.

Figure 5

Comparative deficits in visual activation in schizophrenia patients versus cats treated with the NMDA antagonist 2-amino-5-phosphonovaleric acid (APV). (a) ssVEP amplitude (signal-to-noise ratio) in schizophrenic patients in response to magnocellular-biased stimuli. (From Butler et al. 2005.) (b) Effects of APV infusion into cat lateral geniculate nucleus (LGN) in response to stimulation. (From Kwon et al. 1991.)

Figure 6

Perceptual closure performance in patients and controls. (a) Need for reduced level of fragmentation (more complete figure) for object identification in patients relative to controls. Insets show examples of stimuli at the corresponding levels of fragmentation. (From Doniger et al. 2001.) (b) Effects of stimulus repetition in patients and controls. (c) Closure negativity (N_cl) generation in schizophrenia patients (Sz) versus controls (Ctl) showing reduction in P1 amplitude (open arrow) and Ncl (dashed line). (From Doniger et al. 2002.)