Jenifer L. Vohs

Steady State Responses: Electrophysiological Assessment of Sensory Function in Schizophrenia

Persons with schizophrenia experience subjective sensory anomalies and objective deficits on assessment of sensory function. Such deficits could be produced by abnormal signaling in the sensory pathways and sensory cortex or later stage disturbances in cognitive processing of such inputs. Steady state responses (SSRs) provide a noninvasive method to test the integrity of sensory pathways and oscillatory responses in schizophrenia with minimal task demands. SSRs are electrophysiological responses entrained to the frequency and phase of a periodic stimulus. Patients with schizophrenia exhibit pronounced auditory SSR deficits within the gamma frequency range (35-50 Hz) in response to click trains and amplitude-modulated tones. Visual SSR deficits are also observed, most prominently in the alpha and beta frequency ranges (7-30 Hz) in response to high-contrast, high-luminance stimuli. Visual SSR studies that have used the psychophysical properties of a stimulus to target specific visual pathways predominantly report magnocellular-based deficits in those with schizophrenia. Disruption of both auditory and visual SSRs in schizophrenia are consistent with neuropathological and magnetic resonance imaging evidence of anatomic abnormalities affecting the auditory and visual cortices. Computational models suggest that auditory SSR abnormalities at gamma frequencies could be secondary to gamma-aminobutyric acid-mediated or N-methyl-D-aspartic acid dysregulation. The pathophysiological process in schizophrenia encompasses sensory processing that probably contributes to alterations in subsequent encoding and cognitive processing. The developmental evolution of these abnormalities remains to be characterized.

Steady state visual evoked potential abnormalities in schizophrenia

OBJECTIVE The steady state visual evoked potential (SSVEP) can be used to test the frequency response function of neural circuits. Previous studies have shown reduced SSVEPs to alpha and lower frequencies of stimulation in schizophrenia. We investigated SSVEPs in schizophrenia at frequencies spanning the theta (4Hz) to gamma (40Hz) range. METHODS The SSVEPs to seven different frequencies of stimulation (4, 8, 17, 20, 23, 30 and 40Hz) were obtained from 18 schizophrenia subjects and 33 healthy control subjects. Power at stimulating frequency (signal power) and power at frequencies above and below the stimulating frequency (noise power) were used to quantify the SSVEP responses. RESULTS Both groups showed an inverse relationship between power and frequency of stimulation. Schizophrenia subjects showed reduced signal power compared to healthy control subjects at higher frequencies (above 17Hz), but not at 4 and 8Hz at occipital region. Noise power was higher in schizophrenia subjects at frequencies between 4 and 20Hz over occipital region and at 4, 17 and 20Hz over frontal region. CONCLUSIONS SSVEP signal power at beta and gamma frequencies of stimulation were reduced in schizophrenia. Schizophrenia subjects showed higher levels of EEG noise during photic stimulation at beta and lower frequencies. SIGNIFICANCE Inability to generate or maintain oscillations in neural networks may contribute to deficits in visual processing in schizophrenia.

Eyeblink conditioning deficits indicate timing and cerebellar abnormalities in schizophrenia

Accumulating evidence indicates that individuals with schizophrenia manifest abnormalities in structures (cerebellum and basal ganglia) and neurotransmitter systems (dopamine) linked to internal-timing processes. A single-cue tone delay eyeblink conditioning paradigm comprised of 100 learning and 50 extinction trials was used to examine cerebellar timing circuits in 13 medicated patients with schizophrenia and 13 age- and sex-matched controls. Patients with schizophrenia showed impaired learning of the conditioned response compared to controls and also greater within-subject variability in the timing of their responses. These findings are consistent with models of schizophrenia in which timing deficits underlie information-processing abnormalities and clinical features of the disorder.

Metacognitive reflective and insight therapy for people in early phase of a schizophrenia spectrum disorder.

Schizophrenia often involves a loss of metacognitive capacity, the ability to form complex and integrated representations of self and others. Independent of symptoms and neurocognition, deficits in synthetic metacognition are related to difficulties of engaging in goal-directed activities in social and vocational settings. Within this backdrop, we provide a case report of the effects of Metacognitive Reflective Insight Therapy (MERIT) that assisted a patient suffering from first episode schizophrenia during 2 years of individual psychotherapy. A total of 8 elements of MERIT that stimulate and promote metacognitive capacity are presented. As illustrated in this report, these procedures helped the patient move from a state in which he had virtually no complex ideas about himself or others to one in which he had developed integrated and realistic ideas about his own identity and the identity of others. He then could use these representations to understand and effectively respond to life challenges.

The effect of cannabis use and gender on the visual steady state evoked potential

OBJECTIVE Cannabis use often induces subjective distortions of perception. However, little work has been done examining the electroencephalographic (EEG) correlates of early sensory processing in cannabis users. The present study therefore examined visual function in cannabis users as assessed via the steady state visual evoked potential. (SSVEP). METHODS SSVEPs were examined in current cannabis users (n = 17; 59% male; mean age = 23.2 (S.D. = 5.3)) and drug-naive controls (n = 16; 38% male; mean age = 21.3 (S.D. = 3.1)) to periodic photic stimulation presented at 18 and 25 Hz. The visual SSVEP was quantified via spectral power and the phase-locking factor (PLF) at each frequency of stimulation. The transient N160 event-related potential (ERP) was also evaluated at stimulus onset. RESULTS The results showed that for both frequencies, female subjects in general displayed larger visual SSVEPs. A significant gender X group interaction also occurred at 18 Hz of stimulation, and age of onset of cannabis use positively correlated with 18 Hz spectral power values. Finally, the transient N160 component was shown to be reduced in cannabis users, regardless of gender. CONCLUSIONS The present study was the first to demonstrate altered visual SSVEPs in cannabis users, and extends previous research demonstrating increased steady state responses in female subjects. While decreased SSVEPs provide initial evidence of altered oscillatory properties in primary visual circuits, reduction of the transient N160 component suggests disruption of later-stage visual processing in cannabis users. SIGNIFICANCE These data provide evidence of cannabinoid modulation of sensory/perceptual function in the visual system, and indicates that cannabis use may affect the oscillatory properties of sensory cortical circuits.

The auditory steady-state response (ASSR): a translational biomarker for schizophrenia.

Electrophysiological methods have demonstrated disturbances of neural synchrony and oscillations in schizophrenia which affect a broad range of sensory and cognitive processes. These disturbances may account for a loss of neural integration and effective connectivity in the disorder. The mechanisms responsible for alterations in synchrony are not well delineated, but may reflect disturbed interactions within GABAergic and glutamatergic circuits, particularly in the gamma range. Auditory steady-state responses (ASSRs) provide a non-invasive technique used to assess neural synchrony in schizophrenia and in animal models at specific response frequencies. ASSRs are electrophysiological responses entrained to the frequency and phase of a periodic auditory stimulus generated by auditory pathway and auditory cortex activity. Patients with schizophrenia show reduced ASSR power and phase locking to gamma range stimulation. We review alterations of ASSRs in schizophrenia, schizotypal personality disorder, and first-degree relatives of patients with schizophrenia. In vitro and in vivo approaches have been used to test cellular mechanisms for this pattern of findings. This translational, cross-species approach provides support for the role of N-methyl-D-aspartate and GABAergic dysregulation in the genesis of perturbed ASSRs in schizophrenia and persons at risk.

Deficits in metacognitive capacity distinguish patients with schizophrenia from those with prolonged medical adversity

Research has suggested that many with schizophrenia experience decrements in synthetic metacognition, or the abilities to form integrated representations of oneself and others and then utilize that knowledge to respond to problems. Although such deficits have been linked with functional impairments even after controlling for symptoms and neurocognition, it is unclear to what extent these deficits can distinguish persons with schizophrenia from others experiencing significant life adversity but without psychosis. To explore this issue we conducted logistic regression analysis to determine whether assessment of metacognition could distinguish between 166 participants with schizophrenia and 51 adults with HIV after controlling for social cognition and education. Metacognition was assessed with the Metacognitive Assessment Scale Abbreviated (MAS-A), and social cognition with the Bell Lysaker Emotion Recognition Test. We observed that the MAS-A total score was able to correctly classify 93.4% of the schizophrenia group, with higher levels of metacognition resulting in increased likelihood of accurate categorization. Additional exploratory analyses showed specific domains of metacognition measured by the MAS-A were equally able to predict membership in the schizophrenia group. Results support the assertion that deficits in the abilities to synthesize thoughts about oneself and others into larger representations are a unique feature of schizophrenia.

Early stage vision in schizophrenia and schizotypal personality disorder

Previous studies of visual perception have reported deficits in contrast sensitivity and dot motion discrimination in schizophrenia. We tested whether these deficits also appear in schizotypal personality disorder (SPD). SPD appears to be genetically and symptomatically related to schizophrenia, but without the marked psychosocial impairment associated with psychotic disorders. The present study investigated contrast sensitivity for moving and static gratings, form discrimination and dot motion discrimination in 24 patients with schizophrenia or schizoaffective disorder (SZ), 16 individuals with SPD, and 40 control subjects. SZ, but not SPD subjects, showed impairments on tests of contrast sensitivity for static and moving gratings, form discrimination in noise, and dot motion discrimination. Visual performance did not differ between medicated SZ patients and patients withdrawn from medication. These results confirm early stage visual deficits in schizophrenia regardless of medication status. SPD subjects, in contrast, show intact early stage visual processing despite the presence of marked schizotypal symptoms.

Metacognitive Deficits in Schizophrenia: Presence and Associations With Psychosocial Outcomes.

Abstract Early formulations of schizophrenia suggested that the disorder involves a loss of ability to form integrated ideas about oneself, others, and the world, resulting in reductions in complex goal-directed behaviors. Exploring this position, the current review describes evidence that persons with schizophrenia experience decrements in their ability to form complex ideas about themselves and to ultimately use that knowledge to respond to psychological and social challenges. Studies are detailed that find greater levels of these impairments, defined as metacognitive deficits, in persons with schizophrenia in both early and later phases of illness as compared with other clinical and community groups. Furthermore, studies linking metacognitive deficits with poorer psychosocial functioning and other variables closely linked to outcomes are summarized. Clinical implications are also discussed.

Metacognitive mastery and intrinsic motivation in schizophrenia.

Abstract Deficits in intrinsic motivation (IM) have been linked to poorer outcome in schizophrenia, but its proximal mechanisms remain poorly understood. This study examined whether metacognitive mastery, or the capacity to use knowledge of self, others, and context to identify and cope with psychological difficulties, predicted levels of IM for 6 months among 75 participants with prolonged schizophrenia. Repeated-measures analysis of variance revealed that high metacognitive mastery predicted consistently higher levels of IM; however, intermediate and low mastery did not produce unique IM profiles. The findings suggest that metacognitive mastery may have an important role in IM over time and could be a meaningful treatment target.