Davide Rivolta

Diagnosing prosopagnosia: Effects of ageing, sex, and participant-stimulus ethnic match on the cambridge face memory test and cambridge face perception test

The Cambridge Face Memory Test (CFMT) and Cambridge Face Perception Test (CFPT) have provided the first theoretically strong clinical tests for prosopagnosia based on novel rather than famous faces. Here, we assess the extent to which norms for these tasks must take into account ageing, sex, and testing country. Data were from Australians aged 18 to 88 years (N = 240 for CFMT; 128 for CFPT) and young adult Israelis (N = 49 for CFMT). Participants were unselected for face recognition ability; most were university educated. The diagnosis cut-off for prosopagnosia (2 SDs poorer than mean) was affected by age, participant–stimulus ethnic match (within Caucasians), and sex for middle-aged and older adults on the CFPT. We also report internal reliability, correlation between face memory and face perception, correlations with intelligence-related measures, correlation with self-report, distribution shape for the CFMT, and prevalence of developmental prosopagnosia.

Impaired holistic coding of facial expression and facial identity in congenital prosopagnosia

Research highlights ► Congenital prosopagnosics show weak holistic coding of expression and identity. ► Normal expression recognition can result from compensatory strategies. ► There may be a common stage of holistic coding for expression and identity. ► Holistic coding of identity is functionally involved in face identification ability.

TMS-EEG Signatures of GABAergic Neurotransmission in the Human Cortex

Combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG) constitutes a powerful tool to directly assess human cortical excitability and connectivity. TMS of the primary motor cortex elicits a sequence of TMS-evoked EEG potentials (TEPs). It is thought that inhibitory neurotransmission through GABA-A receptors (GABAAR) modulates early TEPs (<50 ms after TMS), whereas GABA-B receptors (GABABR) play a role for later TEPs (at ∼100 ms after TMS). However, the physiological underpinnings of TEPs have not been clearly elucidated yet. Here, we studied the role of GABAA/B-ergic neurotransmission for TEPs in healthy subjects using a pharmaco-TMS-EEG approach. In Experiment 1, we tested the effects of a single oral dose of alprazolam (a classical benzodiazepine acting as allosteric-positive modulator at α1, α2, α3, and α5 subunit-containing GABAARs) and zolpidem (a positive modulator mainly at the α1 GABAAR) in a double-blind, placebo-controlled, crossover study. In Experiment 2, we tested the influence of baclofen (a GABABR agonist) and diazepam (a classical benzodiazepine) versus placebo on TEPs. Alprazolam and diazepam increased the amplitude of the negative potential at 45 ms after stimulation (N45) and decreased the negative component at 100 ms (N100), whereas zolpidem increased the N45 only. In contrast, baclofen specifically increased the N100 amplitude. These results provide strong evidence that the N45 represents activity of α1-subunit-containing GABAARs, whereas the N100 represents activity of GABABRs. Findings open a novel window of opportunity to study alteration of GABAA-/GABAB-related inhibition in disorders, such as epilepsy or schizophrenia.

Deficits in High- (>60 Hz) Gamma-Band Oscillations During Visual Processing in Schizophrenia

Current theories of the pathophysiology of schizophrenia have focused on abnormal temporal coordination of neural activity. Oscillations in the gamma-band range (>25 Hz) are of particular interest as they establish synchronization with great precision in local cortical networks. However, the contribution of high gamma (>60 Hz) oscillations toward the pathophysiology is less established. To address this issue, we recorded magnetoencephalographic (MEG) data from 16 medicated patients with chronic schizophrenia and 16 controls during the perception of Mooney faces. MEG data were analysed in the 25–150 Hz frequency range. Patients showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces while responses to inverted stimuli were intact. Impaired processing of Mooney faces in schizophrenia patients was accompanied by a pronounced reduction in spectral power between 60–120 Hz (effect size: d = 1.26) which was correlated with disorganized symptoms (r = −0.72). Our findings demonstrate that deficits in high gamma-band oscillations as measured by MEG are a sensitive marker for aberrant cortical functioning in schizophrenia, suggesting an important aspect of the pathophysiology of the disorder.

Face ethnicity and measurement reliability affect face recognition performance in developmental prosopagnosia: evidence from the Cambridge Face Memory Test-Australian.

The Cambridge Face Memory Test (CFMT, Duchaine & Nakayama, 2006) provides a validated format for testing novel face learning and has been a crucial instrument in the diagnosis of developmental prosopagnosia. Yet, some individuals who report everyday face recognition symptoms consistent with prosopagnosia, and are impaired on famous face tasks, perform normally on the CFMT. Possible reasons include measurement error, CFMT assessment of memory only at short delays, and a face set whose ethnicity is matched to only some Caucasian groups. We develop the “CFMT-Australian” (CFMT-Aus), which complements the CFMT-original by using ethnicity better matched to a different European subpopulation. Results confirm reliability (.88) and validity (convergent, divergent using cars, inversion effects). We show that face ethnicity within a race has subtle but clear effects on face processing even in normal participants (includes cross-over interaction for face ethnicity by perceiver country of origin in distinctiveness ratings). We show that CFMT-Aus clarifies diagnosis of prosopagnosia in 6 previously ambiguous cases. In 3 cases, this appears due to the better ethnic match to prosopagnosics. We also show that face memory at short (<3-min), 20-min, and 24-hr delays taps overlapping processes in normal participants. There is some suggestion that a form of prosopagnosia may exist that is long delay only and/or reflects failure to benefit from face repetition.

Characterization of GABAB-receptor mediated neurotransmission in the human cortex by paired-pulse TMS-EEG

GABAB-receptor (GABABR) mediated inhibition is important in regulating neuronal excitability. The paired-pulse transcranial magnetic stimulation (TMS) protocol of long-interval intracortical inhibition (LICI) likely reflects this GABABergic inhibition. However, this view is based on indirect evidence from electromyographic (EMG) studies. Here we combined paired-pulse TMS with simultaneous electroencephalography (paired-pulse TMS-EEG) and pharmacology to directly investigate mechanisms of LICI at the cortical level. We tested the effects of a conditioning stimulus (CS100) applied 100ms prior to a test stimulus (TS) over primary motor cortex on TS-evoked EEG-potentials (TEPs). Healthy subjects were given a single oral dose of baclofen, a GABABR agonist, or diazepam, a positive modulator at GABAARs, in a placebo-controlled, pseudo-randomized double-blinded crossover study. LICI was quantified as the difference between paired-pulse TEPs (corrected for long-lasting EEG responses by the conditioning pulse) minus single-pulse TEPs. LICI at baseline (i.e. pre-drug intake) was characterized by decreased P25, N45, N100 and P180 and increased P70 TEP components. Baclofen resulted in a trend towards the enhancement of LICI of the N45 and N100, and significantly enhanced LICI of the P180. In contrast, diazepam consistently suppressed LICI of late potentials (i.e. N100, P180), without having an effect on LICI of earlier (i.e. P25, N45 and P70) potentials. These findings demonstrate for the first time directly at the system level of the human cortex that GABABR-mediated cortical inhibition contributes to LICI, while GABAAR-mediated inhibition occludes LICI. Paired-pulse TMS-EEG allows investigating cortical GABABR-mediated inhibition more directly and specifically than hitherto possible, and may thus inform on network abnormalities caused by disordered inhibition, e.g. in patients with schizophrenia or epilepsy.

Ketamine Dysregulates the Amplitude and Connectivity of High-Frequency Oscillations in Cortical–Subcortical Networks in Humans: Evidence From Resting-State Magnetoencephalography-Recordings

Hypofunctioning of the N-methyl-D-aspartate receptor (NMDA-R) has been prominently implicated in the pathophysiology of schizophrenia (ScZ). The current study tested the effects of ketamine, a dissociative anesthetic and NMDA-R antagonist, on resting-state activity recorded with magnetoencephalography (MEG) in healthy volunteers. In a single-blind cross-over design, each participant (n = 12) received, on 2 different sessions, a subanesthetic dose of S-ketamine (0.006 mg/Kg) and saline injection. MEG-data were analyzed at sensor- and source-level in the beta (13-30 Hz) and gamma (30-90 Hz) frequency ranges. In addition, connectivity analysis at source-level was performed using transfer entropy (TE). Ketamine increased gamma-power while beta-band activity was decreased. Specifically, elevated 30-90 Hz activity was pronounced in subcortical (thalamus and hippocampus) and cortical (frontal and temporal cortex) regions, whilst reductions in beta-band power were localized to the precuneus, cerebellum, anterior cingulate, temporal and visual cortex. TE analysis demonstrated increased information transfer in a thalamo-cortical network after ketamine administration. The findings are consistent with the pronounced dysregulation of high-frequency oscillations following the inhibition of NMDA-R in animal models of ScZ as well as with evidence from electroencephalogram-data in ScZ-patients and increased functional connectivity during early illness stages. Moreover, our data highlight the potential contribution of thalamo-cortical connectivity patterns towards ketamine-induced neuronal dysregulation, which may be relevant for the understanding of ScZ as a disorder of disinhibition of neural circuits.

Adaptive face space coding in congenital prosopagnosia: Typical figural aftereffects but abnormal identity aftereffects

People with congenital prosopagnosia (CP) report difficulty recognising faces in everyday life and perform poorly on face recognition tests. Here, we investigate whether impaired adaptive face space coding might contribute to poor face recognition in CP. To pinpoint how adaptation may affect face processing, a group of CPs and matched controls completed two complementary face adaptation tasks: the figural aftereffect, which reflects adaptation to general distortions of shape, and the identity aftereffect, which directly taps the mechanisms involved in the discrimination of different face identities. CPs displayed a typical figural aftereffect, consistent with evidence that they are able to process some shape-based information from faces, e.g., cues to discriminate sex. CPs also demonstrated a significant identity aftereffect. However, unlike controls, CPs impression of the identity of the neutral average face was not significantly shifted by adaptation, suggesting that adaptive coding of identity is abnormal in CP. In sum, CPs show reduced aftereffects but only when the task directly taps the use of face norms used to code individual identity. This finding of a reduced face identity aftereffect in individuals with severe face recognition problems is consistent with suggestions that adaptive coding may have a functional role in face recognition.

Investigating the features of the M170 in congenital prosopagnosia

Face perception generates specific neural activity as early as 170 ms post-stimulus onset, termed the M170 when measured with Magnetoencephalography (MEG). We examined the M170 in six people with congenital prosopagnosia (CP) and 11 typical controls. Previous research indicates that there are two neural generators for the M170 (one within the right lateral occipital area – rLO and one within the right fusiform gyrus – rFG), and in the current study we explored whether these sources reflect the processing of different types of information. Individuals with CP showed face-selective M170 responses within the rLO and right rFG, which did not differ in magnitude to those of the controls. To examine possible links between neural activity and behavior we correlated the CPs’ MEG activity generated within rLO and rFG with their face perception skills. The rLO-M170 correlated with holistic/configural face processing, whereas the rFG-M170 correlated with featural processing. Hence, the results of our study demonstrate that individuals with CP can show an M170 that is within the normal range, and that the M170 in the rLO and rFG are involved in different aspects of face processing.

Source-Reconstruction of Event-Related Fields Reveals Hyperfunction and Hypofunction of Cortical Circuits in Antipsychotic-Naive, First-Episode Schizophrenia Patients during Mooney Face Processing

Schizophrenia is characterized by dysfunctions in neural circuits that can be investigated with electrophysiological methods, such as EEG and MEG. In the present human study, we examined event-related fields (ERFs), in a sample of medication-naive, first-episode schizophrenia (FE-ScZ) patients (n = 14) and healthy control participants (n = 17) during perception of Mooney faces to investigate the integrity of neuromagnetic responses and their experience-dependent modification. ERF responses were analyzed for M100, M170, and M250 components at the sensor and source levels. In addition, we analyzed peak latency and adaptation effects due to stimulus repetition. FE-ScZ patients were characterized by significantly impaired sensory processing, as indicated by a reduced discrimination index (A′). At the sensor level, M100 and M170 responses in FE-ScZ were within the normal range, whereas the M250 response was impaired. However, source localization revealed widespread elevated activity for M100 and M170 in FE-ScZ and delayed peak latencies for the M100 and M250 responses. In addition, M170 source activity in FE-ScZ was not modulated by stimulus repetitions. The present findings suggest that neural circuits in FE-ScZ may be characterized by a disturbed balance between excitation and inhibition that could lead to a failure to gate information flow and abnormal spreading of activity, which is compatible with dysfunctional glutamatergic neurotransmission.