Homayoun Bahramali

Arousal dissociates amygdala and hippocampal fear responses: evidence from simultaneous fMRI and skin conductance recording.

The experience and appraisal of threat is essential to human and animal survival. Lesion evidence suggests that the subjective experience of fear relies upon amygdala-medial frontal activity (as well as autonomic arousal), whereas the factual context of threat stimuli depends upon hippocampal-lateral frontal activity. This amygdala-hippocampus dissociation has not previously been demonstrated in vivo. To explore this differentiation, we employed functional magnetic resonance imaging (fMRI) and simultaneous skin conductance response (SCR) measures of phasic arousal, while subjects viewed fearful versus neutral faces. fMRI activity was subaveraged according to whether or not the subject evoked an arousal SCR to each discrete face stimulus. The fMRI-with arousal and fMRI-without arousal data provided a distinct differentiation of amygdala and hippocampal networks. Amygdala-medial frontal activity was observed only with SCRs, whereas hippocampus-lateral frontal activity occurred only in the absence of SCRs. The findings provide direct evidence for a dissociation between human amygdala and hippocampus networks in the visceral experience versus declarative fact processing of fear.

Decomposing skin conductance into tonic and phasic components

Overlapping phasic skin conductance responses (SCRs) obtained using short interstimulus interval (ISI) paradigms such as those employed in cognitive research, confound measurement of each discrete phasic SCR as well as the tonic skin conductance level (SCL). We report a method of resolving this problem using a modelling technique that takes advantage of the stereotyped nature of the within-subject SCR waveform. A four-parameter sigmoid-exponential SCR model that describes the entire response, was developed and extended to five-, six- and eight-parameter skin conductance (SC) models. These SC models were successfully curve-fitted to more than 60 SC segments, each containing one SCR or two overlapping SCRs on a sloping baseline obtained from 20 normal subjects. The SC segments were consequently decomposed into their components: the tail of the previous response, one or two SCRs and the SCL. The SCRs free of the complication of overlap were then quantified. The raw SCRs of the same data set were also measured using a standard method. The standard measurement showed a significant reduction of 15% in amplitude and 140 ms in peak latency compared to our method. The basic four SCR model parameters--onset time, rise time, decay time constant and gain--showed increasing inter-subject variability in that order. These SCR model parameters may be studied as variables in normal and patient groups and as indices of treatment response. This quantitative method also provides a means to assess the relationships between central and autonomic psychophysiologic measures.

Synchronous cortical gamma-band activity in task-relevant cognition.

Widespread synchronous oscillatory activity, particularly in the gamma (‘40 Hz’) band, has been postulated to exist in the brain as a mechanism underlying binding. A new method of examining phase synchronicity across multiple electrode sites in specific EEG frequency bands as a function of time was employed, in a conventional cognitive ERP paradigm in 40 normal subjects. A significant late post-stimulus gamma synchronicity response occurred for task-relevant stimuli, whereas for task-irrelevant stimuli no such response was evident. However, an early response was seen for both task-relevant and irrelevant stimuli. This is the first empirical demonstration that widespread synchronous high frequency oscillations occur in humans in relation to cognition.

Is the target-to-target interval a critical determinant of P3 amplitude?

The P3 amplitude is augmented by decrements in target-probability, increments in the number of nontargets preceding the target, and extensions of the interstimulus interval (ISI). Each of these changes prolongs the target-to-target interval (TTI) and, consequently, results attributed to these factors might, at least partially, be accounted for by the TTI. Recent research also indicates that the P3s elicited by targets in one-, two-, and three-stimuli tasks (in which the TTI remains invariant) are similar. However, the TTI has not been examined systematically in previous research. The present study had subjects listen to a randomized ISI (0.5, 1, 2, or 4 s) version of the auditory oddball task in which targets occurred after one, two, three, four, or five nontargets. Event-related potentials were analyzed based on ISI, sequential structure, and TTI. The study examined sequence and ISI effects independent of TTI effects and demonstrated that extensions of ISI affected N1 but not P3 amplitude, extensions of TTI enhanced P3 amplitude independent of sequential structure, and sequential structure failed to influence P3 amplitude when TTI was controlled.

Savant-like numerosity skills revealed in normal people by magnetic pulses.

Oliver Sacks observed autistic twins who instantly guessed the exact number of match-sticks that had just fallen on the floor, saying in unison “111”. To test the suggestion that normal individuals have the capacity for savant numerosity, we temporarily simulated the savant condition in normal people by inhibiting the left anterior temporal lobe of twelve participants with repetitive transcranial magnetic stimulation (rTMS). This site has been implicated in the savant condition. Ten participants improved their ability to accurately guess the number of discrete items immediately following rTMS and, of these, eight became worse at guessing as the effects of the pulses receded. The probability of as many as eight out of twelve people doing best just after rTMS and not after sham stimulation by chance alone is less than one in one thousand.

Late Component ERPs are Associated with Three Syndromes in Schizophrenia

Previous studies have revealed various abnormalities in late-component ERP amplitude and latency in schizophrenia, considered as a diagnostic category. The aim of this study was to investigate the within-sample associations between late-component ERPs and three primary syndromes of schizophrenia Reality Distortion, Psychomotor Poverty and Disorganisation. Subjects included 40 schizophrenics and 40 age and sex matched nonpsychiatric controls. Auditory ERPs (N100, N200, P200, P300) were elicited using an auditory oddball paradigm. Between-group analyses of target data showed reduced N100, N200 and P300 amplitude, increased P200 amplitude and delayed N200 latency in schizophrenics compared to controls. For non-target data, schizophrenics showed similarly reduced N100 amplitude and delayed N200 latency. Within-group analyses of target data showed that the three syndromes (determined by principal component analysis of PANS ratings) were differentiated by ERP latency, but not amplitude (Disorganisation-delayed left hemisphere P200 and P300 latency; Reality Distortion earlier global, midline and left hemisphere N200 latency; Psychomotor Poverty delayed posterior N100 latency). Notably, only Disorganisation showed a divergent pattern of associations with non-target ERP data: reduced P200 amplitude and delayed N100 latency.

Dynamics of SCR, EEG, and ERP activity in an oddball paradigm with short interstimulus intervals

Studies of concurrent central, and autonomic activity using a conventional event-related potential (ERP) oddball paradigms, are considered useful in elucidating the relationship between central and autonomic responses, but the autonomic response tends to overlap. A new method was used to decompose and score overlapping skin conductance responses (SCR). This method enabled examination of dynamic relationships of phasic SCR, prestimulus electroencephalogram (EEG), and ERP to auditory target stimuli in 50 normal adults. SCR amplitude was negatively correlated to EEG and N200 amplitude. The SCR amplitude changes over time exhibited an exponential decline opposite to those of N200, alpha, and beta. All the fitted exponential functions had a time constant of 1-2 min. The findings suggest that a N200 component, active in the auditory sensory discrimination, is concomitant with the SCR. The narrow range of the time constant may provide a clue to the conjoint processes underlying central and autonomic adaptive functions.

The topography of quantified electroencephalography in three syndromes of schizophrenia.

This study investigated the association between quantified electroencephalography (qEEG) and three psychopathological syndromes, derived by a factor analysis of the symptom profile of a group of 40 subjects diagnosed with schizophrenia. An initial comparison with aged and sex matched normal controls showed an overall increase in slow wave activity in subjects with schizophrenia. The symptomatology of the subjects with schizophrenia was then factor analysed into three psychopathological syndromes that closely resembled Liddles (1987b) original delineation. Correlations were undertaken between the three syndrome scores and qEEG. The “psychomotor poverty” factor was associated with increased beta activity most marked posteriorly and increased delta activity (accounted for by the effects of medication). The “disorganisation” factor was associated with widespread negative correlations in the alpha and beta bands and the “reality distortion” factor was associated positively with left anterior alpha activity. These distinct patterns of qEEG that clearly differentiate between the three syndromes, may contribute towards elucidating the underlying pathophysiological processes in schizophrenia. The results support the use Of symptom based syndromes in reducing the diversity of findings in schizophrenia.

Evoked related potentials associated with and without an orienting reflex

LATE component event related potentials (ERP) and concomitant electrodermal activity (EDA) measures of the orienting reflex (OR) were undertaken in 50 normal subjects. Our group recently developed a model to quantify electrodermal activity in conventional ERP paradigms (auditory oddball) with short interstimulus intervals (ISI). The method was used to classify the presence or absence of skin conductance response following each auditory target stimulus. Using a conventional paradigm in which data is traditionally averaged, single-trial target ERPs were sorted into those with a skin conductance response OR (ERP+OR) and those without (ERP−OR) an OR, and ERP sub-averages of the two groups were derived. The ERP+OR showed significantly larger P300 amplitudes and relatively earlier N200 and P300 latency than those of the ERP−OR. These findings suggest that using concomitant SCR-ERP measures, separate ERP related processes can be determined, that are complementary to the traditional average measure.

Event-Related Potentials to Threat-Related Faces in Schizophrenia

Specialised network disturbances such as abnormalities in processing faces, may be associated with functional disturbances of interpersonal communication in schizophrenia. This study focused on the temporal dimension, investigating facial processing deficits in patients with schizophrenia (and non-patient controls) in a passive event-related potential (ERP) paradigm. ERPs invoked to an angry and neutral face stimulus were recorded in 27 patients with schizophrenia and 27 age and sex matched normal controls. Patients with schizophrenia showed a significant generalised delay, and diminished P200 amplitude (primarily frontal) for both stimuli - with more widespread regions of disturbance associated with the angry face. Normal controls, on the other hand, showed relatively reduced posterior P200 amplitude for angry compared to neutral faces, and a lateralised pattern of engagement in response to both stimuli. These findings indicate suboptimal processing of neutral faces in patients with schizophrenia, further exacerbated for affect laden angry faces.