Electrophysiological examination of Formal Thought Disorder in schizophrenia

Asian Journal of Psychiatry 5 (2012) 327–338

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Electrophysiological examination of Formal Thought Disorder in schizophrenia Deepshikha Ray a,*, Daya Ram b a b

Department of Psychology, University of Calcutta, Kolkata, India Central Institute of Psychiatry, Kanke, Ranchi, India

A R T I C L E I N F O

A B S T R A C T

Article history: Received 15 September 2011 Received in revised form 18 June 2012 Accepted 7 July 2012

Quantitave EEG profile was recorded for 60 age and sex matched drug free/naive schizophrenia patients, divided into two groups based on the presence and absence of Formal Thought Disorder (FTD) and a group of 30 matched healthy participants. Coherence and power spectrum analysis revealed that as compared to normal controls, schizophrenia patients with FTD had decreased regional power and intra hemispheric coherence; those without FTD had increased regional power and increased intra hemispheric coherence. Inter hemispheric coherence was greater in schizophrenia patients with FTD and lesser in those without FTD, as compared to healthy participants. The data were interpreted in terms of neural dis-connection which in FTD can be attributed to the existence of both a deficit and excess of neural connections, which compensate each other. ß 2012 Elsevier B.V. All rights reserved.

Keywords: Schizophrenia Formal Thought Disorder Aberrant connectivity Meta-plasticity

1. Introduction Language is fundamentally a generative system of soundmeaning connections emerging from coordinated and temporally integrated sensory, cognitive, and motor functions of the brain. Individuals with schizophrenia show abnormalities in all these domains of brain function, including symptoms specific to perceiving, comprehending, learning, and expressing language. Formal Thought Disorder or disorganized speech stands out to be one of the most elusive symptoms of schizophrenia. From the earliest descriptions of schizophrenia, disordered association (thought disorder) has been recognized as a major feature of the illness. It has also been proposed that many, if not all, other features of schizophrenia may be derived from a cognitive impairment primarily affecting association mechanisms. Bleuler (1911, 1950) first identified a disturbance in associations as one of the so-called four fundamental symptoms of schizophrenia, which along with autism, ambivalence, and affect, are often referred to as the ‘‘four A’s’’ of schizophrenia. According to Bleuler (1911, 1950), formal thought disturbance reflects a breakdown in the associative threads that serve to interweave words, thoughts, and ideas into coherent discourse. A more recent formulation of psychological disintegration is the idea that some experiential symptoms of schizophrenia can be explained by a failure to integrate the intention to act with the perceptual registration of the consequences of such action. At a neurobiological level, this

* Corresponding author. E-mail address: [email protected] (D. Ray). 1876-2018/$ – see front matter ß 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ajp.2012.07.005

integrative abnormality might correspond to a failure to integrate signals from the intentional (prefrontal) regions and the perceptual (temporal) cortices. Recent physiological and anatomic studies have stressed increasingly the importance of resonant, reciprocal interaction between multiple cortical areas during information processing task rangings from visual perception to language production. Synchronization of EEG activity at high oscillatory frequencies (20–100 Hz) has been proposed to reflect the degree of functional connectivity between cortical areas. Several lines of research, including post-mortem and brain imaging studies, suggest that schizophrenia is characterized by abnormalities in concerted action between spatially distributed networks (Hubl et al., 2004) and reduced cerebral functional connectivity in schizophrenia patients (Bleich Cohen et al., 2009, 2012; Li et al., 2010). Schizophrenia has therefore been described as a ‘‘dysconnectivity disorder’’ (Peled, 1997). However, these findings have been inconsistent. Early studies reported a variety of findings – most typically increased coherence – in contrast to more recent reports that show decreased coherence during different tasks in schizophrenics, in relation to health individuals (Peled, 2004; Winterer et al., 2001; Strelets et al., 2003; Slewa-Younan et al., 2004). Functional imaging studies of thought disorder have correlated the trait for this symptom with resting activity in the inferior frontal cingulated and temporal cortex (Liddle et al., 1992) while articulation of thought disordered speech ‘‘online’’ has been associated with relatively reduced activity in inferior frontal, cingulated and superior temporal cortex, but increased activity in the fusiform region (Mc Guire et al., 1997). But, none of these studies have been consistently replicated. Since 1970s investigators have consistently shown that schizophrenic patients display

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augmented low frequency power and diminished alpha band power (Iacono, 1985; Sponheim et al., 1994). Liemburg et al. (2012) investigated resting state network connectivity of the auditory, language and attention networks and observed decreased connectivity in patients, as compared to controls, between auditory and language networks. Conversely, increased connectivity was present in patients, as compared to controls between attention and language networks; but there was no relationship with severity of symptoms. Schizophrenia is a disorder with diverse symptoms affecting almost all aspects of mental functioning, for example perception, concept formation, language, volition, motor activity, social interaction, and emotion. There is evidence that such deficits are global as well as specific, marked by distinct patterns of association and dissociation of performance across different cognitive tasks. The dominant etiopathological models of schizophrenia in recent times consider that a mixture of genetic, epigenetic and environmental factors induce early anatomical brain lesions in circuits critical for cognition and emotion. These brain insults might affect the normal positioning of neurons and the establishment of connectivity as well as the synaptic pruning through childhood and adolescence, configuring the onset of the clinical syndrome years later (Selemon and Goldman-Rakic, 1999). Alterations in cortical circuit development may result in decreased synaptic connectivity in some regions, but in other brain areas, there may be an excess of neuronal connectivity. Despite Formal Thought Disorder (FTD) being a cardinal symptom of schizophrenia, and in the face of contradictory literature on the connectivity pattern in schizophrenia, research on schizophrenia has rarely focused on trying to relate the issue of functional integration with the symptom of FTD. Hence, the present study purports to explore the relationship between FTD, as one of the core pathologies of schizophrenia, and the status of functional integration in the brain of individuals with schizophrenia with and without FTD. It is believed that resting state functional connectivity may be considered as a reliable tool for identification of dysfunctional networks in the brain associated with psychiatric disorders such as schizophrenia. Analogous to resting state functional activity, the present study has used resting state electrophysiological measurement to assess the substrates of neural connectivity in two subpopulations of schizophrenia. Since the existence of inadequate functional integration in schizophrenia is evident from different studies, we can predict that diminished functional integration will be present in the schizophrenia population, as compared to normal controls. But, the exact nature of this inadequacy has not yet been fully clarified (Breakspear et al., 2003; Foucher et al., 2005) and the significance of EEG power abnormalities in schizophrenia remains unclear. Also, in-spite of the sub-categorization on the basis of presence and absence of FTD, we have actually chosen schizophrenia patients with ‘‘positive’’ symptoms. Hence, we have kept our expectations open regarding the profile of activation – connectivity in the schizophrenia population as contrasted with healthy counterparts and as compared between the two subgroups (Figs. 1–4). 2. Methods 2.1. Participants The sample consisted of 60 right handed, male schizophrenia patients, diagnosed as per the ICD 10 criteria and 30 age and sex matched normal controls. Initially a detailed case history was taken from each of the participants through thorough interview. In case of the patient participants, the information was corroborated from the informants, who were usually the primary caregivers. The diagnosis of schizophrenia was established by psychiatrists in the Out Patient Department of the hospital. Subsequently, the researcher, a trained clinical psychologist, re-confirmed the

Fig. 1. Graph showing inter hemispheric coherence. FTD represent formal thought disorder; SD represent standard deviation.

diagnosis based on the case history and mental status examination. The presence of comorbid psychiatric or significant general medical conditions were also ruled out in the process. The participants of the ‘‘Normal Control’’ group were screened out for the presence of any psychopathology by using the General Health Questionnaire (Shamsunder et al., 1986). Only participants with a score of <1 were selected for the study. Presence of past history or family history of psychiatric morbidity was also ruled out from the intensive case history. Thirty schizophrenia patients were grouped as ‘‘With Formal Thought Disorder’’ based on a score of one or more on the Thought, Language and Communication Scale (Andreasen, 1979). Thirty schizophrenia patients were grouped as ‘‘Without Formal Thought Disorder’’, based on a score of zero on the Thought, Language and Communication Scale (Andreasen, 1979). The ratings were made after a patient had been evaluated with an ordinary psychiatric interview, lasting for at least 50 min. For an appreciable period of time the patient was permitted to talk spontaneously, without any interruption, in order to observe his speech during this condition. Subsequently, the patient was interrupted at some point in order to see how he responds to this. Most of the ratings are described quantitatively i.e. in terms of how often they occur during an interview, based on the assumption that most interview takes about fifty minutes. The scale is scored as mild (occasional instances of Thought Language and Communication (TLC) disorder), moderate (impaired verbal output which leads to disturbance in communication from time to time), severe (significant impairment in communication for substantial part of the interview), and extreme (communication is impossible). The evaluation and rating of FTD were done by both the researcher and the supervisor. Those ratings that were taken into consideration were decided upon on the basis of consensus. As negative symptoms of schizophrenia have been differentially hypothesized to indicate a distinct syndrome, with unique neurophysiological as well as psycho-social correlates (Goldman-Rakic, 1994; Wing and Brown, 1997), presence of negative symptoms was ruled out based on the presence of a negative composite score in the Positive and Negative Syndrome Scale (PANSS) (Kay et al., 1987). Kay et al. (1987) had conceived a ‘‘bipolar composite scale’’ to express the direction and magnitude of the difference between positive and negative symptoms, by subtracting the negative subscale score from the positive subscale score, which ranges from ‘‘ 42 to +42’’. Accordingly, such a score reflects the degree of predominance of one syndrome over the other and its valence is an index of typological characterization. None of the participants had a score of more than three in any of the items of negative subscale. Handedness was assessed using the Sidedness Bias Schedule (Mandal et al., 1992). The criteria for selection of participants with

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Fig. 2. Graphs showing left intra-hemispheric coherence. FTD represent formal thought disorder; SD represent standard deviation.

Fig. 3. Graph showing right intra-hemispheric coherence.

Fig. 4. Graph showing power spectrum.

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schizophrenia were either drug naı¨ve or drug free (i.e. free from oral antipsychotics for at least 4 weeks; free from depot antipsychotics for at least 8 weeks; free from ECT for at least 24 weeks) 2.2. Ethical committee approval The research protocol was at first submitted to the Institutional Review Board of Central Institute of Psychiatry, Kanke, Ranchi for approval. The methods used in the research followed the broad definitions of the Declaration of Helsinki. The healthy participants and the participants with schizophrenia without FTD were provided with the rationale of the research in which they were going to take part. Their willingness to participate was recorded in a written ‘‘Informed Consent’’ form. However, informed consent could not be directly taken from schizophrenia patients with FTD, as their symptomatic status did not permit them to comprehend verbal information in totality and to express their decision coherently. Hence, their family members were taken into cognizance and permission was sought from them on behalf of their wards. 2.3. EEG acquisition After being administered the relevant clinical scales, all the participants were subjected to recording of Quantitative EEG (QEEG). It was ensured that the participants did not smoke or consume caffeine within the past three hours. The subjects were made to lie in a supine position, in a light and sound attenuated room and were asked to minimize their eye and limb movements as much as possible. It was also taken care of that all the participants had washed their head with glycerine soap and that the hair was thoroughly dried prior to recording. Sixty Ag – Ag–Cl electrodes were placed on standard scalp positions as per the International 10 – 10 System. The following 60 leads were selected – F1-FC1-C1-CP1-P1-F2-FC2-C2-CP2-P2-FP1-F3-FC3-C3-CP3-P3O1-FP2-F4-FC4-C4-CP4-P4-O2-F5-FC5-C5-CP5-P5-F6-FC6-C6-P6F7-FT7-T7-TP7-P7-F8-T8-TP8-P8-F9-FT9-T9-F10-FT10-T10-T1T2-FpZ-FZ-FCZ-CZ-CPZ-PZ-OZ. Fifteen minutes of EEG data for each subject was recorded using the ‘‘Nihon Kohden Neurofax Electroencephalograph EEG – 1100 K’’. Data was sampled at 1000 Hz per channel and stored in ASCII format for subsequent offline analysis. A time constant (TC) was fixed at 0.03 Hz and Hi-cut frequency filter was set at 300 Hz. Skin resistance at each site was kept at 5 KV. Analogue to digital (AD) conversion was by 16 bits. Eye movement potentials were recorded using two electrodes placed one-centimetre lateral to the outer canthus of each eye. For Power Spectral Analysis, all the above-mentioned 60 leads were taken. The EEG coherence was measured across channel pairs, to explore the relationship of psychopathology with cortical synchrony. The inter-hemispheric channels that were chosen: FP1-FP2, F3-F4, F7-F8, FT9- FT10, C3-C4, CP3-CP4, P3-P4, P5-P6, T7-T8, and T9-T10. The left sided intra-hemispheric channels were FP1-C3, FP1-P3, FP1-P5, FP1T7, FP1-T9, F3-C3, F3-CP3, F3-P5, F3-P7, F3-T7, F7-P3, F7-P5, F7-T7 F7-T9, F7-O1, C3-O1, FT9-C3, FT9-CP3, FT9-P3, FT9-P5, and FT9-T7. The right sided intra-hemispheric channels were FP2-C4, FP2-P4, FP2P6, FP2-T8, F4-T4, F4-C4, F4-CP4, F4-P6, F4-T8, F8-P4, F8-P6, F8-T8, F8-T10, F8-O2, C3-O2, FT10-C4, FT10-CP4, FT10-P4, FT10-P6, and FT10-T8. Drowsiness and Eye Movement artefacts were screened through visual inspection. Subsequently, one minute of artefact free data was subjected to ‘‘Signal Processing’’. 2.4. EEG waves recorded and analysed Beta and Gamma waves were recorded for this study. Beta waves were categorized into slow beta (Beta1), moderate beta

(Beta2) and fast beta (Beta3). Slow beta had rhythmical oscillations of the frequency 13–19 Hz per second; moderate beta had rhythmical oscillations of the frequency 19–24 Hz per second; fast beta oscillations were of the frequency range 24–30 Hz per second. Gamma waves encompassed rhythmical oscillations beyond 30 Hz per second and up to 100 Hz per second. 2.5. Data analysis Data from the ‘‘Signal Processing’’ was skewed. Log conversion was done to normalize the data. Descriptive statistics like mean and standard deviation (SD) were computed. Comparison between the three groups was done using Analysis of Variance, Universally understood. Post Hoc Analysis was done by computing Least Significant Differences (LSD). 3. Results 3.1. Socio demographic and clinical profile of the participants The socio demographic characteristics of the sample have been provided in Table 1. All the participants (N = 90) are male and right handed. The three groups of participants are matched in terms of age, education, religion, and socio economic status. The mean age of the schizophrenia patients with FTD is 33.3 years (SD = 7.7); mean age of schizophrenia patients without FTD is 36.9 (SD = 10.7); mean age of the healthy participants is 36.9 (SD = 10.7). The patient group and the normal control group were not comparable in terms of employment status. All the participants belonging to the normal control group were employed. All the participants with schizophrenia were in their active state of illness and therefore currently unemployed (Table 2a). The clinical variables for the group of participants with schizophrenia were classified into categorical variables viz. duration of illness: less than 6 months, 6 months to 1 year, greater than 1 year; number of episodes: first, second, greater than two episodes. The patient groups are comparable in terms of duration of illness and drug status. 80% of the patient participants (including both groups) had duration of illness of less than 6 months; the duration of illness ranged between 6 months and 1 year for 11.7% of the participants; 8.3% had illness duration of greater than 1 year. Fifty-eight percent of the patients (with and without FTD) were undergoing their first episode, 28% had two episodes and only 14% had more than two episodes. The predominant diagnosis in case of the schizophrenia patients with FTD was Undifferentiated; Paranoid was the major diagnosis for schizophrenia patients without FTD. Twenty-one patients (70%) with FTD were drug naı¨ve and nine (30%) were drug free; whereas 20 (67%) patients without FTD were drug naı¨ve and 10 (33%) were drug free. Out of the 19 patients (with and without schizophrenia) who were drug free, 16 patients were on oral antipsychotics; three patients had a history of depot antipsychotics viz. fluphenazine decanoate but these patients had poor drug adherence for more than a year. Hence, none of them had clinically significant doses of depot antipsychotics that could influence the electrophysiological profile (Table 2b). 3.2. Power spectrum profile of the participants The three groups of participants differ significantly in terms of Power Spectrum (p < 0.05). The mean power spectrum for fast oscillations (beta1, beta2, beta3, gama1, gama2) is maximum for the schizophrenia group without FTD, minimum for the schizophrenia group with FTD, and the power spectrum for the normal controls lie in between. The results show that out of 119 instances, in 54 instances, the mean power spectrum (for fast oscillations viz. beta1, beta2, beta3, gama1, gama2) is minimum for the

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Table 1 Distribution of socio-demographic and clinical characteristics across the three groups. Variables

Age

Socio-economic status Education

Religion

Residence

Occupation Marital status Duration of illness

No. of episodes

Diagnosis

Medication status TLC score

18–23 24–29 30–35 36–41 42–47 48–53 54–59 Low Middle Primary Secondary Graduate & above Hindu Muslim Christian Rural Semiurban Urban Unemployed Employed Unmarried Married <6 months 6 months–1 year >1 year First Second >Two Paranoid Undifferentiated Unspecified Drug naı¨ve Drug free No Mild Moderate Severe Profound

Schizophrenia with FTD (N = 30) Frequency

Schizophrenia without FTD (N = 30) Frequency

Normal controls (N = 30) Frequency

2 8 9 6 3 1 1 23 7 5 19 8 3 15 14 12 10 10 30 0 20 12 22 5 3 18 8 4 4 20 6 21 9 – 0 0 18 12

2 4 9 5 6 2 2 28 2 11 10 9 9 13 8 10 11 9 30 0 17 13 26 2 2 17 9 4 20 5 5 20 10 30 –

4 5 6 6 5 2 2 24 6 11 15 4 9 11 10 11 9 10 0 30 14 16

Kruskal–Wallis/F/ Mann–Whitney

p

1.48

0.23

5.31

0.07

2.21

0.33

3.84

0.15

0.03

0.98

2.21

1.0

1.07

0.58

392.00

0.22

424.00

0.67

204.00

0.00

435.00

0.78

0.00

0.00

This table reveals that the majority of patients, both with as well as without Formal Thought Disorder (FTD), come from the age group 30–35 years. The majority of patients hail from low socio-economic status and are from a rural background, most of them are educated up to the secondary level and have Islam as their religion. All of the patients, since they were assessed during their acute phase of their illness, were unemployed. The majority of patients both from the group having FTD and the group devoid of FTD, had been suffering from the illness for a period of less than six months, at-least in the present episode. Similarly, in the normal control group also, most subjects belong to the age group of 30 to 41 years. The majority of participants of the normal control group hail from low socio-economic status and are mostly educated up to secondary level. All of them are employed; majority of them are married and have Islam as their religion. The results table also indicates that in terms of the discrete socio-demographic variables, there is no significant difference across the three groups (schizophrenia with FTD, schizophrenia without FTD, and normal controls). Kruskal Wallis has been computed to analyse the significance of the difference between the groups (while comparing group differences between three groups) on the discrete socio-demographic variables; Mann–Whitney U has been computed to analyse the significance of the difference between the groups (while comparing group differences between two groups). The p values for the variables ‘‘socioeconomic status’’, ‘‘education’’, ‘‘religion’’, ‘‘residence’’, ‘‘occupation’’, ‘‘marital status’’, ‘‘duration of illness’’ are respectively <0.07, 0.33, 0.15, 0.98, 1.0, 0.58, 0.22. Analysis of Variance (ANOVA) has been computed to test the significance of the difference between the three groups on the continuous variable ‘‘age’’. The F ratio is 1.48 and the p value is <0.23. This implies that there is no significant difference among the three groups on the socio demographic variable age.

schizophrenic group with FTD, is maximum for the schizophrenic group without FTD and falls in between for normal controls. Also, significant power spectrum for fast oscillations exists across the channels FZ, FCZ, T1, T10 (Table 2c). 3.3. Coherence profile of the participants The results reveal that there is a significant difference (p < 0.05) between the three groups (i.e. schizophrenics with FTD, schizophrenics without FTD and normal controls) in terms of intra as well as inter hemispheric coherence, on the bands: beta1, beta2, beta3, gama1 and gama2. The results further indicate that in terms of intra-hemispheric coherence (both left and right), the mean coherence is minimum for the schizophrenic group with FTD, maximum for the schizophrenic group without FTD and the mean coherence for the normal control group lies in between. In terms of the inter-hemispheric coherence, the mean coherence for the

schizophrenic group with FTD is maximum, the mean coherence for the schizophrenic group without FTD is minimum and the mean coherence for the normal control group lies in between (Table 3). The results further indicate that out of 13 instances, in 10 instances, the mean coherence for left intra hemispheric region (fast oscillations) is minimum for the schizophrenic group with FTD, maximum for the schizophrenic group without FTD and the mean coherence falls in between for the normal control group. The results table also reveals that the significant left intra-hemispheric coherence in the region from ‘‘frontal to central’’, comprises of the bands gama2, gama2, gama1, gama2, beta1, beta1, beta1, gama1, beta1, beta2, beta1, gama1, gama2, beta1, beta2, beta3, beta1, gama1, beta3 and the respective channels FP1C3, F3C3, FT9C3, FT9CP3, FT9CP3, FP1P5, F3P5, F7P5, F7P5, FT9P5, FT9P5, FP1T9, F7T9, FT9T7, FT9T7, FT9T7, F7T7, FT10P4, FT10T8. All the coherences are significant at or below p < 0.05. The significant

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Table 2a Comparison between the three groups in terms of coherence, left intra-hemispheric, and fast oscillations. Regions

Frontal to central

Frontal to parietal

Frontal to temporal

Channel

FP1C3 F3C3 FT9CP3 FT9CP3 FP1P5 F3P5 F7P5 F7P5 FT9P5 FP1T9 F7T9 FT9T7 FT9T7 FT9T7 F7T7

Band

Gama2 Gama2 Gama1 Gama2 Beta1 Beta1 Beta1 Gama1 Beta1 Beta1 Gama1 Beta1 Beta2 Beta3 Beta1

Schizophrenia with FTD Mean  SD

0.40  0.32 0.32  0.29 0.33  0.30 0.37  0.34 0.13  0.13 0.11  0.17 8.1  8.7 0.31  0.35 6.3  5.3 0.10  8.4 0.71  0.43 0.11  9.4 0.13  0.15 0.18  0.20 0.15  0.14

Normal controls Mean  SD

0.41  0.34 0.49  0.42 0.44  0.37 0.46  0.40 0.22  0.23 0.23  0.22 0.20  0.26 0.49  0.44 0.19  0.21 0.19  0.19 0.43  0.35 0.32  0.39 0.32  0.39 0.38  0.47 0.18  0.19

Schizophrenia without FTD Mean  SD

F

0.67  0.48 0.67  0.50 0.75  0.51 0.79  0.56 0.28  0.22 0.14  0.14 0.16  0.13 0.80  0.83 0.19  0.20 0.20  0.16 0.57  0.42 0.48  0.51 0.52  0.51 0.60  0.53 0.28  0.22

p

3.183 4.248 7.627 6.780 4.522 3.663 3.336 4.296 5.269 3.802 3.124 7.577 7.511 7.581 3.952

0.05 0.02 0.001 0.002 0.01 0.03 0.04 0.02 0.01 0.03 0.05 0.001 0.001 0.001 0.02

LSD

FTD vs. NFTD

Normal vs. FTD

NFTD vs. normal

0.01 0.01 0.01 0.02 0.03 0.76 0.23 0.02 0.001 0.02 0.45 0.04 0.001 0.001 0.05

0.001 0.001 0.001 0.02 0.01 0.12 0.23 0.00 0.001 0.000 0.45 0.000 0.000 0.000 0.000

0.04 0.001 0.001 0.03 0.03 0.23 0.98 0.01 0.03 0.02 0.45 0.01 0.01 0.01 0.01

The result of this table shows that out of 13 instances, in 10 instances, the mean coherence for left intra hemispheric region (fast oscillations) is minimum for the schizophrenic group with FTD, maximum for the schizophrenic group without FTD and the mean coherence falls in between for the normal control group. The result table also reveals that the significant left intra-hemispheric coherence in the region from ‘‘frontal to central’’, comprises of the bands gama2, gama2, gama1, gama2, beta1, beta1, beta1, gama1, beta1, beta2, beta1, gama1, gama2, beta1, beta2, beta3, beta1, gama1, beta3 and the respective channels FP1C3, F3C3, FT9C3, FT9CP3, FT9CP3, FP1P5, F3P5, F7P5, F7P5, FT9P5, FT9P5, FP1T9, F7T9, FT9T7, FT9T7, FT9T7, F7T7, FT10P4, FT10T8. All the coherences are significant at or below p < 0.05. The significant left intra-hemispheric coherence in the region from ‘‘frontal to parietal’’, comprises of the bands beta1, beta1, beta1, gama1, beta1, beta2 and the respective channels FP1P5, F3P5, F7P5, F7P5, FT9P5, FT9P5. The coherence values are significant at or below p < 0.04. The significant left intra-hemispheric coherence in the region from ‘‘frontal to temporal’’, comprises of the bands beta1, gama1, beta1, beta2, beta3, beta1 and the respective channels FP1T9, F7T9, FT9T7, FT9T7, FT9T7, FT9T7, F7T7. The coherence values are significant at or below p < 0.05.

Table 2b Comparison between the three groups in terms of coherence, right intra-hemispheric, and fast oscillations. Regions

Frontal to Parietal Frontal to Temporal

Frontal to Central

Channel

FP2P6 FT10P4 FT10T8 F4T8 F4T8 FT10C4 FT10C4

Band

Gama2 Gama1 Beta3 Gama1 Gama2 Beta1 Beta2

Schizophrenia with FTD Mean  SD

0.39  0.35 0.58  0.76 0.15  0.14 0.46  0.33 0.51  0.37 0.13  8.31 0.16  0.13

Normal controls Mean  SD

0.49  0.45 0.14  0.16 6.1s1  7.44 0.71  0.73 0.58  0.56 0.24  0.16 0.27  0.21

Schizophrenia without FTD Mean  SD

0.77  0.73 0.21  0.38 6.57  7.88 0.15  0.65 0.34  0.07 0.27  0.20 0.30  0.20

F

3.210 5.862 7.460 5.645 6.641 5.865 4.869

p

0.05 0.004 0.001 0.01 0.03 0.004 0.01

LSD

FTD vs. NFTD

Normal vs. FTD

NFTD vs. normal

0.01 0.12 0.03 0.32 0.65 0.05 0.01

0.000 0.12 0.000 0.34 0.66 0.000 0.000

0.05 0.21 0.01 0.45 0.54 0.02 0.01

The result of this table displays that out of seven instances, in four instances, the mean coherence for the right intra hemispheric region (for fast oscillations) is minimum for the schizophrenic group with FTD and maximum for schizophrenic group without FTD. The mean coherence for normal control group falls in between. The result table also reveals that the significant right intra-hemispheric coherence in the region from ‘‘frontal to parietal’’ comprises of the band gama1 and the channel FT10P4. The coherence value is significant at p < 0.004. In the region from ‘‘frontal to temporal’’, the significant intra-hemispheric coherence is present at the band beta3 and the corresponding channel is FT10T8. The coherence value is significant at p < 0.001. In the region from ‘‘frontal to central’’, the significant intra-hemispheric coherence spreads across the bands beta1 and beta2 and the coherence value is significant at p < 0.05.

left intra-hemispheric coherence in the region from ‘‘frontal to parietal’’ comprises of the bands beta1, beta1, beta1, gama1, beta1, beta2 and the respective channels FP1P5, F3P5, F7P5, F7P5, FT9P5, FT9P5. The coherence values are significant at or below p < 0.04. The significant left intra-hemispheric coherence in the region from ‘‘frontal to temporal’’, comprises of the bands beta1, gama1, beta1, beta2, beta3, beta1 and the respective channels FP1T9, F7T9, FT9T7, FT9T7, FT9T7, FT9T7, F7T7. The coherence values are significant at or below p < 0.05 The result displays that out of seven instances, in four instances, the mean coherence for the right intra hemispheric region (for fast oscillations) is minimum for the schizophrenic group with FTD and maximum for schizophrenic group without FTD. The mean coherence for normal control group falls in between. The results table also reveals that the significant right intra-hemispheric coherence in the region from ‘‘frontal to parietal’’ comprises of the band gama1 and the channel FT10P4.

The coherence value is significant at p < 0.004. In the region from ‘‘frontal to temporal’’, the significant intra-hemispheric coherence is present at the band beta3 and the corresponding channel is FT10T8. The coherence value is significant at p < 0.001. In the region from ‘‘frontal to central’’, the significant intra-hemispheric coherence spreads across the bands beta1 and beta2 and the coherence value is significant at p < 0.05. It is further shows that out of 26 instances, in 14 instances, the mean coherence for inter hemispheric region (for fast oscillations) is maximum for the schizophrenic group with FTD, minimum for the schizophrenic group without FTD and the mean coherence falls in between for normal controls. The result further reveals that in the ‘‘Anterior Frontal’’ region, significant inter-hemispheric coherences are obtained at the bands beta2, beta3, gama1, gama2 and the corresponding channel is FP1FP2. The coherence values are significant at or below p < 0.04. In the ‘‘Frontal’’ region, significant

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Table 2c Comparison between the three groups in terms of coherence, inter-hemispheric, fast oscillations. Regions

Anterior Frontal

Frontal

Central

Parietal

Temporal

Channel

FP1FP2 FP1FP2 FP1FP2 FP1FP2 F3F4 F7F8 F7F8 F7F8 C3C4 CP3CP4 CP3CP4 CP3CP4 P3P4 P3P4 P3P4 P3P4 P5P6 P5P6 P5P6 T7T8 T7T8 T7T8 T9T10 T9T10 T9T10 T9T10

Band

Beta2 Beta3 Gama1 Gama2 Beta3 Beta3 Gama1 Gama2 Gama1 Beta3 Gama1 Gama2 Beta1 Beta3 Gama2 Beta3 Gama1 Gama2 Beta3 Gama1 Gama2 Beta1 Beta2 Beta3 Gama1 Gama2

Schizophrenia with FTD Mean  SD

0.25  0.24 0.25  0.23 0.42  0.40 0.40  0.38 0.19  0.26 0.42  0.32 0.69  0.34 0.71  0.38 0.53  0.41 0.13  0.21 0.27  0.39 0.22  0.27 8.54  0.14 0.11  0.12 0.23  0.19 0.11  0.11 0.44  0.28 0.45  0.28 0.22  0.19 0.61  0.46 0.62  0.47 0.15  0.10 0.72  0.24 0.77  0.30 0.97  0.41 0.97  0.40

Normal controls Mean  SD

0.11  0.22 0.11  0.22 0.17  0.20 0.16  0.21 7.29  5.76 0.20  0.16 0.30  0.31 0.29  0.32 0.23  0.24 4.47  3.83 0.10  9.86 0.10  0.12 0.19  0.35 0.18  0.40 9.57  0.10 0.18  0.40 0.21  0.25 0.20  26 0.11  0.11 0.30  0.35 0.30  0.33 0.15  0.13 0.43  0.33 0.40  0.39 0.44  0.44 0.43  0.43

Schizophrenia without FTD Mean  SD

0.12  0.23 0.13  0.20 0.24  0.38 0.22  0.34 0.12  0.14 0.24  0.23 0.36  0.54 0.33  0.44 0.33  0.38 5.79  4.82 0.11  9.89 0.11  0.11 0.37  0.51 0.40  0.59 0.14  0.15 0.40  0.59 0.20  0.21 0.20  0.22 0.13  0.14 0.21  0.19 0.20  0.19 0.14  9.63 0.43  0.39 0.41  0.39 0.29  0.33 0.28  0.32

F

3.391 3.657 4.104 4.454 3.348 7.228 4.701 7.003 5.475 3.458 4.693 3.588 4.478 4.919 3.876 5.645 4.073 8.676 8.488 5.400 9.794 9.917 5.757 7.845 7.760 8.469

p

0.04 0.03 0.02 0.01 0.04 0.001 0.01 0.002 0.01 0.02 0.01 0.03 0.01 0.02 0.005 0.02 0.000 0.000 0.01 0.000 0.000 0.004 0.01 0.000 0.01 0.01

LSD

FTD vs. NFTD

Normal vs. FTD

Normal vs. NFTD

0.02 0.02 0.02 0.02 0.23 0.01 0.65 0.04 0.12 0.32 0.03 0.04 0.04 0.65 0.04 0.55 0.40 0.40 0.04 0.04 0.12 0.65 0.04 0.04 0.68 0.54

0.000 0.000 0.001 0.001 0.43 0.001 0.76 0.001 0.43 0.55 0.001 0.001 0.001 0.65 0.001 0.55 0.12 0.21 0.002 0.001 0.40 0.76 0.002 0.002 0.65 0.12

0.03 0.03 0.04 0.04 0.76 0.03 0.99 0.03 0.76 0.76 0.01 0.01 0.01 0.65 0.04 0.55 0.12 0.12 0.04 0.05 0.12 0.43 0.04 0.04 0.89 0.21

FTD: formal thought disorder; SD: standard deviation; LSD: least significant difference, NFTD: without formal thought disorder. The results of this table show that out of 26 instances, in 14 instances, the mean coherence for inter hemispheric region (for fast oscillations) is maximum for the FTD schizophrenic group, minimum for the NFTD schizophrenic group and the mean coherence falls in between for normal controls. The results of this table reveal that in the ‘‘Anterior Frontal’’ region, significant inter-hemispheric coherences are obtained at the bands beta2, beta3, gama1, gama2 and the corresponding channel is FP1FP2. The coherence values are significant at or below p < 0.04. In the ‘‘Frontal’’ region, significant inter-hemispheric coherences are present at the bands beta3, beta3, gama1, gama2 and the corresponding channels are F3F4, F7F8, F7F8, F7F8. The coherence values are significant at or below p < 0.04. In the ‘‘Central’’ region, significant inter-hemispheric coherences are obtained at the bands gama1, beta3, gama1, gama2 and the corresponding channels are C3C4, CP3CP4, CP3CP4, CP3CP4, CP3CP4. The coherence values are significant at or below p < 0.03. In the ‘‘Parietal’’ region, significant inter-hemispheric coherences are present at the bands beta1, beta3, gama2, beta3, gama1, gama2, beta3 and the corresponding channels are the P3P4, P3P4, P3P4, P3P4, P5P6, P5P6, and P5P6. The coherence values are significant at or below p < 0.02. In the ‘‘Temporal’’ region, significant inter-hemispheric coherences have been obtained at the bands gama1, gama2, beta1, beta2, beta3, gama1, gama2 and the corresponding channels are T7T8, T7T8, T7T8, T9T10, T9T10, T9T10, T9T10. The coherence values are significant at or below p < 0.04.

inter-hemispheric coherences are present at the bands beta3, beta3, gama1, gama2 and the corresponding channels are F3F4, F7F8, F7F8, F7F8. The coherence values are significant at or below p < 0.04. In the ‘‘Central’’ region, significant inter-hemispheric coherences are obtained at the bands gama1, beta3, gama1, gama2 and the corresponding channels are C3C4, CP3CP4, CP3CP4, CP3CP4, CP3CP4. The coherence values are significant at or below p < 0.03. In the ‘‘Parietal’’ region, significant inter-hemispheric coherences are present at the bands beta1, beta3, gama2, beta3, gama1, gama2, beta3 and the corresponding channels are the P3P4, P3P4, P3P4, P3P4, P5P6, P5P6, and P5P6. The coherence values are significant at or below p < 0.02. In the ‘‘Temporal’’ region, significant inter-hemispheric coherences have been obtained at the bands gama1, gama2, beta1, beta2, beta3, gama1, gama2 and the corresponding channels are T7T8, T7T8, T7T8, T9T10, T9T10, T9T10, T9T10. The coherence values are significant at or below p < 0.04. 4. Discussion In this study, the EEG data was not acquired during performance of any cognitive task. Hence, the coherence and power spectrum values can be considered as independent of specific task related cognitive processes. It is a well acceptable fact that poorer task performance in patients as compared to controls acts as a potential confound. Thus the electrophysiological indicators

obtained in this study may be inferred as corresponding to the core cognitive processes employed by schizophrenic and nonschizophrenic participants. It can be reasonably assumed that the power spectrum and coherence values in the group of healthy participants are the ‘‘standard’’ or ‘‘typical’’ values. Hence, values greater as well as lesser than the power spectrum and coherence values of the normal control group are deviants and can be considered as ‘‘not optimum’’. From the findings of the study, it is apparent that cortical activation (as indexed by power spectrum) is less than the normal controls in schizophrenia patients with FTD and more than the normal controls in schizophrenia patients without Formal Thought Disorder (NFTD). It is interesting to note that when there is cortical hyper-activation, as in the case of the NFTD group, the intrahemispheric coherence is also greater than normal but the interhemispheric coherence is less than normal. When there is cortical hypo-activation, as in the case of the FTD group, the intrahemispheric coherence is less than normal but, the interhemispheric coherence is more than normal. Thus a trend emerges where over-excitability of the cortex is related to enhanced intrahemispheric connectivity along with suppressed inter-hemispheric connectivity; alternately, under-excitability of the cortex is associated with diminished intra-hemispheric connectivity and increased inter-hemispheric connectivity. To put it differently, an apparently contrasting pattern of functional connectivity exists in schizophrenia – attenuated regional functional interaction co

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Table 3 Comparison between the three groups in terms of power spectrum, fast oscillations. Channel

F1 F1 F1 F1 FC1 FC1 FC1 FC1 FC1 C1 C1 C1 C1 CP1 CP1 CP1 CP1 CP1 P1 P1 P1 P1 F2 F2 F2 F2 F2 FC2 FC2 FC2 C2 C2 C2 P2 P2 O1 O1 O1 FP2 F4 F4 F4 FC4 FC4 FC4 FC4 FC4 C4 C4 C4 CP4 CP4 CP4 P4 P4 O2 O2 F5 F5 C5 C5 CP5 CP5 CP5 CP5 P5 P5 P5 P5 F6 F6 FC6

Band

Beta 2 Beta 3 Gamma1 Gamma2 Beta 1 Beta 2 Beta 3 Gamma1 Gamma2 Beta 1 Beta 2 Gamma1 Gamma2 Beta 1 Beta 2 Beta 3 Gamma2 Gamma2 Beta 1 Beta 3 Gamma1 Gamma2 Beta 1 Beta 2 Beta 3 Gamma1 Gamma2 Beta 3 Gamma1 Gamma2 Beta 3 Gamma1 Gamma2 Beta 2 Beta 3 Beta 3 Gamma1 Gamma2 Gamma2 Beta 3 Gamma1 Gamma2 Beta 1 Beta 2 Beta 3 Gamma1 Gamma2 Beta 3 Gamma1 Gamma2 Beta 3 Gamma1 Gamma2 Gamma1 Gamma2 Gamma1 Gamma2 Gamma1 Gamma2 Beta 1 Beta 3 Beta 2 Beta 3 Gamma1 Gamma2 Beta 2 Beta 3 Gamma1 Gamma2 Gamma1 Gamma2 Beta 3

Schizophrenia with FTD Mean  SD

3.93  0.83 3.50  0.88 2.39  0.88 4.13  1.03 4.08  0.90 3.76  0.98 3.34  1.084 2.17  1.00 2.17  1.0 3.76  1.07 3.46  1.13 1.88  1.19 1.89  1.18 4.17  0.84 3.75  0.97 3.20  0.86 2.14  1.03 2.11  1.03 4.69  0.73 3.56  0.69 2.42  0.92 2.40  0.89 4.26  0.71 3.98  0.77 3.53  0.66 2.42  0.85 2.41  0.84 3.42  0.81 2.27  1.06 2.27  1.05 3.02  1.07 1.93  1.24 1.91  1.25 8.15  5.58 7.57  5.31 3.82  0.69 2.73  0.95 2.73  0.94 2.73  0.94 3.67  0.60 2.78  0.82 2.74  0.80 4.24  0.70 4.00  0.65 3.58  0.65 2.53  0.81 2.53  0.80 3.52  0.73 2.42  0.94 2.41  0.93 3.44  0.71 2.30  0.94 2.31  0.95 2.32  0.98 2.31  0.98 2.40  0.91 2.39  0.91 2.79  0.94 2.77  0.92 4.28  0.70 3.69  0.68 3.94  0.75 3.52  0.65 2.52  0.80 2.52  0.77 3.82  0.77 3.36  0.67 2.36  0.79 2.36  0.77 2.47  0.84 2.47  0.84 3.66  0.67

Normal controls Mean  SD

4.61  0.93 3.38  1.02 3.35  1.0 4.82  1.13 4.71  1015 4.43  1.17 4.22  1.14 3.16  1.27 3.13  1.25 4.46  1.41 4.15  1.34 2.88  1.50 2.86  1.47 4.71  1.11 4.24  1.12 3.88  1.13 2.97  1.28 2.94  1.27 5.12  0.81 4.11  0.90 3.20  1.11 3.18  1.09 4.67  0.85 4.49  0.89 4.27  0.84 3.16  0.90 3.15  0.89 4.12  0.95 2.99  1.07 2.97  1.06 3.75  1.23 2.72  1.33 2.70  1.33 5.24  2.69 4.89  2.82 4.26  1.01 3.37  1.18 3.38  1.17 3.38  1.17 4.25  0.63 3.44  0.76 3.43  0.77 4.69  0.75 4.53  0.72 4.29  0.68 3.28  0.83 3.31  0.83 4.10  0.72 3.16  0.81 3.14  0.81 3.95  0.75 2.89  0.95 2.92  0.95 2.92  1.01 2.90  1.00 2.86  1.04 2.87  1.05 3.29  1.25 3.30  1.24 4.72  0.78 4.30  0.78 4.34  0.70 4.12  0.79 3.41  0.90 3.43  0.91 4.27  0.65 3.96  0.74 3.30  0.93 3.29  0.93 3.25  0.97 3.25  0.97 4.14  0.87

Schizophrenia without FTD Mean  SD

4.61  0.89 3.32  0.86 3.30  0.85 4.69  10.7 4.87  0.94 4.62  1.01 4.22  0.99 3.30  0.91 3.28  0.91 4.82  0.89 4.49  0.99 3.11  0.90 3.10  0.90 4.90  0.68 4.48  0.83 4.03  0.73 3.17  0.77 3.14  0.76 5.09  0.56 4.15  0.60 3.30  0.61 3.30  0.61 4.86  0.82 4.61  0.87 4.25  0.80 3.22  0.78 3.22  0.79 4.08  0.87 3.06  0.78 3.06  0.79 3.92  0.90 2.94  0.78 2.95  0.80 6.29  3.83 5.86  3.85 4.30  0.72 3.54  0.71 3.54  0.70 3.54  0.70 4.03  0.76 3.19  0.89 3.18  0.89 4.56  0.68 4.35  0.80 4.01  0.71 3.01  0.76 3.04  0.76 3.92  0.74 3.02  0.74 3.02  0.74 3.84  0.70 2.96  0.77 2.99  0.79 3.01  0.72 3.00  0.73 3.03  0.65 3.03  0.65 3.41  0.80 3.42  0.78 4.58  0.60 4.03  0.70 4.36  0.6 3.96  0.69 3.20  0.85 3.20  0.84 4.11  0.69 3.74  0.59 3.07  0.70 3.07  0.69 3.16  0.63 3.16  0.63 4.10  0.62

F

5.972 8.981 10.825 10.935 5.146 5.407 7.453 9.815 9.676 6.705 6.123 8.537 8.510 5.386 4.413 6.820 8.267 8.203 3.545 6.014 8.921 9.120 4.518 4.795 8.951 8.453 8.447 6.029 5.988 5.884 5.842 6.485 6.464 3.613 3.186 3.174 5.956 6.095 6.095 5.768 4.886 5.010 3.270 3.703 8.224 6.685 7.449 4.997 6.634 6.604 4.175 4.944 5.146 5.043 5.075 4.106 4.226 3.121 3.528 3.087 5.450 3.207 5.856 9.055 9.538 3.160 6.131 10.861 10.984 8.071 8.071 3.997

p

0.004 0.000 0.000 0.000 0.01 0.01 0.001 0.000 0.000 0.002 0.003 0.001 0.001 0.01 0.01 0.002 0.001 0.001 0.03 0.004 0.000 0.000 0.01 0.01 0.000 0.000 0.000 0.004 0.004 0.004 0.004 0.002 0.002 0.03 0.05 0.004 0.003 0.003 0.003 0.004 0.01 0.01 0.04 0.03 0.001 0.002 0.001 0.01 0.002 0.002 0.02 0.01 0.01 0.01 0.01 0.02 0.02 0.05 0.03 0.05 0.01 0.04 0.004 0.000 0.000 0.05 0.003 0.000 0.000 0.001 0.001 0.02

LSD

FTD vs. NFTD

Normal vs. FTD

Normal vs. NFTD

0.01 0.32 0.67 0.12 0.01 0.01 0.02 0.01 0.001 0.02 0.04 0.03 0.02 0.003 0.11 0.01 0.01 0.01 0.32 0.01 0.02 0.02 0.03 0.03 0.98 0.04 0.05 0.67 0.01 0.02 0.01 0.03 0.01 0.98 0.68 0.04 0.001 0.001 0.003 0.65 0.65 0.99 0.78 0.32 0.68 0.54 0.88 0.94 0.95 0.71 0.65 0.04 0.04 0.03 0.03 0.01 0.02 0.01 0.01 0.92 0.79 0.65 0.65 0.99 0.78 0.32 0.68 0.54 0.88 0.94 0.95 0.71

0.0002 0.09 0.34 0.15 0.0002 0.003 0.004 0.005 0.04 0.01 0.01 0.001 0.001 0.000 0.23 0.000 0.000 0.000 0.13 0.000 0.000 0.001 0.001 0.001 0.87 0.002 0.002 0.66 0.000 0.000 0.001 0.000 0.002 0.99 0.78 0.002 0.003 0.003 0.002 0.65 0.65 0.99 0.78 0.13 0.54 0.78 0.66 0.94 0.78 0.72 0.65 0.000 0.003 0.003 0.001 0.001 0.001 0.000 0.000 0.97 0.71 0.65 0.65 0.99 0.78 0.13 0.54 0.78 0.66 0.94 0.78 0.72

0.002 0.87 0.23 0.11 0.001 0.002 0.002 0.01 0.01 0.01 0.01 0.01 0.02 0.01 0.32 0.01 0.03 0.02 0.45 0.01 0.04 0.04 0.04 0.04 0.76 0.02 0.03 0.99 0.01 0.01 0.03 0.05 0.01 0.99 0.88 0.05 0.01 0.02 0.01 0.65 0.65 0.99 0.78 0.54 0.78 0.65 0.65 0.79 0.98 0.92 0.98 0.03 0.03 0.02 0.02 0.02 0.03 0.04 0.05 0.71 0.92 0.65 0.65 0.99 0.78 0.54 0.78 0.65 0.65 0.79 0.98 0.92

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Table 3 (Continued ) Channel

FC6 FC6 CP6 CP6 P6 P6 F7 F7 FT7 FT7 T7 T7 P7 P7 F8 F8 F8 FT8 FT8 F9 F9 F9 FT10 T10 T10 T1 T2 T2 T2 T2 T2 FPZ FPZ FPZ FPZ FPZ AFZ AFZ AFZ AFZ FZ FZ FZ FZ FZ FCZ FCZ FCZ

Band

Gamma1 Gamma2 Gamma1 Gamma2 Gamma1 Gamma2 Gamma1 Gamma2 Gamma1 Gamma2 Gamma1 Gamma2 Gamma1 Gamma2 Beta 3 Gamma1 Gamma2 Beta 3 Gamma1 Beta 3 Gamma1 Gamma2 Beta 3 Beta 1 Beta 2 Beta 1 Beta 1 Beta 2 Beta 3 Gamma1 Gamma2 Beta 1 Beta 2 Beta 3 Gamma1 Gamma2 Beta 1 Beta 3 Gamma1 Gamma2 Beta 1 Beta 2 Beta 3 Gamma1 Gamma2 Beta 1 Beta 2 Beta 3

Schizophrenia with FTD Mean  SD

2.57  0.87 2.57  0.85 2.82  0.84 2.81  0.82 2.52  0.86 2.54  0.85 2.52  0.88 2.52  0.8 2.52  0.84 2.51  0.84 2.64  0.88 2.63  0.87 2.73  1.04 2.73  1.02 3.63  0.82 2.78  0.98 2.77  0.96 3.62  0.77 2.76  0.94 3.65  0.75 2.68  0.91 2.68  0.91 3.02  1.07 1.93  1.24 1.91  1.25 4.16  0.72 4.40  0.86 4.28  0.90 4.06  1.03 3.57  1.20 3.59  1.20 4.40  0.86 3.88  0.93 3.57  0.95 2.87  0.92 2.90  0.92 4.25  0.73 3.66  0.69 2.82  0.89 2.83  0.86 4.30  0.75 4.01  0.78 3.55  0.71 2.55  0.84 2.52  0.83 4.28  0.83 3.94  0.90 3.49  0.79

Normal controls Mean  SD

3.41  0.96 3.41  0.95 3.41  0.88 3.40  0.89 3.12  0.78 3.12  0.80 3.14  0.90 3.14  0.89 4.71  1015 4.43  1.17 3.14  0.96 3.17  0.95 3.17  0.99 3.19  0.99 4.17  0.96 3.78  1.02 3.78  1.02 4.71  1015 4.43  1.17 4.12  0.80 3.43  1.09 3.46  1.08 3.75  1.23 2.72  1.33 2.70  1.33 3.96  1.02 3.69  1.48 3.38  1.49 3.19  1.60 2.69  1.57 2.73  1.56 3.9  1.47 3.12  1.13 2.89  1.18 2.32  1.06 2.36  1.08 4.90  0.79 4.28  0.79 3.41  0.95 3.38  0.94 4.89  0.90 4.61  0.90 4.35  0.85 3.26  0.90 3.26  0.90 4.92  0.99 4.62  0.98 4.40  0.96

Schizophrenia without FTD Mean  SD

3.41  0.64 3.40  0.65 3.21  0.79 3.23  0.79 3.05  0.81 3.07  0.81 3.09  0.80 3.08  0.81 4.87  0.94 4.62  1.01 3.22  0.75 3.21  0.75 3.42  0.90 3.43  0.89 3.3  0.72 3.41  1.06 3.41  1.04 4.87  0.94 4.62  1.01 3.73  0.65 3.05  0.74 3.07  0.76 3.92  0.90 2.94  0.78 2.95  0.80 3.54  1.05 3.11  1.13 2.97  1.05 2.75  0.99 2.3  1.05 2.36  1.04 3.11  1.13 3.03  1.10 2.62  1.14 2.05  1.31 2.10  1.32 4.58  0.84 4.02  0.95 3.30  0.95 3.28  0.96 4.88  0.75 4.61  0.89 4.27  0.86 3.27  0.81 3.26  0.82 4.94  0.83 4.67  1.00 4.34  0.97

F

10.138 10.315 3.970 3.907 4.911 4.688 4.839 4.660 5.229 5.205 3.943 4.244 3.857 4.086 3.204 4.710 7.350 3.013 4.921 3.531 4.886 5.215 3.596 4.672 5.990 3.435 8.972 9.819 8.622 7.297 7.260 8.872 5.859 6.002 4.243 3.904 8.872 3.222 3.394 3.089 5.165 4.933 8.819 6.953 7.644 5.391 5.457 9.331

p

0.000 0.000 0.02 0.02 0.01 0.01 0.01 0.01 0.01 0.01 0.02 0.01 0.01 0.02 0.04 0.001 0.001 0.05 0.01 0.03 0.01 0.01 0.03 0.01 0.004 0.04 0.000 0.000 0.000 0.001 0.001 0.000 0.004 0.004 0.02 0.02 0.000 0.01 0.04 0.01 0.04 0.05 0.000 0.01 0.01 0.01 0.01 0.000

LSD

FTD vs. NFTD

Normal vs. FTD

Normal vs. NFTD

0.65 0.01 0.01 0.03 0.03 0.03 0.04 0.32 0.22 0.32 0.03 0.03 0.03 0.04 0.32 0.22 0.32 0.03 0.001 0.12 0.43 0.32 0.02 0.01 0.02 0.65 0.65 0.99 0.78 0.32 0.68 0.54 0.88 0.94 0.95 0.71 0.65 0.32 0.11 0.21 0.22 0.21 0.11 0.01 0.01 0.02 0.02 0.07

0.65 0.004 0.001 0.002 0.002 0.002 0.001 0.12 0.55 0.11 0.002 0.002 0.002 0.001 0.12 0.55 0.11 0.004 0.004 0.32 0.12 0.33 0.001 0.001 0.004 0.65 0.65 0.99 0.78 0.13 0.54 0.78 0.66 0.94 0.78 0.72 0.65 0.26 0.11 0.43 0.32 0.12 0.12 0.002 0.005 0.000 0.000 0.09

0.98 0.01 0.01 0.02 0.02 0.03 0.03 0.11 0.43 0.12 0.02 0.02 0.03 0.03 0.11 0.43 0.12 0.04 0.03 0.43 0.12 0.22 0.003 0.001 0.04 0.65 0.65 0.99 0.78 0.54 0.78 0.65 0.65 0.79 0.98 0.92 0.98 0.13 0.11 0.99 0.54 0.45 0.32 0.02 0.02 0.001 0.01 0.20

FTD: formal thought disorder; SD: standard deviation; LSD: least significant difference, NFTD: without formal thought disorder. This table shows that out of 119 instances, in 54 instances, the mean power spectrum (for fast oscillations viz. beta1, beta2, beta3, gama1, gama2) is minimum for the FTD schizophrenic group, is maximum for the NFTD schizophrenic group and falls in between for normal controls. Also, significant power spectrum for fast oscillations exists across the channels F1, FC6, FZ, FCZ, T1, T7, T8, T10, FT8, FT9.

exists with strengthened inter regional functional interaction and vice versa. This otherwise anomalous finding seems to be parsimonious with the concept of ‘‘reduced efficiency’’, introduced in the working memory literature of patients with schizophrenia. In low memory load conditions patients with schizophrenia show greater prefrontal activity than controls and normal performance, whereas at high load conditions patients show a reduction in prefrontal activity with impaired performance (Manoach et al., 1999). This is explained as a shift in the normal inverted – U relationship between memory load and prefrontal activation. In healthy subjects, activity increases commensurate with load until memory capacity is exceeded, at which time both activity and performance drops. In schizophrenia however, the memory system operates at a higher intensity to maintain normal performance at lower load levels and so reaches the capacity threshold earlier.

Increased activation at lower load levels reflect compensatory processing and is a sign of inefficiency in the system. It is possible that a similar mechanism could explain the reversed pattern coherence in subpopulations of schizophrenia. Such contrasting patterns of cerebral activity in schizophrenia have been reported in a number of studies (Posner et al., 1988). Hypoactivity in the prefrontal cortex that appears in provoking tasks is accompanied by hyperactivity in the temporal lobe; temporal hyperactivity coinciding with auditory hallucination is associated with frontal hypoactivity. These findings further lend support to the abnormal fronto-temporal dynamic equilibrium characteristic of schizophrenia. If the cortical activation and functional interaction within the subpopulation of schizophrenia is focussed upon, the NFTD group has been found to show increased intra hemispheric coherence associated with increased regional power, indicating that there is

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cortical hyper activation (increased power spectrum) in a resting state in this subgroup of schizophrenia. A majority of electrophysiological studies in schizophrenia have suggested that there is a state of sustained hyper arousal in schizophrenia (Flekkoy, 1975). Lerner et al. (1977) had also found hyper activation of the left hemisphere in paranoid schizophrenia. Karny and Nachson (1995) had suggested that non-paranoid schizophrenia shows hypo activation; the majority of the patients in the NFTD group were paranoid. The brain can be conceptualized as a resource dependent system i.e. with limited processes and structures that are available at a given moment for performance of cognitive tasks. Increased power may be an indicator of an engaged processing state of the brain; alternately, coherence indicates which areas of the brain are related by working together in resting and task conditions. This means that more and more neurons are already activated in resting state in the NFTD subpopulation of schizophrenic patients. Such a process might be leading to reduced neuronal efficacy and a surplus engagement of neuronal networks within the same region, as indicated by increased coherence. Therefore, when new cognitive demands are made on them, patients perform poorly, as a lesser number of neurons is available for new recruitment to perform parallel processing. In favour of this argument, the studies of Callicott et al. (2003) can be cited. Increased amplitude of EEG waves in the frontal, temporal regions in schizophrenia have been reported by Callicott et al. (2003), and such increases have been found to be associated with dys-regulation in working memory performance. Manoach et al. (2000) had also found out that relative to normal subjects, schizophrenic subjects exhibited deficient Working Memory performance, at least an equal magnitude of right DLPFC activation, significantly greater left Dorsolateral Prefrontal Cortex, universally understood activation, and increased spatial heterogeneity of DLPFC activation. It should be mentioned at this juncture that all these studies were conducted on schizophrenia patients who did not have formal thought disorder. Conversely, the presence of decreased intra hemispheric coherence concomitant to decreased regional power in the FTD group points in favour of the ‘‘dis-connection hypothesis’’ (Friston, 1999) in schizophrenia. In other words, schizophrenia could be related to disturbed binding and integration of multiple and disparate neural activities underlying cognitive brain functions and consciousness. The theory of Andreasen et al. (1999), also suggests that the symptoms of schizophrenia are caused by ‘‘cognitive dysmetria’’, a disruption in the timing and integration of information related to thought and speech. At the same time, the findings reveal increased inter hemispheric coherence in the FTD group. Shergill et al. (2007) and Whitford et al. (2007) had assessed functional connectivity by measuring the co-variances in functional magnetic resonance imaging (fMRI) signals during the execution of specific cognitive tasks. In these studies, concomitant with a decrease of connectivity pattern in particular areas, a significant increase in neuronal connectivity was also observed in different areas. Interestingly, in a very recent study by Bleich Cohen et al. (2012) decreased interhemispheric functional connectivity was related to more negative symptoms among the schizophrenia patients. If neuronal synchronization is the temporally coincident firing of different groups of neurons, then synchronization provides effective conditions for optimal communication between neurons. At the same time, concurrent firing of synchronized neuronal populations also augment the excitability for particular neurons and the activation level of the involved cortical region. A similar kind of electrophysiological phenomena is perhaps taking place in the NFTD group. If a cerebral region is hyper-excitable (evident in the schizophrenia subgroup without FTD), groups of neurons may be excessively stimulating each other in that region. These ‘neuronal shortcuts’ might rigidly produce the same perceptive,

cognitive or motor output, regardless of the input received from other neurons, thus implying a functional autonomization (GarciaToro, 1999). Furthermore, this over activation of certain cerebral regions could imply the compensatory hypo-excitability of other interconnected areas which may manifest itself in decreased functional interaction. Less than optimal cortical activation may thus be assumed to reflect discordant firing of neuronal groups or, in other words, a haphazard neuronal network organization. Coming back to the finding of functionally opposite patterns of connectivity in the two subgroups of schizophrenia – if a cerebral region is hypo-excitable (present in the schizophrenic subgroup with FTD), a stimulus of sufficient intensity may fail to elicit a proportionate response and thus demonstrate a relative deficit of excitatory neurotransmission. Due to impairment in re-entrant signalling, the stimulus might have limited possibilities to generate and maintain the spatial-temporal patterns of neuronal activity. This implies that this region, now hypoactive, would not be able to perform the assigned mental functions. In addition, there would be neighbouring or interconnected cerebral regions that would receive less inhibitory input, and become more excitable, as reflected in the increased inter hemispheric coherence in the FTD group. It follows that in the schizophrenic brain (with and without FTD) there is unevenness between the excitatory and inhibitory ratio of neuronal action. If there is an imbalance in one region of the brain, that region becomes either hyper or hypo excitable. In such a case, the activity of the brain is fragmented into several functional autonomous regions, hyper or hypoactive, which may be responsible for the symptoms of schizophrenia. Such an adequate balance is fundamental for the neural network’s adaptive responding and may also be referred to as ‘‘optimal plasticity’’. Abraham and Robins (2005) suggest that neither extreme stability nor excessive plasticity is suitable for synaptic efficacy and a balance between plasticity and inertia may be needed to enable both change and continuity of the knowledge embedded in neural systems. Abrahams and Bear (1996) coined ‘‘metaplasticity’’ to explain this modifiability in synaptic plasticity. They posited the concept of ‘‘plasticity – disequilibrium’’ – (a) hypo plastic neural networks – where the connectivity patterns of neural networks are more dominant and resistant to change; (b) hyper plastic neural networks – synaptic connectivity is unstable and easily affected by incidental co-occurrences of inputs or outputs. But both represent an imbalance in the neural stability/plasticity and contribute to inefficient top down regulation of experience and behaviour by context, thereby leading to schizophrenic symptomatology. The findings of the present study demonstrate that in the schizophrenic brain there is the coexistence of over connected and under-connected brain regions. It might be suggested that in schizophrenia there is a more generalized pattern of ‘‘aberrant connectivity’’, which includes both pathological increases and decreases in neuronal connectivity in different brain regions, produced by a reciprocal compensatory mechanism. Such an idea was also proposed by Gaspar and his co researchers (2008). Guterman (2005) had said that predominantly reality distorting patients (analogous to the NFTD group) have insufficient plasticity connections. This may lead to well-focussed but inflexible prepotent responding to proximal stimulation and to insufficient top down biasing of the activity in the implementing networks. By contrast, in predominantly disorganized patients (akin to the FTD group), the associative neural networks are functionally unstable resulting in dis-mantling and de-prioritization of pre-potent responses in the mental and motor domains. Paradoxically, the over flexible organization of neural networks produce a similar outcome as inelastic and rigid organization; in both cases there is a weakening of the control exercised by changing inner circumstances over the on-going activity of the implementing systems; once again favouring the findings obtained in our study.

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Certain methodological issues need to be discussed. One of the strongest points of this study is the inclusion of a large sample size (60 un-medicated schizophrenia patients). The absence of clinically significant medication status adds on to the strength as the participants were subjected to EEG which is vulnerable to the influence of psychotropic medication. As is obvious from the demographic data, most of the patients hailed from low socio economic status, which inadvertently restricts the use of expensive psychotropic medications and the compliance. So the life time effects of psychotropic medication are ruled out by default. The exclusion of female participants could be considered as a limitation in the generalizability of the results. The participants were not matched in terms of IQ though some studies have related it with more thought disorder in adult patients. However, the patients and their healthy counterparts were matched in terms of educational level and socio economic status, which helped in excluding possible social factors from influencing the results. 5. Conclusion It would be an over simplification to state that in schizophrenia there is a predominance of cerebral hypoactivity in those who have FTD and cerebral hyperactivity in those who do not display FTD. Given the highly interconnected structure of the CNS, it would be expected that hyper and hypo active domains would be intertwined. It is not the presence of two functionally opposed domains (hypo and hyper active and hypo and hyper connected) which contributes to psychopathology. Rather, it is their loss of dynamic equilibrium or compensatory nature, along with a variety of predisposing and precipitating factors, each entwined in a circular causal relationship that lead to psychopathology. FTD in schizophrenia can be conceptualized as a form of integrative failure to regulate the synchrony between thought and actions, due to neural misconnections. The formation of such mis-connections is engendered by plasticity processes, wherein deficit or absence of inter-hemispheric connections may be compensated for by the formation of inappropriate intra-hemispheric connections and vice versa. Role of funding agency This research was not aided by any funding agency. This research was part of a PhD fellowship under the Ministry of Health and Family Welfare, Government of India, and was undertaken in the Central Institute of Psychiatry, Kanke, Ranchi, India. Contributors The synopsis of research was prepared by Deepshikha Ray and supervised by Daya Ram. Data collection was done by Deepshikha Ray. Tabulation and interpretation of data along with relevant statistical analysis was done by Deepshikha Ray. Preparation of the initial draft write up was done by Deepshikha Ray and Daya Ram. Preparation of the final write up was done by Deepshikha Ray. Conflict of interest There is no conflict of interest. Acknowledgements The authors acknowledge the cooperation of the staff of Central Institute of Psychiatry and all the participants of the study.

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