Spontaneous dense array gamma activity in children and adolescents with volatile solvent dependence.

OBJECTIVES: Children and adolescents with volatile solvent/inhalant dependence have neurocognitive deficits. The study aimed to explore resting state gamma activity, which is a marker of cognitive function, in children and adolescents with inhalant dependence. The study also investigated differences in gamma activity across groups differing in inhaled amounts.
MATERIALS AND METHODS: Clinical and electroencephalographic (EEG) data were collected from nine patients with inhalant dependence. 30-50 Hz spectral power was calculated using Welch's averaged periodogram method. The data were analyzed using descriptive statistics, bi-variate correlation, and nonparametric Mann-Whitney U-test.
RESULTS: While significant positive correlation was found between duration of dependence and gamma spectral power in left frontal region, no significant differences were found on comparison of the groups on gamma spectral power.
CONCLUSION: A complex neurobiological interaction is involved in the synaptic modulation brought about by inhalant use and this could be understood by studying changes in EEG parameters especially gamma activity.

Introduction

In recent years, there is a growing concern regarding the harmful effects of organic volatile substances on physical and psychological health. The use of volatile substances is often initiated during childhood or adolescence as these are cheap and easily available products.[1] Majority of the users are either school dropouts or irregular to the school,[2] a finding that reflects impaired neurocognitive functions, leading to lower scholastic performance and school drop-out, especially if the substance abuse starts during preadolescence.[3] The limited available literature suggests that a significant proportion of users also have hematological, biochemical, and neurological involvement, as well as show abnormal findings in somatosensory and brainstem-evoked potentials.[14] Among various electroencephalographic frequency bands, gamma activity is better related to cognitive functions such as sensory processing, attention, and working memory.[5] And recently, spontaneous or resting state gamma activity has been emphasized citing its bearing on evoked/induced activity and the need for minimal subject cooperation.[67]

Literature on the effect of volatile substances on spontaneous electroencephalographic (EEG), particularly gamma activity is lacking. The current paper intends to share the preliminary findings of the effects of volatile solvents on spontaneous/resting state gamma activity in children and adolescents with volatile solvent dependence syndrome. Specifically, we aimed at exploring the differences in gamma activity across groups differing in inhaled concentrations as higher concentrations are known to produce significantly greater inflection on brain activity.[8]

Materials and Methods

Nine right-handed, volatile-dependent subjects diagnosed according to International Classification of Disease, 10th Revision, Diagnostic Criteria for Research (mean age: 14.67 ± 1.58 years; mean age of onset: 9.33 ± 1.3 years; mean years of education: 3.0 ± 1.7 years; mean duration of substance use: 5.33 ± 1.5 years) without any co-morbid substance dependence, affective/psychotic illness, significant head injury, and epilepsy were recruited through purposive sampling for the current hospital based cross-sectional study, after approval of the Institute's Ethical Committee. Five subjects used dendrite and four subjects used whitener. Five of the subjects had either a single living parent or had lost both parents. Four subjects had co-morbid conduct disorder and one had specific learning disorder.

After appropriate preparation, 10 min of resting EEG activity (Nihon-Kohden Neurofax EEG-1100K machine (Nihon Kohden Corporation, Japan); sampling frequency of 512 Hz; 16 bits resolution analog digital conversion; time constant - 0.1 Hz; Hi cut frequency filter - 120 Hz and epoch length - 1 s) [Figure 1] was recorded, using 192 scalp electrodes placed according to 10-5 international system of electrode placements [Figure 2]. Sixty seconds of visually selected artifact free EEG data were converted to American Standard Code for Information Interchange format for offline analysis. Spectral power was analyzed using Welch averaged modified periodogram's power spectral density estimate. The study focused on the 31–50 Hz gamma frequency band. Log transformation was performed for spectral power values as on Shapiro-Wilk test they were nonnormally distributed. First, a correlational analysis was performed between clinical variables like duration of dependence and age of onset with gamma spectral values. Subsequently, the patient group was divided into two groups based on amount of solvent abused per day (Group 1: Low dose - <15 g dendrite or 20 ml of whitener; Group 2: High dose - >15 g dendrite or 20 ml of whitener; the division was arbitrarily based on the median amount of inhalant abused in the group, as absolute inhalation concentrations could not be ascertained in terms of parts per million). Mann–Whitney U-test was done to compare the two groups on gamma measures. Level of significance was taken as <0.05.

Figure 1

A screenshot of electroencephalographic recording on 192 channels

Figure 2

A subject's recording using custom made 192 electrodes cap. Recording setup also can be seen

Results

Significant positive correlation was found between duration of dependence and gamma spectral power in left frontal region (r = 0.673; P < 0.05). No other significant correlation was found. In comparison of the groups on gamma spectral power, no significant differences were found [Table 1].

Table 1

Comparison of gamma spectral power across the two groups

Discussion

In the brain cells solvents act on specific receptors (N-methyl-D-aspartate and gamma-aminobutyric acid [GABA]) to produce effects.[9] Interestingly, maturation of gamma power, during adolescence and early adulthood also has been found to be compatible with changes in the GABAergic neurotransmission and myelination of axonal fibers during this period.[5] Specifically considering inhalants as gateway drugs, a multifarious interaction between GABAergic and dopaminergic has been indicated in the reward pathway of addiction[10] and specifically with respect to the “gateway hypothesis” of substance dependence.[11] Now, left prefrontal functional circuitry has been shown to modulate inhalant-induced changes in synaptic plasticity of mesolimbic dopamine neurons.[12] The study's finding of a significant association between longer duration of inhalant dependence with increased frontal gamma power implicates a vice versa relationship, that is, chronic synaptic changes in mesolimbic dopamine neurons leading to impaired left frontal functionality. Moreover, recently volatile solvents have been shown to alter synaptic transmission in key brain circuits that are thought to underlie addiction pathology like the medial prefrontal cortex apart from the mesolimbic dopamine system.[13]

As with various other substances, patients of volatile solvent dependence have been shown to present with an array of cognitive dysfunction. Deficits in visual attention, visual recognition memory, and visual paired associate learning have been demonstrated.[14] Recent longitudinal data on cognitive deficits in patients with volatile solvent abuse reveal that while, deficits on visual motor, learning and memory, paired associate learning, and executive functions exist for solvent abusers upon treatment entry, only paired associate learning performance resolve within weeks of abstinence and executive function improves gradually over months to years of abstinence with a risk of not recovering ever.[15] To the best of the authors’ knowledge, no study has so far investigated cognitive functions and gamma activity together in patients with volatile solvent dependence. However, all these cognitive deficits have been linked to aberrant gamma oscillations in other disorders like schizophrenia. Pertinent to our study finding, gamma abnormalities in frontal region have been specifically linked to cognitive deficits in working memory and executive functions.[16] Further, these cognitive deficits and aberrant gamma oscillations have been structurally related to left inferior dorsolateral prefrontal regions.[17]

No significant difference on gamma activity between groups divided based on intake dose suggests that neuronal modulation of inhalants does not depend on the dose of intake. However, with the limited sample size of the study, this finding should be considered preliminary and studies on gamma activity with larger samples should address more of such issues.