Attention-Deficit/Hyperactivity Disorder (ADHD) is an impairing neurodevelopmental disorder that remains inadequately understood. Along with the observable behavioral symptoms of inattention and hyperactivity/impulsivity, there is robust evidence of structural, functional, and neurochemical brain differences in ADHD [1
] particularly in regions involved in vital executive functions (EFs) that regulate the ability to identify, extract, and interpret what is relevant for executing the correct response, as well as monitoring, inhibiting, and changing the prepotent response as needed [4
]. The pathophysiology of ADHD remains unclear, although converging evidence suggests that alterations in brain structure, function, and physiology likely arise from an interaction of genetic and environmental causes and experience [5
]. For example, structurally, prominent volumetric decreases are evident in the posterior-inferior lobules of the cerebellar vermis in both male and female children with ADHD [9
]. There are decreases in prefrontal volume, particularly the right prefrontal cortex [9
]. Also reported are regional differences in cerebral blood flow in the cerebellum, striatum [14
] and prefrontal cortex (PFC) [15
]. Moreover, differences in baseline oscillatory activity between those with ADHD and controls have been observed in frontal regions, particularly the PFC [16
]. Consistent with the neuroimaging findings, psychological research indicates clearly that subtle but impairing problems in EFs are correlates of ADHD, regardless of gender or age [18
While the majority of ADHD research focuses on deficits in EF, it is apparent that not all individuals with ADHD have EF deficits [18
] and that not all neuropsychological difficulties can be explained by EF theory alone [20
]. Moreover, EF tasks in which individuals with ADHD do show deficits often include processing and responding to simple sensory stimuli that vary in predictability. This suggests that deficits in anticipatory or perceptual processing of simple stimuli could also contribute to impairments on tasks that assess higher-order functions. Accordingly, an important goal of ADHD research is to address not only the concept of multiple forms
of impairment but also of multiple sources
of impairment. Emerging evidence not only shows abnormalities in neural regions governing higher order function but also in regions governing basic function such as somatosensory cortex [21
], motor cortex [21
] and visual cortex [27
]. Although people with ADHD have shown behavioural deficits in responding to simple stimuli during sensorimotor tasks [28
], methodological shortcomings in the limited studies available have precluded an adequate understanding of the role of neural networks in processing predictable and non-predictable stimuli in ADHD. Specifically, existing studies have relied almost exclusively on behavioural measures (i.e., accuracy, reaction time), which cannot assess moment-by-moment activities that are driving these processes on the order of milliseconds.
Our aim was to examine basic sensory processing of predictable and non-predictable stimuli in those with ADHD using magnetoencephalography (MEG), a non-invasive functional neuroimaging technique that records neural activity on the order of a millisecond. This high temporal resolution combined with novel source reconstruction techniques capable of mm spatial resolution makes MEG an optimal technique for capturing spatial and temporal information during sensory processing for which the time scale is on the order of milliseconds. MEG studies of the human somatosensory system using median nerve stimulation have shown that only the contralateral primary somatosensory cortex (SI) responds to unilateral tactile information whereas bilateral secondary somatosensory cortices (SII) show activity in response to unilateral stimulation [31
]. The earliest somatosensory activity occurs at approximately 20 ms post-stimulation in SI just caudal to the central sulcus in the corresponding topographical location. Subsequent somatosensory activation occurs in the bilateral parietal opercula located in the dorsal regions of the lateral sulci [32
]. Source activity in SI and SII, following median nerve stimulation, is composed of both alpha and beta cortical rhythms [35
]. In association with MEG, median nerve stimulation has been used to examine evoked responses to somatosensory stimuli in order to examine somatosensory cortical function [31
] and ascending pathways from the peripheral receptors to the spinal cord, brainstem, thalamus, and cortex [38
]. This technique has also been used to examine physical and cognitive impairments in individuals with Alzheimer's [39
], stroke patients [40
], and infantile autism [41
], for example. Using MEG, we investigated the oscillatory changes during somatosensory activation in adults with and without ADHD.
The general assumption of cortical oscillations is that populations of neurons exist in varying states of synchrony as they respond to externally or internally generated events. Event-related desynchrony (ERD) and event-related synchrony (ERS) phenomena are thought to represent decreases and increases, respectively, in synchronization within a specific frequency range in relation to an event [42
]. Previous MEG studies of cortical activity following median nerve stimulation in healthy adults report brief suppression of mu (an alpha wave variant oscillating at approximately 10 Hz) and beta (15–30 Hz) cortical activity in primary and secondary somatosensory cortex (ERD) followed by a marked increase in beta band activity above baseline (late-ERS, known as beta rebound
]. Basic or complex sensory processing requires a dynamic interaction between groups of neurons oscillating at particular frequencies and differing degrees of coupling. Oscillations in the alpha and beta bands are of particular interest in ADHD research as these frequencies are thought to mediate perception [43
] and attention [45
]. To our knowledge, MEG has not yet been used to investigate changes in SI alpha or beta oscillations in individuals with ADHD. Accordingly, our aim was to characterize ERD and ERS in the alpha and beta bands in SI and SII in response to randomly and predictably presented electrical stimulation of the median nerve in adults with and without ADHD. Comparison of random versus predicted median nerve stimulation is a novel approach to determine whether basic somatosensory processing differs between those with ADHD and healthy controls and if stimulus predictability differentially influences somatosensory processing in those with ADHD compared to controls.
The neural basis of predictive responding to the absence of a stimulus in both SI and SII will be described in a subsequent report.