Ian J. Kirk

Supramammillary cell firing and hippocampal rhythmical slow activity.

Extracellular multi-unit activity was recorded from sites in the supramammillary area of urethane anaesthetized rats, while simultaneously recording the hippocampal EEG. The pattern of supramammillary area cell discharge was found to be rhythmic and in phase with concurrent hippocampal rhythmical slow activity (RSA). Septal application of procaine (20%, 1-5 microliters), that abolished hippocampal RSA, did not abolish the rhythmicity of supramammillary cell firing. These data suggest that the frequency of hippocampal RSA may be determined in the supramammillary area rather than in the medial septum as has previously been supposed.

Comparison of the N300 and N400 ERPs to picture stimuli in congruent and incongruent contexts.

OBJECTIVES The aim of this study was to examine the N300 and N400 effect to pictures that were semantically incongruous to a prior object name. Based upon theories of object identification, the semantic incongruity was manipulated to occur early or late in the object processing stream. METHODS High-density visual event-related potentials were measured in response to passively viewed black and white line drawings of common objects. Pictures were preceded with an object name at either the basic (categorical) or subordinate (specific) level. The object either matched or mismatched with the name. With subordinate level names, mismatches could be within- or between-category. RESULTS The N400 effect was found for both basic and subordinate level mismatches. The N400 was found for both the subordinate-within and subordinate-between. Comparison of the scalp distributions between these N400 effects suggested a common effect was found for all conditions. The N300 effect, however, was only found for between-category mismatches, and only when semantic expectations were high in the match baseline (subordinate matches). CONCLUSIONS The findings are consistent with theories of object identification that suggest that objects are initially categorized prior to being identified at more specific levels. The N300 appears to reflect the categorisation while the N400 effect appears to be responsive to all semantic mismatches. Comparison of scalp topographies, functional differences, and different estimated cortical source locations suggest that the N300 and N400 are two distinct semantic effects that reflect aspects of object identification.

The neurophysiological correlates of face processing in adults and children with Asperger's syndrome

Past research has found evidence for face and emotional expression processing differences between individuals with Aspergers syndrome (AS) and neurotypical (NT) controls at both the neurological and behavioural levels. The aim of the present study was to examine the neurophysiological basis of emotional expression processing in children and adults with AS relative to age- and gender-matched NT controls. High-density event-related potentials were recorded during explicit processing of happy, sad, angry, scared, and neutral faces. Adults with AS were found to exhibit delayed P1 and N170 latencies and smaller N170 amplitudes in comparison to control subjects for all expressions. This may reflect impaired holistic and configural processing of faces in AS adults. However, these differences were not observed between AS and control children. This may result from incomplete development of the neuronal generators of these ERP components and/or early intervention.

Long‐term potentiation of human visual evoked responses

Long‐term potentiation (LTP) is a candidate synaptic mechanism underlying learning and memory that has been studied extensively at the cellular and molecular level in laboratory animals. To date, LTP has only been directly demonstrated in humans in isolated cortical tissue obtained from patients undergoing surgery, where it displays properties identical to those seen in non‐human preparations. Inquiry into the functional significance of LTP has been hindered by the absence of a human model. Here we give the first demonstration that the rapid repetitive presentation of a visual checkerboard (a photic ‘tetanus’) leads to a persistent enhancement of one of the early components of the visual evoked potential in normal humans. The potentiated response is largest in the hemisphere contralateral to the tetanized visual hemifield and is limited to one component of the visual evoked response (the N1b). The selective potentiation of only the N1b component makes overall brain excitability changes unlikely and suggests that the effect is due instead to an LTP process. While LTP is known to exist in the human brain, the ability to elicit LTP from non‐surgical patients will provide a human model system allowing the detailed examination of synaptic plasticity in normal subjects and may have future clinical applications in the assessment of cognitive disorders.

Induction of LTP in the human auditory cortex by sensory stimulation.

High‐frequency, repetitive, auditory stimulation was used to determine whether induction of a long‐lasting increase of the human auditory evoked potential (AEP) was possible. Recording non‐invasively with electroencephalogram scalp electrodes, stable increases in amplitude were observed in the N1 component of the AEP, which is thought to reflect activity within auditory cortex (N1). The increase was maintained over an hour and was shown to be independent of alterations in the state of arousal. This is the first demonstration of the induction of long‐lasting plastic changes in AEPs, and suggest that this represents the first direct demonstration of long‐term potentiation in the auditory cortex of normal, intact humans.

An ERP investigation of the Stroop task: The role of the cingulate in attentional allocation and conflict resolution

The majority of studies support a role of the anterior cingulate cortex (ACC) in the attentional control necessary for conflict resolution in the Stroop task; however, the time course of activation and the neural substrates underlying the Stroop task remain contentious. We used high-density EEG to record visual-evoked potentials from 16 healthy subjects while performing a manual version of the traditional Stroop colour-word task. Difference waveforms for congruent-control and incongruent-control conditions were similar in amplitude and had a similar spatial distribution in the time window of 260-430 ms post stimulus onset. Source estimation indicated particularly middle cingulate involvement in congruent-control and incongruent-control difference waveforms. In contrast, the difference waveform for the incongruent-congruent contrast was observed later (in the time window of 370-480 ms), had a different spatial distribution, and source estimation indicated that the anterior cingulate underlies this difference waveform. As congruent-control and incongruent-control differences have a similar timeframe and cingulate source, we propose that this indicates early attentional allocation processes. That is, the identification of two sources of information (the word and the colour it is printed in) and the selective attention to one. The later peak in the incongruent-congruent difference wave, originating in anterior cingulate, likely reflects identification (and subsequent resolution) of conflict in the two sources of information.

Translating Long-Term Potentiation from Animals to Humans: A Novel Method for Noninvasive Assessment of Cortical Plasticity

Long-term potentiation (LTP) is a synaptic mechanism underlying learning and memory that has been studied extensively in laboratory animals. The study of LTP recently has been extended into humans with repetitive sensory stimulation to induce cortical LTP. In this review article, we will discuss past results from our group demonstrating that repetitive sensory stimulation (visual or auditory) induces LTP within the sensory cortex (visual/auditory, respectively) and can be measured noninvasively with electroencephalography or functional magnetic resonance imaging. We will discuss a number of studies that indicate that this form of LTP shares several characteristics with the synaptic LTP described in animals: it is frequency dependent, long-lasting (> 1 hour), input-specific, depotentiates with low-frequency stimulation, and is blocked by N-methyl-D-aspartate receptor blockers in rats. In this review, we also present new data with regard to the behavioral significance of human sensory LTP. These advances will permit enquiry into the functional significance of LTP that has been hindered by the absence of a human model. The ability to elicit LTP with a natural sensory stimulus noninvasively will provide a model system allowing the detailed examination of synaptic plasticity in normal subjects and might have future clinical applications in the diagnosis and assessment of neuropsychiatric and neurocognitive disorders.

Influence of Task Complexity on Manual Asymmetries

The degree of manual asymmetry is generally assumed to vary with task complexity. However, task complexity as a factor in manual asymmetries has rarely been examined directly. Further, the results of psychophysical studies indicate that manual asymmetry increases with task complexity, while physiological studies consistently report a reduction of manual asymmetries in more complex tasks. The use of different tasks (rather than different complexity levels within a given task) in many psychophysical studies might result in this inconsistency. This study investigated the influence of task complexity on manual asymmetries in 70 right-handed subjects. We used three complexity levels within a finger-tapping paradigm. A strong advantage of the preferred hand was particularly pronounced in the simple finger-tapping task. When the task was more complex, the advantage of the preferred hand, and thus, the manual asymmetry significantly decreased or disappeared. These results support previous suggestions that simple motor tasks involve localised neural networks confined to one cerebral hemisphere, while complex motor tasks are controlled by more widely distributed neuronal assemblies that involve both hemispheres. However, the influence of task complexity on manual asymmetry seems not to be monotonic.

The unusual symmetry of musicians: Musicians have equilateral interhemispheric transfer for visual information

Previous behavioural research has shown that spatial attention is bilaterally represented in musicians, possibly reflecting more equal neural development between the hemispheres. We investigated this theory electrophysiologically with another measure that has shown asymmetry, interhemispheric transfer time (IHTT). Sixteen right-handed musicians and 16 matched non-musicians responded to stimuli presented to the left and right visual fields while 128-channel EEG was recorded. IHTT was calculated by comparing the latencies of occipital N1 components between hemispheres. Non-musicians showed significantly faster IHTT in the right-to-left direction than in the left-to-right direction and a shorter N1 latency in the left than in the right hemisphere. In contrast, the musician group showed no directional difference between hemispheres in IHTT, and no hemispheric difference in latency. These results indicate that musicians have more bilateral neural connectivity than non-musicians, reflected in an unusual lack of asymmetry. It is suggested that plastic developmental changes caused by extended musical training in childhood result in equally efficient connections to both hemispheres.

Impaired sensorimotor integration in focal hand dystonia patients in the absence of symptoms

Background Functional imaging studies of people with focal hand dystonia (FHD) have indicated abnormal activity in sensorimotor brain regions. Few studies however, have examined FHD during movements that do not provoke symptoms of the disorder. It is possible, therefore, that any differences between FHD and controls are confounded by activity due to the occurrence of symptoms. Thus, in order to characterise impairments in patients with FHD during movements that do not induce dystonic symptoms, we investigated the neural correlates of externally paced finger tapping movements. Methods Functional MRI (fMRI) was used to compare patients with FHD to controls with respect to activation in networks modulated by task complexity and hand used to perform simple and complex tapping movements. Results In the ‘complexity network,’ patients with FHD showed significantly less activity relative to controls in posterior parietal cortex, medial supplementary motor area (SMA), anterior putamen and cerebellum. In the ‘hand network,’ patients with FHD showed less activation than controls in primary motor (M1) and somatosensory (S1) cortices, SMA and cerebellum. Conjunction analysis revealed that patients with FHD demonstrated reduced activation in the majority of combined network regions (M1, S1 and cerebellum). Conclusion Dysfunction in FHD is widespread in both complexity and hand networks, and impairments are demonstrated even when performing tasks that do not evoke dystonic symptoms. These results suggest that such impairments are inherent to, rather than symptomatic of, the disorder.