Jeff P. Hamm

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.

Cerebral asymmetry for mental rotation: effects of response hand, handedness and gender.

We assessed lateralization of brain function during mental rotation, measuring the scalp distribution of a 400–600 ms latency event-related potential (ERP) with 128 recording electrodes. Twenty-four subjects, consisting of equal numbers of dextral and sinistral males and females, performed a mental rotation task under two response conditions (dominant vs non-dominant hand). For males, ERPs showed a right parietal bias regardless of response hand. For females, the parietal ERPs were slightly left-lateralized when making dominant hand responses, but strongly right-lateralized when making non-dominant hand responses. These results support the notion that visuo-spatial processing is more bilaterally organized in females. However, left hemisphere resources may be allocated to response preparation when using the non-dominant hand, forcing visuo-spatial processing to the right hemisphere.

High-density mapping in an N400 paradigm: evidence for bilateral temporal lobe generators

OBJECTIVE The aim of this study was to obtain a more detailed description of N400 scalp topography than has previously been reported. METHODS High-density (128 channel) visual event-related potentials were measured in an N400 paradigm using semantically incongruous sentence endings. RESULTS The stimuli elicited an N400 with a centroparietal scalp distribution. In addition, P400s with similar timing and functional characteristics were observed at non-standard recording locations inferior to the temporal lobes. CONCLUSIONS The data are consistent with intracranial evidence for bilateral activation of anterior medial temporal lobe structures. These structures are oriented such that the positive regions of their scalp fields lie largely outside of the area sampled by standard electrode montages. P400s at other non-standard scalp locations, including infraorbital and infraoccipital sites, may reflect volume conduction from the same generators, or activation of non-temporal lobe generators.

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.

Non-identical neural mechanisms for two types of mental transformation: event-related potentials during mental rotation and mental paper folding

Reaction times, accuracy and 128-channel event-related potentials (ERPs) were measured from 14 normal, right-handed subjects while they performed two different parity-judgment tasks that require transformations of mental images: a relatively simple task requiring a single transformation (mental letter rotation), and a more complex task involving a coordinated sequence of transformations (mental paper folding). Reaction times increased monotonically with larger angular displacements from the upright (for mental rotation) and with number of squares carried (for mental paper folding). Both the tasks resulted in amplitude modulation of an approximately 420-700 ms latency ERP component at parietal electrodes. Scalp topographies indicated that right parietal cortex was activated during mental rotation, but bilateral parietal regions were activated during mental paper folding. Our results support the notion of a right hemispheric superiority for tasks involving simple, single mental rotations, but indicate greater involvement of the left hemisphere when a more complex sequence of transformations are required. This task-dependent lability of hemispheric function may account for some of the inconsistent results reported by previous neuroimaging and electrophysiological studies.

Functional neuroanatomy of mental rotation

Brain regions involved in mental rotation were determined by assessing increases in fMRI activation associated with increases in stimulus rotation during a mirror-normal parity-judgment task with letters and digits. A letter–digit category judgment task was used as a control for orientation-dependent neural processing unrelated to mental rotation per se. Compared to the category judgments, the parity judgments elicited increases in activation in both the dorsal and the ventral visual streams, as well as higher-order premotor areas, inferior frontal gyrus, and anterior insula. Only a subset of these areas, namely, the posterior part of the dorsal intraparietal sulcus, higher-order premotor regions, and the anterior insula showed increased activation as a function of stimulus orientation. Parity judgments elicited greater activation in the right than in the left ventral intraparietal sulcus, but there were no hemispheric differences in orientation-dependent activation, suggesting that neither hemisphere is dominant for mental rotation per se. Hemispheric asymmetries associated with parity-judgment tasks may reflect visuospatial processing other than mental rotation itself, which is subserved by a bilateral fronto-parietal network, rather than regions restricted to the posterior parietal.

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.