Personalized transcranial alternating current stimulation improves sleep quality: Initial findings.

Insufficient sleep is a major health issue. Inadequate sleep is associated with an array of poor health outcomes, including cardiovascular disease, diabetes, obesity, certain forms of cancer, Alzheimer's disease, depression, anxiety, and suicidality. Given concerns with typical sedative hypnotic drugs for treating sleep difficulties, there is a compelling need for alternative interventions. Here, we report results of a non-invasive electrical brain stimulation approach to optimizing sleep involving transcranial alternating current stimulation (tACS). A total of 25 participants (mean age: 46.3, S.D. ± 12.4, 15 females) were recruited for a null-stimulation controlled (Control condition), within subjects, randomized crossed design, that included two variants of an active condition involving 15 min pre-sleep tACS stimulation. To evaluate the impact on sleep quality, the two active tACS stimulation conditions were designed to modulate sleep-dependent neural activity in the theta/alpha frequency bands, with both stimulation types applied to all subjects in separate sessions. The first tACS condition used a fixed stimulation pattern across all participants, a pattern composed of stimulation at 5 and 10 Hz. The second tACS condition used a personalized stimulation approach with the stimulation frequencies determined by each individual's peak EEG frequencies in the 4-6 Hz and 9-11 Hz bands. Personalized tACS stimulation increased sleep quantity (duration) by 22 min compared to a Control condition (p = 0.04), and 19 min compared to Fixed tACS stimulation (p = 0.03). Fixed stimulation did not significantly increase sleep duration compared to Control (mean: 3 min; p = 0.75). For sleep onset, the Personalized tACS stimulation resulted in reducing the onset by 28% compared to the Fixed tACS stimulation (6 min faster, p = 0.02). For a Poor Sleep sub-group (n = 13) categorized with Clinical Insomnia and a high insomnia severity, Personalized tACS stimulation improved sleep duration by 33 min compared to Fixed stimulation (p = 0.02), and 30 min compared to Control condition (p < 0.1). Together, these results suggest that Personalized stimulation improves sleep quantity and time taken to fall asleep relative to Control and Fixed stimulation providing motivation for larger-scale trials for Personalized tACS as a sleep therapeutic, including for those with insomnia.

Individual differences in TMS sensitivity influence the efficacy of tDCS in facilitating sensorimotor adaptation.

BACKGROUND: Transcranial direct current stimulation (tDCS) can enhance cognitive function in healthy individuals, with promising applications as a therapeutic intervention. Despite this potential, variability in the efficacy of tDCS has been a considerable concern. OBJECTIVE: /Hypothesis: Given that tDCS is always applied at a set intensity, we examined whether individual differences in sensitivity to brain stimulation might be one variable that modulates the efficacy of tDCS in a motor learning task. METHODS: In the first part of the experiment, single-pulse transcranial magnetic stimulation (TMS) over primary motor cortex (M1) was used to determine each participant's resting motor threshold (rMT). This measure was used as a proxy of individual sensitivity to brain stimulation. In an experimental group of 28 participants, 2 mA tDCS was then applied during a motor learning task with the anodal electrode positioned over left M1. Another 14 participants received sham stimulation. RESULTS: M1-Anodal tDCS facilitated learning relative to participants who received sham stimulation. Of primary interest was a within-group analysis of the experimental group, showing that the rate of learning was positively correlated with rMT: Participants who were more sensitive to brain stimulation as operationalized by our TMS proxy (low rMT), showed faster adaptation. CONCLUSIONS: Methodologically, the results indicate that TMS sensitivity can predict tDCS efficacy in a behavioral task, providing insight into one source of variability that may contribute to replication problems with tDCS. Theoretically, the results provide further evidence of a role of sensorimotor cortex in adaptation, with the boost from tDCS observed during acquisition.

Evidence of a novel somatopic map in the human neocerebellum during complex actions.

The human neocerebellum has been hypothesized to contribute to many high-level cognitive processes including attention, language, and working memory. Support for these nonmotor hypotheses comes from evidence demonstrating structural and functional connectivity between the lateral cerebellum and cortical association areas as well as a lack of somatotopy in lobules VI and VII, a hallmark of motor representations in other areas of the cerebellum and cerebral cortex. We set out to test whether somatotopy exists in these lobules by using functional magnetic resonance imaging to measure cerebellar activity while participants produced simple or complex movements, using either fingers or toes. We observed a previously undiscovered somatotopic organization in neocerebellar lobules VI and VIIA that was most prominent when participants executed complex movements. In contrast, activation in the anterior lobe showed a similar somatotopic organization for both simple and complex movements. While the anterior somatotopic representation responded selectively during ipsilateral movements, the new cerebellar map responded during both ipsi- and contralateral movements. The presence of a bilateral, task-dependent somatotopic map in the neocerebellum emphasizes an important role for this region in the control of skilled actions.

Timing of rhythmic movements in patients with cerebellar degeneration.

A distinction in temporal performance has been identified between two classes of rhythmic movements: those requiring explicit timing of salient events marking successive cycles, i.e., event timing, and continuous movements in which timing is hypothesized to be emergent. Converging evidence in support of this distinction is reviewed, including neuropsychological studies showing that individuals with cerebellar damage are selectively impaired on tasks requiring event timing (e.g., tapping). Recent behavioral evidence in neurologically healthy individuals suggests that for continuous movements (e.g., circle drawing), the initial cycle is marked by a transformation from event to emergent timing, allowing the participant to match their movement rate to an externally defined cycle duration. We report a new experiment in which individuals with cerebellar ataxia produced rhythmic tapping or circle drawing movements. Participants were either paced by a metronome or unpaced. Ataxics showed a disproportionate increase in temporal variability during tapping compared to circle drawing, although they were more variable than controls on both tasks. However, two predictions of the transformation hypothesis were not confirmed. First, the ataxics did not show a selective impairment on circle drawing during the initial cycles, a phase when we hypothesized event timing would be required to establish the movement rate. Second, the metronome did not increase variability of the performance of the ataxics. Taken together, these results provide further evidence that the integrity of the cerebellum is especially important for event timing, although our attempt to specify the relationship between event and emergent timing was not successful.

Further evidence that Whorfian effects are stronger in the right visual field than the left.

The Whorf hypothesis holds that differences between languages induce differences in perception and/or cognition in their speakers. Much of the experimental work pursuing this idea has focused on the domain of color and has centered on the issue of whether linguistically coded color categories influence color discrimination. A new perspective has been cast on the debate by recent results that suggest that language influences color discrimination strongly in the right visual field but not in the left visual field (LVF). This asymmetry is likely related to the contralateral projection of visual fields to cerebral hemispheres and the specialization of the left hemisphere for language. The current study presents three independent experiments that replicate and extend these earlier results by using different tasks and testing across different color category boundaries. Our results differ in one respect: although we find that Whorfian effects on color are stronger for stimuli in the right visual field than in the LVF, we find that there are significant category effects in the LVF as well. The origin of the significant category effect in the LVF is considered, and two factors that might account for the pattern of results are proposed.

Ipsilateral corticospinal projections do not predict congenital mirror movements: a case report.

Congenital mirror movements (CMMs) are involuntary, symmetric movements of one hand during the production of voluntary movements with the other. CMMs have been attributed to a range of physiological mechanisms, including excessive ipsilateral projections from each motor cortex to distal extremities. We examined this hypothesis with an individual showing pronounced CMMs. Mirror movements were characterized for a set of hand muscles during a simple contraction task. Transcranial magnetic stimulation (TMS) was then used to map the relative input to each muscle from both motor cortices. Contrary to our expectations, CMMs were most prominent for muscles with the strongest contralateral representation rather than in muscles that were activated by stimulation of either hemisphere. These findings support a bilateral control hypothesis whereby CMMs result from the recruitment of both motor cortices during intended unimanual movements. Consistent with this hypothesis, bilateral motor cortex activity was evident during intended unimanual movements in an fMRI study. To assess the level at which bilateral recruitment occurs, motor cortex excitability during imagined unimanual movements was assessed with TMS. Facilitory excitation was only observed in the contralateral motor cortex. Thus, the bilateral recruitment of the hemispheres for unilateral actions in individuals with CMMs appears to occur during movement execution rather than motor planning.

The human striatum is necessary for responding to changes in stimulus relevance.

Various lines of evidence suggest that the striatum is implicated in cognitive flexibility. The neuropsychological evidence has, for the most part, been based on research with patients with Parkinson's disease, which is accompanied by chemical disruption of both the striatum and the prefrontal cortex. The present study examined this issue by testing patients with focal lesions of the striatum on a task measuring two forms of cognitive switching. Patients with striatal, but not frontal lobe lesions, were impaired in switching between concrete sensory stimuli. By contrast, both patient groups were unimpaired when switching between abstract task rules relative to baseline nonswitch trials. These results reveal a dissociation between two distinct forms of cognitive flexibility, providing converging evidence for a role of the striatum in flexible control functions associated with the selection of behaviorally relevant stimuli.

Illusory conjunctions are alive and well: a reply to Donk (1999).

When presented with a red T and a green O, observers occasionally make conjunction responses and indicate that they saw a green T. These errors have been interpreted as reflecting separable processing stages of feature detection and integration with the illusory conjunctions arising from a failure at the integration stage. Recently, M. Donk (1999) asserted that the phenomenon of illusory conjunctions is an artifact. Conjunction reports are actually the result of confusing a nontarget item (O in the example above) for a target item (the letter T) and (correctly) reporting the color associated with the (incorrectly) selected target. The authors demonstrate that although target-nontarget confusion errors are a potential source of conjunction reports, there is a plethora of findings that cannot be accounted for by this confusion model. A review of the literature indicates that in many studies, illusory conjunctions do result from a failure to properly integrate features.

Comparison of the basal ganglia and cerebellum in shifting attention.

The basal ganglia and cerebellum have traditionally been associated with motor performance. Recently, there has been considerable interest regarding the contributions of these subcortical structures to aspects of cognition. In particular, both the basal ganglia and cerebellum have been hypothesized to be involved in the control of attentional set. To date, no neuropsychological studies have directly compared the effects of basal ganglia and cerebellar dysfunction on the same attention shifting tasks. To this end, we employed an alternating attention task that has been used to demonstrate putative attentional control deficits in children with cerebellar pathology, either related to autism or neurological insult. When adult patients with either Parkinson's disease or cerebellar lesions were tested on this task, a similar pattern of deficits was observed for both groups. However, when the motor demands were reduced, cerebellar patients showed a significant improvement on the alternating attention task, whereas the Parkinson patients continued to exhibit an impairment. This dissociation suggests that attentional deficits reported previously as being due to cerebellar dysfunction may be, at least in part, secondary to problems related to coordinating successive responses. In contrast, attention-shifting deficits associated with basal ganglia impairment cannot be explained by recourse to the motor demands of the task.

The coupled oscillator model of between-hand coordination in alternate-hand tapping: a reappraisal.

Single and alternating hand tapping were compared to test the hypothesis that coordination during rhythmic movements is mediated by the control of specific time intervals. In Experiment 1, an auditory metronome was used to indicate a set of timing patterns in which a 1-s interval was divided into 2 subintervals. Performance, measured in terms of the deviation from the target patterns and variability, was similar under conditions in which the finger taps were made with 1 hand or alternated between the 2 hands. In Experiment 2, the modality of the metronome (auditory or visual) was found to influence the manner in which the produced intervals deviated from the target patterns. These results challenge the notion that bimanual coordination emerges from coupling constraints intrinsic to the 2-hand system. They are in accord with a framework that emphasizes the control of specific time intervals to form a series of well-defined motor events.

Moving to directly cued locations abolishes spatial interference during bimanual actions.

Interference is frequently observed during bimanual movements if the two hands perform nonsymmetric actions. We examined the source of bimanual interference in two experiments in which we compared conditions involving symmetric movements with conditions in which the movements were of different amplitudes or different directions. The target movements were cued either symbolically by letters or directly by the onset of the target locations. With symbolic cues, reaction times were longer when the movements of the two hands were not symmetric. With direct cues, reaction times were the same for symmetric and nonsymmetric movements. These results indicate that directly cued actions can be programmed in parallel for the two hands. Our results challenge the hypothesis that the cost to initiate nonsymmetric movements is due to spatial intetference in a motor-programming stage. Rather the cost appears to be caused by stimulus identification, response-selection processes connected to the processing of symbolic cues, or both.

Asymmetries in a unilateral flanker task depend on the direction of the response: the role of attentional shift and perceptual grouping.

Four experiments were conducted using a flanker task with 1 distractor appearing either on the left or right side of a central target. Responses were made on a keyboard aligned parallel to the displays. A larger flanker effect was obtained when the distractor was on the same side as the response. Two factors account for this asymmetry. First, when the flanker and target are identical, the 2 form a group that is assigned a spatial tag, creating a form of the Simon effect on the basis of the compatibility between the response keys and the group. Second, preparation of a lateralized response appears to entail a shift of visual attention in the corresponding direction, thus enhancing processing of the flanker on the response side. Consistent with the 2nd hypothesis, participants were more likely to correctly recognize letters that were briefly presented at the distractor position on the same side as the response.

Sequential priming in hierarchically organized figures: effects of target level and target resolution.

Three experiments are reported in which participants identified target letters that appeared at either the global or local level of hierarchically organized stimuli. It has been previously reported that response time is facilitated when targets on successive trials appear at the same level (L. M. Ward, 1982; L. C. Robertson, 1996). Experiments 1 and 2 showed that this sequential priming effect can be mediated by target-level information alone, independent of the resolution, or actual physical size, of targets. Target level and resolution were unconfounded by manipulating total stimulus size, such that global elements of the smaller stimuli subtended the same amount of visual angle as local elements of the larger stimuli. Experiment 3, however, showed that when level information is less useful than resolution in parsing targets from distractors, resolution does become critical in intertrial priming. These data are discussed as they relate to the role of attention in local vs. global (part vs. whole) processing.

Manual laterality and hitting performance in major league baseball.

Asymmetrical hand function was examined in the context of expert sports performance: hitting in professional baseball. An archival study was conducted to examine the batting performance of all Major League Baseball players from 1871 to 1992, focusing on those who batted left (n = 1,059) to neutralize the game asymmetry. Among them, left-handers (n = 421) were more likely to hit with power and to strike out than right-handers (n = 638). One possible account, based on the idea of hand dominance and an analogy to tennis, is that batting left involves a double-handed forehand for left-handers and a weaker and more reliable double-handed backhand for right-handers. The results are also interpretable in the light of Y. Guiard's (1987) kinematic chain model of a between-hands asymmetrical division of labor, which provides a detailed account of why left batting is optimal for left-handers.

Effects of divided attention on temporal processing in patients with lesions of the cerebellum or frontal lobe.

Prefrontal cortex and cerebellum have both been implicated in temporal processing tasks although the exact contribution of each system remains unclear. To investigate this issue, control participants and patients with either prefrontal or cerebellar lesions were tested on temporal and nontemporal perceptual tasks under 2 levels of attentional load. Each trial involved a comparison between a standard tone and a subsequent comparison tone that varied in frequency, duration, or both. When participants had to make concurrent judgments on both dimensions, patients with frontal lobe lesions were significantly impaired on both tasks whereas the variability of cerebellar patients increased in the duration task only. This dissociation suggests that deficits on temporal processing tasks observed in frontal patients can be related to the attention demands of such tasks; cerebellar patients have a more specific problem related to timing.

Abstract and effector-specific representations of motor sequences identified with PET.

Positron emission tomography was used to identify neural systems involved in the acquisition and expression of sequential movements produced by different effectors. Subjects were tested on the serial reaction time task under implicit learning conditions. In the initial acquisition phase, subjects responded to the stimuli with keypresses using the four fingers of the right hand. During this phase, the stimuli followed a fixed sequence for one group of subjects (group A) and were randomly selected for another group (group B). In the transfer phase, arm movements were used to press keys on a substantially larger keyboard, and for both groups, the stimuli followed the sequence. Behavioral indices provided clear evidence of learning during the acquisition phase for group A and transfer when switched to the large keyboard. Sequence acquisition was associated with learning-related increases in regional cerebral blood flow (rCBF) in a network of areas in the contralateral left hemisphere, including sensorimotor cortex, supplementary motor area, and rostral inferior parietal cortex. After transfer, activity in inferior parietal cortex remained high, suggesting that this area had encoded the sequence at an abstract level independent of the particular effectors used to perform the task. In contrast, activity in sensorimotor cortex shifted to a more dorsal locus, consistent with motor cortex somatotopy. Thus, activity here was effector-specific. An increase in rCBF was also observed in the cingulate motor area at transfer, suggesting a role linking the abstract sequential representations with the task-relevant effector system. These results highlight a network of areas involved in sequence encoding and retrieval.

Response channel activation and the temporoparietal junction.

When we learn to make one motor response to one visual stimulus and a different motor response to another, representations of these stimulus-response associations must be maintained to efficiently transduce perception into action. When an irrelevant distractor is presented adjacent to a target stimulus, interference is observed when the two stimuli are associated with conflicting responses, presumably due to response channel activation by the incompatible information. We have explored the neural bases of these interference effects. In a previous study, patients with hemispatial neglect showed normal interference from contralesional flankers. In another study, patients with lesions of the lateral prefrontal cortex were found not to show interference from distractors presented in the contralesional hemifield. The current study provided a more anatomically detailed investigation of the effects of posterior association cortex lesions on flanker interference. Patients with chronic, unilateral lesions involving the temporoparietal junction (TPJ), two of whom had hemispatial neglect, were compared with patients with lesions of the posterior association cortex not involving the TPJ. All patients performed a color discrimination task at fixation while a congruent or incongruent colored flanker was briefly presented (16.7 ms) in the adjacent contralesional or ipsilesional hemifield. Patients with TPJ lesions showed no interference effects from the contralesional flankers. These results suggest that the TPJ, in combination with the dorsolateral prefrontal cortex, is involved in transducing perception into action.

Dissociable contributions of the prefrontal and neocerebellar cortex to time perception.

We report a series a three psychophysical experiments designed to differentiate the contributions of the neocerebellar and prefrontal cortex to time perception. Comparison of patients with focal, unilateral neocerebellar or prefrontal lesions on temporal discrimination of 400-ms and 4-s intervals (Expt. 1) indicated that neocerebellar damage impaired timing in both millisecond and seconds ranges, whereas prefrontal damage resulted in deficits that were robust only at the longer duration. Patients with prefrontal lesions, however, also exhibited working memory deficits on a non-temporal task (Expt. 2), biases in point of subjective equality indicative of attentional deficits, and were disproportionately sensitive to strategic manipulations in a long-duration discrimination task (Expt. 3). In contrast, the pervasive timing deficits of cerebellar patients were relatively insensitive to strategic support and could not be readily explained by general deficits in working memory or attention. These findings support the hypothesis that neocerebellar regions subserve a central timing mechanism, whereas the prefrontal cortex subserves supportive functions associated with the acquisition, maintenance, monitoring and organization of temporal representations in working memory. Such functions serve to bridge the output of the central timing mechanism with behavior. Together, these regions appear to participate in a working memory system involved in discrimination of durations extending from a few milliseconds to many seconds.

The psychological refractory period effect following callosotomy: uncoupling of lateralized response codes.

A callosotomy patient was tested in 2 dual-task experiments requiring successive speeded responses to lateralized stimuli. The patient showed a robust psychological refractory period (PRP) effect. Three aspects of the data indicate that, unlike for the control participants, the PRP effect for the split-brain patient should not be attributed to a response selection bottleneck. First, the patient did not show an increase in reaction time (RT) when the 2 tasks required responses from a common output system compared with when different output systems were used. Second, inconsistent stimulus-response mappings for the 2 tasks increased RTs for the control participants but had minimal effect on the performance of the split-brain patient. Third, the consistency manipulation was underadditive with stimulus onset asynchrony but was additive or overadditive for the normal participants. These results suggest that the persistent PRP effect following callosotomy should be attributed to a bottleneck associated with response initiation, a strategy adopted to comply with the task demands, or a combination of these factors.